Biomedical subjects

R A Preston

Publications and source records attributed to R A Preston.

At least 37 records · Page 2Linked to original sources

PubMed1998

Linkage and association between inflammatory bowel disease and a locus on chromosome 12.

Genetic epidemiological studies have shown that genetic factors are important in the pathogenesis of the idiopathic inflammatory bowel diseases (IBD), Crohn disease (CD), and ulcerative colitis (UC). A genome screen in the United Kingdom found linkage of IBD to a 41-cM region of chromosome 12, surrounding D12S83. We aimed to replicate this linkage and to narrow the region of interest. Nonparametric linkage analyses at microsatellites surrounding D12S83 were performed in 122 North American Caucasian families containing 208 genotyped IBD-affected relative pairs. Transmission/disequilibrium tests (TDTs) were also performed. We confirmed that IBD is linked to chromosome 12 (peak GENEHUNTER-PLUS LOD* score 2.76 [P = .00016] between D12S1724 and D12S90). The evidence for linkage is contributed by both the group of CD-affected relative pairs (peak GENEHUNTER-PLUS LOD* score 1.79 [P = .0021] between D12S1724 and D12S90) and the group of UC-affected relative pairs (peak GENEHUNTER-PLUS LOD* score 1.82 [P = .0019] at D12S335). The TDT is positive at the D12S83 locus (global chi2 = 16.41, 6 df, P = .012). In conclusion, we have independently confirmed linkage of IBD to the chromosome 12 region that we investigated. A positive TDT at D12S83 suggests that we have greatly narrowed the chromosome 12 region that contains an IBD locus.

Chromosomes, Human, Pair 12↗

PubMed1998

University of Miami Division of Clinical Pharmacology therapeutic rounds: drug-induced hyperkalemia.

Drug-induced hyperkalemia is an important but often overlooked problem encountered commonly in clinical practice. It may occur in the ambulatory as well as the impatient setting. Every evaluation of a hyperkalemic patient should include a careful review of medications to determine if a drug capable of causing or aggravating hyperkalemia is present. Medications generally produce hyperkalemia either by causing redistribution of potassium (beta2 -adrenergic blockers, succinylcholine, digitalis overdose, hypertonic mannitol) or by impairing renal potassium excretion. Drugs cause impaired renal potassium excretion by (1) interfering with the production and/or secretion of aldosterone (nonsterodial anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, heparin, cyclosporine, and FK 506) or (2) blocking the kaliuretic effects of aldosterone (potassium-sparing diuretics, trimethoprim, pentamidine, and nefamostat mesilate). Because severe renal insufficeiency is generally required to cause hyperkalemia, an elevated serum potassium concentration in a patient with mild-to-moderate renal failure should not be ascribed to renal failure alone. A careful search for "hidden" potassium loads and for causes of impaired tubular secretion of potassium (including drugs) is necessary. Finally, it is important to recognize that the causes of hyperkalemia may be additive. Patients may have more than one cause of hyperkalemia at the same time. Therefore, all potential causes of hyperkalemia, including drugs, should be systematically evaluated in every hyperkalemic patient.

AIDS-Related Opportunistic Infections↗

PubMed1998

University of Miami Division of Clinical Pharmacology Therapeutic Rounds: ischemic renal disease.

Ischemic renal disease (IRD) is defined as a significant reduction in glomerular filtration rate and/or loss of renal parenchyma caused by hemodynamically significant renal artery stenosis. IRD is a common and often overlooked clinical entity that presents in the setting of extrarenal arteriosclerotic vascular disease in older individuals with azotemia. IRD is an important cause of chronic renal failure and end-stage renal disease (ESRD), and many patients with a presumed diagnosis of hypertensive nephrosclerosis may actually have undiagnosed ischemic nephropathy as the cause of their ESRD. The primary reason for establishing the diagnosis of IRD is the hope that correction of a renal artery stenosis will lead to improvement of renal function or a delay in progression to ESRD. There are six typical clinical settings in which the clinician could suspect IRD: acute renal failure caused by the treatment of hypertension, especially with angiotensin-converting enzyme inhibitors; progressive azotemia in a patient with known renovascular hypertension; acute pulmonary edema superimposed on poorly controlled hypertension and renal failure; progressive azotemia in an elderly patient with refractory or severe hypertension; progressive azotemia in an elderly patient with evidence of atherosclerotic disease; and unexplained progressive azotemia in an elderly patient. It is important for the clinician to identify IRD, because IRD represents a potentially reversible cause of chronic renal failure in a hypertensive patient.

