Strontium-90: effects of chronic ingestion on farrowing performance of miniature swine.

In experiments involving the ingestion of strontium-90 by nearly 800 female miniature swine and extending over three generations, no significant differences in litter size, percentage of stillborn, or birth weight were observed between controls and animals ingesting up to 625 microcuries of strontium-90 per day. At 625 microcuries per day, these animals were ingesting more than a million times the peak value of strontium-90 ever reported in the American diet. Animals on 3100 microcuries per day did not survive the gestation period. From these studies, it is evident that feeding levels of strontium-90 high enough to affect fetal or neonatal mortality in this species will not permit maternal survival long enough for the bearing of young.

The effect of sulfonylurea drugs on rabbit myocardial contractility, canine purkinje fiber automaticity, and adenyl cyclase activity from rabbit and human hearts.

Long-term clinical studies have associated tolbutamide therapy with an increased incidence of cardiovascular deaths. The effects of this and other sulfonylurea drugs on contractility and rate of isolated rabbit atria, automaticity of isolated dog Purkinje fibers, and adenyl cyclase activity in particulate preparations of rabbit and human hearts were studied. At concentrations that are attained clinically, tolbutamide (10 mg/100 ml) increased contractility of driven rabbit atria to 124+/-5% of control, acetohexamide (3.9 mg/100 ml) to 140+/-5%, chlorpropamide (8.3 mg/100 ml) to 139+/-6%, and tolazamide (3.1 mg/100 ml) to 119+/-6%. These effects were accentuated in the presence of 2.5 x 10(-4) M theophylline and were not blocked by 1 x 10(-5) M propranolol. Adenyl cyclase was activated by each of these drugs at concentrations below those which increase contractility. The drugs also increased the rate and slope of phase 4 depolarization in spontaneously beating Purkinje fibers, but did not alter the spontaneous rate of isolated rabbit atria. Since inotropic and chronotropic stimulation can be deleterious in some clinical settings, these findings may be of significance in interpretation of cardiovascular mortality data.

Ion effects on calcium accumulation by cardiac sarcoplasmic reticulum.

The effects of monovalent cations on the active calcium-accumulating ability of cardiac sarcoplasmic reticulum were assessed. Grana prepared in an ion-free system accumulated calcium when ATP and Mg(++) were present. Sodium ion and to a lesser extent lithium but not K(+) reduced the amount of calcium taken up. The reduction of calcium binding by Na(+) is not due to inhibition of uptake but to a rapid release of the radiocalcium bound. The amount of calcium released by sodium does not appear to be enough to explain contraction on the basis of sodium influx into muscle, but may be significant in the regulation of tension.

Calcium and adenosine triphosphate binding to renal membranes.

Calcium binds to membranous structures isolated from rabbit kidney cortex homogenates. The binding is enhanced by ATP and Mg(++) in combination. Other nucleotides, ITP and GTP, do not have this property. In contrast to similar preparations of nerve and muscle, the binding is not augmented by oxalate (3-100 mM). Also, binding of calcium cannot be correlated with ATP hydrolysis. p-Chloromercuribenzoate and the mercurial diuretic agent mercaptomerin inhibit the binding of calcium. This system can be distinguished from the binding of calcium by mitochondria by lack of azide inhibition and by failure of ADP-succinate to substitute for ATP. (14)C- and gamma-(32)P-labeled ATP bind to the renal membranes in the absence of calcium, but only the (32)P binding increases when calcium is added. The ratio of (32)P bound to (45)Ca bound is 2:1. The above data are consistent with a hypothesis that calcium is metabolically bound to renal membranes and that this binding is associated with membrane phosphorylation. Such a formulation may have pertinence to the conformational state of renal membranes and subsequent permeability characteristics. It also allows for the concept that membrane stability requires metabolic participation, as well as calcium ions.

Ethnic differences in mini-mental state examination (MMSE) scores: where you live makes a difference.

