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Biomedical subjects

M Tanner

Publications and source records attributed to M Tanner.

At least 19 recordsLinked to original sources

Dual-colour chromogenic in situ hybridization for testing of HER-2 oncogene amplification in archival breast tumours.

Chromogenic in situ hybridization (CISH), which uses an enzymatic reaction to detect the hybridized DNA probe, is a new alternative to fluorescence in situ hybridization (FISH) for the assessment of HER-2 oncogene amplification status in breast cancer. The main advantage of CISH over FISH is the use of bright-field microscopy, which is rapid and allows the histopathological evaluation of tumour tissue sections. The main disadvantage of CISH has been the use of a single probe, thereby making it necessary to hybridize the control probe (chromosome 17 centromere) on an adjacent tissue section. The present paper presents an efficient protocol for dual-colour CISH (dc-CISH) based on the co-hybridization of probes to the HER-2 oncogene and chromosome 17 centromere. The probes were detected sequentially with antibodies to digoxigenin and biotin and with secondary antibody polymers labelled with horseradish peroxidase and alkaline phosphatase. The peroxidase reaction was visualized with tetramethyl benzidine (green reaction product) and the alkaline phosphatase reaction with New Fuchsin (red reaction product). The accuracy of the method was verified by comparing the results for four cell lines and 40 tumour samples with those obtained using FISH (Vysis Inc.). The results of FISH and dc-CISH showed high concordance (91%, Kappa coefficient = 0.82). It is concluded that dual-colour CISH, which is a new alternative to FISH enables the assessment of copy number ratio (HER-2/17 centromere) in conjunction with proper histopathological evaluation and the ease of bright-field microscopy.

Breast Neoplasms↗

Evaluation of multiple immune parameters after vaccination with modified live or killed bovine viral diarrhea virus vaccines.

The development of immunity to vaccine antigen was examined using three prime/boost strategies and the progression of immune activities was evaluated over the course of 8 weeks. Calves were vaccinated and multiple immune parameters were evaluated using several methods to assess humoral or cellular immunity from the same samples in parallel. The three vaccination protocols used were a killed vaccine followed by a killed boost (killed/killed), MLV vaccine and boost (MLV/MLV), or a MLV vaccine and killed boost (MLV/killed). All the vaccines used included modified live IBR/PI3 viruses to make the bystander context as similar as possible. The Singer strain of BVDV was used as the source antigen in the killed vaccine, and the NADL strain of BVDV was used in the MLV vaccine. Controls received a vaccine containing only MLV IBR/PI3. The assessment panel measured SN titers, as well as lymphocyte proliferation, cytokine mRNA expression, intracellular cytokine production, and released IFN-gamma after in vitro stimulation with three strains of BVDV virus. MLV/MLV and MLV/killed groups developed significant SN titers to the type 1 BVDV virus strains, Singer and NADL, and low crossover titers were also seen to the type 2 strain, 890 over the evaluation period. These two groups showed significant proliferation in response to the NADL virus as compared to controls. Multiple immune assessments were conducted simultaneously to attempt to provide a broader, more in depth evaluation of immune response to these BVDV vaccination protocols. We observed that the correlation among most of the assays conducted were weak; the correlation between SN titers and cellular proliferation assays demonstrated a moderate correlation.

Animals↗

Species identification of non-tuberculous mycobacteria from humans and cattle of Chad.

In Chad, during a study on tuberculosis in humans and cattle, 52 non-tuberculous mycobacteria (NTM) strains were isolated. By means of INNO-LiPA, PRA-hsp65 amplification and sequencing of 16S rDNA, NTM species of 25/52 isolates were identified. M. fortuitum complex (8) was the most frequent species, followed by M. nonchromogenicum (4) and M. avium complex (4). PRA method could identify M. fortuitum 3rd variant among isolates derived from cattle specimens. This finding could confirm the existence of farcy in the Chadian cattle population as M. fortuitum 3rd variant and putitative pathogen M. farcinogenes can't be distinguished by the methods used in this study. Half of the NTM isolates could not be specified and we considered them as contaminants from the environment.

Animals↗

Effect of an armed conflict on human resources and health systems in Côte d'Ivoire: prevention of and care for people with HIV/AIDS.

