HSD3B1 (1245A>C) germline variant and clinical outcomes in metastatic castration-resistant prostate cancer patients treated with abiraterone and enzalutamide: results from two prospective studies.

BACKGROUND: A common polymorphism (1245A>C) in the HSD3B1 gene is associated with increased de novo synthesis of androgens and worse outcomes in men treated with androgen-deprivation therapy for metastatic castration-sensitive prostate cancer. The objective of the study was to determine whether this polymorphism is associated with outcomes for metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone or enzalutamide. PATIENTS AND METHODS: A total of 547 patients treated with abiraterone or enzalutamide from two prospective cohorts were evaluated. The HSD3B1 genotype was determined by targeted sequencing and/or TaqMan single-nucleotide polymorphism genotyping. In cohort 1, patients were randomized to receive abiraterone + prednisone or enzalutamide. In cohort 2, patients received either agent according to investigator's choice. Prostate-specific antigen (PSA) response rate, time to PSA progression (TTPP), time to progression (TTP) and overall survival were determined. Associations between HSD3B1 genotypes and outcomes were evaluated via univariate Cox regression. Multivariable Cox model was used to determine the independent association of each covariate. RESULTS: The HSD3B1 variant genotype (CC) was present in 15% of patients and was associated with worse TTP [hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.02-1.67, P = 0.032] and PSA response rates (48% for CC versus 62% and 65% for AA and AC, respectively [P = 0.019]), with no significant difference in TTPP (HR 1.28, 95% CI 0.99-1.66, P = 0.064). The effect of genotype was similar for treatment with abiraterone or enzalutamide with a negative test for interaction for TTPP (P = 0.997) and TTP (P = 0.749). Multivariable analysis did not show a significant association between genotype and TTP or TTPP. CONCLUSIONS: The HSD3B1 (CC) genotype was associated with shorter TTP and lower PSA response rate in patients with mCRPC treated with abiraterone or enzalutamide. However, the CC genotype did not provide prognostic information beyond that conferred by standard clinical variables, suggesting that it may not be a suitable stand-alone biomarker in mCRPC.

Open darn repair vs open mesh repair of inguinal hernia: a systematic review and meta-analysis of randomised and non-randomised studies.

OBJECTIVES: To compare the outcomes of open darn repair vs open mesh repair in patients undergoing inguinal hernia repair. METHODS: We performed a systematic review and conducted a search of electronic information sources to identify all observational studies and randomised controlled trials (RCTs) investigating outcomes of open darn repair vs open mesh repair for inguinal hernias. Hernia recurrence was considered as the primary outcome measure. The secondary outcome measures included surgical site infection (SSI), haematoma, seroma, neuralgia, urinary retention, length of hospital stay, time to return to normal activities or work, testicular atrophy, operative time and chronic pain. Random or fixed effects modelling was applied to calculate pooled outcome data. RESULTS: Six RCTs, enrolling 1480 patients with 1485 hernias, and 4 observational studies, enrolling 1564 patients with 1641 hernias, were included. Meta-analysis of RCTs showed no significant difference in terms of recurrence (RD 0.00, 95% CI - 0.01 to 0.01, P = 0.86), SSI (OR 0.83, 95% CI 0.46-1.49, P = 0.52), haematoma (OR 1.21, 95% CI 0.62-2.38, P = 0.57), seroma (OR 0.83, 95% CI 0.42-1.65, P = 0.60), neuralgia (OR 1.05, 95% CI 0.29-3.73, P = 0.94), urinary retention (OR 1.44, 95% CI 0.64-3.21, P = 0.38), length of hospital stay (MD 0.09, 95% CI - 0.28 to 0.46, P = 0.63), time to return to normal activities or work (MD 0.88, 95% CI - 0.90 to 2.66, P = 0.33), testicular atrophy (RD 0.00, 95% CI - 0.02 to 0.02, P = 1.00), and operative time (MD 2.69, 95% CI - 1.75 to 7.14, P = 0.62) between the darn repair and mesh repair groups. Meta-analysis of observational studies also showed no significant difference in terms of recurrence (RD 0.00, 95% CI - 0.02 to 0.02, P = 0.99), SSI (OR 0.47, 95% CI 0.14-1.62, P = 0.23), haematoma (OR 1.07, 95% CI 0.45-2.55, P = 0.89), seroma (OR 0.12, 95% CI 0.01-2.27, P = 0.16), neuralgia (OR 0.25, 95% CI 0.05-1.21, P = 0.08), urinary retention (OR 1.53, 95% CI 0.20-11.96, P = 0.69), time to return to normal activities or work (MD 2.13, 95% CI - 2.18 to 6.44, P = 0.33), testicular atrophy (RD - 0.01, 95% CI - 0.02 to 0.01, P = 0.49), and operative time (MD - 4.76, 95% CI - 13.23 to 3.71, P = 0.27) between the two groups. The evidence was inconclusive for chronic pain. The quality of available evidence was moderate. CONCLUSIONS: Our results suggest that open darn repair is comparable with open mesh repair for inguinal hernias. Considering that consequences of mesh complications in inguinal hernia repair, albeit rare, can be significant, open darn repair provides an equally credible alternative to open mesh repair for inguinal hernias. Further studies are required to investigate patient-reported outcomes and to elicit a superior non-mesh technique.

