Randomized trial of bilateral oophorectomy versus tamoxifen in premenopausal women with metastatic breast cancer

A randomized clinical trial was performed to compare the efficacy of bilateral oophorectomy with that of tamoxifen at a dose of 10 mg twice daily in premenopausal women with metastatic breast cancer, and to examine the efficacy of each as a crossover treatment. Initial treatment responses were seen in ten of 27 patients (37%) treated with oophorectomy and seven of 26 patients (27%) treated with tamoxifen. The difference was not statistically significant. Crossover responses were seen in five of 15 patients (33%) treated with oophorectomy, including three responses in ten prior tamoxifen nonresponders; and two of 18 patients (11%) treated with tamoxifen. Time to progression distributions were not significantly different during initial treatment, and no significant differences in survival were noted. Thus, there was no overall disadvantage to the use of tamoxifen as opposed to oophorectomy as initial hormonal therapy, and a failure to respond to tamoxifen did not preclude a response to subsequent oophorectomy. Exploratory data analysis within subsets indicated consistent differential treatment effects in the visceral dominant patients. Of the 16 such patients treated with oophorectomy, eight (50%) experienced objective responses but there were no responses in the 14 patients treated with tamoxifen. In the nine visceral dominant crossover patients who had not responded to initial tamoxifen, three (33%) subsequently responded to oophorectomy. Time to progression distributions within the visceral dominant subset appeared to be better for the patients treated initially with oophorectomy. However, one must be very cautious in drawing conclusions from exploratory subset analyses, especially with the small sample size. Further studies would be required to test any hypothesis of differential organ site responsiveness.     

Induction of ultraviolet cataracts in vitro: prevention by pyruvate.

Ultraviolet (UV) radiation is one of the important cataract risk factors. The present studies examined the hypothesis that this effect is due to the UV penetration through the cornea and subsequent induction of a photochemical generation of reactive species of oxygen (ROS) in the aqueous and lens. The hypothesis was ascertained by rat lens organ culture studies conducted under UV (365 nm), with media containing micromolar levels of riboflavin, with and without pyruvate, the latter acting as an ROS scavenger. The implication of ROS in the UV-induced damage was confirmed by measurements of peroxide generation. Damage to the lens was assessed physiologically by measuring the decrease in its active transport of rubidium ions. Biochemically, it was assessed by measuring the lowering of adenosine triphosphate and glutathione. The incorporation of pyruvate in the medium protected the lens against these deleterious effects. That the beneficial effect of pyruvate is attributable to its ROS-scavenging property was proven by the peroxide depletion in its presence, commensurate with its own utilization in parallel. A protective effect of this keto acid against UV-induced tissue damage has been shown for the first time, suggesting its clinical usefulness against UV irradiation-induced pathologies. Hence, further studies on the possible protective effects of such alpha-keto acids against UV damage are in progress.     

Practical selection criteria for unenhanced cranial CT in patients with acute headache

We studied clinical predictors of cranial computed tomography (CT) abnormalities in patients with acute or acutely worsened headache. Data were collected from chart review of 333 consecutive patients presenting to an emergency department and who were clinically selected for cranial CT. Patients with a positive neurologic examination were at 10.7 times greater risk for a positive CT than the rest of the sample (p<1.5 – 10⁻¹⁰). Using only neurologic examination to select patients for CT would have missed 30.3% of the positive scans. The amnesia, depressed sensorium, and hypertension variables had CT yields approximating 10% or greater even in the presence of a negative neurologic examination. Together with a positive neurologic examination, these variables detected 87.9% of the patients in this sample with positive scans; their absence had a negative predictive value of 98.0%. Of the four patients with positive scans who would have been missed using this strategy, one was discharged directly from the emergency department anyway and the other three developed positive neurologic examinations within 24 hours. One died of causes unrelated to the intracranial pathology. Positive neurologic examination, hypertension, history of amnesia, or a depressed sensorium provide reasonable initial guidelines to select for CT patients with an acute headache.     

Octreotide as first-line treatment for women with metastatic breast cancer

Summary Octreotide is a synthetic somatostatin analogue which has shown inhibitory activity against human breast cancer cells in culture. Ten patients with metastatic breast cancer and no prior hormonal therapy exposure received octreotide at 150 g subcutaneously thrice daily. No objective responses were observed and the median time to treatment failure was short at 57 days.     

