NATURE AND HEALING OF TIBIAL SHAFT FRACTURES IN ALCOHOL ABUSERS

Alcohol abuse is associated with an increased risk of osteopeniaand fractures. Previous histomorphometric studies on iliac crestbone have found decreased bone formation and increased boneresorption in alcohol abusers but it has not been establishedwhether alcohol abuse has any effect on the anatomical locationor the healing time of tibial shaft fractures. We studied, retrospectively,199 adult male patients hospitalized for isolated tibial shaftfracture in the city of Malmö, Sweden, between 1980 and1990. Forty-nine of the patients had earlier been registeredat the Department of Alcohol Diseases and were judged to beproblem drinkers. Abusers sustained their tibial shaft fracturesmore often by falling at ground level (P<0.0001) or froma higher level (P=0.009) and the fractures were more often obliquethan transverse (P=0.002) as compared with non-abusers. Healingtime was impaired in abusers who had sustained a transversefracture (P=0.035), but no difference was observed in healingtime in those with an oblique fracture. We found no differencebetween the abusers and the non-abusers regarding duration ofhospital stay, fracture location, amount of displacement, occurrenceof open fractures or the rate of complications.     

Factors contributing to blood pressure elevation during norepinephrine and phenylephrine infusions in dogs

To examine the factors contributing to the rise in systemic blood pressure during α- and β- adrenergic stimulation, phenylephrine, an α-adrenergic agonist, and norepinephrine, an α- and β-adrenergic agonist, were infused intravenously to anesthetized dogs until mean aortic blood pressure was raised equally by 40–60 mmHg. Changes in preload were estimated by changes in left ventricular end-diastolic pressure or segment length recorded by an ultrasonic technique. By obstructing the inferior vena cava (IVC), the increase in preload could be reduced to control level during phenylephrine and norepinephrine infusions without altering peripheral resistance (mean aortic blood pressure/cardiac output). Normalization of preload reduced the pressure response by 2/3 during phenylephrine infusion and by 1/4 during norepinephrine infusion. However, after β-adrenergic blockade by propranolol, normalization of preload reduced the pressure response by 2/3 during both phenylephrine and norepinephrine infusions. Thus, during α-adrenergic stimulation, the increase in preload is a more important factor than the increase in peripheral resistance. Norepinephrine raised stroke volume by 24±5%. When the increase in stroke volume was prevented by IVC obstruction, the pressure response to norepinephrine was halved. Thus, during norepinephrine infusion the rise in stroke volume caused by β-adrenergic stimulation is as important as α-adrenergic stimulation for the pressure response.     

Mechanism of blood pressure elevation during angiotensin infusion

The mechanism of increased preload and its contribution to the rise in blood pressure during intravenous angiotensin infusion were studied in anesthetized dogs. In open-chest dogs angiotensin increased mean aortic blood pressure by 58±12 mmHg. Left ventricular end-diastolic dimension, measured as myocardial chord length (MCL) by ultrasonic technique, increased by 7±1 %. By inflating a balloon in the inferior vena cava, end-diastolic MCL was reduced to control value and the rise in mean aortic blood pressure was almost halved to 32±10 mmHg above control value. A similar preload effect was recorded in closed-chest dogs using end-diastolic left ventricular pressure as an estimate of left ventricular volume. During angiotensin infusion to the upper body only, end-diastolic MCL did not increase. When redistribution of the splanchnic blood volume was prevented, the effect of angiotensin on end-diastolic MCL was reduced to 1/3. Angiotensin reduced liver but not splenic dimension measured by ultrasonic technique. We conclude that about half of the rise in blood pressure during angiotensin infusion is due to increased end-diastolic volume caused by blood redistribution. About 2/3 of this increase in preload is due to redistribution from the splanchnic bed, mainly from the liver.     

Determinants of pulmonary blood volume. Effects of acute changes in pulmonary vascular pressures and flow

To examine the effects of pulmonary vascular pressures and flow on pulmonary blood volume (PBV), experiments were performed at constant heart rate and zone 3 conditions (mean left atrial pressure (LAP) above airway pressure) in six anesthetized, open-chest dogs. PBV was calculated as the product of electromagnetic aortic flow and pulmonary mean transit time for ascorbate, obtained without blood withdrawal by polarographic recording of aortic ascorbate changes. In three series of experiments LAP was raised similarly in three steps, from 4.5 to 14.8 mmHg: by mitral constriction which reduced pulmonary blood flow, by blood volume expansion which more than doubled pulmonary blood flow, or by a combination of the two procedures which kept pulmonary blood flow constant. In all three series, LAP and mean pulmonary arterial pressure (PAP) rose in proportion, but PBV was better correlated to PAP (r=0.87±0.02) than to LAP (r=0.66±0.09). These experiments suggest that PAP is the most important factor in determining PBV under zone 3 conditions, whether PAP is raised by increasing pulmonary blood flow or by mitral constriction.     

