A time-series study of the health effects of water-soluble and total-extractable metal content of airborne particulate matter.

OBJECTIVES: To assess whether adverse acute cardiopulmonary health outcomes are associated with concentration of trace metals in airborne particulate matter. METHODS: Daily PM(10) and PM(2.5) were collected for 1 year in Edinburgh, UK, and the water-soluble and total-extractable content of 11 trace metals determined in each sample. Time series were analysed using generalised additive Poisson regression models, including adjustment for minimum temperature and less smoothing of trends. Methods were explored of extending the time series of metal concentration in daily PM(10) for the previous 7 years using multiple regression of the variation in metal content for the 1 year of measurements and the associated variation in air mass source region and other concurrently-measured potential predictor variables. RESULTS: The 1 year of direct measurements showed no evidence of significant associations of particle-bound metal concentration with health outcomes beyond that expected by chance. Analysis of the extended time series showed significant positive associations with cardiovascular admissions both for total PM(10) and for a number of the metals (eg, Cu, Fe, Ni, V, Zn) but the metal effects were no longer significant after adjusting for PM(10). CONCLUSIONS: Within the limitations of the study power, the epidemiological results have not provided evidence for associations between particle-bound metal concentrations and adverse health outcomes that are substantially greater than for total PM. The generally strong correlations between metal and total PM suggest that quantifying independent effects of PM metal exposure on health will be difficult, even using more powerful time series of direct measurements.

Poisons admissions in Edinburgh 1981-2001: agent trends and predictors of hospital readmissions.

Self-poisoning is a major public health problem. This study describes patterns of admissions and readmissions from self-poisoning to the Royal Infirmary of Edinburgh from 1981 to 2001. A database on hospital discharges with a diagnosis (ICD-9/10) of poisoning between 1981 and 2001 was used. Annual admissions were described for seven main drug categories, and proportions of patients readmitted within 1-5 years from first admission, were computed for each category. Cox proportional hazards regression was used to evaluate prognostic factors for readmission risk over 1981-2001. For both sexes, admissions increased from the early to mid 1990s, and declined thereafter. The proportion readmitted varied with the drug taken at first admission, from 11.9% (95% CI: 10.8-13%) for non-opiate analgesics, to 17.6% (16.5-18.7%) for benzodiazepines. Deprivation was positively related to readmission risk after first admissions with paracetamol (P < 0.001) and benzodiazepines (P < 0.001). Timing of first admissions involving paracetamol (P < 0.01), benzodiazepines (P < 0.001), antidepressants (P < 0.001), non-opiate analgesics (P < 0.001), and opiates (P < 0.05), was inversely associated with readmission risk. In patients admitted for drug overdose, readmission risk is influenced by type of drug taken at first admission. Information on drug type used in self-poisoning may assist in identifying patients at risk for future events, and in reducing hospital readmissions.

Continued drug use and other cofactors for progression to AIDS among injecting drug users.

OBJECTIVE: To evaluate the effects of continued drug use and other cofactors on progression to AIDS among HIV-infected injecting drug users. DESIGN: A prospective study. SETTING: The Muirhouse Medical Group in Edinburgh, Scotland, UK. SUBJECTS: A total of 156 HIV-infected injecting drug users. MAIN OUTCOME MEASURES: Progression to AIDS and low absolute CD4 counts. RESULTS: Of this group, 48% will have progressed to AIDS 10 years after seroconversion. Age and low absolute T4 counts had a significant effect on progression to AIDS, with older patients progressing more rapidly. Sex had no significant effects on progression. Absolute CD4+ counts and the CD4:CD8 ratio were significant predictors of progression among the group. Concurrent heroin injecting increased the risk of progression to AIDS. No significant effects were observed for use of other drugs. CONCLUSIONS: Our findings suggest that continued drug use may have an accelerating effect on progression to AIDS. Age also had an accelerating effect on progression, but sex had no significant effects. In general, the study group did not appear to progress at a different rate from other similar groups of HIV-infected individuals, despite the fact that this was a relatively young cohort. These data were based on accurate estimates of seroconversion dates.

