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Biomedical subjects

M Granström

Publications and source records attributed to M Granström.

At least 19 recordsLinked to original sources

Comparison of the performance of serological kits for Helicobacter pylori infection with European and Asian study populations.

Most commercial kits for the detection of Helicobacter pylori were developed and validated with Western populations, and some have been found to perform less well with Asian populations. This study compared the performances of three serological kits with Swedish and Vietnamese peptic ulcer patients and asymptomatic individuals. The Pyloriset EIA-GIII and HM-CAP ELISA kits indicated that Asian populations had lower antibody titres to H. pylori than European populations. Despite the difference, the Pyloriset EIA-GIII kit performed well with Vietnamese peptic ulcer patients and population controls. The HM-CAP ELISA kit had a significantly lower performance with Asian populations that could not be improved by adjustments to the cut-off level. The Helicoblot 2.1 immunoblot kit performed equally well with Vietnamese and Swedish populations, although the response rate to the 35-kDa band was significantly lower with Vietnamese individuals.

Adult↗

Long-term follow-up of Helicobacter pylori eradication therapy in Vietnam: reinfection and clinical outcome.

AIM: To assess the long-term Helicobacter pylori reinfection rates, as well as the clinical outcome in peptic ulcer disease patients in Vietnam. METHOD: At a 1-year evaluation of H. pylori eradication treatment in 226 peptic ulcer patients, long-term H. pylori status was assessed with serology and/or culture, peptic ulcer status by gastroscopy, and DNA-fingerprinting performed with random amplified polymorphic DNA and restriction fragment polymorphism. RESULT: Follow-up was performed a mean 11 months after the post-treatment evaluation on day 30 after beginning of treatment. The overall reinfection rate was 23.5%, with 58.8% of the strains being identical to the pre-treatment isolates and 41.2% being different. Peptic ulcer was found in 22.9% of the reinfected patients and in 6.3% of the non-reinfected. At the long-term follow-up of successful eradication cases, 89.8% of the patients were free of peptic ulcer disease. The corresponding result was 58.7% in patients in whom H. pylori eradication failed. CONCLUSION: Following successful H. pylori eradication, reinfection with H. pylori in patients in Vietnam was found to be higher than in industrialized countries but the long-term recurrence of peptic ulcer disease was still low. Helicobacter pylori eradication treatment is therefore of value also in developing countries as the rate of peptic ulcer disease was low at the 1-year follow-up.

Adolescent↗

Assessment of the cag pathogenicity island status of Helicobacter pylori infections with serology and PCR.

The serological characterisation of Helicobacter pylori strains has been questioned, e.g., when the presence or absence of the cag pathogenicity island (PAI) is determined. This study compared CagA-reactive serum antibodies, assessed with immunoblot, with cag PAI status, as determined by PCR. CagA serology results were available for 101 individuals contributing 202 bacterial samples for cag PAI PCR. There was a high degree of correlation between the two methods (kappa coefficient, 0.82; 95% confidence interval, 0.68-0.97). Combined with suggested biological explanations for the discrepancies, this finding supports the application of well-evaluated serological assays in the assessment of the cag PAI status of H. pylori infections in clinical and epidemiological studies.

Antibodies, Bacterial↗

Helicobacter pylori eradication in children and adolescents by a once daily 6-day treatment with or without a proton pump inhibitor in a double-blind randomized trial.

AIM: To evaluate two simplified Helicobacter pylori eradication treatment alternatives for children and adolescents. METHODS: Study subjects were identified by enzyme-linked immunosorbent assay and immunoblot in a family screening project. Helicobacter pylori infected 10-21 year olds were offered treatment, individuals with abdominal pain underwent upper endoscopy and those with peptic ulcers were excluded. Participants were randomized to either azithromycin 500 mg daily and tinidazole 500 mg two tablets daily in combination with lansoprasole 30 mg daily for 6 days (ATL-group) or with placebo (ATP-group). Urea Breath Test was performed at inclusion and after a minimum of 6 weeks after end of therapy. RESULTS: In total, 131 individuals were randomized, of whom 31 (24%) had undergone upper endoscopy. Full compliance was achieved in 93% (122 of 131). The intention-to-treat eradication rate was 67% (44 of 66) and 58% (38 of 65) for the ATL- and the ATP-group, respectively. CONCLUSION: The double-blind randomized clinical trial did not identify a simplified, successful once daily H. pylori treatment for children and adolescents. Thus, twice daily proton pump inhibitor (PPI)-based triple therapies for 7 days remain as the choice of treatment in children. Further, powerful and controlled studies are needed to elucidate the best treatment strategies for H. pylori eradication in this age group.

