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Biomedical subjects

C P Williams

Publications and source records attributed to C P Williams.

At least 19 recordsLinked to original sources
PubMed2004

Troponin I, laboratory issues, and clinical outcomes in a district general hospital: crossover study with "traditional" markers of myocardial infarction in a total of 1990 patients.

AIMS: Review of the clinical outcomes and practical issues of replacing traditional cardiac enzymes with troponin I (cTnI) in a district general hospital. METHODS: Crossover study of three sequential three month stages during which serial cardiac enzymes were replaced with a single cTnI measurement available at three set times within 24 hours for the duration of the second three month stage. The study was carried out in a 630 bed district general hospital with 1990 admissions of suspected cardiac ischaemia over the study period as a whole. Account was taken of seasonal factors. RESULTS: The introduction of troponin was associated with 8.5% more patients with non-ischaemic heart disease (IHD) being discharged on the day after admission, saving approximately 107 bed days each year. Approximately 50% more patients were diagnosed with myocardial infarction during the cTnI stage. There was no increase in readmission within one month or early death with cTnI. Approximately 3% false positive and 1.5% false negative cTnI results were recorded. All false positive cTnI results were coding errors or attributable to known assay interference effects. All false negatives were potentially explained by sample timing factors. The lack of standardisation in troponin assay services impacts clinically. CONCLUSION: Younger patients without IHD were discharged earlier during the cTnI stage in apparent safety. Blood sample timing needs to be verified when cTnI is used as an adjunct to early discharge. There were no unexplained false positives or negatives. Standardisation related issues arose.

Aged↗
PubMed2004

The effect of oral folic acid on glutathione, glycaemia and lipids in Type 2 diabetes.

Plasma homocysteine is an established risk factor for vascular disease and precursor of the anti-oxidant glutathione. This study was designed to investigate the relationship of changes in homocysteine (Hcy) induced by oral folate to glutathione and measures of glycaemia and lipid metabolism in Type 2 diabetes (T2DM). Twenty-seven patients (26 male, 1 female, aged 48-68 years) with T2DM and microalbuminuria were treated with folic acid 10 mg daily for 3 months. During the study, diastolic blood pressure (p=0.04), HbA1c (p=0.04), serum triglycerides (p=0.04) and serum total/HDL-cholesterol ratio (p=0.004) all increased and serum HDL-cholesterol fell (p=0.006). The increased red cell folate correlated with a reduction in microalbuminuria (p=0.001). Overall, plasma glutathione increased (p=0.016) despite reduction in its precursor Hcy (p<0.001). Change in glutathione correlated inversely with change in HbA1c (p<0.02), total cholesterol (p=0.003) and triglycerides (p<0.02) and positively with HDL-cholesterol (p=0.033). Increase in glutathione correlated with levels of vitamin B6 (p<0.05). Metformin treatment protected against the rise in blood pressure (BP) (p=0.02), independently of changes in plasma glutathione. In summary, oral folic acid supplementation in T2DM reduced plasma Hcy and increased glutathione levels. HbA1c, triglycerides and HDL-cholesterol deteriorated during the trial: their levels correlated inversely with changes in glutathione. The increase in glutathione may depend on an adequate supply of B6, as changes in glutathione correlated with vitamin B6 levels. Reduced Hcy and increased glutathione may both mediate improvement in vascular function and outcome. Some aspects of the response to folate may be different in patients on metformin.

Adult↗
PubMed2002

Failure of active extension after traumatic cubitus varus. A case report.

In children cubitus varus is common after malunion of a supracondylar fracture of the humerus. Later problems such as tardy ulnar nerve palsy, snapping of the lateral triceps tendon or ulnar nerve and posterolateral rotatory instability are well documented. We present a case of anteromedial dislocation of the entire triceps tendon with loss of extensor power and describe the method of treatment.

Athletic Injuries↗
PubMed2001

Why oral calcium supplements may reduce renal stone disease: report of a clinical pilot study.

