Diagnostic efficiency of abattoir meat inspection service in Ethiopia to detect carcasses infected with <Emphasis Type="Italic">Mycobacterium bovis</Emphasis>: Implications for public health

Background  

Bovine Tuberculosis (BTB) is a widespread and endemic disease of cattle in Ethiopia posing a significant threat to public health. Regular surveillance by skin test, bacteriology and molecular methods is not feasible due to lack of resource. Thus, routine abattoir (RA) inspection will continue to play a key role for national surveillance. We evaluated efficiency of RA inspection for diagnosis of Mycobacterium bovis infection and discussed its public health implications in light of a high risk of human exposure.     

A longitudinal analysis of neurocognitive function in unipolar depression

Neurocognitive function is reduced in major depression, but uncertainties remain about if and to what extent improvement in neurocognitive function follows remission of depressive symptoms. A total of 30 patients with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) diagnosis of unipolar major depressive disorder (MDD) at baseline were tested neuropsychologically again, after a mean test-retest interval of 2 years. At retest, patients were partly or completely recovered from depression. Remission of depression was followed by improvement in verbal memory function up to the level of healthy controls, but no associations between improvement in depression and improvement in other dimensions of neurocognitive function were found. Neurocognitive function at baseline was not predictive of improvement in depressive symptoms over time. The present study provided some support for the state hypothesis as to the association between neurocognitive impairment and depression.     

Impairment across executive functions in recurrent major depression

Depression is associated with impairment of cognitive functions, and especially executive functions (EFs). Despite the fact that most depressed patients experience recurrence of episodes, the pattern and the severity of executive impairment have not been well characterized in this group of depressed patients. We asked if and to what extent these patients were impaired on a range of neuropsychological tests measuring EFs, and also when confounding factors were adjusted for. Forty-five patients (aged 19-51 years) with moderate to severe (Hamilton score >18) recurrent major depressive disorder (DSM-IV) were compared to 50 healthy controls matched on age, education, gender and intellectual abilities. The subjects were administered a set of neuropsychological tests that assesses sub-components of EFs. The depressed patients were impaired compared to the control group on all selected tests, with a severity of impairment within -1 standard deviation from the control group mean. The group difference was statistically significant for eight of the 10 EFs that were assessed. These were measures of verbal fluency, inhibition, working memory, set-maintenance and set-shifting. The group difference was still significant for all sub-components except for set-shifting (Wisconsin Card Sorting Test) and planning (Tower of London), when additional medication and retarded psychomotor speed was adjusted for. In conclusion, the depressed subjects were mildly impaired across a wide range of EFs. This may have a negative impact on everyday functioning for this group of patients.     

Cancer of the gastric stump: Analyses of 819 patients and comparison with other stomach cancer patients

The clinical characteriscics and prognosis of 819 patients with cancer in a previously resected stomach are described. The data were obtained from the Cancer Registry of Norway from the period 1970–1979. Median age was 69.2 years (range 31–91), with a male-to-female ratio of 4.4:1. The predominant symptoms were general weakness, abdominal pain, and dyspepsia; the majority of patients had a short duration of symptoms. The median cime interval from the primary operation to cancer diagnosis was 28.7 years. Twenty-one percent of the patients had localized disease; 25%, regional disease; and 39%, distant metastatic disease. In 15% of the patients the stage of the disease could not be ascertained. The resectability rate was 41%, with a postoperative mortality rate of 11%. The overall 5-year survival was 10%, but 40% for patients with localized disease having a resection. Pacients younger than 40 at the primary operation had a 5-year survival of 14% as compared to 7% for those older than 40 (p < 0.001). Pacients younger than 70 at cancer diagnosis had a 5-year survival of 13% as compared to 7% for those older than 70 (p < 0.001). Analyses showed that the apparent poor prognosis for patients with stomach stump cancer relacive to patients with other stomach cancer was due to differences in patient characteristics, and when corrected for these variables, the 2 populations had the same prognosis.

