Characterization of CGS 8515 as a selective 5-lipoxygenase inhibitor using in vitro and in vivo models.

CGS 8515 inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B4 synthesis in guinea pig leukocytes (IC50 = 0.1 microM). The compound did not appreciably affect cyclooxygenase (sheep seminal vesicles), 12-lipoxygenase (human platelets), 15-lipoxygenase (human leukocytes) and thromboxane synthetase (human platelets) at concentrations up to 100 microM. CGS 8515 inhibited A23187-induced formation of leukotriene products in whole blood (IC50 values of 0.8 and 4 microM, respectively, for human and rat) and in isolated rat lung (IC50 less than 1 microM) in vitro. The selectivity of the compound as a 5-lipoxygenase inhibitor was confirmed in rat whole blood by the 20-70-fold separation of inhibitory effects on the formation of leukotriene from prostaglandin products. Ex vivo and in vivo studies with rats showed that CGS 8515, at an oral dose of 2-50 mg/kg, significantly inhibited A23187-induced production of leukotrienes in whole blood and in the lung. The effect persisted for at least 6 h in the ex vivo whole blood model. CGS 8515, at oral doses as low as 5 mg/kg, significantly suppressed exudate volume and leukocyte migration in the carrageenan-induced pleurisy and sponge models in the rat. Inhibitory effects of the compound on inflammatory responses and leukotriene production in leukocytes and target organs are important parameters suggestive of its therapeutic potential in asthma, psoriasis and inflammatory conditions.

Effect of simultaneously ingested milk on phenytoin bioavailability.

Adverse gastrointestinal symptoms from milk may reduce the bioavailability of phenytoin. In a prospective crossover study, we studied the effect of simultaneous ingestion of phenytoin and milk in 12 patients with partial epilepsy and no adverse gastrointestinal symptoms. Serum phenytoin levels were measured at the start of the study and after 2 weeks. Patients then switched regimens, and a third phenytoin level was determined 2 weeks later. Serum phenytoin levels were similar for patients taking phenytoin with either milk or water.

Sympathetic neural outflow directly recorded in patients with primary autonomic failure: clinical observations, microneurography, and histopathology.

We evaluated 2 patients with primary autonomic failure, without clinical peripheral neuropathy. One had primary autonomic failure alone (PAF), and the other had autonomic failure and multiple system atrophy (MSA). Direct intraneural recordings demonstrated a marked reduction of sympathetic efferent nerve impulse activity in the PAF patient. The patient with MSA had spontaneous bursts of sympathetic nerve impulses that confirmed the functional integrity of post-ganglionic sympathetic efferent neurons. Neurosecretory activity of these neurons correlated with the electrophysiologic findings. The PAF patient had markedly reduced supine norepinephrine (NE) levels that did not rise upon standing. The supine NE level in the MSA patient was normal. Morphometric study of biopsied sural nerve in the MSA patient showed that unmyelinated fibers were normal, whereas the nerve of the PAF patient showed clear evidence of past degeneration. We suggest that the primary preganglionic sympathetic defect in MSA releases viable postganglionic sympathetic efferents from central control. Decentralized postganglionic elements may fire spontaneously, thus activating peripheral effectors and providing potentially useful signs and symptoms for differential diagnosis.

A randomized, double-blind, placebo-controlled trial of a glycine antagonist in neuropathic pain.