Dependency of renal potassium excretion on Na,K-ATPase transport rate

Potassium secretion may depend on the transport rate of Na, K-ATPase in basolateral cell membranes of distal tubular cells. To examine this hypothesis experiments were performed in anaesthetized dogs during inhibition of proximal potassium reabsorption by acetazolamide or mannitol (fractional potassium excretion 1.2-1.4) or additional stimulation of potassium secretion by ethacrynic acid (fractional potassium excretion 2.1). Ouabain in a dose which inhibits 70–80% of the Na, K-ATPase activity reduced fractional potassium excretion to 0.8-0.9 by an effect on distal tubular secretion since potassium transport in the proximal tubules was not affected. Ouabain-sensitive potassium excretion varied in proportion to ouabain-sensitive sodium reabsorption during variation in glomerular nitration rate, even at urinary sodium concentrations exceeding 80 mmol 1^-1. In experiments without ouabain, saline infusion raised potassium excretion and sodium reabsorption until maximal Na, K-ATPase transport rate was reached, as judged from heat production measurements, but not during further increments in urine flow. After inhibition of Na, K-ATPase activity by hypokalaemia, potassium excretion and cortical heat production remained constant over a wide range of urine flow and sodium excretion. We conclude that potassium secretion is dependent on intact Na, K-ATPase activity and is stimulated by sodium delivery to the distal nephron until maximal transport rate of the enzyme is reached.     

Minimum analogue peptide sets (MAPS) for quantitative structure-activity relationships

The information contents in previously published peptide sets was compared with smaller sets of peptides selected according to statistical designs. It was found that minimum analogue peptide sets (MAPS) constructed by factorial or fractional factorial designs in physicochemical properties contained substantial structure-activity information. Although five to six times smaller than the originally published peptide sets the MAPS resulted in QSAR models able to predict biological activity. The QSARs derived from a MAPS of nine dipeptides, and from a set of 58 dipeptides inhibiting angiotensin converting enzyme were compared and found to be of equal strength. Furthermore, for a set of bitter tasting dipeptides it was found that an incomplete MAPS of 10 dipeptides gave just as good a model as the model based on a set of 48 dipeptides. By comparison other non-designed sets of peptides gave QSARs with poor predictive power. It was also demonstrated how MAPS centered on a lead peptide can be constructed as to specifically explore the physicochemical and biological properties in the vicinity of the lead. It was concluded that small information-rich peptide sets MAPS can be constructed on the basis of statistical designs with principal properties of amino acids as design variables.     

ALCOHOL ABUSE AND HEALING COMPLICATIONS AFTER CERVICAL HIP FRACTURES

Osteonecrosis of the femoral head following femoral neck fracturesis a common condition. Spontaneous osteonecrosis, is, however,a rare disorder, which is observed with increased frequencyin alcohol abusers. In this retrospective study, we followed512 consecutive male patients who had sustained femoral neckfractures between 1984 and 1992; 82 of these 512 patients (16%)had earlier been registered at the Department of Alcohol Diseasesas high consumers of alcohol. The aim of the study was to determinethe relationship between the rate of healing complications andalcohol consumption. No differences were observed in the degreeof fracture dislocation, frequency of femoral head necrosis,and pseudoarthrosis among the abusers. Furthermore, no differenceswere found in causative events, primary operative treatment,post-operative complications, and the number of secondary operations.The abusers were significantly younger, had a higher rate ofearly retirement, and had an increased death rate. Our studysuggests that alcohol complicates the healing process to a lesserextent than earlier thought, and that osteonecrosis of the femoralhead after femoral neck fractures is equally conimon in non-abusersas in abusers.     

How to calculate human muscle fibre areas in biopsy samples—methodological considerations

Cross-sectional muscle fibre areas (type I, IIA and IIB) were determined in duplicate biopsies from the left vastus lateralis (n=11) and in biopsies from right and left vastus lateralis (n=8).The SD for the difference in means between duplicate biopsies was 510 μm² for type I, 1020 μm² for type II A and 860 μm² for type II B.Expressed as coefficient of variation (CV) these SD constituted 10, 15 and 15%, respectively. The variation in fibre size within a sample was considerably less than the variation between samples on the assumption that at least 15–20 areas of each fibre type were measured per sample. No difference in mean fibre area for type I, IIA and IIB fibres was obtained between the right and left muscle. Several artefacts due to the sampling and preparing procedures are discussed and a method for determining muscle fibre areas in biopsy samples is suggested.