Prevention of bone marrow graft failure by an anti LFA-1 monoclonal antibody

Graft rejection is the major cause of failure of HLA mismatched bone marrow transplantation because of residual host immunity. we have proposed to use a monoclonal murine antibody specific for the LFA-1 molecule (25-3) to prevent graft failure in HLA mismatched bone marrow transplantation (BMT). The rationale for this approach is three fold: LFA-1 deficient patients (3/3) do not reject HLA mismatched BMT; anti LFA-1 blocka in vitro the induction of T cell responses and T/ non T cytotoxic functions; LFA-1 is not expressed by other cells than leucocytes. We have accordingly treated twenty two patients with inherited diseases and 8 with leikemia. The bone marrow was T cells depled by E rosetting of Campath antibody. The antibody was given at days -3, -1, +1, +3, +5 at dose of .1 mg/kg/d for the first 9 and then .2mg/kg/d from day -3 to +6. Engraftment occured in 23/30 patients as shown by at least HLA typing. Hematological recovery was rapid, GVH was limited. Side effects of antibody infusion included fever and possibly an increased incidence of early bacteral infection (sepsis, 1 death). Immunological reconstitution occured slowly leading in six cases to EBV-induced B cell poliferation (1 death and in two others to transient auto immune hemolytic anemia. There has been only one secondary graft rejection. Sisteen patients are alive 3 to 26 months post transplant with functional grafts. Although the number of patients treated is still low the absence of late rejection so far, gives hope for long term maintenance of the graft using anti LFA-1. Since the antibody is an IgG 1 unable to bind human complement, and since it is known to inhibit phagocytosis, there is a good suggestion that 25-3 act through functional blocking of host T and non T luymphocytes at both induction and effector levels.

Lamivudine therapy for hepatitis B in renal transplantation

Antiviral therapies are associated with an increased risk of acute rejection in transplant patients. The aim of the present study was to evaluate the efficacy and safety of lamivudine therapy for hepatitis B virus (HBV) infection in renal transplant patients. Six patients were included in this study. They received 150 mg/day of lamivudine during a follow-up period of 24 months. The laboratory tests monitored were HBV DNA, HBsAg, HBeAg, ALT, gamma-GT, serum creatinine and blood cyclosporine levels. The HBV DNA became undetectable in four patients as early as in the third month of treatment. After six months, the viral load was also negative in the other two patients, and remained so until 18 months of follow-up. The medication was well tolerated with no major side effects. Lamivudine was safe and effective in blocking HBV replication in renal transplant patients without any apparent increase in the risk of graft failure for the 24-month period of study.

Glomerular damage as a predictor of renal allograft loss

Interstitial fibrosis and tubular atrophy (IF/TA) are the most common cause of renal graft failure. Chronic transplant glomerulopathy (CTG) is present in approximately 1.5-3.0% of all renal grafts. We retrospectively studied the contribution of CTG and recurrent post-transplant glomerulopathies (RGN) to graft loss. We analyzed 123 patients with chronic renal allograft dysfunction and divided them into three groups: CTG (N = 37), RGN (N = 21), and IF/TA (N = 65). Demographic data were analyzed and the variables related to graft function identified by statistical methods. CTG had a significantly lower allograft survival than IF/TA. In a multivariate analysis, protective factors for allograft outcomes were: use of angiotensin-converting enzyme inhibitor (ACEI; hazard ratio (HR) = 0.12, P = 0.001), mycophenolate mofetil (MMF; HR = 0.17, P = 0.026), hepatitis C virus (HR = 7.29, P = 0.003), delayed graft function (HR = 5.32, P = 0.016), serum creatinine ≥1.5 mg/dL at the 1st year post-transplant (HR = 0.20, P = 0.011), and proteinuria ≥0.5 g/24 h at the 1st year post-transplant (HR = 0.14, P = 0.004). The presence of glomerular damage is a risk factor for allograft loss (HR = 4.55, P = 0.015). The presence of some degree of chronic glomerular damage in addition to the diagnosis of IF/TA was the most important risk factor associated with allograft loss since it could indicate chronic active antibody-mediated rejection. ACEI and MMF were associated with better outcomes, indicating that they might improve graft survival.

Experience of ECMO in Primary Graft Dysfunction after Orthotopic Heart Transplantation

Background:Primary graft dysfunction is the main cause of early mortality after heart transplantation. Mechanical circulatory support has been used to treat this syndrome.Objective:Describe the experience with extracorporeal membrane oxygenation to treat post-transplant primary cardiac graft dysfunction.Methods:Between January 2007 and December 2013, a total of 71 orthotopic heart transplantations were performed in patients with advanced heart failure. Eleven (15.5%) of these patients who presented primary graft dysfunction constituted the population of this study. Primary graft dysfunction manifested in our population as failure to wean from cardiopulmonary bypass in six (54.5%) patients, severe hemodynamic instability in the immediate postoperative period with severe cardiac dysfunction in three (27.3%), and cardiac arrest (18.2%). The average ischemia time was 151 ± 82 minutes. Once the diagnosis of primary graft dysfunction was established, we installed a mechanical circulatory support to stabilize the severe hemodynamic condition of the patients and followed their progression longitudinally.Results:The average duration of extracorporeal membrane oxygenation support was 76 ± 47.4 hours (range 32 to 144 hours). Weaning with cardiac recovery was successful in nine (81.8%) patients. However, two patients who presented cardiac recovery did not survive to hospital discharge.Conclusion:Mechanical circulatory support with central extracorporeal membrane oxygenation promoted cardiac recovery within a few days in most patients.

