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Biomedical subjects

J Katz

Publications and source records attributed to J Katz.

At least 163 records · Page 9Linked to original sources

Estimating the causal effect of compliance on binary outcome in randomized controlled trials.

We examine likelihood based methods aimed at analysing the causal effect of actual exposure to drug treatment on a (repeated) binary outcome in two randomized trials with partial compliance. Starting with the univariate compliance summary 'total treatment dose history', we apply a method for ordinal compliance and monotone dose response, proposed by Goetghebeur and Molenberghs. In a short duration trial of blood pressure reduction, this summary leads to meaningful effect estimators. However, in the analysis of a vitamin A trial, this method reaches a boundary solution; the estimated possible benefit from vitamin A for children who did not receive any pills on the treatment arm is zero. In our formulation the number of pills that were taken captures part of the outcome, and the corresponding effect parameters suffer from this confounding. To gain additional insight, we account explicitly for the temporal structure of compliance. We extend the likelihood based methodology for univariate ordered compliance to more dimensional compliance with only a partial order structure on exposure. The randomization assumptions in the causal formulation of Rubin are translated to this setting. We motivate a set of parametric assumptions on the joint distribution of potential outcomes and observed compliance levels and reanalyse the vitamin A trial. Our findings suggest that one capsule of vitamin A had a large impact on mortality during the first 4 months. The greatest reduction in risk was estimated amongst children who received two doses. This supports findings from a vitamin A trial in Ghana and in Nepal. Finally, we discuss extensions of this method, covering uncensored and censored grouped survival data.

Adult↗

Major histocompatibility complex class II molecules can protect from diabetes by positively selecting T cells with additional specificities.

Insulin-dependent diabetes is heavily influenced by genes encoded within the major histocompatibility complex (MHC), positively by some class II alleles and negatively by others. We have explored the mechanism of MHC class II-mediated protection from diabetes using a mouse model carrying the rearranged T cell receptor (TCR) transgenes from a diabetogenic T cell clone derived from a nonobese diabetic mouse. BDC2.5 TCR transgenics with C57Bl/6 background genes and two doses of the H-2(g7) allele exhibited strong insulitis at approximately 3 wk of age and most developed diabetes a few weeks later. When one of the H-2(g7) alleles was replaced by H-2(b), insulitis was still severe and only slightly delayed, but diabetes was markedly inhibited in both its penetrance and time of onset. The protective effect was mediated by the Abetab gene, and did not merely reflect haplozygosity of the Abetag7 gene. The only differences we observed in the T cell compartments of g7/g7 and g7/b mice were a decrease in CD4(+) cells displaying the transgene-encoded TCR and an increase in cells expressing endogenously encoded TCR alpha-chains. When the synthesis of endogenously encoded alpha-chains was prevented, the g7/b animals were no longer protected from diabetes. g7/b mice did not have a general defect in the production of Ag7-restricted T cells, and antigen-presenting cells from g7/b animals were as effective as those from g7/g7 mice in stimulating Ag7-restricted T cell hybridomas. These results argue against mechanisms of protection involving clonal deletion or anergization of diabetogenic T cells, or one depending on capture of potentially pathogenic Ag7-restricted epitopes by Ab molecules. Rather, they support a mechanism based on MHC class II-mediated positive selection of T cells expressing additional specificities.

Animals↗

Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.

An avian H5N1 influenza A virus (A/Hong Kong/156/97) was isolated from a tracheal aspirate obtained from a 3-year-old child in Hong Kong with a fatal illness consistent with influenza. Serologic analysis indicated the presence of an H5 hemagglutinin. All eight RNA segments were derived from an avian influenza A virus. The hemagglutinin contained multiple basic amino acids adjacent to the cleavage site, a feature characteristic of highly pathogenic avian influenza A viruses. The virus caused 87.5 to 100 percent mortality in experimentally inoculated White Plymouth Rock and White Leghorn chickens. These results may have implications for global influenza surveillance and planning for pandemic influenza.

Amino Acid Sequence↗

[First year's experience of the Post-Operative Cardiac Care Unit, Schneider Children's Medical Center].

