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Biomedical subjects

C A Sharp

Publications and source records attributed to C A Sharp.

At least 19 recordsLinked to original sources
PubMed2003

Radiological and biochemical resolution of nutritional rickets with calcium.

AIMS: To determine the response to oral calcium in Nigerian children with rickets. METHODS: In a teaching hospital in Western Nigeria, 26 children (13 boys, 13 girls, aged 2-5 years) with confirmed rickets received calcium lactate (2.7 g/day). RESULTS: Within one month of treatment leg pain was relieved and the children were more active. The mean x ray score improved from 3.3 at baseline to 1.7 at three months and 0.9 at six months (arbitrary scoring system, 0-6). Twelve cases were healed radiologically after six months, 11 others improved considerably, two showed no significant improvement, and a non-compliant patient was worse. There was progressive reversal of biochemical features. Median plasma alkaline phosphatase fell from 519 (range 178-1078) to 283 (209-443) IU/l (p = 0.04) in four months, while mean 1,25-dihydroxyvitamin D fell from 473 (251-1057) to 281 (155-481) pmol/l (p = 0.04), and mean plasma calcium increased from 2.26 (1.63-2.54) to 2.37 (2.06-2.54) mmol/l (p = 0.13). Parathyroid hormone fell from 5.3 (0.4-21.5) to 1.7 (0.45-7.4) pmol/l. Type I collagen carboxy terminal cross linked telopeptide was very high at baseline (20 (7.2-103) to 14 (11-24) micro g/l) (p = 0.03) and fell promptly to normal. CONCLUSION: Calcium supplementation alone effected healing of rickets in most of these Nigerian children and may provide sufficient treatment in this environment.

Calcium↗
PubMed2002

Regional differences in mechanical and material properties of femoral head cancellous bone in health and osteoarthritis.

Osteoarthritis (OA) is a debilitating condition common among the aging population. In this study we have determined mechanical and material properties of cancellous bone cores from two differently loaded regions of femoral heads obtained from healthy subjects and those with end-stage osteoarthritis. Densitometric properties were determined prior to compression testing for Young's modulus (EC) and yield strength (sigma(y)), after which bones were powdered for analysis of collagen and mineral content. In both OA and normal cancellous bone, volumetric bone mineral density (BMDv), apparent density (rhoA), E(C), and sigma(y) were systematically greater in the superior than in the inferior region (P<0.05). In the OA inferior region, median BMDv (0.434 g-cm(-3)) and rA (0.426 g-cm(-3)) were significantly greater than in normals (0.329 and 0.287 g-cm(-3), respectively, both P<0.05) reflecting an increased amount of tissue. The mineral:collagen ratio was decreased in OA, but this was only significant in the superior region (P<0.008). Relationships between EC and both BMDv and rho(A) were weaker in OA bone cores (r(2) = 0.66 and r(2) = 0.59) than in normals (r(2) = 0.86 and r(2) = 0.77, respectively). Likewise, sigma(y) and both BMDv and rho(A) were weaker in OA (r(2) = 0.74 and r(2) = 0.70) than in normals (r(2) = 0.83 and r(2) = 0.77, respectively). For the same value of density measure, EC and sigma(y) tended to be lower in OA bone when compared with normal bone. In conclusion, femoral head cancellous bone mass in end-stage osteoarthritis is increased but undermineralized, and is neither stiffer nor stronger than normal cancellous bone.

Absorptiometry, Photon↗
PubMed2001

Effect of chronic renal failure on bone turnover and bone alkaline phosphatase isoforms.

