T-cell tolerance and autoimmunity in transgenic models of central and peripheral tolerance

Experiments with transgenic mice expressing genes encoding both antigens in defined tissues and T-cell receptor genes of known specificities have enhanced our understanding of the mechanisms involved in the pathogenesis of autoimmune states. They have also shed light on the means by which potentially autoreactive cells may be prevented from exerting their autoaggressive potential. The value of the transgenic approach is that it can overcome the low frequency of peptide-specific T cells occurring in normal animals, and also provide a tissue-specific, cognate antigen that is absent in controls. These factors allow reactive T cells to be isolated or quantified by flow cytometry and their responses to antigen in vitro and in vivo be defined.     

Is there an abnormal fasting duodenogastric reflux in nonulcer dyspepsia?

A quantitatively and/or qualitatively abnormal duodenogastric reflux (DGR) could be involved in the pathogenesis of nonulcer dyspepsia (NUD). The aims of this prospective study were to look for (1) a pathological DGR profile during fasting and (2) an eventual correlation between DGR profile and clinical symptoms. Twenty-six NUD patients were investigated. Seven other operated patients with a surgical procedure facilitating DGR episodes and 27 healthy volunteers served as control groups. A clinical score was determined for each patient from a standardized questionnaire. Gastric aspiration was performed for 6 hr in fasting subjects. The aspirates were pooled into 17 samples. In each sample the concentration and the output of total bile acids was determined. If the concentration was larger than 30 mol/liter in pooled samples, the concentrations of free bile acids and the distribution of the conjugated bile acids was determined. The percentage of aliquots with a total bile acid concentration larger than 50 mol/liter (without upper limit), and the percentage with a concentration larger than 2500 mol/liter was also obtained. No significant difference was demonstrated between the healthy volunteers and NUD patients, whatever the parameter considered. However, there was a significant increase in each of the quantitative parameters for the group of operated patients in comparison with the NUD patient group. No significant correlation was found between the clinical score and the DGR profile in NUD patients. Apparently, DGR episodes do not play a primary role in the pathogenesis of NUD.Part of this work was presented at the 4th European Symposium on Gastrointestinal Motility, Krakow, Poland. September 22–24, 1988.Hepatogastroenterology, 35:178, 1988 (abstract).     

Assessment of Photoinduced Frontal Polymerization Processes for a Stable 1K System

Frontal polymerization (FP) has attracted increasing interest in recent years in various applications. This polymerization method can be very promising for the polymerization of thick materials with high fillers content in the range of 50–80% (weight) by local application of a reasonable amount of energy. In this work, recent advances in controllable and predictive behavior for photoinduced frontal photopolymerization are reported. Here, tert-butyl peroxybenzoate (Luperox-P) is selected to initiate thermal polymerization at depth because its high polymerization ability and its decomposition temperature is in a promising range, i.e., neither extremely high (monomer decomposition) nor very low (storage stability issues). Thermal imaging experiments are used to follow the temperatures in the samples in real time. The number of cured layers and the depth of cure are also determined. This paper investigates various factors such as the contents of both photo and thermal initiators, the light intensity, the fiber contents, the irradiation time, etc., resulting in a statistical design of experiments with the factors: 1) content of Luperox P and 2) the irradiation time used to investigate the influence on photoinduced frontal polymerization. Markedly, FP appears to be fully controllable for a storage-stable, tunable 1K system.     

Indocyanine green angiography of choroidal tumors

Background: Fluorescein angiography (FA) has been widely used in the diagnostic evaluation of cboroidal tumors. Indocyanine green angiography (ICG-A), which permits better visualization of choroidal vasculature than FA, has been recently introduced into clinical practice. Only few reports exist on the ICG-A characteristics of choroidal tumors. Methods: The fluorescein and indocyanine green angiograms of 61 patients were assessed. These included 14 patients with choroidal nevi, 30 with malignant melanomas, 7 with suspected melanomas or atypical nevi, 5 with hemangiomas and 5 with metastases. Results: The outline of pigmented tumors was more accurate on ICG-A than on FA. Characteristic patterns were seen in all intra-ocular tumors with ICG-A, so it was possible to distinguish hemangiomas from malignant lesions. Characteristic features of malignant melanomas include abnormal vascular pattern and marginal late dye leakage. None of the benign lesions showed these features. In suspected melanomas, the presence of abnormal choroidal vascular patterns and/or late dye leakage on ICG-A may indicate malignancy. Conclusion: The study suggests that ICG-A can yield additional information that is useful in differentiating amongst choroidal tumors. Better delineation of pigmented lesions with ICG-A allows more accurate treatment planning and follow-up.     