Aged↗

PubMed1998

University of Miami Division of Clinical Pharmacology Therapeutic Rounds: managing hypertension in patients with kidney disease-implications for preservation of renal function.

Renal parenchymal hypertension is defined as hypertension caused by disease of the kidneys. Impaired renal sodium excretion leading to extracellular fluid volume (ECFV) expansion is the most clinically important mechanism leading to hypertension in patients with kidney disease. Most patients with renal parenchymal hypertension have sodium-sensitive hypertension, and, consequently, sodium restriction and loop diuretics constitute the initial steps in effective antihypertensive therapy in patients with renal disease. The loop diuretics (furosemide, ethacrynic acid, bumetanide, torasemide) are used for the management of ECFV and hypertension in patients with renal disease because thiazide diuretics are generally not effective in patients with serum creatinine values above 2.0 mg/dL or creatinine clearances below 30 mL/min. The Joint National Committee VI recommends the use of angiotensin-converting enzyme (ACE) inhibitors in patients with hypertension and chronic renal disease to control hypertension and to slow progressive renal failure. Antihypertensive treatment with ACE inhibitors may favorably alter renal hemodynamics, thereby slowing the progression of renal dysfunction. ACE inhibitors have been found to be useful agents in preventing the progression of renal disease in the settings of established insulin-dependent diabetes mellitus (IDDM) nephropathy, non-insulin-dependent diabetes mellitus (NIDDM) nephropathy, IDDM patients with normal blood pressures and microalbuminuria, NIDDM patients with microalbuminuria and normal renal function, and a variety of non-diabetic renal diseases, especially in the setting of significant proteinuria. Calcium antagonists are effective for treating hypertensive patients with chronic renal impairment, and the initial results for calcium antagonists and for combination calcium antagonist-ACE inhibitor therapy have been encouraging. Although promising, the calcium antagonists and the new angiotensin II antagonists have not been studied as intensively as ACE inhibitors in regard to their ability to slow the progression of renal insufficiency.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Genetic diversity among strains of Moraxella catarrhalis: analysis using multiple DNA probes and a single-locus PCR-restriction fragment length polymorphism method.

Moraxella (Branhamella) catarrhalis, a causative agent of otitis media, sinusitis, and exacerbation of bronchitis, has acquired widespread ability to produce beta-lactamase and can be nosocomially transmitted. The typing methods used in epidemiological analyses of M. catarrhalis are not optimal for genetic analyses. Two methods, a multiple-locus Southern blot (SB) method and a single-locus PCR-restriction fragment length polymorphism (RFLP) method, were developed and used to assess genetic diversity and potential clinical and geographic relationships in M. catarrhalis. Nine randomly cloned M. catarrhalis DNA fragments were used as probes of SBs containing DNA from 54 geographically and clinically diverse strains. For comparison, a PCR-RFLP method was developed as a quick, inexpensive, and discriminating alternative. A highly variable 3.7-kb genomic region (M46) was cloned and sequenced, and 3.5 kb of the cloned DNA was targeted for PCR amplification. DNAs from the 54 strains were subjected to PCR-RFLP. SB analysis distinguished all strains that had no apparent epidemiological linkage (40 of 54), and PCR-RFLP distinguished fewer strains (21 of 54). Epidemiologically linked strains appeared genetically identical by both methods. PCR-RFLP was compared to pulsed-field gel electrophoresis (PFGE) for 8 of the 54 strains and 23 additional strains. PCR-RFLP distinguished fewer strains than PFGE typing (16 of 31 versus 20 of 31 strains), but PCR-RFLP was more useful for inferring interstrain relatedness. Separate cluster analyses of multilocus SB and single locus PCR-RFLP data showed high genetic diversity within and across geographic locations and clinical presentations. The resultant dendrograms were not entirely concordant, but both methods often gave similar strain clusters at the terminal branches. High genetic diversity, nonconcordance of cluster analyses from different genetic loci, and shared genotypes among epidemiologically linked strains support a hypothesis of high recombination relative to spread of clones. Single-locus PCR-RFLP may be suitable for short-term epidemiological studies, but the SB data demonstrate that greater strain discrimination may be obtained by sampling variation at multiple genomic sites.

