Do nonsteroidal anti-inflammatory drugs interfere with blood pressure control in hypertensive patients?

Exacerbation of hypertension by nonsteroidal anti-inflammatory drugs in hypertensive patients remains controversial among physicians and investigators. Because of the many differences among studies of oral nonsteroidal anti-inflammatory drugs and blood pressure control in patients with hypertension, the authors critically evaluated the published clinical evidence on this subject using standardized methodologic criferia. A search of the literature from 1965 to 1986 identified 31 relevant studies, of which only eight were double-blind randomized controlled trials that provided the most clinically useful information. Of these eight best-designed studies, five of the six that studied indomethacin concluded that it may interfere with antihypertensive effectiveness in selected patients with treated, stable hypertension. The remaining double-blind randomized studies included comparisons of other nonsteroidal anti-inflammatory drugs. Their limited results suggest that sulindac is less likely than piroxicam, naproxen or indomethacin to cause an attenuation of antihypertensive therapy. More research on this subject is needed, with greater attention to methodologic details and identification of predisposing risk factors for impairment of blood pressure control by nonsteroidal anti-inflammatory drugs. Received from the Department of Internal Medicine, University of Cincinnati, Medical Center, and the Department of Pharmacy. University Hospital, Cincinnati, Ohio.     

Tibolone and its metabolites induce antimitogenesis in human coronary artery smooth muscle cells: role of estrogen, progesterone, and androgen receptors

Tibolone, a hormone replacement drug, protects postmenopausal women against osteoporosis and climacteric symptoms without inducing adverse effects on the endometrium and breast. Compared with other estrogens, little is known about the cardiovascular effects of tibolone. Because abnormal growth of smooth muscle cells (SMCs) is a prerequisite for coronary artery disease, here we investigated the effects of tibolone on SMC growth. We examined the effects of tibolone and its metabolites on human arterial SMC growth (DNA synthesis, cellular proliferation, cell migration, collagen synthesis) and MAPK expression. Fetal calf serum-induced SMC growth, phosphorylated MAPK expression, and platelet-derived growth factor-induced SMC-migration were concentration-dependently inhibited by tibolone and its endogenous estrogenic and progestogenic/androgenic metabolites in the following order of potency: Delta 4-tibolone>3 beta-OH-tibolone congruent with 3 alpha-OH-tibolone. The antimitogenic effects of tibolone were partially blocked by ER antagonist (ICI182780), progesterone receptor antagonist (RU486) but not by the androgen receptor antagonist (flutamide); moreover, RU486 was more potent than ICI182780. The antimitogenic effects of tibolone were completely blocked by RU486 plus ICI182780. In addition, the inhibitory effects of equimolar concentrations of the three tibolone metabolites summed up to the inhibitory effects of tibolone. In conclusion, tibolone inhibits SMC growth and MAPK phosphorylation via both its estrogenic and progestogenic metabolites, and these inhibitory effects involve both progesterone and ERs. Hence, tibolone may induce antivasoocclusive actions and protect women against coronary artery disease.     

Effect of ventilation by high-frequency oscillation on lung and chest wall mechanics in the dog

High-frequency oscillation (HFO) has been shown to be effective in maintaining gas exchange, but the effects of high-frequency, small-volume ventilation on the mechanical properties of the respiratory system are unknown. A volume displacement plethysmograph was used to study lung volumes and static pressure-volume (PV) curves during HFO in pentobarbital-anesthetized dogs. During long-term studies, adequate gas exchange was maintained with a stroke volume of 2.5 ml/kg and frequencies between 15 and 30 Hz. The effect of 5–7 hours of HFO on lung and chest wall mechanics was studied in 8 dogs. In another 8 dogs the relationship of volume history and respiratory muscle tone to occlusion airway pressure and lung volume during short-term HFO was investigated. With prolonged HFO, a small but significant decrease in total lung capacity occurred by 5 hours and the static respiratory system PV curve shifted slightly to the right. These changes were reversed by muscle paralysis and may be explained by a change in respiratory muscle tone. Static lung compliance and the hysteresis ratio (an index of tissue properties) remained unchanged. The relationship of occlusion airway pressure and lung volume during short-term HFO was dependent on the lung volume history and was influenced by respiratory muscle tone only at low airway pressures. These findings suggest that during prolonged HFO a small increase in chest wall stiffness may result. However, occlusion airway pressure and lung volume at the onset of HFO are mainly dependent on the volume history of the lung. Presented in part at the Fall Meeting of the American Physiological Society, Toronto, Canada, October 12–17, 1980     

A novel method for evaluating the antimicrobial activity of tuberculosis treatment regimens.

OBJECTIVE: To evaluate the clinical response to antituberculosis chemotherapy rapidly. METHOD: Sputum viable counts from a previously published clinical trial comparing a standard regimen and one containing isoniazid, rifampicin and ciprofloxacin were re-evaluated using an exponential decay model. The results were fitted to a one or two phase exponential decline. The decline in viable counts followed a curve described by a single-phase exponential decay model. From these data the time taken to reduce the viable count by 50% (vt50) was calculated to estimate the bactericidal effect of the regimens. RESULTS AND CONCLUSION: This method shows promise as a means for early identification of patients who are responding poorly as a result of resistance or poor immune response and for comparing anti-tuberculosis regimens in clinical trials. The failure to show a two-phase exponential decay curve suggested that either the sputum does not contain bacteria upon which only drugs with a sterilising activity act or that they are not present in sufficient numbers to have a significant impact on the total viable count. Further studies are required to understand the physiological state of organisms being sampled in sputum.     

Perceptions of Families of Individuals with Autism Spectrum Disorder during the COVID-19 Crisis

Caring for an individual with autism spectrum disorder (ASD) in ideal circumstances can be stressful, and the Coronavirus disease (COVID-19) pandemic created a high degree of disruption to life and stress to families living with an individual with ASD. We conducted an online survey of families in Michigan that revealed higher levels of stress in caregivers of younger individuals with ASD and those with greater severity of ASD symptoms. Stress around therapeutic service disruption, finances, and illness predominated and greater stress was reported for caregivers of individuals receiving greater intensity of services pre-COVID-19. Respondents voiced concerns about receiving respite care during COVID-19, and those expressing interest in respite also reported greater symptom severity in the person with ASD.

     

Treatment of haemorrhoids by rubber band ligation.

Outpatient treatment of haemorrhoids by elastic band ligation without anaesthetic was performed in 75 patients. Clinical review showed that 65 returned to work within 24 h of ligation, 8 in 48 h and 2 after 48 h. No patient required hospitalisation for either rectal bleeding or pain after ligation. In the first week after treatment 36 were completely symptom-free, 26 had minimal discomfort and 13 had moderate pain with a sense of imcomplete evacuation in the rectum, and some frequency of call to stool lasting up to 7 days in 1. Follow-up at 8-26 months (mean 10 months) showed that 59 were symptom free, only occasional rectal bleeding occurred in 7 and more frequent irregular bleeding in 2. Religation of residual haemorrhoids was performed in 7 and 2 and a haemorrhoidectomy. For the majority of patients hospitalisation and loss of work were avoided.