BACKGROUND: We investigated patients who had unexplained hepatic iron overload and normal transferrin saturation. METHODS: 65 patients with a median liver iron concentration of 65 mumol/g dry weight of liver (normal < 36 mumol/g), hyperferritinaemia (566 micrograms/L; normal < 400 micrograms/L), and normal transferrin saturations (32%) were compared with genetic haemochromatosis (GH) controls including homozygous (matched for sex and serum ferritin concentration) and heterozygous individuals. Relatives of patients who had ratios of liver iron concentration to age greater than 1.9 were also studied. FINDINGS: The 65 patients were significantly older and had significantly less hepatic iron overload than individuals with genetic haemochromatosis. The frequency of HLA-A3 antigen was significantly lower in these patients than in individuals with homozygous (p < 0.0001) or heterozygous (p < 0.0002) GH. Five HLA-identical siblings of the patients had normal serum ferritin concentrations. Most of the patients (95%) had one or more of the following conditions; obesity, hyperlipidaemia, abnormal glucose metabolism, or hypertension. INTERPRETATION: We have found a new non-HLA-linked iron-overload syndrome which suggests a link between iron excess and metabolic disorders. The current diagnostic criteria for genetic haemochromatosis should be reviewed.

Adolescent↗

PubMed1995

Defective cytokine expression but adult-type T-cell receptor, CD8, and p56lck modulation in CD3- or CD2-activated T cells from neonates.

Expression of IL-2, interferon-gamma, and IL-3 mRNA and proteins was investigated in peripheral blood mononuclear cells from cord blood after activation with phytohemagglutinin, CD2, or CD3 MAb. The results showed that interferon-gamma and IL-3 expression was decreased in cord peripheral blood mononuclear cells when compared with expression observed in adult peripheral blood mononuclear cells, irrespective of the stimulation used. In addition, in newborn cells a defect in IL-2 secretion and mRNA expression was observed in response to CD2 or CD3 MAb but not in response to phytohemagglutinin-mediated activation. We further analyzed the modulation of nonlymphokine genes under the same protocol of stimulations. The results indicate that in newborn cells, despite a reduced lymphokine expression observed after CD2 or CD3 MAb activation, the up-regulation of the T-cell receptor, CD8, and p56lck was similar to that found in adult cells, as was also found after phytohemagglutinin activation of both types of cells. These data are in favor of a deficient T-cell responsiveness to CD2 or CD3 MAb in newborn cells. This impairment of the T-cell response appears to selectively affect lymphokine gene expression because the modulation of other genes also implicated in T cell activation is not altered.

Adult↗

PubMed1995

[Importance of atrioventricular synchrony in hypertrophic obstructive cardiomyopathy treated by cardiac pacing].

This study was undertaken to evaluate the effect of permanent dual-chamber cardiac pacing in hypertrophic obstructive cardiomyopathy resistant to medication, paying particular attention to atrioventricular synchrony. Sixteen patients, mean age 59 +/- 13 years (range 36 to 80 years) were divided into two groups after in initial catheter study performed under temporary VDD pacing between March 1990 and April 1993. In group I (n = 11), the gradient was decreased by more than 50% whereas in group II (n = 5), the gradient was unchanged or reduced by less than 50%. The reduction of the gradient was immediately significant in group I, the mean value falling from 104 +/- 33 mmHg (range 60 to 170 mmHg) to 25 +/- 13 mmHg (range 10 to 60 mmHg) (p < 0.0001). In group II, the gradient only decreased initially from 132 +/- 13 mmHg (range 120 to 150 mmHg) to 88 +/- 25 mmHg (range 50 to 130 mmHg) (p < 0.003) but improved atrioventricular synchrony, obtained secondarily either by pharmacological prolongation of the PR interval (association of betablocker and verapamil) or by ablation of the atrioventricular junction, improved the haemodynamic benefits. The residual gradient recorded on the 7th day was only 26 +/- 15 mmHg (range 10 to 50 mmHg) (p < 0.0001). The comparison of the two populations showed that the mean PR interval was shorter in group II (p < 0.016) and the mean value of the optimal AV Delay (the longest AV Delay with complete ventricular capture) was also lower (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1994

Vitamin D metabolism by alveolar immune cells in tuberculosis: correlation with calcium metabolism and clinical manifestations.

