Long-term exercise training prevents mammary tumorigenesis-induced muscle wasting in rats through the regulation of TWEAK signalling.

AIM: Exercise training has been suggested as a non-pharmacological approach to prevent skeletal muscle wasting and improve muscle function in cancer cachexia. However, little is known about the molecular mechanisms underlying such beneficial effect. In this study, we aimed to, firstly, examine the contribution of TWEAK signalling to cancer-induced skeletal muscle wasting and, secondly, evaluate whether long-term exercise alters TWEAK signalling and prevents muscle wasting. METHODS: Female Sprague-Dawley rats were randomly assigned to control and exercise groups. Fifteen animals from each group were exposed to N-Methyl-N-nitrosourea carcinogen. Animals in exercise groups were submitted to moderate treadmill exercise for 35 weeks. After the experimental period, animals were killed and gastrocnemius muscles were harvested for morphological and biochemical analysis. RESULTS: We verified that exercise training prevented tumour-induced TWEAK/NF-κB signalling in skeletal muscle with a beneficial impact in fibre cross-sectional area and metabolism. Indeed, 35 weeks of exercise training promoted the upregulation of PGC-1α and oxidative phosphorylation complexes. This exercise-induced muscle remodelling in tumour-bearing animals was associated with less malignant mammary lesions. CONCLUSION: Data support the benefits of an active lifestyle for the prevention of muscle wasting secondary to breast cancer, highlighting TWEAK/NF- κB signalling as a potential therapeutic target for the preservation of muscle mass.

Set theory and the nosology of hematological malignancies: lymphomas are characterized by lymphoid differentiation, while leukemia definitions have no common property.

The dividing line between leukemia and lymphoma is usually not very clear. We put forward the hypotheses that simple concepts of set theory are valuable tool in order to verify the consistency of the available definitions of leukemia and lymphoma. Set theory is the branch of mathematics that leads with collections or sets of objects and has many applications. A set can be described by listing the properties that its members must have in order to belong to the set. We developed a group of organizational properties regarding cellular origin (designated [O] for origin), progression [P] and differentiation [D] of the malignant hematopoietic cells. We selected definitions of leukemia and lymphoma from medical literature and analyzed these definitions according to properties [O], [P] and [D]. Fourteen definitions were selected for analysis (seven of leukemia and seven of lymphoma). For each definition, we listed the properties that define leukemia and lymphoma as a set of hematological malignancies. The main property that characterizes the set of lymphomas was the lymphoid differentiation. This property was present in all seven definitions of lymphoma and should be regarded a necessary condition to define this neoplasia. Definitions of leukemia were not uniform and no common property was present in all of them. Altogether, these results demonstrate that current definitions do not permit a precise classification of hematological malignancy as leukemia or lymphoma. The definitions of leukemia are not uniform and this term could be modified.

Pseudomonas aeruginosa: study of antibiotic resistance and molecular typing in hospital infection cases in a neonatal intensive care unit from Rio de Janeiro City, Brazil.

This study had the objective of to analyze the demographic and bacteriologic data of 32 hospitalized newborns in an neonatal intensive care unit of a public maternity hospital in Rio de Janeiro city, Brazil, seized by Pseudomonas aeruginosa sepsis during a period ranged from July 1997 to July 1999, and to determine the antimicrobial resistance percentage, serotypes and pulsed field gel electrophoresis (PFGE) patterns of 32 strains isolated during this period. The study group presented mean age of 12.5 days, with higher prevalence of hospital infection in males (59.4%) and vaginal delivery (81.2%), than females (40.6%) and cesarean delivery (18.8%), respectively. In this group, 20 (62.5%) patients received antimicrobials before positive blood cultures presentation. A total of 87.5% of the patients were premature, 62.5% presented very low birth weight and 40.6% had asphyxia. We detected high antimicrobial resistance percentage to b-lactams, chloramphenicol, trimethoprim/sulfamethoxazole and tetracycline among the isolated strains. All isolated strains were classified as multi-drug resistant. Most strains presented serotype O11 while PFGE analysis revealed seven distinct clones with isolation predominance of a single clone (75%) isolated from July 1997 to June 1998.

Molecular epidemiology of methicillin resistant Staphylococcus aureus isolated from newborns in a hospital in Rio de Janeiro, Brazil

Methicillin resistant Staphylococcus aureus (MRSA) is an organism that is frequently transmitted in hospitals and perinatal units. The MRSA is considered a public health problem in neonatology because of its strong potential for dissemination in the wards associated with high rates of morbidity and mortality. In this study we describe the bacteriological, epidemiological and molecular characteristics of MRSA isolated from anterior nares and blood cultures of newborns hospitalized in a public maternity hospital in the city of Rio de Janeiro, Brazil. The frequency of MRSA isolated from nasal swabs of newborns was 47.8 percent (43/90). The genetic analysis of MRSA strains from anterior nares, showed 8 different pulsed field gel electrophoresis patterns (PFGE). Upon analysis of PFGE patterns of the 12 MRSA strains isolated from blood cultures, 8 different patterns were observed, 9 (75 percent) strains were genetic related to nasal secretion isolates patterns. In conclusion, our data demonstrate the importance of screening of newborns for the presence of MRSA in Brazilian hospitals and the usefulness of genetic typing of these pathogen during epidemiologic studies. This should lead to a better knowledge on the significancy and spreading of MRSA in the hospitals

Molecular epidemiology of methicillin resistant Staphylococcus aureus isolated from newborns in a hospital in Rio de Janeiro, Brazil.

