Biomedical subjects

M Borenstein

Publications and source records attributed to M Borenstein.

At least 19 recordsLinked to original sources

PubMed2007

Frontomaxillary facial angle at 11+0 to 13+6 weeks' gestation-reproducibility of measurements.

OBJECTIVE: To assess the intra- and interobserver reproducibility in the measurement of the frontomaxillary facial (FMF) angle at 11+0 to 13+6 weeks' gestation and to investigate the effect of deviations from the exact mid-sagittal view on these measurements. METHODS: Three-dimensional (3D) volumes of the fetal face were used by two operators to measure the FMF angle in 50 chromosomally normal and 50 trisomy 21 fetuses. The measurements were taken in the exact mid-sagittal view and repeated after lateral rotation of the head by 5 degrees, 10 degrees and 15 degrees away from the vertical position of the occipitofrontal diameter axis. Mean difference and 95% limits of agreement between paired measurements of FMF angle by the same and by two different sonographers were determined. RESULTS: In the mid-sagittal plane the maxillary bone was rectangular shaped. Rotation away from this plane became easily recognizable because at a mean of 7 degrees (range, 4-10 degrees) the shape of the maxilla changed with the appearance of the zygomatic process of the maxilla and at a mean of 8 degrees (range, 4-12 degrees) the tip of the nose became invisible. In both the normal and trisomy 21 fetuses the FMF angle measured at 5-15 degrees was not significantly different from the one measured in the mid-sagittal plane. In 95% of the cases, the difference between paired measurements of the FMF angle by the same sonographer at the mid-sagittal plane was between -2.3 degrees and 3.0 degrees and at 15 degrees it was -1.0 degrees to 6.8 degrees. At the mid-sagittal plane, the difference in measurements between two sonographers was -3.1 to 3.0 degrees. CONCLUSION: The landmarks that define the mid-sagittal plane of the fetal face are the tip of the nose and the rectangular shaped maxilla. Measurement of the FMF angle is highly reproducible.

Adolescent↗

PubMed2006

Placental volume in twin and triplet pregnancies measured by three-dimensional ultrasound at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To compare the placental volume at 11 + 0 to 13 + 6 weeks' gestation between singleton and multiple pregnancies and to examine the possible effect of chorionicity on placental volume. METHODS: The placental volume was measured by three-dimensional (3D) ultrasound using the Virtual Organ Computer-aided AnaLysis (VOCAL) technique in 290 consecutive twin and 37 triplet pregnancies at 11 + 0 to 13 + 6 weeks of gestation. For the comparison of twin, triplet and singleton placental volumes each measurement was expressed as a multiple of the median (MoM) for singletons, previously established from the study of 417 normal fetuses at 11 + 0 to 13 + 6 weeks of gestation. RESULTS: Median twin and triplet placental volumes were 1.66 and 2.28 MoM for singletons, respectively. In twins the placental volumes increased significantly with gestation from a median of 83.6 mL (5th and 95th centiles: 56.0 mL and 124.9 mL) at 11 + 0 weeks to 149.3 mL (5th and 95th centiles: 100.0 mL and 223.1 mL) at 13 + 6 weeks. The median MoM in monochorionic twins was not significantly different from that in dichorionic twins with fused placentas or dichorionic twins with separate placentas. In triplets the placental volumes increased significantly with gestation from a median of 114.9 mL (5th and 95th centiles: 77.6 mL and 170.1 mL) at 11 weeks to 217.9 mL (5th and 95th centiles: 147.2 mL and 322.5 mL) at 13 + 6 weeks. There were no significant differences in total placental volume between monochorionic and dichorionic triplets, monochorionic and trichorionic triplets, or dichorionic and trichorionic triplets. CONCLUSIONS: Placental volume in multiple pregnancies does not depend on chorionicity, and the rate of placental growth between 11 and 13 + 6 weeks is not significantly different between singletons, twins and triplets. Moreover, for a given gestational age the placental volume corresponding to each fetus in twins and triplets is 83% and 76%, respectively, of the placental volume in singletons.

Adolescent↗

PubMed2006

Three-dimensional evaluation of mid-facial hypoplasia in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation.

