An 8-week open-label trial of a 6-day course of mifepristone for the treatment of psychotic depression

OBJECTIVE: Several investigations suggest that mifepristone leads to the rapid amelioration of psychotic depression. However, these studies were of short duration (1 week or less) and included subjects who were taking other psychotropic medications. The goals of this study were to extend these findings by conducting an 8-week trial of mifepristone for subjects with psychotic depression who were taking no concomitant psychiatric medications. METHOD: Twenty subjects with a DSM-IV major depressive episode with psychotic features (for convenience we use the term psychotic depression) taking no psychotropic medications were given a 6-day course of mifepristone and followed as inpatients for a total of 8 weeks. Nonblinded ratings using the Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions scale (CGI) were performed at baseline and at the end of weeks 1, 4, and 8. The Brief Psychiatric Rating Scale (BPRS) was also administered at baseline and after weeks 4 and 8. Subjects were recruited between February 2003 and December 2003. RESULTS: Significant improvements in HAM-D and CGI scores were shown after 1 week and between weeks 1 and 4 but not between weeks 4 and 8. BPRS scores improved significantly after week 4, while the improvement in BPRS scores between weeks 4 and 8 was of borderline significance. CONCLUSION: Mifepristone appears to be a useful intervention for psychotic depression, leading to significant improvements even after a 1-week course of administration. Issues related to its optimal dosing and to prediction of response are discussed, as are the implications of lack of a placebo group and the use of nonblinded ratings in the present study.     

Investigation of Burkholderia cepacia nosocomial outbreak with high fatality in patients suffering from diseases other than cystic fibrosis

Over a 1-y period, 26 inpatients at the Jordan University Hospital in Amman were detected with bacteraemia (23 cases) or respiratory tract colonized with B. cepacia (3 cases). A combination of genetic identification and molecular typing has proved that all cases were caused by a single epidemic strain of B. cepacia genomovar IIIa. Nosocomial infections could be documented in 21/26 (81%) patients, mostly with severe underlying or malignant diseases other than cystic fibrosis, but the source of infection was undetected. The overall mortality related to infection with B. cepacia was 42%. All B. cepacia isolates were resistant to ampicillin, amikacin, carbenicillin and gentamicin; and mostly susceptible to piperacillin, chloramphenicol, cotri-moxazole, tetracycline, ceftazidime, and tazocin (62-88%). This study demonstrates the nosocomial and high fatality of B. cepacia genomovar IIIa in Jordanian patients suffering from diseases other than cystic fibrosis.     

MR colonography: How does air compare to water for colonic distention?

PURPOSE: To prove the feasibility of air-distended magnetic resonance colonography (MRC) and compare it with water-based distention. MATERIALS AND METHODS: In five volunteers, the colon was imaged twice: once after distending the colon with air and a second time after distending the colon with water. A total of 50 patients, who had been referred to colonoscopy for a suspected colorectal pathology were randomized into water-distention (N = 25) and air-distention (N = 25) groups. A contrast-enhanced T1-weighted three-dimensional volume interpolated breath-hold (VIBE) sequence was collected. Comparative analysis was based on qualitative ratings of image quality and bowel distention, as well as contrast-to-noise ratio (CNR) measurements for the colonic wall with respect to the colonic lumen. In addition, patient acceptance was evaluated. RESULTS: Inflammatory changes and colorectal masses were correctly identified on MRC in eight patients each. One 4-mm polyp identified at colonoscopy was missed on water-distended MRC. There were no false positive findings. No significant differences were found between air- and water-distention regarding discomfort levels and image quality. The presence of air in the colonic lumen was not associated with susceptibility artifacts. CNR of the contrast-enhanced colonic wall, as well as bowel distention, were superior on air-distended three-dimensional data sets. CONCLUSION: MRC can be performed using either water or air for colonic distention. Both techniques permit assessment of the colonic wall and identification of colorectal masses. While discomfort levels are similar for both agents, MRC with air provides higher CNR and better colonic distention.     

