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Biomedical subjects

B F Johnson

Publications and source records attributed to B F Johnson.

At least 55 records · Page 3Linked to original sources

Effects of lovastatin in diabetic patients treated with chlorpropamide.

Patients with non-insulin dependent diabetes mellitus (NIDDM) have a higher risk of atherosclerotic cardiovascular disease than nondiabetic subjects. In seven patients with both hypercholesterolemia and NIDDM controlled by chlorpropamide, lovastatin (20 mg b.i.d. for 6 weeks) lowered low-density lipoprotein cholesterol by 28%, total cholesterol by 24%, and apolipoprotein B by 24%. Lovastatin levels for a 4-hour period (measured as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitory activity) were similar to those measured previously in nondiabetic patients. Lovastatin did not alter chlorpropamide kinetics or glycemic profiles. No patient had an elevation in serum transaminases or creatinine phosphokinase, and no patient had any other laboratory or clinical drug-related adverse experience during the study. Lovastatin was as effective in reducing low-density lipoprotein cholesterol in patients with NIDDM as in nondiabetic subjects. Diabetic control was unaltered, and no evidence of alteration in lovastatin or chlorpropamide blood levels was noted.

Acyl Coenzyme A↗

Pattern of end growth of the fission yeast Schizosaccharomyces pombe.

The patterns of end growth of individual cells of Schizosaccharomyces pombe, wild-type cells (strain 972 h-), cells exposed to 8 mM hydroxyurea, and cdc mutants (cdc11-123 and cdc2-33), were investigated by time-lapse photomicrography. It was reconfirmed that there are three patterns of end growth: cells growing at the old end, at the new end, and at both ends from the beginning of the cell cycle. Cells that initiated growth at the old (new) end increased their growth rate at the new (old) end and became constant in their growth rate at the old (new) end when cells had their growth rate higher than a critical value: 0.08, 0.09, 0.08, and 0.11 microns/min in wild-type cells, cells exposed to hydroxyurea, cdc11-123 cells, and cdc2-33 cells, respectively. The critical value is proportional to the doubling time in length.

Cell Division↗

The relevance of plasma lipid changes with cardiovascular drug therapy.

Evidence is reviewed that thiazide diuretics increase plasma levels of triglycerides and LDL-cholesterol, and that most beta-blockers increase triglycerides and depress HDL-cholesterol. By contrast, indapamide, pindolol, and calcium channel blockers have little effect, and alpha 1-blockers and alpha 2-stimulants may improve the HDL- to LDL-cholesterol ratio.

Cardiovascular Agents↗

Basosquamous carcinoma, a wolf in sheep's clothing? Report of 3 cases.

Basosquamous carcinoma of the skin is a lesion with specific histological features and recognized metastatic potential. Three cases of metastatic basosquamous carcinoma are reported, two of which were rapidly fatal. They illustrate that diagnostic features may be absent in a small biopsy and that metastasis is usually associated with a poor prognosis.

Aged↗

Use of electron microscopy to characterize the surfaces of flocculent and nonflocculent yeast cells.

The surfaces of flocculent and nonflocculent yeast cells have been examined by electron microscopy. Nonextractive preparative procedures for scanning electron microscopy allow comparison in which sharp or softened images of surface details (scars, etc.) are the criteria for relative abundance of flocculum material. Asexually flocculent budding-yeast cells cannot be distinguished from nonflocculent budding-yeast cells in scanning electron micrographs because the scar details of both are well resolved, being hard and sharp. On the other hand, flocculent fission-yeast cells are readily distinguished from nonflocculent cells because fission scars are mostly soft or obscured on flocculent cells, but sharp on nonflocculent cells. Sexually and asexually flocculent fission-yeast cells cannot be distinguished from one another as both are heavily clad in "mucilaginous" or "hairy" coverings. Examination of lightly extracted and heavily extracted flocculent fission-yeast cells by transmission electron microscopy provides micrographs consistent with the scanning electron micrographs.

Flocculation↗

Acetate assimilation by the fission yeast, Schizosaccharomyces pombe.

The fission yeast Schizosaccharomyces pombe utilizes acetate at subinhibitory concentrations in the presence of D-glucose. The nonionized form of acetate is preferentially utilized, oxidized to 14CO2, and assimilated into lipids and proteins. Acetyl CoA synthetase activity greatly increases in the yeast cells grown in media containing acetate. However, glyoxylate cycle enzymes are not detectable in Schizosaccharomyces pombe. [1-14C]Acetate is incorporated into stereols, sterol esters, neutral lipids, and phospholipids. Assimilation of [1-14C]acetate into the peptide structure of proteins was confirmed by a proteolytic digestion experiment.

Acetates↗

Tenckhoff catheter replacement or intraperitoneal urokinase: a randomised trial in the management of recurrent continuous ambulatory peritoneal dialysis (CAPD) peritonitis.