The aim of this study was to investigate the relationship between the pulmonary vitamin D metabolism in tuberculosis and the calcium metabolism abnormalities and other clinical characteristics of the disease. The metabolism of 25-hydroxyvitamin D3 (25(OH)D3) by alveolar immune cells recovered by bronchoalveolar lavage (BAL) was evaluated in parallel to the results of calcium metabolism, 25(OH) D and 1,25 dihydroxyvitamin D (1,25(OH)2D) plasma levels and other clinical parameters obtained in 14 tuberculosis patients. Whilst predominant metabolites produced by lavage cells in patients and controls were 5(E)--and 5(Z) -19-nor-10-oxo-25(OH)D3, 1,25(OH)2D3 was produced by cells from all tuberculosis patients but not by cells from controls. Calcium metabolism abnormalities were observed in only some patients, but the production of 1,25 (OH)2D3 by lavage cells was found to correlate both with 1,25(OH)2D levels (r = 0.67) and post-load urinary calcium excretion (r = 0.59). 1,25(OH)2D3 production by lavage cells was increased in patients of black origin, and those presenting with hilar adenopathy without pulmonary infiltrates, and was correlated with the number of lymphocytes recovered by lavage (r = 0.87). We conclude that 1,25(OH)2D3 production by alveolar immune cells makes a major contribution to the abnormalities in calcium metabolism seen in tuberculosis patients, and may be partly dependent on the clinical characteristics evaluated here.

Adult↗

PubMed1993

LDL sialic acid content in patients with coronary artery disease.

Low density lipoproteins (LDL) are considered to be the most atherogenic of lipoproteins. These LDL can be modified and oxidative modifications are now well known. In addition, other atherogenic modifications of LDL exist, such as desialylation. In the present study sialic acid content was determined in LDL preparations obtained from patients with coronary artery disease (CAD+) and compared with that of healthy subjects and patients without coronary heart disease (CAD-). The sialic acid concentration was found to be statistically lower (P < 0.05) in the LDL of CAD+ patients (11.6 +/- 2.7 micrograms/mg of protein) than in the LDL of controls (16.5 +/- 5.6 micrograms/mg of protein) or in the LDL of CAD- patients (15.3 +/- 3.8 micrograms/mg of protein). In subgroups of CAD+ patients divided according to the severity of the disease, no statistically significant difference was observed in LDL sialic acid content. This work confirms the presence of desialylated LDL in the sera of patients with atheroma.

Adult↗

PubMed1993

Retrieval of a lost coronary stent from the descending aorta using a PTCA balloon and biopsy forceps.

We report a case of unsuccessful stenting of a right coronary artery after acute dissection during percutaneous transluminal coronary angioplasty (PTCA). The stent was lost in the descending aorta and we used an original technique to remove it from the arterial bed by using both a very low profile balloon and a 6F bioptome.

Aortic Dissection↗

PubMed1993

Role of the renin-angiotensin system on the renal functional reserve in renal transplant recipients.

To determine the renal functional reserve in renal transplant recipients, we measured the glomerular filtration rate by inulin clearance and the renal plasma flow by PAH clearance before and during an amino acid infusion (Totamine, 6 to 8 mg/kg/min for 90 to 120 min) in 18 transplanted patients with stable renal function. To test the role of the renin-angiotensin system on the renal functional reserve, we performed a crossover placebo-controlled randomized trial of acute blockade of the renin-angiotensin system by injection of perindoprilat (2 mg i.v.), an inhibitor of angiotensin converting enzyme before amino acid infusion, each patient being studied twice at seven day intervals. Amino acid infusion induced a time-dependent increase in the glomerular filtration rate (P = 0.04), whether or not the renin-angiotensin system was blocked. Maximal increases were from 49.1 +/- 4.1 to 58.9 +/- 5.4, mean +/- SE (18.5%), in control conditions and from 52.4 +/- 5.6 to 62.1 +/- 5.5 ml/min/1.73 m2 (19.7%) after perindoprilat. The increase in glomerular filtration rate was less pronounced in patients taking cyclosporin A than in patients treated with steroid and azathioprine. Amino acid infusion also induced a significant and time-dependent increase (15.2 to 20.2%) in the renal plasma flow (P < 0.01) whether or not perindoprilat had been given. Furthermore, perindoprilat alone increased renal plasma flow by 13.6%, and this effect seemed additive with that of amino acids. Perindoprilat injection decreased filtration fraction (from 0.20 +/- 0.01 to 0.19 +/- 0.01). This parameter returned to basal values after amino acid infusion (0.20 +/- 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

A prospective study of patients with CT detected pallidal calcifications.

