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Biomedical subjects

M Higginbotham

Publications and source records attributed to M Higginbotham.

10 recordsLinked to original sources
PubMed2001

Angiotensin receptor blockers: evidence for preserving target organs.

Hypertension is a major problem throughout the developed world. Although current antihypertensive treatment regimens reduce morbidity and mortality, patients are often noncompliant, and medications may not completely normalize blood pressure. As a result, current therapy frequently does not prevent or reverse the cardiovascular remodeling that often occurs when blood pressure is chronically elevated. Blockade of the renin-angiotensin system (RAS) is effective in controlling hypertension and treating congestive heart failure. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) inhibit the activity of the RAS, but these two classes of antihypertensive medications have different mechanisms of action and different pharmacologic profiles. Angiotensin-converting enzyme inhibitors block a single pathway in the production of angiotensin II (Ang II). In addition, angiotensin I is not the only substrate for ACE. The ACE inhibitors also block the degradation of bradykinin that may have potential benefits in cardiovascular disease. Bradykinin is, however, the presumed cause of cough associated with ACE inhibitor therapy. Data from clinical trials on ACE inhibitors serve to support the involvement of the RAS in the development of cardiovascular disease. Angiotensin receptor blockers act distally in the RAS to block the Ang II type 1 (AT1) receptor selectively. Thus, ARBs are more specific agents and avoid many side effects. Experimental and clinical trials have documented the efficacy of ARBs in preserving target-organ function and reversing cardiovascular remodeling. In some instances, maximal benefit may be obtained with Ang II blockade using both ARBs and ACE inhibitors. This review describes clinical trials that document the efficacy of ARBs in protecting the myocardium, blood vessels, and renal vasculature.

Angiotensin Receptor Antagonists↗
PubMed2000

Role of titin in nonmuscle and smooth muscle cells.

Extensive investigation of vertebrate striated muscle titin has yielded significant insight into its structure and function in striated muscle. We have begun to investigate other members of the titin protein family found in vertebrate smooth muscle and nonmuscle cells. Smooth and nonmuscle titins resemble striated muscle titin in molecular size and morphology but differ in their interactions with myosin II filaments and in the structural contexts in which they exist in vivo. Divergence of these titins from the muscle titin paradigm demonstrates the versatility of this remarkable family of giant proteins.

Animals↗
PubMed2000

Low-dose enoximone improves exercise capacity in chronic heart failure. Enoximone Study Group.

OBJECTIVES: This study was designed to evaluate the effects of low-dose enoximone on exercise capacity. BACKGROUND: At higher doses the phosphodiesterase inhibitor, enoximone, has been shown to increase exercise capacity and decrease symptoms in heart failure patients but also to increase mortality. The effects of lower doses of enoximone on exercise capacity and adverse events have not been evaluated. METHODS: This is a prospective, double-blind, placebo-controlled, multicenter trial (nine U.S. centers) conducted in 105 patients with New York Heart Association class II to III, ischemic or nonischemic chronic heart failure (CHF). Patients were randomized to placebo or enoximone at 25 or 50 mg orally three times a day. Treadmill maximal exercise testing was done at baseline and after 4, 8 and 12 weeks of treatment, using a modified Naughton protocol. Patients were also evaluated for changes in quality of life and for increased arrhythmias by Holter monitoring. RESULTS: By the protocol-specified method of statistical analysis (the last observation carried-forward method), enoximone at 50 mg three times a day improved exercise capacity by 117 s at 12 weeks (p = 0.003). Enoximone at 25 mg three times a day also improved exercise capacity at 12 weeks by 115 s (p = 0.013). No increases in ventricular arrhythmias were noted. There were four deaths in the placebo group and 2 and 0 deaths in the enoximone 25 mg three times a day and enoximone 50 mg three times a day groups, respectively. Effects on degree of dyspnea and patient and physician assessments of clinical status favored the enoximone groups. CONCLUSIONS: Twelve weeks of treatment with low-dose enoximone improves exercise capacity in patients with CHF, without increasing adverse events.

Adolescent↗
PubMed1995

Efficacy and safety of pneumococcal revaccination after splenectomy for trauma.