OBJECTIVE: To investigate the mid-facial hypoplasia of fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation, by three-dimensional (3D) evaluation of the maxilla and the nasal bones. METHODS: A 3D volume of the fetal head was obtained before fetal karyotyping at 11 + 0 to 13 + 6 (median 12) weeks of gestation in 80 fetuses that were subsequently found to have trisomy 21 and in 862 fetuses subsequently found to be chromosomally normal. The multiplanar mode was used to obtain a sequence of transverse views of the fetal face and to demonstrate the maxilla, the adjacent rami of the mandible and the nasal bones. The maxillary depth, defined as the distance between the alveolus of the maxilla in the midline anteriorly and the midpoint of the line joining the rami posteriorly, was measured. Ossification of the nasal bones was considered to be normal if both bones were more echogenic than the overlying skin. RESULTS: In the chromosomally normal group the maxillary depth increased linearly with crown-rump length (CRL) from 3.1 mm at a CRL of 45 mm to 4.8 mm at a CRL of 84 mm, and in the trisomy 21 fetuses the depth was significantly smaller than normal (mean difference = - 0.3 mm, P < 0.001). There was no significant association between the delta maxillary depth and delta nuchal translucency thickness in either the trisomy 21 or the chromosomally normal fetuses. Impaired ossification of the nasal bones was observed in 3.1% of the chromosomally normal fetuses and in 60.0% of those with trisomy 21. The mean maxillary depth was significantly smaller in fetuses demonstrating impaired ossification than in those with normal ossification of the nasal bones (mean difference = -0.2 mm; 95% CI, -0.3 to -0.1, P = 0.001). CONCLUSIONS: In a high proportion of fetuses with trisomy 21 there is sonographic evidence of mid-facial hypoplasia at 11 + 0 to 13 + 6 weeks of gestation.

Adolescent↗

PubMed2006

Brachycephaly and frontal lobe hypoplasia in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks.

OBJECTIVE: To investigate the incidence of brachycephaly and frontal lobe hypoplasia in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation. METHODS: A three-dimensional (3D) volume of the fetal head was obtained before fetal karyotyping at 11 + 0 to 13 + 6 (median, 12 + 5) weeks of gestation in 100 fetuses that were subsequently found to have trisomy 21 and in 300 fetuses subsequently found to be chromosomally normal. The multiplanar mode was used to obtain a sequence of transverse views of the fetal head and to demonstrate the biparietal and suboccipitobregmatic views. We measured the biparietal diameter (BPD), the occipitofrontal diameter (OFD) and the frontothalamic distance (FTD) between the inner table of the frontal bone and the posterior thalami. RESULTS: In the chromosomally normal group the BPD, OFD and FTD increased linearly with crown-rump length (CRL) from 16.7 mm, 19.0 mm and 12.1 mm at a CRL of 45 mm to 26.7 mm, 31.7 mm and 18.7 mm, respectively, at a CRL of 84 mm. In the trisomy 21 fetuses, compared to normal fetuses, there was shorter BPD (mean difference = -0.63 mm; 95% CI, -0.97 to -0.30 mm, P < 0.0001), OFD (mean difference = -1.41 mm; 95% CI, -1.75 to -1.07 mm, P < 0.0001) and FTD (mean difference = -0.77 mm; 95% CI, -1.02 to -0.54 mm; P < 0.0001) and higher BPD to OFD ratio (mean difference = 0.022; 95% CI, 0.012 to 0.032, P < 0.0001) but no significant difference in the FTD to OFD ratio (mean difference = 0.004; 95% CI, -0.006 to 0.013, P = 0.448). CONCLUSIONS: In fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation there is evidence of brachycephaIy but not of frontal lobe hypoplasia.

Adolescent↗

PubMed2003

Erythrodermic, recalcitrant psoriasis: clinical resolution with infliximab.

This report describes the case of a patient with erythrodermic psoriasis who had failed all previous therapies and been hospitalized numerous times over a 12-year period that responded dramatically to treatment with infliximab. The potential utility of infliximab as a therapeutic alternative for erythrodermic psoriasis is discussed.

Antibodies, Monoclonal↗

PubMed2001

Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison.

