In vitro leishmanicidal activity of aurones.

A series of aurones with drug-potential for Leishmania infections was identified in vitro using both a direct cytotoxicity assay against extracellular promastigotes of Leishmania donovani, L. infantum, L. enriettii, and L. major, and a test against intracellular amastigote forms of L. donovani residing within murine macrophages. The most active aurone (6-hydroxy-2-[phenylmethylene]-3(2H)-benzofuranone) had an EC50 of 0.45 microgram/ml in the extra-, and an EC50 of 1.40 micrograms/ml in the intracellular assay. Other aurones were active between 0.06-12.50 micrograms/ml and 0.04-7.81 micrograms/ml, respectively. When tested against murine bone marrow-derived macrophages as a mammalian host cell control, the compounds showed only moderate cytotoxicity (EC50 2.32 to > 25.0 micrograms/ml). This is the first report on aurones as a new class of natural products with leishmanicidal activity.     

Ruptured aneurysm of the posterior spinal artery of the conus medullaris.

A case of a posterior spinal artery aneurysm of the conus medullaris is presented. The patient presented with severe lower back pain with radiation into the right leg. Spinal angiography was consistent with a partially thrombosed arteriovenous malformation (AVM) or an aneurysm. At operation a partially thrombosed aneurysm of the posterior spinal artery was found at the level of conus medullaris, which, after review of the literature, is the first case treated with total microsurgical excision.     

Aspirin use and survival after coronary bypass surgery.

From Jan. 1, 1968, through Dec. 31, 1981, 5618 patients in a single cardiovascular surgery practice underwent coronary bypass surgery. Detailed clinical information was obtained during hospitalization and entered into a data base. All surviving patients were surveyed for aspirin use four times: in 1984, 1985, 1986, and 1987. A subgroup of 2395 patients gave consistent answers on every returned survey. The group that answered consistently "yes" had a 5-year survival rate of 79%; those who answered consistently "no" had a 5-year survival rate of 67%. Stepwise logistic regression showed that, after adjusting for patient characteristics, the relative risk of death was 58% (confidence interval 47% to 70%) for consistent aspirin users compared with consistent non-aspirin users. This study provides evidence that regular aspirin use after bypass surgery may enhance survival.     

Evaluation of right ventricular function in patients with idiopathic dilated and ischemic cardiomyopathy by equilibrium radionuclide ventriculography

We performed equilibrium radionuclide ventriculography in 12 patients with idiopathic dilated cardiomyopathy, 11 patients with ischemic cardiomyopathy and 11 normal subjects to determine whether measurements of right ventricular function could be used to distinguish dilated cardiomyopathy from ischemic cardiomyopathy. The left ventricular ejection fraction in patients with dilated cardiomyopathy (26 +/- 8%, mean +/- SD) or ischemic cardiomyopathy (32 +/- 5%) was significantly lower than in normals (69 +/- 6%, p less than 0.001). The right ventricular ejection fraction (RVEF) in normals was 57 +/- 7%. RVEF was decreased in 11 of 12 patients with dilated cardiomyopathy and the mean value (32 +/- 10%) was significantly lower than that in patients with ischemic cardiomyopathy (56 +/- 7%, p less than 0.001), none of whom had decreased RVEF. Our data show that right ventricular dysfunction commonly exists in patients with dilated cardiomyopathy but not in patients with ischemic cardiomyopathy. This finding may be useful in the differentiation between dilated and ischemic cardiomyopathy.     

Pulmonary artery aneurysm in Behcet’s disease: a case report

The pulmonary artery is the second most common site of arterial involvement in Behcets disease. A 32-year-old man presented with bilateral ankle edema, abdominal discomfort, and hemoptysis. He had a history of recurrent oral and genital aphthous ulcerations for 1 year. The diagnosis of Behcets disease was made on the basis of the criteria published by the International Study Group for Behcets Disease. His chest X-ray revealed left hilar enlargement. A helical computed tomography (CT) scan showed a pulmonary aneurysm with intramural thrombosis in the left pulmonary artery and enlarged hepatic veins. Treatment with colchicine and cyclophosphamide was given for 24 months, and helical thoracic CT was performed again. Helical CT showed that the pulmonary aneurysm was reduced by treatment. Helical CT could be used in Behcets disease for the diagnosis and follow-up of pulmonary involvement.     

Establishing a clinic-based pancreatic cancer and periampullary tumour research registry in Quebec

Background

Enrolling patients in studies of pancreatic ductal adenocarcinoma (pdac) is challenging because of the high fatality of the disease. We hypothesized that a prospective clinic-based study with rapid ascertainment would result in high participation rates. Using that strategy, we established the Quebec Pancreas Cancer Study (qpcs) to investigate the genetics and causes of pdac and other periampullary tumours (pats) that are also rare and underrepresented in research studies.

Methods

Patients diagnosed with pdac or pat were introduced to the study at their initial clinical encounter, with a strategy to enrol participants within 2 weeks of diagnosis. Patient self-referrals and referrals of unaffected individuals with an increased risk of pdac were also accepted. Family histories, epidemiologic and clinical data, and biospecimens were collected. Additional relatives were enrolled in families at increased genetic risk.

