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Biomedical subjects

N Y Haboubi

Publications and source records attributed to N Y Haboubi.

At least 19 recordsLinked to original sources

Are differences in stage at presentation a credible explanation for reported differences in the survival of patients with colorectal cancer in Europe?

Popular reporting of a comparison of cancer survival rates across 17 European countries, based on data collected by national and regional cancer registries, has left an impression of inadequate treatment of patients in the UK. A subsequent study has suggested that the poor survival rates reported for the UK can, in large part, be explained by more advanced stage at presentation. We believe this conclusion to be unsound and use this study as an example to illustrate the methodological difficulties which may arise during such international comparisons. As the NHS cancer plan aspires to achieve for the UK parity with the best cancer care in Europe, careful thought needs to be given to identifying countries with which the UK can usefully compare itself and the most appropriate indicators for this comparison.

Adenocarcinoma↗

The novel combination of fat clearance and immunohistochemistry improves prediction of the outcome of patients with colorectal carcinomas: a preliminary study.

To evaluate the significance of micrometastases in relation to survival rate, specimens from 48 colorectal carcinoma patients were analysed after fat clearance. The number and size of the lymph nodes harbouring metastases and the significance of micrometastases for patients' survival were assessed. We found that although the majority of metastatic lymph nodes (71.8%) were 5 mm or less in diameter, their size had no effect on survival. Immunohistochemical staining of lymph nodes revealed that 15 of 25 patients with Dukes' stage B diagnosed by routine staining had micrometastases, 86% of these lymph nodes being less than 5 mm in diameter. The survival rate of this subgroup was found to be considerably poorer than that of Dukes' stage B patients with no micrometastases. None of the three patients with Dukes' stage A carcinoma had micrometastases. Since most of the metastases and micrometastases occur in lymph nodes of 5 mm and less and can be easily missed by routine examination, we suggest that fat clearance and routine immunohistochemical analysis of Dukes' stage B improve the prediction of outcome of colorectal cancer patients.

Aged↗

Localisation and semiquantitative assessment of hepatic procollagen mRNA in primary biliary cirrhosis.

BACKGROUND: Chronic liver disease is characterised by excessive deposition of collagen and other extracellular matrix proteins, produced mainly, but not exclusively, by activated hepatic stellate cells in the perisinusoidal space. In primary biliary cirrhosis (PBC) fibrosis is concentrated mainly around the portal tracts. AIMS: To examine the hypothesis that, in addition to hepatic stellate cells, portal tract fibroblasts might play a significant role in the deposition of collagen in PBC. METHODS: Fifty liver biopsy specimens from patients with PBC were studied. An in situ hybridisation technique was adapted to localise and measure semiquantitatively type I procollagen mRNA in formalin fixed, paraffin wax embedded sections, using an 35S labelled cRNA probe specific for the alpha 1 chain of rat type I procollagen. Hepatic fibrogenic activity was also assessed using serum type III procollagen peptide (PIIINP). RESULTS: In PBC, type I procollagen gene expression was significantly increased. Signal was localised mainly in and around inflamed portal tracts, to cells which had the appearances of portal fibroblasts. Signal activity in these cells correlated with the degree of portal fibrosis and inflammation and also with serum PIIINP concentrations. CONCLUSIONS: Results are consistent with the hypothesis that the excessive extracellular matrix, deposited within the liver in PBC, is synthesised not only by hepatic stellate cells but also by portal tract fibroblasts. The semiquantitative assessment of procollagen mRNA in liver biopsy specimens may provide a useful method of evaluating the rate of synthesis of collagen and therefore disease activity in patients with PBC.

Biomarkers↗

Melanosis coli is associated with an increase in colonic epithelial apoptosis and not with laxative use.

We have investigated the clinical presentation, laxative use and histopathology of 38 patients with a histological diagnosis of melanosis coli and measured the colonic epithelial apoptosis in these cases. The presence of lipofuscin was confirmed in all cases. Fifteen of the cases had constipation, whilst eight had diarrhoea. Neither constipation nor diarrhoea was present in 13 cases and both were present, at different times, in two. Laxatives had been used in all those with constipation, in only one with diarrhoea and in none of the others. The mean apoptotic count was significantly increased in those with melanosis coli compared with the controls. In the majority of cases with constipation there was no other abnormality, whilst an additional diagnosis was present in the majority of the remainder. Colonic epithelial apoptosis was increased in melanosis coli and the majority of cases were not associated with laxative use. These results support the proposed role of apoptosis in melanosis coli, but indicate that melanosis coli is a non-specific marker of increased apoptosis with many possible causes, of which the use of laxatives is only one.

