Fasting serum insulin in relation to fat distribution, serum lipid profile, and blood pressure in European women: the European Fat Distribution Study.

Samples of 38-year-old women were randomly selected from five European centers: Ede (The Netherlands), Warsaw (Poland), Gothenburg (Sweden), Verona (northern Italy), and Afragola (Naples-southern Italy). In total, 452 healthy women were studied. Anthropometric measurements were taken by one operator in each country after common training of all operators and blood parameters of all women were determined in one laboratory. Body mass index (BMI) was different among centers, mainly due to the higher values in southern Italy. Women from southern Europe had more central fat distribution than women from north European centers. Fasting serum insulin was higher in women from Poland and The Netherlands than in the other three centers. After adjustment for BMI, fasting insulin was significantly related to subscapular skinfold, subscapular to triceps skinfold ratio, waist circumference, and waist to thigh circumference ratio, although the partial correlations varied somewhat between the centers. In the pooled data, waist circumference showed the highest correlations with fasting serum insulin when adjusted for BMI. Fasting serum insulin showed significant partial correlations, adjusted for BMI, with lipid profile and blood pressure only in women from the two Italian centers. In the pooled data, fasting serum insulin was significantly positively correlated with serum triglycerides and total cholesterol and negatively to high-density lipoprotein (HDL) cholesterol and HDL/total cholesterol, independently of BMI and waist circumference. While blood pressure was not related to insulin in the pooled women, when adjusted for BMI and waist circumference; here as well, there were some differences in relationships between the centers.(ABSTRACT TRUNCATED AT 250 WORDS)

Variations in time of serum pancreatic enzyme levels in chronic pancreatitis and clinical course of the disease.

Thirty-four patients with chronic calcified pancreatitis were evaluated clinically and biochemically (at a time when painful relapses were not present) every 9 mo for 3 yr; 25 of them were also studied at 4 and 9 yr. Serum elastase-1, trypsin, lipase, and amylase in the same sera were measured at each visit; levels on entry and variations during the study were compared with the clinical and functional data of the patients. On entry, low levels of elastase-1 were found in 11.7% of the patients, high levels in 41.1%; in contrast, high levels of trypsin and lipase were found in only a small number of patients (5.8 and 11.7%, respectively), whereas low levels were present in a substantial number (47.8 and 32.3% for trypsin and lipase, respectively). Over time, we found a significant (p = 0.000002) reduction in elastase-1 levels. Such reduction was not found for trypsin, lipase, or amylase. The reduction of serum elastase-1 was significantly (p less than 0.003) more frequent in patients presenting a reduction in painful relapses than in patients with a stable or increased attach rate; this association was weaker (p less than 0.05) for lipase and trypsin, and absent for amylase. No correlation was found between circulating enzymes and either alcohol consumption or age of patients. In patients with severe exocrine impairment, low levels of elastase were found in only 20% of the cases, whereas trypsin and lipase were reduced in 73.3 and 53.3% of the cases, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A simple test for predisposition to LDL oxidation based on the fluorescence development during copper-catalyzed oxidative modification.

When human low density lipoprotein (LDL) obtained from 10 volunteers was incubated in air at 37 degrees C in the presence of various concentrations of copper, an increase in fluorescence was observed with emission maximum at 430 nm when excitation was performed at 360 nm. The fluorescence increase was inhibited by ethylenediamine tetraacetic acid and by 4-methyl-2,6-di-tert-butylphenol. The fluorescence was found to be tightly bound to the protein moiety. Furthermore, Cu2+ modification of LDL was associated with a decrease in the reactive amino groups of apolipoprotein B and in the uptake of the lipoprotein by rabbit fibroblasts. Under our conditions, the fluorescence increase showed two consecutive periods; an inhibition period during which the fluorescence increased only weakly, and a propagation period with a rapid increase in fluorescence that was linear for at least 5 h. Both periods were influenced by copper concentration. The study also shows that the extent of fluorescence generated upon LDL oxidation varied greatly in the volunteers. Thus, while the results demonstrate that the fluorescence increase may likely monitor the extent of the apoB derivatization, the calculation of the fluorescence development rate of the propagation period together with the duration of the inhibition period may constitute a quantitative measurement of the susceptibility of apoB to be derivatized.

Isoamylase determination by isoelectric focusing in pancreatic disorders. A potential clinical aid.

