Low molecular weight heparin (tinzaparin) vs. placebo in the treatment of mild to moderately active ulcerative colitis

BACKGROUND: Heparin has anti-inflammatory and immunomodulatory activity which may be of therapeutic benefit in the treatment of ulcerative colitis. AIM: To test whether low molecular weight heparin, given subcutaneously, would provide a significant therapeutic response compared with placebo in the treatment of mild to moderate ulcerative colitis. STUDY DESIGN: A prospective, double-blind, randomized, placebo-controlled, multi-centre trial comparing tinzaparin 175 anti-Xa IU/kg/day (innohep, LEO Pharma) subcutaneously for 14 days followed by tinzaparin 4500 anti-Xa IU/day subcutaneously for 28 days with placebo, administered subcutaneously once daily for up to 42 days. The primary outcome measure was the mean change in colitis activity from baseline to the end of study treatment assessed by the sum of scores of stool frequency, rectal bleeding, sigmoidoscopic appearance and histology. Secondary outcome measures included changes in individual activity indices and laboratory parameters. Patients were assessed at weekly intervals for 6 weeks and within 1 week of completing treatment. RESULTS: One hundred patients with active ulcerative colitis (up to six bloody stools per day, no fever, no tachycardia or systemic disturbances) were randomized. Forty-eight received tinzaparin and 52 received placebo. The difference in the mean percentage change in colitis activity from baseline to end of treatment (tinzaparin-placebo) was not statistically significant (P = 0.84). There was no difference between tinzaparin and placebo in any secondary outcome measure. One major bleed (rectal), occurred in a patient receiving placebo. CONCLUSION: This is the largest trial to date of heparin in ulcerative colitis. The results show no benefit of low molecular weight heparin over placebo in mild to moderately active ulcerative colitis.     

Difficulties in the diagnosis of intracystic tumors of the female breast

The objective of the current study was to determine the accuracy of radiological and cytological diagnoses of intracystic and papillary lesions in distinguishing between true papillary benign and malignant lesions. Seventy cytological reports of intracystic proliferations were selected from our cytopathological database at the Breast Health Corporation, Budapest, Hungary, dating back to the last 7 years. Retrospective analysis of the diagnostic approaches--mammography, ultrasonography, clinical examination and cytology--was performed in selected cases. The results of imaging and cytological examination are routinely reported on a categorical scale ranging from 1 to 5. 44 patients underwent surgical excision: histology showed benign lesions in 21 and malignant lesions in 23 cases. Twelve patients, who did not undergo biopsy and presented a stable disease at follow-ups, were also included in the group of benign lesion. Fifteen patients were not available for follow-up. Concerning the total investigated cases the mean categorical values of mammography, ultrasonography and cytology were 2.24, 2.78 and 3.05 respectively. The malignant and benign groups significantly differ from each other concerning the mean age of the patients (p=0.0216), the distribution of the coded mammographical results (p= 0.0171) the cytological results (p=0.0001), and average tumor size measured on mammogram images (p=0.0199). The two group does not significantly differ over the distribution of mammographical density patterns (p=0.1075), radiomorphological appearance (p=0.1101), average tumor size measured on ultrasonography (p=0.2665), and patient complaints (p=0.2634). The evaluation of ultrasonography shows borderline significance (Pearson Chi-square test: p=0.0616, M-L Chi-square test: p=0.0404) between the malignant and benign groups. Differential diagnosis between malignant and benign intracystic and papillary lesions is feasible using common radiological diagnostics. However, more efficient teamwork is needed with the cooperation of a well-trained cytologist and radiologist, who are able to produce precise images of the lesions, and guides the aspiration of the adequate samples for cytology, which is the most valuable examination.     