BACKGROUND: Nerve injury results in increases in spinal glutamate, which opens the NMDA ionophore channel, causing an influx of calcium. A glycine-binding site must be occupied for the channel to open. GV196771 is a selective antagonist of the glycine-binding site of the NMDA ionophore. OBJECTIVE: To determine the efficacy of GV196771 in subjects with chronic neuropathic pain in a proof-of-concept study. METHODS: With informed consent, 63 subjects (31 placebo, 32 GV196771) with neuropathic pain (diabetic neuropathy, postherpetic neuralgia, complex regional pain syndrome, or peripheral nerve injury), a visual analogue score averaging > or =30 mm during the screening period, and a well-defined primary area of mechanical allodynia were recruited for the study. A multicenter, randomized, double-blind, placebo-controlled, parallel-group study design was utilized. Subjects came to the research center for a total of five visits over a 21-day period, which consisted of a 14-day treatment period followed by a 7-day washout period. Spontaneous and evoked pain scores, mechanical sensory testing, quantitative sensory testing, Short Form McGill Pain Questionnaire, patient global satisfaction, and safety assessments were made during the study. RESULTS: There was no significant effect of GV196771 on spontaneous or evoked pain, quantitative sensory testing, or patient global satisfaction. There was a significant effect of GV196771 on the area of dynamic and static allodynia on days 7 and 14. The overall incidence of adverse events during treatment was similar for GV196771 (56%) and placebo (71%). The incidence of drug-related adverse events during treatment was higher for placebo (42%) than GV196771 (28%). CONCLUSIONS: Although the glycine antagonists show anti-hyperalgesic action in animal models of neuropathic pain, GV196771 does not appear to be an effective treatment in subjects with chronic neuropathic pain. This may be due to insufficient penetration of GV196771 to central sites of action, differences between the human and animal glycine receptors, or differences between neuropathic pain in animal models and humans.

Synthesis and diuretic profile of 3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloro-2,6-pyrazinediamine, an amiloride-type diuretic.

The synthesis of an analogue of amiloride in which the acylguanidine moiety has been replaced by a 1,2,4-oxadiazol-3-amine unit is described. This substance (3, CGS 4270) exhibited a diuretic profile similar to that of amiloride when evaluated in the rat and the dog. In the rat, combination with hydrochlorothiazide increased diuresis and saluresis and returned potassium levels to control values. A series of 5-aryl-1,2,4-oxadiazol-3-amines not directly related to amiloride was prepared, but these substances had no diuretic activity.

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 5. Synthesis and evaluation of enantiomers of 8-[[(4-chlorophenyl)sulfonyl]amino]-4-(3-pyridinylalkyl)octanoic acid.

The enantiomers of 8-[[(4-chlorophenyl)sulfonyl]amino]-4-(3-pyridinylpropyl)octanoic acid (1) and its pyridinyl ether analog (2) were synthesized using the highly diastereoselective method of alkylation of acyloxazolidinone. These enantiomerically pure compounds were compared with the corresponding racemic compounds 1 and 2 for their in vitro activity. Compounds 1, 1R, and 1S and 2,2S, and 2R were equipotent as thromboxane receptor antagonists (TxRAs) and thromboxane synthase inhibitors (TxSIs) (IC50 = 2-30 nM). Upon oral administration to guinea pigs, the enantiomers inhibited the ex vivo U 46619-induced platelet aggregation with potency similar to that of the corresponding racemic compound. This indicates that the enantiomers have pharmacologic profile and bioavailability similar to that of the corresponding racemic compound.

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 4. 8-[[(4-Chlorophenyl)sulfonyl]amino]-4-(3-(3-pyridinyl) propyl)octanoic acid and analogs.

The title compound (10a) and its analogs were synthesized and found to possess two activities, the inhibition of the biosynthesis of thromboxane A2 and antagonism of its receptors. The in vitro and in vivo profile of these compounds as thromboxane receptor antagonists (TxRAs) and thromboxane synthase inhibitors (TxSIs) is described. 10a and its analogs displayed very potent TxRA activity in human washed platelets (IC50 approximately 10(-7)-10(-9) M) and dog saphenous vein (pA2 approximately 9) and also potent TxSI activity (IC50 approximately 10(-9) M). The good bioavailability and the long duration of action of some of these compounds was demonstrated using ex vivo measurement of the TxRA activity upon oral administration to guinea pigs. Compounds 10a, 20, and 33 potently inhibited arachidonic acid induced bronchoconstriction in guinea pigs.

Highly selective adenosine A2 receptor agonists in a series of N-alkylated 2-aminoadenosines.

