Screening for thyroid dysfunction in the elderly.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to N Haboubi.
Explore the source record for details and available documents.
Eosinophils are a recognized feature of inflammatory bowel disease (IBD), but their tissue distribution and functional importance in Crohn's disease (CD) and ulcerative colitis (UC) remain obscure. This study describes an improved immunohistochemical protocol to identify eosinophils in full thickness bowel wall specimens of IBD (n=40) and their in situ relationships with the chemoattractants eotaxin and RANTES. Eosinophils were identified using immunohistochemistry with a combination of monoclonal antibodies (EG1+EG2+MBP), an ultrasensitive technique superior to other methodologies, and their tissue distributions were related to those for eotaxin, RANTES, mast cells and neutrophils. Increased numbers of eosinophils (up to 400 cells/mm(2)) were observed in active, fulminant inflammation in both CD and UC, this being related to the severity of inflammation and not the diagnosis of the two disorders. The chemoattractants eotaxin (CCL11) and RANTES (CCL5) were upregulated in IBD tissues showing eosinophilia. Neutrophils and mast cells were commonly associated with eosinophil accumulations. Eosinophil numbers and their in situ activation are increased in active rather than chronic IBD. The observations strongly suggest a pivotal role for the eosinophil and its potent mediators in many pathophysiological symptoms of CD and UC, where it represents the major proportion of all granulocytic cells in active inflammatory bowel disease.
Trimetrexate (TMTX) is a new antifolate which avoids competition for cellular uptake with folinic acid (FA). A regimen of sequential TMTX, FA and 5-fluorouracil (5-FU) has shown efficacy in patients with colorectal cancer. Therefore, we treated 34 previously untreated patients with metastatic colorectal cancer with a weekly chemotherapy regimen consisting of 110 mg/m(2) of TMTX intravenously, then 24 h later 200 mg/m(2) of FA (i.v.) and 500 mg/m(2) of 5-FU (i. v.). Thereafter, 7 doses of oral FA (15 mg) were given at 6-hourly intervals. A treatment cycle consisted of 6 weeks of treatment, then 2 weeks of rest. All patients were treated as outpatients unless complications arose. Thirty-three patients were assessable for tumor response, and all 34 patients were assessable for toxicity. Twelve patients (36%; 95% confidence interval: 25-49%) achieved a partial response. The median duration of response was 8.5 months, and median survival was 14 months. The most common toxicity was diarrhea of grade 3/4, observed in 22% of treatment cycles; this decreased to 8% with early loperamide treatment. Hematologic toxicity was mild. The sequential administration of TMTX, FA and 5-FU is an active regimen in the first-line treatment of metastatic colorectal cancer and warrants further studies.
An increased prevalence of colorectal neoplasia has been reported in acromegalic patients, and recommendations have been made for early colonoscopic screening and regular surveillance. This assumption, however, is frequently drawn from studies using selected control populations. To clarify colonoscopic management in these patients, we undertook a 2-center prospective screening colonoscopy study in 122 acromegalics (age range, 25-82 yr). In the absence of ideal age-matched controls, we calculated prevalence rates of occult adenocarcinomas and adenomas in the general population using cumulative data in the published literature from 8 autopsy studies (model 1, n = 3,559) and 4 screening colonoscopy studies (model 2, n= 810), applying linear regression models. Of the 115 patients with complete examinations, adenocarcinomas were discovered in 3 (2.6%), and at least 1 adenoma was found in 11, giving an overall prevalence of neoplasia of 12% (14 of 115). Prevalence rates for age bands 30-40, 40-49, 50-59, 60-69, and 70+ yr were 0%, 8%, 12%, 20%, and 21%, respectively. Compared with the 2 control models, the prevalence of occult colorectal cancer was not significantly increased (acromegalics vs. models 1 and 2, 2.6% vs. 2.3% and 0.9%), nor was there an increase in the prevalence of adenomas in any age band. Pathological characteristics showed some differences, in that adenomas in acromegalics tended to be right sided (68% vs. 57% and 56%), larger (for > or =10 mm, 27% vs. 13% and 9%), and of advanced histology (for tubulovillous, 27% vs. 4% and 22%). No associations were found between the presence of colonic neoplasia and the duration of disease, total GH exposure, cure status, and serum insulin-like growth factor I. This study has failed to demonstrate an increased prevalence of neoplasia in acromegalic patients compared with the expected prevalence in the general population and questions the need for an aggressive colonoscopic screening policy.