BACKGROUND: Biochemical markers of bone turnover are used to monitor metabolic bone disease associated with renal failure. We have applied a comprehensive panel of markers to patients with chronic renal failure (CRF), with particular focus on the isoforms of bone alkaline phosphatase (BALP). METHODS: Twenty CRF patients undergoing hemodialysis (N = 9) and peritoneal dialysis (N = 11) were measured for serum parathyroid hormone (PTH), osteocalcin, total ALP, and four BALP isoforms (B/I, B1x, B1, and B2) by high-performance liquid chromatography. These BALP isoforms were also compared with BALP measured by three commercial immunoassays (Alkphase-B, Tandem-R Ostase, and Tandem-MP Ostase). Type I collagen turnover was assessed by serum samples using the type I procollagen intact amino- and carboxy-terminal propeptides (PINP and PICP) and two fragments (ICTP and CrossLaps) derived from the carboxy-terminal telopeptide of mature matrix collagen by different degradative pathways. RESULTS: Mean levels of bone turnover markers were elevated in CRF, with marked increases in those markers, osteocalcin, ICTP, and CrossLaps, cleared by the kidney. Total ALP activities were increased corresponding to elevated B/I and B2 isoform levels. The B1 isoform level was not significantly different from healthy controls. B1x was detected in 60% of the patients but was not resolved in healthy individuals. Kendall's tau rank correlation showed that B1x correlated significantly (P < 0.05) with B1 (0.53) and PINP (0.55), and was the only marker to correlate with PTH (0.49). B1x was not significantly correlated with any of the commercial BALP immunoassays. Interestingly, the immunoassay calibrators contained high activities of the B/I peak (39 to 80%) compared with human serum (4%). CONCLUSION: There are selective differences between the BALP isoforms in CRF compared with healthy adults. The commercial BALP immunoassays are comparable with each other but are unable to distinguish the BALP isoform-specific differences in CRF patients.

Adult↗
PubMed2000

An epidemiological survey of methicillin-resistant Staphylococcus aureus in a tertiary referral hospital.

Over a 30-month period from July 1995 to December 1997, new detections of methicillin-resistant Staphylococcus aureus (MRSA) were prospectively studied in a tertiary referral hospital. The aims of the study were to determine the incidence of colonization of patients admitted to each of the hospital's 39 clinical units and ascertain where each patient had become colonized. Epidemiological information (time to detection, ward movement, admission to other hospitals, data on MRSA isolations in hospital wards) and phage typing were used by the hospital's infection control unit to make this determination. Routine containment procedures included cohorting, flagging and triclosan body washes. Surveillance cultures were collected infrequently. Patients known to be colonized with MRSA were excluded from orthopaedic and haematology wards. During the study period, 995 patients were found to be newly colonized. The incidence of colonization varied from nil to 72 per 1000 admissions, being highest in the main intensive care unit and in services which frequently used that unit. The incidence of colonization in elective orthopaedic surgery (< 1 per 1000) and haematology (3 per 1000) was very low. Determining the place where patients acquired MRSA was made difficult by the high frequency of endemic phage types and frequent patient transfer between wards. Epidemiological data suggested that the main intensive care unit and surgical wards nursing patients with colorectal, urological and vascular diseases were the places where most patients became colonized. MRSA was never acquired by patients nursed in wards which practised an exclusion policy towards patients known to be colonized with MRSA. Our data suggest that in tertiary referral hospitals, where MRSA is not only endemic but frequently imported from other hospitals, it is possible to establish areas where MRSA is never acquired.

Adolescent↗
PubMed1999

A prospective survey of current methicillin-resistant Staphylococcus aureus control measures.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is now endemic in tertiary referral hospitals among the developed world. By prospective survey, the effect of two measures aimed to reduce the spread of MRSA was determined. First, a surgical ward with persistently high levels of MRSA detection was cleaned and renovated. Second, the medical records of all MRSA-colonized patients were electronically flagged, facilitating immediate application of control measures on readmission. METHODS: Data were collected for 995 newly colonized patients admitted between 1 July 1995 and 31 December 1997. Methicillin-resistant Staphylococcus aureus detection was determined before and after implementation of the interventions, along with the likely place of MRSA acquisition and the monthly incidence of MRSA detection for all inpatients. Chi-squared testing with odds ratios and 95% confidence intervals determined associations between the effect of control measures studied and MRSA detection rates. RESULTS: New MRSA detection was 21.6 per 1000 admissions before refurbishment compared with 20.4 per 1000 admissions to the surgical ward after refurbishment. New MRSA detection averaged 6.4 per 1000 hospital admissions before the introduction of record flagging and patient cohorting, compared with 6.2 per 1000 admissions after. CONCLUSION: Neither ward refurbishment, nor introduction of flagging, significantly reduced rates of colonization during the study period. In hospitals that receive MRSA-colonized patients and provide intensive care facilities, spread of MRSA is a major problem. Effective containment demands separate wards for MRSA-colonized and non-colonized patients. The need for such containment should be considered in design of the modern hospital.

