Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation

Life-threatening complications such as graft versus host disease and infection remain major barriers to the success of allogeneic hemopoietic stem cell transplantation (SCT). While pretransplantation conditioning and posttransplantation immunosuppression are important risk factors for infection, the reasons that similarly immunosuppressed transplant recipients show marked variation in frequency of infection after allogeneic SCT are unclear. Mannose-binding lectin (MBL) deficiency is a risk factor for infection in other situations where immunity is compromised. We investigated associations between MBL2 gene polymorphisms and risk of major infection following allogeneic SCT. Ninety-seven related allogeneic donor-recipient pairs were studied. Clinical data including survival, days of fever, graft versus host disease incidence and severity, and infection were collected by case note review. Five single-nucleotide polymorphisms in the MBL2 gene were genotyped using the polymerase chain reaction and sequence-specific primers. MBL2 coding mutations were associated with an increased risk of major infection following transplantation. This association was seen for donor (P =.002, odds ratio [OR] 4.1) and recipient (P =.04, OR 2.6) MBL2 genotype. MBL2 promoter variants were also associated with major infection. The high-producing haplotype HYA was associated with a markedly reduced risk of infection (recipient HYA P =.0001, OR 0.16; donor HYA P =.001, OR 0.23). Donor MBL2 coding mutations and recipient HYA haplotype were independently associated with infection in multivariate analysis. These results suggest that MBL2 genotype influences the risk of infection following allogeneic SCT and that both donor and recipient MBL2 genotype are important. These findings raise the possibility that MBL replacement therapy may be useful following transplantation.     

Antigen—Antibody Complexes in Inflammatory Bowel Disease

One hundred and sixty patients have been studied to assess the significance of circulating antigen–antibody complexes in inflammatory bowel d sease (IBD). Sera from patients with ulcerative colitis and Crohn's disease were assayed for Clq-binding antigen–antibody complexes (CIC) and the results compared with those obtained from 52 patients with other inflammatory gastrointestinal diseases (GI controls) and 26 normal volunteers (normal controls). Significantly elevated CIC levels were found in patients with active IBD compared with inactive IBD or normal controls. However, similar high levels were also found in the GI control group. CIC levels in a group of undernourished patients with Crohn's disease fell significantly after treatment with an oral nutritional supplement. The results suggest that CIC-mediated inflammation is likely to be associated with intestinal mucosal disease in a non-specific manner.     

DNA densitometry of colorectal cancer.

DNA analysis was assessed by densitometry for 281 cases of colorectal adenocarcinoma. Detection of aneuploidy in a single case rose from 65% if one, to 92.5% when three or more sections, were analysed. Although aneuploid tumours had significantly larger nuclear areas than near diploid tumours (p = 0.009), densitometric measurements showed no association with clinicopathological variables. DNA content determined by densitometry was compared with that from flow cytometry on 465 tissue sections from 241 cases. Aneuploidy assessed by flow cytometry was significantly associated with that determined by densitometry (p < 0.01 for all comparisons), ploidy state being similar in 381 sections (82%, kappa = 0.63, p < 0.001), and 187 cases (77.6%, kappa = 0.57, p < 0.001). Univariate survival analysis showed that DNA densitometric variables had no significant association with survival in (a) all cases, (b) cases without lymph node metastases, or (c) cases without distant metastases. Multivariate regression analysis of densitometric and clinicopathological variables identified Dukes's stage, patient age, and tumour differentiation as the combination of variables most closely related to survival. Densitometric measurement of DNA content could not significantly improve on the prognostic model containing these three variables. It is concluded that, although the assessment of DNA content by densitometry is comparable with that of flow cytometry, conventional histological variables remain the best predictors of prognosis in colorectal cancer.     

Disodium cromoglycate in the treatment of chronic proctitis.

The effect of topical disodium cromoglycate (DSCG) has been examined in 30 patients with chronic active proctitis using a double-blind crossover trial. Each treatment period was four weeks and patients were given DSCG 200 mg by enema twice daily and 100 mg orally three times each day. Twenty-six patients completed the trial successfully, 14 responded to DSCG treatment, two improved with placebo, and 10 responded to neither. Patients who responded to DSCG had significantly more eosinophils in their rectal biopsies than those who failed to respond and in some instances the counts were very high. The findings support the hypothesis than an allergic reaction is important in the pathogenesis of proctitis.     

