Radiofrequency volumetric tissue reduction for treatment of turbinate hypertrophy: a pilot study

BACKGROUND: Apoptosis maintains cell homeostasis. Altered apoptosis is involved in carcinogenesis. It was our aim to investigate whether reflux esophagitis may alter apoptosis in the esophageal mucosa and whether antireflux surgery may restore normal apoptosis. METHODS: Apoptosis was studied preoperatively and postoperatively in esophageal biopsies of 39 patients with various grades of reflux esophagitis and in Barrett's mucosa using the TUNEL method. Biopsies were also taken from lesions of the squamous epithelium adjacent to the Barrett's mucosa. RESULTS: Apoptosis increased with the severity of esophagitis. Apoptosis was low in Barrett's epithelium. Squamous epithelium adjacent to Barrett's mucosa showed increased apoptosis. After surgery apoptosis decreased in squamous epithelium, and it remained low in Barrett's epithelium. CONCLUSIONS: Apoptosis in reflux esophagitis may be protective against increased proliferation. Low apoptosis following antireflux surgery indicates that surgery is effective to prevent reflux-induced cell proliferation. Inhibition of apoptosis in Barrett's may promote carcinogenesis. This may not change following surgery.     

Influence of chemical treatments on glutathione S-transferases of maize with activity towards metolachlor and cinnamic acid

The subcellular distribution of glutathione S-transferase (GST) activity extracted from shoots of 3-day-old etiolated seedlings of maize (Zea mays L., Northrup-King 9283 hybrid) and the induction of soluble and membrane-bound GST activity by the safener benoxacor, the herbicide metolachlor and their combination (CGA-180937) were investigated. GST activity extracted from maize shoots was detected in both cytosolic and microsomal fractions and utilized 1-chloro-2,4-dinitrobenzene (CDNB), metolachlor, and trans-cinnamic acid (CA) as substrates. Soluble GST activity extracted from maize shoots was greater than microsomal with CDNB or metolachlor as substrate. Membrane-bound GST activity was greater than soluble with cinnamic acid as substrate. Washing the microsomal preparations from maize shoots with Triton X-100 increased GST(CA) activity. Pretreatment with the safener benoxacor or a formulated combination of the herbicide metolachlor with benoxacor induced soluble GST(CDNB), GST(metolachlor) and GST(CA) activities in maize shoots. Benoxacor and CGA-180937 induced also membrane-bound GST(CDNB) and GST(CA) activities in maize shoots, but did not affect membrane-bound GST(metolachlor) activity. These results confirm that maize contains multiple GST isozymes that differ in their substrate specificity and inducibility by safeners or other chemicals.     

Prospective study of high grade anal squamous intraepithelial neoplasia in a cohort of homosexual men: influence of HIV infection, immunosuppression and human papillomavirus infection

OBJECTIVE: To determine the risk of developing high grade anal squamous intraepithelial neoplasia (HG-AIN) in relation to HIV infection and immunosuppression, after controlling for the effects of human papillomavirus (HPV) infection. DESIGN: Prospective cohort study of 158 HIV-seropositive and 147 HIV-seronegative homosexual men presenting to a community-based clinic with initially negative anal cytologic and colposcopic findings. METHODS: Subjects completed self-administered questionnaires, underwent cytologic screening, and standardized unaided and colposcopic examination of the proximal anal canal for presence of abnormalities suggestive of AIN. Anal specimens were screened for HPV DNA. RESULTS: HG-AIN developed in eight (5.4%) and 24 (15.2%) HIV-seronegative and -seropositive men, respectively. Risk of HG-AIN among HIV-seronegative men was associated with detection of anal HPV types 16 or 18 by Southern transfer hybridization (STH), detection of HPV 16 or 18 at the lower levels by polymerase chain reaction but not by STH, and with number of positive HPV tests; HG-AIN risk among HIV-seropositive men was associated with detection of HPV 16 or 18 only by STH, detection of HPV types other than 16 or 18, CD4 count < or = 500 x 10(6)/l, and number of positive HPV tests. HIV-induced immunosuppression remained an independent predictor of HG-AIN after adjusting for type and level of detection of HPV; HIV infection predicted HG-AIN risk after adjustment for number of positive HPV tests. CONCLUSIONS: The association of HG-AIN with HIV, independent of HPV type, level of HPV detection and number of positive HPV tests, suggests that this increased risk cannot be entirely explained by an effect of HIV on HPV detection. Future studies focusing on factors more specific to the local microenvironment in the anal canal should help clarify these issues.     

Outcome of plasma exchange therapy in thrombotic microangiopathy after renal transplantation

Thrombotic microangiopathy (TMA) in renal transplant recipients is commonly associated with calcineurin inhibitors (CNIs), though several factors such as vascular rejection, viral infections and other drugs may play a contributory role. We report a series of 29 patients with TMA, all of whom were on CNIs. Though plasma exchange (PEx) is widely used to treat TMA, therapeutic guidelines are not well defined. All our patients were treated with PEx and discontinuation of CNIs. Thrombotic microangiopathy was diagnosed at a median of 7 days post-transplant. The mean decrease in Hgb and platelets during TMA was 66% and 64%, respectively, and peak serum creatinine during TMA was 7.4 +/- 2.9 mg%. Mean duration of PEx therapy was 8.5 (range 5-23) days. Recovery of platelet count to 150K/mcL and Hgb to 8-10 g/dL were used as endpoints for PEx. Twenty-three/29 (80%) patients recovered graft function after PEx. Twenty/23 (87%) patients who recovered were placed back on CNl. Nineteen/20 (95%) patients tolerated reinstitution of CNl without recurrence of TMA. In post-transplant TMA, PEx was associated with a graft salvage rate of 80%, reversal of hematological changes can be used as the endpoint for PEx therapy and CNl can be reintroduced without risk of recurrence in the majority of patients.     

Martingales without tears

This pedagogical paper presents a casual introduction to martingales, or fair gambling processes. Our objective is to describe the concept of a martingale and its application to common statistical tests used in the analysis of survival data, but without the mathematical rigor required for formal proofs. We use heuristic arguments to demonstrate that the logrank statistic evaluated over followup time is a fair gambling process, and introduce some mathematical notation and terminology along the way. We then employ the counting process approach to show that the logrank statistic computed over followup time can be expressed as the difference of two martingale transforms, and thus is a martingale. These ideas are first time introduced in the context of a discrete time process, and are then generalized to a continuous time process. With slight modifications, the same idea extends from the logrank to other weighted Mantel-Haenszel statistics computed over time.