Identification of a novel recurrent gain on 20q13 in chronic lymphocytic leukemia by array CGH and gene expression profiling.

BACKGROUND: The presence of genetic changes is a hallmark of chronic lymphocytic leukemia (CLL). The most common cytogenetic abnormalities with independent prognostic significance in CLL are 13q14, ATM and TP53 deletions and trisomy 12. However, CLL displays a great genetic and biological heterogeneity. The aim of this study was to analyze the genomic imbalances in CLL cytogenetic subsets from both genomic and gene expression perspectives to identify new recurrent alterations. PATIENTS AND METHODS: The genomic imbalances and expression levels of 67 patients were analyzed. The novel recurrent abnormalities detected with bacterial artificial chromosome array were confirmed by FISH and oligonucleotide microarrays. In all cases, gene expression profiling was assessed. RESULTS: Copy number alterations were identified in 75% of cases. Overall, the results confirmed FISH studies for the regions frequently involved in CLL and also defined a new recurrent gain on chromosome 20q13.12, in 19% (13/67) of the CLL patients. Oligonucleotide expression correlated with the regions of loss or gain of genomic material, suggesting that the changes in gene expression are related to alterations in copy number. CONCLUSION: Our study demonstrates the presence of a recurrent gain in 20q13.12 associated with overexpression of the genes located in this region, in CLL cytogenetic subgroups.

Pollination biology and the impact of floral display, pollen donors, and distyly on seed production in Arcytophyllum lavarum (Rubiaceae).

In animal-pollinated plants, two factors affecting pollen flow and seed production are changes in floral display and the availability of compatible mates. Changes in floral display may affect the number of pollinator visits and the availability of compatible mates will affect the probability of legitimate pollination and seed production. Distyly is a floral polymorphism where long-styled (pin) and short-styled (thrum) floral morphs occur among different individuals. Distylous plants frequently exhibit self and intra-morph incompatibility. Therefore changes in morph abundance directly affect the arrival of compatible pollen to the stigmas. Floral morph by itself may also affect female reproductive success because floral morphs may display differences in seed production. We explored the effects of floral display, availability of neighboring compatible mates, and floral morph on seed production in the distylous herb ARCYTOPHYLLUM LAVARUM. We found that floral display does not affect the mean number of seeds produced per flower. There is also no effect of the proportion of neighboring legitimate pollen donors on seed production in pin or thrum flowers. However, floral morphs differed in their female reproductive success and the thrum morph produced more seeds. Hand pollination experiments suggest that differences in seed production between morphs are the result of pollen limitation. Future research will elucidate if the higher seed production in thrum flowers is a consequence of higher availability of pollen donors in the population, or higher efficiency of the pin morph as pollen donor.

Clinical indicators for success of misoprostol treatment after early pregnancy failure.

OBJECTIVE: To identify clinical indicators for success of misoprostol treatment after early pregnancy failure. METHODS: A total of 473 women with early pregnancy failure received 800 microg of vaginal misoprostol on treatment day 1. At the follow-up visit on day 3, a second dose was given if expulsion was incomplete. On day 8, vacuum aspiration was offered if expulsion had not occurred. Ultrasonography was used as gold standard for success. A Classification and Regression Tree analysis was undertaken to derive two decision trees for the success of misoprostol treatment on study days 3 and 8. RESULTS: Heavy bleeding after the first dose and an open cervical os were identified as clinical indicators of treatment success on day 3. Treatment success occurred in 84% of women with either or both indicators. Reporting passage of tissue after a second misoprostol dose and old blood in the vagina were potential indicators of treatment success or failure on day 8. A woman with either of these indicators has a 65% chance of treatment success after the second dose. Conversely, a woman with neither indicator on day 8 has a 94% chance of treatment failure. CONCLUSION: Standard clinical findings may be useful as indicators for success or failure of medical management of early pregnancy failure in settings with limited or no access to ultrasonography. More research to identify even better indicators is warranted.