Correção do nariz desviado utilizando spreader graft no lado convexo do desvio

O nariz desviado é resultado de um conjunto de alterações anatômicas e por isso existe um grande número de técnicas para sua correção, sendo que um único método não deve ser utilizado em todos os casos. OBJETIVO: Avaliar um novo método para a correção destas deformidades, o uso do spreader graft no lado convexo do nariz desviado. FORMA DE ESTUDO: Prospectivo. MATERIAL E MÉTODO: Seis pacientes com nariz desviado foram submetidos à rinoplastia com colocação de spreader graft no lado convexo do desvio nasal e acompanhados por um período de 2 anos. RESULTADOS: Todos os pacientes apresentaram melhora da estética facial. Conclusão: Este estudo mostrou ser possível utilizar o spreader graft no lado convexo do desvio nasal em casos específicos.

How logrolling can explain the failure of the government coalition in Brazil

This article presents an analysis of the behavior of federal representatives in the Brazilian House of Representatives between 1995 and 1998, when a series of constitutional amendments were presented by the president to be voted on by Congress. The objective is to show that the lack of a stable government coalition resulted in costs to society that were not anticipated by the government. The study argues that a logroll - a trade of votes - was the strategy used by the government in order to guarantee the number of votes necessary to approve the amendments. This strategy created a vicious system in which representatives would only vote with the government if they had benefits in return.

Seasonal variation in hospitalizations due to heart failure in Niterói city, Southeastern Brazil

The objective of the study was to describe seasonality of hospitalizations for heart failure in tropical climate as it has been described in cold climates. Seasonal Auto-regressive Integrated Moving-Average model was applied to time-series data of heart failure hospitalizations between 1996 and 2004 in Niteroi (Southeastern Brazil), collected from the Brazilian National Health Service Database. The standard seasonal variation was obtained by means of moving-average filtering and averaging data. The lowest and the highest annual hospital admissions were 507 (1997) and 849 (2002), respectively; the lowest and the highest monthly rates were 419 (December) and 681 (October), respectively. Peak admission rates were seen during the fall and winter. Although weak, the seasonality observed indicates that slight variations result in increased hospitalizations for heart failure.

Exporting "failure": why research from rich countries may not benefit the developing world

The '10/90 gap' was first highlighted by the Global Forum for Health Research. It refers to the finding that 90% of worldwide medical research expenditure is targeted at problems affecting only 10% of the world's population. Applying research results from the rich world to the problems of the poor may be a tempting, potentially easy and convenient solution for this gap. This paper had the objective of presenting arguments that such an approach runs the risk of exporting failure. Health interventions that are shown to be effective in the specific context of a Western industrialized setting will not necessarily work in the developing world.

Cyclosporine versus tacrolimus: cost-effectiveness analysis for renal transplantation in Brazil

OBJECTIVE To analyze the cost-effectiveness of treatment regimens with cyclosporine or tacrolimus, five years after renal transplantation.METHODS This cost-effectiveness analysis was based on historical cohort data obtained between 2000 and 2004 and involved 2,022 patients treated with cyclosporine or tacrolimus, matched 1:1 for gender, age, and type and year of transplantation. Graft survival and the direct costs of medical care obtained from the National Health System (SUS) databases were used as outcome results.RESULTS Most of the patients were women, with a mean age of 36.6 years. The most frequent diagnosis of chronic renal failure was glomerulonephritis/nephritis (27.7%). In five years, the tacrolimus group had an average life expectancy gain of 3.96 years at an annual cost of R$78,360.57 compared with the cyclosporine group with a gain of 4.05 years and an annual cost of R$61,350.44.CONCLUSIONS After matching, the study indicated better survival of patients treated with regimens using tacrolimus. However, regimens containing cyclosporine were more cost-effective.

Acute renal failure after rifampicin

A patient with miliary tuberculosis and a chronic urogenital focus is described, who had a borderline renal function at diagnosis and developed overt renal failure upon daily treatment with rifampin (RMP), isoniazid (INH) and ethambutol (EMB). This is the first Brazilian report of BMP induced renal damage. A renal biopsy taken on the third day of oliguria showed recent tubular necrosis with acute interstitial inflammation and granuloma formation. The aspect of the granulomatous lesion hightly suggested drug etiology because of the lack of palisading, high incidence of neutrophils and absence of facid-fast bacilli. This is the first presentation of an acute granulomatous interstitial nephritis probably due to RMP. Furthermore the pathogenesis of the renal damage caused by tuberculosis and RMP are discussed.

