Thiazolidinedione effects on blood pressure in diabetic patients with metabolic syndrome treated with glimepiride.

The aim of our study was to compare the long-term effect of pioglitazone and rosiglitazone on blood pressure control of diabetic patients with metabolic syndrome treated with glimepiride. We evaluated 91 type 2 diabetic patients with metabolic syndrome. All were required to have been diagnosed as diabetic for at least 6 months, and to have failed to achieve glycemic control by dietary changes and the maximum tolerated dose of the oral hypoglycemic agents sulfonylureas or metformin. All patients took a fixed dose of 4 mg/day glimepiride. We administered pioglitazone (15 mg/day) or rosiglitazone (4 mg/day) for 12 months in a randomized, double-blind fashion, and evaluated body mass index (BMI), glycemic control, blood pressure and heart rate (HR) throughout the treatment period. A total of 87 patients completed the study and were randomized to receive double-blind treatment with pioglitazone or rosiglitazone. An increase in BMI was observed after 12 months (p < 0.05) in both groups. After 9 and 12 months, there were significant decreases in glycated hemoglobin (HbA(1c)), mean fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), and postprandial plasma insulin (PPI) in both treatment groups (p < 0.05 at 9 months and p < 0.01 at 12 months for all parameters). Furthermore, homeostasis model assessment index (HOMA index) improvement was obtained at 9 and 12 months (p < 0.05 and p < 0.01, respectively) in both groups. Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p < 0.05, respectively) was observed in both groups after 12 months. There were no significant changes in transaminases at any point during the study. We can conclude that the association of a thiazolinedione to the glimepiride treatment of type 2 diabetic subjects with metabolic syndrome is associated to a significant improvement in the long-term blood pressure control, related to a reduction in insulin-resistance.     

<Emphasis Type="Italic">Toxoplasma gondii</Emphasis> infection in patients with hematological malignancies

Toxoplasmosis is one of the most common parasitic infections in humans, but in most cases it does not cause serious illness; this protozoan can nevertheless cause devastating disease in immunocompromised hosts such as HIV-positive individuals. Only rarely is toxoplasmosis documented in hematological patients, and among them, those who undergo a transplant procedure are more frequently affected. In a retrospective multicenter survey, we collected data on six cases of toxoplasmosis in hematological patients. In the majority of cases, patients had undergone transplant procedures (five had undergone autologous or allogeneic transplantation). This complication needed special care in diagnosis, usually based on serology, neuroradiology, and PCR examination. However, in our experience the appropriate therapeutic approach was successful in the majority of cases.     

Genomic organization and structure of Bruton agammaglobulinemia tyrosine kinase: localization of mutations associated with varied clinical presentations and course in X chromosome-linked agammaglobulinemia.

X chromosome-linked agammaglobulinemia is a life-threatening disease that involves a failure in normal development of B lymphocytes and is associated with missense mutations in BTK, a gene encoding a cytoplasmic tyrosine kinase (Bruton agammaglobulinemia tyrosine kinase, EC 2.7.1.112), a member of the Tec family of protein-tyrosine kinases. The genomic organization has been determined by using conventional restriction fragment mapping, extended DNA sequencing, and PCR fragment-sizing approaches. The DNA sequences of the 18 coding exons composing BTK and their flanking-region sequences are reported; an additional exon(s) encodes a 5' untranslated segment. Single-base-pair substitutions and 4-nt deletions resulted in amino acid replacement, premature termination, frameshift, and exon deletion in a group of X chromosome-linked agammaglobulinemia patients exhibiting different clinical presentations and courses. The nature of the mutations is interpreted in terms of the genomic organization of the BTK gene and the disease course in individual patients. Several examples are found in which the same mutation occurs in unrelated patients, and one of these mutations occurs at the same codon that is substituted in the murine form of BTK, resulting in X chromosome-linked immunodeficiency disease. Considerable variation in presentation and disease course in X chromosome-linked agammaglobulinemia appears associated with the nature and position of different missense mutations.     

