Vitamin D and its Major Metabolites: Serum Levels after Graded Oral Dosing in Healthy Men

We determined the quantitative relationships between graded oral dosing with vitamin D₃, 25(OH)D₃, and 1,25(OH)₂D₃ for short treatment periods and changes in circulating levels of these substances. The subjects were 116 healthy men (mean age, 28 + 4 years, with usual milk consumption of 40.47 l/day and mean serum 25(OH)D of 67 + 25 nmol/l). They were distributed among nine open-label treatment groups: vitamin D₃ (25, 250 or 1250 mg/day for 8 weeks), 25(OH)D₃ (10, 20 or 50 mg/day for 4 weeks) and 1,25(OH)₂D₃ (0.5, 1.0 or 1.0 mg/day for 2 weeks). All treatment occurred between January 3 and April 3. We measured fasting serum calcium, parathyroid hormone, vitamin D₃, 25(OH)D and 1,25(OH)₂D immediately before and after treatment. In the three groups treated with vitamin D₃, mean values for circulating vitamin D₃ increased by 13, 137 and 883 nmol/l and serum 25(OH)D increased by 29, 146 and 643 nmol/l for the three dosage groups, respectively. Treatment with 25(OH)D₃ increased circulating 25(OH)D by 40, 76 and 206 nmol/l, respectively. Neither compound changed serum 1,25(OH)₂D levels. However, treatment with 1,25(OH)₂D₃ increased circulating 1,25(OH)₂D by 10, 46 and 60 pmol/l, respectively. Slopes calculated from these data allow the following estimates of mean treatment effects for typical dosage units in healthy 70-kg adults: an 8-week course of vitamin D₃ at 10 mg/day (400 IU/day) would raise serum vitamin D by 9 nmol/l and serum 25(OH)D by 11 nmol/l; a 4-week course of 25(OH)D₃ at 20 mg/day would raise serum 25(OH)D by 94 nmol/l; and a 2-week course of 1,25(OH)₂D₃ at 0.5 mg/day would raise serum 1,25(OH)₂D by 17 pmol/l. Received: 4 August 1997 / Accepted: 14 October 1997     

Meal effects on calcium absorption

The effect of coingestion of a meal on calcium absorption efficiency was investigated using Ca carbonate, milk, and a new Ca delivery system, CCM. Six experiments with 168 rats and two experiments with 46 normal young women showed that coingestion of a light meal of varied composition enhanced absorption efficiency from all three sources by 10-30% above levels achieved when the test load was ingested without other foods. The differences taken as a whole were highly statistically significant.     

25-Hydroxyvitamin D in the Range of 20 to 100 ng/mL and Incidence of Kidney Stones

Objectives. Increasing 25-hydroxyvitamin D serum levels can prevent a wide range of diseases. There is a concern about increasing kidney stone risk with vitamin D supplementation. We used GrassrootsHealth data to examine the relationship between vitamin D status and kidney stone incidence.Methods. The study included 2012 participants followed prospectively for a median of 19 months. Thirteen individuals self-reported kidney stones during the study period. Multivariate logistic regression was applied to assess the association between vitamin D status and kidney stones.Results. We found no statistically significant association between serum 25-hydroxyvitamin D and kidney stones (P = .42). Body mass index was significantly associated with kidney stone risk (odds ratio = 3.5; 95% confidence interval = 1.1, 11.3).Conclusions. We concluded that a serum 25-hydroxyvitamin D level of 20 to 100 nanograms per milliliter has no significant association with kidney stone incidence.An issue of possible concern related to the use of vitamin D supplementation is a reported increase in risk of kidney stones.1 Mounting evidence indicates that a 25-hydroxyvitamin D (25[OH]D) serum level in the range of 40 to 60 nanograms per milliliter (ng/mL) is needed for substantial reduction in risk of a wide range of diseases including breast cancer,2 colorectal cancer,3 multiple sclerosis,4 and type 1 diabetes.5,6 However, few people can achieve 25(OH)D in the range higher than 40 ng/mL without supplementation.7GrassrootsHealth is a nonprofit public health research organization that runs a large population cohort study of participants who reach and sustain, if desired, a 25(OH)D serum level of their choice and tracking subsequent health outcomes. GrassrootsHealth has assembled a database that includes information on serum 25(OH)D concentrations, demographic characteristics, and health status measures. These data include values from 5552 individuals with daily supplemental intakes averaging 3600 international units (IU) per day and an average 25(OH)D level of 45 ng/mL, which is higher than the ranges found in most other cohorts.2,4In this study we investigated whether serum 25(OH)D concentration in the range of 20 to 100 ng/mL was associated with incidence of kidney stones in all participants who provided data at 2 or more sampling times.     

Sensory neuropeptides induce histamine release from bronchoalveolar lavage cells in both nonasthmatic coughers and cough variant asthmatics

BACKGROUND: Sensory neuropeptides have been suggested to play a role in the pathogenesis of a number of respiratory diseases including asthma and chronic non-productive cough. OBJECTIVES: To investigate the action of sensory neuropeptides on airway mast cells obtained by bronchoalveolar lavage (BAL). METHODS: BAL was performed on 23 nonasthmatic patients with cough (NAC), 11 patients with cough variant asthma (CVA) and 10 nonatopic controls. Washed lavage cells were stimulated (20 min, 37 degrees C) with calcitonin gene-related peptide (CGRP), neurokinin A (NKA) and substance P (25 and 50 micromol/L). RESULTS: The neuropeptides tested induced histamine release in all groups studied. Only CGRP (50 micromol/L) induced significantly more histamine release from both NAC and CVA patients compared with control subjects (P = 0.038 and 0.045, respectively). CONCLUSION: Regardless of aetiology, mast cells from patients with chronic cough appear to have an increased responsiveness to CGRP compared with controls. The results of the present study suggest that the role of CGRP in chronic cough should be further investigated.     