BACKGROUND: Despite the demonstrated efficacy of clozapine in severely refractory schizophrenia, questions remain regarding its efficacy for primary negative symptoms, comparison with a moderate dose of a first-generation antipsychotic, and adverse effects during a longer-term trial. This study examined its efficacy in partially responsive, community-based patients, compared clozapine with moderate-dose haloperidol, and extended treatment to 6 months. METHODS: Randomized, double-blind, 29-week trial comparing clozapine (n = 37) with haloperidol (n = 34). Subjects with schizophrenia who were being treated in community settings at 3 collaborating clinical facilities were enrolled. RESULTS: Subjects treated with haloperidol were significantly more likely to discontinue treatment for lack of efficacy (51%) than were those treated with clozapine (12%). A higher proportion of clozapine-treated subjects met an a priori criterion of improvement (57%) compared with haloperidol-treated subjects (25%). Significantly greater improvement was seen in symptoms of psychosis, hostile-suspiciousness, anxiety-depression, thought disturbance, and total score measured on the Brief Psychiatric Rating Scale. No differences were detected in negative symptoms using the Brief Psychiatric Rating Scale or the Schedule for Assessment of Negative Symptoms. Subjects treated with clozapine experienced more excess salivation, dizziness, and sweating and less dry mouth and decreased appetite than those treated with haloperidol. CONCLUSIONS: Compared with a first-generation antipsychotic given in a moderate dose, clozapine offers substantial clinical benefits to treatment-refractory subjects who can be treated in the community. Advantages are seen in a broad range of symptoms but do not extend to negative symptoms.

Adult↗

PubMed1999

Effects of topical corticosteroids on inflammatory mediator-induced eicosanoid release by human airway epithelial cells.

BACKGROUND: Airway epithelial cells are among the first cells to come in contact with aerosolized corticosteroids. However, the relative potencies and time course of action of the several commonly used aerosolized corticosteroids on eicosanoid production by airway epithelial cells are unknown. OBJECTIVES: This study compared the effects of fluticasone, budesonide, and triamcinolone on eicosanoid output by human airway epithelial cells in vitro. We also determined the spectrum of eicosanoids affected and the mechanism for corticosteroid action. METHODS: Cultured BEAS-2B airway epithelial cells (a transformed cell line) were exposed to corticosteroids (1 nmol/L to 1 micromol/L) for 2 to 48 hours and then assayed for basal- and bradykinin (BK)-stimulated eicosanoid output. The eicosanoid profile was identified by HPLC in tritiated arachidonic acid prelabelled cells, and PGE2, the major eicosanoid product, was quantitated by RIA. The effect of corticosteroids on the immunoreactivity of key proteins involved in eicosanoid metabolism (ie, cyclooxygenase [COX], phospholipase A2 [PLA2], and Clara cell protein, a PLA2 inhibitor) was determined by Western blotting. RESULTS: Eicosanoid output was largely confined to prostaglandins with values of 5 +/- 2 and 82 +/- 35 ng PGE2/10(6) cells for basal- and BK stimulation, respectively (n = 8). All 3 corticosteroids inhibited basal- and BK-induced PGE2 output in a dose- and time-dependent manner. Fluticasone and budesonide completely eliminated PGE2 output in nanomolar concentrations in contrast to triamcinolone, which required micromolar concentration. The rank order of potency was: fluticasone = budesonide > triamcinolone. The time course of action for PGE2 inhibition also differed, with budesonide acting more slowly than the other 2 corticosteroids (P = .04). All 3 corticosteroids markedly reduced COX2 with little effect on COX1, cPLA2 (Type IV), or iPLA2 (Type VI) immunoreactivity or their relative distribution in cytosol versus membrane fractions. Clara cell protein immunoreactivity was undetectable in control and corticosteroid-treated cell lysates. CONCLUSION: These results show that in a human airway epithelial cell line, the 3 inhaled corticosteroids commonly used to treat asthma differ in onsets of action as inhibitors of prostaglandin synthesis and vary considerably in potency. All 3 corticosteroids act mechanistically in similar fashion by inhibiting COX2 synthesis.

Administration, Topical↗

PubMed1998

Dietary myo-inositol therapy in hyperglycemia-induced embryopathy.

