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Biomedical subjects

I Katz

Publications and source records attributed to I Katz.

At least 19 recordsLinked to original sources

HIV-related nephropathy: a South African perspective.

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is an important cause of renal failure in those of African origin. A number of other kidney diseases occur in HIV-positive patients. We conducted a retrospective review of renal biopsies in HIV-positive Black African patients to determine the prevalence of both 'classic HIVAN' and non-HIVAN pathologies in this group. Clinical and laboratory data from HIV-positive patients who underwent renal biopsy from 1st January 2003 to 31st December 2004 were collected. Similar information on HIV-negative patients biopsied during the same period was also recorded by way of comparison to try and assess the influence of the virus on renal histologic patterns. HIV-positive group - 99 biopsies were suitable for study. The main histologic categories were 'classic HIVAN' (27%) and HIV immune complex kidney disease ('HIVICK') (21%). The subepithelial immune deposits in 'HIVICK' induced a newly described 'ball-in-cup' basement membrane reaction. Other glomerulonephritides included membranous, post-infectious disease, mesangial hyperplasia, and immunoglobulin A nephropathy. Overlapping clinical presentations prevented pre-biopsy histologic predictions. HIV-negative group - There were no examples of collapsing focal segmental glomerulosclerosis or nonspecific immune complex disease, but increased numbers of minimal change and membranoproliferative disease. 'Classic HIVAN' accounted for less than a third of the nephropathies occurring in HIV-positive Black South Africans. 'HIVICK' is another important cause of chronic kidney disease in this group. Future research is needed into the earlier detection and treatment of these diseases, which have a high mortality in our context.

AIDS-Associated Nephropathy↗

The benefits of a broader perspective in case-finding for disease management of depression: early lessons from the PROSPECT Study.

The PROSPECT (Prevention of Suicide in Primary Care Elderly - Collaborative Trial) Study evaluates collaborative care for the treatment of current depressive disorders in older primary care patients. Using screening data, we evaluate implications of expanding the focus to additional patients who report taking psychotropic medication or having a history of depression. Some 13.8% of the patients screened were taking a psychotropic medication and 7.3% were both taking an antidepressant and had a Center for Epidemiologic Studies - Depression Scale (CES-D) score of > 15. Patients who reported current antidepressant use and those with a history of depression also had elevated CES-D scores. Conversely, most patients having an elevated CES-D score also reported taking an antidepressant or having a history of depression. These latter criteria for potential caseness yielded a larger number of patients than those identified by the CES-D alone. More comprehensive approaches to the management of depression should attend to patients already taking psychotropic medication and symptomatic patients with a history of depression, as well as those with current syndromal depression.

Aged↗

Atrazine degradation under denitrifying conditions in continuous culture of Pseudomonas ADP.

The simultaneous removal of atrazine and nitrate in continuous culture under denitrifying conditions using Pseudomonas sp. strain ADP was investigated. Under all operational conditions the nitrate removal efficiency was always higher than 90%, while atrazine degradation deteriorated with time due to contamination by foreign denitrifying bacteria, lacking the ability to degrade atrazine. Recovery of atrazine degradation ability was achieved by applying aerobic conditions with atrazine as the sole nitrogen source.

Aerobiosis↗

A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne.

BACKGROUND: Isotretinoin is very frequently the drug of choice for the management of severe recalcitrant nodular acne. Recently, a new micronized and more bioavailable formulation of isotretinoin has been developed that permits once-daily administration in lower doses than usually used with standard isotretinoin (Accutane), regardless of whether it is taken with or without food. OBJECTIVE: Our purpose was to determine whether micronized isotretinoin and standard isotretinoin are clinically equivalent. METHODS: In this multicenter, double-blind, double-dummy study, 600 patients with severe recalcitrant nodular acne were treated with either 0.4 mg/kg of micronized isotretinoin once daily without food (n = 300) or 1.0 mg/kg per day of standard isotretinoin in two divided doses with food (n = 300). Lesion counts were monitored over 20 weeks. RESULTS: Both treatment groups in this well-controlled clinical trial experienced an equivalent reduction in the number of total nodules (facial plus truncal). In addition, an equivalent proportion of patients achieved 90% clearance of the total number of nodules. Both formulations had similar results for other efficacy variables. CONCLUSION: Once-daily use of the micronized and more bioavailable formulation of isotretinoin under fasted conditions is clinically equivalent to the standard twice-daily formulation under fed conditions in the treatment of severe recalcitrant nodular acne.

