Steven Opal reviews the phenomenon of bacterial communities and discusses the role played by bacterial communication and cooperation in host-pathogen interactions, particularly in urinary tract infection. PLoS Medicine, Rosen and colleagues [Escherichia coli commonly exist and are likely of to be of clinical significance in uncomplicated bacterial cystitis. This novel finding is remarkable in many respects, not the least of which is the circuitous route by which our understanding about bacterial communities has evolved in the pathogenesis of infectious diseases.In this issue of lleagues  present Since the inception of the germ theory of disease over 150 years ago, it has generally been assumed that potential pathogens invade the host essentially as solitary microorganisms (“lone soldiers”). Successful pathogens must find a susceptible host and then gain access to host tissues through a defect in epithelial barriers. The pathogen must replicate rapidly, and either overwhelms the host's innate and adaptive immune system, or successfully evades antimicrobial defenses by avoiding host recognition and clearance mechanisms .Vibrio fischeri, which forms an unusual symbiotic relationship with the Hawaiian bobtail squid (Euprymna scolopes). The bioluminescent V. fischeri is taken up by light organs along the body of the squid and, when high concentrations of bacteria are attained, the bacterium induces its luciferase genes to generate visible light.This traditional view of microbial pathogenesis was turned on its head about 30 years ago when three microbiologists, Nealson, Platt, and Hastings [PLoS Medicine:This Research in Translation article discusses the following new study published in 10.1371/journal.pmed.0040329Rosen DA, Hooton TM, Stamm WE, Humphrey PA, Hultgren SJ (2007) Detection of intracellular bacterial communities in human urinary tract infection. PLoS Med 4(12): e329. doi:Analyzing urine specimens from women with bladder infections, David Rosen and colleagues find evidence for intracellular bacterial communities, which have been associated with recurrent urinary tract infections in mice.V. fischeri.The bacteria benefit from this mutualistic relationship, as the squid provides a source of nutrients for the bacteria. Meanwhile, the squid benefits from the microbial light source, which provides a unique form of camouflage for the squid during nighttime mating rituals. The adult squid populations congregate in large numbers along the water's surface for mating. On moonlit nights, the squid's body is silhouetted against a starlit sky and is thus readily detectable from below by predatory fish. Light organs on the underside of the squid provide a “starry sky camouflage” by their association with the light-generating clusters of Vibrio species is only activated with high bacterial densities. But how do individual bacterial cells know their relative concentration within the light organ of the squid? The answer was discovered when V. fischeri was found to produce a soluble “quorum sensing” molecule that co-activates the operon for luciferase production in neighboring bacteria when the organisms are in high concentration [The bioluminescent potential of this ntration .E. coli, use quorum sensing genes to regulate critically important virulence genes during microbial invasion.This observation was initially viewed as a mere curiosity unique to marine microbiology until genome searches revealed homologous quorum sensing genes among many clinically relevant microbial pathogens . RemarkaV. fischeri and uses acyl homoserine lactone (acyl HSL) molecules for signaling. This system is widely used by medically important gram-negative bacterial pathogens. The second system, found in gram-positive bacteria, is a functionally homologous version of quorum sensing that uses a series of short cyclic peptides and a two-component receptor–kinase signaling pathway. A third hybrid system, found in both gram-positive and gram-negative bacterial species, uses some elements similar to the acyl HSL system of gram-negative bacteria and the receptor–kinase system of gram-positive bacteria [At least three separate systems of quorum sensing and auto-induction molecules exist in bacteria. The first is highly homologous to the system found in bacteria ,6.What is now clear is that bacterial communication and cooperation is a ubiquitous phenomenon and that these communications systems are control elements in host–pathogen interactions . The entPseudomonas aeruginosa can sense human gamma interferon, alerting the bacterial pathogen to physiologic stress within the infected host [Recent evidence now reveals that these communication pathways can cross kingdom boundaries . Bacterited host .Quorum sensing is essential to the production of healthy and fully developed biofilms. These palisade-like complex multicellular structures are relatively stable communities of bacterial populations living in a sessile, protected environment . Their sBiofilm communities develop rapidly on catheter surfaces and on mucous membranes along epithelial surfaces. Bacterial communities residing on urinary catheter surfaces are relatively refractory to the lytic action of many antibiotics. This resistance undermines the capacity of antimicrobial agents to eradicate infections on biofilmladen foreign bodies within the genitourinary system .Qazi et al., 2006 [S. aureus; this pathway could favor the quorum sensing gram-negative pathogens over S. aureus when in competition for limited resources during microbial invasion of the host.l., 2006  The sameShiner et al., 2005 [l., 2005  This manWu et al., 2005 [P. aeruginosa uses its quorum sensing apparatus to detect and signal transcriptional programs for virulence expression in response to human interferon gamma. This interferon marker signals an inflammatory stress in the host during microbial invasion by the microbial pathogen.l., 2005  P. aerugNovick et al., 2003 [l., 2003  An excelSmith et al., 2003 [P. aeruginosa and their respective roles in biofilm formation and bacterial pathogenesis.l., 2003  This papE. coli cystitis. Up to 41% of urine specimens in women with cystitis have evidence of filamentous bacterial forms, a morphologic hallmark of recent residence among sessile bacterial communities. Similar findings have previously been reported in the murine model of cystitis [Rosen and colleagues  now go ocystitis . CytologAcyl homoserine lactone: a highly soluble, cyclic homoserine moiety covalently linked to short fatty acids that functions as a quorum sensing signal molecule for many gram-negative bacteriaAuto-induction molecule: diffusible low-molecular weight signal molecule recognized by the microorganism that produced the molecule and capable of inducing changes in the transcription of specific genesHalophilic: capable of living in a salty environmentOpen reading frames: Sequences of DNA that include the start codon AUG and appropriate translation sequences that generate a functional protein productOperon: a series of adjacent open reading frames transcribed from a single promoter site that generates gene products working on the same metabolic pathwayQuorum sensing: ability to detect the density of a bacterial population and alter genetic programs in response to that population densityReceptor–kinase signaling pathway: two-component system consisting of a membrane receptor to detect extracellular ligands, linked to an intracellular phosphorylating enzyme, which alters the transcriptional programs of the bacterial cellToll-like receptor: Pattern recognition receptor used by the innate immune system to detect and respond to highly conserved microbial mediators such as bacterial lipopolysaccharide or bacterial flagellinE. coli have the capacity to invade epithelial lining cells, where they find sanctuary from immune surveillance and urinary clearance mechanisms [Uropathogenic chanisms ,16. The There are numerous implications of these findings for the pathogenesis of urinary tract infections, and for the possible treatment options available to prevent recurrent infection in UTI-prone women. These sessile bacterial communities might easily provide a sequestered site from antimicrobial defenses, allowing for repopulation of the urinary tract after a seemingly appropriate course of antimicrobial agents for bacterial cystitis. The formation of IBCs is a Toll-like receptor (TLR4)-dependent process in the murine system  and is lE. coli? Staphylococcus aureus regulates many of its virulome invasion genes through its auto-inducing peptides and quorum sensing system [S. aureus or other gram-positive bacterial pathogens use communal intracellular invasion strategies.The current study was performed in young, sexually active women. Many women had a history of recurrent bacterial cystitis. What is the prevalence of IBCs in children, the elderly, or men or women experiencing their first episode of UTI? Does the presence of IBCs in first episodes of UTI indicate a greater propensity for treatment failure or relapsing urinary tract infection? What is the prevalence of IBCs in patients with upper urinary tract infections or complicated urinary tract infections associated with urinary obstruction or foreign bodies? Are similar IBCs identifiable with pathogens other than g system ,5. It woThe findings of Rosen et al.  raise th


Earlier studies on the kinetics, glucosedependenceand sensitivity to metabolic inhibitorsof the interaction between NAT and KATP channelssuggested a distinct signaling pathways with NATcompared to REP, glyburide (GLY) or glimepiride(GLI). To obtain further evidence for this concept,the present study compared the insulin secretion invitro from rat islets stimulated acutely by NAT, GLY,GLI or REP at equipotent concentrations during 1-hrstatic incubation following overnight treatmentwith GLY or tolbutamide (TOL). The islets fullyretained the responsiveness to NAT stimulationafter prolonged pretreatment with both SUs, whiletheir acute response to REP, GLY, and GLI wasmarkedly attenuated, confirming the desensitizationof islets. The insulinotropic efficacy of NAT in isletsdesensitized to SUs may result from a distinctreceptor/effector mechanism, which contributes tothe unique pharmacological profile of NAT.Chronic exposure of pancreatic islets to sulfonylureas(SUs) is known to impair the ability of isletsto respond to subsequent acute stimulation bySUs or glucose. Nateglinide (NAT) is a novelinsulinotropic agent with a primarily site of actionat


