Prenatal exposure to maternal cigarette smoking and structural properties of the human corpus callosum.

Alterations induced by prenatal exposure to nicotine have been observed in experimental (rodent) studies. While numerous developmental outcomes have been associated with prenatal exposure to maternal cigarette smoking (PEMCS) in humans, the possible relation with brain structure is less clear. Here we sought to elucidate the relation between PEMCS and structural properties of human corpus callosum in adolescence and early adulthood in a total of 1,747 youth. We deployed three community-based cohorts of 446 (age 25-27 years, 46% exposed), 934 (age 12-18 years, 47% exposed) and 367 individuals (age 18-21 years, 9% exposed). A mega-analysis revealed lower mean diffusivity in the callosal segments of exposed males. We speculate that prenatal exposure to maternal cigarette smoking disrupts the early programming of callosal structure and increases the relative portion of small-diameter fibres.

Smokin' hot: adolescent smoking and the risk of psychosis.

OBJECTIVE: Daily smoking has been associated with a greater risk of psychosis. However, we are still lacking studies to adjust for baseline psychotic experiences and other substance use. We examined associations between daily smoking and psychosis risk in a 15-year follow-up while accounting for these covariates in a prospective sample (N = 6081) from the Northern Finland Birth Cohort 1986. METHODS: Self-report questionnaires on psychotic experiences (PROD-screen), tobacco smoking and other substance use were completed when the cohort members were 15-16 years old. Tobacco smoking was categorized into three groups (non-smokers, 1-9 cigarettes and ≥10 cigarettes/day). Psychosis diagnoses were obtained from national registers until the age of 30 years. RESULTS: Subjects in heaviest smoking category were at increased risk of subsequent psychosis (unadjusted HR = 3.15; 95% CI 1.94-5.13). When adjusted for baseline psychotic experiences the association persisted (HR = 2.87; 1.76-4.68) and remained significant even after adjustments for multiple known risk factors such as cannabis use, frequent alcohol use, other illicit substance use, parental substance abuse, and psychosis. Furthermore, number of smoked cigarettes increased psychosis risk in a dose-response manner (adjusted OR = 1.05; 1.01-1.08). CONCLUSION: Heavy tobacco smoking in adolescence was associated with a greater risk for psychosis even after adjustment for confounders.

Structural properties of the human corpus callosum: Multimodal assessment and sex differences.

A number of structural properties of white matter can be assessed in vivo using multimodal magnetic resonance imaging (MRI). We measured profiles of R1 and R2 relaxation rates, myelin water fraction (MWF) and diffusion tensor measures (fractional anisotropy [FA], mean diffusivity [MD]) across the mid-sagittal section of the corpus callosum in two samples of young individuals. In Part 1, we compared histology-derived axon diameter (Aboitiz et al., 1992) to MRI measures obtained in 402 young men (19.55 ± 0.84 years) recruited from the Avon Longitudinal Study on Parents and Children. In Part 2, we examined sex differences in FA, MD and magnetization transfer ratio (MTR) across the corpus callosum in 433 young (26.50 ± 0.51 years) men and women recruited from the Northern Finland Birth Cohort 1986. We found that R1, R2, and MWF follow the anterior-to-posterior profile of small-axon density. Sex differences in mean MTR were similar across the corpus callosum (males > females) while these in FA differed by the callosal segment (Body: M>F; Splenium: F>M). We suggest that the values of R1, R2 and MWF are driven by high surface area of myelin in regions with high density of "small axons".

Brief report: validity of Finnish registry-based diagnoses of autism with the ADI-R.

AIMS: The aim of the study was to explore the validity of registry-based diagnoses of autism in Finland using the Autism Diagnostic Interview - Revised (ADI-R). This study was designed for the Finnish Prenatal Study of Autism and Autism Spectrum Disorders (FIPS-A), an ongoing research project where registry-based diagnoses will be used for epidemiological studies. METHODS: In this small pilot study, a clinical sample of 95 subjects diagnosed with childhood autism or pervasive developmental disorder/pervasive developmental disorder - not otherwise specified (PDD/PDD-NOS) or Asperger's syndrome according to the Finnish Hospital Discharge Register (FHDR) was gathered nationwide. A small control group consisting of siblings without any registered diagnoses of those being examined was also included in the study. Diagnoses were further re-evaluated by interviewing parents with the ADI-R. RESULTS: The mean scores of autistic subjects clearly exceeded cut-off limits for autism on all three ADI-R domains and 96% of the subjects with registered diagnosis of childhood autism fulfilled the criteria based on the instrument as well. CONCLUSION: These results suggest that the validity of Finnish registry-based diagnoses of childhood autism can be considered good. Our findings lay important groundwork for further population- based studies of the aetiology of autism.

