L'Evolution post-imaginale du tissue adipeux femelle de Locusta migratoria et son controle endocrine

In the adult female of Locusta migratoria, during the differentiation of the periovarian fat body, there is an extensive development of rough ER and Golgi apparatus; 2 weeks after ecdysis, lipid droplets decrease in number and size, and glycogen particles are no longer detectable. At the same time, the nuclear volume is doubled and even quadrupled for a third of the adipocytes. Once this transformation is achieved, Golgi complexes cease secreting glycoprotein granules, but produce microvesicles in great number which might give rise to multivesicular bodies (mvb). These mvb are not involved in protein uptake but rather in transporting enzymes to cytolysosomes, which are conspicuous in the oldest females. These “protein granules” could contribute to elaboration of egg precursor proteins besides those normally synthesized by the rough ER. The postecdysis evolution of fat bodies does not reflect the different steps of sexual life of the female, neither the ovarian maturation nor the later ovarian cycles. Indeed, in 2-week-old ovariectomized females, the fat body maturation is realized: Moreover, there is a slight acceleration in the differentiation process of periovarian fat body cells, and peripheric cells are involved in an unusual maturation, when compared to control females. Allatectomy brings an overcharge of lipid droplets in periovarian and peripheric fat body cells. Neither proliferation of rough ER or Golgi nor an increase of nuclear volume takes place, but a certain involution of cytoplasmic organelles is observed. Implantation of corpora allata in 1-month-old allatectomized females leads to a rapid restoration of the capacity of differentiation in “female fat body.”In conclusion, the results obtained after allatectomy and after castration suggest a strict control by the juvenile hormone in determining fat body maturation. A study concerning the initial cause of hyperactivity of the corpora allata after ovariectomy is in progress.     

Neoadjuvant chemotherapy in sarcoma

This document describe s the proposed clinical practices guidelines for neoadjuvant chemotherapy in soft tissue sarcomas proposed by the French Sarcoma Group.Neo-adjuvant chemotherapy remains an experimental therapeutic procedure in soft tissue sarcomas. Neo-adjuvant chemotherapy may be proposed in three different types of situations: 1) a locally advanced tumor, non accessible to R0 or 1 removal of the lesion. Its objective is there to allow for R0 or R1 surgical removal of the tumor. 2) A locally advanced tumor, accessible to R0 or 1 removal of the lesion, but with a mutilating surgery (amputation). Its objective is there to allow for R0 or R1 conservative surgical removal of the tumor. In both situation, the strategy should be discussed beforehand in a multidisciplinary specialized consultation for sarcoma. 3) In the case where complete (R0 or R1) surgical removal of the tumor can be performed, neooadjuvant chemotherapy has no demonstrated role. The only randomized phase III clinical trial testing neo-adjuvant chemotherapy in this setting, i.e. the STBSG 62871 STBSG trial, failed to demonstrate any benefit in terms of overall or progression free survival. The selection of the type of chemotherapy regimen given in the neoadjuvant setting should be discussed in a multidisciplinary setting, considering the age and the general status of the patient; young patients, without associated concomittent illnesses should be proposed for a combined chemotherapy regimen, combining doxorubicin (> or = 50 mg/m2) and ifosfamide (> 5 g/m2) on the basis of randomized trials demonstrating an improvement of response rate versus single agent therapy with doxorubine. In elderly and/or frail patients, conversely, single agent doxorubicin may be the preferred option.     

Intensified and daily hemodialysis in children might improve statural growth

In children conventional hemodialysis does not often improve growth. We determined linear growth in five children on in-center intensified and daily hemodialysis (IDd) regimen, with a mean age of 8 years 7 months at enrolment. Four of five were on growth hormone started for a median of 28.5 months before IDd. IDd was delivered 5 to 6 times weekly, for three hours each session. Mean follow up of IDd was 18.6 months. Dropout from IDd was kidney transplantation (n=4) or transfer to another center (n=1). IDd and free diet improved appetite, thereby protein intake, was above 2 g/kg/BW. Median weekly Kt/V_urea was 9.1 (8.7 to 10.4). Predialysis phosphorus blood levels were higher at the start (2.04±0.34 mmol/L) than at end of IDd (1.39±0.41 mmol/L) without need for carbonate of calcium in four of five cases. During conventional dialysis ht SDS decreased from −0.8 to −1.44, which occurred predominantly before rhGH start. Conversion to IDd significantly increased growth velocity to a mean of 13 cm/year (10.3–18) with a mean change of +1.84 ht SDS/year (0.4 to 2.7). This preliminary report suggests the potential efficacy of IDd regimen in promising growth velocity, either directly from a higher dialysis dose or indirectly through an improved nutritional status.     

