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Biomedical subjects

M Tanner

Publications and source records attributed to M Tanner.

At least 73 records · Page 4Linked to original sources
PubMed2000

The burden of hydrocele on men in Northern Ghana.

The social and economic impact of lymphatic filariasis was studied in Northern Ghana. Qualitative methods of gathering information revealed that even though the disease was a problem to both men and women, men with hydrocele suffered a greater psychosocial burden. Particular attention was paid to them, distinguishing men with small hydroceles and men with large ones. Out of frustration men with small hydroceles sought health care from a wider range of places than men with larger ones. The pain associated with adenolymphangitis (ADL) renders them inactive for up to 5 days. Complications of lymph scrotum and ridicule from community members were a problem. Unmarried men in particular found it difficult to find a spouse with their condition, and various degrees of sexual dysfunction were reported amongst married men. The clinical significance and the value of time and attention for counseling to mitigate the effects of the disease on damaged male identity and the need for gender studies to address male issues and the need for including psychosocial issues in the calculating of disability adjusted life years (DALY's) is also discussed.

Adolescent↗
PubMed2000

MYB oncogene amplification in hereditary BRCA1 breast cancer.

Comparative genomic hybridization analysis has demonstrated that breast tumors from BRCA1 and BRCA2 germ-line mutation carriers contain a large number of chromosomal copy number gains and losses. A high regional copy number gain at 6q22-q24 was observed in one BRCA1 tumor, and fluorescence in situ hybridization analysis indicated a strong amplification of the MYB oncogene (15 copies of MYB compared with 1 copy of chromosome 6 centromere). Fluorescence in situ hybridization analysis revealed amplification of MYB in 5 (29%) of 17 BRCA1 breast tumors, whereas none of 8 BRCA2 tumors and 13 breast cancer cell lines, and only 2 of 100 sporadic breast tumors exhibited altered MYB copy numbers. Gene amplification resulted in mRNA overexpression as determined by Northern blot and cDNA microarray analysis, and protein overexpression by immunohistochemical staining. We conclude that MYB amplification is infrequent in sporadic breast cancer but common in breast tumors from BRCA1 mutation carriers, suggesting a role of this cell cycle regulator and transcription factor in the progression of some BRCA1 tumors. However, we cannot rule out the significance of other genes in the 6q22-q24 amplicon.

Blotting, Northern↗
PubMed2000

Tegumental changes in adult Schistosoma mansoni harboured in mice treated with praziquantel enantiomers.

Praziquantel administered to the host causes damage to the tegument of Schistosoma mansoni. In this study, the effects of racemic praziquantel (Pra) and its enantiomers, levo-praziquantel (L-Pra) and dextro-praziquantel (D-Pra) were compared using scanning electron microscopy (SEM). Mice infected with S. mansoni for 49 days were treated with a single dose of Pra (300 mg/kg), L-Pra (150 mg/kg) or D-Pra (150 or 600 mg/kg). Groups of three mice were killed after 4 and 24 h, and schistosomes collected by perfusion and examined by SEM. Treatment with Pra or L-Pra, for 4 or 24 h, caused tegumental damage to S. mansoni including severe swelling, vacuolization, fusion of the tegumental ridges and loss or shortening of the spines on the tubercles, collapse and peeling. After treatment with D-Pra at 150 mg/kg, no apparent damage was observed. When the dosage was increased to 600 mg/kg, after 4 h lesions on the tegument similar to those induced by Pra or L-Pra were seen, but less severe. After 24 h, there was evidence of recovery. The study thus clearly showed that L-Pra was more active than D-Pra in causing tegumental damage. D-Pra showed a qualitatively similar activity at a higher concentration. It is possible that this effect was due at least to some extent to the small amount of L-Pra (<2%) which was present in the preparation of D-Pra used.

Animals↗
PubMed2000

Measuring exposure to Schistosoma japonicum in China. III. Activity diaries, snail and human infection, transmission ecology and options for control.

