Immunological alterations induced by polyamine derivatives on murine splenocytes and human mononuclear cells

Three polyamine derivatives assigned as bis-naphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd) and spermine (BNIPSpm) were studied to determine their effects on the proliferation of murine splenocytes and human peripheral blood mononuclear cells (PBMC) induced by the mitogens, Con A, LPS and PHA. All compounds showed a dose dependent inhibitory effect on mouse and human T cell proliferation induced by the mitogens, with BNIPPut exhibiting the most potent antiproliferative activity, followed by BNIPSpd and by BNIPSpm, respectively (Put > Spd > Spm), when considering human T cells. This suppressive activity also affects the capacity of mouse spleen cells to produce Th1 cytokines, namely IL-2 and INF-gamma after in vitro stimulation with Con A. The polyamine-induced inhibition also occurred in the case of LPS-stimulated B cells with a marked decrease of CD69 expression by these cells. Furthermore, the ability for these polyamine derivatives to induce apoptosis on Con A-stimulated splenocytes could be related to their antiproliferative activity.     

Effect of the hypothyroidism-castration association on bone and parathyroids from adult female rats

The effect of hypothyroidism on bone metabolism and the parathyroids in states of deficiency or sufficiency of sex steroids was studied in 32 two-months-old female Wistar rats distributed in 4 groups of 8 animals each: intact euthyroid (IE), castrated euthyroid (CE), intact hypothyroid (IH) and castrated hypothyroid (CH). After 120 days of treatment, animals were sacrificed and plasma taken to assess free T4. Hyperplasia or hypertrophy of all parathyroids were evident only in IH and CE groups. Of all groups, IH rats presented the most extensive osteopenia, reaching lumbar vertebrae, dental alveolae (jaw and mandible) and long bones. In this group osteopenia resulted from the reduced bone growth, inhibition of bone apposition and return of bone resorption. Although osteopenia in the CH group was almost always more intense in relation to osteopenia presented by CE rats, its intensity was variable when compared to IH rats and dependent on the region studied. Even though it also caused necrosis of higher metabolism bones, the association hypothyroidism-castration did not potentialize the resultant osteopenia of the isolated action of hypothyroidism or castration until 120 days of treatment.     

Blinded review as a method for quality improvement in surgical pathology

CONTEXT: Several studies have shown that blinded review, because it is less biased and may improve vigilance, is an excellent method for detecting errors and improving performance in gynecologic cytology. The value of blinded review in surgical pathology is not known. OBJECTIVE: To determine the value of blinded review in surgical pathology. METHODS: Five hundred ninety-two biopsy cases were reviewed without knowledge of the original diagnosis or history, and the results were compared with those of the original diagnosis. RESULTS: Complete agreement was obtained in 567 (96%) of 592 cases. The technique of blinded review of biopsy material had a sensitivity of 98%, failing to identify a lesion in 7 cases; no cases of malignancy were missed. The specificity was 100%. Differences in diagnostic threshold were the most common source of disagreement. False-negative cases were identified by the technique and were clinically significant. Power studies show that the number of cases requiring review to identify significant errors are large, but potentially achievable by blinded review. CONCLUSION: Blinded review is a sensitive and effective method for identifying areas of disagreement, including false-negative cases, and for decreasing errors in surgical pathology biopsy material.     

Associations between migrancy, health and homelessness: a cross-sectional study

There is limited awareness of the link between differing health problems and migrancy of homeless people. The present cross-sectional study sought to quantify the extent of migrancy of homeless people from their place of birth (PLOB) and evaluate whether a history of problematic drug use, alcohol misuse or enduring mental health problems were associated with migrancy from their PLOB. The work was conducted at an inner-city health centre for the homeless in the north of England. Place of birth was created as an entry on the computerised registration records. The PLOB was collected and recorded for each homeless person registering with the service over the study period. Information was also extracted regarding diagnoses of problematic illicit drug use, problematic alcohol use and enduring mental health problems for each homeless person. The study identified statistically significant differences for the migration of homeless people from their PLOB for age, problematic drug use and problematic alcohol use. Problematic alcohol use is independently associated with an increased likelihood of migration from the PLOB. Conversely, a history of illicit drug use is associated with a reduced possibility of migration from the PLOB when accessing primary healthcare services. There was no significant difference for migration from the PLOB for mental health. Not all homeless people migrate from their PLOB and health problems of drug use, mental health or alcohol use are independently associated with different patterns of migration. Understanding the migrancy of homeless people is important when planning and targeting appropriate health and social services to address their varying health, social and psychological needs.     

Multicentric study of Brazilian patients with 21-hydroxylase deficiency: a genotype-phenotype correlation

We analyzed the clinical and molecular data of 205 patients with the three different clinical forms of 21-hydroxylase deficiency, in whom the clinical and molecular diagnosis were already defined. The most frequent mutations were I2 splice in the salt wasting form, I172N in the simple virilizing and V281L in the nonclassical form, presenting similar frequencies as those observed in other populations. We found a lower frequency of 21-hydroxylase gene deletion, similar to that previously identified in Argentinean and Mexican populations. Five new mutations were described in our population: G424S, H28+C, Ins 1003 1004 A, R408C and IVS2-2A>G. The genotype was classified in three groups according to the impairment of enzymatic activity observed in vitro, Group A: 0-2%, Group B: 3-7% and Group C: >20%. Group A mutations correlated with the salt wasting form, the Group B with simple virilizing form and Group C with the non classical form. The severity of genotype showed a positive correlation with higher 17OH-progesterone and testosterone levels. The I2 splice mutation in homo or hemizygosis confers classical form phenotype with both salt wasting and simple virilizing forms, precluding the prediction of the clinical form through genotype in pre and neonatal diagnosis. The good genotype-phenotype correlation in patients with 21-hydroxylase deficiency shows the usefulness of genotype to predict the clinical form for genetic counseling, prenatal diagnosis and to confirm neonatal screening diagnosis, except in cases with I2 splice mutation.     

Imaging of acute myocardial infarction in pigs with Indium-111 monoclonal antimyosin scintigraphy and MRI

Indium-111 antimyosin F(ab')2 was used in a series of scintigraphic studies on experimentally induced myocardial infarctions in pigs. Antimyosin distribution recorded by planar images of in vivo pigs and by single photon emission computed tomography (SPECT) of excised hearts delineated areas of myocardial necrosis if infarct volume exceeded 3.3 cm3. Scintigraphic images were compared with magnetic resonance images (MRI) obtained from excised hearts and with photographs of slices of the hearts. Infarct size and localization determined with antimyosin were compared. The MR images, with or without gadolinium-DTPA (Gd-DTPA), of the in vivo pigs were all false-negative; some myocardial wall thinning and high bloodpool signals were visible. Results show that both the antimyosin and the MR technique are specific methods for the visualization of induced myocardial necrosis in this animal model. However, the use of antimyosin is limited to a period ranging from 24 to 72 hours after infarction.     

Predictive value of common genetic variants in idiopathic pulmonary fibrosis survival

Journal of Molecular Medicine - Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown etiology. The role of genetic risk factors has been the...