Factors affecting reorganisation of memory encoding networks in temporal lobe epilepsy.

AIMS: In temporal lobe epilepsy (TLE) due to hippocampal sclerosis reorganisation in the memory encoding network has been consistently described. Distinct areas of reorganisation have been shown to be efficient when associated with successful subsequent memory formation or inefficient when not associated with successful subsequent memory. We investigated the effect of clinical parameters that modulate memory functions: age at onset of epilepsy, epilepsy duration and seizure frequency in a large cohort of patients. METHODS: We studied 53 patients with unilateral TLE and hippocampal sclerosis (29 left). All participants performed a functional magnetic resonance imaging memory encoding paradigm of faces and words. A continuous regression analysis was used to investigate the effects of age at onset of epilepsy, epilepsy duration and seizure frequency on the activation patterns in the memory encoding network. RESULTS: Earlier age at onset of epilepsy was associated with left posterior hippocampus activations that were involved in successful subsequent memory formation in left hippocampal sclerosis patients. No association of age at onset of epilepsy was seen with face encoding in right hippocampal sclerosis patients. In both left hippocampal sclerosis patients during word encoding and right hippocampal sclerosis patients during face encoding, shorter duration of epilepsy and lower seizure frequency were associated with medial temporal lobe activations that were involved in successful memory formation. Longer epilepsy duration and higher seizure frequency were associated with contralateral extra-temporal activations that were not associated with successful memory formation. CONCLUSION: Age at onset of epilepsy influenced verbal memory encoding in patients with TLE due to hippocampal sclerosis in the speech-dominant hemisphere. Shorter duration of epilepsy and lower seizure frequency were associated with less disruption of the efficient memory encoding network whilst longer duration and higher seizure frequency were associated with greater, inefficient, extra-temporal reorganisation.

Comparative efficacy of tyrosine kinase inhibitor treatments in the third-line setting, for chronic-phase chronic myelogenous leukemia after failure of second-generation tyrosine kinase inhibitors.

We compared the efficacy of ponatinib and second-generation tyrosine kinase inhibitors (2G-TKIs: bosutinib, dasatinib, and nilotinib) in chronic phase CML resistant/intolerant to ≥1 prior 2G-TKI. Estimated probabilities of CCyR with 2G-TKI ranged from 22% to 26%, compared with 60% (95% CrI 52-68%) with ponatinib. The estimated probability of ponatinib providing higher response rate than all other included treatments was 99% (CCyR) and 97% (MCyR). Use of further 2G-TKI may provide limited benefit in CP-CML patients resistant/intolerant to prior 2G-TKI treatment. Compared with 2G-TKIs, ponatinib is estimated to provide substantially higher probability of achieving CCyR and MCyR; safety was not compared.

Temporal lobe epilepsy and affective disorders: the role of the subgenual anterior cingulate cortex.

OBJECTIVE: Reduced deactivation within the default mode network (DMN) is common in individuals with primary affective disorders relative to healthy volunteers (HVs). It is unknown whether similar network abnormalities are present in temporal lobe epilepsy (TLE) patients with a history of affective psychopathology. METHODS: 17 TLE patients with a lifetime affective diagnosis, 31 TLE patients with no formal psychiatric history and 30 HVs were included. We used a visuo-spatial 'n-back' paradigm to compare working memory (WM) network activation between these groups. Post hoc analyses included voxel-based morphometry and diffusion tensor imaging. The Beck Depression Inventory-Fast Screen and Beck Anxiety Inventory were completed on the day of scanning. FINDINGS: Each group activated the fronto-parietal WM networks and deactivated the typical DMN in response to increasing task demands. Group comparison revealed that TLE patients with lifetime affective morbidity showed significantly greater deactivation in subgenual anterior cingulate cortex (sACC) than either the TLE-only or the HVs (p<0.001). This effect persisted after covarying for current psychotropic medication and severity of current depressive/anxiety symptoms (all p<0.001). Correlational analysis revealed that this finding was not driven by differences in task performance. There were no significant differences in grey matter volume or structural connectivity between the TLE groups. CONCLUSIONS: Our results provide novel evidence suggesting that affective psychopathology in TLE has a neurobiological correlate, and in this context the sACC performs differently compared with network activity in primary affective disorders.

