RESUMEN

BACKGROUND: Hereditary haemochromatosis (HH) is one of the commonest genetic disorders in European populations. Transferrin saturation (TFS) measurement has been advocated as a phenotypic screening test to improve detection. We undertook a prospective study to examine the value of routine TFS measurement in detecting new cases of HH in unselected liver clinic attenders. METHODS: Non-fasting TFS was measured in new patients. HH mutations were determined in those with elevated TFS (>45%) and all who underwent liver biopsy. Liver biopsy was performed in 349 patients, including all found to be C282Y homozygotes or compound heterozygotes. RESULTS: Of 667 new patients attending over 5 years, 156 had TFS >45% and 18 had significant mutations (12 C282Y homozygotes and six compound heterozygotes). Eleven of the 12 C282Y homozygotes identified had an elevated TFS and 10 had significant hepatic siderosis. Only two of the six compound heterozygotes had an elevated TFS and hepatic siderosis. CONCLUSIONS: The prevalence of new HH cases in patients of European origin attending a liver clinic, detected by phenotypic screening over a 5-year period, was 2.8%. All were identified by a TFS cut off >45%, but TFS >60% provided the best combination of sensitivity and specificity for detecting C282Y homozygosity.

Asunto(s)

RESUMEN

BACKGROUND: Two common mutations of the haemochromatosis associated gene (HFE) (cys282tyr (C282Y) and his63asp (H63D)) have been implicated in haemochromatosis and as modulators in cardiovascular disease. OBJECTIVE: To investigate the role of these mutations in the pathogenesis of idiopathic dilated cardiomyopathy. DESIGN AND SETTING: Case-control and prospective cohort study of patients attending a cardiomyopathy unit in a tertiary referral cardiac centre. METHODS: 207 unrelated white patients with dilated cardiomyopathy, followed up for 259 patient years, and 200 controls were tested for HFE C282Y and H63D mutations by polymerase chain reaction and restriction digestion. RESULTS: 31/207 patients (15%) v 24/200 controls (12%) carried C282Y (adjusted odds ratio (OR) 1.2 (95% confidence interval 0.7 to 2.2)), 74/207 (36%) v 53/200 (27%) carried H63D (OR 1.6 (1.1 to 2.5)), and 10/207 (4.8%) v 4/200 (2%) were compound heterozygotes (OR 2.6 (0.8 to 8.5)). Four patients and six controls were H63D homozygous and one was C282Y homozygous. There was a progressive increase in mean serum iron ([Fe]) and transferrin saturations from patients with no mutation ([Fe] = 16.3 micromol/l, transferrin saturation = 23.7%) through H63D heterozygotes (17.5 micromol/l, 25.8%), C282Y heterozygotes (17.1 micromol/l, 26.6%), H63D homozygotes (20.0 micromol/l, 33.5%), compound heterozygotes (26.8 micromol/l, 41.7%), and C282Y homozygotes (34 micromol/l, 71%). At follow up (median 90 months) the rate of death or cardiac transplantation was 52/207 (25%). C282Y heterozygotes had less ventricular dilatation (mean (SD): 59.9 (1.7) mm v 64.9 (0.9) mm, p < 0.05), better fractional shortening (24 (1. 7)% v 18.8 (1.4)%, p < 0.01), and a trend towards improved survival without transplantation. [Fe] and transferrin saturation did not correlate with disease severity and were not associated with reduced survival. CONCLUSIONS: The frequency of the H63D mutation is significantly increased in patients with idiopathic dilated cardiomyopathy. As H63D has a relatively minor effect on iron status, the mechanism of this association may be unrelated to iron metabolism.