Influence of risk group and zidovudine therapy on the development of HIV encephalitis and cognitive impairment in AIDS patients.

OBJECTIVE: To determine the associations between HIV encephalitis and other central nervous system (CNS) pathology, viral burden, cognitive impairment, zidovudine therapy and risk group in AIDS patients. DESIGN: Planned autopsy study in AIDS patients evaluated prospectively for numerous clinical parameters. SETTING: Regional academic centre for clinical care and pathology examination of patients with HIV infection. PATIENTS: Edinburgh cohort of HIV-positive patients prospectively assessed for cognitive impairment, immunosuppression and clinical course. Unbiased series of consecutive autopsies in 27 homosexual men and 39 drug-using patients with AIDS. INTERVENTIONS: Zidovudine therapy monitored in all patients. MAIN OUTCOME MEASURES: Determination of CNS viral burden and pathology including immunocytochemically confirmed HIV encephalitis in injecting drug users (IDU) versus homosexual AIDS patients with known CD4 counts and cognitive function. RESULTS: HIV encephalitis was present in 59% of IDU and 15% of homosexuals: 88% of patients with encephalitis had displayed cognitive impairment. HIV encephalitis was strongly associated with a high viral load and HIV p24 immunopositivity. Opportunistic infections and lymphomas were more common in homosexuals (63%) than in IDU (31%) and were associated with the degree of immunosuppression before death. Within both groups, prolonged zidovudine treatment was associated with a lower incidence of HIV encephalitis. CONCLUSIONS: This study documents two separate CNS outcomes in AIDS patients in that HIV encephalitis occurs independently of opportunistic infections and lymphomas and shows different associations with risk group, immunosuppression and antiviral treatment before death.

Long-term effect of wholemeal bread on stool weight, transit time, fecal bile acids, fats, and neutral sterols.

Stool weight, fecal constituents, bile acids, fat, neutral sterols, and intestinal transit time were recorded in 28 subjects over 18 mo. During the first 12 mo the subjects ate white bread. They were studied for an initial period of 7 days, and after 6 mo (study period 1). For the first 6 mo they ate their usual intake of bread, they then increased their white bread intake by 62 g/day for 6 mo (study period 2). The subjects ate a self-selected diet throughout the 18 mo study. During the last 6 mo (study period 3) the subjects replaced white bread by the same amount of wholemeal bread as in study period 2. No increase in stool weight occurred until study period 3 when there was an increase of 20%. There developed a linear relationship between stool weight and intestinal transit time which was not found during the initial first and second study periods. A seasonal influence on serum cholesterol was not observed during the wholemeal bread period. Fecal bile acid excretion was unchanged throughout the experiment.

Alcohol consumption and nutrient intake in middle-aged Scottish men.

The relation between alcohol consumption and dietary intake was examined in 164 middle-aged Scottish men taking part in a study of risk factors for coronary heart disease (CHD). A 7-d weighed dietary record was used to assess alcohol and nutrient intake. The mean daily intake of alcohol was 26 g (SD 31 g). Energy derived from alcohol tended to replace energy derived from other nutrients and increasing intake of alcohol was associated with a decrease in the amounts of carbohydrate, total fat, and saturated and monounsaturated fatty acids in the diet. Those with a low alcohol intake (0.1-9 g alcohol/d) had a higher intake of total fiber, cereal fiber, polyunsaturated fatty acids, and linoleic acid and a smaller proportion smoked cigarettes. The differences are small but may contribute to the lower mortality from CHD reported by other studies in those with a low alcohol intake.

Vitamin C and the risk of acute myocardial infarction.

