American College of Zoological Medicine recommendations on veterinary curricula.
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Biomedical subjects
Publications and source records attributed to G Kaufman.
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Preterm delivery (PTD) appears to be a complex trait determined by both genetic and environmental factors. Few studies have examined genetic influence on PTD. The overall goal of our study is to examine major candidate genes of PTD and to test gene-environment interactions. Our study includes 500 preterm trios, including 500 preterm babies and their parents and 500 maternal age-matched term controls. We will perform the transmission/disequilibrium test (TDT) on candidate genes thought to be important in each of the four biological pathways of PTD: (1) decidual chorioamionotic inflammation: interleukin 1 (IL-1), IL-6, and tumour necrosis factor (TNF); (2) maternal and fetal stress: corticotropin-releasing hormone (CRH); (3) uteroplacental vascular lesions: methylenetereahydrofolate reductase (MTHFR); and (4) susceptibility to environmental toxins: GSTM1, GSTT1, CYP1A1, CYP2D6, CYP2E1, NAT2, NQO1, ALDH2, and EPHX. We will also perform standard case-control analyses on the 500 preterm cases and 500 term controls to examine gene-environment interactions. The major environmental, nutritional and social factors as well as clinical variables known or suspected to be associated with PTD will be used to test for gene-environment interactions. This study integrates epidemiological and clinical data as well as genetic markers along major pathogenic pathways of PTD. The findings from this study should improve our understanding of genetic influences on PTD and gene-environment interactions.
Recently all existing Trichophyton mentagrophytes colonies within our laboratory, which had originally appeared normal, rapidly and at an early stage became perforated. Therefore the aims of this study were to expose the cause of these major morphological changes and to find out if this phenomenon may occur in other fungal cultures. Microscopic examination of specimens taken from the damaged colonies showed many mites at different developmental stages, which were subsequently identified as the acarus, Tyrophagus putrescentiae. The laboratory experiments demonstrated that mites feed on the spores and hyphae of all the dermatophytes, moulds and yeasts tested. For the time being Tyrophagus putrescentiae is an unpleasant pest which damages fungal cultures but future use of the acari in biological control may be considered.
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The copper-containing hemocyanins are a class of oxygen-transport proteins whose structures differ in arthropods and molluscs. Crystal structure analyses and amino acid sequence comparisons show that disulfide bonding is a common feature in both arthropod and mollusc hemocyanins. Reduction of the disulfide bonds of a representative set of arthropod and mollusc hemocyanins results in complete loss of their oxygen-binding capacities. Thus, retention of the disulfide bonds is essential to the functional integrity of the oxygen-binding sites in the subunits of this class of oxygen carriers, despite the very different architectures of the arthropod and mollusc molecules. Depending upon the specific hemocyanin, partial to virtually complete restoration of the oxygen-binding capacity occurs when the disulfide-bond reductant is removed by dialysis. The rate at which the functional, active-site geometry is lost and the extent to which it can be restored varies markedly with hemocyanin type, aggregation state, and experimental conditions. Consequently, a comparison of these differences provides a simple, but powerful, way to probe internal and environmental factors that govern physiologically important structure-function relationships in this entire class of oxygen-transport proteins.
OBJECTIVE: To determine if 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in preventing fatal and nonfatal strokes in patients at increased risk of coronary artery disease. DESIGN: Meta-analysis of randomized controlled trials. Clinical trials were identified by a computerized search of MEDLINE (1983 to June 1996), by an assessment of the bibliographies of published studies, meta-analyses and reviews, and by contacting pharmaceutical companies that manufacture statins. Trials were included in the analysis if their patients were randomly allocated to a statin or placebo group, and reported data on stroke events. Thirteen of 28 clinical trials were selected for review. Data were extracted for details of study design, patient characteristics, interventions, duration of therapy, cholesterol measurements, and the number of fatal and nonfatal stroke events in each arm of therapy. Missing data on stroke events were obtained by contacting the investigators of the clinical trials. MAIN RESULTS: Among 19,921 randomized patients, the rate of total stroke in the placebo group was 2.38% (90% nonfatal and 10% fatal). In contrast, patients who received statins had a 1.67% stroke rate. Using an exact stratified analysis, the pooled odds ratio (OR) for total stroke was 0.70 (95% confidence interval [CI] 0.57, 0.86; p =.0005). The pooled OR for nonfatal stroke was 0.64 (95% CI 0.51, 0.79; p =.00001), and the pooled OR for fatal stroke was 1.25 (95% CI 0.71, 2.24; p =.4973). In separate analyses, reductions in total and nonfatal stroke risk were found to be significant only for trials of secondary coronary disease prevention. Regression analysis showed no statistical association between the magnitude of cholesterol reduction and the relative risk for any stroke outcome. CONCLUSIONS: The available evidence clearly shows that HMG-CoA reductase inhibitors reduce the morbidity associated with strokes in patients at increased risk of cardiac events. Data from 13 placebo-controlled trials suggest that on average one stroke is prevented for every 143 patients treated with statins over a 4-year period.
