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Biomedical subjects

M C Haven

Publications and source records attributed to M C Haven.

At least 19 recordsLinked to original sources

Effects of nicotine on bone and calciotropic hormones in aged ovariectomized rats.

The objective of this investigation was to assess the effects of chronic nicotine administration on bone status and serum calcium and calciotropic hormone levels in aged, estrogen-replete (intact, sham-operated) and estrogen-deplete (ovariectomized) female rats. Eight-month-old sham-operated (sham) and ovariectomized (ovx) retired breeder rats were maintained untreated for 3 months to allow for the development of osteopenia in the ovx group. The animals were then administered either saline, low dose nicotine (6.0 mg/kg/day), or high dose nicotine (9.0 mg/kg/day) via osmotic minipumps for 3 months. Blood was drawn at necropsy for determination of serum nicotine, cotinine, Ca, PTH, 25(OH)D, and 1,25(OH)(2)D. Right tibiae were collected and processed undecalcified for cancellous and cortical bone histomorphometry. Histomorphometric endpoints evaluated at the proximal tibial metaphysis included cancellous bone volume (BV/TV), osteoclast surface (Oc.S), osteoid surface (OS), mineralizing surface (MS), mineral apposition rate (MAR), and bone formation rate (BFR). Histomorphometric endpoints evaluated at the tibial diaphysis included cortical area (Ct.Ar), marrow area (Ma.Ar), and periosteal and endocortical MS, MAR, and BFR. Ovariectomy resulted in lower cancellous BV/TV and Ct.Ar and higher cancellous, endocortical, and periosteal MS and BFR. The presence of nicotine in serum confirmed successful delivery of the drug via osmotic minipumps. Administration of nicotine at the high dose resulted in lower serum 25(OH)D levels but differences in serum Ca or PTH were not detected with either nicotine treatment. Differences with nicotine treatment were also not detected for Oc.S at the proximal tibia. While treatment with nicotine at the high dose resulted in higher MS and BFR, in both sham and ovx rats, there were no differences due to nicotine treatment in cancellous BV/TV. Marrow area was greater in rats treated with nicotine than in rats treated with vehicle. However, differences with nicotine treatment were not detected in Ct.Ar in either intact or ovx rats. Overall, these findings indicate that steady state nicotine exposure does not alter bone mass in intact or ovx rats but may have detrimental effects on body storage of vitamin D.

Journal Article↗

Effects of nicotine on bone mass, turnover, and strength in adult female rats.

This study investigated the effects of nicotine, the chemical responsible for tobacco addiction, on bone and on serum mineral and calcitropic hormone levels in adult, female rats to help resolve a current controversy regarding the impact of nicotine on bone health. Seven-month-old rats received either saline (n = 12), low-dose nicotine (4.5 mg/kg/day, n = 2), or high-dose nicotine (6.0 mg/kg/day, n = 12) administered subcutaneously via osmotic minipumps for 3 months. Blood, femora, tibiae, and lumbar vertebrae (3-5) were collected at necropsy for determination of serum mineral and hormonal concentrations, bone density (femora and vertebrae), bone turnover (tibiae), and bone strength (femora). The presence of nicotine in serum (111 +/- 7 and 137 +/- 10 ng/ml for the low- and high-dose nicotine groups, respectively) confirmed successful delivery of the drug via osmotic minipumps. Nicotine-induced treatment differences were not detected in serum calcium, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D. However, serum phosphorus and parathyroid hormone (PTH) were higher in rats treated with high-dose nicotine, and serum calcitonin was lower in rats treated with both high- and low-dose nicotine than in control rats. Nicotine treatment had no effect on tibial cancellous or cortical bone turnover or femoral bone mineral content (BMC) and density (BMD). Femoral ultimate load and vertebral BMC were lower in rats treated with high-dose nicotine than in control rats. We conclude that nicotine at serum concentrations 2.5-fold greater than the average in smokers has limited detrimental effects on bone in normal, healthy female rats.

Absorptiometry, Photon↗

Effects of nicotine on bone and calciotropic hormones in growing female rats.

