The Brucellae and Their Success as Pathogens

Brucellae are tiny, aerobic, slow growing, catalase and oxidase positive Gram negative coccobacilli or small rods, which may reach man through exposure to tissues of mammalian hosts via cuts or aerosols, or as food infections mostly through dairy products. As parasites brucellae are extraordinarily successful, causing very long-lasting infections in all mammalian social animals, such as ungulates, canids, and rodents; recently they have been found to also cause disease in pinnipeds and cetaceans. Brucellae as members of the alpha Proteobacteria, have suffered major losses of genomic material as they adapted to their facultative intracellular parasite role, and are able to initiate infection with minimal disturbance of the innate immune system, thus reaching a privileged intracellular niche where they multiply. Brucellae are likely to be among the toughest organisms to control through public health and agricultural policies, even involving detection-slaughter strategies.     

Cadherin-catenin adhesion system and mucin expression: a comparison between young and older patients with gastric carcinoma

BACKGROUND: Young patients are thought to develop gastric carcinomas with a molecular genetic profile that is distinct from that of gastric carcinomas occurring at a later age. The aim of this study was to compare the clinicopathological features and expression patterns of the markers E-cadherin and beta-catenin, and mucins (MUC1, MUC2, MUC5AC, and MUC6) in young and older patients. METHODS: The clinicopathological features and overall survival data of 62 young patients (age 40 years). A tissue microarray method and immunohistochemistry were used in order to analyze marker expression in paraffin-embedded tissue blocks obtained from both groups. RESULTS: The young group presented a higher percentage of diffuse-type tumors in comparison to the older group (P<0.01). The rates of positivity for E-cadherin and beta-catenin membranous expression patterns and mucin (MUC2, MUC5AC and MUC6) positivity were higher in the young group (P<0.01). Although young patients showed a lower frequency of alterations in marker expression and had significantly better survival rates than the older patients, neither age nor the marker expression pattern were found to be independent prognostic factors of survival. Only stage, tumor size, and tumor location persisted as prognostic factors for patients with gastric cancer. CONCLUSION: Biological markers of cellular adhesion and gastric differentiation were differently expressed in young and older patients. Our findings support the hypothesis that young patients develop carcinomas with a different genetic pathway compared to the pathway of tumors occurring at a later age, and we suggest further investigations to assess the prognostic relevance of the markers to specific subgroups.     

Residual symptoms in depression: can treatment be symptom-specific?

BACKGROUND: Most patients with depression continue to have symptoms after treatment. It is well documented that these "residual" symptoms are common and are associated with increases in suboptimal long-term outcomes such as relapse and disability. While it is clear that residual symptoms, as a group, contribute to poor outcomes, individual residual symptoms have received relatively little attention. To some extent, this lack of attention reflects an uncertainty in the field about the relationship of the syndrome of depression to the symptoms by which the syndrome is defined. METHOD: Recognizing that for clinicians and patients symptom relief is the goal of treatment, this article reviews the evidence that a symptomatic approach to individual residual symptoms is both feasible and useful. Evidence was gathered through a MEDLINE review of articles published in English from 1966 to 2002. Multiple keywords relating to symptoms, depression, and treatment were used. RESULTS: Many of the agents that psychiatrists use for augmentation of depression treatment, such as psychostimulants and alerting agents, atypical antipsychotics and mood stabilizers, and buspirone and benzodiazepines, have specific symptomatic effects, which raises the question of whether we are augmenting the core antidepressant effect or providing symptomatic relief. Fatigue, anxiety, sexual dysfunction, and sleep disturbances are all symptoms that are commonly leftover after treatment of depression. Some data indicate that treatment of these residual symptoms is efficacious and may affect the long-term outcome of depression. DISCUSSION: This discussion of the treatment of residual depressive symptoms raises a variety of research questions that should be addressed. Also implicit in this discussion are theoretical questions on the relationship between symptoms and syndrome.     

