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Biomedical subjects

S Feldman

Publications and source records attributed to S Feldman.

At least 181 records · Page 10Linked to original sources
PubMed1989

Medication errors in neonatal and paediatric intensive-care units.

In a 4-year prospective quality assurance study, 315 iatrogenic medication errors were reported among the 2147 neonatal and paediatric intensive-care admissions, an error rate of 1 per 6.8 admissions (14.7%). The frequency of iatrogenic injury of any sort due to a medication error was 66/2147 (3.1%)--1 injury for each 33 intensive-care admissions. 33 (10.5%) errors were potentially serious, 32 (10.2%) caused mild patient injuries, and 1 patient had acute aminophylline poisoning after receiving five intravenous doses of the drug at a dosage ten times higher than prescribed, owing to a calculation error during dilution. A longitudinal monitoring system helps to identify iatrogenic complications due to medication errors and may help in implementing preventive measures.

Child↗
PubMed1989

Paraventricular nucleus neuronal responses following electrical stimulation of the midbrain dorsal raphe: evidence for cotransmission.

In order to determine the responses of paraventricular nucleus neurones following activation of central serotonergic pathways, single unit activity was recorded and responses following electrical stimulation of the midbrain dorsal raphe nucleus were examined. Excitation was recorded from approximately 50% of the cells, independent of whether they were antidromically identified as projecting to the median eminence or unidentified. Approximately 20% of cells were inhibited by the stimulation, the majority of these being unidentified. Parachlorophenylalanine-induced inhibition of serotonin synthesis reduced hypothalamic serotonin levels by 77% and caused a significant reduction in the proportion of cells excited by the stimulation, whereas the inhibitory responses were not affected. Intracerebroventricular administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine, which caused similar reductions in hypothalamic serotonin content (77%), reduced still further the proportion of excitatory responses and also reduced the proportion of cells inhibited by the stimulation. The data obtained suggest that serotonin acts as an excitatory neurotransmitter in the paraventricular nucleus; this is discussed particularly with respect to the regulation of the hypothalamo-hypophysial-adrenocortical axis. The loss of inhibitory responses in 5,7-dihydroxytryptamine treated, as opposed to the parachlorophenylalanine treated, animals suggests that the serotonergic fibers innervating the recorded cells may contain a cosecreted substance that may have important physiological actions in the control of neuronal activity in the region recorded.

5,7-Dihydroxytryptamine↗
PubMed1989

Adrenoceptor specificity in the central regulation of adrenocortical secretion.

Electrical stimulation of the ventral noradrenergic ascending bundle, through chronically implanted electrodes, resulted in significant elevations of the levels of plasma corticosterone in rats. Injection of either alpha 1- or alpha 2-adrenergic antagonists, at doses of 20 nmol, through chronic cannulae, implanted above the dorsal aspect of the hypothalamic paraventricular nucleus prior to stimulation of the ventral noradrenergic ascending bundle attenuated the stimulation-evoked increases in corticosterone in plasma levels. For alpha 1-antagonists, ergotamine tartrate was more effective than was prazosin hydrochloride and for alpha 2-antagonists, yohimbine hydrochloride was more effective than tolazoline hydrochloride; these results being consistent with the pharmacological binding characteristics. The beta-antagonist, propranolol hydrochloride was without effect upon the stimulation-evoked increases in levels of corticosterone in plasma. Injection of 6-hydroxydopamine hydrobromide into the paraventricular nucleus, a few days before the stimulation, prevented the corticosterone response. In rats with cannulae in the paraventricular nucleus alone, noradrenaline bitartrate (10 and 20 nmol) increased levels of corticosterone in plasma in a dose-dependent manner, as did the postulated co-transmitter, neuropeptide Y, at doses of 10 and 20 pmol. Noradrenaline (10 nmol) and neuropeptide Y (10 pmol), administered together, were found to potentiate each other. The alpha 1-agonist, 1-phenylephrine hydrochloride, and the alpha 2-agonist, clonidine hydrochloride, significantly increased levels of corticosterone in plasma as did the beta-agonist, isoproteronol hydrochloride. The data obtained demonstrate a facilitatory action of noradrenaline at the level of the paraventricular nucleus upon adrenocortical secretion and that this effect was probably mediated by both alpha 1- and alpha 2-adrenoceptors, the role of beta-receptors being unclear.2 +

Adrenal Cortex↗
PubMed1989

Catecholaminergic projections to tuberoinfundibular neurones of the paraventricular nucleus: II. Effects of stimulation of the ventral noradrenergic ascending bundle: evidence for cotransmission.