A randomised trial, comparing Tenckhoff catheter replacement as a one-stage procedure and i.p. urokinase, was undertaken in the management of recurrent continuous ambulatory peritoneal dialysis (CAPD) peritonitis. In addition to appropriate i.p. antibiotic treatment, 17 patients received i.p. urokinase (5000 i.u.) on the second and fourth days of antibiotic treatment, and 14 patients underwent CAPD catheter replacement. An additional six patients also underwent catheter replacement following the recurrence of peritonitis after urokinase treatment. The subsequent recurrence rate of peritonitis following CAPD catheter replacement (5%) was significantly less than after urokinase (41%) (p less than 0.001). Fourteen patients remained free of peritonitis for at least three months after catheter replacement, and five patients were peritonitis-free following urokinase for this period.

Catheters, Indwelling↗

Dietary supplementation with omega-3 fatty acids prolongs platelet survival in hyperlipidemic patients with atherosclerosis.

Enhanced dietary omega-3 fatty acid consumption is thought to be associated with a reduced incidence of atherothrombotic disorders. This effect may be mediated in part through suppression of in vivo platelet activity by omega-3 fatty acids. We observed that platelet survival, a sensitive indicator of in vivo platelet activity was prolonged from 6.4 +/- 1.5 days to 7.7 +/- 1.4 days by moderate amounts of dietary omega-3 fatty acid supplementation for 6 weeks in a group of hyperlipidemic patients with preexisting, established atherothrombotic disorders. This effect on platelet survival was associated with a decrease in platelet arachidonic acid levels from 26.7 +/- 3.5% to 20.9% +/- 2.5% and a rise in platelet eicosapentaenoic and docosahexaenoic acid measurements from essentially undetectable to 2.8% +/- 1.6% and 1.9% +/- 1.0%. Plasma total cholesterol, low-density lipoprotein cholesterol, and serum apolipoprotein B levels rose significantly during the omega-3 fatty acid supplementation period. Platelet aggregation did not change. This study demonstrates that a modest amount of dietary omega-3 fatty acid supplementation can significantly effect in vivo platelet activity in a population at high risk for recurrent atherothrombotic disorders.

Adult↗

Dilevalol in severe hypertension. A multicenter trial of bolus intravenous dosing.

Dilevalol, the R-R optical isomer of labetalol, a nonselective beta-antagonist with vasodilation from selective beta 2 agonism, was administered in sequential multiple bolus intravenous injections of 10 to 100 mg in total doses ranging from 35 to 585 mg (mean dose, 414 mg) to 101 patients with supine diastolic blood pressures above 120 mm Hg. Mean blood pressure was reduced from 200 (+/- 3)/129 (+/- 1) mm Hg to 149 (+/- 2)/101 (+/- 1) mm Hg, a mean reduction of 51/28 mm Hg. The therapeutic goal was established as a reduction in supine diastolic blood pressure to less than 100 mm Hg or a reduction of at least 30 mm Hg. This was achieved in 62 (61%) of 101 patients, with an additional 7 patients having a final supine diastolic blood pressure of 100 mm Hg. Treatment with dilevalol was less successful in black male patients than in the group at large. There was a tendency for older patients to respond better than younger patients. Prior recent treatment of patients with beta-adrenergic antagonists decreased the effectiveness of the drug. Significant orthostatic hypotension was not noted. Sixty-four patients were transferred to oral dilevalol treatment in combination with a diuretic, and blood pressure in this group averaged 160/100 mm Hg after 1 month of therapy. Dilevalol appears to be a safe and effective drug that can be used intravenously successfully in the majority of patients with severe hypertension and provides an alternative to therapy with other agents. It also is a useful agent for oral treatment of these patients after successful intravenous therapy.

Administration, Oral↗

Separation of proteins by reversed-phase high-performance liquid chromatography. II. Optimizing sample pretreatment and mobile phase conditions.

The effects of separation variables such as temperature, pH and composition of the mobile phase (including additives such as chaotropes, ion-pairing agents and surfactants), sample size and sample pretreatment for reversed-phase high-performance liquid chromatography (RP-HPLC) of proteins is examined. Experimental optimization of these parameters using the preferred instrumental and column conditions described previously lead to well behaved chromatographic performance for most proteins. This allowed us to achieve the required level of performance for the first dimension (RP-HPLC) separation of most protein samples by the chromatophoresis process.

Bacterial Proteins↗

The relation of the kinetics of pirmenol to its antiarrhythmic efficacy.

