Influence of gastric mucosal status on success of stepwise acid suppressive therapy for dyspepsia.

BACKGROUND: The most effective initial treatment strategy of dyspepsia is still under debate. Individual biological characteristics, such as condition of gastric mucosa, might contribute to selection of the most appropriate acid suppression treatment strategy. AIM: To assess whether pre-treatment testing of gastric mucosal status is relevant for treatment success in an RCT comparing step-up and step-down therapies in newly diagnosed dyspepsia patients. METHODS: Baseline serum samples were collected to assess gastric mucosal status using serum levels of pepsinogens-I&II, gastrin-17, and Helicobacter pylori IgA/IgG-antibodies. The 6-month treatment success was compared between step-up and step-down for patients with serum diagnoses: normal; gastritis; corpus atrophy or antrum atrophy. RESULTS: In all, 519 patients (M/F: 249/270, age: 47 (18-85) years, 29%H. pylori+) were randomized to step-up (n = 293) or step-down (n = 226). Normal mucosa, gastritis and corpus atrophy were diagnosed serologically in 70%, 28% and 2% of the patients, evenly distributed between the strategies (P = 0.65). Treatment success was achieved in respectively, 69%, 70% and 70% for the serum diagnosis groups, and did not differ between the strategies. CONCLUSIONS: Dyspepsia treatment success could not be predicted by gastric mucosal status. Therefore, serum diagnosis of gastric mucosal status is no useful tool for patient allocation to acid suppressive treatment strategies.

Chromogranin A, a significant prognostic factor in small cell lung cancer.

Chromogranin A (CgA) is a protein present in neuroendocrine vesicles. Small cell lung cancer (SCLC) is considered a neuroendocrine tumour. It is possible to demonstrate CgA expression in SCLC by immunohistochemical methods. Since CgA is released to the circulation it might also work as a clinical tumour marker. We used a newly developed two-site enzyme-linked immunosorbent assay for CgA in plasma from 150 newly diagnosed patients with SCLC. Follow-up was for a minimum of 5 years. Thirty-seven per cent of the patients had elevated pretreatment values and the values were significantly related to stage of disease. Multivariable analysis by Cox's proportional hazard model including nine known prognostic factors disclosed performance status as the most influential prognostic factor followed by stage of disease, CgA and LDH. A simple prognostic index (PI) could be established based on these four pretreatment features. In this way the patients could be separated into three groups with significant different prognosis. The median survival and 95% confidence intervals for the three groups were as follows: 424 days (311-537), 360 days (261-459) and 174 days (105-243).

Fasting gall bladder volume and lithogenicity in relation to glucose tolerance, total and intra-abdominal fat masses in obese non-diabetic subjects.

OBJECTIVE: To investigate whether total body fat mass or fat distribution and associated metabolic disturbances in glucose and lipid metabolism influence the well known gallstone pathogenetic factors in obese subjects in order to explain why some obese subjects develop gallstones and some do not. DESIGN: Cross sectional study of gallstone pathogenetic factors, body composition, fat distribution, glucose and lipid metabolism. SUBJECTS: 57 healthy overweight subjects (aged 26-64y, body mass index (BMI) 30-45 kg/m2). MEASUREMENTS: Total and intra-abdominal fat masses were measured by dual X-ray absorptiometry and abdominal CT scanning, respectively. The lithogenic index was measured in aspirated bile. The gallbladder volume was determined by ultrasound and the gallbladder ejection fraction% by dynamic cholescintigraphy. Plasma cholecystokinin (CCK) concentrations during a meal were measured with a specific radioimmunoassay. Insulin sensitivity was measured by the Minimal Model and glucose tolerance by an oral glucose tolerance test (OGTT). Serum lipid concentrations were measured by standard methods. RESULTS: The gallbladder volume in the fasting state increased with increasing intra-abdominal fat mass (P=0.006) and was increased in subjects with impaired glucose tolerance (41 vs 27 ml, P=0.001). The lithogenic index was > 1 in all subjects and correlated with total fat mass (P=0.04). CONCLUSION: Gallstone pathogenesis in obesity seems to be influenced by the total body fat mass and its regional distribution possibly via mutual association with the glucose tolerance.

Plasma cholecystokinin and its precursors in hepatic cirrhosis.

