Effects of chronic treatment by amiodarone on transmural heterogeneity of canine ventricular repolarization in vivo: interactions with acute sotalol.

OBJECTIVE: The present study was designed to examine the effects of chronic amiodarone on the different ventricular cell subtypes in situ and to evaluate its interactions with sotalol. METHODS: Three groups of dogs were studied. Group I (n = 8) received no treatment. Group II (n = 7) and group III (n = 8) received, respectively, 100 and 200 mg amiodarone orally twice a day for 6 weeks to 8 months. In vivo studies were performed under halothane anesthesia 14 h after the last administration of amiodarone. Three leads ECG, femoral blood pressure and left ventricular intramural monophasic action potentials (MAP) were continuously recorded. Bradycardia was obtained by clamping the sinus node and beta-blockade and the heart was driven by atrial pacing. Three weeks before the in vivo experiments, the cellular electrophysiologic properties of right ventricular tissues obtained by cardiac biopsy in six treated and six control dogs were studied with standard microelectrodes. RESULTS: Amiodarone produced a dose-dependent decrease in plasma levels of triiodothyronine (T3; 5.9 +/- 0.4 pM in control dogs, 3.1 +/- 0.2 pM in group III, P < 0.001) without affecting thyroxine (T4). Under anesthesia, the QT interval was 14% larger in group III compared to group I at a paced cycle length (PCL) of 1500 ms (P < 0.05). This is consistent with the 10% increase in endocardial MAP duration in group III at the same PCL (P < 0.05). There was no significant increase in transmural dispersion of MAP duration. In group I, sotalol induced a significant reverse use-dependent increase in MAP duration. This effect was reduced in group II and completely suppressed in group III. Amiodarone prevented the sotalol-induced increase in transmural dispersion of ventricular repolarization which was 69 +/- 12 ms in untreated dogs, 41 +/- 8 ms in group II (P < 0.05) and 34 +/- 8 ms (P < 0.05) in group III at PCL = 1500 ms. Amiodarone also prevented the sotalol-induced ventricular tachyarrhythmias. In vitro, the action potential duration was longer in amiodarone-treated dogs that in control ones (208 +/- 5 ms versus 188 +/- 9 ms at PCL = 1000 ms, P < 0.05). The sotalol-induced prolongation of repolarization was reduced in amiodarone-treated dogs. CONCLUSION: Chronic treatment of dogs with amiodarone induced a moderate prolongation of the QT interval and MAP duration without affecting transmural dispersion of repolarization and inhibited the effects of acute sotalol, including the prolongation of repolarization, the increase in transmural dispersion of repolarization and the induction of arrhythmias.

Aluminium-related osteodystrophy and desferrioxamine treatment: role of phosphorus.

We investigated (1) the prevalence of aluminium overload among 96 patients with symptomatic bone disease haemodialysed from 1987 to 1989 in the Sao Paulo area, Brazil; (2) the effect of 6 months desferrioxamine (DFO) treatment (1-2g/week). All patients underwent a first bone biopsy. Aluminium overload (extent of stainable bone aluminium more than 20% trabecular surface) was observed in 74 of 96 patients. Forty overloaded patients were divided into patients with high bone formation rate (BFR) (group 1; n = 17) and patients with low BFR (group 2; n = 23), and had a second biopsy after DFO therapy. In both groups aluminium surface was reduced after treatment (P < 0.001), osteoblast surface (P < 0.02-P < 0.01) and plasma parathyroid hormone (iPTH) (P < 0.01) increased. In group 1 BFR remained high. In group 2 BFR remained low in 16 patients (2a) and increased in seven (P < 0.02) (2b). In group 2a plasma phosphorus was below that in group 2b patients, before (P < 0.03) and after (P < 0.01) DFO. The histological features of group 2a patients resembled hypophosphataemic osteomalacia, those of group 2b patients aluminium osteodystrophy. These data show a high prevalence of aluminium overload in Brazilian patients. Low-dose DFO therapy was safe, decreased bone pain, prevented fractures, and reduced stainable bone aluminium. Bone lesions only partially improved, suggesting that low phosphorus intake and/or plasma calcitriol concentrations may have prevented improvement of bone formation and mineralization.

Utility of thallium-201 and iodine-123 metaiodobenzylguanidine in the scintigraphic detection of neuroendocrine neoplasia.

Metaiodobenzylguanidine (MIBG) is a specific marker for neuroendocrine tumours, such as phaeochromocytoma, neuroblastoma, medullary thyroid cancer (MTC) and paraganglioma, but it suffers in some cases (especially in MTC) from a lack of sensitivity. Thallium is a well-known marker of cellularity with a great sensitivity and a lack of specificity. In order to determine whether the association of these two markers is able to improve the detection of neuroendocrine lesions, 137 scintigraphic examinations using MIBG and thallium were performed in 101 patients referred for suspicion or follow-up of neuroendocrine tumours. Thallium chloride was first injected (1 MBq/kg), images being acquired about 20 min after injection; 123I-MIBG (4 MBq/kg) was then injected and images acquired 5 and 24 h later. In patients with phaeochromocytoma or neuroblastoma, thallium scintigraphy appeared of little help since no tumoural site was discovered by thallium accumulation alone. In contrast, thallium examination seemed of interest in the detection of paraganglioma and MTC, the association of the two radiopharmaceuticals increasing the number of detected sites.

[Biliary scintigraphy. Application to the study of chronic cholestasis]. / Scintigraphie biliaire. Application à l'étude des cholestases chroniques.

In a sample population of 49 subjects (7 normal, 42 with various liver diseases), the parameters of the activity/time curve of trimethylbromo-iminodicetic acid (TBIDA) biliary scintigraphy were compared with the clearances of bromosulfophthalein (BSP) and indocyanine green (ICG). Correlation between T1/2 and P2 BSP slope was r = 0.50 (n = 33; P < 0.01). Correlation between Tmax TBIDA and fractional ICG clearance (P ICG) was r = 0.65 (n = 44; P < 0.001). In 23 cases of chronic cholestasis correlations remained significant (T1/2-P2 BSP: r = 0.53; n = 17; P = 0.02; Tmax-P ICG: r = 0.59; n = 17; P < 0.01). A prospective study of 11 cases of chronic intrahepatic cholestasis (primary biliary cirrhosis 8, primary sclerosing cirrhosis 3) showed that these two types of tests varied concordantly. Biliary scintigraphy, therefore, seems to be an accurate method to explore hepatocellular mass (degree of hepatic insufficiency) and cholestasis. The validation of biliary TBIDA scintigraphy as hepatobiliary functional exploration method and the possibility to study intrahepatic "regions of interest" defined a priori would make it possible to obtain a functional estimate of hepatic segments or lobes, for example before wide liver excision.

Correction of severe secondary hyperparathyroidism in two dialysis patients: surgical removal versus percutaneous ethanol injection.

Two chronic hemodialysis patients had recurrent, severe secondary hyperparathyroidism. The first had no sonographically visible parathyroid gland in the neck. Computed tomography (CT) scan indicated the existence of a parathyroid mass in the upper mediastinum, which was removed surgically. The second patient had two intracervical, hyperplastic parathyroid glands visible on ultrasound examination. He volunteered for nonsurgical removal via sonographically guided percutaneous injection of ethanol. In both patients, serum total calcium concentration decreased dramatically to values near 1.5 mmol/L 24 hours after treatment. In patient 1, serum immunoreactive parathyroid hormone (iPTH) (1-84) decreased from 1,582 pg/mL before surgery to 34 pg/mL after 24 hours (normal range, 10 to 65 pg/mL). In contrast, serum iPTH (1-84) decreased only progressively in patient 2, from 1,680 pg/mL before ethanol injection to 865 pg/mL after 24 hours and to 378 pg/mL after 72 hours to reach 30 pg/mL after 14 days. Thus, patient 2 had a striking decrease of plasma calcium immediately after parathyroid gland destruction, even though circulating iPTH was still very high. The reason for such a discrepancy remains unexplained at present, and further study will be necessary to solve this issue.

[Thyroid cancer revealed by a suppressive hot nodule]. / Cancer thyroïdien révélé par un nodule chaud extinctif.

We report the case of a 62-year old woman in euthyroidism who presented with a thyroid cancer located within a hot nodule. The nodule was partially extinctive, and the triiodothyronine test showed incomplete suppression. Fine needle cytology showed no malignant cells. Systematic lobectomy was performed, and the diagnosis of cancer was made at pathology. This rare situation does not mean that all non-toxic hot nodules must be removed, but if surgery is decided an extemporaneous histological examination is mandatory. Besides, such cases provide an additional argument in favour of surgery or treatment of toxic adenomas.