In September 2002, an armed conflict erupted in Côte d'Ivoire which has since divided the country in the government-held south and the remaining territory controlled by the 'Forces Armées des Forces Nouvelles' (FAFN). There is concern that conflict-related population movements, breakdown of health systems and food insecurity could significantly increase the incidence of HIV infections and other sexually-transmitted infections, and hence jeopardize the country's ability to cope with the HIV/AIDS epidemic. Our objective was to assess and quantify the effect this conflict had on human resources and health systems that provide the backbone for prevention, treatment and care associated with HIV/AIDS. We obtained data through a questionnaire survey targeted at key informants in 24 urban settings in central, north and west Côte d'Ivoire and reviewed relevant Ministry of Health (MoH) records. We found significant reductions of health staff in the public and private sector along with a collapse of the health system and other public infrastructures, interruption of condom distribution and lack of antiretrovirals. On the other hand, there was a significant increase of non-governmental organizations (NGOs), some of which claim a partial involvement in the combat with HIV/AIDS. The analysis shows the need that these NGOs, in concert with regional and international organizations and United Nations agencies, carry forward HIV/AIDS prevention and care efforts, which ought to be continued through the post-conflict stage and then expanded to comprehensive preventive care, particularly antiretroviral treatment.

Cote d'Ivoire↗

Amplification of the epidermal growth factor receptor in astrocytic tumours by chromogenic in situ hybridization: association with clinicopathological features and patient survival.

Chromogenic in situ hybridization (CISH) was used to detect amplification of the epidermal growth factor receptor (EGFR) gene in tissue microarrays of tumours derived from 287 patients with grade II-IV diffuse astrocytomas. Amplification was found in 32% of the tumours with a highly significant association with histological grade (4% in grade II, 21% in grade III and 39% in grade IV; P < 0.001). Amplification of the EGFR gene was more common in primary than in secondary glioblastomas (41%vs. 16%, P = 0.033). Overexpression of EGFR mRNA and protein (wild-type and vIII variant) was found to correlate with EGFR gene amplification (P = 0.028, P = 0.035 and P = 0.014 respectively), but wild-type EGFR protein was also frequently overexpressed in tumours without EGFR gene amplification. Patients with older age (P < 0.001) and tumours with lack of p53 overexpression (P = 0.03) and higher apoptosis rate (P < 0.001) had significantly more EGFR gene amplifications than their counterparts. No such correlation with apoptosis was found in glioblastomas. The survival of patients with EGFR gene-amplified grade III tumours was significantly shorter than in those with grade III non-amplified tumours (P = 0.03). No such difference was noted in glioblastomas (grade IV tumours). Our data verify the central role of EGFR in the pathobiology of astrocytic tumours, and highlight the advantages of CISH as a simple and practical assay to screen for EGFR gene amplification in astrocytic tumours.

Adolescent↗

Malaria: burden of disease.

Despite more than 100 years since Laveran described plasmodium species and Ross confirmed that they were transmitted by female anopheline mosquitoes, malaria remains a leading cause of morbidity and mortality worldwide. Although the areas where transmission takes place have reduced, and they are by now confined to the inter tropical areas, the number of people living at risk has grown to about 3 billion, and is expected to go on increasing. Not only does malaria cause around 500 million cases every year, and between 1 and 3 million deaths, but it also carries a huge burden that impairs the economic and social development of large parts of the planet. The failed attempt to eradicate malaria gave way to the control policy that was followed by a huge resurgence of malaria during the late 70s and 80s. Together with the emergence and spread of resistance to chloroquine and the weak health infrastructure in many of the endemic countries, particularly in Africa, the malaria situation worsened worldwide. The last decade of the 20th century was witness to the international community becoming increasingly aware of the unacceptable situation that the burden of malaria represented to large parts of the world. Renewed efforts to describe the problem, design and evaluate new control strategies, design and develop new drugs, better understand the biology of the parasite and the immunity it induces in the human host, develop candidate vaccines, together with new financial support constitute renewed hope that may lead to new trends in global health.

Chloroquine↗

[Prevalence, genetic diversity and multiplicity of Plasmodium falciparum infection in school children in central Cote d'Ivoire].

A study was carried out in the village of Taabo, located in the vicinity of a large man-made lake in central Côte d'Ivoire. The objectives were (i) to determine the level of prevalence, genetic diversity and multiplicity of Plasmodiumfakiparum infection in schoolchildren and (ii) to compare the diagnostic performance of light microscopy and polymerase chain reaction (PCR). A total of 424 schoolchildren ranging in age from 5 to 15 years underwent diagnostic testing using both light microscopy of blood smears and PCR. Multiplicity of P. falciparum infection was investigated in 196 children (46.2%). The prevalence of malaria was 54.7% based on light microscopy and 83.9% based on PCR. Genotyping based on polymorphism in the length of the restriction fragment of the gene encoding the merozoite surface protein-2 (msp2) showed that 86.5% of cases involved multiple infection with a geometric mean of 3.87 genotypes per positive child. There was a strong positive correlation between multipcity of infection and parasite density in the 56-year old age group. A total of 50 genotypes including six observed for the first time were identified and classified into families with similar-sized sequence groups: 26 x FC27 (52%) and 24 x 3D7 (48%). In comparison with PCR, the sensitivity and specificity of light microscopy for diagnosis of P. falciparum was 81.3% and 88.2% respectively. Data are discussed in the light of similar studies carried out in sub-Saharan Africa and elsewhere. These findings can serve as a basis for monitoring the longterm effect of major water resource management projects on the prevalence, genetic diversity and multiplicity of P. falciparum infection.

