NIH conference. Membranous nephropathy.

Membranous nephropathy is a worldwide problem that accounts for about 20% of the cases of the adult-onset nephrotic syndrome. This disease places many patients at risk for both end-stage renal failure and the complications of hyperlipidemia. Immune-mediated injury to the glomerular capillary wall in patients with membranous nephropathy is characterized by subepithelial immune complex formation and generation of the membrane attack complex of complement. Glomerular capillary hypertension, hyperlipidemia, and possibly cytokines could contribute to the glomerular sclerosis seen in the advanced stages of the disorder. In some cases, production of pathogenic antibody can be suppressed by treating the underlying condition. The mechanisms of action of immunosuppressive agents are being investigated and treatments are being tested in clinical trials to optimize the balance of efficacy and toxicity. Alternate-day treatment with corticosteroids is often recommended for nephrotic patients with idiopathic membranous nephropathy, but this approach has not been proved beneficial. Ongoing studies are evaluating whether cytotoxic drugs or cyclosporin A combined with prednisone is more effective than treatment with corticosteroids alone. Lipid-lowering drug therapy is warranted in cases of the persistent nephrotic syndrome to avert the cardiovascular sequelae of hyperlipidemia.     

An open-label efficacy pilot study with pimecrolimus cream 1% in adults with facial seborrhoeic dermatitis infected with HIV

BACKGROUND: Seborrhoeic dermatitis (SD) is a common dermatosis in human immunodeficiency virus (HIV)-positive patients, many of whom do not respond satisfactorily to conventional topical treatments such as corticosteroids and antifungals. OBJECTIVE: A pilot study to investigate the efficacy and tolerability of pimecrolimus cream 1% in HIV-positive patients with facial SD. METHODS: In a single-centre study, 21 HIV-infected patients with mild to severe SD were treated twice daily with pimecrolimus cream 1% for 14 days. Thereafter, treatment was discontinued and patients followed up for 5 weeks. Skin involvement at baseline and on days 7, 14, 21, 35 and 49 was assessed using a four-point clinical score and digital photography. MAIN OUTCOME MEASURES: Efficacy and safety of pimecrolimus cream 1% treatment and incidence of relapse in the follow-up phase. Results Marked improvement was seen in clinical parameters at day 7, with >or= 90% patients clear of symptoms at day 14. Relapse was observed at day 35 but signs were milder than at baseline. All patients responded to therapy, despite their immunological status. Pimecrolimus did not alter CD4(+) and CD8(+) T-cell counts or viral load during the treatment period. CONCLUSION: Pimecrolimus cream represents a new, effective therapeutic option for facial SD in HIV patients.     

Is pre‐operative radiotherapy necessary in T1‐T3 rectal cancer with TME?

OBJECTIVE: The indications for pre-operative radiotherapy in rectal cancer are still unclear with the exception of T4 tumours. The aim of this study was to assess local and overall recurrence in patients with T1-T3 rectal cancers undergoing total mesorectal excision (TME). METHODS: Prospective data was collected from 150 patients with rectal cancer treated in one surgical centre between July 1997 and July 2002. One hundred and twenty-nine primary resections were carried of which 102 were with curative intent. Seventy-nine patients with T1-T3 tumours were included in the analysis. Nine had local resections and 70 underwent TME; 19 of the 70 patients were node positive and 51 were node negative. RESULTS: At a median follow-up of 37 months (range 19-79 months) there were 3 (4.3%) isolated local recurrences. One node positive patient developed isolated local recurrence compared with 2 node negative patients. The node positive patient died from a myocardial infarction while the two node negative patients died as a consequence of local recurrence. Three (4.3%) of 70 patients developed systemic relapse all of whom were node positive. The cancer specific mortality rate over the same follow-up period was 3/19 for node positive patients and 2/51 for node negative patients. Of 9 patients who had local resections, none developed local recurrence or systemic relapse. CONCLUSIONS: With TME the rate of local recurrence in T1-T3 tumours is low. Our results do not support the use of pre-operative radiotherapy for these patients.     

Three-dimensional reconstruction of magnetic resonance images of the temporomandibular joint by I-DEAS.

Evaluation of the temporomandibular joint has been limited by the inability of current technology to image complex morphology and motion in three dimensions. An engineering design program, I-DEAS, has been used to construct solid models from magnetic resonance images. A dried skull with an acrylic resin temporomandibular disc replica, immersed in water, provided sagittal and coronal MR images. Linear dimensions and disc volumes obtained from the models were compared with the original and found to be consistent, within the limits imposed by the slice thickness. We have applied the method to the living joint in an asymptomatic volunteer, and report our initial experience in demonstrating the spatial relationships and motion of the joint components.     

In-vitro maturation of human germinal vesicle stage oocytes: role of cumulus cells and epidermal growth factor in the culture medium

In-vitro maturation (IVM) of oocytes is a promising technique to reduce the costs and avert the side-effects of gonadotrophin stimulation for in-vitro fertilization (IVF). The pregnancy rates from oocytes matured in vitro are much lower than those of in-vivo stimulation cycles indicating that optimization of IVM remains a challenge. Therefore, we investigated the effect of supplementation of the medium with gonadotrophins, oestradiol and epidermal growth factor (EGF) and the effect of retaining or removing the cumulus cells on nuclear and cytoplasmic maturation of immature oocytes. Human germinal vesicle (GV) oocytes obtained after gonadotrophin stimulation for intracytoplasmic sperm injection (ICSI) were cultured in a complex defined medium either supplemented with gonadotrophins, oestradiol and physiological concentrations of EGF (2 ng/ml) or gonadotrophins and oestradiol alone. The cumulus cells were either removed or kept intact. In GV stage oocytes cultured without cumulus (group I) significantly more oocytes reached the metaphase II (MII) stage at 30 h in media supplemented with EGF (64.3 versus 33.9%, P < 0.003). For oocytes cultured with intact cumulus (group II), more oocytes reached MII at 30 h than in group I, but there was no difference in medium with or without EGF supplementation (81.8 and 79.8% respectively). Cytoplasmic maturation of MII oocytes was judged from their capability to activate and fertilize after ICSI. In group I, the rates of activation and normal fertilization were similar. However, in group II, significantly more oocytes underwent normal fertilization in the EGF-supplemented than the unsupplemented group (71.7 versus 45.6%, P < 0.05). The cleavage rates of the fertilized oocytes were similar in the sibling oocyte subgroups cultured with or without EGF supplementation, but the overall cleavage rates were higher in cumulus-intact compared to cumulus-denuded oocytes (88.9 versus 47.8%, P < 0.001). Thus, supplementation of the maturation medium with EGF and maintenance of the cumulus during culture improve the nuclear and cytoplasmic maturation of human oocytes in vitro.