Kjetil Melby

Abnormal Intestinal Motor Patterns Explain Enteric Colonization With Gram-Negative Bacilli in Late Radiation Enteropathy

BACKGROUND & AIMS Bacterial overgrowth and intestinal pseudo-obstruction may succeed abdominal radiotherapy, and absence of intestinal migrating motor complex (MMC) has been reported in bacterial overgrowth. The aims of this study were to address the relationship between intestinal patterns of motility and gastrointestinal microflora and to elucidate the pathogenesis of late radiation enteropathy. METHODS Forty-one consecutive female patients with symptoms of late radiation enteropathy were examined by prolonged ambulatory manometry, culture of gastric and duodenal samples with quantification of gram-negative bacilli (GNB) by the glucose gas test, the [14C]D-xylose breath test, and determination of pH and short-chain fatty acids in gastric juice. RESULTS The intensity of MMC explained 61% (P < 0.001) and 71% (P < 0.001) of the variability of GNB in the stomach and duodenum, respectively, corresponding to the severity of disease. Abnormal MMC index and presence of irregular bursts were the best predictors of GNB (86%; P < 0.001, multiple regression). Fasting gastric pH explained gastric bacterial counts (63%; P < 0.001) but did not predict GNB. CONCLUSIONS Impaired motility emerges as a causal factor for gastrointestinal colonization with GNB, whereas hypochlorhydria facilitates unspecific gastric colonization. Abnormal motility and GNB in the proximal small intestine are essential factors in the pathogenesis of severe late radiation enteropathy.

Helicobacter pylori infection and risk of cardia cancer and non-cardia gastric cancer: A nested case-control study

BACKGROUND Helicobacter pylori infection is an established risk factor for gastric adenocarcinoma. Potential confounding by socioeconomic factors has not been adequately assessed, and the magnitude of the relative risk in relation to gastric subsites, morphologic subtypes, sex, age, and follow-up time need further study. METHODS We conducted a serologic case-control study nested within the Norwegian JANUS cohort. Between 1972 and 1986 serum was collected from 101,601 subjects who were followed up with regard to cancer development through 1992. RESULTS Among 208 gastric adenocarcinoma cases, we found a strong positive association between H. pylori infection and non-cardia gastric cancer (odds ratio (OR), 5.15; 95% confidence interval (CI), 2.83-9.37), and a statistically significant negative association with cardia cancer (OR, 0.40; 95% CI, 0.20-0.77). Adjustment for socioeconomic factors and smoking did not materially alter the effect estimates. The association between the infection and non-cardia cancer was stronger for tumors distal to the angulus and tended to be stronger in women than in men. The results were similar across Laurén morphologic subtypes. CONCLUSIONS These results strengthen the evidence of H. pylori infection as a risk factor in non-cardia gastric cancer. A negative association with H. pylori infection was found for cardia cancer.

Two distinct aetiologies of cardia cancer; evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status

Background: Non-cardia gastric adenocarcinoma is positively associated with Helicobacter pylori infection and atrophic gastritis. The role of H pylori infection and atrophic gastritis in cardia cancer is unclear. Aim: To compare cardia versus non-cardia cancer with respect to the premorbid state of the stomach. Methods: Nested case–control study. To each of 129 non-cardia and 44 cardia cancers, three controls were matched. Serum collected a median of 11.9 years before the diagnosis of cancer was tested for anti-H pylori antibodies, pepsinogen I:II and gastrin. Results: Non-cardia cancer was positively associated with H pylori (OR 4.75, 95% CI 2.56 to 8.81) and gastric atrophy (pepsinogen I:II <2.5; OR 4.47, 95% CI 2.71 to 7.37). The diffuse and intestinal histological subtypes of non-cardia cancer were of similar proportions and both showed a positive association with H pylori and atrophy. Cardia cancer was negatively associated with H pylori (OR 0.27, 95% CI 0.12 to 0.59), but H pylori-positive cardia cancer showed an association with gastric atrophy (OR 3.33, 95% CI 1.06 to 10.5). The predominant histological subtype of cardia cancer was intestinal and was not associated with gastric atrophy compared with the diffuse subtype ((OR 0.72, 95% CI 0.19 to 2.79) vs (OR 3.46, 95% CI 0.32 to 37.5)). Cardia cancer in patients with atrophy had an intestinal: diffuse ratio (1:1) similar to non-cardia cancer (1.9:1), whereas cardia cancers in patients without atrophy were predominantly intestinal (7:1). Conclusion: These findings indicate two aetiologies of cardia cancer, one associated with H pylori atrophic gastritis, resembling non-cardia cancer, and the other associated with non-atrophic gastric mucosa, resembling oesophageal adenocarcinoma. Serological markers of gastric atrophy may provide the key to determining gastric versus oesophageal origin of cardia cancer.

