Biomedical subjects

R Prince

Publications and source records attributed to R Prince.

At least 19 recordsLinked to original sources

PubMed2005

Subtherapeutic ocular penetration of caspofungin and associated treatment failure in Candida albicans endophthalmitis.

Candida endophthalmitis represents the most serious ocular complication of candidemia. The pharmacokinetics and pharmacodynamics of fluconazole, amphotericin B, and flucytosine are fairly well established in endophthalmitis therapy. There remains a paucity of clinical data regarding the utility of new antimycotic agents in the treatment of fungal chorioretinitis and endophthalmitis. We report a case of clinical failure of caspofungin in the management of Candida albicans endophthalmitis associated with poor vitreous penetration.

Adult↗

PubMed2001

Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.

BACKGROUND: Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. METHODS: We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. RESULTS: New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-microg and 40-microg parathyroid hormone groups; the respective relative risks of fracture in the 20-microg and 40-microg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46, respectively [95 percent confidence intervals, 0.25 to 0.88 and 0.25 to 0.861). As compared with placebo, the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points. Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo. Parathyroid hormone had only minor side effects (occasional nausea and headache). CONCLUSIONS: Treatment of postmenopausal osteoporosis with parathyroid hormone (1-34) decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated. The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects.

Bone Density↗

PubMed2001

Final results of a randomized trial comparing the MULTI-LINK stent with the Palmaz-Schatz stent for narrowings in native coronary arteries.

The MULTI-LINK (ML) stent is a novel second generation coronary stent. The ACS MultiLink Stent Clinical Equivalence in De Novo Lesions Trial (ASCENT) randomized 1,040 patients with single, de novo native vessel lesions to treatment with the ML stent or the benchmark Palmaz-Schatz (PS) stent, to demonstrate that the ML stent was not inferior to (i.e., equivalent or better than) the PS stent in terms of target vessel failure by 9 months. Successful stent delivery was achieved in 98.8% versus 96.9% of patients, with a slightly lower postprocedural diameter stenosis (8% vs 10%, p = 0.04), and no difference in 30-day major adverse cardiac events (5.0% vs 6.5%) for the ML stent versus the PS stent. The primary end point of target vessel failure at 9 months was seen in 15.1% of ML-treated patients versus 16.7% of PS-treated patients, with the ML proving to be equal or superior to the PS stent (p <0.001 by test for equivalency). In a prespecified subset, angiographic restudy showed a nonsignificant trend for reduced ML restenosis (16.0% vs 22.1%). Thus, the ML stent showed excellent deliverability and acute results, with 9-month clinical and 6-month angiographic outcomes that were equivalent or better than the PS stent.

Aged↗

PubMed2001

Self-treatment by Kenyan and Ugandan schoolchildren and the need for school-based education.

Studies on Kenyan and Ugandan primary schoolchildren's knowledge of medicines and self-treatment practices show that children aged between 10 and 18 years have a broad knowledge of herbal and biomedical remedies and that they use them frequently, often without adults' involvement. They use pharmaceuticals, including prescription-only drugs, but lack knowledge about indications and dosages. There is a gap between the children's life worlds and the school health education as it is presently designed and taught in Kenya and Uganda. It limits itself to disease prevention and health promotion, and does not teach treatment or medicine-use. Self-treatment based on insufficient knowledge poses a threat to children's health and to the health of the wider community. Therefore, education on the critical and appropriate use of medicines needs to be developed and tested for possible use in Kenya, Uganda and other countries in which home-treatment is common. The proposed education on medicines should go beyond providing information on accurate dosage and indication: it should create critical awareness with regard to medicine-use, enabling children to use them appropriately and cautiously. Kenyan and Ugandan primary schoolchildren are active agents within pluralistic medical fields. By taking the children seriously as competent health care agents, the dangers of self-treatment could be reduced, and the potential of children could be guided to fruitful use. Educational interventions cannot solve the problems of self-treatment, which are related to the wider social and economic context, but they could contribute to increased awareness as a necessary condition for change.

