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Biomedical subjects

S Feldman

Publications and source records attributed to S Feldman.

At least 73 records · Page 4Linked to original sources
PubMed1997

Incidence and natural history of chemically defined varicella-zoster virus hepatitis in children and adolescents.

Of 786 children and adolescents enrolled in a multicenter trial of acyclovir for chickenpox, 27 (3.4%) met the case definition of varicella-zoster virus (VZV) hepatitis (serum aspartate aminotransferase level > or = 100 U/l). The clinical and cutaneous manifestations of chickenpox in the 15 placebo recipients with this complication did not differ significantly from those in 45 matched controls (p > 0.05), indicating that liver involvement by VZV is not a consequence of more extensive disease. Although acyclovir modified the course of chickenpox overall, it did not prevent VZV hepatitis; that is, the proportions of affected subjects with liver involvement postenrollment did not differ significantly between the drug and placebo recipients (50% vs 80%, p > 0.05). Serum aspartate aminotransferase levels that were elevated on day 4 postenrollment had returned to normal (< or = 60 U/l) by day 28 in 88% of the placebo group and in 83% of the drug-treated group. With 2 exceptions, all values were normal by 88 days postenrollment. We conclude that chemically defined VZV hepatitis is an infrequent, self-limiting complication of chickenpox in otherwise healthy children and adolescents.

Acyclovir↗
PubMed1996

Involvement of amygdalar alpha adrenoceptors in hypothalamo-pituitary-adrenocortical responses.

We have previously demonstrated that the facilitatory effect of the amygdala on the hypothalamo-pituitary-adrenocortical (HPA) axis responses to photic stimulation depends on the presence of norepinephrine (NE) in this region. In the present study we investigated the effect of alpha 1- and beta-adrenoceptor blockers, injected into the central amygdala nucleus, on the HPA responses. In intact freely moving rats, short photic stimulation caused depletion of CRH-41 from the median eminence, due to its release into the portal circulation and a rise in serum ACTH and corticosterone levels. This effect was markedly inhibited by injection of prazosin, an alpha 1-adrenoceptor blocker, but atenolol, a beta 1 blocker, had no effect. These data further indicate that amygdala NE plays a role in the activation of the HPA axis following neural stimuli and that this effect is mediated by alpha 1-adrenoceptors in the central amygdala.

Adrenal Cortex↗
PubMed1996

Lecithin:cholesterol acyltransferase overexpression generates hyperalpha-lipoproteinemia and a nonatherogenic lipoprotein pattern in transgenic rabbits.

Cholesterol esterification within plasma lipoprotein particles is catalyzed by lecithin:cholesterol acyltransferase (LCAT). The impact of the overexpression of this enzyme on plasma concentrations of the different plasma lipoproteins in an animal model expressing cholesteryl ester transfer protein was evaluated by generating rabbits expressing human LCAT. A 6.2-kilobase human genomic DNA construct was injected into the pronuclei of rabbit embryos. Of the 1002 embryos that were injected, 3 founder rabbits were characterized that expressed the human LCAT gene. As in mice and humans, the principal sites of mRNA expression in these rabbits is in the liver and brain, indicating that the regulatory elements required for tissue-specific expression among these species are similar. The alpha-LCAT activity correlated with the number of copies of LCAT that integrated into the rabbit DNA. Compared with controls, the high expressor LCAT-transgenic rabbits total and high density lipoprotein (HDL) cholesterol concentrations were increased 1.5-2.5-fold with a 3.1-fold increase in the plasma cholesterol esterification rate. Analysis of the plasma lipoproteins by fast protein liquid chromatography indicates that these changes reflected an increased concentration of apolipoprotein E-enriched, HDL1-sized particles, whereas atherogenic apolipoprotein B particles disappeared from the plasma. The concentrations of plasma HDL cholesterol were highly correlated with both human LCAT mass (r = 0.93; p = 0.001) and the log LCAT activity (r = 0.94; p < 0.001) in the transgenic rabbits. These results indicate that overexpression of LCAT in the presence of cholesteryl ester transfer protein leads to both hyperalpha-lipoproteinemia and reduced concentrations of atherogenic lipoproteins.

Animals↗
PubMed1996

Norepinephrine depletion in the amygdala inhibits CRF-41, ACTH, and corticosterone responses following photic simulation.

The effects of amygdaloid norepinephrine depletion by 6-hydroxydopamine on changes in corticotropin releasing factor-41 (CRF-41) and serum adrenocorticotropic hormone (ACTH) and corticosterone levels, following neural stimuli were investigated. In intact animals, photic or acoustic stimulation caused CRF-41 depletion from the median eminence and a rise in serum ACTH and corticosterone levels. In rats with amygdalar norepinephrine depletion there were no changes in basal CRF-41, ACTH, or corticosterone levels. However, the above responses of the hypothalamo-pituitary adrenocortical axis were blocked following photic, but not acoustic, stimulation. These results indicate that the facilitatory role of the amygdala on the above responses following photic stimulation depends on the presence of norepinephrine in this region.

