Immunogenicity of subcutaneous TNF inhibitors and its clinical significance in real-life setting in patients with spondyloarthritis.

KEY MESSAGES: Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1-2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients.

Arginase activity in peripheral blood of patients with intestinal schistosomiasis, Wonji, Central Ethiopia.

Morbidity and mortality caused by schistosomiasis usually results from immunopathology. But the underlying mechanisms are not yet clearly understood. Th2-type immune response is thought to be dominant during chronic schistosomiasis, and upregulation of arginase-I is one component of this milieu. A cohort study was conducted to assess arginase activity in peripheral blood of humans with intestinal schistosomiasis in Wonji-Shoa Sugar Estate, Central Ethiopia. Laboratory-confirmed 30 Schistosoma mansoni-infected patients and 18 apparently healthy controls were recruited. Faecal egg count was carried out by Kato-Katz technique. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated from whole blood. Activity of arginase in plasma and PBMC lysates was measured, and results were compared with that of controls. Twenty-one of 30 patients had light infection, whereas moderate and heavy intensity infections were observed in eight and only one patient(s), respectively. A significant increase in both PBMC (patients: 59.96 + 82.99, controls: 25.44 + 24.6 mU/mg protein, P < 0.0001) and plasma (patients: 1.61 + 2.19, controls: 0.31 + 0.73 mU/mL plasma, P < 0.0001) arginase activity was observed during human S. mansoni infection. Arginase activity increases in peripheral blood of patients with intestinal schistosomiasis.

The Benefits and Barriers of Using Point-of-Care Ultrasound in Primary Healthcare in the United States.

An effective healthcare system should embrace practices that enhance overall quality and productivity. Training primary care physicians in Point-of-Care Ultrasound (POCUS) has become part of the processes that improve the quality of patient care and serve to guide the diagnostic impression quickly and effectively. With the purpose of highlighting the applications and challenges of POCUS use in US primary health care, we conducted a narrative review based on PubMed-indexed and Cochrane Library English text publications searched in May-July 2022 using a combination of key terms including point of care ultrasound, primary care, and US healthcare. Many studies have shown that POCUS has a positive impact on fostering medical attention and reducing morbidity, mortality, and healthcare costs. Besides assisting in procedures, POCUS has a head-to-toe application in evaluating inflammatory and infectious conditions, acute abdomen, cardiopulmonary function, musculoskeletal and vascular pathologies. However, its uniform implementation is limited across the US healthcare system due to multitudes of barriers such as lack of training, resource scarcity, and low reimbursement. Training primary care physicians in general and emergency care providers, in particular, is key to scaleup POCUS use. Large size studies are paramount to further explore the effectiveness of POCUS and identify key challenges to its implementation.

The effect of raw carrot on serum lipids and colon function.

Two hundred grams of raw carrot eaten at breakfast each day for 3 weeks significantly reduced serum cholesterol by 11%, increased fecal bile acid and fat excretion by 50%, and modestly increased stool weight by 25%. This suggests an associated change in bacterial flora or metabolism. The changes in serum cholesterol, fecal bile acids, and fat persisted 3 weeks after stopping treatment.

Intestinal Parasitic Infections among Under-Five Children and Maternal Awareness about the Infections in Shesha Kekele; Wondo Genet; Southern Ethiopia

Background: Few studies have reported the magnitude of intestinal parasitic infections among under-five children in tropical countries. Moreover; there is little information on maternal awareness about intestinal parasitosis. Objective: To determine the prevalence of intestinal parasitosis among under-five children; and assess maternal awareness about it in Shesha Kebkele; Wondo Genet; Southern Ethiopia. Methods: A cross-sectional study involving 288 under-five children was conducted and stool samples were collected and examined for intestinal parasites using Kato-Katz and formol-ether concentration methods. In addition; a total of 130 mothers of under-five children were interviewed regarding their awareness about intestinal parasitic infections. Results: Of the 288 children; 245 (85.1) were found infected with one or more intestinal parasites. The prevalence of Trichuris trichiura; Schistosoma mansoni and Ascaris lumbricoides; hookworm; and Hymenolepis nana infections as determined by Kato-Katz were 74.7; 37.2; 25.7; 5.9; and 4.5; respectively. On the other hand; the prevalence of Strongyloides stercoralis; Giardia lamblia; Entamoeba histolytica/dispar; and Entamoeba coli infections as determined by formol-ether concentration method were 0.69; 13.2; 0.35; and 2.1; respectively. Most mothers were reasonably aware of the mode of transmission of ascariasis; amoebiasis and giardiasis while they had very limited knowledge of bilharzia and hookworm transmission. Almost all of the respondents reported that infections with intestinal parasites could cause retardation of growth and death in children unless treated. Conclusion: Intestinal parasitic infections were prevalent in varying magnitude among under-five children in Wondo Genet area; Southern Ethiopia. Mothers in the study area had a fairly good knowledge of the impact of infections but limited knowledge of the mode of transmission of intestinal parasitic infections. Improvement of sanitation and health education are required besides preventive chemotherapy to control worms (except for schistosomiasis in under-five which need treatment on an individual basis) and other intestinal parasitic infections in the area. (Ethiop. J. Health Dev. 2010;24(3):185-190)