Here we report the unusual case of a patient who suffered from acute optic neuropathy following hemispherical subdural hematoma. Although confirmed up to now only through necropsy studies, our case strongly suggests a local, microcirculatory deficit identified through magnetic resonance imaging A 70-year-old Caucasian German who developed a massive left hemispheric subdural hematoma under oral anticoagulation presented with acute, severe visual impairment on his left eye, which was noticed after surgical decompression. Neurologic and ophthalmologic examinations indicated sinistral optic neuropathy with visual acuity reduced nearly to amaurosis. Ocular pathology such as vitreous body hemorrhage, papilledema, and central retinal artery occlusion were excluded. An orbital lesion was ruled out by means of orbital magnetic resonance imaging. However, cerebral diffusion-weighted imaging and T2 maps of magnetic resonance imaging revealed a circumscribed ischemic lesion within the edematous, slightly herniated temporomesial lobe within the immediate vicinity of the affected optic nerve. Thus, the clinical course and morphologic magnetic resonance imaging findings suggest the occurrence of pressure-induced posterior ischemic optic neuropathy due to microcirculatory compromise.in vivo magnetic resonance imaging diagnostics which may remain unconsidered by computed tomography.Although lesions of the second cranial nerve following subdural hematoma have been reported individually, their pathogenesis was preferentially proposed from autopsy studies. Here we discuss a dual, pressure-induced and secondarily ischemic pathomechanism on the base of  In these studies, microcirculatory compromise of the optic nerve was proven as a pathogenic mechanism . In thisA 70-year-old Caucasian man of German nationality receiving warfarin therapy for the primary prevention of chronic atrial fibrillation was admitted to our hospital due to symptoms of a coronary syndrome. An initial international normalized ratio (INR) of 1.7 was elevated to therapeutic ranges (INR = 2.5). Three days later, the patient was found comatose after a first-ever generalized seizure. Cerebral computed tomography (CT) revealed a subdural hematoma measuring 16 mm at its maximum thickness and covering almost the entire left convexity which caused a massive midline shift Figure . Rapid cTwo days after extubation and recovery from anaesthesia, the patient complained of severe sinistral visual loss. Neurologic and ophthalmologic examinations confirmed a severely reduced visual acuity on his left eye with concomitant afferent pupillary defect. A normal vascular fundoscopy and the lack of papilledema led to the working diagnosis of posterior ON. Four days after the surgery, a follow-up DWI of the cerebral MRI Figure  showed aThe corresponding hyperintensity of T2-weighted images indicated focal brain edema in line with regional hypoperfusion and the preceding uncal shift Figure . Thus, pin vivo findings do not at all elucidate its aetiology. Generally, reports do not present the existence of papilledema or of radiologic in vivo evidence of optic nerve compression by mass effects [To date, only a few cases of ON following subdural hematoma are presented, and their pathomorphologic  effects . In cont effects .The pathophysiology of ON has been discussed in the context of diverse aetiological events, and adequate diagnostic approaches have already been proposed. Table At present, only a few cases refer to the diagnostic value of MRI in ON. By means of MRI, unilateral  and simuin vivo. Radiological signs of herniation were discrete, although highly sensitive MRI revealed a mechanic, pressure-induced brain lesion of the mesiobasal temporal lobe in proximity to the affected optic nerve. However, focal ischemic injury was missed in detecting basal brain shift by CT. Since MRI pathologies fulfilled the criteria of ischemic compromise, we suggest that the local increase in intracranial pressure (ICP) exceeded the perfusion pressure of both structures, namely the formation of the uncus and the nearby passing optic nerve. Consistent with this notion of a microcirculatory deficit, the lesion did not follow the characteristic extent of a vascular territory.Using the MRI technique, we now provide a pathophysiologic insight on ON following space occupying subdural hematoma early We suggest that rare cases of acute ON following subdural hematoma are due to local pressure-induced optic nerve infarction. This pathomechanism may remain neglected when massive brain shift is lacking or when CT is the only diagnostic means. The use of serial MRI may help balance the discrepancy between the paucity of clinical reports and frequent neuropathological findings of anterior visual pathway damage in space-occupying brain injury .ADC: apparent diffusion coefficient; AION: anterior ischemic optic neuropathy; CT: computed tomography; DWI: diffusion-weighted imaging; FLAIR: fluid attenuated inverse recovery; ICP: intracranial pressure; INR: international normalized ratio; MRI: magnetic resonance imaging; ON: optic neuropathy; PION: posterior ischemic optic neuropathy.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.AK and CP interpreted the patient data and clinical course regarding the neurological disease. HF, OW and CT were major contributors in conceiving and writing the manuscript. All authors read and approved the final manuscript.


Helix pomatia (HPA), is associated with metastatic competence and poor patient prognosis in a range of human adenocarcinomas. These glycoproteins remain poorly characterised, and their functional role has yet to be elucidated. This study describes characterisation of a range of human breast/breast cancer cell lines for the expression of the N-acetylgalactosaminylated glycoproteins of interest, and their comparison with normal breast epithelium and a range of clinical breast carcinoma samples. Confocal and light microscopy studies revealed cytochemical HPA-binding patterns consistent with a fundamental disruption in normal glycobiosynthetic pathways attending increasing metastatic potential. We report the most complete comparative analysis of HPA-binding ligands from cultured breast cells, clinical breast carcinoma samples and normal breast epithelium to date. Lectin blotting identified 11 major HPA-binding glycoprotein bands common to both clinical tumour samples and breast cell lines and 6 of these bands were also expressed by samples of normal breast epithelium, albeit at much lower levels. Moreover, very marked quantitative but not qualitative differences in levels of expression consistent with metastatic capability were noted. © 2001 Cancer Research Campaignhttp://www.bjcancer.comOver-expression of N-acetylgalactosamine glycoproteins as detected by binding of the lectin from


We have previously documented the development and subsequent disappearance of cytolytic activity mediated by lymphocytes from lymph nodes draining Moloney sarcomas destined either to regress or grow progressively. We now report that these tumour-draining lymphnode cells (LNC) that were no longer cytotoxic, spontaneously regenerated peak levels of killing after culture in vitro for 4 days in the absence of exogenous tumour antigen. Cytolytic activity, which was antigenically specific, was mediated by T lymphocytes. Resurgence of cytolytic activity in vitro was accompanied by proliferative changes  which peaked on the 3rd day of culture. Although normal, nonimmune LNC underwent quantitatively similar proliferative changes in culture, the killing that developed was weak and antigenically nonspecific. Transfer of cultured, tumour-draining LNC to immunologically compromised, syngeneic mice conferred complete protection from Moloney sarcoma progression. Adoptive transfer could be delayed for 6 days after tumour induction without loss of protection. These results suggest that there exists in Moloney sarcoma-bearing mice a mechanism that limits the differentiation of pre-killer cells into cytolytically active T lymphocytes, and that such inhibition is eliminated when LNC are explanted into culture.


This report presents histopathological evidence of mycotic infection of the gingival epithelium followed by inverted verrucous giant cell epitheliomata of the gingiva. Sections from biopsy tissue revealed intercellular spaces of the parabasal squamous epithelium parasitized by Periodic Acid Schiff stain positive branching septate hyphae and conidia of morphological appearance of Trichophyton. Epithelial cells presented epitheliomatous proliferation with formation of giant cells showing phagocytosed fragments of mold. Some fungi are known for carcinogenic metabolites and signaling. Dermatop13, differential leucocyte count - P68L29E2M1, fasting blood sugar 95 mg/dL, serum urea 29 mg/dL and serum creatinine 1.1 mg/dL. Screening tests for human immunodeficiency virus, hepatitis and syphilis were negative.A 52-year-old goldsmith's ash washerman with a history of extraction of aching right upper second molar tooth 2 years back followed by painful on-and-off swelling, managed by the patient by frequenting dentists' prescriptions and consumption of countryside liquor a bottle a day, was referred to this hospital. Gingival biopsy with clinical diagnosis of leukoplakia/squamous carcinoma was submitted for histopathological diagnosis. The patient had no history of fungal infection of the skin or nails. The total leucocyte count was 8,000 cells/mmSections from the biopsy tissue revealed surface dyskeratosis with underlying keratinocytic hyperplasia of the gingival epithelium. Basal and parabasal layers presented with epitheliomatous proliferation of cells with formation of giant cells. Retepegs were broadened and elongated with keratinocytes in a pearl arrangement forming the core and hyperplastic cells dotted by giant cells at the periphery . At placPeriodic Acid Schiff (PAS) stained sections revealed septate branching fungal hyphae of mold parasitizing intercellular clefts in basal and parabasal squamous layers, with the cells around undergoing immunoactive and giant cell transformations . Some ofLow-mitotic basal–parabasal epitheliomatous proliferation with dyskeratotic–acanthocytic hyperplasia, pearl formation and papillary clubbing and elongation of retepegs are the features diagnostic of epitheliomatous-inverted papilloma or verrucous–hyperplastic leukoplakia, which di4th century. Oral mycosis, particularly periodontal infection caused by dermatophytosis, and host-defensive activity of human cells in response to trichophyton have also been reported,[Histopathological evidence in the present case was diagnostic of mycotic giant cell epitheliomatous inverted papilloma of the gingiva. Oropharyngeal proliferative verrucous leukoplakia and its related lesions, like invreported,7 besidesreported,2 TrichopDermatophytes are known for cutaneous infections and for invading and parasitizing superficial keratinocytic layers, while keratin is believed to be the source of nourishment for the mold. In the pDermatophytes are rarely known to infect the wet epithelium of the gum, except through periodontal mycosis leading to gingival hyperplasia. History Trichophyton mold can infest and parasitize the basal and parabasal layers of the gingival squamous epithelium. The portal of entry may be periodontal.Acanthocytes around the hyphae of the mold may respond by giant cell epitheliomatous response and verrucous keratinocytosis.Intercellularly parasitizing PAS-positive hyphae, phagocytosed segments of hyphae and conidia may be demonstrable in the giant cell epitheliomatous areas.No fungal hyphae or identifiable fragments of mold may be visible in areas of the gingival epithelium undergoing advanced keratinocytic change.Giant cells in the epithelioma call for detailed meticulous histopathological examination for the pathogenic organism.