Résistance a la dessiccation de Biomphalaria glabrata adultes infestés par plusieurs miracidiums de Schistosoma mansoni / Resistance to desiccation of Biomphalaria glabrata adults by polyinfection of Schistosoma mansoni miracidia

1200 adult Biomphalaria glabrata were submitted during 6 weeks to anhydrobiosis condition. Some snails were health, some were previously infected 3 days or 12 days ago with 8 ñ 2 miracidia of Schistosoma mansoni, others were shedding cercariae . The snails were put on soil or buried into hermetically closed, or ventilated, plastic boxes. There was no survival of snails kept in sealed boxes, or among positive snails, but 44% of control health snails and 40,6% of infected (for 3 or 12 days) snails in ventilated boxes were living at the term of the desiccation stage. Survival was better for "on soil" snails than for "buried" snails, but difference was shown between 3-days and 12-days infection. The surving desiccated B. glabrata had a lesser death rate and a lesser cercarial production than infected snails kept in water. An inferior production of male cercariae comparatively to female and to "mixed" cercariae was demonstrated by statistical analysis of the cercarial sheddings. In all positive snails, periodic variations of cercarial production was shown, whatever the sex of those cercariae. In addition many pauses of the sheddings were established by the authors

[Resistance to desiccation of Biomphalaria glabrata adults infested by various miracidia of Schistosoma mansoni]. / Résistance á la dessiccation de Biomphalaria glabrata adultes infestés par plusieurs miracidiums de Schistosoma mansoni.

1200 adult Biomphalaria glabrata were submitted during 6 weeks to anhydrobiosis condition. Some snails were healthy, some were previously infected 3 days or 12 days ago with 8 +/- 2 miracidia of Schistosoma mansoni, others were shedding cercariae. The snails were put on soil or buried into hermetically closed, or ventilated, plastic boxes. There was no survival of snails kept in sealed boxes, or among positive snails, but 44% of control healthy snails and 40.6% of infected (for 3 or 12 days) snails in ventilated boxes were living at the term of the desiccation stage. Survival was better for "on soil" snails than for "buried" snails, but no difference was shown between 3-days and 12-days infection. The surviving desiccated B. glabrata had a lesser death rate and a lesser cercarial production than infected snails kept in water. An inferior production of male cercariae comparatively to female and to "mixed" cercariae was demonstrated by statistical analysis of the cercarial sheddings. In all positive snails, periodic variations of cercarial production was shown, whatever the sex of those cercariae. In addition many pauses of the sheddings were established by the authors.

Radioiodinated meta-iodobenzylguanidine uptake in medullary thyroid cancer. A French cooperative study.

Fifty meta-iodobenzylguanidine (MIBG) scintiscans were performed in three groups of medullary thyroid cancer (MTC) patients. Group 1 (n = 11) included treated patients with normal calcitonin levels; Group 2 (n = 24) included patients with elevated calcitonin levels due to sporadic and isolated MTC; Group 3 (n = 15) included patients with elevated calcitonin levels due to familial MTC or multiple endocrine neoplasia Type IIA syndrome (MEN). In Group 1 three pheochromocytoma were depicted by MIBG scintiscan. In Group 2 MTC was seen in a small number of patients (3 of 24). In Group 3, besides adrenal hyperplasia and pheochromocytoma four patients, MIBG scintigraphy showed where MTC had localized and spread in almost half of patients (7 of 15). MIBG uptake occurred in patients with relatively high calcitonin level (greater than 0.6 nmol/l). These data indicate that in patients with familial MTC or MEN syndrome, MIBG scintiscan can be useful not only in detecting associated pheochromocytoma, but also in showing MTC.

[The influence of anhydrobiosis on the infestation of Biomphalaria glabrata by Schistosoma mansoni miracidium]. / Influence de l'anhydrobiose sur l'infestation de Biomphalaria glabrata par un miracidium de Schistosoma mansoni.

410 Biomphalaria glabrata (Caribbean strain of Guadeloupe) have been infected with one miracidium of Schistosoma mansoni, 110 snails, used as controls have been kept into water; the survival rate was 96.4% after 4 weeks and 25.4% produced cercariae. 300 snails were kept on wet soil, and submitted for 6 weeks to progressive desiccation. The survival rate was 23.4% but only 9 of them produced cercariae. Periodic variations of the production of male and female larvae have been shown by the weekly test of the cercariae productions. In previously desiccated snails, the production of male and female cercariae is similar while in controls the production of female larvae is more important. In experimental snails, the larval development seems to be stopped during anhydrobiosis. The production of cercariae is just delayed for the length of the dry keeping.

Uptake of 131I-MIBG by medullary carcinoma of thyroid in familial cases.

Medullary carcinoma of the thyroid (MCT) and pheochromocytoma are APUD tumors. MIBG (Meta Iodo Benzyl Guanidine) uptake by pheochromocytomas is now well known but very few cases of MIBG uptake in sporadic MCT have been described. We report here the two first cases of inherited MCT with MIBG uptake.

