Functional versus standardized assessment procedures: implications for educational programming.

Teacher perceptions of the educational value of two distinct assessment procedures for assessing an 8-year-old student with severe to profound multiple disabilities were compared. Direct service providers (N = 38) from a public school system, randomly distributed into three groups, were asked to use an 8-item Likert-type survey to rate one of three assessment packages: standardized, functional-ecological, and a combined package. Results for four of the eight items were statistically significant. The functional-ecological approach was perceived to be most beneficial for educational intervention. Implications for greater emphasis on a functional-ecological assessment procedure versus standardized procedures were discussed.


Increased receptor binding of low-density lipoprotein from individuals consuming a high-carbohydrate, low-saturated-fat diet.

The substitution of saturated fat by complex carbohydrate, according to current dietary recommendations, results in a decrease of plasma and low-density lipoprotein (LDL) cholesterol levels. To determine whether this decrease might result from structural and thus functional changes in LDL particles, the binding internalization and degradation of 125I-LDL were measured using TR715-19 cells, a mutant CHO line into which has been transfected the human LDL receptor, and in which measurements of binding are highly reproducible. Eleven nondiabetic subjects (35 +/- 4 years, 27% +/- 3% body fat) were studied after they had 15% protein, and 560 mg cholesterol/d and the other containing 21% fat (6% saturated), 65% carbohydrate, 14% protein, and 524 mg cholesterol/d.LDL cholesterol levels decreased form 125 +/- 6 to 108 +/- 5 mg/dl (P < .01) on the high-carbohydrate diet. There was an increase in the binding affinity of LDL (Kd 6.6 +/- 2.6 v 7.3 +/- 2.7 micrograms/mL +/- SD; P < .02), and internalization (P < .10), and degradation (P < .05) were also higher. The data suggest that decreasing dietary saturated fat may cause alterations in LDL composition that result in increased receptor clearance; this may partially explain the LDL-decreasing effect of this dietary change.


Type I hyperlipoproteinemia caused by lipoprotein lipase defect in lipid-interface recognition was relieved by administration of medium-chain triglyceride.

We have previously reported lipoprotein lipase with a defect of lipid-interface recognition in a patient with type I hyperlipoproteinemia. In this patient, lipoprotein lipase from post-heparin plasma (PHP) hydrolyzed monomeric substrate tributyrin, but scarcely hydrolyzed triolein emulsified with Triton X-100 and that in very-low-density lipoproteins ([VLDL] d < 1.006 g/mL), and did not bind to VLDL. The triglyceride (TG) level of this patient did not decrease to less than 1,000 mg/dL with a low-fat diet (1,400 kcal containing 10 g fat/d). When the patient took 30 g medium-chain TG (MCT) in addition to the 1,400-kcal diet, her serum TG level decreased to 250 mg/dL and her clinical signs improved. The low clearance rate of serum TG with heparin injection improved after intake of MCT. Caproic acid levels were maintained at 1.4% and 2.6% in chylomicrons and VLDL after MCT intake, respectively. The patient's lipoprotein lipase hydrolyzed triolein emulsified with 2% tricaprin at the same rate as that of control lipoprotein lipase. The patient's lipoprotein lipase-catalyzed hydrolyzing rate of triolein in chylomicrons obtained after MCT administration was also enhanced up to 70% of that of control lipoprotein lipase. These findings suggest that hypertriglyceridemia caused by lipoprotein lipase with a defect in lipid-interface recognition could be relieved with the administration of medium-chain TG, and that one of the mechanisms of this effect might be a modification of TG-rich lipoproteins by MCT.


The influence of indomethacin, theophylline, and propranolol on ethanol augmentation of glucose-induced insulin secretion.

The effect of indomethacin, theophylline, and propranolol on ethanol augmentation of insulin secretion after intravenous glucose stimulation was studied. Intravenous glucose tolerance tests were performed with and without pretreatment with oral ethanol. The role of indomethacin was evaluated in six healthy subjects; the effect of theophylline and propranolol on ethanol augmentation in insulin secretion was studied in five and six subjects, respectively. Ethanol pretreatment was followed by increased insulin (P < .01) and C-peptide areas (P < .01) after intravenous glucose (Area, 0 to 20 minutes). Indomethacin suppressed the ability of ethanol to augment insulin (P < .01) and C-peptide (P < .01) responses. Neither theophylline nor propranolol affected ethanol augmentation of insulin secretion. In conclusion, indomethacin probably interferes with the mechanism for ethanol augmentation of glucose-induced insulin secretion. It is suggested that inositol phospholipids take part in the effect of ethanol to augment insulin secretion, and that indomethacin interferes with the metabolism of inositol phospholipids.


In vivo assessment of the metabolic alterations in glucagonoma syndrome.

Stable-isotope methodology and indirect calorimetry were used to evaluate metabolic abnormalities in a patient with glucagonoma syndrome manifested by 17% body weight loss, hypoaminoacidemia, and hyperglycemia. Energy expenditure (26 kcal/kg) was the same as that predicted by the Harris-Benedict equation. The rate of appearance (Ra) of intracellular leucine (2.70 mumol/kg/min), an index of protein breakdown, was normal, although the percentage of leucine flux oxidized (31%), an index of amino acid catabolism, was 50% greater than the normal mean value. Glucose Ra in plasma (12.9 mumol/kg/min), representing hepatic glucose production, and glycerol Ra in plasma (3.04 mumol/kg/min), a measurement of whole-body lipolysis, were 15% and 25% greater, respectively, than mean values found in normal volunteers. These results suggest that long-term alterations in energy, leucine, glucose, and lipid metabolism in patients with glucagonoma are minimal. However, small long-term metabolic alterations caused by glucagon excess, in conjunction with chronic negative energy balance, could be responsible for the weight loss, hypoaminoacidemia, and hyperglycemia observed in this patient population.


Effects of intralipid-induced hypertriglyceridemia on plasma high-density lipoprotein metabolism in the cynomolgus monkey.

Low plasma levels of high-density lipoprotein (HDL) and apolipoprotein (apo) A-I often accompany human hypertriglyceridemia. In an animal model of hypertriglyceridemia, the lipoprotein lipase (LPL)-inhibited cynomolgus monkey, we reported that plasma levels of apo A-I were decreased and the fractional catabolic rate (FCR) of HDL apo was increased. To explore whether hypertriglyceridemia alone would alter plasma apo A-I levels and catabolism, hypertriglyceridemia was produced by intravenous (IV) infusion of 20% Intralipid into female cynomolgus monkeys. Baseline plasma triglyceride (TG) levels averaged 106 mg/dL. With infusion of 200 mg/kg/h Intralipid TG, plasma TG levels peaked at 967 mg/dL (range, 413 to 1,069; n = 6). More prolonged or more severe hypertriglyceridemia caused serious complications in several monkeys. Despite the severe hypertriglyceridemia, HDL TG content, HDL apoproteins, and plasma apo A-I levels did not markedly change, suggesting that very little HDL remodeling had occurred. Kinetic studies of HDL protein and apo A-I were performed in four pairs of monkeys. The two tracers were removed from the plasma at identical rates. In five pairs of animals, apo A-I turnover during control and Intralipid-induced hypertriglyceridemia was not significantly different. We hypothesize that apo A-I FCR is a function of HDL composition. Because Intralipid infusion did not alter HDL composition to the same degree as did LPL inhibition, its effects on HDL apo catabolism were not apparent.


Apolipoprotein E and lipoprotein lipase reduce macrophage degradation of oxidized very-low-density lipoprotein (VLDL), but increase cellular degradation of native VLDL.

Oxidized low-density lipoprotein (Ox-LDL) has been shown to be taken up by the macrophage-scavenger receptor at an enhanced rate in comparison to native LDL, with consequent cellular cholesterol accumulation. In the present study, we analyzed macrophage interaction with very-low-density lipoprotein (VLDL) from normolipidemic subjects (N-VLDL) that was oxidized in the presence of 10 mumol/L copper ions. Oxidized VLDL (Ox-VLDL) contained increased conjugated dienes and malondialdehyde (MDA) equivalents and showed increased electrophoretic mobility. Gradual fragmentation of VLDL apolipoproteins (apo) was noted, with apo B-100 being the first to be fragmented, followed by apo E and apo C. Degradation of Ox-VLDL by mouse peritoneal macrophages (MPM) was increased almost twofold in comparison to N-VLDL. Upon incubation of VLDL with lipoprotein lipase (LPL), the LPL-treated lipoprotein demonstrated up to 50% increased degradation by macrophages in comparison to control N-VLDL. However, the degradation of LPL-treated Ox-VLDL was decreased by up to 20% in comparison to control Ox-VLDL. Similarly, the addition of apo E to VLDL enhanced its cellular degradation by 56%, whereas a 20% reduction in the degradation of apo E-treated Ox-VLDL was demonstrated in comparison to nontreated Ox-VLDL. These results showed that LPL and apo E, two important regulatory substances in cellular metabolism of plasma lipoproteins, increased macrophage degradation of native VLDL, but reduced the degradation of Ox-VLDL. These inhibitory effects on macrophage uptake of Ox-VLDL suggest that apo E and LPL may possess antiatherogenic potential.


Effects of estrogen replacement on plasma lipoproteins and apolipoproteins in postmenopausal, dyslipidemic women.

The effects of oral estrogen replacement (ethinyl estradiol 0.02 mg/d) on plasma triglyceride, total cholesterol, very-low-density lipoprotein (VLDL) cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) A-I and B levels and LDL particle size were assessed in 20 postmenopausal women with a previous hysterectomy and various forms of dyslipidemia (LDL cholesterol > or = 4.14 mmol/L [160 mg/dL] and/or HDL cholesterol < or = 1.03 mmol/L [40 mg/dL]). All subjects were studied while on a standard cholesterol-lowering diet, and were sampled in the fasting state before beginning estrogen therapy and after a mean of 13 weeks of estrogen therapy. Lipids were measured by standardized enzymatic techniques, apos were measured by enzyme-linked immunoassays, and LDL particle size was measured by gradient gel electrophoresis. Mean values for plasma lipid parameters (mmol/L) at baseline and during estrogen replacement were as follows: triglyceride, 2.11 and 2.75 (30% increase); total cholesterol, 7.45 and 6.52 (13% decrease); VLDL cholesterol, 1.09 and 1.22 (12% increase); LDL cholesterol, 5.09 and 3.70 (27% decrease); and HDL cholesterol, 1.27 and 1.58 (24% increase). Mean values for apo A-I were 163 and 254 mg/dL (56% increase), and for apo B they were 170 and 148 mg/dL (13% decrease). The LDL particle score was 4.09 and 4.52 (11% smaller). Changes in all parameters were statistically significant (P = .05) except for VLDL cholesterol. These data indicate that estrogen replacement is effective in decreasing LDL cholesterol and apo B concentrations and increasing HDL cholesterol and apo A-I concentrations in dyslipidemic postmenopausal women, but it should not be used in patients with baseline fasting triglyceride levels higher than 2.82 mmol/L (250 mg/dL) unless it is accompanied by a progestin. Our data indicate that this form of estrogen replacement could lower the risk of coronary artery disease (CAD) by more than 50% in these women, based on favorable alterations in plasma lipoproteins.


