Reduction of epidural fibrosis in lumbar surgery with Oxiplex adhesion barriers of carboxymethylcellulose and polyethylene oxide.

BACKGROUND CONTEXT: Postsurgical epidural adhesions and fibrosis after surgery for lumbar disc herniation are a consequence of normal wound healing. The presence of fibrosis renders reoperations risky, and in some patients fibrosis may lead to nerve root tethering. PURPOSE: One approach to minimizing the risk of developing epidural adhesions is to provide a barrier between the dural membrane and the healing connective tissues. The purpose of these studies was to evaluate such a barrier device. STUDY DESIGN/SETTING: In vivo investigation in an animal model at a university laboratory. PATIENT SAMPLE: Rabbit. OUTCOME MEASURES: Gross and histomorphic evaluation. METHODS: Barriers comprised of carboxymethylcellulose (CMC) and polyethylene oxide (PEO) (Oxiplex; FzioMed, Inc., San Luis Obispo, CA) were studied as devices to reduce epidural adhesion formation in rabbit laminotomy and laminectomy models. The barriers tested were either a gel alone (gel) or a gel covered with a film (gel/film combination). Two laminotomy or laminectomy sites (depending on the surgical method) were created in each rabbit at L4 and L6. One site was treated with a CMC/PEO gel, or CMC/PEO gel/film combination, and the other site served as a surgical control. Two surgical models that differed in the extent of adhesion formation at untreated injury sites and the method of injury generation were used. RESULTS: Model A, which did not incorporate dural abrasion, resulted in up to 40% adhesion-free laminectomy sites in controls. Model B, which did incorporate abrasion of the dural membrane, resulted in less than 10% adhesion-free laminotomy sites in controls. Compositions of CMC/PEO gels (2.5% to 10% PEO) and films (22.5% PEO) were tested in both models. Efficacy parameters included measuring the number of sites free of epidural fibrosis and reduction in the severity of fibrosis (adhesions). Both gels and gel/film combinations consistently reduced the frequency and the extent of epidural fibrosis in both models. Gels of CMC/PEO containing a higher content of PEO (10%) and a higher molecular weight of PEO (4.4 mD) were most effective in Model B and resulted in up to 84% laminotomy sites with minimal or no epidural fibrosis, whereas controls exhibited over 90% of the sites with epidural fibrosis. Histological evaluation of the surgical sites indicated that the reduction of epidural fibrosis was accompanied by normal bone healing. In addition, these experiments demonstrated that the gel/film combination provided no additional benefit to that obtained by the gel alone. CONCLUSIONS: Gels of CMC/PEO reduced epidural fibrosis and did not impair normal heal ing.     

Pravastatin therapy is associated with reduction in coronary allograft vasculopathy in pediatric heart transplantation.

BACKGROUND: Hydroxymethylglutaryl CoA reductase inhibitors (statins) have been demonstrated to reduce the risk of developing coronary allograft vasculopathy (CAV) following heart transplantation in adults and are used routinely in many centers. CAV and lipid abnormalities have been reported to be less prevalent in pediatric heart transplant recipients. It is not known whether statins reduce the risk of CAV in this population METHODS: A retrospective review was performed to analyze the risk factors for developing CAV following pediatric heart transplantation with particular attention to the impact of pravastatin therapy. The study population was comprised of 129 pediatric patients who underwent 142 heart transplants at our institution from 1988 to 2003. The outcome variable was freedom from CAV, CAV being determined by coronary angiography or autopsy. RESULTS: CAV was identified in 25 recipients at a median of 3.7 years after transplantation. There were 331 patient-years of pravastatin therapy. Pravastatin therapy resulted in a reduction in total cholesterol levels, 162 +/- 29 to 137 +/- 20 mg/dl, p = 0.01. In multivariate analysis the use of pravastatin was associated with a lower incidence of CAV (p = 0.03), whereas an increased frequency of late rejection (p = 0.003) and earlier year of transplantation (p = 0.04) were associated with increased risk of CAV. CONCLUSIONS: The routine use of pravastatin was associated with a lower risk following pediatric heart transplantation. Further studies into the relationship between lipid abnormalities, inflammation and rejection, and the development of CAV in children are warranted.     