Isoamylase analysis by isoelectric focusing was performed in the serum of 30 healthy volunteers, 65 patients with acute or chronic pancreatic diseases, nine with acute abdomen, four with macroamylasemia, and four with duodenal duplication. In controls, up to four fractions (2 salivary, 2 pancreatic) were found; the pancreatic fractions were as a mean 44.7% (SD 8.6) of total. In chronic pancreatitis, only patients with steatorrhea showed a significant reduction of pancreatic isoamylase (p less than 0.001). In all patients with acute pancreatitis or pseudocysts, an additional fraction (similar to the so-called P3 fraction) was resolved. Moreover, additional isoenzymes were found in all patients with severe acute pancreatitis or pseudocysts, and not in controls or patients with mild forms, acute abdomen or duodenal duplication. A similar pattern was shown in a stored control serum after 10 mo at -20 degrees C. These fractions disappeared after successful surgical drainage. No specific alteration was found in pancreatic cancer. Amylase fractionation by isoelectric focusing can be used to confirm an acute pancreatitis, and to monitor patients with pancreatic pseudocysts and collections after surgical drainage.

Lack of pancreatic maldigestion in atopic dermatitis.

Twenty adult patients affected by atopic dermatitis (AD) were submitted to the p-aminobenzoic acid (PABA) test in order to evaluate the proteolytic pancreatic function. All but one showed a normal PABA test. These results seem to exclude a proteolytic maldigestion as a pathogenetic factor in AD.

Acute and chronic pancreatitis: an up-date.

According to the 1988 Marseilles-Rome classification inflammatory pancreatic diseases are represented by acute (AP) and chronic pancreatitis (CP), pancreatic fibrosis and abscesses (due to infection of cystic cavities). Each form is defined by specific etiological, pathomorphological, functional and evolutive aspects. In our experience with 348 AP cases, gallstones and chronic alcohol abuse, alone or together, represent the major causative factors (over 70% of cases). Mortality observed in necrotizing AP only, varies from 26% of idiopathic to 8% of biliary cases. Ductal scars, exocrine and endocrine impairment were observed in about 45% and 20% respectively as sequelae of necrotizing AP, whatever the etiology. As far as CP is concerned, the main etiological factor is chronic alcohol consumption (82% of cases). The clinical evolution of CP may be roughly divided in two phases, the earlier (within 5 years from onset) characterized by frequently recurrent pain, calcifications and cystic cavities and the later when pain spontaneously regresses and steatorrhea and diabetes tend to appear. Heavy alcohol intake, smoking and frequent relapses are related to a less favourable course. About 60% of the patients underwent surgery within 5 years from onset. Pain relief was achieved in the large majority. Reduction in alcohol intake and the natural tendency of the disease to burn out, probably aid pain relief. Mortality in CP is due to diseases secondary to alcohol and smoking abuse (cardiovascular and neoplastic) more than to CP alone. We believe that multiple parameters are required for a complete definition of each pancreatic patient.

Pancreatic calcifications in patients with chronic pancreatitis. A sign of long-lasting or severe disease?

Pancreatic calcifications are particularly frequent in patients with severe pancreatic insufficiency and long-lasting chronic pancreatitis. To clarify whether calcifications point to a more severe form of the disease, irrespective of its duration, we have retrospectively analyzed patients with chronic pancreatitis submitted to the secretin-cerulein test in our center over a six-year period. Out of 120 patients, calcifications were found in 55. Higher alcohol intake and longer duration of the disease were found in patients with calcifications, compared with patients without calcifications (p less than 0.001). In both groups, lipase and chymotrypsin were more severely impaired than bicarbonate; a greater reduction of pancreatic exocrine function was found in patients with calcifications, compared to those without (p less than 0.001, Mann-Whitney U-test). When the patients were classified according to the duration of the disease or the severity of exocrine function impairment, higher percentages of patients with calcifications were found in the classes with more advanced disease. A log-linear analysis showed that the prevalence of calcifications was associated with pancreatic function impairment, even within the same class of duration of the disease. It is likely that calcifications mark more severe forms of chronic pancreatitis, even in the early phases of the disease.

Treatment of reflux gastritis: double blind comparison between clebopride and domperidone. A preliminary report.

