Identification of 26 new constitutional RB1 gene mutations in Spanish, Colombian, and Cuban retinoblastoma patients

Constitutional mutations in the RB1 gene predispose to retinoblastoma development. Hence genetic screening of retinoblastoma patients and relatives is important for genetic counseling purposes. In addition, RB1 gene mutation studies may help decipher the molecular mechanisms leading to tumors with different degrees of penetrance or expressivity. In the course of genetically screening of 107 hereditary and non-hereditary retinoblastoma patients (11 familiar bilateral, 4 familiar unilateral, 49 sporadic bilateral and 43 sporadic unilateral) and kindred from Spain, Colombia and Cuba, using direct PCR sequencing, we observed 45 distinct mutations and four RB1 deletions in 53 patients (9 familiar bilateral, 2 familiar unilateral, 31 sporadic bilateral and 11 sporadic unilateral). Most of these mutations (26/45, 57%) have not been reported before. In 32 patients, the predisposing mutations correspond to nonsense (mainly CpG transitions) and small insertions or deletions whose expected outcome is a truncated Rb protein that lacks the functional pockets and tail. Five single aminoacid replacements and seventeen mutations affecting splicing sites were also observed in retinoblastoma patients. Two of these sixteen mutations are of unclear pathogenic nature.     

Stereologic study of the cerebellar Purkinje cells submitted to alcoholic intoxication in Wistar rats

BACKGROUND: to analyze the effect of the alcohol on the cells of Purkinje. METHOD: Wistar rats received alcoholic solutions orally in different concentrations 4%, 12% and 24%. The animals were sacrificed with 4, 8 and 12 weeks and the cerebella were randomly cut and embedded in paraffin. Sections of 6 micrometer (H&E) were stereologically analyzed. RESULTS: The differences among the density for area and density of surface of the cells of Purkinje of all of the experimental groups (E) and the respective controls (C) were significant. With 12 weeks the cell of Purkinje volume density decreased among the groups C and E in the concentrations of 4% and 12%, but not for the concentration of 24%, probably due to smaller liquid ingestion by the animals. CONCLUSION: The alcohol has toxic effect on the Purkinje cellular body in the three studied concentrations from 4 weeks.     

Identification of sentinel lymph node in stage I-II breast cancer with lymphoscintigraphy and surgical gamma probe: comparison of Tc-99m MIBI and Tc-99m sulfur colloid

AIM: To evaluate the efficacy of the surgical gamma probe (SGP) after peritumoral injection of Tc-99m MIBI and filtered Tc-99m sulfur colloid (SC) in sentinel lymph node (SLN) detection in stage I and II breast cancer for deciding on the need for axillary dissection. MATERIALS AND METHODS: Thirty patients with stage I-II breast cancer had peritumoral injection of Tc-99m MIBI (74 MBq/0.2 mL [2 mCi/0.2 mL] at 4 different locations) and 42 different patients had peritumoral injection of filtered Tc-99m sulfur colloid (50 MBq/0.2 mL [1.3 mCi/0.2 mL] at 4 different locations). Anterior, lateral, and anterolateral spot images were acquired at 10, 30, 45, 60, and 120 minutes and 24 hours are injection in 5 patients. During surgery, counts were obtained from the injection site, affected breast tissue, internal mammary, axillary, and supraclavicular regions and the contralateral side using the gamma probe. Peritumoral blue dye was also injected during surgery. The first lymph nodes with counts at least twice the background tissue and/or with blue dye uptake were surgically isolated. Modified radical mastectomy and axillary dissection were performed. RESULTS: Histopathologic evaluation was made on SLN and other excised tissues. In the Tc-99m sulfur colloid group, lymphatic drainage and lymph nodes were demonstrated with lymphoscintigraphy in 31 of 42 patients. SLN was detected by SGP in 35 of 42 patients. In the Tc-99m MIBI group, lymphatic drainage and lymph nodes were visualized with lymphoscintigraphy in 23 of 30 patients. SLN was detected in 25 of 30 patients with SGP in this group. CONCLUSION: In patients with stage I-II breast cancer, SLN could be successfully demonstrated with lymphoscintigraphy and SGP by the peritumoral injection of filtered Tc-99m sulfur colloid and Tc-99m MIBI.     

