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Biomedical subjects

H W Schnaper

Publications and source records attributed to H W Schnaper.

At least 73 records · Page 4Linked to original sources
PubMed1990

Use of quinapril in the elderly patient.

Quinapril hydrochloride is a nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor that has been extensively tested and found effective when administered once-a-day to hypertensive patients of both sexes and all degrees of hypertension and cardiac compromise, including those with left ventricular hypertrophy, with and without congestive heart failure. Observations with earlier ACE inhibitors led to reports that this class of drugs was relatively ineffective in older hypertensive patients. To ascertain the role of quinapril (greater than or equal to 10 mg/day) in older patients, its blood pressure-lowering effects in 1,175 hypertensive patients less than or equal to 65 years of age were compared with those in 304 patients greater than 65 years of age. An excellent response was observed in patients greater than 65 years of age with mild to moderate hypertension (diastolic BP, 95 to 105 mm Hg) and moderate to severe hypertension (diastolic BP, 106 to 115 mm Hg). The reductions in blood pressure achieved with quinapril were at least comparable to those obtained in the younger hypertensives, and were numerically (but not statistically) greater in the mild to moderate group (-14 mm Hg v-12 mm Hg). In addition, the percentage of patients who experienced adverse experiences was lower in the greater than 65 group than in the less than or equal to 65 group (15% v 19%). The main adverse experiences reported included dizziness, headache, cough, fatigue, and hypotension. These findings indicate that quinapril is at least as safe and effective in older hypertensives as in younger patients.

Aged↗
PubMed1990

Putative N-terminal sequence of murine soluble immune response suppressor (SIRS): significant homology with short neurotoxin 1.

Soluble immune response suppressor (SIRS) is a low-molecular-weight protein (approximately 10,000 daltons) produced by mitogen- or interferon-activated T lymphocytes that can block development of humoral or cell-mediated immune responses in vivo or in vitro. As previously reported, murine SIRS is heterogeneous, eluting in two broad peaks on high performance reverse phase chromatography as well as displaying several broad isoelectric point forms. A putative N-terminal 21 amino acid sequence has been obtained for one of the less hydrophobic isoforms, SIRS-alpha 7. The sequence of SIRS-alpha 7 is unique in mammals but shows a remarkable homology to the family of short neurotoxins (short neurotoxin 1) found in sea snake, adder, and cobra species. A degenerate oligonucleotide probe based on the protein sequence was synthesized and was shown to hybridize to SIRS messenger RNA as measured by SIRS synthesis in a rabbit reticulocyte lysate system. A synthetic polypeptide based on the 21-residue sequence was also prepared and coupled to thyroglobulin or keyhole limpet hemocyanin. These were used to prepare rabbit antisera that neutralize SIRS bioactivity and precipitate authentic SIRS.

Amino Acid Sequence↗
PubMed1990

The management of hypertension in older patients.

Hypertension need not be a natural consequence of aging; nevertheless, as many as 70% of individuals aged 70 years or more have diastolic blood pressures greater than or equal to 90 mm Hg and/or systolic blood pressures greater than 160 mm Hg. Well-controlled trials have documented significant reductions in cardiovascular mortality with treatment of diastolic elevation. Double-blind, long-term, open-label studies have been conducted of quinapril, a new angiotensin-converting enzyme (ACE) inhibitor, in 451 older patients compared with 1,887 younger patients. Results of these studies showed that quinapril is equally effective in older and younger patients. The studies also demonstrated that the safety of quinapril in the treatment of older patients is comparable with that in younger patients, in terms of both the incidence of adverse events and the types of adverse events reported. However, because many older patients have impaired renal function, which can prolong the half-life of renally excreted ACE inhibitors such as quinaprilat (the active metabolite of quinapril), they should be started on lower doses of quinapril (5 mg) than are used in younger patients. The shorter half-life and duration of action of quinaprilat compared with other once-daily ACE inhibitors may make quinapril better suited than these other agents for use in older patients.

Aged↗
PubMed1989

Effectiveness of doxazosin in systemic hypertension.

