Efficacy of intranasal or subcutaneous luteinizing hormone-releasing hormone agonist inhibition of ovarian function in the treatment of endometriosis

We have previously reported reversible hypogonadism induced by the intranasal administration of the luteinizing hormone-releasing hormone agonist buserelin as a new therapeutic approach for endometriosis. Thirteen patients were randomized to receive intranasal buserelin (400 micrograms 3 times a day) or subcutaneous buserelin injection (200 micrograms once daily) for a 6- to 9-month period. Both routes of administration were effective in inhibiting serum estradiol levels to near the menopausal range after 1 month of treatment. The two dosage regimens had also a comparable efficacy in alleviating endometriosis symptoms and in reducing the revised American Fertility Society scoring at laparoscopic examination. The implant score mainly decreased by more than 70%. The occurrence of side effects was similar in both groups, and side effects were mainly hot flushes, dyspareunia secondary to decreased vaginal secretion, and decreased libido. Results of hemogram, urinalysis, and serum biochemical and hormonal tests remained in the normal range. The ovulatory cycle rapidly returned after the cessation of treatment, and three pregnancies occurred in six previously infertile patients. Intranasal and subcutaneous buserelin were well accepted and equally effective in inhibiting the pituitary-ovarian function, which caused mild menopausal symptoms but an important regression of endometriosis.     

Clinical involvement of the tonsillar immune system in IgA nephropathy

The temporal association of tonsillitis and hematuria or proteinuria in IgA nephropathy suggests that there might be a link between the physiological properties of the secondary lymphoid organ that tonsils represent and the mesangial deposition of IgA characteristic of this nephropathy. A number of clinical and ex-vivo data support this hypothesis. One of the earliest was the demonstration of the dimeric nature of mesangial IgA, composed of IgA monomers linked by a J chain, yet lacking the polyIg receptor acquired by secretory IgA during transcytosis through epithelial cells. This molecular structure is that of IgA synthesized in human tonsils, the epithelium of which lacks polyIg receptor. Moreover, tonsils from patients with IgA nephropathy display an abnormal partition of IgG and IgA producing plasma cells associated with a significantly developed web of high endothelial venules. IgA nephropathy could thus be in part related to an alteration of IgA precursors homing in tonsils. Tonsillectomy thus would present the advantage of removing an abnormally functioning source of dimeric IgA. Performed early enough in the course of the renal disease, tonsillectomy could suffice to halt the development of the nephropathy and restore the kidneys to health.     

Evidence for a mitochondrial impact of trimetazidine during cold ischemia and reperfusion

In organ transplantation, ischemia-reperfusion injury (IRI) has been implicated in delayed graft function (DGF) as well as in short- and long-term complications. Using an autotransplant pig kidney model, changes in renal function and morphology were determined after different periods of cold ischemia in kidneys preserved in the University of Wisconsin solution (UW), high-Na(+) version of UW (HEH) or Celsior (CEL) a newly developed high-Na(+) solution, with or without trimetazidine (TMZ). Kidney function was better preserved in CEL, UW and particularly HEH in combination with TMZ, particularly after 48 and 72 h. Mitochondria integrity was improved in TMZ-preserved groups. This study indicates that TMZ is efficiently protective against IRI even after prolonged preservation and in different preservation solutions.     

Anti-HBs cellular immune response in kidney recipients before and 4 months after transplantation

Patients with renal failure represent a population at risk for hepatitis B, since only 50 to 60% of them develop protective humoral responses after vaccination. As this could be due to an altered regulation of cellular immune responses, the objectives of the present study were to evaluate the proliferative abilities of lymphocytes from patients with chronic renal failure after stimulation in vitro with a mitogen (pokeweed mitogen [PWM]) or HBsAg. In order to differentiate between the immunodeficiency associated with renal failure and that due to immunosuppression posttransplantation, the same subjects were tested before and 4 months after kidney transplantation. The lymphoproliferation assay used was performed by flow cytometry, which is based on sequential analysis of the cell cycle and which allows analysis of cytokine production. Serologically, the group of 36 patients tested comprised 22% nonresponders, 30% poor responders, and 48% responders. Lymphocyte growth was observed for all patients after stimulation with PWM, indicating that these cells had the capacity to proliferate in vitro. The level of lymphoproliferation in response to PWM was significantly reduced after transplantation, yet both before and after transplantation, all serologic nonresponders developed cellular responses to at least two vaccines. No correlation between humoral and cellular responses was shown. Proliferating cells were lymphocytes, which mostly secreted interleukin 4 (IL-4) and IL-10 for the three serologic groups. This study suggests that even when repeated vaccination fails to induce significant antibody levels in patients with renal failure, specific HBs cellular responses develop, and these may prove to be efficient in protecting these patients against hepatitis B.     