Liver repopulation after cell transplantation in mice treated with retrorsine and carbon tetrachloride

BACKGROUND: Efficiency of engraftment after liver cell transplantation is less than 1% under conventional conditions. Our aim was to develop a high-efficiency, nonsurgical, no-genetic-advantage mouse model of liver repopulation with transplanted cells. METHODS: Mice were conditioned with nonlethal doses of a cell cycle inhibitor, retrorsine, 70 mg/kg, to irreversibly block proliferation of native hepatocytes. After the drug was eliminated, 2 million freshly isolated beta-galactosidase-labeled liver cells were transplanted into the spleens of C57BL/6J recipient mice. To stimulate donor cell proliferation, three doses of carbon tetrachloride (CCl4), 0.5 ml/kg, were given. Several control groups were studied to evaluate the contribution of each treatment to liver repopulation. RESULTS: Repopulation, as measured by cell isolation from recipient livers 1-7 months after transplantation, was on average 20%. Repopulation was 10% if CCl4 was given only once, between 0.5% and 1% if only retrorsine or CCl4 were used, and 0.05% if no conditioning was used. Phenotypically, whole livers turned blue on exposure to X-gal staining, whereas negative (control) livers remained pale brown. More than 55% of liver repopulation resulted from clusters containing 21 or more cells, some of which contained more than 200 cells, suggesting seven or more rounds of cell division in a subset of transplanted cells. CONCLUSION: This murine study demonstrates high levels of repopulation after liver cell transplantation into nongenetically modified livers, using a cell cycle inhibitor and chemical liver injury to provide transplanted cells a proliferative advantage. Liver repopulation was effected mostly by a small fraction of transplanted cells. Analogous nonsurgical liver cell transplantation strategies, but with clinically applicable drugs, could be devised for the treatment of liver-based metabolic diseases.     

Can cure in patients with osteosarcoma be achieved exclusively with chemotherapy and abrogation of surgery?

BACKGROUND: Contemporary therapy for osteosarcoma is comprised of initial treatment with chemotherapy and surgical extirpation of the primary tumor in the affected bone. In view of the major advances forged by chemotherapy in the treatment of the primary tumor, an attempt was made to destroy the tumor exclusively with this therapeutic modality and abrogate surgery. METHODS: Thirty-one consecutive patients were treated. All had localized disease (absence of metastases) at the time of diagnosis. Initial treatment with chemotherapy was comprised of high-dose methotrexate and leucovorin rescue (MTX-LF) in 3 patients and intraarterial cisplatin in 28 patients. Clinical, radiologic, angiographic, radionuclide, and histologic investigations were utilized to assess the efficacy of treatment. After a response at 3 months, entry into the study was permitted and treatment was maintained for a total of 18-21 months with a combination of agents comprised of MTX-LF, intraarterial cisplatin, and doxorubicin. Patients were monitored closely for disease recurrence with the investigations outlined earlier. Two informed consents were required: one at the time of diagnosis and another at 3 months after the initial response had been attained. RESULTS: Only 3 of 31 patients were cured with the administration of chemotherapy alone. Local recurrence and pulmonary metastases were not reported to develop in these 3 patients during a follow-up period of 204+ to 225+ months. Four other patients also possibly were cured with chemotherapy alone. At their request, several months after the cessation of chemotherapy, they underwent surgical extirpation of the tumor. No evidence of viable tumor was found. These patients remained free of disease for 192+ to 216+ months. Thus, only seven patients did not develop local recurrence and/or pulmonary metastases. Among the remaining 24 patients, 9 developed local recurrences without pulmonary metastases 14-74 months (median, 30 months) after the initial response. Eight of the nine patients were rendered tumor free by extirpation of the local recurrence. Two of these eight patients subsequently died, one of the acquired immunodeficiency syndrome (AIDS) and the other of varicella septicemia. The ninth patient refused amputation and died of metabolic complications. Three other patients developed local recurrences 20-69 months and pulmonary metastases 10-98 months after achievement of the initial response. These patients were rendered tumor free by extirpation of the local recurrence and metastasectomy. One of these patients also later died of AIDS. In the remaining 12 patients, local recurrences developed 5-29 months (median, 14 months) after the initial response was achieved. The patients also developed pulmonary metastases 11-60 months after the initial response. In eight patients the local recurrences were extirpated and metastasectomy was performed; however, these patients later died of recurrent pulmonary metastases. The remaining four patients refused to undergo extirpation of the local recurrence. The pulmonary metastases were not resected. They failed to respond to alternate therapy. Thus, the tumor-free survival rate was 23% (7 of 31 patients): 3 patients who were treated with chemotherapy only and 4 patients who were treated with chemotherapy plus surgery. The overall survival rate (patients who remained free of disease and those who underwent resection for local recurrence and metastasectomy) was 48% (15 of 31 patients). Prior to the deaths from AIDS and varicella septicemia, the overall survival was 58% (18 of 31 patients). CONCLUSIONS: Utilizing the regimen employed in the current study, only 3 of 31 patients with osteosarcoma (10%) were cured exclusively with chemotherapy. Four additional patients who underwent extirpation of the primary tumor without disease recurrence and in whom no viable tumor was found in the resected specimens possibly could increase the number of patients who potentially were cured with chemotherapy to 7 (23%). With an overall expected cure rate of 50-65% with "conventional" sin whom no viable tumor was found in the resected specimens possibly could increase the number of patients who potentially were cured with chemotherapy to 7 (23%). With an overall expected cure rate of 50-65% with "conventional" strategies, the results of the current study do not justify the adoption of current forms of chemotherapy as exclusive treatments for osteosarcoma.     