Measuring quality in general practice. Pilot study of a needs,process and outcome measure.

1. As part of the Scottish Shadow Fundholding Evaluation (1990-92), quality of care was assessed in 6 practices with 49 general practitioners using a pre-consultation health needs questionnaire, consultation length as a process measure (previously shown to be a proxy measure for quality) and a post-consultation satisfaction/outcome measure which contained a subset of six questions assessing whether patients felt enabled by their consultation. This report describes secondary analysis of the available dataset undertaken to explore whether the approach used to evaluate quality of care for patients with specific clinical problems could be extended to the generality of general practice consultations. 2. Chapters 1 and 2 of the report describe earlier work developing both the concepts and instruments used in the Shadow Evaluation, and general findings already reported. The reliability and the construct validity of the measure of enablement are examined and found to be satisfactory. 3. Strong correlations between more time at consultations and more enablement for more patients are found at population level for patients with psychological problems, with social problems and with physical problems. More complex problems require more time to achieve equal benefit. 4. Mean consultation length and mean enablement score correlate well with each other and can be used as summary statistics of quality. Where trends require explanation or exploration, other measures of the use of time and the level of benefit gained are more helpful; both sets of analyses can be derived from the same datasets (Chapter 3). 5. Analyses at practice level show that practices which spend more time at consultations enable patients more whatever the nature of problems presented. The rank orders of time spent at consultation and of enablement are highly correlated (Chapter 4). 6. Analyses at doctor level show that doctors who spend more time at consultations enable patients more and that those who spend less time enable patients less. The numbers of patients available for study were not sufficient to explore this association within subgroups of clinical presentations. As in previous studies, we found that doctors who take longer time are likely to be more patient centred, and those who take less time are likely to be less patient centred. Case-mix varies between doctors, but seems to be independent of whether a doctor is more or less patient centred (Chapter 5). 7. The methods developed in this study give useful insights into the definition and delivery of quality of care in general practice (Chapter 6). The measures now need to be tested in different clinical, cultural and organizational settings and results compared with those found using routinely available NHS data on prescribing and achievement of other clinical and management targets (Chapter 7).     

Evaluation of smoking prohibition policy in a health maintenance organization.

Four months after Group Health Cooperative of Puget Sound adopted a policy prohibiting smoking in its 35 facilities, we assessed attitudes and behavior of a sample of 447 employees. Results indicated that 85 per cent of employees approved of the decision to go smoke-free, the rate of reported smoking decreased, and a large proportion of non-smokers believed that their own and co-workers' work performance had improved. Suggestions for successful implementation of future programs are provided.     

Effects of caffeine on bone and the calcium economy.

Caffeine-containing beverage consumption has been reported to be associated with reduced bone mass and increased fracture risk in some, but not most, observational studies. Human physiological studies and controlled balance studies show a clear but only a very small depressant effect of caffeine itself on intestinal calcium absorption, and no effect on total 24-h urinary calcium excretion. The epidemiologic studies showing a negative effect may be explained in part by an inverse relationship between consumption of milk and caffeine-containing beverages. Low calcium intake is clearly linked to skeletal fragility, and it is likely that a high caffeine intake is often a marker for a low calcium intake. The negative effect of caffeine on calcium absorption is small enough to be fully offset by as little as 1-2 tablespoons of milk. All of the observations implicating caffeine-containing beverages as a risk factor for osteoporosis have been made in populations consuming substantially less than optimal calcium intakes. There is no evidence that caffeine has any harmful effect on bone status or on the calcium economy in individuals who ingest the currently recommended daily allowances of calcium.     

Safe and cost effective use of alteplase for the clearance of occluded central venous access devices.

PURPOSE: To determine whether cryopreserved solutions of the thrombolytic agent alteplase could be used as a safe, effective, and economically reasonable alternative to urokinase in patients presenting with occluded central venous access devices (CVADs). MATERIALS AND METHODS: Alteplase has been reported as an efficacious alternative to urokinase for treatment of occluded CVADs. However, the practicality of using alteplase as the thrombolytic of choice for this indication remained conjectural. To make this approach economically feasible, alteplase was diluted to 1 mg/mL and 2.5-mL aliquots were stored at -20 degrees C until use. A need to confirm that the cryopreserving and thawing of the reconstituted solution did not compromise the safety and efficacy reported from prior trials was recognized. A quality assessment initiative was undertaken to concurrently monitor the safety and efficacy of this approach. Patients presenting with occluded CVADs received a sufficient volume of the thawed alteplase solution to fill the occluded catheter(s). Data, including efficacy, adverse reactions, dwell time, and catheter type, were collected over a 5-month period. RESULTS: One hundred twenty-one patients accounting for 168 attempted clearances were assessable for safety and efficacy. One hundred thirty-six (81%) of the 168 catheter clearance attempts resulted in successful catheter clearance (95% confidence interval, 74% to 86%). No adverse events were reported. CONCLUSION: Cryopreserved 1-mg/mL aliquots of alteplase are safe and effective in the clearance of occluded CVADs when stored at -20 degrees C for 30 days. The ability to cryopreserve alteplase aliquots makes it an economically reasonable alternative to urokinase in the setting of CVAD occlusion.