Raymond G. Hoffman

Relationship of body fat topography to insulin sensitivity and metabolic profiles in premenopausal women

The relationship of body fat distribution to metabolic profiles was determined in 80 healthy premenopausal white women of a wide range of obesity levels [percentage of ideal body weight (% IBW) 92-251]. Distribution of fat between the upper and lower body was assessed from the waist/hips girth ratio (WHR), which varied from 0.64 to 1.02. In 23 women, in vivo insulin sensitivity was also determined from the steady-state plasma glucose (SSPG) level at comparable insulin levels of approximately 100 microU/mL attained by the intravenous infusion of somatostatin, glucose, and insulin. Increasing WHR was accompanied by progressively increasing fasting plasma insulin levels (r = 0.47, P less than 0.001), insulin and glucose areas after glucose challenge (r = 0.53, P less than 0.001; r = 0.50, P less than 0.001, respectively) and fasting plasma triglyceride concentrations (r = 0.48, P less than 0.001). Obesity level was similarly correlated with these metabolic indices. Partial and multiple regression analysis and analysis of variance with a linear contrast model revealed that the effects of body fat topography were independent of, and additive to, those of obesity level. Within obese subjects alone (%IBW: 130), %IBW had no predictive value, but WHR remained a significant predictor of plasma glucose, insulin, and triglyceride concentrations. The WHR also correlated with the plasma cholesterol level, but this association was largely dependent on its relationship to %IBW. Both WHR and %IBW correlated with the insulin resistance index, SSPG (r = 0.60, P less than 0.01; r = 0.61, P less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Minimal increase in use of breast-conserving surgery from 1986 to 1990.

Substantial geographic and hospital-based variations have been documented in the use of breast-conserving surgery (BCS) in 1986. The authors studied the patterns of adoption of this procedure from 1986 to 1990. National Medicare inpatient claims were used to study women aged 65 to 79 who underwent an operation for local or regional breast cancer in 1986 (38,679 patients) or 1990 (43,083 patients). Breast-conserving surgery was used for 5,509 (14.1%) of the Medicare patients in 1986 and 6,476 (15.0%) in 1990. The only region with an increase in BCS use from 1986 to 1990 was New England. Many hospitals had low volumes of operations, with a median of six to seven patients annually. Ten percent of the hospitals performed 55% of the conservative operations. Large hospitals, urban hospitals, and those with higher patient volumes or a cancer center were somewhat more likely to have increased use of BCS by 1990. Despite the substantial evidence supporting BCS as an alternative to mastectomy, the overall use of BCS in Medicare inpatients increased minimally from 1986 to 1990. Many patients are treated in hospitals with little experience with BCS. Hospitals using more BCS in 1986 were somewhat more likely to increase the use of BCS by 1990.

THE PATHOPHYSIOLOGIC AND ROENTGENOLOGIC EFFECTS OF CHEST IRRADIATION IN BREAST CARCINOMA

We studied the effects of radiation therapy on lung function in 21 patients who underwent modified radical mastectomy and radiotherapy for breast carcinoma. The patients had pulmonary function studies and chest X rays prior to radiation therapy and at six weeks, and three, six, and twelve months following radiation therapy. All pulmonary function studies showed a small but statistically significant decline within the first three months following radiation therapy. Changes in the moderate and large airways continued to occur after three months. None of the changes in pulmonary function were reversible. Radiographic changes occurred in 12 patients. These changes occurred later than the lung function changes (median time for the changes was twelve months) and were unrelated to changes in lung function.

Randomized Study of Adjuvant Chemotherapy for Head and Neck Cancer

The ability of surgery and radiotherapy to control advanced squamous cell carcinoma of the head and neck has reached its maximal potential. We initiated a randomized, prospective, stratified study of adjuvant chemotherapy. Patients with stage II disease of the pyrlform sinus and stage III and IV disease of the oral cavity, larynx, hypopharynx, oropharynx, nasopharynx, and paranasal sinuses were eligible. Patients were randomized to receive either standard therapy alone or two courses of 5-fluorouracil (B-CMF) chemotherapy prior to and two courses after the completion of standard therapy. Standard therapy consisted of preoperative irradiation followed by radical surgery. Of 133 patients with advanced disease, 83 were included In the study—43 In the chemotherapy group and 40 In the control group. Rates of residual and recurrent disease, as well as distant metastases, were similar for the two groups. The survival rates of patients without persistent disease at the end of treatment showed no significant difference for the two groups. The study has been discontinued because statistical analysis Indicated that the addition of more patients would not materially Increase the statistical significance of the study.

