Effect of lowering dietary calcium intake on fractional whole body calcium retention.

Although fractional calcium absorption is known to vary inversely with calcium intake, the extent and timing of individual hormonal and calcium absorption responses to altered calcium intake have not been defined. We measured fractional whole body retention of orally ingested 47Ca, an index of calcium absorption, in nine normal women after they had eaten a 2000-mg calcium diet for 8 weeks and a 300-mg calcium diet for 1, 2, 4, and 8 weeks. After the diet change, serum intact PTH (32.2% increase; P = 0.005), serum 1,25-dihydroxyvitamin D [1,25-(OH)2D; 43.8% increase; P = 0.003], and fractional whole body calcium retention (42.8% increase; P = 0.004) increased within 1 week. Although the PTH and calcium retention responses remained fairly constant throughout the low calcium intake period, serum 1,25-(OH)2D concentrations declined toward baseline after week 1. Thus, the late increase in calcium retention may have resulted from calcium absorption that was independent of 1,25-(OH)2D stimulation.

Studies on the mechanism of inhibition of hepatic cAMP accumulation by vasopressin.

Vasopressin elicited a dose-dependent inhibition of glucagon-induced cAMP accumulation in isolated hepatocytes. This response was not diminished by incubation of cells with the calmodulin antagonists trifluoperazine or chlorpromazine and was only slightly reduced in Ca2+-depleted hepatocytes. Half-maximal inhibition of cAMP accumulation occurred at 8 X 10(-11) M vasopressin, a dose which does not increase cytosolic Ca2+ in hepatocytes. Direct activation of adenylate cyclase by forskolin was significantly inhibited by vasopressin in Ca2+-depleted cells. It is concluded that inhibition of hormone-induced cAMP accumulation by vasopressin in liver is not dependent on cellular Ca2+ mobilisation but may involve direct inhibition of adenylate cyclase.

Dietary calcium intake and bone loss from the spine in healthy postmenopausal women.

Controversy exists over the relationship between calcium intake and axial bone loss. We measured bone density of the spine (L2-4) by dual photon absorptiometry (DPA) two times, 7 mo apart, in 76 healthy postmenopausal women aged 40-70 y. Ca intake was assessed by food-frequency questionnaire. Women with a Ca intake less than 405 mg/d lost spine density at a rate that was significantly greater than that of women with an intake greater than 777 mg/d, p = 0.026. There appears to be a threshold of Ca intake below which increased Ca in the diet is likely to be beneficial in reducing spine mineral loss.

Synthesis of N-substituted 4-(4-hydroxyphenyl)piperidines, 4-(4-hydroxybenzyl)piperidines, and (+/-)-3-(4-hydroxyphenyl)pyrrolidines: selective antagonists at the 1A/2B NMDA receptor subtype.

Antagonists at the 1A/2B subtype of the NMDA receptor (NR1A/2B) are typically small molecules that consist of a 4-benzyl- or a 4-phenylpiperidine with an omega-phenylalkyl substituent on the heterocyclic nitrogen. Many of these antagonists, for example ifenprodil (1), incorporate a 4-hydroxy substituent on the omega-phenyl group. In this study, the position of this 4-hydroxy substituent was transferred from the omega-phenyl group to the benzyl or phenyl group located on the 4-position of the piperidine ring. Analogues incorporating pyrrolidine in lieu of piperidine were also prepared. Electrical recordings using cloned receptors expressed in Xenopus oocytes show that high-potency antagonists at the NR1A/2B subtype are obtained employing N-(omega-phenylalkyl)-substituted 4-(4-hydroxyphenyl)piperidine, 4-(4-hydroxybenzyl)piperidine, and (+/-)-3-(4-hydroxyphenyl)pyrrolidine as exemplified by 21 (IC(50) = 0.022 microM), 33 (IC(50) = 0.059 microM), and 40 (IC(50) = 0.017 microM), respectively. These high-potency antagonists are >1000 times more potent at the NR1A/2B subtype than at either the NR1A/2A or NR1A/2C subtypes. The binding affinities of 21 at alpha(1)-adrenergic receptors ([(3)H]prazosin, IC(50) = 0.54 microM) and dopamine D2 receptors ([(3)H]raclopride, IC(50) = 1.2 microM) are reduced by incorporating a hydroxy group onto the 4-position of the piperidine ring and the beta-carbon of the N-alkyl spacer to give (+/-)-27: IC(50) NR1A/2B, 0.026; alpha(1), 14; D2, 105 microM. The high-potency phenolic antagonist 21 and its low-potency O-methylated analogue 18 are both potent anticonvulsants in a mouse maximal electroshock-induced seizure (MES) study (ED(50) (iv) = 0.23 and 0.56 mg/kg, respectively). These data indicate that such compounds penetrate the blood-brain barrier but their MES activity may not be related to NMDA receptor antagonism.

A comparison of the Charlson comorbidity index derived from medical record data and administrative billing data.