Current Neuropharmacology devoted to the theme of AED conversions and related issues. In this series of articles, we reviewed the role of AED monotherapy in newly diagnosed epilepsy, the practice of transitional polytherapy during AED monotherapy conversions in patients experiencing breakthrough seizures or adverse effects, chronic maintenance polytherapy for refractory epilepsy, and the related topics of strategies for minimizing adverse effects, appropriate blood level monitoring, and patient-related factors in AED conversions. Successful conversion between AED monotherapies and polytherapy drug sequencing requires that practitioners possess and apply a thorough knowledge of epilepsy, AED pharmacology, and clinical reasoning, while being sensitive and reactive to patient reported adverse effects of treatment.The process of conversion between AED monotherapies is frequently necessary in epilepsy care, yet little practical guidance is available to practitioners. This article introduces an issue of  That which grows fast, withers as rapidly. That which grows slowly, endures.”Dr. Josiah Gilbert Holland, Founder of Scribner’s Monthly“When the music changes, so does the dance.”African ProverbThe first antiepileptic drug (AED) monotherapy utilized successfully manages nearly half of epilepsy patients; however, conversion to a second monotherapy is necessary for those who fail to become seizure-free or who do not tolerate an initially chosen AED, and chronic polytherapy is necessary in many patients who develop refractory epilepsy . Over thMonotherapy is widely favored over polytherapy by neurologists in the treatment of newly diagnosed epilepsy, limited evidence for this “monotherapy maxim” notwithstanding. Abundant evidence is available when initiating adjunctive AED therapy in refractory epilepsy, on practical grounds an important setting for use of newer AEDs since when a new AED becomes available, it is generally first limited to use in refractory patients having the greatest need for improved seizure control, until its safety and tolerability profile and expanded evidence for use in other settings is well established. While it is probable that all AEDs proven effective in adjunctive polytherapy settings are also efficacious for use as monotherapy, available evidence guiding AED monotherapy remains somewhat limited, leading to relatively narrow FDA indications in United States practice. Several newer AEDs have randomized controlled trial evidence for monotherapy application, while clinical experience and lesser evidence lead to FDA “grandfathering” of older AEDs for monotherapy indication in newly diagnosed epilepsy. However, relatively little evidence is available to guide clinicians as they implement changes between monotherapy or polytherapy AED regimens for patients with epilepsy. A panel of epilepsy neurologists and clinical pharmacologists was recently convened to address this important topic. The goal of the SPECTRA panel (Study by a Panel of Experts: Considerations for Therapy Replacement in Antiepileptics) was to develop consensus regarding practical issues in AED monotherapy conversions. This panel developed consensus on a key overriding treatment principle: to fully titrate an adjunctive drug prior to tapering a baseline drug when possible. The panel also developed drug-specific consensus recommendations that expand and complement available prescribing information that is useful in planning AED monotherapy conversions as well as AED sequencing in chronic polytherapy regimens .Current Neuropharmacology focuses on the topic of AED conversions in epilepsy care. This series of articles begins with a practical review of AED monotherapy in newly diagnosed epilepsy, next examines factors involved in monotherapy conversions during the process of transitional polytherapy, then outlines important considerations in ensuring successful chronic polytherapy. A discussion of the rationale and strategies for minimizing adverse effects in epilepsy care is then followed by a review of principles for appropriate blood level monitoring. Finally, this issue considers important patient-related factors in AED conversions. The above-referenced motivational sentiment of 19th century physician, author, and poet Josiah Holland well anticipated the approach to epilepsy treatment favored herein: initiate AED treatment as monotherapy, sequence medications as needed to achieve seizure control or improve a patient’s acceptance and tolerability of therapy, and titrate most medications slowly and carefully to ensure maximal success. However, as the ensuing proverb reminds us, conversion between different AEDs may require specific modifications to ensure treatment success. The SPECTRA data summarized herein provides clinicians with a helpful new approach to guide conversions between AED therapies, and the accompanying review articles offer further relevant guidance for clinicians implementing AED conversions in epilepsy care.This issue of


Respiratory papilloma is a rare lesion that arises in the larynx, trachea and bronchus.We describe a patient with laryngeal papilloma that spread to the trachea and whichwas effectively treated by Nd-YAG laser. Two years after the initial treatments of thelaryngeal and tracheal papillomas, a recurrent lesion (solitary papilloma) was observedon the membranous portion of the trachea. We examined the recurrent lesion by bronchoscopyincluding bronchoscopic ultrasound (US), helical computed tomography (CT)and tracheal biopsies. Respiratory papillomatosis sometimes shows either malignanttransformation or invasion to tracheal wall without displaying cytohistological atypia.Therefore, we concluded that bronchoscopic US and helical CT were useful for decidingon therapeutic strategy in cases of recurrence of tracheal papilloma.


Circumscribed choroidal hemangiomas are vascular tumors associated with secondary changes in the overlying retinal pigment epithelium and neuro-sensory retina. Spectral-domain optical coherence tomography, a recent advancement in fundus imaging techniques provides high resolution images of the retina. We describe spectral domain Optical coherence tomography findings in a case of circumscribed choroidal hemangioma which was successfully treated with photodynamic therapy.A 41-year-old white male presented with decreased vision in his right eye. Fundus evaluation showed findings consistent with circumscribed choroidal hemangioma. Spectral-domain optical coherence tomography revealed a large serous retinal detachment overlying the tumor with an intact photoreceptor layer. The patient underwent photodynamic therapy and a repeat tomography scan confirmed the resolution of serous detachment with return of normal foveal contour.Spectral domain optical coherence tomography is an emerging modality in imaging of the retina and reveals ultrastructural changes occurring in various retina pathologies. In this case report we illustrate the use of spectral domain optical coherence tomography for the first time to document retinal changes overlying a choroidal hemangioma and its role as a non-invasive tool in planning the treatment and prognosticating the final visual outcome following treatment for circumscribed subfoveal choroidal hemangiomas. Choroidal hemangiomas are vascular hamartomas of the choroid and can cause visual loss due to subfoveal location, associated exudative retinal detachment, cystoid macular edema or subretinal fibrosis ,2. A numSpectral domain OCT, in recent times, has been an important advancement in OCT technology, having enhanced speed and sensitivity in acquiring retinal images. It acquires upto 40000 scans in a short period of time and renders a 3-dimensional image with cross-sectional sections providing detailed ultrastructural changes within the retina . PDT. PDT8]. In conclusion, SD OCT is an emerging tool in the imaging of retina and provides high definition ultrastructural changes associated with vitreo-retinal disorders. In this case report we illustrate the use of SD OCT for the first time to document retinal changes overlying a choroidal hemangioma and its role as a non-invasive tool in planning the treatment and prognosticating the final visual outcome following treatment for circumscribed subfoveal choroidal hemangiomas.CCH: circumscribed choroidal hemagioma; ICG: indocyanine green; PDT: photodynamic therapy; RPE: retinal pigment epithelium; SD OCT: spectral domain optical coherence tomography.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.KC and SG identified the case and directly participated in management. They also revised the manuscript and verified its intellectual content. VB and RM worked in collaboration to collect data, acquire clinical photographs, and draft, revise, and reference the manuscript.


In these patients, the number of apoptotic lymphocytes was significantly increased within tumour and peripheral blood. Furthermore, sFasL was present in the corresponding supernatants and induced apoptosis of Jurkat cells in a dose-dependent manner. These findings suggest that mFasL-positive colon cancer cells release sFasL, and thus may induce apoptosis of host lymphocytes as a potential mechanism for immune evasion. © 2001 Cancer Research Campaignhttp://www.bjcancer.comExpression of membrane-bound Fas ligand (mFasL) on colon cancer cells serves as a potential mechanism to inhibit host immune function by inducing apoptosis of host lymphocytes. Membrane-bound FasL can be cleaved and released as a soluble mediator (sFasL), which may spread the apoptosis induction effect. Our study examined whether colon adenocarcinoma cells release sFasL, and induce apoptosis of host lymphocytes without direct cell–cell contact. In 12 consecutive patients with colon adenocarcinoma mFasL was identified in the tumours, sFasL was measured in the sera and apoptosis identified in tumour-infiltrating and peripheral blood lymphocytes. To analyse the function of sFasL, colon cancer cells were primarily cultured; sFasL was isolated from supernatants, measured, incubated with Fas-bearing Jurkat cells, and the resulting apoptosis was analysed. Serum levels of sFasL were significantly elevated in all colon cancer patients with mFasL expression in tumour tissues (


Five species of sigmodontine rodents have been identified in Argentina as the putative reservoirs of six circulating hantavirus genotypes. Two species of Oligoryzomys are associated with the genotypes causing hantavirus pulmonary syndrome, Oligoryzomys flavescens for Lechiguanas and O. longicaudatus for Andes and Oran genotypes. Reports of human cases of hantavirus pulmonary syndrome prompted rodent trapping  at potential exposure sites in three disease-endemic areas. Antibody reactive to Sin Nombre virus was found in six species, including the known hantavirus reservoir species. Risk for peridomestic exposure to host species that carry recognized human pathogens was high in all three major disease-endemic areas.


We present a case of a man admitted to our Hospital for right acute scrotum that six months before had undergone a right hernioplasty with mesh implantation. Clinical history and testicular color Doppler sonography (CDS) patterns suggested an orchiepididymitis following acute prostatitis. After 48h the clinical picture worsened and testicular CDS showed a decreased telediastolic velocity that suggested testicular ischemia. The patient underwent surgical exploration: spermatic cord appeared stretched by an inflammatory tissue in absence of torsion and releasing of spermatic cord was performed.In patients with genitourinary infection who previously underwent inguinal mesh implantation, testicular CDS follow-up is mandatory. The acute scrotum constitutes the most common urological emergency and color Doppler sonography (CDS), along with the physical exam, represents the imaging modality more frequently employed in the clinical assessment of acute scrotum.The two most important entities that must be ruled out in every case of acute scrotal pain are torsion of spermatic cord and orchiepididymitis, while other causes occur more rarely. In case of inguinal hernia repair using mesh techniques the spermatic cord is potentially affected by chronic inflammatory tissue remodeling that may impair testicular perfusion inducing acute scrotum.A rare case of testicular ischemia following mesh hernia repair and acute prostatitis that presented as acute scrotum is reported herein.A 23-year-old man was admitted for right orchialgia arising 24h before admission; although he referred urinary symptoms  and fever of five days’ duration, no therapy was previously administered. Six months before, the patient underwent a mesh implantation to treat a recurrent right inguinal hernia. At admission, history, genitourinary exam, blood and urine test and transrectal CDS suggested an acute prostatitis; testicular CDS revealed normal signal in correspondence of the testis and epididymis. The patient was hospitalized and submitted to antibiotic therapy. After 48h the clinical picture worsened: testicular pain and fever increased, CDS showed a decreased TDV (telediastolic velocity) on intratesticular artery  and a hiSpermatic cord torsion, orchiepididymitis and trauma constitute the main causes of acute scrotum, although the differential diagnosis refers essentially to the torsion of spermatic cord vs. inflammatory lesions. A careful physical exam and anamnesis combined with CDS parameters often address toward the diagnosis of testicular ischemia that, more rarely, can be secondary to severe epididymitis, inguinal hernia repair, spontaneet al. performed an experimental study in 15 adult male pigs that underwent transinguinal preperitoneal implantation of polypropylene mesh and shouldice repair on the contralateral side. The authors reported that mesh repair led to a decrease of arterial perfusion, testicular temperature and seminiferous tubules.[et al.[et al.[The use of mesh during hernia repair is associated with a relative reduction in the risk of hernia recurrence of around 30-50%; however, there is no apparent difference in recurrence between laparoscopic and open mesh methods of hernia repair. Experime tubules. Dilek ets.[et al. reportedl.[et al. showed tl.[et al. reportedIn our case report testicular ischemia was secondary to spermatic cord compression by an inflammatory and scar tissue in absence of torsion and only after releasing of spermatic cord the patient became asymptomatic.In conclusion, in patients with genitourinary infection who previously had an inguinal mesh implantation, clinical observation and CDS follow-up is mandatory to treat in time this unusual complication.