In the past 10 years there has been a growing preference for early, complete correction of congenital heart disease. The first year of operation of this cardiac unit is described. 216 operations were performed: 15% in the neonatal age group and 35% in the newborn to 1-year-old groups; 2% were palliative procedures. Mortality was 4.9%. Average stay in the ICU was 3.2 days, with a median of 2.25. Average length of ventilation was 35 hours, with a median of 17.5. Complications were: diaphragm paralysis in 13 (6%), 2/3 of which were recurrent operations; in 2 patients (0.9%) we had to plicate the diaphragm. There was severe neurological damage in 2 which deteriorated to brain death in 1. There was peripheral, reversible neurological damage in 4 (1.8%), and acute renal failure in 3%, with half of them requiring dialysis. 75% of these children died and there was superficial infection in 4.1%, deep wound infection in 1.3%, bacteremia in 4.1%, superior vena cava syndrome in 3 (1.3%) and chylothorax in 2 of them (0.9%). 1 patient (0.45%) required a ventricle-peritoneal shunt after acute viral meningitis. We are encouraged by our results to offer early complete correction to all children with congenital heart disease.

Child↗

Marital therapy in the treatment of depression: toward a third generation of therapy and research.

Two generations of outcome research demonstrate the potential efficacy of marital therapy in the treatment of depression. After reviewing treatment outcome studies on marital therapy for depression, we examine basic research linking aspects of the marital relationship to depressive symptoms. In doing so, we highlight a number of theoretical perspectives and research findings that can inform work with couples in which one spouse is depressed. Finally, we identify potential innovations that may lead to a third generation of marital interventions for depression and several avenues of inquiry for a third generation of outcome research on marital therapy for depression.

Conflict, Psychological↗

Vision-specific function and quality of life after cataract extraction in south India.

PURPOSE: To assess visual and overall patient function after intracapsular (ICCE) and extracapsular (ECCE) cataract extraction in rural South India. SETTING: Aravind Eye Hospital, Tirunelveli, Tamil Nadu, South India, and the Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Baltimore, Maryland, USA. METHODS: This study evaluated preoperative visual acuity and demographic information and postoperative visual acuity and functional status measures in 71 patients having ECCE with posterior chamber intraocular lens (IOL) placement and 73 patients having ICCE with aphakic spectacle correction at Aravind-Tirunelveli Eye Hospital, Tamil Nadu, India. The principal outcomes assessed were visual acuity; quality-of-life score (possible range 0 to 100%); visual function measurement (possible range 0 to 100%). RESULTS: Patients in the ECCE group scored 10.17 (P = .0001) points higher than those in the ICCE group on the visual function scale after adjustment for differences in age, sex, level of education, marital status, residence, and type of employment. The ECCE group scored 7.69 points higher on visual function when adjusting for the differences in best corrected visual acuity, which was also better in the ECCE group. In the quality-of-life assessment, 77.1% in the ECCE group and 46.6% in the ICCE group scored 90% or better (OR 3.85; P = .006). CONCLUSIONS: Patients in rural south India having ECCE with posterior chamber IOL implantation obtained better postoperative visual function, quality of life, and visual acuity than those receiving ICCE with aphakic spectacle correction. These differences, which were not significantly affected by adjustment for age, sex, education, marital status, type of residence, and occupation, indicate that ECCE is clearly superior to ICCE.

Adult↗

Oral clonidine premedication does not prolong analgesia after herniorrhaphy under subarachnoid anesthesia.

