Recovery of Functional Memory T Cells in Lung Transplant Recipients Following Induction Therapy with Alemtuzumab

Profound T-cell depletion with the monoclonal antibody alemtuzumab facilitates reduced maintenance immunosuppression in abdominal and lung transplantation. While the phenotype of the post-depletional T cells has been characterized, little is known about their function. In the present study, global and CMV-specific T-cell function was assessed longitudinally in 23 lung transplant (LTx) recipients using T-cell assays (ImmuKnow and T Cell Memory, Cylex, Columbia, MD) during the first year posttransplant after induction therapy. Recovery of mitogen responses were seen at 2 weeks posttransplantation (65%PHA; 58% Con A), despite the low number of circulating T cells (<2%). These responses declined at 4-5 months (24%PHA; 54% Con A) and were partially reconstituted by 9 months (46% PHA; 73% Con A). CMV-specific responses recovered in 80% of R+ patients as early as 2 weeks posttransplant (n = 5) and 72% of patients had a memory response by 3 months (n = 11). In contrast, only 2 of 5 patients who did not exhibit memory responses pre-transplant (R-) developed transient CMV-specific T-cell responses. Our results show that profound depletion of T cells induced by alemtuzumab spares the functional subset of CMV-specific memory T cells. Conversely, CMV R- patients predepletion may require a prolonged period of prophylaxis.     

Differences in the Course of Alcohol Withdrawal in Women and Men: A Polish Sample

A retrospective study compared the course of alcohol withdrawal, including delirium tremens, in women and men hospitalized in the Nowowiejski Hospital in Warsaw from 1973 to 1987. Medical records pertaining to 1179 patients were analyzed; 13.8% of these patients were women and 86.2% were men. The study showed that women began intensive alcohol drinking later than men ( p < 0.0001), but the period between the onset of alcohol abuse and the first occurrence of alcohol withdrawal was shorter in women than in men ( p < 0.0001). In the period of heavy drinking before hospitalization, women consumed significantly less alcohol then men ( p < 0.0001); moreover, women drank nonbeverage alcohol less frequently than men ( p < 0.05). Women were hospitalized substantially longer than men ( p < 0.0001), whereas the duration of alcohol withdrawal symptoms at the time of hospitalization was comparable in both groups. Withdrawal seizures were significantly more frequent among men than among women ( p < 0.001). Significant differences in the patients'somatic conditions were not noted between the groups, with the exception of anemia and decreased potassium concentration, which were more frequently observed in women (both p < 0.0001), and of increased concentration of ALT and hypoproteinemia, which were more frequent in men (respectively, p < 0.05 and p < 0.01). Co-existing personality disorders, depressive disorders, and anxiety disorders—as well as abuse of benzodiazepines and barbiturates—were more frequently observed in women ( p < 0.0001). The period between the first hospitalization due to alcohol withdrawal and the time of death was significantly shorter in men than in women ( p < 0.05). The results point to differences in the conditions and the course of alcohol dependence and alcohol withdrawal between women and men.     

ACTH in the plasma and cerebrospinal fluid in patients with multiple sclerosis

In 1984 and at the beginning of 1985 the authors carried out radioimmunoassays (SORIN-CIS kit) the plasma levels of ACTH in 116 multiple sclerosis patients (m-52, f-64) and in 10 cases this radioimmunoassay was done in the cerebrospinal fluid (m-5, f-5). The control group comprised 90 patients with ischialgia and neuroses. The normal value in the plasma was from 0 to 80.86 pg/ml, and in the fluid it was from 0 to 77.08 pg/ml. In multiple sclerosis patients the plasma ACTH level was from 0 to 286.9 pg/ml, in the cerebrospinal fluid from 0 to 89 pg/ml. The values of ACTH were significantly higher in multiple sclerosis patients, mainly in males. In the fluid the level of ACTH was significantly higher in the studied patients. No significant differences in ACTH levels were found between males and females with multiple sclerosis, and in the control group this level was higher in females. Raised ACTH level was found mainly in multiple sclerosis with lung duration of the disease (10 years) at the time of exacerbations. The authors continue studies on the axis hypothalamus-hypophysis-adrenals, on various hormones, prostaglandins, beta-endorphin, biochemical markers, cAMP, cCMP, arylosulphatase A and B MBC etc.     

Transient demineralization of the hip--case report]

Transient osteoporosis of the hip is an uncommon disorder of unclear etiology. It is often confused with other diagnosis including osteonecrosis of the femoral head. Authors describe a case of transient osteoporosis of the hip of 32 years woman. The symptoms occurred in third trimester of pregnancy. The primary symptoms were right hip pain and decreased range of motion of the right hip. In diagnostic process helpful were clinical examination, X-ray, ultrasonography, MRI and microscopic examination. As a treatment authors used walking on crutches, calcitonin and calcium preparate. After a few months remission of symptoms and normalization in accessory investigations were obtained.     

Effects of interpleural bupivacaine (0.5%) on canine diaphragmatic function.

Several authors have questioned the potential for phrenic nerve paralysis with interpleural analgesia. This study was designed to examine the potential for phrenic nerve paralysis with the use of interpleural bupivacaine in dogs. Seven dogs were anesthetized, tracheally intubated, and allowed to breathe spontaneously with halothane/oxygen while in the supine position. After a midline laparotomy, two wires were inserted into the costal portion of each hemidiaphragm for measurement of electromyographic (EMG) signals. A balloon catheter was placed in the abdominal cavity to measure abdominal pressure. The abdomen was then closed. Airway pressure was measured through a side port in the endotracheal tube. Bilateral interpleural catheters were inserted with the loss-of-resistance technique. Each dog was used for two experiments, one on each side, except for one animal. To assess the contribution of the ipsilateral diaphragm to total respiratory effort, the airway was occluded at functional residual capacity for three consecutive breaths, and EMG, airway pressure, and abdominal pressure were measured. In five of nine experiments with bupivacaine, there was complete loss of EMG activity on the side of the injection. In two dogs, there was partial loss of diaphragmatic function, and in the remaining two, there was no change in EMG. In the normal saline solution group (n = 4), there was no change in the EMG. Two dogs that received bilateral bupivacaine injections developed paradoxical respiration with negative inspiratory intraabdominal pressures. Phrenic nerve paralysis or paresis can occur with interpleural blockade. The factors affecting the occurrence of this complication remain to be elucidated.     