2-Pyridinylmethylsulfinylbenzimidazoles↗

The importance of the level of metronidazole resistance for the success of Helicobacter pylori eradication.

AIMS: To evaluate the role of antibiotic susceptibility for the treatment outcome of proton pump inhibitor-dependent and independent Helicobacter pylori eradication regimens. METHODS: In a placebo-controlled clinical study of peptic ulcer patients with H. pylori infection, patients were randomized to receive lansoprazole, clarithromycin and tinidazole twice-daily, clarithromycin and tinidazole once-daily with lansoprazole or with placebo. Helicobacter pylori status was assessed by culture and antibiotic susceptibility by E-test minimal inhibitory concentration (MIC) in 205 clinical isolates. RESULTS: Primary resistance to clarithromycin and metronidazole was 1 and 76%, respectively. In metronidazole susceptible strains eradication rates were similar at > 90% for all treatment groups (P = 0.49). With low-level metronidazole resistance (4 microg/mL < MIC < 256 microg/mL), eradication rates were similar at >75% (P = 0.80). The major difference was found at high-level metronidazole resistance (MIC >or= 256 microg/mL) with 95%, 58% and 21% eradication in the lansoprazole, clarithromycin and tinidazole twice-daily, lansoprazole, clarithromycin and tinidazole once-daily and placebo, clarithromycin and tinidazole once-daily groups, respectively (P < 0.001). CONCLUSION: In the absence of antibiotic resistance, a once-daily therapy of only clarithromycin and tinidazole can achieve a high rate of H. pylori eradication. Such a combination could offer a simpler and cheaper treatment option for developing countries. The standard, twice-daily proton pump inhibitor-based triple therapy was shown to be efficient in H. pylori eradication even in the presence of high-level metronidazole resistance.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Helicobacter pylori eradication and peptic ulcer healing: the impact of deleting the proton pump inhibitor and using a once-daily treatment.

AIM: To compare cheaper and simpler once-daily regimens, with and without a proton pump inhibitor, with standard, twice-daily, triple therapy. METHODS: A randomized, placebo-controlled, treatment trial in Vietnam allocated 296 Helicobacter pylori-infected patients with peptic ulcer of >or= 5 mm to one of three regimens: (i) twice-daily: lansoprazole 30 mg, clarithromycin 250 mg and tinidazole 500 mg; (ii) once-daily: lansoprazole 60 mg, clarithromycin 500 mg and tinidazole 1000 mg; (iii) once-daily: placebo, clarithromycin 500 mg and tinidazole 1000 mg. H. pylori status was assessed by culture and immunoblot, ulcer healing by endoscopy and side-effects by structured questionnaires. RESULTS: Per protocol eradication (N = 256) was higher with standard therapy (87%) than with once-daily therapy (72%), and both were better than once-daily therapy without proton pump inhibitor (39%). Per protocol ulcer healing after standard therapy (83%) was not significantly better than that after once-daily therapy (73%), but better than that after therapy without proton pump inhibitor (65%). Side-effects were reported at similar rates in all groups. CONCLUSIONS: Proton pump inhibitor was needed for optimal eradication and ulcer healing. Twice-daily administration showed improved success rates when compared with once-daily therapies. Peptic ulcer healing was achieved even in patients treated with antibiotics only, confirming the central role of H. pylori in the pathophysiology of peptic ulcer disease.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Unexpected decrease with age of Helicobacter pylori seroprevalence among Swedish blood donors.

