Quality-of-life instruments in hypertension

This review considers the choice of dimensions to be assessed and the practical problems of measuring quality of life in hypertensive patients. The dimensions of symptomatic well-being, psychological well-being, sleep, sexual function and cognitive function should be assessed. Symptomatic well-being may be measured by many different instruments, and that devised by the authors has been used extensively. The results in different trials may therefore be examined for consistency and sensitivity. Psychological well-being has been assessed by the Psychological General Well-Being Index, the Symptom Rating Test and the Profile of Mood States. The response of these instruments is discussed. The assessment of sleep, sexual function and cognitive function is also described. It is recommended that quality-of-life instruments to be employed in trials of antihypertensive drugs are known to be sensitive to the effects of such drugs.     

Contribution of environmental factors to variability in human drug metabolism.

Drug metabolism in 96 London factory and office workers has been studied after simultaneous single doses of antipyrine (phenazone) and paracetamol (acetaminophen). Metabolic clearance of both drugs was significantly greater in subjects eating meat more than once a week than in those who ate meat less frequently. The precise contribution of diet could not be clearly defined since 90% of "meat-eaters" were European while all except one of the "vegetarians" were Asian. Clearance of both drugs increased with both alcohol and cigarette consumption. Regular intake of coffee and/or tea had a similar effect but, in the case of paracetamol, this did not attain statistical significance. Antipyrine clearance was lower among women who took the oral contraceptive pill than among those who did not, while paracetamol clearance was not significantly different. These findings may have implications for the use of drugs which are administered regularly in order to achieve steady-state plasma and tissue concentrations.     

Black tea and mammary gland carcinogenesis by 7,12- dimethylbenz[a]anthracene in rats fed control or high fat diets

Epidemiological studies suggest that tea may reduce cancer risk, and in laboratory rodents, chemopreventive effects of tea or purified extracts of tea have been demonstrated in lung, gastrointestinal tract and skin. There is some evidence of chemoprevention by tea in the mammary gland, but the data are not conclusive. In order to evaluate more fully the possible influence of black tea on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary gland tumors in the female S-D (Sprague-Dawley) rat, three large studies were performed: experiment 1, tumorigenesis in rats fed AIN-76A diet and given 25 mg/kg DMBA and 1.25 or 2.5% whole tea extract or water to drink; experiment 2, tumorigenesis in rats given 15 mg/kg DMBA and the same diet and fluids as in experiment 1; experiment 3, tumorigenesis in rats fed control or HF (high fat, corn oil) diet and given 15 mg/kg DMBA and 2% tea or water to drink. Tea was given throughout the experiment; DMBA was given by gastric gavage at 8 weeks of age. There was no consistent effect of tea on tumorigenesis in rats fed AIN-76A diet; there was, however, evidence in experiment 3 of a reduction of tumorigenesis by tea in rats fed the HF diet. In experiment 3, rats fed the HF diet and given water showed the expected increase in tumor burden (number and weight) compared with rats fed control diet. However, rats fed the HF diet and given 2% tea showed no increase in tumor burden; their tumor burden was significantly lower than in rats fed the HF diet and given water (P < 0.01) and was not different from rats fed control diet and given water or tea. In addition, in experiment 3, the number of malignant tumors per tumor- bearing rat was increased by the HF diet in water-drinking rats (P < 0.01) but not in tea-drinking rats. Therefore, it appears that tea partially blocked the promotion of DMBA-induced mammary tumorigenesis by the HF diet.      

Escherichia coli tetracycline efflux determinants in relation to tetracycline residues in chicken

ObjectiveTo screen for Escherichia coli (E. coli) resistant to tetracycline, followed by identification of tet efflux genes by polymerase chain reaction (PCR). In addition, detection of tetracycline residues in chicken livers and kidneys were conducted using high performance liquid chromatography-tandem quadrupole mass spectrometry (HPLC-MS-MS).MethodsStrains of E. coli were isolated from samples of chicken colon and screened for tetracycline resistance. Tetracycline genes conferring resistance (Tc^r) were detected by polymerase chain reaction (PCR). Most of the isolates were resistant to tetracycline (97.9%).ResultsPCR analysis indicated that Tc^r E. coli R-plasmids contained tet(A), tet(B) and a combination of both efflux genes. None of the isolates contained other efflux tet genes tet (C, D, E and Y). High performance liquid chromatography-tandem quadrupole mass spectrometry (HPLC-MS-MS), a sensitive technique, was used to detect residues of chlortetracycline (CTC), oxytetracycline (OTC), doxycycline (DC) in chicken livers and kidneys. The samples containing tetracycline residues were at 0.13-0.65 pg/μL levels.ConclusionsTetracycline and other antibiotics are commonly used in the poultry and meat production industry for prevention of microbial infections. Multiple antibiotic resistant bacteria in Oman have increased to alarming levels, threatening public health, domestic and may have adverse effect on environment.     

Informant ratings of cognitive decline of elderly people: relationship to longitudinal change on cognitive tests

Formal assessment of cognitive decline with cognitive tests can be difficult, requiring either two measurement points or a comparison of 'hold' with 'don't hold' tests. Informant-based assessment provides an alternative approach because informants can adopt a longitudinal perspective and directly rate cognitive change. A study was carried out to assess the validity of informant ratings collected by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A community sample of 500 subjects aged 74 or over underwent four cognitive tests on two occasions 3½ years apart. On the second occasion, informants filled out the IQCODE. Subjects rated as having moderate or severe decline were found to have greater change on the cognitive tests. These findings support the validity of informant ratings of cognitive decline.     

The effect of azathioprine (Imuran) on the kinetics of monocytes and macrophages during the normal steady state and an acute inflammatory reaction

The effect of azathioprine on the kinetics of peripheral blood monocytes and peritoneal macrophages was studied in normal mice and in mice in which an inflammatory reaction was provoked. Two dosage levels were used: a high dose of 200mg/kg which is the maximum tolerated daily dose in mice, and low dose of 3 mg/kg which is about equivalent to a nontoxic, immunosuppressive, anti-inflammatory dose in man. The number of peripheral blood monocytes decreases gradually during azathioprine treatment of normal mice, the extent and duration being dependent on the dose and duration of administered over a period of 9 days gives an almost complete reduction, and a low dose (3 mg/kg) given for the same period results in a reduction of about 50%. This effect seems to be reversible, because when treatment is stopped the number of monocytes starts to increase 24-48 hr later. The number of peritoneal macrophages is only affected when a high dose (200 mg/kg) is given over a long period; a low dose has virtually no effect. In mice in which an inflammatory reaction was prevoked in the peritoneal cavity, the normally occurring increase in the numbers of both peripheral blood monocytes and peritoneal macrophages was suppressed, the extent being dependent on the dose of azathioprine administered. Labeling studies with 3H-thymidine indicated that the reduction of peripheral blood monocytes and peritoneal macrophages in the inflammatory exudate is due to a diminished monocyte production.     

Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.     

Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial

BACKGROUND: To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial by an open-label follow-up study lasting 4 years. METHODS: The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double-blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open-label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5-25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up. RESULTS: Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P = 0.01) and 15% (P = 0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively. CONCLUSIONS: Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension.