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Biomedical subjects

M Hayat

Publications and source records attributed to M Hayat.

At least 19 recordsLinked to original sources

Survey of Theileria lestoquardi antibodies among Sudanese sheep.

The prevalence of Theileria lestoquardi antibodies in Sudanese sheep from nine geographical areas in Sudan was determined using indirect fluorescent antibody "IFA" test. Out of 315 samples examined, 51 (16.2%) were found positive and ranged between 23.4% in River Nile State and 10% in Kasala and Darfour Provinces with an overall prevalence of 16.2% indicating widespread distribution of the infection. We also report on presence of antibodies reactive to Theileria annulata in sheep sera.

Animals↗

Quantitation of intraepithelial lymphocytes in human duodenum: what is normal?

BACKGROUND: An increase in intraepithelial lymphocytes (IELs) is mandatory for the histological diagnosis of coeliac disease (CD). Currently, duodenal biopsies are used almost exclusively to establish the diagnosis, yet published work continues to cite an upper limit of 40 lymphocytes/100 epithelial cells, a figure derived from jejunal biopsies over 30 years ago. AIM: To establish the normal range for IEL counts in distal duodenal biopsies. MATERIALS/METHODS: Twenty subjects (seven men, 13 women; median age, 34 years; range, 20-65) with a normal sugar permeability test and concurrent distal duodenal biopsies were identified. The number of IELs and epithelial cell nuclei in an uninterrupted length of surface (villous) epithelium (> 500 cells) was counted. An image analysis system was used to assess villous architecture by calculating the villous height to crypt depth ratio. RESULTS: The range of IEL counts in 20 subjects was 1.8-26/100 villous epithelial cells, with a mean value of 11 and SD of 6.8. The mean villous to crypt ratio was 1.82 (SD, 0.38; range, 1.22-2.46). There was no correlation between IEL counts and villous to crypt ratio (Spearman rank correlation, -0.066; p = 0.80). CONCLUSIONS: These results suggest that 25 IELs/100 epithelial cells (mean +2 SD) should be taken as the upper limit of the normal range for duodenal mucosa.

Adult↗

Influence of a partner's HIV serostatus, use of highly active antiretroviral therapy, and viral load on perceptions of sexual risk behavior in a community sample of men who have sex with men.

OBJECTIVE: To assess the perceptions of gay and bisexual men concerning the risk of HIV transmission through various sexual practices with a new sex partner depending on that partner's disclosed HIV status, antiretroviral treatment status, and viral load. METHODS: Study participants read four different scenarios describing sexual situations with a new partner and rated each scenario for risk of HIV transmission. HIV status and antiretroviral treatment status disclosed by the new sex partner were varied across four scenarios: unknown HIV status; HIV-negative; HIV-positive and not taking highly active antiretroviral therapy (HAART); and HIV-positive and taking HAART with an undetectable viral load. RESULTS: Study participants were 472 men attending a gay pride festival who reported that they were HIV-negative. Eighty-nine percent of the men were white, and the mean age of the study participants was 35.8 years. Of the four scenarios, sex with an HIV-positive partner not taking HAART was rated as posing the greatest risk. Sex with an HIV-positive partner taking HAART who had an undetectable viral load was not consistently viewed as riskier than sex with an HIV-negative partner or a man with an unknown HIV status. CONCLUSIONS: The current study provides preliminary evidence for the effect of disclosure of HIV serostatus, use of HAART, and the presence of an undetectable viral load on the perceptions of sexual risk for HIV-negative men. The findings suggest that some gay and bisexual men judge risk based on the perceived HIV status of their sex partners and not on the general assumption that all sex partners entail equal risk, as many prevention campaigns have emphasized.

Adult↗

Expression of Interleukin-18, a Th1 cytokine, in human gastric mucosa is increased in Helicobacter pylori infection.

Interleukin-18 (IL-18), a cytokine that promotes Th1 responses, is processed to the active mature protein by caspase-1. The effects of Helicobacter pylori infection on gastric IL-18 and caspase-1 were examined. In antral mucosa, IL-18 mRNA expression was greater (P<.01) in H. pylori-positive (n=40) than in H. pylori-negative patients (n=29) with normal mucosa. Inactive precursor (24 kDa) and mature (18 kDa) IL-18 were present in antral biopsy specimens from uninfected and infected subjects. In corpus mucosa, mature IL-18 and a 16-kDa protein, corresponding to inactive IL-18, were present. Active caspase-1 p20 subunit was detected in antral and corpus mucosa of infected and uninfected subjects. These data show that, although H. pylori infection is associated with increased antral IL-18 mRNA expression, mature IL-18 protein and active caspase-1 p20 are present in mucosa of both H. pylori-infected and -uninfected subjects. IL-18 may have an important role in promoting gastric Th1 responses in H. pylori infection.

