Medication Outcome in ECT-Resistant Depression

The outcome of antidepressant treatment in 12 cases of electroconvulsive therapy (ECT)-resistant depression is presented. Eight patients had been refractory to a clinically adequate course of ECT (Hamilton Depression Scale improvement <20%) and four were partial responders (improvement 20-49%). All remitted completely on antidepressant medication within 2.2 +/- 1.1 (mean +/- SD) months of the ECT course. Remission was associated with clomipramine treatment (139 +/- 49.7 mg/day) in seven cases and maprotiline (125 mg/day) in one case. Four patients who did not respond to a tricyclic antidepressant alone remitted following supplementation (of clomipramine in 2 cases, clomipramine + haloperidol in 1 case, and imipramine in 1 case) with lithium carbonate. Although a delayed therapeutic response to ECT cannot be excluded, the results suggest that ECT may alter the sensitivity of refractory patients to antidepressant medication.     

Measurement of mesothelioma on thoracic CT scans: a comparison of manual and computer-assisted techniques

Our purpose in this study was to evaluate the variability of manual mesothelioma tumor thickness measurements in computed tomography (CT) scans and to assess the relative performance of six computerized measurement algorithms. The CT scans of 22 patients with malignant pleural mesothelioma were collected. In each scan, an initial observer identified up to three sites in each of three CT sections at which tumor thickness measurements were to be made. At each site, five observers manually measured tumor thickness through a computer interface. Three observers repeated these measurements during three separate sessions. Inter- and intra-observer variability in the manual measurement of tumor thickness was assessed. Six automated measurement algorithms were developed based on the geometric relationship between a specified measurement site and the automatically extracted lung regions. Computer-generated measurements were compared with manual measurements. The tumor thickness measurements of different observers were highly correlated (r > or = 0.99); however, the 95% limits of agreement for relative inter-observer difference spanned a range of 30%. Tumor thickness measurements generated by the computer algorithms also correlated highly with the average of observer measurements (r > or = 0.93). We have developed computerized techniques for the measurement of mesothelioma tumor thickness in CT scans. These techniques achieved varying levels of agreement with measurements made by human observers.     

Presence of a very small population of Thy-1+, L3T4+ cells producing large amounts of IL-3 in young athymic nude mice.

A mixture of phorbol myristate acetate (PMA) and ionomycin was found to stimulate spleen and lymph node cells (LNC) from 6 to 8 week-old-athymic BALB/c nude mice, as well as from control +/+ mice, to secrete interleukin-3 (IL-3) in vitro. The specificity of the IL-3 bioassay was attested to by the use of rabbit anti-IL-3 antibodies, and by the detection of an accumulation of IL-3 mRNA. Cytotoxic treatment with relevant antibodies showed that the cells responsible for the IL-3 production in athymic nude mice was Thy-1+, L3T4+, Ly2-, while both L3T4+ and Ly 2+ cells produced IL-3 in control +/+ mice. Although the levels of IL-3 secreted by nude LNC varied among experiments, nude LNC were able to produce IL-3 at a level comparable to or higher than +/+ LNC. In addition, nude LNC consistently secreted two to three times more granulocyte-macrophage colony-stimulating factor (GM-CSF) than +/+ LNC, and the majority of GM-CSF secretion was dependent on the presence of L3T4+ cells. In contrast, IL-2 production by nude LNC was markedly limited. Since the flow microfluorometry analysis failed to demonstrate the presence of L3T4+ cells (less than 1%) in nude LNC, compared with 40-50% L3T4+ cells in +/+ LNC, our results suggest that athymic nude mice have a small population of Thy-1+, L3T4+ cells characterized by its ability to secrete IL-3 and GM-CSF at a very high rate.     

Aggravation of experimental cutaneous leishmaniasis in mice by administration of interleukin 3

Previous studies from our laboratory have shown that some in vitro maintained Leishmania major-specific L3T4+ T cells were capable of exacerbating cutaneous leishmaniasis after adoptive transfer to normal syngeneic mice. Results presented in this report show that these cells released substantial amounts of interleukin 3 (IL 3) and granulocyte-macrophage colony-stimulating factors after specific stimulation in vitro. In order to assess the involvement of such lymphokines in the exacerbation of cutaneous leishmaniasis by these L3T4+ T cells, the effect of the administration of important doses of IL 3 on the course of infection with L. major was investigated. The treatment of genetically susceptible BALB/c mice with IL 3 resulted in an enhancement of the size of lesions and favored the multiplication of parasites at anatomical sites distant from the primary lesion. Although IL 3 did not modify the development of lesions in genetically resistant CBA mice, this lymphokine promoted the growth of Leishmania in lymph node draining the lesion. Finally, the addition of IL 3 to macrophages parasitized in vitro enhanced the survival of intracellular Leishmania major.     

