Treatment of vertigo

Vertigo is the illusion of motion, usually rotational motion. As patients age, vertigo becomes an increasingly common presenting complaint. The most common causes of this condition are benign paroxysmal positional vertigo, acute vestibular neuronitis or labyrinthitis, Ménière's disease, migraine, and anxiety disorders. Less common causes include vertebrobasilar ischemia and retrocochlear tumors. The distinction between peripheral and central vertigo usually can be made clinically and guides management decisions. Most patients with vertigo do not require extensive diagnostic testing and can be treated in the primary care setting. Benign paroxysmal positional vertigo usually improves with a canalith repositioning procedure. Acute vestibular neuronitis or labyrinthitis improves with initial stabilizing measures and a vestibular suppressant medication, followed by vestibular rehabilitation exercises. Meniere's disease often responds to the combination of a low-salt diet and diuretics. Vertiginous migraine headaches generally improve with dietary changes, a tricyclic antidepressant, and a beta blocker or calcium channel blocker. Vertigo associated with anxiety usually responds to a selective serotonin reuptake inhibitor.     

First episode psychosis: a novel methodology reveals higher than expected incidence; a reality-based population profile in Northumberland, UK

RATIONALE, AIMS and OBJECTIVES: To document the natural history/clinical course of an unselected population presenting with first episode psychosis across a Mental Health Trust. METHOD: An observational database was set up covering all patients over 15 years of age. Data were collected at presentation and annual follow-up intervals. RESULTS: A total of 227 patients presented during the 3 years initial study period with a first episode psychosis. The commonest diagnoses were psychotic depression 19%, paranoid schizophrenia 11%, persistent delusional disorder 7% and bipolar affective disorder 7.5% giving an annual incidence of 30.36 per 100 000 population. At presentation, half had been admitted to hospital, nearly half of whom were detained under the Mental Health Act, and only a quarter were currently employed. Twenty-six per cent had an episode of deliberate self-harm and 14% had harmed others. A recurring pattern emerged of over half the patients being no longer in contact with mental health services 1 year after presentation. Data collection is ongoing. CONCLUSIONS: Clinical and managerial cooperation achieved a practical framework for data collection. This approach in an unselected population of patients yielded new insights into the course of first episode psychosis. The higher incidence than expected from the literature has implications for local strategic planning and provides a framework for detailed evaluation of a complex patient group.     

Ehrlichia chaffeensis seroprevalence among children in the southeast and south-central regions of the United States

BACKGROUND: The reported annual incidence of human monocytic ehrlichiosis, which is due to infection with Ehrlichia chaffeensis, is as high as 5.5 per million in some states, but serosurveys suggest much higher infection rates in some populations. OBJECTIVE: To estimate the prevalence of E chaffeensis infection among children aged 1 to 17 years living in the southeast and south-central United States. DESIGN: Cross-sectional serosurvey. SETTING: Seven academic pediatric medical centers in the southeastern and south-central United States. PATIENTS: Nineteen hundred ninety-nine children (approximately 300 at each center) having their blood drawn for any reason. MAIN OUTCOME MEASURE: The presence of antibody at 2 different cutoff titers to E chaffeensis, as detected by indirect immunofluorescence assay. RESULTS: Overall, 250 children (13%) had E chaffeensis antibody titers of 1:80 or higher and 61 (3%) had titers of 1:160 or higher. Age-adjusted seroprevalence rates varied widely between sites. At 1:80 or higher, the highest rate was in Winston-Salem, NC (22%), and the lowest was in Louisville, Ky (2%). At 1:160 or higher, the highest rate was in Kansas City, Mo (9%), and the lowest was in Oklahoma City, Okla (<1%). In univariate analyses, no associations were found between seroprevalence at either cutoff value and sex, race, source of specimen, or residence demographics. However, age was a significant predictor of seroprevalence at both cutoff values. In multiple logistic regression analysis, study site and age remained strong predictors of seroprevalence, but living in a nonurban ZIP code was not significantly related. CONCLUSION: Infection with E chaffeensis, or related ehrlichiae, may be more common in children than previously recognized.     