AIMS: To investigate whether increasing the daily baseline of gut calcium can cause a gradual downregulation of the active intestinal transport of calcium via reduced parathyroid hormone (PTH) mediated activation of vitamin D, and to discuss why such a mechanism might prevent calcium oxalate rich stones. To demonstrate the importance of seasonal effects upon the evaluation of such data. METHODS: Within an intensive 24 hour urine collection regimen, daily calcium supplementation (500 mg) was given to five stone formers for a 10 week period during a six month crossover study. In a further population of patients on follow up for previous renal stone disease, observations were made on 1066 24 hour urine samples collected over five years in respect of seasonal effects relevant to the interpretation of the study. RESULTS: In the group of patients on calcium supplements the following results were found. During calcium supplementation, the proportion of urine calcium to oxalate was higher (increased calcium to oxalate molar ratio), the 24 hour urine product of calcium and oxalate did not rise, and urine oxalate was lower during the first six weeks of supplementation. Twenty four hour urine calcium was 10.2% higher than baseline in the final four weeks of the 10 weeks of supplementation. Twenty four hour urine phosphate was 11.4% lower during the first six weeks of supplementation, but then rose while the patients were still on supplementation; renal tubular reabsorption of phosphate (TmP/GFR) mirrored the urine phosphate changes inversely. PTH was higher after stopping supplementation, but 1,25-(OH)2-cholecalciferol changes were not detected. In the 1066 urine samples collected over five years the following results were found. Calcium and oxalate excretion correlated positively and not inversely. Urine calcium and phosphate excretion were 5.5% and 2.5% higher, respectively, in "light" months of the year compared with "dark" months. A post summer decline in both urine calcium and urine phosphate was relevant to the interpretation of the study. CONCLUSIONS: Regular calcium supplementation does not raise the product of calcium and oxalate in urine and the proportion of oxalate to calcium is reduced. The underlying mechanisms of the changes seen in phosphate, calcium, and PTH and the observations on 1,25-(OH)2-cholecalciferol are not clear. Observed changes in phosphate could possibly be part of a calcium regulating feedback loop operating over a period of weeks. In evaluating these mechanisms background seasonal effects are important. It is possible that "programming" of the gut mucosa in terms of calcium transport is a major determinant of the relation between calcium and oxalate concentrations in urine and their relative abundance. Increased oral calcium, in association with a reduction of the relative proportion absorbed, may be pertinent to the prevention of calcium oxalate rich stones.

Administration, Oral↗
PubMed2000

Importance of identifying the inconspicuous penis: prevention of circumcision complications.

OBJECTIVES: To report the incidence of inconspicuous penis in those referred to a pediatric urologist for circumcision or revision of circumcision. METHODS: We performed a chart review of 129 boys referred to one pediatric urologist during a 3-year period for circumcision. RESULTS: Of 129 patients, 30 (23%) had evidence of an inconspicuous penis on the physical examination. Eight (9%) of 94 patients referred for the initial circumcision and 22 (63%) of 35 patients referred for a circumcision revision had evidence of an inconspicuous penis on physical examination. CONCLUSIONS: Inconspicuous penis is an umbrella term used to categorize several anatomic anomalies that occur in newborn boys. The incidence of inconspicuous penis at physical examination in children referred for circumcision revision is remarkable. Circumcision is best delayed in these newborn patients until a later time.

Adolescent↗
PubMed1999

Isolation and characterization of the mouse cytosolic phosphoenolpyruvate carboxykinase (GTP) gene: evidence for tissue-specific hypersensitive sites.

A 72 kilobase pair DNA fragment that contains the mouse phosphoenolpyruvate carboxykinase (PEPCK) gene locus, pck1, was isolated from a genomic bacterial artificial chromosome library. The region from approximately -5.5 to +6.6 kilobase pairs relative to the pck1 transcription start site was sequenced and exhibits a high degree of homology to the rat and human genes. Additionally, the chromatin structure of the PEPCK gene in mouse liver resembles that seen in rat. Backcross panel analysis of a microsatellite sequence confirms that the gene is located on chromosome 2. Hypersensitive site analysis was performed on nuclei isolated from the adipocyte cell line 3T3-F442A in the preadipose and adipose states. Several hypersensitive sites are present in the undifferentiated 3T3-F442A cells, before PEPCK mRNA is detected. The same sites are present after differentiation, however, the sensitivity of mHS 3 increases relative to the others. We conclude that the chromatin is open in 3T3-F442A cells and that factors are able to bind in the undifferentiated state but that something else is required for transcription.

3T3 Cells↗
PubMed1999

Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity.