The objective of this article is to compare the Charlson comorbidity index derived from medical record data (Chart Index) with the same index derived from billing data (ICD-9 Index) to determine how well each predicted inpatient and 30-day mortality, length of stay, and complications among Medicare beneficiaries hospitalized for carotid endarterectomy. Economic and time constraints have increased the need for risk adjusters derived from administrative data, yet few studies have compared these measures with those derived from chart review. Using logistic regression, the Chart Index was found to be a significant predictor of inpatient mortality, 30-day mortality, length of stay, and complications, after controlling for age, gender, and neurologic and medical risk factors (P values = 0.004, 0.056, 0.0001, and 0.042, respectively). The ICD-9 Index approached significance as a predictor of the outcomes (P values = 0.092, 0.100, 0.093, and 0.080, respectively). The Chart Index was shown to be superior to the ICD-9 Index within this patient sample.

Analysis of variations in mortality rates with small numbers.

OBJECTIVE: We present a Monte Carlo technique to evaluate if observed mortality rates differ from model-predicted rates for situations when the number of deaths is small. DATA SOURCES: We used Medicare hospital claims and model-predicted mortality rates from the Health Care Financing Administration (HCFA) for the 169 acute care hospitals in Georgia. The HCFA data provided model-predicted mortality rates at 30 days postadmission for 17 conditions and procedures of interest. The model-predicted rates calculated by HCFA were adjusted for patient factors, including demographic characteristics, principal diagnosis, and comorbidities. STUDY DESIGN: We test the hypothesis that model-predicted 30-day mortality rates at the 169 hospitals differ significantly from the observed 30-day mortality rates. Our approach uses a test statistic that resembles a chi-square statistic, and Monte Carlo simulations to estimate the distribution of the test statistic under the null hypothesis of no differences between the observed and predicted rates. We illustrate the method using two conceptually similar simulation models. We use results of the simulations to estimate p-values and compare these results with p-values associated with the nominal chi-square distribution. DATA EXTRACTION METHODS: We extracted 30-day observed and predicted mortality rates for Medicare beneficiaries for federal fiscal year 1990 for 17 conditions and procedures of interest. PRINCIPAL FINDINGS: If the number of deaths in some hospitals is small, p-values calculated using the nominal chi-square distribution can be misleading, thus supporting the usefulness of our simulation method. CONCLUSIONS: The Monte Carlo simulation is an appropriate approach to the analysis of hospital mortality or small area analysis for situations in which the number of deaths is small.

Initial antibiotic management of community acquired pneumonia.

The purpose of this study, conducted by the MAG, the CARE program of the GHA, and the GMCF, is to describe the initial antibiotic management of community acquired pneumonia among hospitalized patients in Georgia and to compare these patterns of care with those recommended by the American Thoracic Society guidelines.

Salmonellae from dogs in Vom, Northern Nigeria.

Examination by culture of single faecal samples from 120 domestic dogs in the Vom area of Nigeria showed 22 (18 per cent) of the animals to be excreting Salmonella organisms. One of the dogs yielded two and another three different serotypes. The total number of Salmonella serotypes isolated in the survey was 21. Dogs may be important in Nigeria as agents for the transmission of salmonellosis to man and domestic livestock.

Measurement of 47calcium retention with a whole-body counter.

A method for measuring the retention of orally administered 47Ca using a whole-body counter (WBC) is described. One microcurie 47Ca in 90 ml of lowfat milk was given along with 5 microCi 51Cr as a stool marker. The retention of 47Ca was determined at 7 days if less than 2% of the administered 51Cr was present in the body. Correlation between calcium retention by the whole-body-counting and the excreta-recovery methods was highly significant (r = 0.835, P less than 0.0001; N = 17). In 5 subjects, each studied twice while on constant self-selected diets, calcium retention was measured by the WBC method with a precision (standard deviation) of +/- 2.6% of the administered dose or +/- 13.9% of the mean retained fraction. Whole-body measurement of 47Ca retention has the advantages over other techniques that no collections of blood or stool are needed, no residency on a metabolic ward is required, and the radiation exposure (13 mrem) is so low that multiple studies may be performed in the same subject.

Bone density of the radius, spine, and hip in relation to percent of ideal body weight in postmenopausal women.

Bone mineral content (BMC) and bone mineral density (BMD) of the spine (L2-L4) and hip (at femoral neck, Ward's triangle, and greater trochanter sites) were determined by dual-photon absorptiometry (DPA), and of the radius by single-photon absorptiometry (SPA) in healthy postmenopausal women aged 40-70 years. The relationships of BMC and BMD to years since menopause were examined separately in 97 women who were above 115% of ideal body weight (IBW) and in 128 women below. The heavier women had significantly greater mean BMC and BMD at each site than did the normal-weight women. In the normal-weight women, there was a significant negative correlation between BMD and years since menopause at each measurement site except the greater trochanter. In the obese women, BMD decreased with increasing years since menopause at the radius site only and BMC declined with increasing years after menopause at the hip (femoral neck and Ward's triangle region) as well as the radius. Thus, body size is a significant determinant of BMD in this population. The pattern of loss of BMD from Ward's triangle and femoral neck regions of hip are similar to that of the spine. The BMC and BMD findings in the hip suggest that remodeling occurs at this weight-bearing site which has a favorable effect on bone strength.

