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Biomedical subjects

S Feldman

Publications and source records attributed to S Feldman.

At least 235 records · Page 13Linked to original sources
PubMed1985

Effects of neural stimuli on paraventricular nucleus neurones.

The electrical activity of 122 neurones mostly located within the parvocellular components of the hypothalamic paraventricular nucleus (PVN) was recorded in urethane-anaesthetized male rats. Spontaneous activity and responses to single-shock stimulation of the following sites were recorded: median eminence (ME), neurohypophysis (PIT), preoptic area (POA), nucleus accumbens (ACB), subiculum (SUB), sciatic nerve (ScN), and photic (Ph) stimulation. Stimulation of ME antidromically invaded 14% of the cells recorded, the spontaneous firing rate of these neurones was significantly slower than that of the rest of the population. The responses of the neurones identified as projecting to ME, to the above stimuli, were generally found to be in the same direction as for the whole population but the proportions of the majority responses were greater. Identified cells mainly responded with orthodromic excitation following POA, SUB, ScN, and Ph stimulation whereas ACB stimulation produced a greater proportion of inhibitiory responses. High degrees of convergence were found following afferent stimuli. The possibility that some of the neurones projecting to ME may be candidates for the corticotropin-releasing factor (CRF-) cells, is discussed.

Animals↗
PubMed1985

Similar hematologic changes in children receiving trimethoprim-sulfamethoxazole or amoxicillin for otitis media.

We report the hematologic changes in 90 black children who were randomized to receive a 10-day course of either trimethoprim-sulfamethoxazole (TMP-SMZ) or amoxicillin as therapy for acute otitis media. Absolute neutrophil counts less than 1500/mm3 developed at least once during the 23-day evaluation in 28 (57%) of the 49 children given TMP-SMZ and in 22 (54%) of the 41 who received amoxicillin. Incidence of leukopenia, thrombocytopenia, and anemia was negligible in both groups. Pancytopenia did not occur in any child. Absolute neutrophil counts had increased to greater than 1500/mm3 by the end of the study period in all of the patients but six, whose recovery required an additional 1 to 63 days. Decreased neutrophil counts in antibiotic-treated subjects remained within the range of findings for healthy black children, suggesting that a count less than 1500/mm3 may be an inappropriate criterion for an adverse drug effect. Neither TMP-SMZ nor amoxicillin produced hematologic effects that would detract from their continued use in children with infections caused by antibiotic-susceptible organisms.

Amoxicillin↗
PubMed1985

Mycotic cervical lymphadenitis following oral mucositis in children with leukemia.

Four children developed mycotic cervical lymphadenitis while receiving cytotoxic chemotherapy for acute leukemia. Neutropenia, oral mucositis, and broad-spectrum antibiotic administration preceded the appearance of lymphadenitis in each case. Enlarged tender cervical lymph nodes of mycotic origin were not clinically distinguishable from lymphadenitis of bacterial or viral origin. Although cervical lymphadenitis was the initial clinical manifestation of deep fungal infection, computerized tomography of the chest and abdomen subsequently demonstrated asymptomatic pulmonic, splenic, or hepatic lesions characteristic of fungal abscesses in all four children. These findings demonstrate the importance of microbiologic identification of the etiologic agents of cervical lymphadenitis following mucositis and neutropenia in children with leukemia.

Acute Disease↗
PubMed1985

Pharmacokinetics of cefotaxime in the postpartum patient.