OBJECTIVES: To examine differences in correlates of the Mini-Mental State Examination (MMSE) in a population-based sample of older Mexican Americans and European Americans and to provide empirical validation of the MMSE as an indicator of cognitive impairment in survey research in older Mexican Americans by comparing MMSE classification against performance on timed tasks with varying levels of cognitive demand. DESIGN: A population-based cross-sectional study. SETTING: Trained bilingual staff administered the MMSE as part of the San Antonio Longitudinal Study of Aging (SALSA) home-based assessment battery. PARTICIPANTS: 827 community-dwelling Mexican Americans and European Americans, 65 and older, residing in three socioeconomically and culturally distinct neighborhoods (barrio, transitional, suburban). MEASUREMENTS: The MMSE was compared against a variety of demographic, biomedical, and sociocultural variables ascertained by self-report and against performance-based measures of functional tasks representing varying levels of cognitive demand (Structured Assessment of Independent Living Skills (SAILS) subscales for food manipulation and money management). RESULTS: Mexican Americans were 2.2 times more likely than European Americans to have MMSE scores <24. Multiple logistic regression analysis revealed that neighborhood was an independent predictor of low MMSE scores in Mexican Americans, with the relationship between ethnic group and MMSE explained by neighborhood. After adjusting for neighborhood type, no differences were noted between Mexican Americans and European Americans. Independent of other factors examined, low education was associated with low MMSE scores in both Mexican Americans and European Americans. Mexican Americans with MMSE scores <24 took significantly longer to complete four out of five performance-based food manipulation tasks and all three money management tasks. CONCLUSIONS: Neighborhood type was a predictor of cognitive impairment. Education affected MMSE scores similarly in both ethnic groups. MMSE scores <24, indicative of cognitive impairment, were uniformly associated with functional impairment in both the Mexican Americans and European Americans. Among older Mexican Americans, MMSE-classified cognitive impairment was significantly associated with poorer performance on timed tasks with varying levels of cognitive demand independent of other correlates. A similar pattern of association was observed in European Americans. Thus, the MMSE appears to be a valid indicator of cognitive impairment in survey research in both older Mexican Americans and European Americans.

Prevalence, incidence, and risk factors associated with hip fractures in community-dwelling older Mexican Americans: results of the Hispanic EPESE study. Establish Population for the Epidemiologic Study for the Elderly.

OBJECTIVES: To determine the rates and risk factors associated with hip fractures in the community-dwelling older Mexican-American population. DESIGN: A prospective survey of a regional probability sample of older Mexican Americans aged 65 and over. SETTING: The 1993-1996 Hispanic Established Population for the Epidemiologic Study of the Elderly (H-EPESE), a probability sample of noninstitutionalized Mexican Americans, aged 65 and over, living in the Southwestern states of Texas, New Mexico, Colorado, Arizona, and California. PARTICIPANTS: In 1993-1994 and in 1995-1996, 2895 persons, aged 65 and over, considered Mexican American, were selected at baseline as a weighted probability sample. Sample weights were used to extrapolate to the estimated 498,176 older Mexican Americans residing in the Southwest US. MEASUREMENTS: Self-reported hip fracture and functional measures by in home interviews. RESULTS: Hip fracture prevalence was 4.0% at baseline. The overall incidence of hip fractures for women was 9.1 fractures/1000 person-years. The incidence rate for men was 4.8 fractures/1000 person-years. Extrapolation from these data to the entire older Mexican American population indicated that approximately 5162 new fractures occurred in the population during the 2 year study period. In women, hip fractures were associated independently with advanced age, not being married/living alone, having had a stroke, limitations with activities of daily living and instrumental activities of daily living. In men, only the latter limitations were associated independently with hip fracture. CONCLUSIONS: This study indicates that older Mexican American people may have hip fracture incidence rates that place them at highest risk among the Hispanic subgroups. In light of a sparse literature on this population, the fracture estimates derived from this work contributes to our understanding of the true fracture estimates in this population. Based on the extrapolated population rates, hip fracture in this population is a significant public health problem. Adequate preventive measures need to be implemented in this growing US population.

New-onset incontinence and markers of frailty: data from the Hispanic Established Populations for Epidemiologic Studies of the Elderly.