Altered gastro-duodenal motility seems to be a major factor of alkaline gastritis. Therefore prokinetic drugs have been extensively used for the treatment of this disease. Aim of this study has been to compare the effects of domperidone with those of a more recent drug of the orthopramide class, clebopride. Thirty patients affected by reflux gastritis have been randomly allocated to one of the two treatments. Clinical symptoms, endoscopic and histologic appearance of gastric mucosa, gastric pH and bile acid concentration in gastric juice have been evaluated before and after a four week course of therapy. A statistically significant improvement was observed for the clinical symptoms in the subjects treated with clebopride. Even if no statistical difference has been pointed out for the other parameters between and within the two groups, a slight trend in favour of clebopride was observed. It is concluded that clebopride is at least as effective as domperidone for the treatment of reflux gastritis but that more prolonged studies and different administration schedules are requested for a better evaluation.

Androgenicity in relation to body fat distribution and metabolism in 38-year-old women--the European Fat Distribution Study.

We studied fat distribution and metabolic risk factors in 434 38-year old women selected from population registrars in 5 cities in different parts of Europe. In the present study we focussed on the geographical variation in serum concentrations of free testosterone and its relation to measures of obesity, fat distribution and indicators of cardiovascular risk (serum lipids, insulin, and blood pressure). There were significant differences in free testosterone levels (F = 5.4, p less than 0.001) with lowest levels in Polish women (mean +/- SEM: 1.56 +/- 0.08 pg/ml) and highest in women from Italy (2.07 +/- 0.12 pg/ml). In the pooled data, free testosterone levels were correlated with several anthropometric variables (strongest with subscapular/triceps ratio r = 0.27, with subscapular skinfold and waist/thigh circumference ratio r = 0.25 p-values less than 0.001). In addition, free testosterone was positively correlated with serum total cholesterol (r = 0.11), HDL/total cholesterol fraction (r = 0.12), serum insulin (r = 0.20) and diastolic blood pressure (r = 0.15). These associations remained significant after adjustment for body mass index and waist/thigh ratio (not for diastolic blood pressure) but were no longer significant after further adjustment for insulin levels. There were considerable differences in strength of the associations mentioned between the 5 centers. We conclude that degree of obesity, fat distribution and serum levels of free testosterone all, to a limited degree, contribute to the metabolic profile of randomly selected 38-year old women but that adjustment for such variables increases the differences in metabolic profiles between women from different centers of Europe.

Near infrared spectrometry for faecal fat measurement: comparison with conventional gravimetric and titrimetric methods.

This investigation was aimed at comparing a new method for measuring faecal fat excretion, carried out with a semi-automated instrument by using near infrared analysis (NIRA), with the traditional titrimetric (Van de Kamer) and gravimetric (Sobel) methods. Near infrared analysis faecal fat was assayed on the three day stool collection from 118 patients (68 chronic pancreatitis, 19 organic diseases of the gastrointestinal tract, 19 alcoholic liver disease, 12 functional gastrointestinal disorders). A strict linear correlation was found between NIRA and both the titrimetric (r = 0.928, p less than 0.0001) and the gravimetric (r = 0.971, p less than 0.0001) methods. On homogenised faeces, a mean coefficient of variation of 2.1 (SD 1.71)% was found. Before homogenisation (where a mean coefficient of variation of 7% was found) accurate results were obtained when the mean of five measurements was considered. In conclusion, the assay of faecal fat excretion by the near infrared reflessometry appears a simple, rapid and reliable method for measuring steatorrhoea.

Plasma cortisol concentration following breakfasts of different composition in healthy subjects.

We measured plasma cortisol concentrations following breakfasts of different fat:carbohydrate ratio in 23 healthy subjects. A meal-related peak of plasma cortisol concentration was not found, as well as any difference in plasma cortisol levels following the two meals. Since the two meals elicited plasma glucose and plasma insulin levels which were significantly different, it is suggested that plasma cortisol is not acutely affected by ambient glucose and insulin concentrations. The same results were found when the study group was subdivided in nonobese (n = 13) and obese (Body Mass Index greater than n = 10), thus confirming the previous statement in the presence of different body weights.

Indicators of fat distribution, serum lipids, and blood pressure in European women born in 1948--the European Fat Distribution Study.