STUDY OBJECTIVE: To determine the effect of oral clonidine premedication on duration of sensory and motor block, postoperative analgesia, hemodynamic stability, sedation, and respiratory parameters after subarachnoid anesthesia (SA). DESIGN: Prospective, double blind, randomized, placebo-controlled study. PATIENTS: 80 ASA physical status I patients were randomized into four equal groups to receive oral premedication with either clonidine 5 mcg/kg (C5), clonidine 2.5 mcg/kg (C2.5), diazepam 100 mcg/kg (D), or placebo (PL). MEASUREMENTS AND MAIN RESULTS: The following parameters were measured: duration of motor and sensory block, requirement for postoperative analgesia; systolic (SBP), diastolic (DBP), and mean (MBP) blood pressures; heart rate (HR); sedation and anxiolysis scales; respiratory rate (RR); oxyhemoglobin saturation; and complications. (1) The duration of sensory and motor block did not differ significantly among the groups. (2) There were no differences in the time to first request for analgesia and in requirements for analgesia in the first 24 postoperative hours. (3) Clonidine premedication before SA did not produce episodes of significant hypotension. HR did not differ significantly among the groups. Baseline SBP was significantly higher (p = 0.037) in group PL than in groups C5 and C2.5. Three minutes after SA significant decrease in the following parameters was observed: SBP in group PL compared with the other three groups (p = 0.004), DBP in group PL vs. groups C5 and C2.5 (p = 0.002), and MBP in group PL vs. groups C5 and C2.5 (p = 0.003). (4) Sedation and anxiolysis were more pronounced (p = 0.0001) in groups C5 and C2.5 than in groups D and PL and in group C5 than in group C2.5. (5) RR was significantly lower (p = 0.0024) in group C5 than in groups D and PL. (6) Complications consisted of three episodes (15%) of bradycardia in the C5 group and two of bradypnea (10%) in the same group. CONCLUSIONS: In healthy patients, premedication with oral clonidine provided useful sedation and anxiolysis and stable hemodynamics, without prolongation of sensory and motor block. Side effects occurred only with clonidine 5 mcg/kg. Thus, a dose of 2.5 mcg/kg is recommended.

Administration, Oral↗

Bell's palsy associated with herpes simplex gingivostomatitis. A case report.

Bell's palsy is a sudden, isolated, peripheral facial paralysis caused by various known and sometimes unknown factors. The case of an 18-year-old man who developed Bell's palsy after onset of primary herpetic gingivostomatitis is presented. Although Bell's palsy has already been associated with herpes simplex virus type 1, the described case is the first in the literature in which enzyme-linked immunosorbent assays for immunoglobulin G to herpes simplex virus type 1 and herpes simplex virus type 1 culture were both positive. The recent literature regarding the possible relationship between herpes simplex virus type 1 and Bell's palsy is reviewed and discussed.

Adolescent↗

Leptin and the pituitary-thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects.

OBJECTIVE: To study interactions between leptin and the pituitary-thyroid axis, both in euthyroid and dysthyroid states. SUBJECTS AND MEASUREMENTS: We investigated the relationships of plasma leptin to levels of free thyroid hormones and TSH in 18 patients with newly diagnosed hyperthyroidism, 22 with newly diagnosed primary hypothyroidism, and 32 lean (body mass index [BMI] < 30) and 37 obese (BMI > 30 kg/m2) euthyroid subjects. Hypothyroid patients were restudied during thyroxine replacement treatment. RESULTS: Median [interquartile range] plasma leptin concentrations were highest in obese euthyroid subjects (31.5 [19.0-48.0] and in untreated hypothyroid patients (19.2 [11.5-31.5]), and lowest levels in untreated hyperthyroid patients (8.9 [5.5-11.1]) and lean euthyroid control subjects (6.6 [3.9-14.4] micrograms/l (Kruskall-Wallis one-way analysis of variance; P < 0.0001). In euthyroid subjects, plasma leptin levels were higher in obese than in lean subjects (P < 0.00001). In obese subjects plasma levels of TSH correlated with percentage body fat (r = 0.67; P < 0.001) and plasma leptin (r = 0.61; P < 0.001). In untreated hyperthyroid subjects plasma leptin was unrelated to free T3, and in untreated hypothyroidism plasma leptin was unrelated to either free T3 or TSH concentrations (all P = NS). In untreated hyperthyroid, but not hypothyroid, patients plasma leptin concentrations correlated with BMI (r = 0.57; P = 0.02). Treatment of hypothyroidism with thyroxine resulted in a significant reduction in plasma leptin concentrations from 20.8 (11.8 to 31.6) to 12.9 (4.6-21.2) micrograms/l (P = 0.005), but BMI did not change significantly in the hypothyroid subjects being studied prospectively. CONCLUSIONS: (i) In euthyroid subjects, plasma leptin and TSH levels correlate, and both are positively correlated with adiposity. (ii) Plasma leptin was significantly elevated in hypothyroid subjects, to levels similar to those seen in obese euthyroid subjects. (iii) Treatment of hypothyroidism resulted in a reduction in the raised plasma leptin levels. The data are consistent with the hypothesis that leptin and the pituitary-thyroid axis interact in the euthyroid state, and that hypothyroidism reversibly increases leptin concentrations.