Bacteria, biofilm and honey : A study of the effects of honey on 'planktonic' and biofilm-embedded chronic wound bacteria

Chronically infected wounds are a costly source of suffering. An important factor in the failure of a sore to heal is the presence of multiple species of bacteria, living cooperatively in highly organized biofilms. The biofilm protects the bacteria from antibiotic therapy and the patients immune response. Honey has been used as a wound treatment for millennia. The components responsible for its antibacterial properties are now being elucidated. The study aimed to determine the effects of different concentrations of ‘Medihoney™’ therapeutic honey and Norwegian Forest Honey 1) on the real-time growth of typical chronic wound bacteria; 2) on biofilm formation; and 3) on the same bacteria already embedded in biofilm. Reference strains of MRSE, MRSA, ESBL Klebsiella pneumoniae and Pseudomonas aeruginosa were incubated with dilution series of the honeys in microtitre plates for 20 h. Growth of the bacteria was assessed by measuring optical density every 10 min. Growth curves, biofilm formation and minimum bactericidal concentrations are presented. Both honeys were bactericidal against all the strains of bacteria. Biofilm was penetrated by biocidal substances in honey. Reintroduction of honey as a conventional wound treatment may help improve individual wound care, prevent invasive infections, eliminate colonization, interrupt outbreaks and thereby preserve current antibiotic stocks.

Fasting hypochlorhydria with gram positive gastric flora is highly prevalent in healthy old people.

Fifteen healthy old people mean age 84 years (range 80-91 years), were examined to assess the effect of advanced age on the microecology of the upper gastrointestinal tract. Twelve of 15 (80%) were hypochlorhydric with pH 6.6 (0.3) (mean (SEM) and a mean bacterial count of 10(8) colony forming units (CFU) per ml (range 10(5)-10(10)) in fasting gastric aspirate. Normochlorhydric subjects had low counts (< or = 10(1) CFU/ml). The microbial flora was dominated by viridans streptococci, coagulase negative staphylococci, and Haemophilus sp. Only one subject harboured significant concentrations of Gram negative bacilli with Escherichia coli (10(4-5) CFU/ml) and Klebsiella (10(4-5)). Strict anaerobes were not found. The total concentration of short chain fatty acids in gastric aspirate was 10.6 (2.9) mmol/l (mean (SEM). Absence of significant, intraluminal fermentation of xylose to CO2 was shown by the 14C-d Xylose breath test, and ambulatory manometry showed preserved fasting motility pattern of the small intestine. Serum immunoglobulins were normal. Advanced age is accompanied by fasting hypochlorhydria and colonisation with mainly Gram positive flora in the upper gut. Other factors than old age and fasting hypochlorhydria are required for colonisation with Gram negative bacilli.

Prevalence of Toxoplasma gondii specific immunoglobulin G antibodies among pregnant women in Norway.

During one year from June 1992 serum IgG antibodies to Toxoplasma gondii among 35,940 pregnant women were measured in a cross-sectional study conducted in Norway. The overall prevalence was 10.9%. The lowest prevalences were detected in the north (6.7%) and in the inland counties (8.2%). A significantly higher prevalence was detected in the southern counties (13.4%) where a mild, coastal climate prevails. Women with foreign names had a higher prevalence (22.6%) than women with Norwegian names (10.0%). The high prevalence among women living in the capital city (Oslo) as compared to other cities and rural areas (13.2% vs. 10.1% and 10.2% respectively), was explained by the higher proportion of foreign women in Oslo. Prevalence significantly increased with age in women over 34 years old. This increase was only detected among women with Norwegian names. An increase in prevalence according to number of children was detected. Women without children had a prevalence of 8.8% while women with three children or more had a prevalence of 14.9%. Multivariate analyses showed that being seropositive was independently associated with county of residence, age, nationality and number of children.