A wide variety of 2-substituted aminoadenosines were prepared for comparison with the moderately A2 receptor selective adenosine agonist 2-anilinoadenosine (CV-1808). High selectivity combined with significant affinity at the A2 receptor in rat membranes was observed for those amines bearing a two-carbon chain to which was attached an aryl, heteroaryl, or alicyclic moiety. 2-(2-Phenethylamino)adenosine (3d), a 14-fold A2 selective compound, was modified by introduction of a variety of substituents in the benzene ring and the side chain. Some of these changes led to improved A2 affinity and increased selectivity. Replacement of the phenyl moiety by cyclohexenyl produced a 210-fold selective agonist 3ag (CGS 22989) whereas the cyclohexanyl analogue 3af (CGS 22492) was 530-fold selective at the A2 site. These compounds showed hypotensive activity in rat models over a range of doses without the bradycardia observed with less selective agonists.

Coordinated effects of electromagnetic field exposure on erythropoietin-induced activities of phosphatidylinositol-phospholipase C and phosphatidylinositol 3-kinase.

Initial studies with the erythropoietin-sensitive human hematopoietic cell line, TF1, demonstrated both multifarious effects of pulsed electromagnetic field (EMF) exposure on lipid signal transduction and antiproliferative effects of EMF. Stimulation of TF1 cells with erythropoietin resulted in increased phosphatidylinositol 3-kinase activity within 2 min. Addition of wortmannin, an inhibitor of phosphatidylinositol 3-kinase, produced a decrease in cell proliferation as measured by accumulation of cells in the G0/G1 phase of the cell cycle and suppression of erythropoietin-induced DNA synthesis. Similar effects on cell proliferation were seen under EMF treatment. Phosphatidylinositol 3-kinase activity in erythropoietin-stimulated TF1 cells, measured in whole-cell extracts, increased 34% within 2 min and remained above basal levels for at least 20 min. EMF decreased erythropoietin-stimulated phosphatidylinositol 3-kinase activity to lower than basal levels. Additionally, translocation of the 85-kDa regulatory subunit (p85) of phosphatidylinositol 3-kinase to the membrane was prevented by EMF. Phosphatidylinositol-specific phospholipase C was activated, as reflected by increases in diacylglycerol and inositol trisphosphate at 15-60 s after EMF treatment. These results provide the first evidence of subtle coordinated changes by EMF associated with loss of phosphatidylinositol 3-kinase activity, inhibition of the translocation of p85 to the membrane, and activation of phosphatidylinositol-phospholipase C.

The effect of antibiotic therapy on recovery of intracellular bacteria from bronchoalveolar lavage in suspected ventilator-associated nosocomial pneumonia.

Intracellular bacteria (ICB) within recovered cells (> 7 percent) obtained via bronchoalveolar lavage (BAL) have been described as predictive of subsequent positive quantitative protected specimen brush (PSB) cultures in patients not receiving antibiotics. To determine the effect of prior or current antibiotic therapy on ICB relative to subsequent PSB culture, we prospectively evaluated 49 consecutive episodes of clinically suspected ventilator-associated pneumonia in 36 patients. Three patient groups were defined based on antibiotic administration: group 1 (current antibiotics), n = 31, samples obtained from patients currently receiving antibiotics; group 2 (recent antibiotics), n = 5, samples obtained from patients who received antibiotics > 48 h but < 72 h prior to sampling; and group 3 (no antibiotics), n = 13, samples from patients receiving no previous antibiotics within 7 days prior to sampling. Overall, PSB cultures (> or = 10(3) cfu/ml) were positive in 14 of 49 (29 percent) samples. In group 1, 2 of 31 (6 percent) samples were positive while 5 of 5 (100 percent) samples in group 2, and 7 of 13 (54 percent) in group 3 were positive. The presence or absence of ICB accurately predicted both positive and negative PSB cultures in 43 of 49 episodes. Of 43 correct predictions, 34 were negative predictions (negative ICB, negative PSB culture). The vast majority of these (29) were obtained from group 1, patients currently receiving antibiotics. In contrast, of nine positive predictions (+ICB, +PSB) virtually all (seven) occurred in group 3, patients receiving no antibiotics. In group 3, 13 of 13 PSB cultures were accurately predicted, either positive or negative, by the presence or absence of ICB. Of seven positive PSB cultures in groups 1 and 2, only 2 (28 percent) were accurately predicted by ICB. From both samples, the cultured organism was resistant to all administered antibiotics. These data suggest both prior and current antibiotic therapy reduces recovery of ICB from BAL and reduces predictive accuracy of ICB for subsequent positive PSB cultures. However, negative prediction by ICB for subsequent negative PSB cultures was good. In contrast, ICB obtained from patients not receiving antibiotics are highly predictive of subsequent PSB culture results, both positive and negative. We do not recommend BAL for evaluation of ICB in patients currently receiving antibiotics or with a recent history of antibiotic use.