Adolescent↗

Involvement of the appendix in pseudomembranous colitis.

Pseudomembranous colitis (PMC) is an inflammatory disorder usually limited to the large intestine and is the consequence of antibiotic associated Clostridium difficile overgrowth with production of its toxin. It has a characteristic gross and microscopic appearance. PMC-like changes, usually associated with peri-operative hypotension and with more extensive gastrointestinal tract involvement, have also been described. In neither clinical setting has pseudomembranous appendicitis been recorded. A case of pseudomembranous appendicitis in a 76 year old woman is described.

Aged↗

Serum type III procollagen aminopeptide for assessing liver damage in methotrexate-treated psoriatic patients.

This study was designed to establish whether measurement of a serological marker of fibrosis might reduce the need for liver biopsy in psoriatic patients receiving methotrexate (MTX). Levels of type III procollagen aminopeptide (PIIINP-O and PIIINP-B) and laminin P1 (LamP1-B) were measured in 147 serum samples taken at the time of liver biopsy in 87 patients receiving long-term MTX treatment for severe psoriasis. Biopsies were classified as: (1) normal, (2) steatosis, (3) inflammation, (4) fibrosis, or (5) cirrhosis. Groups 3-5 were considered to show clinically relevant abnormality. Compared with controls, PIIINP-O was significantly raised in the group of MTX-treated psoriatics (P < 0.001). Within this group, levels were significantly higher in patients with inflammation, fibrosis or cirrhosis compared with those with normal histology or steatosis alone (P < 0.0001). In contrast, PIIINP-B and LamP1-B did not distinguish between controls and MTX-treated patients or between histological groups. Forty-two patients had two or more biopsies with simultaneous PIIINP-O measurement. PIIINP-O levels at the time of the first biopsy were normal in six of the seven patients whose histology was initially normal and subsequently became abnormal. A single measurement of PIIINP-O thus did not predict which patients might develop abnormal histology following further MTX. In a group of 17 patients, PIIINP-O was measured 3-monthly for up to 6 years during MTX treatment. PIIINP-O was elevated at some time during follow-up in all three patients who developed abnormal histology but was consistently normal in eight of the 11 patients whose histology remained or became normal. Our findings indicate that PIIINP-O is of value in detecting liver damage and, particularly if measured serially, may reduce the need for liver biopsy in MTX-treated patients. Although the test does not detect all patients with fibrosis, it would appear that the risk of missing significant liver damage in patients with persistently normal PIIINP-O is low.

Adult↗

Histopathological changes in haemorrhoid associated mucosa and submucosa.

The histological features of haemorrhoids are detailed in this study with special attention to the mucosal changes. These include significant crypt distortion, with stromal hyperplasia which bear a remarkable resemblance to the changes seen in mucosal prolapse syndrome. We propose that the mucosal prolapse syndrome should include haemorrhoids as part of the spectrum.

Adult↗

Abnormalities of serum type III procollagen aminoterminal peptide in methotrexate-treated psoriatic patients with normal liver histology do not correlate with hepatic ultrastructural changes.

In a previous study, it was shown that the serum levels of type III procollagen aminoterminal peptide (P3NP) were significantly greater in patients receiving methotrexate (MTX) treatment for psoriasis than in untreated control patients with psoriasis. Although levels were highest in patients with hepatic fibrosis and cirrhosis, serum P3NP concentrations in those patients with normal liver histology on light microscopy were also shown to be significantly higher than in controls. In the present study, liver biopsies from 22 such 'normal' patients were examined by electron microscopy, in order to determine whether P3NP levels correlated with ultrastructurally demonstrable fibrosis. Fibrosis in the perisinusoidal space of Disse was present in as many as 82% of biopsies. Although the prevalence of such fibrosis in psoriasis patients who have not received MTX is unknown, the high prevalence of Disse space fibrosis and of raised P3NP in MTX-treated patients suggests that MTX causes subtle liver damage in a majority of treated patients. However, we were unable to show a statistical correlation between P3NP and the degree of Disse space fibrosis.