Acne Vulgaris↗

Safety of a new micronized formulation of isotretinoin in patients with severe recalcitrant nodular acne: A randomized trial comparing micronized isotretinoin with standard isotretinoin.

BACKGROUND: Isotretinoin is a very effective drug for treating severe recalcitrant nodular acne. A new micronized formulation of isotretinoin has been shown to be clinically equivalent to standard isotretinoin with improved bioavailability and minimal food effect. The safety profile of the micronized formulation has not been described previously. OBJECTIVE: The objective of this article is to report the incidence and intensity of adverse events found in a comparative, double-blind efficacy study that showed clinical equivalence of the new micronized formulation of isotretinoin and the standard isotretinoin formulation (Accutane). METHODS: Six hundred patients with severe recalcitrant nodular acne were treated with micronized isotretinoin (n = 300) under fasted conditions or standard isotretinoin (n = 300) under fed conditions. One cohort received single daily doses of 0.4 mg/kg of micronized isotretinoin without food and the other cohort received 1.0 mg/kg per day of standard isotretinoin in two divided doses with food. Adverse events were monitored during 20 weeks of drug therapy. RESULTS: The proportion of adverse events in most body systems was generally lower in patients receiving micronized isotretinoin than in those receiving standard isotretinoin. CONCLUSION: Micronized isotretinoin appears to have a safety profile similar to that of standard isotretinoin and to carry a lower risk of mucocutaneous events and hypertriglyceridemia.

Acne Vulgaris↗

Cognitive and psychomotor effects of paroxetine and sertraline on healthy elderly volunteers.

The authors evaluated the cognitive and psychomotor effects of serotonin reuptake inhibitors in healthy elderly volunteers. Paroxetine, sertraline, and placebo were compared for 3 weeks of testing in a double-blind study with behavioral testing at baseline and at the end of each week. MANOVA models demonstrated no between-group differences; however, mixed-model random regression analyses revealed that Day 14 plasma paroxetine levels correlated negatively with delayed verbal recall and paired-associate learning scores. In contrast, plasma sertraline levels correlated positively with Day 7 immediate verbal recall, Day 14 tapping, and Day 21 delayed verbal recall scores, and negatively with divided-attention task scores on Day 21. Plasma paroxetine levels were associated with mild behavioral impairment at Day 14, with no other significant adverse effects. Plasma sertraline levels were associated with mild and transient behavioral changes, as well as early termination in several subjects.

Aged↗

Assessing individual patients for cognitive benefits from acetylcholinesterase inhibitors.

To evaluate an objective method for individually assessing Alzheimer patients for cognitive benefits from acetylcholinesterase inhibitors, we conducted a secondary analysis of data from 234 subjects enrolled in a 30-week efficacy trial of tacrine hydrochloride. We determined which patients showed treatment-related improvement on the Alzheimer Disease Assessment Scale--Cognitive subscale (ADAS-Cog) and the MiniMental State Examination (MMSE). Four weeks after administration of the maximum dose, 14% showed significant improvement from baseline in their ADAS-Cog scores, and 30.6% showed significant improvement in their MMSE scores. Examination of response patterns over time revealed that 65% of patients showed no improvement in MMSE scores during the 120-160-mg phases of the trial, whereas 18% showed consistent improvement in MMSE scores during that time. Three percent of patients showed improvement in their MMSE scores only for the 160-mg assessment. How the methodology from this study can be generalized to other Alzheimer patients is discussed. We calculated prediction intervals to document the magnitude of fluctuation in performance that is normal for Alzheimer patients similar to those in this study. Patients who change more than the limit specified by the prediction interval have statistically significantly improved performance. We determined that an improvement on the MMSE of three or more points across a time period of 6 weeks marks statistically significant change for an individual. For intervals between 6 and 16 weeks, improvement of four or more points on the MMSE is statistically significant. The results indicate that monitoring individual patients for statistically significant improvements in cognitive functioning is feasible, sensitive to drug-related changes in performance, and could facilitate drug monitoring in patients.