Dromotropic effects of drug combinations. Initial results bearing on a combination of deslanoside and ajmaline]

The electrophysiological effects of the cardiotropic drugs have been studied in man by the agency of endocavitary electrocardiography. The effects of drug combinations, which are often prescribed therapeutically, have been studied less often. The authors report the results of a preliminary study of the combination of deslanoside with ajmaline in 26 patients; its effects were compared with those using each drug separately. This combination seems to have true dromotropic effects; although deslanoside alone, in the doses used, does not modify conduction below the bundle of His, it can still act synergistically with ajmaline at this level. A detailed study of the pharmacological effects as a function of the original status of conduction shows that at the level above the bundle His, the dromotropic action is quantitively less on healthy conducting tissue than on abnormal tissue. The effects of ajmaline on the conduction times below the bundle seem to be similar whether or not there is any conduction defect under basal conditions. The difficulties in obtaining and interpreting such measurements in man are discussed in the hope of arriving at a general protocol for studying drug combinations.     

Electrophysiological effects of the combined administration of digoxin and propranolol in man]

The electrophysiological effects of the combined administration of digoxin and propranolol were studied in 40 patients, compared with the effects of digoxin alone and considered in relation to anomalies of the conduction pathways. The cycle of the sinus node was only lengthened by digoxin in patients who had an anomaly of sinus node function. In contrast the addition of propranolol always increased it (from 1 109 +/- 53 ms to 1 232 +/- 58 ms). Sinus node recovery time was only increased by combined administration (from 1 331 +/- 101 ms to 1 450 +/- 68 ms). Changes in sino-atrial conduction intervals were not very marked. The AH interval was increased by digoxin (from 97 +/- 4 ms to 109 +/- 6 ms), with propranolol exerting a synergistic effect (119 +/- 6 ms). When there was pre-existing supra-His block only combined administration increased the conduction defect. The HV interval and QRS duration were not altered. The effective atrial refractory period was increased by combined administration (from 264 +/- 10 ms to 304 +/- 14 ms) except in subjects who had supra-His block. The effective refractory period of the AV node (385 +/- 26 ms) was increased by digoxin (450 +/- 37 ms). This effect was potentiated by propranolol (478 +/- 34 ms) except in those subjects who had supra-His block. In three cases in which there were two conduction pathways at A V node level the refractory periods of the rapid and slow pathways were increased by digoxin, with a synergistic effect from propranolol. The ventriculo-atrial conduction time changed from 151 +/- 24 ms to 172 +/- 22 ms following digoxin, then to 193 +/- 34 ms after the addition of propranolol.     

Improvement and normalisation of the QRS complex by stimulation of the bundle of His in complete left branch block]

The asynchronism of ventricular activation resulting from a major degree of left bundle branch block (QRS greater than or equal to 0.12 s) may be suppressed by stimulation of the distal portion of the His Bundle, whether the block be intermittent (3 cases) or permanent (17 cases). The selective stimulation of the His Bundle normalises ventricular depolarisation whilst non-selective stimulation narrows the QRS complex by the fusion of the activation wave fronts from the His Bundle and the interventricular septum. The reestablishment of synchronous ventricular conduction by His Bundle stimulation is generally interpreted as a sign of longitudinal dissociation in the proximal portion of the His Bundle. This results does not, however, exclude the possibility of a very localised lesion at the origin of the left bundle, responsible for a conduction delay, and suppressed by stimulation carried out close to the zone of block (summation effect, electrotonic influence).     

Methemoglobinemia associated with loxoscelism

In twenty five patients who presented the cutaneous form of loxoscelism, serum haptoglobin and lactic dehydrogenase, erythrocyte glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, methemoglobin, bilirubin and reticulocytes were investigated after bite. No hemolysis was detected but an increase in methemoglobin was found in 54% of the cases; in 7% it was between 1.1% and 2%, in 27% it ranged from 2.1% to 4%, and in 20% from 4.1% to 8%. Blood samples of a normal, blood group 0 individual and of a patient who exhibited methemoglobinemia after Loxosceles bite were incubated separately with antisera against Loxosceles gaucho, Crotalus terrificus, Bothrops jararaca, with Loxosceles gaucho venom and 0.3% phenol. No methemoglobin was found after 1, 4, 8 and 15 days in both sets of samples. At the 25th day all the samples, including the controls, exhibited similar methemoglobin reductase decrease. The data suggest that the methemoglobinemia which occurs in 50% of the patients probably arises from in vivo venom metabolism, inasmuch as the crude venom does not induce methemoglobinemia.