Biomedical subjects
Publications and source records attributed to A Hurwitz.
In a family with five daughters, three suffered from primary amenorrhea. The diagnosis of familial idiopathic gonadotropin deficiency (FIGD) was established. The entire family underwent HLA evaluation, and no linkage between the HLA and FIGD was found.
Four patients with oligoamenorrhea manifesting hormonal and clinical features of polycystic ovarian disease (PCOD) were selected for treatment. All patients had high luteinizing hormone (LH) levels and a basal LH/follicle-stimulating hormone (FSH) ratio of greater than 3. Three of them had high androgen levels with normal adrenal cortical function. The four patients were treated for 12 cycles by pulsatile LH-releasing hormone (LH-RH) subcutaneously. Frequency of pulses varied between once in every 120 to once in every 400 minutes in consecutive cycles, in an attempt to reverse LH/FSH ratio. The dose of LH-RH varied between 20 and 40 micrograms/pulse. Treatment was monitored hormonally by the determinations of LH, FSH, 17 beta-estradiol, prolactin, progesterone, testosterone (T) (total and free), androstenedione (delta 4A), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) every 2 days. The most striking change was the lowering of the LH/FSH ratio to the normal range, due to LH decrease and FSH increase with a pulse frequency of 180 to 240 minutes. DHEA-S levels reversed to normal in two patients and were reduced in one patient. T and delta 4A levels returned to normal with elevation to normal of SHBG. These hormonal improvements did not result in ovulation as expected (2 of 12 cycles). It may be assumed that either subcutaneous administration is inadequate in PCOD patients or that the frequency of pulses needed to correct the hormonal disturbances in PCOD patients differs from that needed for ovum maturation and ovulation.
A case of prenatal diagnosis of hypoplastic left ventricle by means of echocardiography is presented. The method of detecting this syndrome is described and the importance of its prenatal diagnosis emphasized.
Thirty ambulatory Parkinson's disease patients diagnosed with Stage I, II, and III illness were visited at home by 15 senior baccalaureate nursing students on a weekly basis for one year. The purpose of the home visit was to assess the patient, implement a regimen of mild exercise, and increase the patient's social network. Twenty-nine patients completed one year of weekly exercise sessions under the supervision of a nursing student. This article includes a demographic description of the sample, an outline of the exercise regimen, a report on the assessment tool that was used to collect the data, and a discussion of the program's educational value for the students. Peripheral activities such as organization of the support group and education of caregivers are discussed. Requirements of the study are explained. Analysis of the collected data is under way. An empirical report is forthcoming this year.
Levels of sulphobromophthalein (BSP) in plasma and liver were elevated by the opiate, morphine, and by the alpha 2-adrenoceptor agonist, clonidine. Neither morphine, 1 mg kg-1, nor clonidine, 0.01 mg kg-1, affected BSP levels significantly. When given together at these doses, they caused BSP levels in plasma and liver to be raised. At 20 mg kg-1, the effect of morphine on BSP levels was maximal, as was that of clonidine, 1.0 mg kg-1. However, the effect of these drugs given together on plasma BSP exceeded the maximal effect of either alone. Yohimbine, an alpha 2-adrenoceptor antagonist, did not affect BSP levels, nor did the opiate antagonist, naloxone. Each of these antagonists reversed the hepatobiliary effects of its respective agonist, as shown by return of BSP levels to those of saline-treated mice. Yohimbine did not reverse morphine, nor did naloxone reverse clonidine. The additive effects of morphine and clonidine and the specificities of their respective antagonists strongly suggest the involvement of discrete receptors mediating their essentially identical hepatobiliary effects.
Morphine administration (20 mg/kg s.c.) slowed renal elimination of phenol red in mice, raising plasma levels of this dye and reducing its levels in urine. After 9 days of twice daily morphine injections up to 100 mg/kg, an acute 20 mg/kg morphine challenge did not produce analgesia or hypothermia as in naive mice. This multiple dose morphine regimen also induced tolerance to the effects of the narcotic on plasma and urine levels of phenol red. Morphine, 20 mg/kg, reduced plasma p-aminohippurate clearance by 72% in naive mice but only by 56% in tolerant mice. However, reduction of iothalamate clearance after an acute morphine challenge did not show a statistically significant difference between naive and tolerant mice. These findings suggest that tolerance is more readily induced to the effects of narcotic on renal blood flow and/or tubular function than to reduction of glomerular filtration. Tolerance to the acute effects of morphine on phenol red disposition is probably due to lessened response of blood flow or tubular function in chronically dosed mice.