Sterilisation has been increasing in the United States in recent decades. Using the National Survey of Families and Households, this paper examines sterilisation among married couples using event history techniques, viewing husband and wife sterilisation as competing risks. Wives are more likely to experience sterilisation and at shorter durations of marriage. Number of children has a curvilinear effect on sterilisation, increasing and then decreasing its likelihood. Wives who are older than their husbands are more likely to get sterilised themselves. Black and Hispanic husbands are more likely to undergo sterilisation.
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At a time when the government is proposing to allow nurses to become equal partners with GPs and a consultative report commissioned by the NHSE found that nurse practitioners provide cheaper and better services for patients (NHSE 1996), this article describes the role of a nurse practitioner working in a GP fundholding practice in the UK. The author considers issues of autonomy and accountability surrounding the development of the role. Its relationship to the development of nursing and caring is examined in the light of some doctors' and nurses' scepticism and ambivalence. The benefits to patients are presented to highlight the value of a properly structured nurse practitioner role integrated into primary care provision.
Hospital discharge records were used to study the relationship between human immunodeficiency virus (HIV) epidemic and hospitalized patients with tuberculosis in New York State from 1987 through 1992. The discharges of patients coinfected with HIV and tuberculosis increased by 270%, rising from 1,573 in 1987 to 5,825 in 1992. This constitutes an increase from 19.8 to 49.1% of all discharges of patients with tuberculosis. Discharges of tuberculosis patients who were not infected with HIV decreased slightly during this time, going from 6,359 to 6,039. Postdischarge treatment plans, HIV prevention, HIV testing, and HIV educational programs for the tuberculosis population require special consideration, given the significant rise of HIV in the tuberculosis-infected population.
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OBJECTIVE: Our purpose was to describe the total costs involved in the delivery, prenatal, and neonatal care for triplet pregnancies. STUDY DESIGN: Twenty triplet pregnancies were born at our institution over the 1-year period between July 1, 1992, and June 30, 1993. Total charges for prenatal care, physician fees, antepartum admissions, delivery, postpartum inpatient and outpatient care, and neonatal inpatient and outpatient care were extracted from the hospital billing computers. RESULTS: Our 20 triplet pregnancies were delivered of 54 live born infants at an average gestation of 30.2 weeks. Mothers averaged 16.7 inpatient hospital days. Total cost of prenatal care, outpatient laboratories and ultrasonography, delivery, and maternal inpatient care averaged $27,491. Neonates averaged 13.7 hospital days. Total neonatal costs for the inpatient stay and short term-postpartum (< 6 week) outpatient period was $36,856 per family. Total average cost per family was $64,347. CONCLUSION: Combined maternal and neonatal costs per individual baby delivered was approximately $21,000. Although expensive, this cost is far from prohibitive, even in times of close attention to health care expenditures.
Oligonucleotides are synthesized and purified in a single column filled with a mixture of nucleoside-loaded and underivatized, high-cross link, non-swelling polystryene beads. A new oligonucleotide production system has been developed to completely automate-the entire process of sequence entry, phosphoramidite synthesis, cleavage, deprotection, purification, quantitation, and sample collection. Up to 48 primer-length, high-purity oligonucleotides can be produced in a 24 hour period of unattended automation on the ABI 3948 DNA Synthesizer. Synthesis, cleavage, and purification occur within the unique OneStepTM column. Analyses by MicroGel capillary electrophoresis, anion-exchange HPLC, PAGE, and enzymatic digestion/HPLC routinely exhibit > 90% product purity. Stringent PCR, automated fluorescent sequencing, and genetic analysis experiments show the positive effects of the total automation of purified oligonucleotide production.