BACKGROUND: Low-fat soluble-antioxidant status is associated with an increased risk of heart disease. OBJECTIVE: The aim of this study was to examine whether low plasma concentrations of vitamin C confer an independent risk of acute myocardial infarction (AMI). DESIGN: Male patients (n = 180) aged <65 y with a first AMI and without an existing diagnosis of angina (>6 mo) who were admitted within 12 h after onset of symptoms were compared with apparently healthy volunteers (n = 177). Plasma concentrations and dietary intakes of vitamin C were determined during hospitalization and 3 mo later. RESULTS: Compared with the control subjects, the patients had higher total cholesterol and lower HDL-cholesterol concentrations and more of them smoked. The relative risk of AMI for the lowest compared with the highest quintile of plasma vitamin C during hospitalization (14.5 and >60.5 micromol/L, respectively) was 8.37 (95% CI: 3.28, 21. 4) after adjustment for classic risk factors. At 3 mo, mean (+/-SEM) plasma vitamin C concentrations in patients had increased significantly, from 19.6 +/- 1.2 to 35.1 +/- 1.9 micromol/L (P < 0. 001) and no longer conferred a risk of AMI [relative risk: 1.02 (95% CI: 0.51, 2.03)]. Habitual dietary vitamin C intake of patients (before AMI) did not differ significantly from that of control subjects. The increase in plasma vitamin C after recovery from the infarction could not be explained by a similarly large increase in dietary vitamin C. CONCLUSIONS: A low plasma concentration of vitamin C was not associated with an increased risk of AMI, irrespective of smoking status. The apparent risk of AMI due to a low plasma vitamin C concentration was distorted by the acute phase response.

Fecal weight and composition, serum lipids, and diet among subjects aged 18 to 80 years not seeking health care.

Sixty-two subjects not seeking health care, aged 18 to 80 yr, recorded diet intake, collected feces for 7 days, and gave fasting blood lipids. There was a great variation in stool weight passed (19 to 278 g/24 h). Fecal constituents (bile acids, sterols, fat, electrolytes) correlated strongly with fecal mass. Fecal mass correlated inversely with transit time. There was no relationship between age and fecal weight or transit time. Multiple regression analysis showed that only dietary fiber contributed to stool weight. No single component of fiber appeared to be responsible for this relationship with stool mass. Multiple regression analysis of serum cholesterol showed a relationship only with age and fecal neutral sterols.

Zinc and rehabilitation from severe protein-energy malnutrition: higher-dose regimens are associated with increased mortality.

A randomized, double-blind trial was undertaken to measure the effects of zinc supplementation on catch-up growth in severe protein-energy malnutrition, with particular reference to linear growth. One hundred forty-one children between the ages of 6 mo and 3 y were enrolled after admission to a nutritional rehabilitation unit in Dhaka, Bangladesh, and randomly assigned to receive elemental zinc by mouth, 1.5 mg/kg for 15 d, 6.0 mg/kg for 15 d, or 6.0 mg/kg for 30 d, and thereafter they were followed for a total of 90 d. Anthropometric outcome measures included change in knee-heel length, midupper arm circumference, subscapular and triceps skinfold thicknesses, and change in height-for-age, weight-for-age, and weight-for-height z scores. Higher zinc doses were not associated with significant change in any anthropometric measurement, but mortality was significantly greater in children who received high-dose zinc (6.0 mg/kg) initially as opposed to those who received low-dose zinc supplementation (1.5 mg/kg) (Yates-corrected chi-square P value of 0.033 and a risk ratio of 4.53; 95% CI: 1.09 < risk ratio < 18.8). We conclude that there is no benefit to using high-dose zinc supplementation regimens and that they could contribute to increased mortality in severely malnourished children.

Homovanillic acid and 5-hydroxyindoleacetic acid in lumbar cerebrospinal fluid in children with afebrile and febrile convulsions.

The concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in lumbar cerebrospinal fluid (CSF) from five groups of children: (1) afebrile controls (2) febrile controls, (3) children with afebrile convulsions, which included children with established idiopathic epilepsy, (4) children with first febrile convulsions, and (5) children with repeated febrile convulsions. There were no significant differences between the metabolite levels in the five diagnostic groups. The CSF concentrations of 5-HIAA and HVA in these children, with a mean age of 2.5 years, were about twice the levels found in adults.