Most alpha-receptor blocking drugs require divided daily administration because of a short plasma half-life. This multicenter study examined the effectiveness and safety of once-daily administration with doxazosin, a quinazoline analog alpha 1-receptor blocking drug with a plasma half-life of 19 hours. Patients with diastolic blood pressure (BP) of 90 to 115 mm Hg entered 4 weeks of single-blind placebo therapy and then were randomized to double-blind treatment with doxazosin (63 patients) or placebo (67 patients). After 10 weeks of titration, standing arterial BP was lowered by 14/11 mm Hg with doxazosin and by 0.5/0.9 mm Hg with placebo (p less than 0.001). Measured hourly for 12 hours after the dose, all standing and supine arterial BP values were significantly lower in the doxazosin group at each hour. Pulse rate increased slightly in both groups int he double-blind phase, but the increase with doxazosin never significantly exceeded that of placebo. Dizziness was the most common complaint with doxazosin, but syncope did not occur. Side effects were mild and transient and did not necessitate withdrawing any participants from the study. Body weight increased by 1.5 kg in the doxazosin group and decreased by 0.2 kg in the placebo group (p less than 0.01). Safe and effective in once-daily administration, doxazosin is suitable for initial therapy in mild and moderate hypertension.

Adult↗
PubMed1989

Influence of beta 2 agonism and beta 1 and beta 2 antagonism on adverse effects and plasma lipoproteins: results of a multicenter comparison of dilevalol and metoprolol.

Dilevalol combines vasodilation due to selective beta 2 agonism and nonselective beta antagonism. We studied 311 patients randomized to dilevalol and 138 to metoprolol in a multicenter trial. After a 4-week placebo washout, dilevalol was titrated from 200 to 1,600 mg once daily and metoprolol from 100 to 400 mg to a goal supine diastolic blood pressure less than 90 and greater than or equal to 10 mm Hg decrease from baseline. Responders were followed for 1 year. The average age of patients was 51 years; 72% were men and 54% were white. Both drugs reduced blood pressure effectively to a similar level. Fewer patients discontinued dilevalol than did those taking metoprolol (9 vs 16%; p less than 0.03). More metoprolol-treated patients withdrew because of depression (6 vs less than 1%; p = 0.03) and impotence (5 vs less than 1%; p = 0.03). Lipoprotein levels before and after treatment were measured in 99 patients treated for 53.5 weeks with dilevalol (mean dose 438 mg). Dilevalol increased high-density lipoprotein (HDL) cholesterol by 2.5 mg/dl to 47.2 (p = 0.05), reduced low-density lipoprotein (LDL) cholesterol by 2.5 mg/dl, increased HDL/LDL by 0.03, and decreased total cholesterol/HDL cholesterol by 0.18. Triglycerides increased by 21 mg/dl (p = 0.06). In patients with an initial HDL cholesterol less than 35 mg/dl, dilevalol increased it by 9 mg/dl. In patients treated with metoprolol, the only significant change (p = 0.02) was a 41.9-mg/dl increase in triglyceride levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1989

Practical issues in drug selection and dosing.

Current guidelines recommend initiating antihypertensive therapy at a diastolic blood pressure greater than 90 mm Hg when nonpharmacologic measures have been unsuccessful. The risk of heart attack and stroke is increased regardless of whether the elevation of blood pressure is primarily systolic alone, diastolic alone, or both. In treating mild to moderate hypertension and in prevention and wellness programs in normotensive persons with a family history of the disease, the initial approach should be nonpharmacologic. Patients who remain hypertensive should proceed to drug therapy. Low-dose thiazide diuretics remain the preferred first step in elderly patients. In patients younger than age 40 years, especially those with tachycardia, a beta blocker may be used as the first step. Treatment should be initiated with less than a full dose, only proceeding to a full dose if necessary. If there is any appearance of extrasystoles, or a decrease in potassium levels to below 3.5 mEq/liter in the elderly, a potassium-sparing diuretic combination should be used. Although there is growing evidence that the effects of diuretic drugs on potassium may contribute to arrhythmias and sudden death, there is also increasing data suggesting that conserving electrolytes during diuretic therapy may obviate these ill effects.

