Expression of differential nitric oxide synthase isoforms in human normal gastric mucosa and gastric cancer tissue

The present study investigated the expression and distribution of three isoforms of nitric oxide synthase (NOS) in different anatomical regions of the human stomach and in gastric neoplastic tissues by immunohistochemistry using specific antibodies. Intracellular localization of individual isoenzymes of NOS was detected in normal gastric mucosa. Gastric cancer tissues had a marked reduction of all three NOS isoforms expression. The expression of the endothelial NOS, neuronal NOS and inducible NOS in the tumor tissue was significantly lower than in normal gastric mucosa (P = 0.01, P = 0.02, P < 0.01, respectively). In the tumor tissue the expression of inducible NOS was significantly lower than the expression of both constitutive forms of NOS (P < 0.01). There was a tendency to higher expression of both constitutive forms of NOS in earlier stages T2 of the tumor compared to advanced T4 tumor. In contrast, the expression of inducible NOS was higher than in the advanced T4 tumor than in the earlier stages T2 of the tumor. The mapping of the expression of endothelial NOS, neuronal NOS and inducible NOS in human stomach showed higher expression of NOS isoforms in the distal third than in the proximal third of the stomach (P = 0.03, P = 0.04, P = 0.01, respectively). We conclude that there is greater expression of NOS in the stomach corpus and in antrum than in the proximal third of the normal human stomach mirroring the anatomical predilection of common pathological changes in this part of the human stomach. Furthermore, there was loss of the expression of individual isoenzymes in gastric neoplasms.      

Factors predictive of response and survival in patients with metastatic colorectal cancer in Taiwan

5-Fluorouracil in combination with leucovorin has been shown to be active in therapeutic trials of metastatic colorectal carcinoma. In this study, we administered these drugs to 72 patients with metastatic colorectal carcinoma. Thirty-six of them without previous exposure to 5-fluorouracil were treated with weekly bolus injections of 5-fluorouracil (425 mg/m2) and leucovorin (25 mg/m2) supplemented with oral levamisole. Another 36 patients with or without prior 5-fluorouracil treatment received 5-fluorouracil 3,000 mg/m2 and leucovorin 300 mg/m2 in a 48-hour continuous infusion every two weeks. Clinical efficacy and toxicity were assessed by WHO criteria. Variables were tested for relations to response and survival by univariate and multivariate analysis. The response rate was 19.4% in weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P = 0.527). Median survivals in the two arms were 18.4 months (weekly) and 21 months (biweekly) respectively (P = 0.708). Gastrointestinal side effects including nausea, vomiting, diarrhea and mucositia were the major toxicities of these regimens. By multivariate analysis, the only factor to influence response rate was the site of metastases (P = 0.009). The only factor to affect survival was performance status of the patient (P = 0.0001). We concluded that the two 5-fluorouracil based regimens are well-tolerated and shown to have a response rate comparable with previous reports of similar regimens in patients with metastatic colorectal cancer. Only liver metastases seemed to have a better response to therapy. Performance status is the most important prognostic factor in patients with metastatic colorectal cancer.      

Langerhans' cell histiocytosis with thyroid involvement masquerading as thyroid carcinoma

A 28-year-old woman was admitted to our Hospital with a chief complaint of progressive gingival swelling and loosening of teeth over about a year. According to past history, she had received total thyroidectomy 2 years previously due to thyromegaly. The thyroidectomy specimen was at first interpreted as 'poorly differentiated carcinoma of the thyroid'. One year ago, she began to be aware of gingival swelling and loosening of teeth. A gum biopsy was taken and the pathologic features were similar to her 'thyroid carcinoma'. Subsequent investigations, including immunohistochemical stain, showed the gum was heavily infiltrated with histiocyte-like Langerhans' cells which were positive for S-100 protein. Ultrastructural examination of the cells under electron microscope revealed many typical intra-cytoplasmic Birbeck granules. Langerhans' cell histiocytosis was diagnosed. Langerhans' cell histiocytosis with thyroid involvement is extremely rare and may run a relatively indolent course. Even on a retrospective examination, it may easily be confused with poorly differentiated carcinoma of the thyroid. We suspect that this error may have been made on other occasions and that the occurrence of this condition may be underreported.      

HIV infection in haemophilia--a European cohort

Ten haemophilia centres in northern Europe have pooled data on 202 haemophilic children who were infected with HIV between 1979 and 1986. All cases were under 16 years of age on 1 July 1985. The age at infection ranged from 1-15 years. Thirty seven cases (18%) had progressed to AIDS by 1 July 1991 and 15 of these have died. Persistent generalised lymphadenopathy has been noted in 102 patients of whom 18 (17%) have developed AIDS. Twenty three of the remaining patients (23%) have not. CD4+ T cell counts have fallen steadily. Of 36 patients who have had shingles since seroconversion, 19 (53%) had counts below 0.2 x 10(9)/l. Thirty five out of 145 patients without shingles (24%) had similar values. The mean IgA concentration in patients with CD4+ T cell counts above 0.5 x 10(9)/l was 2.38 g/l, between 0.2 and 0.5 was 3.07 g/l, and in those with CD4+ T cell counts below 0.2 x 10(9)/l the mean IgA concentration was 4.58 g/l. Treatment patterns have altered between 1989 and 1991, with increased use of zidovudine in patients without AIDS and a marked increase in primary prophylaxis against pneumocystis pneumonia. This has been associated with a decline in the incidence of pneumocystis as an indicator disease in new AIDS cases from 56% in 1989 to 20% in 1991. These observations indicate that persistent generalised lymphadenopathy does not worsen the outlook, but shingles does. Rising IgA concentrations are markers for disease progression. Modern prophylactic regimens are delaying the onset of indicator disease, but CD4 values continue to fall steadily.     

Relationship between the HLA Associated Specificities 4a and 4b and the Lymphocyte C3 Receptor

Contrary to previous reports, we have obtained no evidence that 4a and 4b antisera specifically inhibit C3 rosette formation by human lymphocytes. Pretreatment of lymphocytes with various whole 4a and 4b antisera resulted in partial inhibition which was often nonsepcific. Ultracentrifugation of the sera to remove immune complexes removed C3 rosette inhibitory activity although specific cytotoxic activity remained. It is probable that immune complexes in antisera will have fixed C3 which will have been converted to C3d and so be able to block the C3d receptor. This is the receptor mainly measured in these and in the previous experiments.     

Eliciting relative preferences for two methods of colorectal cancer screening

Two methods of mass population screening for colorectal cancer - faecal occult blood testing and sigmoidoscopy - have been the subject of randomized controlled trials in the UK. A national screening programme is currently under consideration and the choice of screening method remains open. To be successful, a programme will require high levels of uptake, and uptake is likely to depend upon subjects' attitudes towards the screening method introduced. Although a preferred screening method has already been identified from a questionnaire survey, we undertook a further interview study (n = 106), with a view to comparing the results of two different approaches to eliciting public preferences. In comparison with the questionnaire study, a higher proportion of interview subjects stated a preference. Interview subjects were generally more favourably disposed towards sigmoidoscopy, excepting those with previous experience. Compared with the questionnaire survey, the interviews provided richer information on the reasons for preferences offered. Individual preferences were evidently subjective and dependant on attitudes towards a variety of method characteristics, such as discomfort, convenience and perceived sophistication. Characteristics such as age and low income, which had predicted preferences in the questionnaire study, predicted preferences in the interview study also. The difference between the results obtained by the different elicitation techniques can be explained in terms of the differential provision of information and sample selection. Conclusions made about public preferences are likely to depend on the technique employed in eliciting them.