BACKGROUND: Urinary incontinence in older adults has many distinct etiologies and is associated with lower self-reported health. However, it is unclear whether the new onset of urinary incontinence marks newly emergent frailty. METHODS: Using a longitudinal population-based survey of older Mexican Americans (N = 2660) across five south-western states, this study compared the strength of association between markers of physical frailty such as activities of daily living (ADLs), instrumental activities of daily living (IADLs), and performance (timed walk, timed chair rise, and tandem balance) with baseline incontinence (prevalent disease) and new-onset incontinence (incident disease). RESULTS: We found that 14.1% of the participants (n = 329) were incontinent at baseline (prevalent cases) and 11.6% (n = 208) were newly incontinent 2 years later (incident cases). Controlling for other covariates, prevalent incontinence was only associated with a 60% increased risk of having difficulty walking 8 ft. Incident incontinence was associated with a twofold increased risk of impairment in ADLs and IADLs, and poor performance on all three physical measures. CONCLUSIONS: Incident incontinence is associated with an increased risk of more global functional impairment. Thus, incident disease may be an important early marker for signaling the onset of frailty among persons who become incontinent after the age of 65 years.

Pharmacokinetics of prazosin in man.

Prazosin was administered orally to 24 normotensive human subjects in the form of capsules or as a solution. Plasma concentrations indicate that drug is almost completely bioavailable from the capsules, although levels peak more slowly than from drug in solution. Drug leaves plasma with a half-life of approximately 2.3 hours. Examination of data from each subject on repeated dosing indicates considerable intrasubject consistency in pharmacokinetic response despite intersubject variability. The absence of the pharmacologically active metabolites in plasma suggests that the hypotensive response derives from drug only. Prazosin is bound to human plasma proteins to the extent of 97%.

The effects of amrinone on contractility, Ca2+ uptake and cAMP in smooth muscle.

Amrinone, a known positive inotropic agent in the heart, was found to cause a dose-dependent (10--100 micrograms/ml) inhibition of norepinephrine (NE) or high-K+-induced contractions of rabbit aorta. Amrinone also inhibited carbachol or high-K+-induced contractions of guinea-pig taenia coli. Neither total tissue 45Ca uptake nor the rate of 45Ca uptake induced by 80 mM K+ in rabbit aorta was altered by pretreatment with amrinone. On the other hand, a similar pretreatment with amrinone inhibited NE (10(-6) or 10(-5) M) induced tissue 45Ca uptake. Amrinone (100 micrograms/ml) caused about a 70% increase in cAMP concentration over resting levels. It is concluded that amrinone causes a nonspecific inhibition of smooth muscle contractility by acting probably at multiple sites to decrease the availability of Ca2+ required for activation. One or more of these mechanisms may involve cAMP.

Factors influencing comparative bioavailability of spironolactone tablets.

The bioavailability of spironolactone from 10 tablet formulations, selected to provide a wide range of specifications and in vitro dissolution rates, was assessed from the plasma and urinary levels of its major unconjugated metabolite, canrenone, in a study of balanced incomplete block design using 11 healthy subjects. Significant but weak correlations existed between the amount of spironolactone in solution at 40 min in vitro and the area under the plasma concentration-time curve for canrenone and urinary canrenone excretion. The correlations between in vitro dissolution and bioavailability parameters appeared to be weakened by two tablet formulations, one with dibasic calcium phosphate as the principal excipient and the other formulated from micronized spironolactone bulk drug. Measurement of in vitro dissolution of spironolactone tablets is of value for quality control purposes, provided no major alteration is made in the formulation.

Bioavailability and pharmacokinetics of norethisterone in women after oral doses of ethynodiol diacetate.

Measurement by radioimmunoassay of plasma norethisterone (NE) has been used to compare the bioavailability of tablets containing ethynodiol diacetate (EDA) with that of a standard oral solution of this progestogen in 12 normal women. The tablets investigated were from three batches which showed different in vitro dissolution rates. There were no significant differences in the bioavailability of the tablet formulations, which were essentially bioequivalent to the solution. Peak blood levels of NE were reached within 4h of EDA administration in solution or tablets. After the peak, NE plasma levels declined in two phases, with a mean terminal elimination half lives of 4 to 6.9h. The pharmacokinetics of NE after EDA administration showed some similarity to those observed by other workers after oral doses of NE itself.