Use of psychoactive substances in three medical specialties: anaesthesia, medicine and surgery

In order to determine the prevalence of psychoactive substance use in three specialty groupings, 1,624 questionnaires were sent to physicians in medicine, surgery and anaesthesia; all had trained at the same academic institution. A response rate of 57.8% was achieved. Comparison of prevalence of impairment rates showed no differences between Surgery (14.4%), Medicine (19.9%) and Anaesthesia (16.8%). Substance abuse was clearly associated with a family history of abuse; 32.1% of the abusers had a family history of such abuse compared with 11.7% of the non-abusers. Increased stress at various career stages did not appear to increase substance abuse; problem areas during medical life times were similar for each specialty. Substances most frequently used were marijuana (54.7%), amphetamines (32.9%); and benzodiazepines (25.1%). Seventy-three used psychoactive drugs which were non-prescribed. Drug counselling programmes were judged inadequate by most. Use of alcohol and drugs by faculty members was reported by a number of respondents.RésuméDans le but de déterminer l’habitude des produits psychoactifs chez trois groupes de spécialistes, 1,624 questionnaires ont été expédiés à des internistes, des chirurgiens et à des anesthésistes. Tous avaient reçu leur formation à la même institution. Le taux de réponse a été de 57,8%. La fréquence ne diffère pas entre chirurgiens (14,4%), internistes (19,9%) et anesthésistes (16,8%). L’usage des toxiques est nettement associée à une histoire familiale d’abus des drogues; 32,1% des utilisateurs avaient une histoire familiale positive comparativement à 11,7% des non utilisateurs. L’augmentation du stress à des moments variés de la vie profesionnelle ne semble pas influer sur l’abus des toxiques; les périodes de difficultés professionnelles sont identiques pour les trois disciplines. Les substances les plus utilisées sont la marihuana (54,7%), les amphétamines (32,9%) et les benzodiazépines (25,1%). Soixantetreize des répondants ont fait usage de médicaments psychoactifs non prescrits. La plupart ont jugé les programmes d’aide inadéquats. L’utilisation de l’alcool et des drogues par le personnel médical a été rapportée par une certain nombre de répondants.

Seizures Induced by the Cocaine Metabolite Benzoylecgonine in Rats

Summary: The half‐life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 μmol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE‐Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine‐induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE‐Injected rats that did not have seizures had significantly more locomotor activity than cocaine‐injected animals without seizures. The finding that cocaineand BE‐induced seizures differ in several respects suggests more than one mechanism for cocaine‐induced seizures and emphasizes the importance of a cocaine metabolite, BE.

Comparison of efficacy of automatic implantable cardioverter defibrillator in patients older and younger than 65 years of age

PURPOSE The efficacy of the automatic implantable cardioverter defibrillator (AICD) was compared in elderly patients and younger patients with life-threatening ventricular tachyarrhythmias. Clinical characteristics, surgical complications, and long-term survival rates were compared between the two age groups. PATIENTS AND METHODS A retrospective study was conducted of 54 elderly patients (greater than 65 years) and 79 younger patients (less than 65 years) who had had AICDs implanted for recurrent symptomatic ventricular tachycardia and/or ventricular fibrillation. RESULTS In 85% of elderly patients and 78% of younger patients, coronary artery disease was the underlying disease (NS). The mean left ventricular ejection fraction was 31.4 +/- 14.3% in the elderly patients and 35.7 +/- 17.6% in the younger patients (NS). Concomitant myocardial revascularization was performed in 37% of elderly patients and 29% of younger patients (NS); however, only 4% of elderly patients had concomitant left ventricular resection or cryoablation, compared with 15% of younger patients (p less than 0.001). Two patients in each age group died perioperatively (4% versus 3%, NS), and no significant difference in surgical morbidity or length of hospital stay following AICD implantation was noted between the age groups. In conjunction with AICD, elderly patients more commonly received antiarrhythmic drugs, with 54% of elderly patients taking amiodarone at the time of hospital discharge compared with 29% of the younger patients (p less than 0.008). In contrast, beta-blockers were more commonly used in younger patients (16% versus 2%, p less than 0.03). At a mean follow-up of 25 months, 11 (20%) elderly patients and 16 (20%) younger patients had died. Six deaths in elderly patients and five deaths in younger patients were classified as arrhythmic deaths (NS); however, only one younger patient and three elderly patients died suddenly (NS). Calculated survival curves demonstrated similar survival rates in the two age groups with approximately 90%, 87%, and 80% of the patients alive at 1, 2, and 3 years, respectively. Theoretic survival curves calculated from appropriate AICD shocks demonstrated significantly lower survival compared with actual survival. CONCLUSION It is concluded that AICD is a very effective treatment for life-threatening ventricular tachyarrhythmias, and this benefit applies to elderly patients as well as younger patients.

