Interpreting cerebrospinal fluid pleocytosis in HIV in the era of potent antiretroviral therapy

Background  

Cerebrospinal fluid (CSF) pleocytosis may be seen in asymptomatic HIV-infected individuals. This finding complicates interpretation of CSF abnormalities when such individuals are evaluated for other central nervous system infections. The goal of this study was to determine the relationship between CSF pleocytosis, central nervous system (CNS) antiretroviral penetration, adherence to antiretroviral medication regimens, neurological symptoms and performance on neuropsychological tests.     

High-dose (131)I-tositumomab (anti-CD20) radioimmunotherapy for non-Hodgkin's lymphoma: adjusting radiation absorbed dose to actual organ volumes.

Radioimmunotherapy (RIT) using (131)I-tositumomab has been used successfully to treat relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Our approach to treatment planning has been to determine limits on radiation absorbed dose to critical nonhematopoietic organs. This study demonstrates the feasibility of using CT to adjust for actual organ volumes in calculating organ-specific absorbed dose estimates. METHODS: Records of 84 patients who underwent biodistribution studies after a trace-labeled infusion of (131)I-tositumomab for RIT (January 1990 and April 2003) were reviewed. Serial planar gamma-camera images and whole-body NaI probe counts were obtained to estimate (131)I-antibody source-organ residence times as recommended by the MIRD Committee. The source-organ residence times for standard man or woman were adjusted by the ratio of the MIRD phantom organ mass to the CT-derived organ mass. RESULTS: The mean radiation absorbed doses (in mGy/MBq) for our data using the MIRD model were lungs = 1.67; liver = 1.03; kidneys = 1.08; spleen = 2.67; and whole body = 0.3; and for CT volume-adjusted organ volumes (in mGy/MBq) were lungs = 1.30; liver = 0.92; kidneys = 0.76; spleen = 1.40; and whole body = 0.22. We determined the following correlation coefficients between the 2 methods for the various organs: lungs, 0.49 (P = 0.0001); liver, 0.64 (P = 0.004); kidneys, 0.45 (P = 0.0004); spleen, 0.22 (P = 0.0001); and whole body, 0.78 (P = 0.0001), for the residence times. For therapy, patients received mean (131)I administered activities of 19.2 GBq (520 mCi) after adjustment for CT-derived organ mass compared with 16.0 GBq (433 mCi) that would otherwise have been given had therapy been based only using standard MIRD organ volumes-a statistically significant difference (P = 0.0001). CONCLUSION: We observed large variations in organ masses among our patients. Our treatments were planned to deliver the maximally tolerated radiation dose to the dose-limiting normal organ. This work provides a simplified method for calculating patient-specific radiation doses by adjusting for the actual organ mass and shows the value of this approach in treatment planning for RIT.     

A novel model to study bacterial adherence to the transplanted airway: Inhibition of Burkholderia cepacia adherence to human airway by dextran and xylitol

BACKGROUND: Lung infection with Burkholderia cepacia complex before lung transplantation in patients with cystic fibrosis is a major risk factor for decreased post-operative survival rates compared with those of patients colonized with the more common opportunistic pathogen Pseudomonas aeruginosa. Because adherence to mucosal surfaces is an important initial step in infection, we investigated the use of non-toxic neutral polysaccharides and a sugar alcohol to prevent adherence of B cepacia complex to allograft airway epithelium. METHODS: We used human airway explants prepared from donor tracheobronchial tissue to test the effect of dextrans and xylitol in inhibiting the binding of Burkholderia cepacia complex. We used immunofluorescence and electron microscopy to determine the distribution of bacteria in the explants. RESULTS: Burkholderia cepacia complex bound to the explants and was found only in the surface mucus layer. Dextran 40 kd applied before adding the bacteria decreased the number of bound organisms by 80% to 99%. Smaller molecular mass dextrans (4 and 20 kd) were ineffective. Xylitol inhibited bacterial binding by 67% to 85%. Both agents seemed to decrease the thickness of the surface mucus, suggesting that they may indirectly inhibit bacterial binding by removing adherent surface mucus. CONCLUSIONS: Treating donor lungs with dextran 40 kd or xylitol before (and possibly after) surgery may inhibit the adherence of Burkholderia cepacia complex to airways and may prevent or decrease subsequent infection of the allografts.     