Maternal serum markers of lipid metabolism in relation to neonatal anthropometry.

OBJECTIVE: The objective of this study is to examine associations between lipids (high-density lipoprotein, low-density lipoprotein, total cholesterol, triglycerides and lipoprotein (a)) measured on average three time points during pregnancy and neonatal anthropometrics. STUDY DESIGN: Stored samples from a preeclampsia trial measured as part of a case-control study from five US centers (1992 to 1995) were used. The sample included women without pregnancy complications (n=136) and cases of gestational diabetes (n=93), abnormal glucose tolerance (AGT; n=76), gestational hypertension (n=170) and preeclampsia (n=177). Linear regression and linear mixed-effects models estimated adjusted associations between lipids and birth weight z-score, ponderal index (PI), length and head circumference. RESULTS: Among women without complications, cross-sectional associations between total cholesterol measured at different gestational ages increased PI 2.23 to 2.55 kg m-3 per-unit increase in cholesterol. HDL was inversely associated with birth length (ß's=-2.21 and -2.56 cm). For gestational hypertension, triglycerides were associated with birth weight z-score (ß's=0.24 to 0.31). For preeclampsia, HDL was associated with lower birth weight z-scores (ß's=-0.49 and -0.82). Women with gestational diabetes or AGT had inconsistent associations. Examining the level changes across pregnancy, each 0.0037 mmol l-1 increase in HDL was associated with decreased birth weight z-score (ß=-0.22), length (ß=-0.24 cm) and head circumference (ß=-0.24 cm), whereas each 0.028 mmol l-1 increase in triglycerides was associated with increased birth weight z-score (ß=0.13) and head circumference (ß=0.19 cm). CONCLUSIONS: Although associations varied by complications, in general, growth-promoting fuels such as total cholesterol and triglycerides were associated with increased neonatal size, whereas high HDL was associated with smaller size. Maternal HDL that failed to decrease over pregnancy was associated with smaller neonate size.

SLUG (SNAI2) overexpression in embryonic development.

The Snail-related zinc-finger transcription factor, SLUG (SNAI2), is critical for the normal development of neural crest-derived cells and loss-of-function SLUG mutations have been proven to cause piebaldism and Waardenburg syndrome type 2 in a dose-dependent fashion. However, little is known about the consequences of SLUG overexpression in embryonic development. We report SLUG duplication in a child with a unique de novo 8q11.2-->q13.3 duplication associated with tetralogy of Fallot, submucous cleft palate, renal anomalies, hypotonia and developmental delay. To investigate the effects of Slug overexpression on development, we analyzed mice carrying a Slug transgene. These mice were morphologically normal at birth, inferring that Slug overexpression is not sufficient to cause overt morphogenetic defects. In the adult mice, there was a 20% incidence of sudden death, cardiomegaly and cardiac failure associated with incipient mesenchymal tumorigenesis. These findings, while not directly implicating Slug in congenital and acquired heart disease, raise the possibility that Slug overexpression may contribute to specific cardiac phenotypes and cancer development.

Recomendaciones para manejo de pacientes con enfermedad hepática crónica y trasplantados hepáticos durante pandemia por COVID-19 / Recommendations for the management of patients with chronic liver disease and liver transplanted recipients during the COVID-19 pandemic

The SARS-CoV-2 virus and the associated disease COVID-19 has quickly become a pandemic. People with underlying chronic diseases or in an immunosupressed state are at risk of having a worse outcome. Cirrhotic patients and liver transplant recipients are considered to be in this higher risk group due to their immunosuppressed state. The aim of this article is to present recommendations based on expert opinion regarding the management of patients with compensated and decompensated liver pathologies who take medication for their immunosuppressed state in medical check-ups and basic treatment management both of patients with and without the COVID-19 disease.

