Biomedical subjects
J Bernstein
Publications and source records attributed to J Bernstein.
Taxonomy and treatment--a classification of fracture classifications.
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Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children.
The ability to predict the course in children with newly diagnosed minimal change nephrotic syndrome (MCNS) may have significant therapeutic implications. Previous attempts based on data available at disease onset have not been successful. Therefore, it was investigated whether characterization of the initial response to adrenocortical steroids and the course during the early months of disease are predictive of the subsequent outcome. Three hundred-eighty-nine children with MCNS, diagnosed at onset, were treated with standard prednisone regimens and monitored for up to 17 yr (mean, 9.4 yr). They were classified, after 8 wk of therapy, as initial responders (complete remission) or initial nonresponders (continued proteinuria). Subsequent classifications included nonrelapsers, infrequent relapsers, and frequent relapsers. At 8 yr of follow-up, 80% of patients were in remission. Three-fourths of initial responders who remained in remission during the first 6-month period after initial therapy (nonrelapsers; 40% of the entire series) either continued in remission during their entire course or relapsed rarely. In contrast, initial relapsers, both frequent and infrequent, achieved a nonrelapsing course only after an average of 3 yr. Unremitting proteinuria during the initial 8 wk of treatment was followed by progression to ESRD in 21%. When proteinuria during the initial 8 wk continued through the subsequent 6 months, progression to renal failure occurred for 35%. Although 95% of children with MCNS do well, 4 to 5% die from complications or undergo progression to ESRD. Documentation of the early course aids in identifying those at increased risk for a poor outcome. More aggressive therapy may be indicated for these individuals.
The challenge of moving from welfare to work.
Despite overall low unemployment rates in 1996, various subgroups of the population had rates much higher than the average. This brief article considers the labor market profile of welfare recipients and examines the unemployment and underemployment rates of groups with similar demographic characteristics. In some cases, such rates are three and four times the overall national average.
Disposition and metabolism of olanzapine in mice, dogs, and rhesus monkeys.
Olanzapine (OLZ) is a novel antipsychotic agent with a high affinity for serotonin (5-HT2), dopamine (D1/D2/D4), muscarinic (m1-m5), adrenergic (alpha 1), and histamine (H1) receptors. The pharmacokinetics, excretion, and metabolism of OLZ were studied in CD-1 mice, beagle dogs, and rhesus monkeys after a single oral and/or intravenous dose of [14C]OLZ. After oral administration, OLZ was well absorbed in dogs (absolute bioavailability of 73%) and to the extent of at least 55% in monkeys and 32% in mice. The terminal elimination half-life of OLZ was relatively short in mice and monkeys (approximately 3 hr) and long in dogs (approximately 9 hr). In mice and dogs, radioactivity was predominantly eliminated in feces; but, in monkeys, the major route of elimination of radioactivity was urine. Dogs and monkeys excreted in urine, respectively, 38% and 55% of the dose over a 168-hr period, whereas the fraction of the dose excreted in urine of mice over the collection period (120 hr) was 32%. OLZ was subject to substantial first-pass metabolism; at the tmax, OLZ accounted for 19%, 18%, and 8% of the radioactivity, in mice, dogs, and monkeys, respectively. The ratio of AUC OLZ to AUC radioactivity was, respectively, 10%, 14%, and 4% in mice, dogs, and monkeys. The principal urinary metabolites in mice were 7-hydroxy OLZ glucuronide, 2-hydroxymethyl OLZ, and 2-carboxy OLZ accounting for approximately 10%, 4%, and 2% of the dose. Metabolites that were present in urine in lesser amounts were 7-hydroxy OLZ, N-desmethyl OLZ, and N-desmethyl-2-hydroxymethyl OLZ. In dogs, the major metabolite accounting for approximately 8% of the dose was 7-hydroxy-N-oxide OLZ. Other metabolites identified were 2-hydroxymethyl OLZ, 2-carboxy OLZ, N-oxide OLZ, 7-hydroxy OLZ, and its glucuronide and N-desmethyl OLZ. The major metabolite in monkey urine was N-desmethyl-2-carboxy OLZ, and accounted for approximately 17% of the dose. In addition, N-oxide-2-hydroxymethyl, 2-carboxyl OLZ, and 2-hydroxymethyl OLZ were identified in monkey urine. Thus, in mice and dogs, OLZ was metabolized through aromatic hydroxylation, allylic oxidation, N-dealkylation, and N-oxidation reactions. In monkeys, OLZ was biotransformed mainly through double oxidation reactions involving the allylic carbon and methyl piperazine nitrogen. Whereas the oxidative metabolic profile of OLZ in animals was similar to that of humans, animals were notable for not forming appreciable amounts of the principal human metabolite (i.e. 10-N-glucuronide OLZ).
Inspiring women: the fifth annual Birth Gazette Conference.