Use of the ISO 9308-1 procedure for the detection of E. coil in water utilizing two incubation temperatures and two confirmation procedures and comparison with defined substrate technology.

Disinfected and non-disinfected samples have been used to determine the accuracy of the ISO procedure (ISO 9308-1) for detection of E. coli in drinking water. Samples were analysed using the ISO procedure at both 36 and 44 degrees C and using the defined substrate technology method Colilert-18/Quanti-Tray (Colilert-18). Utilizing the confirmation procedure described in ISO 9308-1, large numbers of false positive E. coli results were obtained using the ISO primary isolation procedure at 36 degrees C. However, when glucuronidase production was used as the confirmation procedure, the 'confirmed' count of E. coli was lowest with ISO 9308-1 performed at 36 degrees C. When TTC medium was incubated at 36 degrees C confirmation using production of indole at 44 degrees C resulted in 29% more 'E. coli' being recovered than when confirmation was performed using production of glucuronidase. When 44 degrees C was used as the primary isolation temperature the difference between the number of 'confirmed' E. coli identified using the two confirmation procedures was less than 1% and was not significant. Identification of isolates which 'confirmed' when using production of indole at 44 degrees C as the test method but which failed to produce beta-D-glucuronidase, showed that the majority of these isolates were Klebsiella oxytoca.

Dopaminergic function and intertemporal choice.

The discounting of delayed rewards, also known as temporal or delay discounting, is intrinsic to everyday decisions and can be impaired in pathological states such as addiction disorders. Preclinical and human studies suggest a role for dopaminergic function in temporal discounting but this relationship has not yet been verified using molecular imaging of the living human brain. Here, we evaluated dopaminergic function in temporal discounting using positron emission tomography (PET) with two different dopaminergic ligands assessing three populations in whom temporal discounting has been shown to be impaired. First, we show using [11C]raclopride PET that in pathological gamblers, greater temporal discounting correlates with decreased ventral striatal binding potential, convergent with translational findings of lower nucleus accumbens D2/D3 receptor density in high-impulsive rodents. Temporal discounting also correlates with lower ventral striatal dopamine release in response to high-reward magnitude suggesting that dopamine-mediated devaluation of larger delayed rewards may drive choice preferences. Second, we show using [18F]fluorodopa PET that in Parkinson's disease, temporal discounting correlates with greater left caudate dopaminergic terminal function. Finally, in subjects with Parkinson's disease and dopamine medication-induced behavioral addictions, temporal discounting is further correlated with greater dopaminergic terminal function in the anterior putamen. These findings provide insights into the relationship between striatal dopamine function and temporal discounting, and its potential role in pathological disorders and mechanisms underlying treatment interventions.

Genetic analysis in Finnish families with inflammatory bowel disease supports linkage to chromosome 3p21.

In inflammatory bowel diseases (IBD), certain chromosomal candidate loci have been repeatedly identified by independent studies in different populations. To investigate the contribution of the loci on chromosomes 1, 3, 7, 12, 14, and 16 to the susceptibility of IBD in Finnish population, where the predominant feature is the excess of ulcerative colitis (UC) families compared to Crohn's disease (CD) families, we carried out linkage analyses using 93 Finnish, multiply-affected IBD families. We observed nominal evidence for linkage to chromosome 3p21, consistent with earlier reports. The lod scores peaked at D3S2432, with a maximum two-point lod score of 1.68 (P=0.0027). In addition, we studied whether risk of IBD is associated with functional variants of two positional candidate genes; the chemokine receptor CCR5 gene on chromosome 3p21 and the interleukin-4 receptor alpha-subunit gene (IL4RA) on chromosome 16. We did not find any significant correlation between a 32-bp deletion variant of CCR5 or a single nucleotide change A1902G (Gln576Arg) of IL4RA, and IBD phenotypes, with the exception that in the UC group homozygosity for the G1902 allele of IL4RA was less frequent (0.019 vs 0.049, P=0.038). In conclusion, our study, carried out in a genetically homogenous population, suggests that chromosome 3 may contain a susceptibility gene for IBD.