El virus SARS-CoV-2 asociado a la enfermedad COVID-19, se han instalado a nivel de pandemia mundial. Las personas portadoras de enfermedades crónicas o estados de inmunosupresión se encuentran en riesgo de desarrollar un curso más grave. Se considera que los pacientes con cirrosis hepática, patología autoinmune o trasplante hepático se encontrarían dentro de este grupo de mayor riesgo por su estado de inmunosupresión. Presentamos recomendaciones de manejo basadas en opinión de experto, en pacientes con patología hepática compensada y descompensada e inmunosuprimidos farmacológicos, en relación a controles médicos y manejo de terapia de base tanto en pacientes sin COVID-19 como en pacientes infectados.

Incidence of non-Hodgkin's lymphoma in patients treated for Hodgkin's disease.

The purpose of this study was to evaluate the incidence of non-Hodgkin's lymphoma (NHL) as a second tumor in patients treated for Hodgkin's disease (HD), as well as to establish the role of different variables in its appearance. Between January 1973 and June 1988, 101 patients with HD were treated according to the stage, with chemotherapy and/or radiotherapy. Complete remission was obtained in 87 patients. Five patients developed secondary NHL between the 77th and 124th month of complete remission. The median follow up was 73 months (range 3-227 months). The incidence of second NHL in our series was, 0%, 4.6% (CI 0-11%) and 17% (CI 4-32%) at 5, 10 and 15 years respectively. Cox's stepwise regression analysis performed with all initial and treatment covariates (sex, age, splenectomy, histology, stage and treatment modality) showed that the only statistically significant variable was the treatment received (p < 0.01). Cumulative incidence of NHL at 15 years, ranged from 0% for patients treated with radiotherapy or chemotherapy alone to 39.6% for those who received combined therapy (p = 0.002). We can conclude that the use of chemotherapy plus radiotherapy for treatment of HD increases the risk for the development of second NHL.

[Prognostic value of the tissue expression of human chorionic gonadotropin (beta-HCG) in infiltrating transitional carcinoma of the bladder]. / Valor pronóstico de la expresión tisular de gonadotrofina coriónica humana (beta-HCG) en el carcinoma transicional infiltrante de vejiga.

Study of the ectopic secretion of Human Chorionic Gonadotrophin (beta-HCG) in the tumoral tissue of 62 patients diagnosed with infiltrant transitional carcinoma of the bladder. The inmunohistochemical tests showed specific stains in 15/62 patients. Bi-varied analysis showed that vesical tumours with beta-HCG ectopic expression present associated nodular disease with a significantly higher prevalence (p = 0.02). Survival of patients with beta-HCG+ tumours was overall lower that of patients with beta-HCG-tumours, but this difference did not reach statistical significance. Multivariate analysis of survival showed no prognostic value for the tissue expression of beta-HCG, when it is considered as an isolated variable. Complete local response was seen in 5/6 beta-HCG+ patients treated with pre-operative chemo and radiotherapy and in 1/4 patients treated with pre-operative radiotherapy. Tissular expression of beta-HCG is a poor prognostic factor due to its relationship with another 2 variables of larger predictive capability: the presence of metastatic nodular disease and the infiltration of venous and/or lymphatic structures of the vesical wall.

[Prognostic value of local vascular infiltration in infiltrating transitional carcinoma of the bladder]. / Valor pronóstico de la infiltración vascular local en el carcinoma transicional infiltrante de vejiga.

The present retrospective study analyzes the evolution and survival of 79 patients with bladder infiltrant transitional carcinoma (T2-T3), which were treated with radical cystectomy and bilateral ilio-obturating lymphadenectomy. Pre-operative radiotherapy (57/79) and neo-adjuvant chemotherapy (24/79) was used as supplementary therapy. The univariate analysis showed the relationship between tumour vascular infiltration (TVI) and presence of nodes micrometastasis (p = 0.002). The variables with greater forecast power in the multivariate analysis for survival were a decline in the post-radio and/or neo-adjuvant chemotherapy tumoral stage (p = 0.000) and TVI (p = 0.001). Survival decreased significantly in patients with TVI (p = 0.008), this finding denoting a worse prognosis than the presence of nodular micrometastasis (p = 0.01).

