2'3'Cyclic nucleotide 3'phosphodiesterase immunohistochemistry shows an impairment on myelin compaction in hypothyroid rats.

The effects of hypothyroidism on oligodendroglial differentiation and myelination are for the first time studied by immunohistochemical localization of an early oligodendroglial marker, the 2'3'cyclic nucleotide 3'phosphodiesterase (E.C. 3.1.4.37-CNPase), in developing rats. Two groups received methimazol; one during gestation (H) and another postnatally (PN). One H sub-group received thyroxine after birth (T). We observed a delay in CNPase expression followed by a decrease in the number of CNPase immunoreactive fibers in both H and PN groups. The T sub-group was not different from controls. Furthermore, the immunoreactive fibers, in mature hypothyroid animals, showed a continuous pattern of staining in contrast with a discontinuous one in controls. Myelinogenesis is a highly regulated timed event. CNPase links myelin related proteins to the cytoskeleton also interacting with membrane lipids during extension and wrapping of the oligodendroglial process around the axon (ensheathment phase). In mature myelinated fiber the CNPase is absent from compact myelin sheath, being located only in the inner and outer loops and in paranodal loops. Thus, our data suggest a disorder in myelin compaction and point once more to the post-natal period as critical for the mechanisms that are thyroid hormone regulated in myelinogenesis.

Association of Alport's syndrome with HLA-DR2 antigen in a group of unrelated patients.

A few family studies have evaluated HLA antigens in Alport's syndrome; however, there are no large population studies. In the present report, we studied 40 unrelated white patients with Alport's syndrome seen at the Unit of Renal Transplantation, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil. HLA-A, -B, -DR and -DQ antigens were typed using a complement-dependent microlymphocytotoxicity assay. A control white population (N = 403) from the same geographical area was also typed for HLA antigens. Although the frequencies of HLA-A and -B antigens of patients were not statistically different from controls, the frequency of HLA-DR2 antigen observed in patients (65%) was significantly increased in relation to controls (26%; P < 0.001). The relative risk and etiologic fraction for HLA-DR2 antigen were 5.2 and 0.525, respectively. Although few immunological abnormalities have been shown in Alport's syndrome, in this report we emphasize the association of HLA molecules and Alport's syndrome. Besides the well-known inherited molecular defects encoded by type IV collagen genes in Alport's syndrome, the major histocompatibility alleles may be in linkage disequilibrium with these defective collagen genes.

Antibody titers to Toxoplasma gondii in renal transplant patients.

Of 70 renal transplant patients submitted to the indirect immunofluorescence reaction test for toxoplasmosis, 16 (23%) had titers higher than 1/4,000, as compared to 0/41 for chronic hemodialysis patients and 0/50 for blood donors. The indirect immunofluorescence reaction titers in the renal transplant patients correlated with time since initiation of immunosuppressive therapy. Six percent (2/33) of the patients had been on immunosuppressors for less than one year, 30.7% (4/13) for 1 to 2 years, and 41.6% (10/24) for 2 or more years. The frequency of negative titers among the immunosuppressed patients was similar to that observed for blood donors and chronic hemodialysis patients. Fifty percent (8/16) of the patients with higher immunofluorescence reaction titers also had significantly high (greater than or equal to 320) positive titers in the complement fixation test. The results indicate that: 1) the immunosuppressive scheme used for the transplant patients may favor the reactivation of infection from latent Toxoplasma gondii foci, and 2) even though the patients were immunosuppressed, their antitoxoplasma antibody levels were high enough to be detected by the serologic test.

Transmission of Chagas' disease through transplanted kidney: occurrence of the acute form of the disease in two recipients from the same donor.

Two cases of acute Chagas' disease acquired after renal transplantation are reported. The two patients received the kidney from the same donor. The present paper confirms this form of transmission of Chagas' disease and reinforces the need to exclude kidney donors with Trypanosoma cruzi infection.