Carotid endarterectomy among Medicare beneficiaries: a statewide evaluation of appropriateness and outcome.

BACKGROUND AND PURPOSE: We sought to examine the appropriateness and the surgical outcomes of carotid endarterectomy (CE) in unselected community hospitals to identify opportunities for improvement. METHODS: We performed a retrospective review of all CEs performed on Medicare beneficiaries in Georgia in 1993 (n = 1945). Conclusions regarding appropriateness were based on current guidelines as interpreted by a physician reviewer and were supported by the aggregate results of structured, blinded overreading by clinicians with relevant expertise. Adverse outcomes were confirmed and rated as to severity by a physician. Outcomes were correlated with demography, vascular anatomic findings, comorbidity, surgical techniques, and hospital characteristics. RESULTS: The majority of the patients (51%) were asymptomatic at presentation. CEs were performed appropriately in 96.1% of the cases in accordance with current guidelines. There was no significant difference in the rate of appropriateness between the symptomatic (96%) and the asymptomatic patients (96.4%). Survival without stroke or myocardial infarction (MI) was 94.3%. The 30-day mortality was 1.9%; moderate to severe strokes occurred in 1.8%, stroke-related death in 0.7%, MI in 1.1%, and MI-related death in 0.5%. Those hospitals performing <10 CEs in the observed year had a statistically significant higher morbidity and mortality as well as an increase in less severe complications such as hematomas, wound dehiscence, wound infection, and pneumonia than did hospitals with higher volume of CEs.. Older patients and women had statistically significantly higher morbidity and mortality. Patients with a Charlson Severity Index score of > or =1 had a risk for adverse outcomes 3.4 times higher than patients with a score of 0 after adjustment for age and sex. CONCLUSIONS: The great majority of CEs performed in Georgia on Medicare patients were appropriate, according to current guidelines. Slightly more than half of the patients were asymptomatic as defined in the Asymptomatic Carotid Atherosclerosis Study. In hospitals performing

The isolation of salmonellas from British pork sausages and sausage meat.

Between 1969 and 1974, 1467 packets (3309 samples) of pork sausages and sausage meat produced by two large and two medium sized manufacturers and several local butchers were examined for the presence of salmonellas. Of these, 435 packets (786 samples) were found to contain salmonellas, but there was a wide variation in the isolation rates according to the producer. The salmonella incidence in samples from several small and two medium sized producers was low (0-11%) while the results from the two large producers investigated showed a striking difference, the rate of salmonella contamination in the product of one was low (about 2%) and in that of the other consistently high (40-60%). A comparison of liquid enrichment media, incubation temperatures and selective agar media was also carried out to determine the most efficient combination for the isolation of salmonellas from minced meat products. The results showed that (a) incubation of enrichment cultures at 43 degrees C. yielded a consistently greater number of salmonella isolations that at 37 degrees C., regardless of plating medium, (b) tetrathionate broth A (Rolfe) was superior to selenite broth as en enrichment medium at both 37 and 43 degrees C. and (c) brilliant green agar gave better results than deoxycholate citrate sucrose agar and bismuth sulphite agar as a selective medium.

Antigenic relationships among type strains of Yersinia enterocolitica and those of Escherichia coli, Salmonella spp., and Shigella spp.

The antigenic type strains for Yersinia enterocolitica antigens O:1 to O:34 were examined and their antigenic relationships with the type strains of Escherichia coli, Shigella spp., and Salmonella spp. were determined. Y. enterocolitica O:5,27 was antigenically identical to E. coli O97 and Y. enterocolitica O:11 was antigenically identical to E. coli O98.

Precision of dual-photon absorptiometry.

Precision of dual-photon absorptiometry (DPA) measurements was determined in a lumbar spine phantom and in humans. Approximately half of the measurements were made before and half after a 153gadolinium source change. The phantom was measured with different amounts of acrylic, which simulates human soft tissue, in order to evaluate the influence of body thickness on bone mineral density (BMD). Results of scans analyzed with two software versions from Lunar Radiation Corp., the widely used 08B and a prototype 08C, are compared. DPA with a cold source significantly overestimated BMD in the phantom in the presence of large amounts (more than 25 cm) of soft tissue equivalent with version 08B but not with the newer version 08C. Similarly, in nine subjects, there was a significant decrease in spine BMD after a source change when scans were analyzed with version 08B (mean difference 0.026 g/cm2, P = 0.002) but not with 08C (0.01 g/cm2, P = 0.234). No systematic effect of source change on femoral BMD measurements was observed. The SD of the mean difference of two measurements of the nine subjects was 0.019 g/cm2 (1.6% of the mean value) for the spine with software version 08B and 0.024 g/cm2 (2.0%) with version 08C, 0.03 g/cm2 (3.3%) for the femur neck, 0.03 g/cm2 (4.0%) for the greater trochanter, and 0.04 g/cm2 (4.9%) for Ward's triangle region of the proximal femur. The spine phantom was scanned on two other commercial bone densitometers in order to assess inter-instrument variation.(ABSTRACT TRUNCATED AT 250 WORDS)