Bone disease in primary biliary cirrhosis: Lack of association with distal renal tubular acidosis

Background and Aims: Primary biliary cirrhosis (PBC) might be complicated by osteoporosis, whose etiology remains unknown but seems to be multifactorial. Prevalence rates of 30% to 60% for distal renal tubular acidosis (DRTA) have been reported in PBC patients, generally as incomplete DRTA. Although it is undisputed that a reduced bone mineral density (BMD) is the expected outcome among patients who have been suffering from longstanding chronic metabolic acidosis, it is unclear if incomplete DRTA is also associated with metabolic bone disease in PBC patients. The present study was undertaken to compare the BMD of PBC patients with and without DRTA.
Methods: The BMD of 23 PBC patients (11 with DRTA and 12 without), all with normal clearance of creatinine, was assessed by dual energy radiograph absorptiometry. The diagnosis of DRTA was made if the urine pH was above 5.4 in all samples after the oral acid overload, showing tubular inability to acidify urine in the presence of test-induced systemic metabolic acidosis.
Results: Densitometric signs of osteoporosis were found in 82% of DRTA cases and in 83% of patients without DRTA (difference not significant). There were no significant differences in BMD measurement, T and Z scores of patients with and without DRTA.
Conclusions: The present study could not support a correlation between the presence of DRTA and the bone loss observed in PBC patients.     

Ten-year survival in 290 patients with endometrial cancer: prognostic factors and therapeutic approach

Summary. Between 1970 and 1976, 290 patients with endometrial cancer were treated at the 1st Obstetrics and Gynecology Clinic of the University of Milan. The median age was 62 years. Surgery was completed in 262 (90.3%) patients. Abdominal hysterectomy was used in 158 (70.9%) stage I and 40 (71.4%) stage II/III patients; vaginal hysterectomy in 55 (24.7%) stage I and nine (16.1%) stage II/III patients. Resection of the upper vagina was performed in 168 patients. Postoperative external beam radiotherapy was used in stage II/III patients and in 44 (19.7%) stage I high-risk patients. Ten-year survival, determined by the life-table method, was 84.8% in stage I (223 patients), 53.4% in stage II (37 patients), 64.4% in stage III (19 patients), and 9.1% in stage IV (11 patients). Factors associated with poorer prognosis were: late age at diagnosis (P<0.001); deep myometrial invasion (P<0.001); poorly differentiated histological grade ( P =0.11); lack of resection of the upper vagina ( P = 0.13). The role and importance of surgery is discussed, with special emphasis on the selective use of the vaginal route in aged, obese and medically high-risk patients.     

Human immunodeficiency virus infection among heterosexuals in the northeastern part of Italy

A cross-sectional, seroprevalence study was conducted between1984 and 1991 to investigate prevalence and risk factors forhuman immunodeficiency virus (HIV) infection in heterosexualsin the northeastern part of Italy. Two hundred and eighty-twoheterosexuals self-referring for HIV testing (109 men and 173women), without history of intravenous drug use or of otherrisk factors for HIV infection, constituted the study group.The overall seroprevalence was 17% (95% confidence interval(Cl): 13–22%), similar in men (18%) and in women (17%),and it tended to increase over time. Age was directly associatedwith HIV antibody seropositivity in men, and inversely relatedin women. Fifteen men and 63 women were steady partners of anHIV-positive person. Among them, 33% of men and 27% of womenwere infected with HIV (odds ratio (OR)=2.8, 95% Cl: 0.7–11.4in men; OR=3.5, 95% Cl: 1.4–8.6 in women). Men with promiscuousoccasional partners had a nearly 3-fold higher risk of infection(95% Cl: 0.8–12.7). Among women, a significantly increasedrisk emerged among those who reported intravenous drug usersamong their occasional partners (OR=5.7). Sixty per cent ofmales and 76% of females never used a condom with occasionalpartners and 70% of males and 72% of females never used onewith steady partners.     

