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Biomedical subjects

B F Johnson

Publications and source records attributed to B F Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1983

Multiclinic comparison of labetalol to metoprolol in treatment of mild to moderate systemic hypertension.

The antihypertensive effects of oral labetalol, a new alpha- and beta-adrenergic blocking agent, and metoprolol, a relatively beta1 selective adrenergic blocker, were evaluated in 91 patients with mild to moderate hypertension (standing diastolic blood pressure of 90 to 115 mm Hg) in a double-blind parallel group multicenter clinical trial. The effects of the two drugs on plasma lipids and lipoprotein fractions were also assessed. Following a four-week placebo phase, 44 patients were randomized to receive labetalol and 47 metoprolol. During a four-week titration phase, the labetalol dose was increased from 100 mg twice daily to a maximum of 600 mg twice daily to achieve a standing diastolic blood pressure of 90 mm Hg that was decreased by 10 mm Hg or more. Metoprolol was titrated from 50 mg to 200 mg twice daily. An eight-week maintenance period followed during which hydrochlorothiazide could be added. At the end of the maintenance phase, the doses of labetalol and metoprolol were tapered over a two to four day period after which patients received a placebo for one week. Blood pressure in the supine and standing position was measured at each visit. Labetalol and metoprolol both significantly (p less than 0.01) lowered the supine and standing blood pressure from baseline with no significant difference found between the two treatment groups. Both drugs lowered the heart rate; however, the rate-lowering effect was significantly greater with metoprolol (p less than 0.01). There were no significant effects of either drug on plasma lipids or lipoprotein fractions. Fatigue was the most frequently reported complaint with both drugs. Dizziness, dyspepsia, and nausea were more common with labetalol; bradycardia was more common with metoprolol. There was no blood pressure "overshoot" after withdrawing drug treatment; however, a heart rate "overshoot" was seen after metoprolol was tapered off and stopped. Labetalol is as safe and effective as metoprolol in the treatment of patients with mild to moderate hypertension.

Adult↗
PubMed1983

Multicenter clinical evaluation of long-term efficacy and safety of labetalol in treatment of hypertension.

The long-term efficacy and safety of labetalol, an antihypertensive agent with combined beta- and alpha-blocking activity, were evaluated alone (number = 193) and in combination with a diuretic (number = 144) in an open-label multicenter trial of 337 hypertensive patients aged 21 to 75 years, including initially 205 (61 percent) men and 219 (65 percent) Caucasians. There were 219 (65 percent) mild, 85 (25 percent) moderate, and 33 (10 percent) severe hypertensive patients. Labetalol (100 to 1,200 mg twice a day) alone or in combination with a diuretic reduced the mean standing blood pressure by 13/11 and 25/16 mm Hg to 135/88 and 130/91 mm Hg, respectively (p less than 0.01), and supine blood pressure by 6/7 and 18/13 mm Hg to 141/86 and 138/90 mm Hg (p less than 0.01), respectively. Blood pressure reductions observed at one month were maintained after one year; 206 (62 percent) patients had 10 mm Hg or greater reductions and 184 (56 percent) patients were maintained at diastolic blood pressures less than 90 mm Hg. Most frequently reported drug-related side effects included fatigue (14 percent), dizziness (12 percent), nausea (11 percent), nasal stuffiness (8 percent), headache (4 percent), and male sexual dysfunction (14 percent). Side effects were generally of mild to moderate intensity and often transient. In addition, in 27 (8 percent) patients reversible asymptomatic transaminase elevations to greater than twice normal developed at some time during the study. In 13 (4 percent) patients these alterations resolved during continued labetalol therapy, but in five (2 percent) patients these marked elevations led to discontinuation of the drug. A total of 32 (9.5 percent) patients were terminated prematurely due to side effects (most commonly genitourinary or gastrointestinal) possibly attributable to the drug. These findings indicate that labetalol with or without a diuretic is a potentially effective, safe, and relatively well-tolerated long-term antihypertensive therapy.

Adult↗
PubMed1983

A comparison of minoxidil and hydralazine in non-azotemic hypertensives.

In 36 patients with normal renal function receiving hydrochlorothiazide and propranolol, lying diastolic blood pressure remained above 95 mmHg. In a double-blind trial, Step 3 therapy with 5-40 mg/day of minoxidil reduced blood pressure somewhat more effectively than 25-200 mg/day of hydralazine. The percentage of patients with lying diastolic blood pressure below 90 mmHg was 69 versus 35% at four weeks, and 55 versus 40% at 28 weeks. Transient falls in blood pressure within 4 h of any dose were greater with hydralazine which usually needed to be given in divided daily doses. Minoxidil caused tachycardia, and more adverse effects. Minoxidil is more effective, produces more consistent blood pressure control throughout the day, and may often be administered once daily.

Adult↗
PubMed1982

Suppression of the lexC (ssbA) mutation of Escherichia coli by a mutant of bacteriophage P1.

