Hypertension optimal treatment (HOT) study: home blood pressure in treated hypertensive subjects

The Hypertension Optimal Treatment Study is a prospective trial conducted in 26 countries. The aims are to (1) evaluate the relationship between three levels of target office diastolic blood pressure (BP) (< or = 80, < or = 85, or < or = 90 mm Hg) and cardiovascular morbidity and mortality in hypertensive patients and (2) examine the effects on cardiovascular morbidity and mortality of 75 mg aspirin daily versus placebo. A total of 19,193 patients between 50 and 80 years of age had been randomized by the end of April 1994. Treatment was initiated with felodipine 5 mg daily, and additional therapy was given in accordance with a set protocol. The present substudy of 926 patients performed in nine countries aimed to (1) compare home with office BP in a representative subsample of the HOT population after the titration of treatment was completed and (2) clarify whether the separation into the target groups could be expanded into the out-of-office setting. The differences between office and home measurements in diastolic BP of 0.2 mm Hg (SD, 9; 95% confidence interval, -0.36 to 0.81; P=.40) and systolic BP of 0.5 mm Hg (SD, 15; 95% confidence interval, -0.53 to 1.46; P=.21) were not significant. The group differences in home BP were 1.9 mm Hg (< or = 80 versus < or = 85) and 1.2 mm Hg (< or = 85 versus < or = 90) for diastolic BP (F=11.69; ANOVA, P<.0001) and 2.6 and 2.1 mm Hg for systolic BP (F=8.44, P=.0002). Thus, office and home BPs measured with the same semiautomatic device are comparable in treated hypertensive subjects in the HOT Study, and the separation into the target groups based on office readings prevails at home.     

Maternal respiratory arrests, severe hypotension, and fetal distress after administration of intrathecal, sufentanil, and bupivacaine after intravenous fentanyl

The transjugular intrahepatic portosystemic shunt procedure is an effective intervention for patients with bleeding esophageal varices. Potential complications are numerous but rarely serious. A case of hemopericardium, cardiac tamponade, and death caused by perforation of the right atrium and aorta by a stent after embolization from the liver during stent placement is reported.     

The independence of intrinsic radiosensitivity as a prognostic factor for patient response to radiotherapy of carcinoma of the cervix

A study was made of the prognostic value of pretreatment measurements of tumour radiosensitivity (surviving fraction at 2 Gy, SF2) in 128 patients with stage I-III carcinomas of the uterine cervix undergoing radiotherapy. The median follow-up time was 47 months. In a univariate analysis stratifying patients according to the median value, radiosensitivity was a significant prognostic factor for overall survival, local control and metastasis-free survival. The 5-year survival rate for tumours with SF2 values below the median was 81% and was significantly greater than the rate of 51% for those with SF2 values above the median. In bivariate analyses, SF2 was shown to be independent of disease stage, tumour grade, patient age, colony-forming efficiency and tumour diameter. In a multivariate analysis, radiosensitivity was the most important variable and, after allowing for this, only stage was a significant independent predictor of treatment outcome. These data indicate that, in carcinoma of the cervix treated with radiotherapy, pretreatment tumour intrinsic radiosensitivity is an important prognostic parameter and contributes to prognosis independently of other established and putative parameters.     

N-Acetyltransferase 2 (NAT2) and Glutathione S-Transferase μ (GSTM1) in Bladder-cancer Patients in a Highly Industrialized Area

The gene encoding the 33 kDa piroplasm surface protein of Theileria sergenti isolated in Korea was cloned and the nucleotide sequence was determined by dideoxy chain termination method. The cloned gene corresponds to 869 bp encoding an open reading frame 283 amino acids. Comparison of the sequence between Korean and Japanese isolates showed 99.4% homology rate in the nucleotide sequence and 98.9% homology rate in the amino acid sequence.     

Motor control and cardiovascular responses during isoelectric contractions of the upper trapezius muscle: evidence for individual adaptation strategies

Ten females (25-50 years of age) performed isometric shoulder flexions, holding the right arm straight and in a horizontal position. The subjects were able to see the rectified surface electromyogram (EMG) from either one of two electrode pairs above the upper trapezius muscle and were instructed to keep its amplitude constant for 15 min while gradually unloading the arm against a support. The EMG electrodes were placed at positions representing a "cranial" and a "caudal" region of the muscle suggested previously to possess different functional properties. During the two contractions, recordings were made of: (1) EMG root mean square-amplitude and zero crossing (ZC) frequency from both electrode pairs on the trapezius as well as from the anterior part of the deltoideus, (2) supportive force, (3) heart rate (HR) and mean arterial blood pressure (MAP), and (4) perceived fatigue. The median responses during the cranial isoelectric contraction were small as compared to those reported previously in the literature: changes in exerted glenohumeral torque and ZC rate of the isoelectric EMG signal of -2.81% x min(-1) (P = 0.003) and 0.03% x min(-1) (P = 0.54), respectively, and increases in HR and MAP of 0.14 beats x min(-2) (P = 0.10) and 0.06 mmHg x min(-1) (P = 0.33), respectively. During the contraction with constant caudal EMG amplitude, the corresponding median responses were -2.51% x min(-1) (torque), 0.01% x min(-1) (ZC rate), 0.31 beats x min(-2) (HR), and 0.93 mmHg x min(-1) (MAP); P = 0.001, 0.69, 0.005, and 0.003, respectively. Considerable deviations from the "isoelectric" target amplitude were common for both contractions. Individuals differed markedly in response, and three distinct subgroups of subjects were identified using cluster analysis. These groups are suggested to represent different motor control scenarios, including differential engagement of subdivisions of the upper trapezius, alternating motor unit recruitment and, in one group, a gradual transition towards a greater involvement of type II motor units. The results indicate that prolonged low-level contractions of the shoulder muscles may in general be accomplished with a moderate metabolic stress, but also that neuromuscular adaptation strategies differ significantly between individuals. These results may help to explain why occupational shoulder-neck loads of long duration cause musculoskeletal disorders in some subjects but not in others.     

Grapefruit juice-terfenadine single-dose interaction: magnitude, mechanism, and relevance

Effective management of human health and ecological hazards in the manufacturing and maintenance environment can be achieved by focusing on the risks associated with these operations. The NDCEE Industrial Health Risk Assessment (IHRA) Program is developing a comprehensive approach to risk analysis applied to existing processes and used to evaluate alternatives. The IHRA Risk-Based Tiered Approach (RBTASM) builds on the American Society for Testing and Materials (ASTM) Risk-Based Corrective Action (RBCA) effort to remediate underground storage tanks. Using readily available information, a semi-quantitative ranking of alternatives based on environmental, safety, and occupational health criteria was produced. A Rapid Screening Assessment of alternative corrosion protection products was performed on behalf of the Joint Group on Acquisition Pollution Prevention (JG-APP). Using the RBTASM in pollution prevention alternative selection required higher tiered analysis and more detailed assessment of human health risks under site-specific conditions. This example illustrates the RBTASM for a organic finishing line using three different products (one conventional spray and two alternative powder coats). The human health risk information developed using the RBTASM is considered along with product performance, regulatory, and cost information by risk managers downselecting alternatives for implementation or further analysis.     

Proconvulsant and anticonvulsant effects of Evans blue dye in rodents

The effect of i.c.v. administration of Evans blue to sound sensitive DBA/2 mice and to genetically epilepsy-prone rats was studied. In mice, Evans blue (3.3-52 nmol) induced: hyperlocomotion, wild running, scratching, clonic muscle spasms, tonic seizure (latency 10-45 min), followed by death or recovery. The CD50 value for clonic seizures for Evans blue was 35(23-53) nmol. Pretreatment (45 min) with Evans blue (13-52 nmol, i.c.v.) dose-dependently reduced the incidence of sound-induced seizures in DBA/2 mice (ED50 value against clonic seizures = 30 [15-58] nmol, i.c.v). In rats, Evans blue (104 nmol, i.c.v.) induced electroencephalographic seizures in the hippocampus and cortex and behavioural limbic seizures with a latency of 15-20 min. A reduction in the mean score (from 5 to 2-3) for behavioural seizures was observed which lasted for 4-5 days in rats electrically-kindled daily in the hippocampal CA3 subsector. Sound-induced clonic seizures in kindled and non-kindled rats were reduced for 3-4 days after administration of Evans blue (104 nmol, i.c.v.).     

