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Biomedical subjects

A Nahum

Publications and source records attributed to A Nahum.

69 records · Page 4Linked to original sources
PubMed1983

Identification of a mutant human insulin predicted to contain a serine-for-phenylalanine substitution.

Using information gained from (i) the relative HPLC retention of an abnormal insulin present in the serum of a hyperinsulinemic diabetic patient and (ii) the loss of an Mbo II restriction site in one of the patient's insulin gene alleles, it was recently predicted that the mutant insulin contained a serine-for-phenylalanine substitution at position B24 or B25. We have now prepared human [SerB24]insulin and [SerB25]insulin by solid-phase peptide synthesis and semisynthesis using an improved approach whereby the protecting groups can be removed from the final product in a single step. During reversed-phase HPLC analysis, the two semisynthetic insulins were clearly separated from normal insulin and from each other. Analysis of the patient's immunoaffinity-purified serum insulin by HPLC and radioimmunoassay showed that the insulin eluted at the position of [SerB24]insulin and coeluted with the analog when the two were studied in admixture. Additional studies showed that [SerB24]insulin and [SerB25]insulin have about 16% and 0.5% of the activity of normal insulin, respectively, in stimulating glucose oxidation by isolated rat adipocytes. We conclude that the patient's abnormal insulin (insulin Los Angeles) is human [SerB24]insulin and that abnormal insulins with amino acid replacements at both positions B24 and B25 can be associated with human diabetes.

Amino Acid Sequence↗
PubMed1983

Reductive methylation of insulin. Production of a biologically active tritiated insulin.

Reductive methylation of the three amino groups of porcine insulin was accomplished by incubation with formaldehyde and sodium cyanoborohydride. The two amino termini and the epsilon amino group of B29 lysine were each dimethylated within 1 h of incubation. The fully methylated insulin bound more tightly to a reverse phase column than did native insulin, had a slightly more acid isoelectric point, and maintained approximately 50% biological activity when examined with an insulin sensitive cultured cell line. Reductive methylation with sodium cyanoboro [3H] hydride resulted in a [3H] methylated insulin with a specific activity of 6 Ci/mmol.

Glycine↗
PubMed1978

Effect of the mouse mutants testicular feminization and sex reversal on hormone-mediated induction and repression of enzymes.

The mouse mutants testicular feminization and sex reversal have been used to investigate hormone-mediated induction and repression of enzymes. Tfm/Y animals were already known to be androgen insensitive, rendering the androgen-inducible enzymes ADH and beta-glucuronidase noninducible because of an inherited deficiency of a cytosol androgen-receptor complex. The animals display female secondary sexual characteristics. Sxr/+,XX animals display male primary and secondary sexual characteristics with small testes. We demonstrate (1) that the Tfm mutation is pleiotropic, preventing repression of an androgen-repressible enzyme (ornithine aminotransferase) as well as induction of androgen-inducible enzymes, (2) that an estrogen-inducible enzyme (histidine decarboxylase) is not affected by the Tfm mutation, and (3) that Sxr/+,XX animals produce enough androgen for malelike activities of androgen-sensitive enzymes. It was also discovered that histidine decarboxylase repressed by androgen in normal animals, rather than being unaffected by it in Tfm/Y animals, is in fact induced. This unexpected phenomenon is discussed and an explanation is suggested for it.

Alcohol Oxidoreductases↗
PubMed1977

[Not Available].

Explore the source record for details and available documents.

Egypt↗
PubMedDate not supplied

Response to pancuronium after loss of atracurium-induced neuromuscular blockade.

