Giant mediastinal liposarcoma: a case report.

Liposarcomas are extremely rare in the mediastinum. They may achieve considerable size before causing any symptoms. Mediastinal liposarcomas may invade surrounding structures like the pericardium or the superior vena cava. Complete surgical excision is the optimal treatment in resectable cases. Excision of adjacent structures like the pericardium may be needed if the tumor infiltrates them. We report on a case of a giant liposarcoma of the mediastinum involving both hemithoraces and extending into the neck, which was successfully managed by complete surgical excision.     

Is Coronary Graft Doppler More Sensitive for Indiviual Graft Flows Than TEE During CABG Surgery?

Abstract    In this case report we describe a situation where despite a normal TEE exam immediately postcardiopulmonary bypass, there was no flow in the left internal mammary artery graft to the left anterior descending artery. This was picked up by coronary Doppler and subsequently repaired.     

Establishment and characterization of an in vitro model of acquired resistance to cisplatin in a human testicular nonseminomatous germ cell line.

Clinically, human testicular nonseminomatous germ cell tumors exhibit remarkable sensitivity to platinum-based chemotherapy. To define better the mechanistic basis for this unusual sensitivity, the biochemical determinants of platinum-induced cytotoxicity have been investigated in a human testicular tumor cell line (GCT27) established from a previously untreated patient and in an in vitro derived 5.6-fold cisplatin-resistant stable variant (GCT27cisR). Compared to 12 ovarian and 5 cervical human tumor cell lines, the parent GCT27 line was among the most sensitive to the cytotoxic effects of both cisplatin (dosage producing 50% inhibition, 0.2 microM) and carboplatin (dosage producing 50% inhibition, 2.9 microM), thus reflecting clinical data. A 4-day exposure sulforhodamine B-staining assay was used to determine that GCT27cisR was cross-resistant to carboplatin and iproplatin and the classical bifunctional alkylating agents melphalan and chlorambucil. Partial cross-resistance was observed to tetraplatin, methotrexate, and mitomycin C. No cross-resistance was observed to Adriamycin, etoposide, vinblastine, bleomycin, 1-beta-D-arabinofuranosylcytosine, and 5-fluorouracil. Intracellular cisplatin accumulation across the dose range 2.5-100 microM (for 2 h) was 1.6 +/- 0.39-fold (mean +/- SD) greater for the parent line. There was no significant difference in glutathione levels between the two lines. The acquired resistance line was 1.9-fold more resistant than the parent line to the cytotoxic effects of cadmium chloride. There was no significant difference between the two lines, however, in the total amounts of platinum bound to DNA after cisplatin exposure (25, 50, or 100 microM for 2 h). The removal of total platinum adducts from DNA was significantly faster for GCT27cisR compared to the parent line (half-times of removal, 32 and 67 h, respectively). These data suggest that the abnormal sensitivity of the parent testicular tumor cell line to platinum-containing anticancer drugs may be due predominantly to an inherent defect in the ability of these cells to remove platinum from their DNA. This defect is apparently lost in the acquired resistance counterpart. Reduced intracellular accumulation and increased cytoplasmic concentrations of metallothionein may also contribute, in part, to the acquisition of cisplatin resistance in this model.     

Postoperative cerebellar herniation in a large intrapetrous aneurysmal bone cyst.

An 18-year old boy presented with a tumour involving a large part of the petrous bone. A radical resection of a petrous bone 'aneurysmal bone cyst' was achieved. A large defect in the dura adjoining the posterior surface of the petrous bone was made during surgery. Post-operative MR imaging showed complete tumour resection but herniation of cerebellum into the operative defect, a phenomenon probably assisting to seal the site of cerebrospinal fluid fistula.     

Specificity of antibodies to immunodominant mycobacterial antigens in pulmonary tuberculosis.

A serological survey was performed in groups of patients with active sputum smear-positive or smear-negative pulmonary tuberculosis, healthy household contacts, and controls. Sera were tested for titers of antibodies which bound to each of five purified mycobacterial antigens by enzyme immunoassay and for competition of binding to single epitopes, using six radiolabeled monoclonal antibodies directed toward corresponding molecules. The evaluation of diagnostic specificity was based on a positive score represented by titers above the cutoff point of 2 standard deviations above the mean titer of a control group. For smear-positive samples, the best sensitivity (83%) was achieved by exclusive use of the 38-kilodalton (kDa) antigen or its corresponding monoclonal antibodies. For smear-negative samples, levels of antibodies binding to the 19-kDa antigen showed a lower sensitivity of 62% compared with the control group or 38% compared with the contact group. Titers of antibody binding to the 14-kDa antigen were raised in Mycobacterium bovis BCG-vaccinated contacts, indicating that the greatest potential of this antigen may be in the detection of infection in a population for which tuberculin testing is unreliable. The results demonstrated the differing antibody responses to each of the tested antigens and distinct associations with the stage of infection or disease.     