360° virtual reality video for the acquisition of knot tying skills: A randomised controlled trial.

BACKGROUND: 360° virtual reality (VR) video is an exciting and evolving field. Current technology promotes a totally immersive, 3-dimensional (3D), 360° experience anywhere in the world using simply a smart phone and virtual reality headset. The potential for its application in the field of surgical education is enormous. The aim of this study was to determine knot tying skills taught with a 360-degree VR video compared to conventional 2D video teaching. MATERIAL AND METHODS: This trial was a prospective, randomised controlled study. 40 foundation year doctors (first year postgraduate) were randomised to either the 360-degree VR video (n = 20) or 2D video teaching (n = 20). Participants were given 15 min to watch their allocated video. Ability to tie a single handed reef knot was then assessed against a marking criteria developed for the Royal College of Surgeons, England, (RCSeng) Basic Surgical Skills (BSS) course, by a blinded assessor competent in knot tying. Each candidate then underwent further teaching using Peyton's four step model. Knot tying technique was then re-assessed. RESULTS: Knot tying scores were significantly better in the VR video teaching arm when compared with conventional (median knot score 5.0 vs 4.0 p = 0.04). When used in combination with face to face skills teaching this difference persisted (median knot score 9.5 vs 9.0 p = 0.01). More people in the VR arm constructed a complete reef knot than in the 2D arm following face to face teaching (17/20 vs 12/20). No difference between the groups existed in the time taken to construct a reef knot following video and teaching (median time 31.0s vs 30.5s p = 0.89). CONCLUSION: This study shows there is significant merit in the application of 360-degree VR video technology in surgical training, both as an independent teaching aid and when used as an adjunct to traditional face to face teaching.

A phase II study of the HDAC inhibitor SB939 in patients with castration resistant prostate cancer: NCIC clinical trials group study IND195.

BACKGROUND: SB939 is a potent oral inhibitor of class 1, 2, and 4 histone deacetylases (HDACs). These three HDAC classes are highly expressed in castration resistant prostate cancer (CRPC) and associated with poor clinical outcomes. We designed a phase II study of SB939 in men with metastatic CRPC. METHODS: Patients received SB939 60 mg on alternate days three times per week for 3 weeks on a 4-week cycle. Primary endpoints were PSA response rate (RR) and progression-free survival (PFS). Secondary endpoints included objective response rate and duration; overall survival; circulating tumor cell (CTC) enumeration and safety. Exploratory correlative studies of the TMPRSS2-ERG fusion and PTEN biomarkers were also performed. RESULTS: Thirty-two patients were enrolled of whom 88 % had received no prior chemotherapy. The median number of SB939 cycles administered was three (range 1-8). Adverse events were generally grade 1-2, with five pts experiencing one or more grade three event. One patient died due to myocardial infarction. A confirmed PSA response was noted in two pts (6 %), lasting 3.0 and 21.6 months. In patients with measurable disease there were no objective responses. Six patients had stable disease lasting 1.7 to 8.0 months. CTC response (from ≥5 at baseline to <5 at 6 or 12 weeks) occurred in 9/14 evaluable patients (64 %). CONCLUSION: Although SB939 was tolerable at the dose/schedule given, and showed declines in CTC in the majority of evaluable patients, it did not show sufficient activity based on PSA RR to warrant further study as a single agent in unselected patients with CRPC.

Identification of a potent anti-IL-15 antibody with opposing mechanisms of action in vitro and in vivo.

