Primary vertebral echinococcosis: four cases reports and review of literature

Primary vertebral echinococcosis has been considered to be a hypothetical and exceptional possibility. It affects bones in 1% of reported cases. Spine is involved in 45-50% of these. The disease preferentially affects the thoracic spine. It begins as a single primary cyst containing daughter cysts. We report four cases of primary vertebral echinococcosis, extending into the extradural space without any other primary site of infection. We conclude that primary vertebral echinococcosis, although rare should be considered in destructive lesions of the vertebrae and spine in regions that the disease is endemic. Advanced imaging studies should be performed to diagnose the disease. Early decompressive surgery of the spine, with chemotherapy, is the treatment of choice for these patients.     

Posttraumatic meningitis: incidence, bacteriology, and outcomes

BACKGROUND AND PURPOSE: The aim of our study was to search for the incidence, the responsible organisms and the favoring causes of death of post-traumatic meningitis (PTM). METHODS: This retrospective study was conducted over a seven-year period (January 1st, 1996 - December 31, 2002) in the ICU and the neurosurgery department of the Habib-Bourguiba University Hospital, Sfax, Tunisia. RESULTS: Over the study period, 38 patients presented PTM (0.96% of patients hospitalized for head injury), 92% of them had received antibiotic prophylaxis on admission. Mean time between head injury and the diagnosis of PTM was 9+/- 8 days (range: 2-34 days). The most common isolated organisms were multidrug resistant A. baumanii, and K. pneumoniae and reduced susceptibility S. pneumoniae. Factors predictive of prognosis in the 14 days following the diagnosis of meningitis were Glasgow coma score (GCS) on the day of diagnosis of PTM, absence of nuchal rigidity, CSF protein, CSF/blood glucose ratio, and S. pneumoniae as the causal agent of PTM. CONCLUSIONS: Antibioprophylaxis in patients with head trauma must be avoided to prevent the emergence of multidrug resistant bacteria when PTM occurs. GCS on the day of diagnosis of PTM, CSF protein concentration, CSF/blood glucose ratio, and S. pneumoniae as the causal agent of PTM are predictive factors of mortality of patients with PTM.     

Zur Ultrastruktur des peripheren vegetativen Nervensystems

Ohne ZusammenfassungMit 4 Textabbildungen     

P73 functionally replaces p53 in Adriamycin-treated, p53-deficient breast cancer cells

p53-Related genes, p73 and p63, encode 2 classes of proteins, TA-p73/p63 and DeltaN-p73/p63. TA-p73/p63 demonstrate p53-like properties including gene transactivation and cell death promotion, whereas DeltaN-p73/p63 lack these p53-like functions. Although p53-deficient cancer cells are often less responsive to chemotherapy, they are not completely drug resistant, suggesting that other apoptotic pathways are at work. Here, we compared for the first time to our knowledge p73 and p63 activation in various breast cancer (BC) cell lines after Adriamycin (ADR) treatment, an agent considered as mandatory in breast cancer chemotherapy. Our study was carried out using 1 p53-proficient BC cell line (MCF7 cells) and 3 BC cell lines deficient in p53 response (MCF7/ADR(IGR), MDA-MB157 and T47D) after ADR-induced genotoxic stress. We report that in cells with no p53 response after ADR treatment, TAp73, but not TAp63 or DeltaN-p73/p63, may replace p53 in triggering not only apoptosis but also cell cycle arrest or DNA repair effectors such as p21, GADD45, 14-3-3sigma and p53R2. We also demonstrate that TAp73 siRNA inhibits the accumulation of TAp73 in response to ADR treatment in MDA-MB157 cells and confers protection against ADR. ADR-induced downregulation of the DeltaNp73 isoform in the T47D cell line with nonfunctional mutant p53 further supports anti-apoptotic function of the isoform antagonistic to both p53 and TA-p73/p63. Exogenous TAp73 and DeltaNp73 overexpression in p53-response-deficient cell lines further confirms these results. cDNA microarray techniques demonstrated that the cellular response induced by p73 during ADR treatment could involve specific genes.     