Methicillin resistant Staphylococcus aureus (MRSA) is an organism that is frequently transmitted in hospitals and perinatal units. The MRSA is considered a public health problem in neonatology because of its strong potential for dissemination in the wards associated with high rates of morbidity and mortality. In this study we describe the bacteriological, epidemiological and molecular characteristics of MRSA isolated from anterior nares and blood cultures of newborns hospitalized in a public maternity hospital in the city of Rio de Janeiro, Brazil. The frequency of MRSA isolated from nasal swabs of newborns was 47.8% (43/90). The genetic analysis of MRSA strains from anterior nares, showed 8 different pulsed field gel electrophoresis patterns (PFGE). Upon analysis of PFGE patterns of the 12 MRSA strains isolated from blood cultures, 8 different patterns were observed, 9 (75%) strains were genetic related to nasal secretion isolates patterns. In conclusion, our data demonstrate the importance of screening of newborns for the presence of MRSA in Brazilian hospitals and the usefulness of genetic typing of these pathogen during epidemiologic studies. This should lead to a better knowledge on the significancy and spreading of MRSA in the hospitals.

Epidemiological analysis of bacterial strains involved in hospital infection in a university hospital from Brazil.

Hospital infections cause an increase in morbidity and mortality of hospitalized patients with significant rise in hospital costs. The aim of this work was an epidemiological analysis of hospital infection cases occurred in a public University Hospital in Rio de Janeiro. Hence, 238 strains were isolated from 14 different clinical materials of 166 patients hospitalized in the period between August 1995 and July 1997. The average age of the patients was 33.4 years, 72.9% used antimicrobials before having a positive culture. The most common risk conditions were surgery (19.3%), positive HIV or AIDS (18.1%) and lung disease (16.9%). 24 different bacterial species were identified, S. aureus (21%) and P. aeruginosa (18.5%) were predominant. Among 50 S. aureus isolated strains 36% were classified as MRSA (Methicillin Resistant S. aureus). The Gram negative bacteria presented high resistance to aminoglycosides and cephalosporins. A diarrhea outbreak, detected in high-risk neonatology ward, was caused by Salmonella serovar Infantis strain, with high antimicrobial resistance and a plasmid of high molecular weight (98Mda) containing virulence genes and positive for R factor.

Mapping the gene causing hereditary primary hyperparathyroidism in a Portuguese kindred to chromosome 1q22-q31.

A Portuguese kindred with autosomal dominant isolated primary hyperparathyroidism (HPT) that was associated with parathyroid adenomas and carcinomas was investigated with the aim of determining the chromosomal location of this gene, designated HPTPort. Leukocyte DNA from 9 affected and 16 unaffected members and 7 parathyroid tumors from 4 patients was used in comparative genomic hybridization (CGH), tumor loss of heterozygosity (LOH), and family linkage studies. The CGH studies revealed abnormalities of chromosomes 1 and 13, and the results of LOH studies were consistent with the involvements of tumor suppressor genes from these regions. Family segregation studies mapped HPTPort to chromosome 1q22-q31 by establishing linkage with eight loci (D1S254, D1S222, D1S202, D1S238, D1S428, D1S2877, D1S422, and D1S412) (peak two-point LOD scores = 3. 46-5.14 at 0% recombination), and defined the location of HPT Port to a 21 cM region flanked centromerically by D1S215 and telomerically by D1S306. Thus, HPTPort has been mapped to chromosome 1q22-q31, and a characterization of this gene will help to elucidate further the mechanisms that are involved in the development of parathyroid tumors.

Spontaneously occurring anti-PTH autoantibodies must be considered in the differential diagnosis of patients with elevated serum PTH levels.

We investigated the cause of elevated immunoreactive circulating parathyroid hormone (PTH) levels in two females of 41 (case 1) and 39 (case 2) years of age with low/normal serum calcium levels and hypocalcemia, respectively, and, in the latter case, hyperprolactinemia. Serum samples from both patients were fractionated by Sephadex G-100 Superfine chromatography. Fractions were assayed for PTH and prolactin (PRL) by immunoradiometric assays (IRMA) and for immunoglobulin G (IgG) by radial immunodiffusion. Sera from both patients were incubated with protein A and protein G Sepharose, centrifugated and the supernatant was assayed for PTH by IRMA. Sera were also subjected to affinity chromatography with an anti-human-IgG-agarose column. IgG and PTH or PRL were measured in the fractions by radial immunodiffusion and IRMA, respectively. In both cases the majority of serum PTH immunoreactivity eluted in the same fractions of IgG after gel filtration and was precipitated by protein A (89% in patient 1 and 96% in patient 2) and protein G (83% in patient 1 and 100% in patient 2), thus, behaving as IgG. In case 1, 79% of PTH was also retained by an anti-hIgG agarose column. High PRL levels in patient 2 were due to macroprolactinemia since most of PRL eluted as big,big (40%) and big-PRL (45%) after gel filtration. Forty-eight percent of PRL from patient 2 was retained by the anti-hIgG column indicating the presence of an anti-PRL autoantibody. These data suggest that spontaneously occurring anti-PTH autoantibodies must be considered in the differential diagnosis of patients with elevated serum PTH levels.

