Shwachman syndrome: Exocrine pancreatic dysfunction and variable phenotypic expression

BACKGROUND & AIMS: Shwachman syndrome is an inherited condition with multisystemic abnormalities, including exocrine pancreatic dysfunction. The aim of this study was to evaluate the occurrence and progression of features in a large cohort of patients. METHODS: Clinical records of 25 patients with Shwachman syndrome were reviewed. RESULTS: Mean birth weight (2.92 +/- 0.51 kg) was at the 25th percentile. However, by 6 months of age, mean heights and weights were less than the 5th percentile. After 6 months of age, growth velocity was normal. Severe fat maldigestion due to pancreatic insufficiency was present in early life (fecal fat, 26% +/- 17% of fat intake; age, < 2 years). Serial assessment of exocrine pancreatic function showed persistent deficits of enzyme secretion, but 45% of patients showed moderate age-related improvements leading to pancreatic sufficiency. Neutropenia was the most common hematologic abnormality (88%), but leukopenia, thrombocytopenia, and anemia were also frequently encountered. Patients with hypoplasia of all three bone marrow cellular lines (n = 11) had the worst prognosis; 5 patients died, 2 of sepsis and 3 of acute myelogenous leukemia. Other findings included hepatomegaly and/or abnormal liver function test results and skeletal abnormalities. CONCLUSIONS: A wide and varied spectrum of phenotypic abnormalities among patients with Shwachman syndrome is described. Pancreatic acinar dysfunction is an invariable abnormality. Patients with severe bone marrow involvement may have a guarded prognosis. (Gastroenterology 1996 Dec;111(6):1593-602)     

X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox

Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X- linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease.     

Highly sensitive p-type 4H-SiC van der Pauw sensor

This paper presents for the first time a p-type 4H silicon carbide (4H-SiC) van der Pauw strain sensor by utilizing the strain induced effect in four-terminal devices. The sensor was fabricated from a 4H-SiC (0001) wafer, using a 1 μm thick p-type epilayer with a concentration of 10¹⁸ cm⁻³. Taking advantage of the four-terminal configuration, the sensor can eliminate the need for resistance-to-voltage conversion which is typically required for two-terminal devices. The van der Pauw sensor also exhibits an excellent repeatability and linearity with a significantly large output voltage in induced strain ranging from 0 to 334 ppm. Various sensors aligned in different orientations were measured and a high sensitivity of 26.3 ppm⁻¹ was obtained. Combining these performances with the excellent mechanical strength, electrical conductivity, thermal stability, and chemical inertness of 4H-SiC, the proposed sensor is promising for strain monitoring in harsh environments.

This paper presents for the first time a p-type 4H silicon carbide (4H-SiC) van der Pauw strain sensor by utilizing the strain induced effect in four-terminal devices.     

Correlates of treatment satisfaction and well‐being among patients with type II diabetes

Aim

To examine the impact of patient characteristics, anthropometric measurement and patient clinical variables on their appraisal of treatment satisfaction and well‐being.

Background

Treatment satisfaction and well‐being are instrumental in achieving diabetes care goals. Nursing practices and healthcare policies may inform interventions in these areas.

Introduction

The prevalence of diabetes is high in the Middle East. An understanding of relationships between clinical and socio‐demographic variables and well‐being and treatment satisfaction is needed to improve care and patient outcomes.

Methods

A total of 1002 patients completed tools measuring well‐being, treatment satisfaction and socio‐demographic characteristics. A series of bivariate and multivariate analysis were conducted to identify factors associated with well‐being and treatment satisfaction.

Results

Males reported better treatment satisfaction and well‐being than females. Older participants, those who were compliant to diet, with controlled diabetes, and no neuropathy reported higher treatment satisfaction scores and well‐being scores. Insulin therapy was associated with better treatment satisfaction.

Discussion

Females, participants who were not prescribed diabetic diets and those with complications were more likely to be negatively impacted by diabetes. Individuals with diabetes who were treated with insulin had higher treatment satisfaction than those who used oral hypoglycaemic agents.

Conclusion and implication for nursing and health policy

These findings are important in assisting nurses and other healthcare professionals in identifying patients with diabetes with low treatment satisfaction who may present a greater risk for poor well‐being. Additionally, they lend support to developing policies for frequent screenings and special therapeutic interventions that are needed to maximize patients’ treatment satisfaction and well‐being in the Middle East and elsewhere.     