Primary Helicobacter pylori resistance to metronidazole and clarithromycin in the Finnish population.

AIM: To systematically determine Helicobacter pylori primary antimicrobial resistance in Finland and the associated demographic and clinical features. METHODS: A total of 342 adult patients referred for gastroscopy at 23 centres in different parts of Finland and positive for the rapid biopsy urease test were recruited. Clinical and demographic data were collected via a structured questionnaire. Patients with positive H. pylori culture and successful antibiotic sensitivity determination by the E-test method (n = 292) were included in the present analysis. RESULTS: The study population consisted of 134 men and 158 women, mean age 56 years (95% CI, 55-58 years). Resistance to metronidazole was 38% (110 of 292) and to clarithromycin 2% (seven of 292). Resistance to metronidazole was higher in women than in men (48% vs. 25%, P < 0.001). Previous use of antibiotics for gynaecological infections predicted metronidazole resistance (P = 0.01), and previous use of antibiotics for respiratory (P = 0.02) and dental infections (P = 0.02) the clarithromycin resistance. We observed no major geographical variations in metronidazole resistance. CONCLUSIONS: The primary metronidazole resistance of H. pylori was 38% and was common in women previously treated for gynaecological infections. Primary clarithromycin resistance was uncommon (2%) and may associate with previous dental and respiratory infections.

Ten year follow up study of lymphocytic gastritis: further evidence on Helicobacter pylori as a cause of lymphocytic gastritis and corpus gastritis.

AIMS: To examine the course of lymphocytic gastritis and its relation to Helicobacter pylori (H pylori) infection in a 10 year follow up. METHODS: Ninety six patients were originally examined for dyspepsia in 1981. Gastroscopies with stepwise biopsies were performed on all the patients initially and after an interval of 10 years. RESULTS: Nine per cent of the patients (9/96) had features of lymphocytic gastritis in gastric biopsy at the first examination, and 12.5% (12/96) at the second examination; 7/9 patients (78%) had persistent lymphocytic gastritis during the follow up; in two the diagnostic features of lymphocytic gastritis had disappeared, and five had a new diagnosis of lymphocytic gastritis at the second examination. At the second examination 9/12 lymphocytic gastritis patients (75%) were H pylori positive histologically, while all had specific antibodies to H pylori. The lymphocytic gastritis patients had higher grades of gastritis (p = 0.009), neutrophilic and eosinophilic granulocytes, mononuclear inflammatory cells, and foveolar hyperplasia in the corpus mucosa, but smaller numbers of H pylori, than the H pylori positive patients without lymphocytic gastritis. The appearance of lymphocytic gastritis during the 10 year interval was associated with increases in the grades of corpus gastritis and neutrophilic granulocytes (p = 0.043 for both). During the follow up, the patients with lymphocytic gastritis, but not the H pylori positive patients without lymphocytic gastritis, appeared to have a significant increase in the grade of intestinal metaplasia in the corpus mucosa (p = 0.043). CONCLUSIONS: In some patients H pylori may cause a gastritis that predominates in the corpus and is associated with an increase in the intraepithelial lymphocyte count. This form of gastritis may cause progression of intestinal metaplasia.

Could Helicobacter pylori infection increase the risk of coronary heart disease by modifying serum lipid concentrations?

