Diet and exercise intervention have favourable effects on blood pressure in mild hypertensives: the Oslo Diet and Exercise Study (ODES)

The purpose of this study was to investigate the effect of 1-year diet intervention, exercise intervention and both combined on blood pressure (BP) in normotensives and mild hypertensives. Two hundred and nineteen sedentary middle aged men and women with slightly deranged coronary heart disease (CHD) risk factors were randomised to a control, a diet, an exercise and a diet + exercise group. Based on baseline diastolic BP, participants were divided into tertiles, giving baseline average BP of 141.4/96.7 in tertile 1, 130.7/87.6 in tertile 2 and 121.9/79.0 in tertile 3. The 1-year net-difference in BP between the intervention groups and the control group decreased across the tertiles; in tertile 1 being -11.2/-6.7 (p < 0.05), -11.3/-6.7 (p < 0.05 for systolic BP only) and -7.0/-5.1 (NS) in the combined, diet and exercise group respectively. Triglycerides, HDL cholesterol, and insulin variables were significantly and favourably changed, the changes being most marked in the combined group. The results show that diet and diet + exercise are about equally effective in reducing BP, and the effects may be dependent on the baseline level. Within the upper tertile of baseline BP, the decline in BP in the combined intervention and the diet group are almost comparable to those obtained with drug treatment. In addition, other important CHD risk factors were all changed in a beneficial direction.     

Collection and transfusion of blood and blood components in the United States, 1989

A poor response to L-DOPA in addition to parkinsonian, cerebellar, and autonomic signs is commonly regarded as indicative of clinical multiple system atrophy (MSA). We compared the motor response to a single oral administration of 250 mg L-DOPA/25 mg carbidopa in eight MSA patients and eight Parkinson's disease (PD) patients with the "on-off" phenomenon, evaluating L-DOPA peripheral pharmacokinetics. Motor response was consistently good in all PD patients, but only four MSA patients had a (moderate) response. Pharmacokinetic parameters did not differ between the groups. The varying extent of putaminal damage could be responsible for the differing motor response to L-DOPA in MSA patients.     

Collection and transfusion of blood and blood components in the United States, 1994

BACKGROUND: Collections and transfusions of blood in the United States in 1994 were measured and compared with those in 1992. STUDY DESIGN AND METHODS: Completed survey questionnaires were returned by all 147 regional blood centers, 1340 American Association of Blood Banks (AABB) member hospitals, and 523 non-AABB hospitals. Statistical tests verified the representativeness of the sample. RESULTS: The United States domestic blood supply in 1994 (13,340,000 units) was 3.3 percent less than in 1992. It included allogeneic blood (11,773,000 units), autologous blood (1,013,000 units), and directed donations (334,000 units). Of these, 432,000 units were rejected on testing, 11,107,000 units were transfused to 3,398,000 patients, and 1,801,000 units were discarded or unaccounted for. Platelet transfusions amounted to 7,866,000 units. Compared with the totals for 1992, transfusions of single-donor platelets (714,000 packs or 4,284,000 units) increased by 17.6 percent, while transfusions of platelet concentrates (3,582,000 units) fell by 23.6 percent. Fresh-frozen plasma transfusions (2,621,000 units) increased by 16.2 percent over the number for 1992. CONCLUSIONS: The US blood collection rate in 1994 was 74.6 units per 1000 population of donor age, the lowest recorded level since 1971. The US RBC transfusion rate in 1994 was 42.8 units per 1000 population, about the same as 1979. Transfusions of single-donor platelets, 16.5 units per 1000 population, exceeded transfusions of platelet concentrate (13.8/1000) for the first time. Plasma transfusions were 10.1 units per 1000 population. The US blood supply in 1994 was adequate to meet patient demands.     

Methylephedrine concentrations in blood and urine specimens

Methylephedrine is a sympathomimetic amine that appears in many over-the-counter cough and cold medications throughout the world. The abuse of methylephedrine-containing medications has been reported in Japan. Although methylephedrine is not available in the United States, it was identified in 15 cases received by the Forensic Toxicology Laboratory, Division of Forensic Toxicology, Office of the Armed Forces Medical Examiner, Armed Forces Institute of Pathology over a two-year period; 12 of the 15 cases were collected from patients or decedents located within the confines of the continental United States. Methylephedrine was identified in each case by gas chromatography-nitrogen-phosphorus detection following an alkaline extraction and subsequently confirmed using full scan electron impact mass spectrometry. Quantitation of underivatized methylephedrine was performed using the same technique. Blood methylephedrine concentrations ranged from less than 0.05 to 0.28 mg/L (n = 14), and the mean methylephedrine concentration in urine was 1.6 mg/L (range, 0.15-6.8, n = 11 [excluding case 6]). A literature search revealed little information pertaining to the interpretation of methylephedrine concentrations in the blood. Six of the 15 cases presented here were positive for methylephedrine in the blood. Three of these cases were postmortem cases, and the other three cases were nonfatal aircraft mishaps. There is no evidence in any of these cases that methylephedrine was present at toxic concentrations; therefore, it appears from the cases reviewed in this study that blood methylephedrine concentrations less than 0.3 mg/L are not associated with significant toxicity.     