Eight-weekly intravenous antibiotics is beneficial in severe bronchiectasis.

AIM: The aim of our study was to assess the impact of 8-weekly intravenous (IV) antibiotics on exacerbation frequency and health-related quality of life in bronchiectasis. METHODS: Patients were recruited prospectively from June 2008 to December 2010. Patients with recurrent exacerbations (five or more exacerbations per year) and subjectively reporting ill health between antibiotic courses were recruited. Eight-weekly IV antibiotics (for 14 days) were initiated. Patients were followed up for 1 year. Main outcome was reduction in exacerbation frequency and improvement in health-related quality of life (HRQoL) at 1 year after starting intravenous antibiotic therapy. Other outcomes recorded were forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), incremental shuttle walk test (ISWT), 24-h sputum volume, sputum microbiology, body mass index (BMI), markers of inflammation--white cell count (WCC), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). RESULTS: In total, 19 patients were recruited. Mean age was 64.1 years and 52.6% were female. With 8-weekly antibiotics, there was a significant reduction in the number of exacerbations [mean (SE): 9.3 (0.5) in the year before vs. 8.0 (0.4) in the year after; P = 0.02]. In 63.2%, Leicester Cough Questionnaire (LCQ) improved by ≥1.3 U (P = 0.006)] and in 42.1% St. George's Respiratory Questionnaire (SGRQ) improved by ≥4 U (P = 0.03). Exercise capacity increased by 58.7 m (P = 0.004). There was no improvement in the other end points. CONCLUSION: Treatment with 8-weekly intravenous antibiotics in severe bronchiectasis reduced exacerbation frequency and improved exercise tolerance and health-related quality of life.

A pilot study of pulmonary rehabilitation and chest physiotherapy versus chest physiotherapy alone in bronchiectasis.

AIM: The aim of our study was to assess the efficacy of pulmonary rehabilitation in addition to regular chest physiotherapy in non cystic fibrosis bronchiectasis. METHODS: Thirty patients with clinically significant bronchiectasis and limited exercise tolerance were randomized into either the control group receiving chest physiotherapy (8 weeks) or into the intervention group, receiving pulmonary rehabilitation in addition to chest physiotherapy (8 weeks). Both groups were encouraged to maintain their exercise program and or chest physiotherapy, following completion of the study. RESULTS: End of training (8 weeks) No improvement in control group. In the intervention group, incremental shuttle walk test (ISWT) improved by 56.7 m (p = 0.03), endurance walk test (EWT) by 193.3 m (p = 0.01), Leicester Cough Questionnaire (LCQ) improved by 2.6 units (p < 0.001) and St. George's Respiratory Questionnaire (SGRQ) by 8 units (p < 0.001). At 20 weeks (12 weeks post end of training) No improvement in control group. In the intervention group, ISWT improved by 80 m (p = 0.04) and EWT by 247.5 m (p = 0.003). LCQ improved by 4.4 units (p < 0.001) and SGRQ by 4 units (p < 0.001). CONCLUSION: Pulmonary rehabilitation in addition to regular chest physiotherapy, improves exercise tolerance and health related quality of life in non cystic fibrosis bronchiectasis and the benefit was sustained at 12 weeks post end of pulmonary rehabilitation. Clinical trials regn no. NCT00868075.

Physiological stress assessment of female workers at kitchen workstation.

This paper explores the extent of the physiological stresses of female workers at kitchen workstation while performing the various activities. For this a survey of eighty homemakers and experiment on sixteen respondents having similar physical and physiological parameters was done. Five activities in which the respondents faced maximum problems were selected and were standardized. Physiological stresses including cardiovascular, muscular, and energy expenditure during these activities were then assessed. Study revealed that fatigue during the selected five activities i.e. cutting, grating, rolling, kneading, dish washing, was felt mainly at the wrist, fore arm, followed by discomfort in the shoulders, upper arm, lower back and neck. Energy expenditure for these activities ranged from 7.0 to10 kJ\min, total cardiac cost of work (TCCW) was between 200.81 to 364.30 beats, physiological cost of work (PCW) was 12.82 to 26.26 beats\min; maximum for grating and minimum for rolling. The percent increase in heart rate was maximum for grating 38.56 and minimum for rolling 16.20. Reduction in grip and pinch strength of right hand was found more as compared to the left hand.

