Radiculopathy following intrathecal baclofen pump implantation]

INTRODUCTION: Intrathecally delivered baclofen has been used as a treatment for severe spasticity since 1984. After a successful intrathecal baclofen trial, a programmable drug delivery system was implanted. Few early complications such as infection or hematoma are observed after this surgery. OBJECTIVE: To describe an unusual and unknown complication of intrathecal baclofen therapy. METHOD: We report 2 cases of complications of intrathecal baclofen therapy, radiculalgy, that appeared early after pump implantation. The clinical symptoms and computed tomography (CT) results are described. RESULTS: The first patient described pain, which evoked left S1 radiculopathic features. The second had left L5 radiculopathic involvement. The mean pain level was estimated on a 10-point visual analog scale as 7.5 (range 4-9). Lumbar CT scan showed a conflict between the symptomatic root and the catheter and eliminated other causes of the symptoms. Treatment with analgesic drugs was successful in 1 patient. The other presented with proximal disconnection of the catheter, which led to surgical replacement of the catheter. The pain disappeared after this surgery. CONCLUSION: Intrathecal baclofen therapy with a subcutaneously implanted progammable pump can be complicated by radiculalgy secondary to a conflict between the catheter and symptomatic root. The diagnosis is made by CT lumbar scan. If medical treatment is not sufficient, surgery could be proposed to replace the catheter.     

Discovering genes: the use of microarrays and laser capture microdissection in pain research

The DNA microarray is a powerful, high throughput technique for assessing gene expression on a system-wide genomic scale. It has great potential in pain research for determining the network of gene regulation in different pain conditions, and also for producing detailed gene expression maps in anatomical areas that process nociceptive stimuli. However, for the potential of this high throughput technology to be realised in pain research, microarrays need to be combined with other technologies. Laser capture microdissection is capable of isolating small populations of homogenous cells, allowing distinct areas involved in nociceptive processing to be examined. In combination with sophisticated PCR-based amplification protocols this technique provides sufficient amounts of messenger RNA (mRNA) for application to microarrays. Aside from the technological issues, a difficult task in any microarray study is the analysis of the resulting enormous data set to reveal the key genes, whose regulation is central to the phenotypic changes observed. For this to be achieved, the methods of data analysis, pattern searching and feature recognition, and bioinformatics have to be properly deployed all within the context of an appropriate statistical design. These issues are especially relevant to pain research where interindividual and interpopulation variation is likely to be high, and where polymorphisms can greatly affect nociceptive sensitivity and susceptibility to pain conditions. Methods for assessing the function of new candidate genes identified in microarray screening experiments are also discussed.     

Comparative effects of quinolones on human mononuclear leucocyte functions

The effects of three quinoline derivatives--pefloxacin, ciprofloxacin and ofloxacin--were investigated in mitogen-stimulated human peripheral blood mononuclear leucocytes (MNL). At concentrations of 50 mg/l or more, pefloxacin, ciprofloxacin or ofloxacin significantly inhibited MNL proliferation in response to phytohaemagglutinin. This inhibition was more marked with ciprofloxacin than pefloxacin or ofloxacin. To determine the possible mechanism(s) involved in the inhibition of MNL proliferation following exposure to pefloxacin, ciprofloxacin or ofloxacin, we assessed (1) interleukin-1 (IL-1) activity in supernatants from monocytes treated with the quinolones and (2) the effects of 2-mercaptoethanol (2-ME) a thiol compound which acts as an antioxidant agent and the effect of indomethacin (INDO) an inhibitor of prostaglandin E2 synthesis. 2-ME and INDO did not prevent the decrease in the proliferation. IL-1 activity was shown to be decreased for the same range of antibiotic concentrations as observed for the inhibition of MNL proliferation. Cellular viability of the MNL or monocytes was not modified by any of the quinolones at the concentrations tested. Taken together, these results suggest that pefloxacin, ciprofloxacin and ofloxacin act as immunomodulators. The mechanism involved with the cascade of events that leads to the lymphocyte proliferation and the clinical relevance need further investigation.     

Proteolysis of the class II-associated invariant chain generates a peptide binding site in intracellular HLA-DR molecules.

HLA-DR molecules are heterodimeric transmembrane glycoproteins that associate intracellularly with a polypeptide known as the invariant (I) chain. Shortly before expression of the HLA-DR alpha beta dimer on the cell surface, however, the I chain is removed from the intracellular alpha beta I complex by a mechanism thought to involve proteolysis. In this report, we show that treatment of purified alpha beta I with the cysteine proteinase cathepsin B results in the specific proteolysis of the HLA-DR-associated I chain in vitro. As a consequence of this, the I chain is removed and free alpha beta dimers are released from alpha beta I. Although alpha beta I fails to bind an immunogenic peptide, the released alpha beta dimers acquire the ability to bind the peptide after proteolysis of the I chain. These results suggest that the I chain inhibits immunogenic peptide binding to alpha beta I early during intracellular transport and demonstrate that proteolysis is likely to be the in vivo mechanism of I chain removal.     

