Cutaneous Vasculopathy and Neutropenia Associated With Levamisole-Adulterated Cocaine

BackgroundLevamisole has recently been implicated as a cause of cutaneous vasculopathy in cocaine abusers. The objective of this study was to describe this relatively new entity by reviewing published cases identified through a literature search.MethodsPublished reports identified through a search of PubMed database (from 1964 to November 2011) were reviewed to record clinical, serological and pathologic findings.ResultsA cohort of 32 patients had a mean age of 44 ± 9 years with a female predominance (75%). Rash predominately affected lower extremities (87.5%), followed by face (78%) and ears (69%) and typically presented as purpuric plaques, which were seen in a retiform pattern in 16 (50%) and had central necrosis in 11 patients (34%). Leukopenia and neutropenia were found in 20 patients (63%). Antinuclear cytoplasmic antibody (ANCA) was positive in 30 patients (94%); p-ANCA in 28 patients (87.5%), c-ANCA in 19 (59%) and both in 17 patients (53%). Skin biopsy results were available for 29 patients: 14 (48%) had pure thrombotic vasculopathy, 4 (14%) had pure small vessel vasculitis and 11 (38%) had evidence of both. Treatment information was available for 30 patients. Only supportive care was given to 11 patients (37%), steroids to 16 (53%) and surgical treatment for 5 (17%). Clinical course of lesions was available for 24 patients. Rash resolved in 11 patients (46%) and improved in 13 (54%). During median follow-up of 21 days (range, 7–270 days), 10 of 22 patients had recurrences related to cocaine use.ConclusionLevamisole-induced cutaneous vasculopathy in cocaine users is characterized by a female predominance, a retiform purpuric rash with a predilection for lower extremities, autoantibody production, leukopenia and/or neutropenia and recurrences with future cocaine use.     

Quality and patient safety in the diagnosis of breast cancer

The media, medical legal, and safety science perspectives of a laboratory medical error differ and assign variable levels of responsibility on individuals and systems. We examine how the media identifies, communicates, and interprets information related to anatomic pathology breast diagnostic errors compared to groups using a safety science Lean-based quality improvement perspective. The media approach focuses on the outcome of error from the patient perspective and some errors have catastrophic consequences. The medical safety science perspective does not ignore the importance of patient outcome, but focuses on causes including the active events and latent factors that contribute to the error. Lean improvement methods deconstruct work into individual steps consisting of tasks, communications, and flow in order to understand the affect of system design on current state levels of quality. In the Lean model, system redesign to reduce errors depends on front-line staff knowledge and engagement to change the components of active work to develop best practices. In addition, Lean improvement methods require organizational and environmental alignment with the front-line change in order to improve the latent conditions affecting components such as regulation, education, and safety culture. Although we examine instances of laboratory error for a specific test in surgical pathology, the same model of change applies to all areas of the laboratory.     

The contribution of single antigen measles, mumps and rubella vaccines to immunity to these infections in England and Wales.

OBJECTIVE: To obtain information on the use of single antigen measles, mumps and rubella vaccines to improve estimates of population immunity and help predict outbreaks. DESIGN: We requested information from providers of single antigen vaccines and from the Medicine and Healthcare products Regulatory Agency on requests for importation of single antigen measles and mumps vaccines. SETTING: England and Wales. MAIN OUTCOME MEASURES: Number of doses of single measles, mumps and rubella vaccine, by age of child (in months), year given and area of residence, and number of children who have received all three single vaccinations. RESULTS: Of 27 providers identified, 13 held single site clinics: nine were individual general practitioners and five held clinics at multiple sites. Data were received from 9/27 (33%) providers operating 40/74 (54%) clinic sites. We received information on 60 768 vaccinations administered by single vaccine providers and 269 917 doses requested for importation. For children born in 2001/2002, the minimum estimates for the proportion who received single measles vaccine are 1.7% in 2001 and 2.1% in 2002, with a reasonable maximum estimate of 5.6% over the 2 years. For single mumps vaccine, the minimum estimates are 0.3% in 2001 and 0.02% in 2002, with a maximum estimate of 4.0%. CONCLUSION: The contribution of single vaccines to immunity is small in comparison to that of the combined measles, mumps and rubella vaccine (MMR). For recent birth cohorts this contribution could increase routine coverage for measles-containing vaccines by around 2%, still below the level of immunity required to sustain elimination.     