We used activity diaries and snail detection to relate water contact and Schistosoma japonicum infection among a cohort of 178 residents on two islands in the Dongting Lake, China. Water exposure to each of 12 mapped water zones around the islands was calculated (m(2) min/day) for each subject. Infected Oncomelania hupensis hupensis snails in this area are focal and were found in only five of the 12 zones, with the highest rate being 5.7%. Thirty-one subjects (17%) were re-infected with a mean intensity of 63.2 epg. Mean water contact was 7.9 m(2) min/day; 98% of water exposure was due to economic activity and only 2% due to swimming or bathing, washing and other necessities of daily life. Males had more exposure and infection than females (P<0.05). Infected subjects had more exposure (10.2 m(2) min/day) than those not infected (7.44 m(2) min/day) (P<0.05). Compared with uninfected subjects, those infected had 2.9 times more exposure in infected-snail zones (P<0.01). Also, human infection intensity (epg) correlated well with exposure to infected snail zones (r=0.552, P<0.01). People <20 years old had the highest re-infection (21.4%) and intensity (3.77 epg). Median exposure for 20-49-year-olds (9.00 m(2) min/day) was nearly double that of those aged <20 or >50 years old (5.5 m(2) min/day). We conclude that map-referenced water contact and snail evaluation boosts accuracy of activity-diary measurements in large transmission foci for the Asian schistosome. Protecting against faecal contamination of snail inhabited sites, and against occupational exposure for island residents, should be a priority of future research. Potential strategies for migrating buffaloes and families living on visiting fishing boats are explored.

Adult↗
PubMed2000

Tegumental changes in 21-day-old Schistosoma mansoni harboured in mice treated with artemether.

Alterations in the tegument of 21-day-old Schistosoma mansoni, caused by artemether administered to the infected mice, were studied using scanning electron microscopy (SEM). Mice were infected with S. mansoni cercariae, and after 21 days a single dose of artemether (400 mg/kg) was administered intragastrically. After 24, 72 h and 7 days groups of three mice were killed and the schistosomules collected by perfusion, fixed and processed routinely, and examined by SEM. After 24 h, all male and female worms examined showed alterations in the tegument, characterised by swelling, vesiculation and fusion of tegumental ridges; peeling, erosion and collapse of damaged tegumental surface, and also destruction of the oral sucker and acetabulum. After 72 h, severe damage to the tegument was seen, usually including extensive peeling, swelling and vesiculation, and host leukocytes were adhered to the damaged surface. Some worms were surrounded by clusters of host leukocytes or had even disintegrated. Seven days after treatment, some schistosomules still showed severe tegumental damage, but in some cases the damage was less than at earlier times, which suggested that those schistosomules that had survived were beginning to recover. The ability of artemether to cause severe damage to the tegument correlates with its high efficacy in killing 21-day-old schistosomules.

Administration, Oral↗
PubMed2000

Oral artemether for prevention of Schistosoma mansoni infection: randomised controlled trial.

BACKGROUND: Chemotherapy with praziquantel is the current strategy of choice to control schistosomiasis. However, in view of concern about praziquantel tolerance or resistance, new drugs are needed. Artemether, a derivative of the antimalarial drug artemisinin, kills immature schistosomes of Schistosoma japonicum, and reduces the incidence of infection in field trials. Laboratory studies have also showed activity by this drug against S. mansoni. We report a randomised double-blind placebo-controlled clinical trial of artemether to prevent S. mansoni infection. METHODS: The trial was done in an area of western Côte d'Ivoire endemic for S. mansoni. 354 schoolchildren were enrolled. Stool specimens were screened over four consecutive days, followed by two mass treatments with praziquantel 4 weeks apart. All S. mansoni negative children were randomly assigned to placebo (n=151) or artemether 6 mg/kg (n=138) orally six times once every 3 weeks. Adverse events were assessed 24 h after treatment. Perceived illness episodes were recorded once a week by interviewing the children with a standardised questionnaire. 3 weeks after the final medication S. mansoni infections were assessed by screening stool samples. Blood samples were examined for Plasmodium falciparum before the first and after the last artemether treatment. FINDINGS: Oral artemether showed no adverse reactions. The group that received artemether had a significantly lower incidence of S. mansoni infection (31/128 versus 68/140, relative risk: 0.50 [95% CI 0.35-0.71], p=0.00006). The geometric mean egg output among positive children in the artemether group was significantly lower than in placebo recipients (19 vs 32 eggs/g stool, p=0.017). There was also a significant reduction in the prevalence of P. falciparum. INTERPRETATION: Oral artemether is safe and shows a prophylatic effect against S. mansoni. The use of artemether may be recommended in appropriated situations as an additional tool for more effective schistosomiasis control measures. However the application needs to be carefully assessed especially in view of the concern that it could select for resistant plasmodia.