Prospective Open-Label Study of Botulinum Toxin Type A in Patients with Axillary Hyperhidrosis: Effects on Functional Impairment and Quality of Life

BACKGROUND: Patients with primary axillary hyperhidrosis experience substantial functional impairment and reduced health-related quality of life (HRQOL). Few studies have comprehensively evaluated the effects of botulinum toxin type A (BoNT-A) on these symptoms. OBJECTIVE: To prospectively assess the effects of BoNT-A on functional impairment associated with primary axillary hyperhidrosis. METHODS: Patients treated with BoNT-A 50 U per axilla at baseline were assessed 4 and 12 weeks later. Outcome measures included functional impairment as assessed by the Hyperhidrosis Disease Severity Scale and the Hyperhidrosis Impact Questionnaire and dermatology-specific HRQOL as assessed by the Dermatology Life Quality Index. RESULTS: At weeks 4 and 12 after BoNT-A treatment, 85% and 90% of patients achieved the a priori definition of treatment responder. Patients reported less occupational and emotional impairment, spent less time managing their hyperhidrosis, and had fewer difficulties in social situations. Adverse events were uncommon (5.5%), were mild, and did not require treatment. At study end, 53% of patients reported no dermatology-specific HRQOL impairment and 90% were satisfied with treatment. CONCLUSIONS: Significant, meaningful, rapid, and durable reductions in disease severity and functional impairment, as well as improvements in HRQOL, were seen following BoNT-A treatment. BoNT-A was safe and well tolerated, producing high levels of patient satisfaction.     

Characterization of human hepatocytes isolated from non-transplantable livers

INTRODUCTION: The successful use of hepatocytes depends on a reliable demonstration of the functional and morphological integrity of isolated cells. Herein we investigated whether the isolation and cryopreservation of primary human hepatocytes can compromise cell viability and liver-specific characteristics. MATERIAL/METHODS: Hepatocytes were isolated from encapsulated human liver segments by a modified 2-step perfusion technique. Isolated cells were Percoll-purified, cryopreserved, and stored in liquid nitrogen for 1-12 months. For rapid assessment of fresh and cryopreserve/thawed hepatocyte yield and viability, the cells were stained with trypan blue or labeled with fluorochromes. For immunocytochemical analysis, the cells were labeled with monoclonal antibodies for the presence of the following antigens and chemokines: CD3, CD45Ro, CD45Ra, CD34, CD68, CD90, CD95, CD20, HLA-DR, Ki67, PCNA, Bcl-2, p53, CXCR3, CXCR4, and SDF-1. The cells were tested for several specific functions, such as ureagenesis, energy status, MTT activity, lactate dehydrogenase leakage, and total CYP450 content. RESULTS: Assessment of both freshly isolated (Percoll-purified) and cryopreserved/thawed hepatocytes revealed a low constitutive level of contamination by non-parenchymal cells compared with crude (unpurified) preparations and tissue sections. All viable hepatocytes showed intact morphology and retained CYP450 protein, energy status, and urea synthesis. CONCLUSIONS: Modifications in hepatocyte preparations, such as depletion of dead, damaged, and nonparenchymal cells, improves cell purity, which can be adapted to further evaluation of hepatocyte immunogenicity. These data illustrate the importance and feasibility of human hepatocyte banking.     

VEGF (vascular endothelial growth factor) concentration in serum and pleural fluid of patients with pleural malignancy and pleural tuberculosis

The purpose of this study was comparison of VEGF (vascular endothelial growth factor) levels in serum and pleural fluid and estimation of this test usefulness in diagnosis of pleural effusions. VEGF levels were measured by ELISA method in 68 patients (45 males and 23 females) aged 19-81 years. By Light's criteria in 16 cases transudate and in 52 cases exudate was recognized. By means of fluid cytology, pleural biopsy, microbiology or thoracoscopy in 10 cases pleural metastases from distant organs, in 15 cases coexisting pulmonary neoplasm, in 11 cases mesothelioma and in 16 cases tuberculosis were determined as a cause of fluid accumulation in pleural space. The mean VEGF levels were significantly higher (p < 0.001) in patients with exudates than in patients with transudates (3833 pg/ml and 325 pg/ml respectively). Based on likelihood ratios analysis, as a cut off value in differentiation of exudates and transudates a value 700 pg/ml was accepted. The sensitivity of this test was 75% and the specificity 93% and likelihood ratio (LR) 12.5. The mean VEGF level in exudates was seven times higher than mean VEGF level in serum (3833 pg/ml and 573 pg/ml respectively). Mean VEGF levels in malignant exudates (4615 pg/ml) were significantly higher than in tuberculous exudates (2073 pg/ml). As a cut off value in differentiation between malignant and tuberculous exudates a value of 4500 pg/ml was accepted. We conclude that our results suggests the local VEGF production in pleural cavity and the significant role of this cytokine in pleural exudates accumulations and also suggests the usefulness of VEGF estimation in pleural fluid in differentiation transudates from exudates and malignant from tuberculous pleural fluids.