An assay system is described in which effector cells added along with suitable target cells inhibit, in a quantitative fashion, the subsequent uptake of 3H-thymidine by those target cells. Effector cells active in this assay, using embryonic fibroblast cells as targets, develop spontaneously in cultures of mouse lymphoid cells, but are apparently different from those described earlier by investigators of activity in cytotoxic assays. Further evidence is presented to show the development of spleen-derived effector cells with cytostatic activity (for embryonic fibroblast target cells) in mice during the course of normal pregnancy, or growth of spontaneously appearing mammary adenocarcinomas. Indeed, such effector cells can also be found within the growing solid mass itself. Different populations of tumour cells isolated from a solid tumour apparently differ in their susceptibility to growth inhibition by tumour-bearer-derived cytostatic effector cells, a phenomenon which may be related to metastatic spread of tumour cells.


Symptomatic prostatic cyst presenting as obstructive lower urinary tract symptoms (LUTS) is an infrequent diagnosis in males. Midline cysts are much more likely to obstruct the bladder outlet. We report our experience with four such cases in the last one year, along with a short review of the literature. Two of these cases had additional presenting symptoms besides LUTS - febrile Urinary tract infection (UTI) with perinephric abscess and primary infertility. One case had an anterior midline prostatic cyst which is an extremely rare entity. The remaining three had midline posterior cysts. All cases were treated with transurethral marsupialization, had good relief of symptoms and no adverse effects. Prostatic cysts, an erstwhile infrequent diagnosis in males, are usually asymptomatic and mostly detected incidentally during abdominal or trans-rectal ultrasonography (TRUS). Etiological factors include chronic prostatitis as a predominant cause of lateral prostatic cysts and congenital causes for midline cysts. Existent literature on midline prostatic cysts is mostly in the form of isolated case reports, which highlights their uncommon occurrence and even lower propensity for causing symptoms. We report our experience with managing symptomatic benign midline prostatic cysts, including a rare variant of an anterior midline prostatic cyst for which only three cases have been reported so far.Four young males  presented to us with lower urinary tract symptoms (LUTS) and/or other associated symptoms . ObstrucInitial evaluation included a urine microscopic analysis and culture, uroflowmetry and a screening abdominal ultrasonography which documented the presence of a prostatic cyst . AdditioAll patients underwent cystoscopy and transurethral incision of the prostatic cyst ; Case 4 The widespread use of TRUS for evaluating bladder outlet obstruction, infertility, UTI, hemospermia, ejaculatory pain, chronic pelvic pain, prostatic carcinoma or guiding prostatic biopsy has resulted in more frequent identification of prostatic cysts. Most proSymptomatic prostatic cysts are reported to be associated with prostatic abscess, chronic/recurrent prostatitis; as a cause of chronic pelvic pain, upper or lower UTI, infertility, hemospermia and rarely malignancy.4Lower urinary tract symptoms surprisingly are uncommon presenting symptoms, though midline cysts more frequently present with LUTS than laterally placed cysts. The large intraprostatic cyst may compress the prostatic urethral lumen, cause ejaculatory duct obstruction or stretch the prostatic capsule causing pelvic pain.Etiologically, prostatic cysts include the utricle, mullerian duct cyst, hemorrhagic prostatic cyst, hydatid cyst and cysts associated with prostatitis. Midline cysts, located posteriorly at the prostatic floor, are mostly developmental in origin and arise from remnants of fetal tissue – utricle or müllerian duct. Utricular cysts are endodermal in origin, contain no spermatozoa and are located near the verumontanum, whereas müllerian cysts are mesodermal in origin, contain spermatozoa and are located more posterior and nearer the prostate base. Some cysts are primarily prostatic glandular in origin and are acquired later in life. Most lateral prostatic cysts are related to chronic prostatitis, where they may play a causative role or may be consequent to it. Anterior midline cysts of prostatic origin are extremely rare with only three cases reported in the literature so far.–7 Case 1In some cases it may be fairly easy to directly relate the presence of the prostatic cyst as the etiology behind the patient's clinical symptoms. Though the diagnosis of a midline prostatic cyst can be made on TRUS examination, the functional implication of the midline prostatic cyst cannot be determined by TRUS alone. Thus, inet al., reported durable, recurrence-free results in a series of patients with medial prostatic cyst treated with transurethral incision.[et al., reported excellent outcome with transurethral resection of midline prostatic cyst projecting into the prostatic urethra and presenting as obstructive LUTS.[Various therapeutic options for managing midline prostatic cysts described include transrectal aspiration with or without sclerotherapy, transurethral marsupialization and open surgery. Dik et aincision. Similarlive LUTS.


Mycobacterium ulcerans is an infection of the subcutaneous tissue leading to chronic necrotising skin ulcers. The pathogenesis is associated with the cytocidal and immunosuppressive activities of a macrolide toxin. Histopathological hallmark of progressing disease is a poor inflammatory response despite of clusters of extracellular bacilli. While traditionally wide excision of the infected tissue was the standard treatment, provisional WHO guidelines now recommend an eight week pre-treatment with streptomycin and rifampicin.Buruli ulcer caused by We conducted a detailed immunohistochemical analysis of tissue samples from Buruli patients who received antibiotic treatment. Cellular immune response along with bacterial load and distribution were monitored. We demonstrate that this treatment leads to the development of highly organized cellular infiltration surrounding areas of coagulative necrosis. Diffuse infiltrates, granulomas and dense lymphocyte aggregation close to vessels were observed. Mycobacterial material was primarily located inside mononuclear phagocytes and microcolonies consisting of extracellular rod-shaped mycobacteria were no longer found. In observational studies some patients showed no clinical response to antibiotic treatment. Corresponding to that, one of five lesions analysed presented with huge clusters of rod-shaped bacilli but no signs of infiltration.M. ulcerans, lacking patient compliance or poor drug quality are responsible for the absent clinical responses in some patients. In future, analysis of local immune responses could serve as a suitable surrogate marker for the efficacy of alternative treatment strategies.Results signify that eight weeks of antibiotic treatment reverses local immunosuppression and leads to an active inflammatory process in different compartments of the skin. Structured leukocyte infiltrates with unique signatures indicative for healing processes developed at the margins of the lesions. It remains to be analysed whether antibiotic resistance of certain strains of  Buruli ulcer (BU) is a debilitating disease of the skin presenting with extensive tissue destruction and suppression of local host defence mechanisms. Surgical removal of the affected area has been the standard therapy until in 2004 WHO recommended eight weeks' treatment with the anti-mycobacterial drugs rifampicin and streptomycin. We performed a detailed histological analysis of the local immune response in biopsies from five children medicated according to WHO provisional guidelines. One patient still revealed all histopathological signatures of an active BU lesion with huge bacterial clusters in areas of fatty tissue necrosis. Different factors can contribute to treatment failure, such as poor patient compliance and resistant bacterial strains. In four patients, different compartments of the skin presented active immune processes with only limited residues of bacterial material persisting. We demonstrated that antibiotic treatment not only directly controls the infectious agent but is also associated with fulminant host immune responses. Characterization of the healing process in BU due to therapy is highly relevant to increase our knowledge of the impact of treatment strategies to fight the disease. Mycobacterium ulcerans is a chronic necrotizing skin disease mainly affecting subcutaneous and adipose tissue M. ulcerans bacteria Buruli ulcer (BU) caused by BU is considered to be the third most common mycobacterial infection after tuberculosis and leprosy. Clinical lesions usually start as painless subcutaneous nodules that may develop into plaques or oedema. If left untreated, extensive ulcerations with typical undermined edges of the dermis develop. Spontaneous healing can occur, often leaving the patient behind with extensive scarring, retractions and deformities Until recently, surgery has been the only WHO recommended treatment for BU M. ulcerans strains indicate that infiltrating cells are killed due to the cytotoxic and apoptosis inducing activity of mycolactone M. ulcerans may be captured by phagocytes during different stages of infection, it appears to persist only transiently inside these host cells Histopathological hallmarks of progressing BU are a poor inflammatory response and growing regions of necrosis of the dermal and adipose tissue eventually leading to the collapse of the overlying epidermis . ClusterMycobacterium ulcerans disease, WHO, 2001), IS2404 PCR, microscopic detection of acid-fast bacilli and observation of characteristic histopathological changes. After receiving informed consent the immunologically non responding patient was tested for HIV positivity. Ethical approval for analysing patient specimens was obtained from the ethical review board of the Noguchi Memorial Institute for Medical Research and the National Ethics Committee of Cameroon.Surgical specimens from five patients aged between six and 11 years with ulcerative lesions were obtained from the Amasaman Health Centre in Ghana and the Ayos district hospital in Cameroon . Lesions3 were collected from different areas of the excised lesions to characterize the gradient of histopathological changes from necrotic areas to healthy appearing tissue at the excision margins  and Haematoxylin/Eosin (HE) was performed on all collected tissue specimen. Staining for acid-fast bacteria was performed according to WHO standard protocol (WHO Diagnostic booklet). In brief, sections were deparaffinized and rehydrated followed by incubation with ZN carbolfuchsin for 30 min at RT. Subsequently slides were washed in cool tap water for 5–10 min and individually differentiated with acid-alcohol. Counterstain was completed with haematoxylin and slides were mounted with Eukitt mounting medium.Pictures taken with a Nikon optiphot-2 microscope were saved using analySIS soft imaging system and processed with Adobe Photoshop CS.M. leprae and highly cross-reactive with other mycobacteria, was used to stain M. ulcerans for confirmation of ZN staining results. Staining of common mycobacterial antigens with polyclonal anti-leprae antibody (pAbLep) antiserum and haematoxylin counterstain revealed an accumulation of mycobacteria  highly organized epithelioid granulomas of different size and state of differentiation, primarily located in deeper dermal tissue ; (ii) leHistopathological characteristics of BU were still found in all four patients. These included psoriasiform and pseudoepitheliomatous epidermal hyperplasia and depigmentation  with excThe distribution of mycobacterial material was assessed by ZN staining  and immu+ T lymphocytes  (+ B cells appeared at the outer margins of the T lymphocyte layer (+ antigen-presenting cells (APCs) in particular Langhans' giant cells (+ phenotype (+ (proliferating) cells (+ polymorphonuclear neutrophilic leucocytes (PMNL) nor CD56+ natural killer (NK) cells could be detected in granuloma formations.A panel of antibodies specific for leukocyte markers  were usephocytes  with CD4 T cells  always o T cells . These ls (dDCs) . Occasiote layer . Cytoplant cells insert ant cells . Staininnt cells , arrow. henotype . Variablg) cells  presenteg) cells insert. + PMNL (+ NK cells showed a similar distribution with even lower cell counts (not shown). Foci of PMNL and NK cells with signs of apoptosis were located within necrotic tissue . Small clusters of CD20+ B lymphocytes were scattered within infiltrates Click here for additional data file.Table S1Main data of enrolled patients(0.03 MB DOC)Click here for additional data file.