Adolescent↗

Frequency of Norovirus in stool samples from patients with gastrointestinal symptoms in Switzerland.

To determine the frequency of sporadic community-acquired Norovirus (NV) infection in the German-speaking part of Switzerland, an evaluation of gastroenteritis cases seen in physicians' practices between July 2001 and July 2003 was conducted. A total of 699 stool specimens documented to be free of common bacterial pathogens was screened for the presence of NV by RT-PCR. NV was detected in 125 (17.9%) of these specimens. In the seasonal analysis, the highest rate of NV-positive samples (38.3%) was found between January and March 2002. After July 2002, the study was expanded to additionally test for NV in stool samples containing a known bacterial pathogen. Among 132 such specimens, NV was detected in only one. This suggests that NV mixed-infections are playing a marginal role in Switzerland.

Caliciviridae Infections↗

Risk factors for infections with Norovirus gastrointestinal illness in Switzerland.

Viral infections, particularly those caused by noroviruses (NV, genus Norovirus), are the most common cause of community-acquired gastroenteritis in Europe, with respect to both endemic and epidemic occurrence. For the first time, a general practitioner-based case-control study was performed between July 2001 and July 2003 in the German-speaking part of Switzerland in order to identify risk factors for sporadic NV infections. The consumption of different foodstuffs and of bottled mineral water did not show any significant association with the risk of NV gastroenteritis, nor was there any significant effect of individual ABO histo-blood group or household size on the incidence of NV gastroenteritis. The findings are consistent with person-to-person transmission as the most important route of transmission for community-acquired, sporadic NV infection, in that 39% of all patients reported they had had contact with ill persons before their illness. The fact that 33% reported contact with ill persons, mainly within family groups, after their own illness suggested that a substantial proportion of patients were part of family mini-outbreaks.

Adolescent↗

Morbidity and nutrition patterns of three nomadic pastoralist communities of Chad.

As a part of an interdisciplinary research and action programme, morbidity and nutritional patterns were assessed in three nomadic communities: Fulani and Arab cattle breeders and Arab camel breeders, of two prefectures in Chad. The predominant morbidity pattern of Chadian nomadic pastoralists (representing approximately 10% of the total population of the country) had not been documented so far. A total of 1092 women, men and children was examined by a physician and interviewed during two surveys in the dry season and one in the wet season (1999--2000). Participants with no complaint were rare. Pulmonary disorders (e.g. bronchitis) were most often diagnosed for children under 5 years of age. Of the adult participants, 4.6% were suspected of tuberculosis. Febrile diarrhoea occurred more often during the wet season when access to clean drinking water was precarious. Malaria was only rarely clinically diagnosed among Arabs during the dry season, whereas Fulani, who stayed in the vicinity of Lake Chad, were also affected during this period. A 24-h dietary recall showed that less Arab women than men consumed milk during the dry season (66% versus 92%). Malnutrition was only documented for 3 out of 328 children (0--14 years). Arab women in childbearing age had a higher proportion of children not surviving when compared to Fulani women (0.2 versus 0.07). This study identified several implications for reseach and interventions in nomadic settings. Innovative and integrated health services for nomads can possibly be extended to many settings as nomadic pastoralists have in common a similar way of life driven by the needs of their animals.

Adolescent↗

Impact of migration on illness experience and help-seeking strategies of patients from Turkey and Bosnia in primary health care in Basel.

Migration, particularly among refugees and asylum seekers, poses many challenges to the health system of host countries. This study examined the impact of migration history on illness experience, its meaning and help-seeking strategies of migrant patients from Bosnia and Turkey with a range of common health problems in general practice in Basel, Switzerland. The Explanatory Model Interview Catalogue, a data collection instrument for cross-cultural research which combines epidemiological and ethnographic research approaches, was used in semi-structured one-to-one patient interviews. Bosnian patients (n=36) who had more traumatic migration experiences than Turkish/Kurdish (n=62) or Swiss internal migrants (n=48) reported a larger number of health problems than the other groups. Psychological distress was reported most frequently by all three groups in response to focussed queries, but spontaneously reported symptoms indicated the prominence of somatic, rather than psychological or psychosocial, problems. Among Bosnians, 78% identified traumatic migration experiences as a cause of their illness, in addition to a range of psychological and biomedical causes. Help-seeking strategies for the current illness included a wide range of treatments, such as basic medical care at private surgeries, outpatients department in hospitals as well as alternative medical treatments among all groups. Findings provide a useful guide to clinicians who work with migrants and should inform policy in medical care, information and health promotion for migrants in Switzerland as well as further education of health professionals on issues concerning migrants health.