Chi-Square Distribution↗
PubMed1999

Isoforms of bone alkaline phosphatase: characterization and origin in human trabecular and cortical bone.

Alkaline phosphatase (ALP) is a glycoprotein and functions as an ectoenzyme attached to the cell membrane by a hydrophobic glycosyl-phosphatidylinositol (GPI) anchor. Three bone ALP (BALP) isoforms in human serum were separated and quantitated by high-performance liquid chromatography. B/I, a minor fraction, is composed on average of bone (70%) and intestinal (30%) ALP, and two major isoforms, B1 and B2. Treatment with GPI-specific phospholipase C (GPI-PLC) did not influence the activities or retention times for B1 and B2, indicating that the biochemical differences between B1 and B2 are likely to be due to different glycosylation patterns. The B/I fraction in serum, on average 4% of total ALP, was found to be composed of B1 and B2 isoforms, each with an intact hydrophobic GPI cell membrane anchor. We investigated the origin of these three BALP isoforms and osteocalcin in human femora from five healthy individuals (four males), mean age 51 years, obtained from a tissue bank. Bone was sampled from three sites: cortical bone, trabecular bone from the diaphysis, and trabecular bone from the greater trochanter. Trabecular bone, from both sites, had higher BALP activities compared with cortical bone. Conversely, the osteocalcin content of cortical bone was more than 3-fold greater than that of trabecular bone. Cortical bone had approximately 2-fold higher activity of B1 compared with B2, whereas trabecular bone had approximately 2-fold higher activity of B2 compared with B1. We observed a previously undescribed BALP isoform (B1x) in all bone samples. B1x was also observed in sera from some patients (60%) with severe renal insufficiency and on chronic dialysis therapy (n = 20). The isoforms of BALP may provide information relating to bone metabolism within specific bone compartments.

Adult↗
PubMed1998

Population pharmacokinetics of gentamicin in patients with cancer.

AIMS: The purpose of this study was to describe the population pharmacokinetics of gentamicin in patients with cancer, to identify possible relationships between clinical covariates and population pharmacokinetic parameter estimates and to examine the relevance of existing dosage nomograms in light of the population model developed in these patients. METHODS: Data were collected prospectively from 210 patients with cancer and were analysed with package NONMEM. Data were split into two sets: a population data set and an evaluation set. Creatinine clearance was estimated using measured creatinine concentrations and using 'low' creatinines set to a minimum of 60 micromol l(-1), 70 micromol l(-1) or 88.4 micromol l(-1) RESULTS: A two compartment model was fitted to the concentration-time curve. Two best models were obtained, one that related clearance to estimated creatinine clearance (minimum creatinine value 60 micromol l(-1)) and the other that related clearance to age, creatinine concentration and body surface area. Volume of the central compartment was influenced by body surface area and albumin concentration. For both models 90% of measured concentrations lay within the 95% confidence interval of the simulated concentrations and the mean prediction errors were -7.2% and -6.6%, respectively. A final analysis performed in all patients identified the following relationship CL (1 h(-1))=0.88 x (1 + 0.043 x creatinine clearance) and central volume of distribution V1 (1)=8.59 x body surface area x (albumin/34)(-0.39). The mean population estimate of intercompartmental clearance (Q) was 1.301 h(-1) and peripheral volume of distribution (V2) was 9.801. Coefficient of variation was 18.5% on clearance and 28.2% on Q. Residual error expressed as a standard deviation was 0.36 mg l(-1) at 1.0 mg l(-1) and 1.32 mg l(-1) at 8.0 mg l(-1). The mean population estimate of clearance was 4.21 h(-1) and volume of distribution (Vss) was 24.61 (0.381 kg(-1)). The mean population estimates of half-lives were 1.8 h and 8.0 h. CONCLUSIONS: In the context of published nomograms this analysis indicated that both the traditional approach and the new, 'once daily' approach should achieve satisfactory concentrations in cancer patients although serum concentration monitoring is required to confirm optimal dosing in individual patients.