In a prospective study pallidal calcification was detected in 30 of 1478 (2%) adult patients, on CT brain scans. In 8 cases (26%), the calcifications were detected either years after, or during the course of, conditions known to cause basal ganglia calcification, including AIDS in four cases. Eight patients (three with AIDS) had disturbances of calcium and phosphorus metabolism. It was concluded that: a) pallidal calcification is not uncommon and aetiological factors may be recognised more often than previously reported; b) AIDS is emerging as a significant cause of pallidal calcification in young adults, and c) in AIDS and other conditions, abnormal calcium and phosphate metabolism may act in conjunction with local vascular changes.

Adult↗

PubMed1993

[Hypokalemia without arterial hypertension by licorice poisoning].

We report a case of chronic intoxication with glycyrrhizinic acid, at a dosage of 1000 to 1500 mg per month over a period of 11 months, in a former alcoholic. This intoxication was revealed by profound hypokalaemia and rhabdomyolysis. However, blood pressure remained constantly normal. Analysis of the literature shows that liquorice intoxication, which blocks renal 11 beta-hydroxysteroid dehydrogenase evolves more frequently as isolated hypokalaemia than as a picture of pseudo-primary hyperaldosteronism accompanied with hypertension. Hypokalaemia with urinary potassium wasting and without hypertension should therefore lead to considering liquorice intoxication, which can be confirmed by disclosing shut-off of the renin-angiotensin-aldosterone axis, and by the increase of the urinary ratio of [cortisol metabolites (5 alpha tetrahydrocortisol + 5 beta tetrahydrocortisol)]/[cortisone metabolite (5 beta tetrahydrocortisol)] together with increase of urinary free cortisol excretion.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1993

Lipid factors as predictors of coronary disease.

Explore the source record for details and available documents.

Adult↗

PubMed1992

Correlation between up-regulation of lymphokine mRNA and down-regulation of TcR, CD4, CD8 and lck mRNA as shown by the effect of CsA on activated T lymphocytes.

Full activation of different T cell populations via the TcR/CD3 complex leads to transient expression of lymphokine mRNA and to transient and specific down-modulation of TcR, CD4, CD8 and p56lck mRNA (Multi-Receptor Complex or MRC mRNA). This transient down-modulation is due to both a decrease in transcription and stability of these mRNA and is temporally and quantitatively related to lymphokine mRNA induction. We showed that cyclosporin A (CsA), which blocks lymphokine expression also inhibits MRC mRNA down-modulation at the transcriptional level, and does not affect mRNA stability. The fact that CsA inhibits both lymphokine expression and MRC mRNA down-modulation at transcriptional level supports a model in which similar signals trigger the inverse regulation of these two sets of genes via identical transcriptional factors.

Blotting, Northern↗

PubMed1992

[Influence of exercise on the permeability of accessory pathways and supraventricular arrhythmia in Wolff-Parkinson-White syndrome].

The influence of adrenergic stimulation on the effective anterograde refractory period of the accessory pathways and on supraventricular arrhythmias, was studied in 20 patients (average age 38 +/- 16 years) with an untreated permanent Wolff-Parkinson-White syndrome and a resting anterograde refractory period < or = 400ms. Repeated electrophysiological studies with a single endocavity catheter positioned near the atrial pole of the accessory pathway were performed under basal conditions and during a standardised exercise test on a bicycle ergometer. The effective anterograde refractory period of the accessory pathway, the length of the tachycardia cycle during reciprocating orthodromic tachycardia, the average heart rate, the percentage of preexcited QRS complexes during induced atrial fibrillation, were measured in all patients under basal conditions and at the peak of exercise. Exercise significantly reduced the anterograde refractory period of the accessory pathway (287 +/- 49 ms at rest versus 238 +/- 24 ms on exercise: p < 0.001), the cycle of orthodromic tachycardia (302 +/- 32 vs 260 +/- 22 ms p < 0.001), the minimal R-R interval (270 +/- 65 vs 227 +/- 46 ms: p < 0.05) and % of preexcited QRS complexes (75 +/- 33 vs 51 +/- 39: p < 0.05) in atrial fibrillation whilst increasing the average heart rate (165 +/- 42 vs 202 +/- 39 bpm: p < 0.02). Adrenergic stimulation significantly improves anterograde conduction in the accessory pathway. The reduction in the % of preexcited QRS complexes in atrial fibrillation could indicate a preferential action of catecholamines on the nodo-hisian pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

[Results of coronary-angiographic evaluation after endocavitary fulguration of the accessory pathways].