Types of cyclic AMP binding proteins in human breast cancers.

Total level and type of cyclic AMP binding proteins have been measured in 117 breast cancers. Six major molecular species of binding proteins were detected. The pattern and relative proportion of binding proteins varied between individual tumours. However, there were highly significant correlations between the expression of different binding proteins, including positive relationships between 52 and 67 kD proteins, 43 kD and both 39 and 37 kD proteins and inverse correlations between 48 and 52 kD, 37 and 67 kD proteins. The expression of three binding proteins (48, 43 and 39 kD) was also positively related to total binding whereas that of the remaining three bindings proteins (67, 52 and 37 kD) was negatively correlated with total levels. It may be that differential expression of certain types of binding protein are the underlying rationale for our previously published finding that tumours with high levels of high binding protein are associated with poor prognosis.

A case for synchronous reduction of testicular androgen, adrenal androgen and prolactin for the treatment of advanced carcinoma of the prostate.

The present study was undertaken mainly to investigate whether prolactin manipulation combined with maximal androgen blockage improves the effectiveness of treatment in advanced prostatic cancer. The efficacy of oral hydrocortisone as an alternative to commercial anti-androgens in reducing the adrenal androgens, and of bromocriptine in reducing the prolactin level were also examined. A consecutive series of 30 patients with untreated and advanced prostatic cancer were entered into a three-arm prospective randomised trial. 10 patients received subcapsular orchiectomy alone (arm 1), another 10 had subcapsular orchiectomy plus flutamide (arm 2), and the remaining 10 had subcapsular orchiectomy plus oral hydrocortisone and bromocriptine (arm 3). Clinical and biochemical parameters, including trans-rectal ultrasound-determined prostatic volumes, hormonal profiles and radionuclide bone scan were evaluated at regular intervals. At 12 months, serum testosterone was reduced by more than 90% in all arms, however, maximum suppression of androstenedione, prolactin, and reduction of prostatic volumes were only observed in arm 3; this was reflected by the significant improvement in clinical response in arm 3 compared with other arms. This study suggests that a combined maximal suppression of androgens and prolactin offers a significant improvement in response over conventional treatments without prolactin suppression in the treatment of advanced prostatic cancer. Importantly, a better clinical outcome in arm 3 was still apparent at the end of 36 months.

Effects of safflower oil and evening primrose oil in men with a low dihomo-gamma-linolenic level.

Low levels of essential polyunsaturated fatty acids of the n-6 series are associated with coronary heart disease. Linoleic acid, but not gamma-linolenic acid requires the activity of delta 6-desaturase for its conversion to dihomo-gamma-linolenic and arachidonic acid. Evening primrose oil (EPO) and safflower oil (SO) are rich in linoleic acid, but EPO contains also 9% gamma-linolenic acid. The effect of EPO (10, 20 and 30 ml/day) and SO (20 ml/day) for 4 months on the deposition of linoleic acid metabolites in adipose tissue of 4 groups of 6-9 men with low adipose dihomo-gamma-linolenic acid was examined. EPO but not SO increased adipose dihomo-gamma-linolenic acid level from 0.080 +/- 0.005% to 0.101 +/- 0.005% (P less than 0.01; 20 ml/day for 4 months). Adipose dihomo-gamma-linolenic/linoleic acid ratio increased with EPO from 0.99 +/- 0.16 X 10(2) to 1.13 +/- 0.14 X 10(2) and fell on SO from 1.04 +/- 0.10 X 10(2) to 0.90 +/- 0.07 X 10(2) (P less than 0.01). Similar qualitative changes in the relative amount of dihomo-gamma-linolenic acid in serum triglyceride and cholesteryl ester fractions were observed. At the dose of 20 ml/day, SO and EPO did not differ in their effect on serum cholesterol (7.13 +/- 0.43 vs. 7.33 +/- 0.42 mmol/l (NS)), LDL-cholesterol (5.10 +/- 0.32 vs. 4.88 +/- 0.46 mmol/l (NS)) nor did the 2 oils differ in their effect on HDL-cholesterol. These results suggest that linoleic acid is not readily converted to dihomo-gamma-linolenic acid due to a low activity of delta 6-desaturase in these highly selected men. EPO was not an effective hypocholesterolaemic agent in this study.