BACKGROUND/AIMS: The liver influences the metabolism of several peptide hormones. The metabolic effect may, however, change considerably by diseases in the liver. This study examined whether hepatic cirrhosis influences the occurrence and concentrations of procholecystokinin (proCCK) and its products in plasma. METHODS: The sum of proCCK and its products (both processing intermediates and bioactive fragments) in plasma were measured by a recently developed "processing-independent analysis". Bioactive forms of CCK in plasma were measured using a highly specific radioimmunoassay directed against the C-terminal epitope of CCK. RESULTS: In plasma from patients with primary biliary cirrhosis the basal concentration of the total proCCK product was increased. Moreover, a mixed meal increased plasma concentrations of both bioactive CCK (i.e. carboxyamidated an 0-sulfated CCK peptides) and the total proCCK product in primary biliary cirrhosis. In contrast, plasma concentrations of bioactive CCK and the total proCCK product were normal in patients with alcoholic liver cirrhosis-both pre- or postprandially. The fraction of bioactive CCK in plasma from patients with both biliary and alcoholic cirrhosis was also normal. Hence, in primary biliary cirrhosis, alcoholic cirrhosis and in controls, respectively, bioactive CCK constituted 15%, 15% and 17% of the total proCCK product in the basal state; 70%, 58% and 53% 30 min after and 48%, 56% and 51% 90 min after the meal. As shown by gel chromatography, plasma from patients with primary biliary cirrhosis and controls sampled 30 min after a meal contained CCK-33, -22 and -8-like peptides. In addition, plasma contained non-amidated (approximately non-bioactive) proCCK products corresponding in size to CCK-83, -58 and -33. Ninety minutes after a meal, CCK-8 predominated in plasma from patients with primary biliary cirrhosis, whereas plasma from controls displayed a CCK profile similar to that obtained 30 min post-prandially. CONCLUSIONS: The results show that CCK-8 is metabolized at a slower rate in patients with primary biliary cirrhosis.

Quantitation of procholecystokinin and its products in plasma by processing-independent analysis.

A procedure for processing-independent quantitation of procholecystokinin (proCCK) and its products has been applied to plasma. The procedure is based on tryptic cleavage after Lys61 and Arg71 with subsequent monospecific radioimmuno-analysis of fragment 62-71 of human proCCK, which again corresponds to fragment 1-10 of CCK-22. The detection limit of the analysis was 0.2 pmol/l. Plasma was extracted with ethanol. In plasma from 13 healthy volunteers the basal concentration with the above-mentioned radioimmunoassay was 1.1 +/- 0.1 pmol/l (mean +/- S.E.M.) before, and 13.7 +/- 0.6 pmol/l after, incubation with trypsin. Two hours after ingestion of a mixed meal, the plasma concentration was 2.0 +/- 0.1 pmol/l before, and 21.7 +/- 1.2 pmol/l after tryptic cleavage. With a conventional CCK radioimmunoassay specific for the C-terminally amidated and O-sulfated bioactive epitope, the concentration was 1.0 +/- 0.1 pmol/l in the basal state and 4.2 +/- 0.4 pmol/l 2 h after a meal. Tryptic cleavage did not increase the concentrations of amidated, bioactive CCK peptides. In plasma from 37 patients with the carcinoid syndrome, the basal concentration of proCCK and its products was 14.1 (2.8-150.4) pmol/l (median (range)), compared with 0.3 (0-18.8) pmol/l for carboxyamidated CCK. Only two patients had significantly elevated CCK concentrations. We conclude that processing-independent analysis is useful for quantitation of proCCK and its products in plasma, since it quantitates CCK cell secretion more accurately than conventional CCK assays.

A processing-independent assay for human procholecystokinin and its products.

In order to develop a processing-independent analysis for procholecystokinin (proCCK) and its products, antibodies were raised against the synthetic fragment 62-71 of human proCCK. All rabbits (n = 8) responded to the immunization. One (No. 89,009) produced antibodies of particularly high titer (1:350,000), homogeneity (Sips' index approximately 1.0) and binding affinity (K0 eff approximately 0.88 x 10(12) l/mol). A radioimmunoassay using this antiserum and [125I]tyrosine-extended fragment 62-71 measured the total CCK mRNA product after tryptic cleavage at Lys61 in normal and neoplastic tissue independent of the degree of precursor processing. In addition to previously known CCK producing tumors, CCK was found also in a thoracic round-cell tumor (Askin tumor) and in brain tumors (gliomas and astrocytomas). These tumors processed proCCK poorly. Thus, they contained 11 and 23 (mean n = 5) pmol/g of proCCK and its products before, versus 71 and 99 (mean) pmol/g after tryptic cleavage, respectively. Accordingly, gel chromatography revealed significant amounts of unprocessed proCCK, large molecular forms of glycine-extended CCKs and the well-known carboxyamidated and tyrosine O-sulfated bioactive CCK-83, -58, -33, -22 and -8. We conclude that monospecific antibodies directed against the N-terminus of sequence 62-71 of human proCCK are suitable for processing-independent analysis (PIA) for proCCK and its products. Moreover, we suggest that such PIA should be used for quantitation of CCK gene expression at peptide level in normal tissue and tumors.