A new mutant of bacteriophage P1 designated lxc that suppresses the phenotype of lexC and ssbA mutants of Escherichia coli was isolated and characterized. The properties of lexC mutants suppressed by the lxc mutation include temperature sensitive growth at 42 degrees C, sensitivity to ultraviolet light and alkylating agents, and a nonmutagenic response following exposure to ultraviolet irradiation. A bac mutant of bacteriophage P1 that suppresses the temperature sensitivity of dnaB mutants does not affect the phenotype of lexC or ssbA mutants. Neither the lxc or bac mutations affect the ultraviolet light sensitivity of strains with the mutations uvrA155, lexA102, or recA56.

Coliphages↗
PubMed1982

Sexual development in a homothallic fission yeast: synthesis of readiness proteins resolved by gel electrophoresis.

Sexual development of a homothallic strain of Schizosaccharomyces pombe was monitored by radiolabelling and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Of more than 60 bands detected by Coomassie brilliant blue and by autoradiography, about 30 bands synthesized during development were discrete enough for experimental analysis. About a dozen bands are preferentially vegetative, another dozen preferentially developmental. However, vegetative bands as a group are also synthesized during development. Their synthesis is relatively unaffected by low concentrations of cycloheximide or by chloramphenicol and is not temperature sensitive at 37 degrees C nor catabolite repressible. Only band 40 (ca. 40 000 daltons) seems to be exclusively vegetative. The synthesis of developmental bands 13, 18, 24, 30, and alpha, all of which first appear during late-log phase, is catabolite repressible. Developmental band 51 is also synthesized throughout the vegetative phase. The synthesis of bands 24, 30, 51, and alpha is temperature sensitive at 37 degrees C during the development, but that of band 18 is not. The synthesis of band 13 during development is not temperature sensitive, but its earlier synthesis during late-log phase is. The synthesis of all these six developmental bands is immediately inhibited by cycloheximide, but not by chloramphenicol. Their appearance as a group of radioactive bands is greatly diminished in cultures grown in cycloheximide, in chloramphenicol, or in ethidium bromide. Developmental bands 13, 18, 24, and 30 may be called readiness proteins. They first appear prior to the earliest morphological signs of sexual activity. Their developmental synthesis is inhibited by conditions that inhibit sexual development. Such inhibitory conditions include anaerobiosis, restrictive temperature, aging in stationary phase, the presence of inhibitors of cytoplasmic protein synthesis and of mitochondrial function, and catabolite repression. Readiness proteins may be regulating the switch from vegetative metabolism.

Ascomycota↗
PubMed1982

The emerging problem of plasma lipid changes during antihypertensive therapy.

After hypertension and smoking, abnormalities of plasma lipids are major coronary risk factors. Increases in low density lipoprotein (LDL) cholesterol, or decreases in high density lipoprotein (HLD) cholesterol or the ratio HDL/LDL are associated with increased risk. Whereas LDL delivers cholesterol to arterial wall cells. HDL aids clearance and/or inhibits uptake of LDL cholesterol. Some agents used to reduce risks of high blood pressure can also disturb lipoprotein levels and may increase associated coronary risk levels. Thiazides increase triglycerides (TG) and increase total cholesterol. However, the HDL/LDL ratio shows no important change in our recent studies.TG elevation may result from increased synthesis secondary to increased plasma levels of glucose and insulin. In several studies, propranolol also caused elevation of TG. This has been the most consistent finding in the few studies of other beta blockers, including metoprolol, atenolol, and pindolol. These studies have generally shown no change in total cholesterol, but some showed reduction in HDL cholesterol in patients on propranolol.

Adrenergic beta-Antagonists↗
PubMed1981

Theophylline serum protein binding in obstructive airways disease.

The percentage of theophylline bound to protein in sera obtained from patients with obstructive airways disease was determined by ultrafiltration. The bound theophylline fraction in 71 serum specimens collected from 51 patients was 60.7 +/- 10.0% (mean +/- SD) and from 30.8% to 83.2%. The correlation between unbound serum theophylline concentration and total concentration (range 0.8 to 90 mg/l) was linear (r = 0.97, p less than 0.001). Theophylline binding correlated poorly with serum albumin (r = 0.39) and total serum protein (r = 0.35), although the correlations were statistically significant (p less than 0.05), Theophylline binding in women did not differ from that in men. The extent of theophylline binding in younger patients was greater than in patients over 55 yr (64.3 +/- 8.5% and 57.0 +/- 10.4%, p less than 0.005). Variation in theophylline binding in 12 patients from whom two or more serum samples were collected was relatively small. Analysis of variance showed interpatient variation in theophylline binding (p less than 0.01) but not between sampling occasions in the same patient. The demonstrated variability in serum protein binding of theophylline should influence theophylline distribution and elimination kinetics and may be another determinant of clinical response. Patients with lower binding levels should have higher plasma levels of unbound drug after a loading dose and will need more frequent dosing.

