Referral patterns and exercise response in the rehabilitation of female coronary patients aged greater than or equal to 62 years.

Gender-related differences in cardiac rehabilitation referral patterns and response to an aerobic conditioning program were examined in 226 hospitalized older coronary patients (aged greater than or equal to 62 years). Overall, the outpatient cardiac rehabilitation participation rate in this population was 21%. Older women were less likely to enter cardiac rehabilitation than were older men (15 vs 25%; p = 0.06), despite similar clinical profiles. This was explained primarily by a greater likelihood of primary physicians to strongly recommend cardiac rehabilitation to men. Before conditioning, women who entered cardiac rehabilitation were less fit than were men; peak oxygen consumption was 18% lower in women (16 +/- 5 vs 20 +/- 5 ml/kg/min; p = 0.02). However, both groups improved aerobic capacity similarly in response to a 12-week aerobic conditioning program, with maximal oxygen consumption increasing by 17% in women and by 19% in men. Thus, older female coronary patients are less likely to be referred for cardiac rehabilitation, despite a similar clinical profile and improvement in functional capacity from the training component.

The efficacy and distribution of suramin in the treatment of the 9L gliosarcoma.

Suramin inhibits the stimulation of brain tumor deoxyribonucleic acid synthesis in vitro at concentrations of 200 to 400 mg/ml. This report evaluates suramin in the rodent 9L tumor model. Survival was analyzed by treating 10 tumor-bearing animals with suramin (7 mg/kg/d intraperitoneally) for 7 days, beginning 1 week after implantation, and compared with 20 untreated animals. Tissue distribution was analyzed with reverse-phase high-pressure liquid chromatography in homogenized organs of normal animals. Tumor concentration was measured over time in animals treated with a range of suramin doses, beginning 2 weeks after implantation. Suramin imparted no benefit as tumor-bearing control animals and treated animals survived 24.7 +/- 3.4 days and 24.5 +/- 1.5 days, respectively. In the animals receiving 7 mg/kg/d, renal concentrations of suramin were highest--339.8 +/- 30.9 mg/g as late as 25 days after treatment. Concentration in the brain peaked at only 3.3 +/- 1.3 mg/g after 10 days. Concentration in the tumor peaked at 74.4 +/- 16.5 mg/g the day of the last injection, significantly less than estimated by in vitro studies of efficacy. After injections of 35 mg/kg/d, tumor levels reached 230.9 +/- 139.2 mg/g with no evidence of inhibition of tumor progression. The response to a 7 mg/kg direct brain inoculation of suramin was assessed and compared with saline as a control. Animals treated with suramin died after 1 to 3 hours. Intracerebral hematoma volume at the injection site was 13.9 +/- 10.7 mm3 and 1.9 +/- 3.32 mm3 in the suramin-treated and control animals, respectively (P = 0.02), confirming the reported anticoagulant activity of suramin. Suramin is without efficacy in the 9L model because of poor systemic delivery. Alternative direct inoculation results in lethal local hemorrhage. Further consideration is necessary before the broad clinical application of this drug.

Reduced muscarinic receptor plasticity in frontal cortex of aged rats after chronic administration of cholinergic drugs.

Age-related differences in muscarinic receptor plasticity were observed in young, adult and senescent Fischer 344 rats (3, 9 and 27 months old, respectively) following the chronic, intracerebroventricular (ivt) administration of a cholinergic agonist, oxotremorine, or antagonist, methylatropine. After three weeks treatment of young rats with ivt oxotremorine, the maximum number (Bmax) of 3H-QNB binding sites in frontal cortex, determined by saturation experiments, was reduced by 27%, with no apparent change in the affinity (Kd) of 3H-QNB for the muscarinic receptor. Conversely, chronic ivt methylatropine administered to 3 month old animals caused a 29% increase in Bmax with no significant change in Kd. Adult animals showed a somewhat lesser degree of muscarinic receptor plasticity (16% down-regulation after oxotremorine, 22% up-regulation after methylatropine). However, 3H-QNB binding parameters in frontal cortex from senescent rats were not significantly altered following identical treatments with oxotremorine or methylatropine. Thus, muscarinic receptor adaptation to chronic, cholinergic drug administration was impaired in aged animals. This reduced receptor plasticity with aging could have important implications for the long-term drug treatment of elderly patients and for the therapeutic efficacy of cholinergic drugs in age-related neurological disorders, such as Alzheimer's disease.