Adolescent↗

PubMed2001

Resistance training over 2 years increases bone mass in calcium-replete postmenopausal women.

Understanding the stress/strain relationship between exercise and bone is critical to understanding the potential benefit of exercise in preventing postmenopausal bone loss. This study examined the effect of a 2-year exercise intervention and calcium supplementation (600 mg) on bone mineral density (BMD) in 126 postmenopausal women (mean age, 60 +/- 5 years). Assignment was by block randomization to one of three groups: strength (S), fitness (F), or nonexercise control (C). The two exercise groups completed three sets of the same nine exercises, three times a week. The S group increased the loading, while the F group had additional stationary bicycle riding with minimal increase in loading. Retention at 2 years was 71% (59% in the S group, 69% in the F group, and 83% in the C group), while the exercise compliance did not differ between the exercise groups (S group, 74 +/- 13%; F group, 77 +/- 14%). BMD was measured at the hip, lumbar spine, and forearm sites every 6 months using a Hologic 4500. Whole body BMD also was measured every 6 months on a Hologic 2000. There was no difference between the groups at the forearm, lumbar spine, or whole body sites. There was a significant effect of the strength program at the total (0.9 +/- 2.6%; p < 0.05) and intertrochanter hip site (1.1 +/- 3.0%; p < 0.01). There was a significant time and group interaction (p < 0.05) at the intertrochanter site by repeated measures. This study shows the effectiveness of a progressive strength program in increasing bone density at the clinically important hip site. We concluded that a strength program could be recommended as an adjunct lifestyle approach to osteoporosis treatment or used in combination with other therapies.

Aged↗

PubMed2000

Precision error of fan-beam dual X-ray absorptiometry scans at the spine, hip, and forearm.

The current study investigated short-term precision of fan-beam dual X-ray absorptiometry scans using a sample of subjects typically seen in a routine practice. Seventy-two women were scanned twice each in array fan-beam mode at the lumbar spine and 71 at the hip on a Hologic QDR 2000. Sixty-five were scanned at the forearm on a Hologic QDR 4500A in array mode. Each of the two scans was analysed without reference to its companion scan (independent analysis). The second assessment was also reanalyzed using the manufacturer's "Compare" function (compared analysis). Coefficients of variation (CVs) were calculated for the two forms of analysis at all the sites measured. Paired t-tests were performed to see whether the "Compare" function improved precision. The CV at the lumbar spine was 1.1% in both forms of analysis. The "Compare" function did not improve precision significantly at this site. The highest precision at the hip was found at the (Total) site of the hip (1.2-1.0%, independent and compared analyses, respectively) and the lowest at Ward's triangle. The Compare function significantly improved precision at Ward's triangle. The forearm had the best precision of all the sites measured with the Total site of the forearm being highest (0.5-0.7%) and the ultradistal site lowest (1.6-1.8%). The Compare function significantly decreased precision at the mid-distal and Total sites of the forearm. In conclusion, the highest precision was found at the Total site of the hip, the Total site of the forearm, and the spine. The Compare function did not significantly improve precision at the spine or hip (with the exception of Ward's triangle) and decreased precision at the forearm.

Absorptiometry, Photon↗

PubMed1998

Mode switching kinetics produced by a naturally occurring mutation in the cytoplasmic loop of the human acetylcholine receptor epsilon subunit.

We describe the genetic and kinetic defects in a congenital myasthenic syndrome caused by heteroallelic mutations of the acetylcholine receptor (AChR) epsilon subunit gene. The mutations are an in-frame duplication of six residues in the long cytoplasmic loop (epsilon1254ins18) and a cysteine-loop null mutation (epsilonC128S). The epsilon1254 ins18 mutation causes mode switching in the kinetics of receptor activation in which three modes activate slowly and inactivate rapidly. The epsilon1245ins18-AChR at the endplate shows abnormally brief activation episodes during steady state agonist application and appears electrically silent during the synaptic response to acetylcholine. The phenotypic consequences are endplate AChR deficiency, simplification of the postsynaptic region, and compensatory expression of fetal AChR that restores electrical activity at the endplate and rescues the phenotype.