Adrenergic beta-Antagonists↗
PubMed1989

Efficacy and safety of triamterene/hydrochlorothiazide combinations in mild systemic hypertension.

After a 3-week placebo lead-in (Period 1), 78 patients with sitting diastolic blood pressures (BPs) of greater than or equal to 90 and less than or equal to 105 mm Hg entered a 4-week period (Period 2) during which they received triamterene (TMT) 37.5 mg/hydrochlorothiazide (HCTZ) 25 mg/day. Four weeks of therapy with TMT 37.5 mg/HCTZ 25 mg resulted in a statistically significant decrease in mean BP of -15.0/-9.6 mm Hg. Mean BP changed from 145/95 to 130/85 mm Hg. Fifty-nine percent of patients were classified as responders as defined by study criteria. An additional 4 weeks of therapy (Period 3) for responders produced no further change in BP. Nonresponders as a group continued to have a further decrease in BP in Period 3. However, only patients in whom therapy was transferred to TMT 75 mg/HCTZ 50 mg had a statistically significant decrease. All patients who changed to the higher dose combination achieved goal BP by the end of the study. Of the nonresponders who continued to take TMT 37.5 mg/HCTZ 25 mg, 69% achieved goal diastolic BP by the end of Period 3. Three patients were withdrawn because of adverse experiences, 1 of which was considered treatment related. Of 58 reports of adverse experiences, 8 were considered possibly related and 2 probably related to therapy. There was a total of 8 clinically significant abnormal laboratory values, 1 of which was considered to have a possible relation to therapy.

Antihypertensive Agents↗
PubMed1989

The immune system in minimal change nephrotic syndrome.

Numerous examples of abnormal immune responsiveness have been described in minimal change nephrotic syndrome (MCNS). The of MCNS with allergy and with certain genetic markers of immune responsiveness, as well as the excellent response of proteinuria to immunomodulatory agents, has suggested a causal relationship between the immunological and renal abnormalities. However, the nature of this relationship is uncertain. Before it can be clarified, the basic mechanism(s) involved in disturbed immunity in patients with MCNS must be better characterized. Studies of humoral and cellular immune function support the hypothesis that immune regulation is abnormal. However, conclusive evidence of participation by a defined immunoregulatory system in the events leading to immune dysfunction has not been obtained. Thus, considerable work remains to be done in determining the nature and cause of abnormal immunity in MCNS prior to investigating its potential role in the pathogenesis of proteinuria.

Antibody Formation↗
PubMed1989

Divalent metal requirement for soluble immune response suppressor (SIRS) activity.

Soluble immune response suppressor (SIRS) is an immunosuppressive protein which requires activation to SIRSox by peroxide. This observation suggested that SIRS could be a metalloprotein. To investigate this possibility, purified hybridoma-derived SIRS was treated with chelating agents and dialyzed prior to activation with H2O2. EDTA, EGTA, or desferrioxamine prevented suppression of murine plaque-forming cell responses by SIRSox, whereas sodium citrate and penicillamine did not inhibit suppression. Suppressive activity was reconstituted by subsequent treatment of SIRS with FeSO4 (0.5 microM), NiSO4 (500 microM), or MgSO4 (500 microM), but not by FeCl3, MnSO4, CuSO4, ZnSO4, CaCl2, or CrCl3. Reconstitution of activity occurred only if FeSO4 was added at least 3 hr prior to treatment with H2O2. These data indicate that SIRS requires a divalent metal ion, probably ferrous iron, for activity, and suggest that SIRS is a metalloprotein.

Animals↗
PubMed1989

Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) pilot study.

The pilot study of the Systolic Hypertension in the Elderly Program was a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension. It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months. Mean age of the participants was 72 years; 63% were women, and 82% were white. Pretreatment blood pressures averaged 172/75 mm Hg. Participants were randomly assigned to treatment with chlorthalidone or placebo as Step I medication. Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups, respectively, with 60% and 33% of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit. All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk, and rates for definite "first stroke" were 8.3 and 12.8 per 1,000 years of risk. Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates. A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates.

