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Biomedical subjects

M Cohen

Publications and source records attributed to M Cohen.

At least 811 records · Page 45Linked to original sources

Insulin--not always a life sentence: withdrawal of insulin therapy in non-insulin dependent diabetes.

The extent of unnecessary insulin administration was assessed by reviewing the records of 350 patients with non-insulin-dependent diabetes (NIDDM). Subjects were included only if previously told that insulin therapy was to be permanent, and not if the need for insulin was known to be temporary (e.g. post-operatively). Fifty-one such patients were identified, 26 men and 25 women, mean age 59.5 (range 24-79) yr, with mean duration of diabetes 10.7 (1-34) yr. Insulin had been administered for a mean of 4.8 (0.3-34) yr in a mean daily dosage of 52.5 (12-280) units. Twenty-nine subjects (57%) were more than 110% of ideal body mass. Insulin therapy was ceased on an outpatient basis, using self blood glucose monitoring in nearly all cases. Mean duration of follow-up since ceasing insulin is 16 (3-48) months. Body mass in overmass subjects fell from (mean +/- S.D.) 92.3 +/- 20.5 to 82.1 +/- 17.8 kg (p less than 0.001). Mean HbA1 level fell from 12.0 +/- 2.2 to 11.0 +/- 2.0% (p less than 0.05). Sixteen patients are currently treated with diet, and 35 require diet and oral hypoglycemic agents. It appears that insulin therapy in NIDDM is often commenced for "dietary failure" rather than true secondary failure of oral hypoglycemic agents. Despite progressive increase in dosage, insulin may not improve diabetic control, and may cause weight gain. A management program of diet and exercise, based on self blood glucose monitoring allows reduction in dosage and withdrawal of insulin without hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Role of specific membrane and genetic changes in the mechanism of tumour promotion. Studies with promoter-resistant variants.

Several cell culture model systems in current use for studying tumour promotion mechanism are reviewed briefly. The conclusions that can be drawn from studies with the JB6 mouse epidermal system are summarized. Promoter-induced mitogenic stimulation, epidermal growth factor receptor binding and stimulated hexose transport are apparently not required for promotion of neoplastic transformation in JB6 cells by phorbol esters and other promoters. Phorbol ester receptor binding (or protein kinase C activation) and switched-off collagen synthesis may be required, but definitive proof is not available. Decreased cell surface trisialoganglioside synthesis and one or more genes that determine promotion sensitivity appear to distinguish sensitive from resistant cells and to be required for promotion of neoplastic transformation in JB6 cells.

Animals↗

Risks and benefits of open-heart surgery in patients 70 years of age and older.

From January 1978 to December 1982, 165 consecutive patients aged 70 to 81 years underwent various open-heart surgical procedures at the St. Boniface General Hospital in Winnipeg. Preoperatively, most of the patients were in functional class III or IV (New York Heart Association classification). Overall operative mortality for the series was 10.9%. Isolated coronary artery bypass surgery, performed in 71 patients, had an operative mortality of 2.8%. Results were also good in isolated single and double valve replacement in 58 patients (operative mortality 8.6%); there were no deaths in a group of 27 patients who underwent isolated aortic valve replacement. Thirty-six patients with various combined, extensive procedures had the poorest result (operative mortality 30.5%). More than 90% of surviving patients were in functional class I or II postoperatively. The complication rate, although high, was acceptable. Immediate and long-term clinical improvement in the majority of patients justifies a surgical approach except in patients who require combined, extensive procedures.

Aged↗

Computed tomography of mandibular ameloblastoma.

Three cases of ameloblastoma of the mandible--unicystic, multicystic, and malignant types--are presented. Computed tomography (CT) may play an important role in delineating the extent of these tumors, which require extensive radical surgery. The cystic component of these lesions is well demonstrated by CT and suggestive of the diagnosis.

Adult↗

Iron-storage deficiency and iron supplementation in pregnancy.

Haematological parameters were determined in 146 pregnant patients seen before 20 weeks' gestation. Eighteen per cent had both reduced serum ferritin and raised serum transferrin values without significant anaemia, suggesting covert iron-storage deficiency. One group then received 120 mg elemental iron daily and the other no iron supplementation. Repeat haematological assessment 20 weeks later indicated that in 48% of patients a significant decrease in haemoglobin concentration occurred if no iron was given. Supplementary iron prevented this decrease from occurring in patients with iron stores, but was insufficient to restore depleted stores or to prevent depletion of iron stores in 34% of patients with adequate stores. It is suggested that patients with depleted iron stores require therapeutic doses of iron, whereas those with adequate stores require little or no iron supplementation.