Patients with pre-existing neurological disease present a unique challenge to the anaesthesiologist. The cause of postoperative neurological deficits is difficult to evaluate, because neural injury may occur as a result of surgical trauma, tourniquet pressure, prolonged labour, or improper patient positioning or anaesthetic technique. Progressive neurological diseases such as multiple sclerosis may coincidentally worsen perioperatively, independently of the anaesthetic method. The most conservative legal approach is to avoid regional anaesthesia in these patients. However, high-risk patients, including those with significant cardiopulmonary disease, may benefit medically from regional anaesthesia and analgesia. The decision to proceed with regional anaesthesia in these patients should be made on a case-by-case basis. Meticulous regional anaesthetic technique should be observed to minimise further neurological injury.Neurological injury directly related to regional anaesthesia may be caused by trauma, neurotoxicity and ischaemia. Direct needle- or catheter-induced trauma rarely results in permanent neurological injury. The overall incidence of persistent paraesthesias has been estimated at 0.08% after spinal anaesthesia and at 2% after brachial plexus block1The needle-bevel configuration may influence the frequency and severity of peripheral nerve damage during regional anaesthesia. In an in vitro study, Selander et alNeurological deficits after regional anaesthesia may be a direct result of local anaesthetic toxicity. Clinical and laboratory findings indicate that anaesthetic solutions are potentially neurotoxicNeural ischaemia may occur as a result of systemic or local vascular insufficiency. Systemic hypotension with or without a spinal anaesthetic may produce spinal cord ischaemia in the watershed areas between radicular vessels, resulting in flaccid paralysis of the lower extremities . The use of local anaesthetic solutions containing epinephrine or phenylephrine may theoretically result in local ischaemia, especially in patients with microvascular disease, but clinical data are lacking8Previous spinal surgery has been considered to represent a relative contraindication to the use of regional anaesthesia. Many of these patients experience chronic back pain and are reluctant to undergo epidural or spinal anaesthesia, fearing exacerbation of their pre-existing back complaints. Several postoperative anatomical changes make needle or catheter placement more difficult and complicated after major spinal surgery. In a study 105 of 48 patients with chronic low back pain after spinal fusion, 8 showed significant spinal stenosis on computed tomographic scans and requited surgical decompressionThe guidelines for epidural anaesthesia after spinal surgery are unclear. Daley et alCrosby and HalpernHubbertThus, historically it was concluded that epidural anaesthesia may be successfully performed in patients who have had previous spinal surgery, but successful catheter placement may be possible on the first attempt in only 50% of patients, even by an experienced anaesthesiologist. Although adequate epidural anaesthesia is eventually produced in 40-95% of patients, there appears to be a higher incidence of traumatic needle placement, unintentional dural puncture and unsuccessful epidural needle or catheter placement, especially if spinal fusion extends to between L-5 and S-1.A more recent investigation examined the overall success and neurological complication rates among 937 patients with spinal stenosis or lumbar disc disease undergoing neuraxial block between 1988 and 2000Success rates did not differ between patients who had previous surgery and those who had undergone a spinal procedure. Ten  patients experienced new or progressive neurological deficits compared with preoperative findings. Although the majority of the deficits were related to surgical trauma or tourniquet ischaemia, the neuraxial block was the primary aetiology in 4 patients.The preliminary nature of these data warrants care in their interpretation. However, overall, patients with spinal stenosis or lumbar disc disease may undergo successful neuraxial block without a significant increase in neurological complications. Importantly, this includes patients who have undergone prior (minor) spinal surgery.Progressive neurological disease is considered by some to be a relative contraindication to regional anaesthesia, because of the difficulty in determining the cause of new neurological deficits that appear perioperatively. There are no controlled clinical studies identifying regional anaesthesia as a significant factor in increased risk of neurological injury, only anecdotal reports are available. The medicolegal issue, however, remains, and if regional anaesthesia is indicated for other pre-existing medical conditions or by patient request, the patient should be informed of the risk of neurological complications, including coincidental progression of preoperative deficits, associated with anaesthesia and surgery. This discussion, along with preoperative neurological status, should be fully documented in the patient's record.Patients with preoperative neurological deficits may undergo further nerve damage more readily from needle or catheter placement, local anaesthetic systemic toxicity, and vasopressor-induced neural ischaemia. Although the use of paraesthesia techniques is not contraindicated, care should be taken to minimize needle trauma and intraneuronal injection. Dilute local anaesthetic solutions should be used whenever feasible to decrease the risk of local anaesthetic systemic toxicity.The use of epinephrine-containing solutions is controversial. The potential risk of vasopressor-induced nerve ischaemia must be weighed against the advantages of predicting local anaesthetic intravascular injections, improved quality of block, and decreased blood levels of local anaesthetics. Because epinephrine also prolongs and block and therefore neural exposure to local anaesthetics, the appropriate concentration and dose of local anaesthetic solutions must be considered. Patients with microvascular disease in combination with an underlying peripheral neuropathy, such as those with diabetes, may be most sensitive to the vasoconstrictive effects of epinephrine.Efforts should also be made to decrease neural injury in the operating room through careful patient positioning. Postoperatively, these patients must be followed closely to detect potentially treatable sources of neurological injury, including constrictive dressings, improperly applied casts and increased pressure on neurologically vulnerable sites. New neurological deficits should be evaluated promptly by a neurologist for formal documentation of the patient's evolving neurological status and the arrangement of further testing and long-term follow-up.


In brain mapping studies of sensory, cognitive, and motor operations, specific waveforms of dynamic neural activity are predicted based on theoretical models of human information processing. For example in event-related functional MRI (fMRI), the general linear model (GLM) is employed in mass-univariate analyses to identify the regions whose dynamic activity closely matches the expected waveforms. By comparison multivariate analyses based on PCA or ICA provide greater flexibility in detecting spatiotemporal properties of experimental data that may strongly support alternative neuroscientific explanations. We investigated conjoint multivariate and mass-univariate analyses that combine the capabilities to (1) verify activation of neural machinery we already understand and (2) discover reliable signatures of new neural machinery. We examined combinations of GLM and PCA that recover latent neural signals (waveforms and footprints) with greater accuracy than either method alone. Comparative results are illustrated with analyses of real fMRI data, adding to Monte Carlo simulation support.


Avery and Avery, who find comparing conventional Japanese and organic Swedish beef production misleading, propose relying on “comprehensive life cycle analyses” (LCAs) to quantify emissions from conventional U.S. beef production. However, neither study they cite  appears These results indicate that the intensification of beef production systems may be counterproductive because net emissions of carbon dioxide as well as nitrogen and other pollutants would increase.For a more comprehensive analysis, additional production aspects must be considered. A better comparison of conventional versus organic beef production may be an LCA of greenhouse gas (GHG) emissions from three Irish systems reported by In contrast to conventional production, organic farming can reduce nitrous oxide emissions by avoiding excessive amounts of manure, as stocking densities are limited to land available for manure application. Organic agriculture typically also uses less fossil-fuel energy, in part because thousands of feed transport miles may be reduced .2O in pasture soil organic matter , the Intergovernmental Panel on Climate Change  concludeMost of the observed increase in global average temperatures since the mid-20th century is very likely due to the observed increase in anthropogenic GHG concentrations.The link between GHG mitigation and organic or extensive animal agriculture systems is well established, as are the other environmental and public health benefits of less-intensive production systems. Understanding the efficacy of less technology-dependent mitigation strategies is critical as the effects of global warming become more evident.


Studies on the zebrafish model have contributed to our understanding of severalimportant developmental processes, especially those that can be easily studied in theembryo. However, our knowledge on late events such as gonad differentiation in thezebrafish is still limited. Here we provide an analysis on the gene sets expressed inthe adult zebrafish testis and ovary in an attempt to identify genes with potentialrole in (zebra)fish gonad development and function. We produced 10 533 expressedsequence tags (ESTs) from zebrafish testis or ovary and downloaded an additional23 642 gonad-derived sequences from the zebrafish EST database. We clustered thesesequences together with over 13 000 kidney-derived zebrafish ESTs to study partialtranscriptomes for these three organs. We searched for genes with gonad-specificexpression by screening macroarrays containing at least 2600 unique cDNA insertswith testis-, ovary- and kidney-derived cDNA probes. Clones hybridizing to only oneof the two gonad probes were selected, and subsequently screened with computationaltools to identify 72 genes with potentially testis-specific and 97 genes with potentiallyovary-specific expression, respectively. PCR-amplification confirmed gonad-specificityfor 21 of the 45 clones tested . Our study, which involvesover 47 000 EST sequences and specialized cDNA arrays, is the first analysis of adultorgan transcriptomes of zebrafish at such a scale. The study of genes expressed inadult zebrafish testis and ovary will provide useful information on regulation of geneexpression in teleost gonads and might also contribute to our understanding of thedevelopment and differentiation of reproductive organs in vertebrates.