BACKGROUND: Bile acid toxicity has been shown in the gastric, colonic, and hepatic tissues; the effect on oesophageal mucosa is less well known. AIMS: To determine the spectrum of bile acids refluxing in patients with gastro-oesophageal reflux disease and its relation to oesophageal pH using a new technique of combined oesophageal aspiration and pH monitoring. METHODS: Ten asymptomatic subjects and 30 patients with symptoms of gastro-oesophageal reflux disease (minimal mucosal injury, erosive oesophagitis (grade 2 or 3 Savary-Miller), Barrett's oesophagus/stricture; n=10 in each group) underwent 15 hour continuous oesophageal aspiration with simultaneous pH monitoring. Bile acid assay of the oesophageal samples was performed using modified high performance liquid chromatography. RESULTS: The peak bile acid concentration and DeMeester acid scores were significantly higher in the patients with oesophagitis (median bile acid concentration 124 micromol/l; acid score 20.2) and Barrett's oesophagus/stricture (181 micromol/l; 43. 3) than patients with minimal injury (14 micromol/l; 12.5) or controls (0 micromol/l; 11.1). The predominant bile acids detected were cholic, taurocholic, and glycocholic acids but there was a significantly greater proportion of secondary bile acids, deoxycholic and taurodeoxycholic acids, in patients with erosive oesophagitis and Barrett's oesophagus/stricture. Although bile acid reflux episodes occurred at variable pH, a temporal relation existed between reflux of taurine conjugates and oesophageal acid exposure (r=0.58, p=0.009). CONCLUSION: Toxic secondary bile acid fractions have been detected in patients with extensive mucosal damage. Mixed reflux is more harmful than acid reflux alone with possible toxic synergism existing between the taurine conjugates and acid.

Adult↗
PubMed1999

Differences in rates of glycation (glycation index) may significantly affect individual HbA1c results in type 1 diabetes.

Ten type 1 diabetic patients recorded their daily home blood glucose values, pre- and post-prandially, for 12 weeks. Blood was collected weekly for HbA1c and total haemoglobin measurement. A rolling 28-day mean of all blood glucose values and a glycation index (the ratio of the HbA1c to the rolling mean blood glucose) were calculated. In the pooled patients' data, there was a large scatter of results about the HbA1c versus mean blood glucose regression line. There was less variation in the results of individual patients. The glycation indices showed marked inter-individual variation, and in 60% of patients there was an inverse relationship between glycation index and mean blood glucose, suggesting a non-linear relationship between mean blood glucose and HbA1c. Patients should be monitored on the basis of their own previous results, and in some patients blood HbA1c may be a less sensitive index of mean blood glucose concentration at higher glucose levels.

Adult↗
PubMed1996

Abnormal myocardial calcium handling in the early stage of adriamycin cardiomyopathy.

Metabolic changes have been shown to precede mechanical abnormalities in the early stages of adriamycin cardiotoxicity. This study examines the early changes in calcium homeostasis and their mechanical implications in a model of adriamycin cardiomyopathy. Hearts isolated from control and adriamycin-treated rats were coronary-perfused and isovolumic left ventricular (LV) pressure, coronary perfusion pressure and calcium transients from aequorin-loaded cardiomyocytes were recorded. Treated rats received three injections of adriamycin (6 mg/kg) for a period of 1 week. They were sacrificed for experiments 1-2 or 4-5 weeks after the final injection. The LV systolic and end-diastolic pressures were similar in both groups at varied external calcium concentrations (0.5-2.0 mM). However, systolic levels of myoplasmic calcium were substantially higher in the adriamycin-treated hearts, the difference being less at higher external calcium concentrations. Similar responses in both groups to paired pulse stimulation, increased stimulation frequency and caffeine (0.5-2.0 mM) were observed. However, adriamycin-treated hearts exhibited a smaller rise in LV developed pressure, as well as in systolic and diastolic calcium levels, in response to elevated coronary perfusion pressure. The elevated intracellular systolic calcium level is suggestive of an early but persistent effect of adriamycin on the calcium release channels of the sarcoplasmic reticulum. That the elevated systolic myoplasmic calcium levels are not accompanied by an increase in inotropy suggests a decrease in myofibrillar calcium sensitivity in this model of the early stage of adriamycin cardiomyopathy.

Animals↗
PubMed1996

Inappropriate phosphate excretion in idiopathic hypercalciuria: the key to a common cause and future treatment?

