Renopancreatic Transplantation: Evaluation of 15 Years in 131 Patients.

BACKGROUND: The most common multiple-organ transplant is the simultaneous pancreas-kidney transplantation (SPK). It is usually offered to patients who have insulin-dependent diabetes mellitus and those with diabetic nephropathy and renal failure that has already been established. In this study we present the results of 15 years of SPK in a transplant hospital center in Paraná, Brazil, and evaluated survival, immunosuppression, and transplant-related problems. METHODS: This study was a retrospective analysis of 131 SPK transplants performed at the Angelina Caron Hospital between January 2001 and December 2015. RESULTS: The mean age of SPK recipients was 34 years, with slight a predominance of males (50.4%). Mean graft ischemia time was 11 hours. Exocrine drainage was predominantly vesical, but this approach was abandoned after 2011. As for immunosuppression, induction was performed with basiliximab or thymoglobulin and maintained with prednisone, mycophenolate mofetil, tacrolimus, and/or sirolimus. Patient survival increased from 68.1% in 2001 to 2005 to 77.6% in 2011 to 2015. Graft survival at the end of the period was 85.7% for kidney and 75.5% for pancreas. The main surgery-derived problems for pancreas and kidney was thrombosis (15% and 6%, respectively). The main clinical problems were rejection of the pancreas (18.3%) and urinary infection of the kidney (33.3%). The main cause of death was intra-abdominal sepsis (11.4%). CONCLUSION: There was an improvement in survival rates over the time frame observed, but it remains necessary to adopt measures to reduce transplant-derived problems, including review of the antibiotic therapy protocol and measures to avoid graft thrombosis.

Infliximab partially impairs the anti-Mycobacterium tuberculosis immune responses of severe psoriasis patients with positive tuberculin skin-test.

BACKGROUND: Infliximab and etarnecept are now widely used for treating severe psoriasis. However, these drugs, especially infliximab, increased the risk of tuberculosis reactivation. Surprisingly, epidemiological data suggest that the tuberculosis rate in patients taking infliximab in São Paulo State, Brazil, is similar to that of some developed, non-endemic countries. OBJECTIVE: The aim of this study was to better understand the effect of infliximab on Mycobacterium tuberculosis (Mtb) immune responses of psoriasis patients in an endemic setting (Brazil). METHODS: We evaluated the tuberculosis-specific immune responses of severe psoriasis patients and healthy individuals, both tuberculin skin test (TST) positive, in the presence/absence of infliximab. Patients had untreated severe psoriasis, no co-morbidities affecting the immune responses and a TST >10 mm. Healthy TST(+) (>10 mm) individuals were evaluated in parallel. PBMC cultures from both groups were stimulated with different Mycobacterium tuberculosis (Mtb) antigens (ESAT-6, 85B and Mtb lysate) and phytohemagglutinin, with or without infliximab (5 µg/mL). Parameters evaluated were TNF-α, IFN-γ and IL-10 secretion by ELISA, overnight IFN-γ ELISpot and lymphocyte proliferative response (LPR). RESULTS: Infliximab almost abolished TNF-α detection in PBMC supernatants of both groups. It also significantly reduced the LPR to phytohemagglutinin and the Mtb antigens as well as the IFN-γ levels secreted into day 5 supernatants in both groups. There was no concomitant exaggerated IL-10 secretion that could account for the decreases in these responses. ELISpot showed that, contrasting with the central-memory responses above, infliximab did not affect effector-memory INF-γ-releasing T-cell numbers. CONCLUSIONS: Infliximab affected some, but not all aspects of the in vitro antituberculosis immune responses tested. The preserved effector-memory responses, putatively related to exposure to environmental mycobacteria, may help to explain the lower than expected susceptibility to tuberculosis reactivation in our setting.

Sagital abdominal diameter, but not waist circumference is strongly associated with glycemia, triacilglycerols and HDL-C levels in overweight adults.