OBJECTIVE: To describe a previously unreported event in which a patient became refractory to atracurium-induced neuromuscular blockade, but subsequently was adequately paralyzed with a standard dosage of pancuronium. CASE SUMMARY: A previously healthy 17-year-old woman who sustained multiple trauma developed tolerance to an atracurium infusion she was receiving while undergoing mechanical ventilation. On day 3 of neuromuscular blockade, she became unresponsive to atracurium as evidenced by excessive physical movement, increased peak airway pressures, and overbreathing assist control ventilation. Repeat boluses and increases in the atracurium infusion rate to a maximum of 1.27 mg/kg/h failed to provide a desired clinical response. A bolus dose of pancuronium 0.15 mg/kg was administered and the constant infusion was then changed to pancuronium 0.078 mg/kg/h. Within minutes, decreased respirations, peak airway pressures, and agitation were noted. The pancuronium infusion rate was then tapered to 0.045 mg/kg/h over 72 hours and continued to maintain adequate neuromuscular blockade. DISCUSSION: Potential pharmacokinetic and pharmacodynamic causes of loss of neuromuscular blockade in this patient are postulated. Possible explanations for loss of neuromuscular blockade include increased degradation of atracurium and/or a change in acetylcholine receptor physiology. CONCLUSIONS: The development of resistance to a specific neuromuscular blocking agent in the intensive care setting does not necessarily imply cross-tolerance or resistance to alternative agents. Also, loss of respiratory control by one neuromuscular blocking agent may be overcome by changing agents.

Adolescent↗
PubMedDate not supplied

Atracurium resistance in a critically Ill patient.

A previously healthy 25-year-old man with metastatic testicular teratocarcinoma became resistant to atracurium-induced neuromuscular blockade as evidenced by train-of-four (TOF) monitoring combined with clinical assessment. Subsequently he had an adequate response with a standard dosage of pancuronium. During the first 10 days of neuromuscular blockade, the atracurium requirements escalated from 0.31 to 1.7 mg/kg/hour, guided by TOF monitoring, movement, and spontaneous respirations. The infusion was discontinued but later reinstituted. Despite a total atracurium loading dose of 1.4 mg/kg followed by an infusion rate titrated to 1.7 mg/kg/hour, inadequate paralysis persisted. Atracurium was terminated and an intravenous infusion of pancuronium 0.10 mg/kg/hour was started. Over the next 3 days the pancuronium infusion was titrated down to a range of 0.04-0.06 mg/kg/hour, followed by a maintenance infusion of 0.01-0.05 mg/kg/hour for 5 days. A pharmacokinetic alteration, such as increased metabolism or elimination, may have caused the atracurium resistance.

Adult↗
PubMedDate not supplied

Prolonged neuromuscular blockade in two critically ill patients treated with atracurium.

Recent literature suggests that the risk of prolonged neuromuscular blockade associated with atracurium compared with other nondepolarizing neuromuscular blocking agents may be minimal. Two patients experienced prolonged weakness associated with the administration of atracurium. Both received atracurium 0.5-0.7 mg/kg/hour in combination with methylprednisolone 500-600 mg/day. Electromyographic results and creatine kinase levels were suggestive of muscular weakness in both patients. Despite high-dose corticosteroid therapy, the electromyographic evidence supporting prolonged weakness did not suggest typical corticosteroid myopathy. Although some clinicians advocate routine administration of atracurium in critically ill patients due to the relative lack of reports of prolonged weakness, this may be premature. Although there are fewer reports of atracurium-associated prolonged weakness compared with pancuronium and vecuronium, the patients we describe suggest that it may occur.

Aged↗
PubMedDate not supplied

A retrospective analysis of long-term use of nondepolarizing neuromuscular blocking agents in the intensive care unit, and guidelines for drug selection.

Nondepolarizing neuromuscular blocking agents (NNMBAs) are frequently administered to patients in the intensive care unit (ICU). We conducted a retrospective study of patients in intensive care who received infusions (> 48 hrs) of commonly used NNMBAs. The goals were to describe NNMBA use in our ICUs, determine patient characteristics, and assess the cost of the individual drugs. We found that atracurium was prescribed for 68% of study patients; 68% of the patients did not have renal, hepatic, or cardiovascular disease; dosages of NNMBAs varied; a statistically significant increase in dosage requirements over time occurred with atracurium; assessment of neuromuscular blockade was 100% subjective; and 41% and 17% of patients receiving atracurium and vecuronium, respectively, experienced prolonged neuromuscular weakness documented subjectively. As a result of this study, guidelines for agent selection were developed to facilitate cost effective use of NNMBA in our ICUs. Using these guidelines would potentially significantly decrease drug expenditures in this setting.