In a single-blind study the multiple oral dose kinetics of pirmenol were related to its efficacy in eight patients with frequent (mean, 631; range, 167-1374 beats/hour) premature ventricular contractions (PVC). Oral pirmenol was started at 100 mg bid for 48 hours and increased to 150 mg bid in six patients to obtain more than 70% suppression of PVC counts. Efficacy was achieved without side effects. Pirmenol decreased heart rate but not PR interval, QRS duration, or QTc interval. Peak plasma levels after the first 100-mg dose occurred at 1 to 3 hours and ranged from 0.6 to 1.9 micrograms/mL. Plasma elimination half-life ranged from 9.7 to 31 hours (mean, 18.3). From 67.4 to 171.3 mg pirmenol (mean, 102.3 mg) were recovered in the urine in 48 hours after the last dose. Cumulative excretion in divided urine collections was consistent with a mean elimination half-life of 15 to 20 hours. The pharmacokinetics of pirmenol support oral twice-daily administration. The minimum PVC suppressing plasma level is between 0.5 and 1.5 micrograms/mL.

Aged↗

Comparative effects of verapamil and isradipine on steady-state digoxin kinetics.

The effects on the steady-state digoxin pharmacokinetics of verapamil (240 mg/day) and a new dihydropyridine calcium channel blocker, isradipine (15 mg/day), were compared. Nineteen healthy white men, aged 23 to 40 years, ingested 0.25 mg digoxin tablets every 12 hours for two consecutive periods of 2 weeks. Each subject also received one of the calcium channel blockers during one of these periods, with agent and sequence randomized. Analyst-blind RIA serum digoxin determinations demonstrated that the nine subjects who received isradipine, 5 mg t.i.d., had a small increment in peak digoxin level from 2.3 +/- 0.6 to 2.9 +/- 0.7 ng/ml (p less than 0.05) but no significant change in steady-state level or AUC over 12 hours. By contrast, the 10 subjects who received verapamil, 80 mg t.i.d., showed significant increases in steady-state (0.9 +/- 0.1 to 1.3 +/- 0.2 ng/ml; p less than 0.001) and peak serum digoxin concentrations (2.5 +/- 0.7 to 3.6 +/- 0.8 ng/ml; p less than 0.001) and in AUC (15.7 +/- 1.7 to 23.6 +/- 2.9 ng . hr/ml; p less than 0.001). Neither calcium channel blocker reduced renal digoxin clearance. Verapamil increases digoxin levels without affecting renal clearance. Isradipine has no clinically important interaction with digoxin.

Adult↗

A randomized placebo-controlled comparison of amlodipine and atenolol in mild to moderate systemic hypertension.

Amlodipine, a new long-acting dihydropyridine calcium antagonist, was compared with placebo and atenolol in 125 patients with mild to moderate systemic hypertension [supine diastolic blood pressure (DBP) 90-114 mm Hg]. Patients received placebo for 4 weeks, followed by a random allocation to an 8-week double-blind, once-daily treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The changes in 24-h post-dose blood pressure (BP) from baseline to final visit for amlodipine (mean daily dose 8.8 mg, range 5-10 mg) were -12.8 +/- 2.0/ -10.1 +/- 1.2 mm Hg in supine BP and -11.5 +/- 2.3/-9.8 +/- 1.1 mm Hg in standing BP (p less than 0.001); for atenolol (mean daily dose 83.7 mg, range 50-100 mg), the changes from baseline were -11.3 +/- 2.3/-11.7 +/- 1.3 mm Hg in supine BP and -13.3 +/- 3.1/-12.3 +/- 1.5 mm Hg in standing BP (p less than 0.001); for placebo, the changes from baseline were -0.9 +/- 2.8/-3.5 +/- 0.9 mm Hg in supine BP and -1.6 +/- -2.6/-4.0 +/- 1.0 mm Hg in standing BP. In the study, goal response was defined as a supine DBP of less than 90 mm Hg or its decrease by greater than or equal to 10 mm Hg. The response rates were similar for atenolol (65%) and amlodipine (61%). Both active therapies were significantly more effective than placebo. Heart rate was significantly lowered by atenolol only.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pseudo-exponential growth in length of the fission yeast, Schizosaccharomyces pombe.

The growth patterns of individual cells of the fission yeast (Schizosaccharomyces pombe wild-type cells, strain 972 h-; cells exposed to hydroxyurea; and cdc mutants, 11-123, 2-33) were investigated by time-lapse photomicrography. Wild-type cells showed one, two, or three linear-growth segments followed by a constant-length stage. Cells with two segments were most frequent. Hydroxyurea cells that divided as oversized cells (about three times the birth length) had three linear-growth segments in a cycle. Mutant cdc11-123 cells did not divide but had a constant-length stage separating the cycles; both the first and second cycles consisted of two linear-growth segments, and cells were oversized at the second constant-length stage (about 3.5 times the birth length). Elongating cdc2-33 cells that did not divide and were oversized (about five times the birth length) while under observation, showed four linear-growth segments. Cells of all strains showed 30 to 40% increase in growth rate at the rate-change point and maintained approximate exponential (pseudo-exponential) growth. We conclude that the normal growth pattern of individual fission-yeast cells is the pseudo-exponential pattern.

Hydroxyurea↗