Evaluation of an immunoturbidimetric microalbuminuria assay.

We have evaluated an immunoturbidimetric method for the estimation of urinary albumin. The method, besides being easy to perform and cost-effective, was sensitive enough to detect an even slightly increased albumin excretion (detection limit 5 mg/l). Within-run reproducibility was 1.8 and 2.1%, and between-run reproducibility 2.9 and 4.3% in samples containing 16.1-17.8 mg/l and 50.6-54.0 mg/l of albumin, respectively. The recovery of albumin added to the samples was 98.6-106.6%. Results obtained by this method correlated well with the results obtained by radial immunodiffusion (r = 0.980, n = 44) and radioimmunoassay (r = 0.982, n = 41). The immunoturbidimetric method can be easily adapted for several clinical chemistry analysers.

Gingival recession in schoolchildren at 7, 12 and 17 years of age in Espoo, Finland.

The present study was undertaken in response to a growing concern among clinicians about an increase in gingival recession among children and adolescents. Groups of 50 boys and 50 girls aged respectively 7, 12, and 17 yr were examined at Espoo Health Centre in 1983. Gingival recession was measured on the facial and lingual aspects of all permanent teeth. Whenever the gingival margin was located on root cementum, the distance from the gingival margin to the enamel border was measured to the nearest 0.5 mm. Recession was categorized as "slight" (0.5 or 1 mm) or "extensive" (1.5-3.5 mm). The prevalence of gingival recession was 5% at 7 yr, 39% at 12 yr, and 74% at 17 yr of age. More girls than boys had recession in the two youngest age groups. At 17 yr recession was equally common in both sexes and both "slight" and "extensive" recession was most often recorded on facial surfaces of first molars, premolars and canines. The alarmingly high prevalence of gingival recession at young age warrants further study of both the reasons and the consequences of early cementum exposure.

Gingival bleeding after chlorhexidine mouthrinses.

During a clinical trial for evaluating the antiplaque effect of two flavoured chlorhexidine rinses, the observation was made that bleeding after gentle massage of the gingival margin occurred more often after chemical than after mechanical oral hygiene measures. In order to ascertain the validity of this unexpected observation, the same dental students participated in a repetition of the trial 18 months later. The results of the two trials indicate that gingival bleeding after gentle massage of the margin with the side of a periodontal probe actually occurs more frequently after rinsing twice daily with a 0.2% aqueous chlorhexidine solution for 1 week than after meticulous mechanical oral hygiene measures during an equally long time period. The average frequency of bleeding, in per cent of all examined gingival units, ranged from 1.3% after mechanical cleaning of the teeth to 5.4% after rinsing with chlorhexidine for 1 week. Neither the frequency of bleeding nor the difference between mechanical and chemical plaque control were considered to be of clinical significance. Further microbiological and histological studies are being conducted in an attempt to clarify the reason for the observed bleeding tendency.

Plaque-inhibiting effect of two flavored chlorhexidine mouth rinses.

An experimental study was designed for assessement of whether two recently marketed flavored chlorhexidine mouthrinses, Hibitane Dental (ICI) and Plak-Out (Hawe), have a good plaque-inhibiting effect as the 0.2% aqueous solution of chlorhexidine gluconate. Thirteen dental students used in different sequences each one of the three rinses fro 1 week by rinsing twice daily for 1 min. During the rinsing periods no other oral hygiene measures were allowed. Between two rinsing periods the subjects cleaned their teeth mechanically for 1 week. At the start of each test and control period, the teeth were professionally cleaned with rubber cups and an abrasive paste. At the end of the five 1-week periods the mesial, lingual and facial aspects of the teeth in the right halves of the jaws of each participant were scored for the Plaque Index by the same investigator. After the mechanical cleaning, higher PII scores were recorded than after the chlorhexidine rinses. No difference could be observed among the PII scores after rinsing with the aqueous or the two flavored chlorhexidine solutions.