Cellular and molecular correlates to plasticity during recovery from injury in the developing mammalian brain.

In summary, our studies indicate that the perinatal mammalian brain shows considerable plasticity in response to trauma. Studies carried out both in vivo in the perinatal mouse brain and in vitro in cell line culture and organotypic slice cultures of developing brain tissue, indicate that the cytokine, interleukin-1 beta (IL-1 beta) regulates early healing responses that restore the integrity of the damaged structure and create conditions conducive to the sprouting of new connections involved in plasticity. In response to a lesion placed in the cerebral cortex in a late third trimester embryo, astrocytes form a line that delimits damaged tissue being removed by phagocytic macrophages from tissue that will remain part of the neural parenchyma. By six days after birth, this line of delimiting astrocytes (LDA) appears to become the new glial limiting membrane or glial limitans at the lesion site. A gliotic scar covers the new glial limitans, but no gliosis appears within the neural parenchyma itself. The expression of IL-1 beta is upregulated in astrocytes that form the LDA and is also upregulated in the parenchyma internal to the LDA. Experiments done in vivo where the type 1 interleukin-1 receptor was blocked via injection of interleukin-receptor antagonist protein (IL-ra) indicated that both LDA formation and wound closure were dependent upon interleukin type 1 receptor activation. To test the idea that IL-1 beta could directly influence astrocyte shape and orientation, in vitro studies were carried out on astrocytic C6 glioma cells in culture. IL-1 beta induced changes in cell shape and orientation similar to those seen in in vivo formation of the LDA. Addition of IL-1ra blocked IL-1 beta induced changes in C6 cells. IL-1 beta, then, acting upon its type 1 receptor, regulates astrocytic activities that, in vivo, produce successful healing in the perinatal brain. Studies in organotypic slice cultures of early postnatal mouse hippocampus parallel in vivo studies. Phagocytic cells, in this case, "reactive/activated" microglia, reach peak numbers immediately after injury induced by culture preparation. The round microglia were replaced over 10 days in culture by "resting/ramified" microglia. Over the first 2 days of culture, astrocytes appeared thin and elongated, resembling cells that form the LDA in vivo. Over the next 8 days in cultures, astrocytes underwent hypertrophy to form a gliotic scar over the surface of the culture. The scar resembled that seen external to the LDA after healing in in vivo experiments. IL-1 beta was abundantly expressed throughout the culture period by cells showing a variety of morphologies. Finally, neurite sprouting, an indicator of circuit reorganization and plasticity, occurred rapidly in the hippocampal dentate gyrus in both in vivo and in vitro paradigms. A prenatally placed lesion in the entorhinal cortex that partially deafferents the developing dentate gyrus, induced novel sprouting of the axons of dentate granule cells, the mossy fibers, into the dentate molecular layer. Similar sprouting occurred in vitro in organotypic slice culture of deafferented hippocampus. In culture, sprouting was first observed at the time of onset of astrocyte hypertrophy, indicating that astrocyte derived factors may play a role in regulating circuit reorganization. Viewed together, in vivo and in vitro studies indicate that IL-1 beta upregulation in neural tissue correlates with glial activities that underlie rapid healing and repair in the perinatal brain, and that glial activities associated with deafferentation may play a role in inducing compensatory neurite sprouting and cicuit reorganization.

