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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.

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)

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)

This prospective randomized study involved 28 patients with moderate essential hypertension who for one year, took either hydrochlorothiazide [Esidrex (E) 25-50 mg per day] or a combination of altizide 15 mg--aldactone 25 mg [Aldactazine (A) 1 or 2 tablets per day] without potassium supplements. Blood pressure, plasma potassium, exchangeable potassium, ventricular premature contractions measured by Holter and plasma magnesium were monitored. Blood pressure was brought to normal in both treatment groups (p < 0.001). Plasma potassium fell by 0.19 mmol/l with A (NS) and 0.35 mmol/l (p < 0.01) with E. Changes in potassium pool were not significant. There was a non-significant reduction in the number of ventricular premature contractions in both groups. There was no correlation between the few cases of frank hypokaliema, fall in potassium pool and complex ventricular premature contractions. A review of the literature offers no solid arguments suggestive of significant potassium risk associated with these diuretics. Any such risk can be eliminated by the use of low doses, combined if necessary with a potassium-sparer or a hypotensive agent of another group.

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.

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.

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)

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)

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)

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.

The p56lck tyrosine kinase is most likely to be involved in signal transduction of T lymphocyte activation. After full activation through the TcR/CD3 complex lck mRNA is transiently down-modulated. This down-modulation was due to an early decrease of both transcription and stability of the lck mRNA. To study the involvement of transcriptional and post-transcriptional factors in this regulations, we have analysed the effect of cycloheximide, a protein synthesis inhibitor, on the steady-state of the lck mRNA. Cycloheximide superinduced lck mRNA by increasing its stability, although cycloheximide concomitantly decreased lck transcription. This suggests that the constitutive level of lck mRNA observed prior to activation is controlled by transcriptional activator(s) and post-transcriptional destabilizing factor(s). Second, lck mRNA down-modulation observed after full activation was inhibited by cycloheximide. It increased lck mRNA stability whereas lck transcription remained low. Therefore, full activation might increase the synthesis and/or activity of destabilizing factor(s). Cyclosporin A also inhibited the down-modulation of lck mRNA by increasing its transcription with no effect on its stability. Since, lck mRNA down-modulation was always associated with lymphokine mRNA induction, and since CsA blocks both lymphokine transcription and lck decrease of transcription, this indicates that these genes might share common regulatory pathways leading to their inverse transcriptional regulation.

The behavior of ventriculoatrial conduction (VAC) during exercise remains unknown. In order to determine its characteristics and the consequences it might have on dual chamber pacemaker technology and programming, 17 patients underwent an electrophysiological study (EPS) of atrioventricular conduction (AVC) and of VAC during a protocol including three steps: supine rest, upright position, and finally during cycloergometric exercise; the measurements were done at progressively increasing pacing rates. During a preimplantation EPS, Wenckebach points AVC-W and VAC-W and conduction times, AVCT and VACT (as a function of pacing rate), were measured in ten consecutive patients using temporary leads and an external device. In another study, AVCT, VACT, AVC-W, and VAC-W were measured by telemetric recordings under identical conditions in seven patients implanted earlier with a DDD pacemaker. A 1/1 VAC was observed in 7/17 patients (41%) at rest, and in 13/17 patients (76%) at the end of the protocol; VAC was never observed in 4/17 patients (23%), but occurred in six of the ten patients initially free, three standing at rest and three on exercise. For all patients, the VAC behavior remained of "nodal" type, indicated by a progressive increase in VACT as pacing rate rose up to the VAC-W point. Neither the existence of exercise-induced VAC nor the maximal VACT-W could be predicted from AVC or VAC data obtained at rest. However, at the same pacing rates, standing up and exercise induced a shortening effect on VACT, and improved the VAC-W by an average of 33%. These results suggest that the electrophysiological behavior of VAC does not obey any general rule and cannot be predicted individually. It would thus appear unwise to base pacemaker mediated tachycardia (PMT) protection solely on long postventricular atrial refractory period (PVARP) programming in DDD patients. This work also revealed the potential risks of a rate responsive auto-adaptive PVARP algorithm as proposed in certain new devices.

Twelve patients with isolated symptomatic sinus node dysfunction or bradycardia-tachycardia syndrome with atrial chronotropic incompetence during exercise testing were managed by single chamber rate responsive atrial pacing (AAIR) when AV conduction was normal, or by a dual chamber DDDR pacemaker programmed in the AAIR mode when AV conduction was abnormal, and followed up for 12.5 +/- 9.8 months. The patients were assessed clinically, by 3 monthly ECG and Holter recordings and comparative exercise tests in AAI and AAIR modes at the 6th month. One patient with an AAIR system was excluded at M21 because of symptomatic AV block requiring reimplantation of a DDD pacemaker. Ten of the 11 remaining patients are asymptomatic and have an excellent quality of life; one patient had invalidating symptoms on exercise attributed to the "AAIR pacemaker syndrome" which were corrected by reprogramming the pacemaker and modifying the medical therapy. The comparative exercise stress tests showed a significantly higher heart rate in the AAIR mode compared to AAI pacing at the initial and intermediate exercise levels (30 to 70 W); on the other hand, the heart rates were not significantly different at the highest exercise levels although in the AAI mode, the terminal acceleration sometimes occurred in junctional rhythm whereas it was usually an atrial paced rhythm in the AAIR mode. The total duration of exercise was longer in the AAIR mode (+22%; p less than 0.01) when the 8/11 patients with chronotropic incompetence during the baseline study were considered. The spike-R interval adapted normally to exercise in only one case: in the other patients, the interval remained constant or, in the worst of cases (N = 4), it increased paradoxically, to result in the "AAIR pacemaker syndrome": this phenomenon is observed mainly in patients treated by antiarrhythmics and/or betablockers. The AAIR mode would therefore seem to be a simple, effective and reliable method of treating patients with sinus node dysfunction and chronotropic incompetence; however, the failure of adaptation of the PR interval is a real limitation to its use and may constitute an argument in favour of the choice of a DDR pacemaker in these patients.

Many cases of immuno-allergic thrombocytopenia complicated by serious thromboembolism induced by heparin or other heparinoids such as pentosan polysulphate have been reported. This case is of interest for two reasons: first of all, it was induced by pentosan polysulphate and then reactivated by secondary administration of heparin; secondly, it was complicated successively by an infero-apical myocardial infarction with probable spontaneous lysis of a coronary thrombosis because coronary arteriography performed one month later was normal, and then by massive biventricular thrombosis requiring surgical thrombectomy under cardiopulmonary bypass. Tests of platelet aggregation were positive to standard heparin and to several low molecular weight fractions. The outcome was favorable when the responsible substances were withdrawn.

Sixteen patients, 14 of whom described stress related symptoms, present a severe atrio-ventricular block (A-V B), identified during a stress test while the ECG at rest showed a 1/1 atrioventricular conduction (AV). The electrophysiological study (EPS) creates the A-B Block through atrial stimulation and specifies the location of the A-V B: intra-hissian in 8 patients (7 with small QRS an 1 with widened QRS) and infra-hissian in 8 patients (all with widened QRS). Non-invasive methods constitute the prime approach in the diagnostic work-up of stress symptoms. The ideal treatment consists of a dual-chamber cardiac stimulation.

To investigate the extrarenal production of 1,25(OH)2D3 in tuberculosis, we extensively evaluated a patient with tuberculosis, hypercalcemia, and an elevated plasma concentration of 1,25(OH)2D3. Fresh total cells and cultured alveolar macrophages obtained by bronchoalveolar lavage were demonstrated to synthesize 1,25(OH)2D3 prior to and after nine months of successful antituberculous therapy. The continued capacity to produce 1,25(OH)2D3 was associated with a persistent lymphocytic alveolitis in this patient. This extrarenal production of 1,25(OH)2D3 probably contributed to the increased levels of plasma 1,25(OH)2D observed in our patient. Nevertheless, a close correlation between plasma 1,25(OH)2D and serum calcium was not observed. These findings suggest that although extrarenal production of 1,25(OH)2D3 occurs in tuberculosis, it need not be a predominant factor producing the abnormalities in calcium homeostasis observed in such patients.

