A national alcohol and trauma center survey. Missed opportunities, failures of responsibility

The results of a national survey of trauma centers concerning their assessment and response to the problem of alcohol and trauma are reported. Surveys were returned from 154 trauma centers located in 43 states and the District of Columbia. The profile of the 125,000 patients treated at the centers is a 30-year-old man sustaining blunt trauma, usually in a vehicular crash. Two-thirds of centers estimated that the majority of their patients had abused alcohol. While acknowledging alcohol as a significant cause of trauma, only 55.2% of centers routinely obtain admitting blood alcohol levels. Less than a third of the centers employ alcoholism counselors. Most trauma centers are not providing services that allow them to fulfill their responsibility to detect and initiate treatment of alcohol abuse, a major cause of traumatic injury.     

Humoral control of water and electrolyte excretion during water restriction

The goals of the present study were twofold: first, to assess the renal excretory and hormonal responses to chronic water restriction in dogs whose sodium retaining mechanisms had been stimulated through dietary sodium (Na+) deprivation; second, to determine the mediator(s) of the natriuresis which was observed with water restriction in these sodium deprived dogs. Three groups of dogs maintained on a low Na+ diet (5 mEq/day) for two weeks underwent a three day period of water restriction. In normal, intact dogs Group 1 (N = 5), water restriction resulted in a significant increase in Na+ excretion with a net cumulative loss of 26.3 +/- 2.6 mEq over three days. The natriuresis was associated with a significant increase in plasma vasopressin (PAVP) (1.7 to 10.2 pg/mliter) and a significant fall in plasma aldosterone (PALDO) from the levels observed with Na+ restriction alone (24.9 to 12.4 ng/dliter). The natriuresis could not be explained by decreases in food intake as determined by control studies in four dogs. Group 2 (N = 6) dogs had a decrease in PALDO with water restriction that was prevented by means of continuous i.v. aldosterone infusion (6.0 micrograms/kg/day). Dogs in this group failed to demonstrate a natriuresis during three days of water restriction, despite the fact that PAVP rose from 3.3 +/- 0.8 to a peak level of 14.95 +/- 1.9 pg/mliter. Group 3 (N = 6) dogs underwent selective neurohypophysectomy, thus preventing the rise in PAVP during three days of water restriction. In this group, PALDO also remained unchanged from the Na+ deprived level during water restriction, and no natriuresis was observed. We conclude: 1) that the natriuresis which occurs with water restriction is a potent physiological response that occurs even in the Na+ restricted state; and 2) this natriuresis can be explained by a fall in PALDO and not the rise in PAVP.     

ROLE OF NITRIC OXIDE IN THE CONTROL OF THE RENAL MEDULLARY CIRCULATION

1. Nitric oxide (NO) has been implicated as an important controller in the short- and long-term regulation of arterial pressure. Studies performed in our laboratory have demonstrated that chronic intravenous administration of the NO synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME) selectively decreases renal medullary blood flow, causes sodium and water retention and leads to hypertension. 2. To determine the importance of the renal medullary effects in this model of hypertension, further studies were conducted to examine the influence of selective stimulation or inhibition of renal medullary NO on whole kidney function and cardiovascular homeostasis. With the use of a unique catheter to directly infuse into the renal medullary interstitial space, stimulation (bradykinin or acetylcholine) or inhibition (L-NAME) of renal medullary NO selectively increased or decreased renal medullary blood flow. 3. The changes in medullary flow in these experiments were associated with parallel changes in sodium and water excretion independent of alterations in renal cortical blood flow or glomerular filtration rate. 4. Studies were then undertaken to examine the long-term effects of selective NO inhibition in the renal medulla on cardiovascular homeostasis. Chronic infusion of L-NAME directly into the renal medullary interstitial space of uninephrectomized Sprague-Dawley rats led to a selective decrease in renal medullary blood flow that was sustained throughout the 5 day L-NAME infusion period. The decrease in medullary blood flow was associated with retention of sodium and the development of hypertension and the effects were reversible. 5. The data reviewed indicate that NO in the renal medulla has a powerful influence on fluid and electrolyte homeostasis and the control of blood pressure.     