[Risk of vertebral fracture after menopause: identification of subjects at high risk by dual photon absoprtionometry]. / Risque fracturaire vertébral après la ménopause: détection des sujets a haut risque par absorptiométrie biphotonique.

Dual photon absorptionometry of bone is used to detect in an exposed population those subjects who are high risk of fracture and also to follow up the evolution of these patients. 37 women who have suffered fractures have been compared to 41 women without fractures of similar age distribution. A highly significant correlation between body height and Bone Mineral Content (BMC) of the lumbar spine is found in the control group thus allowing the calculation of the expected BMC value for each patient. A crushing index is defined as the ratio of the observed BMC value to the expected one. Using this index, instead of the two more usual modes of BMC expression, leads to an improvement of the predictive estimation of fracture risk. The predictive value of such indices should still be improved. With this aim, further determinations of indices are desirable. The following requirements should be borne in mind: The physical data should be easily obtainable e.g. body height and weight and the meaning of the index based on these easily verifiable factors they should be easily understood.

[Experimental schistosomiasis III. Observations on the infestation of Biomphalaria glabrata by a miracidium of Schistosoma mansoni]. / Schistosomose expérimentale III. Observations sur l'infestation de Biomphalaria glabrata par un miracidium de Schistosoma mansoni.

380 B. glabrata infected with 1 miracidium of S. mansoni produced 87 positive snails (22,9%), 38 of which sending out male cercariae and 49 female cercariae. The snails belonged to 3 experimental series kept at 27 degrees and 24 degrees C for 15 weeks under continuous lighting. There was no difference between the proportions of both sexes. The survival of the positive snails was favoured by the male sex. The shedding of female cercariae was greater than shedding of male. During those 15 weeks, the cercarial shedding of both sexes showed large and recurring changes. A certain correlation seems to exist between the sex of cercariae, the abundance and the frequency of cercarial shedding, and the longevity of the parasitized snails. All those factors could take a part in the epidemiology of the schistosomiasis.

[Chromosome abnormalities associated with Phl and acturial survivorship curve in chronic myeloid leukemia. Probabilistic interpretation of blastic transformation of CML]. / Anomalies chromosomiques surajoutées au Phi et courbe actuarielle de survie dans la leucémie myéloide chronique. Interprétation probabiliste de la transformation blastique des LMC.

Sixty-six patients with chronic myelogenous leukemia, all with Philadelphia chromosome, have been studied for chromosomic abnormalities associated (CAA) to Ph', as well as for actuarial curve of survivorship. Patients dying from another disease were excluded from this study. Frequency of cells with CAA was measured and appeared strongly higher after blastic transformation than during myelocytic state; probability to be a blastic transformation is closely correlated with this frequency. On the other hand, actuarial curve of survivorship is very well represented by an exponential curve. This suggests a constant rate of death during disease evolution, for these patients without intercurrent disease. As a mean survivance after blastic transformation is very shorter than myelocytic duration, a constant rate of blastic transformation could be advanced: it explains possible occurrence of transformation as soon as preclinic state of a chronic myelogenous leukemia. Even if CAA frequency increases after blastic transformation, CAA can occur a long time before it and do not explain it: submicroscopic origin should be searched for the constant rate of blastic transformation would express the risk of a genic transformation at a constant rate during myelocytic state.

[Diagnostic value of parasitologic examinations and of indirect immunofluorescence test in S. haematobium schistosomiasis (author's transl)]. / Valeur diagnostique des examens parasitologiques et de la réaction d'immunofluorescence indirecte dans la schistosomose à S. haematobium.

A study has been carried out in 690 patients admitted in a Paris hospital and from Mali, Senegal and Mauretania origin, in order to compare the three available techniques for the diagnosis of infection with S. haematobium: urine centrifugation deposit control, biopsy of rectal mucosa and indirect immunofluorescence test. The prognostic value of each of these three techniques has been reevaluated. (Formula: see text), Living eggs have been detected in 55 p. 100 of the patients by direct examinations and a prevalence of 75 p. 100 has been computaned for S. haematobium.

A technique for multiple, high-rate blood samplings via an external cannula in rats.

A method for obtaining multiple, high-rate blood sample collections from rats without the use of anesthesia and anticoagulant is described. The surgical procedure consists of a bypass of the carotid via a cannula; this cannula forms a loop above the rat's head and is available for blood sampling. The method permits the investigation of high-frequency oscillations in blood components of rat.