Adult↗

Neonatal vitamin A supplementation: effect on development and growth at 3 y of age.

We reported recently that neonatal supplementation with 52 micromol vitamin A reduced infant mortality by 64%; acute side effects were limited to a 3% excess rate of a bulging fontanelle. The current study was conducted to identify developmental changes at 3 y of age associated with neonatal vitamin A supplementation or a bulging fontanelle. Children who had a bulging fontanelle (n = 91) and 432 children who had normal fontanelles after receiving vitamin A or placebo were evaluated with the Bayley Scales of Infant Development. Mean scores for the mental, psychomotor, and behavioral rating scale (BRS) plus 3 subscales of the BRS were not significantly different for treatment-fontanelle-specific groups. In regression models predicting each score, a bulging fontanelle had a small negative effect in all models; when 1 child who was injured from birth was removed from the analysis the effect of a bulging fontanelle was not significant in any model (P > or = 0.35). Vitamin A supplementation had a small beneficial effect on all developmental scores, which was significant for one of the BRS subscales (orientation-engagement) and also for a second (motor quality) when the outlier child was removed. Compared with children with normal fontanelles in the placebo group, children with a bulging fontanelle in the vitamin A group tended to grow less (-0.5 cm, P = 0.33), whereas those with normal fontanelles in the vitamin A group grew significantly more (0.68 cm, P < 0.05), over the first 3 y of life. This study provides no evidence that neonatal vitamin A supplementation is associated with biologically significant adverse growth or developmental sequelae.

Body Height↗

Night blindness of pregnancy in rural Nepal--nutritional and health risks.

BACKGROUND: Night blindness (XN) is the most common clinical symptom of vitamin A deficiency among children in developing countries. Yet little is known about the aetiology or associated risks of maternal XN. Emerging evidence from South East Asia suggests that it may be more frequent than previously thought in women of reproductive age, especially during pregnancy. METHODS: A population-based, case-control study was conducted to reveal the epidemiology of XN among pregnant Nepali women. Night blind cases were identified by history through a weekly community surveillance system. Controls were randomly selected from a pool of pregnant women without XN and pair-matched for gestational age of the cases. A home-based assessment was done within a week of selection, at which 7-day food frequency and morbidity histories were collected, anthropometry measured, and capillary blood drawn for serum retinol, beta-carotene and haemoglobin (Hb) estimation. RESULTS: Cases and controls did not differ by age or number of previous pregnancies. However, cases were more likely to be from the lower castes, be illiterate, live in poorer quality homes, and own no land. The mean serum retinol level of cases was approximately 0.30 mumol/l lower than controls (P < 0.001), indicating a low vitamin A status of night blind pregnant women. Mean Hb level was significantly lower (by 0.7 g/dl, P < 0.004), and the risk of severe anaemia (Hb < 7.0 g/dl) higher among cases than controls (odds ratio = 3.0, 95% CI: 1.25-7.23). Cases were more under-nourished than controls reflected by lower mean weight (-2.6 kg), body mass index (-0.8), arm circumference (-0.9 cm) and triceps skinfold (-0.8 mm). Night blindness was associated with less frequent consumption of preformed vitamin A (milk products, fish and meat) and provitamin A (dark green leafy vegetables and mangoes) foods, especially in summer. Night blind women were 2-3 times more likely to report symptoms of urinary/reproductive tract infections such as lower abdominal pain, painful and burning urination, or vaginal discharge, symptoms of diarrhoea/dysentery, of pre-eclampsia or eclampsia, and of nausea, vomiting or poor appetite throughout pregnancy than controls. CONCLUSION: Women who experience XN during pregnancy have a low vitamin A status, although several other risk factors appear to cluster among these women as well. Night blind women are also more likely to be anaemic, ill, and acutely under-nourished, and to be consuming a nutritionally poorer diet in pregnancy than non-night blind pregnant women. A simple history of XN can identify women at high risk during pregnancy who may require special nutritional support, antenatal care and counselling.