Helicobacter pylori infection and hyperemesis gravidarum: a systematic review and meta-analysis of case-control studies

Objective. To summarize the evidence from epidemiological studies examining the association between Helicobacter pylori infection and hyperemesis gravidarum. Design. Systematic review and meta‐analysis of case–control studies. Material and methods. We searched the Medline/PubMed, Embase, Cinahl, ISI Web of Science and Biological Abstracts databases from 1966 to 17 June 2008 and finally Google Scholar. A total of 25 case–control studies were identified. Both fixed‐effect and random‐effect models were used to synthesize the results of individual studies. The Cochran Q, τ2 of between‐study variance and index of heterogeneity (I2) were used to evaluate heterogeneity. Heterogeneity between studies was examined by subgroup and random effect meta‐regression analyses. Publication bias was evaluated. Results. Publication bias was not observed. The random model pooled estimate was odds ratio = 3.32, 95 % confidence interval (CI): 2.25–4.90. A high heterogeneity was pinpointed (I2 = 80 %, 95 % CI: 65–89). Subgroup analysis and meta‐regression showed a weaker association in studies with a clear definition of hyperemesis gravidarum compared to studies without this condition, and weaker association in recent studies compared to earlier studies. Meta‐regression showed that these two study characteristics explained 40% of heterogeneity between studies. Conclusions. Exposure to H. pylori appears to be associated with an increased risk of hyperemesis gravidarum. The residual heterogeneity might have different reasons. Given the high prevalence of H. pylori, the public health consequence of H. pylori with regard to hyperemesis gravidarum may be important.

Interlaboratory comparison of polymerase chain reaction for the detection of Toxoplasma gondii DNA added to samples of amniotic fluid

To investigate the accuracy of the polymerase chain reaction (PCR) method for the detection ofToxoplasma gondii in clinical specimens, aliquots of amniotic fluid to which known amounts ofToxoplasma gondii DNA had been added were tested by five European Centres. Four laboratories were able to detect DNA at levels equivalent to ten tachyzoites or less, including two that detected DNA equivalent to a single parasite. Two laboratories erroneously found one of eight negative control samples to be positive. These findings confirm that the high level of sensitivity associated with the PCR method can be readily achieved under routine laboratory conditions, but they also underscore the potential for both false-positive and false-negative findings to occur. Furthermore, the results confirm the urgent need for an external quality assurance scheme to support laboratories employing PCR in a clinical context for the detection ofToxoplasma gondii.

Diagnosis of congenital Toxoplasma gondii infection by polymerase chain reaction (PCR) on amniotic fluid samples : The Norwegian experience

As part of a screening project for detection of Toxoplasma gondii infection among pregnant women in Norway, nested polymerase chain reaction (PCR) aimed at the detection of T. gondii in amniotic fluid samples was included in the diagnostic routine. The results were compared with the routine criteria for congenital infection: i) T. gondii detected in amniotic fluid or cord blood by mouse inoculation, ii) specific IgM or IgA in serum collected after birth, and/or iii) specific IgG persisting beyond one year of age. The PCR was based on the B1 gene with an internal control gene amplified together with the B1 gene. One hundred and two amniotic fluid samples collected during pregnancy and/or at delivery from 67 pregnant women with serological evidence of primary T. gondii infection were available for examination by both B1‐PCR and mouse inoculation. Six samples were positive and 86 samples were negative by both methods (90% concordance). One sample was mouse inoculation positive and B1‐PCR negative while nine samples were B1‐PCR positive and mouse inoculation negative, of which five were associated with four infants without proven infection. 59% and 41% of samples associated with infected infants were positive by B1‐PCR and mouse inoculation, respectively. The difference was mainly due to a lower detection rate by mouse inoculation after antiparasitic treatment. The specificity of B1‐PCR was 94%. Even though B1‐PCR performed on amniotic fluid samples did not detect all infected infants, it represented a valuable tool in addition to conventional methods in the diagnosis of congenital T. gondii infection.

Bacteriological Findings and Clinical Symptoms

Clinical symptoms, bacterial content in breast milk and treatment were recorded in 43 women in Oslo with puerperal mastitis. Patients with a favorable (n = 35) and unfavorable outcome (n = 8) (defined as abscess formation and/or symptom relief after more than 7 days) were compared. The group with unfavorable outcome was characterized by increased delay between symptoms and time for consultation, higher score of clinical symptoms and higher frequency of Staphylococcus aureus. A higher frequency of S. aureus was found in the affected breasts than in the unaffected breasts. There was no difference concerning the frequency of coagulase‐negative staphylococci and overall bacterial counts, either between milk from affected and non‐affected breasts, or between milk from non‐affected breasts and milk from healthy donors. The present investigation indicates that penicillin treatment is questionable when considering that untreated cases healed almost as quickly as treated ones, and that 70% of the S. aureus strains were resistant to phenoxymethylpenicillin. It is concluded that present bacterial examinations in breast milk are of limited help in deciding who needs antibiotic treatment.