Use of turkey anti-human beta2-microglobulin antisera for identification of DR antibodies.
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Biomedical subjects
Publications and source records attributed to J W Benson.
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To examine the role of catecholamines in glucopenia-induced glucagon secretion, urinary epinephrine and norepinephrine and plasma immunoreactive glucagon (IRG) were measured during insulin-induced hypoglycemia in normal and insulin-dependent diabetic-man. Despite equivalent levels of hypoglycemia the mean plasma IRG increment in diabetes was only 15% of normals. The increases in epinephrine and norepinephrine were comparable in diabetics and normals; thus, the blunted response in plasma IRG to the stimulus of low blood sugar in diabetics cannot be explained by a generalized defect in catecholamine secretion. It is suggested that an alpha-cell glucoreceptor defect may account for the abnormal response to glucopenia in diabetics. To evaluate the possibility that impaired sensitivity to circulating catecholamines could explain the alpha cell dysfunction in diabetics, exogenous epinephrine was infused in normals and insulin-dependent diabetics. Elevated plasma IRG during epinephrine infusion was observed in only 50% of normals. The diabetics were hyperresponsive; mean increment in plasma IRG 3 times that of normals. The data demonstrate enhanced rather than impaired sensitivity to catecholamines in diabetes mellitus.
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Experiments with 14C-labeled urea in human volunteers show that urea is sequestered in the epidermis, where it turns over more slowly than in general body water. Sequestered urea, presumed to be concentrated through insensible evaporation of water, is the source of the excess urea found in sweat. Physiologic and clinical implications of the existence of this urea pool are discussed.
Hypoglycemia stimulates immunoreactive glucagon (IRG) secretion and increases the activity of the sympathetic nervous system. To ascertain if the augmented alpha cell activity evoked by glucopenia is mediated by the adrenergic nervous system, the glucagon response to insulin-induced hypoglycemia of five subjects with neurologically complete cervical transections resulting from trauma, thereby disrupting their hypothalamic sympathetic outflow, was compared to six healthy volunteers. In addition to clinical neurological evaluation, completeness of sympathectomy was verified by failure to raise plasma norepinephrine levels during hypoglycemia compared to the two- and threefold increase observed in controls. Total IRG response (IRG area above basal 0-90 min) and peak IRG levels achieved were the same in the quadriplegics and the controls. Although the glucagon rise tended to be slower, and the peak levels attained occurred later in the quadriplegic patients than in the controls, this response was appropriate for their sugar decline, which was slower and reached the nadir later than in the control subjects. These observations that the glucagon release during insulin-induced hypoglycemia is normal in subjects whose hypothalamic sympathetic outflow has been interrupted provide strong evidence that the sympathetic nervous system does not mediate the glucagon response to hypoglycemia.
To determine if both phases of glucagon secretion are excessive in diabetes, arginine was admimistered intravenously as pulses and as infusions to normal subjects, insulin-dependent diabetics, and noninsulin-requiring diabetics. The acute phase of glucagon secretion, in response to arginine pulses at four different doses (submaximal to maximal alpha-cell stimulating), was indistinguishable in terms of timing, peak levels attained, and total increments comparing controls and diabetics. During the first half of the arginine infusion (500 mg/kg over 30 min) the glucagon rise in controls and diabetics was similar (P greater than 0.1), whereas during the last half of the infusion excessive glucagon levels were seen in the diabetics. No difference in the glucagon responses to arginine administered as either a pulse or an infusion was observed between the two types of diabetics. The acute phase responses of insulin to intravenous, maximal stimulating doses of glucose (20 g) and arginine (2.5 g) were measured in five insulin-independent diabetics. Although the acute insulin response to arginine was normal, there was marked attentuation of the early beta-cell response upon stimulation by glucose. From these results we conclude that although in diabetes excessive glucagon levels are observed with chronic arginine stimulation, the acute phase of glucagon secretion in response to arginine is normal. In addition, the beta-cell in noninsulin-requiring diabetics, although acutely hyporesponsive to glucose, remains normally responsive to another stimulus, arginine.
