Imiquimod, a patient-applied immune-response modifier for treatment of external genital warts

Genital human papillomavirus infection is one of the most common sexually transmitted diseases. Imiquimod is a new agent, an immune-response modifier, that has been demonstrated to have potent in vivo antiviral and antitumor effects in animal models. The present prospective, multicenter, double-blind, randomized, vehicle-controlled trial evaluated the efficacy and safety of daily patient-applied imiquimod for up to 16 weeks for the treatment of external genital warts. Wart recurrence was investigated during a 12-week treatment-free follow-up period. In the intent-to-treat analysis, baseline warts cleared from 49 of 94 (52%) patients treated with 5% imiquimod cream, 13 of 90 (14%) patients treated with 1% imiquimod cream, and 3 of 95 (4%) vehicle-treated patients; the differences between the groups treated with vehicle and imiquimod were significant (P < 0.0001). For subjects who completed the follow-up period, recurrence rates after a complete response were 19% (9 of 48 patients) in the 5% imiquimod cream group, 17% (2 of 12) in the 1% imiquimod cream group, and 0% (0 of 3) in the vehicle-treated group. There were no systemic reactions, although local skin reactions (generally of mild or moderate severity) were common, particularly in the 5% imiquimod cream group. Local reactions caused two patients to discontinue treatment. The most frequently reported local skin reactions were erythema, excoriation or flaking, and erosion. Patient-applied 5% imiquimod cream is effective for the treatment of external genital warts and has a favorable safety profile.     

Correlates of peak expiratory flow rate: a study of sand stone quarry workers in desert

BACKGROUND: Pulmonary infections continue to be a major cause of morbidity and mortality in patients with sickle cell disease (SCD). METHODS: In this study cell-mediated immunity in vitro was evaluated in 62 SCD patients (62 steady state and 16 with acute pneumonia) and compared with 44 normal controls (30 healthy and 14 with acute pneumonia). Lymphocyte blastogenic responses to phytohemagglutinin, tetanus toxoid and Candida albicans antigen were assessed in all subjects. In addition production of tumor necrosis factor, alpha- and gamma-interferon (IFN) were assayed. RESULTS: The results revealed comparable blastogenic responses to all three stimuli in all subjects except SCD patients with pneumonia. This group showed poor responses to all stimuli. The mean counts per minute were decreased 65 to 90% when compared with the other patients. Cytokine production of IFN-alpha and TNF was equivalent in all subjects. Conversely IFN-gamma production in both SCD groups, steady state (35 +/- 6 U/ml) and SCD with pneumonia (14 +/- 6 U/ml), was significantly decreased when compared with those in normal healthy controls (65 +/- 14 U/ml) and with pneumonia (48 +/- 17 U/ml). On analysis of individual titers 15 of 62 (24%) steady state and 10 of 16 (63%) SCD patients with pneumonia were deficient in IFN-gamma production in vitro. CONCLUSIONS: Acute pulmonary infections seem to have a profound effect on cell-mediated immunity in SCD. IFN-gamma deficiency, along with quantitative and qualitative T cell abnormalities, may represent significant factors to explain the frequent and severe infections seen in SCD.     

Experimental pyeloureterectomy and calyceal neck transection with autotransplantation and bladder advancement

OBJECTIVE: To determine whether Dexon mesh, closely applied to the kidney, provides purchase for sutures to permit bladder/parenchymal apposition on autotransplantation and that, if this line of apposition were some distance from but surrounding renal papillae, urothelium would proliferate to cover exposed parenchyma to form a widely patent lumen; this should facilitate removal of the whole of an upper tract collecting system, retaining renal parenchyma alone. MATERIALS AND METHODS: To test this possibility and explore the practicability of the concept, nine dogs underwent bilateral nephrectomy followed by unilateral autotransplantation: the other kidney was discarded. Because the canine renal pelvis is intrarenal, the ureter was stretched maximally before passing fine scissors into the renal hilum to transect the collecting system as close to the kidney as possible in six of the nine dogs. In the remaining three dogs, partial nephrectomy was performed with division of the calyceal necks under vision. Thinned bladder wall was sutured to Dexon mesh some distance from the collecting tubules; omentum was applied to the suture line. RESULTS: Three dogs were killed prematurely at < 2 weeks because of perioperative complications. Four were killed at 2, 4, 5 and 8 weeks and two at 12 months. Dexon mesh proved to be an effective anchoring fabric, providing close apposition of bladder wall and parenchyma. There was no adhesion of the kidney to peritoneal contents. Urothelial proliferation to cover exposed parenchyma occurred early and by 12 months, a thin stroma was interposed between parenchyma and epithelium. The kidney was preserved in all but one removed electively, this dog having both cystitis and pyelonephritis at 12 months. CONCLUSIONS: This study showed that autotransplantation of a kidney after removal of its collecting system and advancement of thinned bladder wall to renal parenchyma is practicable, with regenerated urothelium bridging the deficiency by covering exposed parenchyma, to create a widely patent lumen.