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Biomedical subjects

J W Benson

Publications and source records attributed to J W Benson.

At least 19 recordsLinked to original sources

Preclinical pharmacology of cholera toxin.

Cholera toxin was selected for pharmacologic evaluation by the National Cancer Institute on the basis of antiproliferative activity against small-cell and non-small-cell lung-cancer cell lines. A feature common to the sensitive cell lines was abundant expression of GM1 ganglioside, the cellular receptor for cholera toxin. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to quantitate cholera toxin in biological fluids. A sigmoidal relationship was observed between the cholera toxin plasma concentration and the absorbance at 490 nm (OD490) of the product of horseradish peroxidase-catalyzed oxidation of o-phenylenediamine over the range of 6.25-1,600 ng/ml. Logit transformation of the OD490 data was linear over the entire concentration range and assay variability was less than 25%. Cholera toxin was stable in murine and human whole blood and plasma. Following i.v. administration of 1,500 micrograms/kg to male CD2F1 mice, cholera toxin plasma elimination was described by a two-compartment open model. The half-lives (t1/2 alpha, t1/2 beta), plasma clearance, and steady-state volume of distribution were 0.7 min, 49 min, 24 ml min-1 kg-1 912 ml/kg, respectively. Cholera toxin was not detected in plasma following an s.c. dose of 1,500 micrograms/kg. Urinary recovery following intravenous drug administration was less than 0.1%.

Animals↗

Partial deletion 8q without Langer-Giedion syndrome: a recognisable syndrome.

We report two de novo cases of del(8)(pter----q24.1:) with breakpoints involving the distal part of band 8q24.1. The clinical features were similar and there were no obvious stigmata of Langer-Giedion syndrome (LGS). There are three other cases reported with a deletion of chromosome 8 at approximately the same breakpoint, one without LGS and some similarities to our cases, the other two with LGS. Our findings would support the observation that the critical segment for the assignment of LGS is proximal to or involves the proximal part of 8q24.1, but a review of published reports suggests that the aetiology of LGS may be a more complex issue.

Chromosome Deletion↗

Two year study of cryptosporidium infection.

During a two year period 48 children admitted to hospitals in the Blackburn district were found to have cryptosporidium in stool samples. Cryptosporidium accounted for 6% of the 742 cases of childhood gastroenteritis, being as common as campylobacter. Altogether, 89% of children with cryptosporidiosis had diarrhoea, which was usually offensive and watery, and 80% vomited, the mean duration of both symptoms being six days. A substantial proportion were moderately ill with dehydration and persistent vomiting. Over half of all cases were aged 2 years or more and 37% were over 5 years. Most of the ill children were over 2 years, in contrast with other cases of gastroenteritis. Eight children were less than the 3rd centile for weight and three of these were investigated for failure to thrive. Only 6% of cases occurred in Asian children, but Asians accounted for 32% of all admissions with gastroenteritis and 59% of admissions with shigella. This unexpected ethnic difference may be due to limited contact with animals among Asians or to differences in diet.

Asia↗

Multicentre trial of ethamsylate for prevention of periventricular haemorrhage in very low birthweight infants.

The effectiveness of ethamsylate in the prevention of periventricular haemorrhage (PVH) in very low birthweight infants was evaluated by means of a multicentre, placebo-controlled, double-blind trial. In 330 infants without evidence of PVH on initial cranial ultrasound examination there was little difference between ethamsylate and placebo groups with respect to subependymal haemorrhage, but intraventricular and parenchymal haemorrhages developed in 30/162 infants (18.5%) in the treated group, compared with 50/168 (29.8%) in the control group (p less than 0.02). The incidence of intraventricular and parenchymal haemorrhage in survivors was 20/137 (14.6%) in the ethamsylate group and 37/146 (25.3%) in the controls (p less than 0.05). In 30 infants with evidence of PVH on the initial scan, ethamsylate treatment seemed to limit parenchymal extension. Analysis of the total cohort of 360 infants showed that the proportion of infants in whom an increase of two or more grades of severity of PVH was recorded during the trial was lower in the treated than in the placebo group (p less than 0.01). No adverse effects were attributed to ethamsylate therapy. The reported incidence of patent ductus arterious was lower in the treated than in the placebo group (p less than 0.02). Mortality was similar in the two groups.

Benzenesulfonates↗

Long-term metabolic control with insulin pump therapy. Report of experience with 127 patients.