OBJECTIVE: To assess the outcome of patient education after splenectomy and vaccination and to determine the safety and efficacy of pneumococcal revaccination 2 or more years after primary vaccination. MAIN OUTCOME MEASURES: Titers to serotype no. 6 and no. 23 pneumococcus and cutaneous and systemic reaction to revaccination. RESULTS: A total of 112 consecutive postsplenectomy patients receiving pneumococcal vaccine were identified; 45 were contacted and offered revaccination; 24 patients demonstrated a lack of understanding of the postsplenectomy state (unaware of splenectomy n = 2, unaware of splenectomy risk n = 8, unaware of vaccine n = 23); 3 patients had infections requiring hospitalization (pneumonia, strep throat and tonsillitis, pneumonia and bacteremia); 40 patients agreed to revaccination, and 33 patients returned for follow-up titers; 16 of 33 (48%) demonstrated at least a two-fold increase in at least one titer. Only 15% described the revaccination as worse than a tetanus shot. CONCLUSIONS: (1) Despite physician-patient conversations, pamphlets, and Medic Alert bracelets, patient retention was poor. (2) All splenectomy patients should be revaccinated and reeducated between two and six years after splenectomy. (3) Revaccination after two years was well tolerated. (4) There were no fatal episodes of pneumococcal sepsis in over 200 patient years.

Adult↗
PubMed1991

Effects of exercise training on bone density in older men and women.

OBJECTIVES: To determine the effects of up to 14 months of aerobic exercise on measures of bone density in older adults. DESIGN: Randomized controlled trial with subjects assigned to either an aerobic exercise condition, non-aerobic yoga, or a wait list non-exercise control group for 4 months. Aerobic fitness and bone density were evaluated in all subjects at baseline (Time 1) and after 4 months (Time 2). A semi-crossover design was utilized with all subjects completing 4 months of aerobic exercise, followed by another evaluation (Time 3). All subjects were then given the option of 6 additional months of aerobic exercise, after which they had a fourth evaluation (Time 4). SETTING: An outpatient exercise rehabilitation facility at a large, major medical center. SUBJECTS: One-hundred-one healthy men (n = 50) and women (n = 51) over age 60 (Mean age = 67.0), recruited from the community. INTERVENTION: The exercise program included stretching, cycle ergometry, and walking three times per week for 60 minutes throughout the course of the study. OUTCOME MEASURES: Aerobic fitness (VO2max) as assessed by cycle ergometry, and bone density (bone mineral content) measured by single photon absorptiometry. RESULTS: Subjects achieved a 10%-15% increase in VO2max after 4 months of exercise training, and 1%-6% further improvement with additional training. Aerobic fitness was associated with significant increases in bone density in men, but not women, who maintained aerobic exercise for 14 months.

Aged↗
PubMed1982

Mexiletine vs. lignocaine in the management of ventricular arrhythmias after open-heart surgery.

We made an open comparison of lignocaine and mexiletine in the treatment of ventricular arrhythmias occurring after open-heart surgery. Thirty patients whose arrhythmia did not respond to correction of metabolic disturbances were randomly allocated to receive treatment either with lignocaine or with mexiletine in fixed dosage schedules (15 in each group). Failure to control the rhythm or recurrent abnormality led to administration of a further dose and, if this was unsuccessful, to crossover to the alternative agent. The two drugs were comparable in efficacy, but mexiletine was slightly more effective when administered after lignocaine than the converse.

Arrhythmias, Cardiac↗
PubMed1980

Prospective angiographic assessment of factors affecting early patency of saphenous vein-coronary artery bypass grafts.

Between November 1977 and September 1978, early post-operative angiography was performed in 50 of 53 consecutive patients undergoing coronary artery bypass surgery. An average of 2.4 grafts per patient were applied. The overall patency rate was 82% and was not affected by the degree of proximal native vessel stenosis. Grafts to circumflex marginal vessels had a significantly lower (P < 0.05) patency rate (72%) than grafts to the left anterior descending (84%) and its diagonal branches (85%), or to the right coronary artery (90%). Ten single grafts were applied and all were patent. Forty-nine of the 50 patients had at least one patent graft. Fifty-three per cent of the grafts were considered of excellent quality and 25% patent but of fair quality only. There was a 100% patency rate for vessels of 2 mm diameter or more, which is significantly better (P < 0.01) than for vessels of 1-2 mm diameter (78%) or for vessels of less than 1 mm diameter (50%). There was a suggestion of a lower patency rate (74%) for vessels with evidence of distal disease, compared with vessels without such disease (85%). An assessment of the overall quality of the recipient vessel was made, taking both diameter and disease into account. This showed improved results for better quality vessels in terms of graft patency (P < 0.1) and graft quality (P < 0.05).

Coronary Angiography↗