Administration, Oral↗
PubMed2000

Heritability of gastrointestinal nematode faecal egg counts in West African village N'Dama cattle and its relation to age.

Offspring-dam regression was used to estimate the heritability of strongyle faecal egg counts (FEC) of traditionally raised West African N'Dama cattle in the Central River Division in The Gambia. Faecal samples were taken monthly from June-October 1992, and again from July-October 1993, including 179-463 dams and their calves sampled on each occasion. The only proven genetic relationship was the dam-offspring relationship. Gastrointestinal strongyle FEC was expressed as epg (eggs per gram faeces). Regression of offspring FEC on dam FEC, showed a heritability (h(2)) of 0.18 (95% Confidence Limits 0.10, 0.25). Heritabilities were higher at the beginning and end of the rainy season than during the months of the peak rainy season. This is in line with earlier suggestions that genetic control of faecal egg counts is most effective during periods of low parasite transmission. There was a significant (p<0.001) increase in heritability of 0.086+/-0.018 with each year of age of the corresponding offspring. In view of the virtual absence of national cattle breeding systems in West Africa, which are a precondition for exploitation of heritable traits in cattle, integrated control using improved management and strategic prophylaxis remain the methods of choice to control gastrointestinal nematodes in the given conditions.

Africa, Western↗
PubMed2000

Sequence diversity of the merozoite surface protein 1 of Plasmodium falciparum in clinical isolates from the Kilombero District, Tanzania.

Merozoite surface protein 1 of Plasmodium falciparum (PfMSP-1) is regarded as a key candidate antigen for malaria vaccine development. It exhibits significant antigenic polymorphism and has been divided into 17 building blocks based on the analysis of sequence diversity. Differences in the antigenic composition of PfMSP-1 in local P. falciparum populations may result in differences in the efficacy of vaccines, which contain sequences of particular allelic variant(s) of PfMSP-1. To contribute to the required knowledge of genetic diversity of malaria parasites in geographically diverse regions, we have used the polymerase chain reaction (PCR) to analyze the sequence diversity of blocks 1-4 of PfMSP-1 in disease isolates from the Kilombero District in Tanzania. In the semi-conserved block 1, in which dimorphic amino acid variances have been described at three positions, we found three of the five previously described combinations of these three pairs of amino acids. In addition one combination was found, which has not been reported before in parasite isolates from different locations worldwide. Of the two sequence variants, which were dominating, one (S44-Q47-V52) corresponded to the 83.1 sequence incorporated into the SPf66 malaria peptide vaccine, while the other one (G44-H47-I52) differed from the previous in all three dimorphic amino acids. The partial protection observed in a phase III SPf66 trial conducted in the Kilombero District in children aged 1-5, thus does not seem to be associated with a clear dominance of favourable variants of block 1 of PfMSP-1 in this area. All three different principle types of block 2, the major polymorphic region of PfMSP-1, were found in the Tanzanian isolates. Most of the sequences contained K1-type tripeptide repeats, but clones with MAD20-type repeats or no repetitive sequence (RO33-type block 2) were also present. K1- and MAD20-type tripeptide repeat motifs were never mixed within one parasite clone. In one sequence a hexapeptide repeat was found at the end of block 2, which has not been reported before. Dimorphism in 13 of the 17 previously described variable positions of the semi-conserved block 3 and three of four recombination types of block 4 (K/K, M/K and M/M) were found among the Tanzanian isolates. Apart from previously described dimorphic amino acid positions, polymorphism was rare in the non-repeated building blocks. Selection and spreading of parasite variants, which contain amino acid exchanges at other than the dimorphic positions thus, is not a common event. Parasite isolates frequently harboured more than one PfMSP-1 allele. Three of the four heterogeneous isolates analysed contained two different general types of sequences. One isolate contained at least four distinct clones, demonstrating the high endemicity of malaria in the Kilombero District, which is a well-established site for malaria vaccine field trials.