To determine the long-term efficacy of insulin-pump therapy, we analyzed trends in glycosylated hemoglobin concentrations in 127 patients with Type I diabetes using insulin pumps for periods ranging from 13 to 47 months. In the first year of pump therapy the average glycosylated hemoglobin concentration improved in 83 per cent of the patients, as compared with the value before pump therapy. Although only 11 of the 127 subjects had normal glycosylated hemoglobin values before pump therapy, 33 had a normal average value during the first full year of pump use (P = 0.0001). This favorable trend persisted for the three-year duration of the study. Seventeen of the 19 patients who subsequently discontinued insulin-pump therapy had improved glycosylated hemoglobin values during the period of pump use. Eleven of the 19 patients remained available for follow-up study; the glycosylated hemoglobin concentration became worse in 7 when they returned to conventional treatment. We conclude that the improvement in metabolic control repeatedly demonstrated in short-term studies with the insulin pump can be maintained for a period of years.

Adult↗

Psychological differences noted in aircrewmembers undergoing systematic desensitization and their subsequent functioning.

This study presents the results of a 3-year follow-up of patients treated for flight anxiety via relaxation/desensitization. Noted differences between successfully and unsuccessfully treated patients are discussed as well as the long-range effectiveness of relaxation/desensitization. Significant differences were noted on MMPI (Minnesota Multiphase Personality Inventory) scale elevations and major presenting symptoms. There was a significant relationship between specific MMPI profiles and failure to successfully treat flight anxiety. Individuals most likely to benefit from therapy were those subjects who exhibited normal MMPI profiles and manifested airsickness as their major presenting symptom.

Aerospace Medicine↗

Acute complications associated with insulin infusion pump therapy. Report of experience with 161 patients.

We determined the frequency of acute complications associated with insulin pump therapy in 161 insulin-dependent patients followed up for a total of 2,978 patient-months. Diabetes control improved substantively with pump therapy, but 42% of the patients experienced one or more acute complications while using insulin pumps. Infected infusion sites, ketoacidosis, and hypoglycemic coma occurred once in every 27, 78, and 175 patient-months, respectively. More patients experienced ketoacidosis after the onset of pump therapy than in an equivalent interval immediately before the onset of pump therapy. Ketoacidosis also occurred in more patients using pump therapy than in a comparison group of 165 patients receiving conventional insulin injections surveyed during an equivalent period. The frequency of hypoglycemic coma was not significantly changed by pump therapy.

Acute Disease↗

The use of relaxation/densensitization in treating anxiety associated with flying.

This study describes the use of relaxation/densensitization therapy in treating anxiety associated with flying. Treated were 46 male and 1 female flight students who attended 3-6 sessions lasting 1 h each. This therapy uses a behavioral approach in treating anxiety associated with flying. Relaxation/densensitization incorporates the use of relaxation exercises and in-depth mental imagery. Six months after completion of therapy, all subjects were followed up to determine the therapy's effectiveness. There was a high success rate (79%) of subjects successfully completing training.

Adult↗

Clinical use of the insulin infusion pump in 100 patients with type I diabetes.

We investigated the efficacy of insulin-pump therapy in insulin-dependent diabetics, aged 18 to 69 years, by comparing the metabolic control achieved in 100 patients using this technique with that previously obtained by conventional insulin therapy. Patients were followed during pump therapy for as long as 15 months. Fasting and nonfasting blood glucose levels (mean +/- S.E.M.) decreased from 201 +/- 6 and 213 +/- 6 mg per deciliter (11.2 +/- 0.3 and 11.8 +/- 0.3 mmol per liter), respectively, to 158 +/- 5 and 145 +/- 3 mg per deciliter (8.77 +/- 0.3 and 8.05 +/- 0.2 mmol per liter) after one month of pump therapy (P less than 0.001). Ninety-three patients had improved blood sugar control; 71 per cent had a mean blood sugar concentration of 150 mg per deciliter (8.3 mmol per liter) or less after six months. Glycosylated hemoglobin values became normal in 44 per cent of 88 patients who had follow-up determinations. In over 500 patient-months there were four episodes of ketoacidosis and five episodes of serious hypoglycemia. Three patients abandoned pump therapy. We conclude that insulin-pump therapy is acceptable to patients and that it can be successfully applied to clinical practice and large-scale research studies.

Adolescent↗

Comparison of glucagon responses to 2-deoxy-D-glucose and hypoglycemia in man.