Ductal Carcinoma In Situ: The Impact of Screening on Clinical Presentation and Pathologic Features

Abstract: It has been suggested that mammographic screening may produce an overdiagnosis bias leading to unnecessary treatment for inconsequential ductal-carcinomain-situ lesions. To assess the malignant potential of ductal carcinoma in situ, we compared pathologic features and presentation of ductal carcinoma in situ in patients treated before (1969–1985) and after (1986–1990) the intensified use of screening at our institution. We reviewed 204 cases of ductal carcinoma in situ in patients treated between 1969 and 1990. Histologic slides were available for 145 patients. Pathologic features evaluated included histologic subtype and nuclear grade. When the prescreening era was compared with the postscreening era, the incidence of palpable mass decreased from 54% to 12%, ductal discharge decreased from 14% to 3%, Paget's disease decreased from 10% to 3%, and mammographically detected lesions increased from 19% to 80%. The incidence of comedo subtype increased from 14% to 36% (p = 0.0195). Seven percent of palpable masses and 38% of mammographically detected ductal-carcinoma-in-situ lesions were of the comedo subtype, which presented almost exclusively as a mammographic abnormality (p < 0.0015). Grade 1 lesions decreased from 38% to 28%, and grade 3 lesions increased from 24% to 33%. Palpable masses tended to be lower grades and mammographically detected lesions tended to be higher grades. The malignant potential of mammographically detected lesions as determined by grade and histologic subtype is greater than that of symptomatic ductal carcinoma in situ. Mode of presentation does not appear to be a useful prognostic factor. Mammographically detected ductal carcinoma in situ is not an inconsequential finding and should not be treated as such.     

Acute pancreatitis: a comparison of the severity of illness in cases first diagnosed before and after death, using a modified prognostic index.

The severity of disease in a series of patients in whom acute pancreatitis was diagnosed at autopsy was assessed by the retrospective application of a standard prognostic index modified for post-mortem use. The results were compared with cases dying of acute pancreatitis which was recognized during life and appropriately treated. No difference in disease severity could be identified between the two groups. This suggests that patients dying of acute pancreatitis unrecognized during life have a severe form of the disease and do not die because a mild attack is treated inappropriately. The condition appears to be unrecognized in such patients because it presents with atypical features.     

A search for a transmissible agent in Crohn's disease.

Controversy exists as to whether a transmissible agent is responsible for Crohn's disease. Previous reports have suggested that sarcoid-like granulomas can develop in animals following inoculation of homogenates derived from bowel affected by Crohn's disease. This study involved the injection of Crohn's tissue homogenates into experimental animals under a variety of conditions which might be expected to favour the demonstration of such an agent. Homogenates have been inoculated into the ileum of rats, mice, and rabbits and also given inoculated into ileum and footpads of rats which have previously been rendered lymphoedematous by surgical interruption of the draining lymphatics. Bowel homogenates from a total of 17 patients with Crohn's disease have been injected into 91 experimental animals. No macroscopic or microscopic changes indicative of Crohn's disease were detected. Thus study does not support the suggestion that a transmissible agent is present in Crohn's disease.     

The relationship between blood and urine alcohol concentrations at autopsy

The relationship between the blood alcohol concentration and the urine alcohol concentration was studied in 109 routine coroner's autopsies. Although the average ratio for urine alcohol concentration to blood alcohol concentration lay close to the ratio of 4:3 quoted in the literature, the actual ratios determined were widely scattered around this value. Thus the use of this simple ratio to estimate the blood alcohol concentration from the urine alcohol concentration at post-mortem was unreliable. An equation determined by employing linear regression analysis was similarly unhelpful in enabling one to derive a precise value for the blood alcohol concentration from a given urine alcohol concentration. It was concluded that the main value in determining the urine alcohol concentration at autopsy was to exclude the possibility of the alcohol present in the blood sample having been generated during the post-mortem interval.