Dysmorphogenesis in diabetic mothers occurs more frequently than in the general population. This phenomenon is believed to be caused by the teratogenic effects of metabolic fuel mixtures with associated membrane injury and aberrations in the biochemical constituents. The present experiment was designed to determine: 1) if hyperglycemia-induced membrane injury is associated with intracellular and/or extracellular lipid disturbances; 2) if supplemental myo-inositol therapy prevents hyperglycemia-induced embryopathy; 3) if a correlation exists between dietary myo-inositol, serum and tissue levels of myo-inositol, and conceptus development; and 4) the cellular content of arachidonic acid following myo-inositol supplementation. Sixty-five female Sprague-Dawley rats were mated, and divided into three groups. One group was nondiabetic normal controls, and two groups had diabetes experimentally induced with streptozotocin. Of the diabetic groups, one received a normal diet, while the other received a myo-inositol-supplemented diet during the period of organogenesis. Blood samples were collected on days 0 and 12 of pregnancy. Embryos and yolk sacs were analyzed for myo-inositol and arachidonic acid levels, using mass spectrochromatography. Dietary myo-inositol supplementation of diabetic mothers resulted in a significant decrease in the incidence of neural tube defects when compared with diabetics not receiving supplements (9.5 vs. 20.4%; P < 0.05). This protective effect was incomplete, based on the incidence observed in the nondiabetic controls (9.5 vs. 3.8%; P < 0.05). The myo-inositol embryonic tissue levels in the diabetic group which had been fed a regular diet without supplementation were significantly lower than in the nondiabetic group. Dietary therapy successfully restored myo-inositol levels in the yolk sacs, as suggested by similar tissue levels in diabetics receiving myo-inositol supplementation and normal controls (18.7 +/- 1.3 vs. 19.1 +/- 2.0 ng/mg; P = ns). Dietary therapy, however, failed to restore myo-inositol levels in the embryos, suggesting hyperglycemia-induced faulty transport of nutrients from the yolk sac to the embryo. No correlation was noted between maternal blood levels of myo-inositol, with or without supplementation, and the clinical outcome. Tissue arachidonic acid levels were markedly reduced in the conceptuses of diabetic mothers with (0.4 +/- 0.1 micrograms/mg) or without (0.25 +/- 0.08 micrograms/mg) myo-inositol supplementation when compared to the nondiabetic controls (3.33 +/- 0.24 micrograms/mg). These data demonstrate that diabetes-induced embryopathy is associated with a deficiency state in both myo-inositol and arachidonic acid. The myo-inositol deficiency is not demonstrated at the serum level, but rather at the tissue level, suggesting a paracrine action. Dietary supplementation of myo-inositol is associated with an increase in tissue myo-inositol levels and a decrease in malformations. This therapy holds promise for use as a dietary prophylaxis against diabetic embryopathy.

Animals↗

PubMed1997

Cardiovascular effects of different infusion rates of sufentanil in patients undergoing coronary surgery.

OBJECTIVE: Pharmacokinetics and haemodynamic effects of a total dose of 15 micrograms.kg-1 sufentanil, an opioid anaesthetic agent, were studied in patients undergoing aortocoronary bypass surgery at three infusion rates of 30 (group I), 5 (group II), and 2 (group III) micrograms.kg-1.min-1, respectively. RESULTS: Plasma concentrations of sufentanil could be optimally characterized by a linear biexponential pharmacokinetic model. Non-compartmental analyses indicated that there was no significant difference in the values of clearance (11.6, 13.3, 14.3 ml.min-1.kg-1), steady-state volume of distribution (0.220, 0.255 and 0.331 l.kg-1) and mean residence time (18.8, 13.3 and 14.3 min) among the groups. The observed mean Cmax values of 421 (group I), 125 (group II), and 53 (group III) ng.ml-1 and observed mean AUC values from 0 to 3 min were all consistent with the dosing regimens. There were large inter-individual variations in haemo-dynamic response. Compared to plasma data, a delay in haemodynamic effects was found. Times to reach peak haemodynamic effect ranged from 4.3 to 4.9 min for group I, from 4.6 to 6.1 min for group II, and from 9.9 to 11.3 for group III. Except heart rate, peak haemodynamic effects in these study patients generally ranged from 20.9% to 35.2%. Significant reductions in the area under the effect-time profiles of mean arterial blood pressure and systemic vascular resistance were observed in group II and group III, but not in group I. Significant reductions in the area under the effect-time profiles of left ventricular stroke work index were observed in group III only. No effect on heart rate was found in any group. CONCLUSION: Our findings suggested that a slower infusion rate of sufentanil at a dose of 15 micrograms.kg-1 tends to give a greater reduction in mean arterial blood pressure, systemic vascular resistance, and left ventricular stroke work index than does a faster infusion rate.