Placental transfer and uptake of 2-deoxyglucose in control and diabetic rats.

Placental glucose transfer and sequestration were investigated in anesthetized control and streptozotocin-diabetic rats by perfusing the fetal side of one placenta in situ while infusing a mixture of [3H]D-glucose (to measure net transfer after metabolism) and [14C]2-deoxyglucose (to estimate tissue sequestration) into the maternal circulation. No difference was found between transfer ratios (perfusate/simultaneous maternal plasma ratio) of [3H]D-glucose (0.35 +/- 0.06, mean +/- SD) and [14C]2-deoxyglucose (0.36 +/- 0.06) in control rats. Ratios were reduced (P < .001) to the same extent in diabetic rats ([3H]D-glucose, 0.13 +/- 0.06; [14C]2-deoxyglucose, 0.15 +/- 0.07). Placental glucose utilization, estimated by the quantity of [14C]2-deoxyglucose-6-phosphate present, was increased from 66 nmol.min-1.g-1 in control to 595 nmol.min-1.g-1 (P < .001) in diabetic rats. Transfer to the perfusion fluid of unlabeled D-glucose was increased (P < .001) in diabetic rats (2.32 mumol/mL) compared with control rats (0.77 mumol/mL) due to elevated (P < .001) maternal plasma glucose levels. Upon phosphorylation, 2-deoxyglucose becomes trapped within the placenta, and therefore these results indicate that all the glucose destined for direct transfer to the fetus is protected from phosphorylation while traversing the placenta, and that diabetes appears to increase placental glucose utilization, but does not induce futile cycling of glucose in an attempt to protect the fetus from an excessive influx of glucose from the mother in the rat.


Altered tissue polyamine levels due to ornithine-alpha-ketoglutarate in traumatized growing rats.

All cells contain significant amounts of polyamines (PA), and their concentrations are highly regulated. Metabolic activity within a tissue may be reflected in the amount of intracellular PA. Since trauma involves accelerated death and regeneration of tissues, the related levels of PA in extracellular and intracellular fluids may reflect altered protein metabolism. Trauma induces an increased excretion of urinary PA, and the tissues responsible for this whole-body activity are not known. During posttraumatic nutritional management, supplementation with ornithine-alpha-ketoglutarate (OKG) seems to improve nitrogen economy. The present study evaluates the significance of muscle, liver, and intestine PA responses in traumatized (bilateral femur fractures) rats to the feeding of an isonitrogenous liquid diet supplemented with or without OKG. Uninjured control rats were pair-fed with respective traumatized rats. After 2 days of starvation and 4 days of feeding, the traumatized and control rats were killed and the tissues were excised and analyzed. Starvation decreases and refeeding increases urinary PA excretion. Trauma-induced PA response is predominantly seen in muscle tissues, and this may be responsible for parallel increases in PA excretion. Liver PA responses show a varying tendency confirming the increased protein synthetic activity due to trauma. Intestine has the highest intracellular PA levels, and there is a general smaller (statistically insignificant) increase in all the individual PA contents due to trauma. OKG supplementation augments tissue and urine PA responses in control rats; however, in trauma rats muscle PA levels show very little change, although nitrogen retention is significantly better (88% to 77%). Mechanistic studies are needed to evaluate the significances of the time-dependent, injury-induced, individual intracellular PA levels.


An apparently anomalous relationship between insulin and C-peptide concentrations in their initial response to intravenous glucose.

Intravenous glucose tolerance tests (IVGTTs) with determination of plasma glucose, insulin, and C-peptide concentrations were performed in 136 men and 154 women. It was found that in 4% of men and 12% of women the plasma concentration of insulin exceeded that of C-peptide during the initial response to glucose. Subjects exhibiting this phenomenon had lower fasting and post-glucose C-peptide concentrations than those who did not; however, there were no statistically significant differences in glucose or insulin concentrations. The phenomenon was age-related, being absent from individuals aged 35 years and under, while in older age groups it appeared to be more prevalent in women than in men, suggesting an additional effect of menopause. However, in three follow-up IVGTTs performed in a subgroup of postmenopausal women over a period of 18 months, the phenomenon failed to recur in any of the individuals who first exhibited it, although it did occur in others. Our observations suggest the existence of an age-related but intermittent decrease in pancreatic insulin secretion, which does not lead to any significant change in plasma insulin concentrations, possibly as a result of reduced hepatic uptake of insulin. One consequence appears to be an excess of insulin over C-peptide during the early part of the IVGTT, which is probably related to the different distributional kinetics of the two peptides.


Oxidative modification of lipoprotein(a) and the effect of beta-carotene.

Lipoprotein (a) [Lp(a)] particles isolated and purified from human plasma were found to be oxidatively modified when incubated in vitro with human mononuclear cells or Cu2+. This modification, which involved lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS), caused marked changes in the structure and biological properties of Lp(a). Relative to native Lp(a), oxidized particles showed decreases of free amino groups, protein fragmentation, increased negative charge, and high aggregation ability. They were taken up and degraded readily by macrophages in vitro, inducing cholesteryl ester accumulation. When apolipoprotein (a) [apo(a)] was clipped off by exposure to dithiothreitol (DTT), the remaining particle was degraded by macrophages at a significantly lower rate. This observation implies that oxidative modification of apo(a) may have an influence on Lp(a) recognition by scavenger receptors of macrophages. Under the same experimental conditions, low-density lipoprotein (LDL) concentrations equal to those of Lp(a) showed a lower susceptibility to oxidation. This was probably due to higher vitamin E (30% more) and beta-carotene (40% more) content compared with Lp(a), when expressed as a function of cholesterol concentration and measured in the same subject. The addition of beta-carotene to Lp(a) in vitro partially protected Lp(a) against oxidation and aggregation. As a result, uptake of oxidized Lp(a) by macrophages decreased markedly. We conclude that Lp(a) particles are prone to oxidation and that the increased risk of coronary artery disease associated with elevated Lp(a) levels may be related in part to their oxidative modification and uptake by macrophages, resulting in the formation of macrophage-derived foam cells.


Probucol protects lipoprotein (a) against oxidative modification.

Probucol, which decreases cholesterol levels and has antioxidant properties, was administered orally to patients with familial combined hyperlipidemia and high plasma lipoprotein(a) [Lp(a)] levels. The drug had no effect on Lp(a) concentrations after 4 weeks, but was found to be distributed in both Lp(a) and low-density lipoprotein (LDL). Before treatment, in each case LDL and Lp(a) isolated from the same individual were readily oxidized by copper, resulting in increased electrophoretic mobility and enhanced uptake and degradation by macrophages of both lipoproteins. After probucol treatment, both lipoproteins acquired resistance to in vitro oxidation by copper. Furthermore, probucol prevented their enhanced uptake and degradation by the macrophages. It is surmised that oxidized Lp(a) may carry an atherogenic potential that could be opposed by probucol administration.


Effect of hemodialysis on lipid peroxidation and antioxidant system in patients with chronic renal failure.

Plasma lipid peroxidation, activity of erythrocyte superoxide dismutase (SOD) and catalase, and serum antioxidant activity (AOA) in uremic patients were examined before and after hemodialysis. An increased level of lipid peroxidation, a decreased serum AOA level, and elevated SOD and normal catalase activity before hemodialysis were observed in uremic patients compared with controls. Hemodialysis was found to produce increased lipid peroxidation, a simultaneous decrease of SOD activity, and lack of any changes in serum AOA and erythrocyte catalase. It is suggested that intensification of lipid peroxidation during hemodialysis could account for accelerated progress of atherosclerosis in patients with renal insufficiency.


Potentiation of the thermogenic antiobesity effects of ephedrine by dietary methylxanthines: adenosine antagonism or phosphodiesterase inhibition?

Current concepts about the mechanisms underlying the therapeutic effects of dietary methylxanthines (caffeine, theophylline, and theobromine) favor their actions as antagonists of adenosine receptors, and attribute their other possible modes of action, namely those associated with translocation of intracellular calcium, inhibition of phosphodiesterase enzyme (PDE) activity, or the release of catecholamines, to high (near-toxic) doses. From studies measuring the respiration rate of brown adipose tissue (BAT), evidence is provided here that at concentrations compatible with therapeutic doses, the ability of methylxanthines (25 to 50 mumol/L) to potentiate the thermogenic effect of the sympathomimetic drug, ephedrine (0.25 mumol/L), particularly under conditions of caloric restriction, involves a minor contribution of adenosine antagonism, but could mainly be explained by the inhibition of PDE activity. In view of current interest in the pharmacological stimulation of metabolic rate to assist the management of obesity with low-calorie regimens, the targeting of PDE activity is therefore a rational approach in the search for drugs that could potentiate sympathomimetic stimulation of metabolic rate.


Is body fat loss a determinant factor in the improvement of carbohydrate and lipid metabolism following aerobic exercise training in obese women?

