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Biomedical subjects

H Halkin

Publications and source records attributed to H Halkin.

At least 73 records · Page 4Linked to original sources

Use of antibodies to intermediate filaments in the diagnosis of metastatic amelanotic malignant melanoma.

Immunofluorescent staining of tissue from a lung tumor detected 12 years after excision of a primary malignant melanoma of the skin was negative for prekeratin and positive for vimentin, indicating that the tumor was not epithelial in origin and excluding carcinoma from the differential diagnosis. Complementary conventional staining with hematoxylin-eosin confirmed the melanocytic origin of the tumor, indicating that it was probably an amelanotic metastasis of the original malignant melanoma. The findings in this case demonstrate the potential usefulness of immunohistochemical microscopic characterization of specific intermediate filament proteins in the diagnosis of otherwise ambiguous cases of amelanotic melanoma.

Antibodies↗

Kinetics of CSF phenytoin in children.

The efficacy of intravenous phenytoin for the treatment of status epilepticus is related to the rapid entry of phenytoin into brain parenchyma. There is no information concerning the correlation between phenytoin serum and CSF concentrations in children, and the application of CSF data to clinical use. We report 7 children (2-11 yrs) who were treated or exposed to phenytoin in doses between 10.5-230 mg/kg. Lumbar puncture was performed 9 times in 6 of the patients. In one patient, an intraventricular catheter permitted successive assessment of CSF phenytoin concentrations. The ratio of CSF/serum phenytoin concentrations was 0.16 +/- 0.08, with gradual increase over the first 8 hours as the serum phenytoin concentration decreased. There was good correlation between therapeutic outcome and CSF phenytoin levels higher than 2 mcg/ml. In one patient the coma state secondary to phenytoin intoxication was associated with high CSF concentration (6 mcg/ml).

Age Factors↗

Components of variability in serum theophylline concentrations during maintenance therapy with a sustained release formulation.

Fifteen adult chronic asthmatic patients were studied on 6 consecutive days of the second week of treatment with a new sustained release theophylline formulation, and 8 were again studied after three months on the same dosing regimen (375 mg b.i.d.). Serum theophylline concentrations were maintained in the therapeutic range (peak - 19.7 +/- 5.0 micrograms/ml; trough - 13.0 +/- 3.2 micrograms/ml) throughout the 12 hour dosing interval, and were greater than 75% of the peak concentration over 8.6 +/- 2.9 h. A degree of drug accumulation was evident in that the 1-h and 5-h levels rose from 12.2 +/- 4.1 and 4.5 +/- 4.8 micrograms/ml during the second week to 16.9 +/- 4.6 and 18.4 +/- 4.5 micrograms/ml, respectively, at three months. Between-patient differences accounted for 61%-71% of the total variation in steady state theophylline concentrations. After accounting for differences due to sampling time and assay error, unexplained random, within-individual variability amounted to 11%-18% of the total. Quantitative estimation of these components of variability may be incorporated into dosage forecasting methods based on single determinations of serum concentration.

Administration, Oral↗

Methyldopa poisoning.

A case of methyldopa overdose, confirmed by quantitative blood analysis, is presented. The clinical manifestations were coma, hypothermia, hypotension, bradycardia, and dry mouth. This combination of clinical findings, previously considered characteristic of phenothiazines or tricyclic antidepressants poisoning, should also raise the suspicion of methyldopa overdose. Methyldopa is a commonly used antihypertensive agent. Surprisingly, reports on overdose are exceedingly rare [1, 2]. We have recently treated a case of methyldopa overdose in which the presenting signs resembled those of psychotropic drug poisoning.

Adult↗

Reduction of mortality in general medical in-patients by low-dose heparin prophylaxis.

The effect of prophylactic low-dose heparin on mortality was tested in 1358 consecutive patients admitted to the medical wards of an acute care hospital. Eligibility for treatment or exclusion was ascertained on admission by predefined contraindications. Eligible patients with even-number hospital records were assigned to treatment (5000 U twice daily), those with odd-number records served as controls. Because determination of eligibility was open to bias, evaluation of treatment was based on comparison of the total even-number group (669 patients, of which 411 were treated with heparin), and the total odd-number group (689 patients, none treated with heparin). Mortality was significantly lower in the even-number group-7.8% (52 of 669 patients) versus 10.9% (75 of 689 patients) in the odd-number group; the difference increased consistently with length of hospitalization (p = 0.025). The estimated reduction in mortality attributable to heparin was 31.1%. We believe that low-dose heparin prophylaxis is appropriate in all immobilized medical patients who are not at risk of bleeding.