Acetylcholine↗

PubMed1998

Localization of estrogen receptor-alpha in human and rabbit skeletal tissues.

Estrogen is essential for the development and maintenance of optimal bone mass in women and men, and acts through activation of estrogen receptors (ER). We have examined the pathways of estrogen action on the skeleton by seeking to localize the "classical" estrogen receptor, ER alpha, to particular cells to test the hypotheses that 1) estrogen directly influences growth plate chondrocytes; and 2) estrogen has a principal action on bone tissue via osteoblasts. ER alpha messenger ribonucleic acid (mRNA) was localized by in situ hybridization in human specimens from five males (11-15 yr old), two females (9 and 11 yr old), and three growing rabbits. In all of the human material examined, ER alpha mRNA was consistently identified in chondrocytes. In all of the rabbit tissue studied, ER alpha mRNA was localized in chondrocytes of the growth plate and the subarticular epiphyseal growth center. ER alpha mRNA signals were readily observed in both active osteoblasts and lining cells on trabecular surfaces of all samples. No clear evidence of positive staining was detectable in osteoclasts or osteocytes in either species. The distribution of ER alpha mRNA coincided with immunolocalization of the ER protein in the human specimens. These data suggest a direct action of estrogen on growth plate chondrocytes that may affect longitudinal growth and subsequent fusion of the growth plate and also on osteoblasts to affect bone formation at trabecular sites.

Adolescent↗

PubMed1997

Geographic structure of mitochondrial and nuclear gene polymorphisms in Australian green turtle populations and male-biased gene flow.

The genetic structure of green turtle (Chelonia mydas) rookeries located around the Australian coast was assessed by (1) comparing the structure found within and among geographic regions, (2) comparing microsatellite loci vs. restriction fragment length polymorphism analyses of anonymous single copy nuclear DNA (ascnDNA) loci, and (3) comparing the structure found at nuclear DNA markers to that of previously analyzed mitochondrial (mtDNA) control region sequences. Significant genetic structure was observed over all regions at both sets of nuclear markers, though the microsatellite data provided greater resolution in identifying significant genetic differences in pairwise tests between regions. Inferences about population structure and migration rates from the microsatellite data varied depending on whether statistics were based on the stepwise mutation or infinite allele model, with the latter being more congruent with geography. Estimated rates of gene flow were generally higher than expected for nuclear DNA (nDNA) in comparison to mtDNA, and this difference was most pronounced in comparisons between the northern and southern Great Barrier Reef (GBR). The genetic data combined with results from physical tagging studies indicate that the lack of nuclear gene divergence through the GBR is likely due to the migration of sGBR turtles through the courtship area of the nGBR population, rather than male-biased dispersal. This example highlights the value of combining comparative studies of molecular variation with ecological data to infer population processes.

Alleles↗

PubMed1996

Exercise effects on bone mass in postmenopausal women are site-specific and load-dependent.