Effect of tenoxicam on fracture healing in rat tibiae

BACKGROUND: Nonsteroidal anti-inflammatory drugs have been implicated in the development of delayed unions and nonunion after fractures in animal models. Previous investigations have identified two important factors as determinants of delayed fracture healing: early drug administration and a dose-dependent effect. OBJECTIVE: The purpose of this investigation was to study the effect of tenoxicam, a nonsteroidal anti-inflammatory drug, on the fracture healing process in rat tibiae. METHODS: Fifty-eight Wistar rats were randomly divided in four groups (I, II, III, and IV). Group I (control group, n=12) was given 0.1ml saline solution per day intramuscularly. Groups II (n=12), III (n=12), and IV (n=12) were administered 10mg per kg per day of tenoxicam intramuscularly. Administration of substances was begun on a week before to 48h after the fracturing procedure and continued during the entire experiment. Callus formation was studied histologically and histomorphologically, using light microscopy. In addition, a histologic grading based on the morphologic stage of fracture healing was carried out at 4 weeks, according to the criteria proposed by Allen et al. RESULTS: There was a significant difference in treatment effect between Group I (saline solution) and Groups II, III, and IV (tenoxicam) (P=0.07). Histologically and histomorphologically, there were qualitative and quantitative delay in callus formation at all tenoxicam groups. This was more pronounced the earlier the nonsteroidal anti-inflammatory drug was started, although no significant difference could be detected between Groups II, III, and IV (P>(alpha=10%)). Four weeks after fracture, Group I (n=3) showed complete osseous union, Groups II (n=3) and III (n=3), complete cartilaginous union, and Group IV (n=3), incomplete osseous union, according to Allen et al. By using this rating scale, the difference between control and drug-treated groups was statistically significant (P<0.1). CONCLUSION: Under studied conditions, this investigation shows that administration of tenoxicam intramuscularly delays fracture healing process in rat tibiae. These results suggest the hypothesis that early drug administration may delay bone healing after experimental fractures in animals, although it could not be detected statistically significant.     

Histopathological analysis of the posterior cruciate ligament in primary osteoarthritis

European Journal of Orthopaedic Surgery & Traumatology - According to some authors, the indication of an arthroplasty maintaining the posterior cruciate ligament (PCL) demands adequate...     

A rare cause of recurrent gastrointestinal bleeding: mesenteric hemangioma

We describe a case of life-threatening small bowel haemorrhage in a 56 year old man, who was found to have partial midgut malrotation at laparotomy. An association between congenital malrotation and gastrointestinal haemorrhage has not previously been reported in this age group. We discuss the association between gut malrotation and small intestinal pathology and describe the principles of management in these patients.     

Early onset proteinuria after renal transplantation: a marker for allograft dysfunction

The objective of this study was to determine whether early proteinuria after renal transplantation affected long-term allograft survival. The 130 patients included 105 men and 25 women of overall mean age, 29.6 +/- 9.6 years. There were 105 living related and, 25 cadaveric donor transplants. Proteinuria was defined as a level in of more than 300 mg/d. Donor and recipient age at transplantation, duration of pretransplant dialysis, donor type (living related or cadaveric), the presence of delayed graft function or acute rejection, panel-reactive antibodies, the number of human leukocyte antigen mismatches, and the systolic blood pressure level were retrospectively recorded for the study subjects. Cox regression analysis was used to determine the effects of proteinuria on allograft survival. Patients with proteinuria demonstrated significantly lower graft survival rates than did those without proteinuria (54.17% vs 82.62%, respectively; P<.002). Proteinuria at the third month after transplantation (P<.004, odds ratio [OR]=3.26, confidence interval [CI]=1.46 to 7.29), donor age (P<.001, OR=1.06, CI=1.02 to 109), and panel-reactive antibodies (P<.041, OR=1.06, CI=1.00 to 1.12) were significantly associated with decreased allograft survival. Early proteinuria after renal transplantation was indicative of a high risk for allograft dysfunction. A reduction of proteinuria may be associated with improved graft survival.     

Posttransplant Proteinuria Is Associated With Higher Risk of Cardiovascular Disease and Graft Failure in Renal Transplant Patients

In this study, we sought to determine whether proteinuria after renal transplantation was associated with cardiovascular disease (CVD), patient survival, and long-term allograft survival. One hundred twenty-six patients included 102 males and 24 females of mean age 30.7 ± 8.9 years. Their mean follow-up was 63.21 ± 19.9 months. All patients were evaluated for CVD, namely, ischemic heart disease, cerebrovascular disease, and peripheral vascular disease. Proteinuria was defined as urinary protein ≥500 mg/d which persisted for >6 months after transplantation. We retrospectively examined pre- and posttransplant data, including sex, age at transplantation, smoking, pretransplant dialysis duration, donor status, number of acute rejection episodes, body mass index, systolic and diastolic blood pressure levels, lipid profile and other biochemical parameters, immunosuppressive regimens, as well as pulse steroid dose. Proteinuria was significantly associated with CVD (P = .001; RR = 6.43; confidence interval [CI] 2.15-19.22). Patients with proteinuria showed significantly lower graft survival rates than those without proteinuria (58.62% vs 80.41%; P = .02). The mean time to appearance of proteinuria was 14.1 ± 11.4 months (range, 1-36 months). There was no significant association between proteinuria and patient survival. Patients with persistent proteinuria displayed a greater number of acute rejection episodes (1.20 ± 1.17 vs 0.62 ± 0.85; P = .004) and higher pulse steroid dosages (4380.0 ± 3123.4 vs 2800.0 ± 2766.7; P = .022). In conclusion, persistent proteinuria is a strong risk factor for CVD among renal transplant patients. Therefore, an etiologic search and antiproteinuric strategy should be considered routinely to improve patient and graft outcomes.