Adult↗

Malignant hyperinflation of the nondependent lung during chest surgery.

Unilateral malignant hyperinflation of the lungs during positive pressure mechanical ventilation was described during aggressive respiratory therapy of unilateral lung disease or in situations of significant difference in compliance between the two lungs. We report a case of malignant hyperinflation of the nondependent lung during chest surgery. The differential diagnosis and treatment with differential lung ventilation are described.

Aged↗

Diagnostic yield and effect on clinical outcomes of push enteroscopy in suspected small-bowel bleeding.

BACKGROUND AND STUDY AIMS: Endoscopic examination of the small bowel (enteroscopy) has become an important modality in the investigation of patients with obscure gastrointestinal bleeding/anaemia. The aim of this study was to look at our clinical experience and also to determine the clinical outcomes following push enteroscopy (PE) in patients with suspected small intestinal bleeding. PATIENTS AND METHODS: The indications for PE were iron-deficiency anaemia/occult or obscure gastrointestinal bleeding (50 patients) and overt gastrointestinal bleeding (28 patients). Out of these 78 patients, a subgroup of 21 unselected patients with suspected small intestinal bleeding (six men, 15 women; mean age 59, range 26-85) was recruited to determine the clinical outcomes following PE. The principal outcome measures in this study were a) whether the procedure led to a change in the management of the patients referred for PE and b) whether it saved them from having further investigations. RESULTS: In those patients with undiagnosed gastrointestinal bleeding/anaemia, small-bowel arteriovenous malformations (AVMs) were detected in 24/78 (31%). Heater probe ablation therapy was performed in 23 patients with small-bowel and gastric AVMs. In total, seven of these 23 patients (30%) re-bled or required transfusion; these seven had repeat enteroscopy and heater probe ablation therapy. Three of these seven re-bled and required further enteroscopy and therapy. PE resulted in a change in management and treatment plans in eight of 20 patients (40%). The certainty of diagnosis increased in seven of 20 patients (35%). It increased from a mean value of 1.35 before PE to 2.40 following PE ( P = 0.01). The test was assigned a median "usefulness score" of 3 by the requesting physicians on an integer scale from 1 (not helpful) to 5 (very helpful). CONCLUSIONS: We conclude that (i) PE can establish a diagnosis in a high proportion of patients with undiagnosed gastrointestinal bleeding/anaemia; (ii) heater probe ablation therapy of vascular lesions can be performed routinely at the time of PE; (iii) a significant proportion of patients (42%) referred for enteroscopy have lesions in the stomach/proximal duodenum that are missed at diagnostic endoscopy; (iv) PE provides helpful information in routine clinical practice and is perceived as a helpful test by requesting physicians; (v) PE improves certainty of diagnosis as perceived by requesting physicians, and plays an important role in altering management plans.

Adult↗

Effects of Helicobacter pylori eradication on the natural history of lymphocytic gastritis.

BACKGROUND: Lymphocytic gastritis is characterised by an accumulation of lymphocytes in the surface epithelium of the stomach. Lymphocytic gastritis has been linked to coeliac disease and Helicobacter pylori infection. AIMS: To determine whether H pylori eradication leads to resolution of the lymphocytic infiltrate and clinical improvement in patients with lymphocytic gastritis, and to determine their HLA status. METHODS: The Leeds Dyspepsia Questionnaire (LDQ) was administered to 13 patients with lymphocytic gastritis. H pylori serology, (13)C urea breath test (UBT), and upper gastrointestinal endoscopy with sampling of the duodenum, antrum, and corpus were done in all cases and the HLA status was determined. Eleven patients had at least one positive test for H pylori. Patients with lymphocytic gastritis and H pylori infection were treated with a one week course of omeprazole, clarithromycin, and metronidazole. Gastric and duodenal intraepithelial lymphocyte (IEL) counts were performed, along with histological assessment of gastric and duodenal biopsies before and after H pylori eradication. RESULTS: Two months after treatment there was a significant reduction in gastric IEL counts in both antrum and corpus. There was no significant change in duodenal IEL counts before and after eradication. According to the Sydney grading there was significant improvement in corpus inflammation after eradication. The patients histologically H pylori positive before treatment became H pylori negative. Dyspepsia scores also improved significantly after treatment. CONCLUSIONS: H pylori eradication treatment in patients with lymphocytic gastritis causes significant improvement in the gastric IEL infiltrate, corpus inflammation, and dyspeptic symptoms. H pylori serology is frequently positive when histology and UBT are negative. Lymphocytic gastritis may represent a specific immune response to H pylori infection.