[Detection of latent tuberculosis infection in peritoneal dialysis patients: new methods]. / Detección de la infección tuberculosa latente en pacientes en diálisis peritoneal: Nuevos métodos.

OBJECTIVE: The risk for tuberculosis (TB) is increased in patients with chronic renal failure and dialysis. Tuberculin skin test (TST) is the classical diagnostic method for screening despite its low sensitivity. New methods based on interferon-gamma have been developed. The aim of this study was to evaluate if Quantiferon® TB-gold In Tube (QFT-GIT) could be useful in the diagnosis of TB infection in patients on peritoneal dialysis (PD). PATIENTS AND METHODS: Fifty-four patients on PD were included in the study. They were evaluated for latent tuberculosis with QFT-GIT, TST and an assessment by an expert pulmonologist using patient's medical history and x-rays. Agreement between test results was determined. RESULTS: The prevalence of a positive TST was 29.6% for the first test and 31.5% for the second (booster effect). A positive chest x-ray increased the rate of detection of patients with latent TB infection up to 42.6% and the expert physician's evaluation to 44.4%. The correlation between QFT-GIT and TST was fair (k=0.36; P=.006), as it was between TST and expert physician's evaluation (k=0.257; P=.06). CONCLUSIONS: According to our experience QFT-GIT represents an important advantage in the diagnosis of latent TB infection in chronic renal failure patients on PD. It may complement but not replace TST.

Elevated serum gamma-glutamyltransferase and hypomagnesemia are not related with new-onset diabetes after transplantation.

BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT) contributes to the risk of cardiovascular disease (CVD) and infection, reducing graft and patient survival in kidney transplant recipients. To reduce CVD and improve outcomes of kidney transplant recipients, it is of great interest to more precisely elucidate the risk factors that contribute to the development of NODAT. A previous study reported that hypomagnesemia is an independent predictor of NODAT. Elevated gamma-glutamyltransferase (GGT) activity increases the risk of incident type 2 diabetes in the general population. The objective of this study was to determine whether magnesium (Mg) and GGT were risk factors for NODAT among our population of kidney transplant recipients. METHODS: We retrospectively analyzed 205 non-previously diabetic kidney transplant recipients. GGT was measured before transplantation as well as at months 1, 2, and 12. Mg was measured at months 1, 2, and 12. NODAT was defined at month 12 and at the end of follow-up according to the "2003 international consensus guidelines." RESULTS: Although 36 patients (17.5%) developed NODAT at month 12, 55 patients (26.8%) displayed it at the end of follow-up. We did not observe any significant difference, either in mean Mg (month 1, 1.73±0.24 vs 1.75±0.30 [P=.824]; month 2, 1.71±0.22 vs 1.68±0.26 [P=.565]; month 12, 1.77±0.27 vs 1.80±0.24 [P=.596]) or GGT values (pretransplantation, 32 ± 27 vs 33±85 [P=.866]; month 1:39±24 vs 48±70 [P=.452]; month 2, 53±96 vs 48±83 [P=.739]; month 12, 40±37 vs 38±53 [P=.830]) between NODAT and non-NODAT patients at month 12 or at the end of follow-up. CONCLUSION: Hypomagnesemia and high GGT activity were not risk factors for NODAT development in kidney transplant recipients.

Both expanded and uncultured mesenchymal stem cells from MDS patients are genomically abnormal, showing a specific genetic profile for the 5q- syndrome.

