Showing papers in "Journal of Internal Medicine in 1992"

Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B

Abstract: In Sweden, prophylactic treatment of boys with severe haemophilia has been practised since 1958 in an attempt to convert the disease from a severe to a milder form. The present study population consisted of 60 severe haemophiliacs (52 A, 8 B), aged 3-32 years. Treatment is started when the boys are 1-2 years of age, the regimens used being 24-40 IU F VIII kg-1 three times weekly in haemophilia-A cases (i.e. greater than 2000 IU kg-1 annually) and 25-40 IU F IX kg-1 twice weekly in haemophilia-B cases. The orthopaedic and radiological joint scores (maximum scores of 90 and 78, respectively) are evaluated as recommended by the World Federation of Haemophilia. Of those subjects aged 3-17 years, 29 out of 35 individuals had joint scores of zero. The oldest group had only minor joint defects. The VIII:C and IX:C concentrations had usually not fallen below 1% of normal. All 60 patients are able to lead normal lives. In conclusion, it appears to be possible to prevent haemophilic arthropathy by giving effective continuous prophylaxis from an early age, and preventing the VIII:C or IX:C concentration from falling below 1% of normal.

A prospective study of the incidence of deep‐vein thrombosis within a defined urban population

Abstract: In a prospective study all positive phlebographies within the well-defined population of the city of Malmo, Sweden, during 1987 were studied in order to determine the incidence of deep venous thrombosis (DVT). Epidemiological data were analysed for the detection of patient groups at increased risk of DVT. The incidence was found to be equal for both sexes, i.e. 1.6 per 1000 inhabitants a year. Risk factors were found to be in accordance with earlier studies. The median age for men was 66 years, compared to 72 years for women. At diagnosis of DVT, 19% of subjects had a known malignancy and within 1 year 5% (19 cases) developed a new malignancy. Of the men, 29% had postoperative or post-traumatic (fracture) DVT, compared to 46% of the women. Fewer patients with DVT than expected (39%) belonged to blood group 0 (31%) (P less than 0.005). Pulmonary embolism (PE) was clinically suspected in only 5% of cases, and diagnosis was verified scintigraphically in 2% of cases. None of these died of PE, but of 6 patients who were found to have PE at autopsy, four died about 4 weeks after the DVT was diagnosed.

Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations.

Abstract: Elevated plasma insulin and triglyceride (TG) and decreased high-density-lipoprotein (HDL)-cholesterol concentrations have been shown to be risk factors for coronary heart disease (CHD). It has been suggested that these metabolic abnormalities are all secondary to resistance to insulin-stimulated glucose uptake. To examine this in more detail, we divided 18 non-diabetic, moderately overweight, sedentary men aged 25-50 years into three groups on the basis of their steady-state plasma glucose levels (SSPG): a low group, (n = 7; SSPG less than 8.3 mmol l-1), a middle group, (n = 6; SSPG 8.3-11.1 mmol l-1), and a high group (n = 5; SSPG greater than 11.1 mmol l-1). The high group had significantly higher fasting (P less than 0.05) and post-oral glucose challenge (P less than 0.01) insulin concentrations, higher fasting TG (P less than 0.05) and lower fasting HDL-cholesterol (P less than 0.05) concentrations than the other two groups. However, there were no statistically significant differences between the groups with regard to body mass index, waist-to-hip ratio or physical endurance capacity as determined by maximal oxygen consumption during a treadmill test. The data suggest that insulin resistance has an effect on the modulation of plasma insulin, TG and HDL-cholesterol concentrations, independent of generalized, abdominal or physical endurance capacity.

Low plasma levels of insulin-like growth factor 1 (IGF-1) in male patients with idiopathic osteoporosis.

Abstract: Experimental studies in vitro indicate that insulin-like growth factor 1 (IGF-1) could be of importance for normal bone growth and remodelling, but the clinical relevance of these observations is unknown. In 12 consecutive young to middle-aged male patients (mean age (+/- SD) 46 +/- 8 years, range 30-57 years) with symptomatic idiopathic osteoporosis, the plasma concentrations of IGF-1 were significantly lower than in healthy subjects (0.51 +/- 0.25 vs. 0.73 +/- 0.23 U ml-1; P less than 0.01). The bone mineral densities in the spine, the femoral neck, and the forearm were significantly different between patients and control subjects. There were positive correlations between the plasma IGF-1 concentrations and the bone densities of the spine and the forearm. Three of the patients received a 5-d course of human recombinant growth hormone (GH). During this short period significant increases in plasma IGF-1 levels and in biochemical indices of bone turnover (serum bone-specific alkaline phosphatase, urinary calcium excretion) were recorded. These observations indicate that circulating IGF-1 could have an important role in maintaining bone mass, and suggest that impairment of IGF-1 production is involved in the pathogenesis of osteoporosis.