Comparison of heroin and cocaine concentrations in saliva with concentrations in blood and plasma

Saliva is an alternate biological matrix for drug testing that has several advantages over more traditional fluids such as blood and urine. Collection is rapid, noninvasive, and relatively easy to obtain. Several reports have detailed the appearance of drugs of abuse in saliva, but few have compared the excretion profiles of drugs administered by different routes. In this study, subjects were administered three smoked and three intravenous doses of heroin in an ascending dose design. Blood and saliva were collected periodically after drug administration and analyzed by gas chromatography-mass spectrometry (GC-MS) for heroin, 6-acetylmorphine, and morphine. In a second study, subjects were administered a single, smoked dose of 40 mg cocaine base and an intravenous dose of 44.8 mg cocaine HO on separate occasions. Plasma and saliva were collected and analyzed by CC-MS for cocaine, anhydroecgonine methyl ester (AEME), and seven additional metabolites. Heroin and 6-acetylmorphine were detected in the first saliva sample collected (2 min) following drug administration by both routes. Peak heroin concentrations were achieved quickly, between 2 and 5 min after intravenous administration and at 2 min after smoke heroin. Peak heroin concentrations in saliva after smoking heroin base ranged from 3534 (2.6 mg) to 20,580 ng/mL (5.2 mg), and after intravenous administration, concentrations ranged from 6 (10 mg heroin HCl to 30 ng/mL (12 mg heroin HCl. Saliva concentrations of heroin declined rapidly after intravenous administration, reaching the limit of sensitivity of the assay (1 ng/mL) by 60 min. Heroin concentrations in saliva after smoking declined slowly; detection times ranged from 4 to 24 h. Cocaine was the major analyte detected in saliva and plasma after smoked and intravenous administration. Peak saliva cocaine concentrations after intravenous administration ranged from 428 to 1927 ng/mL (N = 7); after smoking, they ranged from 15,852 to 504,880 ng/mL (N = 7). Peak plasma cocaine concentrations after intravenous administration ranged from 122 to 442 ng/mL A = 7), and after smoking, concentrations ranged from 46 to 291 ng/mL A = 7). The thermal degradation product of cocaine, AEME, was detected in saliva but not in plasma after smoking. Peak saliva AEME concentrations were achieved at 2 min and ranged from 558 to 4374 ng/mL (N = 7). These are the first reported observations of heroin and metabolites in saliva following heroin smoking and of AEME in saliva after smoking cocaine base. The presence of AEME in saliva may be useful as a marker of the smoked route following cocaine administration.     

Venous thromboembolism--incidence and risk factors in Oslo

Over a period of three years, 378 patients with objectively verified venous thromboembolism were treated at Aker University Hospital. Below the age of 60, men and women had about the same incidence of venous thromboembolism, but that age the incidence was significantly higher among men than among women. Incidence increased exponentially with age, from about 1:10,000 at age 20 to about 1:1,000 at age 50. The incidence found here is lower than in earlier Nordic studies. The great majority of the patients (93%) had deep venous thrombosis in the lower extremities, 11% had symptomatic and verified pulmonary embolism, and 1% had their thrombus in an inner organ vein. 23% of patients were previously treated for venous thromboembolism, and 22% had cancer. Seven women were on oral contraception, and 22 used postmenopausal hormone substitution. An obvious temporary precipitating factor was present in 42% of the patients, while 36% had a spontaneous venous thromboembolism. Hereditary thrombophilic disorder was found in 32% of patients below the age of 60.     

Home blood glucose concentrations in maturity-onset diabetes

Blood glucose concentrations during normal daily activities were measured in 106 patients with maturity-onset diabetes from capillary blood samples collected on to filter paper. Samples were taken before and two hours after main meals, before going to bed, and, in 51 cases, during the night. Fasting and mid-morning values were closely correlated with the mean values over 24 hours irrespective of the type of anti-diabetic treatment being given. Postprandial blood glucose concentrations remained below 11.5 mmol/l (207 mg/100 ml) when the fasting blood glucose value was 7.0 mmol/l (126 mg/100 ml) or less, and repeated fasting blood glucose values exceeding 7.0 mmol/l were associated with raised blood glycosylated haemoglobin concentrations. Diabetic control in maturity-onset diabetes may be satisfactorily monitored by regular measurement of fasting or mid-morning blood glucose values.     