Sarcina ventriculi synthesizes very long chain dicarboxylic acids in response to different forms of environmental stress

Changes in the composition of membrane lipids in a strictly anaerobic, facultative acidophilic eubacterium, Sarcina ventriculi, were studied in response to various forms of environmental stress. Changes in lipid composition and structure occurred in response to changes in environmental pH. At neutral pH, the predominant membrane fatty acids ranged in chain length from C14 to C18. However, when cells were grown at pH 3.0, a family of unique very long chain fatty acids containing 32-36 carbon atoms was synthesized and accounted for 50% of the total membrane fatty acids. These acids were identified as very long chain alpha,omega-dicarboxylic acids ranging in length from 28 to 36 carbons by electron impact mass spectrometry of methyl and (perdeuterio) methyl ester derivatives. These methyl esters all bore a vicinal dimethyl group toward the center of the chain. The assignment of the structures was confirmed by isolating one of the very long chain unusual fatty acids as the ester form after methanolysis and performing further analyses including 1H and 13C NMR spectroscopy and Fourier transform infrared spectroscopy. Coupling this information with the data from gas chromatography/mass spectrometry analysis, the exact structure was confirmed as alpha,omega-15,16-dimethyltricotanedioate dimethyl ester. Addition of alcohols, either metabolic (0.25 M ethanol) or nonmetabolic (0.05 M butanol) to cells grown at pH 7.0, or thermal stress (growth temperature at pH 7.0 was raised from 37 to 45 or 55 degrees C) also resulted in the synthesis of these very long chain fatty acids. Synthesis of these very long chain alpha,omega-dicarboxylic acids was reversed by reducing the temperature back to 37 degrees C. S. ventriculi is also unusual in that the membrane components are not the usual phospholipid components but appear to be predominantly glycolipids.     

Effects of parturition, suckling and pseudopregnancy on variables of disease activity in the B/W mouse model of systemic lupus erythematosus

OBJECTIVE: The pituitary hormone, prolactin, accelerates systemic lupus erythematosus in NZB/NZW F1 (B/W) mice. Our study evaluated disease activity in B/W females experiencing the physiologic hyperprolactinemia of mating, pregnancy, suckling, and pseudopregnancy. METHODS: Nonsuckling postpartum, suckling and pseudopregnant mice were compared to virgin females. Serum prolactin, anti-DNA antibodies (anti-DNA), gp70-anti-gp70 immune complexes, IgM, IgG, albuminuria, and renal function were monitored serially. RESULTS: Females that whelped 2 litters had apparent stimulation of anti-DNA; those that suckled their young had similar premature appearance of anti-DNA as well as delayed, but marked, hypergammaglobulinemia. Pseudopregnant mice, which characteristically secrete repeated surges of prolactin, had significant acceleration of multiple variables of disease activity. CONCLUSIONS: Pregnancy, parturition and suckling did not immediately accelerate lupus in B/W dams, and longevity was not affected in females that had borne litters. Pseudopregnancy was the most effective stimulator of variables of autoimmunity.     

Effect of pH and ionic strength on bovine m-calpain and calpastatin activity

The effects of bovine skeletal muscle m-calpain and calpastatin on the degradation of casein and isolated bovine myofibrils were characterized under various pH values (7.0, 6.2, 5.7) and ionic strengths (32 to 400 mM KCl) at 25 degrees C. Caseinolytic assays indicated that m-calpain activity increased with increasing pH (P < .01) but decreased with increasing ionic strength (P < .01). Regardless of the presence of m-calpain, SDS-PAGE of myofibrils showed increased solubilization of myofibrillar proteins as pH and ionic strength increased. However, only in the presence of m-calpain were changes normally observed during postmortem storage reproduced. Protein release attributed to m-calpain activity increased with pH, but the effects of elevated ionic strength on the ability of m-calpain to hydrolyze myofibrillar proteins were not evident from SDS-PAGE, except for the decreased troponin-T degradation by m-calpain at the higher ionic strengths. A pH x ionic strength interaction was observed for calpastatin activity determined by caseinolytic assays (P < .01). No changes in m-calpain inhibition were detected at pH 7.0 and 6.2 at different ionic strengths. However, at pH 5.7 the ability of calpastatin to inhibit m-calpain decreased with increasing ionic strength. No changes in m-calpain inhibition could be detected with SDS-PAGE. Based on these results, it can be concluded that although m-calpain and calpastatin activities decrease with increasing ionic strength, their activities in the presence of myofibrils were not affected by ionic strengths typically found in postmortem muscle.