Interleukin-1 (IL-1), a prominent 17-kilodalton member of a group of immune mediators referred to as cytokines, is secreted by a variety of immuno- and nonimmunocompetent cells. As IL-1 is an established mediator of inflammation, and ovulation may constitute an inflammatory-like reaction, consideration may be given to the possibility that IL-1 may play an intermediary role in the ovulatory process. Such a hypothesis is supported by the recent demonstration of the gonadotropin-dependent preovulatory induction of IL-1 transcripts at the level of the murine and human ovary. To date, however, the direct effect of IL-1 beta on the ovulatory process has not been examined. The objective of this study was to investigate the potential role of IL-1 beta in ovulation, oocyte maturation (nuclear and cytoplasmic), and subsequent fertilizability of in vitro ovulated oocytes. Rabbit ovaries perfused in vitro were used for these experiments. Ovarian arteries were cannulated in situ, and the ovaries were excised and perfused in vitro with or without IL-1 beta (18 ng/ml). The ovulatory efficiency of 18 ng/ml IL-1 beta-treated ovaries was 73.1%, similar to that of hCG (71.2%). Recovered oocytes were examined for their maturation and were inseminated in vitro to investigate fertilization, cleavage, and embryonic development. The fertilization rates of the 18 ng/ml IL-1 beta-treated and hCG-treated groups were 65.8% and 95.8% (P < 0.01), respectively. Cleavage rates of the IL-1 beta-treated and hCG-treated groups were 50% and 83.3% (P < 0.01), respectively. Most of the cleaved embryos from the IL-1 beta-treated group arrested at the four-cell stage, and only 2.6% of the fertilized embryos developed into the morula stage, whereas 54.2% of the hCG-treated group developed to the morula stage (P < 0.01). A cytotoxic effect of IL-1 beta is unlikely in this model. A more likely explanation is the induction of other factors by IL-1 beta, which may inhibit cytoplasmic maturation. Taken together, our findings demonstrate that in the absence of an ovulatory gonadotropic trigger, IL-1 beta can induce ovulation and oocyte maturation, facilitate fertilization, and influence subsequent embryonic development. Although fertilization and embryonic development occurred after IL-1 beta treatment, these rates were lower than those after hCG treatment. These observations give credence to the possibility that IL-1 may play an intermediary role in the ovulatory process.
Tumor-promoting phorbol esters are believed to affect ovarian granulosa cell progesterone and prostaglandin (PG) production and possibly ovulation by activating protein kinase-C (PKC). The effects of phorbol esters and PKC inhibitors on ovulation, progesterone, and PG production were examined in an in vitro perfused rabbit ovary. The effect of tranexamic acid, an inhibitor of the conversion of plasminogen activator to plasmin, on phorbol ester-induced ovulation was also examined. Phorbol 12,13-dibutyrate (PdBU), a PKC stimulator, induced ovulation in a dose-related manner in the absence of gonadotropins (56%, 200 nM PdBU; 0%, 0 nM PdBU; P < 0.05). Perfusate progesterone levels were increased only after 600 nM PdBU treatment, and perfusate PGF2 alpha, PGE2, and 6-keto-PGF1 alpha were increased in a dose-dependent fashion (P < 0.05). Staurosporine, a potent inhibitor of the catalytic domain of PKC, and calphostin-C, a specific inhibitor of the diacylglycerol-binding region, inhibited hCG-induced ovulation in a dose-related manner. Gonadotropin-induced ovulation decreased from 73% without staurosporine to 19% with 1.0 microM staurosporine (P < 0.01). Calphostin-C reduced ovulatory efficiency from 60% to 24% (P < 0.01). However, neither inhibitor decreased progesterone or PGF2 alpha production by ovaries exposed to hCG. hCG-induced oocyte maturation was also unaffected by exposure to either staurosporine or calphostin-C. Tranexamic acid reduced phorbol ester-induced ovulatory efficiency from 67% to 37% (P < 0.05). These findings demonstrate that the calcium-dependent PKC pathway is instrumental in gonadotropin-mediated follicular rupture in the rabbit. Although PGs may play an important role in ovulation, they do not appear to be directly responsible for PKC-mediated follicular rupture.
Several immunologic parameters, both humoral and cellular, were studied in the serum and peripheral blood lymphocytes derived from chest x-ray-negative, asymptomatic asbestos workers. All humoral and cellular parameters were intact, except the con-A-induced T cell suppressor activity and T cell division in autologous mixed lymphocyte reaction, which were significantly elevated in the asbestos plant workers. The significance of these increased T cell activities in asbestos exposed people is not clear, and further clinical and immunological follow-up is warranted.
Poisoning with paracetamol (acetaminophen) and phenobarbitone is a common occurrence in the United States and Europe. The removal efficiency of these drugs by a sorbent suspension reciprocating dialyser (SSRD) has been investigated. The SSRD is a parallel plate dialyser with a reciprocating blood flow and free mobile sorbent suspension composed of charcoal and zeolites. This arrangement provided a system with minimal sorbent saturation. High performance liquid chromatography was used for the quantification of the drugs in aqueous and serum fluids. The in-vitro removal efficiency of the dialyser was studied by dialysing a large volume of the drug in solution for 12 to 16 h. The removal efficiency remained relatively constant up to 10 h of dialysis. The in-vivo dialysis studies were performed using normal dogs. Large doses of the drugs were administered orally or intravenously to achieve high blood levels. The clearance values obtained from these studies were comparable with, or in excess of, the values reported in the literature for conventional dialysers. The major advantage of the SSRD is the ability of the unit to be used for prolonged dialysis and to provide a system with minimal sorbent saturation due to mixing and interchange of sorbent granules next to the membrane surface.