Prevalence of hyperinsulinaemia in patients with high blood pressure

Abstract: A total of 41 patients with hypertension were identified in a survey of 732 healthy factory workers. Twenty-three of these individuals were receiving antihypertensive medication, whereas 18 cases were newly discovered. Plasma glucose and insulin responses to oral glucose and fasting plasma triglyceride (TG), cholesterol, and high-density-lipoprotein (HDL) cholesterol concentrations of these 41 individuals were compared with those of 41 other factor workers, with normal blood pressure, matched with the hypertensive group in terms of gender, age, degree of obesity, job in the factory, and leisure-time activity. Patients with hypertension had significantly higher plasma glucose (P less than 0.05) and insulin (P less than 0.05) concentrations in response to oral glucose, as well as a higher plasma TG concentration (P less than 0.05). Similar findings were obtained when the treated and untreated hypertensive groups were analysed separately and compared with their respective control groups. However, there were no differences between the treated and untreated hypertensive groups. Ninety per cent of the normotensive group had a plasma insulin concentration of less than 500 pmol l-1 2 h after the glucose load. Using this value as the criterion for definition of hyperinsulinaemia, 41% of the patients with high blood pressure were hyperinsulinaemic. In addition to meeting this cut-off point, the patients with hypertension and hyperinsulinaemia were also glucose intolerant and dyslipidaemic. In conclusion, approximately 50% of an unselected group of patients with hypertension were hyperinsulinaemic. Insulin levels were comparable in treated and untreated patients with high blood pressure, and hyperinsulinaemic patients also tended to be glucose intolerant and dyslipidaemic.

The role of apolipoprotein E genetic variants in lipoprotein disorders

Abstract: Apolipoprotein E plays a central role in lipoprotein metabolism by serving as a ligand for the binding of lipoproteins to lipoprotein receptors. Both common and rare variants of apoE have been described. The common variants apoE2 and apoE4 have a significant impact on interindividual variation of lipid and lipoprotein levels in normal subjects. The common variant apoE2 and more than half a dozen rare variants are defective in binding to the low-density lipoprotein (LDL) receptor, and all are causally associated with the lipid disorder type III hyperlipoproteinaemia (HLP). The mode of inheritance of the disorder can be either dominant or recessive, depending on the particular mutation(s) in apoE, although the mechanisms involved are not fully understood. The common variant apoE4 and other rare variants have been reported to be associated with a variety of other lipoprotein disorders, but a causal link has not been established.

Drug-induced hepatic injury: an analysis of 1100 cases reported to the Danish Committee on Adverse Drug Reactions between 1978 and 1987.

Abstract: The Danish Committee on Adverse Drug Reactions received 1100 reports of suspected drug-induced hepatic injury during the decade 1978-1987. The causal relationship between drug and hepatic injury was classified as definite in 57 (5.2%) reports, probable in 989 (89.9%) reports, possible in 50 (4.5%) reports and unclassifiable in four (0.4%) reports. Hepatic injuries accounted for 5.9% of all adverse drug reactions reported, and 14.7% of the lethal adverse drug reactions. A total of 47.2% were classified as acute cytotoxic, 16.2% as acute cholestatic and 26.9% as abnormal hepatic function. In 52 (4.7%) cases the hepatic injury was lethal; only 14 (1.3%) cases were chronic. Halothane accounted for 25% of the cases. The incidence of halothane-induced hepatic injury is decreasing, and only one lethal case has been reported since 1981. Next to halothane, sulfasalazine was the drug most often suspected during the last 2 years of the decade. Based on consumption data, the incidence of hepatic injury due to sulindac was estimated to be 18-fold higher than that due to ibuprofen. Paracetamol was reported to induce acute cytotoxic as well as cholestatic reactions in non-alcoholic subjects taking therapeutic doses.

Hyperhomocyst(e)inaemia: an independent risk factor for intermittent claudication.

Abstract: The aim of this study was to test the question of hyperhomocyst(e)inaemia as a risk factor for intermittent claudication (IC) independent of other important risk factors for peripheral atherosclerotic disease, such as smoking, hypertension, diabetes mellitus, hypercholesterolaemia, hypertriglyceridaemia, low levels of high-density-lipoprotein (HLD) cholesterol and age. The study population was recruited from an epidemiological study in Linkoping County, Sweden, where all middle-aged men (n = 15,253, 45-69 years of age) were screened for IC. Seventy-eight subjects with verified IC and 98 healthy sex- and age-matched controls were randomly selected. Plasma levels of homocyst(e)ine (including the sum of free and bound forms of homocysteine and their disulphide oxidation products, homocystine, and homocysteine-cysteine mixed disulphide) were significantly higher (16.74 +/- 5.45 mumol l-1, mean value +/- SD, P = 0.0002) in IC subjects than in controls (13.80 +/- 3.21 mumol l-1), with 23% of the claudicants above the 95th percentile for controls. Stepwise logistic regression analysis revealed that the difference in plasma homocyst(e)ine was independent of the other above-mentioned risk factors. Moreover, the elevation of plasma homocyst(e)ine in claudicants was mainly confined to subjects with serum folate levels of less than or equal to 11.0 nmol l-1. The results suggest that folic acid supplementation should be tried in IC subjects with hyperhomocyst(e)inaemia.