Phase II study of pemetrexed with and without folic acid and vitamin B12 as front-line therapy in malignant pleural mesothelioma.

PURPOSE: This phase II clinical study evaluated the efficacy of pemetrexed for the treatment of malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Patients with a histologically proven diagnosis of MPM, chemotherapy-naive measurable lesions, and adequate organ function received pemetrexed (500 mg/m2) intravenously over 10 minutes every 3 weeks. After a protocol change, most patients also received folic acid and vitamin B12 supplementation to improve safety. RESULTS: A total of 64 patients were enrolled. Nine (14.1%) of the 64 patients had a partial response. The Kaplan-Meier estimate for median overall survival was 10.7 months. Forty-three patients received vitamin supplementation for all courses of therapy, and 21 patients did not. Seven of the nine responders were vitamin supplemented. The median overall survival was 13.0 months for supplemented patients and 8.0 months for nonsupplemented patients. Vitamin-supplemented patients completed more cycles of therapy than nonsupplemented patients (median, six v two cycles, respectively). Grade 3/4 neutropenia (23.4%) and grade 3/4 leukopenia (18.8%) were the most common laboratory toxicities. Fatigue and febrile neutropenia were the most commonly reported nonlaboratory events (grade 3, 6.3%; grade 4, 0.0% each). The incidence of these toxicities was generally lower in the supplemented patients. CONCLUSION: Single-agent pemetrexed for MPM resulted in a moderate response rate (14.1%) and median overall survival of 10.7 months. Patients supplemented with folic acid and vitamin B12 tolerated treatment better (less toxicity and more cycles of treatment) and had a 5-month greater median overall survival than nonsupplemented patients. These results indicate that patients with MPM could benefit from single-agent pemetrexed treatment combined with vitamin supplementation.     

Localization of the tandem pore domain K+ channel TASK-1 in the rat central nervous system

Recently, a new family of potassium channels with two pore domains in tandem and four transmembrane segments has been identified. Seven functional mammalian channels have been reported at this time. These channels give rise to baseline potassium currents because they are not gated by voltage and exhibit spontaneous activity at all membrane potentials. Although the physiological role of these ion channels has yet to be determined, three mammalian members of this family (TREK-1, TASK-1, TASK-2) are activated by volatile anesthetics and may therefore contribute to the central nervous system (CNS) depression produced by volatile anesthetics. In this study we used northern blot analysis and immunohistochemical localization to determine the expression of TASK-1 subunits in the CNS. TASK-1 immunoreactivity was prominently found in astrocytes of the hippocampus, in the median eminence, in the choroid plexus, and the granular layer, Purkinje cell layer, and molecular layer of the cerebellum. In the spinal cord, strong TASK-I immunoreactivity was seen in ependymal cells lining the central canal and in white matter. These findings suggest a role for the TASK-1 channel in the production of cerebrospinal fluid and function of hypothalamic neurosecretory cells.     

Zoster cephalicus mit Beteiligung des Riechorgans

Zusammenfassung Auf die Seltenheit der Mitbeteiligung des Riechnerven beim Zoster cephalicus wird hingewiesen. Bekanntgabe einer eigenen Beobachtung, einen 38jährigen Mann betreffend, mit Zoster cephalicus und geizerscheinungen am Trigeminus derselbern Seite. Alle Ausfalls-bzw. Reizerscheinungen sind in kurzer Zeit restlos zurückgebildet. Als Ursache der Hirnnervenbeteiligung wird periphere Neuritis, hervorgerufen durch den Herpes virus, angenommen. In allen Fällen von Zoster cephalicus empfiehlt sich, nicht nur eine Hör-und Gleichgewichtsprüfung, sondern auch eine Untersuchung des Geruchssinns vorzunehmen, um festzustellen, ob nicht häufiger als bisher bekannt, Geruchsstörungen auch bleibender Art bei diesem Leiden auftreten.     

Hüftgelenkarthroskopie nach Luxatio obturatoria

Traumatic dislocation of the hip is a severe injury. Even in cases of an early uncomplicated repositioning there is a high risk of associated intra-articular injuries, such as lesions of the labrum, ruptures of the ligament of the head of the femur and loose bodies. The degree of damage caused by dislocation of the hip becomes apparent with a highly increased risk of developing postinjury osteoarthritis after dislocation of the hip. Some of the major intra-articular damage resulting from hip dislocation, e.g. loose bodies, can be detected by computed tomography and magnetic resonance imaging and can be effectively addressed by hip arthroscopy, thus aiming at reducing the acute symptoms and the risk of postinjury osteoarthritis. The force effect which causes dislocation of the hip can generate severe associated extra-articular injures as in the case described with an unstable fracture of the pelvis. This supplementary injury had to be considered while planning the operative therapy and rehabilitation.