Synchronous fluctuations of blood insulin and lactate concentrations in humans

Diseases associated with pathological fibroproliferation represent a major cause of morbidity and mortality. Despite the importance of this class of disorders, current therapy is of limited value, and no therapy is available to reduce the fibroblast population size within existing fibrotic lesions. In this regard, constitutive expression of growth-promoting genes can sensitize cells to undergo apoptosis. Studies in our laboratory have demonstrated that lovastatin potently induces apoptosis in fibroblasts constitutively expressing Myc, and that lung fibroblasts isolated from fibrotic lesions constitutively express growth-promoting genes. In this study, we sought to determine if nontransformed lung fibroblasts would manifest susceptibility to lovastatin-induced apoptosis similar to that observed in fibroblasts ectopically expressing Myc. Here we show that clinically achievable concentrations of lovastatin induce apoptosis in normal and fibrotic lung fibroblasts in vitro, as evidenced by acridine orange staining, terminal transferase nick end translation (TUNEL), and DNA laddering. Apoptosis of human lung fibroblasts was dose- and time-dependent, and blocked by exogenous mevalonic acid. Furthermore, apoptosis was associated with decreased levels of mature Ras, a molecule directly implicated in fibroblast rescue from apoptosis. The ability of lovastatin to induce fibroblast apoptosis in vivo was examined using a guinea pig wound chamber model. Lovastatin (5 microM, 8 d) reduced granulation tissue formation in the wound chambers by 64.7%, with associated ultrastructural evidence of fibroblast apoptosis. These findings support further study of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors as potential therapy for patients with fibroproliferative disorders.     

Smoking habits and risk of fatal stroke: 18 years follow up of the Oslo Study

A case of splenic large B-cell lymphoma with hemophagocytic syndrome is reported. The difficulties of diagnosis are emphasized especially when peripheral lymph nodes or bone marrow lymphomatous infiltration are not present. Diagnostic criteria for hemophagocytic syndrome and their relationship with the pathogenesis of the disease are also stressed.     

Risk factors of stroke incidence and mortality. A 12-year follow-up of the Oslo Study

BACKGROUND AND PURPOSE: The objective of this study was to determine the risk factors of stroke incidence and mortality. METHODS: Our data are based on a prospective cohort study of men aged 40 to 49 years after 12 years of follow-up. RESULTS: In age-adjusted Cox proportional-hazards regression analysis of 14,403 healthy men, diastolic blood pressure was a stronger predictor for stroke incidence and mortality than systolic blood pressure. Smoking was a stronger predictor of mortality than of incidence. However, there was no dose-response relation among smokers by increased cigarette consumption. Total serum cholesterol was a significant (P < .05) risk factor for stroke mortality and of borderline significance (P = .08) for stroke incidence. Increased physical activity at leisure was associated with reduced stroke incidence but not mortality. The myocardial infarction risk score comprising systolic blood pressure, total serum cholesterol, and daily cigarette smoking was a strong predictor of mortality and incidence. Body mass index, triglycerides, blood glucose, and physical activity at work were not found to be risk factors for stroke. CONCLUSIONS: Reduction of blood pressure, cessation of smoking, lowered cholesterol, and increased physical activity at leisure are individual measures to reduce the risk of stroke.     

Exercise fitness, cardiac work and blood viscosity factors in patients and normals

A study of 41 cardiovascular patients and normals showed significant correlations between physical fitness (as expressed by a fitness index based on work output) and high shear rate blood viscosity (p less than 0.01); between the cardiac work expressed as double product (= myocardial oxygen demand) and aggregation of red cells (p less than 0.05); between the triple term of cardiac work (fitness index divided by double product) and high shear rate blood viscosity (p less than 0.005) or aggregation of red cells (p less than 0.05), in all cases correlations being negative i.e., higher cardiac work or higher fitness being related to low blood viscosity or lower aggregation of red cells. Significant differences were found between high-fitness and low-fitness groups, the high-fitness group showing from plasma viscosity (p less than 0.0005), lower fibrinogen level (p less than 0.05), and higher albumin/fibrinogen ratio (p less than 0.01).     