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Variation in long-term engraftment of a large consecutive series of lambs transplanted in utero with human hematopoietic cells.
We investigated the survival and chimeric engraftment characteristics of a large consecutive series of lambs that were transplanted with human hematopoietic cells in utero. Approximately 50% of the fetal sheep survived. Neither the transplantation of human cells into fetal sheep, nor the parity of the ewe was associated with increased mortality, as compared with the risk of surgery alone. However, a breed-associated mortality was noted. Sixty percent of surviving recipient lambs contained donor, human hematopoietic cells in blood and bone marrow (BM) cells. Chimerism ranged from 0.0001-1%. Human hematopoietic progenitors were identified in the BM in 8 of 12 chimeric sheep examined. Some lambs engrafted with human cells maintained a human chimerism for up to at least 2 years. Our data demonstrate that a large proportion of fetal sheep are capable of engrafting human cells, albeit at widely variable levels of engraftment.
Tuberous sclerosis has several angiolipomata in both kidneys?
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Cyclophosphamide does not benefit patients with focal segmental glomerulosclerosis. A report of the International Study of Kidney Disease in Children.
Sixty children, with biopsy diagnosed focal segmental glomerulosclerosis (FSGS) and with unremitting nephrotic syndrome despite intensive therapy with adrenocortical steroids, were randomly allocated into a clinical trial comparing prednisone, 40 mg/m2 on alternate days for a period of 12 months (control group), with the same prednisone regimen plus a 90-day course of daily cyclophosphamide, 2.5 mg/kg in a single morning dose (experimental group). One-quarter of the children in each group had complete resolution of proteinuria. The proportions of children with increased, unchanged, and decreased proteinuria by the end of the study were the same in the two groups. Treatment failure was defined as an increase in serum creatinine of 30% or more or greater than 0.4 mg/dl, or onset of renal failure. Treatment failure occurred in 36% of the control group and 57% of the experimental group (P > 0.1). Five patients died during the trial, 3 in the experimental group and 2 in the control group. A Kaplan-Meier survival analysis revealed no significant differences between the two groups. Cyclophosphamide therapy for children with steroid-resistant FSGS is not recommended.
The dynamics of professional commitment: immigrant physicians from the former Soviet Union in Israel.
The paper examines professional commitment among physicians who immigrated to Israel form the former Soviet Union during the early 1990s. This population faces severe limits regarding occupational continuity because of the highly saturated market in which non-negligible groups will, in the long run, of necessity undergo occupational change. The theoretical background for the analysis is drawn from the literature regarding recent changes in professional roles with particular reference to the shifting meaning of work in post-modern societies and its consequences for occupational commitment. The professional context of medical practice in the former Soviet Union and the social and economic constraints of Israeli society in the 1990s set the scene for the analysis. Several dimensions of professional commitment are examined empirically, on the assumption that there are a variety of ways to consider the notion of commitment and that no one measure tells a complete story. Prolonged processes of deprofessionalization of medicine in the Soviet Union, suggest that medicine for most immigrant physicians is not so much a 'calling' to which they are devoted; rather it is a necessary means to gain a livelihood, the only occupation for which they have been trained for many years after stringent selection to medical school and the only job in which they have worked consistently since completing their formal training. Two and a half years after arrival in Israel the immigrant doctors are characterized by a short-range time perspective which makes them unwilling to accept the constraints of the saturated market; intense efforts are made by most to obtain a license despite the fact that only a fraction of them will be able to work in their profession on a regular basis. Despite this over-riding reality, many hope that they will be among the selected few who will be able to obtain a medical post.
Safeguards in embryo donation.
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Dicentric (9;20)(p11;q11) identified by fluorescence in situ hybridization in four pediatric acute lymphoblastic leukemia patients.
Four children with acute lymphocytic leukemia (ALL) and a dic(9;20) are described. All four patients were diagnosed with pre-B-cell All, and the three for whom information was available were CD10+. Age at diagnosis ranged from 23 months to 12 years. All patients achieved remission, with two in continuous remission for 2 years 6 months and 3 years, one patient relapsed, dying 3 years 2 months after diagnosis, and one patient was lost to follow-up. These four patients were initially diagnosed as having a deletion of 9p and loss of one chromosome 20. Re-examination of the karyotypes indicated a possible dic(9;20). The dicentric chromosome was verified using dual-color fluorescence in situ hybridization (FISH) with centromeric probes for chromosomes 9 and 20 on interphase nuclei. Three of the four patients had multiple chromosomal abnormalities in addition to the translocation; one was hypodiploid, one was pseudodiploid, and two were hyperdiploid. This dicentric chromosome was recently described in four adult and nine pediatric patients with ALL [8, 9]. All reported patients had CD10+ pre-B-cell All, and achieved remission, as was the case for our four pediatric dic(9;20) patients. Two of our three patients for whom follow-up is available are in continuous remission as were two adults and five pediatric patients in the previous reports. These studies confirm the dic(9;20) as a recurring abnormality in ALL. Due to the subtle nature of the translocation, FISH is very useful in confirming the chromosomal abnormality.