Adult↗

Spatial risk prediction and mapping of Schistosoma mansoni infections among schoolchildren living in western Côte d'Ivoire.

The objectives of this study were (1) to examine risk factors for Schistosoma mansoni infection among schoolchildren living in western Côte d'Ivoire, and (2) to carry forward spatial risk prediction and mapping at non-sampled locations. First, demographic and socio-economic data were obtained from 3818 children, aged 6-16 years, from 55 schools. Second, a single stool sample was examined from each child by the Kato-Katz technique to assess infection status of S. mansoni and its intensity. Third, remotely sensed environmental data were derived from satellite imagery and digitized ground maps. With these databases a comprehensive geographical information system was established. Bayesian variogram models were applied for spatial risk modelling and prediction. The infection prevalence of S. mansoni was 38.9%, ranging from 0% to 89.3% among schools. Results showed that age, sex, the richest wealth quintile, elevation and rainfall explained the geographical variation of the school prevalences of S. mansoni infection. The goodness of fit of different spatial models revealed that age, sex and socio-economic status had a stronger influence on infection prevalence than environmental covariates. The generated risk map can be used by decision-makers for the design and implementation of schistosomiasis control in this setting. If successfully validated elsewhere, this approach can guide control programmes quite generally.

Adolescent↗

Outbreaks of gastroenteritis due to infections with Norovirus in Switzerland, 2001-2003.

Viral infections, especially those with noroviruses are the most common cause of acute gastroenteritis in Europe. To obtain information about the epidemic situation of noroviruses in Switzerland, an initial study was launched in the German-speaking part of the country to systematically compile Norovirus outbreak information between 2001 and 2003. In total, 73 outbreaks were registered. Most affected were closed settings, e.g. nursing homes (34%) and hospitals (25%). Transmission pathways were identified in 74% of Norovirus outbreaks. In 81% of these cases person-to-person transmission was the primary route of infection and on seven occasions (13%), a foodborne transmission was the possible cause. Furthermore, Norovirus outbreak characteristics of epidemiological importance are highlighted with a discussion of four selected events.

Caliciviridae Infections↗

Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab.

BACKGROUND: HER-2/neu gene amplification has predictive value in breast cancer patients responding to trastuzumab. We wanted to investigate the frequency and clinical significance of HER-2/neu amplification in gastric carcinoma. PATIENTS AND METHODS: The frequency of HER-2/neu and Topoisomerase IIalpha gene amplification was studied in adenocarcinomas of the stomach (n=131) and the gastroesophageal junction (n=100) by chromogenic in situ hybridization (CISH). Sensitivity of a gastric cancer cell line N87 with HER-2/neu amplification to trastuzumab was studied by a cell viability assay and compared with that of a HER-2 amplified breast cancer cell line SKBR-3. Growth inhibition of N87 cells was also verified in vivo in N87 xenograft tumors. RESULTS: HER-2/neu amplification was present in 16 (12.2%) of the 131 gastric and in 24 (24.0%) of the 100 gastroesophageal adenocarcinomas. Co-amplification of Topoisomerase IIalpha was present in the majority of gastric (63%) and esophagogastric junction cancers (68%) with HER-2/neu amplification. HER-2/neu amplification was more common in the intestinal histologic type of gastric cancer (21.5%) than in the diffuse (2%) or the mixed/anaplastic type (5%, P=0.0051), but it was not associated with gender, age at diagnosis or clinical stage. Presence of HER-2/neu amplification was associated with poor carcinoma-specific survival (P=0.0089). HER-2/neu targeting antibody trastuzumab inhibited the growth of a p185(HER-2/neu) overexpressing gastric and breast carcinoma cell lines (N87 and SKBR-3) with equal efficacy. CONCLUSIONS: HER-2/neu amplification is common in the intestinal type of gastric carcinoma, and it is associated with a poor outcome. HER-2 might be a useful target in this disease, and this hypothesis deserves to be investigated in clinical trials.

Adenocarcinoma↗

Malaria transmission dynamics in central Côte d'Ivoire: the influence of changing patterns of irrigated rice agriculture.