Antihypertensive Agents↗
PubMed1989

Comparison of the efficacy and safety of quinapril vs. captopril in treatment of moderate to severe hypertension.

The results of this multicenter double-blind comparative study in 172 patients with moderate to severe hypertension indicate that twice daily quinapril (20-80 mg/day) is significantly more effective than captopril (50-200 mg/day) at reducing blood pressure. Following a minimum of four weeks of treatment, the results in evaluable patients showed a significantly greater reduction of diastolic blood pressure (DBP) in the quinapril group than in the captopril group (18.6 vs 15.3 mm Hg, respectively, p less than 0.05). An intent-to-treat analysis using blood pressure data from all patients having values within an eight-to-sixteen-hour postdose treatment window showed quinapril to produce a significantly greater reduction in DBP than captopril (18.2 vs 14.8 mm Hg, respectively, p = less than 0.05). Throughout the course of the six-week study, quinapril consistently showed efficacy superior to captopril despite a faster captopril dose titration.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Pharmacologic treatment of the elderly hypertensive: comparative efficacy and side effects.

Because of the physiologic changes associated with aging, a nonpharmacologic approach is recommended as initial therapy for the elderly hypertensive. Approximately 80% of this patient population, however, requires pharmacologic therapy, as well. When initiating drug treatment, the physician should remember several guidelines and have some understanding of the mechanisms of action of the available agents. The four drug classes recommended by JNC IV for the treatment of high blood pressure are quite similar in effectiveness. Low-dose diuretics, however, particularly when combined with a potassium-sparing agent, produce significantly fewer adverse reactions than seen with the other classes of drugs. This advantage, coupled with their low cost, makes diuretics the reasonable first choice for the treatment of older hypertensives.

Adrenergic beta-Antagonists↗
PubMed1989

Potassium restoration in hypertensive patients made hypokalemic by hydrochlorothiazide.

Among 447 hypertensive patients, most with a history of diuretic-induced hypokalemia, 252 developed diuretic-induced hypokalemia while receiving hydrochlorothiazide, 50 mg/d. In a randomized study we evaluated the efficacy of three drug regimens in restoring potassium levels while maintaining blood pressure control: hydrochlorothiazide (50 mg/d) plus potassium supplement (20 mmol/d); hydrochlorothiazide (50 mg/d) plus potassium supplement (40 mmol/d); or hydrochlorothiazide (50 mg/d) with triamterene (75 mg/d) in one combination tablet. In all groups, mean serum levels of potassium rose within 1 week and showed no further change thereafter. However, the hydrochlorothiazide/triamterene and hydrochlorothiazide plus 40 mmol of potassium regimens were significantly more effective in restoring serum potassium levels than was the hydrochlorothiazide plus 20 mmol of potassium regimen. A significant increase in magnesium levels was observed only in the group treated with the hydrochlorothiazide/triamterene combination. Each regimen provided continued control of mild to moderate hypertension.

Adult↗
PubMed1988

Immunology.

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Autoimmunity↗
PubMed1988

Immunology.

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Child↗
PubMed1987

A role for histamine type II (H-2) receptor binding in production of the lymphokine, soluble immune response suppressor (SIRS).

Soluble immune response suppressor (SIRS) is an immunosuppressive protein produced by human and murine suppressor cells activated by a variety of agents. Because histamine has been reported to activate suppressor cells, the possibility that it also induced SIRS production was investigated. Human lymphocytes treated with 10(-4) M histamine for less than 1 hr released a suppressive substance into culture supernatants that was physically, functionally and antigenically similar to human SIRS. Cimetidine and ranitidine, structurally distinct histamine type II (H-2) receptor antagonists, prevented histamine-induced SIRS production. In further experiments, suppression of human polyclonal IgM PFC responses by Con A and interferons, substances that activate the SIRS pathway, was inhibited by H-2 receptor antagonists. Activation of lymphocytes to produce SIRS by Con A or interferons was blocked by cimetidine or ranitidine. These data demonstrate that production of SIRS is induced by histamine, and raise the possibility that H-2 receptor binding may play a role in the SIRS pathway.

Antibody Formation↗