Endoscopic evaluation of the effects of indobufen and aspirin in healthy volunteers.

This is an outcomes pharmacodynamic study using Nonsteroidal antiinflammatory agents, particularly acetylsalicylic acid (ASA), have been shown useful in various cardiovascular disorders, but they can be a major cause of iatrogenic gastrointestinal injury. Newer NSAIDs such as indobufen, an inhibitor of platelet aggregation that acts by reversibly inhibiting the platelet cyclooxygenase enzyme, have proven to be as effective as the older NSAIDs and appear to have a better gastrointestinal tolerability profile. When the gastroduodenal tolerability of 10 days of oral treatment with indobufen or ASA was assessed in healthy adult volunteers using endoscopic evaluation and the modified score scale of Lanza, only 1 of 18 (6%) volunteers who received indobufen had an increased erosion score at the completion of therapy, compared with 6 of 18 volunteers who received ASA (33%). Overall, both drugs were well tolerated. These results suggest that indobufen has a lower incidence of gastrointestinal effects than other NSAIDs and should be useful in the management of patients with cardiovascular disease.

Effects of resistance training on insulin-like growth factor-I and IGF binding proteins.

PURPOSE: Our goal was to determine the effects resistance training on circulating IGF-I and on two of its major binding proteins, IGFBP-1 and IGFBP-3. Additional goals were to compare the time course of hormonal changes with the time course of strength changes and to determine the effect of training volume on the extent of hormonal changes. METHODS: Thirty-one men and women (mean age = 37 +/- 7 yr) completed a 25-wk, 3 d x wk(-1) program in which they performed single-set resistance training (1-SET, N = 11), multiple-set resistance training (3-SET, N = 11), or no exercise (Control, N = 9). Before training, and after 13 and 25 wk of training, blood hormones were analyzed and strength was assessed as the sum of one-repetition maximum (1-RM) for leg extension and chest press exercises. RESULTS: During the first 13 wk of resistance training, circulating IGF-I increased by approximately 20% in both the 1-SET and 3-SET groups (P = 0.041). No further increases occurred between 13 and 25 wk. In the 3-SET group, IGFBP-3 decreased 20% between 13 and 25 wk (P = 0.008). Training did not alter IGFBP-1. Increases in 1-RM strength occurred mainly during the first 13 wk of training and were significantly higher with 3-SET training compared to 1-SET. CONCLUSIONS: These findings indicate that increased circulating IGF-I may, at least in part, mediate increases in strength that result from resistance training.

The effects of exercise training on the pharmacokinetics of digoxin.

BACKGROUND: Studies have shown that digoxin binds to the working muscles during an acute bout of exercise, with a concomitant decrease in serum digoxin concentration. This study investigated the effects of 16 weeks of endurance exercise training on the pharmacokinetics of digoxin in old and young adults. METHODS: Twelve subjects, aged 68.5 +/- 4.5 years, and six subjects, aged 30.3 +/- 3.8 years, completed the study. All subjects were healthy, sedentary, and taking no cardiovascular medications. After initial testing and maximum oxygen consumption (VO2max) measurements, subjects were hospitalized for 28 hours for renal function testing and digoxin clearance studies and then randomly assigned to an exercise (EG) or control (CG) group. The EG completed 16 weeks (three 1-hour bouts/week) of aerobic training at 75% to 85% of maximum capacity. The CG did not exercise. All tests were repeated at the end of the 16-week study period. RESULTS: In the older EG subjects, VO2max increased by 3.4 ml/kg/min, or approximately 16% (P = 0.0002). VO2max increased in the younger EG subjects by 1.1 ml/kg/min, but the increase was not significant (P > 0.05). There were no significant changes in body composition, renal function, or time of onset, peak concentration, or elimination phase half-life of digoxin in either the old or young exercise or control groups (P > 0.05 for all variables). CONCLUSION: Although 16 weeks of endurance exercise training improves cardiorespiratory fitness, the pharmacokinetics of digoxin are neither improved nor adversely affected in healthy old and young adults.

Exercise training in the debilitated aged: strength and functional outcomes.

OBJECTIVE: Resistance and endurance training result in gains in fitness in the aged. It is unclear whether the debilitated elderly can perform moderate-intensity training and whether such training results in short-term improvements in strength, endurance, and function in this population. DESIGN: Randomized, controlled trial. SETTINGS AND PATIENTS: Subjects were from a Veterans Affairs nursing home and rehabilitation unit and a community nursing home. They were older than 60 yrs with impairment in at least one physical activity of daily living. Seventy-eight subjects volunteered and 58 (mean age, 75 yrs; 9 women, 49 men) completed the intervention and initial posttest. Only one subject withdrew because of injury or disinterest. INTERVENTION: Thrice-weekly resistance training (using an isokinetic dynamometer) and twice-weekly endurance training for 4 to 8 weeks. MAIN OUTCOMES: Isometric strength in dominant arm and leg, heart rate response to timed endurance test, and activities of daily living score. RESULTS: The mean change in isometric strength across the muscle movements tested was 32.8% in the training group and 10.2% in the control group (difference, 22.6%; 95% confidence interval, 6.2% to 39.0%). No change in heart rate during exercise was seen in the training group. Trained subjects tended to have a greater improvement in functional activity than control subjects, which was statistically significant (p = .04) for those subjects who at enrollment were most dysfunctional (i.e., activities of daily living score less than 13 [maximum score 26]). CONCLUSION: This group of debilitated elderly patients effectively performed resistance training and increased their strength, with the most impaired gaining the most function. Few in the group could effectively perform endurance training.