Aged↗

The occurrence, recrudescence, and worsening of asthma in a population of young adults: impact of varying types of occupation.

OBJECTIVE: To describe the rates of exacerbation of existing asthma and incidence of new disease in Israeli men during military service. DESIGN: All 17-year-old Israeli nationals are obliged by law to appear at the Israel Defense Forces (IDF) recruiting office for medical examination. The medical history of army recruits was noted during the 30-month period after their induction into the IDF, and medical examinations were performed by pulmonary specialists in all suspected cases of asthma. The duty status of the soldiers in combat units (CUs), maintenance units (MUs), and clerical tasks was related to their asthma status. RESULTS: Of a total of 59,058 recruits, 1.0% developed asthma during the 30 months of this study; of those in CUs, 1.2% developed asthma; of those in MUs, 0.8% developed asthma; and of those performing clerical tasks, 0.6% developed asthma. The relative risk for developing or worsening of asthma was related to both the preexisting asthma status of the recruit and the environment in which he carried out his military service. The annual incidence of occupational-related asthma in MUs was found to be 800/million: five to six times the rates reported elsewhere. CONCLUSIONS: Service in CUs was associated with an increased frequency of exacerbation of asthma among recruits with previous disease and with the appearance of disease de novo. "Normal" conscripts with a history of childhood asthma are at a higher risk of developing overt asthma when compared to subjects with no such history. We found a 25% relative excess of incident cases of asthma in soldiers posted in MUs compared to those performing clerical tasks [(0.8 to 0.6%)/0.8%]. This difference is probably attributed to the difference in occupational hazards in these categories. Further studies are needed to determine if this represents the elicitation of underlying preexisting airway lability by new work demands or other environmental conditions, or if this represents a new development of airway lability because of specific immune or nonimmune factors.

Adolescent↗

Clinical dose ranging studies with finasteride, a type 2 5alpha-reductase inhibitor, in men with male pattern hair loss.

BACKGROUND: Androgenetic alopecia is a common condition of adult men. Finasteride, a type 2 5alpha-reductase inhibitor, decreases the formation of dihydrotestosterone from testosterone. OBJECTIVE: Two separate clinical studies were conducted to establish the optimal dose of finasteride in men with this condition. METHODS: Men from 18 to 36 years of age with moderate vertex male pattern hair loss received finasteride 5, 1, 0.2, or 0.01 mg/day or placebo based on random assignment. Efficacy was determined by scalp hair counts, patient self-assessment, investigator assessment, and assessment of clinical photographs. Safety was assessed by clinical and laboratory measurements and by analysis of adverse experiences. RESULTS: Efficacy was demonstrated for all end points for finasteride at doses of 0.2 mg/day or higher, with 1 and 5 mg demonstrating similar efficacy that was superior to lower doses. Efficacy of the 0.01 mg dose was similar to placebo. No significant safety issues were identified in the trials. CONCLUSION: Finasteride 1 mg/day is the optimal dose for the treatment of men with male pattern hair loss and was subsequently identified for further clinical development.

5-alpha Reductase Inhibitors↗

Pulmonary function threshold for distinguishing ventilatory- and nonventilatory-limited patients with airflow obstruction.