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Resumen Se describen las caracteríscicas clinicas y el pronóstico en 819 pacientes con cáncer en estómagos sometidos a resección previa. Los datos fueron obtenidos del Registro de Cáncer de Noruega para el período 1970–1979. Le edad promedio fue 69.2 años (rango 31–91), con una relación nombre a mujer de 4.4:1. Los síntomas dominantes fueron debilidad general, dolor abdominal y dispepsia, y la mayoría de los pacientes exhibió una evolución corta de su sintomatología. El intervalo promedio entre la operación primaria y el diagnóstico del cáncer fue de 28.7 años. Veintiuno por ciento de los pacientes presentó enfermedad localizada, 25% enfermedad regional y 39% enfermedad metastásica distante. El estadio clínico de la enfermedad no pudo ser establecido en 15% de los casos. La tasa de resección fue de 41%, con una letalidad postoperatoria de 11%. La supervivencia global a 5 años fue de 10%, pero fue de 40% para los pacientes con enfermedad localizada sometidos a resección. Pacientes con edades menores de 40 años en el momento de la operación primaria tuvieron una supervivencia a 5 años de 14% en comparación con 7% para aquellos mayores de 40 (p < 0.001). Pacientes menores de 70 en el momento del diagnóstico de cáncer tuvieron una supervivencia a 5 años de 13%, contra 7% para aquellos mayores de 70 (p < 0.001). El análisis demostró que el aparentemente pobre pronóstico para pacientes con cáncer del muñón gástrico en relación a pacientes con otros tipos de cáncer de estómago se debe a diferencias en las características de los pacientes y que cuando se corrigen tales variables las 2 poblaciones exhiben un pronóstico similar.

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Résumé Les caractéristiques cliniques et le pronostic de 819 cas de cancers du moignon gastrique consignés de 1970 à 1979 dans le Registre Norvégien du Cancer sont décrits par les auteurs. Ces faits concernent des sujets dont la médiane d'âge est de 69.2 ans (31 à 91) avec un rapport entre l'homme et la femme de 4.4:1. Les symptômes révélateurs les plus fréquents sont l'asthénie, la douleur abdominale et la dyspepsie qui se manifestent généralement en peu de temps. Le temps moyen entre la résection gastrique distale et le diagnostic de cancer du moignon gastrique est de 28.7 ans. Vingt et un pour cent des malades présentent des lésions localisées, 25% une atteinte régionale et 39% des métastases à distance. Dans 15% des cas le stade de l'affection ne put être précisé. Le taux de réséctabilité fut de 41% avec une léthalité postopératoire de 11%. La survie globale à 5 ans a été de 10% mais elle a atteint 40% en cas de résection pour lésion limitée. Le taux de survie à 5 ans a été de 14% quand le malade avait subi la gastrectomie avant l'âge de 40 ans. Il a été seulement de 7% quand il était âgé de plus de 70 ans (p < 0.001). Quand le diagnostic de cancer du moignon a été porté chez un malade âgé de moins de 70 ans, le taux de survie a été de 13 ans; il s'est abaissé à 7% quand le malade avait dépassé cet âge (p < 0.001). Les analyses démontrent que le mauvais pronostic apparent de ce type de cancer par rapport à celui du cancer gastrique en général est du aux caractéristiques différentes du malade. Dès lors que ces variables sont corrigées le pronostic est identique.

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Supported by a grant from the Norwegian Society for Fighting Cancer.     

A sub-site-specific analysis of the relationship between colorectal cancer and parity in complete male and female norwegian birth cohorts

Register and census data for complete cohorts of Norwegian men and women born between 1935 and 1969 have been used to examine the relationship between reproductive factors and the incidence of colorectal cancer. Among 1.1 million men and 1.1 million women under observation, 491 male and 859 female cases of colorectal cancer were diagnosed during the period of follow-up. Our hazard model estimates clearly show that in these young cohorts, women with 2 or more children run a lower risk of having a malignant tumor in the cecum or ascending colon than do other women of the same age and in the same birth cohort. No association with parity is found with respect to cancer in the transverse or descending colon, whereas a downward trend in the effect estimates, followed by an upturn, appears for the rectum, sigmoid colon and rectosigmoid junction. Such correlations, which also hold when we control for education and place of residence, are not found for men. The observed relationship between parity and cancer incidence is not likely to be exclusively explained by life-style differentials. Presumably, there is a biological effect of the number of pregnancies and deliveries, net of age at first birth and other reproductive factors, on the development of colorectal cancer.     