Adolescent↗
PubMed1997

Elevated collagen turnover in Nigerian children with calcium-deficiency rickets.

Calcium deficiency is a major etiological determinant of rickets in Nigerian children and is accompanied by undermineralization of the developing bone matrix which is composed largely of type I collagen. We have assessed types I and III collagen metabolism by measuring the circulating concentrations of teh N- and C-terminal pro-peptides (intact PINP and PICP) and the C-terminal telopeptide (ICTP) of type I collagen, and the N-terminal pro-peptide (PIIINP) of type III collagen in 94 healthy Nigerian children and in 44 children aged 1-5 years with active calcium-deficiency rickets. In active rickets the mean levels of the four collagen metabolites were approximately twofold higher than in the healthy children, despite a wide variation of individual values. Mean intact PINP was 812 +/- 279 versus 403 +/- 189 microg/liter; PICP was 573 +/- 265 versus 348 +/- 299 microg/liter; PIIINP was 16.8 +/- 8.6 versus 10.8 +/- 3.6 microg/liter, and ICTP was 28.4 +/- 17.2 versus 11.9 +/- 4.1 microg/liter (all P < 0.001), in rachitic and healthy children, respectively. Healthy children younger than 3 years had higher levels of all the collagen metabolites than those between 3 and 5 years (all P < 0.05). Alkaline phosphatase was greater in rickets than in the healthy group (P < 0.001) whereas mean osteocalcin levels were slightly lower (P = 0.009). 1,25(OH)2D correlated with all the collagen propeptides, but not with ICTP in the healthy children. No such correlations were found in rickets, where there was a poor inverse correlation between 1,25(OH)2D and ICTP. These data suggest that collagen turnover is elevated in cases of calcium-deficiency rickets, where vitamin D status is adequate, possibly indicating increased turnover of undermineralized osteoid.

Bone Development↗
PubMed1996

Plasma osteocalcin in healthy Nigerian children and in children with calcium-deficiency rickets.

Osteocalcin is an osteoblast-specific protein believed to be associated with events occurring during bone mineralization, which has been widely used clinically as an indicator of osteoblast function. Plasma osteocalcin concentrations (pOC) were studied in 94 (59 male, 35 female) healthy and 44 (21 male, 23 female) rachitic Nigerian children, all one to five years of age. The study was aimed at establishing a reference range for healthy Nigerian children determining any changes in plasma osteocalcin levels occurring in children with calcium-deficiency rickets. In the controls, pOC levels ranged from 3-89 ng/ml, with a mean value of 23 +/- 19 ng/ml. The values were higher in girls (29 +/- 21 ng/ml) than in boys (21 +/- 18 ng/ml), though not significantly. The controls had values consistent with other published pediatric ranges from Europe and North America. In the younger rachitic children (under 3 years) the mean pOC was lower than in the controls (P = 0.04) despite the much elevated plasma levels of 1,25(OH)2D. In the controls, pOC correlated with 1,25(OH)2D (r = 0.59, P = 0.003), alkaline phosphatase (r = 0. 22, P = 0.03), and inorganic phosphate (r = 0.27, P = 0.01). These correlations were lost in the rickets group. The findings in the controls confirm the known association between plasma 1,25(OH)2D and circulating osteocalcin levels, whereas the findings in the rickets group suggest that the stimulatory effects of 1,25(OH)2D on osteocalcin may depend on other permissive factors, such as normal circulating levels of calcium and phosphate.

Alkaline Phosphatase↗
PubMed1996

Etiology of rickets in Nigerian children.

We studied 26 Nigerian children with active rickets (13 boys, 13 girls), aged 1 to 5 years, and compared results of biochemical studies with those of healthy control subjects. The plasma 1,25-dihydroxyvitamin D level was elevated (568 +/- 317 pmol/L) and the 25-hydroxyvitamin D level was (36 +/- 28 mol/L) in the children with rickets compared with the control subjects (369 +/- 134 nmol/L and 69 +/- 22 nmol/L, respectively). The results suggest that rickets in Nigeria is largely the result of calcium deficiency and that vitamin D deficiency and possibly end organ resistance may be contributory factors.