Survival of vascular access during daily and three times a week hemodialysis.

AIM: A major cause of morbidity for hemodialysis patients is vascular access failure and/or occlusion. It is commonly believed that an increased frequency of dialysis sessions, among other factors, might lead to a higher rate of fistula complications. MATERIALS AND METHODS: To evaluate if patients on daily hemodialysis carry a higher risk of vascular access occlusion, we examined the incidence rate of access occlusion and the survival function of native vascular accesses in patients undergoing daily dialysis (DD; n = 24) as compared to patients on standard three times a week hemodialysis (TWD; n = 124). RESULTS: The mean follow-up time was 3.6 years. In the TWD group 42 patients had a first-access closure, whereas only 2 patients out 24 had a similar event in the DD group. The proportion of first-access closure was 33.9% for TWD and 8.3% for DD (p < 0.01). The incidence rate was 9.8 (95% CI: 7.2 -13.2) and 2.2 (95% CI: 0.4 - 7.1) events per 100 patient-years for TWD and DD, respectively. The rate difference was 7.6 (95% CI 3.4 - 11.9) events per 100 patient-years, and the unadjusted risk ratio was 4.5 (95% CI: 1.2 - 16.9; p < 0.01). The mean vascular access survival before closure was 3.3 years in TWD and 3.7 years in DD. Survival curves, obtained considering the first-access closure as the endpoint, showed a significant difference between DD and TWD (log-rank 5.16; p < 0.05). In a Cox-proportional hazard model the relative risk (RR) of vascular-access closure in TWD remained significant (RR = 4.3; 95% CI 1.1 - 18.2) after adjustment for age. CONCLUSION: The results of this observational study, conducted on a limited number of DD patients, suggest that daily dialysis might not have an adverse prognostic significance for access closure.

Effects of fosinopril or sustained-release verapamil on blood pressure and serum catecholamine concentrations in elderly hypertensive men.

A randomized, double-blind, placebo-controlled clinical trial showed 14 of 18 (78%) of the elderly hypertensive men in this study had an uncomplicated and beneficial response to either fosinopril or verapamil. There was a well-tolerated reduction in systolic blood pressure (SBP) and diastolic blood pressure (DRP). There were no significant adverse drug events. Only the sitting SBP and the sitting DBP were significantly lowered by fosinopril and verapamil SR. Because reduction in both SBP and DBP in elderly hypertensives has been shown to be beneficial, these findings take on further importance when considering the choice of medication for antihypertensive therapy in the elderly. The increase in norepinephrine in the fosinopril-treated patients may explain why patients treated with long-term angiotensin-converting enzyme inhibitors alone or in combination with diuretics rarely complain of orthostatic symptoms.

Androgens, anabolic-androgenic steroids, and inhibitors.

Androgens are steroid hormones responsible for male sexual characteristics, testosterone being the principal androgen secreted by the testes. Androgens have both masculinizing and growth-stimulating or anabolic effects. Synthetic analogs of androgens have been used by professional, as well as amateur, athletes for possible performance enhancement. The subject of androgens, pharmacologic actions, organ system effects, therapeutic uses, adverse reactions, and abuse potential are reviewed.

Altered IGF-I and IGFBPs in senescent male and female rats.

The effects of senescence on muscle characteristics and the insulin-like growth factor I (IGF-I) pathway were assessed in male and female BN/F344 rats. The mass and total ATPase activity of gastrocnemius and plantaris muscles were reduced with age and to a greater extent in males than in females. The mass and total ATPase activity of soleus muscle were not significantly altered with age. Circulating IGF-I was also significantly reduced with age, 60% in females and 21% in males. Circulating IGF-binding protein 3 (IGFBP-3) was reduced with age. In liver and gastrocnemius muscle, mRNAs for IGF-1, IGFBP-2, and IGFBP-3 were analyzed in young and aged males of two strains, BN/F344 and Sprague-Dawley. In BN/F344 rats, liver mRNAs were unchanged with age. Also in BN/F344 rats, muscle mRNAs for IGFBP-2, and IGFBP-3 displayed nonsignificant trends toward increase with age. In aged Sprague-Dawley males, liver mRNA for IGF-I was increased 15% and muscle mRNA for IGFBP-2 was increased 110%. Thus, different age-related changes in the growth hormone (GH)/IGF pathway occur in males and females between the sexes and strains. These changes may play a role in the muscle atrophy associated with senescence.

Hypertension in the elderly with coexisting benign prostatic hyperplasia.