Limited research in young adults and immature animals suggests a detrimental effect of tobacco on bone during growth. This study investigated the effects of nicotine, the major alkaloid component of tobacco, on calciotropic hormone concentrations and bone status in growing female rats. One-month-old animals received either saline (n = 10), nicotine at 3.0 mg/kg/day (n = 10), or nicotine at 4.5 mg/kg/day (n = 10) administered subcutaneously via osmotic minipumps for either 2 or 3 months. Sera, femora, tibiae, and lumbar vertebrae (3-5) were collected at necropsy. The concentrations of serum calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, calcitonin, and insulin-like growth factor-I were determined. Bone variables evaluated included mineral content and density (vertebrae and femora), cancellous and cortical histomorphometry (tibiae), and bone strength (vertebrae and femora). Statistically significant differences in serum mineral and hormone concentrations were not associated with nicotine dose or exposure time. No significant nicotine treatment effects were detected for bone mineral content and density, bone histomorphometry, or bone strength. We conclude that nicotine treatment for 2 or 3 months at serum concentrations in the upper range of those found in smokers has no detrimental effect on bone mass, volume, or strength in the growing rat.

Animals↗

The effect of caffeinated, non-caffeinated, caloric and non-caloric beverages on hydration.

OBJECTIVE: To examine the effect of various combinations of beverages on hydration status in healthy free-living adult males. METHODS: In a counterbalanced, crossover manner, 18 healthy adult males ages 24 to 39, on four separate occasions, consumed water or water plus varying combinations of beverages. Clinical guidelines were used to determine the fluid allowance for each subject. The beverages were carbonated, caffeinated caloric and non-caloric colas and coffee. Ten of the 18 subjects consumed water and carbonated, non-caffeinated, citrus soft drink during a fifth trial. Body weight, urine and blood assays were measured before and after each treatment. RESULTS: Slight body weight loss was observed on all treatments, with an average of 0.30% for all treatments. No differences (p>0.05) among treatments were found for body weight changes or any of the biochemical assays. Biochemical assays conducted on first voids and 24-hour urines included electrolytes, creatine, osmolality and specific gravity. Blood samples were analyzed for hemoglobin, hematocrit. electrolytes, osmolality, urea nitrogen, creatinine and protein. CONCLUSIONS: This preliminary study found no significant differences in the effect of various combinations of beverages on hydration status of healthy adult males. Advising people to disregard caffeinated beverages as part of the daily fluid intake is not substantiated by the results of this study. The across-treatment weight loss observed, when combined with data on fluid-disease relationships, suggests that optimal fluid intake may be higher than common recommendations. Further research is needed to confirm these results and to explore optimal fluid intake for healthy individuals.

Adult↗

Long-term effects of nicotine on bone and calciotropic hormones in adult female rats.

This study determined the effects of nicotine on serum concentrations of several calciotropic hormones, and bone formation and resorption end-points in 7 month old, adult female rats. Animals were administered either saline (n= 9/group), low dose nicotine at 3.0 mg/kg/day (n=10/group) or high dose nicotine at 4.5 mg/kg/day (n=11/group) by subcutaneous osmotic minipumps. At the end of a three months treatment period, serum concentrations of calcium, phosphorus, parathyroid hormone, calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were determined. Femora, tibiae, and lumbar vertebrae (3-5) were collected and bone parameters evaluated included mineral density and content (femora and vertebrae), strength (femora and vertebrae) and histomorphometry (tibiae). Animals given nicotine had significantly lower levels of 25-hydroxyvitamin D than controls [20.8+/-1.4 ng/ml for the low dose group and 20.7+/-1.0 ng/ ml for the high dose group versus 27.6+/-1.3 ng/ml for the control group (mean+/-S.E.M.), P<0.01]. The high dose nicotine group had smaller vertebral areas (5.4+/-0.2 mm2 versus 6.2+/-0.2 mm2, P<0.05) and a lower bone mineral content than the controls (0.024+/-0.001 g versus 0.030+/-0.001 g, P<0.05). Tibial endocortical mineral apposition rate was also significantly lower in the high dose nicotine group than in the control group (1.06+/-0.13 microm/day versus 1.42+/-0.08 microm/day. P<0.05). No significant treatment differences were detected in bone density, cancellous bone histomorphometry, or bone strength. Results from the present study suggest that nicotine administration may adversely affect bone formation and decrease body storage of vitamin D.