The presence of cytogenetic aberrations on mesenchymal stem cells (MSC) from myelodysplastic syndrome (MDS) patients is controversial. The aim of the study is to characterize bone marrow (BM) derived MSC from patients with MDS using: kinetic studies, immunophenotyping, fluorescent in situ hybridization (FISH) and genetic changes by array-based comparative genomic hybridization (array-CGH). In all 36 cases of untreated MDS were studied. MDS-MSC achieved confluence at a significantly slower rate than donor-MSC, and the antigenic expression of CD105 and CD104 was lower. Array-CGH studies showed DNA genomic changes that were proved not to be somatic. These results were confirmed by FISH. To confirm that genomic changes were also present in freshly obtained MSCs they were enriched by sorting BM cells with the following phenotype: CD45(-)/CD73(++)/CD34(-)/CD271(++). They also showed genomic changes that were confirmed by FISH. To analyze the relationship of these aberrations with clinical-biological data an unsupervised hierarchical cluster analysis was performed, two clusters were identified: the first one included the 5q- syndrome patients, whereas the other incorporated other MDS. Our results show, for the first time that MSC from MDS display genomic aberrations, assessed by array-CGH and FISH, some of them specially linked to a particular MDS subtype, the 5q- syndrome.

Detección de la infección tuberculosa latente en pacientes en diálisis peritoneal: Nuevos métodos / Detection of latent tuberculosis infection in peritoneal dialysis patients: new methods

Introducción: El riesgo de tuberculosis (TB) está aumentado en pacientes con insuficiencia renal crónica y en diálisis. La prueba de la tuberculina (PT) es el test de cribado clásico en estos pacientes, a pesar de su baja sensibilidad. En los últimos años se han desarrollado nuevos métodos diagnósticos que se basan en la producción de interferón gamma tras la estimulación con antígenos de M. tuberculosis. El objetivo de este estudio fue evaluar si el Quantiferon® TB–gold In Tube (QFT–GIT) puede contribuir en el diagnóstico de la infección tuberculosa en pacientes en diálisis peritoneal (DP). Pacientes y métodos: Se incluyeron 54 pacientes en DP. Se valoró la posibilidad de infección tuberculosa latente mediante el QFT–GIT, la PT y la valoración clinicorradiológica por parte de un neumólogo experto. Se estudiaron las concordancias entre los tests. Resultados: La prevalencia de un resultado positivo para el test de la tuberculina fue del 29,6% para el primer test y del 31,5% para el segundo (valorando el efecto booster). Una radiografía de tórax positiva aumentaba la detección de infección tuberculosa latente hasta un 42,6% y la del neumólogo hasta un 44,4%. El nivel de correlación entre el QFT–GIT y la PT fue moderado (kappa = 0,36; p = 0,006), al igual que entre la PT y la valoración del neumólogo (kappa = 0,257, p = 0,06). Conclusiones: El QFT–GIT aporta algunas ventajas en el diagnóstico de la infección tuberculosa en pacientes con insuficiencia renal crónica en DP, y puede complementar a la prueba de la tuberculina (AU)

Objective: The risk for tuberculosis (TB) is increased in patients with chronic renal failure and dialysis. Tuberculin skin test (TST) is the classical diagnostic method for screening despite its low sensitivity. New methods based on interferon–gamma have been developed. The aim of this study was to evaluate if Quantiferon® TB–gold In Tube (QFT–GIT) could be useful in the diagnosis of TB infection in patients on peritoneal dialysis (PD). Patients and methods: Fifty–four patients on PD were included in the study. They were evaluated for latent tuberculosis with QFT–GIT, TST and an assessment by an expert pulmonologist using patient's medical history and x–rays. Agreement between test results was determined. Results: The prevalence of a positive TST was 29.6% for the first test and 31.5% for the second (booster effect). A positive chest x–ray increased the rate of detection of patients with latent TB infection up to 42.6% and the expert physician's evaluation to 44.4%. The correlation between QFT–GIT and TST was fair (ê=0.36; P=.006), as it was between TST and expert physician's evaluation (ê=0.257; P=.06). Conclusions: According to our experience QFT–GIT represents an important advantage in the diagnosis of latent TB infection in chronic renal failure patients on PD. It may complement but not replace TST (AU)

Renal siderosis in patients with heart-valve prostheses: clinical implications.