Amino Acid Sequence↗
PubMed2000

Chromogenic in situ hybridization: a practical alternative for fluorescence in situ hybridization to detect HER-2/neu oncogene amplification in archival breast cancer samples.

Determination of HER-2/neu oncogene amplification has become necessary for selection of breast cancer patients for trastuzumab (Herceptin) therapy. Fluorescence in situ hybridization (FISH) is currently regarded as a gold standard method for detecting HER-2/neu amplification, but it is not very practical for routine histopathological laboratories. We evaluated a new modification of in situ hybridization, the chromogenic in situ hybridization (CISH), which enables detection of HER-2/neu gene copies with conventional peroxidase reaction. Archival formalin-fixed paraffin-embedded tumor tissue sections were pretreated (by heating in a microwave oven and using enzyme digestion) and hybridized with a digoxigenin-labeled DNA probe. The probe was detected with anti-digoxigenin fluorescein, anti-fluorescein peroxidase, and diaminobenzidine. Gene copies visualized by CISH could be easily distinguished with a x40 objective in hematoxylin-stained tissue sections. HER-2/neu amplification typically appeared as large peroxidase-positive intranuclear gene copy clusters. CISH and FISH (according to Vysis, made from frozen pulverized tumor samples) correlated well in a series of 157 breast cancers (kappa coefficient, 0.81). The few different classifications were mostly because of low-level amplifications by FISH that were negative by CISH and immunohistochemistry with monoclonal antibody CB-11. We conclude that CISH, using conventional bright-field microscopy in evaluation, is a useful alternative for determination of HER-2/neu amplification in paraffin-embedded tumor samples, especially for confirming the immunohistochemical staining results.

Archives↗
PubMed2000

Amplification and deletion of topoisomerase IIalpha associate with ErbB-2 amplification and affect sensitivity to topoisomerase II inhibitor doxorubicin in breast cancer.

Topoisomerase IIalpha (topoIIalpha) is a key enzyme in DNA replication and a molecular target for many anti-cancer drugs called topoII inhibitors. The topoIIalpha gene is located at chromosome band 17q12-q21, close to the ErbB-2 oncogene (HER-2/neu), which is the most commonly amplified oncogene in breast cancer. Because of the physical proximity to ErbB-2, copy number aberrations may also occur in the topoIIalpha gene. These topoIIalpha gene copy number aberrations may be related to the altered chemosensitivity to topoII inhibitors that breast cancers with ErbB-2 amplification are known to have. We used fluorescence in situ hybridization to study copy number aberrations of both topoIIalpha and ErbB-2 in nine breast cancer cell lines and in 97 clinical breast tumors, which were selected for the study according to their ErbB-2 status by Southern blotting. TopoIIalpha-protein expression was studied with Western blot and sensitivity to doxorubicin (a topoII inhibitor) with a 96-well clonogenic in vitro assay. Two of the five cell lines with ErbB-2 gene amplification (SK-BR-3 and UACC-812) showed amplification of topoIIalpha. In MDA-361 cells, ErbB-2 amplification (14 copies/cell) was associated with a physical deletion of topoIIalpha (four copies of chromosome 17 centromere and two copies of topoIIalpha). The topoIIalpha amplification in UACC-812 cells was associated with 5.9-fold-increased topoIIalpha protein expression and 2.5-fold-increased sensitivity to the topoII inhibitor, doxorubicin, whereas the deletion in MDA-361 leads to decreased protein expression (45% of control) and a 2.4-fold-increased chemoresistance in vitro. Of 57 ErbB-2-amplified primary breast carcinomas, 25 (44%) showed ErbB-2-topoIIalpha coamplification and 24 (42%) showed a physical deletion of the topoIIalpha gene. No topoIIalpha copy number aberrations were found in 40 primary tumors without ErbB-2 amplification. TopoIIalpha gene amplification and deletion are common in ErbB-2-amplified breast cancer and are associated with increased or decreased sensitivity to topoII inhibitors in vitro, respectively. These findings may explain the altered chemosensitivity to topoII inhibitors reported in ErbB-2-amplified breast cancers.

