Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review.

BACKGROUND: Pregnant and postpartum women with severe hypertension are at increased risk of stroke and require blood pressure (BP) reduction. Parenteral antihypertensives have been most commonly studied, but oral agents would be ideal for use in busy and resource-constrained settings. OBJECTIVES: To review systematically, the effectiveness of oral antihypertensive agents for treatment of severe pregnancy/postpartum hypertension. SEARCH STRATEGY: A systematic search of MEDLINE, EMBASE and the Cochrane Library was performed. SELECTION CRITERIA: Randomised controlled trials in pregnancy and postpartum with at least one arm consisting of a single oral antihypertensive agent to treat systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 110 mmHg. DATA COLLECTION AND ANALYSIS: Cochrane RevMan 5.1 was used to calculate relative risk (RR) and weighted mean difference by random effects. MAIN RESULTS: We identified 15 randomised controlled trials (915 women) in pregnancy and one postpartum trial. Most trials in pregnancy compared oral/sublingual nifedipine capsules (8-10 mg) with another agent, usually parenteral hydralazine or labetalol. Nifedipine achieved treatment success in most women, similar to hydralazine (84% with nifedipine; relative risk [RR] 1.07, 95% confidence interval [95% CI] 0.98-1.17) or labetalol (100% with nifedipine; RR 1.02, 95% CI 0.95-1.09). Less than 2% of women treated with nifedipine experienced hypotension. There were no differences in adverse maternal or fetal outcomes. Target BP was achieved ~ 50% of the time with oral labetalol (100 mg) or methyldopa (250 mg) (47% labetelol versus 56% methyldopa; RR 0.85 95% CI 0.54-1.33). CONCLUSIONS: Oral nifedipine, and possibly labetalol and methyldopa, are suitable options for treatment of severe hypertension in pregnancy/postpartum.

HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms?

OBJECTIVE: The aim of the study was to determine the prevalence and risk factors for HIV-associated fatigue in the era of highly active antiretroviral therapy (HAART). METHODS: A cross-sectional survey of 100 stable HIV-infected out-patients was carried out. Severity of fatigue was measured using the Fatigue Impact Scale (FIS). Symptoms of orthostatic intolerance (dysautonomia) were evaluated using the Orthostatic Grading Scale (OGS). Data for HIV-infected patients were compared with those for 166 uninfected controls and 74 patients with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (encephalopathy) (ME). RESULTS: Ninety-one per cent of HIV-infected patients were on HAART and 78% had suppressed plasma HIV viral load (≤ 40 HIV-1 RNA copies/mL). Fifty-one per cent of HIV-infected patients reported excessive symptomatic fatigue (FIS ≥ 40), and 28% reported severe fatigue symptoms (FIS ≥ 80). The mean FIS score among HIV-infected patients was 50.8 [standard deviation (SD) 41.9] compared with 13.0 (SD 17.6) in uninfected control subjects, and 92.9 (SD 29.0) in CFS patients (P < 0.001 for comparison of HIV-infected patients and uninfected controls). Among HIV-infected patients, fatigue severity was not significantly associated with current or nadir CD4 lymphocyte count, HIV plasma viral load, or whether on HAART. Prior dideoxynucleoside analogue (d-drug) exposure (P = 0.016) and the presence of clinical lipodystrophy syndrome (P = 0.011) were associated with fatigue. Additionally, fatigue severity correlated strongly with symptomatic orthostatic intolerance (r = 0.65; P < 0.001). CONCLUSIONS: Fatigue is very common and often severe in HIV-infected out-patients, despite viral suppression and good immune function. In a subgroup of patients, prior d-drug exposure may contribute to fatigue, suggesting a metabolic basis. Dysautonomia may also drive fatigue associated with HIV infection, as in other chronic diseases, and CFS/ME, and should be further evaluated with the potential for a shared therapeutic approach.

Pseudothrombocytopenia: a laboratory artifact with potentially serious consequences.

When a low platelet count is unexpected or is unaccompanied by signs or symptoms of hemorrhage, pseudothrombocytopenia should be suspected. The platelet number and morphologic features should be examined on a smear prepared from blood anticoagulated with EDTA. Platelet counts should be repeated either by obtaining a finger-stock specimen with an ammonium oxalate Unopette and counting by phase microscopy or by collecting both an EDTA- and a sodium citrate-anticoagulated venous sample, performing a platelet count on both test tubes, and examining a blood smear from each test tube. If a Coulter Model S Plus IV or V or the Technicon H6000 is used for performance of platelet counts, examination of the histogram display of the Coulter instrument or the peroxidase X-Y display of the Technicon H6000 should alert the instrument operator to the presence of EDTA-induced platelet clumping and prevent the reporting of a spuriously low platelet count.

Evaluation of the Toa E-5000 Automated Hematology Analyzer.