Adult↗

The pattern of involvement of the gastric mucosa in lymphocytic gastritis is predictive of the presence of duodenal pathology.

AIM: To determine whether the pattern of involvement of the gastric mucosa in lymphocytic gastritis is predictive of the presence or absence of duodenal pathology. METHODS: 50 cases (M:F, 26:24; median age 57 years) diagnosed as lymphocytic gastritis between 1986 and 1998 with concurrent duodenal (D2) biopsies were identified from a computer search of the pathology records and validated by counting gastric intraepithelial lymphocytes. Gastric and duodenal intraepithelial lymphocyte counts were performed on haematoxylin and eosin (H&E) and anti-CD3 stained sections. D2 biopsies were assessed for villous atrophy and chronic inflammatory cell infiltration by subjective grading, and gastritis was classified and graded according to the updated Sydney system. A case was designated corpus predominant when the corpus chronic inflammation grade exceeded that of the antrum. If it was less, then the case was antrum predominant, and if they were equal it was diffuse (pan-) gastritis. The ratio between the corpus and antral intraepithelial lymphocyte count in individual patients was calculated. RESULTS: Of 50 cases of lymphocytic gastritis, 21 were classified as corpus predominant. With one exception (a case of mild villous atrophy), all were accompanied by normal duodenal morphology. Cases with a corpus predominant gastritis had median duodenal intraepithelial lymphocyte counts of 19 (H&E) and 14.1 (CD3), whereas 29 subjects with an antrum predominant or diffuse gastritis had median counts of 39.9 (H&E) and 37.9 (CD3). Fifteen of these 29 cases (52%) showed villous atrophy; all were graded as moderate or severe. Patients with any degree of villous atrophy had a mean corpus/antrum intraepithelial lymphocyte ratio (H&E) of 0.59 (representing antral predominance), while those with normal duodenal morphology had a ratio of 2.39 (p < 0.0001). CONCLUSIONS: The pattern of involvement of gastric mucosa in lymphocytic gastritis is closely related to the associated duodenal pathology. Those with the corpus predominant form are unlikely to have duodenal pathology, while those with an antral predominant or diffuse form should have distal duodenal biopsies taken to exclude villous atrophy.

CD3 Complex↗

VIP (etoposide, ifosfamide and cisplatinum) as a salvage intensification program in relapsed or refractory Hodgkin's disease.

Forty-two patients with refractory (15 patients) or relapsed (27 patients) Hodgkin's disease (HD) were included in a prospective single center study evaluating the efficacy of a regimen VIP combining etoposide 75 mg/m2/day days 1-5, ifosfamide 1.2 g/m2/day days 1-5 and cisplatinum 20 mg/m2/day days 1-5, one course every 4 weeks as salvage therapy in patients with refractory or relapsed Hodgkin's disease, potentially eligible for high-dose chemotherapy with reinjection of hematopoietic stem cells (HSC). If patients were considered chemosensitive after two courses of VIP, high-dose chemotherapy followed by the reinjection of HSC was planned. After two courses of VIP, 67% achieved an objective response including 38% complete responses. Overall, 28 patients went on to high-dose therapy with reinjection of HSC, and 46% of grafted patients are in a sustained complete remission. When the overall patient population is considered, 33% are in complete remission (CR) with a median follow-up of 37 months. A CR of less than 12 months and refractory disease were associated with a poor survival. These results showed that the VIP regimen is effective in relapsed or refractory HD and allows high-dose therapy to be given in the case of most responding patients. However, results in patients with refractory disease or a first complete remission of less than 12 months need to be further improved.

Adolescent↗

The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: an analysis of the AML 8A study of the EORTC Leukaemia Cooperative Group and GIMEMA. European Organization for Research and Treatment of Cancer. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.

