Control of vascular reactivity in pregnancy

Human pregnancy is characterized by a blunted pressor responsiveness to vasopressor substances. This was first reported by Dieckmann and Michel in 1937 in experiments in which they measured vascular reactivity to the pressor effects of a crude preparation of vasopressin. Recently, this has been reported to occur in response to epinephrine, norepinephrine (NE), and angiotensin II (AII). Gant and associates reported that the increasing vascular sensitivity to infused AII not only was characteristic of women who developed pregnancy-induced hypertension, but in fact preceded the development of pregnancy-induced hypertension. Although a variety of factors may mediate this blunted pressor responsiveness, the most likely candidate appears to be the localized production within endothelium and/or vascular smooth muscle of prostaglandins. Indeed, administration of indomethacin or aspirin results in an increased sensitivity to infused AII in normotensive previously AII-refractory women. Administration of the steroid hormone 5 alpha-dihydroprogesterone reverses this apparent prostaglandin-mediated response. In addition, administration of the phosphodiesterase inhibitor, theophylline, results in a restoration of vascular refractoriness to infused AII in women with pregnancy-induced hypertension or in women destined to develop pregnancy-induced hypertension. Although a variety of known and possibly unknown compounds might also effect the control of vascular reactivity during human pregnancy, the prostinoids appear to play a pivotal role in mediation of control of vascular reactivity during human pregnancy.     

Evaluation of immunolocalization in gastrointestinal cancer

Tumor localization by a 131I-labeled monoclonal antibody to CEA has been evaluated in a series of 50 patients with clinically suspected primary or recurrent gastrointestinal cancer. Eighty-five percent of the primary tumors were correctly detected, as were 43% of associated nodal metastases. Localization was compared with computerized tomography in the detection of recurrent disease. Each technique correctly identified 61% of the sites but missed 39%. In addition, labeled antibody localization produced a significant number of false-positive images. Radioactivity accumulated by tumors, both primary and secondary, was significantly higher than that in surrounding normal tissue (P less than .01). However, less than 0.8% of the injected radioactivity and 0.01% of the injected antibody were detectable in the tumors. Radiolabeled antibody was rapidly cleared from the circulation, and this may reflect a recipient reaction to the foreign protein.     

Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus.

OBJECTIVE: This report documents that the gastric bypass operation provides long-term control for obesity and diabetes. SUMMARY BACKGROUND DATA: Obesity and diabetes, both notoriously resistant to medical therapy, continue to be two of our most common and serious diseases. METHODS: Over the last 14 years, 608 morbidly obese patients underwent gastric bypass, an operation that restricts caloric intake by (1) reducing the functional stomach to approximately 30 mL, (2) delaying gastric emptying with a c. 0.8 to 1.0 cm gastric outlet, and (3) excluding foregut with a 40 to 60 cm Roux-en-Y gastrojejunostomy. Even though many of the patients were seriously ill, the operation was performed with a perioperative mortality and complication rate of 1.5% and 8.5%, respectively. Seventeen of the 608 patients (< 3%) were lost to follow-up. RESULTS: Gastric bypass provides durable weight control. Weights fell from a preoperative mean of 304.4 lb (range, 198 to 615 lb) to 192.2 lb (range, 104 to 466) by 1 year and were maintained at 205.4 lb (range, 107 to 512 lb) at 5 years, 206.5 lb (130 to 388 lb) at 10 years, and 204.7 lb (158 to 270 lb) at 14 years. The operation provides long-term control of non-insulin-dependent diabetes mellitus (NIDDM). In those patients with adequate follow-up, 121 of 146 patients (82.9%) with NIDDM and 150 of 152 patients (98.7%) with glucose impairment maintained normal levels of plasma glucose, glycosylated hemoglobin, and insulin. These antidiabetic effects appear to be due primarily to a reduction in caloric intake, suggesting that insulin resistance is a secondary protective effect rather than the initial lesion. In addition to the control of weight and NIDDM, gastric bypass also corrected or alleviated a number of other comorbidities of obesity, including hypertension, sleep apnea, cardiopulmonary failure, arthritis, and infertility. Gastric bypass is now established as an effective and safe therapy for morbid obesity and its associated morbidities. No other therapy has produced such durable and complete control of diabetes mellitus.     

Isolated diastolic heart failure--what is it?

Epidemiological evidence suggests that 20 to 40% of all patients with heart failure have normal systolic function. Isolated diastolic dysfunction may be the principle pathophysiological mechanism in these patients. The diagnosis of isolated diastolic heart failure is problematic and not merely based on demonstrating normal systolic function. The prognosis in isolated diastolic heart failure is more favourable than in systolic heart failure. At the present time, there is no licensed treatment for isolated diastolic heart failure and treatment is largely empirical.     

Functional magnetic resonance imaging study of cognitive control in the healthy relatives of schizophrenia patients.

BACKGROUND: The predisposition, or diathesis, to schizophrenia is highly heritable. The manner in which this genetic diathesis is manifest in the central nervous system is largely unknown, although healthy relatives of schizophrenia patients show executive processing deficits associated with prefrontal cortical impairments. METHODS: The current study evaluated brain activity in 21 healthy relatives of schizophrenia patients and 20 demographically similar control subjects during correct trials on a stimulus-response incompatibility task. During the first part of each trial, participants represented and maintained the instruction for that trial; during the second part, participants used the instruction either to make an automatic response or to overcome this prepotent response. RESULTS: Behaviorally, relatives were slower when overcoming the prepotent response. Analyses focused on the first part of the trial indicated that both groups showed activity in middle frontal (Brodmann areas 46 and 9) and anterior cingulate (Brodmann area 32) gyri. However, control subjects showed significantly greater activity in dorsal prefrontal cortex (Brodmann areas 9, 8, and 6) when preparing to overcome the prepotent response, whereas patients' relatives showed prefrontal activity later, when making the response. CONCLUSIONS: Using an event-related design showed distinct prefrontal brain abnormalities associated with the genetic diathesis to schizophrenia.     

Modifiable risk factors for non-adherence to immunosuppressants in renal transplant recipients: a cross-sectional study.

BACKGROUND: Non-adherence to immunosuppressants is a major cause of renal transplant failure. Interventions to improve adherence need to target modifiable risk factors. METHODS: Adherence was measured using the 'gold standard' measure of electronic monitoring in 58 adult renal transplant recipients from a UK transplant unit. Subjects were identified from a stratified random sample of 153 recipients recruited to a larger cross-sectional study comparing different measures of adherence. Inclusion criteria included age over 18 years and a functioning renal transplant, transplanted 6-63 months previously. Exclusion criteria included residence outside the region served by the unit and inability to give informed consent. Health beliefs, depression and functional status were measured using standardized questionnaires (Beliefs about Medicines Questionnaire, Illness Perception Questionnaire, Revised Clinical Interview Schedule and SF-36) and semi-structured interview. Transplant and demographic details were collected from the notes. RESULTS: Seven [12%, 95% confidence interval (CI) 4-20%] subjects missed at least 20% of days medication and 15 (26%, 15-37%) missed at least 10% of days. Lower belief in the need for medication and having a transplant from a live donor were the major factors associated with non-adherence. Depression was common, although not strongly associated with non-adherence. CONCLUSIONS: Beliefs about medication are a promising target for interventions designed to improve adherence. The lower adherence in recipients of transplants from live donors needs confirming but may be clinically important in light of the drive to increase live donation.