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Biomedical subjects

H W Schnaper

Publications and source records attributed to H W Schnaper.

At least 19 recordsLinked to original sources
PubMed1992

Angiotensin-converting enzyme inhibitors for systemic hypertension in young and elderly patients.

Whereas many physicians have been reluctant to treat hypertension in the elderly because of perceived limited benefits and the risk of side effects associated with traditional antihypertensive agents such as diuretics and beta blockers, studies and clinical experience have shown that elderly as well as younger patients can benefit from treatment. In recent years, angiotensin-converting enzyme (ACE) inhibitors have been found to be safe and effective in both young and elderly hypertensive patients without many of the adverse effects associated with traditional agents. ACE inhibitors possess characteristics that meet many of the special needs of elderly patients, including reduction of left ventricular mass, lack of metabolic and lipid disturbances, no central nervous system effects, no risk of induction of cardiac failure, and low risk of orthostatic hypotension.

Aging↗
PubMed1992

Early occurrence of end-stage renal disease in a patient with infantile nephropathic cystinosis.

We report the case of a patient with infantile nephropathic cystinosis who required renal transplantation at age 30 months. Exhaustive evaluation did not identify a cause of progressive renal failure other than cystinosis. The patient's genetic lesion was allelic with those of other patients with cystinosis; fusion of this patient's fibroblasts with fibroblasts from another patient with infantile nephropathic cystinosis did not demonstrate complementation of the biochemical defect.

Clone Cells↗
PubMed1992

MIDAS: hypertension and atherosclerosis. A trial of the effects of antihypertensive drug treatment on atherosclerosis. MIDAS Research Group.

Although clinical trials of the efficacy of antihypertensive treatment have demonstrated impressive reductions in the incidence of stroke, the reduction in coronary artery disease mortality has been less impressive. It may be that the antihypertensive drugs used in these trials induced metabolic disturbances, or produced inadequate regression of left ventricular hypertrophy, thus blunting the reduction in risk of coronary artery disease expected with blood pressure-lowering. Isradipine, a dihydropyridine calcium antagonist known to be an effective antihypertensive agent, has also displayed pronounced antiatherogenic effects in animals. Thus, a reasonable hypothesis could be that isradipine not only reduces the level of blood pressure, but also may have a positive effect on the evolution of atherosclerotic plaque in coronary and carotid arteries, thereby leading to prevention of clinical sequelae of atherosclerosis. On this basis, a 3-year clinical trial is being carried out in the United States--the Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS)--to establish the efficacy of isradipine in inhibiting atherogenesis and retarding the progression of atherosclerosis in carotid arteries of hypertensive patients. The primary end point of the study is intima-media thickness and the extent of atherosclerotic plaque in the carotid arteries, as measured by B-mode ultrasonography.

Antihypertensive Agents↗
PubMed1991

Steroid-dependent nephrotic syndrome following renal transplantation for congenital nephrotic syndrome.

A boy developed recurrent steroid-responsive nephrotic syndrome following renal transplantation for congenital nephrotic syndrome. The first episode was associated with mild tubulointerstitial rejection on kidney biopsy. Subsequent episodes showed normal histology by light microscopy and epithelial foot process fusion on electron microscopy, consistent with minimal change nephrotic syndrome. Serum analysis for soluble immune response suppressor was negative pre-nephrectomy, positive during each bout of nephrotic syndrome, and negative during each remission. This case represents de novo occurrence of steroid-sensitive minimal change nephrotic syndrome following renal transplantation for congenital nephrotic syndrome. We stress the need for histological examination of the renal allograft to diagnose rejection, recurrent disease, or de novo disease.

Child, Preschool↗
PubMed1991

Dose-response relationship of ramipril in patients with mild-to-moderate hypertension.

The dose-response relationship of ramipril was examined in 216 subjects with mild-to-moderate essential hypertension in a double-blind, placebo-controlled, multicenter study. Ramipril capsules (1.25, 2.5, 5, or 10 mg) or placebo capsules were administered once daily for 12 weeks. Significant reductions in supine and standing diastolic and systolic blood pressures were seen at end point in the ramipril 2.5, 5, and 10 mg treatment groups compared with placebo. The antihypertensive effect was greater at higher doses. The minimum effective dose of ramipril was 2.5 mg once daily.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Control of interleukin 1 (IL-1) activity. I. Inhibition of IL-1 activity by soluble immune response suppressor (SIRS) in vitro.