Transfer of gametes into the fallopian tubes--is choice of side important?
The aim of this study was to define pregnancy rates for gamete intra-Fallopian transfer (GIFT) with respect to the ovary from which most oocytes were collected (i.e. a gross index of ovarian stimulation) and the Fallopian tube (ipsilateral or contralateral) into which gametes were replaced. The only inclusion criterion was the ability to transfer gametes into the Fallopian tubes at GIFT. No other factors that could influence outcome were considered. In this retrospective review of the clinic's database, no relationship was found between pregnancy rate and placement of gametes into the Fallopian tube coincident with the ovary from which most oocytes were collected. Thus when performing unilateral tubal transfer at GIFT gametes may be returned to the side most convenient to the operating surgeon without fear of compromising pregnancy potential.
Animal rights v animal research: a modest proposal.
The practical problem of assuaging the opponents of animal research may be solved without formally addressing (or resolving) the underlying ethical questions of the debate. Specifically, a peaceful boycott of the "fruits" of animal research may lead to a wider cessation of such research, than, say, vocal or even violent protest. To assist those who might wish to participate in such a boycott- and, moreover, to critically inform them of the implications of their actions-1 offer a modest proposal: the use of an "animal research advance directive", a form which enumerates precisely which "fruits of research" are declined.
HMOs and health services research: the penalty of taking the lead.
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Evaluation of the Neer system of classification of proximal humeral fractures with computerized tomographic scans and plain radiographs.
The intraobserver reliability and inter-observer reproducibility of the Neer classification system were assessed on the basis of the plain radiographs and computerized tomographic scans of twenty fractures of the proximal part of the humerus. To determine if the observers had difficulty agreeing only about the degree of displacement or angulation (but could determine which segments were fractured), a modified system (in which fracture lines were considered but displacement was not) also was assessed. Finally, the observers were asked to recommend a treatment for the fracture, and the reliability and re-producibility of that decision were measured. The radiographs and computerized tomographic scans were viewed on two occasions by four observers, including two residents in their fifth year of postgraduate study and two fellowship-trained shoulder surgeons. Kappa coefficients then were calculated. The mean kappa coefficient for intraobserver reliability was 0.64 when the fractures were assessed with radiographs alone, 0.72 when they were assessed with radiographs and computerized tomographic scans, 0.68 when they were classified according to the modified system in which displacement and angulation were not considered, and 0.84 for treatment recommendations; the mean kappa coefficients for interobserver reproducibility were 0.52, 0.50, 0.56, and 0.65, respectively. The interobserver reproducibility of the responses of the attending surgeons regarding diagnosis and treatment did not change when the fractures were classified with use of computerized tomographic scans in addition to radiographs or with use of the modified system in which displacement and angulation were not considered; the mean kappa coefficient was 0.64 for all such comparisons. Over-all, the addition of computerized tomographic scans was associated with a slight increase in intraobserver reliability but no increase in interobserver reproducibility. The classification of fractures of the shoulder remains difficult because even experts cannot uniformly agree about which fragments are fractured. Because of this underlying difficulty, optimum patient care might require the development of new imaging modalities and not necessarily new classification systems.
Pancreatic islet cells express a family of inwardly rectifying K+ channel subunits which interact to form G-protein-activated channels.
Insulin secretion is associated with changes in pancreatic beta-cell K+ permeability. A degenerate polymerase chain reaction strategy based on the conserved features of known inwardly rectifying K+ (KIR) channel genes was used to identify members of this family expressed in human pancreatic islets and insulinoma. Three related human KIR transcript sequences were found: CIR (also known as cardiac KATP-1), GIRK1, and GIRK2 (KATP-2). The pancreatic islet CIR and GIRK2 full-length cDNAs were cloned, and their genes were localized to human chromosomes 11q23-ter and 21, respectively. Northern blot analysis detected CIR mRNA at similar levels in human islets and exocrine pancreas, while the abundance of GIRK2 mRNA in the two tissues was insufficient for detection by this method. Using competitive reverse-transcription polymerase chain reaction, CIR was found to be present at higher levels than GIRK2 mRNA in native purified beta-cells. Xenopus oocytes injected with M2 muscarinic receptor (M2) plus either GIRK2 or CIR cRNA expressed only very small carbachol-induced currents, while co-injection of CIR plus GIRK2 along with M2 resulted in expression of carbachol-activated strong inwardly rectifying currents. Activators of KATP channels failed to elicit currents in the presence or absence of co-expressed sulfonylurea receptor. These results show that two components of islet cell KIR channels, CIR and GIRK2, may interact to form heteromeric G-protein-activated inwardly rectifying K+ channels that do not possess the typical properties of KATP channels.