Angiogenesis is essential for tumor growth and metastasis. There are conflicting reports as to whether microvessel density (IMD) in breast cancers is associated with prognosis. This could be due to the use of different antibodies to endothelial cell markers, variation in tissue pretreatment protocols, and nonstandardized counting methods. We have assessed the IMD in 106 breast carcinomas using a pan-endothelial marker, CD34, and a recently described mAb to CD105, which preferentially reacts with endothelial cell in angiogenic tissues. IMD values (separated as above or below median) for CD105 expression showed a statistically significant correlation with overall (P = 0.0029) and disease-free survival (P = 0.0362). In contrast, blood vessel counts using a panendothelial marker CD34 did not correlate with overall or disease-free survival (P = 0.2912 and P = 03153, respectively). When IMD values were subdivided into quartiles and assessed for their prognostic values, there was a statistically significant difference in the overall survival across CD105, but not CD34, values (P = 0.0017 and P = 0.7997, respectively) and also disease-free survival (P = 0.0431 and P = 0.5066, respectively). Further analysis of IMD values demonstrated that there were no deaths in the lowest quartile for CD105 and it differed from the other three quartiles. However, examination of clinical details of patients in the lowest quartile failed to reveal clustering of patients known to be associated with low-risk factors. Multivariate analysis confirmed that IMD values using CD105 were an independent prognostic factor. These results suggest that the ability to quantitatively distinguish between tumor neovascularization and preexisting vessels may be important in the assessment of tumor angiogenesis, but requires confirmation in a greater number of patients with a longer follow-up.
Explore the source record for details and available documents.
Seventeen patients with small cell lung cancer entered a phase II trial testing the feasibility of adding high dose epirubicin (100-120 mg/m2, day 1) in combination with etoposide (60-80 mg/m2, days 1-5) and cisplatin (70 mg/m2, day 1) courses repeated every three weeks. Complete responders received thoracic (40 Gy) and prophylactic cranial (30 Gy) irradiation. Sixteen patients were evaluable for response and toxicity. Myelosuppression was the dose-limiting side effect. Neutropenic fever was observed in eight patients (53%) and stomatitis in six (40%). No patient had a greater than 14% decline in the cardiac ejection fraction. Strict adherence to the dose-schedule designed was impossible as doses were trimmed and delayed in 30% of instances. The overall objective response rate was 81% (95% confidence limits, 62% to 100%), in limited disease there were complete remissions in 57%. With a 16 months median follow-up, overall median survival was 13 months. This study was unable to prove the feasibility of epirubicin escalation when added to etoposide-cisplatin combination, hampering the dose-intensification Norton-Simon model test.
The clinicopathologic staging of colorectal cancer is the subject of recent debate. We studied morphologic variables in a series of tumors resected from 284 patients. Half had been prospectively, randomly allocated to receive a 4-day schedule of preoperative pelvic radiotherapy followed by immediate surgery. There was a significant (P less than 0.01) difference in the distribution of tumors of various histopathologic grades between irradiated (XS) and unirradiated (S) patients and borderline differences in the predictive values of venous spread, tumor grading, and local spread. However, these differences were less marked in 180 tumors examined by one review pathologist. They were thought to be due to misinterpretation of changes induced by radiotherapy. No differences were detected in the distribution of tumors of various sizes and Dukes' stage in the XS and S groups. The review pathologist recorded a borderline (P = 0.049) difference in the distribution of tumors of various CEA staining patterns between the XS and S groups. In a Cox regression model. Dukes' staging remained the most important predictive variable for survival and pelvic recurrence in the XS and S groups. Dukes' staging was apparently unchanged by this schedule of preoperative radiotherapy, but Broders' grading may be unreliable. Any new clinicopathologic staging system for colorectal cancer should record when preoperative radiotherapy is delivered. More studies of radiotherapy effects are required.
A prospective study of prognostic factors has been carried out in a group of 186 patients with tethered rectal carcinomas. Of these, 97 were randomized to surgery alone and 89 to receive preoperative radiotherapy (20 Gy in four fractions). DNA ploidy was determined by flow cytometry. DNA aneuploidy was detected in 60 patients (62 per cent) in the surgery only group, but in only 33 patients (37 per cent) after radiotherapy (P less than 0.01). There was a significant reduction in local recurrence in irradiated patients (P less than 0.0001). DNA diploid tumours were less likely to recur locally. This was more marked in the radiotherapy group (P = 0.01) than in the surgery only group (P = 0.06). After radiotherapy, only the surgeons' assessments of a 'curative' resection and DNA ploidy were independent predictors of local recurrence in multivariate regression analysis, whilst Dukes' classification was not. In conclusion, DNA ploidy may indicate response to radiotherapy and is an important predictor of subsequent local tumour progression.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
5 of 8 infarcted human myocardial tissues were shown to contain an angiogenesis factor which resembles that obtained from solid tumours. The concentration of angiogenesis factor, measured by radioimmunoassay, was similar to that in tumours. It is suggested that the myocardial-infarct angiogenesis factor modulates collateral enlargement or ingrowth of new blood vessels in the infarcted tissues.
A fall in serum tri-iodothyronine (T3) is the earliest abnormality in thyroid hormonal function tests in non-thyroidal illnesses. Our study shows an association of low serum T3 with patient mortality in elderly hospitalised patients.
A 24-year-old man with anorexia, repeated bouts of vomiting, and wasting was found to have florid thyrotoxicosis and hypercalcaemia. Pamidronate promptly reduced the serum calcium concentration to normal, and simultaneously abated the abdominal symptoms, which did not recur in spite of continuing severe hyperthyroidism, which was eventually controlled by radioactive iodine ablation of thyroid activity.