A scarcity of pharmacokinetic data are available on cefotaxime in the obstetric patient. Fifteen patients received either 1 or 2 gm of cefotaxime after cesarean section. After intravenous administration of the designated dose, serial blood samples were analyzed for cefotaxime and its active metabolite, desacetyl cefotaxime (DCTX), by high-pressure liquid chromatography. The mean (+/- SD) peak concentrations of cefotaxime were 14.1 +/- 7.9 micrograms/ml and 40.0 +/- 32.5 micrograms/ml for the 1- and 2-gm dosage regimens, respectively. Detectable trough concentrations were 0.87 +/- 0.24 and 1.0 +/- 0.26, respectively, with many values falling below the sensitivity limits of the assay (0.5 micrograms/ml). The mean peak concentrations of DCTX for the two doses were 5.5 +/- 1.9 micrograms/ml and 10.9 +/- 6.2 micrograms/ml, respectively. Measurable trough levels for DCTX were more frequently identified, than for cefotaxime, at the end of the dosing interval due to an extended half-life as compared to its parent compound. Pharmacokinetic parameters of cefotaxime demonstrated large volumes of distribution and high clearance rates. Our data suggest altered pharmacokinetics of this agent in the obstetric patient when compared to previous studies in nonpregnant patients. This may be important in the seriously ill gravida where dosage adjustments in cefotaxime administration may be needed.

Adult↗
PubMed1985

Oral and intravenous trichloroethylene pharmacokinetics in the rat.

The pharmacokinetics of trichloroethylene (TCE) was studied in male Sprague-Dawley rats (300-350 g). TCE was administered intravenously and orally at doses of 5, 10, and 25 mg/kg to nonfasted rats and orally at 10 mg/kg to rats fasted for 8-10 h. The disappearance of TCE from the blood of intravenously dosed animals was best described by a two-compartment open pharmacokinetic model. The volume of the central compartment (Vc) approximated the rats' blood volume (50-70 ml/kg). The volume distribution (V beta) and total body clearance (CLT) decreased with increase in dose. The terminal half-life (t1/2) was about 120 min and was not affected by increases in dose. TCE was rapidly absorbed after oral dosing, with blood concentrations peaking between 6 and 10 min. The oral to intravenous bioavailability of TCE was 60-80% in nonfasted animals. The terminal t1/2 in fasted, orally dosed rats was identical to that when fasted rats were given the same dose intravenously. In fasted rats, bioavailability of an oral dose was greater than 90%, and peak levels in the blood were 2-3 times as high as in nonfasted rats.

Administration, Oral↗
PubMed1985

Use of influenza A virus vaccines in seronegative children: live cold-adapted versus inactivated whole virus.

We report the safety and antigenicity of influenza A vaccines in seronegative children one to seven years of age. A natural H1N1 challenge that occurred shortly after completion of the vaccination program permitted an evaluation of efficacy. Twenty-eight subjects were inoculated with live cold-adapted (ca) influenza A/Washington/897/80 (H3N2), 29 with ca influenza A/California/10/78 (H1N1), 24 with inactivated whole-virus influenza A/Bangkok/79 (H3N2), and 30 with a placebo. The ca vaccines were well tolerated, whereas the inactivated vaccine caused adverse reactions in about one-third of the children. Fifty-seven percent of the ca H1N1 recipients showed serological responses, contrasted with 84% and 100% of subjects receiving the ca or inactivated H3N2 vaccines, respectively. None of the 16 children with induced H1N1 antibody developed clinically apparent influenza-like illness, compared with eleven of the 51 initially seronegative children who did not receive the ca H1N1 vaccine and with four of the 12 who failed to respond. Results of the efficacy field trial suggest protection against infection and symptomatic illness in children inoculated with ca H1N1, despite its failure to stimulate high levels of hemagglutinin-inhibiting antibody.

Antibodies, Viral↗
PubMed1985

Prevention of experimental allergic encephalomyelitis by anterior hypothalamic lesion in rats.

Bilateral electrical lesions were performed in the anterior hypothalamus (AH) and hippocampus (HC) of female Lewis rats. AH but not HC lesions were found to inhibit the appearance of clinical signs typical of experimental allergic encephalomyelitis (EAE). The incidence of EAE was 17.2% and the duration was 1.33 +/- 0.07 days after AH lesions compared with an incidence of 85% and duration of 4.81 +/- 0.6 days in the controls. Destruction of the AH was followed by decreased levels of antibodies to myelin basic protein and increased reactivity of splenic lymphocytes to concanavalin A, but did not affect the extent of mononuclear cell infiltration within the brain and spinal cord.