Patients with chronic obstructive pulmonary disease (COPD) may demonstrate great variability between results on the pulmonary function test (PFT) compared to those on the cardiopulmonary exercise test (CPXT). The purpose of this study was to correlate PFT and CPXT indices and to identify PFT threshold values for predicting exercise capacity in patients with airflow limitation. Fifty-seven patients (48 men and 9 women) of mean age 66.4 +/- 4.8 years with COPD and 40 age-matched control patients underwent PFT and CPXT. Based on the CPXT results, the patients were divided into ventilatory-limited (VL) and nonventilatory-limited (NVL), and the findings were correlated with the PFT indices. Linear regression analysis was used to determine the relationship between dyspnea index (VEmax/MVV) and forced expiratory volume in one second (FEV1). The cutoff value for VL was FEV1 < 38% and for NVL FEV1 > 68%. The prominent limiting symptom (61%) in the VL group was dyspnea sensation, with leg discomfort presenting in only 14%; corresponding rates in the NVL group were 38% and 31%. We conclude that the FEV1 is a reliable index for distinguishing VL from NVL COPD patients during CPXT at two extremes: below 38% of the predicted value (VL) and above 68% of the predicted value (NVL).

Aged↗

Antepartum management protocol. Timing and mode of delivery in gestational diabetes.

We sought to determine whether strict glycemic control during diabetic pregnancy combined with elective early induction of labor reduces the rate of cesarean delivery and fetal birth trauma. We used a population-based longitudinal design covering three periods corresponding to changes in the management protocol for diabetic pregnancy at our center: 1) 1980-1989: no set level of maternal glycemia, elective cesarean section when estimated fetal weight was 4,500 g or more, and no elective early induction; 2) 1990-1992: desired mean maternal glycemia < or = 5.8 mmol/l, elective cesarean section when estimated fetal weight was 4,000 g or more, and elective early induction at 40 weeks for large-for-gestational-age fetuses; 3) 1993-1995: desired mean maternal glycemia < or = 5.3 mmol/l, elective cesarean section when estimated fetal weight was 4,000 g or more, and elective early induction at 38 weeks for large-for-gestational-age fetuses. Outcome of diabetic pregnancies was compared for the three periods, relative to that of the normal population. There was a gradual, constant, and significant decline in the incidence of macrosomia (17.9, 14.9, and 8.8%, respectively; P < 0.05) and large-for-gestational-age fetuses (23.6, 21.0, and 11.7%; P < 0.05) coupled with a gradual, nonsignificant decrease in cesarean deliveries (20.6, 18.4, and 16.2%) and in cases of shoulder dystocia (1.5, 1.2, and 0.6%), to rates close to those of the normal population. Our data show that maintaining strict control of maternal diabetes and adhering to an active management protocol for early elective delivery based on the estimated fetal weight have a significant effect on reducing the rate of macrosomia, thereby affecting the incidence of both traumatic births and cesarean deliveries.

Blood Glucose↗

Evidence that the receptor for soluble CD14:LPS complexes may not be the putative signal-transducing molecule associated with membrane-bound CD14.

Membrane-bound CD14 acts as a receptor for lipopolysaccharide (LPS) on monocytes/macrophages and neutrophils. Studies have suggested that the activation of monocytes/macrophages by the binding of LPS to membrane-bound CD14 may require the association of a signal-transducing molecule with membrane-bound CD14. The observation that non-CD14 expressing cells, such as endothelial cells, can nevertheless be activated by a complex of LPS and a soluble form of CD14 (sCD14) suggests that the receptor for this complex may be identical to the signal transducing molecule associated with membrane-bound CD14. The studies described show that two CD14-specific MoAb are able to block the LPS-induced activation of endothelial cells but do not affect the response of monocytes to LPS. This suggests that the interaction of the sCD14:LPS complex with endothelial cells is distinct from the interaction of membrane-bound CD14 with its putative signal-transducing molecule.

Antibodies, Monoclonal↗

[Findings of periodic thoracic X-ray screening of Israel Defense Forces career personnel].

