Biomedical subjects
Publications and source records attributed to R L Young.
A 35-year-old woman with alcoholic liver disease presented with physical stigmas and laboratory confirmation of Cushing's syndrome. With discontinuance of alcohol, her signs of Cushing's syndrome resolved and the urinary free cortisol and the urinary 17-hydroxycorticosteroid response to dexamethasone returned to normal. These findings broaden the spectrum of deranged glucocorticoid chemistry that can occur in alcohol-induced cushingoid syndrome.
The characteristics of the glucose and insulin responses during the glucose tolerance test (GTT) in obese people as a group have not been established. We analyzed glucose and insulin levels during GTT in 160 healthy obese patients who averaged 42% over ideal body weight. Statistical upper limit of normal for 2-h glucose was 260 mg/dl in women and 206 mg/dl in men. Although there was a significant correlation between insulin and glucose levels in both sexes and between insulin and degree of obesity in women, r values were relatively low (r less than 0.4 for all). High insulin levels and delayed peak insulin were present in the majority of patients with normal GTT and absent in many of the most obese patients. Results indicate that upper limits of normal glucose for GTT in the obese are much higher than currently accepted criteria.
A double-blind randomized study to evaluate the effect of proflavine in the treatment of genital herpesvirus infection was conducted. One hundred fifty-seven women were studied, of whom 75 were treated with proflavine (treated women) and 82 were treated with placebo (control group). There were 62 women with primary disease and 95 with recurrent infection. Under the conditions by which this study was conducted, there was no apparent difference in the time of healing of lesions, development of recurrences, or virus isolation following treatment in the proflavine-treated and control groups.
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Transsphenoidal microdissection has been proposed as a preferred means of treating Cushing's disease. This procedure allows the surgeon to remove a pituitary microadenoma and at the same time to preserve normal tissue. Two cases described here were treated by this method. An interesting and important observation was that neither patient appeared to be cured for 2 to 6 weeks after surgery, as assessed by dexamethasone suppression. Later, normal suppressibility occurred and the course of each patient was compatible with cure. Patients treated by this method should not be automatically retreated because of adrenocorticotropic hormone (ACTH) non-suppressibility in the early postoperative period.
A 41-year-old man had thyrotoxicosis, diffuse goiter, exophthalmos, high titer of antithyroglobulin antibodies but undetectable long-acting thyroid stimulator. Initially, he had both elevated serum thyroxine (T4) and reverse triiodothyronine (rT3) levels, but normal serum triiodothyronine (T3) and free triiodothyronine (FT3) levels and 24-hour radioactive iodine uptake. Observations prior to radioactive iodine therapy uptake. Observations prior to radioactive iodine therapy showed a persistently normal T3 level in spite of development of atrial fibrillation. Iodine excess was not present, nor were any drugs or systemic illnesses that cause preferential monodeiodination of T4 to rT3 instead of T3. The data support the concept that (1) thyroxine is not just a prohormone for triiodothyronine but is metabolically active itself; (2) Graves' disease can be a cause of T4-thyrotoxicosis. We conclude that a normal serum T3 level does not rule out thyrotoxicosis.
Patients treated with 10 mCi of I-131 for toxic diffuse goiter in the period January 1974--June 1976 were evaluated for development of hypothyroidism. Fifty percent were hypothyroid within 3 mo and 69% within 1 yr of treatment. Our data suggest that there is a higher incidence of hypothyroidism after standard doses of I-131 in the 1970s as contrasted with treatment groups in the 1950s and 1960s. The pathophysiology of this increased incidence is not known with certainty; however, infrequent use of thionamide medication, together with recent increases in dietary iodine, may render the gland more radiosensitive.