Animals↗
PubMed1985

Neural pathways mediating adrenocortical responses.

The effects of hypothalamic deafferentations and brain lesions on adrenocorticotropin (ACTH) and corticosterone (CS) responses after neural stimuli were studied in rats. It was found that the various modalities are mediated by different neural pathways. Photic and acoustic stimuli utilize a posterior input, whereas the sciatic and olfactory modalities are mediated by anterior afferents and forebrain limbic structures. The effects of limbic extrahypothalamic structures on the hypothalamus are transmitted by both anterior and posterior inputs. The medial forebrain bundle (MFB) was found to have a differential role in the mediation of ACTH and CS responses. To identify the neurotransmitters involved, rats were injected with 6-hydroxydopamine in the MFB and 5,7-dihydroxytryptamine in the raphe nuclei. The depletion of hypothalamic norepinephrine and serotonin caused inhibition of the adrenocortical responses only after photic stimulation, and only of responses to limbic stimuli in the former group. In view of the location of corticotropin-releasing factor in the paraventricular nucleus, responses to afferent stimuli were studied in this region in identified neurons projecting to the median eminence. Stimuli that increased or decreased CS secretion facilitated or inhibited cell firing, respectively, thus demonstrating a possible electrophysiological correlate of neuroendocrine regulation.

5,7-Dihydroxytryptamine↗
PubMed1985

Drug absorption in spinal cord injury.

The absorption characteristics of drugs in spinal cord injury (SCI) were studied using an actively transported drug [riboflavin (RBF)] and a passively absorbed drug [acetaminophen (ACE)]. RBF absorption was studied following oral administration of 150mg RBF as 5'-phosphate flavin mononucleotide in ten clinically complete quadriplegic patients (C1 to C7, two to 15 months post-onset) and six control subjects matched for age, sex, and weight. Urinary excretion was measured under fasting (F) and nonfasting (NF) conditions for time to peak, peak excretion rate, and percent dose recovered. The results showed a significant difference (p less than 0.05) for all parameters between F and NF conditions for both the SCI and able-bodied groups. However, there was no significant difference for the same parameters between the two groups. ACE absorption was studied in five SCI clinically complete quadriplegic patients (C1 to C7, two to 15 months post-onset following the administration of a 650mg tablet. Serum samples were analyzed for ACE content and showed: time of peak, 1.35 +/- 0.6hr; maximum serum level, 6.8 +/- 2.68 micrograms/ml; half-life, 2.89 +/- 1.81hr; absorption lag time, 18.1 +/- 1.8min; area under the serum level-time curve, 21.8 +/- 6.7 micrograms/.hr/ml. When compared to able-bodied population data in the literature, there was a significant increase in the time to peak and lag time, and a decrease in the maximum ACE serum concentration obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1984

A temporal study of post-adrenalectomy increase in ACTH secretion in the rat: effect of various hypothalamic deafferentations.

Adult male rats, intact (N) or with complete (CHD), anterior (AHD), or posterior (PHD) hypothalamic deafferentations were bilaterally adrenalectomized. At 3, 6, 12 and 20 days post-adrenalectomy they were decapitated and trunk blood was collected for ACTH determinations. In N rats, ACTH markedly elevated up to 850 pg/ml. A similar ACTH response was found in PHD rats but the values were lower by approximately 20%. In contrast, in either AHD or CHD rats, ACTH responses were markedly attenuated and reached a plateau of about 350 pg/ml. These data suggest that: (1) neural inputs entering the medio-basal hypothalamus (MBH) from both the caudal and rostral directions are important for obtaining maximal ACTH responses following adrenalectomy; (2) at least part of this ACTH response is mediated by sites inside the MBH or in the pituitary.