Acoustic Stimulation↗
PubMed1996

Maternal-fetal pharmacokinetics of zidovudine in rats.

The disposition of zidovudine (AZT) was investigated in near-term (day 20) pregnant rats after intravenous bolus administration of AZT at 50 mg/kg. A compartmental pharmacokinetic model was developed to describe AZT concentrations in maternal plasma (1), placenta (2), fetus (3), amniotic fluid (4), and the maternal tissue compartment (5). Model equations were fitted simultaneously to all concentration data by NONLIN least-squares regression. The model that best described the AZT concentration data (F test, AIC, sum of weighted squared residuals) incorporated bidirectional transfer between maternal plasma reversible placenta, placenta reversible fetus, placenta reversible amniotic fluid, and maternal plasma reversible tissue compartment. Transfer rate constants (1/h) were as follows: k12, 0.58 +/- 0.41; k21, 47.64 +/- 46.61; k23, 67.50 +/- 42.03; k32, 13.09 +/- 8.80; k24, 0.62 +/- 0.03; k42, 0.32 +/- 0.06; k15, 5.75 +/- 7.00; k51, 4.12 +/- 1.01; and k10, 1.51 +/- 0.80. AZT rapidly distributed into tissue and placenta compartments. However, AZT accumulated more slowly into amniotic fluid. Intercompartmental distributional clearances suggest that the mechanism of maternal-placental, placental-fetal, and fetal-amniotic fluid transfer of AZT was by passive diffusion. This maternal-fetal model for AZT may offer a useful approach for describing the placental transfer kinetics of other antiviral nucleosides as well.

Amniotic Fluid↗
PubMed1996

Drug interactions with neuromuscular blockers.

Drugs administered to patients undergoing anaesthesia may complicate the use of the neuromuscular blockers that are given to provide good surgical conditions. The various sites of interaction include actions on motor nerve conduction and spinal reflexes, acetylcholine (ACh) synthesis, mobilisation and release, sensitivity of the motor end plate to ACh and the ease of propagation of the motor action potential. In addition, many drugs affect the pharmacokinetics of neuromuscular blockers, especially as most drugs depend to a greater or lesser extent upon renal excretion. The clinically significant interaction between nondepolarisers and depolarisers may be due to blockade of the pre-synaptic nicotinic receptors by the depolarisers, leading to decreased ACh mobilisation and release. Synergism between nondepolarisers probably results from post-synaptic receptor mechanisms. Volatile anaesthetic agents affect the sensitivity of the motor end-plate (post-synaptic receptor blockade) in addition to having effects on pre-synaptic nicotinic function. The effects of nondepolarisers are likely to be potentiated and their action prolonged by large doses of local anaesthetics due to depression of nerve conduction, depression of ACh formation, mobilisation and release, decreases in post-synaptic receptor channel opening times and reductions in muscular contraction. Most antibacterials have effects on pre-synaptic mechanisms. Procainamide and quinidine principally block nicotinic receptor channels. Magnesium has a marked inhibitory effect on ACh release. Calcium antagonists could theoretically interfere with neurotransmitter release and muscle contractility. Phenytoin and lithium decrease ACh release, whilst corticosteroids and furosemide (frusemide) tend to increase the release of the transmitter. Ecothiopate, tacrine, organophosphates, propanidid, metoclopramide and bambuterol depress cholinesterase activity and prolong the duration of the neuromuscular block. The probability of clinically significant interactions increases in patients receiving several drugs with possible effects on neuromuscular transmission and muscle contraction.

Adrenal Cortex Hormones↗
PubMed1996

Combined orthodontic and prosthetic therapy. Special considerations.

The adult patient may present with a complex medical and dental history. Comprehensive treatment planning with appropriate consultation among the restorative dentist and other dental specialists is a prerequisite for a successful treatment outcome. This article reviewed the role of orthodontic treatment in the restoration of the partially edentulous patient. The case illustrations presented show the value of collaborative efforts in a multidisciplinary team approach. Although there may be initial reluctance on the part of some patients to seek multiple specialty consultations, the rewards are great for the patient and the dentists who subscribe to this treatment philosophy.

Adolescent↗
PubMed1995

The role of limbic structures in the modulation of ACTH responses following adrenalectomy.