Health-related utility among adults with atopic dermatitis treated with 0.1% tacrolimus ointment as maintenance therapy over the long term: findings from the Protopic CONTROL study.

BACKGROUND: Long-term maintenance treatment with 0.1% tacrolimus ointment for the prevention of flares has been demonstrated to be well tolerated and effective in adults for the treatment of atopic dermatitis (AD) but its impact on health-related utility has not been reported. OBJECTIVES: The purpose of this study was to estimate utility changes associated with the use of tacrolimus ointment in the maintenance treatment of adults with AD. METHODS: Data were collected from a clinical trial investigating long-term maintenance treatment with 0.1% tacrolimus ointment in adults with AD. All patients were treated with twice-daily tacrolimus ointment during an open-label period (OLP) of up to 6 weeks, with subsequent randomization to a double-blind disease-control period (DCP) of 12 months comparing tacrolimus ointment, used twice weekly as maintenance treatment, vs. the emollient vehicle as standard treatment. Health-related utility (EQ-5D(index)) was estimated by Monte Carlo simulation from SF-12 responses by application of a published response mapping algorithm and the U.K. tariff for EQ-5D responses and SF-6D responses, respectively. RESULTS: Evaluable data were available for 257 patients stratified into mild, moderate or severe AD with a median age at screening of 28 years [interquartile range (IQR) 22-38] and 40% male. At screening the median EQ-5D(index) across the strata was 0.848 units (IQR 0.704-0.882) for mild cases, 0.796 (0.737-0.876) for moderate cases, and 0.760 (0.661-0.823, P < 0.001) for those with severe disease. At the end of the OLP, mean utility improvement across all strata was 0.027 [95% confidence interval (CI) -0.011 to 0.065, P = 0.165] for mild cases, 0.046 (95% CI 0.015-0.064, P = 0.002) for moderate cases and 0.076 (95% CI 0.035-0.118, P < 0.001) for those with severe disease. At the end of the blinded DCP, repeated measures analysis showed an age- and sex-adjusted mean change of 0.045 units (P < 0.001) for subjects treated with tacrolimus ointment over those treated with emollient vehicle. CONCLUSIONS: Patients with AD of all severities showed considerable decrements in health-related utility. However, treatment with 0.1% tacrolimus ointment was associated with clinically significant improvement in health-related utility for patients with moderate and severe AD, which was sustained over a 12-month maintenance period compared with those using standard treatment with an emollient vehicle.

Cost-effectiveness analysis of micafungin versus caspofungin for treatment of systemic Candida infections in the UK.

OBJECTIVE: To evaluate the cost-effectiveness of micafungin compared to caspofungin in the treatment of systemic Candida infections (SCIs) in the UK, including invasive candidiasis and candidaemia. RESEARCH DESIGN AND METHODS: Cost-effectiveness of both echinocandin antifungal drugs was estimated using decision analysis. Response to treatment, resource utilisation, and costs in the model were derived from a phase 3, head-to-head comparative trial. The model includes only data directly related to the treatment of the systemic Candida infection over the study duration (a maximum period of 14 weeks). Transition probabilities were calculated based on the efficacy results from the clinical trial. MAIN OUTCOME MEASURES: The model's effectiveness outcome is surviving patients who are successfully treated, based on the absence of signs and symptoms, radiographic abnormalities, and culture/histologic evidence associated with the fungal infection. In addition, subgroup analyses were performed to identify cost-effectiveness in several specific patient groups. RESULTS: The total medical treatment costs for the micafungin group were pound 29,095, which is similar to the total costs for the caspofungin group (pound 29,953). In the micafungin arm 60% of the patients and in the caspofungin arm 58% of the patients were successfully treated and alive. Cost-effectiveness ratio of micafungin was pound 48,771, and of caspofungin pound 52,066 per successfully treated patient. Because the costs are lower and the effectiveness is higher for micafungin in comparison with caspofungin, micafungin is more cost-effective than caspofungin. However, probabilistic sensitivity and subgroup analysis show that the differences cannot be considered significant due to a large variance although micafungin remained the most cost-effective option throughout all but one of the sensitivity analyses. CONCLUSIONS: Costs and effects of micafungin compare to those of caspofungin in the treatment of systemic Candida infections in the UK. The results indicate that micafungin is cost-effective compared to caspofungin, although the difference was not found to be significant.