AIMS: To present experimental evidence in support of a proposed common cause for absorptive hypercalciuria, renal hypercalciuria, renal phosphate leak and enhancement of 1,25-(OH)2-vitamin D concentrations in patients presenting with renal stone disease; and to suggest further investigation with a view to new management. METHODS: An oral calcium loading test was administered to 15 patients with renal stones and 10 normal controls in the fasting state: urine and blood were collected hourly. After the second urine sample, 400 mg calcium dissolved in water was administered orally. Serum calcium, albumin, parathyroid hormone (PTH), and phosphate were measured together with urine calcium clearance and urinary phosphate from which the TmPO4/glomerular filtration rate (GFR) ratio was calculated. Serum 1,25-(OH)2-vitamin D was measured in the first serum sample. In addition, 24 hour urine calcium results were collected retrospectively from the patients' case notes over the previous 18 months. RESULTS: In the basal state, renal stone patients had an overall greater phosphaturia (lower TmPO4/GFR: median 1.72 compared with 2.10 in controls) and increased calcium clearance. Serum corrected calcium and PTH concentrations did not differ between the groups. After calcium loading, serum calcium and urine calcium clearance rose in both groups, with patients with renal stones experiencing a greater percentage fall in phosphaturia. In both groups TmPO4/GFR fell (greater phosphaturia) with increased serum corrected calcium, with the patients showing notably greater phosphaturia for any given calcium concentration. Patients also had notably greater phosphaturia compared with the serum calcium concentration for any given PTH value. Serum 1,25-(OH)2-vitamin D was higher in patients than controls and for any 1,25-(OH)2-vitamin D concentration phosphaturia measured against serum calcium was greater in patients than controls. 1,25-(OH)2-vitamin D did not correlate with phosphaturia relative to serum calcium concentrations within the patient and control groups. CONCLUSIONS: It is proposed that patients with idiopathic hypercalciuria have an "inappropriately' high phosphate excretion for any given serum calcium concentration. Loss of phosphate may induce increased activation of 1,25-(OH)2-vitamin D. Some of the commonly described causes of stone formation may be manifestations of a single mechanism.

Adult↗
PubMed1995

Cell specific differences in DNase I hypersensitivity between the two promoters of the rat glucokinase gene.

Glucokinase (GK) gene transcription occurs in the liver and the beta cell of the endocrine pancreas where it is subject to different modes of regulation. This is accomplished largely through the use of two linked, cell-specific promoters separated by at least 12 kbp. We have used DNase I hypersensitivity to explore the chromatin structure surrounding the two promoters in cells that express either the liver or beta cell form of the GK gene, as well as cells that do not express GK. In RIN38 cells, a beta-cell-derived cell line, hypersensitive sites are detected over both the proximal and distal promoters. In liver, hypersensitive sites are present in the proximal promoter but not the distal promoter. Interestingly, in H4IIEC3 cells, a hepatoma cell line that has lost the ability to express GK, hypersensitive sites are also found in the proximal promoter but not the distal promoter.

Animals↗
PubMed1995

Heat shock protein studies in type 1 and type 2 diabetes and human islet cell culture.

Heat shock proteins (HSP) play an important role in auto-immunity and infection. Glutamic acid decarboxylase (GAD) the prime antigen in Type 1 diabetes has similar amino acid sequences to HSP65. An ELISA was developed using a plant-derived HSP65 antibody. HSP65 antibody was present in the serum of all normal subjects (median 1.64 AU, IQ range 1.49-1.74). Lower levels were found in established Type 1 diabetes (1.41 AU, 1.32-1.61, p < 0.001) and Type 2 diabetes (1.45 AU, 1.35-1.59, p < 0.006). In Type 1 HSP antibody levels fell with age (p = 0.007) and with duration (p = 0.008) and women with Type 1 had lower levels than men (p = 0.009). Human islet cell culture subjected to heat shock revealed an approximate four fold increase in heat shock protein antigen in the surrounding medium. The release of HSP antigen from stressed islet cells together with the finding of HSP antibody in the serum of all subjects suggest that HSP65 should not be completely discarded as having a possible role in the development of Type 1 diabetes. Low levels of HSP antibody in patients with established diabetes is probably a manifestation of impaired immunity induced by the diabetic state.

Adolescent↗
PubMed1994

Expression and processing of parathyroid hormone-related protein in a pancreatic endocrine cell tumour associated with hypercalcaemia.