To determine whether patients with a HLA-identical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention-to-treat principles was performed within the framework of the EORTC-GIMEMA randomized phase III AML 8A trial. Patients in complete remission (CR) received one intensive consolidation course. Patients with a histocompatible sibling donor were then allocated allogeneic bone marrow transplantation (alloBMT), the patients without a donor were randomized between autologous BMT (ABMT) and a second intensive consolidation (IC2). 831 patients <46 years old and alive >8 weeks from diagnosis were included. HLA typing was performed in 672 patients. AlloBMT was performed during CR1 in 180 (61%) out of 295 patients with a donor. Another 38 patients were allografted: five in resistant disease, 14 during relapse and 19 in CR2. ABMT was performed in 130 (34%) out of 377 patients without a donor in CR1, in six (2%) patients during relapse and in 38 (10%) patients during CR2. The disease-free survival (DFS) from CR for patients with a donor was significantly longer than for patients without a donor (46% v 33% at 6 years; P=0.01, RR 0.78, 95% confidence interval 0.63-0.96). The overall survival from diagnosis for patients with a donor was longer, but not statistically significant, than for patients without a donor (48% v 40% at 6 years; logrank P=0.24). When patients were stratified according to prognostic risk groups, the same trend in favour of patients with a donor was seen for survival duration and the DFS remained significantly longer for this group of patients.

Adolescent↗

Phase II trial of fludarabine monophosphate in patients with mantle-cell lymphomas.

PURPOSE: The aim of this phase II trial was to assess the efficacy of fludarabine monophosphate in untreated and pretreated mantle-cell lymphomas (MCL). PATIENTS AND METHODS: Fifteen patients with MCL were included in the study. In two cases, fludarabine was the first-line therapy, the second in four cases, the third in five cases, and the fourth in four cases. The diagnosis of MCL was based on the criteria of the European Lymphoma Task Force (ELTF), with morphologic, immunologic, and cytogenetic data. Patients were treated with intravenous fludarabine 25 mg/m2/d for 5 days every 4 weeks. RESULTS: Toxicity of fludarabine was mild: World Health Organization (WHO) grade 3 and 4 granulocytopenia occurred in 15 of 56 assessable cycles (cy) (27%), there was no grade 3 or 4 thrombocytopenia, one grade 3 bacterial lung infection, and no treatment-related death. There were five partial responses (33%) but no complete response. The duration of these responses was short and ranged from 4 to 8 months. CONCLUSION: These results suggest that fludarabine can be moderately effective in the treatment of MCL. Fludarabine appears to be far less effective than in chronic lymphocytic leukemia (CLL) and follicular non-Hodgkin's lymphoma (NHL). Therefore, fludarabine should be evaluated in association with other chemotherapeutic agents in MCL.

Adult↗

Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy--the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report. European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group.

PURPOSE AND METHODS: Optimization of remission-induction and postremission therapy in elderly individuals with acute myeloid leukemia (AML) was the subject of a randomized study in patients older than 60 years. Remission-induction chemotherapy was compared between daunomycin (DNR) 30 mg/m2 on days 1, 2, and 3 versus mitoxantrone (MTZ) 8 mg/m2 on days 1, 2, and 3, both plus cytarabine (Ara-C) 100 mg/m2 on days 1 to 7. Following complete remission (CR), patients received one additional cycle of DNR or MTZ chemotherapy and were then eligible for a second randomization between eight cycles of low-dose (LD)-Ara-C 10 mg/m2 subcutaneously every 12 hours for 1 2 days every 6 weeks or no further treatment. RESULTS: A total of 242 patients was randomized to DNR and 247 to MTZ. Median age of both study groups was 68 years. Secondary AML was documented in 26% and 25% of patients in either arm. The probability of attaining CR was greater (P = .069) with MTZ (47%) than with DNR (38%). Median duration of neutropenia was 19 (DNR) and 22 days (MTZ). The greater response rate to MTZ therapy correlated with reduced occurrence of chemotherapy resistance (32% v 47%, P = .001). With a median follow-up of 6 years, 5-year disease-free survival (DFS) is 8% in each arm. Overall survival estimates are not different between the groups (6% v 9% at 5 yrs). Poor performance status at diagnosis, high WBC count, older age, secondary AML, and presence of cytogenetic abnormalities all had an adverse impact on survival. Secondary AML and abnormal cytogenetics predicted for shorter duration of CR. Among complete responders, 74 assessable patients were assigned to Ara-C and 73 to no further therapy. Actuarial DFS was significantly longer (P = .006) for Ara-C-treated (13% [SE = 4.0%] at 5 years) versus nontreated patients (7% [SE = 3%]), but overall survival was similar (P = .29): 18% (SE = 4.6%) versus 15% (SE = 4.3%). Meta-analysis on the value of Ara-C postremission therapy confirms these results. CONCLUSION: In previously untreated elderly patients with AML, MTZ induction therapy produces a slightly better CR rate than does a DNR-containing regimen, but it has no significant effect on remission duration and survival. Ara-C in maintenance may prolong DFS, but it did not improve survival.