Asunto(s)

RESUMEN

Renal blood flow is reduced in patients with chronic respiratory failure caused by chronic obstructive pulmonary disease (COPD), and changes in renal hemodynamics are likely to be important in the pathogenesis of the edematous state of cor pulmonale. We therefore examined the hypothesis that this renal vasoconstriction is reversible by comparing the effects of oxygen therapy and the renal vasodilator dopamine on renal hemodynamics in both hypoxemic patients with COPD and those who were also hypercapnic. We assessed renal hemodynamics noninvasively with color-flow Doppler ultrasound. In order to validate the technique we recorded renal hemodynamics in a group of healthy volunteers before and during a dopamine infusion, and in a subgroup we simultaneously measured effective renal plasma flow (ERPF) with para-aminohippurate clearance. In the healthy volunteers there was a 22.5% rise in time-adjusted mean arterial velocity (Tamx) measured by Doppler compared with a 22% rise in ERPF with dopamine. This rise was significant (p < 0.05). In hypoxemic, normocapnic subjects Tamx rose by 25% with oxygen (p < 0.005), 20% with dopamine (p < 0.005), and 24% with both therapies. There was no significant change in aortic flow whether the subjects received air, oxygen, or dopamine (p = 0.77). In the hypercapnic patients there was no significant change in aortic or renal velocities while receiving oxygen or dopamine (p = 0.85 and 0.86). We conclude that color-flow Doppler velocity measurements can accurately detect changes in renal blood flow. Oxygen and dopamine are equipotent renal vasodilators in hypoxic COPD, but the effect is not additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

RESUMEN

The stability of plasma parathyroid hormone-related protein (PTHrP) as measured by the Nichols Institute assay at room temperature was assessed over a period of 72 h in blood samples collected in protease inhibitor tubes and EDTA tubes at 0, 6, 24, 48 and 72 h from 10 patients with hypercalcaemia of malignancy. Mean plasma PTHrP concentrations in blood samples collected in protease inhibitor tubes remained stable for up to 48 h but had decreased by 10% at 72 h. The mean EDTA plasma PTHrP at zero time was 67% of the protease inhibitor tube value and this had fallen to 39% at 72 h. The stability of parathyroid hormone (PTH) in separated blood samples was also assessed by collection into heparin and plain tubes as well as EDTA and protease inhibitor tubes. Serum PTH concentrations progressively declined throughout the 72 h study period although the zero time values were significantly higher than corresponding plasma PTH concentrations. Plasma PTH concentrations appeared to be stable when blood was collected in heparin, EDTA and protease inhibitor tubes during the 72 h period, except in one subject with markedly elevated plasma amylase activity.

Asunto(s)

RESUMEN

Old people are commonly receiving diuretics on admission to hospital. Diuretics are recognized as a risk factor for electrolyte disturbances; controversy exists about the relative risks of different combinations (in particular, co-amilozide [Moduretic]). We recorded the drug history and serum electrolytes in 1000 consecutive admissions to a geriatric hospital, and examined the relative prescribing rates of various diuretics in the community. Full results were obtained in 929 patients. A history of diuretic prescription was present in 353 (38%) of the patients; the mean serum sodium in this group (95% CI 136.0-137.1 mmol/l) was lower than in the 586 not prescribed diuretics (137.1-137.9 mmol/l). The difference was small but statistically significant (95% CI difference = 0.3-1.6 mmol/l; P less than 0.01). Hyponatraemia (serum sodium less than 130 mmol/l) was not significantly commoner in the 41 patients prescribed co-amilozide than in patients prescribed other diuretics. In general patients prescribed potassium-retaining diuretics had a lower serum sodium than the others. There was a significant positive correlation between the serum potassium and the log [serum urea] (r = 0.26, P less than 0.001) and a weak negative correlation existed between sodium and potassium (r = -0.14; P less than 0.001). There was an association between the prescription of potassium-retaining diuretics and a higher serum potassium; also an association between the prescription of a loop or thiazide diuretic and a lower serum potassium. These interactions were shown by multiple regression analysis to be independent and additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

RESUMEN

Thirteen patients with mild primary hyperparathyroidism who were taking thiazide diuretics intermittently for periods of up to 18 months were followed up for a mean of 5.3 years. No significant difference was found in either plasma total calcium corrected for albumin or whole blood ionized calcium in these patients between the periods on or off thiazides. We conclude that thiazide diuretics are not contraindicated in such patients.