We have studied the clinical and morphological implications of renal siderosis, reviewing the autopsy protocols of 33 patients with valve prostheses in the heart. Seventeen patients had variable amounts of iron in the proximal tubules of the kidney. Renal siderosis was more frequent in women, in patients with longest time of evolution from the surgical procedure, and in patients with two valve prostheses. Histologically three degrees of renal siderosis may be defined: mild and moderate degrees of iron overload do not alter the kidney architecture, but kidneys, with severe siderosis show tubular atrophy and interstitial fibrosis. Episodes of acute renal failure (ARF) were more frequent in patients with more pronounced iron deposits, especially in the premortem stages. We conclude that renal siderosis may damage the proximal tubular epithelium of patients with valve prostheses in the heart; patients with renal overload of iron are more susceptible to episodes of ARF.

Chondroid metaplasia in the tunica media of the aorta in dogs submitted to saphenous vein aorto-cava by-pass.

We submitted twelve dogs to aorto-superior vena cava by-pass with saphenous vein. Six months later, all dogs had developed areas of chondroid metaplasia in the tunica media of the aorta, near the area of anastomosis. Three dogs also had bony metaplasia. The Foci of metaplasia had no relation to sutures. This lesion begins with a build-up store of glycosaminoglycans in the tunica media. Later, elastic fibers show a fenestration and dissolution, while chondrocytes replace smooth muscle fibres. We suggest that the rupture of the vasa vasorum during operation and the traction and pulsation of the by-pass over the area of suture could be the cause of this direct metaplasia.

Patterns of medical employment: a survey of imbalances in urban Mexico.

This article quantifies the magnitude and correlates of the major imbalances affecting the employment of physicians in the urban areas of Mexico. Since the early 1970s the country has experienced a rapid increase in the supply of doctors, which its health system was unable to absorb fully. In 1986, we conducted a survey in the 16 most important cities based on a probability sample of households where someone with an MD degree lived. A total of 604 physicians were interviewed for a response rate of 97 percent. The unemployment rate was 7 percent of potentially active physicians; 11 percent held a nonmedical job, and another 11 percent exhibited low productivity and/or income. All in all, we project that 23,500 physicians in these cities were either unemployed or underemployed. This medical employment pattern was analyzed against five independent variables: generation (i.e. the year in which the physician started medical school), gender, social origin, medical school quality, and specialty. Apart from generation, type of specialty exhibited the strongest correlation with the employment situation of a physician. The results suggest that higher education and health care in Mexico may be producing rather than correcting social inequalities. Policy alternatives are discussed to restore a balance between the training of physicians, their gainful employment, and the health needs of the population.

Single daily dose amikacin in paediatric patients with severe gram-negative infections.

Twenty-five children with serious Gram-negative infections were treated in a prospective study with amikacin 20 mg/kg administered in a single daily dose as a 30 min iv infusion for 4 to 12 days. In nine cases the amikacin was combined with beta-lactam antibiotics. Escherichia coli were the most frequent bacteria isolated followed by K. pneumoniae, Providencia and Enterobacter spp. and Pseudomonas aeruginosa with MICs ranging from 1 to 16 mg/l. Mean (+/- S.D.) peak and trough concentrations of days 1 and 4 of therapy ranged from 49 +/- 13.5 to 53.6 +/- 13.4 mg/l and 6 + 1.4 to 7.7 +/- 4.1 mg/l respectively. All patients were clinically and bacteriologically cured. No significant adverse reactions were observed. The results suggest that administration of a single daily dose of 20 mg/kg amikacin should be considered practical and safe in children. Further studies are needed.