The treatment of hypertension in the elderly can be safely achieved with low-dose diuretic therapy. Men with prostatism may benefit from peripheral alpha-blocking drugs. However, drugs such as doxazosin or terazosin may further lower blood pressure and at times may be associated with orthostatic hypotension, especially if diuretics are given concomitantly. Tamsulosin achieves relaxation of the smooth muscle of the prostate, as do terazosin and doxazosin, but without provoking changes in blood pressure, especially orthostatic hypotension. There appears to be no adverse interaction with any other antihypertensive medication or with low-dose diuretics. To manage such patients with hypertension and prostatism, hydrochlorothiazide 6.25 to 12.5 mg/day and tamsulosin 0.4 mg/day would be an adequate combination. Low-dose diuretics have been shown to be effective in both isolated systolic hypertension as well as fixed diastolic hypertension in the elderly. If other antihypertensives need to be added, then a low dose of a long-acting calcium-entry blocker, a central alpha-agonist (a transdermal clonidine for better compliance), an angiotensin-converting enzyme inhibitor (if renal vascular disease has been ruled out), or an angiotensin II receptor blocker, e.g., losartan or valsartan, should be considered.

Treatment of nocturia in the elderly.

The aging process, behavioural habits and a multitude of pathological conditions are the main contributors to the development of nocturia in the elderly. Age-related physiological changes can alter the regular pattern of urine excretion and lead to increased nocturnal frequency of voiding. In addition, aging is associated with anatomical and physiological changes of the urinary tract itself that predispose to increased urinary frequency without affecting urine volume. Several urinary and extra-urinary tract conditions may have nocturia as a prominent symptom. These conditions can be grouped as those associated with bladder overactivity, bladder outlet obstruction, bladder hypotonicity and an increased urine volume. A detailed assessment that gathers clues from the medical history, physical examination and laboratory is of utmost importance in identifying the specific causes. Overactive bladder can be idiopathic or associated with different triggers such as UTI, bladder stones, bladder tumours and CNS diseases that disrupt the normal inhibitory signals to the bladder. It may be cured by the successful elimination of the trigger conditions. Therapeutic modalities include behavioural therapies with scheduled voiding, anticholinergic drugs and in women the use of transvaginal electrical stimulation. Benign prostatic hyperplasia is the most common cause of bladder outlet obstruction in men. Different drug classes (e.g. peripheral alpha-adrenoceptor blockers and 5 alpha-reductase inhibitors) are now available for the treatment of mild to moderate symptoms. Surgery is reserved for patients with severe symptoms or with complications, with new and less invasive surgical techniques being preferred. Bladder hypotonicity is usually caused by peripheral neuropathies, spinal cord lesions and the indiscriminate use of drugs with anticholinergic actions. Treatment involves discontinuation of implicated drugs, short term use of cholinergic drugs and urinary catheterisation. Increased urine volumes and nocturia are frequently seen in hyperosmolar and oedematous states. Excessive ingestion of fluids, caffeinated or alcoholic beverages are habits that commonly produce nocturia. Although more definitive studies are awaited, low dose loop diuretics given a few hours prior to bedtime and desmopressin nasal spray or tablets may be useful alternatives for the control of nocturic symptoms in elderly patients with nocturnal polyuria syndrome. Whenever nocturia is present, clinicians should try to identify its causes by means of a thorough history, physical examination and pertinent complimentary tests. Once the specific cause or causes are found, most cases can be satisfactorily managed with behavioural, pharmacological or surgical therapies.

Tau protein in cerebrospinal fluid: a new diagnostic and prognostic marker in Alzheimer disease?

Tau is the main protein of paired helical filaments. It can be detected and measured in cerebrospinal fluid (CSF) and for this reason it has been proposed as a possible in vivo marker of Alzheimer disease (AD). To evaluate the usefulness of CSF tau in the diagnosis of AD we measured it in patients with AD, frontal lobe dementia (FLD), vascular dementia (VD), and in healthy controls by means of a specific enzyme-linked immunosorbent assay test. Individuals with AD had significantly higher tau levels than FLD, VD, and controls. Individuals with late onset AD had significantly higher levels than those with early onset disease. In AD, CSF tau level did not correlate with age, duration, or severity of the disease, whereas a correlation with age was found in FLD and controls. In the nine AD patients in whom CSF tau measurement was repeated after 2 years, mean levels did not differ from baseline, although a worsening of cognitive performances occurred. The overlap among the different groups and the absence of any modification over time suggest that CSF tau measurement, more than in confirming or staging overt AD, might be useful in revealing the disease at its preclinical phase.

Evaluation and treatment of hypertension in active individuals.

Hypertension is a very common vascular disease. It is seen in adolescents, obese persons, postmenopausal women, and the elderly. A nonpharmacologic approach to treatment is a critical first step in management. The modalities include a diet low in salt and saturated fat, exercise, less than 2 ounces of alcohol daily, and abstinence from smoking. Dynamic (aerobic) exercise is effective in lowering blood pressure (BP) only if performed regularly. Weight reduction by diet must be combined with exercise if there is to be a reduction in BP. Strength training is not to be considered as an alternative to aerobic training for reducing BP. Antihypertensive mediation can be added to nonpharmacologic interventions for additional BP reduction. Beta-blockade is not a contraindication to exercise training.