Analgesics, Opioid↗

PubMed1997

Dietary intake of myo-inositol and neural tube defects in offspring of diabetic rats.

OBJECTIVE: Embryopathy in diabetic mothers occurs at a rate four to five times higher than that observed in the general population. The current investigation was undertaken to assess the use of dietary myo-inositol supplementation as a pharmacologic prophylaxis to obviate the teratogenic effects of hyperglycemia in an in vivo study. STUDY DESIGN: Seventy Sprague-Dawley rats were mated and after conception were randomly divided into five groups: one group was nondiabetic normal controls and four groups had diabetes experimentally induced with streptozotocin. Of the diabetic groups, one received the usual diet, whereas the others received, respectively, 0.08, 0.16, and 0.5 mg/day supplemental myo-inositol orally. RESULTS: With the myo-inositol supplementation (0.08 mg/day), the incidence of neural tube defects was significantly reduced from 20.4% to 9.5% (p < 0.01). The most effective dosage of myo-inositol was 0.08 mg/day. Increasing the dose of myo-inositol beyond that level did not significantly reduce the rate of neural tube defects. However, the resorption rate was increased to 29.8%. CONCLUSION: These data demonstrate that myo-inositol supplementation reduces the incidence of diabetic embryopathy and may serve as a pharmacologic prophylaxis against diabetes-induced congenital malformations.

Animals↗

PubMed1997

Hypothesis testing and effect size estimation in clinical trials.

LEARNING OBJECTIVES: This paper provides the reader with an overview of several key elements in study planning and analysis. In particular, it highlights the differences between significance tests (statistical significance) and effect size estimation (clinical significance). DATA SOURCES: This paper focuses on methodologic issues, and provides an overview of trends in research. PAPER SELECTION: References were selected to provide a cross-section of the approaches currently being used. The paper also discusses a number of logical fallacies that have been cited as examples in earlier papers on research design. CONCLUSIONS: Significance tests are intended solely to address the viability of the null hypothesis that a treatment has no effect, and not to estimate the magnitude of the treatment effect. Researchers are advised to move away from significance tests and to present instead an estimate of effect size bounded by confidence intervals. This approach incorporates all the information normally included in a test of significance but in a format that highlights the element of interest (clinical significance rather than statistical significance). This approach should also have an impact on study planning--a study should have enough power to reject the null hypothesis and also to yield a precise estimate of the treatment effect.

Clinical Trials as Topic↗

PubMed1996

Incidence and correlates of tardive dyskinesia in first episode of schizophrenia.

BACKGROUND: There is controversy over whether tardive dyskinesia (TD) is solely a consequence of antipsychotic drug treatment or in part may reflect an intrinsic aspect of the disease process. Pathophysiologic factors could, independently or in concert with drug effects, lead to the development of dyskinetic signs. METHODS: We studied prospectively 118 patients in their first episode of psychosis who were treatment-naive or had less than 12 weeks of antipsychotic drug exposure at study entry. Patients received standardized antipsychotic drug treatment and were evaluated for up to 8 1/2 years with regular assessments of psychopathologic signs and symptoms and side effects. RESULTS: The cumulative incidence of presumptive TD was 6.3% after 1 year of follow-up, 11.5% after 2 years, 13.7% after 3 years, and 17.5% after 4 years. Persistent TD had a cumulative incidence of 4.8% after 1 year, 7.2% after 2 years, and 15.6% after 4 years. Taken individually, both antipsychotic drug dose, entered as a time-dependent covariate, and poor response to treatment of the first psychotic episode were significant predicters of time to TD. When antipsychotic drug dose and treatment response were examined together, treatment responders had significantly lower hazards for presumptive TD than nonresponders (hazard ratio, 0.29; 95% confidence interval, 0.09 to 0.97). Dose was a trend-level predicter, with each 100-mg chlorpromazine equivalent unit increase in dose associated with a 5% increase in the hazard of presumptive TD (hazard ratio, 1.05; 95% confidence interval, 0.99 to 1.11). CONCLUSION: Poor response to the treatment of a first episode of psychosis and, to a lesser extent, antipsychotic drug dose are important factors in the development of TD. This suggests that there may be a disease-related vulnerability to TD manifest with antipsychotic drug exposure. Potential pathophysiologic factors might include neurodevelopmentally induced structural neuropathologic characteristics, sensitization of nigrostriatal dopamine neurons, and the induction of glutamatergically mediated neurotoxic effects.