Asunto(s)

RESUMEN

Two healthy individuals who drank water accidentally contaminated at source with aluminium sulphate solution were investigated 6-7 months later. Bone biopsy specimens showed discrete lines of positive staining for aluminium, the distribution being compatible with acute exposure some months previously. These findings show that under certain conditions normal individuals can absorb aluminium via the gut, and that such aluminium can be deposited in bone.

Asunto(s)

RESUMEN

The lactulose/mannitol dual sugar absorption test is a non-invasive test of intestinal permeability. Its widespread use has been limited by the difficulties of analysis for carbohydrates in urine at low concentrations. We describe a "high-pressure" liquid-chromatographic method for determining lactulose and mannitol in urine, in which anion-exchange chromatography and pulsed amperometric detection are used. Sample preparation is simple and fast, and lactulose and mannitol and the internal standards arabinose and cellobiose are well resolved within 15 min. Analytical response of the method is linear with concentrations to 3 g/L, and one can detect as little as 0.3 mg of lactulose per liter of urine. Analytical recovery was between 90% and 107% for all sugars analyzed, and there was good agreement with results by a gas-chromatographic method (r = 0.993 lactulose, 0.984 mannitol). The method may potentially be applied to the study of other carbohydrates present in biological fluids at low concentrations.

Asunto(s)

RESUMEN

We have compared the [14C]triolein breath test for fat malabsorption with fecal fat excretion corrected for marker pellet recovery in 23 subjects with chronic liver disease. The breath test identified 15 of the 17 subjects with abnormal fecal fat excretion (sensitivity 88%). However, four of the six subjects with normal fecal fat excretion gave abnormal breath test results (specificity 33%). While three of the four subjects with falsely abnormal breath tests had alcoholic liver disease, the explanation for the low specificity is unclear and may not be confined to patients with alcohol-related disease. We are therefore unable to recommend the breath test as a screen for steatorrhea in patients with chronic liver disease.

Asunto(s)

RESUMEN

Thyroid hormone action at the cellular level was investigated in euthyroid women who were receiving replacement thyroxine, and whose plasma T4 levels were above the upper reference limit for healthy subjects. There is evidence that erythrocyte sodium pump sites are reduced in number in patients with hyperthyroidism. These sites were measured by the ouabain binding capacity. Plasma T4, free T3 and TSH were also measured, the latter by a high sensitivity fluoroimmunoassay. Three groups of women were investigated; 30 patients receiving T4 with elevated plasma T4 concentrations, 30 age-matched healthy women, and 10 untreated thyrotoxic patients. Erythrocyte ouabain binding was significantly reduced in the thyroxine treated patients, although not to the degree observed in the thyrotoxic patients. Plasma free T3 concentration was increased in 12 of 30 treated patients. TSH was undetectable in 23 of 30 treated patients. The ouabain binding results provide some evidence for increased thyroid hormone action at cellular level in thyroxine treated patients.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

Plasma retinol and retinol-binding protein (RBP) were measured in 39 pre-term infants, 15 of whom were small-for-gestational age (SGA), within 48 h of birth. Retinol concentrations were inversely correlated with gestational age and birth weight, but there was no significant difference between the well grown pre-term infants and the SGA infants. RBP concentrations were not correlated with gestation or birth weight, but the values in SGA infants were significantly lower than in well grown infants (P less than 0.01). Although RBP was highly correlated with retinol in well grown infants (P less than 0.001), no such correlation was observed in SGA infants. The significance of this is discussed.