A three-phase evaluation of the Toa E-5000 Automated Hematology Analyzer was performed. The first phase consisted of evaluation of linearity, carryover, precisions, accuracy, sample stability, and effectiveness of the mixing and sampling mechanism. The second phase was comparison of erythroid and platelet parameters with results from a Coulter Counter Model S-Plus IV. The third phase consisted of comparison of the trimodal leukocyte differential count of the Toa E-5000 in 300 patients with four other differential methods. The first-phase studies showed excellent performance characteristics. Stability of samples at room temperature was good for a minimum of 12 hours, but storage for longer than 12 hours requires refrigeration to maintain stable values. The erythrocyte and platelet parameters showed good correlation with the Coulter S-Plus IV values except for the erythrocyte distribution width that is calculated differently. The third-phase studies are published elsewhere.

Evaluation of the Coulter Counter model S-Plus IV.

Evaluation of linearity, carry-over, precision, and accuracy of a Coulter Counter model S-Plus IV prototype showed that they meet the manufacturer's specifications. The instrument also was compared with an earlier model. Correlations of the lymphocyte and granulocyte values in the three-part differential count with manual eye-count and a Technicon Hemalog D90 results were very close to the correlation of eye-count to Hemalog D90 results. The percentage of mononuclear cells showed acceptable correlation to the manual eye-count when monocytes were combined with blasts, eosinophils, and basophils. The medical effectiveness of the three-part differential was determined by comparison with manual eye-counts in 1,084 samples. The false positive and false negative values were 7.38% and 7.84%, respectively. The instrument has acceptable limits of operation. When combined with analysis of histograms by trained personnel, the three-part differential count is capable of screening for abnormalities that require further analysis.

Comparison of four leukocyte differential methods with the National Committee for Clinical Laboratory Standards (NCCLS) reference method.

The authors compared four leukocyte differential counting methods with the National Committee for Clinical Laboratory Standards Reference Leukocyte Differential Method H20-T to determine the clinical sensitivity of the methods. The three-part differential performed by the Coulter Counter Model S-Plus IV and the Toa E-5000, when combined with instrument flags and defined laboratory checking limits for red blood cell and platelet values, are safe and efficacious screening methods for the presence of morphologic abnormalities. The Geometric Data Hematrak 590 proved comparable in clinical sensitivity to a random 100-cell eye-count differential.

Digital rat brain: a computerized atlas.

Digital brain mapping provides the techniques required for 3 dimensional (3D) reconstruction and display. This paper describes work which extends the data published in the Paxinos and Watson (1982) atlas of the rat brain to a computerized form. The product of these experiments is a 3D digital neuroanatomic atlas. The data were transformed from 2D outlines to 3D volumes each associated with a specific neuroanatomic structure. The system which manages this transformation also provides tools to manipulate the composition, orientation and appearance of the displays interactively.

Three-dimensional comparison of peripheral benzodiazepine binding and histological findings in rat brain tumor.

Experiments were undertaken to determine the in vivo utility of the mixed benzodiazepine ligand [3H]flunitrazepam and the selective peripheral benzodiazepine ligand [3H]PK 11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide] to outline the borders of rat C6 glial tumors in three dimensions. Intravenous injection of [3H]flunitrazepam resulted in a tumor/cortex ratio of radioactive densities between 2.7 and 1.5 within the first 60 minutes after injection. [3H]PK 11195 demonstrated a higher tumor/cortex ratio (5.3) than [3H]flunitrazepam. For three-dimensional studies, images were generated from thionin-stained histological sections and autoradiograms. The mixed type benzodiazepine ligand [3H]flunitrazepam was superior in showing some of the normal anatomical structures surrounding the tumor, whereas [3H]PK 11195, a specific peripheral ligand, demonstrated higher tumor/brain contrast and superior topographical correlation between histological and autoradiographic images. Implications of peripheral benzodiazepine receptor ligands for positron emission tomography are discussed.

Animating the 3D structure and function of brain.

Three dimensional (3D) reconstructions of brain anatomy and physiology have greatly improved our understanding of complex spatial and densitometric relationships. The complexity and sophistication of these imaging techniques has steadily improved in the last few years and there are many situations in which the static display of 3D models contains more information than can be easily appreciated. Animating a sequence of these displays adds another dimension to the visualization, understanding and communication of 3D data. This paper describes those situations that warrant animations, the techniques necessary to compute them and the results that can be obtained.

Informatics and computational neuroanatomy.

Rapid and convenient access to digital image archives, as well as archive-based computational tools, are fundamental to many hypothesis-driven investigations of brain anatomy and function in health and disease. The complexity and density of brain image data requires the design of intelligent tools which allow scientific and clinical data, collected at numerous research centers, to be compared, integrated, and disseminated. We describe our results in the development of image data navigational tools, a World Wide Web repository of image analysis software, and strategies to represent populations of brain image data involving atlas descriptions of its variance.