Blood donors are often used as proxies for the general population in studies of Helicobacter pylori epidemiology. Our aim was to test if the age-specific seroprevalence rates among blood donors match with the corresponding rates in a random population sample. This descriptive study was based on sera obtained from 3,502 blood donors representing all Swedish counties and cities. An age-stratified random population sample of 1,030 from Stockholm County served as comparison. Sera were analyzed by an in-house enzyme-linked immunosorbent assay for H. pylori immunoglobulin G antibodies. In the population sample, we found the expected increase with age in the seroprevalence of H. pylori infection. This was true also among young blood donors, while the prevalence-by-age curve showed a deflection downward among blood donors who are >/= 50 years of age. In this age group, the probability of being seropositive was reduced by 73% (95% confidence interval [CI], 63 to 81%) relative to the population sample. Overall, the adjusted odds ratio for H. pylori seropositivity among blood donors was decreased by 43% (95% CI, 28 to 55%). Thus, it appears that blood donors who are H. pylori seropositive selectively disappear from the blood donor cohort. We speculate that H. pylori-seropositive blood donors may tolerate repeated bleedings less well than do noninfected individuals and/or that the general well-being among those who are infected may be somewhat impaired. Our unexpected observation indicates that blood donors may be less suitable as proxies for the general population in analytic studies of H. pylori infection and that the underlying cause needs further study.

Adolescent↗

The accuracy of serologic diagnosis of Helicobacter pylori infection in school-aged children of mixed ethnicity.

UNLABELLED: The present study evaluated two non-invasive diagnostic methods for H. pylori infection in children, i.e. an in-house ELISA using sonicated Campylobacter jejuni antigen for absorption of cross-reacting antibodies and an immunoblot kit (Helico Blot 2.0, Genelabs, Singapore). 13C -Urea breath test (13C-UBT) was used as reference METHOD: Sera and questionnaires were collected from 695/858 (81%) Swedish school children with mixed ethnic backgrounds within a cross-sectional, community-based study. Of 133 children with an ELISA OD value of > or = 0.1, all were screened with immunoblot and 107 made a 13C-UBT. The negative controls were 34/37 children from three school classes with an ELISA OD value of < 0.1 and volunteering for a 13C-UBT. An adjusted cut-off level for the ELISA of OD value 0.22 resulted in a sensitivity of 97.8%, a specificity of 95.8% and a concordance index of 97.2%. The Helico Blot 2.0 had a sensitivity of 97.8%, a specificity of 93.8% and a concordance index of 96.5%. The best concordance was seen for the 26.5 kDa (98.6%), 30 kDa (95.7%) and 19.5 kDa (91.5%) antigens. The corresponding concordance index for CagA was 78%, for VacA 73.8% and for the 35kDa antigen 68.8%. A significant difference in the distribution of the 19.5 and 26.5 kDa bands but not of CagA/VacA was noted by ethnic background. With an adjusted cut-off level for the enzyme-linked immunosorbent assay (ELISA), both non-invasive methods were found to have an adequate performance in a pediatric population. The differences in antibody response patterns by ethnic background represent a caveat in the interpretation of serological studies.

Adolescent↗

Helicobacter pylori infection in Swedish school children: lack of evidence of child-to-child transmission outside the family.

BACKGROUND & AIMS: Helicobacter pylori infection is mainly acquired in early childhood, but the exact routes of transmission remain elusive. To distinguish between risks of intrafamilial and extraneous child-to-child transmission, we studied H. pylori seroprevalence among Swedish school children with varying family backgrounds. METHODS: In a cross-sectional study, 695 of 858 (81%) 10-12-year-olds in 36 school classes in Stockholm donated blood and answered a questionnaire. Infection was detected by enzyme-linked immunosorbent assay and confirmed by immunoblot and urea breath test. RESULTS: Overall, 112 (16%) children were infected. The seroprevalence was 2% among 435 children with Scandinavian parents and 55% among 144 children with origin in high prevalence areas (Middle East and Africa). Among children born in Scandinavia, the odds ratios (adjusted for gender, socioeconomic status, and family size) for being seropositive were 39.1 (95% confidence interval, 16.7-91.3) and 5.6 (1.8-17.3) when having parents born in high and medium prevalence areas, respectively, relative to children with Scandinavian parents. Importantly, the prevalence of infection among the classmates was not a risk factor for H. pylori infection. CONCLUSION: Our data indicate that intrafamilial transmission is far more important than child-to-child transmission outside the family. The H. pylori prevalence in the parental generation may be a crucial determinant for the child's risk of contracting the infection.

