Intestinal permeability in the newborn

Passive intestinal permeability in 33 newborn babies was studied using feeds containing lactulose and mannitol. Each marker is thought to pass across the gut wall by a different route; lactulose by a paracellular and mannitol by a transcellular pathway. Neither is metabolised and both are wholly and solely excreted by the kidney; urinary recovery is a measure of the intestinal uptake. Babies born before 34 weeks' gestation exhibited a higher intestinal permeability to lactulose than more mature babies, and all preterm babies showed an appreciable decline in lactulose absorption during the first week of oral feeds. Babies of 34 to 37 weeks' gestation achieved a 'mature' intestinal permeability to lactulose within four days of starting oral feeds. These findings may reflect the immaturity of the gut of the preterm baby rather than a process essential to adaptation to enteral nutrition.     

Modulation of sympathetic activity by corticotropin-releasing hormone and atrial natriuretic peptide

BACKGROUND: Heart rate variability represents a reliable marker to delineate the status of autonomic nervous system (ANS) function and alterations due to stress in vivo. Interestingly, up to now the effects of corticotropin-releasing hormone (CRH), a key regulator of the stress hormone system, upon heart rate variability are not sufficiently described. Hence, we attempted to investigate the ANS-effects of a CRH bolus and the modulatory influences of atrial natriuretic peptide (ANP), one of the most important functional antagonist of CRH actions.METHODS: 12 healthy male volunteers were administered 100 microg CRH as bolus injection at 15:00. Six randomly chosen subjects received 150 microg ANP dissolved in normal saline and six subjects a normal saline infusion from 14:45 to 15:15. From 13:00 to 17:00 an ECG was recorded and mean heart rate (HR), total power (TP), very low frequency (VLF), low frequency (LF), LF in normalized units (LF [nu]), high frequency (HF) domains and the LF/HF-ratio in the interval from 14:00 to 16:00 were determined.RESULTS: After administration of CRH a significant increase in HR and a fast reduction of TP were observed, which lasted about 1 h. Based upon spectral domain analyses the sympathetic activity after CRH administration as indicated by LF [nu] increased by 31% (mean location) during saline. Applying ANP this increase was reduced to 19% (mean location). The VLF component, which is considered to be based in part also on sympathetic influences, indicates comparable effect. During saline the VLF after CRH bolus remained largely unchanged, but was reduced to 66% by ANP. Though the vagal activity indicated by the HF component was reduced after CRH, no significant differences emerged between both treatments. The changes of the LF/HF-ratio were pronounced in both groups. During saline this ratio increased by about 111%, during ANP only by 43% (mean location).CONCLUSIONS: Based upon HRV analysis the CRH administration induced sympathotonic effects which were antagonized by ANP. The observed vagal changes were less pronounced and need further investigation. Further studies of autonomic effects by alterations of CRH secretion in depression and anxiety disorder are strongly warranted.     

Adrenal insufficiency

Adrenal insufficiency is caused by either primary adrenal failure (mostly due to autoimmune adrenalitis) or by hypothalamic-pituitary impairment of the corticotropic axis (predominantly due to pituitary disease). It is a rare disease, but is life threatening when overlooked. Main presenting symptoms such as fatigue, anorexia, and weight loss are non-specific, thus diagnosis is often delayed. The diagnostic work-up is well established but some pitfalls remain, particularly in the identification of secondary adrenal insufficiency. Despite optimised life-saving glucocorticoid-replacement and mineralocorticoid-replacement therapy, health-related quality of life in adrenal insufficiency is more severely impaired than previously thought. Dehydroepiandrosterone-replacement therapy has been introduced that could help to restore quality of life. Monitoring of glucocorticoid-replacement quality is hampered by lack of objective methods of assessment, and is therefore largely based on clinical grounds. Thus, long-term management of patients with adrenal insufficiency remains a challenge, requiring an experienced specialist. However, all doctors should know how to diagnose and manage suspected acute adrenal failure.     

Is there any relationship between functional dyspepsia and chronic gastritis associated with Helicobacter pylori infection?