AIM: To correlate the sagittal abdominal diameter (SAD) and waist circumference (WC) with metabolic syndrome-associated abnormalities in adults. METHODS: This cross-sectional study included onehundred twelve adults (M=27, F=85) aging 54.0±11.2 yrs and average body mass index (BMI) of 30.5±9.0 kg/m². The assessment included blood pressure, plasma and anthropometric measurements. RESULTS: In both men and female, SAD and WC were associated positively with body fat% (r=0.53 vs r=0.55), uric acid (r=0.45 vs r=0.45), us-PCR (r=0.50 vs r=0.44), insulin (r=0.89 vs r=0.75), insulin resistance HOMA-IR (r=0.86 vs r=0.65), LDL-ox (r=0.51 vs r=0.28), GGT (r=0.70 vs r=0.61), and diastolic blood pressure (r=0.35 vs r=0.33), and negatively with insulin sensibility QUICKI (r=-0.89 vs r=-0.82) and total cholesterol/TG ratio (r=-0.40 vs r=-0.22). Glycemia, TG, and HDL-c were associated significantly only with SAD (r=0.31; r = 39, r=-0.43, respectively). CONCLUSION: Though the SAD and WC were associated with numerous metabolic abnormalities, only SAD correlated with dyslipidemia (TG and HDL-c) and hyperglycemia (glycemia).

Two patients coinfected with Mycobacterium leprae and human immunodeficiency virus type 1 and naive for antiretroviral therapy who exhibited type 1 leprosy reactions mimicking the immune reconstitution inflammatory syndrome.

Two case reports of patients with human immunodeficiency virus type 1 (HIV-1) infection who developed leprosy are presented. Both developed type 1 leprosy reactions in the absence of antiretroviral therapy. Reactions have been described for a number of HIV-1- and Mycobacterium leprae-coinfected patients and have been considered to be part of an immune reconstitution inflammatory syndrome (IRIS) since the reactions were usually linked to the administration of highly active antiretroviral therapy. The reports of our two patients suggest that the type 1 reactions in patients with leprosy and HIV may not always be an IRIS manifestation but may be akin to the classical reactional state described for the natural course of leprosy infection, which occurs in leprosy patients due to the fluctuations of the antimycobacterial immune response, whether they are coinfected with HIV or not.

Treatment delay and radiological errors in patients with bone metastases

During routine investigations, we are surprised to find that therapy for bone metastases is sometimes delayed for a considerable period of time. To determine the extent of this delay and its causes, we reviewed the medical records of symptomatic patients seen at our hospital who had been recently diagnosed as having bone metastases for the last four years. The treatment delay was defined as the interval between presentation with symptoms and definitive treatment for bone metastases. The diagnostic delay was defined as the interval between presentation with symptoms and diagnosis of bone metastases. The results of diagnostic radiological examinations were also reviewed for errors. The study population included 76 males and 34 females with a median age of 66 years. Most bone metastases were diagnosed radiologically. Over 75 percent of patients were treated with radiotherapy. The treatment delay ranged from 2 to 307 days, with a mean of 53.3 days. In 490 radiological studies reviewed, we identified 166 (33.9 percent) errors concerning 62 (56.4 percent) patients. The diagnostic delay was significantly longer for patients with radiological errors than for patients without radiological errors (P < 0.001), and much of it was due to radiological errors. In conclusion, the treatment delay in patients with symptomatic bone metastases was much longer than expected, and much of it was caused by radiological errors. Considerable efforts should therefore be made to more carefully examine the radiological studies in order to ensure prompt treatment of bone metastases

Treatment delay and radiological errors in patients with bone metastases.

During routine investigations, we are surprised to find that therapy for bone metastases is sometimes delayed for a considerable period of time. To determine the extent of this delay and its causes, we reviewed the medical records of symptomatic patients seen at our hospital who had been recently diagnosed as having bone metastases for the last four years. The treatment delay was defined as the interval between presentation with symptoms and definitive treatment for bone metastases. The diagnostic delay was defined as the interval between presentation with symptoms and diagnosis of bone metastases. The results of diagnostic radiological examinations were also reviewed for errors. The study population included 76 males and 34 females with a median age of 66 years. Most bone metastases were diagnosed radiologically. Over 75% of patients were treated with radiotherapy. The treatment delay ranged from 2 to 307 days, with a mean of 53.3 days. In 490 radiological studies reviewed, we identified 166 (33.9%) errors concerning 62 (56.4%) patients. The diagnostic delay was significantly longer for patients with radiological errors than for patients without radiological errors (P < 0.001), and much of it was due to radiological errors. In conclusion, the treatment delay in patients with symptomatic bone metastases was much longer than expected, and much of it was caused by radiological errors. Considerable efforts should therefore be made to more carefully examine the radiological studies in order to ensure prompt treatment of bone metastases.

New sesquiterpene lactones from Elephantopus mollis and their leishmanicidal activities.