3'-azido-3'-deoxythymidine (AZT) induces apoptosis and alters metabolic enzyme activity in human placenta

The anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) is the drug of choice for preventing maternal-fetal HIV transmission during pregnancy. Our aim was to assess the cytotoxic effects of AZT on human placenta in vitro. The mechanisms of AZT-induced effects were investigated using JEG-3 choriocarcinoma cells and primary explant cultures from term and first-trimester human placentas. Cytotoxicity measures included trypan blue exclusion, MTT, and reactive oxygen species (ROS) assays. Apoptosis was measured with an antibody specific to cleaved caspase-3 and by rescue of cells by the general caspase inhibitor Boc-D-FMK. The effect of AZT on the activities of glutathione-S-transferase, beta-glucuronidase, UDP-glucuronosyl transferase, cytochrome P450 (CYP) 1A, and CYP reductase (CYPR) in the placenta was assessed using biochemical assays and immunoblotting. AZT increased ROS levels, decreased cellular proliferation rates, was toxic to mitochondria, and initiated cell death by a caspase-dependent mechanism in the human placenta in vitro. In the absence of serum, the effects of AZT were amplified in all the models used. AZT also increased the amounts of activity of GST, beta-glucuronidase, and CYP1A, whereas UGT and CYPR were decreased. We conclude that AZT causes apoptosis in the placenta and alters metabolizing enzymes in human placental cells. These findings have implications for the safe administration of AZT in pregnancy with respect to the maintenance of integrity of the maternal-fetal barrier.     

Two methods for rapid serological diagnosis of acute leptospirosis

Leptospirosis is a common and underdiagnosed zoonosis. Two rapid assays for serological diagnosis of acute leptospirosis in diagnostic laboratories, the immunoglobulin M (IgM)-dipstick assay and the indirect hemagglutination assay (IHA), were evaluated and compared with standard assays. Sera were examined from 104 patients admitted to a hospital for investigation in a leptospirosis diagnostic protocol. Specimens for serology were taken on days 1 and 4 of the patients' hospital stay. Antibodies were detected using an IgM-enzyme-linked immunosorbent assay (ELISA), microscopic agglutination test (MAT), an IgM-dipstick assay, and an IHA. Fifty-one patients were found to have leptospirosis. The sensitivity of the IgM-dipstick assay was 98%, its specificity was 90.6%, its positive predictive value was 90.9%, and its negative predictive value was 98%. The sensitivity of the IHA was 92.2%, its specificity was 94.4%, its positive predictive value was 95.9%, and its negative predictive value was 92.7%. The standard IgM-ELISA and MAT, were positive in the first samples tested from 67 and 55% of the cases, respectively, and the rapid IgM-dipstick assay and IHA were positive in 71 and 49%, respectively, in the first sample tested. Both rapid assays are highly sensitive and specific. Neither requires specialized equipment, and both are suitable for use in diagnostic laboratories.     

Effects of anticancer drugs on the metabolism of the anticancer drug 5,6-dimethylxanthenone-4-acetic (DMXAA) by human liver microsomes

AIMS: To investigate the effects of various anticancer drugs on the major metabolic pathways (glucuronidation and 6-methylhydroxylation) of DMXAA in human liver microsomes. METHODS: The effects of various anticancer drugs at 100 and 500 microM on the formation of DMXAA acyl glucuronide (DMXAA-G) and 6-hydroxymethyl-5-methylxanthenone-4-acetic acid (6-OH-MXAA) in human liver microsomes were determined by high performance liquid chromatography (h.p.l.c.). For those anticancer drugs showing significant inhibition of DMXAA metabolism, the inhibition constants (Ki) were determined. The resulting in vitro data were extrapolated to predict in vivo changes in DMXAA pharmacokinetics. RESULTS: Vinblastine, vincristine and amsacrine at 500 microM significantly (P < 0.05) inhibited DMXAA glucuronidation (Ki = 319, 350 and 230 microM, respectively), but not 6-methylhydroxylation in human liver microsomes. Daunorubicin and N-[2-(dimethylamino)-ethyl]acridine-4-carboxamide (DACA) at 100 and 500 microM showed significant (P < 0.05) inhibition of DMXAA 6-methylhydroxylation (Ki = 131 and 0.59 microM, respectively), but not glucuronidation. Other drugs such as 5-fluoroucacil, paclitaxel, tirapazamine and methotrexate exhibited little or negligible inhibition of the metabolism of DMXAA. Pre-incubation of microsomes with the anticancer drugs (100 and 500 microM) did not enhance their inhibitory effects on DMXAA metabolism. Prediction of DMXAA-drug interactions in vivo based on these in vitro data indicated that all the anticancer drugs investigated except DACA appear unlikely to alter the pharmacokinetics of DMXAA, whereas DACA may increase the plasma AUC of DMXAA by 6%. CONCLUSIONS: These results indicate that alteration of the pharmacokinetics of DMXAA appears unlikely when used in combination with other common anticancer drugs. However, this does not rule out the possibility of pharmacokinetic interactions with other drugs used concurrently with this combination of anticancer drugs.