Soluble immune response suppressor (SIRS), a nonspecific inhibitor of cellular and humoral immune responses and cellular proliferation, reversed IL-1-induced inhibition of autologous rosette formation by thymocytes. In addition, SIRS prevented the IL-1-induced increase in resistance of thymocytes to the lytic action of hydrocortisone. Kinetic experiments showed that the action of SIRS on thymocytes was rapid (less than 15 minutes), although a longer time was required to exert protective effects on thymocytes. SIRS also inhibited the stimulation of thymocyte proliferation induced by Con A and IL-1 a costimulatory assay of IL-1 activity. Moreover, SIRS inhibited the IL-1-stimulated expression of complement receptors on neonatal B cells. The inhibitory effects of SIRS were selectively directed towards IL-1, since SIRS did not interfere with induction of LAK cells by IL-2, and did not reverse inhibition of autologous rosette formation induced by factors other than IL-1, such as IL-4, a proline rich polypeptide and lactoferrin. The results presented in this report demonstrate that SIRS may be a selective inhibitor of IL-1 activity with respect to T and B cells, rendering them unresponsive to IL-1 activation and/or maturation signals.

Animals↗
PubMed1990

Acebutolol effects on lipid profile.

The relation between lipid profile and the incidence of coronary artery disease has been confirmed by the results of epidemiologic and intervention studies. Among antihypertensive agents, beta blockers, particularly those without intrinsic sympathomimetic activity (ISA), are generally reported to have negative effects on lipids, which may increase the risk of coronary artery disease. The ongoing Treatment of Mild Hypertension Study, now in its third year, has evaluated 847 patients to date with regard to lipid profile. Additional end points measured in this multicenter, randomized, controlled, double-blind study include blood pressure reduction and target organ deterioration. During the trial, all patients received nutritional and behavioral counselling to modify their diet, exercise habits and alcohol and sodium consumption to control their hypertension by nonpharmacologic means. In addition, some patients were randomized to receive low doses of 1 of the 5 classes of antihypertensive medication: acebutolol, a beta blocker with ISA (n = 124); amlodipine, a calcium channel blocker (n = 122); chlorthalidone, a diuretic (n = 125); doxazosin, an alpha blocker (n = 128); enalapril, an angiotensin-converting enzyme inhibitor (n = 127) or placebo (n = 221). At 1 year, acebutolol showed a statistically significant (p less than 0.001) decrease in total cholesterol (-12.7 mg/dl) compared with placebo (-5.2 mg/dl) and with chlorthalidone (1.0 mg/dl); a significant (p less than 0.001) decrease in low-density lipoprotein cholesterol (-6.0 mg/dl) compared with placebo (+0.7 mg/dl) and with chlorthalidone (+8.0 mg/dl) and no change in high-density lipoprotein cholesterol (-0.4 mg/dl).

Acebutolol↗
PubMed1990

A regulatory system for soluble immune response suppressor production in steroid-responsive nephrotic syndrome.

Patients with nephrotic syndrome frequently have suppressed immune responses. Previously, it has been determined that subjects with steroid-responsive nephrotic syndrome (SRNS) produce the lymphokine, soluble immune response suppressor (SIRS). In the present group of experiments, a potential pathway of suppressor cell activation was investigated. Sera from patients with SRNS stimulated normal CD8+ lymphocytes to produce SIRS. Serum SIRS-inducing activity was abrogated by treatment with proteinase K or boiling, but was not affected by dialysis, acidification to pH 2, or heating to 56 degrees C. This serum factor could be distinguished functionally and antigenically from SIRS and from interferon (IFN) alpha or IFN gamma. Supernatants of cultured patient lymphocytes enriched for CD4+ cells were also found to activate normal CD8+ lymphocytes to produce SIRS. The lymphocyte-derived activity showed similar characteristics to those of the serum factor. Molecular weight of both factors was estimated to be 13,000 to 18,000 daltons by gel filtration chromatography, and activity of serum and lymphocyte supernatant from the same patients eluted with similar patterns on reversed-phase HPLC. These data suggest that serum SIRS-inducing activity is derived from a suppressor-inducer lymphocyte, and indicate the presence of a regulatory mechanism for SIRS production in steroid-responsive nephrotic patients.

Child↗
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↗