Molecular Biology of the Long QT Syndrome: Impact on Management

The long QT syndrome (LQTS) is a familial disease characterized by prolonged ventricular repolarization and high incidence of malignant ventricular tachyarrhythmias often occurring in conditions ofadrenergic activation. Recently, the genes for the LQTS linked to chromosomes 3 (LQT3), 7 (LQT2), and 11 (LQTl) were identified as SCN5A, the cardiac sodium channel gene and as HERG and KvLQTl potassium channel genes. These discoveries have paved the way for the development of gene-specific therapy for these three forms of LQTS. In order to test specific interventions potentially beneficial in the molecular variants of LQTS, we developed a cellular model to mimic the electrophysiological abnormalities of LQT3 and LQT2. Isolated guinea pig ventricular myocytes were exposed to anthopleurin and dofetilide in order to mimic LQT3 and LQT2, respectively. This model has been used to study the effect of sodium channel blockade and of rapid pacing showing a pronounced action potential shortening in response to Na⁺channel blockade with mexiletine and during rapid pacing only in anthopleurin-treated cells but not in dofetilide-treated cells. Based on these results we tested the hypothesis that QT interval would shorten more in LQT3 patients in response to mexiletine and to increases in heart rate. Mexiletine shortened significantly the QT interval among LQT3 patients but not among LQT2 patients. LQT3 patients shortened their QT interval in response to increases in heart rate much more than LQT2 patients and healthy controls. These findings suggest thatLQT3 patients are more likely to benefit from Na⁺ channel blockers and from cardiac pacing because they are at higher arrhythmic risk at slow heart rates. Conversely, LQT2 patients are at higher risk to develop syncope under stressful conditions, because of the combined arrhythmogenic effect of cate-cholamines with the insufficient adaptation of their QT interval. Along the same line of development of gene-specific therapy, recent data demonstrated that an increase in the extracellular concentration of potassium shortens the QT interval in LQT2 patients suggesting that intervention aimed at increasing potassium plasma levels may represent a specific treatment for LQT2. The molecular findings on LQTS suggest the possibility of developing therapeutic interventions targeted to specific genetic defects. Until definitive data become available, antiadrenergic therapy remains the mainstay in the management of LQTS patients, however it may be soon worth considering the addition of a Na + channel blocker such as mexiletine for LQT3 patients and of interventions such as K⁺ channel openers or increases in the extracellular concentration of potassium for LQTl and LQT2 patients.     

Characterization of an Immunoregulatory Cell Subset Involved in the Upregulation of the Autoimmune Response to Rat Male Accessory Glands

PROBLEM: We studied the regulation of the autoimmune response to rat male accessory glands (RAG) using liposomes as adjuvants. METHOD: Adult male Wistar rats were submitted to three intraperitoneal (i.p.) immunizations with 750 μg of saline extract of RAG associated with liposomes. The delayed type hypersensitivity (DTH) response studied approximately 10 days after each immunization developed after the first immunization, having a remission state after the second one and a clear increase after the third injection. In a further study, spleen mononuclear (SpM) cells obtained form immunized rats 10 days after the third immunization (DTH positive) or from normal rats were separated as adherent (VV +) or nonadherent (VV —) to Vicia villosa population. In VV + SpM cells from immunized or normal animals an enhanced percentage of OX8 + cells (P<.05 and P< .01, respectively) was found, but in VV — SpM cells from the same groups of rats an enhanced percentage of W3/25 + cells (P <.01 and P <.05, respectively) was found when they were studied by immunofluorescence. Later on, we transferred total VV + or VV — SpM cells from i.p. immunized rats to immunized recipients 10 days after the second immunization (DTH negative). The DTH response was enhanced in recipients of total or VV+ SpM cells (P<.01). It was also observed that the transfer of VV — SpM cells from immunized rats or total or VV + SpM cells from normal rats did not reduce the suppression state observed after the second injection (P = NS). The total SpM cells obtained 10 days after the third immunization (DTH positive) were able to transfer autoimmune response to RAG to normal animals (P<.01), whereas VV + SpM cells did not show that capacity (P = NS).