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Theo-24 (G. D. Searle & Co.) is an ultra-slow-absorbing formulation of theophylline suitable for once-a-day dosing in slow and normal metabolizers of theophylline. Relative to fasting conditions, increased rate and extent of theophylline absorption occur when this product is administered immediately after a breakfast with a high fat content. Our study demonstrated that factors such as meal composition (fat content) or dosing time relative to meal intake can modify the high fat-induced changes in absorption. For consistent, slow absorption, patients taking high doses (greater than or equal to 900 mg) of Theo-24 once a day should take this product in the morning under fasting conditions or with a breakfast containing less than or equal to 10 gm fat. If a high-fat breakfast (greater than 55 gm fat) is taken, then Theo-24 should be administered at least 1 hour before the meal.
An investigation of real time sonographic features of the normal fetal brain at six levels in the axial plain was undertaken between the 26th and 40th week of gestation. Structures such as cerebrum, midbrain, basal ganglia, ventricular system, vascular system, and cerebellum can be routinely identified if ultrasound is performed systematically. The sonographic appearance of detailed brain anatomy at each level is presented with the hope that it may provide a systematic form of scanning the fetal brain. With such standardization of technique many erroneous interpretations may possibly be avoided.
Morphine raised the levels of intravenously administered ampicillin in the plasma of mice. Despite higher ampicillin levels in plasma after administration of morphine, levels of this antibiotic in bile and urine were not elevated. After ligation of the common bile duct, ampicillin levels in plasma were elevated. Morphine caused a further rise in drug levels in plasma of duct-ligated mice. Ampicillin levels in plasma were higher in mice made anephric by prolonged ligation of their external urethras. In such animals, morphine also caused ampicillin levels in plasma to be even higher. These experiments suggest that morphine impairs both renal and hepatobiliary elimination of ampicillin. These effects of morphine were completely reversed by naloxone. In contrast to effects on intravenously administered ampicillin, morphine markedly reduced drug levels in plasma when ampicillin was given by gastric intubation. This resulted from delayed absorption because of retardation of gastric emptying by morphine.
The amniotic and chorionic membranes obtained at term and term amniotic fluid contain a soluble protease activity which cleaves [14C]-labeled globin at acid pH. In contrast, a salt extract of the pellet fraction obtained from the fetal membranes displays only negligible protease activities at the pH range of 4-8. Specific activities of the proteases in the soluble and salt-extractable fractions of fetal membranes which were intact before onset of labor were not significantly different from the respective activities in cases of premature rupture of fetal membranes (PROM). However, the protease activity of the amniotic fluid was found to increase with advancing gestational age and to reach maximal activity at term. A heat-sensitive and nondializable protease inhibitory activity was found in term amniotic fluid. This inhibitory activity acted on the cytosolic protease of amniotic membranes from control and PROM cases, but not on the soluble protease of chorionic membranes, and had a similar potency in fluids from PROM cases or fluids collected at term. These results do not support a role for fetal membrane proteases, amniotic fluid proteases, or amniotic fluid protease inhibitory activities in the etiology of PROM. However, the observed changes in amniotic fluid protease activity with fetal age suggest a physiological role for the enzyme in normal fetal development.
Aerosolized atropine causes anticholinergic side effects. We evaluated gastroparesis, a previously unreported side effect of inhaled atropine, in a double-blind, placebo-controlled, crossover study. Six young asthmatics received atropine (0.05 mg/kg) or placebo at 4-h intervals for 3 dosages, on 2 separate days at least 1 wk apart. Subjective complaints, pulse, visual accommodation, and citric-acid-stimulated salivary flow were recorded 30 min after each dose on each study day. A radionuclide (99mTc) study of gastric emptying time was done 30 min after the final dose on each study day. Atropine prolonged mean gastric half emptying time (112 +/- 59 min) compared with placebo (65 +/- 34 min) (p less than 0.05). However, gastric emptying after atropine was in the abnormal range in only 2 patients. Stimulated salivary flow decreased after atropine (1.97 +/- 1.7 g saliva) compared with flow after placebo (4.1 +/- 1.2 g) (p less than 0.05). No changes in visual accommodation or pulse rate were seen. Dry mouth and decreased salivation correlated with delayed gastric emptying (r = 0.76, p less than 0.05). Anticholinergic side effects of aerosolized atropine include prolonged gastric emptying in some patients. Gastroparesis after inhaled atropine is suggested by the symptom of dry mouth.