Physical activity and serum lipids and lipoproteins in elderly women.

OBJECTIVE: The relationship between cardiorespiratory exercise and serum lipid and lipoprotein levels was studied in elderly women. DESIGN: Randomized controlled experimental design with a follow up of 12 weeks; cross-sectional comparison at baseline. SETTING: Community-living elders in university exercise facilities. PARTICIPANTS: Thirty-two apparently healthy, sedentary elderly Caucasian women, 67 to 85 years of age. Ten highly conditioned elderly women, 65 to 84 years of age, who were active in endurance competitions and had been training for 11.2 +/- 1.2 years, were recruited at baseline for cross-sectional comparisons. INTERVENTIONS: Sedentary subjects were randomized to either a walking or calisthenic group. Intervention groups exercised 30 to 40 minutes, 5 days a week for 12 weeks, with the walking group training at 60% heart rate reserve and the calisthenic group engaging in mild range-of-motion and flexibility movements that kept their heart rates close to resting levels. MEASUREMENTS: Serum lipids and lipoproteins, maximal aerobic capacity (VO2 max), four skinfolds, and dietary intake at baseline and after 5 and 12 weeks. RESULTS: When the highly conditioned group and combined group of sedentary subjects were compared at baseline, serum high-density lipoprotein cholesterol (HDL-C; 1.61 +/- 0.14 vs 1.27 +/- 0.05 mmol/L, respectively; P = 0.048) and triglycerides (1.29 +/- 0.15 vs 2.00 +/- 0.15, respectively; P = 0.002), but not total serum cholesterol (5.72 +/- 0.36 vs 5.72 +/- 0.19 mmol/L, respectively) and low-density lipoprotein cholesterol (LDL-C; 3.62 +/- 0.36 vs 3.72 +/- 0.18 mmol/L, respectively), were significantly different. Twelve weeks of moderate cardiorespiratory exercise improved the VO2max of the sedentary subjects 12.6% but did not result in any change in body weight, energy intake, dietary quality, or any of the serum lipids or lipoproteins. CONCLUSION: Highly conditioned and lean elderly women, when compared with their sedentary counterparts, had higher HDL-C and lower triglycerides, but similar total serum cholesterol and LDL-C values. However, twelve weeks of moderate cardiorespiratory exercise were not associated with an improvement in serum lipid or lipoprotein profiles in previously sedentary elderly women.

Orbital myositis as a paraneoplastic syndrome.

We describe a patient with bilateral orbital myositis, multiple cranial neuropathies, a sensory polyneuropathy, serum and cerebrospinal fluid paraproteins, and high-grade non-Hodgkin's lymphoma. Neurologic symptoms began more than 1 year before diagnosis of the lymphoma. Results of extraocular muscle biopsy showed extensive destruction of myofibers and granulomatous features, with no evidence of direct tumor involvement. The cranial neuropathies and orbital myositis improved with immunosuppressive therapy, while the patient's tumor progressed. We believe the orbital myositis and the multiple neurologic abnormalities were paraneoplastic effects of the lymphoma. To our knowledge, this is the first case of orbital myositis identified as a paraneoplastic syndrome.

Multiple endocrine neoplasia presenting as primary amenorrhea: a case report.

BACKGROUND: Primary amenorrhea is rarely secondary to hyperprolactinemia. This case highlights the importance of obtaining a complete family history to identify patients who may have hyperprolactinemia secondary to multiple endocrine neoplasia type 1 syndrome. CASE: A 16-year-old female presented with primary amenorrhea and was noted to have hyperprolactinemia. Her family history revealed an extensive family tree consistent with multiple endocrine neoplasia type 1 syndrome. She was diagnosed subsequently with the syndrome, having both pituitary and parathyroid adenomas. CONCLUSION: A detailed family history of patients with hyperprolactinemia secondary to a pituitary adenoma may prompt a serum calcium measurement, which may identify patients at risk for development of multiple endocrine neoplasia type 1 syndrome.