BACKGROUND AND PURPOSE: Interleukin-15 (IL-15) is important in the activation and proliferation of lymphocytic cell populations and is implicated in inflammatory disease. We report the characterization of a novel monoclonal antibody DISC0280 which is specific for human IL-15. EXPERIMENTAL APPROACH: DISC0280 was characterized in a direct binding assay of IL-15 with IL-15 receptor α (IL-15Rα) and by its ability to alter IL-15 mediated proliferation of a range of cell lines (cytotoxic T lymphocyte line-2, M-07e, KIT225). A pharmacodynamic model injecting male C57/BL6 mice with IL-15 or IL-15/IL-15Rα, with or without DISC0280, and assessing changes in lymphocytic cell populations and serum cytokines was utilized. KEY RESULTS: DISC0280 inhibited the binding of IL-15 to IL-15Rα and also potently inhibits IL-15 dependent proliferation of cells expressing IL-15Rα, shared interleukin 2/ interleukin 15 receptor ß chain (IL-15Rß) and common gamma chain (γ(c) ). DISC0280 also inhibited the IL-15 dependent proliferation of M-07e cells that only express IL-15Rß/γ(c) subunits. Human IL-15 injected into mice caused an increase in NK1.1(+) and CD3(+) cells in the spleen and peripheral blood and these effects were unexpectedly potentiated by giving DISC0280 with human IL-15. This increase in cells caused by DISC0280/IL-15 co-administration was greater than that observed when IL-15 was administered complexed with soluble IL-15Rα. CONCLUSIONS AND IMPLICATIONS: The ability of DISC0280 to bind to the IL-15Rα-binding site on IL-15 allows trans-presentation of IL-15 by DISC0280 in vivo, similar to the trans-presentation by soluble IL-15Rα. DISC0280 may be therefore suitable as a clinical substitute for IL-15.

Cells deficient in the base excision repair protein, DNA polymerase beta, are hypersensitive to oxaliplatin chemotherapy.

A significant proportion of human cancers overexpress DNA polymerase beta (Pol beta), the major DNA polymerase involved in base excision repair. The underlying mechanism and biological consequences of overexpression of this protein are unknown. We examined whether Pol beta, expressed at levels found in tumor cells, is involved in the repair of DNA damage induced by oxaliplatin treatment and whether the expression status of this protein alters the sensitivity of cells to oxaliplatin. DNA damage induced by oxaliplatin treatment of HCT116 and HT29 colon cancer cells was observed to be associated with the stabilization of Pol beta protein on chromatin. In comparison with HCT116 colon cancer cells, isogenic oxaliplatin-resistant (HCT-OR) cells were found to have higher constitutive levels of Pol beta protein, faster in vitro repair of a DNA substrate containing a single nucleotide gap and faster repair of 1,2-GG oxaliplatin adduct levels in cells. In HCT-OR cells, small interfering RNA knockdown of Pol beta delayed the repair of oxaliplatin-induced DNA damage. In a different model system, Pol beta-deficient fibroblasts were less able to repair 1,2-GG oxaliplatin adducts and were hypersensitive to oxaliplatin treatment compared with isogenic Pol beta-expressing cells. Consistent with previous studies, Pol beta-deficient mouse fibroblasts were not hypersensitive to cisplatin treatment. These data provide the first link between oxaliplatin sensitivity and DNA repair involving Pol beta. They demonstrate that Pol beta modulates the sensitivity of cells to oxaliplatin treatment.

Considerations for non-invasive in-flight monitoring of astronaut immune status with potential use of MEMS and NEMS devices.

The dynamics of how astronauts' immune systems respond to space flight have been studied extensively, but the complex process has not to date been thoroughly characterized, nor have the underlying principles of what causes the immune system to change in microgravity been fully determined. Statistically significant results regarding overall immunological effects in space have not yet been established due to the relatively limited amount of experimental data available, and are further complicated by the findings not showing systematically reproducible trends. Collecting in vivo data during flight without affecting the system being measured would increase understanding of the immune response process. The aims of this paper are to briefly review the current knowledge regarding how the immune system is altered in space flight; to present a group of candidate biomarkers that could be useful for in-flight monitoring and give an overview of the current methods used to measure these markers; and finally, to further establish the need and usefulness of incorporating real-time analytical techniques for in-flight assessment of astronaut health, emphasizing the potential application of MEMS/NEMS devices.

Static and quasi-static calibration of a bio-MEMS device.