Economic evaluation of maintenance treatment with tacrolimus 0.1% ointment in adults with moderate to severe atopic dermatitis.

BACKGROUND: Rational health care decision-making based on outcomes and economic evidence is essential to provide the best possible care for individual patients with atopic dermatitis (AD). OBJECTIVES: To describe treatment outcomes and to evaluate resource utilization and associated cost of maintenance use of tacrolimus ointment (MU) vs. standard use of tacrolimus ointment (SU) in adults with AD. METHODS: A pan-European, phase III multicentre randomized clinical trial was conducted. Patients with mild to severe AD were randomized to tacrolimus 0.1% ointment (MU) or vehicle (SU) twice per week for 12 months. Disease exacerbations were treated by using open-label tacrolimus 0.1% ointment twice daily. Resource utilization data were collected prospectively alongside the clinical trial. Costs of pooled resource data were determined using German unit cost data. Direct and indirect costs were considered from third party payer, patient and societal perspectives. RESULTS: All patients with moderate and severe AD were included in a subanalysis, 75 patients in the MU arm (57% moderately affected) and 59 patients in the SU arm (59% moderately affected). In patients with moderate AD, the number of disease exacerbations in the MU arm was 2.4 vs. 5.5 in the SU arm (P<0.001); in patients with severe AD corresponding figures were 2.3 vs. 7.4 (P<0.001), respectively. Mean+/-SD total annual cost per patient was euro1525+/-1081 (MU) vs. euro1729+/-1209 (SU) in patients with moderate AD and euro2045+/-2013 (MU) vs. euro2904+/-1510 (SU) in patients with severe AD. CONCLUSIONS: Maintenance treatment with 0.1% tacrolimus ointment is more effective and leads to cost savings and improved health-related quality of life in comparison with standard use of 0.1% tacrolimus ointment, especially in patients with severe AD.

Macaques co-immunized with SIVgag/pol-HIVenv and IL-12 plasmid have increased cellular responses.

BACKGROUND: The cell mediated immune profiles following immunization with a recombinant DNA vaccine was assessed in the simian-human immunodeficiency virus (SHIV) and Macaque model. Earlier work demonstrated increased numbers of antigen specific CD8 and CD4 effector cells able to secrete IFN-gamma. METHOD: The vaccine strategy included co-immunization of a DNA based vaccine alone or in combination with a macaque IL-12 expressing plasmid (pmacIL12). Antigen activated lymphocytes were studied for activation of a set of immunological molecules. RESULTS: The current study demonstrates lymphocytes isolated and activated from the group that was immunized with DNA and pmacIL12 had a higher level of IFN-gamma producing cells. We also observed a different immunological profile when comparing the cells isolated from macaques immunized with DNA as compared to those animals that also received pmacIL12. CONCLUSION: The observed immune profiles are reflective of the co-delivery of pmacIL12 and demonstrates that IL-12 can increase the magnitude and polyfunctionality of the cellular immune response.

Surgery for morbid obesity.