Adult↗

PubMed1997

Interior structure and seasonal mass redistribution of Mars from radio tracking of Mars Pathfinder.

Doppler and range measurements to the Mars Pathfinder lander made using its radio communications system have been combined with similar measurements from the Viking landers to estimate improved values of the precession of Mars' pole of rotation and the variation in Mars' rotation rate. The observed precession of -7576 +/- 35 milliarc seconds of angle per year implies a dense core and constrains possible models of interior composition. The estimated annual variation in rotation is in good agreement with a model of seasonal mass exchange of carbon dioxide between the atmosphere and ice caps.

Atmosphere↗

PubMed1997

Prevention of diabetic nephropathy.

Normalization of blood pressure--and use of an ACE inhibitor or AT1-receptor blocker for patients with abnormal albumin or creatinine levels--can prevent or significantly slow the rate of progression toward end-stage renal disease.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis.

BACKGROUND & AIMS: We recently identified a single R117H mutation in the cationic trypsinogen gene in several kindreds with an inherited form of acute and chronic pancreatitis (HP1), providing strong evidence that trypsin plays a central role in premature zymogen activation and pancreatitis. However, not all families studied have this mutation. The aim of this study was to determine the disease-causing mutation in kindreds with hereditary pancreatitis that lack the previously identified mutation. METHODS: Clinical features of the HP1 kindreds were compared with those of the new kindreds (HP2), and genetic linkage analysis, screening for mutations through DNA sequencing, and screening an unaffected population were performed. RESULTS: The onset of symptoms was delayed and hospitalizations were fewer in HP2 compared with HP1 (P < 0.05). Linkage of the disease gene to chromosome 7q35 was established (logarithm of the odds, 3.73). Mutational screening identified a single A to T mutation resulting in an asparagine to isoleucine transition mutation at position 21 (N21I) in cationic trypsinogen. The mutation was absent in 94 unrelated individuals, representing 188 unique chromosomes. CONCLUSIONS: The identification of a second mutation in the cationic trypsinogen gene (HP2) suggests a dominant role of trypsin in premature protease activation-mediated forms of acute pancreatitis. The pathogenesis of hereditary pancreatitis also suggests that chronic pancreatitis may result from recurrent acute pancreatitis.

Acute Disease↗

PubMed1997

Ischemic renal disease: an emerging cause of chronic renal failure and end-stage renal disease.

Ischemic renal disease (IRD) is defined as a clinically important reduction in glomerular filtration rate or loss of renal parenchyma caused by hemodynamically significant renal artery stenosis. IRD is a common and often overlooked clinical entity that presents itself in the setting of extrarenal arteriosclerotic vascular disease in older individuals with azotemia. Eleven to 14% of end-stage renal disease (ESRD) cases are attributable to chronic IRD. A high percentage of patients entering ESRD programs are hypertensive. Many patients with a presumed diagnosis of hypertensive nephrosclerosis actually have undiagnosed ischemic nephropathy as the etiology of their ESRD. It is important for the clinician to identify IRD, because IRD is a potentially reversible cause of chronic renal failure in a hypertensive patient. Atherosclerotic renal artery disease is common among patients with coronary artery disease and aortic and peripheral vascular disease. Atherosclerotic renal artery disease is a progressive disorder, and its progression is associated with loss of renal mass and functioning. A decrease in glomerular filtration rate sufficient to cause an elevation of the serum creatinine concentration requires injury to both kidneys. Consequently, IRD can arise from one of two main clinical situations: bilateral hemodynamically significant renal artery stenosis leading to bilateral renal ischemia; and hemodynamically significant renal artery stenosis in a solitary functioning kidney, or in a kidney that is providing the majority of a patient's glomerular filtration. The primary reason for establishing the diagnosis of IRD is the hope that correction of a renal artery stenosis will lead to improvement of renal function, or a delay in progression to ESRD. There are six major clinical settings in which the clinician could suspect IRD: acute renal failure caused by the treatment of hypertension, especially with angiotensin converting enzyme inhibitors; progressive azotemia in a patient with known renovascular hypertension; acute pulmonary edema superimposed upon poorly controlled hypertension and renal failure; progressive azotemia in an elderly patient with refractory or severe hypertension; progressive azotemia in an elderly patient with evidence of atherosclerotic disease; and unexplained progressive azotemia in an elderly patient. Noninvasive testing modalities that have been used recently include the angiotensin converting enzyme inhibitor renal scan, duplex Doppler sonography, magnetic resonance angiography, and the spiral computed tomography. Treatment methods include percutaneous transluminal angioplasty, endovascular stenting, and surgical revascularization. The results of treatment for preservation of renal function have been encouraging, with stabilization or improvement in renal function observed in a significant proportion of cases.