Differential induction of cytochrome P-450 by the enantiomers of trans-stilbene oxide

Optically pure (+)- and (-)-trans-stilbene oxide (TSO) enantiomers were administered to immature male Sprague-Dawley rats. (+)-TSO was the more potent inducer of liver microsomal cytochrome P-450-dependent monooxygenases. The greater potency of (+)-TSO may be explained on the basis of stereoselective metabolism since a far greater concentration of TSO was found in liver microsomes of (+)-TSO-treated rats. Furthermore, of the enzymes known to metabolize TSO, cytosolic epoxide hydrolase turned over the (-)-TSO enantiomer at a faster rate, consistent with the greater persistence of the (+)-enantiomer. Although this report is of chiral effects in potency of enzyme induction, stereoselective metabolism (i.e. disposition) rather than inherent structural characteristics (recognition) may be responsible for these effects.     

Deaths of heroin users in a general practice population

Recent evidence suggests that heroin users in the UK are 16 times more likely to die than otherwise expected, although causes of death are varied. The present investigation examines deaths of heroin users at a large Scottish general practice over a four-year period prior to 1 July 1985. A mortality rate of 9.72 per 1000 heroin-user patients per year was observed, roughly half that previously reported, although this difference did not prove to be statistically significant. A higher proportion of the observed deaths were attributed to heroin, and fewer to the misuse of other drugs, and it is speculated that this may reflect the practice's policy of not prescribing opiates to heroin users. Factors associated with heroin-user deaths are examined and areas identified where general practitioners may help to avert some of these deaths.     

Importance of community size in practice location decisions of final year residents

Final year residents in training in Louisiana were surveyed regarding plans for medical practice and their perceptions of the importance of various factors in choosing practice locations. Most specialty groups selected smaller communities at similar rates. Growing up in small towns is associated with wanting to practice in small towns while concerns about opportunities for the family and income of the region are associated with wanting to practice in a larger city.This study was supported by the Louisiana Council for Statewide Planning for Physician Manpower through Contract No. 23058, Louisiana Department of Health and Human Resources.Ms. Samaha is a data analyst for the Louisiana Council for Statewide Planning for Physician Manpower; Robert R. Franklin, M.D. is Executive Secretary of the Council and Assistant Professor, Department of Biostatistics and Epidemiolgy, Tulane University School of Public Health and Tropical Medicine; Janet C. Rice is Assistant Pofessor, Department of Biostatistics and Epidemiology at the Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana 70112.     

Apoptosis: understanding the new molecular pathway.

Advances in science have increased the knowledge of how cells die in the body (apoptosis). A basic understanding of this process can improve nurses' ability to review new scientific literature and enable them to provide safer bedside care.     

Levels of Psychological Distress Experienced by Family Carers of Children and Adolescents with Intellectual Disabilities in an Urban Conurbation

Background The aim of the present study was to identify factors associated with the level of psychological distress reported by family carers of children with intellectual disability living in a large urban conurbation. Method Information was collected by postal questionnaire (or interview for family carers who did not have English as their first language) from the family carers of 408 children with intellectual disability (31% of all children within the area administratively identified as having an intellectual disability). Results Results indicated that 47% of primary carers scored above the threshold for psychological distress on the GHQ and that scoring above the threshold was strongly related to the emotional and behavioural needs of the index child and South‐Asian ethnicity and moderately associated with the severity of the child's delay in communication. Conclusions The rates of psychological distress (47% overall, 70% among South‐Asian carers) were markedly higher than that found in previous studies of carers supporting a child with intellectual disabilities. It is suggested that these elevated rates of psychological distress may be mediated by socio‐economic deprivation.