Comparison of the potential therapeutic effects of interleukin 2 or interleukin 4 secretion by a single tumour.

Engineering of a variety of rodent tumour cells to secrete either interleukin 2 (IL-2), or interleukin 4 (IL-4), has been demonstrated to reduce their tumorigenicity. However the mechanisms of action of secreted IL-2 and IL-4 have not been compared in a single rodent tumour. Here we demonstrate that the weakly immunogenic murine fibrosarcoma FS29 had reduced growth rate and in some cases was rejected by syngeneic animals, when modified to secrete either IL-2 or IL-4, but not IL-5. Immunohistochemical analysis of tumour nodules undergoing regression showed stimulation of a largely lymphocytic infiltrate by IL-2 and a macrophage and granulocyte infiltrate, with a small number of lymphocytes by IL-4. Indeed, secretion of low levels of IL-2 and IL-4 in combination resulted in optimal rejection, suggesting that the two cytokines might mobilise different and complementary effector cell mechanisms. Both IL-2 and IL-4-secreting cells failed to induce the rejection of admixed, unmodified FS29 cells. The loss of cytokine secreting cells from such admixtures occurred more rapidly for IL-2-secreting cells. Injection of IL-4-secreting, but not IL-2-secreting FS29 cells could protect mice from a delayed challenge with unmodified FS29 cells. These data suggest that IL-4 secretion stimulates the better long-term host anti-tumour response.     

Fournier''s gangrene of the scrotum following day case vasectomy.

A case of Fournier's gangrene of the scrotum is reported in a 31-year old man who had outpatient vasectomy during an intercurrent diarrheal illness. The surgery was done through a midline incision, under local anesthesia of plain 2% lignocaine, with a preoperative chlorhexidine scrub. Although his scrotum was red and swollen within 3 hours, he did not have medical care until admission to hospital 48 hours later. At admission he had Fournier's gangrene of the scrotum and penis, Gram-negative septic shock, and acute renal failure. In the intensive care unit he was treated with continuous dialysis, parenteral metronidazole, benzylpenicillin, Ceftazidime and inotropes. He had a cardiorespiratory arrest after emergency radical debridement. After resuscitation he developed adult respiratory distress syndrome and disseminated intravascular coagulation. Pathological exam showed necrosis of the dermis and subcutaneous layers, thrombosis and beta-hemolytic streptococci. After adding gentamicin and vancomycin, 2 weeks of ventilator care, 4 more surgical debridements, a left orchidectomy, and a despite a grossly abnormal EEG recording, the man regained consciousness and recovered. His scrotal and penile skin re-epithelialized over 3 months. Patients requesting vasectomy should be assessed for local and systemic illness before performing the procedure.     

Nasopharyngeal glioma: A unique presentation in infants

Despite the complex embryological development of the nose and surrounding structures, significant developmental nasal anomalies are rare. Of the various anomalies like-nasopharyngeal cysts, hairy polyps, dermoids, haemangiomata, fibromas, mucocoeles, lipoma, aplasias. We are presenting a rare case of Heterotopic Brain Tissue in the nasopharynx. This 1.5-month-old patient was operated through transpalatal route and mass excised. Histopathologicaly it consisted of various central nervous tissue elements. Seven months post surgery patient is thriving well.     

Trigger fingers and thumb: when to splint, inject, or operate.

Fifty trigger fingers were treated by splinting of the metacarpophalangeal joint at 10 to 15 degrees of flexion for an average of 6 weeks (range, 3 to 9 weeks). Another 50 trigger fingers were injected with 0.5 ml of betamethasone sodium phosphate and acetate suspension (Celestone) and 0.5 ml of lidocaine. All patients were followed up for a minimum of 1 year (range, 1 to 4 years). Treatment was successful in 33 (66%) of the splinted digits and 42 (84%) of the injected digits. Fifty percent of the 10 splinted thumbs and 70% of the 40 splinted fingers had a successful outcome. Of the 17 unsuccessfully treated digits in the splinted group, 15 were later cured with injections and 2 required surgery. All of the 7 unsuccessfully treated digits in the injected group were cured with surgery. Patients with marked triggering, symptoms of more than 6 months' duration, and multiple involved digits had a higher rate of failure in both groups. Splinting offers an alternative for patients who have a strong objection to cortisone injection.     

Human breast cancer cells contain a phosphoramidon-sensitive metalloproteinase which can process exogenous big endothelin-1 to endothelin-1: a proposed mitogen for human breast fibroblasts.

Endothelin-1 (ET-1) levels are elevated in human breast tumours compared with normal and benign tissues, and in the presence of insulin-like growth factor 1 (IGF-I) ET-1 is a potent mitogen for human breast fibroblasts. In this study we have examined the ability of intact human breast cancer cell lines to process exogenously added big ET-1 (1-38) to the active mature ET-1 peptide by using a specific radioimmunometric assay. In both hormome-dependent (MCF-7, T47-D) and hormone-independent (MDA-MB-231) breast cancer cell lines the putative endothelin-converting enzyme (ECE) exhibited apparent Michaelis-Menten kinetics when converting added big ET-1 to ET-1. Both basal ET-1 production and exogenously added big ET-1 to ET-1 conversion were greatly reduced in all three cell lines in response to the metalloproteinase inhibitor phosphoramidon but were insensitive to other classes of protease inhibitors. Inhibition was also observed when cells were incubated in the presence of the divalent cation chelators 1,10-phenanthroline and EDTA. In MCF-7 cells the optimal pH for the ECE activity using a saponin cell permeabilisation procedure was found to residue within a narrow range of 6.2-7.26. Our results indicate that human breast cancer cells contain a neutral phosphoramidon-sensitive metalloproteinase which can process big ET-1 to ET-1. In the breast this conversion could contribute substantially to the local extracellular levels of this proposed paracrine breast fibroblast mitogen.     

单纯2型糖尿病患者的风险分层：对冠状动脉钙化成像联合选择性心肌灌注成像的前瞻性评价

目的:确定在单纯2型糖尿病患者中亚临床动脉粥样硬化和心肌缺血的患病率和临床预测因素,并评价其与近期临床预后的关系。方法和结果:以501例无心血管疾病史的无症状2型糖尿病患者(年龄53±8岁,61%为男性)为研究对象,前瞻性检测受试者的已知危险因素和冠状动脉钙化(CAC)评分。所有CAC评分>100Agatston单位(AU)的患者(n=127)以及CAC≤100AU患者中的随机抽样(n=53),接受心肌灌注成像(M PS)检查。46.3%的患者有明显的CAC(>10AU)。在中位期为2.2年的随访(IQR1.9～2.5)中,共发生20例次事件,分别为2例冠状动脉性死亡、9例非致死性心肌梗…