The leishmanicidal compounds isolated from whole plants of Elephantopus mollis H.B.K. were identified as follows. Three new sesquiterpenoid lactones, 2,5-epoxy-2beta-hydroxy-8alpha-(2-methylpropenoyloxy)-4(15),10(14),11(13)-germacratrien-12,6alpha-olide, (4betaH)-8alpha-(2-methylpropenoyloxy)-2-oxo-1(5),10(14), 11(13)-guaiatrien-12,6alpha-olide and (4betaH)-5alpha-hydroxy-8alpha-(2-methylpropenoyloxy)-1(10),11(13)-guaiadiene-12,6alpha-olide, were isolated from Peruvian and Brazilian collections together with four known sesquiterpenoids, molephantin, elephantopin, isoelephantopin and 2-deethoxy-2beta-methoxyphantomolin. They exhibited potent in vitro leishmanicidal activities against Leishmania major. The alpha-methylene-gamma-butyrolactone moiety was found to be essential to the potent leishmanicidal effect observed.

Study of immunohistochemical expression of insulin-like growth factor I and proliferating cell nuclear antigen in thyroid gland papillary carcinoma and its metastasis.

BACKGROUND: Several tumor factors are associated with papillary thyroid cancer. Most studies do not compare the expressions of these factors in the primary tumors and in their associated cervical metastasis. METHODS: Paraffin sections of 20 patients with papillary carcinoma of the thyroid gland with lymph node metastasis were studied. The presence and distribution of insulin-like growth factor I (IGF-I) and proliferating cell nuclear antigen (PCNA) was analyzed, through immunohistochemical technique, in both primaries and lymph node metastasis. The results were correlated with clinical-pathologic data (sex, age, size of primary, multicentricity, thyroid capsule invasion, lymphatic and blood vessels invasion, development of distant metastasis, and associated thyroid diseases). RESULTS: The qualitative analysis showed the reaction for IGF-I was present in more than 90% of the neoplastic cells in both primaries and lymph node metastasis. No correlation with the clinical-pathological features was observed. Regarding the PCNA, the mean percentage of nuclei stained showed no statistical difference between primaries and metastasis (p = 0.598). Except for age, clinicopathologic data had no influence on the mean percentage of nuclei stained. A correlation was verified between the percentage of cells stained by PCNA in primary tumors and the patients' age (p < 0. 01). CONCLUSIONS: The expressions of these tumor factors are equally intense for both primary and metastatic tissue in papillary thyroid cancer. Despite the small size of the sample, the expressions of IGF-I and PCNA could not be associated to clinical-pathologic features, except for the age. As patients over 40 years old had higher expression of PCNA, this marker may have prognostic significance for patients with papillary thyroid cancer.

Determination of mercury levels in biological samples using the incomplete cubane-type sulfur-bridged nitrilotriacetato molybdenum complex by a spectrophotometer.

Spectrophotometric determination of mercury levels in biological samples was investigated using incomplete cubane-type sulfur-bridged molybdenum complex, K2[Mo3S4(Hnta)3] 9H2O, ("NTA" complex; H3nta = nitrilotri acetic acid). The urine or organs of mice, which were either exposed to metallic mercury vapor or injected intraperitoneally with mercuric ion, were decomposed from four to twelve hours with a mixed solution of potassium permanganate and sulfuric acid. After the pretreatment, mercury in the urine and organs of mice was captured by the "NTA" complex. Absorbance of the resultant solution in the urine or organs of mice was also measured by a spectrophotometer under conditions similar to that of the exhalation.

Iatrogenias em dermatologia / Iatrogenics in dermatology

No 50§ Congresso Brasileiro de Dermatologia, realizado em setembro de 1995 em Belém, Pará, foi constituído um grupo de trabalho cujo tema de discussäo foi iatrogenias em dermatologia. Como o tema é muito extenso, foram selecionados pelo coordenador do grupo três assuntos considerados de maior interesse: 1. Iatrogenia no tratamento medicamentoso da acne; 2. Iatrogenia e corticosteróides sistemicos e tópicos; e 3. Iatrogenia em certos procedimentos cosmiátricos. Os relatores fizeram ampla revisäo bibliográfica que foi previamente entregue aos participantes do grupo para discussäo. Durante o congresso os temas foram apresentados pelos relatores e, após, discutidos com o grupo. Neste trabalho será apresentada uma sinopse da discussäo desse grupo.

Comparative safety and efficacy of two immune globulin products in Kawasaki disease.

