Intrathecal Ziconotide in the Treatment of Chronic Nonmalignant Pain: A Randomized,Double‐Blind,Placebo‐Controlled Clinical Trial

Objective. The safety and efficacy of intrathecal (IT) ziconotide was studied in a randomized, double‐blind, placebo‐controlled trial. Materials and Methods. Patients (169 ziconotide, 86 placebo) with severe chronic nonmalignant pain unresponsive to conventional therapy and a visual analog scale of pain intensity (VASPI score) ≥ 50 mm were treated over a 6‐day period in an inpatient hospital setting. Initial starting dose was 0.4 µg/hour and was titrated to analgesia or intolerance (maximum dose 7.0 µg/hour). The starting and maximum doses were reduced to 0.1 µg/hour and 2.4 µg/hour, respectively, due to adverse events (AEs). Results. The mean percent reduction in VASPI score from baseline was 31.2% and 6.0% for ziconotide‐ and placebo‐treated patients, respectively (p ≤ 0.001). During the initial titration phase, a significantly greater percentage of patients in the ziconotide group compared to the placebo group reported AEs, including abnormal gait, amblyopia, dizziness, nausea, nystagmus, pain, urinary retention, and vomiting. Conclusion. Ziconotide provided significant analgesia in patients for whom conventional therapy failed. However, there was a considerable incidence of ziconotide‐associated AEs due to the rapid titration and high doses administered.     

Models,strategies, and tools

This paper presents a case for careful consideration of theory in planning to implement evidence-based practices into clinical care. As described, theory should be tightly linked to strategic planning through careful choice or creation of an implementation framework. Strategies should be linked to specific interventions and/or intervention components to be implemented, and the choice of tools should match the interventions and overall strategy, linking back to the original theory and framework. The thesis advanced is that in most studies where there is an attempt to implement planned change in clinical processes, theory is used loosely. An example of linking theory to intervention design is presented from a Mental Health Quality Enhancement Research Initiative effort to increase appropriate use of antipsychotic medication among patients with schizophrenia in the Veterans Health Administration.     

Choristomas of the seventh and eighth cranial nerves.

Choristomas, masses of normal tissues in aberrant locations, contain smooth muscle fibers and fibrous tissues. We describe the MR imaging features of two choristomas located in the internal auditory canals and arising from the facial and vestibulocochlear nerves. Both lesions enhanced with contrast material. In one case, enhancement was seen in the geniculate ganglion and greater superficial petrosal nerve. In the other, a medial component enhanced less than the lateral component did.     

Associations between soil lead and childhood blood lead in urban New Orleans and rural Lafourche Parish of Louisiana.

This study evaluates associations between soil lead concentrations (SPb), age of housing, and blood lead levels (BPb) of children in metropolitan New Orleans and Lafourche Parish, Louisiana. The database includes over 2,600 SPb and 6,000 BPb samples paired by their median values and pre-1940 housing percentages for 172 census tracts. Associations were evaluated with Fisher's exact test and Spearman's rho test and modeled with the least sum of absolute deviations regression. Census tracts with low SPb are associated with new housing, but census tracts with high SPb are evenly split between old and new housing [Fisher's exact test, p = 8.60 X 10(-13) for the percentage of housing built before 1940 (percent pre-1940 housing) versus SPb]. The p-value for SPb versus BPb is 12 orders of magnitude stronger than the p-value for percent pre-1940 housing versus BPb. Census tracts with low BPb are associated with new housing, but census tracts with high BPb are split evenly between old and new housing (Fisher's exact test, p = 1. 67 X 10(-12) for percent pre-1940 housing versus BPb). Census tracts with high SPb are associated with high BPb and census tracts with low SPb are associated with low BPb (Fisher's exact test, p = 3.18 X 10(-24) for BPb versus SPb). The Spearman's rho test of the association of SPb and BPb in Orleans and Lafourche Parishes yielded a p-value of 6.12 X 10(-24). The least sum of absolute deviations regression model of the data is BPb = 1. 845 + 0.7215 (SPb)0.4. A comparison of the modeled BPb versus observed BPb has an r(2) of 0.552 and a p-value of 2.83 X 10(-23) that this relation was due to chance. If blood lead in children is more closely associated to soil lead than to the age of housing, then primary lead prevention should also include soil lead.     

Factors affecting the toxicity of rotting carcasses containing Clostridium botulinum type E

Mice killed shortly after receiving c. 2000 spores of a type E strain of Clostridium botulinum per os were incubated at one of five chosen temperatures together with bottles of cooked meat medium seeded with a similar inoculum. After incubation the rotting carcasses were homogenized. Sterile membrane filtrates of the homogenates (10%, w/v) and pure cultures were then titrated for toxicity. Some of the main findings were confirmed with two further type E strains. Toxicity produced at 37 degrees C was poor in both carcasses and cultures (200-20,000 mouse intraperitoneal LD/g or ml). It was good in both systems at 30 and 23 degrees C, usually reaching 20,000-200,000 LD/g or ml, and in carcasses occasionally more; at 30 degrees C maximal toxicity was reached more quickly in carcasses than in cultures. Prolonged incubation (36-118 days) at 30 or 23 degrees C resulted in complete loss of toxicity in virtually all carcasses but not in cultures. At 16 degrees C the development of toxicity in carcasses was strikingly greater than in cultures. At 9 degrees C neither system produced more than slight toxicity after prolonged incubation. Trypsinization increased the toxicity of cultures but not usually of carcasses. Unfiltered carcass homogenate (10%, w/v) with maximal intraperitoneal toxicity was harmless for mice by mouth in doses of 0.25 ml. These findings differed in important respects from those made earlier with a type C strain.     