The standard preparation for cleansing the gastrointestinal tract for diagnostic studies such as barium enema usually involves dietary restrictions, purgatives, and cleansing enemas. This preparation is time consuming, often uncomfortable for the patient, and frequently unsuccessful. In this study, we examined the efficacy of saline lavage (without dietary restrictions or cleansing enemas) as a gentle, alternative method for cleansing the bowel, and compared lavage to the standard castor oil method of bowel preparation. Lavage cleansing was preferred by 75% of patients who had previously experienced a castor oil preparation. Although 11% of patients could not consume an adequate (4-liter) lavage volume, there was no significant difference in preparation success rate between the remaining lavage patients and the castor oil patients. Total preparation time for lavage (3 +/- 1 hr) was 60% less than for castor oil. The anticipated dehydration produced by castor oil and the hydration produced by lavage were confirmed. No significant changes were noted, however, in serum electrolytes with either method of preparation. Additional early studies are promising for the lavage method when used in inflammatory bowel disease patients and as a cleansing preparation for colonoscopy.
The inadequacies of traditional methods for control of advanced oral carcinomas at their sites of origin prompted evaluation of combined chemotherapy and cryosurgery in seventy-three patients treated since 1969. Our experience with thirty-nine unlikely candidates for salvage by other therapy is the subject of this report. The majority had recurrent disease after other therapy. The observed morbidity potential of combined chemotherapy and cryosurgery with earlier experience led to abbreviations and refinements of method that are described and consist mainly of the following. (1) A two day postcryosurgical infusion (intra-arterial) of 5-fluorouracil (1 gm per twenty-four hours, or less) in lieu of methotrexate, the systemic toxicity and therapeutic efficacy of which seem less predictable with cryosurgery. (2) Electrosurgical subtotal tumor resection at the time of initial cryosurgery to reduce swelling and magnitude of in situ tissue slough. (3) Use of a flexible copper mesh cryoprobe that enhances feasibility of in-depth wide field cryosurgery. (4) Systematic use of multiple marginal wound biopsies as a principal guide to repetitive cryosurgery or other therapeutic adjunct selection. A special warning that available toxicologic data for independent drug therapy may not be applicable in patients after cryosurgery is given. Current experience indicates that negative biopsy after such combined therapy may be 85 per cent reliable in foretelling lesion outcome. Among the thirty-nine patients reported, twenty remain alive from six months to six years, only two of whom have clinically evident recurrent disease. If such could be reasonably accomplished, comparative evaluation of single methods should precede attempts to combine two or more modes of therapy. Since neither chemotherapy nor cryosurgery, as known today, can eliminate nodal metastases, each must be regarded as potentially adjunctive to other methods for achieving the ultimate goal of a cancer-free patient. It is within this context that combined chemotherapy and cryosurgery have been applied to unfavorable candidates for cure with seemingly worthwhile gains. Potential applicability for patients with less formidable stages of disease cannot be extrapolated from this experience. Large scale controlled clinical trials must provide the ultimately conclusive test of efficacy for such combined forms of therapy before decisive revision of traditional standards of practice might result.
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In late 1986, several vials of Humulin N (NPH human insulin, recombinant DNA origin) came to our attention because of a clumped, white coating on the inside of the vials. To determine the frequency of this phenomenon, we surveyed 100 consecutive patients who used Humulin N. Ten patients had encountered 21 vials of flocculated insulin in the previous 12 mo, reflecting an incidence of 1 per 72 vials. Insulin drawn from affected vials was markedly reduced in potency: 20.9 +/- 3.4 U/ml vs. the labeled potency of 100 U/ml. Several patients reporting flocculated insulin, including one hospitalized with ketoacidosis, experienced unusual and unexplained elevation in blood glucose concentration for several days before flocculation was observed. Patients who use NPH human insulin should be aware of this phenomenon and carefully inspect their vials for evidence of insulin precipitation before each injection.