Microbiota That Affect Risk for Shigellosis in Children in Low-Income Countries

Pathogens in the gastrointestinal tract exist within a vast population of microbes. We examined associations between pathogens and composition of gut microbiota as they relate to Shigella spp./enteroinvasive Escherichia coli infection. We analyzed 3,035 stool specimens (1,735 nondiarrheal and 1,300 moderate-to-severe diarrheal) from the Global Enteric Multicenter Study for 9 enteropathogens. Diarrheal specimens had a higher number of enteropathogens (diarrheal mean 1.4, nondiarrheal mean 0.95; p<0.0001). Rotavirus showed a negative association with Shigella spp. in cases of diarrhea (odds ratio 0.31, 95% CI 0.17–0.55) and had a large combined effect on moderate-to-severe diarrhea (odds ratio 29, 95% CI 3.8–220). In 4 Lactobacillus taxa identified by 16S rRNA gene sequencing, the association between pathogen and disease was decreased, which is consistent with the possibility that Lactobacillus spp. are protective against Shigella spp.–induced diarrhea. Bacterial diversity of gut microbiota was associated with diarrhea status, not high levels of the Shigella spp. ipaH gene.     

Effect of nutrition counselling with a digital job aid on child dietary diversity: Analysis of secondary outcomes from a cluster randomised controlled trial in rural Bangladesh

Adequate dietary diversity among infants is often suboptimal in developing countries. We assessed the impact of nutrition counselling using a digital job aid on dietary diversity of children aged 6–23 months using data from a cluster randomised controlled trial in Bangladesh. The trial had five arms, each with 25 clusters. The four intervention arms provided counselling using a digital job aid and different prenatal and post-natal combinations of lipid-based supplements and the comparison arm with usual practice. We enrolled 1500 pregnant women and followed them until the children reached their second birthday. We developed a tablet-based system for intervention delivery, data collection and project supervision. We combined the four intervention arms (n = 855), in which community health workers (CHWs) provided age-appropriate complementary feeding counselling, to compare against the comparison arm (n = 403). We calculated the outcome indicators from the children's 24-h dietary recalls. Overall, the intervention increased the mean dietary diversity score by 0.09 (95% confidence interval [CI]: 0.2–0.16) and odds of minimum dietary diversity by 18% (95% CI: 0.99–1.40). However, there was a significant interaction on the effect of the intervention on dietary diversity by age. The mean dietary diversity score was 0.24 (95% CI: 0.11–0.37) higher in the intervention than in the comparison arm at 9 months and 0.14 (95% CI: 0.01–27) at 12 months of age. The intervention effect was non-significant at an older age. Overall, consumption of flesh food was 1.32 times higher in the intervention arm (odds ratio [OR] 1.32, 95% CI: 1.11–1.57) in 6–23 months of age. The intervention significantly improved child dietary diversity score in households with mild and moderate food insecurity by 0.27 (95% CI: 0.06–0.49) and 0.16 (0.05–27), respectively, but not with food-secure and severely food-insecure households. Although the study did not evaluate the impact of digital job aid alone, the findings indicate the utility of nutrition counselling by CHWs using a digital job aid to improve child feeding practices in broader programmes.     

DNA of Helicobacter spp. and common gut bacteria in primary liver carcinoma

BACKGROUND AND AIM: Gastric and enteric Helicobacter species have been associated with the pathogenesis of some extragastric diseases. METHODS: We retrospectively investigated the presence of DNA of Helicobacter species in samples of the cancer and the surrounding tumour-free liver tissues of patients with hepatocellular carcinoma (HCC, n=12) and cholangiocarcinoma (CC, n=13). The patients were from an area with low liver cancer incidence and with low hepatitis B and C prevalence. Patients with a benign liver disease (n=24) were included as controls. Paraffin-embedded liver samples were examined by a Helicobacter genus-specific PCR assay as well as group-specific PCR assays for Enterobacteriaceae, Bacteroides, Lactobacillus and Enterococcus. PCR products of positive samples were characterised by denaturing gradient gel electrophoresis (DGGE) and DNA sequencing. RESULTS: PCR assay detected Helicobacter DNA in seven of 12 (58%) and eight of 13 (62%) normal liver tissue specimens from HCC and CC patients, respectively. Two cancer samples from HCC patients were Helicobacter-positive but none of the CC cancers. In the control group, three of 24 (12.5%) patients with a benign liver condition were positive for Helicobacter species (p<0.01 compared to results of tumour-free liver tissue from the cancer patients). DGGE and DNA sequence analysis showed that 90% of the detected PCR products were "H. pylori-like". DNA of some other enteric bacteria was detected in the liver of one cancer patient and one control (4% of all patients). CONCLUSION: The presence of DNA of Helicobacter species in liver specimens, but not of other common gut bacteria, was associated with human hepatic carcinogenesis.