Adult↗

PubMed1996

Dietary vitamin E prophylaxis and diabetic embryopathy: morphologic and biochemical analysis.

OBJECTIVE: In this study we sought to determine whether dietary supplementation with vitamin E, a known antioxidant, would reduce the incidence of diabetic embryopathy in an in vivo rat model. STUDY DESIGN: Eighty-day-old Sprague-Dawley rats were assigned to one of five groups: two control groups (groups 1 and 2) and three diabetic groups (groups 3, 4, and 5). One group of controls (group 2) and one group of diabetic rats (group 4) received dietary supplements of vitamin E (440 mg/day). The other three groups (groups 1, 3, and 5) received a normal diet only. Group 5 received insulin therapy to control glucose levels. On day 6 of gestation diabetes was induced in groups 3, 4, and 5 with streptozotocin (65 mg/kg). Animals were killed on day 12; embryos were examined for size, protein content, evidence of malformations, and superoxide dismutase activity. RESULTS: In both groups (groups 3 and 4) of diabetic rats the mean blood glucose level than was significantly higher in controls. Insulin-treated animals (group 5) had glucose levels that were comparable to those of controls. The unsupplemented diabetic group had a neural tube defect rate of 21.48% +/- 9.6% (percentage of neural tube defects per rat) and a resorption rate of 21.37% +/- 20.39% (percentage of resorptions per rat) as compared with rates in the supplemented diabetic group of 6.92% +/- 4.08% and 2.17% +/- 3.74%, respectively (p < 0.01). Groups 1, 2, and 5 had similar neural tube defect rates (6.63% +/- 5.0%, 5.01% +/- 4.87%, and 3.55% +/- 5.92%, respectively. Vitamin E levels, measured by high-performance liquid chromatography, were significantly higher in maternal serum and embryos in the supplemented groups (p < 0.001) than in controls. Superoxide dismutase activity was reduced in the diabetes groups and was not affected by vitamin E therapy. CONCLUSIONS: Supplementation with the antioxidant vitamin E confers a significant protective effect against diabetic embryopathy and may potentially serve as a dietary prophylaxis in the future. We postulate that this protective effect is mediated by a reduction in the oxidative load induced by hyperglycemia.

Animals↗

PubMed1996

Dietary polyunsaturated fatty acid prevents malformations in offspring of diabetic rats.

OBJECTIVE: The purpose of the current study was to determine whether a dietary source of arachidonic acid could serve as a pharmacologic prophylaxis to obviate the teratogenic effects of hyperglycemia. STUDY DESIGN: Eighty-day-old Sprague-Dawley rats were mated, and after conception were randomly allocated to five groups: two groups were nondiabetic normal controls and three groups had diabetes experimentally induced with streptozocin. Of the two control groups, one was fed a normal diet (group 1) and the other group (group 2) received a normal diet and 1.0 ml of safflower oil, a polyunsaturated fatty acid known to increase serum arachidonic acid levels. In the three diabetic groups (groups 3, 4, and 5) glucose levels were allowed to remain > 350 mg/dl by withholding daily insulin therapy. Group 3 received a normal diet without supplementation; group 4 received a normal diet plus normal saline solution sham feedings, whereas group 5 received a normal diet supplemented with 1.0 ml of safflower oil. The oral agents (normal saline solution and polyunsaturated fatty acid) were administered with a tuberculin syringe. RESULTS: Diabetic rats not receiving insulin therapy and receiving normal diets produced offspring with malformation rates of 20% compared with control rates of 4.8%. Supplemental normal saline solution or safflower oil given orally to controls did not alter the growth or malformation rates. These rates were similarly unaffected in the diabetic rats receiving oral supplementation of normal saline solution. However, with safflower oil supplementation to diabetic rats the incidence of neural tube defects was decreased from 20.0% to 7.6% (p < 0.0001). An inverse relationship was observed between the malformation rate and the serum arachidonic acid level: 17.83 (SD 5.84 micrograms/ml) in the nondiabetic controls, with a malformation rate of 4.8%, versus 14.18 (SD 2.58 micrograms/ml) in the diabetic rats, with a malformation rate of 20.0% (p < 0.05). With safflower oil supplementation serum levels of arachidonic increased from 14.18 +/- 2.58 micrograms/ml to 19.99 +/- 7.99 micrograms/ml (p < 0.05); this was associated with a concomitant decline in the malformation rate. CONCLUSION: These data demonstrate that diabetic embryopathy is associated with a deficiency state in essential fatty acid, corroborating our previous in vitro findings. Furthermore, the use of a dietary polyunsaturated fatty acid that specifically increases arachidonic levels significantly reduced the incidence of diabetic embryopathy. These findings may serve as a basis for developing strategies of pharmacologic prophylaxis against diabetes-induced congenital malformations.