Comparison of survival among patients with breast cancer treated at First Teaching Hospital,Changchun, China,and Saint-Sacrement hospital,Quebec, Canada

The aim of this study was to compare the survival of 116 patients with breast cancer initially treated at the First Teaching Hospital (FTH) of Norman Bethune University of Medical Sciences located in Changchun, China, from 1986 to 1991 with the survival of 886 patients seen in the “Hipital du Saint-Sacrement” (HSS) located in Quebec City, Canada, from 1987 to 1992. The clinical data were collected from the hospital records at FTH. The vital status for Chinese patients was obtained from letters of follow-up or the records of local police offices. The list of patients treated at HSS and the data for each woman were extracted from computerized data banks. The major variables studied included age at diagnosis, tumor size at pathology (cm), number of lymph nodes involved, breast surgery and adjuvant treatments of breast cancer (chemotherapy, radiotherapy, immuno-therapy). Age at diagnosis was substantially lower among patients with breast cancer seen at FTH compared to those treated at HSS (x) ₁ ² =60.95,P<0.0001). The average age at diagnosis for Chinese women was about 10 years less than that for Canadian women. Patients in the two hospitals differed with respect to tumor size at pathology (x ₂ ² =6.67,P=0.036). The proportion of patients with tumor size larger than 2.0 cm was larger at FTH (48.3%) than at HSS (41.1%). The mean tumor size at pathology was 3.0 cm (standard deviation =2.1 cm) for patients treated at FTH, but 2.6 cm (standard deviation=1.8 cm) for women treated at HSS (P=0.07). The proportion of women with lymph node involvement was greater at FTH (61.1 % than that at HSS (37.3%) (x ₁ ² =16.51,P<0.0001). Surgical treatment of breast cancer varied considerably. In Changchun, radical mastectomy was frequent for any stage of breast cancer patients, but partial mastectomy was never performed. The situation was reversed in Quebec. The five year observed survival was 74.2% (standard error, 0.05) among breast cancer patients seen at FTH compared to 76.0% (standard error, 0.02) among women treated at HSS. After adjustments of confounding factors, there were no significant difference in five year observed survival between the patients treated at the two hospitals (P=0.42).     

Obesity and subcutaneous fat patterning in relation to survival of postmenopausal breast cancer patients participating in the DOM-project

Summary The effect of obesity and fat distribution on survival of breast cancer patients was studied prospectively in 241 women with a natural menopause who participated in a breast cancer screening project, the DOM-project in Utrecht, The Netherlands. Mean follow-up time was 9.1 years and endpoint of interest was death from breast cancer. Fat distribution was assessed by contrasting groups of subscapular and triceps skinfold thickness.No significant differences in survival time between more obese (Quetelet's index 26 kg/m²) and leaner (Quetelet's index < 26 kg/m²) patients or between patients with central fat distribution and patients with peripheral fat distribution were observed. Analyses were stratified by axillary node status, estrogen receptor status, and way of detection (by first screening or afterwards). Results of the stratified analyses were suggestive of a modifying effect of these factors.The absence of an association between obesity and survival time might be explained by two counteracting mechanisms. On the one hand obesity might be related to impaired survival, due to a tumor growth promoting effect of extra-ovarian estrogens. On the other hand obesity might be related to improved survival in a screened population, because obese patients profit more from screening by earlier detection of tumors than leaner counterparts.     

Interventional Radiology for Treating Soft Tissue Sarcomas

The role of interventional radiology for soft tissue sarcomas is only occasionally addressed in the literature. However, different techniques such as embolization, selective chemotherapy, chemoembolization, and acrylic cement osteoplasty can be helpful with the primary tumor, recurrences, and metastases. This article discusses these techniques and their complications in treatment of soft tissue sarcomas.     

