Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation

Campath-1H (alemtuzumab) induction was used for renal transplantation in combination with sirolimus as immunosuppression. We previously reported a high (28%) rate of early rejection with this regimen, and now report 3-year outcomes. Twenty-nine patients were recipients of either deceased donor or non-HLA (Human Leukocyte Antigen) identical living donor primary renal allografts. Clinical parameters including infection, malignancy, kidney function, and kidney histology were followed prospectively for 3 years. Three-year cumulative graft and patient survival were 96% and 100%, respectively. Twenty patients were maintained on steroid-free immunosuppressive regimens, and 15 patients were maintained on monotherapy for immunosuppression (12 on sirolimus). No serious infectious complications were observed and two patients developed basal cell skin cancer. The 3-year results of our initial pilot study demonstrate good graft (96%) and patient (100%) outcomes. Campath-1H induction has yielded a high proportion of patients maintained on immunosuppressive monotherapy (57%) without serious infectious- and no malignancy-related complications. The reported regimen yielded novel insights into both Campath-1H and sirolimus therapy in renal transplantation. Because of the higher incidence of early rejection, we recommend a modified strategy of immunosuppression including a brief course of a calcineurin inhibitor.     

Ultrasound imaging of the lower urinary tract after successful tension-free vaginal tape (TVT) procedure.

OBJECTIVES: To evaluate changes in the mobility of the whole urethra, in the proximal urethra (funneling) and in the thickness of the urinary bladder wall, after a successful tension-free vaginal tape (TVT) procedure. METHODS: This prospective longitudinal study included 52 women with urodynamically confirmed stress urinary incontinence who had undergone a successful TVT procedure. Ultrasound examination was performed before the TVT procedure and at a median of 3 (range, 3-6) months after surgery. For all women, the changes to the urethra and urinary bladder induced by surgery were examined. For three mobility groups (low, intermediate and high urethral mobility before surgery) we compared the changes induced by the operation and the typical position and mobility of the tape. RESULTS: The position of the urethra at rest was not influenced by surgery. The operation significantly decreased the mobility of all parts of the urethra during Valsalva. The absolute changes of the vector of the urethral movement differed according to the mobility group (average decrease, 6 mm; decrease for women with low, intermediate and high mobility, respectively, 2-3 mm, 4-6 mm and 9 mm). The change in relative mobility was the same in all groups. The operation decreased funneling (width and depth) during maximal Valsalva. After surgery there was an increase in the thickness of the bladder wall (by 0.64 and 0.73 mm, respectively, at the anterior part and trigone). CONCLUSIONS: A successful TVT procedure did not influence the position of the urethra at rest but significantly decreased the mobility of the urethra during Valsalva and also decreased funneling at maximal Valsalva.     

Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on the pituitary-thyroid-axis.

The lack of estrogen during menopause is associated with various symptoms including osteoporosis, cardiovascular diseases, and menopausal symptoms. For many years, conventional hormone replacement therapy has been successfully used to treat these conditions. However, in light of recent studies that draw attention to potential hazards of conventional HRT, various attempts were undertaken to search for alternatives of classical HRT. Phytoestrogens are supposed to ameliorate various discomforts associated with menopause. Resveratrol (RES) is present in red wine, grapes and peanuts and has been implicated in cardioprotection and prevention of adverse side effects observed after regular HRT. As the pituitary-thyroid axis is a target of estrogen action, we first assessed the effects of E2 administration on thyroid hormone stimulating hormone releasing hormone (TRH)-induced thyroid stimulating hormone (TSH) secretion from pituitary cell cultures in vitro. Our data reveal that E2 treatment augments the TRH-induced TSH secretion. We furthermore designed a long-term study of three months to assess the effects of subcutaneous and oral administration of 17beta-estradiol (E2), as well as the actions of RES on the pituitary-thyroid axis in ovariectomized (OVX) female rats. Our results demonstrate that serum levels of 1.0 and 8.1 microM RES lead to a significant increase in total serum triiodthyronine (T3) levels. OVX induces TSHbeta mRNA in the adenohypohysis and E2 treatment attenuates this effect. Treatment of rats with subcutaneous implants of E2 does not affect the pituitary-thyroid axis, whereas orally applied E2 benzoate (E2B) increases plasma TSH and total thyroxine (T4) in OVX rats. In all animals, we could not detect changes in thyroid morphology as assessed by hematoxylin-eosin (HE) and Perjod-Acid Schiff's (PAS) staining.     