A bio-MEMS device that has been designed to stimulate cells by oscillatory actuation in the vertical direction has been calibrated. The displacement of this device was determined experimentally by a laser interferometer when actuated by a static voltage, and by an atomic force microsope when actuated quasi-statically at 0.1 Hz. Both experimental calibrations were compared to a simple model.

An Experimental Method for Measuring Mechanical Properties of Rat Pulmonary Arteries Verified With Latex.

This paper describes a test method for measuring the mechanical properties of small, nonlinear membrane samples from a rat model for pulmonary hypertension. The size and nonlinearity of the pulmonary artery samples poses a challenge for developing a test method that will generate quality, reproducible data in the pressure range experienced by the hypertensive pulmonary artery. The experimental method described here has sufficient precision to yield a combined relative standard uncertainty of 4 %. The method is calibrated against 75 µm thick latex and the data agree well with the neo-Hookian model.

Dramatic response of teratoma-associated non--germ-cell cancer with all-trans retinoic acid in a patient with nonseminomatous germ cell tumor.

A patient with nonseminomatous germ cell cancer, treated with standard chemotherapy, subsequently developed a pathologically confirmed metastatic undifferentiated adenocarcinoma (non-germ-cell elements) arising from residual teratoma. Disease was present in both lobes of the liver and was deemed unresectable at the time of presentation. The patient was treated on a National Cancer Institute-sponsored institutional protocol with all-trans retinoic acid. After 60 days of oral therapy at a dose of 150 mg/m2/d (50 mg/m2 three times daily), the patient was found to have complete radiologic resolution of his hepatic metastases. He subsequently underwent surgery and his complete response was pathologically confirmed.

Responses of rat subicular neurons to convergent stimulation of lateral entorhinal cortex and CA1 in vivo.

There has been little electrophysiological examination of the afferent projection from lateral entorhinal cortex to dorsal subiculum. Here we provide evidence that synaptic inputs from lateral entorhinal cortex and CA1 converge onto single dorsal subicular neurons in vivo. Subicular responses to CA1 stimulation consisted of excitation and/or long-duration inhibition. Neurons excited by CA1 activation usually showed inhibition to entorhinal stimulation. The latter inhibition was usually of short duration, however, long duration inhibition was seen in a significant proportion of responses. Entorhinal stimulation produced excitatory responses in four bursting cells and it was these cells that also tended to show the longest inhibition. Only bursting cells could be driven antidromically by entorhinal stimulation. Biocytin-filled multipolar and pyramidal cells displayed excitation-inhibition sequences to CA1 and inhibition to entorhinal stimulation. These data strongly suggest that subicular inhibitory neurons receive excitatory input from CA1 and display mutual inhibition. The source of entorhinal-evoked inhibition is less clear. The relative sparseness of observed entorhinal-evoked responses suggests that the input to dorsal subiculum from any one part of lateral entorhinal cortex is spatially restricted. These data show that excitation-inhibition sequences can be seen in subicular pyramidal and multipolar cells and that single subicular neurons receive convergent inputs from CA1 and entorhinal cortex. We show for the first time that bursting cells can be driven both orthodromically and antidromically by direct entorhinal stimulation. These data support the existence of a reciprocal excitatory connection between lateral entorhinal cortex and dorsal subiculum and suggest further that this connection may involve only bursting subicular neurons.

A Phase II study of paclitaxel and ifosfamide for patients with advanced refractory carcinoma of the urothelium.

BACKGROUND: Cisplatin-based combination chemotherapy for patients with advanced transitional cell carcinoma (TCC) of the urothelium has limitations, and new therapies need to be evaluated. METHODS: Ifosfamide 1.0 gm/m2 on Days 1-4 and paclitaxel 135 mg/m2 by 24-hour infusion on Day 4 were administered to 26 patients with locally unresectable or metastatic TCC. Cycles were repeated every 21 days for a maximum of 6 cycles; dose escalation was dependent on whether Grade 3 or 4 toxicities occurred. RESULTS: There were 24 males and 2 females, with a median age of 66 years and a median Eastern Cooperative Oncology Group performance status of 0. The median number of cycles administered was 3. Twelve patients had Grade 3 or 4 hematologic toxicities, including 1 patient who died of a gastrointestinal hemorrhage while pancytopenic. There were no episodes of neutropenic fever. Two patients each had a complete response (CR) that lasted 5 and 28 months, respectively (response rate: 15%; 95% CI: 2-45%), among the 13 patients who had received prior chemotherapy. Of the 13 patients without prior chemotherapy, there were 3 with complete responses and 1 with a partial response ranging from 8 to 25+ months (RR: 30.7%; 95% CI: 9-61%). CONCLUSIONS: The combination of ifosfamide and paclitaxel is well tolerated and can produce objective responses in patients who are chemonaïve or have had prior therapy. For previously untreated patients, the addition of ifosfamide does not appear to result in a better response rate than single agent paclitaxel; and for previously treated patients, the addition of paclitaxel does not appear to result in a better response rate than single agent ifosfamide.

