Combination of intravenous S-ketamine and oral tranylcypromine in treatment-resistant depression: A report of two cases.

Ketamine, a rapid-acting antidepressant and anti-suicidal agent, is thought to increase brain monoamine levels by enhancing monoamine release or inhibiting presynaptic monoamine-reuptake. Here we present two female inpatients suffering from treatment-resistant depression with recurrent severe suicidal crises receiving a combination of intravenous S-ketamine and oral tranylcypromine, which is a well-known irreversible monoamine oxidase (MAO) inhibitor. Since inhibition of monoamine-reuptake with concurrent blockade of MAO might trigger sympathomimetic crisis, this combination is considered hazardous. Nonetheless, cardiovascular parameters remained stable in both patients, while good anti-suicidal effects were observed. Hence, we put serious doubt on whether monoamine-reuptake inhibition is a relevant pharmacological effect of ketamine in humans.

Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes.

With the objective of discovering novel putative intervention sites for anticancer therapy, we compared transcriptional profiles of breast cancer, lung squamous cell cancer (LSCC), lung adenocarcinoma (LAC), and renal cell cancer (RCC). Each of these tumor types still needs improvement in medical treatment. Our intention was to search for genes not only highly expressed in the majority of patient samples but which also exhibit very low or even absence of expression in a comprehensive panel of 16 critical (vital) normal tissues. To achieve this goal, we combined two powerful technologies, PCR-based cDNA subtraction and cDNA microarrays. Seven subtractive libraries consisting of approximately 9250 clones were established and enriched for tumor-specific transcripts. These clones, together with approximately 1750 additional tumor-relevant genes, were used for cDNA microarray preparation. Hybridizations were performed using a pool of 16 critical normal tissues as a reference in all experiments. In total, we analyzed 20 samples of breast cancer, 11 of LSCC, 11 of LAC, and 8 of RCC. To select for genes with low or even no expression in normal tissues, expression profiles of 22 different normal tissues were additionally analyzed. Importantly, this tissue-wide expression profiling allowed us to eliminate genes, which exhibit also high expression in normal tissues. Similarly, expression signatures of genes, which are derived from infiltrating cells of the immune system, were eliminated as well. Cluster analysis resulted in the identification of 527 expressed sequence tags specifically up-regulated in these tumors. Gene-wise hierarchical clustering of these clones clearly separated the different tumor types with RCC exhibiting the most homogeneous and LAC the most diverse expression profile. In addition to already known tumor-associated genes, the majority of identified genes have not yet been brought into context with tumorigenesis such as genes involved in bone matrix mineralization (OSN, OPN, and OSF-2) in lung, breast, and kidney cancer or genes controlling Ca(2+) homeostasis (RCN1,CALCA, S100 protein family). EGLN3, which recently has been shown to be involved in regulation of hypoxia-inducible factor, was found to be highly up-regulated in all RCCs and in half of the LSCCs analyzed. Furthermore, 42 genes, the expression level of which correlated with the overall survival of breast cancer patients, were identified. The gene dendogram clearly separates two groups of genes, those up-regulated such as cyclin B1, TGF-beta 3, B-Myb, Erg2, VCAM-1, and CD44 and those down-regulated such as MIG-6, Esp15, and CAK in patients with short survival time.

Hormone replacement therapy with tibolone: effects on sexual functioning in postmenopausal women.

OBJECTIVE: Because hormonal changes in postmenopausal women may be accompanied by sexual problems and a worsening of various aspects of libido, the aim of this study was to assess the effect of tibolone (Liviel(R)) on sexual life. METHODS: Postmenopausal first-time users of hormone replacement therapy (HRT) were included in this open, multicenter study. Patients were treated with tibolone 2.5 mg daily for at least 4 months. Both at baseline and after 4 months of treatment, patients were asked to complete two different questionnaires rating the women's subjective assessment of their sexual problems or desires. RESULTS: One hundred and eighty-four women were enrolled to receive HRT with tibolone. Overall, a significant increase in women's satisfaction with their sexual lives and a significant improvement in different aspects of libido was found. CONCLUSION: Tibolone has beneficial effects on several aspects of sexual life in postmenopausal women. These effects may be due to both an increase in genital blood flow and the central estrogenic/androgenic activity.