PIP: Bioavailability and pharmacokinetics of norethisterone (NE) were studied in 12 women, aged 21-37 years, after oral doses of ethynodiol diacetate (EDA). Plasma NE levels, measured by radioimmunoassay, were used to compare the bioavailability of EDA tablets (Ovulen 50; 1 mg EDA plus .05 mg ethinyl estradiol) with that of a standard oral solution of EDA. The 3 different batches of tablets studied showed different in vitro dissolution rates, 82.6%, 94.6%, and 99% at 3 hours. No marked differences were seen in the bioavailability of the tablet formulations, which were essentially bioequivalent to the solution. Peak plasma NE levels were reached within 4 hours of EDA administration in solution or tablets. Following the peak, NE plasma levels declined in 2 phases, with mean terminal elimination 1/2-lives of 4-6.9 hours. These results have shown that small variations in in vitro dissolution rates do not affect the bioavailability of NE from tablets containing EDA.

A measurement model of adolescent smoking.

Self report measures of smoking may contain substantial measurement error. If these errors are nonrandom, then they may be correlated with substantive variables in epidemiologic or intervention studies, thus confounding and biasing estimates of structural relations. In efforts to circumvent such bias, investigators have supplemented questionnaires with biological indicators of exposure to tobacco smoke. However, errors in biological indicators may also include systematic errors that produce biased estimates. The current study was designed to estimate the variance of systematic and random errors in self report and two biologic measures of smoking in adolescents. A linear model was fit to data from 342 males and 250 females with repeated measures separated by 1 year. Thiocyanate and self report were found to have substantial nonrandom error components that were correlated with psychosocial variables. In contrast, errors in carbon monoxide in expired air were not autocorrelated, and were uncorrelated with psychosocial variables.

Patterns of prescription drug utilization in elder Mexican Americans: results from the Hispanic EPESE Study. Established Population for the Epidemiologic Study of the Elderly.

The objective of this study was to determine the patterns of prescription medication usage among community-dwelling Mexican-American elders. This was a cross-sectional survey of a regional probability sample of 2,895 community-dwelling Mexican Americans, aged 65 and over. Of the sample, 58.1% used at least one prescribed medication within the two weeks prior to their participation in the study. Women were significantly more likely than men to use analgesics, non-steroidal anti-inflammatory agents, prescription nutritional supplements, and other central nervous system and endocrine medications. Subjects aged 75 and over were more likely to use cardiovascular medications, nutritional supplements, ophthalmic preparations and antihistamines, while those in the age groups 65-69 and 70-74 were more likely to use hypoglycemic and endocrine medications. Interestingly, there was a significantly decreased usage of hypoglycemic medications in the older age group (aged 75 and over) as compared with the younger age groups (65-69 and 69-74). This may indicate that Mexican American elders are dying at younger ages from complications related to diabetes mellitus and are not alive to use hypoglycemic medications at ages 75 and over. Also, men used more hypoglycemic medication than women (77% vs 70%). There was no relationship between use of medication and severity of diabetic illness.

Effects of a psychosocial intervention on survival among patients with stage I breast and prostate cancer: a matched case-control study.