Nocardia infection in renal transplant recipient: diagnostic and therapeutic considerations.

In the present report the authors discuss the diagnostic difficulties, therapeutic measures and the clinical course of Nocardia infection which occurred among renal transplant recipients at the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (UH-FRP), from 1968 to 1991. Among 500 individuals submitted to renal transplant, 9 patients developed Nocardiosis at varying times after transplant (two months to over two years). All the patients had pulmonary involvement and their most common symptoms were fever, cough and pleural pain. Dissemination of the process is common and three patients presented cutaneous abscesses, four CNS involvement and one had pericarditis due to Nocardia. The diagnostic is quite difficult since there is no specific clinical picture, concomitant infections are frequent and the microorganism presents slow growth in culture (ranging from four to forty days, in our experience). In this report, three cases were only diagnosed by necropsy. The treatment of choice is a combination of Sulfamethoxazole and Trimethoprim (SMX-TMP). In the present series, overall mortality was 77% (7 cases) and in five of the patients who died the diagnosis was late. All the patients who had CNS involvement died.

Causes of death in renal transplant recipients: a study of 102 autopsies from 1968 to 1991.

A study was conducted on 102 patients submitted to renal transplant who died and were autopsied at the University Hospital, Faculty of Medicine of Ribeirão Preto, Brazil, from 1968 to 1991. The cause of death, based on a review of medical records and autopsy reports, was assigned to one of the following categories: infectious (69.6%); cardiovascular (12.7%); gastrointestinal (7.8%); graft rejection (6.9%); tumoral (2.0%); and undetermined (1.0%). Among the 71 cases of death caused by infection, 28 (39.4%) showed disseminated agents involving two or more organs. Isolated pneumonia involved 17 patients (23.9%), followed by acute pyelonephritis in the transplanted kidney in 10 patients (14.1%). The most frequent agents were: bacteria (58.0%), divided into 'non-classified' (83.0%), Nocardia (10.6%) and Mycobacterium (6.4%); fungi (27.5%) represented by Cryptococcus (22.7%), Aspergillus, Candida and Pneumocystis carinii (18.1% each), Histoplasma (13.6%), Mucor and Paracoccidioides brasiliensis (4.5% each); viruses (6.2%) represented by Herpes simplex (60.0%); metazoa (5.0%, S. stercoralis), and protozoa (2.5%, T. cruzi). Cytomegalovirus (CMV) was identified in the lungs of 12 patients and was not directly correlated with death but was associated with other agents. In conclusion, immunodepressed patients such as renal transplant recipients should be carefully monitored for infection due to the high mortality rate.

Longitudinal study of the indirect immunofluorescence and complement fixation tests for diagnosis of Chagas' disease in immunosuppressed patients submitted to renal transplantation.

Clinical and serological follow-up of 7 patients submitted to renal transplantation and presenting positive serological reactions to Chagas' disease before immunosuppression did not show significant changes in indirect immunofluorescence and complement fixation titres for Chagas' disease, or signs and symptoms indicating exacerbation of the disease during follow-up. In addition, 18 of 66 recipients of renal transplants considered to be non-chagasic before immunosuppression showed at least one positive result to the indirect immunofluorescence test for Chagas' disease during the study period. The results suggest that the immunosuppression state induced in chagasic patients submitted to renal transplant did not promoted exacerbation of the chronic infection in these patients and not interfere with the serological response of chronic chagasics, thus permitting the use of these serologic reactions for diagnostic purposes in these cases. However, the positive results of the indirect immunofluorescence test in non-chagasic patients indicate the need for judicious interpretation of the indirect immunofluorescence test for the diagnosis of Chagas' disease in renal transplanted patients.

[Candidiasis in kidney transplant patients]. / Candidíase em pacientes transplantados renais.