BACKGROUND: Obesity is associated with increased morbidity and mortality. Surgery for morbid obesity is considered when other treatments have failed. A number of procedures are available, but the effects of these surgical procedures compared with medical management and with each other are uncertain. OBJECTIVES: To assess the effects of surgery for morbid obesity. SEARCH STRATEGY: Studies were obtained from computerized searches of multiple electronic bibliographic databases, supplemented with hand searches of selected journals and consultation with experts in obesity research. Date of the most recent searches: December 2004. SELECTION CRITERIA: Randomised controlled trials comparing different surgical procedures, and randomised controlled trials and prospective cohort studies comparing surgery with non-surgical management for morbid obesity. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and checked independently by two reviewers. Two reviewers independently assessed trial quality. MAIN RESULTS: Twenty-six trials were included. Two randomised controlled trials and three prospective cohort studies compared surgery with non-surgical management, and 21 randomised controlled trials compared different surgical procedures. The quality of most of the trials was poor; just three trials had adequate allocation concealment. A meta-analysis was not possible due to differences in the surgical procedures performed, measures of weight change and length of follow-up. Compared with conventional management, surgery resulted in greater weight loss (21 kg weight loss at eight years versus weight gain), with improvements in quality of life and comorbidities. Some complications of surgery occurred, such as wound infection. Gastric bypass was associated with greater weight loss, better quality of life and fewer revisions, reoperations and/or conversions than gastroplasty, but had more side-effects. Greater weight loss and fewer side-effects and reoperations occurred with adjustable gastric banding than vertical banded gastroplasty, but laparoscopic vertical banded gastroplasty produced more patients with an excellent or good result and fewer late complications than laparoscopic adjustable silicone gastric banding. Vertical banded gastroplasty was associated with greater weight loss but more vomiting than horizontal gastroplasty. Some postoperative deaths occurred in the studies. Weight loss was similar between open and laparoscopic procedures. Fewer serious complications occurred with laparoscopic surgery, although conversion to open surgery was sometimes required. Most studies found that laparoscopic surgery had a longer operative time. But, it resulted in reduced blood loss and quicker recovery. AUTHORS' CONCLUSIONS: The limited evidence suggests that surgery is more effective than conventional management for weight loss in morbid obesity. The comparative safety and effectiveness of different surgical procedures is unclear.

Systematic review of the Sugarbaker procedure for pseudomyxoma peritonei.

BACKGROUND: Pseudomyxoma peritonei, a rare progressive disease process within the peritoneum, is characterized by an abundance of mucinous fluid; if left untreated, the condition is fatal. The aim of this article is to assess the clinical effectiveness and costs of the Sugarbaker procedure for pseudomyxoma peritonei. METHODS: A systematic review of the literature up to April 2004 was undertaken, with modelling of costs. RESULTS: Five retrospective case-series reports met the inclusion criteria. Survival after operation was approximately 95 per cent at 2 years and 60-68 per cent at 10 years, with 41-52 per cent of patients having no evidence of disease at the end of follow-up. A Monte Carlo simulation model estimated the marginal cost for one patient over a maximum of 5 years to be about pound 9700 (standard deviation pound 1300). CONCLUSION: Evidence of the effectiveness of the Sugarbaker procedure for pseudomyxoma peritonei is limited in quantity and quality, but suggests there may be some benefit for patients. The marginal cost of the operation is about pound 9700, provided that trained and experienced staff are available to perform the procedure.

Clinical and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes.

OBJECTIVES: To assess the clinical and cost-effectiveness of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) in the delivery of intensive insulin therapy for the treatment of diabetes mellitus. DATA SOURCES: Electronic databases, references of retrieved articles and manufacturer submissions. Experts in the field were consulted. REVIEW METHODS: For the systematic review of clinical and cost-effectiveness, studies were assessed for inclusion according to predefined criteria by two reviewers. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer. Data on clinical effectiveness were synthesised through a narrative review with full tabulation of all eligible studies, with meta-analysis performed where appropriate. RESULTS: Twenty studies comparing CSII with MDI were identified. Quality was generally poor. In adults with Type 1 diabetes, glycated haemoglobin improved by 0.61% (95% CI -1.29 to 0.07) in longer term studies, although this improvement was smaller when a study using bovine ultralente was excluded. A reduction in insulin dose with CSII of about 12 units per day (-11.90, 95% CI -18.16 to 5.63) was found in short-term studies, with smaller differences in longer term studies. Body weight and cholesterol levels were similar between treatments. Hypoglycaemic events did not differ significantly between CSII and MDI in most trials, but some found fewer events with CSII and one found more hypoglycaemia and hypoglycaemic coma with CSII. There was no consistency between the studies in patient preference, but progress has been made both with insulin pumps and injector pens since the publication of many of the older studies. No difference in glycated haemoglobin between CSII and MDI was found in pregnancy; one study found less insulin was required by patients with CSII, but two other studies found no significant difference. One study of adolescents found lower glycated haemoglobin and insulin dose with CSII whereas a second study found no significant difference. In CSII analogue insulin was associated with lower glycated haemoglobin levels than soluble insulin. No economic evaluations comparing CSII with MDI were identified. The estimated additional cost of CSII compared to MDI varies from GBP1091 per annum to GBP1680 per annum, according to the make of the insulin pump and the estimated life of the device. These estimates include the costs for the insulin pump, the consumables associated with delivery of CSII, and an allowance for the initial education required when patients switch from MDI to CSII. The largest component of the annual cost for CSII is the cost of consumable items (e.g. infusion sets). CONCLUSIONS: When compared with optimised MDI, CSII results in a modest but worthwhile improvement in glycated haemoglobin in adults with Type 1 diabetes. It has not been possible to establish the longer term benefits of such a difference in glycated haemoglobin, although there is an expectation that it would be reflected in a reduction in long-term complications. More immediate primary benefits from CSII may be associated with an impact on the incidence of hypoglycaemic events and the dawn phenomenon, and greater flexibility of lifestyle. However, there is limited evidence on this, and information presented to offer context on quality-of-life is based on testimonies from those patients who have had a positive experience of CSII. The estimated cost to the NHS per year for CSII would be around GBP3.5 million in England and Wales if 1% of people with Type 1 diabetes used CSII, GBP10.5 million for 3%, and GBP17.5 million for 5%. Further research should focus on wider benefits of CSII, such as flexibility of lifestyle and quality of life, and on the psychological impact of wearing a device for 24 hours every day. Research into the use of CSII in children of different ages is also needed.