Adult↗

Sequential liver biopsies during long-term methotrexate treatment for psoriasis: a reappraisal.

One hundred and eighty-two liver biopsies were performed over a 10-year period on patients receiving long-term, low-dose, once weekly oral methotrexate (MTX) for severe psoriasis. Forty-nine patients had two or more biopsies during continued treatment and formed the study population for our analysis. The first and last biopsies were compared to determine progression of any histological abnormalities. Liver biopsies were assessed without knowledge of the MTX dose and allocated to one of five groups according to the severity of the histological abnormalities. These were defined as: (1) normal; (2) steatosis alone; (3) inflammation without fibrosis; (4) fibrosis; and (5) cirrhosis. The mean cumulative dose of MTX at the time of the first biopsy was 2743 mg (range 315-10,024), given over 275 weeks (range 26-738). In the interval between the first and last biopsies, patients received, on average, a further 2362 mg (range 390-7155) over 225 weeks (range 60-460). There was improvement in the histological assessment in 12 patients, no change in 28 patients, and deterioration in nine patients. None developed cirrhosis. Liver biopsy findings prompted discontinuation of MTX in four of the 49 patients on long-term treatment. This has to be weighed against the cost and morbidity of the 124 biopsies performed in these patients. Our results suggest that, with careful follow-up, the risk of development or progression of liver disease in patients receiving long-term, low-dose, once weekly oral MTX for psoriasis is modest, and that the requirement for performing routine liver biopsies in these patients needs to be reconsidered.

Biopsy↗

Colonic tubular adenomas and intestinal spirochaetosis: an incompatible association.

Two cases of tubulovillous adenoma and adjacent colonic mucosa were studied in which intestinal spirochaetosis had heavily colonized the non-neoplastic but not the neoplastic epithelium. Ultrastructural and histochemical studies were performed and we postulate that the reason for this disparity is the normal microvillous pattern of the non-neoplastic epithelium which facilitates colonization by the spirochaetes.

Adenoma↗

Serosal reaction in chronic gastric ulcers: an immunohistochemical and ultrastructural study.

AIM: To study the serosal reaction in gastrectomy specimens with benign chronic peptic ulcers. METHODS: Gastrectomy specimens were fixed in neutral buffered formalin and paraffin wax, and examined using immunohistochemical and ultrastructural techniques. RESULTS: Nine of the 22 (41%) cases examined showed reactive hyperplasia of the serosal cells. The cells were predominantly spindle-shaped and were positive on staining with Cam 5.2, AE1/3 and for vimentin. Eight of nine were also positive for smooth muscle actin and five for desmin. Ultrastructural analysis of these cells suggests that they may be myofibroblastic in nature. CONCLUSIONS: These results support the concept of "multipotential" subserosal cells which may differentiate into surface serosa or, in the reactive state, modulate the thin cytoskeletal filaments and become more myofibroblastic. Particular care should be taken not to confuse these reactive serosal cells with carcinoma or smooth muscle tumours in endoscopic biopsy specimens.

Actins↗

Distribution of gelatinase B (MMP-9) and type IV collagen in colorectal carcinoma.

Gelatinase B (92 kD, matrix metalloproteinase-9, MMP-9), an enzyme capable of degrading several connective tissue components, was demonstrated by immunolocalization in all specimens of colorectal carcinoma (n = 40), but its distribution between specimens was variable. MMP-9 expression was more frequently observed in advanced tumour stages and was especially prevalent at the side and deep margins of the tumours, and ulceration sites. MMP-9 staining was observed for transformed epithelial cells, macrophages and neutrophils, but seldom for vascular or stromal cells. By contrast, the enzyme was absent from epithelial cells of normal mucosal tissue. Immunostaining of type IV collagen, the major structural component of basement membranes, revealed a general depletion or loss of these structures both within the tumours and at the tumour margins. Dual immunolocalization of MMP-9 and type IV collagen demonstrated that MMP-9 expression at specific sites in the tumour was often inversely related to the distribution of type IV collagen. MMP-9 expression was most pronounced at the invasive tumour margins and in microfoci where tumour cells were in close proximity to inflammatory cells. Such observations support the concept that localized proteolytic and collagenolytic activities contribute to the invasive properties of colorectal tumours.

Aged↗

An evaluation of five different methods for estimating proliferation in human colorectal adenocarcinomas.