Animals↗

Short-term effects of nicotine on bone and calciotropic hormones in adult female rats.

This study assessed the effects of two months nicotine treatment on bone formation and resorption end-points in adult, female rats. In addition, the concentrations of calciotropic hormones which included parathyroid hormone, calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in rats (7 months old) were determined. All animals received either saline (n = 7/group), nicotine (3.0 mg/kg/day) (n = 7/group) or nicotine (4.5 mg/kg/day) (n = 7/group) via subcutaneous implantation of osmotic minipumps containing either saline or nicotine for a period of two months. Serum, right tibia, left femur and lumbar vertebra (3-5) were collected for determination of hormonal concentrations as well as various parameters, including histomorphometry, bone mineral density, bone mineral content and vertebral strength. Although nicotine-treated rats showed a lower level of 25-hydroxyvitamin D [54.4 +/- 3.1 ng/ml for the 3.0 mg/kg/day and 55.8 +/- 2.8 for the 4.5 mg/kg/day group] (mean +/- S.E.M.) as compared to controls (74.8 +/- 2.8 ng/ml) (P < 0.01, Newman-Keuls test), no significant difference could be detected for the levels of the remaining hormones. Similarly, no statistical differences were detected on histomorphometric end-points, bone mineral density, bone mineral content and vertebral strength of rats. We conclude that, in spite of lowering serum 25-hydroxyvitamin D by about 30%, nicotine administration of two months duration does not alter bone mass, strength or formation and resorption end-points.

Animals↗

Allied health faculty attitudes toward rural clinical practice.

Research findings of allied health practitioners' attitudes toward rural practice are limited. The purpose of this study was to identify attitudes of faculty members in a school of allied health toward rural vs. urban living, clinical education, and practice. A survey consisting of demographic and attitudinal questions was mailed to 233 faculty representing five professions. The response rate was 63.5%. The majority viewed rural living as having both positive and negative aspects. Placement of clinical students in rural areas was seen as enhancing rural recruitment. Rural professional issues were viewed as mixed with the most positive aspect being greater intellectual challenge. There were a few significant attitude differences by gender, age, years of experience, profession, hometown location, and practice location site. The findings of this study generally support previous research and contribute additional knowledge regarding attitudes toward rural practice. Further studies of allied health professionals appear warranted.

Allied Health Personnel↗

Histologic changes in liver allograft biopsies associated with elevated whole blood and tissue cyclosporine concentrations.

Cyclosporine is used in the postoperative management of rejection in liver allograft recipients. Despite its efficacy in the treatment of allograft rejection, the drug exhibits toxicity at elevated whole blood concentrations including nephrotoxicity with associated histologic changes, and evidence of hepatotoxicity as determined by liver function studies. To date, there have been few published reports describing histologic changes in liver biopsies from patients with elevated blood cyclosporine levels. In the present study, we retrospectively examined biopsies from 16 liver allograft recipients, seven patients with elevated whole blood cyclosporine levels (> 1000 ng/ml) and nine control patients who had whole blood cyclosporine levels in the therapeutic range (558 to 993 ng/ml). In each case, frozen liver biopsy tissue was available to measure tissue levels of cyclosporine and metabolites. The blood and tissue drug levels were then correlated with the histologic changes present in the biopsy specimens. Patients with increased cyclosporine levels displayed histologic changes consisting of hypertrophy of the bile ductal epithelium with cytoplasmic vacuoles and the presence of "foamy" material within the hepatic sinusoids that were either absent or occurred less frequently in the control group. The histologic changes correlated best with cyclosporine metabolite levels rather than tissue levels of native drug. When liver function studies were correlated with cyclosporine levels, only gamma glutamyl transpeptidase (GGT) demonstrated a significant positive correlation with the histologic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Assay methods for cyclosporine monitoring following liver transplantation.