Adolescent↗

[Demonstration of drug-specific IgE and IgG antibodies using RIA: clinical importance as shown with nomifensin (Alival)].

Serum samples from 41 patients who developed adverse reactions during therapy with nomifensine were screened by RAST-based immunoassay for specific IgE and IgG antibodies against nomifensine and three of its metabolites. The results were compared with those of 10 patients without side effects and with 8 non-treated controls. Nomifensine-specific IgE antibodies were found in none of the subjects. However, all patients treated with nomifensine (with and without side effects) had specific IgG antibodies. The antibody cross-reacted in all cases with the metabolites. The titers did not discriminate clearly between the different side reactions and only partially between the presence or absence of a side reaction. The finding of specific anti-drug IgG antibodies warrants more detailed investigation of immunological mechanisms, to determine the clinical relevance of these antibodies and identify patients at risk for serious side effects.

Alveolitis, Extrinsic Allergic↗

Self-monitoring of blood glucose levels in non-insulin-dependent diabetes mellitus.

We studied the use of self-monitoring of blood glucose levels and its effect on management in 13 patients with diabetes who were receiving treatment with diet alone, and 53 patients who were receiving oral therapy with hypoglycaemic agents. In the latter group of patients, 40% ceased oral therapy, 17% continued at reduced dosage and 11% at increased dosage, and 11% required insulin therapy. Blood glucose levels improved in virtually all patients. Weight loss occurred in 23 (79%) of the overweight patients. The self-monitoring of blood glucose levels increased motivation and dietary compliance, and allowed the accurate assessment and adjustment of therapy, including the initiation of insulin administration, without the need for an expensive stay in hospital. Self-monitoring is indicated in non-insulin-dependent diabetes mellitus for overweight patients, for the assessment of blood glucose control, for suspected hypoglycaemia in patients taking hypoglycaemic agents, and in patients with an altered renal threshold.

Adult↗

Properties of carbamoyl-phosphate synthetase (ammonia) in rat-liver mitochondria made permeable with toluene.

Some properties of carbamoyl-phosphate synthetase (ammonia) were studied in rat-liver mitochondria made selectively permeable by pretreatment with toluene. The Michaelis constants for NH3, MgATP and HCO-3 were 0.7, 1.2 and 2 mM respectively. N-Acetylglutamate activated the enzyme with a Ka of about 0.1 mM. At saturating concentrations of substrates and effectors the enzyme was inhibited by 50% by carbamoyl phosphate at a concentration of 13 mM. Binding of N-acetylglutamate to carbamoyl-phosphate synthetase required the presence of both free Mg2+ ions and MgATP, and was inhibited by Ca2+ ions and by N-carbamoylglutamate. The known activation of carbamoyl-phosphate synthetase by free Mg2+ is due to an increased affinity of the enzyme for N-acetylglutamate. Binding of N-acetylglutamate to carbamoyl-phosphate synthetase was a slow process: at N-acetylglutamate concentrations below 0.5 mM maximal binding was not completed within 30 min. The rate of binding increased with increasing N-acetylglutamate concentrations. Dissociation of N-acetylglutamate from the enzyme was relatively fast, with a half-time of about 5 min. Under all conditions studied there was a close relationship between carbamoyl-phosphate synthetase activity and the amount of N-acetylglutamate bound to the enzyme. The data are discussed in relation to the control of carbamoyl-phosphate synthetase in the intact hepatocyte.

Animals↗

Determinants of ventricular tachycardia in patients with coronary artery disease and ventricular aneurysm. Clinical, hemodynamic, and angiographic factors.

Many patients with coronary artery disease (CAD) in whom ventricular tachycardia (VT) develops have transmural scars or frank aneurysms. However, only a minority of patients with ventricular aneurysms go on to develop VT. To determine which factors are associated with the development of VT in patients with aneurysms, we retrospectively reviewed the records of 154 patients with CAD and segments of akinesia or dyskinesia, or both, on left ventriculography. Of the 154 patients, 85 had 24-hour Holter monitoring or 48 consecutive hours of continuous electrocardiographic monitoring in an intensive care unit within 6 months of catheterization. VT occurring at least 10 days after myocardial infarction (MI) or in the chronic phase was recorded in 19 patients (Group I); the remaining 66 patients did not have VT (Group II). The clinical, hemodynamic, and angiographic characteristics of these 2 groups showed no significant difference with respect to age, time from first transmural MI to catheterization, congestive heart failure (CHF), ejection fraction, or presence of dyskinesia. Patients with VT had significantly larger aneurysms and a higher prevalence of septal akinesia or dyskinesia. However, stepwise discriminant analysis revealed septal akinesia or dyskinesia to be the only independently significant variable distinguishing the 2 groups. Thus, septal involvement appears to be a major determinant of VT in patients with CAD and ventricular aneurysm.