Intravesical glucidic capsaicin versus glucidic solvent in neurogenic detrusor overactivity: a double blind controlled randomized study

AIMS: Many studies report the use of alcoholic capsaicin instillation to treat neurogenic detrusor overactivity (NDO) in spinal cord injured (SCI) and multiple sclerosis (MS) patients. However, poor tolerability due to the irritative effect of the ethanol solvent limits its use. Our study aimed to evaluate the efficacy and tolerability of a new formulation of capsaicin in a glucidic solution in a multicenter clinical trial. MATERIALS AND METHODS: Thirty-three patients (26MS/7SCI) suffering from urinary incontinence due to refractory NDO were prospectively enrolled in a double-blind placebo controlled study and randomized to capsaicin group (CG, N = 17) or solvent group (SG, N = 16). They respectively received an intravesical instillation of 100 ml capsaicin diluted in glucidic solvent (CG) or glucidic solvent alone (SG). Efficacy (voiding chart, maximum cystometric capacity (MCC)) and tolerability were evaluated on days 0 (D0), 30 and 90. RESULTS: On D0, groups were homogeneous. On D30, significant improvement of overactive bladder syndrome and an increase in MCC were shown in CG, whereas there were no improvement in SG. No significant improvement was shown on D90 in both groups. There were no significant differences between groups regarding prevalence, duration, or intensity of side effects, except for short duration pubic pain during instillation more often reported in CG (58.8%) than in SG (12.5%) (P < 0.01). CONCLUSION: This placebo controlled study using glucidic capsaicin confirms its short-term efficacy in NDO patients. Global tolerance of glucidic capsaicin appeared satisfactory. Long-term efficacy and tolerance of repeated glucidic capsaicin instillations need to be evaluated.     

Cinacalcet chloride is efficient and safe in renal transplant recipients with posttransplant hyperparathyroidism

BACKGROUND: Persistent hyperparathyroidism (HPT) is observed in approximately 50% of kidney transplant recipients one year after transplantation. It may result in hypercalcemia, hypophosphatemia, bone demineralization, vascular calcification, lithiasis, and participate in chronic allograft nephropathy. We evaluated the use of the calcimimetic cinacalcet chloride to correct chronic hypercalcemia in posttransplant HPT, in a prospective single-center study. METHODS: Nine patients with persistent hypercalcemia (>2.6 mmol/L) and stable graft function were treated with cinacalcet (30 mg/day, thereafter adapted to obtain normal serum Ca levels) for six months. Their immunosuppressive schedule included mycophenolate mofetil (MMF), steroids, and cyclosporine A (4), tacrolimus (4), or sirolimus (2). RESULTS: Serum Ca levels significantly decreased from 2.75+/-0.15 to 2.59+/-0.10, 2.42+/-0.29 and 2.44+/-0.25 mmol/L by one, two, and six months, respectively (P<0.02, Wilcoxon test for paired data, for all the data points). Parathyroid hormone (PTH) serum levels decreased from 171+/-102 to 134+/-63 pg/ml by two months (P<0.05) and stabilized thereafter (148+/-99 pg/ml at six months; NS). No changes in glomerular filtration rate (49.8+/-18.6 and 51.3+/-19 ml/min at initiation and six months, respectively) and no variation in serum concentration of the immunosuppressive drugs were observed. Three patients withdrew the treatment because gastrointestinal intolerance. CONCLUSION: Cinacalcet allows the correction of hypercalcemia with no interference in immunosuppressive treatment or renal function. However, whether the increased intolerance observed was due to the association of cinacalcet chloride with other drugs required in renal transplantation (e.g., MMF) needs to be assessed.     