Herpes zoster: a consideration in the differential diagnosis of radiculopathy

Herpes zoster probably occurs more often than generally thought. Since it produces a radicular distribution of pain, it should be included in the differential diagnosis of radiculopathy. A case is presented in which evaluating the radicular low back pain before the characteristic rash appears was misleading. Careful history-taking concerning the exact nature of the pain and sensory changes is needed to differentiate between zoster and radiculopathy, if no rash is evident.     

The neutrophil oxidative burst in diarrhoea – associated haemolytic uraemic syndrome

. Neutrophil-mediated tissue damage has been implicated in the pathogenesis of diarrhoea-associated haemolytic uraemic syndrome (D+ HUS). This study evaluates priming and activation of the neutrophil oxidative burst in D+ HUS using chemiluminescent techniques. Peripheral blood neutrophils from 11 children with acute D+ HUS were examined. No difference was found in the oxidative burst of neutrophils from patients and controls. Serum elastase levels were measured in 8 patients and found to be significantly elevated. Although elastase results suggest neutrophil activation, chemiluminescence studies do not confirm this in the peripheral blood neutrophil. This does not support a significant role for circulating agents in priming and activating the peripheral blood neutrophil. Received August 17, 1995; received in revised form and accepted November 27, 1995     

Segregation analysis of leprosy in families of northern Thailand

Sixty-three families with multiple instances of leprosy were identified through a major leprosy treatment center in northern Thailand. Complex segregation analyses for single major genes or polygenic inheritance were performed using the maximum-likelihood routine POINTER to determine the most likely etiologic model of genetic susceptibility. Liability differences between men and women were considered in these models. When individuals were considered to be affected because they had any form of leprosy, a generalized major gene model with nearly dominant parameters on the liability scale, but additive penetrances, was found to be the most likely. When only those individuals who had tuberculoid forms of leprosy were considered to be affected, a recessive model was found to be the most likely; however, the discrimination between various models was poor. Further analyses are necessary to delineate genetic mechanisms to explain these apparently divergent results. In particular, methods of testing two locus models should be considered.     

Oligoclonal populations of T and B cells in a case of angioimmunoblastic T-cell lymphoma predominantly infiltrated by T cells of the VB5.1 family.

AIMS: Immunohistological and molecular characterisation of a case of peripheral T-cell lymphoma (PTCL) of angioimmunoblastic T-cell lymphoma (AILD) type. METHODS: Frozen and paraffin wax sections of the diagnostic lymph node were stained with a panel of T- and B-cell lineage monoclonal antibodies. DNA was isolated from the paraffin wax embedded biopsy material for T-cell receptor (TCR) and immunoglobulin (Ig) PCR amplification, and resultant PCR products were cloned and sequenced. RESULTS: Immunohistological analysis of the presenting lymph node was consistent with an extensive infiltrate of pleomorphic CD3+CD8+ lymphocytes. Most (>80%) of these infiltrating CD3+ cells were also positive for the TCR VB5.1 gene family product, and were shown to be oligoclonal by TCRB PCR amplification and sequencing. Three oligoclones of B cells were also demonstrable by PCR amplification with Ig heavy chain primers and sequencing, a finding at variance with the diagnosis of AILD. CONCLUSIONS: These data demonstrate the complexity and heterogeneity of PTCL which require extensive histological examination and molecular characterisation.     

Two Novel Pyrrolopyrimidine Lipid Peroxidation Inhibitors U-101033E and U-104067F Protect Facial Motor Neurons Following Neonatal Axotomy

Recent reports suggest that oxygen radical-induced lipid peroxidation plays a role in the retrograde degeneration of motor neurons following facial nerve axotomy in the neonatal rat. The purpose of the present study was to explore this notion further by testing the neuroprotective properties of two novel brain-penetrating, lipid peroxidation inhibitors, U-101033E and U-104067F, in this model of neuronal degeneration. In Experiment 1, 14-day-old rats were pretreated with 3, 10, or 30 mg/kg U-101033E (po) 10 min before right facial nerve axotomy (Day 0) and then posttreated once a day from Day 1 to Day 6, and once every other day from Day 8 to Day 21. Rats were sacrificed 21 days postaxotomy and surviving cholinergic cell bodies were identified using choline acetyltransferase immunocytochemistry. Both 10 and 30 mg/kg U-101033E significantly enhanced motor neuron survival, with survival rates of 65.9–88.9% being noted in comparison to 51.7–62% survival in vehicle controls (P ≤ 0.05). Experiment 2 demonstrated a significant neuroprotective effect of 10 and 30 mg/kg U-104067F using the same dosing schedule. Experiment 3 was designed to test whether shorter periods of drug exposure (e.g., 5 or 7 days) would be sufficient to preserve motor neurons in rats treated with 10 mg/kg U-101033E. The results suggested that as little as 5 days of drug treatment is sufficient to enhance motor neuron survival. Finally, Experiment 4 demonstrated an 18–19% increase in motor neuron survival in rats treated with 10 and 30 mg/kg U-104067F for 5 consecutive days postaxotomy. Taken together, the attenuation of motor neuron degeneration by the two pyrrolopyrimidine lipid peroxidation inhibitors, U-101033E and U-104067F, lends support to the notion that lipid peroxidation contributes to the pathogenesis of axotomy-induced neurodegeneration.