We describe a patient with a neuroendocrine tumour of the pancreas associated with hypercalcaemia which was attributed to production of parathyroid hormone-related protein (PTHrP) by the tumour. Plasma PTHrP 1-86 was significantly raised, and fell following surgical resection of the tumour. PTHrP mRNA and peptide were identified in tumour tissue by in-situ hybridization and immunohistochemistry respectively. PTHrP was quantitated in an extract of tumour tissue by three region-specific immunoassays (PTHrP 1-34 45.2 pmol/g, PTHrP 37-67 81.7 pmol/g, PTHrP 1-86 27.3 pmol/g) and suggested the presence of excess of amino-terminal and mid-region immunoreactivity. On chromatography of the tumour extract the first peak eluted as 22 kDa and comprised approximately equimolar 1-34, 37-67 and 1-86 activities. The second and major peak of 16 kDa contained only 37-67 activity, while the third peak of 6 kDa contained only 1-34 activity. This suggested that the tumour contained a native or intact form of PTHrP together with two major subfragments containing 37-67 and 1-34 activity respectively. Thus chromatographic separation and quantitation of PTHrP by region-specific immunoassays have provided new information on in-vivo proteolytic processing by tumour tissue by indicating that a site of cleavage is located between residues 17 and 61. Our findings are compatible with cleavage at residue 37, a site previously indicated from in-vitro studies.

Adult↗
PubMed1994

Hyperthyroidism and radio-iodine therapy in a district general hospital.

A retrospective analysis was performed of 48 patients with hyperthyroidism (41 women aged 35-80, mean 56.6 years; 7 men aged 31-77, mean 52.1 years) treated with a fixed dose of 550 MBq 131I during a 12 month period May 1991-April 1992. Weight loss was common at presentation but 28.57% of women aged 35-49 years weighed over 80 kg compared to 9.98% in a standard UK population P < 0.05. Patients treated with carbimazole (73%) prior to 131I had higher FT3 levels at presentation (14.0 +/- 4.4 pmol/l) compared to those (27%) who were considered not to require such treatment (8.9 +/- 1.4 pmol/l, P < 0.001). Four months following radio-iodine, 67% were hypothyroid, 25% were euthyroid and 8% remained thyrotoxic and were retreated. Another patient became hypothyroid during 1 year of follow-up. Pre-treatment with carbimazole did not protect against the development of hypothyroidism (carbimazole treated 69% hypothyroid at 4 months, untreated 62% hypothyroid at 4 months). Patients with continuing thyrotoxicosis had very high FT3 levels at presentation (18.6, 21.1, 20 and in one patient reported only as > 10 pmol/l). A rationalized programme of follow-up assessments at 2, 3, 4, 8 and 12 months is suggested for patients treated with this dose of radio-iodine.

Adult↗
PubMed1994

Stability of plasma lactate in vitro in the presence of antiglycolytic agents.

The use of plasma lactate to assess metabolic or circulatory impairment requires definition of critical preanalytical and analytical parameters. Stability has been documented for only 15 min after acquisition when samples were collected with fluoride and transported on ice. We examined time elapsed before analysis, storage temperature, and the antiglycolytic agent used to define preanalytical conditions. Plasma lactate was measured with a Kodak Ektachem 700XR analyzer. In controlled studies on volunteers, storage on ice slowed but did not eliminate the production of lactate; for samples collected with sodium fluoride (F) and potassium oxalate (OX), lactate increased by 0.2 mmol/L after 1 h, then changed little regardless of the storage temperature. For patients' samples collected in F/OX, the mean increase was only 0.15 mmol/L after 24 h. Samples with leukocytosis (neutrophil counts 23 x 10(9)-52 x 10(9)/L) were also stable, with a mean increase of 0.3 mmol/L at 8 h. Use of the antiglycolytic agents F and OX (at 60 and 12 mmol/L, respectively) maintained apparently stable lactate concentrations at room temperature for up to 8 h without special handling.

Acidosis, Lactic↗
PubMed1993

Heat shock protein and the double insult theory for the development of insulin dependent diabetes.

Heat shock proteins (HSP) are the most widely conserved group of proteins in phylogeny and play an important role in infection and autoimmunity. HSP65 has been suggested as the primary antigen in insulin dependent diabetes while an alternative antigen glutamic acid decarboxylase (GAD), has similar amino acid sequences. A 'double insult theory' for the development of insulin dependent diabetes is suggested whereby a bacterial infection leads to the production of HSP antibody. If during a 'window of opportunity' this is followed by a viral infection of the islet cells this could, in certain histocompatibility locus antigen (HLA) groups only, lead to the production of HSPs on the cell surface and a destructive autoimmune reaction.

Animals↗