Child↗

Refinement of the 14C-urea breath test for detection of Helicobacter pylori.

BACKGROUND: Helicobacter pylori is recognized as the main etiological factor for chronic gastritis, peptic ulcer and possibly also gastric malignancies. A 14C-urea breath test was successively refined to correctly diagnose the presence of H. pylori. METHODS: After intake of a 14C-urea cocktail, 14CO2 in breath was trapped in benzethoniumhydroxide/ethanol. Serology by ELISA, followed by Western blot, was used as reference method for confirmation of presence or absence of H. pylori. RESULTS: Breath measurements at 10 and 20 min were determined to be optimal for diagnostic purposes. With 2.5 microCi of 14C-urea, a sensitivity of 86% and specificity of 100% was obtained for the 10-min values. Corresponding data for the 20-min values were 86% and 99%, respectively. When 50 mmol L(-1) citric acid was added to the 2.5 microCi 14C-urea cocktail, separation between positive and negative results became more distinct along with improved sensitivity of 91% and specificity of 100%. As the isotope amount was reduced to 1.0 microCi in the citric acid-containing cocktail, a sensitivity of 93% and specificity of 100% were obtained at both 10 and 20 min. CONCLUSION: Diagnostic urea breath test has a high concordance with H. pylori serology, combining ELISA and Western blot. Stepwise refinements proved the optimal urea breath test cocktail to include 1.0 microCi 14C-urea in citric acid solution with breath measurement at 10 min.

Adult↗

Impact of a vaccination campaign on adult immunity to diphtheria.

OBJECTIVES: to raise the level of immunity to diphtheria in the adult population of Stockholm by a vaccination campaign. The rationale behind the campaign, conducted during 1995-1996, was the re-emergence of epidemic diphtheria in the countries of the former Soviet Union and earlier surveys of immunity to diphtheria showing low levels of protection in adults. DESIGN AND MAIN OUTCOME MEASURES: the impact of the vaccination campaign was measured by recording the age and sex of vaccinees, the type and number of vaccine doses given and any side-effects. The effect on immunity was evaluated in 1998-1999 by measuring the neutralising antibodies in blood samples from 1863 inhabitants, chosen by random stratified sampling. Vaccines and vaccinations: three doses of diphtheria (D) or diphtheria-tetanus (DT) vaccine were given to those without documented previous vaccination; others received a booster dose. The DT vaccine, with the D component purified before toxoiding, contained 15 Lf of D and 7.5 Lf of T per ml, and was given in 0.5 ml doses for the two priming doses and 0.25 ml as booster. RESULTS: 184969 doses of D or DT vaccine were given to 99939 individuals. Of the vaccinees, 65% were 50 years of age or older and 60% were women. The highest rates of reported local reactions were 1.8-5.4% and of systemic reactions, such as fever, 0.2-0.8%. The campaign resulted in a significant increase in antitoxin concentrations in the age cohorts targeted, and especially in women, less well protected than men. CONCLUSIONS: a vaccination campaign, targeting the adult part of a population, can result in a major improvement in immunity to diphtheria with only a few and minor side-effects with a DT vaccine where the D component was purified prior to toxoiding. Extending national immunisation programmes to include adults would, however, seem preferable.

Adult↗

Booster effect of low doses of tetanus toxoid in elderly vaccinees.