Studies in three families (A, B, and C) revealed five patients with congenital adrenal hyperplasia (CAH) due to partial and combined 21- and 11 beta-hydroxylase deficiency. One patient (A-11 1), a 23-yr-old severely virilized chromosomal female, was reared as a male, and two females (B-11 2 and C-1) complained only of hirsutism, acne, and menstrual abnormalities. Patients A-11 2 and B-11 8 (17 1/2 and 10 yr old) were asymptomatic and detected by finding an HLA genotype identical to that of their respectively affected brother and sister. Three patients (A-11 1, A-11 2, and C-1) had moderate hypertension. In spite of the wide range of clinical manifestations, all individuals had elevated androgen levels, while cortisol secretion was severely impaired only in A-11 2. 21-Hydroxylase deficiency was diagnosed on the basis of markedly increased plasma and urinary levels of 17-hydroxyprogesterone (17-OHP) and 21-deoxycortisol and their respective urinary metabolites pregnanetriol and pregnanetriolone. PRA was elevated in three patients, while urinary aldosterone was normal or increased. 11 beta-Hydroxylase deficiency was diagnosed on the basis of increased 11-deoxycortisol and deoxycorticosterone in plasma and tetrahydro-11-deoxycortisol and deoxycorticosterone in urine, particularly after ACTH administration. In contrast to classical 11 beta-hydroxylase deficiency CAH, urinary 18-hydroxycorticosterone and 18-hydroxy-11-deoxycorticosterone were normal or elevated. The nature and mechanism of a combined enzymatic defect are unknown. The coincidental presence in a single individual of the mutant genes for both 21- and 11 beta-hydroxylase deficiency CAH is very unlikely to occur. Two alternative hypotheses may explain our findings. One is the existence of a genetically inherited abnormal (or aberrant) 11 beta-hydroxylase, whose affinity for its normal substrate is changed for an abnormal one (17-OHP). As a result, 11 beta-hydroxylation of 11-deoxycortisol is deficient while 17-OHP 11 beta-hydroxylation is markedly enhanced. Thus, both 11-deoxycortisol and 21-deoxycortisol as well as their urinary metabolites accumulate. The ability for 18-hydroxylation, however, remains normal. In this case, 21-hydroxylase is not deficient, yet 21-deoxycortisol cannot be further hydroxylated to cortisol, since this steroid is not a suitable substrate for the enzyme. Such a disorder may represent a new allelic variant of 11 beta-hydroxylase deficiency CAH, which, similar to 21-hydroxylase deficiency, is completely linked to the HLA complex.(ABSTRACT TRUNCATED AT 400 WORDS)
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Morphine administration acutely reduced plasma clearance of sulfobromophthalein (BSP) in mice and increased hepatic retention of this dye. Increasing morphine doses from 5 to 40 mg/kg s.c. progressively raised plasma and liver BSP levels. Morphine-treated mice, warmed to reverse hypothermia, still had higher plasma and liver BSP levels. The narcotic also raised plasma levels of two dyes which are not conjugated, indocyanine green and dibromosulfophthalein. Naloxone reversed morphine-induced elevation of plasma BSP levels. In bile duct-ligated mice, plasma BSP levels were very high but hepatic BSP levels remained low, both after saline or morphine. Thus, the effects of morphine on BSP disposition differed from those of biliary occlusion. BSP content in bile was reduced by morphine, as dye levels were raised in plasma and hepatic parenchyma. In bile duct-cannulated mice morphine increased BSP levels in plasma and liver whereas reducing the amount of dye eliminated in bile.
Morphine sulfate, 20 mg/kg, or equivalent doses of the opioids, meperidine and fentanyl, elevated plasma levels of lidocaine after i.v. administration of this antiarrhythmic drug. Plasma levels of the lidocaine metabolites, monoethylglycinexylidine and glycinexylidine, were reduced by opioids as lidocaine levels were elevated. The opioid antagonist, naloxone, 1 mg/kg, reversed the effects of morphine, 20 mg/kg, on lidocaine. After morphine, plasma levels of both lidocaine and indocyanine green were elevated, suggesting that the effect of morphine on lidocaine disposition was related to reduced hepatic blood flow. Morphine and meperidine increased lethality of i.v. lidocaine, as shown by marked reduction of LD50 by either opioid.
Lidocaine hydrochloride is commonly infused intravenously to prevent ventricular arrhythmias. In some patients, elevations in serum lidocaine levels can cause serious toxic effects. In a group of 19 patients given a constant infusion of lidocaine, we confirmed the observation that serum lidocaine levels rose significantly between four and 24 hours after initiation of therapy. One of these patients manifested a toxic reaction to lidocaine. The lidocaine infusion rate was modified in a second group of 32 patients on the basis of the four-hour serum level. In these patients, after dosage adjustment, the mean lidocaine level did not rise, and all levels remained within the 2- to 4-mg/L therapeutic range at 24 hours. Without dosage adjustment, half of these levels would have fallen outside the desired range. A simple formula can be used to adjust prophylactic lidocaine infusion rates to attain levels that remain therapeutic, yet nontoxic.