Adult↗

Comparison of chemotherapy alone versus chemotherapy and radiation therapy of extensive small cell carcinoma of the lung.

In a randomized study 145 patients with extensive small cell carcinoma of the lung were treated with chemotherapy alone (Cytoxan, CCNU, methotrexate) or with the same drug regimen and with radiation therapy to the brain, chest, and abdomen. One hundred eighteen of these patients were evaluable. Those patients receiving radiation had a better response rate (55% vs 31%, P = .016) but significantly greater toxicity. There was no significant difference in rates of complete response (7% vs 8%) or in survival (median 18.4 vs 15.3 weeks) between the two groups overall. The median survival of those patients with a partial response to therapy was 18 weeks; for those achieving a complete response it was 46 weeks. However, a clear difference in survival comparing responders with non-responders was evident only for patients who were assigned to chemotherapy alone. Partial regressions have little, if any, correlation with improvement in survival. Therapy in this disease must be oriented toward inducing complete response.

Aged↗

A deletion of heterochromatin only of the Y chromosome in an azoospermic male.

A patient with a deletion of the distal portion of the long arm (q21) of chromosome Y is described clinically and cytogenetically. The proband has a normal male habitus but with azoospermia. The proband was investigated because of infertility. Male relatives were also investigated cytogenetically. The deleted Y chromosome was measured and compared with the normal Y of male family members. The results suggest that no Y euchromatin was lost.

Adult↗

Thymic hormonal activity on human peripheral blood lymphocytes, in vitro. V. Effect on induction of lymphocytotoxicity.

Thymic hormonal effect on lymphocytotoxicity induced in vitro and its target specificity were tested using peripheral blood mononuclear cells (PBMC) of healthy subjects. PBMC were treated by the thymic extract TP-1, a similarly prepared spleen extract (SE) or medium only (1 h, 37 degrees C) and then induced to express cytotoxic activity by exposure to allogeneic tumor cells in mixed cultures or by Con A stimulation. The cytotoxicity developed after several days in culture was assayed on 51Cr labelled tumor cells. TP-1 caused a significant mean enhancement of cytotoxicity induced and assayed on Raji lymphoma cells (mean % specific lysis, 31.5 +/- 2.9 without TP-1 and 53.7 +/- 3.6 with TP-1; n = 42; p less than 0.01). The scatter of individual responses to TP-1 was wide, however, and included also some cases of TP-1 induced suppression. Similar wide scatter of TP-1 effects with emphasis on TP-1 induced enhancement was observed with other tumor cell lines or with Con A as inducers. Usually, SE had no effect on induced cytotoxicity. Target selectivity (specificity) of induced cytotoxicity was tested by induction and assay on several tumor cell lines with crossing over, as well as by cold competition assay. When target selectivity was present, it was not masked by TP-1 induced enhancement. Moreover, in some cases, target selectivity became more pronounced after TP-1 treatment. However, TP-1 enhanced also Con A induced non-specific cytotoxicity. No effect of TP-1 on natural killer cell activity of fresh PBMC could be demonstrated. It is suggested that both selective cytotoxicity (T-cell dependent) and non-selective one maybe modulated directly by TP-1 and indirectly by TP-1 modified secondary interactions in culture. This profound regulatory effects could be demonstrated in the PBMC of immune-intact healthy adults.

Cell Line↗

Radiation induced osteochondroma in long-term survivors of childhood cancer.

The records of 200 long term survivors of childhood cancer where reviewed. Radiation induced osteochondromata were detected in 12 patients (6%). Radiation had been administered in doses ranging from 1250 R (approximately 1500 rad) to 5500 rad between the ages of 8 months and 11 1/2 years. Radiation-induced osteochrondromata were detected 3 to 13 1/2 years later, with a median of 5 years. The osteochrondomata were single in 7 patients and multiple (2-4) in 5. Two occurred at sites of previous thoracotomy. Factors related to radiation induced osteochondromata are discussed.

Bone Neoplasms↗