Immunoglobulin and HLA-DP genes contribute to the susceptibility to juvenile dermatitis herpetiformis.

HLA-DQ genes and gluten diet are the main factors involved in the pathogenesis of Dermatitis Herpetiformis (DH), as well as Coeliac Disease (CD). However other genetic factors are probably relevant, since about 10% of the patients with DH and CD lack the DQA1*0501/B1*0201 heterodimer while the majority of individuals presenting this genotype and also being exposed to gluten diets did not suffer from these diseases. To evaluate the role of other genes, 36 Northern Italian children with DH were analysed for DNA polymorphisms at HLA-DP and immunoglobulin (Ig) heavy chain loci. DPA1*0201 and DPB1*1301 frequencies were higher in patients than in controls (Pc = 0.0357 and Pc = 0.0273). With respect to immunoglobulin heavy chain restriction fragment length polymorphisms (RFLP), the 4.6 kb SacI RFLP at the switch alpha 2 gene was more frequent in patients (0.13) than in controls (0.019; Pc = 0.036). Moreover, rare alleles or duplications in the switch regions occurred more frequently in the patients than in the controls. These results support the hypothesis of a multifactorial inheritance of DH, the HLA and Ig constant heavy chain genes being some of the loci contributing to the susceptibility. In accordance with previous CD studies, these data also confirm that DP subregion is probably involved in the pathogenesis of DH.     

Polymorphisms in angiotensin-converting enzyme gene and severity of renal disease in Henoch-Schoenlein patients

Background. The influence of angiotensin converting enzyme (ACE) gene polymorphism on the progression of primary IgA nephropathy (pIgAN) is still debated. Even though the allele frequency was reported to be similar to controls, in some studies D/D patients had a faster decline of renal function and need of dialysis. Since Henoch-Schoenlein purpura (HSP) nephritis is considered a systemic vasculitis with renal lesions indistinguishable from pIgAN, we investigated the effect of the ACE polymorphism on presentation and progression of HSP IgAN. Methods. We examined the insertion (I) and deletion (D) polymorphism in intron 16 of ACE gene by PCR amplification of genomic DNA of 82 patients (37 children), with biopsy-proven IgAN associated with HSP enrolled in a collaborative study. Results. No significant association with clinical presentation at onset or with final outcome was found (functional impairment at outcome in 31.8% D/D, 27.4% I/D, and 11.1% I/I). Patients homozygous for the D allele had a greater number of extrarenal relapses (P=0.0028). No association was found between the ACE genotype and the presence of hypertension at onset and at the end of the follow-up. No difference was found between adults and children. Conclusions. In this cohort of HSP IgAN, no ACE I/D polymorphisms were found to be associated with progressive deterioration of renal function. Different genes possibly involved in vasculitis might more strictly modulate expression and evolution HSP/IgAN/     

Our experience with pharyngoesophageal reconstruction.

Our experience with 11 cases of cervical esophageal reconstruction following excision of the hypopharynx and conservative neck dissection is reported. For the reconstructive procedure, we utilized a full-thickness skin graft from the penis according to Kaplan and Markowicz in 2 cases and a deltopectoral flap according to Bakamjian in 9. Critical evaluation of the clinical follow-up has led us to prefer the second method. It seems, in fact, to be the solution of choice in this kind of surgery, for the deltopectoral flap offers a generous source of viable skin due to its good blood supply.     

Pilot study of salvage laparoscopic prostatectomy for the treatment of recurrent prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? After primary radiation therapy or cryotherapy for prostate cancer, a biochemical‐only recurrence poses a diagnostic and therapeutic dilemma for clinicians and patients alike. Open radical prostatectomy (ORP) represents the most effective curative treatment option for these patients. Salvage laparoscopic radical prostatectomy seems to offer a safe therapeutic alternative for patients failing primary radiation or cryotherapy.

OBJECTIVE

? To evaluate feasibility, safety and oncological efficacy of salvage laparoscopic radical prostatectomy for pathology‐proven biochemical recurrence after primary radiation therapy or cryotherapy for prostate cancer.

MATERIALS AND METHODS

? This retrospective pilot study examined 15 patients from 2004 to 2010 with biochemical recurrence after external beam radiation therapy (N= 8), brachytherapy (N= 6) or cryotherapy (N= 1). ? Patients were treated with salvage laparoscopic radical prostatectomy (11 conventional, four robotic‐assisted) with bilateral pelvic dissection.

RESULTS

? Median duration of surgery was 235 min. None of the following occurred: conversion to open surgery, transfusion, urethrovesical stenosis or perioperative or postoperative mortality. One patient presented with a rectal injury, repaired using uninterrupted sutures and a colostomy. One patient had anastomotic leak treated with prolonged Foley catheterization. ? Pathological stage was pT2a in three, pT2b in three, pT3a in four, pT3b in three and pT4 in two patients; two patients had nodal metastasis. Within an 8‐month median follow‐up, 11 patients were disease‐free and three had persistent postoperative prostate‐specific antigen (PSA) elevation; the remaining patient experienced PSA recurrence after 21 months. ? Seven patients achieved continence (no pads) by 8.4 months (median), one patient manifested severe incontinence corrected by implanting an artificial sphincter, and seven patients with a 12.6‐month mean follow‐up continued to need one or two pads per day. ? Erectile dysfunction was present in five patients before surgery and in 14 patients after surgery.

CONCLUSION

? Salvage laparoscopic radical prostatectomy seems to offer a safe therapeutic alternative for patients failing primary radiation or cryotherapy. However, larger studies with longer‐term data are required.     

Assessment of the steady-state pharmacokinetic interaction between etravirine administered as two different formulations and tenofovir disoproxil fumarate in healthy volunteers

Objective

Two open‐label, randomized, cross‐over trials in healthy volunteers were conducted to investigate the pharmacokinetic interaction between etravirine and tenofovir disoproxil fumarate.

Methods

Etravirine was administered as either 800 mg twice a day (bid) (phase II formulation in Study 1) or 200 mg bid (phase III formulation in Study 2) for 8 days followed by a 12 h pharmacokinetic evaluation. After a minimum of 14 days washout, tenofovir disoproxil fumarate 300 mg once a day was administered for 16 days. Volunteers were randomized to receive co‐administration of etravirine with tenofovir disoproxil fumarate on either days 1–8 or days 9–16 followed by a 12 h pharmacokinetic evaluation for etravirine on day 8 or 16, respectively. Plasma and urine tenofovir concentrations were determined on days 8 and 16 over 24 h.

Results

The least square mean (LSM) ratio [90% confidence interval (CI)] for the area under the plasma concentration–time curve from 0 to 12 h (AUC_{12 h}) for etravirine co‐administered with tenofovir disoproxil fumarate vs. etravirine alone was 0.69 (0.61–0.79) and 0.81 (0.75–0.88) in Studies 1 and 2, respectively. The LSM ratio (90% CI) for the effect of etravirine on tenofovir AUC_{24 h} was 1.16 (1.09–1.23) in Study 1 and 1.15 (1.09–1.21) in Study 2.

Conclusions

These alterations are not considered clinically relevant for either drug and no dose adjustment is necessary when etravirine and tenofovir disoproxil fumarate are co‐administered.