Medical therapy for recurring catamenial pneumothorax following pleurodesis.

BACKGROUND: Catamenial pneumothorax, a rare complication of systemic endometriosis, has been difficult to treat successfully. Successful medical therapy is associated with amenorrhea. CASE: A 44-year-old white woman with recurring catamenial pneumothorax underwent thoracotomy and abrasive pleurodesis. Following the procedures, pneumothorax occurred again and she was treated with the GnRH analogue leuprolide acetate, 3.75 mg monthly intramuscularly. After 6 months, her therapy was changed to continuous hormonal suppression with norethindrone, 0.7 mg/day. After 6 months of this therapy and into the third episode of vaginal bleeding, the patient had another recurrent pneumothorax. CONCLUSION: Leuprolide acetate followed by continuous hormonal suppression with norethindrone was successful for 1 year in resolving recurring postsurgical catamenial pneumothorax, but the problem recurred with the resumption of vaginal bleeding during progestin therapy. Successful medical therapy requires amenorrhea.

Beneficial effects of combined thromboxane synthase inhibition/receptor blockade with CGS 22652 in a canine model of coronary thrombosis.

Various antiplatelet agents were examined for their effectiveness as adjuncts to thrombolytic therapy in a canine model of thrombin-induced coronary thrombosis. Aspirin (5 mg/kg i.v. bolus), CGS 15435A (thromboxane synthase inhibitor (TxSI), 0.1 mg/kg i.v. bolus +0.04 mg/kg per h) and BM 13.505 (thromboxane receptor antagonist (TxRA), 0.5 mg/kg i.v. bolus +0.2 mg/kg per h) administered concurrently with streptokinase (750,000 units/h) were examined for their effects on reperfusion and reocclusion, as were a combination therapy with CGS 15435A + BM 13.505 or the dual TxRA/TxSI inhibitor, CGS 22652 (1 mg/kg i.v. bolus +0.4 mg/kg per h). All dogs received heparin (150 U/kg bolus + 50 U/kg per h) throughout the experimental protocol. Survival analysis at reperfusion indicated that thrombolysis was significantly improved in dogs treated with CGS 15435A, BM 13.505, CGS 15435A+BM 13.505 or CGS 22652 over that of vehicle-treated animals. Both dual inhibitor groups and the BM 13.505 group were significantly different from aspirin. Aspirin-treated dogs were not different from vehicle. Otherwise, all treatments differed from the vehicle-treated group at reocclusion. Time and incidence of reocclusion for CGS 22652 was significantly improved over that of BM 13.505. Residual thrombus weight was significantly reduced in the CGS 22652-treated and BM 13.505 + CGS 15435A-treated animals. These findings demonstrate that streptokinase-induced thrombolysis is accompanied by TxA2/prostaglandin H2 synthesis and platelet activation and suggest a role for platelet activation during reocclusion following clot lysis. These studies also show it is possible to combine the beneficial effects of both a TxRA and TxSI into a single chemical entity, CGS 22652, which, when administered as adjunctive therapy to streptokinase, results in an apparent synergistic antithrombotic effect.

Treatment of Reis-Bücklers' corneal dystrophy by removal of subepithelial fibrous tissue.

We treated five eyes of three patients with Reis-Bücklers' corneal dystrophy by blunt dissection of the subepithelial fibrous tissue layer. The postoperative follow-up ranged from four months to three years. Four of the five eyes had improved vision, and all four symptomatic eyes had cessation of the recurrent erosions. This simple effective technique eliminated the need for corneal transplantation.

Clinical neurophysiology laboratory tests to assess the nociceptive system in humans.