The medical records of 620 patients submitted to renal transplant from February 1968 to February 1995 were surveyed for Candida infection. Of these, 87 presented 107 episodes of candidiasis. In 42.9% the infection appeared up to 6 months after the transplant. The most frequent involved sites were: urinary tract, respiratory tract, and gastrointestinal tract. The most frequent etiological agents were: C. albicans, C. tropicalis and C. glabrata. Most urinary tract infections occurred in the first 6 months (61.7%) and manifested clinically as a bacterial infection. In the respiratory tract infections were characterized by isolation of the agent in sputum. In the gastrointestinal infections, 9/16 episodes were esophageal. There were 3 deaths directly related to Candidiasis (one pulmonary and 2 disseminated cases). In the urinary tract, and respiratory tract infections there was association of candidiasis with previous antibiotic treatment (76% and 67%, respectively), and with concomitant bacterial infections (34% and 64%, respectively). The overall prevalence of Candida infections was 14.5%. The predominant location was in the urinary tract (51.0%), followed by the respiratory (26.0%) and gastrointestinal tract (15.0%), with a high rate of association with previous antibiotic treatment and bacterial infections.

Exercise may cause myocardial ischemia at the anaerobic threshold in cardiac rehabilitation programs.

Myocardial ischemia may occur during an exercise session in cardiac rehabilitation programs. However, it has not been established whether it is elicited when exercise prescription is based on heart rate corresponding to the anaerobic threshold as measured by cardiopulmonary exercise testing. Our objective was to determine the incidence of myocardial ischemia in cardiac rehabilitation programs according to myocardial perfusion SPECT in exercise programs based on the anaerobic threshold. Thirty-nine patients (35 men and 4 women) diagnosed with coronary artery disease by coronary angiography and stress technetium-99m-sestamibi gated SPECT associated with a baseline cardiopulmonary exercise test were assessed. Ages ranged from 45 to 75 years. A second cardiopulmonary exercise test determined training intensity at the anaerobic threshold. Repeat gated-SPECT was obtained after a third cardiopulmonary exercise test at the prescribed workload and heart rate. Myocardial perfusion images were analyzed using a score system of 6.4 at rest, 13.9 at peak stress, and 10.7 during the prescribed exercise (P < 0.05). The presence of myocardial ischemia during exercise was defined as a difference > or = 2 between the summed stress score and summed rest score. Accordingly, 25 (64%) patients were classified as ischemic and 14 (36%) as nonischemic. MIBI-SPECT showed myocardial ischemia during exercise within the anaerobic threshold. The 64% prevalence of ischemia observed in the study should not be looked on as representative of the whole population of patients undergoing exercise programs. Changes in patient care and exercise programs were implemented as a result of our finding of ischemia during the prescribed exercise.

[Program for the computerized control of a regional system of cadaveric kidneys exchange developed for the São Paulo Interior Transplante]. / Programa para controle computadorizado de um sistema regional de intercâmbio de rins de cadáver desenvolvido para o São Paulo Interior Transplante.

Authors present a computer software developed to control the regional cadaver kidney exchange program in the state of São Paulo (Interior Transplante), and capable of two distinct routines: 1) management of the data bank concerning the enrolled recipients, and 2) selection of patients that are HLA compatible with a given donor, and final selection of kidney recipients based on the following 4 criteria in addition to HLA compatibility: time in waiting list, panel, age, and logistic factors. The software has been in use for one year and has proved to be extremely useful when compared to the previously used method which involved a standard card file.

Acute tubular necrosis in kidney transplant patients treated with enalapril.

We report two cases of acute renal failure in renal transplant patients using cyclosporine-A (CsA) after the introduction of angiotensin-converting enzyme inhibitor (ACEI) to control arterial hypertension. They had no renal artery stenosis or acute rejection. Both patients presented severe acute tubular necrosis (ATN), which subsided after discontinuation of the ACEI. Synergistic toxic effect of ACEI and CsA on the renal tubules might explain ATN in these two cases.