Plasticity of responses to synaptic inputs in rat ventral striatal neurons after repeated administration of the dopamine D2 antagonist raclopride.

The effects of acute and repeated systemic administration of the dopaminergic D2 antagonist raclopride on responses of ventral striatal neurons were examined in chloral hydrate-anesthetized rats. Stimulating electrodes were placed in the entorhinal and perirhinal cortices, medial thalamus, and prelimbic cortex. Stimulation in water-injected control rats evoked one or occasionally two action potentials. Results were similar in rats injected acutely with raclopride (4 or 8 mg/kg) except that a small proportion of cells (5%) produced burst responses (defined as three or more evoked action potentials). In rats injected with raclopride daily for 7-14 days, burst responses were seen in a larger proportion of cells (17%) and bursts of up to nine action potentials could be evoked. The results suggest that repeated administration of dopaminergic agents can induce striking plastic changes of excitatory responses in a subset of ventral striatal neurons.

Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indian University experience.

PURPOSE: In a previously reported randomized Southeastern Cancer Study Group (SECSG) trial, three cycles of chemotherapy were found to be equivalent to four cycles in patients with favorable-prognosis germ-cell cancer. We have conducted a follow-up analysis of patients treated at Indiana University (Indianapolis, IN) to compare long-term survival between the two groups and to examine factors associated with survival. PATIENTS AND METHODS: Sixty-nine patients with minimal-stage and 49 patients with moderate-stage disseminated germ-cell tumors were randomized to either three or four courses of bleomycin, etoposide, and cisplatin (BEP) administered every 3 weeks. Median follow-up time is 10.1 years (range, 7 months to 12.6 years). Ninety-two percent of patients have an actual follow-up time of > 5 years, and 97.5% of patients have an actual follow-up time of > 3 years. RESULTS: Survival analysis shows no significant difference between the two treatment groups in terms of overall (P = .80) or disease-free (P = .93) survival. Several clinical variables were examined by univariate analysis; only serum human chorionic gonadotropin (HCG) had an impact on survival. There were two disease-related deaths in 104 patients with HCG < or = 1,000 mIU/mL and five disease-related deaths in 14 patients with HCG greater than 1,000 mIU/mL (P < .001). Ninety-eight percent (95% CI, 95.2 to 100) of patients with favorable prognosis germ-cell tumor with an initial HCG of < or = 1,000 mIU/mL are alive without evidence of disease at 5+ years. CONCLUSION: With long-term follow-up, there is no statistically significant difference in survival between three or four cycles of BEP chemotherapy in patients with favorable prognosis germ-cell carcinoma. Serum HCG elevation of greater than 1,000 mIU/mL is a significant predictor of poor outcome in patients with otherwise good-risk disease.

Early effect of carotid endarterectomy on arterial blood pressure measured with an ambulatory monitor.

BACKGROUND: Carotid artery disease and hypertension are associated, and carotid endarterectomy is often followed by acute changes in blood pressure. As the carotid sinus is responsible for short-term blood pressure control, occlusive carotid disease may contribute to the mechanism of preoperative hypertension. METHODS: Ten patients undergoing carotid endarterectomy and eight having a peripheral bypass procedure were studied 2 weeks before and 2 weeks after operation, using home ambulatory blood pressure measurement. RESULTS: A significant fall in both mean systolic (-14.4 mmHg) and mean diastolic (-12.7 mmHg) pressure was observed after carotid endarterectomy (P < 0.006), whereas no change was seen in controls. CONCLUSION: These results suggest that there is an increase in carotid sinus activity in patients following carotid endarterectomy and supports the hypothesis that carotid sinus dysfunction contributes to hypertension in patients with carotid artery disease.

Elements for a report card: one institution's experience moving from theory to trial.

The emerging computerized patient record, the movement toward a unified nursing language, and increasing accountability to the public for clinical outcomes are converging forces that require a coherent plan if nursing is to evaluate outcomes. The article describes a nursing service and school of nursing's approach and beginning experiences in identifying concepts and indicators that are useful to clinicians. These concepts and indicators have the potential to be embedded in a concurrent information system that would feed a data repository used retrospectively by clinicians and researchers. The article also discusses results to date and lessons learned.