Animals↗

PubMed1995

Is hand washing really needed in an intensive care unit?

OBJECTIVES: To determine whether a rigorous antiseptic hand washing of bare hands with 4% chlorhexidine and alcohol reduced fingertip microbial colonization as compared with the use of boxed, clean, nonsterile latex gloves. In addition, to investigate if aseptic donning technique and/or a prior hand washing would reduce the level of glove contamination. DESIGN: Prospective, randomized, crossover design, with each subject serving as his/her own control. SETTING: University intensive care unit. SUBJECTS: Forty-three intensive care nurses. INTERVENTIONS: The fingertips of 20 nurses were cultured before and after a strict antiseptic hand washing and before and after the routine and aseptic donning of sterile gloves. Subsequently, the fingertips of 43 nurses were cultured before and after the casual donning of nonsterile gloves over unwashed hands and before and after a strict antiseptic hand washing. Fingertip cultures were plated directly on agar, incubated for 24 hrs, and counted and recorded as the number of colony-forming units (cfu) for each hand. Different colony types were then subcultured. MEASUREMENTS AND MAIN RESULTS: Hand washing with antiseptic reduced colonization from 84 to 2 cfu (p < .001). The proportion of cases with > or = 200 cfu/hand was reduced from 30% to 9%. Aseptic or casual donning of sterile gloves, with or without prior antiseptic hand washing, resulted in consistently low glove counts between 0 and 1.25 cfu. Nonsterile gloves casually donned over washed or unwashed bare hands diminished the bioburden to 2.17 and 1.34 cfu, respectively. No qualitative difference was found in the microorganisms recovered from gloved or bare hands. CONCLUSIONS: Antiseptic hand washing and the use of nonsterile gloves over unwashed hands confer similar reductions in the number of microorganisms. There is no additional benefit with the use of aseptic donning technique, prior antiseptic hand washing, or the use of individually packaged sterile gloves.

Asepsis↗

PubMed1995

Eicosanoid production in rabbit tracheal epithelium by adenine nucleotides: mediation by P2-purinoceptors.

Adenosine triphosphate (ATP) acting through epithelial nucleotide receptors exerts multiple physiologic actions on airway mucociliary clearance and caliber. However, the effect of ATP on arachidonate metabolism in the airway remains unknown. In this study, the ability of ATP to regulate eicosanoid production was studied in vitro in full-thickness rabbit tracheal strips and separately in rabbit epithelial explant cultures. In the freshly isolated strips, ATP increased prostaglandin E2 (PGE2) release in a dose-dependent fashion, with an activation threshold at 10 microM ATP and a 3.5-fold increase in PGE2 output at 1 mM ATP. Epithelium removal decreased 1 mM ATP-evoked PGE2 release by 68%. Reverse-phase, high-pressure liquid chromatography (HPLC) of media from 3H-arachidonic acid-incubated epithelial explants exposed to 1 mM ATP demonstrated increased output of the cyclooxygenase products PGE2 and prostaglandin F2a (PGF2a). Other identifiable eicosanoids did not increase. The concentration-response for ATP-induced PGE2 release by explants was similar to that of tracheal strips. PGE2 release by 1 mM ATP was 27% of that elicited by ionomycin (10 microM) and was markedly inhibited by indomethacin (10 microM). Purinoceptor agonist-stimulated PGE2 release by the epithelium yielded a rank order of potency of uridine triphosphate (UTP) > or = ATP > 2-methylthio-ATP (2MeSATP) >> alpha,beta-methyleneadenosine-5'-triphosphate (AMP-CPP) > or = adenosine. These results indicate that ATP, acting primarily through an epithelial P2-purinoceptor similar to the P2a subtype, stimulates eicosanoid metabolism in rabbit airway epithelium via the cyclooxygenase pathway, producing PGE2 as the predominant species.

