N-acetylaspartate is an axon-specific marker of mature white matter in vivo: a biochemical and immunohistochemical study on the rat optic nerve.

Axonal pathology is a major cause of neurological disability in multiple sclerosis. Axonal transection begins at disease onset but remains clinically silent because of compensatory brain mechanisms. Noninvasive surrogate markers for axonal injury are therefore essential to monitor cumulative disease burden in vivo. The neuronal compound N-acetylaspartate, as measured by magnetic resonance spectroscopy, is currently the best and most specific noninvasive marker of axonal pathology in multiple sclerosis. The possibility has been raised, however, that N-acetylaspartate is expressed also by oligodendroglial lineage cells. In order to investigate N-acetylaspartate specificity for white matter axons, transected rat optic nerves were analyzed by high-performance liquid chromatography and immunohistochemistry. In transected adult nerves, N-acetylaspartate and N-acetyl aspartylglutamate decreased in concordance with axonal degeneration and were undetectable 24 days posttransection. Nonproliferating oligodendrocyte progenitor cells, oligodendrocytes, and myelin were abundant in these axon-free nerves. At 24 days posttransection, N-acetylaspartate was increased (42%; p = 0.02) in nontransected contralateral nerves. After transection at postnatal day 4, total N-acetylaspartate decreased by 80% (P14; p = 0.002) and 94% (P20; p = 0.003). In these developing axon-free nerves, 25 to 33% of oligodendrocyte progenitor cells were proliferating. These data validate magnetic resonance spectroscopy measurements of N-acetylaspartate as an axon-specific monitor of central nervous system white matter in vivo. In addition, the results indicate that neuronal adaptation can increase N-acetylaspartate levels, and that 5 to 20% of the N-acetylaspartate in developing white matter is synthesized by proliferating oligodendrocyte progenitor cells.     

AIDS and tuberculosis

The diagnostic and therapeutic implications of human immunodeficiency virus (HIV) infection and tuberculosis in South Africa, where tuberculosis remains a major health problem, are reviewed. Mycobacterium tuberculosis is a high-grade pathogen and is able to establish infection early in immunodeficiency. With HIV infection showing significant entry into the heterosexual population in the RSA, an increasing number of cases with both infections can be expected to occur. The radiological appearance in combined infection is variable, ranging from a formal cavitatory picture to the more common finding of diffuse pulmonary infiltration. Intrathoracic adenopathy is a more specific sign of tuberculosis in HIV infection, since it is not associated with persistent generalised lymphadenopathy and pulmonary opportunistic infections, such as Pneumocystis carinii pneumonia. Intercurrent pneumonic infections and other pulmonary manifestations of HIV disease render the interpretation of new infiltrates on chest radiography problematical. Tuberculin skin testing remains useful in HIV infection and should be performed in all HIV-infected patients. The value of tuberculosis serology still remains questionable. Standard antituberculosis drug regimens are effective, but maintenance treatment must be continued for life and should include isoniazid and rifampicin. BCG vaccination is recommended routinely at birth in infants with HIV infection and for asymptomatic HIV-infected individuals who have not previously been immunised.     

Simultaneous assay of felbamate plus carbamazepine, phenytoin, and their metabolites by liquid chromatography with mobile phase optimization

Felbamate is an investigational antiepileptic drug (AED) in clinical trials. A high-performance liquid chromatographic method for the simultaneous analysis of felbamate, phenytoin (PHT), 5-(p-hydroxyphenyl)-5-phenylhydantoin, carbamazepine (CBZ), carbamazepine-10,11-epoxide, and carbamazepine-10,11-diol in serum was developed by a mobile phase optimization technique. Capacity factors for the compounds of interest and 12 other AEDs and metabolites were determined with mixtures of methanol, acetonitrile, or tetrahydrofuran and a 0.01 M ammonium phosphate buffer, pH 6.5, on a reversed-phase C8 column. An optimized mobile phase composition was determined that could separate the compounds of interest and three internal standards in less than 15 min. Serum was extracted with CH2Cl2/ethyl acetate (2:1) after addition of three internal standards. The method was validated for within-day and between-day precision and accuracy for the six compounds. Coefficients of variation were generally less than 10% at all concentrations and less than 5% in the typical therapeutic range for each compound. The lower limit of detection was estimated at 0.2 micrograms/ml for CBZ and its metabolites and 0.5 micrograms/ml for felbamate and PHT. For felbamate, the lowest point on the standard curve was 1.88 micrograms/ml with a between-day variability of 10.3%. The assay was used to determine the serum concentrations of PHT and CBZ and its metabolites in a subject before, during, and after felbamate therapy.     

Granulomatous Pneumocystis carinii pneumonia in a patient with the acquired immunodeficiency syndrome.

A patient with an unusual granulomatous response to infection with Pneumocystis carinii is described. The diagnosis was made by open lung biopsy after two negative bronchoalveolar lavages.     