Thirty-one obese, premenopausal women aged 35.4 +/- 5.1 (SD) years exercised for 90 minutes at approximately 55% of maximal aerobic power (VO2max) four to five times a week for a period of 6 months. The training program induced a significant increase in VO2max (P < .001) and significant improvements in carbohydrate and lipid metabolism, as reflected by decreased plasma insulin (INS) concentrations measured in the fasting state and after glucose (GLU) ingestion (INS area, P < .001), by reduced plasma cholesterol (C) and low-density lipoprotein cholesterol (LDL-C) levels (P < .001), and by increased ratios of high-density lipoprotein cholesterol (HDL-C)/LDL-C and HDL2-C/HDL3-C (P < .05 and P < .001, respectively). Changes in body fat mass were positively associated with changes in the INS area/GLU area ratio (r = .49, P < .05) and with changes in very-low-density lipoprotein triglycerides ([VLDL-TG] r = .49, P < .05). Furthermore, changes in the INS area were positively associated with changes in VLDL-TG (r = .51, P < .05). Although no significant mean change in body composition was observed, important individual variation was noted. Twenty women showed a reduction in body fat mass (mean reduction, 2.63 +/- 2.2 kg), whereas 11 women showed an increase in adipose mass (mean increase, 2.79 +/- 2.36 kg). Comparable increases in VO2max were observed between the two groups. The group that showed a decrease in body fat mass with exercise also had significant improvements in carbohydrate and lipid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)


The morphology and metabolism of intraabdominal adipose tissue in men.

Mass, morphology, and metabolism of total adipose tissue and its subcutaneous, visceral, and retroperitoneal subcompartments were examined in 16 men with a wide variation of total body fat. Computerized tomography (CT) scans showed that the intraabdominal fat mass comprised approximately 20% of total fat mass. Visceral and retroperitoneal fat masses were approximately 80% and 20% of total intraabdominal fat mass, respectively. Enlargement of intraabdominal fat depots was due to a parallel adipocyte enlargement only. Direct significant correlations were found between these adipose tissue masses and blood glucose and plasma insulin levels, blood pressure, and liver function tests, while glucose disposal rate during euglycemic glucose clamp measurements at submaximal insulin concentrations (GDR), plasma testosterone, and sex hormone-binding globulin concentrations correlated negatively. The correlations for glucose, insulin, and GDR were strongest with visceral fat mass. Adipose tissue lipid uptake, measured after oral administration of labeled oleic acid in triglyceride, was approximately 50% higher in omental than in subcutaneous adipose tissues. Adipocytes from omental fat also showed a higher lipolytic sensitivity and responsiveness to catecholamines. Furthermore, these adipocytes were less sensitive to the antilipolytic effects of insulin. Both lipid uptake and lipolytic sensitivity and responsiveness showed strong correlations (r = 0.8 to 0.9) to blood glucose and plasma insulin concentrations and also to the GDR (negative), while no such correlations were found with lipid uptake in subcutaneous or retroperitoneal abdominal adipose tissues. Taken together, these results suggest a higher turnover of lipids in visceral than in the other fat depots, which is closely correlated to systemic insulin resistance and glucose metabolism in men.


Insulin hypersecretion: a distinctive feature between essential and secondary hypertension.

Several studies have demonstrated that patients with hypertension have greater plasma insulin levels than normotensive subjects. The aim of the present study was to clarify if hyperinsulinemia in hypertension is a consequence of either increased pancreatic secretion or decreased hepatic clearance, and to determine whether abnormalities of glucose metabolism are equally present in essential and secondary hypertension. In an observational cross-sectional study, fasting blood glucose, plasma insulin, and plasma C-peptide levels were measured in five patient groups: 34 lean normotensive, 19 overweight normotensive, 25 lean essential hypertensive, 27 overweight essential hypertensive, and 20 secondary hypertensive subjects. The blood glucose/plasma insulin and plasma insulin/plasma C-peptide ratios were calculated as indexes of insulin sensitivity and hepatic insulin clearance, respectively. Subjects with essential hypertension and, to a greater extent, those who were overweight, exhibited significantly higher fasting insulin and C-peptide levels and significantly lower glucose/insulin ratios as compared with lean normotensive subjects. In contrast, no differences were observed between secondary hypertensive and control subjects. Mean blood pressure was significantly and independently correlated to body mass index, plasma insulin and plasma C-peptide levels, and the glucose/insulin ratio. In lean essential hypertensive and secondary hypertensive subjects, the insulin/C-peptide ratios were comparable to controls, indicating normal hepatic insulin clearance. In both overweight groups, a trend to increased insulin/C-peptide ratios was observed. This study shows that in essential hypertensive subjects, hyperinsulinemia is caused by insulin hypersecretion, whereas in overweight subjects, both increased insulin secretion and decreased hepatic insulin clearance might be involved.(ABSTRACT TRUNCATED AT 250 WORDS)


Time-dependent regulation of rat adipose tissue glucose transporter (GLUT4) mRNA and protein by insulin in streptozocin-diabetic and normal rats.

Streptozocin (STZ) administration (125 mg/kg) to normal rats resulted in a rapid (24-hour) decrease in circulating insulin levels, marked hyperglycemia, and weight loss. Adipose tissue glucose transporter 4 (GLUT4) mRNA levels decreased approximately eightfold, whereas GLUT4 protein levels were unchanged. However, GLUT4 protein levels decreased approximately 30% by 48 hours and fivefold by 72 hours of insulin deficiency. Although GLUT4 mRNA levels were rapidly restored by insulin therapy (twofold above control levels within 12 hours), GLUT4 protein levels increased only gradually, reaching peak values of 1.5-fold control levels following 7 to 10 days of insulin treatment. Insulin treatment in normal rats increased adipose GLUT4 mRNA levels nearly 100% by 24 hours, while GLUT4 protein levels increased in a more gradual fashion. The delay in GLUT4 protein induction relative to its mRNA was shorter in normal rats treated with insulin than in insulin-treated diabetic rats. These data demonstrate that insulin-induced changes in adipose GLUT4 protein are considerably delayed relative to its mRNA, and that the diabetic state enhances this difference. The known in vivo time-dependent effects of insulin treatment on adipocyte glucose transport activity can be at least partly explained by altered specific expression of GLUT4 protein.


Ultrastructural analysis of platelet contractile apparatus.

Methods for evaluating the organization, subcellular distribution, and rearrangements in specific constituents of the platelet contractile cytoskeleton are rapidly being developed. The procedures presented and discussed here have yielded useful information. However, a great deal more is required before the role of contractile elements of the cytoskeleton in platelet physiology will be fully understood. The new approaches employing better preservation of platelet structure and immunocytochemistry will undoubtedly provide this knowledge in the near future.


Detection and identification of Mycobacterium tuberculosis, M. bovis/BCG, and M. avium by two-step polymerase chain reaction. Comparison with ELISA using A60 antigen.

We propose a rapid two-step PCR to amplify a 767-bp sequence present in the gene coding for the 65-kD antigen of mycobacteria. The high G+C content (80%) permitted annealing to occur at 70 degrees C, enhancing the specificity. The amplified fragment contains a restriction site for differentiation between M. tuberculosis, M. bovis/BCG, and M. avium. Complete diagnosis can be achieved in less than four hours without labelled probe or nucleic acid transfer.


Assisted evaluation of antibiotic resistance development in Pseudomonas aeruginosa from intensive care units.

421 strains of Pseudomonas aeruginosa were isolated from patients admitted to intensive care units and tested with automated systems for sensitivity to 21 antimicrobial agents. Data were collected in a database for evaluation and monitoring of resistance development. Results showed that assisted monitoring of antimicrobial resistance gives continuously updated information, with particular attention to the different local therapeutical schedules. It is therefore advisable that clinicians constantly exchange information with the microbiology laboratory through a hospital information system in which data from different laboratories are pooled in real time.


Incidence and level of exotoxin A in proteolytic cell-free cultures of clinical isolates of Pseudomonas aeruginosa collected from hospitals in Riyadh, Saudi Arabia.

Mice lethality bioassay revealed that out of 102 proteolytic cell-free cultures of Pseudomonas aeruginosa only 17 (15%) were lethal with values of 19-48 LD50/ml. Antitoxin A antiserum neutralized the lethality providing evidence that the main lethal compound in the cell free cultures was exotoxin A. The neutralization also ruled out the lethal contribution of protease, elastase and phospholipase c. The presence of exotoxin A in a proteolytic environment may indicate less efficient proteolytic action at the stage of toxin production.


Effect of ethylenediamine di-o-hydroxyphenylacetic acid and transferrin on the growth of some bacterial strains in vitro.

The ability of some bacterial strains to obtain iron from ethylenediamine di-o-hydroxyphenylacetic acid (EDDA) or iron-free transferrin, and accordingly grow in their presence, was studied. Growth of Staphylococcus aureus and Yersinia pseudotuberculosis was inhibited by EDDA or by iron-free transferrin. Growth of Streptococcus faecalis, however, was inhibited by iron-free transferrin, but not by EDDA. The other bacterial strains, i.e.; Escherichia coli, Salmonella typhimurium and Shigella dysenteriae were able to grow both in the presence of EDDA or iron-free transferrin. All of the above bacterial strains grow in the presence of iron-saturated transferrin which was not able to bind the iron of the medium and accordingly left the iron of the medium available to them.


Extracellular phenoloxidase activity of micromycetes from various taxonomic groups.

The ability of Micromycetes strains to produce extracellular phenoloxidases was examined on solid malt agar medium using ten different reagents. We established a POx index summarizing the global activity given by the ten reagents used. The results indicated a wide variability depending on the taxonomic groups, the genera and the species. Some groups were relatively homogeneous, either no and low producers of phenoloxidases (Yeasts, Zygomycetes, genera Aspergillus and Penicillium) or medium and high producers of phenoloxidases (Basidiomycetes, Coelomycetes, Tuberculariales and Dematiaceae), while other groups were very heterogeneous (Ascomycetes, Mucedinaceae). The POx index was significantly higher for strains recently isolated than for strains kept in the fungi collection for a long time.


Transfection of E. coli with lambda DNA by electroporation.

In the ambit of the B. subtilis genoma sequencing and mapping project, we have set up an electroporation method to transfect E. coli cells with lambda DNA. This methodology presents features that make it preferable to traditional in vitro packaging for some purposes. Here we will illustrate the experimental procedure and the possible applications.


Frequency of Mobiluncus spp. in bacterial vaginosis in Italy.

Eleven strains of Mobiluncus spp. were isolated from 35 vaginal secretions of patients with bacterial vaginosis (6 Mobiluncus curtisii and 5 Mobiluncus mulieris).