Ceftazidime plus amikacin plus teicoplanin or vancomycin in the empirical antibiotic therapy in febrile neutropenic cancer patients.

A prospective randomized trial was performed to compare teicoplanin to vancomycin as part of the empirical antibiotic therapy of febrile neutropenic cancer patients. Fifty-three patients were randomized to receive ceftazidime (100 mg/kg daily every 8 h), amikacin (15 mg/kg daily every 8 h) and teicoplanin (6 mg/kg once a day) and 53 other patients received ceftazidime, amikacin (same dosages) and vancomycin (30 mg/kg/day every 6 h). In 99 evaluable episodes, the success rates were 54% for patients receiving teicoplanin and 52% for patients receiving vancomycin (p=0.76, 95% CI-18-23). The response rates were similar for patients with unexplained fever and for patients with documented infections. There were no differences in renal toxicity or cutaneous side effects between the two groups. The overall death rate was 18.9%, with 10 deaths in each group. The most important factor associated with death was the diagnosis of a fungal infection (p=0.001). Teicoplanin seems to be well tolerated and as effective as vancomycin in the empirical antibiotic therapy of fever in neutropenic cancer patients.

An unusual case of papillary carcinoma of the thyroid with cutaneous and breast metastases only.

Cutaneous metastases of thyroid carcinoma are infrequent and, when present, are usually located in the vicinity of a widespread primary tumor. Breast metastases from these tumors are even less common. We report the case of a 64-year-old female with a toxic multinodular goiter in whom a fine-needle biopsy, performed in 1985 at the age of 52, was suggestive of papillary carcinoma of the thyroid. Total thyroidectomy for a papillary carcinoma, follicular variant, was performed in 1988. Four months after surgery, a cutaneous metastasis was discovered in the right thigh. Surgical excision of the lesion followed by treatment with radioactive iodine decreased serum Tg levels from 7495 to 3.3 micrograms/l. Under suppressive therapy with L-thyroxine, serum Tg remained undetectable for the next 4 years. Then, serum Tg levels rose to 3.9-5.6 micrograms/l and a second cutaneous metastasis was removed from the abdominal wall. The patient was again treated with radioactive iodine and the post-treatment whole-body scan did not show any area of increased uptake of the radionuclide. However, serum Tg levels under suppression with L-thyroxine remained elevated at 4-20 micrograms/l for the next 2 years. In August 1995, a 1.5 cm nodule was found in the right breast. Cytological examination was suggestive of a breast metastasis from thyroid carcinoma and the lesion was removed by enucleation. This proved to be a metastasis from a papillary carcinoma of the thyroid. Elevated (19-44 micrograms/l) serum Tg levels persisted postoperatively. A third cutaneous metastasis was revealed by 131I scintigraphy in the right buttock and surgically removed in December 1996. Serum Tg levels have remained undetectable since then. To the best of our knowledge, this is a unique case of a papillary carcinoma of the thyroid with a propensity to metastasize only to the skin and breast during a follow-up of 11 years.

[The prevention of insulin-dependent diabetes mellitus]. / Prevenção da diabetes mellitus insulino-dependente.

At the present time, there are markers which we can use to identify individuals with a high susceptibility of developing insulin-dependent diabetes mellitus (IDDM) years before the onset of the disease. Insulin-dependent diabetes mellitus is an autoimmune disease strongly associated with HLA antigens DR3 and DR4. In this manuscript, we discuss the usefulness of several markers, such as islet cell antibodies, insulin autoantibodies and glutamic acid decarboxylase antibodies, to identify individuals with a high susceptibility to IDDM before the disease is clinically evident. Monitoring first phase insulin release during intravenous glucose administration is a useful index of residual beta cell function that can be used to detect individuals who are close to insulin dependence. Several drugs have been used to prevent the development of IDDM. These include immunodepressors, anti-inflammatory agents, non-specific immunomodulators and free radical scavengers. Due to their toxicity, studies employing aziothioprine and cyclosporin were discontinued. Other agents, such as tetrandrin and lymphotoxin, are now restricted to non-human trials. Currently, two large-scale multicentric human trials, one in Europe using nicotinamide (European Nicotinamide Diabetes Intervention Trial, ENDIT) and the other in the USA using insulin (Diabetes Prevention Trial), are now in full activity and will test the benefits of these drugs in the prophylaxis of IDDM in highly susceptible individuals.