Calcium↗
PubMed1996

Ultrasound bone densitometry and dual energy X-ray absorptiometry in patients with spinal cord injury: a cross-sectional study.

Bone is lost following spinal cord injury (SCI) and in the long-term may become osteopenic and liable to fracture. Two non-invasive techniques, ultrasound bone densitometry (USBD) and dual energy X-ray absorptiometry (DXA), have been applied to monitor bone changes after spinal injury. 31 SCI patients were scanned using an ultrasound bone densitometer, to give measurements of speed of sound (SOS), broadband ultrasound attenuation (BUA) and "stiffness'. The time since injury of these patients ranged between 5 weeks to 36 years with a mean of 5.87 +/- 10.21 years. Ultrasonic properties at the calcaneus of these patients were significantly lower than the healthy reference population, and a rapid decline in ultrasound properties occurred in the first 3 months. The fall continued up to 54 months but at a slower rate. The normal linear relationship between SOS and BUA was not altered by SCI. Eighteen patients had DXA measurements at the lumbar spine and the right proximal femur. Bone mineral density (BMD) at the femoral neck was significantly lower than the normal reference population (P < 0.05). SOS and "stiffness' correlated significantly with BMD at the lumbar spine, Ward's triangle, the femoral neck, the greater trochanter and the intertrochanteric site (P < 0.05). BUA correlated significantly at all these sites with the exception of the trochanter. A negative correlation was found between the ultrasonic properties at the calcaneus and BMD at the lumbar spine which is in contrast to the positive relationship in normal subjects. There was a tendency for BMD to increase at the lumbar spine after the first 12 months after injury, although this trend was not significant overall. The "stiffness' at the calcaneus and BMD at the femoral neck were lower than the reference population following 12 months since injury. These results show that bone deficit at the calcaneus occurs rapidly and to a severe degree after SCI, and that ultrasound has an important role to play in the assessment of bone status in these patients.

Absorptiometry, Photon↗
PubMed1996

Effects of low- and conventional-dose transcutaneous HRT over 2 years on bone metabolism in younger and older postmenopausal women.

The minimum dosage of transcutaneous hormone replacement therapy (HRT) able to exert protective effects on postmenopausal bone mass, especially in older women, is uncertain. This study investigates the effects of transcutaneous HRT at two different doses of oestradiol [Estraderm 25 and 50 (E25, E50)] over 2 years in 44 postmenopausal women younger than 67 years and 27 of 67 years and older. Circulating biochemical markers of bone and connective tissue turnover, collagen type I (intact PINP, PICP) and type III (PIIINP) propeptides and type I telopeptide (ICTP), osteocalcin (OC) and alkaline phosphatase (AP) were measured. The responses of the biochemical markers in all the groups were very similar, and most of the observed changes occurred within the first year of treatment. E25 had an effect on the bone markers similar to that of E50, and there was little difference in response according to the patient's age. PINP fell markedly after 1 year in all groups to about half the pretreatment level, with a smaller drop in the second year. PICP responded more variably, and mean values were little changed. There was a slight fall at the higher dose in the younger women, and also in the older women (whose baseline level was higher) on the lower dose. The correlation between PINP and PICP was 0.52 at pretreatment and 0.84 after 2 years of treatment. PIIINP showed no changes. OC and AP both fell in all groups by the first year, but less markedly than PINP. Their response was slightly less pronounced in the older women. ICTP fell marginally in the younger women, and only after 2 years, regardless of dose. Postmenopausal serum oestradiol levels increased after HRT and were associated with decreased binding globulin (SHBG) levels in all groups. After E25 patch application individual serum oestradiol levels were variable and peaked between 13 and 36 h with a median value of 83.8 pmol L-1. Our data suggest that low-dose transcutaneous HRT restores circulating oestradiol levels in postmenopausal osteopenic women of all ages as effectively as conventional-dose HRT and is associated with decreased circulating markers of bone and connective tissue turnover.

Administration, Cutaneous↗