Serum cholesterol levels in axenic mice colonized with Enterococcus faecium and Lactobacillus acidophilus.

Hypocholesterolemic effect was shown in axenic, mono, bicolonized and conventional mice: the effect was different depending on probiotic properties of intestinal microorganisms. Contamination by Enterococcus faecium CX determined the highest effect: haematic cholesterol level decrease was 16.9% in females and 7.8% in males. In mice contaminated by Lactobacillus acidophilus N5 the decrease of haematic cholesterol levels was less and not relevant in mice contaminated by conventional microflora. Enterococcus faecium CX and Lactobacillus acidophilus N5 strains were able to grow in presence of bile salts, to colonize intestinal tract, to survive at gastric conditions and to assimilate cholesterol (E. faecium more than L. acidophilus). The authors consider the possibility to associate probiotic strains with these characteristics for the health of consumers.


The epidemiology of Lyme borreliosis in Italy.

Erythema migrans was described in Italy only in 1971 although Italian dermatologists were familiar with it a long time before. In 1983, the first case of Lyme borreliosis with multisystem involvement was identified. The endemic areas in Italy are the Ligurian coast, the province of Friuli Venezia Giulia, and the region surrounding the town of Bologna. In Liguria, the incidence of Lyme disease is about 17/100,000 inhabitants per year. Serosurveys of the general population and of sentinel animals were useless in determining the diffusion of Lyme borreliosis whereas evaluation of people at risk of tick bites and patients with suggestive signs or symptoms was more effective. Among the clinical manifestations of Lyme borreliosis, cutaneous involvement is four times more frequent than neuroborreliosis and arthritis is less frequent in Italy than in the USA.


[Penicillin resistance in Streptococcus pneumoniae strains].

In this study a total of 87 Streptococcus pneumoniae strains were tested for their susceptibility to penicillin with disk diffusion method by using 5 micrograms methicillin disks. In 68 strains susceptibility to penicillin was also determined by using agar dilution method performed in Mueller-Hinton agar supplemented with 5% sheep blood. Of 63 adult isolates tested with disk-diffusion method 35 strains (55.6%) were susceptible to penicillin, 24 strains (38.1%) had low level resistance and 4 strains (6.3%) had high-level resistance to penicillin. Of 24 S. pneumoniae isolates recovered from children 5 (20.8%) were penicillin susceptible, while 11 (45.8%) had low level resistance and 8 (33.4%) had high level resistance to penicillin. These values were 40 (45.9%), 35 (40.3%) and 12 (13.8%) in total isolates respectively. Of 44 isolates in which MIC values of penicillin were determined by agar dilution method, 34 strains (77.3%) were penicillin susceptible and 10 strains (22.7%) had low level resistance while none of these strains had high level resistance to penicillin. Of 24 children isolates tested with agar dilution method 11 strains (45.8%) were susceptible to penicillin, 8 strains (33.4%) showed low level resistance and 5 strains (20.8%) showed high level resistance to penicillin. For total of 68 isolates these values were 45 (66.1%), 18 (26.4%) and 5 (7.3%) respectively. These findings indicate the need to perform antibiotic susceptibility testing of all pneumococcal isolates to avoid therapeutic failure.


[Complement C3 and C4 levels in serum from acute viral hepatitis].

Serial measurements of C3 and C4 complement components were performed in 50 patients with acute, uncomplicated viral hepatitis, in the beginning of the symptoms and in the peaks of serum transaminases. There were 17 patients diagnosed as having Hepatitis A virus (HAV) infection and 33 patients diagnosed as having Hepatitis B virus (HBV) infection. There were 4 women and 46 men with a mean age of 22.1 years. In the sera of 50 healthy control subjects serum C3 and C4 complement components measured, this group was composed of 15 women and 35 men with a mean age of 26 years. The complement component levels were observed to be reduced in both viral infections, where the reduction in C3 serum concentration was found to be statistically significant but reduction in C4 serum concentration was not.


[The antibiotic properties of macrocyclic trichothecene mycotoxins].

Some trichotecenic mycotoxins (verrucarine A, roridines A and H, T-2-toxin) have been studied for their antibiotic effect on a wide spectrum of the yeast cultures (761 strains). The studied substances differ both in their activity and the action character. The yeast strains promising for development of microbiological methods of indication and detoxification of mycotoxins have been revealed.


[The destruction of cyanides and their metal complexes by natural bacterial trains].

Natural strains of bacteria of Bacillus and Pseudomonas genera able to destroy cyanides are obtained. Natural strain of Pseudomonas fluorescens B-5040 has a property to destroy high concentration of cyanides (100-200 mg/l) and does not lose the destructive activity in the systems with sufficiently high concentration of mercury (Na3ASO4) compounds (500 mg/l).


[Diagnostic value of ELISA for determining the occurrence of antibodies to antigen A60 in active pulmonary tuberculosis].

IgG antibodies against the purified antigen 60 have been detected in the sera of 48 active, 12 inactive pulmonary tuberculosis patients and 46 tuberculosis free controls with ELISA. Diagnostic value of this test has been evaluated in the conditions of our country. The detection of IgG antibodies against antigen 60 has 67% sensitivity, 90% specificity and 81% positive predictive values. It has been decided that these values have no superiority compared to the sputum examination. It was also found out that sensitivity of antigen 60 ELISA IgG test is very low (22%) in the condition of primary pulmonary tuberculosis cases where direct sputum microscopy sensitivity is also very low.


[Factors that affect transduction in microorganisms].

Data from literature concerning general and specialized transduction in microorganisms are given in the paper. The process of exogenic DNA penetration to the cells of bacteria and participation of protein products of separate phage genes in this process are described. The so-called E-proteins in a set with DNA penetrate through a cell membrane. In phage P22 they are protein products of phage genes 7, 16, 20. In P22 mutants with an altered transducing frequencies (HFT and LFT) the due functions are also coded by the phage genes. It is shown that the process of DNA packing in phages P22, phi 80, lambda and others is genetically determined. The gene transfer frequency depends on UV radiation and the very nature of transducing phages itself. In virulent phages the UV radiation up to inactivation level 95-99% evokes a decrease of their "killer" ability, which is accompanied by an increase of survivability of the formed transductants and, as a result, by enhancement of the transduction transfer frequency. An important role of the transduction analysis for fine mapping of a genome of microorganisms and its significance for practice are shown. A mathematical analysis of the data on cotransduction of linkage markers is presented as such that may be used when determining the value of transduced fragment of a chromosome.


[Development of resistance in bacteria interacting with subinhibitory antibiotic concentrations].

In order to determine the role of subinhibitory concentrations of antibiotics in resistance development, we performed an in vitro trial in which E. coli gained resistance after exposure to low concentrations of ampicillin in serial passages, while MIC values for amikacin and gentamicin increased 2 and 4 times, respectively. Pseudomonas also became resistant to ceftazidime whereas the MIC value for ciprofloxacin increased 10 times. There was not any significant change in susceptibility of S. aureus to vancomycin and amoxicillin + clavulanate.


[The stability of plasmid pSG 1912 inheritance by the cells of Streptomyces globisporus 1912 and of heterologous streptomycete strains].

Streptomyces globisporus 1912 strain contains plasmid pSG1912 (11, 2kb) determining some phenotypic properties. The plasmid is able to exist and to provide for exhibition of these properties both in autonomous and integrated state. It is established that plasmid pSG1912 and constructed derivatives are stably inherited by cells of S. globisporus 1912 and heterologous hosts, and besides, molecular size and determined properties being retained.


[Importance of the enzyme-linked immunosorbent assay (ELISA) for the serologic diagnosis of tuberculosis].

Tuberculosis is still a major granulomatosis disease in developing countries. The diagnosis of tuberculosis infection frequently creates problems which is related to clinical, radiological and bacteriological investigations. Recently, immunoenzymatic assays provide hopeful results for the serodiagnosis of tuberculosis. In this study, ELISA was evaluated as a serodiagnostic test for tuberculosis. Sera were obtained from 40 pulmonary tuberculosis patients and 15 healthy volunteer donors. The results showed that ELISA could be used in the serologic diagnosis of pulmonary tuberculosis.


[Bacteriological examination of paper money].

Bacteriological survey of one hundred twenty currency notes was done. Aerobic spore-forming bacilli (91%), Staphylococcus epidermidis (63.3%), Staphylococcus aureus (4.2%), Enterococcus (24.1%), alpha-hem. streptococcus (4.1%), Streptococcus pneumoniae (1.7%), Corynebacterium (7.5%), Lactobacilli (10.8%), Klebsiella pneumoniae (31.7%), Enterobacter (19.2%), E. coli (17.5%), Proteus (1.7%), Pseudomonas aeruginosa (0.8%), Shigella flexneri (0.8%) were isolated from paper money samples. Currency notes in general were bacteriologically contaminated especially with enteric pathogens and potentially pathogens, it was thought that some measures have to be taken to reduce these ill effects.


[Appropriate concentrations of antimicrobial agents in used cadaver pools].

Samples for microbiologic culture were taken from 17 cadaver and 4 cadaver pools in the Department of Anatomy of Gülhane Military Medical Academy (GMMA), Military Faculty of Medicine. Samples were inoculated on bacteriologic and mycologic media and were incubated in aerobic and 10% CO2 atmosphere conditions. From 3 of 4 pools containing different concentration of phenol and formalin, pathogenic bacteria that might be present in normal flora and saprophytic fungi were isolated. In the guidance of these results, in order to keep the cadavers for a long time and laboratory safety, use of formalin and phenol not less than 5% and 4% concentrations of the cadavers respectively and the pools should be taken into consideration.


[The growth of some Bradyrhizobium strains in uremic conditions in the presence of antimicrobial substances].

The growth rate of Bradyrhizobium japonicum USDA 110 and its STRR and AMPR mutant strains (resistant to streptomycin and ampicillin respectively), as well as TAL 945 and TAL 946, TAL 947 (mutants of USDA 110 and USDa 138 respectively) on yeast extract mannitol agar (YEMA) containing different concentrations of Crystal Violet and Brilliant Green. According to our results only the growth of Bacillus megaterium B17 was effected from Crystal Violet while the others were not effected from both of dyes in any concentration.


[Comparative evaluation of the isolation of dermatophytes by direct laboratory evidence and MSDA with MDTM culture media].