Splanchnic Insulin Dynamics and Secretion Pulsatilities in Abdominal Obesity

Insulin secretion, clearance dynamics, and their relationship to peripheral plasma insulin and glucose levels were monitored during three 12-h periods of overnight rest, intake of three meals, and continuous enteral feeding of mixed nutrients. The low-frequency ultradian and the high-frequency insulin secretion pulsatility characteristics during the steady-states of overnight rest and continuous enteral feeding were also examined. In abdominally obese subjects, the insulin secretion rate was consistently higher than normal by 2.3-fold. Peripheral plasma insulin levels were increased by 3.4-fold during the overnight period and by 4- to 5-fold during the two fed states. Endogenous insulin clearance was significantly reduced during feeding. Both low- and high-frequency insulin secretory pulsatilities were detected in the abdominally obese subjects. Pulse periods were within the normal range. Pulse maxima, nadirs, and absolute amplitudes were increased concomitant with the increase in insulin secretion. Ultradian relative pulse amplitudes, however, were blunted. A significantly higher pulse-to-pulse variability was observed in the abdominally obese subjects compared with normal subjects. Furthermore, a significantly higher level of interindividual variability in the nutrient-stimulated insulin secretion and in the ultradian pulse characteristics was observed. Thus in abdominal obesity, the increase in pancreatic insulin output is limited and the secretory pulsatilities are aberrant, suggesting a defect in the insulin secretory process. Diminished insulin clearance contributes to the degree of peripheral hyperinsulinemia compensating for the insulin resistance characteristic of this form of obesity.

Treatment of meningeal relapse in childhood acute lymphoblastic leukemia: II. A prospective study of intellectual loss specific to CNS relapse and therapy.

Changes in intellectual function during the course of treatment for acute lymphocytic leukemia were studied. Twenty-four children had baseline psychological evaluations and annual reevaluations for 3-6 years postdiagnosis. Treatment in all patients included combination chemotherapy, 2,400 cGy prophylactic cranial irradiation, and intrathecal methotrexate. Central Nervous System (CNS) relapse occurred in eight of these children. It was then treated with 3,000 cGy cranial plus 1,800 cGy spinal irradiation. Patients who remained in continuous complete remission showed no decline in global intelligence quotient (IQ). Patients who experienced CNS relapse had a mean decline of 16 IQ points by 3 years postdiagnosis and the long-term survivors displayed a mean loss of 25 IQ points 5-6 years postdiagnosis. Three of the five long-term survivors of CNS relapse function within the retarded range of mental ability and require special education. The other two have learning problems and display poor academic performance relative to same-age peers. There was no association noted between age at diagnosis and ultimate loss of IQ points. This prospective study suggests that children who receive a second course of cranial irradiation for treatment of CNS relapse are at high risk for significant and progressive intellectual loss.

Attitudinal and behavioral correlates of coronary heart disease

Abstract The recognition of an association between coronary heart disease (CHD) and coronary prone behavior (CPB) has raised the question of whether behavior may directly affect coronary atherosclerosis. The relationship of coronary occlusion measured by arteriography and angina pectoris to questionnaire responses selected as consistent with the attitudes and behavior of CPB were examined retrospectively in 2215 employed male patients. Nonbehavioral factors such as serum cholesterol and triglycerides were highly related to occlusion but not to angina. By comparison, most subjective attitudes and some quantitative behaviors consistent with CPB were overrepresented in angina but not in occlusion. Certain neurotic behaviors were also disproportionately represented in angina but not in occlusion. These results indicate that attitudinal and behavioral aspects of CPB contribute to angina pectoris and perhaps indirectly to atherosclerosis. This association was greatest in patients older than 50 years, but comparable to some standard risk factors in younger patients also.