2-Deoxy-D-glucose (2DG), by competitive inhibition of glucose utilization, produces a state of intracellular glucopenia with resultant activation of both the sympathetic and parasympathetic branches of the autonomic nervous system. We have investigated the relationship between the activation of the autonomic nervous system caused by this drug and glucagon secretion. Subjects experienced symptoms identical to those observed during true hypoglycemia and demonstrated a marked rise in both gastric acid secretion and urinary epinephrine excretion. Mean immunoreactive glucagon (IRG) levels rose only slightly post-2DG (maximal mean increment, 18 pg/ml). Insulin-induced hypoglycemia, although eliciting a similar increase in urinary epinephrine excretion, was followed by a severalfold increase in IRG. Thus, although hypoglycemia and 2DG induced similar discharge of the autonomic nervous system, the glucagon response to hypoglycemia was much greater. These observations provide strong evidence that marked increases in sympathetic and parasympathetic discharge in man are weak alpha-cell stimuli and further support the hypothesis that the rise in IRG that occurs during hypoglycemia is not mediated primarily via the autonomic nervous system.

Adult↗

Reduction of plasma triglyceride concentration by acute stress in man.

Three different forms of stress all resulted in acute reduction of plasma triglyceride concentrations. Pyrogen reactions in two hypertriglyceridemic men resulted in the lowering of very-low-density lipoprotein (VLDL) triglyceride levels by 93% and 73% due to decreased secretion of this lipoprotein into plasma. More modest reductions in plasma triglycerides were observed after 2-deoxyglucose-induced intracellular glucopenia and insulin-induced hypoglycemia. With hypoglycemia, the lowering of plasma triglyceride concentration correlated significantly with the stimulation of urinary epinephrine output (r = 0.86) but with neither the urinary norepinephrine response nor with the increase in plasma immunoreactive glucagon levels. To further test whether these changes in plasma triglyceride levels were mediated via the sympathetic nervous system, hypoglycemia was evoked by insulin in subjects with traumatic spinal cord transactions. Two such subjects, who demonstrated sympathetic stimulation in response to hypoglycemia, had evidence of reduced VLDL secretion into plasma, while in two who had no evidence of an adrenergic response. VLDL secretion was not inhibited. Thus, acute lowering of plasma triglyceride concentrations by certain forms of stress appears to be mediated via the sympathetic nervous system.

Acute Disease↗

An electronic method for counting human T and B cell rosettes.

This study reports the adaptation of an electronic particle-counting method for the enumeration of T cell and B cell rosettes of human lymphocytes. This method and the conventional hemocytometer method were compared in parallel on seventeen T cell and seven B cell rosette enumerations in a blind study design. All data were analyzed for statistical significance; correlation coefficents were calculated. There was significant agreement between both methods for T cells at p less than 0.001 (mean particle counter 80.6% +/-11.3 mean hemocytometer 76.7+/-8.2%) and for the B cells at p less than 0.002 (mean particle counter 22.5+/-9.7, mean hemocytometer 23.4+/-5.12). These results demonstrate that the electronic particle counter is useful as a rapid, convenient, semi-automated method for the enumeration of T cell and B cell rosettes.

Adolescent↗

Cytomegalovirus and blood transfusion in neonates.

A fatal case of neonatal cytomegalovirus (CMV) infection attributed to exchange transfusion is described. The incidence of CMV transmission by exchange and other neonatal transfusion was studied, and the use of CMV antibody-free blood for these procedures was shown to be effective in preventing CMV infection in neonates.

Adult↗

Dominant inheritance of large molecular weight immunoreactive glucagon.

Plasma from some individuals contains substances which are reactive with glucagon antiserum, are larger than 3,500-dalton glucagon, and have been proposed as possible precursors of glucagon. We have evaluated three generations of a kindred in which 9 of 15 members evaluated had elevated plasma levels of large molecular weight immunoreactive glucagon (L-IRG) with an average concentration of 822 pg/ml. The distribution of individuals with elevated L-IRG levels in this pedigree is consistent with autosomal dominant inheritance. Gel filtration of plasma revealed that all affected family members had excessive amounts of two L-IRG peaks, one with a molecular weight of approximately 9,000 daltons and another in the 10,000 to 20,000-dalton range. Oral glucose tolerance tests were nondiabetic and elicited a fall in L-IRG levels, whereas L-IRG concentrations rose dramatically during the infusion of arginine. These L-IRG species may be precursors of 3,500-DALTON GLUCAGON AND MAY BE ELEVATED in this kindred because of an inherited defect in either their synthesis or degradation.

Adolescent↗