It is considered that skeletal mass in humans may respond to loading or the number of loading cycles. The aim of this study was to examine the effect of a 1 year progressive resistance training program on the bone mass of 56 postmenopausal women. Assignment was by block randomization to one of two resistance training groups: a strength trained group (3 x 8 repetition maximum) or an endurance group (3 x 20 repetition maximum). The resistance exercises were selected to stress the ipsilateral forearm and hip region. The exercising side was randomly assigned with one side exercised while the alternate side acted as the nonexercise control. Bone mineral density (BMD) was measured every 3 months at the radial forearm and four hip sites using the Hologic QDR 2000 bone densitometer. A linear regression function was fitted for each individual's bone density results, and the slope was compared for the exercise and control side using paired t-tests. The bone mass increase with the strength regimen was significantly greater at the trochanteric hip site (control -0.6 +/- 2.2%, exercise 1.7 +/- 4.1%, p < 0.01), at the intertrochanteric hip site (control -0.1 +/- 2.1%, exercise 1.5 +/- 3.0%, p < 0.05), Ward's triangle (control 0.8 +/- 5.2%, exercise 2.3 +/- 4.0%, p < 0.05), and at the ultradistal radial site (control -1.4 +/- 2.3%, exercise 2.4 +/- 4.3%, p < 0.01). There was no significant increase in BMD with the endurance regimen except at the radius midsite (control -1.0 +/- 2.3%, exercise 0.1 +/- 1.4%, p < 0.01). In both the endurance and the strength group, muscle strength, tested by a one-repetition maximum (1RM) test, increased significantly for all 10 exercises (p < 0.01) and to a similar degree in the two groups. In the strength group but not the endurance group there were significant correlations between the slope of the change in BMD and the percentage increase in strength as follows: trochanter with leg press; intertrochanter with leg press (p < 0.05); and Ward's triangle with hip extension and hip adduction (p < 0.05). Thus these results support the notion of a site-specific response of bone to maximal loading from resistance exercise in that although the trochanter and intertrochanter bone density was elevated by the resistance exercises undertaken, there was no effect on the femoral neck value. Postmenopausal bone mass can be significantly increased by a strength regimen that uses high-load low repetitions but not by an endurance regimen that uses low-load high repetitions. We conclude that the peak load is more important than the number of loading cycles in increasing bone mass in early postmenopausal women.

Adult↗

PubMed1995

Genetic and redox determinants of nitric oxide cytotoxicity in a Salmonella typhimurium model.

Paradoxically, nitric oxide (NO) has been found to exhibit cytotoxic, antiproliferative, or cytoprotective activity under different conditions. We have utilized Salmonella mutants deficient in antioxidant defenses or peptide transport to gain insights into NO actions. Comparison of three NO donor compounds reveals distinct and independent cellular responses associated with specific redox forms of NO. The peroxynitrite (OONO-) generator 3-morpholinosydnonimine hydrochloride mediates oxygen-dependent Salmonella killing, whereas S-nitrosoglutathione (GSNO) causes oxygen-independent cytostasis, and the NO. donor diethylenetriamine-nitric oxide adduct has no antibacterial activity. GSNO has the greatest activity for stationary cells, a characteristic relevant to latent or intracellular pathogens. Moreover, the cytostatic activity of GSNO may best correlate with antiproliferative or antimicrobial effects of NO, which are unassociated with overt cell injury. dpp mutants defective in active dipeptide transport are resistant to GSNO, implicating heterolytic NO+ transfer rather than homolytic NO. release in the mechanism of cytostasis. This transport system may provide a specific pathway for GSNO-mediated signaling in biological systems. The redox state and associated carrier molecules are critical determinants of NO activity.

Base Sequence↗

PubMed1995

Osteoporosis in rheumatoid arthritis. A monozygotic co-twin control study.

OBJECTIVE: To quantify the magnitude and distribution of osteoporosis in rheumatoid arthritis (RA). METHODS: Bone mineral density (BMD) was measured by dual x-ray absorptiometry, in a monozygotic co-twin control study. RESULTS: BMD was reduced at most skeletal sites in the twin with RA compared with the co-twin (lumbar spine 4.6%, femoral neck 9.7%, total body 5.7%). Differences in lean soft tissue (5.6% for total body) correlated with differences in BMD between twins at multiple sites. CONCLUSION: Osteoporosis in RA is generalized and may be related to loss of mobility or muscle mass associated with the disease.

Arthritis, Rheumatoid↗

PubMed1995

The effects of calcium supplementation (milk powder or tablets) and exercise on bone density in postmenopausal women.