The dynamics of malaria transmission was studied comparatively in the villages of Zatta and Tiemelekro, central Cote d'Ivoire, from February 2002 to August 2003. Prominent agroecosystems in these villages are irrigated rice growing and vegetable farming, respectively. Mosquitoes (Diptera: Culicidae) were collected on human bait at night and by pyrethrum knock-down spray sheet collections at four randomly selected sentinel sites in each village. In 2002, for a total of 96 man-nights per village, 7716 mosquitoes were collected in Zatta and 3308 in Tiemelekro. In 2003, with half the sampling effort, 859 and 2056 mosquitoes were collected in Zatta and Tiemelekro, respectively. Anopheles gambiae Giles s.l. was the predominant mosquito and the key malaria vector throughout, followed by An. funestus Giles. Anthropophily among adult female Anopheles exceeded 95% in both villages. Comparison between years revealed that the biting rate of An. gambiae s.l. in Zatta decreased several-fold from 49.3 bites per person per night (b/p/n) in 2002 to 7.9 b/p/n in 2003 (likelihood ratio test (LRT) = 1072.66; P < 0.001). Although the biting rate remained fairly constant in Tiemelekro, the difference between years was significant (16.1 vs. 18.2 b/p/n; LRT = 148.06; P < 0.001). These observations were paralleled by a marked decrease in the infective rate of An. gambiae s.l. in Zatta (4.6-1.2%), and an increase in Tiemelekro (3.1-7.6%). Meanwhile, the entomological inoculation rate of An. gambiae s.l. decreased 21-fold in Zatta, from 789 to 38 infective bites per person per year (ib/p/y), whereas it remained high in Tiemelekro (233 vs. 342 ib/p/y). The interruption of irrigated rice growing in Zatta in 2003, consequential to a farmers' conflict over land, might be the underlying cause for the significant reduction in malaria transmission, whereas more stable conditions occurred in Tiemelekro.

Agriculture↗

No GIST-type c-kit gain of function mutations in neuroblastic tumours.

AIMS: Neuroblastic tumours (NTs) have been shown to respond to imatinib treatment in vivo and in vitro, possibly via inactivating the c-kit receptor. The purpose of this study was to identify gastrointestinal stromal tumour (GIST)-type c-kit gene associated mutations in exons 9, 11, 13, and 17 in NTs to recognise a subset of tumours that would probably respond to imatinib treatment. METHODS: Expression of the c-kit protein was detected immunohistochemically in a total of 37 archival paraffin wax embedded NTs using polyclonal rabbit antihuman c-kit antibody. After immunohistochemistry, c-kit gene associated chromosomal mutations in all cases of NT were detected with denaturing high performance liquid chromatography (HPLC). RESULTS: Denaturing HLPC analysis did not reveal GIST-type mutations in four immunohistochemically detected c-kit positive or in 33 c-kit negative NTs. CONCLUSIONS: c-kit receptor expression and GIST-type c-kit gene mutations are rare events in NTs. Oncogenic activation of c-kit in NTs presumably differs from that of GISTs, which may influence their responsiveness to imatinib treatment. Whether c-kit has an essential role in the pathogenesis of NTs remains to be investigated.

Antineoplastic Agents↗

A potential impact of climate change and water resource development on the transmission of Schistosoma japonicum in China.

There is growing consensus among climate modellers that the unusual global warming observed in the last decades of the 20th century is primarily forced by human activities, namely greenhouse gas increases in the atmosphere. Global warming will trigger alterations in physical and biological systems, including shifts in the spatio-temporal distribution of disease vectors, but the nature and extent of these changes are poorly understood. The purpose of the present study was to assess the potential impact of climate change and water resource development on the distribution of Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum. We employed two 30-year composite datasets comprising average monthly temperatures collected at 623 observing stations throughout China, spanning the periods 1961-1990 and 1971-2000. Temperature changes were assessed spatially between the 1960s and 1990s for January, as this is the critical month for survival of O. hupensis. Our database shows that January temperatures increased at 590 stations (94.7%), and that China's average January temperature in the 1990s was 0.96 degrees C higher than 30 years earlier. The historical 0-1 degrees C January isotherm, which was considered the approximate northern limit of S. japonicum transmission, has shifted from 33 degrees 15' N to 33 degrees 41' N, expanding the potential transmission area by 41,335 km2. This translates to an additional 20.7 million people at risk of schistosomiasis. Two lakes are located in this new transmission area that form part of the proposed South-North water transfer project. Climate change, coupled with water resource developments in China, may pose additional challenges for the control of schistosomiasis.

Animals↗