The P.T.H. radioimmunoassay was done in 38 cases of suspected H.P.T. In confirmed primary H.P.T., the dosage was in positive correlation in 75% of cases; the classic metabolic exploration was in good correlation in 81% of cases. The specificity of the dosage is good but the defect of correlation comes from the antiserum utilised which recognizes the NH2-terminal region of human P.T.H.

Sarcoidosis is frequently attended by hypercalciuria and sometimes by hypercalcaemia. The type of hypercalciuria and its relationships with disease extension and activity have rarely been investigated. In order to clarify these issues we undertook an investigation by a calcium absorption test in 39 patients with untreated thoracic sarcoidosis, and tried to establish correlations with vitamin D3 metabolism and some features of the disease. We found three types of responses. Group I (n = 12) with a normal test had normal 1,25-(OH)2D3 and rare extrathoracic localisations. Group II (n = 14) with absorptive hypercalciuria had higher serum calcium; 1,25-(OH)2D3 (p less than 0.001) and the free 1,25-(OH)2D3 index (p less than 0.05) were raised. Sarcoidosis was more often inflammatory, developing and disseminated. Group III (n = 13) had resorptive hypercalciuria, and hypercalcaemia was frequent. 1,25-(OH)2D3 (p less than 0.01) and the free 1,25-(OH)2D3 index (p less than 0.05) were raised but to the same degree as in Group II. Sarcoidosis was more disseminated and developing than in Groups I and II. In the 39 patients, iPTH and nephrogenous cAMP were low. Post-calcium load urinary calcium/creatinine (Ca/Cr) and 1,25-(OH)2D3 were correlated (p less than 0.05). Extrathoracic extension was associated with higher fasting urinary Ca/Cr (p less than 0.001), and development with higher post-load urinary Ca/Cr (p less than 0.001). Thus, absorptive hypercalciuria is related to the development of sarcoidosis and can be explained by high free 1,25-(OH)2D3, while resorptive hypercalciuria seems to be linked with disease extension. In such a case, the mechanism of osteolysis is not solely accounted for by high 1,25(OH)2 vitamin D3 serum levels, and we postulate that some other factor is at work, related to the extent of the granulomatous process.

Metabolic clearance of synthetic arginine vasopressin (AVP) has been measured in sixteen healthy subjects and ten uraemic patients on maintenance haemodialysis. Plasma AVP was measured using a specific radioimmunoassay at different intervals after a single injection of 2 micrograms AVP. The theoretical curve which fitted best with the disappearance curve was the sum of two exponentials in twenty-two subjects and of three exponentials in the other four. Metabolic clearance rate and the volume of fast initial distribution were 287.1 ml min-1 (m2)-1 and 219.3 ml/kg b.w., respectively, in normal subjects. Metabolic clearance rate was considerably lower in the uraemic group. This emphasizes the role of kidneys in the degradation of AVP and may account, at least in part, for the higher basal plasma value of this hormone observed in uraemic patients.

We are reporting of proximal migration, intracardiac, of a percutaneous caval filter (LEM type), resulting in the death of the patient. It is a true, early (1st week) migration after accurate positioning, opposite L4, and not an incident of insertion.

Cineangiographic data from patients with probable arrhythmogenic right ventricular dysplasia (ARVD) were compared with those from matched controls. Some changes previously thought to indicate ARVD did not do so in this study. The abnormalities specific for ARVD were free wall morphological and wall motion abnormalities, particularly bulges and mamillated akinetic areas.

Bone status, calcium and phosphate metabolism were prospectively evaluated in 98 renal transplant recipients with stable renal function. Aseptic necrosis of bone was found in 30 patients, leading to arthroplasty in 12 patients. Plasma parathyroid hormone and nephrogenic cyclic adenosine monophosphate (cAMP) values were greater and the duration of pre-transplant chronic renal failure longer in patients with aseptic necrosis of bone than in those who were not affected. Cumulative oral corticosteroid doses and the number of acute rejection episodes treated by intravenous methylprednisolone pulses were similar in patients with or without aseptic necrosis of bone. Hyperparathyroidism was confirmed histologically in 14 patients, comprising 4 cases of adenoma and 10 of diffuse hyperplasia. Serum parathyroid hormone correlated positively with serum creatinine (r = 0.47; P less than 0.001) and with cumulative corticosteroid dose (r = 0.30; P less than 0.003). This study suggests that hyperparathyroidism is a factor in the pathogenesis of aseptic bone necrosis. The frequency and severity of bone necrosis may be decreased by early detection and treatment of post-transplant hyperparathyroidism.