BACKGROUND/AIMS: The relationship between functional dyspepsia, H. pylori infection and chronic gastritis is controversial. Our aims were 1) To determine the prevalence of symptoms and the degree of association between symptoms and histopathological findings in different topographical gastric regions in patients with functional dyspepsia and H. pylori infection; 2) To determine the effect of eradication treatment on functional dyspepsia symptoms. METHODOLOGY: Prospective randomized study. 251 consecutive patients with dyspepsia (141 women and 110 men), mean age 48.08, SD 16.68 (without ulcer, gastric malignancy or reflux esophageal disease as determined by endoscopy), and with H. pylori infection, underwent upper endoscopy accompanied by the obtaining of 6 biopsies (cardia, corpus, antrum) at baseline, 3 and 6 months after treatment (pantoprazole 40 mg, once daily, amoxycillin 100 mg b.i.d., clarithromycine 500 mg b.i.d.). Inflammation, activity, H. pylori presence and other mucosal alterations were evaluated semi-quantitatively according to the Sydney system, before treatment and 6 months following treatment. An interview that was carried out before, and 6 months following the treatment, determined seven symptoms (scored as 0-3); epigastric burning and pressure, pain after meal, nausea, vomiting, bloating and belching, pain on empty stomach and anorexia. 95% confidence intervals were calculated for mean values of the symptoms and histological findings. The association between symptoms and histological findings was determined by the Kendall tau-b (K tau-b). Using the t test on a 5% level of significance we tested the null hypothesis that symptoms and histological findings were independent variables. RESULTS: The effectiveness of eradication after 3 months was 87.3% and after 6 months 92.0%. Reinfection rate after 6 months was 6.4% and the overall failure of eradication was 1.6%. Significant decline of chronic inflammation, activity and H. pylori was found in cardia, corpus and antrum (P = 0.001). Glandular atrophy was found to be lower in corpus and antrum (P = 0.001), whereas in cardia an increase was found. Intestinal metaplasia remained unchanged in all gastric regions, whereas a higher degree of foveolar hyperplasia was found, which was most pronounced in corpus and antrum (P = 0.01). There was a significant regression of lymphoid follicles in cardia and antrum (P = 0.001). On the first visit, the mean significant association between symptoms and histological findings was higher, with lower variation of K tau values as compared with the visit 6 months after treatment (K tau-b 0.171, SD 0.05, variation coefficient 30.5% vs. K tau-b 0.167, SD 0.07, variation coefficient 41.5%). According to the topographic distribution of gastritis at the time of the first visit, the mean significant association between symptoms and findings was found to be highest in antrum and corpus as opposed to the visit 6 months after treatment, where the values of association were found to be highest for variables from cardia and lowest for those in gastric corpus. After 6 months both the number of patients complaining of symptoms and dyspepsia score were lower (Wilcoxon P = 0.000). CONCLUSIONS: Advanced morphological changes of gastric mucosa were found to be significantly associated with symptoms of dysmotility. Pain on an empty stomach is predictive of antral inflammation. Cardia showed higher values of mean association with symptoms 6 months after therapy. Eradication treatment results in an improvement of both inflammatory changes and symptoms. In some patients persisting dysmotility symptoms were associated with persistent inflammation in cardia, which was also true for antrum, however to a lesser degree.     

Ki-ras mutations are an early event and correlate with tumor stage in transplacentally-induced murine lung tumors

A previous study from this laboratory demonstrated that treatment of pregnant mice with 3-methylcholanthrene (MC) caused lung tumors in the offspring at 1 year after birth, the incidence of which correlated with fetal inducibility of Cyp1a1. Analysis by PCR amplification and allele- specific hybridization (ASO) of paraffin-embedded tumors generated from that study revealed the presence of point mutations in exon 1 of the Ki- ras gene. This work has now been expanded by PCR amplification and ASO analysis of 31 additional lesions. Point mutations were found in 37 of the 47 (79%) lesions analyzed in this and the previous study, the majority of which were G-->T transversions in the first or second base of codon 12. The mutational spectrum appeared to be dependent on the relative stage of differentiation of the lesion, as both the incidence of mutation and type of mutation produced correlated with malignant progression. Mutations occurred in 60% of the hyperplasias, 80% of the adenomas and 100% of the adenocarcinomas. In the lesions with mutations, GLY12-->CYS12 transversions occurred in 100% of the hyperplasias, 42% of the adenomas and 14% of the adenocarcinomas. The GLY12-->VAL12 transversions occurred in none of the hyperplasias, 42% of the adenomas and 57% of the adenocarcinomas. The remaining mutations, which consisted of ASP12 transitions and ARG13 transversions, occurred only in adenomas (17%) and adenocarcinomas (29%). Between this study and our previous analyses, the identity of the mutations obtained by ASO were confirmed by sequence analysis of eight of the 37 lesions that harbored mutations at the Ki-ras gene locus. There were no differences in the type or incidence of mutations relative to the metabolic phenotype or sex of the mice. These data suggest that mutational activation of the Ki-ras gene locus is an early event in transplacental lung tumorigenesis, and that the type of mutations produced by exposure to chemical carcinogens can influence the carcinogenic potential of the tumor. This may have prognostic significance in determining the malignant progression of the neoplasm.      

Circulating lipids and glycaemic control in insulin dependent diabetic children

The prevalence of dyslipidaemia in children with insulin dependent diabetes mellitus (IDDM) and its relation to glycaemic control was studied in a group of 51 diabetic children and a control population of 132 schoolchildren. The prevalence of dyslipidaemia in the fasting state was increased in the diabetic group (39%) compared with control subjects (17%). Serum cholesterol concentration alone was raised in 25% of diabetic subjects while serum cholesterol and triglycerides were raised in 14%, compared with 16% and 0.7% respectively in control subjects. Serum total cholesterol (5.1 v 4.5 mmol/l), low density lipoprotein cholesterol (3.2 v 2.6 mmol/l), non-esterified fatty acids (0.91 v 0.50 mmol/l), and triglycerides (0.94 v 0.76 mmol/l) were higher in diabetic children. Serum total cholesterol, triglycerides, and apolipoprotein (apo)B concentrations increased with worsening control, while serum high density lipoprotein cholesterol and apoA-I concentrations were unaltered. There were also positive correlations between glycated haemoglobin and total cholesterol, triglycerides, and apoB in diabetic children. Thus, abnormalities in circulating lipids are common in young subjects with IDDM but largely disappear if blood glucose concentrations are reasonably controlled.     

Failure of ablation of a mediastinal parathyroid adenoma by repeated contrast staining

In a patient with primary hyperparathyroidism an attempt was made to ablate a middle mediastinal parathyroid gland by forceful staining with radiographic contrast material. The gland was stained on two separate occasions, two weeks apart. Both times the serum calcium level temporarily fell to the normal range but reverted to abnormal levels. The patient ultimately required surgery for correction of hypercalcemia. The mechanism of staining and possible reasons for failure as well as potential complications are discussed.