In this study, the hair, skin and nail examples taken from 225 patients suspected dermatophytoses clinically were investigated with direct microscopic examination and cultivated methods. Direct microscopic examination were positive in 135 examples (60%) and dermatophytes were isolated from 109 samples (48.4%). In the isolation of dermatophytes, the effectiveness of modified Sabouraud Dextrose Agar (mSDA) was 93.5% (102/109) and the effectiveness of modified Dermatophyte Test Medium (mDTM) was 95.4% (104/109). It was detected that there were no significant difference between these media for the isolation rate.


[Polymerase chain reaction].

The PCR is a method for obtaining millions of copies of a specific DNA sequence in vitro. It appears that this method will lead to several developments in the diagnosis and treatment of many disorders. Especially in genetics and infectious diseases successful results have been achieved. Abnormal gene or infectious agents' genes which may be in less amount in clinical specimens can be amplified with this method. In this way PCR can provide enough genetic material for further diagnostic analysis.


[Antinuclear antibodies and disease specificity].

In this review article, the serum antinuclear autoantibody types which are characteristic especially for rheumatic diseases (ANAs, Anti-ss/ds DNA, Anti-sm, Anti-histone, Anti-RNP, Anti-Ro, Anti-La etc.) were discussed on the basis of their biologic properties, their major role in the diagnosis and monitoring disease activity and response to therapy as well as disease specificity.


Reflections on possible virtues of European medical education.

Political and social development in Europe will lead to increased mobility of doctors between countries as well as opening up new possibilities and horizons for educational institutions. In this emerging process the charge that universities are too traditional to change may not be valid when the virtues of academic traditions in Europe are considered. When those virtues are taken into account, they are seen to facilitate the integration of more current goals for future development into undergraduate medical curricula. The use of external examiners between different countries in Europe will promote greater quality in European medical education.


A conference on ethics for obstetric and gynaecological clerkship students.

Integrating the teaching of medical ethics into medical students' clinical education is challenging, given the competing demands on students' time and the need for teaching to be clinically relevant. This paper describes a model programme for incorporating ethics teaching into the obstetrics and gynaecology clerkship for third-year medical students. The programme is taught by two attending teachers and a medical ethicist with experience teaching in the clinical setting of obstetrics and gynaecology. Objective pretests and posttests showed substantial improvement in students' knowledge, and student feedback has been very positive.


Attitudes of elderly patients to medical students.

The attitudes of elderly patients towards clinical teaching of medical students was assessed by a structured interview carried out by a doctor unknown to the patient immediately prior to discharge. One hundred and thirty alert patients were approached on three acute geriatric medicine wards in the Royal Liverpool (Teaching) Hospital. A total of 106 (81.5%) patients were suitable for inclusion in the study (mean age, 80.2 years). Twenty-nine per cent did not know what a medical student was despite having been interviewed and examined by one. Fifty-nine per cent of patients had no prior knowledge that clinical teaching occurred. Fourteen patients (13 women, 1 man, P < 0.05) objected to being examined. Nineteen women patients were examined by a man student without a chaperone. Students usually (95%) asked permission to interview and examine the patients whereas doctors only asked patients in the context of bedside teaching (33%). Elderly patients were sympathetic towards ('They have to learn') and positive about ('It's good to have them') medical students. However, 29% of patients were not aware that a medical student was going to be a doctor despite being interviewed and examined. We suggest that the term should be used either with explanation or abandoned in favour of 'student doctor'. The level of awareness of clinical teaching was poor and examination of women patients without a chaperone caused distress and should be rectified.


Can communication skills be assessed independently of their context?

In many examinations, communication skills tend to be treated as if they are a single attribute independent of the context of the communication. However, it is clear that such assessments are confounded by candidates' knowledge or lack of knowledge of the medical issues about which they are communicating. In the 1990 Part One examination for Membership of the Royal New Zealand College of General Practitioners candidates were provided with all the essential knowledge relevant to the problem they were to communicate about. Despite this, performance was still seen to be context specific, demonstrating that such specificity is not purely knowledge related. Candidates completing the examination were observed to share information about the cases with candidates about to commerce. There was no evidence that performance was enhanced by such breaches in examination security.


Community-based projects in rural internships: an alternative approach.

Supervision of medical interns posted to various primary health centres and rural health training centres by specialists in preventive and social medicine and other clinical disciplines is becoming less and less effective for a number of unavoidable reasons. Because of lack of proper and timely guidance, interns feel that during the 6-month rural internship they do not get enough experience of rural life. In order to provide them with learning experiences in community medicine and orient them in the social dynamics of the community, a new approach involving interns in small community-based projects, probably for the first time, was tried on a pilot basis at the Rural Health Training Centre (RHTC), Sirur, a field practice area of B.J. Medical College, Pune, Maharashtra, India. Interns working at RHTC Sirur completed these community-based projects successfully. Identification of problems, study design analysis and drawing conclusions, based on observation, were all undertaken by the interns under the guidance of the staff of the Department of Preventive and Social Medicine, B.J. Medical College. The opinion poll at the end of the rural internship revealed that 76% of interns considered this experience valuable for improving their knowledge and skills, and 56% though that interaction during these projects was beneficial to the community as well. This experience with community-based projects for interns during their rural posting provides them with an opportunity for interaction with the community.


Priorities of undergraduate dental education: what do students think?

In recent years there has been an increasing interest in the teaching of behavioural sciences to dental undergraduates, but psychologists and sociologists can meet with resistance to their teaching from both staff and students. In an attempt to understand this resistance further, this paper provides the results of a cross-sectional survey conducted with undergraduate students at two UK dental schools. The results indicate that students believe that training in technical aspects of care (e.g. practice in manual skills, knowledge about anatomy) should assume a substantially higher priority than training in social aspects (e.g. practice in communication skills, knowledge about psychology). The students felt that they were increasingly prepared for both aspects of practice as they progressed through the course, and senior students were more likely to believe that their dental schools should give a higher priority to history-taking and psychological methods to control pain and anxiety than junior students. These results present a considerable challenge for psychologists and sociologists teaching at dental schools and suggest that appropriate curriculum design and integrated teaching may be the way forward.


Continuing education for general dental practitioners using a printed distance learning programme.

This paper describes the development of a printed distance learning programme by a coordinated team approach. The programme has two components, a resource book and three patient management problem leaflets or challenges and is designed to update general dental practitioners on the management of fissure caries. It includes strategies to meet the educational needs of three groups of general dental practitioners with different educational requirements. It is concluded that the approach described meets the CRISIS criteria for effective continuing education and offers a useful approach to distance learning in dentistry.


The market and educational principles in continuing medical education for general practice.

In an attempt to increase participation by established general practitioners (GPs) in continuing medical education (CME) the Department of Health in 1990 created an allowance (the Postgraduate Education Allowance, PGEA) to be spent by GPs on the educational provision of their choice. Although the PGEA has increased attendance by established GPs at educational activities, the market created in CME provision has favoured low cost activity of questionable value. This paper examines criteria for the validation of general practice CME, based on the principles of adult learning, which could be used to manage this market. Failure to adopt an appropriate validating process could lead to the PGEA becoming discredited and the imposition of periodic reaccreditation as a means of enforcing participation by GPs in CME.


Problem-based learning in distance education: a first exploration in continuing medical education.

The Wellcome Tropical Institute has assisted countries in the tropics to establish viable systems of continuing medical education, particularly for young doctors practising in rural areas. As part of this strategy the Institute has developed material for use in distance learning. The first attempt to apply the problem-based learning approach to written material for use by an individual learner in the absence of a tutor led to a trial in Ghana, Kenya and Pakistan to compare a conventionally designed module with a problem-based learning module on the same topic for their respective acceptability, effectiveness and efficiency. The design, implementation and results of these three comparative trials are presented.


An assessment of vocational training.

A retrospective analysis of the opinions of vocationally trained doctors was obtained from a postal questionnaire. Ninety-eight doctors who had trained in the West of Scotland before the introduction of new criteria in 1985 for the appointment and reappointment of training practices were compared with 107 doctors who had trained following the introduction of the criteria, looking at their rating of training, the frequency of tutorials, value of teaching and research encouragement. There was a significant improvement in the rating of training, frequency of tutorials, research encouragement and enjoyment of training in the group who trained after the new criteria were adopted. The study demonstrates the benefits of vocational training for general practice when criteria are set and followed. This training model may be applicable in other branches of medicine.


Effective continuing education: the CRISIS criteria.

The need for continuing medical education (CME) is now well recognized. The challenge is to make it effective. CRISIS, an acronymn, stands for the criteria which must be met to produce effective CME programmes: convenience, relevance, individualization, self-assessment, interest, speculation and systematic. CRISIS is a practical tool, based on 15 years of experience in the production and evaluation of CME programmes at the Centre for Medical Education, University of Dundee. The application of the CRISIS criteria to a CME programme will highlight any areas needing improvement and will guide programme producers in the creation of new CME materials. It will also help those responsible for planning CME activities to choose from a range of existing programmes.


Culinary metaphors in Western medicine: a dilemma of medical students in Africa.

A study was conducted of African medical students in two schools to determine their level of understanding of some culinary metaphors in medicine, particularly those used in the description of certain paediatric conditions. The results showed that the vast majority of medical students and young resident doctors are not familiar with many of the European foods, fruits and beverages that are commonly used in medical textbooks to describe disease conditions. In describing disease, it is suggested that medical educators and authors in Europe should endeavour to use terms that are simple and universal. They should not assume universal knowledge of fruits and dishes available in their environment. Medical educators in Africa should also simplify the description by using appropriate terms.


A model for extraction of both lipid and water soluble toxins using a procedure from Maharishi Ayurveda.

Environmental toxicity from xenobiotic compounds is a major health concern today. This paper presents a hypothetical model for the removal of toxins from the physiology employing procedures of Maharishi Ayurveda, a comprehensive system of natural medicine, which is undergoing renewal. This model combines the use of principles similar to those which are found in lipid extraction, dialysis and bulk flow. A means of testing the hypothesis is also presented.


The origin and spread of human leukemia.