Clinical effectiveness and costs of the Sugarbaker procedure for the treatment of pseudomyxoma peritonei.

OBJECTIVES: This systematic review examines the clinical and cost-effectiveness of the Sugarbaker procedure for treating pseudomyxoma peritonei (PMP) and the costs of the procedure in the UK. DATA SOURCES: Electronic databases, bibliographies of related papers and experts in the field were used as sources for English language studies available up to September 2002. REVIEW METHODS: Evidence of the clinical effectiveness of the Sugarbaker procedure for PMP was synthesised through a narrative review with full tabulation of results of all included studies. The economic modelling used a Monte-Carlo simulation model populated with UK price data to estimate likely UK costs. RESULTS: Five retrospective case-series reports assessing the Sugarbaker procedure met the inclusion criteria for the review, although they were found to be of poor quality when judged against standard criteria for assessing methodological standard. There appears to be some benefit for people with PMP who undergo treatment with the Sugarbaker procedure. Commonly reported complications of the Sugarbaker procedure were anastomotic leaks, fistula formation, wound infection, small bowel perforations/obstructions and pancreatitis. One costing study of poor methodological quality and set in the USA was found. This study, together with UK unit price data and expert advice, was used to populate a Monte-Carlo simulation model to estimate the marginal cost of operating a service to provide treatment for PMP using the Sugarbaker technique rather than standard treatment. The results of the Monte-Carlo simulation model showed that the cost for one patient over a maximum of 5 years would be about 9700 British pounds, with a standard deviation of about 1300 British pounds (although costs incurred in setting up the specific service or training the staff were not included). The US study showed a ten-fold higher cost. The Monte-Carlo analysis showed that the variation around the mean was not very high. The most likely factor influencing the variation of the costs was the length of procedure. No sensitivity analysis could be done of the alternative treatment. CONCLUSIONS: The economic results should be seen as merely an example of the likely marginal costs of the Sugarbaker procedure, as more information about the current alternative is required. Trained and experienced staff are required to implement the procedure and inevitably time and cost will be involved in developing the appropriate teams. Although the procedure requires some specialist equipment and maintenance, such as smoke evacuators, these should have limited effect on setting up the service. PMP is a relatively rare condition with approximately 50 new cases per year in the UK and the impact of an increase in the demand for services should be limited. Evidence is needed for the effectiveness of maximal cytoreductive surgery compared with surgical debulking, using different intraoperative intraperitoneal chemotherapy strategies, and for the effectiveness of treatments in patients who have residual disease following maximal efforts at cytoreduction. Further research involving high-quality prospective cohort studies with economic evaluations would be valuable.