Adenosine Triphosphate↗

PubMed1995

A comparison of European and American dosing regimens of schizophrenic patients on clozapine: efficacy and side effects.

We present a comparison of the results from two studies of patients on clozapine. The American study (n = 84; Hillside Hospital, Glen Oaks, NY) and the European study (n = 63; Innsbruck University Clinics, Innsbruck, Austria) both examine efficacy and side effects in schizophrenic patients on this atypical neuroleptic. There is a very substantial difference in the dosing regimen used on both continents and this is reflected in the studies reported. A question with major clinical implications is whether the higher doses commonly used in the United States lead to a better outcome or a different profile of side effects. Outcome as a function of serum concentration will be examined. Results confirm a lower dose, lower clozapine blood level, and a lesser degree of side effects in the Austrian cohort when compared to the American sample. Surprisingly, the clinical efficacy of the lower dosing regimen was superior to the higher dose. Reasons for this anomaly are explored.

Adult↗

PubMed1995

The effects of corticosteroids on lymphocyte recirculation in humans: analysis of the mechanism of impaired lymphocyte migration to lymph node following methylprednisolone administration.

BACKGROUND: Steroid therapy profoundly inhibits lymphocyte migration into lymph nodes (LN), thereby disrupting lymphocyte recirculation. This study was undertaken in human subjects to examine two nonmutually exclusive hypotheses proposed to explain this steroid effect: (1) steroids decrease the capacity of LN high endothelial venules (HEV) to support lymphocyte adherence; and/or (2) steroids alter the expression of lymphocyte adhesion molecules specific for entry into LNs. METHODS: Human LNs were obtained from cadaveric organ donors before and after methylprednisolone infusion and examined for their capacity to support lymphocyte adherence using an in vitro lymphocyte-HEV adherence assay. Additionally, six healthy volunteers underwent infusions of saline (placebo) and methylprednisolone (3 mg/kg in saline), and peripheral blood lymphocytes were isolated before, immediately after, and at 1, 2, 4, 8, 24, and 48 hours following infusions. At each timepoint, flow cytometric analysis of lymphocyte L-selectin, CD44, and LFA-1 expression was assessed. Short-term tissue culture studies were also performed to examine the direct effects of steroids on the expression of these lymphocyte proteins. RESULTS: LNs obtained from organ donors before and after steroid infusion displayed no differences in the capacity of HEV to support lymphocyte adherence. In controlled steroid infusion studies, lymphopenia was observed within 1 hour and persisted for 8 hours. Cells isolated during the period of lymphopenia did not adhere to LN HEV, and there was a marked decrease in both the percentage and mean fluorescence intensity level of L-selectin+ lymphocytes; minor changes were observed in the percentage of CD44+ and LFA-1+ cells, while the mean fluorescence intensity level decreased for CD44+ cells and increased for LFA-1+ cells. All such changes in adhesion protein levels among circulating cells reversed with the resolution of lymphopenia. However, in tissue culture experiments, steroids did not alter the expression of lymphocyte adhesion proteins. CONCLUSIONS: The decreased migration of lymphocytes to LN following steroid administration is not due to changes in the capacity of HEV to bind lymphocytes, but results from decreases in the level of L-selectin expressed among circulating cells. Culture studies suggest that steroids do not directly alter lymphocyte adhesion protein expression. The possibility that these agents act indirectly by stimulating the release and/or promoting the activity of relevant biologic mediators affecting lymphocyte adhesion protein expression needs further exploration.

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