Platelet membrane alpha 2-adrenergic receptors in depression.

The platelet membrane was used as a model system to examine alpha 2-adrenergic receptors in 30 depressed patients and 30 healthy control subjects. The number of binding sites and their affinity for 3H-UK 14304 (5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline), a potent, highly selective alpha 2-adrenergic receptor agonist, was measured. Plasma magnesium and free 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were assayed in the same sample. A decreased agonist-receptor affinity was found in depressed patients, whereas receptor density was not significantly altered compared with that in control subjects. In bipolar depressed and dysthymic patients, there was a tendency toward a higher density of alpha 2-adrenergic receptors. This trend was not apparent in unipolar, recurrent depressed subjects. Moreover, a positive correlation between Bmax and Kd values was observed in patients but not in control subjects--a finding that suggests that a compensatory phenomenon occurs in depression. After the patients were treated with antidepressant drugs, an increased affinity (decrease in Kd) was observed, together with a decrease in binding sites. Plasma magnesium concentrations were higher in drug-free depressed patients than in control subjects. In addition, magnesium concentrations were negatively correlated with the density of alpha 2-adrenergic receptor binding sites in depressed patients, both before and during treatment. Lastly, a trend toward a negative correlation between plasma MHPG concentration and the number of binding sites was also observed. These results suggest a complex multifactorial regulation of alpha 2-adrenergic receptors, which are probably hyposensitive in depressive syndromes.     

Intra-abdominal fluid collections after liver transplantation

Fluid collections are commonly seen following orthotopic liver transplantation. The majority of these collections are not infected and resolve spontaneously. However, infected collections are associated with significant morbidity and mortality and usually require drainage. Clinical signs of infection are frequently masked following transplantation due to immunosuppression. Intrahepatic collections usually represent abscesses or bilomas and invariably require intervention. Altered anatomical relationships result in signs that frequently help to differentiate these from loculated fluid within hepatic fissures. Other imaging features indicating infection include the presence of gas where none was seen previously, the development of a discrete wall and changes in the surrounding liver.     

Paradoxical sleep rebound without previous debt: the effect of minute doses of clonidine in man

This report describes an experimental condition in which clonidine administration does not modify paradoxical sleep (PS) directly, but is followed by a secondary rebound. After oral consumption of minute doses of clonidine (CLN), 12 subjects showed no direct effect of CLN, but showed a significant increase of PS production in the following placebo night. Four other subjects experienced a decrease of PS under CLN and no rebound the next night. In addition, these four subjects had mechanisms of slow wave sleep production significantly weaker than the first 12 subjects.     

Determination of functional activity of alpha 1-protease inhibitor and alpha 2-macroglobulin in human plasma using elastase

The competitive binding of human alpha 1-antitrypsin and human alpha 2-macroglobulin to porcine pancreatic elastase was studied. Mixtures of these two protease inhibitors, when titrated against elastase give inhibition curves analogous to those obtained with human plasma. This is however not the case when the individual inhibitors are used. A theoretical treatment enabled us to devise an assay method to determine the amounts of functional activity of alpha 1-protease inhibitor and alpha 2-macroglobulin respectively in human plasma.     

Microalbuminuria could improve risk prediction of stroke in patients with transient ischaemic attacks and minor strokes

BackgroundTransient ischaemic attacks (TIA) and minor strokes are important risk factors for recurrent strokes; they precede 23% of strokes within 90 days. Identification of patients at high risk of developing further strokes is essential to allow early intervention and avoid the catastrophic outcome of strokes. Elevated urinary albumin excretion rate (AER) is a risk factor and predicts cardiovascular disease, stroke, and mortality. Elevated AER can be detected with a point-of-care bedside test.MethodsPatient demographics and the ABCD2 score were obtained for 150 consecutive patients with TIA who presented to the daily stroke clinic and the stroke unit. The ABCD2 score composite for age, blood pressure, clinical features, duration, and diabetes is the risk score presently used for stratifying patients with TIA. All patients had their albumin:creatinine ratio (ACR) measured from a urine sample obtained during their visit to the clinic or the stroke unit at Royal Devon & Exeter Hospital. Patients were followed up for any events, cardiovascular events, stroke, or death at day 7, 30, and 90.FindingsNine patients had recurrent strokes or TIAs by day 7 and 13 by day 9. Patients who had a recurrent stroke or TIA at day 7 and day 90 had a significantly higher ACR than those who did not have an event (4·00 mg/mmol [95% CI 1·89–8·40] vs 1·89 [95% CI 1·58–2·25]; p=0·03 and 3·73 [95% CI 2·12–6·56] vs 1·85 [95% CI 1·55–2·22]; p=0·02, respectively). After adjustment for sex and ABCD2 score, the 90-day predictive role of ACR persisted for those with versus those without subsequent events (adjusted ACR 3·48 mg/mmol [95% CI 1·96–6·19] vs 1·87 [95% CI 1·56–2·24], p=0·04). Stratification of the population at an ACR of 3.0 mg/mmol identified 39 patients at higher risk. Cox proportional hazards of progressing to stroke by day 90 if ACR was more than 3·0 mg/mmol was 3·2 (95% CI 1·07–9·45, p<0·04).InterpretationIncreased urinary albumin excretion, as detected by urinary ACR, is significantly elevated in patients who present with TIA or minor strokes and go on to have further strokes. The use of clinic urinary ACR test could improve the risk prediction of currently available stroke risk scores such as the ABCD2 score.FundingNational Institute for Health Research and Stroke Research Network.     