A new contained human immunodeficiency virus type 1 host cell system for evaluation of antiviral activities of interferons and other agents in vitro.

HIV-host infection systems in vitro are important in the pre-clinical assessment of anti-retroviral drug activity. The present report describes the development of a new HIV-host model comprised of an epithelial cell line of HeLa lineage (HeLa-1), transfected with expression vectors bearing tat and rev (TART) genes of HIV-1 as well as the CD4 receptor gene, and HIV-1(delta Tat/Rev), a biologically contained strain of HIV-1 deleted in tat and rev. Measurement of infectivity, by syncytium formation and reverse transcriptase assay, revealed that HeLa-1 is infected with HIV-1(deltaTat/Rev). This virus failed to productively infect the TART-deficient CD4-positive HeLa cells, confirming its contained, non-infectious nature. The HeLa-1/HIV-1deltaTat/Rev system was used to measure the anti-retroviral activity of a human leukocyte-derived interferon (IFN-alphan3) preparation, several nucleoside analogs, and protease inhibitors. The HeLa-1/ HIV-1(deltaTat/Rev model provides a biologically contained system for the study of the HIV pathogenesis and the relative and combined therapeutic effects of anti-retroviral agents in vitro.

Identification of copper-zinc superoxide dismutase gene from enteroaggregative Escherichia coli.

We describe here the identification of sodC gene from enteroaggregative Escherichia coli (EAggEC). A 294 bp gene-specific fragment was amplified from the organism by DNA as well as RT-PCR using primers from bacterial sodC sequences. The metal co-factor present in the protein was confirmed by running samples in native gels and inhibiting with 2 mM potassium cyanide. However, the nonpathogenic E. coli possesses the gene but does not express it. Thus, the presence of copper-zinc superoxide dismutase encoded by sodC was demonstrated for the first time in EAggEC, which means it could be a novel candidate for a virulence marker.

Power Doppler imaging of acute renal transplant rejection.

PURPOSE: We evaluated the usefulness of power Doppler imaging (PDI) in diagnosing acute renal-transplant rejection. METHODS: Twenty-eight patients underwent 33 renal-transplant biopsies for suspected acute rejection. Patterns of renal parenchymal vascularity revealed by PDI in patients with abnormal biopsy results were compared with patterns in a group who had normal biopsy results. PDI examinations were reviewed retrospectively by 2 independent radiologists who had no knowledge of the biopsy results. A PDI diagnosis of acute rejection required marked vascular pruning in both the cortex and medulla. PDI results then were compared with transplant-biopsy results. RESULTS: The sensitivity and specificity of PDI for diagnosing acute renal-transplant rejection were 40% and 100%, respectively. None of the patients with negative biopsy results had PDI abnormalities. The negative predictive value of PDI was 33%, and the positive predictive value was 100%. CONCLUSIONS: In our study, an abnormal sonogram was highly predictive of acute transplant rejection. However, a normal sonogram did not exclude the possibility of rejection.

Post-traumatic hepatic pseudoaneurysms in children.

BACKGROUND: Post-traumatic hepatic artery pseudoaneurysms are rarely seen in children. MATERIALS AND METHODS: We retrospectively reviewed the radiologic studies and medical records of three patients treated at our institution and reviewed the literature. The patients (ages 5-13 years) presented immediately to 2 months after blunt (two patients) and penetrating (one patient) trauma. The hepatic pseudoaneurysms were discovered during work-up for fever (one patient), gastrointestinal bleeding and hyperbilirubinemia (one patient), or widened mediastinum (one patient) on chest radiograph. In two patients, the diagnosis was initially suspected by computed tomography (CT) examination and confirmed by angiography. In the third patient, the diagnosis was made initially by angiography. All three pseudoaneurysms were treated with transcatheter embolization. RESULTS: All three embolizations were initially technically successful. However, there was recurrence in one case, in which embolization distal to the neck of the pseudoaneurysms was not technically possible. With conservative management, however, the residual lesion demonstrated spontaneous occlusion by ultrasound (US) at 6 months. CONCLUSION: This uncommon complication of liver trauma in children can have a delayed presentation, can be clinically unsuspected, and can follow blunt or penetrating trauma. Endovascular embolotherapy is the treatment of choice.