In order to further elucidate the neural mechanisms underlying the control of adrenocortical secretion, responses of paraventricular nucleus (PVN) tuberoinfundibular neurones were examined following stimulation of the ventral noradrenergic ascending bundle (VNAB). Stimulation at low frequencies (0.5/5 Hz) excited the majority (52/64, 81%) of cells but only 15 showed a clear-cut, stimulus-locked, activation with onset latency of 44.5 +/- 10.0 msec and offset at 71.9 +/- 11.3 msec: the remaining 37 excited cells showed overall increases in firing after delivery of 5-10 stimuli. High frequency (50 Hz) trains of stimuli reversed the direction of response to inhibition for 14/52 of the excited cells. Inhibition of (nor)adrenaline synthesis by alpha-methylparatyrosine was without effect upon the firing of cells examined or the distribution and latencies of their responses following low frequency stimulation; high frequency trains reversed the response direction of only 4/35 cells, (p less than 0.05 vs. control rats; chi 2-test). Intracerebroventricular administration of 6-hydroxydopamine, a catecholaminergic neurotoxin, reduced the proportion of cells excited by the stimulation (10/47; p less than 0.005; chi 2-test). Unit responses to painful somatosensory stimuli were recorded from the majority of the cells tested (74%), except following 6-hydroxydopamine treatment, when only 38% were excited (p less than 0.005; chi 2-test). The results demonstrate that the VNAB provides an excitatory input to the PVN and that noradrenaline is probably responsible for this effect but a cotransmitter (neuropeptide Y?) may also be responsible for the observed excitatory responses. Inhibitory responses following high frequency stimulation were probably also mediated by (nor)adrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1989

Pharmacokinetics of intravenous immunoglobulin in very low birth weight neonates.

We studied the pharmacokinetics of single doses of intravenous immunoglobulin (IVIG) of 1000, 750 and 500 mg/kg administered to 21 neonates with birth weights from 750 to 1500 g. No adverse effects were detected. Mean pharmacokinetic values for the large, intermediate and small dose groups, respectively, were: elimination half-life, 19.6, 28.7 and 22.1 days; clearance, 5.2, 5.6 and 3.7 ml/kg/day; volume of distribution, 151, 255 and 130 ml/kg. Mean peak IgG concentrations in serum were 1826, 1476 and 1257 mg/dl for the large, intermediate and small dose groups, respectively. Mean IgG on post-infusion Days 1 to 28 were similar for the intermediate and small dose groups but were higher in the larger dose group. Both large and intermediate doses achieved larger increases in IgG over preinfusion values (delta IgG) than the small dose. The differences in delta IgG between the large and intermediate doses were less notable. The wide variability observed indicates that individualization of intravenous immunoglobulin dosage will be required in these patients.

Drug Combinations↗
PubMed1989

Mixed fusobacterium and actinomyces pulmonary infection. Case report.

This is a report of a twelve-year-old black male who presents a history of left neck pain, left shoulder pain, weight loss and minimal fever. The admission diagnosis was a malignancy, supported by radiographic findings of consolidation of left lower and left upper lobes and periosteal new bone formation along the inferior aspects of the left second, third and fourth ribs. Open biopsy of the chest wall revealed a large abscess cavity. Subsequent cultures on anaerobic blood agar plates grew Actinomyces and Fusobacterium. The patient was treated with penicillin and improved clinically. This case emphasizes the need to culture tissue specimens for a wide array of organisms, including those not commonly seen today. A high index of suspicion is required for the diagnosis of anaerobic infections. Mixed anaerobic infections, including actinomyces, although uncommon in children, should be considered in the etiology of an intrathoracic mass.

Actinomycosis↗
PubMed1988

Vancomycin, ticarcillin, and amikacin compared with ticarcillin-clavulanate and amikacin in the empirical treatment of febrile, neutropenic children with cancer.

We assessed two antibiotic regimens--vancomycin, ticarcillin, and amikacin, as compared with a vancomycin placebo, ticarcillin-clavulanate, and amikacin--as initial empirical therapy for febrile, neutropenic children with cancer. In a randomized, double-blind clinical trial, the planned 10-day treatment was unsuccessful in 15 percent of the vancomycin, ticarcillin, and amikacin group (n = 53), as compared with 38 percent of the group receiving ticarcillin-clavulanate and amikacin (n = 48) (P = 0.010). Of 10 episodes of breakthrough bacteremia, 9 (1 fatal) occurred in patients treated with ticarcillin-clavulanate and amikacin (P = 0.006). Each of the 10 microbial isolates was a gram-positive bacterium with similar susceptibilities to vancomycin and ticarcillin-clavulanate in vitro. Both regimens were well tolerated. None of the patients had detectable renal dysfunction, but those receiving vancomycin, ticarcillin, and amikacin were more likely to have twofold increases in serum hepatic-enzyme activity. Rashes consistent with the "red-man" syndrome occurred in three patients upon the infusion of vancomycin and in three others who received a placebo. We conclude that the combination of vancomycin, ticarcillin, and amikacin is more effective than ticarcillin-clavulanate and amikacin as empirical antibiotic therapy in clinical settings in which gram-positive bacteremias are a serious problem.