Adult↗
PubMedDate not supplied

A retrospective review and assessment of benzodiazepines in the treatment of alcohol withdrawal in hospitalized patients.

Little information has been published concerning differences among the benzodiazepines in treating hospitalized patients with severe symptoms of alcohol withdrawal. We attempted to determine the length and type of hospital stay, and the pattern and appropriateness of administration, dosage requirements, and costs associated with benzodiazepines in patients undergoing alcohol withdrawal. A 1-year retrospective analysis was performed for 57 hospitalized patients. Appropriate therapy was defined as lorazepam for patients 60 years and older or those with hepatic dysfunction, and chlordiazepoxide or diazepam for all other patients. Drug costs were calculated based on acquisition costs. The mean number of days of benzodiazepine treatment and length of stay in the intensive care unit (ICU) were 6.2 days (range 1-30 days) and 3.9 days (range 0-12 day), respectively. Fifty-six patients were admitted to the ICU for management or for monitoring continuous-infusion lorazepam; one patient received chlordiazepoxide on a general ward. Total mean lorazepam infusion required per patient was 324 mg (range 2-5956 mg). The total benzodiazepine acquisition cost was $56,489 (mean $1009, range $0.06-7157/patient). The total costs of benzodiazepine acquisition and ICU charge were $404,346 (mean $7462/patient). Based on our criteria, 41 of 57 patients could have been treated appropriately with chlordiazepoxide, which would have resulted in an estimated drug-acquisition cost savings of at least $37,000. Mean benzodiazepine dosage requirements in patients hospitalized for alcohol withdrawal appear higher than previously reported. Approximately 70% of our patients were not of advanced age and had no evidence of organ dysfunction, and therefore, could have been treated with an oxidized benzodiazepine (i.e., chlordiazepoxide).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

A prospective evaluation of benzodiazepine guidelines in the management of patients hospitalized for alcohol withdrawal.

Our institution adopted guidelines for the selection of benzodiazepines to be administered to patients hospitalized for alcohol withdrawal. We assessed the guidelines' impact on prescribing habits, benzodiazepine dosage requirements and costs, and length of intensive care unit (ICU) stay. A 6-month prospective, observational study was performed in 50 patients who exhibited signs of alcohol withdrawal and received benzodiazepine therapy. Appropriate therapy was defined as lorazepam for patients 60 years and older or those with hepatic dysfunction, and chlordiazepoxide for all other patients. Benzodiazepine costs were calculated based on acquisition cost. Based on our guidelines, 76% of patients were appropriate candidates for a long-acting agent such as chlordiazepoxide; 61% of these candidates actually received such a drug. Using a benzodiazepine conversion to compare doses in chlordiazepoxide equivalents, there was a significant difference in the total mean dose of chlordiazepoxide (1295.5 mg, SD +/- 1571) compared with lorazepam (365.5 mg; SD +/- 446) (p < 0.01). The mean total chlordiazepoxide acquisition cost was $61.74 (range $0.03-585.98) per patient (28 patients); prior to adoption of the guidelines, the mean cost of benzodiazepine therapy was $1008.72 (+/- $1554.45). For patients receiving chlordiazepoxide, the mean days of ICU and hospital stay were 1.1 days (range 0-9 days) and 5.6 days (range 1-17 days), respectively; before adoption of the guidelines, the mean number of days of ICU stay was significantly greater (4.1 days, p < 0.0001). The guidelines resulted in a substantial change in benzodiazepine prescribing patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