OBJECTIVE: To compare the safety and efficacy of various intravenously administered immune globulin (IVGG) products in patients with Kawasaki disease. METHODS: We performed a retrospective matched-pair study of 45 pairs of patients, matched by age, gender, hospital, and illness day when IVGG therapy was initiated. All patients received aspirin, 80 to 100 mg/kg per day; one of each pair received Venoglobulin, 2 gm/kg (product A), and the other received Iveegam, 2 gm/kg (product B). Safety was assessed during and after IVGG infusion by recording rigors, pruritus, hypotension, urticaria, and nausea. Treatment efficacy was evaluated by posttreatment height and duration of fever, and subsequent echocardiographic changes. RESULTS: Untoward reactions during infusions occurred more often with product A (25%) than with product B (2%) (p < 0.025); most reactions were rigors (18% vs 2%) (p < 0.05). Therapy was completed in all patients. Height of fever and proportion of patients febrile each day after product A or B did not differ significantly. No differences were found in the frequency of coronary artery abnormalities 1 year after illness. CONCLUSIONS: No significant differences in efficacy appeared between the two IVGG products, but they differed significantly in non-life-threatening adverse reactions, especially infusion-related rigors. Other IVGG products should be evaluated in a similar fashion.

[An outbreak of tuberculosis involving foreign workers from South America].

A twenty-four year old male Peruvian of Japanese origin, who came to Japan in September 1990 and had been working in a minor factory in a rural area, was admitted to a hospital in March '91 with severe cough. Smear examination of his sputum smear was positive for acid-fast bacilli and his chest X-ray showed multiple cavities (Index case). Subsequent contact examination identified further four patients with pulmonary tuberculosis among his colleagues in the factory, all of whom lived in the same house with the index case. During following three years, further six patients with mycobacteriosis, two Peruvians and four Japanese, were found among the employee of that factory. M. tuberculosis was cultured from the sputa obtained from seven of these eleven patients. Another patient was diagnosed as non-tuberculous mycobacteriosis. Restriction fragment length polymorphism (RFLP) analysis carried out with five strains of M. tuberculosis isolated from these patients revealed the identical RFLP pattern which is uncommon in Japan. Still more, an isolate from another patient was subjected to RFLP analysis by chance, and was found to show the same RFLP pattern. Later epidemiological study revealed that the last patient, a 53 year-old saleswoman of boxlunch, might have some contact with the index case at her booth. Though RFLP analysis was not done for the isolate from the index case, from the identity of RFLP patterns of other isolates, clinical course and epidemiological study, it is considered that six patients were certainly, and two others were probably infected from the index case.(ABSTRACT TRUNCATED AT 250 WORDS)

A highly suspected case of chronic Chagas' heart disease diagnosed in Japan.

A 50-year-old South American Indian woman, a native of Brazil and now a resident of Shiga Prefecture, was admitted to our hospital because of dyspnea on exertion. We initially suspected dilated cardiomyopathy due to an enlarged and diffusely hypokinetic left ventricle (LV) on echocardiogram. Coronary arteriograms were normal, and histological examination of right ventricular endomyocardial biopsy specimens showed findings compatible with chronic myocarditis. Magnetic resonance imaging revealed localized thinning and a small apical aneurysm at the LV. Since she had previously lived in a high-risk region for Chagas' disease, two immunological examinations for Trypanosoma cruzi were performed. The results of both tests were compatible with the disease. Recently, an increasing number of patients with Chagas' disease have been found in the United States among immigrants from South American countries, and the risk of transmission of the disease through contaminated blood transfusion is becoming a national problem. We report this case with reference to the present state of the problem in the United States and the potential problems it presents in Japan because of the marked increase in the number of immigrants from the affected area.

[The cerebrospinal fluid in bacterial meningitis]. / Aspectos dos líquidos cefalorraquidianos nas meningites bacterianas.

Samples of 1815 cerebrospinal fluid (CSF) were studied in a meningitis outbreak during 1989 in São Paulo, Brazil. Neisseria meningitis 56% with 44% type B, Haemophilus influenzae 17%, from which 72% in children (days to 3-year-old) and Streptococcus pneumoniae 14% from which 60% in children (day to 1-year-old) of 443 (24%) of all strains. Cytochemistry study showed: purulent or turbidity aspects in 70 to 79% positive bacterioscopy or culture of CSF; white cells count > 500/mm3; glucose < 45 mg/dl; protein > 90 mg/dl in 90% of all patients. We concluded that: CSF prognostic factors: (aspect and cytochemistry) were correlated with bacterial meningitis. Bacterioscopy and positive cultures were correlated to NM, SP and HI isolation from these patients (Goodman Test).

Expression cloning of genes for GPI-anchor biosynthesis.

