Prospective study of 100 cases of underlay tympanoplasty with superiorly based circumferential flap for subtotal perforations

Objective

Underlay Tympanoplasty with superiorly based circumferential flap for dry subtotal perforations.

Study Design

A prospective study of cases with dry subtotal perforations, which underwent surgery between August 2001–Feb. 2004.

Setting

Study was conducted on patients attending ENT OPD in S.M.S. Medical College and Hospital from August 2001–Feb. 2004 with dry subtotal perforations.

Results

It was noted that 89% of the cases were in the age group of 11 to 40 years, while one case was of 7 years of age and 9% of cases were between the age of 41–50. 50% of the cases had dry ear for less than 3 months while 75% of cases had dry ear for less than 1 year. Graft take rate was 97% with completely healed tympanic membrane. Rejection of the graft was observed in 2% of the cases. Hearing gain of 10–30dB was achieved in 95% of the cases. 7% of the cases suffered minor complications like otitis media with effusion (2%) retraction (2%) and lateralization (1%).

Conclusion

Duration for which ear has been dry did not affect the results. 49% of cases had dry ear for less than 3 months, with good graft take up rate and hearing gain. Pneumatization of mastoids, had a direct relationship with, post operative hearing gain, which ranged from 10–30 dB, in 95% of the cases. We observed, 97% graft take rate. Rejection of the graft was found in only 2% of the cases. 97% of the graft take rate and good hearing gain in our study can be correlated with expertise technique to deal with subtotal perforations.     

Androgen and c-Kit receptors in desmoplastic small round cell tumors resistant to chemotherapy: novel targets for therapy

Purpose Desmoplastic small round cell tumor (DSRCT) is a highly fatal, mainly peritoneal cell origin cancer which predominantly affects young adult males. This predilection in young males led us to examine the role of androgen receptors (AR), testosterone, and growth factors in the biology of DSRCT. Methods Slides were prepared from 27 multi-institutional patients all with end-stage DSRCT. Slides were stained for AR, c-Kit, various growth factors, and drug resistance-associated proteins. Immunohistochemical (IHC) expression was scored semi-quantitatively. Western blot and MTT studies were performed to validate the IHC findings of over-expression of the AR and its functional status by stimulation of growth by dihydrotestosterone, respectively. Six patients with positive AR status were treated solely with combined androgen blockade (CAB) as used for prostate cancer. Results Twenty-two patients were male (81%) and five were female (19%) with a median age at diagnosis of 23. All patients had failed at least two prior multi-agent chemotherapy regimens and 44% had progressed after autologous stem cell transplant. DSRCT samples from 10 of 27 patients were ≥2+ IHC positive for AR (37%,P = 0.0045) and 7 of 20 patients were ≥2+ IHC positive for c-Kit (35%, P = 0.018). We found elevated IHC expression of GST-pi, MRP and thymidylate synthase in smaller subsets of patients. In vitro studies for AR by Western blot and stimulation of growth by dihydrotestosterone in MTT assays suggest that the AR in DSRCT cells is functional. Six patients with positive AR status were treated with CAB alone and three of six attained clinical benefit (1-PR, 1-MR, 1-SD) in a range of 3–4 months. The three patients who responded to CAB had normal testosterone levels before CAB, while the three who did not respond to CAB had baseline castrate levels of testosterone. Conclusions DSRCT has significant IHC expression of AR and c-Kit in heavily pre-treated patients. The presence of significant AR expression in 37% suggests that these patients could possibly respond to CAB. The significance of c-Kit expression in 35% of DSRCT patients is unknown and warrants further investigation.     

A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer

PURPOSE: Intravenous amifostine 200 mg/m2 reduces xerostomia in head-and-neck cancer patients. This Phase II study evaluated subcutaneous (s.c.) amifostine in a similar patient population. PATIENTS AND METHODS: Patients received amifostine 500 mg, administered as two 250-mg s.c. injections 60 min before once-daily radiation for head-and-neck cancer (50-70 Gy in 5-7 weeks). The primary endpoint was the incidence of > or =Grade 2 acute xerostomia. RESULTS: Fifty-four patients received s.c. amifostine and radiotherapy. The incidence of > or =Grade 2 acute xerostomia was 56% (95% CI, 43-69%) and the incidence of > or =Grade 2 late xerostomia at 1 year was 45% (95% CI, 29-61%). The incidence of acute xerostomia was lower than reported previously with no amifostine in a controlled study; rates of acute xerostomia were similar between s.c. and i.v. amifostine in the two studies. The rate of late xerostomia with s.c. amifostine was intermediate between rates for i.v. amifostine and no amifostine, and not statistically significantly different from either historical control. Grades 1-2 nausea and emesis were the most common amifostine-related adverse events. Grade 3 amifostine-related adverse events reported by >1 patient included: dehydration (11%); rash (6%); and weight decrease, mucositis, dyspnea, and allergic reaction (each 4%). Seven patients (13%) had serious cutaneous adverse events outside the injection site. One-year rates of locoregional control, progression-free survival, and overall survival were 78%, 75%, and 85%, respectively. CONCLUSIONS: Subcutaneous amifostine provides a well-tolerated yet simpler alternative to i.v. amifostine for reducing acute xerostomia in head-and-neck cancer patients.     

Simple options for improving signal detection in antidepressant clinical trials

Objective: Previous experience with antidepressant studies highlight the difficulties in discriminating an effective drug from placebo. In hopes of improving signal detection, three easy-to-implement methodologies were employed during the development of a recently approved antidepressant. Experimental Design: Results from alternative and traditional methods could be compared directly because most studies employed both methods. This database included 11 double-blind, placebo-controlled trials (some with multiple dose arms and/or active comparators) yielding 22 treatment arms of antidepressants at or above the minimally effective dose noted in their U.S. labels. Principal Observations: Results agreed with the previous evidence showing that the performance of a likelihood-based, mixed-effects model repeated measures (MMRM) analysis was superior to that of analysis of covariance with missing values imputed using the last observation carried forward (LOCF) approach; MMRM correctly identified drug as superior to placebo in 14/22 (63.6%) comparisons versus 11/22 (50.0%) for LOCF. In agreement with previous studies, use of subscales of the Hamilton Depression Rating scale (HAMD) improved signal detection compared to the HAMD total score. Using MMRM with HAMD subscales correctly identified drug as superior to placebo in up to 17/22 (77.3%) comparisons. Excluding double-blind, placebo lead-in responders did not increase the frequency of correctly identifying drug-versus-placebo differences. Conclusions: The 22 drug-versus-placebo comparisons in this report offer a small amount of evidence and therefore may not be convincing on their own, although results do agree with previous research. Researchers may be able to take advantage of these easy-to-implement methods while we wait for further improvements in other areas.     

Potential role of isoketals formed via the isoprostane pathway of lipid peroxidation in ischemic arrhythmias

Unabated reactive oxygen species (ROS) are potentiated by an ischemia-induced shift in anaerobic metabolism, which generates superoxide anion upon reperfusion and reintroduction of oxygen. ROS can modify protein structure and function in fundamental ways, one of which is by forming reactive lipid species from the oxidation of lipids. In this review, we discuss these pathways and discuss the literature that shows that these species can produce dramatic effects on cardiac ion channel function (eg, Na+ channel function). Furthermore, we review what is known about the generation of such in the highly remodeled post myocardial infarction substrate. We suggest prevention of adduction of these highly reactive compounds would be antiarrhythmic.