Skeletal muscle sodium channel gating in mice deficient in myotonic dystrophy protein kinase

Myotonic dystrophy, a progressive autosomal dominant disorder, is associated with an expansion of a CTG repeat tract located in the 3'-untranslated region of a serine/threonine protein kinase, DMPK. DMPK modulates skeletal muscle Na channels in vitro, and thus we hypothesized that mice deficient in DMPK would have altered muscle Na channel gating. We measured macroscopic and single channel Na currents from cell-attached patches of skeletal myocytes from mice heterozygous (DMPK(+/-)) and homozygous (DMPK(-/-)) for DMPK loss. In DMPK(-/-) myocytes, Na current amplitude was reduced because of reduced channel number. Single channel recordings revealed Na channel reopenings, similar to the gating abnormality of human myotonic muscular dystrophy (DM), which resulted in a plateau of Na current. The gating abnormality deteriorated with increasing age. In DMPK(+/-) muscle there was reduced Na current amplitude and increased Na channel reopenings identical to those in DMPK(-/-) muscle. Thus, these mouse models of complete and partial DMPK deficiency reproduce the Na channel abnormality of the human disease, providing direct evidence that DMPK deficiency underlies the Na channel abnormality in DM.     

Analysis of the symptoms of depression--a neural network approach

The purpose of this study is to determine the individual contribution, or importance number, of the symptoms to an analysis of depression, utilizing a neural network model. In addition, the presence of hopelessness and somatic complaints was examined, to determine their relevance to depression. Using Wave 1 data from Duke University's contribution in the Epidemiological Catchment Area (ECA) study, we created a mathematical model, a neural network, to map the relationship of nine symptoms of major depression, hopelessness and somatic complaints to the presence or absence of the formal diagnosis of depression, and performed a contribution analysis. The contribution analysis using the neural network revealed that the symptoms with the greatest impact on the occurrence of depression, or with the largest importance number for depression, were sadness, loss of interest, tiredness and sleeping trouble, in that order. The most frequently reported symptoms, though, were sadness, sleeping trouble, suicidal ideation, tiredness and poor concentration, in that order. Hopelessness and somatic symptoms were the lowest in their contribution to the diagnosis of depression. The study thus provides the hierarchy of the symptoms of depression and supports the DSM classification of major depression.     

Spontaneous rupture of the liver upon revascularization during transplantation

Spontaneous rupture of the liver has been described in association with many benign and malignant conditions. We report, to our knowledge, the first case of spontaneous rupture of the liver upon revascularization, requiring total hepatectomy and portocaval shunt, followed by successful retransplantation. Routine pathological examination of the explanted liver failed to reveal the etiology of the rupture. However, electron microscopy demonstrated abnormal collagen in the hepatic arterial wall compatible with a collagen disorder such as Ehlers-Danlos type IV disease. We conclude that the donor liver had a previously undiagnosed collagen disorder. Review of the literature does not preclude the use of livers from donors with a history of connective tissue disorders. Based on our experience one should exercise caution when using livers from such donors. With a history of connective tissue disorder in an immediate family member, further tests should be performed in the donor to rule out a subclinical connective tissue disorder. In addition, a review of all patients reported thus far to have undergone total hepatectomy and portocaval shunt, followed by liver transplantation as a two-stage procedure is presented.     

Phase I and pharmacologic study of the human DNA methyltransferase antisense oligodeoxynucleotide MG98 given as a 21-day continuous infusion every 4 weeks

Purpose: MG98 is a second generation phosphorothioate antisense oligodeoxynucleotide which is a highly specific inhibitor of translation of the mRNA for human DNA MeTase I (DNMT 1). This phase I study examined the toxicity and pharmacologic profile of MG98 administered as a continuous 21-day intravenous infusion every 4 weeks. Patients and methods: Fourteen patients with solid cancers received a total of 25 cycles of MG98 at doses ranging from 40 to 240 mg/m²/day. Steady-state concentrations of MG98 were measured as were several pharmacodynamic assessments including mRNA of the target gene, DNMT1, in PBMC. In addition, other potential surrogate markers of drug effects were explored, including hemoglobin F, Vimentin and GADD45. Results: Dose limiting effects were drug-related reversible transaminase elevation and fatigue seen at doses of 240, 200 and 160 mg/m²/day. The dose level of 80 mg/m²/day was felt to be safe and tolerable when delivered on this schedule. No evidence of antitumor activity was observed. Although pharmacokinetic analysis revealed that at the higher dose levels, mean Css values of MG98 were approximately 10-fold times the IC₅₀ values associated with target inhibition in vitro, the extent of MG98 penetration into target tumors in this trial was not determined. No consistent, dose-related changes in correlative markers including DNMT1 mRNA, hemoglobin F, Vimentin and GADD45, were observed. Conclusions: This schedule of MG98 given as a 21-day continuous intravenous infusion every 4 weeks was poorly tolerated in the highest doses; therefore, further disease-site specific evaluation of the efficacy of this agent will utilize a more favorable, intermittent dosing schedule. Pharmacodynamic evaluations undertaken in an attempt to explore and validate the biological mechanisms of MG98 did not show dose-related effects.