Specific Serological Diagnosis of Leprosy with a Recombinant Mycobacterium leprae Protein Purified from a Rapidly Growing Mycobacterial Host

In this report we demonstrate the utility of an monoclonal antibody inhibition enzyme-linked immunosorbent assay based on the Mycobacterium leprae 35-kDa protein, purified from the rapidly growing host Mycobacterium smegmatis, for the serodiagnosis of multibacillary leprosy. The assay proved highly specific (97.5%) and sensitive (90%) and compared favorably with two other established methods routinely utilized for leprosy serodiagnosis.     

Heterotopic heart transplants in Biomphalaria glabrata (mollusca: pulmonata). Fate of congeneric xenografts

Hearts were implanted heterotopically into the hemocoel of NIH albino Biomphalaria glabrata from three xenogeneic donor snails, including two New World (B. obstructa, B. tenagophila) and one Old World (B. alexandrina) species, as well as from wild type allogeneic donors. Recipients were examined histologically at 1, 3, 7, 10, 15, 30, 60, 120, and 180 days postimplantation (PI). Grafts from all four donor species were temporarily infiltrated by recipient hemocytes at early intervals PI and in most instances also became encapsulated. Furthermore, the grafts subsequently showed histopathological alterations and abnormal heartbeat relative to preimplantation controls. However, hemocytic reactions eventually subsided, the implants remained structurally intact, and implant myocardial cells both maintained high levels of intracellular glycogen and continued to contract rhythmically for 6 months. No major differences occurred in fates among different xenografts, or between xenografts and allografts. Our observations of prolonged xenograft survival differ from those of previous investigators, most of whom have reported rapid destruction of implanted xenogeneic tissues in molluscs.     

Alpha-smooth muscle actin as a marker for soft tissue tumours: a comparison with desmin

The immunoreactivity of a range of vascular and non-vascular smooth muscle tumours, rhabdomyosarcomas, and non-myoid lesions has been examined with the use of a monoclonal antibody to smooth muscle-specific actin and the muscle intermediate filament, desmin. In all cases of smooth muscle-derived tumours, the alpha-actin antibody yielded superior results. Staining of the myofibroblasts of fibromatoses was also seen. In contrast to desmin, immunoreactivity was not exhibited by rhabdomyosarcomas. We propose that this monoclonal antibody to alpha-smooth muscle actin is a useful addition to the panel of reagents used for the characterization of soft tissue proliferations and tumours. The technical aspects of the application of this monoclonal antibody to immunohistochemistry are discussed.     

Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis

Hereditary pancreatitis (HP) is a rare inherited disorder, characterised by recurrent episodes of pancreatitis often beginning in early childhood. The mode of inheritance suggests an autosomal dominant trait with incomplete penetrance. The gene, or at least one of the genes, responsible for hereditary pancreatitis has been mapped to the long arm of chromosome 7 and a missense mutation, an arginine to histidine substitution at residue 117 in the trypsinogen cationic gene (try4) has been shown to segregate with the HP phenotype. The aim of this work was to investigate the molecular basis of hereditary pancreatitis. This study was performed on 14 HP families. The five exons of the trypsinogen cationic gene were studied using a specific gene amplification assay combined with denaturing gradient gel electrophoresis (DGGE). The present paper describes three novel mutations, namely K23R and N29I and a deletion -28delTCC in the promoter region. We also found a polymorphism in exon 4, D162D. In eight of these families we found a mutation which segregates with the disease. A segregation analysis using microsatellite markers carried out on the other families suggests genetic heterogeneity in at least one of them. Our findings confirm the implication of the cationic trypsinogen gene in HP and highlight allelic diversity associated with this phenotype. We also show that the pattern of inheritance of HP is probably complex and that other genes may be involved in this genetic disease.     

Medical students' attitudes in a PBL curriculum: trust, altruism, and cynicism.

PURPOSE: Studies have shown that medical students become more cynical and less altruistic as they advance in training. However, these studies were conducted in traditional medical schools, and many used unvalidated tools. This study examined students' attitudes in a problem-based learning (PBL) curriculum using reliable and valid measures. METHOD: Medical students and PGY-1 residents at Mercer University School of Medicine in Macon, Georgia, completed Wrightsman's Philosophies of Human Natures Scale (PHNS) in 1999 and 2000. Chronbach's alpha assessed internal reliability among subscales, and test-retest reliability coefficients confirmed acceptable reliability. For 114 students who completed both surveys, changes in PHNS scores were analyzed, with particular attention to the subscales of trustworthiness, altruism, and cynicism. RESULTS: Students assessed at the beginning of their second year increased the extent to which they believed people are trustworthy and increased their beliefs in how altruistic people are. They also showed a significant decrease in cynicism. There was not a significant change in trustworthiness, altruism, or cynicism among the participants beyond first year. In general, female students held less cynical views about others and believed people to be more trustworthy. CONCLUSIONS: Contrary to prior reports, this study found that more advanced trainees were not more cynical or less altruistic than their more junior counterparts. Indeed, a significant and positive change of attitudes among the participants during their first year of medical school refuted earlier reports. Thus, results of earlier studies and the effect of a PBL curriculum on attitudes of medical students need to be re-examined.