OBJECTIVE: To investigate the relation between Helicobacter pylori infection and coronary heart disease (CHD). DESIGN: A case-control study. SETTING: Northern Finland (about 650,000 inhabitants). PATIENTS: 116 patients with angiographically documented CHD and 116 controls matched for age and gender randomly recruited from the register of the Finnish Social Insurance Institute. MAIN OUTCOME MEASURES: The odds ratio (OR) estimates for the association of H pylori infection with CHD. RESULTS: 64% of the CHD patients and 53% of the controls were seropositive for H pylori; the OR adjusted for age and gender was 1.5 (95% confidence interval (CI) 0.9 to 2.5). An additional adjustment for the common risk factors of CHD, including lipid concentrations, in a logistic regression analysis produced an OR estimate of 1.1 (95% CI 0.6 to 2.1). Among the controls, those who were H pylori positive had significantly (P = 0.03) higher concentrations of serum triglycerides than those who were H pylori negative: the trend among the cases was similar, but non-significant. The concentrations of HDL cholesterol tended to be lower in those who were H pylori positive than in those who were H pylori negative, among both the cases and the controls. CONCLUSIONS: The impact of H pylori infection as an independent risk factor for CHD seems to be minor. On the other hand the results are consistent with the hypothesis that H pylori infection might modify the serum lipid concentrations in a way that could increase the risk of CHD.

Isolation and identification of 12 microcystins from four strains and two bloom samples of Microcystis spp.: structure of a new hepatotoxin.

Sixteen microcystins, cyclic heptapeptide hepatotoxins, were isolated and purified by high performance liquid chromatography (HPLC) and thin layer chromatography (TLC) from four hepatotoxic strains and two Microcystis spp. bloom samples originating from five different lakes in Finland. The structures of a new [Dha7]MCYST-FR and 11 known microcystins MCYST-LR, [D-Asp3]MCYST-LR, [Dha7]MCYST-LR, [D-Asp3, Dha7] MCYST-LR, MCYST-RR, [D-Asp3]MCYST-RR, [Dha7]MCYST-RR, [D-Asp3,Dha7]MCYST-RR, [L-Ser7]MCYST-RR, MCYST-YR and [Dha7] MCYST-YR were assigned based on amino acid analysis, fast atom bombardment mass spectrometry (FABMS) and tandem FABMS. Four other new compounds allowed only determination of their molecular formulas and amino acid components because of inadequate amounts obtained. [Dha7]MCYST-RR was found most frequently in these samples as the main toxin.

Growth of Enterococcus, Lactococcus and Streptococcus strains and environmental isolates in liquid media and their reactions on BEEA.

Growth of known species of Enterococcus, Lactococcus and Streptococcus and Aerococcus viridans in selective and nonselective liquid media routinely used to enumerate faecal streptococci was measured optically at different temperatures. Growth of environmental isolates was measured in some of these media. Growth of the reference strains on Bile esculin azide agar at elevated incubation temperatures was tested. The results revealed only minor differences between media but strong influence of incubation temperature. Some media tended to yield higher cell densities than others. For many species the inoculum size affected maximum turbidity. To combine selective media with selective incubation temperatures seems to be necessary to achieve satisfactory reliability in traditional liquid enumeration methods for faecal streptococci. Because of the diversity of this group, optimal selectivity and recovery can hardly be achieved simultaneously.

MPN-PCR-quantification method for staphylococcal enterotoxin c1 gene from fresh cheese.

PCR detection methods have been extensively used in diagnostic microbiology. However, a lack of a simple and reliable method for quantification of the PCR products has partly hindered the use of PCR in routine food laboratories. The quantification of PCR products can be done by combining the principles of MPN statistics and PCR technique. We have developed a simple and sensitive MPN-PCR assay for detection and enumeration of enterotoxin C producing Staphylococcus aureus NCTC 10655 from fresh cheese. By amplifying single copy chromosomal enterotoxin C gene fragment, we could detect as little as 20 cfu/g. By Moran's test, most of the DNA dilution series appeared to fulfill the basic mathematical assumptions of ordinary MPN methods. The analysis with MPN-PCR took one day to perform compared with three days analysis time with plate counting. This MPN-PCR method can be readily applied with different primer systems without extensive development work.

Sensitivity of ultrasonography in the demonstration of common bile duct stones and its ranking in comparison with intravenous cholangiography and endoscopic retrograde cholangiopancreatography.