Prosocial Behavior Is a Relative Strength in Siblings of Children with Physical Disabilities or Autism Spectrum Disorder

Research on siblings of children with developmental and physical disabilities has emphasized negative influences on siblings’ mental health. Yet, such siblings may be more prosocial compared with siblings of children without disabilities, due to care responsibilities and their experiences with their brother’s or sister’s disability. We compared prosocial behavior between siblings of children with autism spectrum disorder (ASD; n?=?47), physical disabilities (n?=?42), and siblings of children without disabilities (n?=?44) using a multi-informant approach (i.e., child-, mother-, and father-report). Prosocial behavior was measured with the Strengths and Difficulties Questionnaire. Drawing on the theoretical and empirical sibling literature, we also examined whether siblings’ internalizing and externalizing difficulties, adjustment to the sibling situation, and communication with parents correlated with siblings’ prosocial behavior. Child-reported internalizing difficulties and mother–child communication significantly correlated with mother-reported prosocial behavior. Child-reported internalizing and externalizing difficulties significantly correlated with father-reported prosocial behavior. No significant correlates with child-reported prosocial behavior was identified. When adjusting for siblings’ internalizing and externalizing difficulties and mother–child communication, siblings of children with physical disabilities scored significantly higher than siblings of children without disabilities on mother- and father-reported prosocial behavior. Siblings of children with ASD scored significantly higher on mother-reported prosocial behavior. We conclude that prosocial behavior may be a relative strength in siblings of children with developmental and physical disabilities, and that siblings’ prosocial behavior may be influenced by type of disability, mental health, and family communication. Interventions targeting siblings’ mental health and family communication may be helpful in promoting siblings’ prosocial behavior.

     

Immunohistochemical findings in jejunal specimens from patients with IgA deficiency.

Jejunal biopsy specimens from 25 patients with IgA deficiency (IgAd) were studied immunohistochemically to find markers of inflammation. Five of the 25 patients had coeliac disease (CD): they were on a gluten free diet and had normal jejunal morphology. Only two of 15 specimens from control subjects had CD25+ cells in the surface epithelium, while this was seen in 19 out of 20 specimens from IgAd patients (p < 0.0001). A significant increase of CD25+ cells was also noted in the lamina propria of IgAd patients. The median percentage of crypt cells in mitosis (Ki67+ cells) was higher in the specimens from IgAd patients (26%) than in those from controls (13%, p < 0.001). The densities of gamma delta T cell receptor positive cells in the surface epithelium and lamina propria did not differ in the specimens from IgAd patients and those of controls nor was the expression of HLA class II antigens augmented in the surface epithelium. These findings were similar for the IgAd patients whether or not the patient had DQB 0201 allele, a genetic marker which is strongly associated with CD. The inadequacy of the local immunoglobulins in patients with IgAd may lead to increased T cell activation, which is accompanied by the appearance of intraepithelial CD25+ cells and with an increase in the mitotic rate in the crypts.     

Semi-automated Construction of Decision Rules to Predict Morbidities from Clinical Texts

Objective

In this study the authors describe the system submitted by the team of University of Szeged to the second i2b2 Challenge in Natural Language Processing for Clinical Data. The challenge focused on the development of automatic systems that analyzed clinical discharge summary texts and addressed the following question: “Who''s obese and what co-morbidities do they (definitely/most likely) have?”. Target diseases included obesity and its 15 most frequent comorbidities exhibited by patients, while the target labels corresponded to expert judgments based on textual evidence and intuition (separately).

Design

The authors applied statistical methods to preselect the most common and confident terms and evaluated outlier documents by hand to discover infrequent spelling variants. The authors expected a system with dictionaries gathered semi-automatically to have a good performance with moderate development costs (the authors examined just a small proportion of the records manually).

Measurements

Following the standard evaluation method of the second Workshop on challenges in Natural Language Processing for Clinical Data, the authors used both macro- and microaveraged Fβ=1 measure for evaluation.

Results

The authors submission achieved a microaverage F_β=1 score of 97.29% for classification based on textual evidence (macroaverage F_β=1 = 76.22%) and 96.42% for intuitive judgments (macroaverage F_β=1 = 67.27%).