Adolescent↗
PubMed1988

Iontophoretic application of glucocorticoids inhibits identified neurones in the rat paraventricular nucleus.

In an electrophysiological study designed to examine the negative feedback effects of glucocorticoid hormones, we have recorded the electrical activity of 147 neurones in the paraventricular nucleus of the rat hypothalamus. 37 (25%) of the neurones were antidromically identified as projecting to the median eminence and were located at a mean depth of 2.35 +/- 0.08 mm from the base of the brain, corresponding with the corticotropin-releasing factor-rich region of the nucleus. The mean firing rate of the identified cells was 4.7 +/- 0.6 Hz which was not significantly different from that of adjacent, unidentified cells (5.6 +/- 0.6 Hz). Most (17/18, 94%) of these cells tested responded to painful somatosensory stimuli and 26 (74%) of the identified cells were inhibited by iontophoretic application of corticosterone and/or hydrocortisone, whereas only one cell was excited and 8 unaffected. Of the identified cells, only 18 (20%) were inhibited, 36 (41%) were excited and 34 (39%) were non-responsive. The proportion of inhibitory responses was thus greater for the identified cells (P less than 0.005; chi 2-test). For the identified cells, whose spontaneous activity was unaffected by glucocorticoid application, glutamate-evoked responses could usually be depressed by the application. The time course of all responses usually showed an immediate onset, increasing in magnitude and continuing for extended periods following cessation of iontophoresis. Electrophysiologically identified magnocellular neurones were also tested and the majority (7/12, 58%) of vasopressin-secreting neurons were also found to be inhibited, whilst all (8/8, 100%) of the oxytocin-secreting neurones were excited by the glucocorticoid application. These results may represent an electrophysiological correlate of the negative feedback control of adrenocortical secretion and are discussed within this context.

Action Potentials↗
PubMed1988

Measles and rubella antibody status in previously vaccinated children with cancer.

Measles and rubella antibody status were determined by ELISA for 115 previously vaccinated children with cancer. Seventy subjects were receiving chemotherapy, and 45 had successfully completed treatment for their malignancy. Overall, 18% of the subjects were seronegative for measles antibody and 8% for rubella antibody. Only 3% of patients lacked both. In general, seronegative individuals were over age 10 years. Subjects born before 1976 were significantly more likely to be seronegative to measles, 29% vs. 11% (P = 0.02) and to rubella, 16% vs. 4% (P = 0.03) than those born afterwards. Antibody status showed no apparent relationship to the duration of anticancer therapy. Stored serum samples were available for nine seronegative subjects, of whom five were initially seropositive and then lost antibody during or after the completion of anticancer therapy. Our observations suggest that cancer and its associated therapy interfere with antibody production. In view of the increasing survival rates for childhood cancers, additional studies are needed to assess the immune status of these subjects for all vaccine-preventable infections. Pending the outcome of further studies, we suggest that long-term survivors, particularly those born before 1976, or known to be vaccinated at less than 13 months of age, be tested after the completion of therapy for antibody to measles and rubella (and mumps). Also, immune serum globulin should be considered for any previously immunized patient with a close exposure to an active case of measles.

Antibodies, Viral↗
PubMed1988

Pharmacokinetic and phase I study of intravenous DON (6-diazo-5-oxo-L-norleucine) in children.

DON (6-diazo-5-oxo-L-norleucine), a glutamine antagonist, has been subjected to limited clinical trials since 1957. Use of the drug in adults has been curtailed due to sparse reports of effectiveness as well as its dose-limiting toxicities, i.e., severe nausea, vomiting and mucositis. In earlier studies, children given DON orally in combination with 6-mercaptopurine had significant prolongation of remission of acute leukemias during maintenance therapy. As DON is acid-labile and relatively unstable in solution, oral administration does not appear to be ideal for DON. In the trial described in this report, i.v. DON therapy was studied, using i.v. chlorpromazine to control vomiting, in 20 children, 17 of whom were evaluable following treatment at DON dose levels ranging from 150 mg/m2 to 520 mg/m2. Nausea and vomiting, the dose-limiting toxicity for adults, was controlled with chlorpromazine. Mucositis, which has also been observed in adults, did not occur in the children given DON i.v. A maximum tolerated dose was not defined; however, the projected maximum tolerated dose appears to be in excess of 450 mg/m2. DON was measured in plasma using a rapid-sampling HPLC procedure. The total body clearance, plasma t1/2, and area under the plasma concentration curve (AUC) were calculated using a noncompartmental method. The drug is rapidly cleared from plasma (t 1/2 = 3 h), and its volume of distribution is approximately twice that of total body water in children. These pharmacokinetic data, differ from that of adults reported by others. Specifically, the plasma t 1/2 for children is longer: total body clearance (Cl), and volume of distribution at steady state (Vss) are greater. In addition, no dose dependency of t 1/2, Cl or Vss was observed in this study, and the DON pharmacokinetics were linear and predictable. Five of nine children with acute leukemia showed improvement, though insufficient for classification as partial response, and five of eight children with solid tumors also showed improvement. Further trials using DON in combination with thiopurines or other agents appear indicated.