A grading system based on severity of infection to predict mortality in allogeneic stem cell transplant recipients

BACKGROUND: There is, until now, no prognostic grading system for infections occurring in allogeneic stem cell transplant (SCT) recipients. The aim of this study was to determine the prognostic value of a grading system of infectious complications in predicting death. METHODS: For the purposes of a prospective allogeneic SCT trial, we classified severity of infections in 3 grades according to expected rates of mortality (>or= 60% for grade 3). We prospectively recorded the type and time of occurrence of 440 infectious events in 190 consecutive patients until 6 months after transplant. We used multivariate Cox models with time-dependent covariates to analyze the relationship between the grade of severity of each infectious episode and mortality due or not due to infection, adjusting for possible confounders. RESULTS: Only patients with grade 3 infections had a significantly increased risk of death (P<.0001). The risk was not modified when the occurrence of acute graft-versus-host disease or the dose of IVIg administered were considered. Occurrence of a grade 1 and 2 infection had no additional influence. CONCLUSION: Our grading system identifies the most medically important, life-threatening infections and allow high-risk patients to be identified. We suggest grade 3 infections should be given priority in the evaluation of anti-infectious strategies.     

Kienböck's disease in a 14-year-old gymnast: a case report

Kienb?ck's disease is rare in children and there are few reports and therapeutic recommendations in the literature about this condition. We report a case of a 14-year-old female gymnast for whom nonsurgical treatment was followed by complete healing within 12 months. Repeated computed tomography scans provided a sequential coronal, sagittal, and transverse illustration of the progressive healing of the lunate.     

Effect of bile contamination on immediate outcomes after pancreaticoduodenectomy for tumor

BACKGROUND: The influence of preoperative biliary drainage on the postoperative course of patients undergoing pancreaticoduodenectomy (PD) remains controversial. Among drawbacks of biliary drainage, bile contamination and its consequences are incompletely evaluated. This study aimed to compare outcomes after PD in patients with sterile and those with infected bile. STUDY DESIGN: Seventy-nine consecutive patients underwent PD for periampullary tumor with routine bile culture and antibiotic prophylaxis with cefazolin. The postoperative course of 35 patients with infected bile (group B+) was compared with that of 44 patients with sterile bile (group B-). RESULTS: The distribution of tumors was comparable except for ampullary carcinoma, which was more frequent in group B+ patients (p = 0.001). Interventional biliary endoscopy was performed preoperatively in 80% of patients in group B+ versus 14% in group B- (p < 0.001), including 9 isolated sphincterotomies (20% versus 5%, p < 0.03) and 20 endoprosthesis insertions (57% versus 0%, p < 0.0001). More patients in group B+ were classified as American Society of Anesthesiologists (ASA) 2 (p = 0.04). Operative time and blood loss were similar in both groups. One patient died postoperatively (group B+). Overall morbidity was increased in group B+ (77% versus 59%, p = 0.05). Postoperative infectious complications, all demonstrated bacteriologically, were more frequent in group B+: (65% versus 37%, p = 0.003). In group B+, bile was polybacterial in 54% of patients and isolated microorganisms were resistant to cefazolin in 97%. In patients with infectious complications, the same germ was isolated in bile and another sample in 49%. CONCLUSIONS: In patients undergoing PD, bile infection is related to previous interventional biliary endoscopy in 80% of patients and is associated with an increased rate of postoperative infections. During PD for ampullary carcinoma or after interventional biliary endoscopy, a specific antibioprophylaxis should be evaluated.     

Protein inhibitor of neuronal nitric oxide synthase (PIN) is a new regulator of glucose-induced insulin secretion

We previously showed that pancreatic beta-cells express neuronal nitric oxide synthase (nNOS) that controls insulin secretion through two catalytic activities: nitric oxide (NO) production and cytochrome c reductase activity. We now provide evidence that the endogenous protein inhibitor of nNOS (PIN) is expressed in rat pancreatic islets and INS-1 cells. Double-immunofluorescence studies showed a colocalization of PIN with both nNOS and myosin Va in insulin-secreting beta-cells. Electron microscopy studies confirmed that PIN is mainly associated with insulin secretory granules and colocated with nNOS in the latter. In addition, PIN overexpression in INS-1 cells enhanced glucose-induced insulin secretion, which is only partly reversed by addition of an NO donor, sodium nitroprusside (SNP), and unaffected by the inhibitor of cytochrome c reductase activity, miconazole. In contrast, the pharmacological inhibitor of nNOS, Nomega-nitro-l-arginine methyl ester, amplified glucose-induced insulin secretion, an effect insensitive to SNP but completely normalized by the addition of miconazole. Thus, PIN insulinotropic effect could be related to its colocalization with the actin-based molecular motor myosin Va and as such be implicated in the physiological regulation of glucose-induced insulin secretion at the level of the exocytotic machinery.