Effect of methotrexate on homocysteine and other sulfur compounds in tissues of rats fed a normal or a defined,choline-deficient diet

Summary Methotrexate (MTX) affects homocysteine (Hcy) metabolism in both cultured cells and patients, and this may be explained by a lack of the 5-methyltetrahy-drofolate required for salvage of Hcy to methionine. We here report the effect of MTX on Hcy in serum and Hcy, S-adenosylhomocysteine (AdoHcy), S-adenosylmethionine (AdoMet) and reduced glutathione (GSH) in tissues of rats fed either a normal or a defined, choline-deficient (CD) diet. The CD diet alone did not affect the amounts of Hcy in serum and tissues, but decreased the amount of AdoMet in most tissues and increased the GSH content in the liver. MTX increased the amount of Hcy about 2-fold in serum, liver and kidney, and decreased the amount of AdoMet in liver and kidney, whereas the AdoHcy content in these tissues was essentially unaffected. Accordingly, both choline deficiency and MTX treatment reduced the AdoMet to AdoHcy ratio. The increased GSH in the liver induced by CD diet seemed to be abolished by MTX. In the spleen MTX had only a marginal effect on the Hcy and AdoMet content and decreased the GSH content. It is concluded that the increase in serum Hcy during MTX exposure probably reflects a disturbance of the Hcy metabolism in some tissues, and especially in the liver. Altered metabolism of other sulfur-containing metabolites may only partly be related to the inhibition of Hcy salvage, and some metabolic effects of MTX may be modulated by tissue-specific metabolic pathways as well as by the diet.Supported by grants from the Norwegian Cancer Society and the Norwegian Society for Fighting Cancer     

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines. Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance. This study examines the development of cisplatin and oxaliplatin resistance in H69 human SCLC cells in response to repeated treatment with clinically relevant doses of cisplatin or oxaliplatin for either 4 days or 2 h. Treatments with 200 ng/ml cisplatin or 400 ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and H69OX400, respectively) that showed low level (approximately two-fold) resistance after eight treatments. Treatments with 1,000 ng/ml cisplatin or 2,000 ng/ml oxaliplatin for 2 h also produced sublines, however, these were not stably resistant suggesting shorter treatment pulses of drug may be more effective. Cells survived the first five treatments without any increase in resistance, by arresting their growth for a period and then regrowing. The period of growth arrest was reduced after the sixth treatment and the H69CIS200 and H69OX400 sublines showed a reduced growth arrest in response to cisplatin and oxaliplatin treatment suggesting that ‘regrowth resistance’ initially protected against drug treatment and this was further upregulated and became part of the resistance phenotype of these sublines. Oxaliplatin dose escalation produced more surviving sublines than cisplatin dose escalation but neither set of sublines were associated with increased resistance as determined by 5-day cytotoxicity assays, also suggesting the involvement of regrowth resistance. The resistant sublines showed no change in platinum accumulation or glutathione levels even though the H69OX400 subline was more sensitive to buthionine sulphoximine treatment. The H69CIS200 cells were cross-resistant to oxaliplatin demonstrating that oxaliplatin does not have activity against low level cisplatin resistance. Relative to the H69 cells, the H69CIS200 and H69OX400 sublines were more sensitive to paclitaxel and taxotere suggesting that the taxanes may be useful in the treatment of platinum-resistant SCLC. These novel cellular models of cisplatin and oxaliplatin resistant SCLC will be useful in developing strategies to treat platinum-resistant SCLC.     

Polymorphisms in the cytotoxic T lymphocyte antigen-4 gene region confer susceptibility to Addison's disease

The cytotoxic T lymphocyte antigen-4 (CTLA4) gene on chromosome 2q33 encodes a key regulator in the adaptive immune system. The CTLA4 surface molecule is expressed on activated T lymphocytes and involved in down-regulation of the immune response. Previous studies on a possible association between autoimmune Addison's disease and CTLA4 polymorphisms have shown conflicting results. A recent study identified new candidate polymorphisms in the CTLA4 region, influencing gene splicing and thereby the relative abundance of soluble CTLA4. We genotyped 134 patients with Addison's disease and 413 healthy controls from Norway and United Kingdom for these newly identified polymorphisms. Our data demonstrate that the same polymorphisms that have recently been demonstrated to confer susceptibility to autoimmune thyroid disease and type 1 diabetes also confer susceptibility to Addison's disease. This finding suggests that polymorphisms in CTLA4 confer general risk to develop autoimmunity and identifies a potential therapeutic target in the prevention of autoimmune endocrine disorders.     

Allergenic potential of two orthodontic bonding materials

The sensitization potential of two orthodontic bonding materials, one conventional premix product and one nonmix product, was evaluated by a modified guinea pig maximization test. The nonmix product, consisting of a liquid to be applied to the tooth surface and a paste which was placed on the bracket base, caused reaction in 50% of the tested animals. This material should be considered to be a possible cause of allergy in patients or professionals handling it.