Humans↗

PubMed1997

Proteinuria in mild to moderate hypertension: results of the VA cooperative study of six antihypertensive agents and placebo. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

The prevalence and natural history of severe proteinuria in mild to moderate hypertension are not completely defined. We screened 1635 men with a history of hypertension and randomized 1292 with untreated diastolic blood pressure (DBP) 95-109 mmHg to single-drug treatment with either hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem-SR, prazosin, or placebo in a double-blind prospective trial. Twenty-seven of 1635 patients (1.7%) satisfying clinical criteria for primary hypertension were found to have developed proteinuria > 1000 mg/24 hours and were removed from the study. Follow-up data were obtained on 19 of these 27 patients. One patient was found to have focal segmental sclerosis and progressed to end-stage renal disease. Three other patients developed severe (serum creatinine > 3.5 mg/dl) chronic renal failure (one with diabetic nephropathy), one progressed from serum creatinine 1.4 to 2.2 mg/dl, but 14 of the 19 remained with stable serum creatinine < 2.0 mg/dl on follow-up for 6-9 years. Data were available for 1076 of 1155 (93%) treated study patients at end titration, 522/600 (87%) at one year and 322/444 (73%) at two years. There were significant associations for proteinuria with obesity and higher systolic blood pressure. There was a trend toward significant difference in mean 24-hour protein excretion rates at baseline between black (127 mg) and white (139 mg) patients (p = 0.07). There were no statistically significant changes in urinary protein excretion/24 hours between or within the different treatment groups (including placebo). Eighteen patients were removed from the study during the active treatment phase for proteinuria > 1000 mg/24 hours: hydrochlorothiazide 4, placebo 3, diltiazem 3, prazosin 3, atenolol 2, clonidine 2, and captopril 1. We conclude: (1) the prevalence of severe (> 1 g/24 hours) proteinuria in the hypertensive population is significant but does not necessarily imply a poor prognosis; (2) mean 24-hour urinary protein excretion rates did not vary in response to the different classes of antihypertensive drugs; and (3) there was no drug-specific increase in proteinuria detected in this study.

Adult↗

PubMed1997

Clinical characteristics of hereditary pancreatitis in a large family, based on high-risk haplotype. The Midwest Multicenter Pancreatic Study Group (MMPSG)

OBJECTIVES: Because there are no markers for hereditary pancreatitis (HP), diagnosis has relied on clinical features and inferences. Identification of the HP disease gene locus on chromosome 7q35 provides the first genetic marker for HP, allowing an accurate comparison of the clinical diagnosis of HP with the presence of a high-risk HP haplotype. Our objectives were to compare the clinical diagnosis of HP with inheritance of the HP gene and to characterize the common clinical features. METHODS: A detailed questionnaire was administered to 102 study participants of a large HP kindred. Blood samples were taken for DNA extraction and high-risk haplotype determination. Clinical findings were compared with the presence of a high-risk haplotype. RESULTS: A family tree of more than 500 members and eight generations was constructed, and clinical features of the 102 participants were determined. HP occurred before the age of 5 yr in 58% of subjects, who presented with common symptoms of abdominal pain, nausea/vomiting, and frequent attacks. Thirty-five probands, of whom 80% had clinical symptoms, carried the high-risk haplotype, confirming previous estimates of 80% penetrance. Thirty-two of the study participants had been clinically diagnosed with HP, whereas 70 were clinically unaffected. With regard to the presence of the high-risk haplotype, 87.5% of the clinically diagnosed patients were affected by HP (true positive), whereas 12.5% did not carry the high-risk haplotype (false positive). Seven obligate carriers were identified through DNA analysis; three had previously been unrecognized because of lack of affected offspring. CONCLUSIONS: The diagnosis of hereditary pancreatitis on clinical grounds alone may be inaccurate in less severe cases, as is the exclusion of carrier status through family tree analysis. Therefore, a definitive diagnosis of hereditary pancreatitis in equivocal cases or exclusion of a carrier state should include analysis of genetic markers.