Cardiac surgery is associated with excessive bleeding as compared to non-cardiovascular surgery. In many situations excessive bleeding is expected but unexpected bleeding may pose problem during and, or after surgery. Studies have found certain predictors for bleeding like, increased age, emergency surgery, low body surface area, prolonged cardiopulmonary bypass (CPB) time > 150 minutes, combined intracardiac and bypass surgery, number of bypass grafts (> 4), reoperative surgery and preoperative antiplatelets agent. Between 3% to 14% of patients with significant bleeding require re-exploration.3Liberal use of red blood cells transfusion is associated with increased nosocomial infection and mortality in critically ill patients.5Current blood conservation practice guidelines suggest that institutions strategy should start with preoperative evaluation to identify high risk patients and appropriate management of antiplatelet therapy. In all planned surgery thienopyridines (clopidogrel) should be stopped 5 to 7 days prior to surgery except in patients with drug eluting stents, in whom sudden withdrawal of antiplatelets can result in sudden stent thrombosis. Aspirin should only be discontinued in purely elective cases without acute coronary syndrome. The addition of clopidogrel to aspirin increases postoperative haemorrhage. Yende and Wunderink demonstrated that aspirin and clopidogrel increase postoperative bleeding sevenfold.Evidence for transfusion trigger recommends use of haemoglobin level and platelets count for red cells and platelets transfusion respectively. More advanced measurements such as whole body oxygen-carrying capacity, oxygen consumption, oxygen extraction ratios, and oxygen delivery provide more accurate means to estimate the need for red blood cell transfusions.9Intraoperative techniques in blood conservation cannot be underemphasized. Meticulous haemostasis and operative technique can play an important role in reducing blood loss. Acute normovolaemic haemodilution (ANH) has not only been shown to be more cost effective than preoperative autologous donation but also is not limited by time restraints preoperatively. The strategy behind ANH is to lower the red blood cell mass loss during surgery while preserving clotting factors. However, the efficacy of ANH is controversial. Segal et at showed that ANH was only moderately effective in reducing transfusions by 10% or 1 to 2 units less than the control group.11To limit blood transfusions, The Society of Thoracic Surgeons(STS) and The Society of Cardiovascular Anesthesiologists(SCA) guidelines recommend use of aprotinin and lysine analogues epsilon am inocaproic acid (EACA) and tranexamic acid (Cyclokapron) in high risk patients. Aprotinin (Trasylol) and the lysine analogues have very different modes and scope of action but ultimately inhibit fibrinolysis by limiting the action of plasmin. A metaanalysis on aprotinin concluded significant reduction in blood transfusion in patients undergoing CABG, redo CABG and valve replacement.13Factor VIIa is recommended for intractable bleeding, unresponsive to usual hemostatics and non surgical means.Some intervention and modification during CPB are useful in blood conservation. Open reservoir membrane oxygenator system during CPB may reduce blood utilization and improve safety. Similarly activated clotting time (ACT) guided heparin dosing during prolonged CPB not only reduce blood transfusion but also haemostatic system activation, and platelets and proteins consumption as compare to fixed dose heparin supplements. Retrograde autologous priming of the CPB circuit, intraoperative autotransfusion, either with blood directly from cardiotomy suction or recycled using a cell-saving device, shortly after the completion of CPB, salvage of pump blood, either administered without washing or after washing with a cell-saving device should be used for blood conservation.8Lastly, one cannot ignore importance ofa multimodality approach involving multiple stakeholders, institutional support and enforceable transfusion algorithms supplemented with point-of-care testing to prevent blood loss and blood transfusion.8This becomes particularly important in a developing country like India with limited resources, variable quality of blood banking and surgical expertise with exponential growth of cardiac surgical centres. The role of anaesthesiologist is vital for implementing evidence based transfusion practices in cardiac surgery.


Mucobilia is a rare condition characterized by theaccumulation of abundant mucus within the intra- orextrahepatic biliary tree. A variety of hepatobiliaryand pancreatic neoplasms are mucin producingand have been associated with the development ofmucobilia including biliary mucinosis, biliary papillomatosis,mucin-producing cholangiocarcinoma(MPCC), or cystic neoplasms of the pancreas orbiliary tree (cystadenoma or cystadenocarcinoma).We report the case of 46 year-old male with a biliarycystadenocarcinoma of the caudate lobe which resultedin chronic biliary obstruction and relapsingcholangitis. A review of the literature for both mucobiliaand biliary cystadenocarcinoma is providedalong with a discussion addressing the clinical presentation,diagnosis, treatment, and prognosis forthis rare entity.


Vascular abnormalities are uncommon causes of uterine bleeding. Laparoscopic surgeries, however, require expertise and improper techniques can lead to major vascular complications. We report an unusual case of utero-adenexal arterio- venous fistula with arterio - venous malformation due to pelvic trauma caused during laparoscopic sterilisation procedure, which was treated by percutaneous embolisation technique. To the best of our knowledge, this is the first documentation of such a complex vascular injury caused by laparoscopic sterilisation and its endovascular management. Vascular abnormalities are rare but potentially life-threatening causes of uterine bleeding in women of reproductive age, especialA 35-year-old female presented with profuse, irregular, intermittent vaginal bleeding for the past six months. One month prior to onset of the symptoms she underwent a laparoscopic tubal ligation at a peripheral centre. Her past obstetric history was non-contributory. General, systemic and gynaecological examinations were unremarkable except for the presence of significant pallor. Abdominal and transvaginal sonography showed presence of multiple vascular channels in the parametrium and myometrium with a bulky uterus and fluid in the endometrial cavity. Color Doppler imaging, suggested presence of arterio-venous shunting. Pelvic magnetic resonance imaging (MRI)  revealedDurreil and Loubat first described uterine AVM in 1926 and clasUltrasound with Color Doppler remains the primary imaging modality, which shows many hypoechoic or anechoic spaces, with evidence of flow on colour Doppler. Angiography is the gold standard for diagnosing these lesions and is essential to landmark the pattern of blood supply to the lesion pre-operatively. In addition, percutaneous endovascular embolisation preceding surgery can help contain the per-operative blood loss. Angiographic features consist of a complex tangle of vessels supplied by enlarged feeders from the uterine arteries. Early venous drainage indicated an associated AVF as was sAlthough laparoscopy is a relatively safe procedure occasionally serious complications such as major vascular injury (0.1 per 1000) arise. Such casEndovascular embolotherapy may serve as a viable option for management of vascular complications secondary to surgical trauma. The present report highlights a rare vascular complication due to a minimally invasive technique which was managed by another minimally invasive endovascular approach.


Bacterial pathogens have evolved extraordinary mechanisms to efficiently infect host organisms. A majority of these pathogens do so by delivering virulence factors into host cells, which act to dampen host defenses or utilize the host as a niche for replication. Although regulation of virulence factor expression by bacterial pathogens is a well known pathogenic mechanism Yersinia spp., Shigella flexneri, Helicobacter pylori, and diarrheagenic Escherichia coli are well known for their ability to kill host cells. For Yersinia, death of infected macrophages dampens cytokine release and enables the pathogen to propagate with minimal challenges from the immune system Yersinia species is tightly regulated. Yersinia pestis, the etiologic agent of plague, and gastroenteritis-inducing Yersinia pseudotuberculosis and Yersinia enterocolitica all encode a cytotoxic virulence factor called YopJ/P (YopJ in the two former species and YopP in the latter), which are translocated into infected cells via a type III secretion system (T3SS) Y. pseudotuberculosis affects its virulence. Decreased secretion of YopJ was shown to enhance Y. pseudotuberculosis pathogenesis in vivo Y. pestis, enhanced cytotoxicity results in decreased incidence of pneumonic plague in vivo Yersinia is an efficient virulence strategy. Increased apoptosis of infected immune cells decreases production of proinflammatory cytokines; however, some inflammation at the early stages of infection is thought to facilitate tissue damage necessary for movement of bacteria and infected cells to other sites of replication within the host Escherichia coli, enterohaemorrhagic E. coli , and Citrobacter rodentium are attaching and effacing (A/E) pathogens that cause severe diarrheagenic disease espZ mutant (ΔespZ) caused enhanced cytotoxicity in host cells when compared to the wild-type strain espZ strain is severely attenuated for virulence in vivo Enteropathogenic H. pylori causes apoptosis of infected gastric epithelial cells H. pylori has been linked to a secreted toxin called VacA, which induces cytochrome c release from mitochondria  by which S. flexneri enhances NFκB-mediated pro-survival signals are unknown.All of the above pathogens have evolved strategies to attenuate their own host-damaging virulence factors. In many of these scenarios, removal of host-protective mediators actually reduces pathogenicity of the bacteria. The observation that EPEC encodes a host-protective virulence factor that is essential for its pathogenesis suggests that protecting host cells may be a key to the pathogenic strategies of other bacterial pathogens. The concept of host-protective virulence factors is only just emerging, and we believe host-protective virulence factors will become more apparent in other pathogenic strategies and may become interesting targets to combat bacterial disease. Importantly, virulence phenotypes that appear counterintuitive should not be ignored. Future studies into pathogenic mechanisms of virulent bacteria will likely reveal important roles for effectors or regulatory mechanisms that help the host cell and promote bacterial pathogenesis.


Background: Disseminated herpetic infections during pregnancy have             been reported in the literature.            Case: This case presentation describes a pregnant patient who             presented with fever, elevated liver enzymes, and upper abdominal tenderness and             succumbed from fulminant herpetic hepatitis.            Conclusion: Early diagnosis and treatment are essential because of the             high mortality rate.


The authors have determined that epineurial arteriolesof the sciatic nerve are innervated by nonadrenergic,noncholinergic nerves that contribute to the regulation ofvasodilation. Using immunohistochemistry, the authorsdetermined that nerves innervating epineurial arteriolescontain the neuropeptide calcitonin gene–related peptide(CGRP). Using streptozotocin-induced diabetic rats, the authorsdemonstrated that CGRP content in sensory nervesinnervating epineurial arterioles and vasodilation in responseto exogenous CGRP was decreased. In summary,epineurial arterioles of the sciatic nerve are innervated bysensory nerves containing the neuropeptide CGRP. Thediabetes-like condition induced by streptozotocin reducesthe content of CGRP in these nerves and exogenous CGRPmediatedvasodilation. CGRP is likely an important regulatorof vascular tone and compromising its function couldcontribute to nerve ischemia and diabetic neuropathy.