Adrenal Glands↗
PubMed1984

Comparative pharmacokinetics of cefoxitin in postpartum normotensive and pregnancy-induced hypertensive patients.

Limited pharmacokinetic data exist on cefoxitin, a semisynthetic cephamycin antibiotic, in the obstetric patient. Thirteen normotensive and five subjects with severe pregnancy-induced hypertension were identified within the first two postpartum days after cesarean section. After a 2 gm intravenous infusion, serial samples of blood were obtained and analyzed for cefoxitin by high-pressure liquid chromatography. Peak cefoxitin concentrations after infusion were 53.3 +/- 18.6 and 50.8 +/- 25.2 micrograms/ml for the normotensive and pregnancy-induced hypertensive groups, respectively. The only significant difference in pharmacokinetic parameters between these groups was a higher serum trough concentration of cefoxitin in the patients with pregnancy-induced hypertension as compared to the normotensive group. Because of diminished trough levels in our study patients, attention may need to be given to the adjustment of dosages in postpartum women with serious infections.

Adult↗
PubMed1984

Intestinal absorption and metabolism of 6-mercaptopurine in the rat small intestine.

The intestinal absorption of 6-mercaptopurine was examined in the rat by in vitro and in situ techniques for the purpose of establishing absorption characteristics which might explain the poor systemic oral availability of this drug. Experiments were designed to evaluate the significance of intestinal metabolism and active secretion processes. Since mucosal/serosal drug concentration gradients across in vitro segments were not significantly different (P greater than 0.05) for everted and noneverted preparations, with values of 1.21 +/- 0.27 and 0.91 +/- 0.12, respectively, it was concluded that active secretion or absorption mechanisms were absent. Varying the concentration of 6-mercaptopurine from 0.24 to 5.88 mM demonstrated saturability of the biotransformation of 6-mercaptopurine to 6-thiouric acid with a maximum rate of 1.6 X 10(-5) mmoles per min g for jejunal portions. Distal segments displayed 85% higher rates of biotransformation at concentrations of 1.47 mM. Inclusion of allpurinol (2 mM) completely inhibited biotransformation. With in situ loops perfused with 1.47 mM drug, collection of mesentery blood showed that absorption rates of 6-thiouric acid were 0.67 that of the parent drug.

Animals↗
PubMed1984

Deafferentation reduces the hypothalamic cell nuclear binding of corticosterone.

Hypothalamic or hippocampal slices and adenohypophyseal lobes taken from adrenalectomized male rats either intact or with complete hypothalamic deafferentation (CHD) were incubated in Krebs-Ringer bicarbonate buffer in the presence of either 10-50 nM [3H]corticosterone or [3H]dexamethasone with or without 500-fold excess of unlabeled steroid for 15-60 min. The cell nuclear binding in the hypothalamic slices from the CHD rats, was markedly reduced by approximately 50% but remained unchanged in the hippocampi and in the pituitaries. These results suggest that brain sites outside the mediobasal hypothalamus are important for the regulation of corticosterone binding in the hypothalamus.

Adrenalectomy↗
PubMed1984

Inhibition in corticotrophin and corticosterone secretion following photic stimulation in rats with 6-hydroxydopamine injection into the medial forebrain bundle.

Changes in corticotrophin (ACTH) and corticosterone (CS) serum levels, were examined in rats in which either 6-hydroxydopamine or vehicle were injected into the medial forebrain bundle (MFB) and which were sacrificed by decapitation 14 days later. The injection of the neurotoxin, which depleted very significantly the norepinephrine (NE) content of the mediobasal hypothalamus, elevated significantly the basal levels of serum ACTH and CS, but inhibited the rise in the levels of these hormones following photic stimulation. These results would suggest that the hypothalamic NE system has normally an inhibitory effect on basal ACTH and CS secretion and that the hormonal response to photic stimulation is mediated by that system and possibly by NE MFB fibers.

Adrenocorticotropic Hormone↗