The effect of dietary fibre isolates on gastric secretion, acidity and emptying.

1. In six volunteers, the effect of intragastric administration of different water-soluble chemical isolates of dietary fibre on gastric secretion, acidity and emptying was studied. 2. At 30 min after administration of the test meals, the stomach contents were completely aspirated and the volume, pH, phenol red concentration, total titratable acidity and different electrolytes were measured. 3. Compared with the control meal, the pH and unionized (combined) hydrogen concentrations were significantly higher (P less than 0.05) following most of the fibre-containing meals, while the total titratable acid concentration was not significantly different. None of the fibre-containing meals appreciably altered the volume or type of gastric secretion but had a low-grade variable effect on gastric emptying. 4. It is concluded that most dietary fibre isolates, although having a definite and notable buffering effect on the acid in the stomach, have a minimal effect on gastric secretion and a variable and small effect on gastric emptying.

The effect on intestinal disaccharidase activity of feeding galactose to growing rats.

The effect of supplementation of the diet with galactose on the age-related decline of intestinal lactase activity was investigated in 108 growing rats. Starting from 14 days of age, the rats were divided into two groups and fed with chow, and with fluid either as tap water or 5% galactose solution. At 14 days the specific lactase activity was 112.8 +/- 3.2 mumol min-1 (g protein)-1, which decreased to less than 10% of this value at maturity. Galactose supplementation did not prevent the decline. The increase of maltase, sucrase and trehalase was also unaffected. The result suggests that galactose plays no significant role in the regulation of disaccharidase activities in the rat.

The effect of continued feeding of physiological amounts of lactose on the level of intestinal lactase and other disaccharidase enzyme activities in the rat.

Intestinal lactase activity in mammals is high at birth but begins to decline around weaning and reaches very low levels in adult life. The triggering mechanism for this decline is not clear. Because of the association of the decline with weaning, lack of lactose in the diet has been implicated. In 110 growing rats, the effect of continued supplementation of the diet after weaning with physiological amounts of either cows' milk or a 5% lactose solution on intestinal lactase and other disaccharidase enzyme activities was investigated. In both control and test animals, the specific lactase activity decreased from a peak value of 115 +/- 4 mumol min-1 g-1 protein before weaning to about 10% at maturity. There was no significant difference in the level or the pattern of decline between the groups. Sucrase, maltase and trehalase showed the normal maturational changes without being affected by the test diets. The finding suggests that diet, particularly the presence or absence of physiological amounts of lactose, has no appreciable effect on the age related spontaneous decline of intestinal lactase activity or on the pattern of development of the other disaccharidases.

Metabolism of dietary fibre components in man assessed by breath hydrogen and methane.

1. Breath hydrogen and methane were measured in eight normal individuals after acute and separate administration of different chemical components of dietary fibre. 2. Hemicellulose, raffinose and lactulose increased H2 production, while cellulose pectin and lignin did not. Methane production was found to be individual and unaffected by any of the substances. Differences in physical properties of the same chemical appear to have no influences on H2 and CH4 production.

Late-onset hypolactasia in Hong Kong school children.

Three hundred and twenty Chinese school children aged between 6 and 19 years from six schools in Hong Kong were tested for their lactose digestion status. After an overnight fast, the children were challenged with cow's milk, 5 ml/kg bodyweight (i.e. lactose approximately 0.25 g/kg). Malabsorption was assessed by measuring hydrogen concentration from end-expiratory breath samples taken in duplicate before and at 90 and 180 minutes after the challenge. On average, 10% of the children showed an increase in breath hydrogen excretion within 3 h after the challenge, indicating malabsorption of lactose. None of the children complained of gastro-intestinal symptoms or showed any clinical sign of intolerance to the milk. The number of malabsorbers increased significantly (p less than 0.001) with age, starting at about 3% at the age of 8 and reaching about 27% at the age of 18 years. The sharpest rise occurred between 14 and 15 years. It is concluded that, despite the high prevalence of hypolactasia, Hong Kong Chinese children can consume normal amounts of milk without developing any untoward clinical symptom or sign.