This paper presents some currently available neurophysiological tools that are helpful in the clinical setting to evaluate and document neuropathic disturbances that may be associated with pain. The specific tests described in this discussion are quantitative sensory tests (QSTs), autonomic tests (ATs), microneurography (MCNG), and laser evoked potentials (LEPs). Quantitative sensory testing of the nociceptive system includes the thermal stimulation (TST) and current perception threshold (CPT) tests. The ATs applicable to some patients with pain are sudomotor and vasomotor tests. The quantitative sudomotor axon reflex test (QSART), resting sweat output (RSO), and sympathetic skin response (SSR) are the tests for sudomotor involvement. The vasomotor system is tested by measuring skin temperature (surface thermistor or thermography) at rest and, in some cases, after provocative maneuvers. In addition, MCNG (intraneural recording of single nerve fibers or fascicles of nerves) allows examiners to look directly at muscle and skin sympathetic efferent output in normal subjects without pain or with experimental pain and in patients with neuropathic pain. This technique also provides a means of studying the physiology of primary afferent fibers in persons with neurogenic pain. Recent development of LEPs that incorporate the use of painful infrared laser-induced stimuli allow selective study of the nociceptive system, both the central and peripheral portions.

Exercise training and nutrient intake in elderly women.

This study examined the relationship between moderate exercise training (five 30- to 40-minute sessions per week for 12 weeks at 60% of heart rate reserve) and changes in nutrient intake in a group of 30 sedentary elderly women aged 67 to 85 years. Subjects were placed randomly into two groups (those who walked and those who did calisthenics) and were followed for 12 weeks. Measurements were done at three times (baseline, 5 weeks, and 12 weeks). Dietary intake was based on 7-day food records. The 12-week walking program resulted in a significant (12.6%) improvement in maximum oxygen consumption (VO2max) but no change in body weight or skinfold thicknesses compared with the calisthenics program. Despite the improvement in cardiorespiratory fitness, no significant group x time interaction effects were observed for most of the nutrient intake variables tested. To test the effects of high levels of physical activity on nutrient intake, cross-sectional comparisons were made at baseline between highly conditioned and sedentary elderly women. The highly conditioned elderly women had higher energy and nutrient intakes, especially when expressed on a weight-adjusted basis. However, no differences in measures of dietary quality were found. Dietitians should not expect spontaneous improvement in either the quantity or quality of nutrient intake by elderly women who adopt a moderate exercise program. Although nutrient intake was greater in highly conditioned elderly women, their level of fitness and physical activity may be beyond the reach of many elderly women.

Physical activity and immune function in elderly women.

The relationship between cardiorespiratory exercise, immune function, and upper respiratory tract infection (URTI) was studied in elderly women utilizing a randomized controlled experimental design with a follow-up of 12 wk. Thirty-two sedentary, elderly Caucasian women, 67-85 yr of age, who met specific selection criteria, were randomized to either a walking or calisthenic group; 30 completed the study. Twelve highly conditioned elderly women, 65-84 yr of age, who were active in endurance competitions, were recruited at baseline for cross-sectional comparisons. Intervention groups exercised 30-40 min, 5 d.wk-1, for 12 wk, with the walking group training at 60% heart rate reserve and the calisthenic group engaging in mild range-of-motion and flexibility movements that kept their heart rates close to resting levels. At baseline, the highly conditioned subjects exhibited superior NK (119 +/- 13 vs 77 +/- 8 lytic units, P < 0.01) and T (33.3 +/- 4.9 vs 21.4 +/- 2.1 cpm x 10(-3) using PHA, P < 0.05) cell function, despite no differences in circulating levels of lymphocyte subpopulations. Twelve weeks of moderate cardiorespiratory exercise improved the VO2max of the sedentary subjects 12.6%, but did not result in any improvement in NK cell activity or T cell function. Incidence of URTI was lowest in the highly conditioned group and highest in the calisthenic control group during the 12-wk study, with the walkers in an intermediate position (chi-square = 6.36, P = 0.042). In conclusion, the highly conditioned elderly women in this study had superior NK and T cell function when compared with their sedentary counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)