Five different methods of determining cell proliferation have been compared in samples taken from a group of 125 human colorectal tumours labelled in vivo with iododeoxy-uridine (IUdR). The labelling index (LI) was obtained immunocytochemically using monoclonal antibodies against proliferating cell nuclear antigen (PCNA), the Ki67 antigen and IUdR (IUdRimm). Incorporation of IUdR was also determined flow cytometrically (IUdRfcm) and PCNA expression was measured in both formalin- and methanol-fixed tissue (PCNAf and PCNAm respectively). There was significant variation in the results obtained both within and between the different assays. Paired analysis of the data showed that the correlation between the different methods of determining the LI was poor. However, the IUdRfcm LI was significantly correlated with both IUdRimm (r = 0.39; n = 78; P < 0.001 by Spearman's test) and Ki67 LIs (r = 0.32; n = 87; P < 0.001). The IUdRimm LI was also significantly related to the Ki67 LI (r = 0.44; n = 60; P < 0.001). The median IUdRfcm and IUdRimm LIs were significantly higher in the aneuploid vs. the diploid tumours (17.4% vs. 6.2% for IUdRfcm; 23.2% vs. 18.9 for the IUdRimm; P < 0.001 and P = 0.014 respectively by Mann-Whitney U-test) but none of the other proliferative indices showed this relationship. Finally, none of the LIs showed a significant association with the clinical characteristics of the tumours such as stage, grade, age, sex or fixity. The findings of this investigation highlight the need for carefully controlled studies when assessing the value of proliferation markers in solid human tumours.

Adenocarcinoma↗

Leishmaniasis of the tongue treated with liposomal amphotericin B.

A 66-year-old man, immunosuppressed because of a lymphoma and with severe ischaemic heart disease and proteinuria, presented with a swelling on the tongue due to leishmaniasis. His travel history suggested that he had acquired the infection in the Mediterranean area some years earlier. He was treated with liposomal amphotericin B for 21 days and made a good recovery despite a temporary deterioration in renal function. Oral lesions are a rare manifestation of Old World leishmaniasis. Liposomal amphotericin B is a novel treatment that may be well tolerated when there is concern about the toxicity of more established drugs.

Aged↗

Cutaneous epithelioid angiosarcoma: a clinicopathological study of four cases.

Four cases of cutaneous epithelioid angiosarcoma are described together with the potential diagnostic trap of mistaking these tumours for poorly differentiated carcinoma or malignant melanoma. The immunophenotypic profile using four endothelial markers showed positive staining in all cases for factor VIII related antigen in a predominantly paranuclear dot-like fashion and for CD31 (JC70); in three cases for CD34 (QB-END/10) and in two cases with UEA-1. All four cases were cytokeratin (CAM 5.2 and AE1/AE3) negative in contrast to the positive staining reported at non-cutaneous sites. Aberrant S-100 protein expression was seen in one case. In two cases subsequent recurrences showed better differentiation than the original tumour. Electronmicroscopy confirmed the absence of non-endothelial lines of differentiation but failed to reveal Weibel-Palade bodies.

Aged↗

Body weight estimation of elderly patients by nomogram.

OBJECTIVE: To determine a safe and easy way to estimate body weight (BW) accurately in nonambulant elderly patients. DESIGN: An anthropometric study of ambulant patients. PARTICIPANTS: Two hundred eleven ambulant inpatients, 108 males and 103 females. SETTING: Inpatient departments of the University Department of Geriatric Medicine, Cardiff, Wales, UK. MEASUREMENTS: Skinfold thickness of chin, triceps, forearm, wrist, subscapular, sternal angle, waist, suprailiac, knee, and calf; circumference of arm, forearm, thigh and calf; body weight, chest girth, abdominal girth, upper limb length, leg length, and body weight. Measurements were carried out by means of Harpenden Skin-Fold Caliper, tape measure, and bathroom scale. RESULTS: Measured body weight in males was highly correlated with both arm circumference and chest girth. In females, measured body weight was highly correlated with waist skinfold thickness and thigh circumference. Nomograms for weight estimation in males and females were constructed from the regression equations for these measurements. CONCLUSIONS: Convenient estimation of body weight in nonambulant patients may be carried out using nomograms, which, themselves, may be used as progress sheets to assess the effect of dietary supplementation on body weight.

Aged↗