Achievement and safety of a low blood pressure goal in chronic renal disease. The Modification of Diet in Renal Disease Study Group

The Modification of Diet in Renal Disease Study showed a beneficial effect of a lower-than-usual blood pressure (BP) goal on the progression of renal disease in patients with proteinuria. The purpose of the present analyses was to examine the achieved BP, baseline characteristics that helped or hindered achievement of the BP goals, and safety of the BP interventions. Five hundred eighty-five patients with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m2 (0.22 to 0.92 mL/s per 1.73 m2) were randomly assigned to either a usual or low BP goal (mean arterial pressure < or = 107 or < or = 92 mm Hg, respectively). Few patients had a history of cardiovascular disease. All antihypertensive agents were permitted, but angiotensin-converting enzyme inhibitors (with or without diuretics) followed by calcium channel blockers were preferred. The mean (+/- SD) of the mean arterial pressures during follow-up in the low and usual BP groups was 93.0 +/- 7.3 and 97.7 +/- 7.7 mm Hg, respectively. Follow-up BP was significantly higher in subgroups of patients with preexisting hypertension, baseline mean arterial pressure > 92 mm Hg, a diagnosis of polycystic kidney disease or glomerular diseases, baseline urinary protein excretion > 1 g/d, age > or = 61 years, and black race. The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group, but there were no significant differences between BP groups in stop points, hospitalizations, or death. When data from both groups were combined, each 1-mm Hg increase in follow-up systolic BP was associated with a 1.35-times greater risk of hospitalization for cardiovascular or cerebrovascular disease. Lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens without serious adverse effects in patients with chronic renal disease without cardiovascular disease. For patients with urinary protein excretion > 1 g/d, target BP should be a mean arterial pressure of < or = 92 mm Hg, equivalent to 125/75 mm Hg.     

Diet modification alters plasma HDL cholesterol concentrations but not the transport of HDL cholesteryl esters to the liver in the hamster

These studies were undertaken to investigate the mechanism whereby diet modification alters the plasma concentration of high density lipoprotein (HDL) cholesteryl ester and apoA-I and to determine whether diet-induced alterations in circulating HDL levels are associated with changes in the rate of reverse cholesterol transport. Rates of HDL cholesteryl ester and apoA-I transport were measured in hamsters fed a control low-cholesterol, low-fat diet or the same diet supplemented with soluble fiber (psyllium) or with cholesterol and triglyceride (Western-type diet). The Western-type diet increased the plasma concentration of HDL cholesteryl ester by 46% compared to the control diet and by 86% compared to the psyllium-supplemented diet; nevertheless, the absolute rates of HDL cholesteryl ester transport to the liver were identical in the three groups. Diet-induced alterations in circulating HDL cholesteryl ester levels were due to changes in the rate of HDL cholesteryl ester entry into HDL (whole body HDL cholesteryl ester transport) and not to regulation of HDL cholesteryl ester clearance mechanisms. The Western-type diet increased the plasma concentration of HDL apoA-I by 25% compared to the control diet and by 45% relative to the psyllium-supplemented diet. Diet-induced alterations in plasma HDL apoA-I concentrations were also due entirely to changes in the rate of apoA-I entry into HDL (whole body HDL apoA-I transport). These studies demonstrate that the absolute flux of HDL cholesteryl ester to the liver, which reflects the rate of reverse cholesterol transport, remains constant under conditions in which plasma HDL cholesteryl ester concentrations are altered over a nearly 2-fold range by diet modification.     

Morning and Monday: critical periods for the onset of acute myocardial infarction. The GISSI 2 Study experience

The onset of acute myocardial infarction (AMI) is unevenly distributed over the 24 h and the week. While presence of a morning peak is generally agreed upon, contrasting results had been obtained regarding other periods of the day, probably due to differences of origin, size and composition of the populations. The 24 h and weekly distributions were studied within 6 h from the beginning of the symptoms in a population following a Latin life-style, who were enrolled in the GISSI 2 Study (n = 11472). Subgroups (smokers, the elderly (> 65 years), diabetics, hypertensives) were also considered. Six hour periods starting at midnight were tested for uniformity. Circadian non-uniformity was found. Events increased in the morning hours and reduced during the night regardless of the day of the week. The night and day difference was attenuated in smokers and diabetics. Non-uniformity of the events was also found among the days of the week. AMI significantly increased in non-smokers on Monday. We suggest that there is a night-day gradient (characterized by the short time interval between the two frequency extremes) in the time of onset of AMI. The different distribution in smokers stresses the possible unfavourable and masking effect of a heightened sympathetic tone during the day while the general protective role of the night hours is preserved. Moreover, the increased incidence of events on Monday may suggest the importance of the shift from a period of non-scheduled to scheduled activity.