Treatment of orthostatic hypotension with sleeping in the head-up tilt position, alone and in combination with fludrocortisone.

Abstract: We studied the effect of sleeping in the head-up tilt (HUT) position, alone and in combination with fludrocortisone, on orthostatic tolerance and blood pressure (BP) in six patients with hypoadrenergic orthostatic hypotension. A high salt diet of 150-200 mmol Na+ d-1 was also administered. Combined treatment reduced orthostatic dizziness in all patients (P less than 0.001), and increased the maximal standing period to at least 10 min. HUT alone (n = 4) reduced the BP decrease after 1 min of standing from -64/-42/-25 +/- 29/21/17 mmHg to -53/-37/-23 +/- 31/24/20 mmHg (P less than 0.01 for systolic BP). Addition of fludrocortisone to HUT (HUT/fludro) (n = 5) further reduced the BP decrease after 1 min of standing from -63/-40/-24 +/- 20/12/11 mmHg to -21/-19/-8 +/- 12/10/5 mmHg (P less than 0.05 for systolic, mean and diastolic BP, respectively). BP at maximal standing time increased from 58/47/42 +/- 9/8/7 mmHg initially to 95/69/57 +/- 27/22/20 mmHg during combined treatment (P less than 0.05 for systolic and mean BP), and remained unchanged during the 14-month (range 8-70 month) follow-up period. Nocturnal sodium excretion decreased from 8.0 +/- 2.3 mmol h-1 to 5.9 +/- 1.9 mmol h-1 with combined treatment; body weight increased by 1.6 kg on average (range 0.5-2.4 kg) (P less than 0.01). We conclude that the combination of HUT and fludrocortisone effectively minimizes orthostatic symptoms and increases orthostatic BP in patients with hypo-adrenergic orthostatic hypotension.

Physical fitness or physical activity as a predictor of ischaemic heart disease? A 17-year follow-up in the Copenhagen Male Study.

Abstract: Physical fitness and leisure time physical activity are strongly correlated, and both are inversely correlated with risk of ischaemic heart disease. Does this mean, however, that a very fit man has a lower risk of ischaemic heart disease (IHD), even if he is inactive? And does it also mean that an unfit, but active man, does not have a lower risk of IHD than an unfit, inactive man? In the Copenhagen Male Study, we analysed the joint effect of fitness and leisure time activity. In 1970/71, 4999 men aged 40-59 years, were classified according to level of physical fitness, i.e. indirectly measured maximal oxygen uptake, and physical activity, and their mortality was recorded over the following 17 years. In sedentary men, fitness was no predictor of future risk of IHD whatsoever. Age-adjusted baseline values were similar in later IHD cases and survivors (32.3 and 32.1 ml O2 kg-1 min-1, respectively: P = 0.91). In medium or highly active men, however, fitness was a strong predictor. The corresponding fitness values were 33.1 and 34.8 ml O2 kg-1 min-1 (P < 0.001). The least fit (two least fit quintiles) physically active men had a lower IHD mortality rate (6%) than the least fit sedentary men (10%). Adjusted for age, social class and smoking in a multiple logistic regression equation, this was estimated to an RR (95% C.I.) of 1.67 (1.06-2.64) (P = 0.027). The two major new findings of this study were (a) that being very fit, provides no protection against IHD--nor all-cause mortality--in sedentary men, and (b) that unfit but sedentary men have a higher risk of IHD than unfit but active men, i.e. those performing light physical activity for at least 4 h per week.

The bone mineral density in acquired growth hormone deficiency correlates with circulating levels of insulin-like growth factor I.