Adult↗
PubMed1981

Systolic time intervals in measurement of inotropic response to drugs.

During periods of tachycardia induced by atrial pacing in eight patients, moderate increments in dP/dt(max) and (dP/dt)/CPIP (common produced intraventricular pressure) and moderate reductions in left ventricular ejection time (LVET) and Q-S2 were demonstrated. These changes varied between individuals, but reduction in systolic intervals was consistently less than that reported from populations showing a range of resting heart rates. Individual regression formulae relating each variable to paced heart rate were used to calculate rate-dependent and rate-independent changes induced by isoprenaline and ouabain. Despite technical difficulty in precise measurement of systolic intervals, there was an excellent inverse correlation between rate-independent changes in Q-S2 and in both dP/dt(mac) and (dP/dt)/CPIP. Rate-independent change in Q-S2 appears to be a practical, moderately sensitive, and reasonably precise measure of the inotropic effect of a drug which does not radically alter left ventricular end-diastolic pressure or blood pressure. Day-to-day variation in systolic intervals may limit the use of the technique to studies of short duration.

Adult↗
PubMed1980

Long-term antihypertensive drug treatment and blood pressure control in three hospital hypertension clinics.

Prescribing patterns and blood pressure control have been studied in 1101 patients treated at three specialist hypertension clinics in Britain. Seventy-four per cent of the patients were already receiving treatment at the time they were referred by their general practitioners. Though the initial improvement in blood pressure control was satisfactory, there was often some deterioration of control over the long term. The pressure exceeded 140/90 mmHg in the majority of patients followed for a year or more. During 1971-5 diuretics remained first preference, with increasing use of beta-blockers and a distinct decline in the use of sympathetic neurone blockers both by hospital staff and referring practitioners. Multiple drug treatment was common, nearly half the patients requiring more than one antihypertensive drug. In newly treated patients the frequency of cessation of a particular class of drug because of side effects or lack of efficacy ranged from 6 per cent with diuretics to 57 per cent with adrenergic neurone blocking drugs. Long-term blood pressure control still presents many problems, and the results contrast with the more optimistic interpretations sometimes placed on short-term clinical trials of antihypertensive effect.

Antihypertensive Agents↗
PubMed1979

Risk factors for death in treated hypertensive patients. Report from the D.H.S.S. Hypertension Care Computing Project.

A prospective study was performed to determine factors at presentation influencing survival in 2587 treated hypertensive patients who were followed for an average of 4 years. 86% had been referred to hospital clinics with hypertension and 14% were seen solely by their general practitioners. Of the 156 deaths, 81% were from cardiovascular causes. Independent risk factors for cardiovascular death were age, impairment of renal function, smoking habits, and systolic blood-pressure before treatment. Other independent factors of importance were proteinuria, history of myocardial infarction, and retinal changes of accelerated hypertension. Increased weight, serum cholesterol, and serum uric acid were not independent risk factors. Although these results agree substantially with data for normal populations, notable exceptions were impairment of renal function, which was very important in hypertensives, and raised serum cholesterol, which was not an independent risk factor in this hypertensive population.

Age Factors↗
PubMed1979

Comparison of black and white patients attending hypertension clinics in England.

Reports suggest that hypertension and death due to hypertensive disease are commoner among black than among white people. One hundred and thirty-five black patients attending hypertension clinics at three English hospitals were compared with age-, sex-, and clinicmatched white patients. The black women had higher blood pressures and weighed more than the white women, but there were no differences between the men. The black patients had not increased risk from family, obstetric, or smoking history. Proteinuria and nocturia were more common in black patients while urinary infections were less common. Heart size and left ventricular voltage were greater in black patients. Haemoglobin and plasma cholesterol and triglyceride concentrations were smaller and serum globulin concentration greater in black patients. No difference in response to treatment, attributable to race, was observed during the period of clinic attendance, which averaged 1.7 years. There was a slightly greater rate of default among black men during the first year of attendance.

Adult↗
PubMed1979

Temperature sensitivity of flocculation induction, conjugation and sporulation in fission yeast.

Homothallic cultures of Schizosaccharomyces pombe, anaerobically grown to stationary phase in broth at 32 degrees C, were induced by aeration to flocculate. Flocculation was followed by copulation, conjugation, zygote formation, meiosis and sporulation. Cultures grown to stationary phase at 32 degrees C and then aerated at 37 degrees C did not sporulate. Grown to stationary phase at 37 degrees C, cultures were not immediately inducible when aerated at 32 degrees C. To identify which events in the developmental sequence were thermosensitive, we grew and induced cultures at 32 degrees C and then shifted them at various times to 37 degrees C. We observed the following events to be thermosensitive: development of respiratory sufficiency, readiness (inducibility of a culture within 1 h), flocculation induction, copulation, conjugation and early sporulation (including meiosis). Respiration, flocculation and spore maturation were thermoresistant. Conjugation-induced lysis and postdevelopmental deflocculation were enhanced at 37 degrees C.

Ascomycota↗