Defining the roles of perforin, Fas/FasL, and tumour necrosis factor alpha in T cell induced mucosal damage in the mouse intestine.

BACKGROUND AND AIMS: Mucosal flattening and epithelial cell apoptosis are typical features of T cell induced inflammatory diseases of the bowel, such as coeliac disease and graft versus host disease. Mice injected with a T cell activating anti-CD3 antibody develop a severe diarrhoeal illness. We describe the histological features of this enteropathy and define the effector mechanisms involved in T cell induced mucosal injury in this in vivo model. METHODS: Wild-type and genetically modified mice were injected with the anti-CD3 antibody 3C11 (50 microg). Changes in the murine intestine were characterised by light microscopy analysis and terminal uridine nick-end labelling (TUNEL) assay. The role of perforin, Fas/Fas ligand (FasL), tumour necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) in T cell induced mucosal damage was assessed using selected immunodeficient mouse strains. RESULTS: T cell activation caused severe damage, including small intestinal mucosal flattening and apoptosis of crypt epithelial cells. Mucosal damage was unaltered in anti-CD3 treated mice lacking IFN-gamma, Fas, or TNF-alpha receptors. In mice lacking TNF-alpha receptors and Fas (TNF-R1xR2 lpr/lpr strain), enterocyte apoptosis was diminished but there was no significant reduction in tissue damage. Apoptosis and mucosal injury were significantly reduced in perforin knockout mice. Abrogation of both FasL and perforin (perforin KOxgld mice) further significantly reduced tissue damage and apoptotic bodies. CONCLUSIONS: T cell induced mucosal injury is mediated by the combined effect of multiple pathways but predominantly by perforin. The redundancy of the mechanisms of tissue damage will have significant impact on therapeutic strategies aimed at specific and targeted inhibition of inflammatory processes.

Childhood cancer in the south Asian population of England (1990-1992).

Cancer incidence in 1990-92 among English south Asian (residents with ethnic origins in India, Pakistan or Bangladesh) and non-south Asian children is compared. Standardized incidence ratios show significant overall excesses in south Asians (131), largely due to higher rates in south Asian boys, and specific excesses for leukaemia (141), lymphoid leukaemia (141), lymphoma (172) and hepatic tumours (375). Aetiological investigation is required.

Cancer incidence in the south Asian population of England (1990-92).

Cancer incidence among English south Asians (residents in England with ethnic origins in India, Pakistan or Bangladesh) is described and compared with non-south Asian and Indian subcontinent rates. The setting for the study was areas covered by Thames, Trent, West Midlands and Yorkshire cancer registries. The study identified 356 555 cases of incident cancer (ICD9:140-208) registered between 1990 and 1992, including 3845 classified as English south Asian. The main outcome measures were age specific and directly standardized incidence rates for all cancer sites (ICD9:140-208). English south Asian incidence rates for all sites combined were significantly lower than non-south Asian rates but higher than Indian subcontinent rates. English south Asian rates were substantially higher than Indian subcontinent rates for a number of common sites including lung cancer in males, breast cancer in females and lymphoma in both sexes. English south Asian rates for childhood and early adult cancer (0-29 years) were similar or higher than non-south Asian rates. English south Asian rates were significantly higher than non-south Asian rates for Hodgkin's disease in males, cancer of the tongue, mouth, oesophagus, thyroid gland and myeloid leukaemia in females, and cancer of the hypopharynx, liver and gall bladder in both sexes. The results are consistent with a transition from the lower cancer risk of the country of ethnic origin to that of the country of residence. They suggest that detrimental changes in lifestyle and other exposures have occurred in the migrant south Asian population.

An assessment of the Nam Pehchan computer program for the identification of names of south Asian ethnic origin.

BACKGROUND: An assessment was made of the usefulness and accuracy of a computer program for the identification of the south Asian population through the classification of names on a disease register. METHODS: The computer program, Nam Pehchan, was used to classify names as either south Asian or non south Asian. The results were compared with a reference standard, which combined use of the program with visual inspection. The latter was facilitated by a computer-generated dictionary of common non south Asian names. The data set consisted of 356,555 cases of incident cancer (ICD9: 140-208) registered between 1990 and 1992 by Thames, Trent, West Midlands and Yorkshire cancer registries. RESULTS: Nam Pehchan classified 5506 cases as south Asian. Visual inspection identified 2024 false positives (36.8 per cent of all cases identified as south Asian by Nam Pehchan) and 363 false negatives (9.5 per cent of those identified by the reference standard). Compared with the reference standard, Nam Pehchan had a sensitivity of 90.5 per cent and a positive predictive value of 63.2 per cent. CONCLUSION: The Nam Pehchan program quickly identified a high proportion of the names classified as south Asian by the reference standard, but the high false positive rate means that the program alone is not an adequate single strategy. The time-consuming process of inspection of program negatives for large data sets can be substantially reduced by comparison with dictionaries of common non south Asian names.

[Personal experience in the care of thoracic war injuries 1992-1993]. / Nasa iskustva u zbrinjavanju ratnih povreda grudnog kosa u 1992-1993. godini.

The aim of this paper was to clear some dilemmas about the surgical treatment of chest injuries. In the period April 1992-December 1993 in the General Hospital of Foca 160 chest injuries were treated (71 penetrating and 89 unpenetrating injuries) that was 10.2% of the total number of injuries. The explosive injuries were 53.8% of cases and 46.2% sclopetary injuries. Those injuries dominated in 93 wounded and in 57 cases the injuries were associated. The isolated injuries were in 40% and combined ones in 60% of cases. Thirty five thoracotomies and 40 thorax drainages were done while on the rest of the wounded only surgical wound treatment was performed. The active immunization and antibiotic prophylaxis were performed on the wounded. The infection problem was present in one operated person and lethality rate was 4.4%. The treatment results were good due to the appropriate organization of the surgical service and timely primary specialist aid as well as sufficient quantity of blood and timely and adequate surgical procedure.

[Use of acupuncture in the treatment of primary dysmenorrhea]. / Primena akupunkture u lecenju primarnih dismenoreja.

Acupuncture was applied in the treatment of 32 patients with primary dysmenorrhea. Different acupuncture points on several channels were stimulated, depending on shi or xu types. The therapy proceeded in sessions for three consecutive days before the expected menstruation, in the course of three consecutive cycles. A relief of dysmenorrheic pain was already evidenced after the first menstruation. One year after the completed therapy there was a full disappearance of dysmenorrheic pain in 93% and a partial one in 7% of cases.

[Cervical mucus before and after cryotherapy of benign changes in the vaginal part of the cervix uteri]. / Cervikalna sluz pre i posle krioterapije benignih promena na vaginalnom delu grlica maternice.

Bacteriological findings obtained by the Cryo-method of cervical smears before and after the treatment of cervicitis and ectopia in the vaginal part of the uterine cervix of 64 women revealed certain essential changes. Before the Cryo-therapy, pathogenic microorganisms were verified in 49 patients (76.56%), while saprophytic flora was isolated from 15 patients (23.45%). After the treatment, this proportion was significantly changed: saprophytic flora was isolated from 45 patients (70.34%), while pathogenic flora continued persisting in 19 patients (29.67%). Eight weeks following the treatment, instead of a dense, non-elastic, opaque, cellular secretion before the Cryo-therapy, a clear elastic, acellular mucus was recorded.