Glucose tolerance, plasma insulin, HDL cholesterol and obesity: 12-year follow-up and development of coronary heart disease in Edinburgh men.

The insulin response to a standard oral glucose tolerance test (OGTT) and other anthropometric and biochemical risk factors for coronary heart disease (CHD) were measured in a random sample of 107 Edinburgh men, who were initially studied in 1976 when they were 40 and who were reexamined in 1988-89. Fasting glucose and glucose response to OGTT were higher in 1988-89 than in 1976. In contrast, insulin levels did not differ between the initial and follow-up study either before or after the glucose load. Body mass indices increased, except triceps skinfold. Changing patterns in both fasting and OGTT insulin or glucose levels in individuals were related to changes in bodyweight or in subscapular skinfolds. Modifications in serum total and HDL cholesterol were related to changes in fasting insulin and insulin area, respectively, but not to glucose data. Eleven men developed clinical CHD. Neither glucose nor insulin measures obtained in 1976 differed between those with and without CHD. Weight-height index and abdominal skin-folds were higher in those with CHD. HDL cholesterol was significantly lower (P less than 0.05). Abdominal skin-fold but not body mass index remained significant when adjusted for HDL cholesterol. This small study confirms the importance of central obesity and low HDL cholesterol but failed to identify insulin as a risk factor for CHD in this Scottish population.

In vitro thrombogenicity tests of factor IX concentrates. I. A survey of available assays.

Various factor IX concentrates have been examined in a number of in vitro tests of thrombogenicity. The results suggest that some tests are superfluous as in concentrates with activity in any of these tests activation is revealed by a combination of the non-activated partial thromboplastin time, the thrombin (or Xa) generation time and factor VIII inhibitor bypassing activity tests. Assay of individual coagulant enzymes revealed that most concentrates contained more factor IXa than Xa. However only a small number of concentrates, chiefly those that had been purposefully activated, contained appreciable amounts of either enzyme.

Relationships of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina.

Plasma viscosity, molecular markers of activated coagulation and fibrinolysis (fibrinopeptides A and B beta 15-42), coagulation factors (fibrinogen and factor VII) and antiplasmins were measured in 529 men aged 35-54 years and related to new angina pectoris (n = 117) and to coronary risk factors in controls without angina (n = 412). Five major risk factors (cigarette-smoking, blood pressure, cholesterol, triglyceride and body mass index) were each associated with increases in plasma viscosity, coagulation factors, and imbalance of coagulation over fibrinolysis (increased ratio of fibrinopeptide A/fibrinopeptide B beta 15-42). Increased viscosity and fibrinogen in smokers were partly reversed in ex-smokers, but the imbalance of coagulation and fibrinolysis persisted. Cholesterol and triglyceride were also associated with increased antiplasmin activity. In men with angina, only fibrinogen was elevated compared to controls. We suggest that increased plasma viscosity and an imbalance of coagulation over fibrinolysis may be mechanisms by which known risk factors promote arterial thrombosis, but are not present in stable angina.

The outcome of peptic ulcer haemorrhage in relation to consumption of nonsteroidal anti-inflammatory drugs or aspirin.