Protective effect of cactus cladode extract against cisplatin induced oxidative stress, genotoxicity and apoptosis in balb/c mice: combination with phytochemical composition

ABSTRACT: BACKGROUND: Cis-Platinum(II) (cis-diammine dichloroplatinum;CDDP) is a potent antitumor compound widely used for the treatment of many malignancies. An important side-effect of CDDP is nephrotoxicity. The cytotoxic action of this drug is often thought to induce oxidative stress and be associated with its ability to bind DNA to form CDDP-DNA adducts and apoptosis in kidney cells. In this study, the protective effect of cactus cladode extract (CCE) against CDDP-induced oxidative stress and genotoxicity were investigated in mice. We also looked for levels of malondialdehyde (MDA), catalase activity, superoxide dismutase activity (SOD), chromosome aberrations (CA) test, SOS Chromotest, expressions of p53, bax and bcl2 in kidney and we also analyzed several parameters of renal function markers toxicity such as serum biochemical analysis. METHODS: Adult, healthy balbC (20-25 g) male mice aged of 4-5 weeks were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 100 mug/Kg.b.w CDDP. Animals which treated by CDDP and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with CDDP 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with CDDP 3 days a week for 4 weeks. RESULTS: Our results showed that CDDP induced significant alterations in all tested oxidative stress markers. In addition it induces CA in bone morrow cells, increase the expression of pro-apoptotic proteins p53 and bax and decrease the expression of anti-apoptotic protein bcl2 in kidney cells. On the other hand, CDDP significantly increased the levels of urea and creatinine and decreased the levels of albumin and total protein. The treatment of CCE before or after treatment with CDDP showed, (i) a total reduction of CDDP induced oxidative damage for all tested markers, (ii) an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations compared to the group treated with CDDP alone (iii) restriction of the effect of CDDP by differential modulation of the expression of p53 which is decreased as well as its associated genes such as bax and bcl2, (iiii) restriction of serums levels of creatinine, urea, albumin and total protein resuming its values towards near normal levels of control. CONCLUSION: We concluded that CCE is beneficial in CDDP-induced kidney dysfunction in mice via its anti-oxidant and anti-genotoxic properties against CDDP.     

Prolactin and autoimmunity

Sex hormones, especially estrogen and prolactin (PRL), have an important role in modulating the immune response. PRL is secreted from the pituitary gland as well as other organs and cells particularly lymphocytes. PRL has an immune stimulatory effect and promotes autoimmunity. PRL interferes specifically with B cell tolerance induction, enhances proliferative response to antigens and mitogens and increases the production of immune globulins, cytokines and autoantibodies. Hyperprolactinemia (HPRL) in women present with clinical manifestations of galactorrhea, primary or secondary amenorrhea, delayed menarche or a change in the menses either in the amount or in the regularity. Furthermore in the last 2 decades multi-organ and organ specific autoimmune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), Hashimoto's thyroiditis (HT), multiple sclerosis (MS), psoriasis, hepatitis C patients, Beh?et's disease, peripartum cardiomyopathy (PPCM) and active celiac disease were discussed to be associated with HPRL. There is data showing correlation between PRL level and diseases activity in few diseases. Genetic factors may have a role in humans as in animal models. The PRL isoforms based on the differences in the amino acid sequence and size of the cytoplasmic domain have an important effect on the bioactivity on prolactin receptors (PRL-Rs).     

Does kidney transplantation with multiple arteries affect graft survival?

Introduction

We compared short- and long-term outcomes of renal transplants with single versus multiple arteries.

Patients and methods

We retrospectively analyzed data from kidney transplants from 208 living donors performed between 1994 and 2010. Renal grafts were divided into two groups: single renal artery (n = 164) versus multiple renal arteries (n = 44). The groups were compared regarding early and late vascular and urological complications. Patient and graft survivals were compared using Kaplan-Meier survivorship curves with comparisons using the log-rank test.