The etiology of age-related bone loss is unclear but both lack of exercise and dietary calcium deficiency have been implicated in its causation. This 2-year randomized placebo-controlled study was designed to examine the effects of increased dietary calcium and exercise in 168 women who were more than 10 years postmenopausal. The subjects were randomized into one of 4 groups: placebo, milk powder containing 1 g of calcium, calcium tablets 1 g/night, and calcium tablets 1 g/night and an exercise regimen. The exercise group aimed to undertake 4 h of extra weight-bearing exercise per week and were undertaking 10% more activity than other groups at 2 years. Bone mineral density at the lumbar spine, three hip sites, and two sites of the tibia close to the ankle joint were measured at 6 month intervals. Dietary intake was evaluated by a weighed food record, exercise was evaluated by an exercise diary, and blood and urine samples were obtained to examine effects on calcium homeostasis. Individual data points were compared using repeated measures ANOVA and least squares regression. Calcium supplementation by either the calcium tablets or the milk powder resulted in cessation of bone loss at the intertrochanteric hip site (placebo, calcium tablets, calcium and exercise, milk powder -0.81, +0.17, +0.23, and +0.07% per year, respectively; p < 0.05 for all supplementation groups compared with placebo) with similar results at the trochanteric hip site. The calcium and exercise group had less bone loss at the femoral neck site when compared with calcium supplementation alone (placebo, calcium tablets, calcium and exercise, milk powder -0.67, -0.18, +0.28, and -0.18% per year, respectively; p < 0.05 for calcium and exercise compared with calcium alone). There was a significant reduction in the rate of bone loss at the ultradistal site of the tibia (placebo, calcium tablets, calcium and exercise, milk powder -2.5, -1.6, -1.0, and -1.5% per year, respectively; p < 0.05 for all supplementation groups compared with placebo). There was no significant bone loss at the spine site in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

17 beta-estradiol suppresses gene expression of tartrate-resistant acid phosphatase and carbonic anhydrase II in ovariectomized rats.

Tartrate-resistant acid phosphatase (TRACP) and carbonic anhydrase II (CA II) are key enzymes responsible for osteoclastic bone resorption. In this study, we proposed that estrogen loss in postmenopausal osteoporosis may enhance gene expression of TRACP and CA II, and subsequently increase osteoclastic bone resorption. We have, therefore, used the ovariectomized rat model of postmenopausal bone loss to investigate changes at the gene transcriptional level in osteoclastic bone-resorbing enzymes in ovariectomized (OVX) rats, sham ovariectomized (S-OVX) rats, and estrogen-treated ovariectomized (E-OVX) rats. We have demonstrated for the first time that ovariectomy in rats enhances gene expression of TRACP, and CA II. The mRNA levels in OVX were approximately three- and four-fold higher, respectively, than those in S-OVX. Enhancement was observed 1 week after ovariectomy and transcripts remain high during the experimental period of 8 weeks. Administration of 17 beta-estradiol to OVX (E-OVX) reduced gene expression of these osteoclastic bone-resorbing enzymes 18 hours after injection. It appeared that the suppression of the osteoclastic bone-resorbing enzymes by 17 beta-estradiol was most effective during the first 1-2 weeks but the degree of suppression was reduced at 8 weeks after ovariectomy. In conclusion, our results suggest that estrogen prevents bone loss by reducing the mRNA levels of osteoclastic bone-resorbing enzymes in bone tissue.

Acid Phosphatase↗

PubMed1995

Retrograde intramedullary nailing for ankle arthrodesis.

This is a retrospective study of retrograde intramedullary rodding for ankle arthrodesis in 19 ankles in 16 patients. The preoperative diagnosis of 16 patients was diabetic neuropathic arthropathy in seven patients, rheumatoid arthritis in three patients, post traumatic arthrosis in three patients, paraplegia with fixed equinovarus of the foot in two patients, and avascular necrosis of the talus in one patient. Retrograde intramedullary rodding for ankle arthrodesis was done as a salvage procedure in each patient. Fourteen of the 19 ankles had radiographic evidence of solid arthrodesis. In the four patients with five ankles with pseudarthrosis, no case was clinically significant. There was one deep infection and one broken rod. Thirteen of the 16 patients are ambulatory, and nine required either an ankle-foot orthosis or shoe modification. The standard method of ankle fusion using crossed cancellous screws is the procedure of choice because it preserves the subtalar joint. Retrograde intramedullary rodding for ankle arthrodesis should be considered for patients with significant posttraumatic arthrosis and bone loss following distal tibial plafond fractures, concomitant subtalar arthrosis, severe osteopenia, such as in patients with rheumatoid arthritis, or neuropathic arthropathy.