Conclusions

The results demonstrate the feasibility of the authors approach and show that even very simple systems with a shallow linguistic analysis can achieve remarkable accuracy scores for classifying clinical records on a limited set of concepts.     

The impact of sodium chloride and volume depletion in the chronic kidney disease of congenital chloride diarrhea

Congenital chloride diarrhea is due to mutations in the intestinal Cl(-)/HCO(3)(-) exchange (SLC26A3) which results in sodium chloride and fluid depletion leading to hypochloremic and hypokalemic metabolic alkalosis. Although treatment with sodium and potassium chloride offers protection from renal involvement in childhood, the long-term renal outcome remains unclear. Here we describe two cases of congenital chloride diarrhea-associated end-stage renal disease with transplantation. Further, we show that there is a high incidence of mild chronic kidney disease in 35 other patients with congenital chloride diarrhea. The main feature of the renal injury was nephrocalcinosis, without hypercalciuria or nephrolithiasis with small sized kidneys and commensurately reduced glomerular filtration rates. This suggests that diarrhea-related sodium chloride and volume depletion, the first signs of non-optimal salt substitution, promote urine supersaturation and crystal precipitation. The poor compliance with salt substitution along with long-lasting hypochloremic and hypokalemic metabolic alkalosis is likely to induce progressive calcification and renal failure. Both our patients developed nephrocalcinosis in the transplanted kidneys suggesting that this complication is a consequence of intestinal SLC26A3 deficiency. Interestingly, the transporter is expressed in the distal nephron but the recurrence of nephrocalcinosis in the transplanted kidney suggests that it does not play a significant renal role in this syndrome.     

Fungal gut colonization with Candida or Pityrosporum sp. and serum Candida antigen in preterm neonates with very low birth weights.

To evaluate the diagnostic value of gut colonization by yeasts and of candida antigen in serum for predicting fungal infection in very premature neonates, faecal and serum samples were obtained biweekly from 27 newborn babies treated at our neonatal intensive care unit. Altogether 82 sets of serum and faecal samples were obtained. 17 babies were followed for > or = 4 weeks. Blood cultures, both by routine and lysis centrifugation techniques, were performed for bacteria and fungi if infection was suspected. All children were given systemic broad-spectrum antibiotic treatment. Five of the children died, all without evidence of fungal infection. No systemic antifungal treatments were given. Quantitative faecal cultures demonstrated Candida albicans in 3 (11%) (10(3)-10(5) colony forming units/g) and Pityrosporum sp. in 8 (30%) of the preterm neonates. Candida antigen in titre 4 was detected in 1/82 serum samples. The child subsequently died with no other evidence of candida infection. In 56 full term neonates treated at the intensive care unit during the same period and tested by 1 set of samples, faecal colonization with Candida sp. was detected in 2 (4%) and with Pityrosporum sp. in 4 (15%). None were positive for candida antigen. Fungal gut colonization did not lead to clinical infection in the preterm neonates studied. The false positivity rate of the candida antigen test was low (0.7%). The predictive value of the test could not be determined in this study group with no systemic fungal infections. The role of pityrosporum as an inducer of neonatal infections remains to be evaluated.     

Extra-abdominal desmoid mimicking malignant male breast tumor

A rare case of extra-abdominal desmoid tumor is reported. A palpable mass was detected in the right breast of a 47-year-old man. Mammography showed a stellate mass without calcification, and breast ultrasound examination revealed a solid, inhomogeneous, non-calcified lesion. The result of cytological examination of the fine-needle aspiration biopsy specimen was equivocal. Histology of the surgical specimen showed extra-abdominal desmoid tumor. Extra-abdominal presentation of this semimalignant tumor is rare and may mimic malignant breast tumor. Differential diagnosis is difficult and usually based on the result of the histological examination. Received: 2 July 1998; Revision received: 8 September 1998; Accepted: 14 October 1998