Acute Disease↗

Quantitative analysis of T helper 1, T helper 2, and inflammatory cytokine expression in patients after allogeneic bone marrow transplantation: relationship with the occurrence of acute graft-versus-host disease.

BACKGROUND: To further delineate the cytokine involvement in human acute graft-versus-host disease (GVHD), we analyzed cytokine expression in peripheral blood mononuclear cells (PBMC) from patients who developed acute GVHD after allogeneic bone marrow transplantation and from those who did not. METHODS: We used a highly quantitative and sensitive polymerase chain reaction assay based on the coamplification of an internal standard, with the cDNA derived from the mRNA of interest. Results are expressed in copy numbers, after normalization to a fixed amount of actin, allowing comparison between different samples. After a myeloablative regimen, 22 patients with hematological diseases received an unmanipulated allograft from a matched sibling. They were subsequently submitted to prophylactic immunosuppression. We examined the transcription of genes encoding cytokines in PBMC and skin biopsies. We selected T helper 1 (interferon ([IFN]gamma, interleukin [IL]-2), T helper 2 (IL-4, IL-10), and inflammatory (IL-1, IL-6) cytokines. RESULTS: Four weeks after bone marrow transplantation, the bulk of the PBMC population exhibited an increased expression of IL-1 and IL-6, with no major difference between GVHD+ and GVHD- patients. In addition, although IL-2 expression was not detected, increased levels of IFNgamma mRNA were observed in allografted patients, with higher levels in GVHD+ patients. In skin biopsies sampled at the beginning of GVHD, although low expression of IL-1 and IL-6 could be observed, neither type 1 (IL-2, IFNgamma) nor type 2 (IL-4, IL-10) cytokines could be detected. CONCLUSIONS: These studies suggest that the occurrence of human GVHD does not seem to be clearly associated with a T helper 1-type cytokine pattern.

Acute Disease↗

Should cytomegalovirus be tested for in both blood and bronchoalveolar lavage fluid of patients at a high risk of CMV pneumonia after bone marrow transplantation?

To identify and treat patients at high risk of cytomegalovirus (CMV) pneumonia after bone marrow transplantation (BMT), we tested for CMV viraemia weekly, and performed broncho-alveolar lavage (BAL) on day 35 post-transplant in 63 recipients. 36 allogeneic BMT recipients were at a high risk of CMV pneumonia (25 CMV-seropositive recipients and 11 patients receiving marrow from a CMV-seropositive donor). Patients with a positive BAL or viraemia received a 14 d course of ganciclovir or foscarnet. CMV was detected in 29 (46%) of the 63 BMT recipients and excretion of CMV in blood and BAL was significantly linked. However, among the 29 patients who excreted the virus, only 10 (35%) shed CMV in blood and BAL at the same time: 19 patients (65%) had detectable CMV in blood (11 patients) or BAL (eight patients) only. Therefore, on the basis of viraemia or BAL alone, 21/29 patients (70%) and 18/29 patients (60%), respectively, would have received antiviral treatment. BAL increased the CMV detection rate by 13% (8/63 patients) relative to viraemia. With this strategy, the incidence of CMV pneumonia was reduced to 3% in allografted patients. Only two of the 19 autografted patients developed fatal CMV pneumonia. We avoided anti-CMV treatment in 54% of all the BMT recipients. In conclusion, CMV should be tested for in both blood and BAL fluid of BMT recipients at high risk of CMV pneumonia.

Bone Marrow Transplantation↗

Mantle cell lymphomas: characteristics, natural history and prognostic factors of 45 cases.

We reviewed 77 cases considered as lymphocytic lymphomas of intermediate differentiation or diffuse centrocytic lymphomas. Forty-five cases were diagnosed as mantle cell lymphoma (MCL). The architectural pattern was diffuse in 95%, 8 cases presented large blastoid cells and CD5 positivity was observed in 28/34 cases. Of 20 cases studied, 8 presented a t(11;14)(q13;q32). Patient characteristics were: median age 59 years, B symptoms in 38%, 87% stages III-IV, bone marrow involvement in 67% with peripheral leukemic cells in 24%. Forty-four patients were treated with chemotherapy and 7 received radiotherapy. The complete response (CR) rate was 58%. Of the 26 CR, 19 relapsed at a median of 15 months. Disease-free survival was 42% and overall survival was 73% at 3 years. In a univariate analysis, overall survival was related to liver and bone marrow involvement, the presence of peripheral lymphomatous cells and achieving a complete response.

Adult↗