Race/ethnicity and gender differences in the drugs-violence relationship

This article examines the drug relatedness of violent events reported by White, Black, and Hispanic male and female street drug users from New York City. The primary purpose is to determine if the drugs-violence relationship varies for these different populations of drug abusers. Drug relatedness is assessed according to a tripartite conceptual model of the general relationship between drugs and violence. Significant race/ethnicity and gender differences were found in regard to the number of violent events manifesting specific drug-related dimensions of violence, the drugs associated with these violent events, and the primary reasons for the occurrence of these events. The implications of these findings are discussed.     

Adequacy of hormone replacement therapy for osteoporosis prevention assessed by serum oestradiol measurement, and the degree of association with menopausal symptoms.

BACKGROUND: Patients on hormone replacement therapy (HRT) for osteoporosis prevention rather than menopausal symptom control may be asymptomatic, despite inadequate replacement and low serum oestradiol (E2) levels. In the primary health care setting, therapeutic monitoring of HRT is not carried out routinely so that patients with serum E2 levels inadequate to protect bone may be missed. AIM: To determine the proportion of women on transdermal E2 preparations with serum E2 levels insufficient to protect bone and to assess the value of a questionnaire-derived menopausal symptom score (MSS) for detecting these patients. METHOD: A cross-sectional analysis of 45 patients aged 35-70 years using transdermal E2 preparations obtained from a computer register of 14500 patients in a suburban practice. One blood sample was obtained from each patient at the time the MSS questionnaire was completed. Serum E2 concentration was measured using a fluoroimmunoassay and compared with the MSS. Levels below 150 pmol/l were considered to be insufficient to protect bone. The diagnostic accuracy of the MSS in screening for levels below 150 pmol/l was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: The median (95% CI) serum E2 was 147 pmol/l (126-198 pmol/l) and levels were below 150 pmol/l in 24 out of 45 patients. There was no difference in the MSS (median, 95% CI) between those with serum E2 < 150 pmol/l (8.5, 5.0-17) and > or = 150 pmol/l (9.0, 5.0-14; P = 0.477). The degree of association between the serum E2 and the MSS, using the Spearman rank correlation coefficient, rs (95% CI) was small and not significant (-0.04, -0.34 to 0.26; P = 0.398). ROC curve analysis revealed an area under the curve (95% CI) of 0.51 (0.33-0.68). CONCLUSIONS: More than half the women were inadequately replaced to protect against osteoporosis. Furthermore, the MSS was of no value in screening for those with low serum E2 levels. Serum E2 levels should be monitored in women on HRT for osteoporosis prevention and the E2 dosage adjusted accordingly.     

Body pain and treatment response in late-life depression.

OBJECTIVE: The authors investigated the influence of body pain on 1) time to treatment response and 2) suicidal ideation, in late-life depression. They hypothesized that higher levels of body pain would predict a longer time to and lower likelihood of response, and increased levels of suicidal ideation. METHODS: Subjects (N=187) were older adult outpatients (age > or =69 years), with current episodes of major depression, who were openly treated with paroxetine up to 40 mg daily and weekly interpersonal psychotherapy. Response was defined as 3 consecutive weeks of Hamilton Rating Scale for Depression at < or =10. Body pain was measured with the Bodily Pain Index of the SF-36 quality-of-life assessment. Authors used survival-analysis models on the responder sample to test the effect of body pain on response, after controlling for severity of depression. RESULTS: Overall response rate was 75.4%. Nonresponders reported more severe pain at baseline. After covarying for severity of baseline depression, no effect was found for physical pain on time-to-response or degree of suicidality. Bodily pain remained stable during acute treatment for responders, independent of depression response to combination psychotherapy and antidepressant treatment. CONCLUSIONS: Older adult patients with higher levels of physical pain can still respond to antidepressant treatment; however, reported bodily pain may be associated with a more difficult-to-treat depression.     

Severe hypokalemia in thyrotoxic periodic paralysis

Thyrotoxic hypokalemic periodic paralysis is an uncommon but sometimes fatal disease in which early recognition and therapy may prevent untoward complications. The case of a 26-year-old Chinese man who presented to the emergency department with rapidly progressive profound weakness and severe hypokalemia (serum potassium, 1.2 mEq/L) is presented. The patient required endotracheal intubation, ventilatory assistance, and intravenous potassium administration. Emergency medical evaluation and management of this entity are discussed.     

System for prostate brachytherapy and biopsy in a standard 1.5 T MRI scanner.

A technique for transperineal high-dose-rate (HDR) prostate brachytherapy and needle biopsy in a standard 1.5 T MRI scanner is demonstrated. In each of eight procedures (in four patients with intermediate to high risk localized prostate cancer), four MRI-guided transperineal prostate biopsies were obtained followed by placement of 14-15 hollow transperineal catheters for HDR brachytherapy. Mean needle-placement accuracy was 2.1 mm, 95% of needle-placement errors were less than 4.0 mm, and the maximum needle-placement error was 4.4 mm. In addition to guiding the placement of biopsy needles and brachytherapy catheters, MR images were also used for brachytherapy treatment planning and optimization. Because 1.5 T MR images are directly acquired during the interventional procedure, dependence on deformable registration is reduced and online image quality is maximized.