Adult↗

Maturation of renal tubular transport of digoxin.

Previous data have suggested an age-related increase in renal tubular secretion of digoxin in infants and children receiving long-term digoxin therapy. This phenomenon could be the result of a maturational process or secondary to chronic substrate stimulation. To investigate this question, two groups of 2-week-old paired littermate rats received intraperitoneal injections of either digoxin or an equal volume of normal saline (control) on alternate days until sacrificed at 4, 6, and 8 wk of age. An additional group of 12-wk-old rats were studied as controls. 125I-labeled digoxin uptake was measured in renal cortical slices as the cPM/mg wet tissue slice/medium ratio (S/M). Both digoxin-treated and control rats demonstrated significant age-related increments in digoxin uptake. S/M ratios at 4, 6, 8, and 12 wk in he control group were 1.34 +/- 0.06, 1.39 +/- 0.14, 1.62 +/- 0.18 and 1.93 +/- 0.23, respectively (mean +/- S.D.) (r = 0.81; P less than 0.001). S/M ratios in the digoxin-treated animals at 4, 6, and 8 wk were 1.28 +/- 0.16, 1.33 +/- 0.09, and 1.52 +/- 0.23, respectively (r = 0.50; P less than 0.025), but did not differ significantly at each age from those in the control group. 125I uptake was significantly reduced by both dinitrophenol and sodium azide, as well as by a 100% nitrogen atmosphere. These results indicate that renal tubular transport of digoxin is an age-related energy dependent process which probably is not subject to substrate stimulation.

Age Factors↗

Interstitial fluid concentrations of cefsulodin, azlocillin and carbenicillin.

Cefsulodin, azlocillin and carbenicillin were administered by intramuscular injection to rats in a dose of 100 mg/kg. THe serum concentration in frequent samples after administration was determined and compared with the interstitial fluid (IF) concentration, measured with implanted paper discs enveloped in a dialysis tube. The IF concentration of cefsulodin was significantly higher than that of the other two antibiotics. The AUC in the IF was also larger for cefsulodin.

Animals↗

The influence of endotoxin-induced pyrexia on the pharmacokinetics of gentamicin in the rabbit.

Endotoxin-induced pyrexia caused a 2-fold increase in the volume of distribution of intravenously administered gentamicin in the rabbit as compared to the basal state (0.13-0.23 and 0.31-0.65 l for the central and peripheral compartments, respectively). Elimination, half-life was prolonged (46 to 90 min control and pyrexia, respectively), total plasma clearance remaining unchanged (4.6 and 4.9 ml/min, respectively). Endotoxin-induced pyrexia caused a significant increase in the serum concentrations and area under the concentration-time curve of gentamicin administered intramuscularly (355 to 704 microgram . min/ml, control and pyrexia, respectively). The increase in gentamicin concentration area under the curve was positively correlated with the temperature load (P less than .01). As total plasma clearance was not affected by pyrexia, the increased serum concentrations after intramuscular injection may be explained by enhanced absorption from the site of administration.

Animals↗

Colchicine kinetics in patients with familial Mediterranean fever.

Serum colchicine levels were determined by radioimmunoassay after a 1-mg bolus injected intravenously in 4 patients with familial Mediterranean fever and in 6 normal subjects. Mean elimination half-life (t1/2) (+/- SEM) was 157 +/- 20 min in the patients and 65 +/- 15 min in the normal subjects (p less than 0.005). Total clearance was 239 +/- 50 ml/min in the patients and 601 +/- 155 ml/min in the normal subjects (p less than 0.05). Volume of distribution (Vdarea) was 76 +/- 16 and 49 +/- 91 and did not differ significantly. In 8 patients receiving colchicine prophylactically with good clinical response, serum colchicine ranged from 0.3 to 2.4 ng/ml after daily doses of 1 mg orally. In 2 responding patients 2-mg doses orally induced levels from 4 to 10 ng/ml, and in one (a nonresponder) a 3-mg dose induced levels of 7.5 to 13 ng/ml. Of 3 patients receiving 2 mg daily with unsatisfactory clinical responses, serum levels were not detectable in one and in the low range of 1.5 to 5.4 ng/ml in the others. It is suggested that lack of response to colchicine orally in some nonresponders could result from inadequate absorption or altered disposition of colchicine.

Adult↗