Abstract: Insulin-like growth factor I (IGF-I) is an important anabolic factor for osteoblasts in vitro. Low plasma levels of IGF-I have been observed in young men with osteoporosis. In the present study, we have studied bone mineral density (BMD) and the circulating levels of IGF-I and growth hormone (GH) in adults with acquired GH deficiency. BMD was determined by dual-energy x-ray absorptiometry in 17 men and 12 women (age 27-54 years). Spinal BMD was positively correlated with the plasma levels of IGF-I (r = 0.43, P = 0.019), with the median of GH values obtained by repeated sampling at night (r = 0.43, P = 0.0019), and with the peak of GH values during GHRH provocation test (r = 0.49, P = 0.039). The total BMD was positively related to plasma IGF-I and median of GH values, but not to peak GH by GHRH provocation. In a multiple regression analysis model, IGF-I, peak GH by GHRH provocation test and duration of GH deficiency explained 49% of the variation in spinal BMD. As compared to healthy controls, total, but not spinal, bone mass was lower in men with GH deficiency, but no clinical symptoms of osteoporosis were observed. The positive relationships between BMD and circulating IGF-I and other indices of GH secretion suggest that IGF-I has an endocrine effect on bone mass.

Calcium and peak bone mass.

Abstract: On the basis of previous epidemiological, clinical and experimental studies, it was demonstrated that adequate calcium intake during growth may influence peak bone mass/density, and may be instrumental in preventing subsequent postmenopausal and senile osteoporosis. Calcium intake during adolescence appears to affect skeletal calcium retention directly, and a calcium intake of up to 1600 mg d-1 may be required. Therefore, adolescent females at the time of puberty probably represent the optimal population for early prevention of osteoporosis with calcium. Young individuals must be in positive calcium balance to provide the calcium necessary for skeletal modelling and consolidation, but the degree of positive balance required to achieve peak bone mass and density is unknown. To assess calcium requirements in young individuals, and also to evaluate the determinants of calcium metabolism during the period of acquisition of peak bone mass, 487 calcium balances from previously published reports have been collected and analysed according to developmental phase and calcium intake. The results of this analysis showed that calcium intake and skeletal modelling/turnover are the most important determinants of calcium balance during growth. The highest requirements for calcium are during infancy and adolescence, and then during childhood and young adulthood. Infants (adequate vitamin D supply) and adolescents have higher calcium absorption than children and young adults to meet their high calcium requirements. Calcium absorption during the periods of rapid bone modelling/turnover is probably mediated by Nicolaysen's endogenous factor. Urinary calcium increases with age, and reaches a maximum by the end of puberty. The results also show that calcium intake has little effect on urinary calcium excretion during the period of most rapid skeletal formation: a weak correlation is present in children and young adults. On the basis of the above studies it was suggested that the RDA for calcium should be higher than currently established for children, adolescents, and young adults, in order to ensure a level of skeletal retention of calcium sufficient for maximal peak bone mass. In addition to nutrition, heredity (both parents) and endocrine factors (sexual development) appear to have profound effects on peak bone mass formation. Most of the skeletal mass will be accumulated by late adolescence, indicating early timing of peak bone mass.

Hepatotoxicity due to repeated intake of low doses of paracetamol.

Abstract: The cases of two patients with fulminant hepatic failure after intake of therapeutic doses (4-8 g) of paracetamol, and who were admitted to hospital for assessment for liver transplantation, are described. In both patients starvation, due to abdominal pain, nausea and vomiting or diarrhoea, was probably contributing to the toxic effect of the drug. One of the patients also had an excessive alcohol intake. Paracetamol should not be prescribed for patients with alcoholism or with low food intake.

Hypertriglyceridaemia due to genetic defects in lipoprotein lipase and apolipoprotein C-II.

Abstract: Hypertriglyceridaemia, as defined by fasting triglyceride levels of greater than 2.8 mmol l-1, is a prevalent dyslipoproteinaemia in our population. The underlying pathophysiological mechanisms that result in elevations of plasma triglycerides are heterogeneous and, in most cases, incompletely understood. However, in a subset of patients presenting with this lipid disorder, the biochemical and genetic defects that lead to hypertriglyceridaemia have been well characterized. These individuals present with the familial chylomicronaemia syndrome, a rare genetic disorder that is inherited as an autosomal recessive trait, and is characterized by severe fasting hypertriglyceridaemia, massive accumulations of chylomicrons in plasma, and recurrent bouts of pancreatitis. The two major causes of the familial chylomicronaemia syndrome are a deficiency of the enzyme, lipoprotein lipase (LPL), or its cofactor, apolipoprotein (apo) C-II. Together, these two proteins initiate the hydrolysis of triglycerides present in chylomicrons and very low density lipoproteins. In the past decade our understanding of the underlying molecular defects that lead to familial chylomicronaemia has been greatly enhanced by the identification of mutations in the genes for LPL and apoC-II. Characterization of these defects has provided new insights into the structure and function of apoC-II and LPL and established the important role that these two proteins play in normal triglyceride metabolism.