In order to improve the immunity to diphtheria, the recommended booster dose of diphtheria/tetanus vaccine for adults in Sweden was changed in 1986 from 0.5 ml of tetanus vaccine with a small diphtheria dose to 0.25 ml of a diphtheria/tetanus vaccine containing 7.5 Lf tetanus toxoid and 30 Lf diphtheria toxoid/ml. This change resulted in an increase in the dose of diphtheria toxoid from 0.5 Lf to 7.5 Lf, but a decrease in the recommended booster dose of tetanus toxoid from 3.75 Lf to 1.9 Lf. The aim of the present study was to investigate whether this lower dose of tetanus toxoid was also sufficiently protective for elderly people. Two hundred adults (median age 76 years, range 60-92 years) with no history of tetanus vaccination during the past 10 years volunteered for the study. One hundred two vaccinees were inoculated with 1.9 Lf tetanus toxoid (0.25 ml) and 98 with 3.75 Lf tetanus toxoid (0.5 ml). Paired serum samples were analysed by the toxin-binding inhibition assay. Side effects were few and mild, without significant differences between the groups. Response rates were similar, with the 3.75 Lf dose eliciting a marginally higher antitoxin response. The prevaccination geometric mean titre was the same for both groups: 0.03 IU/ml. Postvaccination geometric mean titres were 1.18 IU/ml for the 3.75 Lf group and 1.93 IU/ml for the 7.5 Lf group, respectively (difference not significant). Forty-seven percent of the vaccinees had a prevaccination titre of < or =0.01 IU/ml. Postvaccination, 85% had a titre >0.01 IU/ml. Booster vaccination with tetanus vaccine containing only 1.9 Lf of tetanus toxoid was thus found to induce an excellent immune response in elderly people, with few side effects resulting.

Aged↗

A European multicenter study of immunoblotting in serodiagnosis of lyme borreliosis.

A European multicenter study of immunoblotting for the serodiagnosis of Lyme borreliosis showed considerable variation in results obtained from tests with a panel of 227 serum samples. Six laboratories used different immunoblot methods, and a wide range of bands was detected in all the assays. Multivariable logistic regression analysis of data from individual laboratories was used to determine the most discriminatory bands for reliable detection of antibodies to Borrelia burgdorferi sensu lato. These bands were used to construct individual interpretation rules for the immunoblots used in the six laboratories. Further analysis identified a subset of eight bands, which were important in all the laboratories, although with variations in significance. Possible European rules, all closely related, were formulated from these bands, although there was no single rule that gave high levels of sensitivity and specificity for all the laboratories. This is a reflection of the wide range of methodologies used, especially the use of different species and strains of B. burgdorferi sensu lato. The panel of European rules provides a framework for immunoblot interpretation which may be adapted in relation to the characteristics of Lyme borreliosis in local areas.

Antibodies, Bacterial↗

Community health care nursing in Rajasthan. A registered nurse's perspective.

This study focused on the great shortage of registered nurses (RNs) in primary health care in Rajasthan, India. It dealt especially with the nurses' own opinions about working in primary health care and their reasons for not working in it. Nurses at different levels in the health care organization were interviewed. The study was based on interviews with six RNs individually, three groups of six to eight nursing students each, and three policy-making chief nurses individually. The Minister of Health in Rajasthan also participated in the study. The study showed that the reasons for the lack of RNs in community health care were as follows: a government policy decision to place less educated nurses in the communities; the great shortage of nurses in general; the system whereby a nurse is not able to choose her/his place of work; unwillingness on the part of the nurses to work in community health care because of the great security problems; lack of support from authorities and lack of equipment. In general, community health care nursing as a work area was despised by society at large in Rajasthan.

Community Health Nursing↗

Subcutaneous versus intramuscular injection for booster DT vaccination of adolescents.

The importance of the injection technique in booster vaccination was investigated in an open randomized study with 252 10-year-old Swedish school-children receiving routine DT vaccination either by subcutaneous or by intramuscular route in the upper arm. The adolescents had previously been primed with DT vaccine at 3, 5 and 12 months of age. Adverse reactions, monitored for 2 weeks, showed the same low rates for systemic reactions in both groups, while the intramuscular administration gave significantly less redness (p < 0.001), swelling (p < 0.001), itching (p < 0.01) and pain (p < 0.05). These reactions were also of shorter duration (p < 0.01 to p < 0.001). Girls were found to have more pain and itching than boys (p < 0.001). No significant differences in antibody responses between the two administration routes were found in the 99 samples drawn 2 weeks after the booster. However, girls were found to have a lower response to diphtheria toxoid than boys (p = 0.009). Local reactions to a booster can thus be significantly reduced by choice of injection technique, which may be necessary if increased dosages and/or further valences are to be given to adolescents and adults.

Antibodies, Bacterial↗

Signal transduction-mediated adherence and entry of Helicobacter pylori into cultured cells.