Examination of resistance of the lens capsule against the waterjet

BACKGROUND: Although cataract surgery is highly developed today, there are still problems such as secondary cataract. In polishing the posterior capsule lens, epithelial cells often remain, causing secondary cataracts. Additionally, there are the problems of tissue heating and endothelial cell loss during phacoemulsification by ultrasound. This could be another field for improvement of cataract surgery by using the waterjet. METHODS: After removing the cornea of freshly enucleated porcine bulbs, we used the water jet from 4 to 12 bar. The hit angel on the capsule varied between 45 degrees and 90 degrees. RESULTS: Rupture of the posterior capsule occurred at a mean of 8.5 bar using the jet at 45 degrees and a mean of 8.6 bar using the jet at 90 degrees. CONCLUSION: The waterjet pressure should not be over 4 bar during polishing of the posterior capsule.     

Inducible nitric oxide synthase activity of cloned murine microglial cells

Nitric oxide (NO) is a short-lived diffusable molecule now believed to participate in multiple physiologic functions in the CNS including neurotransmission and the maintenance of vascular tone. Previously, we reported that cell lines obtained by retroviral immortalization of tissue macrophages (M?;) could be induced to synthesize nitrite (NO), a stable end product of the NO synthetic pathway. We have further characterized the induction and activity of this pathway in a panel of seven microglial clones derived from primary embryonic mouse brain cultures. Like M?;, these clones were found to release high levels of NO_-² in response to recombinant interferon-γ (rIFN-γ) as a priming signal together with either bacterial lipopolysaccharide (LPS) or exogenous recombinant tumor necrosis factor-α (rTNF-α). As previously demonstrated for M?;, phagocytosis of zymosan particles during induction of enzyme activity enhanced subsequent NO production, which is of interest in light of the postulated phagocytic role of microglia within the CNS. Biochemical characterization of enzyme activity in intact microglial clones and in isolated cytosolic fractions indicates that the microglial NO synthase present in these murine cell clones represents the M?;-like isotype. These findings suggest that microglial cells could represent a major source of NO within the CNS.     

Jacques Lisfranc 1790–1847

Jacques Lisfranc was born in Saint-Paul-Jarrest (Loire), France, April 2nd, 1790, the son of a physician. Early in his youth he demonstrated a particular interest and aptitude for the field of medicine as he observed and commented upon his father's ministrations to his patients. He accomplished his preliminary studies at the Lyceum in Lyons and then went to Paris to continue his medical training at the Hôtel-Dieu. It was there that he came under the tutelage of Dupuytren. It was soon said that Lisfranc was at least as worthy as his superior. Later the two men developed a certain animosity toward each other which became manifest rather severely in the medical political arenas of the time. Lisfranc received his doctorate of medicine in 1812 at a time that France was involved in the Napoleonic wars. He was commissioned as a surgeon and distinguished himself in campaigns in Saxony and in France. Following the war he established his practice in Paris. Fortuitously, one day Lisfranc rescued a magistrate who fell from his horse. By this serendipitous meeting Lisfranc was invited to join the faculty of medicine at the Hospital of Pity. He rose rapidly to chief of surgery and developed the reputation of being extremely competent, truly a master surgeon. For over 20 years he was affiliated with that institution and wrote numerous articles on such diverse subjects as shoulder disarticulation, the application of the stethoscope in the diagnosis of fractures, and on diseases of the uterus. In addition, he wrote two books which were well received—one onSurgery at the Hospital of Pity and the other onOperative Medicine. ThisClassics presentation has been selected because it has been generally attributed that Lisfranc was the first person to remove a cancerous tumor from the rectum. The technique involves essentially a transanal approach. As was the custom of the day, the report appears as narrated presumably by one of his assistants. Among the many distinctions Lisfranc achieved, he was founding member and ultimately President of the French Academy of Medicine and Chevalier of the Legion of Honor. Lisfranc developed an enormous clinical practice, and in spite of many physical infirmities he persisted in his surgery until the day of his death, May 12, 1847, at the age of 57.