The human leukemias are a group of hematologic neoplasms characterized by uncontrolled proliferation of cells concerned with blood cell production. The cause(s) of human leukemia remains unknown. Bone marrow (BM) is believed to be the site of origin of human leukemias, although the specific locus(i) and/or cell(s) from which it arises have not been definitively identified. Generally, human leukemias and related proliferative diseases are thought to be clonal in nature; affecting a single hematopoietic stem cell, which then proliferates and replaces the marrow of normal hematopoietic stem cell systems. The condition is believed to be malignant in nature. Results of our current morphologic studies on well-fixed, ideally-stained thin sections of plastic-embedded bone marrow biopsies (BMB) from a large number of acute (AML, ALL) and chronic (CGL, CLL) leukemia patients suggest that human leukemias may not be clonal diseases. Instead, a large population of other resident cells--'endosteal cells'--appears to become involved in the process and it is possible that all members of this group enter the activity simultaneously. This change (transformation) in the endosteal cell population might be due to an abnormality (qualitative or quantitative) of diffusable, humoral factors (yet to be identified) that are responsible for the growth and proliferation of these hematopoietic precursor cells. In this context, the human leukemias may be considered not as malignant, but rather the result of an aberration of factor(s) that control hematopoiesis. In this respect, the human leukemias, particularly AML, ALL and CML, might be analogous to pernicious anemia (megaloblastic anemia) as it was understood 40-50 years ago.(ABSTRACT TRUNCATED AT 250 WORDS)


Human cancers and viruses: a hypothesis for immune destruction of tumours caused by certain enveloped viruses using modified viral antigens.

Certain viruses which have been identified as possible aetiological agents of human malignant tumours have 2 common characteristics: a) they persist in the human body for long periods despite the presence of antibodies to them and b) they all possess viral envelopes. The envelopes, consisting of phospho-lipoproteins are derived from host cells viz nuclear envelope in the case of DNA viruses, and the cell membrane in the case of RNA viruses. These host cell elements on the viral envelope modify the antigenicity of the specific surface antigens which are now perceived by the host immune system as partly self. This in turn blackmails the immune system, if it is to avoid serious auto-immune disease, into producing compromise and ineffective antibodies. The hypothesis proposes the dissolution of the viral envelope in vitro and the re-introduction of the viral core into the host. This should provoke a new uncompromised immune response because it will be directed at the viral core only. This response should eliminate the viral core and with it, the whole enveloped virus, as well as the malignant tumour cells which carry the viral genome derived essentially from the viral core. This approach should introduce a new method for treating and preventing tumours caused by enveloped viruses and the chronic diseases caused by such viruses.


Kaposi's sarcoma and HIV.

Recently published informed debate affords strong indication that in patients with the Acquired Immune Deficiency Syndrome, HIV cannot, directly or indirectly, be the cause of Kaposi's sarcoma. This paper provides reasons for disallowing a current alternative theory that Kaposi's sarcoma is due to an unidentified sexually transmitted infectious agent and proposes instead that Kaposi's sarcoma is the result of prolonged and repeated exposure to nitrites and/or semen. If this alternative hypothesis is strengthened by confirmation of its predictions then the relationship of HIV to Kaposi's sarcoma, one of the principal AIDS-associated diseases, becomes somewhat remote. This may facilitate a shift of emphasis and encourage the development of alternative therapies.


Ozonization of blood for the therapy of viral diseases and immunodeficiencies. A hypothesis.

In the last 3 decades major autohemotherapy after exposure to ozone has been used in Europe in uncontrolled trials carried out in patients with many illnesses, particularly chronic viral diseases and neoplasms. It appears that the treatment may activate the host's immune system by inducing the production of immunoactive cytokines and it may now be possible to rationalize the procedure, improve the regimen and assess the outcome. It is apparent, however, that such a therapeutic approach, in order to be acceptable, requires an investigative effort of biologists and clinicians. Once this is done, owing to the large range of medical applications and the simplicity of the procedure, autohemotherapy could become very valuable particularly in underdeveloped countries.


Is syphilis an incurable disease?

Structures which morphologically resemble treponemes have been found in material from patients suffering from latent or late latent syphilis, many of whom have received treatment in the past. These structures were also found in the blood or spinal fluid (SF) of asymptomatic patients with both positive and negative serological tests for syphilis. They have been found in the eye in the presence of active disease as well as in cases without inflammation ('quiet eye'). In latent syphilis, the presence of treponemes after penicillin treatment raises the question of whether the patient is completely cured of syphilis after treatment. Experimental evidence indicates that continued specific antibody production following penicillin treatment depends on the persistence of the specific antigen in the body. This raised three questions: a) Are these stimuli living treponemes? b) Are they still virulent? c) Is syphilis completely curable following penicillin treatment? Our hypothesis is that slowly dividing treponemes are not killed by penicillin. The persistence of living treponemes somewhere in the body may be the proof of this hypothesis. Cases of relapsing neurosyphilis after penicillin treatment have recently been described. We return to the old dilemma: is it a scar-tissue injury or a reactivation of the disease? Since neurosyphilis is asymptomatic, the patient is usually examined because of seroconversion. Only repeated serological analyses and clinical observations of treated cases with immediate penicillin administration can prevent relapse and damage to the central nervous system (CNS) or to other parts of the body.


Could cancer be a physiological phenomenon rather than a pathological misfortune?

The hypothesis presented here is that cancer is not a phenomenon where the normal functions of the human body break down (like diabetes mellitus or renal failure) but rather a well planned and well coordinated physiological response (similar to the inflammatory response). 'Cancer initiating genes' are presumed neoplastic DNA sequences involved in sensing genome deterioration, consequently enhancing preservation. This genetic trait, different from the concept of oncogenes, actively triggers the neoplastic transformation once genome deterioration is sensed. This self destructive, altruistic phenomenon, obviously devastating to the organism, is nevertheless shown to be a possible mechanism of natural selection. The survival advantage of cancer initiation is discussed using both the concepts of group selection and gene selection. Natural selection, the driving force of evolution, is believed to operate solely on the basis of phenotype differences among individuals. In this paper cancer is hypothesized to be a mechanism that directly scrutinizes the gene contents of the individual, therefore representing natural selection based on genotype differences.


Hypothyroid induced hypometabolic state as a possible diagnostic and therapeutic maneuver.

Diseased cells possibly function autonomously without as much dependence upon metabolic cues such as thyroid hormone by comparison to normal cells. Therefore if reversible hypothyroidism can be induced briefly in euthyroid patients, conceivably normal cells can be induced into a hypometabolic state while the diseased cells continue at their baseline or near baseline metabolic level. This induced difference could be utilized to isolate and target abnormal cells better.


Ascorbate status and xerostomia.

Xerostomia, the subjective feeling of dry mouth, affects millions of people particularly the elderly. It is invariably associated with hypofunction of the salivary glands. The amount, rate of secretion, and composition of saliva are regulated by both sympathetic and parasympathetic receptor systems whose stimulation transmits signals through intracellular messengers (cations, nucleotides, phospholipid derivatives) to structures and enzymes within the cell. Salivary glands express a variety of cell-surface receptors including adrenergic (alpha and beta), muscarinic-cholinergic, substance P, vasoactive intestinal peptide hormone, and ATP receptors. Ascorbate which is present in salivary acinar cells in relatively high concentrations, is closely involved in many cellular functions including the metabolism of pyrimidines, intracellular calcium, the catecholamines and other neurotransmitters which regulate salivary gland exocytosis. Ascorbate-dependent carboxyl-terminal peptide alpha-amidation enzyme similar to the pituitary peptidyl-glycine alpha-amidating monooxygase, is also present in salivary glands. It is therefore not fortuitous that the seemingly unrelated numerous factors like aging, drug ingestion, pregnancy, smoking, ionizing radiation, stress, and various pathological states such as cancer, autoimmune disorders, diabetes mellitus, and hypertension often implicated in the causation of xerostomia, all promote increased tissue requirement for and/or depletion of ascorbate.


Relationship between dietary fatty acid, selenium, and degenerative cardiomyopathy.

With the finding of an increasing number of cases of degenerative cardiomyopathy (DCM) amongst patients in Chongqing, Sichuan, People's Republic of China, an attempt has been made to delineate possible etiological factors. In this province endemic for Keshan disease and with considerable consumption of oils high in erucic acid, the latter does not appear to be an operative noxious agent in DCM. Additionally, it does not appear to be caused by excessive oxygen radicals, low levels of antioxidants or low selenium levels. However, lower omega-3 fatty acid levels along with higher serum lipids may be the mechanism, via higher thromboxane levels, of the production of the myocardial degeneration seen in DCM.


The technical feasibility of cryonics.

Cryonic suspension is a method of stabilizing the condition of someone who is terminally ill so that they can be transported to the medical care facilities that will be available in the late 21st or 22nd century. There is little dispute that the condition of a person stored at the temperature of liquid nitrogen is stable, but the process of freezing inflicts a level of damage which cannot be reversed by current medical technology. Could this damage be reversed by future technology? We consider the limits of what medical technology should eventually be able to achieve (based on currently understood chemistry and physics) and whether the repair of frozen tissue is within those limits.


Beyond positivism: a metaphysical basis for clinical practice?

Medicine does not have its own unified body of scientific knowledge. Instead, physicians who are oriented to research make sporadic incursions into the basic sciences such as genetics, biochemistry, immunology, epidemiology, physiology, pharmacology and so on. These latter, taken together, comprise biomedicine which is said to have adopted the positivist epistemology or the Cartesian/Newtonian one that regards the scientist as an uninvolved observer of nature. In effect, medical science has come to rest on a theory of knowledge which links meaning to probability and considers prediction as the scientist's chief task. Like its predecessor, the probability theory of meaning rejects metaphysical speculation and remains connected to observations made, directly or indirectly, by means of the five senses. Despite some brilliant successes touching on relatively uncommon disorders, biomedicine cannot explain most day-to-day clinical activity. An understanding of what transpires between patient and doctor, of its diagnostic potential and therapeutic weight requires hermeneutic, or phenomenological, inquiry which brings about changes in both parties to it. Such a science, as ontological speculation has been called, cannot be deciphered by an epistemology couched in the imagery of physics and chemistry.


Deterministic nonlinear chaos in brain function and borderline psychopathological phenomena.