Cloning genes for glycosylphosphatidylinositol (GPI)-anchor biosynthesis is important to further understand its mechanisms and regulation. We have been using expression cloning methods in which a cDNA library was transfected into GPI-anchor-deficient mutant cells. The transfectants which restored surface expression of GPI-anchored proteins were isolated and the plasmids were rescued. In this way we previously cloned cDNAs of genes for complementation classes A and F, and named them PIG-A and PIG-F, respectively. In the present study we have cloned the gene for class B, termed PIG-B. In each case we used different methods. For cloning PIG-A cDNA we used a cDNA library made with an Epstein-Barr-virus-based vector and human class A mutant JY5 which expresses EBNA-1 protein. The EBNA-1 protein allows stable replication of oriP-containing plasmids in the episomal form. For cloning PIG-F cDNA we chose a transient expression method and cotransfected a human T-cell cDNA library made with a vector bearing an origin of replication of polyoma virus with a plasmid bearing polyoma virus large T into the class F murine thymoma mutant. This cotransfection strategy was unsuccessful for cloning PIG-B due to low transfection efficiency of the class B thymoma mutant SIA-b. Thus, we first established large T-expressing SIA-b cells and then transfected them with a cDNA library. PIG-B cDNA restored the surface expression of Thy-1 on SIA-b cells and also synthesis of mature type GPI-anchor precursors in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression cloning of genes for GPI-anchor biosynthesis

Cloning genes for glycosylphosphatydilinositol (GPI)-anchor biosynthesis is important to further understand its mechanisms and regulation. We have been using expression cloning methods in which a cDNA library was transfected into GPI-anchor-deficient mutant cells. The transfectants which restored surface expression of GPI-anchored proteins were isolated and the plasmids were rescued. In this way we previously cloned cDNAs of genes for complementation classes A and F, and named them PIG-A and PIG-F, respectively. In the present study we have cloned the gene for class B, termed PIG-B. In each case we used different methods. For cloning PIG-A cDNA we used a cDNA library made with an Epstein-Barr-virus-based vector and human class A mutant JY5 which expresses EBNA-1 protein. The EBNA-1 protein allows stable replication of oriP-containing plasmids in the episomal form. For cloning PIG-F cDNA we chose a transient expression method and cotransfected a human T-cell cDNA library made with a vector bearing an origin of replication of polyoma virus with a plasmid bearing polyoma virus large T into the class F murine thymona mutant. This cotransfection strategy was unsuccessful for cloning PIG-B due to low transfection efficiency of the class B thymoma mutant SIA-b. Thus, we first established large T-expressing SIA-b cells and then transfected them with cDNA library. PIG-B cDNA restored the surface expression of Thy-1 on SIA-b cells and also synthesis of mature type GPI-anchor precursors in these cells. The cDNA consists of 1929 bp and codes for a putative new protein of 554 amino acid residues

Levels of benzo[a]pyrene and other polycyclic aromatic hydrocarbons in liquid smoke flavour and some smoked foods.

In order to investigate the levels of the polycyclic aromatic hydrocarbons, mainly benzo[a]pyrene because of its carcinogenicity, 55 samples of smoke flavour and smoked foods were analysed. The samples tested included 11 samples of liquid smoke flavour and 44 samples of smoked foods like bacon, loin, turkey, sausage, ox rib, etc. from different brands. A liquid chromatographic method was developed using a fluorescence detector. Benzo[a]pyrene was found in 73% of the liquid smoke flavour samples analysed. The levels varied from 0.1 to 336.6 micrograms/kg. Three liquid smoke flavour samples showed levels of benzo[a]pyrene above the maximum level recommended by FAO/WHO (10 micrograms/kg). From the total of 44 smoked food samples analysed, benzo(a)pyrene was detected in 23 samples (52%). The levels varied from 0.1 to 5.9 micrograms/kg. Anthracene and fluoranthene, non-carcinogenic polycyclic aromatic hydrocarbons, were found in almost all the samples analysed. Benzo[ghi]perylene, 3,4-benzofluoranthene and 1,2,3,4-dibenzopyrene were not found in any of the 55 samples analysed.

African histoplasmosis. Report of the first case in Brazil and treatment with itraconazole.

We report the first case of African histoplasmosis diagnosed in Brazil. The patient was an immigrant from Angola who had come to Brazil six months after the appearance of the skin lesion. The skin of the right retroauricular area was the only site of involvement. The diagnosis was established by direct mycologic examination, culture and by histopathologic examination of the lesion. The patient was successfully treated with Itraconazole 100mg a day for 52 days. No recurrent skin lesions were observed during the ten month follow-up period.