Asunto(s)

RESUMEN

In order to study the relation between plasma magnesium and blood glucose concentrations in diabetes, diurnal profiles were obtained in nine diabetic patients and five healthy subjects. A significant inverse relationship between the two variables was found in seven of the nine diabetic patients and in one healthy subject. This could not be attributed solely to changes in plasma albumin, and its mechanism is unclear. Plasma magnesium levels in diabetes are closely dependent on blood glucose concentration.

Asunto(s)

RESUMEN

Leucocyte and erythrocyte magnesium was assayed in 17 healthy subjects and 17 insulin dependent diabetic patients. Plasma magnesium concentration (mean +/- standard error of mean) was significantly lower in the diabetic patients (0.80 +/- 0.02 mmol/l), compared with the healthy subjects (0.90 +/- 0.02 mmol/l, p less than 0.001), but the leucocyte and erythrocyte magnesium content was not significantly different in the diabetic patients (34.5 +/- 0.8 and 6.2 +/- 0.2 mmol/kg dry solids) compared with the healthy subjects (35.5 +/- 0.8 and 6.5 +/- 0.11 mmol/kg dry solids). In a separate study skeletal muscle obtained by needle biopsy was also assayed. Plasma magnesium in 10 diabetic patients (0.74 +/- 0.01 mmol/l) was significantly lower than in 16 healthy subjects (0.85 +/- 0.02 mmol/l, p less than 0.001), but there was no significant difference in the mean muscle magnesium content (43.0 +/- 0.7 compared with 40.7 +/- 0.9 mmol/kg dry solids in the diabetic patients).

Asunto(s)

RESUMEN

Bronchial secretions from 21 patients with moderate to severe chest infections were obtained by transtracheal aspiration. Six seriously ill patients showed greatly increased levels of amylase activity in the bronchial secretions compared with those found in the 15 less ill patients. This amylase was almost certainly derived from oropharyngeal contents and its presence suggests that aspiration may be more common in comatose and semi-comatose patients than is generally appreciated.

Asunto(s)

RESUMEN

Three tests were evaluated as screening procedures for fat malabsorption--namely, measurement of serum optical density, serum triglyceride concentration, and 14CO2 breath excretion after the administration of a 60 g fat meal containing 10 muCi glycerol tri[1-14C]oleate. The results of these tests were compared with fat excreted in a three-day faecal collection after adjustment for completeness of collection as assessed by using non-absorbable radio-opaque markers. Fifty-two patients with various symptoms and eight normal subjects were studied. The maximum increase in serum optical density or triglyceride concentration above the fasting value discriminated poorly between subjects with normal and increased adjusted faecal fat excretion. In contrast, seven- or eight-hour cumulative 14CO2 breath excretion provided good discrimination with only four (7%) false-positive and no false-negative results. The simplicity and convenience of breath analysis make it an attractive alternative to analysis of faecal fat excretion in screening for fat malabsorption.

Asunto(s)

RESUMEN

Bronchial secretions from 21 patients with moderate to severe chest infections were obtained by transtracheal aspiration. Six seriously ill patients showed greatly increased levels of amylase activity in the bronchial secretions compared with those found in the 15 less ill patients. This amylase was almost certainly derived from oropharyngeal contents and its presence suggests that aspiration may be more common in comatose and semi-comatose patients than is generally appreciated. (Summary)

Asunto(s)

Asunto(s)

RESUMEN

Leucocyte magnesium concentration was measured in 25 hypomagnesaemic patients following a jejuno-ilean bypass operation for gross obesity. The mean plasma magnesium concentration in the bypass group was 0.67 mmol/l compared with that of 0.90 mmol/l in a group of 17 healthy volunteers, but the leucocyte magnesium concentration in the two groups was not significantly different. The plasma potassium was found to be significantly lower in the bypass group but there was no significant difference in the leucocyte potassium concentration in the two groups. Simultaneous measurements of erythrocyte magnesium, sodium and potassium were made. There was no evidence of intracellular magnesium depletion on the basis of the tissues studied.

Asunto(s)