This prompted us to examine the 3D vascular network of normal colon mucosa, adenomas and invasive carcinomas by means of quantitative microvascular corrosion casting. Fresh hemicolectomy specimens from 20 patients undergoing cancer or polyposis coli surgery were used for corrosion casting, factor VIII and VEGF immunostaining. In addition, immunostaining was done on colorectal tissue from 33 patients with metastatic and non-metastatic carcinomas, polyposis coli and adenomas. This first quantitative analysis of intervessel and interbranching distances, branching angles and vessel diameters in human cancer specimens revealed distinct patterns of the microvascular unit in the tumour centre and periphery. Irrespective of the tumour localization and grading all individual tumours displayed qualitatively and quantitatively the same vascular architecture. This gives further evidence for the existence of a tumour type-specific vascular architecture as recently demonstrated for experimental tumours. Metastatic tumours displayed different vascular architectures only within hot spots, in terms of smaller intervascular distances than in non-metastatic tumours. Pre-cancerous lesions have in part virtually the same vascular architecture like invasive carcinomas. Comparison of VEGF immunostaining also suggests that angiogenesis sets in long before the progress towards invasive phenotypes and that the so-called angiogenic switch is more likely a sequence of events. © 2001 Cancer Research Campaign


Previously we have demonstrated that diabetescauses impairment in vascular function ofepineurial vessels, which precedes the slowingof motor nerve conduction velocity. Treatmentof diabetic rats with aldose reductaseinhibitors, aminoguanidine or myo-inositolsupplementation have been shown to improvemotor nerve conduction velocity and/ordecreased endoneurial blood flow. However,the effect these treatments have on vascularreactivity of epineurial vessels of the sciaticnerve is unknown. In these studies we examinedthe effect of treating streptozotocininducedrats with sorbinil, aminoguanidine ormyo-inositol on motor nerve conduction velocity,endoneurial blood flow and endothelium dependentvascular relaxation of arterioles thatprovide circulation to the region of the sciaticnerve. Treating diabetic rats with sorbinil,aminoguanidine or myo-inositol improved thereduction of endoneurial blood flow and motornerve conduction velocity. However, onlysorbinil treatment significantly improved thediabetes-induced impairment of acetylcholinemediatedvasodilation of epineurial vessels ofthe sciatic nerve. All three treatments were efficaciousin preventing the appropriate metabolicderangements associated with either activationof the polyol pathway or increased nonenzymaticglycation. In addition, sorbinil wasshown to prevent the diabetes-induced decreasein lens glutathione level. However, other markers of oxidative stress were not vividlyimproved by these treatments. These studiessuggest that sorbinil treatment may be moreeffective in preventing neural dysfunction indiabetes than either aminoguanidine or myoinositol.


Photofrin accumulation in malignant and host cell populations of various tumours was studied by flow cytometry analysis of cells dissociated from the tumour tissue. The transplantable mouse tumour models included in this analysis were sarcomas EMT6, RIF, KHT and FsaN, Lewis lung carcinoma, SCCVII squamous cell carcinoma (SCC) and slowly growing moderately differentiated AT17 SCC. An example of spontaneous mouse adenocarcinoma was also examined. Staining with specific monoclonal antibodies was used to identify the various cell populations present in these tumours. The main characteristic of Photofrin cellular accumulation was a very high photosensitiser content found exclusively in a subpopulation of tumour-associated macrophages (TAMs). Photosensitiser levels similar to or lower than in malignant cells were observed in the remaining TAMs and other tumour-infiltrating host cells. Photofrin accumulation in malignant cells was not equal in all tumour models, but may have been affected by tumour blood perfusion/vascularisation. Results consistent with the above findings were obtained with SCC of buccal mucosa induced by 9,10-dimethyl-1,2-benzanthracene in Syrian hamsters. The TAM subpopulation that accumulates by far the highest cellular Photofrin levels in tumours is suggested to be responsible for the tumour-localised photosensitiser fluorescence.


Research on the evolution of reproductive isolation in African cichlid fishes has largely focussed on the role of male colours and female mate choice. Here, we tested predictions from the hypothesis that allopatric divergence in male colour is associated with corresponding divergence in preference.Pseudotropheus zebra complex. We predicted that more distantly-related populations that independently evolved similar colours would interbreed freely while more closely-related populations with different colours mate assortatively. We used microsatellite genotypes or mesh false-floors to assign paternity. Fisher's exact tests as well as Binomial and Wilcoxon tests were used to detect if mating departed from random expectations.We studied four populations of the Lake Malawi P. emmiltos observed under control conditions. By contrast, assortative mating broke down when direct contact between female and male was prevented.Surprisingly, laboratory mate choice experiments revealed significant assortative mating not only between population pairs with differently coloured males, but between population pairs with similarly-coloured males too. This suggested that assortative mating could be based on non-visual cues, so we further examined the sensory basis of assortative mating between two populations with different male colour. Conducting trials under monochromatic (orange) light, intended to mask the distinctive male dorsal fin hues (blue v orange) of these populations, did not significantly affect the assortative mating by female We suggest that non-visual cues, such as olfactory signals, may play an important role in mate choice and behavioural isolation in these and perhaps other African cichlid fish. Future speciation models aimed at explaining African cichlid radiations may therefore consider incorporating such mating cues in mate choice scenarios. Drosophila . Theosophila , the breosophila , and theosophila  providedCichlid fishes specialised to live on rocky shores are known to be philopatric and poor dispersers, with significant genetic structure among populations isolated by habitat discontinuities ,18. It hGasterosteus spp.) in North American lakes that have adapted to different ecological conditions  and  and P. eklebacks ,54,55. THaplochromine cichlids are usually strongly sexually dimorphic in colour. We do not yet know whether olfactory signals involved in mate choice are expressed by both sexes. If so, it would greatly increase the likelihood that mate preferences may be learned by imprinting on the mother during mouthbrooding, a situation that may enhance the probability of speciation . Sexual The three principal implications of the findings presented here are that: (i) behavioural mating preferences in cichlid fish depend, in some populations, not on colour, but on other forms of sensory communication, which in some cases is not visual; (ii) between-population divergence in male colour does not necessarily imply divergent female preferences, so parallel evolution of male colour is not necessarily coupled with parallel evolution of female mating preference; (iii) sensory cues involved in behavioural isolation among haplochromine cichlids may vary among species and lakes and so speciation models based on one particular mate choice scenario may not apply to whole or all radiations of cichlids. This last point is worth bearing in mind because the type of trait involved in species isolation might provide important clues about which evolutionary force has driven population divergence and speciation.JB performed microsatellite genotyping, statistical analyses, and drafted the manuscript. MP performed behavioural experiments. CR provided critical review and discussion of draft versions. MIT performed microsatellite genotyping and contributed to preparation of the final manuscript. OS provided critical review and discussion of draft versions and supervised the data collection for experiment 1. CVO contributed with critical discussion of draft versions. GFT coordinated the study and was involved throughout the design, analysis, interpretation and writing of the work. All authors have read and approved the final manuscript.Pseudotropheus zebra and related species populations.Results of mate choice trials involving  The data presented are statistical analyses of the full data set, including female multiple spawnings and male multiple sirings, in mate choice trials involving either geographically and phylogenetically distant or proximal Pseudotropheus zebra and related species populations.Click here for file


The concept of endotoxin-mediated rather than direct liver injury in biliary obsruction wasinvestigated using the experimental rat model of bile duct ligation (BDL) and small bowelbacterial overgrowth (SBBO). Small identical doses of intravenous endotoxin caused a significantly more severe liver injury in rats with BDL, compared with sham-operatedrats, suggesting the possible contribution of LPS in this type of liver damage. BDL was thencombined with surgically created jejunal self-filling blind loops, which resulted in SBBO. PlasmaLPS level increased significantly, and once again a more severe liver injury, determined by liverhistology and serum gamma-glutamyl transpeptidase levels, was observed compared with thecontrol group of rats with BDL+self-emptying blind loops. The data presented suggest thatsmall amounts of exogenous LPS and/or the ordinarily innocous amounts of LPS constantlyabsorbed from the intestinal tract may be critical in the hepatic damage caused by obstructionof the biliary tract.


Immunofluorescence studies of sera from mice with induced enhancement of tumour growth demonstrated that these sera contained factors ("interfering factors") which in an apparently competitive manner interfered with the subsequent binding of specific antibodies to antigenic sites on the tumour-cell membrane. The factors were tumour-specific but lacked some of the immunoglobulin determinants. They could not be detected by polyvalent FITC-antimouse gamma-globulin. Interfering factors did not seem to be related to IgA or IgE. They were demonstrable in sera from tumour-free animals without growing tumours, thus differing from the tumour-specific "blocking factors".


The value of neuron specific enolase (NSE) immunoreactivity as a marker for small cell lung cancer (SLC) has been assessed using a monoclonal antibody (MCAB) against NSE, MCAB specificity was confirmed using purified enolase isoenzymes, sections of human brain, a panel of lung tumours, neuroendocrine and non-neuroendocrine tumours and normal tissues. Using this MCAB in radioimmunoassay and immunohistochemistry, NSE immunoreactivity was detected in all SCLC material examined. However, considerable reactivity was also observed in a number of non-small cell lung cancer cell lines and tumour biopsy specimens. Furthermore, intratumoral heterogeneity with respect to NSE immunostaining was observed in several cases. Factors which may underlie such intratumoral phenotypic diversity were assessed using flow cytometry together with MCABs directed against both NSE and non-neuronal enolase. Such studies revealed that enolase expression in cells which were no longer actively proliferating differed markedly from that of cells in exponential growth. Furthermore, cells grown under conditions of increasing hypoxia exhibited increased enolase expression relative to those grown under oxygenated conditions. It is concluded from these studies that NSE immunoreactivity per se is an unreliable marker for the SCLC phenotype.


ELISAs for pesticides and herbicides in environmental andagricultural samples are becoming very important in screeningapplications [1-3]. Traditional chromatographic methods areexpensive and results need long turnaround times, making themincompatible with rapid on-site decision making. ELISA methodshave been shown to meet or exceed the performance of gaschromatography—they offer rapid low-cost analysis, therebyincreasing the frequency of sampling and enhancing data quality.Automated ELISA workstations allow the full benefit of these kitsto be realized. Sample preparation, reagent pipetting, incubation,and photometric evaluation can be performed without userintervention. Reliability is increased through the elimination ofoperator error, better accuracy and precision, and often higher speed.Much larger batch sizes are possible and these systems can providesample tracking with report generation for documentationrequirements. In this paper the manual procedures and ELISAmethods are compared and some critical aspects of automating theseELISA kits are discussed.