Awareness,attitude and action about family planning in villages in Maharashtra

A study undertaken in a randomly selected village with a population of 695, a majority of whom were agriculturalists or laborers living in huts or mud houses. All couples in the reproductive age group (125) were interviewed in their homes, husbands and wives separately. Couples belonged to Hindu, Muslim, and Scheduled Caste groups. Of the 250 respondents, 120 were literate. About 96% were aware that births could be prevented, with vasectomy and tubectomy the best known methods. Nearly all the respondents gave friends and relatives as the source of their information; family planning workers and posters were given as the source by less than 1/2. 86% of thoce aware of contraceptive methods found family planning acceptable, most expressing the idea that a small family was easier to raise. All of the 14% opposed to family planning were Muslims whose opposiition stemmed from their religious beliefs. 44 of the couples had adopted family planning -- 24 husbands having had vasectomies and 20 of the wives tubectomies. The reasons most often given for not accepting family planning were desire for more chidlren and fear of complications. Of the sterilized respondents, a large number of the men complained of side effects, and 5 of the women complained of excessive bleeding. All of those who expressed complaints said they would not recommend the operation. It is concluded that while awareness of family planning is at an acceptable level, the problem is to make family planning itself acceptable. 1 recommendation is that sterilized couples should receive special medical attention to make their experiences more positive.     

An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic breast cancer

Increased dietary fat intake and rate of breastepithelial cell proliferation have each been associated withthe development of breast cancer. The goal ofthis study was to measure the effect ofa low fat, high carbohydrate diet on therate of breast epithelial cell proliferation in womenat high risk for breast cancer. Women wererecruited from the intervention and control groups ofa randomized low fat dietary intervention trial, breastepithelial cells were obtained by fine needle aspiration,and cell proliferation was assessed in these samplesusing immunofluorescent detection of Ki-67 and PCNA. Theeffects of needle size and study group oncell yield and cytologic features of the cellswere also examined. Fifty three women (20 inthe intervention group and 33 in the controlgroup) underwent the biopsy procedure. Slides from 38subjects were stained for Ki-67 and from 14subjects for PCNA. No cell proliferation (fluorescence) wasdetected for either Ki-67 or PCNA in anyof the slides. Epithelial cell yield and numberof stromal fragments were greater with a largerneedle size. Numbers of stromal fragments and bipolarnaked nuclei were greater in the low fatas compared to the control group but nodifferences in epithelial cell yield were observed betweenthe two groups. This study confirms that fineneedle aspiration biopsy is a feasible method ofobtaining epithelial cells from women without discrete breastmasses, but suggests that cell proliferation cannot beassessed using Ki-67 and PCNA in such samples.     

Rhino-oculo Cerebral Mucormycosis with Multiple Cranial Nerve Palsy in Diabetic Patient: Review of Six Cases

AIM of the study is to evaluate etiopathogenesis role played by predisposing conditions (Diabetes, Immunosupression), precipitating factors (trauma/surgery/ketoacidosis) and possible role of occupational hazard is discussed briefly. Clinical presentation and management of patients presenting with rhinoorbitocerebral mucormycosis is discussed. The prospective study of patient undergoing treatment of mucormycosis] without control Setting was done in ENT Deptt. NSCB Medical College, Jabalpur (tertiary referral centre of mid India). Subject were patients presenting with invasive fungal rhino sinusitis presenting with orbital involvement and cranial nerve palsies undergoing treatment. The detailed history, clinical examination including cranial nerve examination, blood test, CTscan and biopsy. Nasal endoscopy, CWL surgery and medical management with 6 month follow up. All six patients were diabetic when evaluated on presentation. Two patients had ketoacidosis. Four had history of surgery in recent past. Blood stained nasal discharge and dysaesthesia of face are early warning signs. They had necrotic lesion in nose and infraorbital area with 2, 3, 4, 5, 6 and 7 cranial nerve involvement. Skin necrosis/Mucosal necrosis, facial palsy and diplopia signify advanced disease. Altered sensorium, panopthalmitis & diabetes complicated with ketoacidosis signify bad prognosis. In present study two patients with advanced disease, altered sensorium and ketoacidosis succumbed within 72 hours in spite of anti fungal medicine. Of the four surviving patients, all responded well to treatment but had residual sixth and seventh nerve palsy. One patient defaulted in diabetes control & had recurrence after 6 months. Early diagnosis, aggressive surgical debridement and proper management of underlying metabolic abnormality along with amphotericin B can avert the bad prognosis of rhinoorbitocerebral mucormycosis.