Adolescent↗
PubMed1988

Differential adrenocortical responses to neural stimuli following intracerebroventricular injection of nicotinic acetylcholine receptor antibodies in rats.

The aim of the present study was to investigate the involvement of central nervous system nicotinic receptors for acetylcholine in the adrenocortical responses to neural stimuli. Adult male rats received a daily intraventricular injection of partially purified nicotinic acetylcholine receptor antibodies (anti-AchR), obtained from a patient with myasthenia gravis, for 5 consecutive days. Control animals were treated similarly with immunoglobulins obtained from normal human serum. Blood samples were obtained under basal conditions or following photic, sciatic nerve stimulation, and acoustic stress. Treatment with anti-AchR increased basal ACTH and corticosterone levels (by approximately twofold) but inhibited the response to acoustic stress. The response to photic and sciatic nerve stimulation stress was not affected. This study demonstrated that nicotinic acetylcholine receptors may be differentially involved in the mediation of adrenocortical responses to neural stimuli.

Acoustic Stimulation↗
PubMed1988

Neurogenic stimuli alter preoptic area and amygdala unit activity: central effects of olfactory projections on paraventricular nucleus units.

Unit responses were recorded in the preoptic area and amygdala of conscious male rats during exposure to stressful neurogenic stimuli. Olfactory stimulation elicited increases in preoptic area activity on all occasions and also increased activity in the intercalating, medial, and basomedial nuclei of the amygdala, but not in other regions. Acoustic stimulation had less specific effects, even inhibiting unit activity in the central amygdala. A separate series of experiments using urethane-anesthetized rats was carried out to examine the effects of electrical stimulation of the medial amygdala and olfactory tubercle on single-unit activity within the hypothalamic paraventricular nucleus. Inhibition was the predominant response following olfactory tubercle stimulation while excitatory responses predominated following stimulation of the medial amygdala. This was the case particularly for those paraventricular nucleus units identified as projecting to the median eminence (P less than 0.005 vs unidentified cells). The results obtained may be related to the neural regulation of adrenocortical activity as well as higher central nervous activity and have been discussed within these contexts.

Acoustic Stimulation↗
PubMed1988

Involvement of ventral noradrenergic bundle in corticosterone secretion following neural stimuli.

In view of the involvement of noradrenaline (NA) in the regulation of adrenocortical secretion, its role in the rise of plasma corticosterone following neural stimuli was evaluated in rats. The injection of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) into the ventral noradrenergic bundle in the brain stem, which projects to the hypothalamus, caused an average depletion of NA of 72% and 78% in the mediobasal hypothalamus and the paraventricular nuclei respectively, when compared to the rats injected with vehicle. In the animals injected with 6-OHDA, the basal level of corticosterone in plasma and the response to stress induced with ether were not affected. However, the adrenocortical discharge was very significantly inhibited following photic, acoustic and sciatic nerve stimulation. The present experiments support the results of previous studies on the stimulatory effect of NA on adrenocortical secretion.

Acoustic Stimulation↗
PubMed1988

Hypothalamic norepinephrine mediates limbic effects on adrenocortical secretion.

The purpose of this study was to elucidate the role of norepinephrine (NE) in the mediation of adrenocortical responses following limbic stimuli. The effects of stimulation of the dorsal and ventral hippocampus and the midbrain reticular formation on the plasma corticosterone (CS) levels was studied in rats with vehicle or 6-hydroxydopamine (6-OHDA) injected bilaterally into the paraventricular nucleus of the hypothalamus (PVN). The injection of 6-OHDA caused a very significant reduction in the concentration of PVN NE and blocked the rise in plasma CS following the stimulation of the above three limbic structures. The basal CS level and the response to ether stress were not affected. The present study supports previous observations on the stimulatory role of NE on CS secretion and that the modulatory effects of extrahypothalamic limbic structures on the adrenocortical activity depend on the presence of NE in the PVN.

Adrenal Cortex↗