A series of 75 patients with surgically verified common bile duct (CBD) stones were re-examined in retrospect, in order to ascertain the sensitivity of ultrasonography (US) in the detection of CBD. The sensitivity of US turned out to be 19%. US detected bile duct dilatation in 58% and all the CBD stones detected or suspected were seen in cases with bile duct dilatation. The sensitivity of intravenous cholangiography (IVC) proved to be 24%. Endoscopic retrograde cholangiopancreatography (ERCP), however, was found to be by far the most sensitive method, since it demonstrated 84% of the CBD stones.

Risk of malignancy and death in neurofibromatosis.

OBJECTIVE AND METHODS: Neurofibromatoses are cancer-prone hamartomatoses that involve a variety of tissue and cell types. As part of a population-based clinical and genetic study of neurofibromatosis in northern Finland, all surgical and autopsy specimens of neurofibromatosis patients were retrieved and histologic slides were reviewed. RESULTS: Specimens were available for 69 of the 197 neurofibromatosis type 1 patients identified. Six malignant peripheral nerve sheath tumors and nine other malignant tumors were detected. In this study, the risk for neurofibromatosis-related malignancy was 8%. Nine neurofibromatosis type 1 patients died, at a mean age of 37 years. The cause of death was related to neurofibromatosis in eight. CONCLUSIONS: The risk of developing malignant tumors and early death is increased in patients with neurofibromatosis, the most common malignancy being malignant peripheral nerve sheath tumors. These risks need to be recognized, and the families should be advised to seek genetic counseling and proper follow-up.

Treatment of Helicobacter pylori in patients with lymphocytic gastritis.

BACKGROUND/AIMS: Lymphocytic gastritis is a subtype of chronic gastritis characterized by a marked increase in the number of intraepithelial lymphocytes in the gastric mucosa. Its etiology is unknown, but a proportion of these patients have Helicobacter pylori infection. The aim was to assess the significance of H. pylori treatment in lymphocytic gastritis patients. METHODOLOGY: The 10 patients with lymphocytic gastritis and either serologically or histologically diagnosed H. pylori infection were treated with a triple therapy and followed by serology and histology after 6-18 months. RESULTS: The levels of IgG antibodies for H. pylori decreased below 50% of the pretreatment values in all patients. The maximum numbers of intraepithelial lymphocytes decreased significantly (P = 0.005) from the pretreatment values. CONCLUSIONS: Treatment of H. pylori infection cures lymphocytic gastritis associated with H. pylori infection. H. pylori appears to be one etiological cause of lymphocytic gastritis.

Pancreatitis in patients with chronic inflammatory bowel disease.

We describe six patients with acute pancreatitis associated with chronic inflammatory bowel disease (IBD) and no other etiological factor of pancreatic disease in a series of 513 patients with IBD. Five of the 6 patients had Crohn's disease and one indeterminate colitis; four had simultaneous symptoms of active colitis. The pancreatis was not caused by drugs or duodenal involvement of IBD. Our study suggests that pancreatic disease is one of the extra-intestinal manifestations of IBD, in particular of Crohn's disease.

Elevated serum PIIINP and laminin in inflammatory bowel disease indicate hepatobiliary and pancreatic dysfunction.

BACKGROUND/AIMS: Levels of S-PIIINP (serum aminoterminal propeptide of type III procollagen) have been shown to be increased in patients with primary sclerosing cholangitis and inflammatory bowel disease. The aim of the study was to investigate the serum concentrations of PIIINP and laminin in inflammatory bowel disease patients, their relationship with inflammatory bowel disease-associated hepatobiliary and pancreatic dysfunction, and to correlate them with clinical, endoscopic, and histologic variables. METHODOLOGY: S-PIIINP and S-laminin were measured in 222 consecutive inflammatory bowel disease patients, who were screened for abnormal liver and pancreatic enzymes and for pancreatic exocrine hypofunction with the p-aminobenzoic acid test (215 patients). The patients with abnormal screening results were further scheduled for endoscopic retrograde cholangiopancreatography, liver biopsy, secretin test and ultrasound. RESULTS: S-PIIINP and S-laminin were abnormally high in 19% and 40% of all inflammatory bowel disease patients, respectively. The elevated levels of the fibrosis markers were associated with laboratory signs of either hepatobiliary or pancreatic disease. Hepatobiliary disease was found in 37 (17%) of inflammatory bowel disease patients, 15 of whom had primary sclerosing cholangitis. The median levels of S-PIIINP and S-laminin were significantly higher in patients with hepatobiliary disease than in those without (P < 0.0001 and P < 0.001, respectively), being most strikingly elevated in primary sclerosing cholangitis. Abnormal pancreatic screening tests were found in 67 (30%) patients. High levels of S-PIIINP and S-laminin were also significantly associated with low values in p-aminobenzoic acid (P < 0.001 and P < 0.005) and secretin (P < 0.01 and P < 0.05) tests, but not with inflammatory bowel disease category, endoscopic or histological disease extent, frequency of bowel resection or actual clinical activity. CONCLUSIONS: In inflammatory bowel disease, increased S-PIIINP and S-laminin are associated with hepatobiliary and pancreatic disorders.