Adult↗

Vitamin A or beta-carotene supplementation reduces but does not eliminate maternal night blindness in Nepal.

We investigated the effect of supplementing women weekly with 7000 microg retinol equivalents as preformed vitamin A or beta-carotene vs. a placebo, on the incidence of night blindness during pregnancy and the postpartum period in the rural plains of Nepal. Over a period of approximately 3 y, approximately 29,000 women of child-bearing age, living in 171 wards that were randomized to one of the three supplements, contributed 9932 first pregnancies. A prospective, weekly surveillance identified night blindness in pregnant women, verified further by detailed questioning about nighttime vision. After delivery, women were also interviewed at approximately 3 and approximately 6 mo postpartum to elicit a night blindness history over the preceding 3 mo. Vitamin A supplementation reduced the incidence of night blindness during pregnancy from 10.7% among controls to 6.7% (relative risk 0.62, 95% confidence interval: 0.45-0.85). beta-Carotene supplementation had less of an effect (0. 83, 0.63-1.11). Among women who took >95% of their vitamin A supplements during pregnancy, incidence of verified night blindness was reduced by 67%. Incidence (per 100 person-years) of night blindness during the first 3 mo postpartum was 11.3 in the control, 4.3 in the vitamin A and 8.7 in the beta-carotene groups, yielding corresponding relative risks of 0.38 (0.26-0.55) and 0.77 (0.57-1. 04). In the second 3 mo postpartum, both vitamin A and beta-carotene reduced night blindness by approximately 50%. Vitamin A intakes approaching a recommended amount for pregnancy markedly reduced but did not eliminate night blindness in Nepali women. Greater intakes of vitamin A than provided and/or other nutrients may be needed to prevent maternal night blindness in rural South Asia.

Dietary Supplements↗

Agreement between clinical examination and parental morbidity histories for children in Nepal.

Parental histories are often used to estimate the prevalence and the impact of interventions on child morbidity, but few studies have examined the agreement between parental histories and clinical examination. We compared clinical findings with a same-day parental morbidity history for pre-school-age children in rural Nepal. A 15 per cent sample of children from 40 wards in Sarlahi district, Nepal, was selected for participation and 814 same-day morbidity histories were obtained from parents. A clinician, masked to the parent's history, visited the household 2-4 h later and examined the child for signs of morbidity symptoms about which the parent had previously been questioned. Signs included measurement of temperature, respiratory rate, examination of stools, ear discharge, and presence of persistent cough. Agreement between the history and clinical examination was excellent for ear infection (kappa = 0.75) and history of measles rash (kappa = 0.74), moderate to poor for diarrhoea (kappa = 0.21) and fever (kappa = 0.31), and there was no evidence of agreement for dysentery (kappa = -0.01), rapid breathing (kappa = 0.06), and cough (kappa = 0.09). The prevalence of dysentery, fever, cough, and rapid breathing was lower if clinical signs rather than histories were used. The prevalence of diarrhoea was higher if the presence of a loose stool in a cup rather than a history was used. The prevalence of ear infections and measles was comparable with both methods. The agreement between histories and clinical examination varies by morbidity type, as does the prevalence of morbidity estimated by one or other method.

Adult↗

Population biology, evolution, and immunology of vaccination and vaccination programs.

The purpose of prophylactic vaccination is to reduce morbidity and mortality in a population. Many questions related to the design of vaccines and vaccination programs require a population standpoint for their sharp formulation and laboratory and field studies to understand their immunologic background. Practical suggestions of the workshop included increased studies of age-specific immunity, better immunoepidemiologic surveillance, better design of efficacy studies, and more systematic sampling of parasite strains to study the evolutionary pressure exerted by vaccines. Theoretical immunology has much to contribute. One of the realizations of the workshop was the value of a strong interdisciplinary approach in vaccine development, utilizing relevant contributions from immunology, population biology, mathematical modeling, epidemiology, molecular biology, and virology.

Animals↗