Characteristics of placebo response during long-term treatment of panic disorder

Mixed-panic disorder patients (16/60, 27%) randomly assigned to receive blind placebo during a 40-week treatment study were defined as placebo responders based on combined criteria of Hamilton Anxiety Scale score percentage decreases below the median point (-42%), moderate to marked improvement on both clinician and patient Clinical Global Impressions scores, and panic-free at final treatment visit. These criteria applied separately also resulted in a similar clinical grouping and pattern of response. Differential patterns of response between responders and nonresponders occurred across most clinical measures of panic/anxiety. Responders experienced early improvement within the first week of double-blind treatment. This response progressed during treatment and tended to persist during taper and at followup 1 month later. Post-hoc analysis of demographic and clinical features at entrance into the study failed to characterize this stringently defined group of placebo responders.     

Characterization of adhesive interactions between human endothelial cells and megakaryocytes.

Cell-cell adhesion is essential for many immunological functions and is believed to be important in the regulation of hematopoiesis. Adhesive interactions between human endothelial cells and megakaryocytes were characterized in vitro using the CMK megakaryocytic cell line as well as marrow megakaryocytes. Although there was no adhesion between unactivated human umbilical vein endothelial cells (HUVEC) and megakaryocytes, treatment of HUVEC with inflammatory cytokines such as IL-1 beta, tumor necrosis factor alpha, INF-gamma, or the phorbol ester phorbol myristate acetate (PMA) resulted in a time- and dose-dependent increase in adhesion. Stimulation of marrow megakaryocytes or CMK cells with the cytokines IL-1 beta, GM-CSF, IL-6, IL-3, or PMA augmented their adhesion to endothelium. Monoclonal antibodies against the LFA-1 subunit of the leukocyte adherence complex CD18 inhibited the binding of marrow megakaryocytes or CMK cells to HUVEC. Adhesion blocking experiments also demonstrated that the VLA-4/VCAM-1 pathway was important for megakaryocyte attachment to HUVEC. Adhesion promoted maturation of megakaryocytic cells as measured by increased expression of glycoproteins GpIb and GpIIb/IIIa and by increased DNA content. These observations suggest that alterations in megakaryocyte adhesion may occur during inflammatory conditions, mediated by certain cytokines, resulting in augmented megakaryocyte maturation.     

Pathogenesis of postoperative hyponatraemia following correction of scoliosis in children

Eight paediatric patients undergoing major surgery for correction of scoliosis who were treated postoperatively with hypotonic saline and 5% dextrose have been studied. Plasma sodium, renin and aldosterone, and urine volume, sodium and osmolality were measured. These patients had an impaired ability to excrete a sodium-free water load. In the first 60 h urine volume remained reduced, while in the first 36 h urine sodium remained concurrently high. If the first 36 h postoperation are considered, the sodium-free water given was quantitatively retained and the serum sodium at 36 h was significantly correlated with the amount of free water given (P less than 0.01). To minimize postoperative hyponatraemia and the associated shift of water into the brain causing cerebral oedema, it is recommended that no more than 50 ml/kg sodium-free water be given until urine sodium falls and volume increases.     

Treatment of severe heart failure: quantity or quality of life? A trial of enoximone. Enoximone Investigators.

OBJECTIVES--To determine the effects of enoximone on mortality and quality of life in patients with severe end stage heart failure. DESIGN--A randomised, double blind, placebo controlled trial of the addition of enoximone to conventional treatment. Planned minimum follow up of one year. SETTING--District general hospitals and cardiological referral centres in the United Kingdom. PATIENTS--Planned 200 patients with severe, symptomatic heart failure despite treatment with diuretics and where appropriate and tolerated angiotensin converting enzyme inhibitors and digoxin. RESULTS--The study was ended early by the ethics committee after 151 patients had been recruited because of an excess mortality in the enoximone group: 27 deaths compared with 18 in the placebo group (P < 0.05). Quality of life measured with a disease specific questionnaire showed a clinically significant improvement at week 2 with a mean increase score of 0.48 in the enoximone treated patients compared with 0.14 in those receiving placebo (P = 0.0086). With the Nottingham health profile questionnaire the physical mobility score was improved after three months in the enoximone group, median 21.3 compared with 41.8 in the placebo group (P = 0.008). CONCLUSIONS--In patients with severe heart failure who remain incapacitated despite conventional treatment enoximone reduced survival but had a beneficial effect on the quality of life. Drugs that improve symptoms in severe end stage heart failure should not be discarded lightly.