Mucin production and composition is altered in dextran sulfate sodium-induced colitis in rats

We evaluated the small and large intestinal mucin production in a rat model of human ulcerative colitis by measuring the in vivo fractional synthesis rate (FSR) and the expression of mucins. A chronic colitis was induced by oral administration of 5% dextran sulfate sodium (DSS) for 9 days followed by 2% DSS for 18 days. DSS-treated rats showed increased colonic MUC2,3 mRNA levels compared pair-fed controls. The mucin FSR was unaffected while mucin-containing goblet cells were depleted in the vicinity of lesions. In the small intestine, no inflammatory lesions were observed but ileal MUC2 mRNA levels and mucin FSR were decreased by 46% and 21%, respectively. Finally, DSS-treated rats showed a marked decrease in mucin's threonine + serine content all along the gut, which may lead to a reduction of potential O-glycosylation sites. Our data indicate that the chronic colitis may impair the mucus layer protective function all along the gut.     

The chemokine receptor CX3CR1 controls homing and anti-viral potencies of CD8 effector-memory T lymphocytes in HIV-infected patients

OBJECTIVES: We have recently reported that the polymorphism of the fractalkine receptor, CX3CR1, provides a new marker for prognosis in HIV disease. In order to understand the mechanism by which CX3CR1 participates in the regulation of HIV-immune responses, we investigated its expression and role on T lymphocytes in HIV-infected patients. DESIGN: For that purpose, we analysed the expression of CX3CR1 on CD4 and CD8 effector-memory subsets in HIV-positive individuals by flow cytometric analyses, and studied its potential role in the migration and function of CD8 effector cells. RESULTS: We observed an increased frequency of CD8 cells expressing CX3CR1 that was correlated with disease progression in HIV-infected patients compared with normal individuals. CX3CR1+ was expressed mainly on activated and differentiated CCR7-CD45RA-negative memory lymphocytes. Interestingly, CX3CR1 appeared as the main homing receptor of these cells that have downmodulated most other chemokine receptors. The CD8+CX3CR1+ lymphocytes were engaged in the cytotoxic lineage (perforin+, CD27-negative and CD57+). Ex-vivo analysis showed that CX3C ligand-1 inhibits IFNgamma production in response to T cell receptor engagement. CONCLUSION: CX3CR1 and its ligand could contribute to the specific migratory pattern of late-stage differentiated CD8 cells and participate in the regulation of effector function of CD8 lymphocytes during HIV infection.     

Pudendal nerve entrapment as source of intractable perineal pain

Perineal pain caused by pudendal nerve entrapment is a rarely reported entity, with only a handful of cases in the modern literature. A 25-yr-old male medical student had refractory unilateral orchialgia for 32 mo and concomitant proctalgia for 14 mo. Pain was positional in nature, exacerbated by sitting and partially relieved when standing or recumbent. Pudendal nerve entrapment was diagnosed clinically, with computed tomography-guided nerve blocks providing temporary relief. A prolonged left pudendal nerve distal motor latency on electrodiagnostic testing later confirmed the diagnosis. At surgery, the left pudendal nerve was found flattened in the pudendal canal of Alcock and in contact with the sharp inferior border of the sacrospinous ligament. After surgical decompression and rehabilitation, the patient experienced significant relief of pain and returned to medical school. This case suggests pudendal nerve entrapment should be considered in the differential diagnosis of chronic urogenital or anorectal pain, particularly if the pain is aggravated by sitting or if there is a history of bicycle riding.     

B19 parvovirus-induced fetal hydrops:good outcome after intrauterine blood transfusion at 18 weeks of gestation

We report a successful treatment of a B19 parvovirus-induced fetal hydrops diagnosed at 16 weeks of gestation. This disease could be corrected by means of a unique intraperitoneal blood transfusion performed at 18 weeks, once diagnosis was established. The delivery occurred at 36 weeks, leading to the birth of a healthy baby. This case suggests that transfusion should be attempted, as the spontaneous fetal recovery remains uncertain and shows that intraperitoneal blood transfusion is an effective therapeutic option of the B19 parvovirus-induced anemia, in the absence of a viral myocarditis.