Calcium absorption and calcium bioavailability

Abstract: Calcium is important for bone health. It has been customary to focus on dietary calcium intake, but of central importance for the body needs in the individual patient is the actual calcium absorption. This absorption consists of an active vitamin D-mediated component and a passive diffusional component. A number of different methods are available for the evaluation of calcium absorption. At present the calcium absorption tests using calcium isotopes (radioactive or stable) appear to be the most reproducible way of determining calcium absorption. The major nutrient sources for calcium are milk and milk products, whereas some of the green vegetables have a low bioavailability of calcium. When deciding whether an increased calcium intake is advisable, the following questions must be answered. What is the calcium absorptive status of the patient? How should the calcium supplement be dispensed? What calcium salt should be used? When should calcium supplements be taken? What is the compliance of the patient? When should the treatment be evaluated? The calcium supplement might be taken as milk (or milk products) or, in patients with lactose intolerance, as calcium supplements. Quite a number of calcium supplements are available on the market, and many of them are marketed without proper knowledge of the bioavailability of the actual preparation. For the benefit of our patients it is now reasonable to demand such investigations before marketing calcium supplements.

Use of smokeless tobacco: blood pressure elevation and other health hazards found in a large-scale population survey.

Abstract: Health hazards associated with the use of smokeless tobacco were evaluated in a cross-sectional study of 97,586 Swedish construction workers undergoing health examinations in 1971-74. All users of smokeless tobacco only (5014 subjects) and all exclusive smokers of > or = 15 cigarettes daily (8823 subjects) were compared with all non-users of any tobacco (23,885). Both smokeless tobacco users and smokers showed higher prevalences of circulatory and respiratory disorders. Hypertension was most common in smokeless tobacco users. In the 45- to 56-years age group, the odds ratio for a diastolic blood pressure of > 90 mmHg was 1.8 (95% CI, 1.5-2.1), and for a systolic blood pressure > 160 mmHg, 1.7 (95% CI, 1.3-2.1). Smokers showed the lowest prevalence of hypertension. Disability pensions due to cardiovascular disease were nearly 50% more frequent in both smokeless tobacco users and smokers. These findings indicate that an increased cardiovascular risk is also associated with the use of smokeless tobacco.

Screening for antibodies against gliadin in patients with osteoporosis.

Abstract: . Intestinal disease might contribute to osteopenia. Measurements of IgA antibodies to gliadin have been established as an accepted screening procedure for detection of coeliac disease. When we applied these measurements to 92 patients with verified osteoporosis, 11 subjects (12%) were found to have elevated levels. This is markedly higher than the incidence in healthy subjects (3%). However, the patients with raised levels of IgA antibodies displayed no clinical symptoms and no laboratory evidence of calcium malabsorption. Thus their values for serum calcium, phosphate, parathyroid hormone (PTH), alkaline phosphatase and osteocalcin, as well as the fasting urinary excretion of hydroxyproline and calcium, were similar to those found in other patients with osteoporosis. Intestinal biopsy verified coeliac disease in three patients and was normal in another three. This gives an incidence of verified coeliac disease in this patient group that is approximately tenfold higher than that in the healthy population. Subclinical coeliac disease appears to be unusually over-represented among patients with idiopathic osteoporosis, and screening for gliadin antibodies might therefore be a valuable addition to the routine assessment of the osteopenic patient. The mechanisms underlying the relationship are not clear, but calcium malabsorption is not evident.

Calcium in the prevention and treatment of osteoporosis

Abstract: Osteoporotic fractures have many sources. Low bone mass is one such, and inadequate calcium intake, in turn, is one of the causes of low bone mass. Calcium intake may be inadequate because it is low in its own right or, even if 'normal', it may not be sufficient to compensate for exaggerated obligatory losses. Inadequate calcium intake may cause bone mass to be low either because calcium intake during growth limits achievement of genetically programmed skeletal mass, or because low intake later in life aggravates involutional loss, or both. Ensuring a generous calcium intake throughout life will prevent both of these consequences. However, it is important to stress that even a calcium surfeit will not prevent or reverse bone loss due to inactivity, gonadal hormone deficiency, alcohol abuse or, indeed, any other factor. Calcium is a nutrient, not a drug. The only disorder it can be expected to alleviate is calcium deficiency. However, the evidence suggests that calcium deficiency is prevalent among Western populations, particularly in North America, and that it thereby contributes substantially to their osteoporotic fracture burden. This component of that burden is therefore entirely preventable.

Pseudomonas infections in patients with AIDS and AIDS-related complex.

