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.

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.

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.

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.

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.

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.

Body weight estimation of elderly patients by nomogram.

OBJECTIVE: To determine a safe and easy way to estimate body weight (BW) accurately in nonambulant elderly patients. DESIGN: An anthropometric study of ambulant patients. PARTICIPANTS: Two hundred eleven ambulant inpatients, 108 males and 103 females. SETTING: Inpatient departments of the University Department of Geriatric Medicine, Cardiff, Wales, UK. MEASUREMENTS: Skinfold thickness of chin, triceps, forearm, wrist, subscapular, sternal angle, waist, suprailiac, knee, and calf; circumference of arm, forearm, thigh and calf; body weight, chest girth, abdominal girth, upper limb length, leg length, and body weight. Measurements were carried out by means of Harpenden Skin-Fold Caliper, tape measure, and bathroom scale. RESULTS: Measured body weight in males was highly correlated with both arm circumference and chest girth. In females, measured body weight was highly correlated with waist skinfold thickness and thigh circumference. Nomograms for weight estimation in males and females were constructed from the regression equations for these measurements. CONCLUSIONS: Convenient estimation of body weight in nonambulant patients may be carried out using nomograms, which, themselves, may be used as progress sheets to assess the effect of dietary supplementation on body weight.

An audit of cardiac pacing in the elderly: effect of myocardial infarction on outcome.

OBJECTIVE: To audit the outcome of temporary endocardial pacing in an elderly population. DESIGN: Retrospective case-series analysis. SETTING: The Department of Medicine for the Elderly at the Wrexham Maelor Hospital, a District General Hospital with 612 beds serving a catchment population of 220,000. SUBJECTS: A sample of 50 consecutive elderly patients, with an age range of 65 to 99 years, undergoing transvenous cardiac pacing. MAIN OUTCOME MEASURES: Length of stay in hospital, complications of the pacing procedure, whether a permanent pacemaker was installed, and whether the patient died within 1 month of admission. RESULTS: There was no difference in length of stay between those with a myocardial infarction and those without. Minor complications occurred in three patients (one local infection and two "failures to pace"). Major complications occurred in two patients (septicemia and pneumonia). More patients without a myocardial infarction (86.9%) went on to implantation of a permanent pacemaker than those with an infarction (11.1%, P = 0.001), and fewer of them died (8.7% compared with 48.1%, P = 0.0025). In those patients with a myocardial infarction who died, there was no difference between the proportions who had inferior (7/18) and anterior (5/9) infarctions. CONCLUSION: Cardiac pacing seems to be a safe and reliable procedure in the elderly, although long term morbidity and mortality may be dependent on the presence or absence of myocardial ischaemic disease. Myocardial infarction in the elderly is an event of major significance, carrying with it a high mortality rate, particularly if accompanied by cardiogenic shock and the need for cardiac pacing.

The effect of thyroxine on small intestinal motility in the elderly.

OBJECTIVE: To study the effects of thyroxine on orocaecal transit time in a group of elderly hypothyroid patients on long-term thyroxine replacement therapy. DESIGN: Measurement of the effect of withdrawal and subsequent replacement of thyroxine replacement therapy on orocaecal transit time. PATIENTS: Fifteen elderly, previously hypothyroid patients on full replacement therapy with oral thyroxine were studied. There were 11 females and four males, aged 60-94 years (median 78 years) receiving initially 50-200 micrograms of oral thyroxine daily (median 100 micrograms). MEASUREMENTS: Serum TSH and FT4 were measured by radioimmunoassay and orocaecal transit time assessed using a lactulose hydrogen breath test. These tests were repeated 7 days after withdrawal of thyroxine replacement and again 7 days after subsequent reinstatement of therapy. RESULTS: On withdrawal of therapy, the median transit time increased from 75.0 to 135 minutes (P less than 0.01), the median TSH increased from 1.8 to 2.3 mU/l (P = NS) and the median FT4 decreased from 13.7 to 10.6 pmol/l (P less than 0.01). On reinstatement of therapy, the median transit time decreased to 95 minutes (P = NS), the median TSH decreased to 1.1 mU/l (P = NS) and the median FT4 increased to 14.1 pmol/l (P less than 0.01). CONCLUSIONS: These findings demonstrate the sensitivity of the small bowel to changes in thyroid hormone status and suggest that constipation arising as a result of this hypomotility may well be an early physical manifestation of hypothyroidism.

Factors associated with Colles' fracture in the elderly.