Consumer adverse drug reaction reporting: a new step in pharmacovigilance?

The direct reporting of adverse drug reactions by patients is becoming an increasingly important topic for discussion in the world of pharmacovigilance. At this time, few countries accept consumer reports. We present an overview of experiences with consumer reporting in various countries of the world. The potential contribution of patient reports of adverse drug reactions is discussed, both in terms of their qualitative and quantitative contribution. The crucial question is one of whether patient reports will increase the number and quality of the reports submitted and/or lead to a more timely detection of signals of possible adverse reactions, thus contributing to an enhancement of the existing methods of drug safety monitoring. To date, the data available are insufficient to establish such added value.     

Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency.

Clinical and immunologic features of a recently recognized X-linked combined immunodeficiency disease (XCID) suggested that XCID and X-linked severe combined immunodeficiency (XSCID) might arise from different genetic defects. The recent discovery of mutations in the common gamma chain (gamma c) gene, a constituent of several cytokine receptors, in XSCID provided an opportunity to test directly whether a previously unrecognized mutation in this same gene was responsible for XCID. The status of X chromosome inactivation in blood leukocytes from obligate carriers of XCID was determined from the polymorphic, short tandem repeats (CAG), in the androgen receptor gene, which also contains a methylation-sensitive HpaII site. As in XSCID, X-chromosome inactivation in obligate carriers of XCID was nonrandom in T and B lymphocytes. In addition, X chromosome inactivation in PMNs was variable. Findings from this analysis prompted sequencing of the gamma c gene in this pedigree. A missense mutation in the region coding for the cytoplasmic portion of the gamma c gene was found in three affected males but not in a normal brother. Therefore, this point mutation in the gamma c gene leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Whole-body and segmental bioelectrical-impedance analysis in patients with cirrhosis of the liver: changes after treatment of ascites.

Bioelectrical impedance analysis (BIA) is a simple technique for determining body water and calculating body composition. It has been validated in healthy control subjects but not in patients with liver disease. We examined the ability of BIA to detect changes in total body water (TBW) due to removal of ascites. In 12 cirrhotic patients, BIA of the whole body and of body segments was performed before and after treatment of ascites with paracentesis (n = 12) and diuretics (n = 2). TBW changes predicted by BIA, by using two prediction equations, were significantly less than body weight changes (51% and 45% of the weight loss). BIA of body segments showed highly significant changes in both the trunk and the leg and small changes in the arm. These data indicate that BIA of the whole body is not a suitable technique for monitoring fluid changes in cirrhotic patients with ascites. Changes in BIA of body segments may be due to mobilization of edema after the removal of ascites.     

The Parallel Process in Clinical Supervision With a Schizophrenic Client

The authors analyze a male nurse's account of how he experienced his interaction with a female schizophrenic client during sessions of systematic clinical supervision. Notes taken during 15 sessions were analyzed by means of open coding. The analysis revealed the importance of being aware of the parallel process that occurs among the client, the primary nurse, and the unit staff.     

Relation of 5'-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia.

Ecto-5'-nucleotidase (ecto-5'NT) catalyzes the extracellular dephosphorylation of nucleotides like IMP. Cytoplasmic 5'NT (cyto-5'NT) and non-specific (e.g. acid- and alkaline) phosphatases (AP) regulate the intracellular degradation of nucleotides. High NT and AP activities might cause a resistance to the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We studied the relation between these enzymes and immunophenotype, drug resistance and prognosis in 77 children with acute lymphoblastic leukemia (ALL). Enzyme activities were assessed radiochemically; in vitro drug resistance was measured with the MTT assay. AP activities were higher in T-ALL and B-ALL than in precursor B-ALL. Cyto-5'NT activity was very low in all phenotypes and accounted for a significant proportion of total IMPase activity only in the very immature CD10- c mu- precursor B-ALL. CD10+ ALL cases with high ecto-5'NT activities showed a trend (p = 0.065) for a lower probability of continuous complete remission than those with a low activity. Ecto-5'NT activity was not related to in vitro drug resistance to 6-TG. A weak correlation was found between in vitro 6-TG resistance and cyto-5'NT and AP activities. We conclude that high ecto-5'NT activities do not cause a resistance to 6-thiopurines in childhood ALL. Some patients have high cyto-5'NT and AP activities associated with 6-thiopurine resistance.     