BACKGROUND & AIMS: An ability to invade host cells could be a means for Helicobacter pylori to achieve resistance to antibiotic therapy. The aim of this study was to investigate the mechanisms involved in adherence and entry of H. pylori into cultured cells. METHODS: Coinfection with Yersinia expressing mutant or wild-type YopH tyrosine phosphatase was used. Genistein and cytochalasin D were used as inhibitors of adherence and entry; entry was monitored by a gentamicin-protection assay. Target cells were AGS cells and a beta1-integrin-deficient cell line with its corresponding beta1-integrin-expressing transfectant. RESULTS: H. pylori induced phosphorylation of 125-130-kilodalton proteins, similar in size to the target proteins of Yersinia YopH. Adherence of H. pylori was inhibited by Yersinia organisms expressing enzymatically active YopH but not by inactive YopH. Adherence and entry of H. pylori was considerably higher with beta1-integrin-transfected cells than with beta1-integrin-deficient cells. Antibodies directed against alpha5- and beta1-integrin chains reduced adherence to the alpha5beta1-integrin-expressing gastric cell line AGS. Entry was inhibited by both cytochalasin D and genistein. Entry, but not adherence, was higher for 2 type I strains than for a type II isolate. CONCLUSIONS: Invasion of gastric epithelium via an integrin-mediated pathway could contribute to the ability of H. pylori to establish persistent infection.

Bacterial Adhesion↗

Clinical symptoms and social factors in a cohort of children spontaneously clearing Helicobacter pylori infection.

In a cohort study of 305 Swedish children, repeated blood samples and structured questionnaires were obtained from 6 mo to 11 y of age. Of the 40 children seropositive for Helicobacter pylori in one or more samples, 32 (80%) had cleared the infection by 11 y of age. No association was found between H. pylori seropositivity at any time and reported antibiotic consumption, size of home and family, type of day-care, history of atopic disease, length of breastfeeding or peptic ulcer disease in the family. Girls reported more (p = 0.002) unspecified abdominal pain during childhood than boys, but the difference in H. pylori infection rate (15/150, 10% for boys and 25/144, 17% for girls) was not significantly different (p = 0.09). Unspecified abdominal pain during childhood was reported more often (OR adjusted for gender = 2.2, 95% CI = 1.0-4.4, p = 0.04) for the children seropositive at some point (17/39, 44%) than for the seronegative children (54/217, 25%). RAP at 11 y of age was more often reported by the 9/36 (25%) children seropositive at some time in life than by the 23/172 (13%) seronegatives, but the difference was not statistically significant (OR adjusted for gender = 2.0, 95% CI = 0.8-4.6, p = 0.1). The study shows that H. pylori seropositivity was associated with a parental report of unspecified abdominal pain during childhood. Also, a history of unspecified abdominal pain was more common (OR = 51.6, 95% CI = 15.6-220, p < 0.001) in children reporting RAP at 11 y of age.

Abdominal Pain↗

A ten year follow-up after immunization with a two component acellular pertussis vaccine.

OBJECTIVES: To investigate the duration of antitoxin response and immunity to pertussis 10 years after priming with either two or three doses of a two component acellular pertussis vaccine or with three doses of a whole cell vaccine and then boostered with the acellular vaccine. SUBJECTS: At 11 years of age 207 of 304 (68%) children of the original cohort returned for a blood sample and 262 (86%) participated by answering a questionnaire. METHODS: Neutralizing antibodies to pertussis toxin (antitoxin) were analyzed by the Chinese hamster ovary cell assay. Clinical pertussis and pertussis exposure were investigated by a structured questionnaire. RESULTS: Measurable antitoxin was found in 77% of the samples, with no differences by type of vaccine or by the number of doses given for priming. A significant decrease of antibody concentration (P<0.001) was noted from the previous recall at 4 years of age, and significant titer rises were found for 14% of the children, irrespective of known exposure. Confirmed pertussis during follow-up, as defined in the study, was reported for 14 of 262 (5%) children. CONCLUSIONS: The study showed that antitoxin concentrations are maintained in a situation of endemic pertussis and indicated that the long term protection after an acellular booster was good, irrespective of type of vaccine or the number of doses of acellular vaccine given for priming.

Antibodies, Bacterial↗