Abstract: . We identified and reviewed retrospectively all the cases of infection by Pseudomonas and related genera in patients with AIDS and AIDS-related complex (ARC) who were hospitalized at our Institution over a 36-month period. We recorded 48 episodes of infection in 34 of 355 patients with AIDS, and in two of 73 patients with ARC: 25 pneumonias (9 community-acquired and 16 of nosocomial origin), 20 urinary tract infections, two soft tissue infections and one sepsis. In 14 of 16 patients with nosocomial pneumonia but in only one of nine patients with community-acquired pneumonia did we find coexisting opportunistic lung diseases. The following micro-organisms were isolated: P. aeruginosa in 41 cases. P. fluorescens in three cases. Xanthomonas maltophilia (P. maltophilia) in two cases, P. putida in one case, Comamonas testosteronis (P. testosteronis) and Comamonas acidovorans (P. acidovorans) in one case. Amikacin and ceftazidime, alone or in combination, appear to be the optimal choice of therapy for severe Pseudomonas infections in HIV-infected patients, although in our study six of 47 isolates were resistant in vitro to amikacin, and nine of 31 isolates were resistant to ceftazidime.

EDTA treatment of intermittent claudication--a double-blind, placebo-controlled study.

Abstract: A double-blind, randomized multicentre study was undertaken to evaluate the possible effect of chelation treatment with ethylenediamine-tetraacetic acid (EDTA) in patients with severe intermittent claudication. A total of 153 patients received 20 intravenous infusions of either 3 g Na2EDTA or placebo during a period of 5-9 weeks. Vitamin, mineral and trace element supplements were administered orally. The changes observed in the pain-free and maximal walking distances, measured on a treadmill, were similar in the two groups. During the 3-month (n = 149) and 6-month (n = 123) follow-up period, no long-term therapeutic effect of EDTA could be demonstrated. The ankle-brachial blood pressure index remained unchanged throughout the study period. This study failed to demonstrate any effect of EDTA chelation treatment in intermittent claudication.

Nomenclature and classification of amyloid and amyloidoses

Abstract: The term ‘ amyloidosis’ relates to a heterogeneous group of disorders characterized by extracellular deposition of a proteinaceous fibrillar materialamyloid-in various tissues and organs [l]. The unique amyloid fibril is the principal component of all amyloids irrespective of the clinical expression, tissue. or animal species involved. Its low solubility and relative resistance to proteolytic digestion in physiologic conditions contribute to the irreversible and often progressive course of amyloidosis. In 1964 Henditt Pr Eriksen observed that despite the morphologic similarity in different clinical settings. ainyloid is heterogeneous with respect to the nature of the amyloid fibrils. Subsequent studies of amyloid extracted from different affected tissues revealed that they are composed of various different protein subunits [2]. Thus, the main component of amyloid fibrils is a distinct protein subunit with a molecular weight of 3,000 to 30,000 Da in different fibril preparations [l]. Several apparently unrelated proteins can constitute this amyloid fibril subunit in different cases of amyloidosis. The different amyloid proteins are often related to distinct clinical forms of amyloidosis. Indeed, many types of amyloid disease can now be defined and classified by structural analysis of the fibril proteins [2].

Coronary heart disease, cancer and mortality in male middle-aged light smokers.

Abstract: We examined the effect of light smoking in relation to incidence of coronary heart disease (CHD) in a general population sample consisting of 6879 men aged 47-55 years and free of previous myocardial infarction (MI) at baseline. After a follow-up of mean duration 11.8 years, 11.0% of men smoking 1-4 cigarettes daily (n = 228) had suffered a major CHD event, compared to 3.7% of non-smokers (n = 2049) [adjusted odds ratio 2.8 (1.7-4.7)]. No further increase in risk was observed in men who smoked more. There was an increasing risk of death from cancer with the number of cigarettes smoked per day. Mortality was increased in all categories of cigarette smokers, particularly among the very heavy smokers, who had a mortality risk of 22% compared to 6% among nonsmokers [adjusted odds ratio 4.4 (2.7-7.1)]. Data from an examination 4 years later considered only those men who stated that their smoking habits were identical on both occasions (n = 3981). Among these subjects the incidence of CHD after a mean period of 7.1 years was 10.6% in men smoking 1-4 cigarettes per day, compared to 2.6% in nonsmokers [adjusted O.R. 4.6 (2.1-10.1)]. No dose-response effect was observed. Even very light cigarette smoking considerably increases the risk of CHD in middle-aged men.

Diabetes in Australian aborigines: impact of the western diet and life style.

Abstract: Prehistorians believe that Aborigines came to Australia from South-East Asia at least 40-50 000 years ago [l]. Until European colonization of Australia just over 200 years ago, Aborigines lived as hunter-gatherers all over the continent under widely varying geographical and climatic conditions, ranging from the tropical coastal regions of the north (latitude 1l0-2Oo S), through the vast arid regions of the centre (latitude 20"-30" S), to the cool-temperature regions of the south (latitude 30O-43" S). The ' more fertile coastal areas, both north and south, could sustain larger populations than the arid inland or desert areas. Each tribal group hunted and gathered food in a defined territory, which could be as extensive as 100 000 km2 in the desert regions, or as small as 500 km2 in fertile coastal country [2].