The accumulation of copper by microvillar vesicles isolated from human placenta.

Copper uptake from copper-dihistidine complexes by microvillar vesicles from human placenta was studied. Uptake occurred in two phases: a rapid initial binding followed by approximately linear uptake to equilibrium at approximately 5 min. The uptake showed temperature dependence, was saturable (apparent Vmax 10.5 +/- 1.6 nmol/(mg protein.4 min), apparent Km of 0.6 +/- 0.12 mumol/L) and decreased with increasing osmotic pressure, showing that the Cu uptake arose from accumulation within the vesicles and not from extravesicular binding or isotope exchange. Ceruloplasmin blocked uptake of 64Cu from 64Cu-dihistidine by the vesicles, with 50% inhibition achieved at a protein concentration of 5-10 mumol/L and a 64Cu-dihistidine concentration of 1.5 mumol/L. The effect was specific, because glucose oxidase, a noncopper protein, increased apparent uptake by binding copper and in turn being bound to the nitrocellulose membranes used to separate vesicles from incubation medium. Adding increasing concentrations of histidine also decreased uptake. The data presented indicate that the placenta can accumulate copper from copper-dihistidine, that ceruloplasmin can interfere with uptake and that this system will be very valuable in elucidating the first stage in transfer of copper across the placenta.     

MANAGEMENT OF SEMINOMA OF THE TESTIS: RECOMMENDATIONS BASED ON TREATMENT RESULTS

Background : The results of management of seminoma of the testis at the Department of Radiation Oncology St Vincent's Hospital, Sydney were evaluated retrospectively to: (i) establish that outcomes were in keeping with published results from centres in Australia and overseas; (ii) assess the impact of chemotherapy on management; and (iii) to determine ‘best practice’ management protocols based on our results and a review of the relevant literature. Methods : (i) Assessment of treatment results for stage I and II seminoma of the testis treated by post-orchidectomy radiotherapy and/or chemotherapy at St Vincent's Hospital between 1979 and 1993; (ii) literature review of published data from Australian and overseas centres on the management of seminoma of the testis, and in particular the use of surveillance or chemotherapy either alone, at time of relapse or combined with radiotherapy; and (iii) development of recommendations for use as management protocols in our department. Results : Our data and a review of the literature suggest that post-orchidectomy radiotherapy with chemotherapy for relapse in stage I and IIA disease results in long-term cure rates approaching 100%. Treatment with chemotherapy either routinely or selectively or using a surveillance policy is unlikely to show any improvement in outcome and may be less cost-effective and/or produce increased morbidity and the risk of secondary leukaemia. For stage IIB disease (5–10 cm) the use of initial combination chemotherapy with or without subsequent radiotherapy did not appear to give better outcomes than initial radical radiotherapy alone, reserving chemotherapy or further radiotherapy for relapse. For bulkier stage IIB disease (> 10cm). the use of initial chemotherapy plus consolidation radiotherapy appeared to be an appropriate treatment. Conclusions : Management protocols for seminoma of the testis at St Vincent's Hospital, Sydney Department of Radiation Oncology currently are (i) stage I, IA and IIB (5–10 cm): post-orchidectomy radiotherapy alone with chemotherapy or further radiotherapy for relapse; and (ii) stage IIB (> 10 cm) disease: initial chemotherapy post-orchidectomy followed by radiotherapy to sites of initial disease involvement.