“The Tourist Season Goes Down But Not the Prices.” Tourism and Food Insecurity in Rural Costa Rica

Data from women in two communities in rural Costa Rica were analyzed in order to examine food insecurity in an area undergoing a shift from an agricultural economy to tourism (e.g., eco/adventure tourism). While there were significant differences in socio-economic status between the two communities, the prevalence of food insecurity was high in both, ranging from 67% in the agricultural community to 73% in the tourism community. Not being a member of a food cooperative (OR = 4.85), not having a working stove (OR = 6.27), and increasing body mass index (BMI) (OR = 1.32) predicted food insecurity in both communities. Additionally, the frequency of condiment use was inversely associated with food insecurity (OR = .363). These findings along with other data suggest that food insecurity is a problem in this area. Furthermore, dietary quality associated with food insecurity might be responsible for the high prevalence of obesity among the study participants.     

Disseminated retroperitoneal choriocarcinoma with open fistula to intestine. «Restitutio ad integrum» with chemotherapy alone

We hereby present a clinical case of a germinal tumour with a pulmonary and retroperitoneal dissemination in form of a great adenopathic mass that fistulizes into the duodenum, that obtained a complete resolution with chemotherapy.     

Carcinogenicity of nitrosothiomorpholine and 1-nitrosopiperazine in rats

Summary Two cyclic nitrosamines, nitrosothiomorpholine and 1-nitrosopiperazine, have been tested by long term feeding to rats in drinking water, at 50 mg/l and 200 mg/l. Nitrosothiomorpholine produced tumors, both benign and malignant, of the esophagus and tongue. Nitrosopiperazine appeared to be definitely tumorigenic, although it showed no selectivity of site for tumor induction and induced tumors in a wide range of organs and tissues. Nitrosopiperazine was very much less acutely toxic than dinitrosopiperazine.

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Carcinogene Wirkung von Nitrosothiomorpholine und 1-Nitrosopiperazine bei Ratten

Zusammenfassung Zwei cyclische Nitrosamine, nitroso-thiomorpholine und 1-Nitrosopiperazine, wurden Ratten in Langzeit-Versuchen im Trinkwasser appliziert (50 mg/l bzw. 200 mg/l). Nitroso-thiomorpholine führte zu benignen und malignen Tumoren des Oesophagus und der Zunge. Nitroso-pieerazine zeigte ebenfalls tumorigene Wirkung für eine große Zahl von Organen und Geweben, allerdings keine Organ-Spezifität. Nitroso-piperazine erwies sich als von sehr viel geringerer akuter Toxicität als Dinitroso-piperazin.

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This investigation was supported by Contract # 43-68-959 from the National Cancer Institute, U.S.P.H.S.

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We wish to thank Miss P. Johns, Mrs. J. Stroud for skilled technical assistance.