Ischaemic heart disease incidence by social class and form of smoking: the Copenhagen Male Study--17 years' follow-up.

Abstract: . The Copenhagen Male Study is a prospective, cardiovascular cohort study initiated in 1970 and consisting of 5249 employed men aged 40–59 years. A total of 4710 men, who had reported their smoking habits and were free of ischaemic heart disease, had their mortality recorded over a 17-year period: 585 men suffered a first incident of ischaemic heart disease (IHD), and 248 cases were fatal. There was a strong social gradient in the risk of IHD (Kendall'l Tau B = 0.12, P < 0.001). Adjusting for age, blood pressure, physical activity, body mass index and alcohol consumption in a multiple logistic regression equation, men in the lowest social class had a relative risk (95% confidence interval) of IHD of 3.6 (2.5-5.3) compared to men in the highest social class. We determined whether differences in smoking habits could explain at least some of this large increase in risk. Adjustment for the above factors and also inclusion of the form of tobacco smoked, the amount of tobacco smoked and presence or absence of inhalation, had very little effect on the estimate: the relative risk was 3.5 (2.4–5.2). There was no social gradient in age at the start of smoking. According to smoking habits, comparing social class V with social class I, the relative risk was 7.7 (2.6–22.4) in cigarette smokers, 6.0 (1.1–32.1) in pipe smokers, 3.5 (1.7-7.1) in mixed smokers, 2.25 (0.4–12.9) in cheroot smokers, 3.8 (2.4–5.9) in all smokers, 1.95 (0.8-4.6) in ex-smokers, and 4.7 (1.01–22.2) in non-smokers. In the upper social classes, 50–75% of IHD events could be ascribed to smoking, and in the lowest classes only about 20%. We conclude that the substantial social inequalities in risk of ischaemic heart disease are not accounted for by differences in smoking habits.

Demonstration of a relationship between white blood cell count, insulin resistance, and several risk factors for coronary heart disease in women.

Abstract: In order to evaluate the relationship between peripheral white blood cell (WBC) count, insulin-mediated glucose uptake, and several risk factors for coronary heart disease (CHD), WBC, plasma glucose and insulin responses to a 75-g oral glucose challenge, fasting plasma cholesterol, high-density-lipoprotein (HDL)-cholesterol, and triglyceride concentration, and systolic and diastolic blood pressure were determined in 63 consecutive female volunteers with normal glucose tolerance. The results demonstrated the presence of statistically significant correlation coefficients between WBC count and both insulin-mediated glucose disposal (r = 0.50, P less than 0.001) and insulin response to oral glucose (r = 0.50, P less than 0.001). Furthermore, WBC count correlated with plasma glucose response to oral glucose (r = 0.48, P less than 0.001), fasting plasma triglyceride (r = 0.37, P less than 0.005) and HDL-cholesterol concentrations (r = -0.38, P less than 0.005), and systolic (r = 0.22, P less than 0.1) and diastolic (r = 0.27, P less than 0.05) blood pressure. However, the only two variables significantly correlated with WBC count in multivariate regression analysis were insulin resistance (r = 0.49, P less than 0.01) and insulin response (r = 0.35, P less than 0.05). These data indicate that WBC count is significantly correlated with changes in carbohydrate and lipoprotein metabolism and blood pressure that increase the risk of CHD. However, it appears that these relationships are secondary to resistance to insulin-mediated glucose uptake and hyperinsulinaemia.

Relationship between smoking and diet: The MONICA‐France project

Abstract: The association between smoking habits and diet was examined in a sample of 1126 men, aged 45-64 years, from the general population living in the three French MONICA monitoring areas: Bas-Rhin (BR) (n = 346), Haute-Garonne (HG) (n = 400) and Urban Community of Lille (UCL) (n = 380). Diet was assessed by the 3-day record method. The energy and nutrient intakes were calculated for each of the 3 centres, using the same food composition tables. Alcohol consumption was higher among smokers (P less than 0.001). Taking into account alcohol consumption, age, body mass index, centre, educational level and family size, the analyses showed no difference in non-alcoholic energy intake, proteins, carbohydrates, and total fat. However, smokers had a lower intake of polyunsaturated fatty acids (P less than 0.05) and dietary fibre (P less than 0.01) than non-smokers. With regard to food items, smokers had a higher intake of sucrose (P less than 0.05) and a lower intake of vegetables (P less than 0.001), dairy products (P less than 0.05) and cheese (P less than 0.05). These results suggest that analyses in future epidemiological research regarding the role of diet in the aetiology of tobacco-related diseases should consider this association of potential risk factors.