The role of the HIPP, DF, and the lateral SPT as well as of the central AMG nucleus in ACTH hypersecretion following Adex, was studied in male rats. In animals with bilateral dorsal hippocampectomy, DF section, or SPT lesions there was a much greater increase in ACTH hypersecretion when compared to Adex alone. Implants of CS in the paraventricular nucleus of the hypothalamus prevented the rise in serum ACTH following Adex, and this effect was reversed by hippocampectomy. Bilateral lesions in the AMG prevented the Adex-induced rise of serum ACTH. These results indicate that the dorsal HIPP and its efferent pathways to the hypothalamus have normally an inhibitory effect on Adex-induced ACTH secretion. Their removal permits an elevated ACTH hypersecretion as well as attenuation of the CS feedback effect. The central AMG nucleus, which has a facilitatory effect on the hypothalamopituitary-adrenocortical axis, can also modulate ACTH secretion following Adex.

Adrenalectomy↗
PubMed1995

Posterior hypothalamic deafferentation or 5,7-dihydroxytryptamine inhibit corticotropin-releasing hormone, ACTH and corticosterone responses following photic stimulation.

The effect of posterior hypothalamic deafferentation (PHD) or hypothalamic serotonin (5-HT) depletion by 5,7-dihydroxytryptamine on corticotropin-releasing hormone (CRH), ACTH and corticosterone (CS) responses, following photic stimulation, was investigated in male rats. In intact animals, photic stimulation caused median eminence (ME) CRH depletion and a rise in serum ACTH and CS levels. In rats with PHD, in which previous studies have demonstrated 5-HT depletion, or with neurotoxin induced hypothalamic 5-HT reduction, these responses were markedly inhibited. This indicates that the blockage in the release of ME CRH into the portal circulation in rats with hypothalamic 5-HT depletion is responsible for the inhibition of the pituitary-adrenocortical responses following photic stimulation.

5,7-Dihydroxytryptamine↗
PubMed1995

Predicting endometrial cancer among older women who present with abnormal vaginal bleeding.

We studied 203 women ages 49 or over who presented with abnormal vaginal bleeding and who underwent either endometrial biopsy or dilation and curettage at the Brigham and Women's Hospital. Using information from the clinical history, we predicted their risk for endometrial cancer (36 patients) or complex endometrial hyperplasia (16 patients). Factors independently associated with endometrial cancer/complex hyperplasia included age 70 or older (OR = 9.1, P = 0.0001), diabetes (OR = 3.7, P = 0.02), and nulliparity (OR = 2.7, P = 0.02). After adjusting for age, menopause was borderline significant (OR = 2.6, P = 0.07). Our data estimated a risk of endometrial cancer/complex hyperplasia of 87% for a woman possessing all of these factors, and a risk of less than 3% if she had none of them. Our model provides an inexpensive, simple means for assessing the risk of endometrial cancer and complex hyperplasia in the post- or perimenopausal woman with abnormal bleeding.

Age Factors↗
PubMed1995

Stapled stricturoplasty for Crohn's disease. A new technique.

PURPOSE: Stricturoplasty was originally used to treat multiple fibrotic strictures of tuberculosis. As the pendulum of treatment of Crohn's disease swung toward conservatism and bowel preservation, stricturoplasty was performed in Crohn's disease. Stricturoplasty can be used when there is limited, well-localized disease and should be avoided in the presence of grossly inflamed or infected material. We describe a new technique of stricturoplasty. METHODS: Typically stricturoplasty is performed in a manner similar to a Heineke-Mikulicz pyloroplasty. A stapled stricturoplasty technique has been previously described, but in actuality these are more similar to a bypass procedure. Our technique uses a stapled, open technique similar to the triangulating method of bowel anastomosis. This was performed in one patient to correct six strictures. RESULTS: Our patient did well postoperatively and developed no significant complications. He has no evidence of recurrent strictures. CONCLUSION: We describe a stapled stricturoplasty technique that is truly a stricturoplasty because the bowel lumen is increased; it is similar to the triangulating method of end-to-end stapled bowel anastomosis. It is safe, efficient, and effective. Additionally, it allows radiographic location of the stricturoplasty site, thus allowing determination of effectiveness of the procedure as well as recurrence.

Constriction, Pathologic↗
PubMed1995

Limbic pathways and hypothalamic neurotransmitters mediating adrenocortical responses to neural stimuli.

One of the major phenomena related to the stress response is the activation of the hypothalamo-pituitary-adrenocortical (HPA) axis. This axis consists of corticotropin releasing factor-41 in the paraventricular nucleus of the hypothalamus (PVN), which in response to a variety of stimuli is released into the portal circulation and stimulates pituitary ACTH secretion and subsequently adrenocortical discharge. The mechanisms involved in the activation are not uniform and the responses to various stimuli are mediated by different neural pathways. Since extrahypothalamic limbic structures play a significant role in the HPA function, it is the purpose of this review to describe the neural pathways between the hippocampus, septum and amygdala and the hypothalamus in relation to adrenocortical activity and the differential role of the medial forebrain bundle as well as the effects of various hypothalamic deafferentation on the transmission of the neural impulses to the hypothalamus. Also, the importance of norepinephrine and serotonin in the activation of the HPA axis will be delineated.

Adrenal Cortex↗