The purpose of this study was to determine whether repeated exposure to high sustained +Gz (HS + Gz) stress induced persistent changes in the functional state of the cardiovascular system. Three groups of rabbits--centrifuged, restrained, and control--were studied. After being placed in the restraining system of the centrifuge, the animals were submitted three times in a row to 8-9 +Gz sustained for 40 s. This exposure was repeated three times a week for 3-6 weeks. Restrained animals were not exposed to HS + Gz. Control animals were not restrained. The two types of stress (centrifuge + restraint; restraint alone) determined the appearance of two types of arterial hypertension. Systolic arterial pressure (AP) and left ventricular pressure (LVP) significantly increased in restrained animals. The function of the cardiovascular system was more perturbed in centrifuged rabbits since the significant changes affected not only systolic AP and LVP but alos systemic diastolic AP and the maximum rate of rise of LVP. The myocardium of rabbits repeatedly subjected to HS + Gz exposures, except for those that suffered a fracture of the lumbar spine, was significantly glycogen-depleted.

The expression of genes, implicated in T cell proliferation as well as those coding for the three chains of the T cell receptor (TcR) and for the CD4 and CD8 molecules, has been investigated during activation of various T cell populations maintained in long-term culture. We show that a minimal activation signal, capable of inducing interleukin 2 (IL 2) receptor expression without the expression of IL2 and interferon-gamma, was not associated with a down-regulation of the messengers coding for the T cell multireceptor molecules. In contrast, a strong activation signal via the TcR/CD3 complex or via the CD2 molecule resulted in a reciprocal transient up-regulation of the messengers implicated in T cell proliferation and a down-regulation of the messengers encoding the molecules of the TcR complex of the immunoglobulin super gene family.

Plasma immunoreactive atrial natriuretic factor was measured in 10 patients with chronic atrial fibrillation before and after cardioversion to sinus rhythm, and in 14 patients during electrophysiologic evaluation of paroxysmal supraventricular tachycardia. The mean plasma concentration of atrial natriuretic factor in atrial fibrillation was 138 +/- 48 pg/ml and decreased to 116 +/- 45 pg/ml 1 hour after cardioversion to sinus rhythm (p less than 0.005). The mean plasma concentration of atrial natriuretic factor increased from 117 +/- 53 pg/ml in sinus rhythm to 251 +/- 137 pg/ml during laboratory-induced supraventricular tachycardia (p less than 0.005). Right atrial pressures were recorded in 12 patients; the baseline atrial pressure was 4.3 +/- 1.9 mm Hg and increased to 7.4 +/- 3.6 mm Hg during supraventricular tachycardia (p less than 0.005). A modest but significant linear relation was noted between the changes in plasma atrial natriuretic factor and right atrial pressure measurements during induced supraventricular tachycardia (r = 0.60, p less than 0.05). In conclusion, changes in atrial rhythm and pressure may be an important factor modulating the release of atrial natriuretic factor in the circulation and raised levels of this hormone may be a contributing factor for the polyuria and the hypotension associated with paroxysmal supraventricular tachyarrhythmias.

Tertatolol, a new beta-blocker, and propranolol, considered a reference beta-blocker, were given orally (5 and 160 mg slow release, respectively) for 15 days to two groups of patients with essential hypertension in order to compare their effects on renal hemodynamics. Systolic and diastolic blood pressure, heart rate, and erect plasma renin activity fell significantly in both groups while prostaglandin E2 urinary excretion was unchanged. Tertatolol administration produced increases in glomerular filtration rate, as shown by inulin clearance (+8.9%; p = 0.038) and renal plasma flow, as shown by paraaminohippurate clearance (+13.0%; p = 0.007). In contrast, propranolol administration resulted in a slight decrease in glomerular filtration rate (-2.8%; not significant) and a fall in renal plasma flow (-13.4%; p less than 0.001). Comparison between both treatments showed that glomerular filtration rate and renal plasma flow were higher in the patients treated with tertatolol than in those treated with propranolol whereas filtration fraction was lower, which suggests that tertatolol causes a vasodilation of the glomerular afferent arteriole. These results demonstrate that in contrast to propranolol (160 mg), and despite both drugs exhibiting a comparable antihypertensive activity, tertatolol (5 mg) does not alter but even improves renal perfusion in hypertensive patients.