We have measured sway, hearing and eyesight in a group of elderly patients with Colles' fracture (3 males, 21 females, mean age 75.9 years) and in a control group of elderly fallers (5 males, 19 females, mean age 76.9 years) who had no fractures. The Colles' fracture group had better eyesight than the control group (p = 0.022), but worse hearing, particularly at lower frequencies (p less than 0.0001 at 500 Hz), suggesting a conductive hearing loss. We conclude that those individuals with better eyesight would try to stretch their arm to break a fall, so breaking their wrist. Osteoporotic changes in the auditory ossicles is proposed as a possible cause for the hearing loss in the Colles' fracture group. We conclude that those individuals presenting with Colles' fracture may also have hearing loss and conversely, patients presenting with a conductive hearing loss may be at risk of developing the further symptoms of osteoporosis.

Measurement of height in the elderly.

Height is an essential variable when assessing renal clearance, nutritional status, and absorption. Standard methods of estimating height are impractical in the nonambulant. One hundred sixty-five elderly inpatients were studied. Total standing height, knee-to-floor height, and tibial length were measured. Total arm, upper arm, and forearm measurements were obtained in both erect and supine positions. Measured height correlated best with supine total arm length (R2 = .69), knee-to-floor height (R2 = .63), and erect forearm length (R2 = .61). A nomogram relating both supine total arm length and knee-to-floor height with the patient's measured height has been prepared.

14C triolein breath test: an assessment in the elderly.

14C triolein breath tests are highly sensitive in detecting fat malabsorption in adults, but experience in the elderly is sparse. We have evaluated 48 'normal' subjects over the age of 65 years and compared the results with those of 46 normal subjects under 65 from a previous study. Results were calculated as eight hour cumulative values and expressed as percentages of the administered dose. Reference ranges have been calculated separately for the following age groups: 65 years or less (201 to 460), 66 to 75 (182 to 405) and over 75 (141 to 336). A clear age related decline in eight hour cumulative values was noted. The values fell by 23% between the ages of 17 and 65 years and by 25% between the ages of 65 and 87 years. Pancreatic insufficiency or bacterial colonisation of the small bowel is unlikely, but delayed intestinal absorption or the effects of slower metabolic rate cannot be excluded. This test is simple and practicable in the elderly and the study emphasises the importance of age in the interpretation of results.

14C triolein breath test: a routine test in the gastroenterology clinic?

The absorption of 14C triolein in a standard fat meal was measured in 60 controls and 66 patients with gastrointestinal disorders by 14CO2 breath sampling. A reference range based upon cumulative eight hour values of the controls was independent of height, weight, and sex. The range was of log normal distribution and declined with age (p less than 0.05). Acceptable 'within-day' and 'between-day' reproducibility was found. All patients tested with untreated coeliac disease, pancreatic insufficiency and most with symptomatic small intestinal Crohn's disease had subnormal values. Twenty per cent of those with irritable bowel syndrome had subnormal values. Patients with ulcerative colitis were all normal. The reagents used and the breath samples after collection were stable. In our experience the 14C triolein test is simple, inexpensive, and helpful in the detection of diseases associated with fat malabsorption. It is of value in monitoring the response to treatment of individual patients with coeliac disease.

Multivariate analysis of glycosylated haemoglobin in insulin-treated diabetics.

Glycosylated haemoglobin (HbA1), as an assessment of overall control, was estimated in 858 insulin-treated diabetics attending for changeover to U100 insulin in North East Wales. Details of age, sex, duration of diabetes, insulin regimen and monitoring method were recorded. Multivariate analysis revealed lower HbA1 in patients receiving twice-daily (mean 11.01) as compared with once-daily insulin (11.42, P = 0.011), but no difference was found between urine and blood glucose testers when other variables were taken into consideration. HbA1 was lower in men (mean 10.94) compared with women (mean 11.39, P = 0.004) and there was a positive correlation of HbA1 in men with age (P = 0.046) and in women with duration of disease (P = 0.005).

Ultrastructure of mitosis and cytokinesis in the multinucleate green alga Acrosiphonia.

The processes of mitosis and cytokinesis in the multinucleate green alga Acrosiphonia have been examined in the light and electron microscopes. The course of events in division includes thickening of the chloroplast and migration of numerous nuclei and other cytoplasmic incusions to form a band in which mitosis occurs, while other nuclei in the same cell but not in the band do not divide. Centrioles and microtubules are associated with migrated and dividing nuclei but not with nonmigrated, nondividing nuclei. Cytokinesis is accomplished in the region of the band, by means of an annular furrow which is preceded by a hoop of microtubules. No other microtubules are associated with the furrow. Characteristics of nuclear and cell division in Acrosiphonia are compared with those of other multinucleate cells and with those of other green algae.