There exists a fundamental overall property of the brain which monitors, modulates, and ensures a smoothness of function and which further determines elegance and grace in functioning. This property also imparts a quality of, or a sense of proportion among all other faculties of the brain. It is postulated in this paper that such a property/function, up to now almost taken for granted, is maintained/exercised by a nonlinear deterministic chaotic mode of brain function. If this is the case, borderline psychopathological phenomena, when they flare up, can be explained as resulting from sudden reduction of such a deterministic chaotic mode and the emergence of a pathological order, as the system becomes an oscillating one.


Discontinuity in the competitive interaction of tumor cells with the tumor-bearing host--a hypotheses.

The hypothesis put forward here is that during the growth of a primary tumor ending in metastasis formation, phases occur in which 'unfavourable' conditions arise for the tumor cells. It is proposed that, in order to overcome these 'unfavourable' situations, the tumor cells subsequently secrete a substance designed to have a 'dysfunctional' effect on the normal cells. On the assumption of such a discontinuous secretion by the tumor cells, an investigation is made into the behaviour of certain tumors in humans, together with the findings of previously conducted tests. This leads to the formulation of possible concepts for prophylaxis and treatment. In conclusion, an attempt is made to locate what would be the precise target of such a hypothetical substance.


An explanation for the rarity of extraaxial metastases in brain tumors.

Primary brain tumors invade and metastasize within the central nervous system (CNS), but rarely extraaxially. A model explaining this behavior is presented. In non-CNS tumors metastases occur since subpopulations of cells capable of invasion and metastases are selected by the tissular environment, and in particular by the connective stroma, which opposes invasion. The CNS lacks a connective stroma, therefore a primary tumor can grow easily in it, but subpopulations capable of metastasization are not selected. Implications of the explanation are: 1) metastasization is largely based on the ability to invade the connective stroma, 2) paradoxically, a less favourable host tissue environment can result in a more aggressive tumoral behavior.


Can free radicals induce coronary vasospasm and acute myocardial infarction?

Spontaneous acute occlusion of the coronary artery produces regional myocardial ischemia and infarction. This coronary occlusion could be due to rapid progression of atherosclerosis or vasospasm. The factors that can precipitate an acute attack of myocardial infarction or coronary spasm are not known. It is proposed that a stress-induced rise of unesterified arachidonic acid could trigger a leukocyte respiratory burst with the release of free radicals such as superoxide anion (O2-), hydrogen peroxide, hydroxyl radical, and singlet oxygen. These free radicals have the ability to inhibit prostacyclin (PGI2) formation and enhance the breakdown of endothelium-derived vascular relaxing factor (EDRF) which are potent vasodilators and platelet anti-aggregators. This may lead to rapid progression of atherosclerosis or coronary vasospasm leading to acute myocardial infarction. If this is true, free radical quenchers and inhibitors of leukocyte oxidative burst may be useful in the prevention of progression of atherosclerosis and coronary vasospasm.


Metabolism of the malignant cell, the role of bacterial spores, and a pictorial presentation to substantiate the latter's presence as an etiological factor in carcinogenesis.

The respiration and metabolism of the malignant cell, while in vivo, is anaerobic. This is contrary to a normal animal (human) cell, whose respiration and metabolism is aerobic. There is a factor within the malignant cell which produces a reducing or 'deoxygenating' phenomenon, creating the metabolic anaerobiosis. An animal cell cannot survive without the ultimate oxygen molecule. Yet the malignant cell continues to grow and enlarge despite this oxygen absence. Even more surprising is the fact that the malignant cell requires the circulating flow of blood, otherwise that deficient site or area will ulcerate, slough, or necrotize. Investigative studies clearly indicate that there are present 'spores' of a specific group type of plant micro-organism within the malignant cell, and in the immediate and circumferential area to account for this abnormal physiology. In summarizing all the experimentally uncovered facts, it becomes apparent that the malignant cell, while in vivo, is the consequence of 3 factors of productivity. For the first factor there is the requirement of a tissue site whereby there is an accumulate number of the chronic defense cells as the reticuloendothelial group, squamous, and/or epithelial cells. The second factor requires the presence and phagocytosis of these specific plant bacterial spores that can survive genetically within a sac or cell, and third, for the adequate circulating flow of blood by the host. Because of this, 3 factor product activity, Koch's postulate cannot be fulfilled as a criterion for the etiology of the cancer cell. We have, however, a pictorial summary of the pertinent uncovered facts that, when added together, presents a credible, logical, and valid conclusion to support the concept that these specific bacterial spores contribute to the pathway of activity to associate them as the malefactor in carcinogenesis.


Intrauterine intravascular transfusion for fetal haemolytic anaemia: the Western Australian experience.

To report the first four years' clinical experience with fetal intravascular blood transfusion for the treatment of fetal haemolytic anaemia in Western Australia. King Edward Memorial Hospital, Perth, which is the sole tertiary level perinatal centre in Western Australia with a referral base of approximately 25,000 pregnancies each year. Transfusion was by injection of packed cells from Rh-negative donors into the fetal umbilical vein near the site of insertion into the placenta. Fetal haemoglobin levels were measured before and after each transfusion. In most cases, the fetus was paralysed by intramuscular tubocurarine. Sixty intravenous transfusions were performed in 20 pregnancies. At the time of the initial transfusion, the mean haemoglobin level was 5.8 g/dL (range, 2.5-8.5 g/dL) and six fetuses had signs of hydrops. The case survival rate was 80% and the procedure survival rate was 93%. Three of the deaths occurred in the first five cases. Caesarean section was performed during two of the procedures, one because of bleeding from the cord puncture site and one because of tamponade of the umbilical vessels. Fetal intravascular transfusion is a highly effective treatment for fetal alloimmunisation and allows pregnancies to continue to term and to be delivered vaginally. However, the procedure may be difficult and requires a team approach with ready access to fetal monitoring and emergency caesarean section. Our results suggest that increasing experience of the team is a major factor in improved outcome.


Systemic absorption of glycine irrigation solution during endometrial ablation by transcervical endometrial resection.

To study systemic absorption of glycine irrigation solution and its consequences during transcervical endometrial resection (TCER). A prospective study of 20 consecutive female patients who underwent elective TCER in a teaching hospital. During the operation, patients were monitored with electrocardiography, automated oscillotonometry, pulse oximetry, capnography and a central venous pressure recorder. Plasma sodium and potassium levels were measured at 15-minute intervals. Blood haemoglobin concentration, serum osmolality, and plasma sodium, potassium and glycine concentrations were measured before and after surgery. Plasma glycine concentration increased in all patients after TCER. The highest concentration recorded was 5575 mumol/L. The increase correlated only with the maximum intraoperative decrease in plasma sodium, which was 7 mmol/L in two patients whose plasma glycine level increased by 3001 mumol/L and 5335 mumol/L. Systemic absorption of glycine irrigation solution occurred in all patients during TCER. Serial measurement of plasma sodium was necessary to detect this complication. A decrease in plasma sodium level by 7 mmol/L or more during surgery would indicate fluid absorption that could cause severe hyperglycinaemia and other potential complications.


A mammographic screening pilot project in Victoria 1988-1990. The Essendon Breast X-ray Program Collaborative Group.

To pilot and evaluate the feasibility and acceptability to women of population based mammographic screening in Victoria. Pilot intervention study in a geographically and demographically defined population. Area of contiguous postcodes surrounding the Breast X-ray Unit at the Essendon Hospital. Women aged 50 to 69 years living in the target area. Attendance rates, satisfaction, screening rates, surgical biopsy rates, breast cancer detection rates, and surgical treatment. Forty-one per cent of eligible women in the denominator population attended the Breast X-ray Unit in the two-year period; 16,424 women were screened, including 141 women with previous breast cancer. Of every 1000 women screened, 74 were recalled because of mammograms that were suggestive of malignancy, 19 because of technically inadequate mammograms and 16 because of symptoms. All mammograms were read by two radiologists and consensus was required for 12% of films. Of every 1000 asymptomatic women screened, 12.7 had biopsies performed and in 7.1 cancers were detected. In asymptomatic women, the positive predictive value of an abnormal mammogram was 9.4%, and the positive predictive value of a recommendation for biopsy was 55.9%. A total of 131 malignancies were detected, of which 24 (18%) were carcinoma-in-situ. The benign to malignant biopsy ratio was 1:1.31. In 82% of women in whom cancer was detected the breast was conserved. The Program achieved good standards with respect to mammographic detection, clinical assessment and treatment of women with breast cancer.


Patterns of elder abuse.

To establish the rate of occurrence and patterns of elder abuse, and outcomes of intervention, in an Australian population. Retrospective review of medical records over a 12-month period from July 1990 to June 1991. An area-based geriatric and rehabilitation service attached to a district hospital. Referred patients over 65 years of age, who lived in private homes and who met a predetermined definition of elder abuse. The rate of occurrence of elder abuse in the study population was 4.6%, with 29 cases of psychological abuse, 25 cases of physical abuse, 16 cases of neglect, and 13 cases of material/financial abuse. Patterns of abuse were identified and related to dependency of the older person (42%), psychopathology of the abuser (37%), family violence (14%), and carer stress (5%). Interventions and outcomes varied according to the pattern of abuse. The rate of occurrence and patterns of abuse of the elderly have been established for the first time in an Australian population. Intervention aimed at reducing the impact of elder abuse is effective, and should be tailored to the pattern of abuse that is occurring.


Verbal interactions in general practice. Information, support and doctor satisfaction.

The general practice encounter can be seen as an exchange of information aimed at relief of the patient's presenting symptoms, and it is acknowledged that this goal can most effectively be achieved within the context of the professional's emotional support of the patient. We sought to describe the processes of information exchange and emotional support in detail, and to explore any differences in the speech pattern which were related to the doctors' lesser satisfaction with some consultations. Transcripts of general practice consultations (n = 143) from five medical practitioners were coded and analysed. The verbal interactions of the consultation were described in categories: for doctors, emotional support, informational support, and diagnostic activity; and for patients, relationship oriented and task oriented. Doctors also rated their satisfaction with each consultation. About two-thirds of the speech by both parties was found to be devoted to information exchange in the forms of diagnosis and medical advice, and the rest to the relationship between the participants. Doctors' satisfaction ratings (extremely satisfactory or otherwise) could be predicted from speech and activity variables by means of logistic regression. This study describes the verbal interaction which is the vehicle for medical helping in general practice, and it forms a foundation for needed research on how certain features of the verbal interaction are related to quality of care.


