Electrode dysfunctions in patients with deep brain stimulation: a clinical retrospective study

Background  

Electrode fractures are known hardware problems in patients with deep brain stimulation (DBS) and require surgical revision. Short circuits, loose connections or disconnections of only single contacts of the common quadripolar stimulation electrodes are more subtle dysfunctions and can result in decreased efficacy of DBS. Measuring the impedances of electrodes helps detect such technical dysfunctions. This study evaluates the frequency and clinical implications of abnormal impedance measurements.     

Improved Measurement of Pressure Gradients in Aortic Coarctation by Magnetic Resonance Imaging

Objectives. This study evaluated whether magnetic resonance imaging (MRI) and magnetic resonance (MR) phase velocity mapping could provide accurate estimates of stenosis severity and pressure gradients in aortic coarctation.

Background. Clinical management of aortic coarctation requires determination of lesion location and severity and quantification of the pressure gradient across the constricted area.

Methods. Using a series of anatomically accurate models of aortic coarctation, the laboratory portion of this study found that the loss coefficient (K), commonly taken to be 4.0 in the simplified Bernoulli equation ΔP = KV², was a function of stenosis severity. The values of the loss coefficient ranged from 2.8 for a 50% stenosis to 4.9 for a 90% stenosis. Magnetic resonance imaging and MR phase velocity mapping were then used to determine coarctation severity and pressure gradient in 32 patients.

Results. Application of the new severity-dependent loss coefficients found that pressure gradients deviated from 1 to 17 mm Hg compared with calculations made with the commonly used value of 4.0. Comparison of MR estimates of pressure gradient with Doppler ultrasound estimates (in 22 of 32 patients) and with catheter pressure measurements (in 6 of 32 patients) supports the conclusion that the severity-based loss coefficient provides improved estimates of pressure gradients.

Conclusions. This study suggests that MRI could be used as a complete diagnostic tool for accurate evaluation of aortic coarctation, by determining stenosis location and severity and by accurately estimating pressure gradients.

(J Am Coll Cardiol 1996;28:1818–26)>     

Endotoxin-induced suppression of erythropoiesis: the role of erythropoietin and a heme synthesis stimulating factor

The regulation of erythropoiesis is primarily controlled by erythropoietin (Ep). Recently, however, other factors that both stimulate and inhibit erythropoiesis have been reported. Using an in vitro liquid culture of bone marrow cells, a factor in normal mouse serum was demonstrated that markedly stimulated heme synthesis by marrow erythroid cells. In this study, the role of this heme synthesis stimulating factor (HSF) and Ep in the erythropoietic suppression caused by endotoxin administration to mice was examined. Although HSF levels did not alter appreciably after endotoxin injection, marrow erythroid cells from these animals became unresponsive to the factor. This could be reversed if Ep was added to the culture in vitro or if the hormone was injected into the mice 18 hr prior to harvesting the marrow. This marrow erythroid cell response is identical to that seen in animals in whom Ep levels are markedly reduced, such as that found in exhypoxic polycythemia, and suggest a decrease in the hormone following endotoxin administration. Additional studies demonstrated that when Ep was injected into mice 6 hr after endotoxin administration, an increase in femoral erythroid colony-forming units (CFU-E), proerythroblast number, and 59 Fe incorporation into femoral marrow cells could be demonstrated. These findings, together with the marrow erythroid cell response to the hormone, suggest that the mechanism for suppression of erythropoiesis after endotoxin injection is a reduction in the level of circulating Ep.     

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

The neurobiology of anhedonia and other reward-related deficits

Anhedonia, or markedly diminished interest or pleasure, is a hallmark symptom of major depression, schizophrenia and other neuropsychiatric disorders. Over the past three decades, the clinical definition of anhedonia has remained relatively unchanged, although cognitive psychology and behavioral neuroscience have expanded our understanding of other reward-related processes. Here, we review the neural bases of the construct of anhedonia that reflects deficits in hedonic capacity and also closely linked to the constructs of reward valuation, decision-making, anticipation and motivation. The neural circuits subserving these reward-related processes include the ventral striatum, prefrontal cortical regions, and afferent and efferent projections. An understanding of anhedonia and other reward-related constructs will facilitate the diagnosis and treatment of disorders that include reward deficits as key symptoms.     

