Simple gas chromatography analysis of faecal butyrate: application to patients at risk of pouchitis.

In spite of the fact that pouchitis is the most frequently occurring and troublesome complication found in patients treated by ileo-anal anastomosis for ulcerative colitis, no biological marker currently exists to monitor the outcome of the disease. Since it has been noted faecal butyrate is reduced in patients with pouchitis, we developed a simple gas chromatography method to quantify butyrate in faecal water. This test is based on diethyl ether extraction with the use of methacrylic acid as an internal standard. We demonstrated that butyrate was effectively measured when this technique was applied to eleven patients with ileal-pouch anal anastomosis within the first year after the closure of their ileostomy. We also observed a noticeable reduction in the concentration of butyrate in patients who went on to develop a pouchitis.

Oxidative markers in diabetic ketoacidosis.

UNLABELLED: Oxidative stress has been implicated in the pathogenesis of the chronic complications of diabetes mellitus but little is known in diabetic ketoacidosis (DKA). The aim of this work was to determine whether lipid peroxidation, as assessed by measuring malondialdehyde (MDA, a prooxidant) and antioxidant status (TAS, an index of antioxidant defenses), is modified in DKA, and also whether any observed abnormalities were related to metabolic disturbances. METHODS: four groups of patients were studied, comprising 19 patients with DKA, massive ketonuria and plasma standard bicarbonate levels below 16 mmol/l (group 1); 20 patients with poorly controlled diabetes, glycated hemoglobin (HbA1c) above 8% and plasma bicarbonate levels above 16 mmol/l (group 2); 11 patients with well-controlled diabetes and HbA1c below 8% (group 3); and 10 non-diabetic, non-obese control subjects (group 4). Metabolic parameters, MDA levels and TAS were assessed in the plasma of the four groups of subjects. RESULTS: mean plasma MDA and TAS values were significantly different among the four groups (respectively p < 0.001 and p < 0.01). Mean plasma MDA value was significantly higher in group 1 than in group 3 (p < 0.02) and group 4 (p < 0.001) but was not different from that in group 2. Mean plasma MDA value in group 2 was significantly lower than that in group 4 (p = 0.002). Mean plasma TAS value in group 1 was significantly lower than in groups 3 (p < 0.002) and 4 (p < 0.05). Mean plasma TAS value was significantly lower in group 2 than in group 4 (p<0.05). Plasma MDA values in the diabetic patients (groups 1+2+3) were not related to any clinical characteristics (BMI, age, duration of the disease) or metabolic parameters (glycemia, HbA1c bicarbonates, blood urea nitrogen, phosphatemia, lipids), while plasma TAS values correlated negatively with glycemia, osmolality and HbA1c. A significant relationship was also found between TAS and HbA1c in group 1 (p < 0.05) and between MDA and HbA1c in group 3 (p < 0.05). Correlations were also found between TAS and phosphatemia in group 1 (p < 0.01) and between MDA and phosphatemia in group 2 (p < 0.01). A positive relationship between MDA and cholesterol levels was found in group 1 (p < 0.01). In conclusion, MDA values are increased and TAS values decreased in DKA and poorly controlled diabetes, and tend to correlate more with markers of diabetic imbalance than with markers of acute metabolic disturbances of DKA.

Type 1 multiple endocrine neoplasia (MEN1): contribution of genetic analysis to the screening and follow-up of a large French kindred.

OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal genetic disorder, the clinical phenotype of which includes tumours of the parathyroids and/or anterior pituitary and/or endocrine pancreas. The genetic defect has been mapped to the chromosome 11q13 and the MEN1 gene has been recently identified, thus allowing genetic screening in affected kindreds. The aim of this study was to establish the usefulness of genetic screening in the follow-up of a large MEN1 kindred. PATIENTS: We describe a large kindred of 91 members, of whom 56 had clinical, biochemical and genetic screening. Twenty eight of them have been tested annually for the last 5 years. RESULTS: Although the precise mutation is still undetermined in this kindred, genotypic determination confirmed linkage with the MEN1 gene in affected members and excluded 28 members from annual testing. By drawing our attention to susceptible subjects, genetic screening improved the evaluation of age-related penetrance of the disease in the 3 generations from this kindred. For instance, annual screening showed conversion from unaffected to affected phenotype in 4 subjects aged 14, 14, 15, and 17 years. Moreover, genetics helped us to evaluate the specificity of clinical or biochemical markers, and thus to discard useless investigations. So far however, the genetics have not helped to explain the phenotypic heterogeneity and particularly low incidence of pancreatic tumours in this kindred. CONCLUSION: Genetic screening is very useful in detecting high risk individuals for MEN 1, since it avoids time-consuming and expensive investigations in non-affected subjects. By providing better understanding of the age-related penetrance of this syndrome, it improves the efficiency of screening. Genetic studies allow differentiation between clinical and biochemical features that are useful in follow-up and other confusing or unhelpful parameters.

Changes in serum amylase, lipase and leukocyte elastase during diabetic ketoacidosis and poorly controlled diabetes.

Diabetic ketoacidosis (DKA) is frequently associated with pancreatic enzyme abnormalities. In order to determine the main factors that lead to this increase, serum total amylase (TA), pancreatic amylase (PA), lipase (L) and leukocyte elastase (LE), an early predictor of acute pancreatitis, were measured in four groups of patients on admission. Group 1 consisted of 52 patients with DKA (age: 41.9 +/- 19.2 years; blood glucose (Glc): 27.4 +/- 11.5 mmol/L; pH: 7.20 +/- 0.16; plasma bicarbonate: 10.5 +/- 6.2 mmol/L; blood urea nitrogen (BUN): 0.60 +/- 0.44 g/L; HbA(1C): 12.5% +/- 2.8%). Group 2 consisted of 90 patients with poorly controlled non-ketotic diabetes (age: 53.4 +/- 16.0; Glc: 14.3 +/- 0.6; HCO(3)(-): 26.6 +/- 3.2; BUN: 0.38 +/- 0.20; HbA(1C): 11.3 +/- 2.1). Group 3 consisted of 22 patients with well-controlled diabetes (age: 53.7 +/- 12.8; Glc: 10. 1 +/- 5.2; HCO(3)(-): 27.4 +/- 3.8; BUN: 0.36 +/- 0.19; HbA(1C): 6.8 +/- 0.8). Group 4 (controls) comprised 27 non-diabetic patients (age: 46.0 +/- 15.0; Glc: 4.9 +/- 0.5; HCO(3)(-): 28.4 +/- 2.5; BUN: 0.30 +/- 0.16; HbA(1C): 5.2 +/- 0.7) (means +/- SD). Increased enzyme activities were more frequent in group 1 (TA: 30.7; PA: 27.0; L: 36.5; LE: 73%) than in groups 2 (TA: 8.9; PA: 7.1; L: 8.9; LE: 45. 5%), 3 (TA: 13.6; PA: 9.0; L: 18.1; LE: 31.8%) and 4 (TA: 7.0; PA: 3. 0; L: 0.0; LE: 29.6%). Mean serum enzyme activities were significantly different in the 4 groups (ANOVA, P < 0.01) and were higher in group 1 than in groups 2, 3 and 4 (Student's t-test; group 1 vs 2 or 3 or 4: P < 0.001). In groups 1 + 2 + 3 + 4 (all patients), the four enzymes correlated with one another and also with Glc, BUN and HCO(3)(-) (P < 0.001). In group 1, TA correlated negatively with HCO(3)(-) (P < 0.001) and pH (P < 0.05); PA and L correlated positively with Glc and BUN (P < 0.01) and negatively with HCO(3)(-) (respectively, p < 0.01 and 0.05). PA correlated positively with pH (P < 0.01); LE correlated with Glc (P < 0.05) and BUN (P < 0.01). In conclusion, this study suggests that the serum levels of pancreatic enzymes increase with the degree of diabetic disequilibrium, and mainly correlate with metabolic factors such as hyperglycaemia, dehydration and acidosis. Increased pancreatic enzyme activities in patients with DKA, even in combination with abdominal pain, should not be diagnosed as acute pancreatitis; this could be important, particularly for younger clinicians.