Results

The first 346 completed referrals led to 306 probands being enrolled, including 190 probands affected with pdac, who represent the population focus of the qpcs. Participation rates were 88.4% for all referrals and 89.2% for pdac referrals. Family history, epidemiologic and clinical data, and biospecimens were ascertained from 91.9%, 54.6%, and 97.5% respectively of patients with pdac. Although demographics and trends in risk factors in our patients were consistent with published statistics for patients with pdac, the qpcs is enriched for families with French-Canadian ancestry (37.4%), a population with recurrent germ-line mutations in hereditary diseases.

Conclusions

Using rapid ascertainment, a pdac and pat research registry with high participation rates can be established. The qpcs is a valuable research resource and its enrichment with patients of French-Canadian ancestry provides a unique opportunity for studies of heredity in these diseases.     

Lumbar pain caused byMycoplasma infection

Summary A 45-year-old woman was admitted to hospital following acute onset of lower back pain. Clinical and laboratory investigations established a lumbar paraspinal soft tissue infection withMycoplasma hominis associated with severe spondylarthrosis at L5/S1. A relationship to a recently performed hysterectomy must be considered.

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Lumbago durch Mykoplasma-infektion

Zusammenfassung Fallbericht. Eine 45-jährige Patientin wurde wegen akuter, belastungsunabhängiger Rückenschmerzen hospitalisiert. Die Abklärung ergab eine paraspondyläre Weichteilinfektion mitMycoplasma hominis auf Höhe L5/S1 rechts bei Spondylarthrose L5/S1. Ein ursächlicher Zusammenhang mit der kurz vorher durchgeführten Hysterektomie muß angenommen werden.

     

Defense mechanism and macroscopic tumor growth in lung tissue

A total of 126 resection specimens from malignant lung tumors were cut into serial sections, and tumor volume and macroscopic growth pattern were computed. Four characteristic tumor growth patterns could be separated: Tumors growing in bizarre, irregular shapes; Tumors growing in spheroid shapes; Tumors growing in ellipsoid shapes; Tumors growing in mixed growth pattern. The immunologic response of the host tissue was analyzed grading the number of lymphocytes, plasma cells, macrophages in and at the boundary of the tumor tissue. Lymphocytic subpopulations were analyzed in 46 cases using monoclonal antibodies (BS3/BS4; T3, OKT4, OKT8, OKT11, OKT14). The majority of lymphocytes were T-lymphocytes and monocytes in cases with inflammatory response of host tissue. The ratio of inducer/helper subset (OKT4+) compared to suppressor/cytotoxic subset (OKT8+) was similar in expression as reported for circulating peripheral T-lymphocytes. The different growth patterns depend upon cell type of tumor, immunologic response of the host tissue, and tumor volume. The findings indicate that tumor progression into lung tissue is partly due to "localized metastatic growth" of different tumor cell subpopulations.     

Development of New Prolactin Analogs Acting as Pure Prolactin Receptor Antagonists

Prolactin (PRL) promotes tumor growth, as recently highlighted by the spontaneous appearance of prostate hyperplasia and mammary neoplasia in PRL transgenic mice. Increasing experimental evidence argues for the involvement of autocrine PRL in this process. Human (h)PRL receptor antagonists have been developed to counteract these undesired proliferative actions of PRL. However, all PRL receptor antagonists obtained to date exhibit partial agonism, limiting their therapeutic use as full antagonists. This is the case for the first generation antagonists (the prototype of which is G129R-hPRL) that we developed ten years ago, which display antagonistic activity in some, but not all in vitro bioassays, and fail to inhibit PRL activity in transgenic mice expressing this analog. We recently developed new human PRL antagonists devoid of agonistic properties, and therefore able to act as pure antagonists. This was demonstrated using several in vitro bioassays, including assays able to detect extremely low levels of receptor activation. These new compounds also act as pure antagonists in vivo, as demonstrated by their ability to competitively inhibit PRL-triggered signaling cascades in various target tissues (liver, mammary gland and prostate). Finally, using transgenic mice specifically expressing PRL in the prostate, which have constitutively activated signaling cascades and prostate hyperplasia, these new PRL analogs are able to completely revert PRL-activated events to basal levels. These second generation antagonists are good candidates to be used as inhibitors of the growth-promoting actions of hPRL.     

An important public health problem: rabies suspected bites and post-exposure prophylaxis in a health district in Turkey.

OBJECTIVE: The aim of this study was to describe rabies suspected animal bites and post-exposure prophylaxis (PEP) practices in Narlidere District in Turkey between 1999 and 2001. METHODS: One thousand five hundred and sixty-nine rabies suspected bite cases reported were identified from the District's rabies surveillance forms. RESULTS: Males comprised 66.7% of the cases, and 43.5% of the total were under 20 years old. In 74% of cases the animal involved in the bite was a dog. Only 70% of the animals had an owner, and only 17% of the animals had a rabies vaccination certificate. In terms of treatment, 68% of the human cases received PEP, and 21% of cases had an extra (sixth) vaccination dose, which is a substantial burden on the healthcare system, costing half a million US dollars per year. The place where the bite occurred (rural areas), the age of the recipient (more than 10 years old), the animal type (animals other than dogs and cats), lack of a vaccination certificate for the animal, and place of wound treatment (hospital) were significantly associated with PEP application. CONCLUSIONS: In addition to the currently recommended strategy of controlling the dog population and of vaccinating domesticated animals, adults and children should be educated about bite prevention to reduce the number of animal bites.