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A simple and specific radioimmunoassay was developed for the determination of the anticonvulsant agent clonazepam directly in plasma without extraction. Antibodies to clonazepam were produced in rabbits after immunization with an immunogen prepared by covalently linking the 3-hemisuccinyloxy derivative of clonazepam to bovine serum albumin. When employing 3H-clonazepam as the tracer, the radioimmunoassay has a limit of sensitivity of 5 ng/ml using a 0.1-ml sample of plasma. The antibodies exhibited a high degree of specificity for clonazepam; no cross-reactivity was observed with its 7-amino and 7-acetylamino metabolites nor with a number of other widely prescribed anticonvulsant agents that might be administered in conjuction with clonazepam. Satisfactory agreement was obtained for the plasma levels of clonazepam in humans when samples were assayed by the radioimmunoassay and an established electron-capture GC technique. By virtue ot its simplicity, the radioimmunoassay offers a distinct advantage to the clinician for monitoring plasma clonazepam levels and the compliance of patients undergoing anticonvulsant therapy with the drug.
Eight women had painless thyroiditis, transient thyrotoxicosis, and low radioactive iodine uptakes but were without goiter; they constituted 15% of all thyrotoxicosis cases that we saw during the past year. Standard antithyroid antibody tests by tanned erythrocyte hemagglutination, complement fixation, and colloid and microsomal fluorescence, if present initally, were only weakly psotivie and became negative by 9 months. However, human antithyroglobulin antibody levels by a sensitive radioimmunoassay were elevated initially in all patients. In general, these radioimmunoassayable antibody levels fell, but they had not returned to normal by 9 months. Serial thyroid function tests and standard antithyroid antibody tests were most compatible with subactue thyroidtis. However, the persistence of radioimmunoassayable antithyroblobulin antibodies and recent reports of histologic evidence of lymphocyte thyroiditis in similar patients with goiter leaves open the possibility that this is a previously unrecognized presentation of chronic lymphocytic thyroiditis. Neither the cause nor the ultimate course of this syndrome is known.
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A 38-year-old physician developed polyuria and hypodipsia four days after the onset of an upper respiratory tract infection. Subsequent investigation showed a concentration defect with dehydration that partially corrected with vasopressin injection (Pitressin) administration compatible with partial central diabetes insipidus (DI). Skull roentgenograms, EEG, and lumbar puncture were normal. The polyuria and hypodipsia slowly resolved without treatment. Normal urinary concentration ability was achieved by the 48th day, but a residual elevation in serum osmolarity persisted for one year. Review of the literature failed to show previous documentation of transient DI with elevated serum osmolarity from an acute, febrile illness. The mechanism is speculative, but may be related to a subclinical encephalitis. The true frequency of this syndrome and its relationship to the frequent observation of transient polydipsia and polyuria in "benign" febrile illness remains to be determined.
Two hundred two patients participated in a double-blind random cross-over study of the effectiveness of human chorionic gonadotropin (HCG) vs placebo in a wieght reduction program. Serial measurements were made of weight, skin-fold thickness, dropout rates, reasons for dropping out, and patient subjective response. There was no statistically significant difference between those receiving HCG vs placebo during any phase of this study (P greater than .1).
A simple, specific, and sensitive radioimmunoassay was developed for the determination of the diuretic bumetanide in plasma and urine. Antiserum to bumetanide was obtained from rabbits immunized with an immunogen prepared by covalently coupling the glycine conjugate of bumetanide to bovine serum albumin. Following extraction of the sample at pH 5.5 with ether, radioimmunoassay of the residue from the ether extract allows for the determination of bumetanide with a limit of sensitivity of about 1 ng/ml using 0.1 ml of plasma or urine. The specificity of the radioimmunoassay was established by comparison with specific radiometric and spectrofluorometric techniques. The pharmacokinetic profile of bumetanide in eight human subjects receiving single 2-mg oral doses of the drug was elucidated using the radioimmunoassay. The peak plasma levels ranged from 39 to 50 ng/ml at 1-4 hr after administration and declined with a mean apparent half-life of 1.17 hr. The mean plasma clearance rate was calculated to be 255 ml/min. During the first 24 hr, a mean of 43% of the bumetanide dose was excreted in the urine as intact drug.