Chromosomes, Human, Pair 7↗

PubMed1996

Renal Parenchymal Hypertension: current concepts of pathogenesis and management.

Renal parenchymal disease is a common but often unrecognized cause of hypertension. Chronic renal disease and systemic hypertension may coexist in two distinct settings. First, essential hypertension is an important cause of chronic renal disease. Second, renal parenchymal disease is a well-established cause of secondary hypertension. Renal parenchymal disease is the most common cause of secondary hypertension, accounting for 2.5% to 5.0% of all cases of systemic hypertension. Secondary hypertension may also accelerate the decline in renal function if inadequately controlled. Therefore, hypertension is both a cause and a consequence of renal disease, and it may be difficult to distinguish them clinically.

Humans↗

PubMed1996

Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene.

Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg-His substitution at residue 117 of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis.

Arginine↗

PubMed1996

A gene for hereditary pancreatitis maps to chromosome 7q35.

BACKGROUND & AIMS: Hereditary pancreatitis (HP) is an autosomal-dominant disorder with incomplete penetrance characterized by recurrent bouts of severe epigastric pain with onset usually at 5-10 years of age. A genetic linkage study was designed to identify the HP gene. METHODS: A 500-member pedigree was constructed from a U.S. kindred centered in eastern Kentucky and western Virginia. A genome-wide search strategy was employed using a 36-member subset of this family to determine the genetic locus for HP. Testing for linkage to microsatellite loci was performed at 20-cM intervals. RESULTS: Linkage was established between the HP phenotype and chromosome 7q in this subset of the family. Modeled as an autosomal dominant disorder with 80% penetrance, a maximal multipoint logarithm of the odds score of 4.3 was obtained using a four-point analysis consisting of markers D7S684, D7S661, D7S505, and the HP locus. Two microsatellite markers, D7S661 and D7S505, that correspond to the 7q35 region of chromosome 7 spanning a 6-cM region did not evidence obligate recombinations with HP. The centromeric and telomeric limits are defined by recombinations at D7S684 and D7S483, respectively, which generates a 19-cM locus for HP. Utilizing family members from the extended pedigree, a break in the high-risk haplotype between D7S684 and D7S661 was observed, which suggests it may be possible to exclude an additional 8 cM from the HP locus. A maximal pairwise logarithm of the odds score of 4.73 at a recombination fraction of theta at D7S684 was obtained with the addition of these extended family members. CONCLUSIONS: Linkage of HP to 7q35 represents a major advancement in our understanding of the genetic basis of this disorder.

Chromosome Mapping↗

PubMed1996

JEAB and JABA on the World Wide Web: a report to readers.

The Journal of the Experimental Analysis of Behavior (JEAB) and the Journal of Applied Behavior Analysis (JABA) have both established home pages on the World Wide Web. Their addresses are: http://www.envmed.rochester.edu/wwwrap/beh avior/jeab/jeabhome.htm http://www.envmed.rochester.edu/wwwrap/beh avior/jaba/jabahome.htm An important feature of these pages is a powerful program that permits rapid full-text searches of a database consisting of the nearly 5,000 abstracts that have accompanied articles published in JEAB since 1958 and in JABA since 1968. An electronic version of a single article from each issue of each journal is now made available soon after the paper edition of the journal appears.