Left ventricular aid coronary angiography was performed systematically in 32 consecutive patients (average age 34 +/- 16 years) to assess the potential risk of coronary and myocardial lesions after high energy catheter ablation of an accessory pathway. The control was performed 2 to 6 months after the procedure in 30 patients and as an emergency immediately after the procedure in 2 patients because of prolonged ST segment elevation in 1 and an echocardiographic abnormality in the other. The catheter ablation was performed by a right heart approach in 19 patients and by retrograde catheterisation of the left heart in the other 13. The average number of shocks delivered was 3.6 +/- 2.4 in 1.8 +/- 1.2 session with an average energy of 632 +/- 220 joules. The global success rate was 88%, 70% complete successes and 18% clinical successes. The left ventricular and coronary angiographies were normal in 31 patients, including the 2 patients investigated as an emergency. On the other hand, one totally asymptomatic patient in whom a left lateral bundle of Kent had been ablated 2 months previously by a retrograde transaortic approach, had a large pseudo-aneurysm of the left ventricular posterior wall and coronary angiography showed a fistula between the first lateral branch of the circumflex artery and the left ventricle. At surgery, a localised rupture of the mitral annulus was confirmed. Two factors may at least partially explain this complication: the quantity of energy delivered (1,000 joules) in a single session to a limited area, and the site of ablation on the ventricular side of the mitral annulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

[Arrhythmogenic cardiomyopathies of the right ventricle].

Arrhythmogenic cardiomyopathies of the right ventricle (ACRV) are defined by an association of left delayed type ventricular arrhythmias, ranging from apparently uncomplicated extrasystoles to more severe or even potentially lethal arrhythmias such as polymorphous VT and ventricular fibrillation, with an anatomical substrate consisting of adipose or fibro-adipose degeneration of the myocytes of the free wall of the ventricle, which may be either focal (in particular: apex, anterior surface of the infundibulum and the sub-tricuspid region), or more diffuse. It is then accompanied by RV systolic dysfunction with dilatation of the cavity. This apparently well defined clinico-pathological entity is in fact more complex, if only because of the existence of associated lesions of the left ventricle in 1/3 of cases. The distinction from Uhl disease remains blurred, in particular in diffuse forms. It is most probable that more than one etiology is involved. A dysgenetic mechanism with probable autosomal dominant transmission has apparently been shown in familiar forms which are associated with a particularly severe risk of progression. The hypothesis of sequelae of multifocal myocarditis appears to be the most probable in sporadic forms. In the absence of histological criteria, which it is difficult to demand in view of the variability of results and potential dangers of endomyocardial biopsy involving such thin and fragile ventricular walls, the diagnosis of ACRV is based upon the concomitant existence of: (1) electrophysiological criteria: ventricular arrhythmias, in particular sustained monomorphous VT, with the particular feature of a very high degree of sensitivity to adrenergic stimulation (exercise), the existence of late potentials on the high amplification ECG, a highly specific sign, though unfortunately of poor sensitivity in localized froms, those which are most difficult to identify (2); segmentary morphological and kinetic RV abnormalities, most often resulting in localized akinetic or dyskinetic parietal vaulting, with stasis "in situ". Modern imaging methods (echocardiography, angioscintigraphy with phase analysis, nuclear magnetic resonance imaging, etc.) unfortunately do not yet offer an alternative to selective cineangiography of the RV which is the reference investigation when it is performed and interpreted under strict conditions. Several reports of sudden death or of ventricular fibrillation seen in confirmed cases of ACRV, as well as the publication of a number of autopsy registers indicating that this condition is one of the primary causes of sudden death in young individuals and in athletes, have cast doubt on the benign prognosis initially attributed to this condition.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