Tuberculosis in patients with chronic renal failure

Nine cases of tuberculosis (TB) were diagnosed among 800 uremic patients, followed-up during 11 years, a prevalence of 1125%, 2.5 times higher than that in the general population. Six patients (66.7%) had lymph node involvement (4 cervical and 2 mediastinal). Three patients (33.3%) had pulmonary involvement (2 pleuro-pulmonary and 1 bilateral apical pulmonary). Eight patients were undergoing dialysis and 1 was pre-dialytic. The duration of dialysis ranged from 1 to 60 months. Three patients had previously received immunosuppressive drugs for unsuccessful renal transplantation. Daily fever was present in all but one patient; he was asymptomatic and TB was suspected after routine chest radiography. Biopsy was the diagnostic procedure in 7 patients (77.8%), four by direct cervical lymph node biopsy, 2 by mediastinal, performed by mediastinoscopy and 1 by pleural biopsy. In 2 other patients TB was confirmed by the presence of tubercle bacilli; in sputum (1 patient) and in a bronchial flushing specimen (the other patient). Triple therapy was used in all patients (isoniazid and ethambutol in all), plus rifampicin in 8 and streptomycin in 1. One patient had jaundice and another had optical neuritis. Five patients were cured. The other four died during treatment of causes unrelated to TB or its treatment.

Is rhabdomyolysis an additional factor in the pathogenesis of acute renal failure in leptospirosis?

Leptospirosis is an important cause of acute renal failure in our environment. Although several mechanisms are implicated, the role of rhabdomyolysis in the pathogenesis of acute renal failure in leptospirosis has not been analysed. Sixteen patients with the diagnosis of leptospiroses consecutively admitted to the hospital were prospectively studied. The disease was characterized by sudden onset in all patients and, at admission, jaundice, conjunctival suffusion and myalgias. Mild to moderate proteinuria with unremarkable urinary sediment was recorded in 37.5% of the patients and abnormal levels of urea creatinine were found in 87.5% and 74.0%, respectively. Increased levels of aminotranspherase were documented in all 12 and CPK in all 10 patients studied. Serum myoglobin levels greater than 120µg/l recorded in 56.2%. A correlation between myoglobin and renal failure or severity of disease, however, could not be established.

Hemorrhagic syndrome and Acute renal failure in a pregnant woman after contact with Lonomia caterpillars: a case report

A case of a 37-week pregnant woman who developed a hemorrhagic syndrome and acute renal failure after contact with Lonomia caterpillars is reported. The accident also initiated labour and the patient gave birth to an alive child. Some pathophysiological aspects of the genital bleeding and of the acute renal failure are discussed.

Evaluation of penicillin therapy in patients with leptospirosis and acute renal failure

The effectiveness of specific antibiotic treatment in severe leptospirosis is still under debate. As part of a prospective study designed to evaluate renal function recovery after leptospirosis acute renal failure (ARF) (ARF was defined as Pcr > or = 1.5 mg/dL), the clinical evolutions of 16 treated patients (T) were compared to those of 18 untreated patients (nT). Treatment or non-treatment was the option of each patient's attending infectologist. The penicillin treatment was always with 6 million IU/day for 8 days. No difference was found between the two groups in terms of age, gender, number of days from onset of symptoms to hospital admission, or results of laboratory tests performed upon admission and during hospitalization, but proteinuria was higher in the treated group. There were no significant difference in the other parameters employed to evaluate patients' clinical evolution as: length of hospital stay, days of fever, days to normalization of renal function, days to total bilirubins normalized or reached 1/3 of maximum value and days to normalization of platelet counts. Dialytic treatment indication and mortality were similar between group T and nT. In conclusion, penicillin therapy did not provide better clinical outcome in patients with leptospirosis and ARF.

Acute renal failure after massive honeybee stings

Two clinical cases of patients who survived after numerous attacks of Africanized bees (600 and 1500 bee stings, respectively) are reported. Clinical manifestation was characterized by diffuse and widespread edema, a burning sensation in the skin, headache, weakness, dizziness, generalized paresthesia, somnolence and hypotension. Acute renal failure developed and was attributed to hypotension, intravascular hemolysis, myoglobinuria due to rhabdomyolysis and probably to direct toxic effect of the massive quantity of injected venom. They were treated with antihistaminic, corticosteroids and fluid infusion. One of them had severe acute renal failure and dialysis was required. No clinical complication was observed during hospital stay and complete renal function recovery was observed in both patients. In conclusion, acute renal failure after bee stings is probably due to pigment nephropathy associated with hypovolemia. Early recognition of this syndrome is crucial to the successful management of these patients.