Estrogens and brain function

Cognitive decline is well recognized during ageing but is often accelerated in women after menopause. Studies have shown that there are significant gender differences in brain ageing with significantly greater changes in brain structure, function and metabolism between females and males. Estrogens exert protective effects on neuronal cells in culture but the exact underlying mechanism for their neuroprotective effect in humans is not completely understood. Estrogens have been shown to affect the nervous system in many different ways: via binding to estrogen receptors (ERs) but also via multiple pathways. The results of small randomized trials and larger observational studies suggest a beneficial effect of estrogen therapy on cognitive function in symptomatic postmenopausal women. However, the results of the Women's Health Initiative Study (WHIMS) do not support this, at least not in women over the age of 65. Alzheimer's disease (AD) is two to three times more common in women than in men. Based on currently available data, routine therapeutic use of estrogens in women with AD is not justified but it may have a role in the prophylaxis of AD. The existing evidence supports the use of HRT only in women with menopausal symptoms for a few years following menopause.     

Dysgerminoma of the ovary: A retrospective study

A retrospective analysis of 22 patients with ovarian dysgerminoma who were treated between 1980 and 1987 was carried out. The median age at presentation was 24.5 years. A total of 15 patients were in stage I, one patient was in stage II and six patients were in stage III. Bilateral ovarian involvement was present in four patients. Conservative surgery was carried out in nine patients and 11 patients underwent radical surgery. Two patients had biopsy only. Fourteen patients received adjuvant radiotherapy and three patients received salvage radiation for recurrent disease. The 10-year actuarial survival rate was 81.8%. All 15 patients in stage I were alive and disease-free at a median follow-up of 125 months. Four patients (one in stage II and three in stage III) died of progressive or recurrent abdominopelvic disease. Pelvic recurrence occurred after conservative surgery in two patients in stage IA who had a tumour size greater than 10 cm, but they were salvaged with radical surgery, chemotherapy and radiotherapy. There were seven patients aged 20 years or less. All were alive and disease-free at a median follow-up of 127 months.     

Desmethylimipramine attenuates cocaine withdrawal in rats

Depression and anhedonia are two major symptoms of cocaine withdrawal in humans. Hence, pharmacological treatments effective in depression might also alleviate the symptoms of cocaine withdrawal. In the present study, the effects of acute and repeated administration of a tricyclic antidepressant, desmethylimipramine (DMI), were investigated in naive and cocaine-withdrawing rats. An animal model of cocaine withdrawal was used that employs the elevation in intracranial self-stimulation (ICSS) thresholds following the termination of prolonged periods of cocaine self-administration as a measure of an animal's anhedonic state. The influence of chronic DMI treatment on-adrenergic receptor binding and affinity was also correlated with the behavioral signs of cocaine withdrawal. Neither acute nor repeated DMI treatment influenced reward functions in rats that were not undergoing cocaine withdrawal. However, repeated DMI treatment significantly down-regulated-adrenergic receptors, and shortened the duration of the post-cocaine anhedonia (elevation in thresholds). Furthermore, the magnitude of the-adrenergic receptor down-regulation correlated significantly with the degree of effectiveness of DMI treatment in reversing the post-cocaine anhedonia. However, chronic DMI treatment did reduce the amount of cocaine self-administered by the animals. The reversal of the post-cocaine anhedonia in this animal model of cocaine withdrawal by chronic DMI treatment demonstrates the potential usefulness of the model in identifying new pharmacotherapies for cocaine withdrawal. In addition, the results indicate that tricyclic antidepressants may be able to ameliorate some of the symptoms of cocaine withdrawal.     

Molecular characterization of circulating tumor cells in breast cancer: challenges and promises for individualized cancer treatment

Blood testing using Circulating Tumor Cells (CTCs) has emerged as one of the hottest fields in cancer diagnosis. Research on CTCs present nowadays a challenge, as these cells are well defined targets for understanding tumour biology and improving cancer treatment. The presence of tumor cells in patient’s bone marrow or peripheral blood is an early indicator of metastasis and may signal tumor spread sooner than clinical symptoms appear and imaging results confirm a poor prognosis. CTC enumeration can serve as a “liquid biopsy” and an early marker to assess response to systemic therapy. Definition of biomarkers based on comprehensive characterization of CTCs has a strong potential to be translated to individualized targeted treatments and spare breast cancer patients unnecessary and ineffective therapies but also to reduce the costs for the health system and to downsize the extent and length of clinical studies. In this review, we briefly summarize recent studies on the molecular characterization of circulating tumor cells in breast cancer and discuss challenges and promises of CTCs for individualized cancer treatment.