This article reviews therapeutic drug monitoring for cyclosporine in liver transplantation. Brief descriptions of various immunoassay methods include sample matrix selection, assay reagents, and metabolite cross-reactivity information. Multiple comparisons of the various methods are outlined. Examples of the method-dependent relationship between clinical events and changes in cyclosporine concentration are presented. Other potential predictors of liver allograft function are listed.

Chromatography, High Pressure Liquid↗

A macro-driven Lotus 1-2-3 template for calculating and plotting receiver-operator characteristic curves for clinical laboratory tests.

Receiver-operator characteristic (ROC) curve analysis has become an accepted method of evaluating the efficiency of clinical laboratory tests. The calculations necessary to plot such curves are not difficult, but are repetitive and time consuming. Such calculations are easily done by computers. The availability, ease of use and graphics capabilities of spreadsheet programs such as Lotus 1-2-3 lend themselves to these applications. In this article, we describe such an application.

Clinical Laboratory Techniques↗

Filtration of platelet-poor plasma specimens yields platelet-free plasma. Application for batch analysis of beta-thromboglobulin and platelet factor 4.

The authors investigated filtration of platelet-poor plasma through a 0.2-micron filter for the analysis of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in frozen specimens. Platelets were detected by electron micrograph in the platelet-poor plasma preparation without filtration. No platelets or platelet fragments were seen after filtration. Freezing the unfiltered specimens resulted in a significant increase in the beta-TG and PF4 concentrations, presumably because of release of these proteins from the platelet alpha-granules during freezing and thawing. There was no change in the PF4 levels and only a slight decrease in beta-TG levels after freezing of the filtered specimens. The filtered samples could be frozen for later batch analysis, resulting in considerable cost savings to the laboratory.

Blood Platelets↗

Maternal serum and amniotic fluid alpha-fetoprotein testing: our approach to screening, diagnosis and counseling.

Maternal serum and amniotic fluid alpha-fetoprotein testing has increased significantly in our laboratory and throughout the state since 1985. The results of this test are reported in a novel fashion as multiples of the median. The calculation and reporting of the test results are highly dependent upon gestational age, maternal weight, race and presence or absence of maternal diabetes. When properly interpreted alpha-fetoprotein determinations are a good screening test for early detection of neural tube defects and Trisomy 21 (Down Syndrome). Our approach to screening, diagnosis and counseling is discussed.

Adult↗

Cyclosporine concentrations in blood after liver transplantation: correlation of immunoassay results with clinical events.

To investigate the clinical utility of immunoassays for cyclosporine and metabolites in plasma and whole blood, we monitored 25 patients after orthotopic liver transplantation. We compared cyclosporine as measured by TDx fluorescence polarization immunoassay (of both plasma and whole blood) and by two polyclonal radioimmunoassays (from Sandoz and INCSTAR). We found considerable differences in measured cyclosporine concentrations, which were dependent on method, matrix, and clinical condition. Correlation coefficients between results by the various methods for samples from individual patients ranged from 0.825 to 0.996. The three methods used for monitoring cyclosporine in whole blood gave proportional results (Sandoz less than INCSTAR less than TDx) in individual patients, but results for the two methods for plasma sometimes differed by more than 100%. In some cases, ratios of plasma cyclosporine concentration (result by TDx/result by Sandoz) were correlated with disturbances in hepatic excretory function or kidney function. This ratio may be useful in monitoring for nephrotoxicity.

Adolescent↗

Issues in methodology and applications for therapeutic monitoring of antidepressant drugs.

Measurement of antidepressant drugs in serum provides a useful indicator of optimal dosage and can enable the clinician, in certain circumstances, to easily adjust dosages for individual differences in drug metabolism, alterations in the concentration in serum owing to drug interactions, or failure to achieve an adequate concentration in serum because of noncompliance. Practical therapeutic monitoring of antidepressants, however, is still complicated by a lack of suitable reference methodology or established assay-performance criteria and the diversity of analytical techniques. We review here several contemporary methods of analysis for the tricyclic antidepressant drugs--including gas chromatography with a nitrogen-specific detector, HPLC, and immunoassays--that are available for toxicology screening or for quantifying the most widely monitored tricyclic drugs. We also present an overview of current laboratory issues and practical considerations facing those who analyze for antidepressant drugs.

Antidepressive Agents, Tricyclic↗