Absorbable microparticulate cation exchanger for immunotherapeutic delivery

An absorbable microparticulate cation exchanger was synthesized as a versatile carrier for biologically active proteins. In this work, acid-terminated polyglycolide (or polyglycolic acid) microparticulates (PG-MP) were surface modified for either sustained release of cytokines or as a platform for immunomodulation. The intended goal was to achieve in situ recruitment/maturation of dendritic cells and activation of T cells for tumor immunotherapy. PG-MP were prepared with a volume weighted mean diameter of 7.02 micro (range: 2.09-14.58 micro). Accessible carboxylic acid groups were determined to be 0.3 mmol/g with a corresponding zeta potential of -21.87 mV in phosphate-buffered saline. Under low magnification, scanning electron microscopy (SEM) revealed a highly textured surface due to processing from repetitive jet milling. However, a moderately porous architecture was noted at higher magnification. Electron spectroscopy for chemical analysis was used to characterize the PG-MP surface before and after adsorption of human granulocyte-macrophage colony stimulating factor (GM-CSF). Adsorption of GM-CSF on PG-MP (PG-GMCSF) resulted in a modest increase in the surface atomic concentration of nitrogen (0.97%). Pretreating the surface with poly-L-lysine (PG/Lys-GMCSF) prior to adding GM-CSF produced a nearly threefold increase in the surface nitrogen concentration (4.20% compared to 1.47%). This manipulation not only increased loading content, but also prolonged the release of GM-CSF released from 6 days to 26 days. ESCA on the post-release PG-MP samples (PG-GMCSF and PG/Lys-GMCSF) revealed a similar residual surface nitrogen concentration (2.26% vs. 2.35%). The observation was consistent with irreversibly adsorbed GM-CSF. It is postulated that irreversibly bound GM-CSF is released over time as a function of microparticulate degradation. Biological activity of released GM-CSF was confirmed by the proliferation of a GM-CSF-dependent cell line (TF-1) in the presence of microparticulates. PG-MP mediated activation of T cells was achieved through irreversible adsorption of either antimouse cd3 plus antimouse cd28 monoclonal antibodies (alpha-cd3/cd28-MP) or antihuman CD3 plus antihuman CD28 monoclonal antibodies (alpha-CD3/CD28-MP) on PG-MP. Irreversibly adsorbed antibodies were capable of activating both resting mouse and human T cells. Intracellular flow cytometry on mouse T cells revealed that nearly 50% of the activated cells produced interferon-gamma (IFN-gamma). This was consistent with a TH-1 or cell-mediated response. In vivo efficacy was evaluated in a mouse flank tumor model showing a significant antitumor effect both alone and in combination. Combination therapy was most effective at preventing tumor implantation (8/8 mice) and was able induce tumor regression (4/7 mice) and/or stable disease (3/7 mice) in a regression model. In these studies, immunohistochemistry was used to confirm local recruitment of dendritic cells. In conclusion, the PG-MP represents a novel absorbable cation exchanger that can be readily manipulated to deliver biologically active proteins for immunotherapy.     

Rescue in situ thrombolysis for acute coronary thromboembolism in an angiographically normal coronary artery

Coronary thromboembolism in an angiographically normal coronary artery is extremely uncommon. There are few instances where normal coronary arteries have been documented just prior to an episode of acute thromboembolic insult. We now report such a case of acute coronary thromboembolism in a patient with widely patent coronary vessels documented just prior to the event during preoperative screening angiogram with successful in situ revascularization.     

Brown tumor of the femur associated with double parathyroid adenomas

Severe parathyroid bone disease is a rare clinical presentation of primary hyperparathyroidism. Double parathyroid adenomas are even more rare cause of primary hyperparathyroidism. The authors present a case of double parathyroid adenomas in a 48-year-old man, who presented with painful left lower limb swelling, which was slowly growing in size in the last 20 years. Magnetic resonance imaging revealed a cystic bony lesion and coincidentally, a urinary bladder calculus. Biopsy of the mass revealed giant cell lesion. Laboratory investigations showed hypercalcemia and hypophosphatemia with elevated parathyroid hormone level. A computerized tomography scan of the neck delineated an adenoma of the left superior parathyroid gland, which was surgically removed. The left inferior parathyroid was also enlarged and was removed. Histological diagnosis confirmed double parathyroid adenomas. The rarity and the interesting clinical presentation of such association are discussed.     