Students can learn medicine with computers. Evaluation of an interactive computer learning package in geriatric medicine.

To assess the effectiveness of a computer-aided learning program on dementia. Fourth year medical students were arbitrarily assigned to groups that used a computer-aided learning program (65) or had a tutorial covering similar material (73). These sessions were in addition to a base curriculum in a two-week course in geriatric medicine. The effectiveness of the teaching sessions was judged by the performance on a multiple choice questionnaire about dementia, given to the students on two occasions, one at the beginning and one at the end of the two-week course. Both groups of students scored significantly better on the second test (computer group, 66% [95% confidence interval, 64-69] to 81% [79-83] and tutorial group, 66% [63-67] to 74% [73-77]). The difference between the groups at the start of the course was not significant (F1,136 = 0.61, P = 0.61); however, there was a significant difference between the groups at the end of the course (F1,136 = 21.83, P < 0.001). Both groups improved their knowledge of dementia during the two-week course. Students who used the computer-aided learning programs showed a greater improvement in score. Computer learning programs are effective learning tools and are a useful addition to traditional teaching methods. Further study is required to assess the effects of computer-aided learning programs in long-term studies of dementia knowledge.


Active management of the dying patient.

To document the process of managing the dying patient in the intensive care unit (ICU) and thus to broaden community debate about an issue that is usually only discussed at a theoretical or philosophical level. A six-bed ICU in Liverpool Hospital, a 419-bed teaching institution in the southwestern area of Sydney. Twenty-seven patients, seen over a nine-month period, who had curative treatment withdrawn or withheld. The mean age of the patients was 68 years and the severity of illness, by the APACHE II scoring system, ranged from 12 to 45. Twenty-three of the 27 patients were mechanically ventilated and 11 were receiving inotropic support. Medical staff usually initiated discussions and sought staff consensus that the patient should be allowed to die (on 23 of 27 occasions). Most relatives (25 of 27) accepted this decision. Support therapies and routine care were stopped according to policy guidelines. Sedatives and narcotics were used in some patients (18 of 27). Twenty-one patients died in the ICU and six in the general ward areas. Introduction of a policy to guide management of dying patients in intensive care has been accepted by staff. Most dying patients are now managed in accordance with these guidelines. Further discussion and debate of this important issue, by health professionals and society as a whole, is required.


Elderly patients in the emergency department: a prospective study of characteristics and outcome.

To describe the characteristics of elderly patients presenting to an emergency department and the outcome for these patients at 90 days. Prospective, descriptive study of all patients over 75 years of age presenting in a four week period. Follow-up data were obtained from the case notes, the Registry of Deaths, the Geriatric Assessment Team and, where necessary, contact with the family doctor. The Department of Emergency Medicine at the Royal Hobart Hospital, Tasmania, in late 1989. Death or increased dependence as defined by permanent institutionalisation, moving in with family, or more than 90 days inpatient care. There were 210 presentations by 191 different patients; 116 were admitted to our hospital (55.2%), and three (1.4%) to other hospitals. Follow-up data were obtained for all but five patients. At 90 days from first presentation 23 had died (12.4%) and in a further 19 (10.2%) their dependence had increased. Risk factors for death were fractured neck of femur or cardiac failure. Risk factors for either death or increased dependence were referral by someone outside the immediate family, neurological disease, cardiac failure, an apparent social/placement problem, and being assessed as needing admission. The strongest predictor was a social problem. Age was not a risk factor. A predictive formula for poor outcome in this group can be derived. However, outcome may not be altered by admission, or intervention. In the elderly, it is quality rather than duration of life which should be paramount in considering the benefits of therapy.


Clinical depression is associated with impaired recovery from stroke.

To examine the effect of clinical depression on recovery from stroke. We examined a cohort of inpatients with stroke initially at two months after their stroke and again 14 months later. Patients were included if they: (i) provided informed consent; (ii) were able to understand the interview questions; and (iii) survived to follow-up without suffering another stroke or major medical illness. Of 61 consecutive patients, 49 met these criteria. Depression was diagnosed using a structured clinical interview. Three aspects of recovery were measured: (i) functional status; (ii) activities of daily living; and (iii) cognitive performance. Twenty (41%) of the 49 patients were depressed at initial assessment. There were no significant differences in demographic, clinical, stroke or lesion characteristics between the depressed and non-depressed patients. At follow-up, depressed patients improved less than non-depressed patients in functional status (mean change from baseline, 23% versus 48%) (P = 0.001) and cognitive performance (-1% versus 11%) (P = 0.096). Mean recovery in activities of daily living was not different between the two groups (33% versus 32%) but more of the depressed patients deteriorated over time (20% versus 0%) (P = 0.047). Clinical depression occurring soon after stroke is associated with impaired recovery when patients are assessed 14 months later. Depression has a negative effect on recovery in functional status and cognitive performance and may produce deterioration in physical capacity in a number of patients. Physicians would be well advised to be alert for depression and intervene early. Effective treatment of depression may enhance stroke rehabilitation.


Multiple medication use in the elderly. Use of prescription and non-prescription drugs in an Australian community setting.

To document the extent of polypharmacy or multiple medication use in the elderly. Cross-sectional examination of an age cohort of a community. Community-based study in Dubbo, NSW, in 1988-1989. All non-institutionalised residents aged 60 years and over, numbering 1237 men and 1568 women. Assessment of use of prescription and non-prescription drugs, recent hospitalisation, years of education, psychosocial variables. 18% of men and 25% of women were currently using three or more classes of prescription drugs. The corresponding values for two or more classes of non-prescription drugs were 29% and 44%. Of those who were using multiple prescription drugs 56% of men and 76% of women were also using multiple non-prescription drugs. In a multiple logistic model, the following possible predictors of multiple drug use were included: hospitalisation in the last six months, age, sex, depression, life satisfaction and education. Multiple prescription drug use was significantly predicted by recent hospitalisation (odds ratio [OR] = 2.40; 95% confidence interval [CI], 1.63-3.56), increasing age (e.g. 70-79 years versus 60-69 years; OR = 2.54; CI, 1.97-3.25), female sex (OR = 1.59; CI, 1.25-2.01) and increasing depression (e.g. highest tertile of depression scale versus lowest; OR = 2.52; CI, 1.84-3.42). Multiple non-prescription drug use was significantly predicted by female sex (OR = 2.38; CI, 1.95-2.92) and increasing depression (OR = 2.77; CI, 2.16-3.56). For prescription items, non-prescription items, and both categories in combination levels of use 20% above the population average have been documented. Polypharmacy in the elderly population appears to be predicted by recent hospitalisation, increasing age, female sex and increasing depression. There is potential for drug-drug interaction to occur, but the findings suggest target areas for preventive action.


Intractable leg ulceration caused by cutaneous cholesterol embolism.

To present a case of chronic intractable leg ulceration caused by cholesterol crystal embolism. A 76-year-old Caucasian male with a history of ischaemic heart disease had repeated hospital admissions for diagnosis and treatment of recurrent leg ulceration of more than three years' duration. Definitive diagnosis was made after the third biopsy when the specimen obtained included subcutaneous arteries. Complete healing occurred within three weeks of excision and a skin graft, and subsequent treatment which included systemic steroids. Cholesterol crystal embolism is probably an underdiagnosed cause of intractable leg ulceration and can be identified by a biopsy specimen which includes vessels in subcutaneous fat. Systemic steroids may be helpful in its treatment.


Severe botulism after eating home-preserved asparagus.

To present a case of adult botulism acquired in Queensland. After eating home-preserved asparagus, a 33-year-old man presented with internal and external ophthalmoplegia, bilateral facial nerve palsies, and descending muscle weakness culminating in a sudden respiratory arrest. Electrophysiological testing demonstrated normal nerve conduction velocities and an incremental response of evoked motor potentials on repetitive stimulation, confirming the clinical diagnosis of botulism. Treatment with trivalent antitoxin, oral treatment with vancomycin and supportive mechanical ventilation for four weeks resulted in complete clinical recovery. Plasmapheresis was also used but its contribution to the patient's improvement is dubious. Although botulism is rare in Australia, clinicians should be aware of the clinical presentation and the rapidity of confirmation of the diagnosis by electrophysiological testing. Patients should be nursed in an intensive care setting. Regular testing of vital capacity should be performed to determine the need for mechanical ventilation.


Ellis-van Creveld syndrome in a Western Australian aboriginal community. Postaxial polydactyly as a heterozygous manifestation?

To report two children with Ellis-van Creveld syndrome in an extended kindred of Western Australian Aboriginal descent. Furthermore, to document two family members with isolated postaxial polydactyly of the feet as probable heterozygous manifestations of the Ellis-van Creveld gene. Male and female second cousins with short limbs, postaxial polydactyly and cardiac malformations are described. It is proposed that founder effect and random genetic drift resulted in a relatively high frequency of the Ellis-van Creveld gene in the Aboriginal people of Western Australia. In addition, further evidence is provided for the postulate that isolated postaxial polydactyly is a heterozygous manifestation of the gene.


Pet ownership and risk factors for cardiovascular disease.

To compare risk factors for cardiovascular disease in pet owners and non-owners. Accepted risk factors for cardiovascular disease were measured in 5741 participants attending a free, screening clinic at the Baker Medical Research Institute in Melbourne. Blood pressure, plasma cholesterol and triglyceride values were compared in pet owners (n = 784) and non-owners (n = 4957). Pet owners had significantly lower systolic blood pressure and plasma triglycerides than non-owners. In men, pet owners had significantly lower systolic but not diastolic blood pressure than non-owners, and significantly lower plasma triglyceride levels, and plasma cholesterol levels. In women over 40 years old, systolic but not diastolic pressure was significantly lower in pet owners and plasma triglycerides also tended to be lower. There were no differences in body mass index and self-reported smoking habits were similar, but pet owners reported that they took significantly more exercise than non-owners, and ate more meat and "take-away" foods. The socioeconomic profile of the pet owners and non-owners appeared to be comparable. Pet owners in our clinic population had lower levels of accepted risk factors for cardiovascular disease, and this was not explicable on the basis of cigarette smoking, diet, body mass index or socioeconomic profile. The possibility that pet ownership reduces cardiovascular risk factors should therefore be investigated.