In the spring of 1986, the authors studied the relation between body mass index and anthropometric indicators of fat distribution to cardiovascular risk factors (serum lipids and blood pressure) in approximately 450 women aged 38 years randomly selected from population registers in five European centers. Waist circumference was, in univariate analysis, more strongly related to triglycerides (positive association) and high density lipoprotein (HDL) cholesterol (negative association) than to body mass index or any other anthropometric measurement. Among the centers, we observed considerable variation in the strength of the associations between anthropometric measurements and risk factors. After adjustment for body mass index, most associations between skinfolds and circumferences and risk factors were reduced to statistically nonsignificant levels, but in some centers there were independent contributions of circumferences or circumference ratios to serum lipids, but not to blood pressures. Adjustment for differences in body mass index and fat distribution between the centers did not reduce the differences in cardiovascular risk factors between the different centers but instead revealed that serum cholesterol levels were lowest in the centers of southern Europe (Italy) and that HDL cholesterol levels were higher. Blood pressure was highest in the Swedish women. We conclude that in some female populations, but not in others, indicators of fat distribution are related to serum lipids but not to blood pressure, independent of body mass index.

Intestinal permeability in patients with atopic eczema.

Passive intestinal permeability was measured in 15 adult patients with atopic eczema. Values in the patients did not differ significantly from those in 12 healthy control subjects. These results suggest that altered intestinal permeability is not important in the pathogenesis of atopic eczema in adults.

The fecal chymotrypsin photometric assay in the evaluation of exocrine pancreatic capacity. Comparison with other direct and indirect pancreatic function tests.

Fecal chymotrypsin (FCT) has been measured by a new photometric method (Monotest Chymotrypsin; Boehringer, Mannheim) in 78 patients: 44 with chronic pancreatitis and 34 not affected by any pancreatic disease. The results were compared with those from other tests of pancreatic secretory (secretin-cerulein test) and digestive [serum and urinary p-aminobenzoic acid (PABA) and pancreolauryl] capacity. When FCT values were severely reduced (below 6.7 U/g), from 90 to 100% of the patients also presented abnormal pancreatic secretory and digestive capacity. On the other hand, 87% of the patients with normal FCT (above 20 U/g) presented normal secretory and digestive capacity. Patients with intermediate FCT values (between 6.7 and 20 U/g) showed normal or abnormal pancreatic secretory and digestive capacity with the same probability. Therefore, FCT, carried out as a first test, seems to identify subjects that need no further pancreatic function tests (normal and severely impaired FCT) and patients who need other more complex functional investigations (intermediate FCT values).

Fractional urinary clearance of immunoreactive lipase in chronic pancreatic disease.

Using an immunoenzymatic method, we studied lipase in the serum and urine of 23 controls, 22 chronic pancreatitis patients in symptomatic remission, and in 9 patients with proven pancreatic cancer. Serum and urine lipase and its fractional urinary clearance were compared with those of amylase and immunoreactive trypsin. Lipase immunoreactivity was detectable in the urine of 81.5% of the studied subjects (controls: 82%, chronic pancreatitis: 86%, pancreatic cancer: 66%); its output was higher than the upper limit of controls in 31.8% of chronic pancreatitis and in only 1 of pancreatic cancer, and it was significantly correlated with the urinary output of trypsin (r = 0.487, P less than 0.001), but not with that of amylase. A significant correlation was found between urinary output and serum levels for lipase, but not for trypsin or amylase. Fractional clearance of lipase was of the same magnitude as that of trypsin but only 0.1% that of amylase. 19% of chronic pancreatitis and pancreatic cancer showed a fractional clearance of lipase above the upper limit of controls, compared with 45% for trypsin and 3.2% for amylase. No difference in urinary clearance of the three enzymes was found between chronic pancreatitis and pancreatic cancer. In conclusion, although of no diagnostic relevance in pain-free patients with chronic pancreatic disease, this measurement can provide information on the mechanisms of renal excretion of pancreatic enzymes.

Pancreatic function in chronic inflammatory bowel disease.

This study was prospectively carried out to evaluate the frequency and clinical significance of pancreatic impairment in the course of chronic inflammatory bowel disease (CIBD). Twenty-seven patients affected by ulcerative colitis or Crohn's disease were submitted to a secretin-cerulein test, oral glucose test (OGT) and to indirect immunofluorescence (IFL) for detection of autoantibodies against exocrine and endocrine tissue. A bicarbonate plus enzyme or only an enzyme insufficiency was found in 11/27 patients, whereas isolated lipase decrease was observed in 18 subjects. In the results of the OGT and the indirect IFL test there was no difference between patients and controls. These data demonstrate that pancreatic impairment is a far more frequent occurrence than generally recognized in clinical practice. The decrease of lipase secretion could worsen the consequences of malabsorption in Crohn's disease of the small intestine. Therefore we think that a pancreatic assessment is advisable, at least in Crohn's disease patients with steatorrhea.