Alternative use of botulinum toxin in urology

Botulinum toxin A is used in the treatment of lower urinary tract symptoms due to detrusor sphincter dysynergia and detrusor hyper-reflexia (neurogenic detrusor deficiency). The toxin acts by producing paralysis of muscle tissue and has been shown to be safe and effective in the treatment of conditions caused by increased muscle tonicity and spasticity. Here the literature is reviewed chronologically, the established and emerging indications for the urological use of botulinum toxin evaluated and future applications are also considered.     

Resistance of delayed-rectifier K+ current to cadmium in Drosophila neurons

The delayed-rectifier potassium current (IKDR) is important in repolarizing the membrane potential and determining the level of neuronal excitability. We investigated the effect of cadmium on this potassium current. The whole-cell patch-clamp technique was used to measure IKDR from cultured Drosophila neurons derived from embryonic neuroblasts. The current was measured from neurons before and after the application of 0.1 mM cadmium to the external saline. IKDR was similar in the cadmium-containing saline (383 +/- 47 pA) and the control saline (401 +/- 60 pA). These results indicate that cadmium neurotoxicity does not specifically affect IKDR in Drosophila neurons.     

Oxygen delivery in irradiated normal tissue

Ionizing radiation exposure significantly alters the structure and function of microvascular networks, which regulate delivery of oxygen to tissue. In this study we use a hamster cremaster muscle model to study changes in microvascular network parameters and use a mathematical model to study the effects of these observed structural and microhemodynamic changes in microvascular networks on oxygen delivery to the tissue. Our experimental observations indicate that in microvascular networks while some parameters are significantly affected by irradiation (e.g. RBC transit time), others remain at the control level (e.g. RBC path length) up to 180 days post-irradiation. The results from our mathematical model indicate that tissue oxygenation patterns are significantly different in irradiated normal tissue as compared to age-matched controls and the differences are apparent as early as 3 days post irradiation. However, oxygen delivery to irradiated tissue was not found to be significantly different from age matched controls at any time between 7 days to 6 months post-irradiation. These findings indicate that microvascular late effects in irradiated normal tissue may be due to factors other than compromised tissue oxygenation.     

Descriptive anatomy of the dominant septal perforators using Dual Source coronary CT angiography

Although clinical outcomes for septal ablation in treating left ventricular outflow tract obstructions are generally favorable, a variety of complications have been reported including a high incidence of right bundle branch block. These complications may be attributed to anatomic variability of the dominant septal perforator. We used Dual Source CT Coronary Angiography (DS‐CTA) to determine the location of the termination point of the dominant septal perforator as well as the distance of the termination point from the mitral annulus in patients undergoing DS‐CTA. One‐hundred‐fourteen DS‐CTA scans were retrospectively reviewed by two observers by consensus. The left ventricle was divided into anterior wall, anterioseptum, and inferioseptum. For each segment, the myocardium was divided into three layers (1) right ventricular side, (2) mid portion, and (3) left ventricular side. The zone of termination of the dominant septal perforator was identified as well as the distance of the termination point from the mitral annulus. The dominant septal perforator terminated in the right ventricular side of the anterioseptum in 86 of the 118 visualized terminations (73%) and in the left ventricular anterior wall in 6 visualized terminations (5%). On average, the dominant septal perforator terminated 26.3 ± 8.6 mm from the mitral annulus. In the majority of cases, the dominant septal perforator terminates in the right ventricular side of anterioseptum. In addition, there is great variability in the distribution of the termination point of the dominant septal perforator from the mitral annulus. Clin. Anat. 23:70–78, 2010. © 2009 Wiley‐Liss, Inc.