Activation of coagulation and platelets is affected by the hydrophobicity of artificial surfaces.

Clot formation is a limiting factor in the use of biomaterials. We investigated the effect of surface hydrophobicity on haemostatic activation in vitro, using five polyetherurethanes of varying surface hydrophobicity (C94, C74, C54 and C34), C94 the most, and C34, the least hydrophobic, and compared them with a commercial standard pellethane. Sterilised sacks were filled with heparinised blood, rotated at 37 degrees C for 24 h and sequential samples collected into 0.103 M sodium citrate. Thrombin generation measured by thrombin-antithrombin III complexes showed a difference between the polymers at 3 h through to 6 h (P < 0.05), C94 showing the least activation and C34 the most. Factor XIIa and D-dimer levels increased between 12 (P < 0.05) and 24 h (P < 0.01) for all polyetherurethanes. The ratio of soft:hard segments (which determine hydrophobicity) of the polyetherurethanes showed a direct relationship with the degree of activation of coagulation and fibrinolysis. There was no significant increase in monocyte tissue factor expression at 5 and 105 min. Platelet function as measured by whole blood platelet aggregation showed a reduction with pellethane and C94 after 1 h using collagen, with no changes for C34, Altering surface hydrophobicity has diverse effects on haemostatic pathways, with the most hydrophobic surfaces causing least activation of coagulation but most activation of platelets.

The utility of a single sputum specimen in the diagnosis of tuberculosis. Comparison between HIV-infected and non-HIV-infected patients.

STUDY OBJECTIVES: (1) To assess the utility of a single sputum specimen in the evaluation of HIV-infected patients who are suspected of having tuberculosis (TB). (2) To identify radiographic findings that discriminate between HIV-infected patients with TB and those with pneumonia of other causes. DESIGN: Retrospective cohort analysis. PATIENTS: All patients evaluated at Harborview Medical Center, Seattle, between January 1986 and July 1994 in whom culture of respiratory secretions grew Mycobacterium tuberculosis or Mycobacterium avium-complex. Patients who were coinfected with HIV formed the primary study group. Their chest radiographs were then compared with those of a matched group of patients with pneumonia of other causes. MEASUREMENTS AND RESULTS: We identified 164 patients with TB, 20 of whom were HIV infected. The initial sputum specimen grew M tuberculosis in all HIV-infected patients and 99% of non-HIV-infected patients. Seventy percent of HIV-infected and 71% of non-HIV-infected patients had at least one positive smear. Most of these patients tested positive on their initial smear, and no significant difference was found between HIV-positive and HIV-negative patients (79% and 90%, respectively [p = 0.34]). The addition of a second sputum smear identified all HIV-infected patients and all but one in non-HIV-infected patients who were ultimately determined to be smear positive. A total of 27 HIV-infected patients had a positive acid-fast bacilli sputum smear during the study period, 14 of which were attributable to TB (specificity = 52%). The only radiographic findings that discriminated between HIV-infected patients with TB and those with pneumonia of other causes were the presence of cavitation or a miliary pattern (p = 0.014). CONCLUSIONS: A single sputum specimen was sufficient to establish the diagnosis in all HIV-infected patients with pulmonary TB. A single negative sputum smear made the diagnosis of TB significantly less likely. However, a minimum of two smears were necessary to achieve an acceptable early diagnostic yield. The presenting chest radiograph failed to discriminate between HIV-infected patients with TB and pneumonia of other causes in most cases.

Lack of Fos-like immunoreactivity after spontaneous seizures or reinduction of status epilepticus by pilocarpine in rats.

Acute seizures and status epilepticus induced by pilocarpine lead to the expression of Fos-like immunoreactivity in several specific brain areas in a manner similar to that of other models of limbic seizures. Upon development of status epilepticus after systemic pilocarpine injection, animals develop a state where chronic spontaneous seizures recur. Assessment of Fos-like immunoreactivity after such spontaneous seizures or after status epilepticus reinduction reveals either lack of staining or a weak reaction in a few brain areas including the ventral tip of the dentate gyrus, prepiriform, lateral piriform and perirhinal cortices, and scattered locations throughout temporal neocortex. Our results suggest that status epilepticus induction may lead to a long-lasting state of Fos down-regulation.