Findings of routine, periodic, medical examinations of approximately 5000 Israel Defense Forces (IDF) career personnel, included a screening postero-anterior chest radiograph were reviewed. Previous studies have indicated low efficacy of routine chest X-rays in various populations. We evaluated this screening test among 4593 career military personnel. Their chest X-rays were reviewed retrospectively and in 186 (4%) there were abnormal findings. The rate of pathological findings was positively correlated with age. Additional information was found in the X-rays of 25 subjects (0.54%), but the original interpretations of 51 (1.1%) were found to be false-positive. In view of the very low yield of findings in routine chest X-rays of IDF career military personnel, we recommend X-ray screening only in high-risk populations and subjects over the age of 50.

Adult↗

Atopy, bronchial hyperresponsiveness, and peak flow variability in children with mild occasional wheezing.

BACKGROUND: Children who suffer from recurrent wheezy episodes are often promptly classified as asthmatic. The aim of this study was to evaluate a population of mild wheezy children with repeatedly normal spirometric tests at rest for atopy, bronchial hyperresponsiveness, and peak expiratory flow variability. METHODS: Thirty nine children aged 6-16 years with 1-12 wheezy attacks during the previous year were recruited from a community paediatric primary health care clinic serving an urban Israeli population. The conditions for inclusion were a physician-diagnosed wheeze on auscultation and normal spirometric tests at rest on at least three occasions. Evaluation included skin prick tests for atopy and a physician-completed questionnaire. In addition, two tests of bronchial hyperresponsiveness (BHR) were performed--namely, exercise-induced bronchospasm and inhaled methacholine hyperresponsiveness--as well as diurnal variability of peak expiratory flow (PV). RESULTS: One or more tests of BHR/PV were positive in 27 (69%) but repeatedly negative in 12 (31%). In terms of frequency of wheezing attacks, atopy, and questionnaire responses, there were no differences between BHR/PV and non-BHR/PV children, with the exception of a history of chest radiography proven pneumonia (only noted in the BHR/PV group). Overall, evidence of atopy (mainly indoor allergens) was noted in 21 (56%) of those tested and parental smoking in 29 (74%) of households. Thirty-two (82%) of the children complained of an exercise-related wheeze, yet exercise-induced bronchospasm was only demonstrated in nine (23%). CONCLUSIONS: This selected group of wheezy children appears to be intermediate between a normal and clearly asthmatic population and, despite the recurrent wheezy attacks, some should probably not be classified as asthmatic by conventional criteria. Important aetiological factors in the symptomatology of these children may include parental smoking and atopy as well as other elements such as viral infections.

Adolescent↗

Aerosol deposition as a function of airway disease: cystic fibrosis.

A mathematical model of aerosol deposition has been developed for drug delivery protocols and used successfully to simulate inhalation exposure tests with human subjects. Therefore, we have used the validated model to address the delivery of inhaled pharmaceuticals as a function of disease-induced changes in airway structure. Clinical data from the literature had suggested that progressive lung disease associated with cystic fibrosis (CF) could compromise the successful administration of pharmacologic drugs used in its treatment, hence it was studied. We described the lungs of patients inflicted with CF by different morphologies (representing the processes of airway obstruction, infection and inflammation) than healthy (control) subjects. Affected ventilatory parameters were also examined to demonstrate their effects upon drug disposition. Particle distributions were computed on a generation-by-generation basis. Deposition patterns were dramatically affected by CF-produced alterations in dimensions. The reduced airway caliber in CF enhanced the total dose delivered to the tracheobronchial compartment by 200-300% relative to controls. The spatial distributions of aerosols were completely different in CF patients, being selectively deposited within congested airways. In medical practice the model can be tailored to any specific airway disease. Regarding targeted delivery, the results have relevance to (1) site-specific acting pharmaceuticals in tracheobronchial airways and (2) drugs designed for systemic delivery via deposition in alveolated airways.

Administration, Inhalation↗