Incidence of asthma and net change in symptoms in relation to changes in obesity.

The incidence of asthma has been reported to be associated with obesity. An alternative analysis, of net change in prevalence, does not require exclusion of those with asthma at baseline. Follow-up data were obtained from 9,552 participants in the European Community Respiratory Health Survey and the Swiss cohort Study on Air Pollution and Lung Disease in Adults. Incidence of asthma was analysed by proportional hazards regression, and net changes in symptoms and asthma status by generalised estimating equations, by obesity group. Incidence and net change in ever having had asthma were greater in females than in males, and in participants who remained obese compared with those who were never obese (hazard ratio 2.00, 95% confidence interval 1.25-3.20; excess net change 2.8%, 0.4-5.3% per 10 yrs). The effect of being obese on net change in diagnosed asthma was greater in females than in males, but for net change in wheeze without a cold it was greater in males. The present results are consistent with asthma being more frequently diagnosed in females, especially obese females. These findings may help to explain the reports of a stronger association between asthma and obesity in females than in males.     

Esophageal foreign body causing direct aortic injury.

Foreign bodies in the esophagus are uncommon causes of esophageal perforation. Many nonperforating cases are successfully managed by flexible gastroscopy. However, complicated foreign bodies such as those that result in esophageal perforation and vascular injury are best managed surgically. Gastroscopy remains the primary method of diagnosis. A case of a 59-year-old woman who developed retrosternal and intrascapular pain, odynophagia and hematemesis after eating fish is reported. Flexible gastroscopy showed arterial bleeding from the midthoracic esophagus. Computed tomography scan localized a 3 cm fish bone perforating the esophagus with surrounding hematoma. An aortogram did not reveal an actively bleeding aortoesophageal fistula. The fish bone was surgically removed and the patient recovered with no postoperative complications. This case illustrates the importance of early consideration for surgical intervention when confronted with a brisk arterial bleed from the esophagus with suggestive history of foreign body ingestion.     

Treatment of premature ejaculation: New drugs and treatment strategies

This review discusses treatment options for men with premature ejaculation (PE), a common sexual dysfunction characterized by short ejaculatory latency, decreased sexual satisfaction, and distress. For a number of reasons, including embarrassment and the belief that PE is a normal part of aging, that it has no effective treatment, or that it will resolve itself, few men with PE seek treatment. Although several treatment options exist (eg, behavioral, cognitive, and sex therapy methods; desensitizing drugs; off-label use of antidepressants, phosphodiesterase type 5 inhibitors, or à-blockers), the majority of men with PE are not satisfied with their results. New pharmacologic drugs develped specifically for the treatment of PE are undergoing evaluation in clinical trials. For example, recent clinical research studies have revealed on-demand administration of one such drug, dapoxetine, which achieved significant improvements in ejaculatory latency, control over ejaculation, and satisfaction with sexual intercourse. In addition, partners of men who received dapoxetine likewise reported improved satisfaction with sexual intercourse. Future studies may reveal that integration of pharmacologic drugs with psychologic and/or behavioral therapy techniques may be the optimal approach to the management of PE. PE is a treatable condition, and new drugs in development may provide benefits over those available.     

Preservation of Bile Ductules Mitigates Bile Duct Loss

The finer branches of the biliary tree (FBBT) contain a regenerative compartment. We hypothesized that preservation of the FBBT together with its microvasculature will lead to recovery of biliary damage and prolonged preservation of bile ductules during the development of chronic liver allograft rejection. The interlobular bile ducts, portal bile ductules and extraportal biliary cells with and without microvessels were studied in sequential biopsies in five patients who fulfilled the Banff criteria of early chronic rejection (CR) (imminence group). Biopsies of CR patients (n = 12) served as controls. Biopsies were double immunostained with CD34 (microvessels) and cytokeratin 7 (biliary structures). Proliferation and proangiogenic activity were assessed with Ki67 and VEGF-A immunostaining. Severe damage of bile ducts in the imminence group did not progress to significant bile duct loss. This was associated with a high proliferative activity in all biliary structures and preservation of the microvascular compartment. VEGF-A expression was increased in all but the reperfusion biopsies. In conclusion, both regenerative activity of the FBBT and an intact microvascular compartment are associated with less damage of the biliary tree and could therefore be prerequisites for biliary regeneration.