A new method of expired gas collection for the measurement of breath hydrogen (H2) in infants and small children.

The measurement of hydrogen (H2) in breath is becoming increasingly useful as a diagnostic and research tool, but there is still no satisfactory method of sampling expired air in infants and small children. We tested a modified open-flow hood method where the child's head is put in a perspex box and expired air is collected by sucking air from the box by means of an air pump. Comparison of this method with end-expiratory sampling by a modified Haldane-Priestly and nasopharyngeal catheter gave a correlation coefficient of 0.83 and 0.65, respectively. We conclude that expired air sampling in children with this method is a more satisfactory and as reliable a method as any available at present, and has the added advantage of being quantitative.

The status of lactose absorption in Hong Kong Chinese children.

Lactose malabsorption was investigated in 169 Chinese children aged between two and 16 years using the breath hydrogen test. The challenge was either lactose solution (1 g/kg) or cow's milk (10 ml/kg). Overall, 68% of the children showed a significant increase in breath hydrogen following the lactose challenge while only 17% showed an increase after the cow's milk challenge and 13% after both challenges. The number of malabsorbers increased significantly (p less than 0.001) with age and no associated gastrointestinal symptoms or signs were found in any of the children following the challenges, suggesting a gradual and partial loss of intestinal lactase activity. We conclude that the prevalence of lactose malabsorption in Hong Kong children is very high using the standard lactose tolerance test but when a more realistic amount of lactose and a natural medium such as a glass of milk is used as the challenge, the number of malabsorbers becomes small and clinically insignificant.

Breath methane excretion in Hong Kong Chinese children.

The factors which determine whether an individual is a methane excretor or a nonexcretor are not clearly understood. Genetic makeup, ethnic origin, diet, environment, or an interaction of all these factors have been implicated. In order to delineate the incidence, the age of onset, and environmental factors that may influence the excretion of methane in our community, we investigated a total of 425 Chinese children in Hong Kong (204 females, 221 males). End-expiratory breath samples were collected after an overnight fast and measured by gas-chromatography using a flame ionization detector. Thirty one children (7.3%) excreted at least 1 ppm methane above the ambient level (median = 6.4, range = 1.8-26.0 ppm). There was no difference in methane excretion status and pattern between the sexes or between children who lived at home and those who lived at an institution. There was a general increase in the number of methane excretors with age, but a statistically significant increase was reached only after 14 years of age. The amount of methane excreted was unrelated to age and there were no excretors detected under the age of 5 years. It is concluded that the methane excretion pattern of these children was generally similar to those previously reported from other regions, but the incidence is much lower and the age of onset appears to be more gradual.

The effect of dietary fibre on bile acid metabolism in rats.

1. Forty-eight male rats were fed sequentially for 14 d periods on diets containing different fibre contents. 2. One of the high-fibre diets was a commercial pelleted diet. The other was a low-fibre diet supplemented with 200 g wheat bran/kg. 3. At the end of each feeding period eight rats were killed. Liver microsomal cholesterol 7 alpha-hydroxylase (EC 1.14.1.-) activity and bile acid content of small intestine and colon were determined. 4. The different diets did not significantly alter the total intestinal bile acids, but affected the distribution and qualitative pattern in the colon and small intestine. 5. On the high-fibre diets deoxycholate, and hyodeoxycholate tended to be increased. 6. On the low-fibre diets the alpha, beta- and omega-muricholic acids tended to be increased. 7. Liver microsomal cholesterol 7 alpha-hydroxylase activity was lower in rats on the low-fibre and bran-supplemented low-fibre diets compared with that in rats fed on the commercial pelleted diet.

Breath hydrogen in pneumatosis cystoides intestinalis.

Pneumatosis cystoides intestinalis (PCI) is an uncommon condition of unknown aetiology. Bacterial gas production may be an important aetiological factor, but experimental evidence in humans has been lacking. We have studied breath hydrogen excretion as an index of bacterial gas production in 12 patients with PCI and have shown that four out of five with demonstrable cysts produced unusually high levels of hydrogen while fasting. This abnormality has not been previously reported. One patient showed resolution of PCI after antibiotic treatment. These findings confirm the importance of bacterial gas production in the pathogenesis of PCI.