Gastric carcinoids with minimal or no macroscopic lesion in patients with pernicious anemia.

In a series of 44 patients with pernicious anemia examined by gastroscopy, three cases of gastric carcinoids were found. During the same ten-year period about 11,000 gastroscopies were performed on patients not suffering from pernicious anemia, and only one case of gastric carcinoid was detected. In two of the cases no endoscopic lesion was seen and the carcinoid was detectable only at histological examination, while in one case an unusual combination of carcinoid tumor and tubular adenoma in the same polyp was found. Most of the carcinoids arose in atrophic body mucosa, but in one case the mucosa around the carcinoid showed antral properties. One patient had slightly elevated values of pancreatic polypeptide, while no hormonal activity was found in others. No growth or spread of the carcinoid was observed during follow-up. It is suggested that the same pathogenetic factors may operate in the genesis of gastric carcinoid and gastric carcinoma in patients with pernicious anemia.

Duodenogastric reflux in patients with upper abdominal complaints or gastric ulcer with particular reference to reflux-associated gastritis.

The aim of this survey was to examine the incidence of duodenogastric reflux in patients with abdominal complaints and the relations between the nature and extent of reflux abdominal complaints, the use of drugs, smoking, the drinking of coffee and alcohol and histological changes in the gastric mucosa. A comparison was also made between gastric ulcer patients and patients with upper abdominal complaints with respect to the nature and extent of reflux. The patients examined included 107 with abdominal complaints and 33 with a gastric ulcer. Gastroscopy was performed, followed by determination of intragastric bile acids and lysolecithin and a duodenogastric isotope reflux examination using technetium-99m-diethyliminodiacetic acid (Tc-99m HIDA). Intragastric bile acid concentrations in the patients with upper abdominal complaints were in the range 7-21,458 mumol/l (mean 964 +/- 2342 mumol/l) and lysolecithin concentrations in the range 0-1992 mumol/l (mean 70 +/- 273 mumol/l). Isotope reflux was observed in 48% of the patients, the reflux index varying in the range 0-70% (mean 4 +/- 9%). The patients suffered more frequently from nausea, epigastric fullness and flatulence with increasing reflux, as assessed by the various methods used here, but only the increase in epigastric fullness symptoms with rising intragastric bile acid concentrations was statistically significant (p less than 0.05). Similarly the various measures of reflux were higher in those patients taking anticholinergic, psychotherapeutic or cardiovascular drugs, antacids or metoclopramide than in the patients not taking the respective drugs, although the only statistically significant increases were in intragastric bile acids among the users of antacids and metoclopramide (p less than 0.01 and p less than 0.05, respectively) and the increase in lysolecithin concentrations among those taking metoclopramide (p less than 0.05). Those abstaining from alcohol had an intragastric bile acid concentration over 1000 mumol/l significantly more often than those who drank alcohol (p less than 0.05), but smoking and the drinking of coffee showed no significant correlation with duodenogastric reflux. The body gastritis score increased significantly with the extent of isotope reflux and the concentrations of intragastric bile acids (p less than 0.05 and p less than 0.01, respectively), and the latter also showed a significant correlation with serum gastrin (p less than 0.05). No significant relationship could be detected between intragastric lysolecithin concentrations and the gastritis score.(ABSTRACT TRUNCATED AT 400 WORDS)