Computer Communication Networks↗

PubMed1996

Hypertension in Haitians: results of a pilot survey of a public teaching hospital multispecialty clinic.

Little is known about hypertension in Haitians. We performed a pilot survey of ambulatory Haitian patients in a multispecialty clinic at a large public teaching hospital. Approximately 10% of the clinic population was of Haitian origin. Clinical data were collected on 88 consecutive Haitian patients. Of these 88, 77 (87.5%) were hypertensive (SBP > or = 140 or DBP > or = 90 mm Hg or taking antihypertensive medication). The characteristics of the hypertensive patients were: age 54.1 +/- 13.0 (s.d.) years; 27 men, 50 women; 12/64 (19%) smoked; 7/63 (11%) used alcohol. Diabetes was present in 21/77 (27%). In patients for whom height and weight were available, obesity was present in 52%. Using JNC V criteria, 18 (23%) had Stage 1, 16 (21%) Stage 2, 18 (23%) Stage 3, and 25 (33%) Stage 4 hypertension. Despite 63/77 (82%) being treated for hypertension, only 20 (26%) were controlled (< 140/< 90 mm Hg). Of those under treatment, 29 were taking one drug; 18 (two drugs); 12 (three drugs); and four (four drugs). Target organ damage was evident in 37 (48%), including coronary artery disease (8), CHF (6), chronic renal failure (15), stroke (9), and LVH by ECG (19). There was evidence of severe noncompliance in 32 (42%). We conclude that in this clinic sample, hypertension was highly prevalent and unusually severe in terms of blood pressure (BP) level, refractoriness to treatment, and target organ consequences. Further studies are indicated.

Adult↗

PubMed1995

Subparsec-scale structure and evolution of Centaurus A (NGC5128).

We present a series of 8.4-GHz very-long-baseline radio interferometry images of the nucleus of Centaurus A (NGC5128) made with a Southern Hemisphere array, representing a 3.3-year monitoring effort. The nuclear radio jet is approximately 50 milliarcseconds in extent, or at the 3.5-megaparsec distance of NGC5128, approximately 1 parsec in length. Subluminal motion is seen and structural changes are observed on time scales shorter than 4 months. High-resolution observations at 4.8 and 8.4 GHz made in November 1992 reveal a complex morphology and allow us to unambiguously identify the self-absorbed core located at the southwestern end of the jet.

Journal Article↗

PubMed1995

Response to a second single antihypertensive agent used as monotherapy for hypertension after failure of the initial drug. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

BACKGROUND: An important issue in clinical practice is how to treat patients whose blood pressure does not respond to the first antihypertensive drug selected. OBJECTIVE: To analyze the antihypertensive response of patients who had failed to achieve their diastolic blood pressure goal (< 90 mm Hg at the end of 8 to 12 weeks of titration) with one of six randomly allocated drugs or placebo to the random allocation of an alternate drug. METHODS: We initially randomized 1292 men with diastolic blood pressure of 95 to 109 mm Hg to treatment with hydrochlorothiazide, atenolol, captopril, clonidine hydrochloride, diltiazem hydrochloride (sustained release), prazosin hydrochloride, or placebo. Of 410 men in whom initial treatment failed, 352 qualified for randomization to the alternate drug. RESULTS: Of the 352 patients, 173 (49.1%) achieved their goal diastolic blood pressure, in 133 (37.8%) the alternate drug failed, and 46 (13.1%) left the study for various reasons. Overall response rates were as follows: diltiazem, 63%; clonidine, 59%; prazosin, 47%; hydrochlorothiazide, 46%; atenolol, 41%; and captopril, 37%. The best response rate for patients in whom hydrochlorothiazide failed was achieved with diltiazem (70%); after atenolol failure, clonidine (86%); after captopril failure, prazosin (54%); after clonidine failure, diltiazem (100%); after diltiazem failure, captopril (67%); and after prazosin failure, clonidine (53%). The combined response rate for patients initially randomized to an active treatment was 76.0%, which is similar to that achieved by the combination of two drugs in previous studies. CONCLUSIONS: We conclude that sequential single-drug therapy is a rational approach for treatment of hypertension in patients in whom initial drug therapy has failed.

Adult↗