Developmental patterns from 1 to 4 years of extremely preterm infants who required home oxygen therapy

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains a common complication of prematurity, with those being discharged on home oxygen at particularly high risk of adverse developmental outcomes. AIMS: To compare the developmental patterns, from 1 to 4 years, of extremely preterm infants with BPD discharged from hospital on home oxygen, extremely preterm infants with BPD discharged breathing room air, and extremely preterm infants without BPD. SUBJECTS: Two hundred and seventy-six infants with a gestational age of <28 weeks or birthweight <1000 g, free from sensory and motor disabilities who were followed up longitudinally to 4 years corrected age. OUTCOME MEASURES: Children were assessed on the Griffiths Mental Development Scales at 1 and 2 years corrected age, and the McCarthy Scales of Children's Abilities at 4 years corrected age. RESULTS: The developmental trajectories of the three groups did not differ significantly, however at 1 year corrected age the non-BPD group had significantly higher developmental scores than both BPD groups. At 2 years corrected age the non-BPD group had significantly higher developmental scores than the BPD-home oxygen group, and at 4 years corrected age no differences between the groups were evident. CONCLUSIONS: Extremely preterm children with BPD exhibited an initial developmental lag compared to preterm peers. Children with BPD discharged breathing room air had developmental scores at 2 years corrected age that were comparable to the non-BPD group, but those discharged on home oxygen still had lower developmental scores. At 4 years, no differences between the groups were evident.     

Expansion and hepatocytic differentiation of liver progenitor cells in vivo using a vascularized tissue engineering chamber in mice

Current cell-based treatment alternatives to organ transplantation for liver failure remain unsatisfactory. Hepatocytes have a strong tendency to dedifferentiate and apoptose when isolated and maintained in culture. In contrast, liver progenitor cells (LPCs) are robust, easy to culture and have been shown to replace damaged hepatocytes in liver disease. In this study we investigate whether isolated LPCs can survive and differentiate toward mature hepatocytes in vivo when implanted into a heterotopic mouse tissue engineering chamber model. Healthy Balb/c mice and those put on a choline-deficient ethionin-supplemented diet to induce chronic liver disease were implanted with a tissue engineering chamber based on the epigastric flow through pedicle model, containing either 1?×?10(6) LPCs suspended in Matrigel, or LPC-spheroids produced by preculture for 1 week in Matrigel. Four weeks after implantation the chamber contents were harvested. In all four groups, progenitor cells persisted in large numbers to 4 weeks and demonstrated evidence of considerable proliferation judged by Ki67-positive cells. Periodic acid Schiff staining demonstrated differentiation of some cells into mature hepatocytes. Constructs grown from LPC-spheroids demonstrated considerably greater LPC survival than those from LPCs that were grown as monolayers and implanted as dissociated cells. The combined use of LPC spheroids and the vascularized chamber model could be the basis for a viable alternative to current treatments for chronic liver failure.     

γδ T cell migration: Separating trafficking from surveillance behaviors at barrier surfaces

γδ T cells are found in highest numbers at barrier surfaces throughout the body, including the skin, intestine, lung, gingiva, and uterus. Under homeostatic conditions, γδ T cells provide immune surveillance of the epidermis, intestinal, and oral mucosa, whereas the presence of pathogenic microorganisms in the dermis or lungs elicits a robust γδ17 response to clear the infection. Although T cell migration is most frequently defined in the context of trafficking, analysis of specific migratory behaviors of lymphocytes within the tissue microenvironment can provide valuable insight into their function. Intravital imaging and computational analyses have been used to define “search” behavior associated with conventional αβ T cells; however, based on the known role of γδ T cells as immune sentinels at barrier surfaces and their TCR-independent functions, we put forth the need to classify distinct migratory patterns that reflect the surveillance capacity of these unconventional lymphocytes. This review will focus on how γδ T cells traffic to various barrier surfaces and how recent investigation into their migratory behavior has provided unique insight into the contribution of γδ T cells to barrier immunity.