Systemic lupus erythematosus and related systemic diseases in a nationwide twin cohort: an increased prevalence of disease in MZ twins and concordance of disease features.

Abstract: Concordance rates for systemic rheumatic diseases among monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs ascertained from the older (twins born before 1958) and younger (twins born during the period 1958-1986) parts of the Finnish Twin Cohort were studied. Nine MZ pairs and 10 DZ pairs with at least one member affected by systemic lupus erythematosus (SLE) were identified. Only one MZ pair was concordant for definite SLE by American Rheumatism Association (ARA) criteria. In addition, two more MZ pairs that fulfilled three ARA criteria may have been concordant. None of the DZ pairs were concordant for SLE. MZ twins also had a higher concordance rate for tests of autoantibodies, but the numbers were small. Other systemic rheumatic diseases were infrequent. The cumulative incidence of systemic rheumatic diseases among MZ twin individuals (1.7/1000) was significantly higher than that among DZ twin individuals (0.7/1000).

Secondary amyloidosis (AA).

Abstract: Although secondary amyloidosis (AA) remains a major problem in underdeveloped countries, it is now relatively rare in industrialized nations, and only 5 % of all patients with systemic amyloidosis in the Mayo Clinic practice have this type. In the preantibiotic era, AA was most frequently a complication of tuberculosis and chronic long-standing infections of bone or lung. Since the advent of modern antibiotic therapy, the spectrum has shifted to chronic long-standing rheumatic disorders [l]. Currently, approximately two-thirds of the patients in the United States and Western Europe with AA have an underlying rheumatic disorder, 75% of these disorders being rheumatoid arthritis. The rheumatic disorders themselves are not subtle and are generally long-standing-the median duration of disease being 19 years. The disease is active and has been poorly controlled with standard antirheumatic therapy. Bronchiectasis is also an important cause of AA.

Cognitive function, insulin-dependent diabetes and hypoglycaemia.

Abstract: A series of seven psychometric tests, to evaluate mental concentration and the ability to retain selective attention, lexical fluency, wordlist memorizing and psychomotor speed, was performed on 25 non-diabetic control subjects and 55 insulin-dependent diabetes (IDD) patients of similar social background and professional status. When tested, none of the diabetics was hypoglycaemic and these patients were divided into two groups: Group I: 30 IDD patients unaware of hypoglycaemia, and experiencing frequent and severe episodes of hypoglycaemia. Group II: 25 IDD patients aware of hypoglycaemia. Groups I and II had experienced the disease for the same period of time (17 +/- 13 vs. 14 +/- 11 years, respectively) and they had similar HbA1c levels (7.14 +/- 1.25% vs. 8.6 +/- 1.88%, respectively) and degenerative complications. Compared with the scores of the controls, the Group I scores were lower in four tests: trail-making part A (psychomotor speed; P less than 0.001) and part B (retaining selective attention; P less than 0.01), lexical fluency (P less than 0.01) and Rey auditory-verbal learning test (wordlist learning; P less than 0.05). Group II scores were lower in two tests: trail-making part A (P less than 0.01) and part B (P less than 0.05). In word memorizing, the performance of Group I was inferior to that of Group II (P less than 0.05). In general, these psychometric tests showed that IDD scores were lower than those of the controls, with an average of 67% for Group II and 80% for Group I. Chronic hyperglycaemia and severe hypoglycaemia may have a deleterious effect on cognitive performance. In particular, several severe episodes of hypoglycaemia could be responsible for permanent memory impairment.

Lipoprotein [Lp(a)] and peripheral vascular disease.

Abstract: Lipoprotein(a) [Lp(a)], which combines structural elements of the lipid and fibrinolytic systems, is a major independent risk factor for the development of coronary heart disease. Eighty-four consecutive patients with peripheral vascular disease (of whom 42 had concomitant ischaemic heart disease) and 43 healthy controls were enrolled in a case-control study. We found that the mean Lp(a) concentration in male patients with peripheral vascular disease (PVD) was almost threefold higher than that of controls, while in female patients the Lp(a) concentration was more than twice that of controls. This marked difference was borne out in patients with and without concomitant ischaemic heart disease (IHD). A multivariate logistic regression analysis indicated that Lp(a) is independently associated with PVD when adjusted for age and sex (odds ratio per 100 mg l-1 increase in Lp(a) = 1.35; P < 0.01). A similar association is observed for patients with concomitant IHD (odds ratio per 100 mg l-1 increase in Lp(a) = 1.65; P < 0.01).