A 41-year-old female patient was admitted with streptococcal meningitis on a background of 5-month history of CSF rhinorrhoea. Imaging revealed an extensive skull base lesion involving the sphenoid and ethmoid sinuses, the pituitary fossa with suprasellar extension and bony destruction. Histological examination of an endonasal transethmoidal biopsy suggested a diagnosis of olfactory neuroblastoma. A profuse CSF leak occurred and the patient developed coliform meningitis. A second endonasal endoscopic biopsy was undertaken which demonstrated the tumour to be a prolactinoma. Following endonasal repair of the CSF leak and lumbar drainage, she developed profound pneumocephalus. The patient underwent three further unsuccessful CSF leak repairs. Definitive control of the CSF leak was finally achieved through a transcranial approach with prolonged lumbar drainage. This case illustrates some of the potentially devastating complications which can occur as a consequence of complex skull base lesions. A multidisciplinary approach may be required to successfully manage such cases. Traditionally, complex paranasal and anterior skull base lesions have been managed with either transcranial or transphenoidal microsurgical approaches. The application of endoscopy to neurological surgery and advances in neuronavigation have provided further options to skull base surgeons. One of the commonest complications of skull base lesions and their management is the occurrence of CSF leakage, which can result in the potentially fatal consequences of pneumocephalus and meningitis. Despite advances in microsurgical and endoscopic technology and expertise, definitive management of complex lesions and their resultant complications may require multidisciplinary team management and open transcranial neurosurgery. A 41-year-old female patient was referred to the ENT outpatient clinic with 5-month history of clear fluid discharging from the nose. Fluid samples were sent for tau protein analysis and outpatient imaging was requested. Prior to completion of skull base imaging, the patient was admitted in an acute confusional state, with a nonblanching rash, pyrexia, and signs of meningism. A diagnosis of streptococcal meningitis was made following lumbar puncture and she was commenced on appropriate antibiotics. Magnetic resonance imaging demonstrated an extensive skull base lesion involving the sphenoid and ethmoid sinuses, pituitary fossa, and suprasellar region . ComputeAn endonasal transethmoidal biopsy was undertaken, following which there was profuse CSF rhinorrhoea. Subsequently, the patient developed clinical signs of meningism with pyrexia, neck stiffness, photophobia, and deterioration in neurological status. CSF analysis revealed gram-negative coliforms and antibiotic treatment was commenced.The patient was transferred to the regional neuroscience centre for joint neurosurgical and ENT management. On recovery from the second episode of meningitis, she underwent an endoscopic endonasal biopsy and repair of the anterior pituitary fossa and planum sphenoidale using layered fat graft and artificial dural substitute sealed with Tisseel fibrin sealant . Histological analysis of this biopsy specimen confirmed the tumour to be a prolactinoma. Although her initial serum prolactin level was only 451 miu/mL , it did rise to 953 miu/mL in the immediate postbiopsy period. Following endocrine review, she was commenced on cabergoline.Despite satisfactory intraoperative appearances, CSF rhinorrhoea recurred. A CT cisternogram was undertaken to further characterise the site of CSF leakage . ThroughBoth attempts were unsuccessful and lumbar CSF drainage resulted in profound pneumocephalus . The patOnce sufficient neurological recovery had occurred, a second CT cisternogram  was undeFollowing the fourth unsuccessful attempt, the patient underwent a transcranial repair of the CSF leak through a right-sided pterional craniotomy. Intraoperatively, no dural defect was visible; however, bony defects in the anterior pituitary fossa floor were palpable and therefore sealed with layers of temporalis fascia and muscle grafts secured with Tisseel sealant. A prolonged post-operative period of lumbar CSF drainage (7 days) was also undertaken which resulted in a successful control of CSF rhinorrhoea. The initial and subsequent biopsies were reviewed and showed an identical tumour consisting of sheets of cells with mildly pleomorphic round to oval nuclei and moderate amounts of eosinophilic cytoplasm . MitoticThe difficulties encountered in definitive occlusion of the bony defects resulting in CSF rhinorrhoea in this case are likely to have resulted from a number of causes. Whilst bony destruction is a recognised feature of aggressive prolactinomas, the extensive infrasellar growth pattern seen in this case is unusual . Once thThe potential pitfalls in differentiating olfactory neuroblastoma from prolactinoma and other paranasal tumours on histological examination have previously been described . The hisComplex paranasal and skull base lesions can result in bony defects and problematic CSF leaks. Although dopamine receptor agonists are the treatment of choice for prolactinomas, tumour shrinkage can take several weeks and residual tumour may contribute to recurrence of CSF leakage. Consequently, tumour debulking might be considered in patients with recurrent CSF rhinorrhoea in whom a histological diagnosis of prolactinoma has been confirmed. This case illustrates some of the potentially devastating complications of untreated CSF rhinorrhoea including recurrent meningitis and consequent raised CSF pressure, and pneumocephalus resulting in seizures and reduced conscious level. Management of these lesions requires a multidisciplinary approach involving ENT surgeons, neurosurgeons, neuroradiologists, and endocrinologists. The time at which endoscopic or transphenoidal approaches are abandoned in favour of transcranial surgery will depend on the surgical experience of the team and the anatomy of the site of CSF leakage. Despite advances in neuro-navigation and endoscopic surgery, transcranial repair maybe the only successful solution.


New computational tools were used to find a robust set of DNA oligomers that can distinguish artificial vector sequences from all available background viral and bacterial genomes. Using newly designed computational tools we show that, despite substantial shared sequences between natural plasmids and artificial vector sequences, a robust set of DNA oligomers can be identified that can differentiate artificial vector sequences from all available background viral and bacterial genomes and natural plasmids. We predict that these tools can achieve very high sensitivity and specificity rates for detecting new unsequenced vectors in microarray-based bioassays. Such DNA signatures could be important in detecting genetically engineered bacteria in environmental samples. Synthetic vector sequences are of fundamental importance in molecular biology. Cloning and expression vectors are among a multitude of synthetic sequence types commonly used as part of a basic tool set for DNA amplification and protein production . As the Large-scale computational pipelines have advanced bio-defense by efficiently finding polymerase chain reaction (PCR) assay-based primers that are able to accurately identify dangerous bacterial and viral pathogens -10. The A computational analysis was performed on the available synthetic vector sequences, which form an important basis for current tools in genetic engineering . One of k-mer matching (a k-mer is a nucleic acid sequence of length k). This alignment-free comparative sequence approach  and [GenBank:4323404].The vector sequences with the greatest number of he graph  with theCDS, coding sequence; MCS, multiple cloning site; PCR, polymerase chain reaction, RAM, random access memory.JEA, SNG and TRS conceived and designed experiments. JEA implemented experiments and drafted the manuscript. All authors read and approved the final manuscript.The following additional data are available with the online version of this paper. Additional data file The list of artificial vector identifiers.Click here for additional data fileThe list of natural plasmid identifiersClick here for additional data fileThe complete set of 30-mer signatures used in the cross-validation setClick here for additional data fileThe complete set of 60-mer signatures used in the cross-validation setClick here for additional data file


Metering liquid reagents into reaction mixtures in a controlled andreproducible manner has often been a problem in syntheticchemistry. Carrying out the real simultaneous addition of two ormore liquid reagents (concurrent additions) is even more inconvenient.Difficulties increase when addition volumes become small,when addition times become long, or when the reagents are corrosiveor air-sensitive. We have constructed and tested an inexpensive,automated device for the slow, precise delivery of liquid reagentsinto laboratory-scale reaction mixtures. Controlled by a standardpersonal computer, this slow adder can accommodate liquidvolumes from hundreds of microlitres to litres and addition timesfrom minutes to days. Its glass and Teflon construction makes ituseful for nearly all reagents. By using multiple slow adders, trueconcurrent addition of several liquids can be easily achieved.


Cryostat sections and established in vitro cultures of dimethylnitrosamine(DMN)-induced renal mesenchymal tumours and monolayer cultures of transformed kidney cells derived from rats treated with a carcinogenic dose of DMN were examined by indirect immunofluorescence with human serum containing smooth muscle antibody. Eight mesenchymal tumours examined showed filamentous cytoplasmic staining of spindle cells infiltrating between renal tubules, whilst in normal kidneys interstitial cells were only weakly positive. In established in vitro cultures from 6 mesenchymal tumours, different patterns of staining were observed in morphologically different cell forms, ranging from fine filamentous staining in giant cells to diffuse cytoplasmic fluorescence in small bipolar cells, and cell outline staining in polygonal cells. In addition filamentous staining of microvillous projections and nucleolar staining were observed in some tumour cells. Monolayer cultures of transformed kidney cells showed strong staining of coarse, randomly-orientated cytoplasmic filaments, whilst fibroblasts cultured from normal rat kidney demonstrated an ordered array of fine, parallel filaments. Specificity of the immunofluorescent staining reaction was established by failure to obtain staining with normal serum, with smooth muscle antibody serum neutralized by homogenates of smooth muscle or extracts containing actin derived from smooth muscle. These results indicate that there is an apparent increase of actin-like contractile microfilaments in transformed cells and in renal mesenchymal tumours. The cytoplasmic contracile microfilaments in these cells may play a role in tumour cell mobility and invasion.


Plasmodium falciparum can induce immunity in patients from which further inhibits fertilization of gametes, and consequently oocyst production in the mosquito midgut [P. falciparum-infected blood fed to female Anopheles mosquitoes showed no oocyst production. Twenty-six percent of these oocyst inhibitory plasma distorted morphology and hampered maturity of the gametocytes (Fig.Gametocyte antigens of o midgut . Here, wytes Fig.. A possiAnti-gametocyte antibodies were elicited during natural malaria infection. The oocyst inhibitory antibodies diffused to and interacted with developing intraerythrocytic gametocytes and reduced number of stage II to V gametocytes, and hampered their maturation. Therefore the alternative development of transmission blocking vaccine in the high transmission area should focus on the identification of the gametocyte antigens inducing inhibitory antibodies to reduce gametocytemia.