Antigens, Neoplasm↗
PubMed2000

Effect of artemether against Schistosoma haematobium in experimentally infected hamsters.

The drug, artemether, has been shown to be active against the juvenile stages of Schistosoma japonicum and Schistosoma mansoni in experimentally infected animals, while it is less effective on adult worms. These findings have been confirmed in randomised controlled trials in humans. Consequently, it could be expected that artemether is also active against Schistosoma haematobium. We present here the first results from experiments assessing the effect of artemether on S. haematobium. Hamsters with a single infection received intra-gastrically an initial dose of 300 mg/kg artemether on day 14, 21 or 28, followed by further doses at varying treatment regimens. In all the treatment groups, the total and female worm reduction rates were highly significant, and ranged from 78 to 100% in hamsters harbouring juvenile schistosomes. Hamsters infected three times with S. haematobium, on days 0, 4 and 9, and repeatedly treated with artemether at the same dose as above, showed highly significant total and female worm reduction rates of between 94 and 99%. Artemether was also active against 77-day-old adult S. haematobium, since its administration on two consecutive days resulted in highly significant total and female worm reduction rates of 76-89%. Our findings confirm that artemether is also active against S. haematobium, especially the schistosomules. These results provide a basis for clinical trials in humans, for further assessment of the potential of artemether for schistosomiasis control.

Animals↗
PubMed2000

Epidemiology of Schistosoma japonicum in China: morbidity and strategies for control in the Dongting Lake region.

Dongting Lake, covering a very large surface water area of 2691km(2), is located in Hunan Province in the southern part of the People's Republic of China. It is the second-largest freshwater lake in China and plays an important role in regulating the amount of water in the Yangtze River, China's longest river. The annual water level of the lake changes by as much as 15m, rising in summer and falling in winter. Asian schistosomiasis has been endemic in the Dongting Lake region for centuries and it has had a devastating effect on the public health of the local people. After a difficult struggle for more than four decades, a concerted programme, supported by the World Bank Loan and instigated in 1992, has resulted in remarkable progress in the control of the disease in many endemic areas of the region. However, the great challenge remains to consolidate and maintain the achievements made to date. The Schistosoma japonicum intermediate host (Oncomelania hupensis hupensis) snail habitats are huge, estimated at 1768km(2) in 1996; these are increasing at a rate of 34.7km(2) annually due to high silt deposition from the Yangtze River itself and from the connecting rivers in Hunan province, and construction of embankments in the Dongting Lake region. It is anticipated that the construction of the Three Gorges Super Dam, the largest engineering project ever undertaken, will substantially extend the range of the snail habitats and increase the number of new schistosomiasis cases. In many areas, human re-infections with S. japonicum after drug (praziquantel) treatment remain unacceptably high (up to 20% of those treated are re-infected annually) due to occupational (mainly fishing) water contact. This paper reviews the history and the current status of schistosomiasis control in the lake region, it explores the epidemiological factors which influence the prevalence of the infection and the disease it causes, and it provides insight into future approaches to control which might finally eradicate the infection.

Animals↗
PubMed2000

The prophylactic effects of artemether against Schistosoma japonicum infections.