Adolescent↗

PubMed1994

Cost-effectiveness analysis of hormone replacement therapy and lifestyle intervention for hip fracture.

We compared the cost-effectiveness of interventions to prevent osteoporosis using a decision analytic model for a hypothetical cohort of 100,000 healthy perimenopausal women. The interventions were: oestrogen from age 50 for life, oestrogen from age 50 for 15 years, oestrogen from age 65 years for life, and a lifestyle regime of calcium supplements and exercise. The four interventions were compared with the case of no intervention by examining the effects on medical and nursing home costs, life years gained, quality-adjusted life years (QALYs) gained and costs per QALY gained. Lifetime oestrogen therapy from age 65 years achieved the lowest cost per life year gained and the lowest cost per QALY gained. The lifestyle intervention was the most expensive intervention by all measures but was sensitive to the cost of exercise and to the effects of exercise on cardiovascular mortality. Conventionally, oestrogen therapy begins at the menopause to avoid the rapid decline in bone mass that occurs with normally decreasing oestrogen levels. These results indicate that there is evidence, both in terms of fracture prevention and cost, to justify introduction of treatment at a later age. If a lifestyle intervention regimen can reduce cardiovascular mortality as well as hip fracture, this may provide an alternative means of reducing osteoporotic hip fracture at a reasonable cost.

Aged↗

PubMed1994

Induction of the Escherichia coli aidB gene under oxygen-limiting conditions requires a functional rpoS (katF) gene.

The Escherichia coli aidB gene is regulated by two different mechanisms, an ada-dependent pathway triggered by methyl damage to DNA and an ada-independent pathway triggered when cells are grown without aeration. In this report we describe our search for mutations affecting the ada-independent aidB induction pathway. The mutant strain identified carries two mutations affecting aidB expression. These mutations are named abrB (aidB regulator) and abrD. The abrB mutation is presently poorly characterized because of instability of the phenotype it imparts. The second mutation, abrD1, reduces the expression of aidB observed when aeration is ceased and oxygen becomes limiting. Genetic and phenotypic analysis of the abrD1 mutation demonstrates that it is an allele of rpoS. Thus, aidB is a member of the family of genes that are transcribed by a sigma S-directed RNA polymerase holoenzyme. Examination of aidB expression in an rpoS insertion mutant strain indicates that both rpoS13::Tn10 and abrD1 mutations reduce aidB expression under oxygen-limiting conditions that prevail in unaerated cultures, reduce aidB induction by acetate at a low pH, but have little or no effect on the ada-dependent alkylation induction of aidB.

Acetates↗

PubMed1994

Relationship between calcitrophic hormones and blood pressure in elderly subjects.

The relationship between calcitrophic hormones and blood pressure has been investigated in 583 elderly subjects who were untreated for hypertension. Univariate analysis demonstrated that serum parathyroid hormone, calcitriol, albumin and calcium were correlated significantly with mean blood pressure (r = +0.15, +0.10, +0.14 and +0.11, respectively), as were body mass index and age (r = +0.19 and +0.10, respectively). Parathyroid hormone also was correlated positively with both age and calcitriol (r = +0.34 and +0.15, respectively) and negatively with plasma calcium and albumin (r = -0.09 and -0.09, respectively). Multivariate analysis demonstrated that when allowing for age and body mass index, parathyroid hormone and calcitriol were both significant independent determinants of the mean blood pressure. When other independent variables were included in the analysis, parathyroid hormone but not calcitriol remained a significant predictor of mean blood pressure. This study has demonstrated a weak but significant relationship between blood pressure and calcitrophic hormones in a group of elderly people. The data are consistent with the hypothesis that hypertension may be due in part to calcium deficiency.

Age Factors↗