Results

Both groups were comparable regarding acute rejection episodes, posttransplant hypertension, postsurgery renal artery stenosis, and urologic complications. Only hemorrhagic complications and renal artery thrombosis were significantly higher in the multiple renal arteries group (P = .027 and .03, respectively). Warm ischemia time was significantly longer in the multiple renal arteries group without any influence on the incidence of acute tubular necrosis (P = .2). Mean creatinine clearance at 1 year was 65 versus 50 mL/min/1.73 m² (P = .5) and at 5 years, 60 versus 55 mL/min/1.73 m² (P = .1) for the single versus multiple renal arteries groups, respectively. Return to hemodialysis was necessary for 18.8% of the single and 16.1% of the multiple renal arteries group.

Conclusion

The use of an allograft with multiple renal arteries is a safe, successful surgical procedure, that does not influence patient or graft survivals or increase surgical complication rates provided the surgical team is evolved with technical skill.     

Absence of increased height velocity in the first year of life in untreated children with simple virilizing congenital adrenal hyperplasia

CONTEXT: In congenital adrenal hyperplasia (CAH), elevation of adrenal androgens leads to accelerated growth and bone maturation with compromised adult height. OBJECTIVE/PATIENTS: The objective of the study was to analyze retrospectively early growth and bone maturation in 17 untreated simple virilizing (SV) CAH patients. SETTING: The study was conducted at Radboud University Nijmegen Medical Centre. INTERVENTIONS: Growth data were collected until time of diagnosis. Height was expressed as height sd score and corrected for target height. Bone maturation was determined and expressed as bone age acceleration. MAIN OUTCOME MEASURES: Growth pattern and bone maturation were measured before the diagnosis. RESULTS: In the term group (n = 11), there was no increase in height sd score and corrected for target height in the first year of life [-0.1 sd/yr; 95% confidence interval (CI) -0.5, 0.3] with a consecutive significant (P < 0.001) increase up to 0.9 sd/yr (95% CI 0.7, 1.0). In the premature group (n = 3), there was a catch-up growth of 1.6 sd/yr (95% CI 0.9, 2.3) in the first year followed by a growth of 1.1 sd/yr (95% CI 0.9, 1.5) in the following years. There was a positive linear correlation between bone age acceleration and age of diagnosis (r = 0.8). CONCLUSIONS: Height velocity and bone maturation are not increased in untreated children with mild forms of SV CAH in the first year of life. After this period there is a progressive increase in height velocity and bone maturation in strong relation to the duration of androgen exposition. This observation has implications for the dose of glucocorticoids to be used in SV CAH patients in the first year of life.     

New genetic variant that might improve warfarin dose prediction in African Americans

AIMS

To raise hypotheses with regards to whether genetic variants in the VKORC1, CYP2C9, EPHX1, GGCX and ALB genes might influence warfarin dose in African Americans and Caucasians, independent of the effects of the VKORC1 1173C>T and CYP2C9*2 and *3 variants.

METHODS

From a prospective cohort study, we obtained additional DNA on 36 Caucasian and 22 African American warfarin users who reached maintenance dose and genotyped them for tagSNPs (r² < 0.8) in VKORC1, EPHX1, GGCX and ALB genes, and one exonic CYP2C9 SNP. Linear regression models were fitted to estimate the relationship (P value) between log-transformed maintenance dose and each SNP and the amount of the warfarin dose variability accounted for by each SNP (partial R²).

RESULTS

In African Americans, the VKORC1 rs17886199 A-allele was associated with a lower dose (GG = 46.3 mg and GA = 25.6 mg; P = 0.002), independent of the VKORC1 1173C>T and CYP2C9*2 and *3 variants. Even after applying Bonferroni correction, the P value would still be considered statistically significant. The VKORC1 rs17886199 variant was not found in Caucasians. In Caucasians, the EPHX1 rs1051741 T-allele was associated with a lower dose (CC = 41.3 mg and CT = 30.0 mg; P = 0.04). The latter was no longer statistically significant after applying Bonferroni correction.

CONCLUSIONS

Our pilot study suggests that the VKORC1 rs17886199 variant could influence warfarin maintenance dose among African Americans, even after accounting for the influence of the VKORC1 1173C>T variant. Future studies with a larger sample size will be needed to confirm our findings.