A review of myocardial normothermia: its theoretical basis and the potential clinical benefits in cardiac surgery

Myocardial protection during cardiac surgery aims to preserve myocardial function while providing a bloodless and motionless operating field to make surgery easier. Myocardial protection is achieved by decreasing the oxygen needs using hypothermia and producing electromechanical cardiac arrest using potassium infusion which allows surgery to be performed on a non-beating heart. The deleterious effects of hypothermia include dysfunction of enzymatic systems, development of acidosis, a decrease in tissue oxygen delivery, an increase in blood viscosity and a decrease in erythrocyte deformability. Ninety percent of the decrease in oxygen consumption is obtained by inducing electromechanical arrest and inducing hypothermia has little additional benefit. Maintenance of systemic and myocardial normothermia reduces problems and provides a more physiological approach for cardiopulmonary bypass (CPB). The current results obtained using normothermic protection are very encouraging, and it is an easier inexpensive option. This review summarizes the current knowledge on the benefits of normothermia, based upon experimental and clinical studies.     

Does warm antegrade intermittent blood cardioplegia really protect the heart during coronary surgery?

OBJECTIVE: Intermittent antegrade blood cardioplegia (IABC) has been standardized as a routine technique for myocardial protection in coronary surgery. However, if the myocardium is known to tolerate short periods of ischemia during hypothermic arrest, it may be less tolerant of warm ischemia, so the optimal cardioplegic temperature of intermittent antegrade blood cardioplegia is still controversial. The aim of this study was to compare the effects of warm intermittent antegrade blood cardioplegia and cold intermittent antegrade blood cardioplegia on myocardial pH and different parameters of the myocardial metabolism. METHODS: Thirty patients undergoing first-time isolated coronary surgery were randomly allocated into two groups: group 1 (15 patients) received warm (37 degrees C) intermittent antegrade blood cardioplegia and group 2 (15 patients) received cold (4 degrees C) intermittent antegrade blood cardioplegia. The two randomization groups had similar demographic and angiographic characteristics. Total duration of cardiopulmonary bypass (108+/-17 and 98+/-21 min) and of aortic cross-clamping (70+/-13 and 65+/-15 min) were similar. The cardioplegic solutions were prepared by mixing blood with potassium and infused at a flow rate of 250 ml/min for a concentration of 20 mEq/l during 2 min after each anastomosis or after 15 min of ischemia. Intramyocardial pH was continuously measured during cardioplegic arrest by a miniature glass electrode and values were corrected by temperature. Myocardial metabolism was assessed before aortic clamping (pre-XCL), 1 min after removal of the clamp (XCL off) and 15 min after reperfusion (Rep) by collecting coronary sinus blood samples. All samples were analyzed for lactate, creatine kinase (MB fraction), myoglobin and troponin I. Creatine kinase and troponin I were also daily evaluated in peripheral blood during 6 days post-operatively. RESULTs: The clinical outcomes and the haemodynamic parameters between the two groups were identical. In group 1, XCL off and Rep were associated with higher coronary sinus release of lactate (5.5 +/- 1.8 and 2.2 +/- 0.5 mmol/l) than in group 2 (2.0 +/- 0.7 and 1.6 +/- 0.3 mmol/l, P < 0.05). Mean intramyocardial pH was lower in group 1 (7.23 +/- 0.08) than in group 2 (7.65 +/- 0.30, P < 0.05). There were no significant differences between the two groups with respect of creatine kinase (MB fraction) either after Rep or during the post-operative period. Lower coronary sinus release of myoglobin was detected at Rep in group 1 (170 +/- 53 microg/l) than in group 2 (240 +/- 95 microg/l, P < 0.05). At day 1, a lower release of troponin I was found in group 1 (0.11 +/- 0.07 g/ml) compared to group 2 (0.17 +/- 0.07 ng/ml, P < 0.05). CONCLUSION: With regards to similar clinical and haemodynamic results, myocardial protection induced by warm IAEX is associated with more acidic conditions (intramyocardial pH and lactate release) and less myocardial injury (myoglobin and troponin I release) than cold intermittent antegrade blood cardioplegia during coronary surgery.     

Weight-losing HIV-infected patients on recombinant human growth hormone for 12 wk: a national study

OBJECTIVE: In patients with human immunodeficiency virus, body weight (BW) loss, due mainly to loss of fat-free mass, is associated with progression of disease and mortality. Recombinant human growth hormone (rhGH) may promote BW gain by restoring FFM. METHODS: We investigated the results of adding to highly active antiretroviral therapy of routine rhGH treatment in 34 patients with human immunodeficiency virus who had lost 5% to 20% of their usual BWs. They were recruited by their physicians in Switzerland and were instructed to self-administer the drug. Patients were given 6 mg of rhGH each day for 12 wk. BW and body composition, measured by bioelectrical impedance analysis (50 kHz, tetrapolar), were recorded at baseline and at 4, 8, and 12 wk of treatment. RESULTS: At week 12, BW gain averaged 3.0 +/- 0.5 kg (P < 0.001), fat-free mass gain was 4.8 +/- 0.5 kg (P = 0.001), and body fat mass loss was 1.8 +/- 0.4 kg (P = 0.008). BW and fat-free mass increases and FM decrease were evident by week 4 and tended to plateau by week 8. Therapy was well tolerated; one patient developed carpal tunnel syndrome. Five patients abandoned the study for reasons unrelated to the rhGH treatment. CONCLUSION: Our data strongly support the use of rhGH in the treatment of unintentional BW loss associated with human immunodeficiency virus. The low rate of dropouts and the low incidence of side effects make the use of rhGH suitable for primary care management.