The fight against schistosomiasis in China has been very effective in reducing the number of infections across the country. However, the drug of choice, praziquantel, has no prophylactic effect, which reduces its efficacy in high transmission areas. This situation has prompted efforts to find prophylactic compounds, the most promising of which is the drug artemether. In this article, Xiao Shuhua, Mark Booth and Marcel Tanner review the results of laboratory tests and field trials of artemether against schistosomiasis in China.

Animals↗
PubMed2000

Preventive effect of artemether in experimental animals infected with Schistosoma mansoni.

The effect of artemether, an antimalarial drug developed from the plant Artemisia annua, has been tested against the larval stages of Schistosoma mansoni covering the time from skin penetration to the early adult liver-stage. The results show that the experimental animals used (hamster and mice) do not develop schistosomiasis mansoni if treated with artemether during the first month after infection. The parasite was found to be especially susceptible between the 3rd and 4th week after infection, resulting in worm reductions of 75.3-82.0% compared to non-treated controls. This level was boosted to 97.2-100% when the animals were subjected to various schedules of repeated treatment. Almost complete protection was also reached in parallel experiments with repeated infections carried out to mirror more closely the real situation of trickle infection.

Animals↗
PubMed2000

Effect of praziquantel together with artemether on Schistosoma japonicum parasites of different ages in rabbits.

The efficacy of combined treatment with praziquantel and artemether against infection with Schistosoma japonicum was tested on infected rabbits, in which 7-to 14-day-old schistosomules and 42-day-old adult schistosomes were simultaneously present. Rabbits were treated orally with praziquantel and artemether using various dosages and schedules. The therapeutic effects were evaluated by estimating the mean total worm burden (TWB) and female worm burden (FWB) and comparing them with the worm burdens in control animals treated with praziquantel or artemether alone. When the rabbits received praziquantel in a single dose (50 mg/kg), or daily for 2-6 days (30-60 mg/kg), the TWB was reduced by 28-66% and the FWB by 26-65%. In rabbits treated with artemether the reductions were 44-56% and 35-54%, respectively. Treatment with praziquantel in combination with artemether resulted in a significantly greater reduction of worm burden than was found for the groups treated with praziquantel or artemether alone, using the same dosages and schedules. TWB was reduced by 79-92%, and FWB by 80-93%. The results demonstrated that when rabbits infected simultaneously with schistosomules and adult schistosomes were treated with praziquantel in combination with artemether, the effects of the individual drugs could be increased significantly.

Age Factors↗
PubMed2000

The 1992-1999 World Bank Schistosomiasis Research Initiative in China: outcome and perspectives.

Ongoing efforts over the last 50 years, aiming at the elimination of schistosomiasis in the People's Republic of China, have been spectaculary successful in reducing the prevalence and intensity of the infection. The endemic areas have been reduced to core regions with particular problems such as the middle and lower reaches of the Changjiang River (Yangtze), the land adjacent to the lakes of central China and certain mountainous areas in Sichuan and Yunnan. An effort to eradicate schistosomiasis as a public health problem in these areas, by means of mass chemotherapy in regions of high prevalence and selective chemotherapy in others, provided good results initially but a lasting effect proved unattainable with chemotherapy alone. A small part of the funds available for this effort were used for research and training. Overseen by a Joint Research Management Committee (JRMC), research training was intensified resulting in improved applications and a better quality of the scientific level of the research finally carried out. Several new control tools were produced which may improve future control approaches, which might achieve a more than temporary relief. In evaluating the contributions made, it was found that the great environmental variations between the eight provinces where control activities were implemented was the main reason why general use of chemotherapy only could not be entirely successful. The inclusion of a research component proved beneficial both for the short- and long-term control and the JRMC proved useful in exposing that sustained progress cannot be achieved without back-up by other approaches, e.g. snail control. Suggested future activities include strengthening of intersectoral and industrial collaboration but finding financial support for continuing the JRMC initiative in some form. It is crucial to consolidate progress made.

Animals↗