CONTEXT: Psychosocial factors have been linked to the development and progression of cancer and shown to be relevant in cancer care. However, the evidence that psychosocial interventions affect cancer survival is less conclusive. Few methodologically sound studies have addressed this issue. OBJECTIVE: To investigate the effects of a 6-week psychosocial intervention on survival among patients with stage I breast and prostate cancer. DESIGN: Matched case-control. SETTING: 3 rural hospitals or cancer centers in central Pennsylvania. PATIENTS: 21 breast and 29 prostate stage I cancer patients (treatment group) matched with 74 breast and 65 prostate stage I cancer patients from the same hospitals who did not receive the intervention (control group). INTERVENTION: Six 2-hour health psychology classes conducted by a licensed staff psychologist. MAIN OUTCOME MEASURES: Survival time was compared between the 2 groups and with national norms. RESULTS: The intervention group lived significantly longer than did matched controls. At 4- to 7-year follow-up (median = 4.2 years), none of the breast cancer patients in the intervention group died, whereas 12% of those in the control group died. Twice as many matched-control prostate cancer patients died compared with those in the intervention group (28% vs 14%). Control group survival was similar to national norms. CONCLUSIONS: These results are consistent with prior clinical trials and suggest that short-term psychosocial interventions that encourage the expression of emotions, provide social support, and teach coping skills can influence survival among cancer patients. However, self-selection bias cannot be ruled out as an alternative explanation for the results. These interventions merit further consideration and research.

The use of 22Na as a tracer for long-term bone mineral turnover studies.

Sodium-22 has been studied as a tracer for bone mineral metabolism in rats and dogs. When incorporated into bone during growth from birth to adulthood, the bone becomes uniformly tagged with 22Na, which is released through the metabolic turnover of the bone. The 22Na not incorporated in the bone matrix is rapidly excreted within a few days when animals are fed high, but nontoxic levels of NaCl. The 22Na tracer can be used to measure bone mineral loss in animals during space flight and in research on bone disease.

Disposition of pranolium chloride in dogs, baboons and monkeys.

The general disposition of [14C]-Pranolium Chloride (SC-27761), a potential anti-arrhythmic agent, has been studied in the beagle dog, baboon and rhesus monkey. The compound was moderately absorbed from the gastro-intestinal tract of the three species at 5 mg/kg. There was appreciable inter-animal variation in the amount of absorption, and the absorption was dose-dependent in the monkey. After i.v. dosage the radioactivity was largely cleared via the kidneys. The initial elimination half-lives for Pranolium in the dog and primate were between 0.6 to 3.1 hours after i.v. dosage, but could not be determined after oral dosage. Less than 1% of the dose was localised in monkey fetal tissues, two hours after an i.v. dose was given to pregnant female rhesus monkeys, and the highest concentrations of radiolabel were detected in fetal liver. Pranolium was found to be extensively metabolised and 1-naphthol was identified as a major metabolite. Pranolium was excreted in urine both unchanged and as conjugates, but 1-naphthol was excreted largely as conjugates.

Plasma levels and urinary excretion of orally administered propantheline bromide in man.

After a single oral dose of 30 or 60 mg of propantheline bromide peak plasma levels of the drug were reached within 2 h in six healthy men. Mean peak plasma concentrations were 20.6 and 53.1 ng/ml after 30 mg and 60 mg respectively. The mean apparent absorption and elimination half-lives after 30 mg dose were 0.22 and 1.57 h respectively, and similar half-lives were found at the higher dose level. There was a dose related change in plasma levels and AUCinfinity of the drug, and some 3% to 4% of the administered dose of propantheline bromide was excreted unchanged in urine at each dose level. Comparison of the plasma levels and urinary excretion of the drug with those seen after i.v. administration in an earlier study indicated an apparently low systemic availability of orally administered propantheline bromide. There was tentative evidence of a qualitative relationship between the oral dose administered, plasma concentrations and the effects of propantheline bromide on salivary excretion.

Street youth, their peer group affiliation and differences according to residential status, subsistence patterns, and use of services.

This study characterizes subcultural differences within an inner-city street youth population. Variations in residential status, subsistence patterns, and service utilization according to peer group affiliation were explored. A brief structured interview was administered to 752 youth, ages 12 to 23 years, who had been living on the streets for two or more consecutive months, or who were fully integrated into the "street economy." Subjects were recruited for the study using a stratified probability sampling design, with 30% recruited from community-based service sites and 70% from street locations and at natural "hang-outs." Five street youth groups were identified: "punks/skinheads," "druggies," "hustlers," "gang members," and "loners." The results demonstrated unique patterns with respect to places stayed/slept, means of financial support and economic subsistence, and use of available services according to peer group affiliation. The implications of these findings and recommendations for future research and service provision are discussed.