Biologically active bovine parathyroid hormone (b PTH) 1-34 fragment infused over one hour in normal subjects produced an immediate and sharp increase in the excreted fractions of filtered bicarbonate, sodium and potassium, followed by the return to pre-infusion levels as soon as the administration of b PTH was stopped. There was a gradual but steady increase in the excreted fraction of filtered phosphate but a decrease in the excreted fraction of filtered calcium and magnesium. The excreted fractions of these ions were still abnormal 150 minutes after the completion of PTH infusion. The urinary excretion of 3'5'-cyclic AMP increased immediately about one hundred-fold but returned rapidly to pre-infusion levels. Urinary clearance of cyclic AMP approximated glomerular filtration rate in control periods and was twenty to thirty times greater during b PTH infusion. In subjects overloaded with bicarbonate, b PTH brought about a decrease in bicarbonate T(m) and the same effects on the urinary excretion of other electrolytes. 3'5'-cyclic AMP excretion was clearly higher in control periods and reached higher levels during b PTH infusion when compared to subjects without an alkaline load. 3'5'-cyclic AMP excretion and fractional clearance were also clearly higher in subjects not given b PTH when control periods were compared to periods with bicarbonate infusion or after acetazolamide administration. During distal blockade obtained by simultaneous administration of chlorothiazide and ethacrynic acid, there was a delay in the rise of 3'5'-cyclic AMP excretion after b PTH administration. It can be concluded from these studies that the pattern of excretion of 3'5'-cyclic AMP is similar to that of bicarbonate, sodium and potassium. The increase of 3'5'-cyclic AMP excretion when urinary pH is above 7 suggests a diffusion trapping mechanism for the secretion into the lumen of this nucleotide. Distal diuretics used in distal blockade did not inhibit 3'5'-cyclic AMP production but delayed its secretion into urine.

Beta-blockers can precipitate hypoglycemia and mask its warning signs. Ten male insulin-dependent, otherwise healthy diabetic patients underwent two submaximal exercise tests and two insulin-induced hypoglycemic events (0.2 u/Kg short-acting insulin IV) after six days administration of placebo followed by tertatolol, a non selective beta-blocker (5 mg once daily). Tertatolol modified neither the exercise-induced changes in blood glucose, lactate and plasma unesterified fatty acid levels, nor those of counter regulatory hormones (glucagon, growth hormone, cortisol), while blood pressure, heart rate and plasma renin activity were significantly reduced, proving that tertatolol had actually been ingested, and was active. During the insulin-induced hypoglycemia, similarly tertatolol did not modify the course of the plasma fuels and hormones. Particularly, hypoglycemia was neither deeper nor more prolonged in the presence than in the absence of tertatolol. Warning symptoms were not affected except for palpitations which were not perceived. These results suggest that tertatolol did not precipitate hypoglycemia following exercise, and did not aggravate insulin-induced hypoglycemia in short term administration, and in otherwise healthy diabetic patients.

Interferons, double-stranded RNA and viruses induce the transcription of partly overlapping sets of cellular genes. We have studied the regulation of 11 interferon-inducible genes by these agents and found that four of them were also directly inducible by virus and double-stranded RNA, and two by virus only. We have investigated whether an inhibitor of interferon-beta gene activation, 2-aminopurine, would block this induction process. Induction of these genes by virus and double-stranded RNA was indeed blocked by 2-aminopurine. Since a single cis-acting element can confer inducibility both to interferons, and to virus and double-stranded RNA, we tested the effect of 2-aminopurine on gene activation by interferon-alpha and interferon-gamma. Remarkably, in all the cell lines tested, these induction processes and the establishment of an antiviral state were blocked by the drug. These observations contrast with previous reports. The inhibitory effect of this drug on gene induction was exerted in a selective fashion and at the transcriptional level. This indicate that for the virus-, double-stranded-RNA-, and interferons-mediated gene induction, an early and similar step in signal transduction was affected by 2-aminopurine.