AIM: To compare the outcome of 76 patients who presented with severe peptic ulcer haemorrhage whilst taking nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin with that of 112 patients who were not taking these drugs and who developed peptic ulcer haemorrhage over the same time period. METHODS: The two groups of patients were managed identically and endoscopic therapy was attempted in all cases. RESULTS: The group taking NSAIDs or aspirin tended to be older and had a higher prevalence of cardio-respiratory disease. The severity of bleeding (as assessed by the presence of shock, anaemia and endoscopic stigmata) was similar in the two groups. Outcome in terms of uncontrolled haemorrhage, rebleeding and blood transfusion requirements did not differ significantly in the two groups. The NSAID group had a significantly longer duration of admission, almost certainly attributable to a higher prevalence of co-morbid diseases. CONCLUSIONS: Despite the deleterious effects of NSAIDs and aspirin upon renal and platelet function, the prognosis of peptic ulcer bleeding is not adversely affected by NSAID or aspirin therapy.

Incidence of intraglomerular platelets in steroid sensitive nephrotic syndrome.

Renal biopsies from 44 patients with steroid sensitive nephrotic syndrome were examined with respect to the content of their intraglomerular platelets and compared with 18 normal control patients and with 51 patients with membranous glomerulonephritis and the nephrotic syndrome. The results suggested that platelet activity was not involved in the pathogenesis of steroid sensitive nephrotic syndrome; in the active phase of the number of platelets in glomeruli is lower than that of normal controls, and this may be associated with increased sensitivity to aggregating agents as part of the nephrotic syndrome. After steroid treatment and disappearance of proteinuria, the number of intraglomerular platelets rises to normal values.

Platelet and coagulation factors in proliferative diabetic retinopathy.

Plasma beta-thromboglobulin, platelet factor 4, fibrinogen, fibrinopeptide A, antithrombin III, factor VIII related antigen, alpha 2-macroglobulin, platelet count, and total glycosylated haemoglobin were measured in three well matched groups of subjects: non-diabetic controls, diabetics without retinopathy, and diabetics with proliferative retinopathy. beta-thromboglobulin and platelet factor 4 concentrations were significantly higher in the diabetics with retinopathy than in the controls and platelet factor 4 was also increased in the diabetics without retinopathy compared with controls. Fibrinogen concentration was raised in diabetics without retinopathy compared with controls, diabetics with retinopathy compared with controls, and diabetics with retinopathy compared with those without. Fibrinopeptide A concentration did not differ significantly between groups. Antithrombin III levels were increased in diabetics with retinopathy compared with controls, and in diabetics with retinopathy compared with those without. Factor VIII related antigen values were higher in both the diabetic groups when compared with the controls. Fibrinopeptide A concentration correlated with both beta-thromboglobulin and platelet factor 4 in each of the three groups. Haemostatic abnormalities in diabetes have been shown, although a hypercoagulable state has not been confirmed. These changes in platelet and coagulation function may be secondary to the development of microvascular disease and their role in the pathogenesis of retinopathy remains uncertain.

Glycosylated hemoglobin and its temporal relationship to plasma glucose in non-insulin dependent (type 2) diabetes mellitus.

Total glycosylated hemoglobin (HbAI) and random plasma glucose were measured at monthly intervals for 6 mo in 33 non-insulin dependent (type 2) diabetics. The mean HbAI and mean plasma glucose in individual patients over the 6 mo showed a close correlation (p less than 0.001). A significantly higher HbAI (p less than 0.001) for a given plasma glucose was seen in those patients receiving combined chlorpropamide and metformin therapy (n = 14) than in those receiving chlorpropamide alone (n = 19). For each patient correlation coefficients were calculated between plasma glucose and HbAI with time lags of 0.1 and 2 mo. The coefficients with no time lag showed a significant tendency to be positive (p less than 0.01) whereas those with time lags of 1 or 2 mo were not significant. A constant proportional variability of both HbAI and plasma glucose over time was demonstrated, the mean coefficient of variation for HbAI being 8.4 +/- 2.7% and for plasma glucose 22.3 +/- 9.7%. We conclude that HbAI provides an index of plasma glucose control, not during the preceding few months as was previously thought but, during the previous few weeks. In terms of variability from month to month a single HbAI determination was equivalent to approximately the mean of 3 single plasma glucose values.