Selective inhibition of the monosynaptic spinal reflex by a series of hydroxylated alkylaminoindans

5-Hydroxy-2-piperidino-4,5,6,7-tetrahydroindan (5) and a number of related tetrahydro and dihydro compounds were prepared by selective mono- and dihydroxylation of the dihydro products from the Birch reduction of various alkylaminoalkylindans, tetralins, benzenes, and isoindolines. Some of these compounds showed a remarkably selective inhibition of monosynatpic spinal reflex in the segmental cat preparation.     

Phase IIa safety and immunogenicity of a therapeutic vaccine, TA-GW, in persons with genital warts

A fusion protein vaccine consisting of human papillomavirus 6 L2E7 with Alhydrogel was developed for the treatment of genital warts. Twenty-seven subjects with genital warts received 3 immunizations over 4 weeks in an open-label study. The vaccine was well-tolerated, and all subjects made serum IgG antibodies, predominantly IgG1, against L2E7. Nineteen of 25 tested persons made antigen-specific T cell proliferative responses to L2E7, and peripheral blood mononuclear cells when cultured with L2E7 in vitro produced both interferon-gamma and interleukin (IL)-5, although IL-5 predominated after the final vaccination. Five subjects completely cleared warts within 8 weeks. Subjects whose warts were not cleared by 8 weeks were offered conventional therapy. Recurrence of warts was not seen in any of the 13 persons whose warts cleared by vaccine alone or with conventional therapy. While these preliminary results of the use of this therapeutic immunogen are encouraging, proof of efficacy will require randomized double-blind trials.     

Reproducible manufacturing of dye‐sensitized solar cells on a semi‐automated baseline

A fully operational baseline consisting of dedicated equipment to process nanocrystalline dye‐sensitized solar cell devices has been installed at ECN. This baseline focuses on the production of glass/glass devices with dimensions up to 10×10 cm². Present power conversion efficiencies of 6% obtained for cell areas of 2ċ5 cm² are successfully translated to 100 cm² devices with an active area of 68 cm² by application of identical cell components. The power conversion efficiency with respect to total area was 4%. Processing of a large number of devices in the baseline shows good results in terms of process reliability and yield. The overall yield for a series of 27 devices (10×10 cm²) was 96%, while 84% (22 of the remaining 26 devices) generated a cell efficiency within 7% deviation from the average value (4ċ3%). The reproducibility of the titanium dioxide (TiO₂) colloid synthesis has been investigated. The deviation from the average efficiency (4ċ9%) of three batches of colloid was at most 3ċ2%. These results prove that complete device manufacturing of nc‐DSC by a baseline process, starting with colloid synthesis is reproducible for surfaces up to 10×10 cm². Copyright © 2003 John Wiley & Sons, Ltd.     

Pathophysiology of dehydration

The pathophysiology of dehydration is reviewed. The normal response to dehydration, i.e. decreased effective arterial blood volume or effective circulating volume is described. Due to water retention and drinking following stimulation of ADH secretion and thirst, osmoregulation is overruled by volume conservatory mechanisms, which lead to hyponatremia. Only patients with impaired mental function or those who are unable to drink will develop a progressive water deficit--with or without salt depletion--recognizable by hypernatremia. Decreased effective arterial blood volume and hypernatremia affect cerebral function in a way that perception of external stimuli as well as perception of pain will be impaired. Alert dehydrated patients are disturbed mainly by thirst and dryness of the mouth. Both symptoms are perceived more intensely by young than by elderly persons. Dryness of the mouth increase thirst on its own. Distress by thirst and oral dryness increases as a function of the level and the rapidity of developing hypernatremia. The simple act of filling the oral cavity with fluid and swallowing alleviates thirst in the absence of any change in plasma sodium concentration. Thirst quenching efficacy is increased by administering chilled hypotonic fluid with lemon or other fruit acid added (for stimulation of salivation).     

Optimal reliability-based code calibration

Calibration of partial safety factors is considered in general, including classes of structures where no code exists beforehand. The partial safety factors are determined such that the difference between the reliability for the different structures in the class considered and a target reliability level is minimized. Code calibration on a decision theoretical basis is also considered and it is shown how target reliability indices can be calibrated. Results from code calibration for rubble mound breakwater designs are shown.     

Incremental value of prognostic testing in patients with known or suspected ischemic heart disease: a basis for optimal utilization of exercise technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography

OBJECTIVES: This study assessed the incremental prognostic implications of normal and equivocal exercise technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) and sought to determine its incremental prognostic value, impact on patient management and cost implications. BACKGROUND: The prognostic implications of Tc-99m sestamibi SPECT are not well defined, and risk stratification using this test has not been explored. METHODS: We studied 1,702 patients referred for exercise Tc-99m sestamibi SPECT who were followed up for a mean (+/- SD) of 20 +/- 5 months. Patients with previous percutaneous transluminal coronary angioplasty or coronary artery bypass surgery were excluded. The SPECT studies were assessed using semiquantitative visual analysis. Cardiac death and myocardial infarction were considered "hard" events, and coronary angioplasty and bypass surgery > 60 days after testing were considered "soft" events. RESULTS: Of the 1,702 patients studied, 1,131 had normal or equivocal scan results. A total of 10 events occurred in this group (1 cardiac death and 1 myocardial infarction [0.2% hard events]; 4 coronary angioplasty and 4 bypass surgery procedures [0.7% soft events]). The rates of hard events and referral to catheterization after SPECT were similarly low in patients with a low (< 0.15), intermediate (0.15 to 0.85) and high (> 0.85) post-exercise treadmill test (ETT) likelihood of coronary artery disease. With respect to scan type, patients with normal, probably normal or equivocal scan results had similarly low hard event rates. In the 571 patients with abnormal scan results, there were 43 hard events (7.5%) and 42 soft events (7.4%) (p < 0.001 vs. 1,131 patients with normal scan results for both). When the complete spectrum of scan responses was considered, SPECT provided incremental prognostic value in all patient subgroups analyzed. However, the nuclear scan was cost-effective only in patients with interpretable exercise ECG responses and an intermediate to high post-ETT likelihood of coronary artery disease and in those with uninterpretable exercise ECG responses and an intermediate to high pre-ETT likelihood of coronary artery disease. CONCLUSIONS: Normal or equivocal exercise Tc-99m sestamibi study results are associated with a benign prognosis, even in patients with a high likelihood of coronary artery disease. Although incremental prognostic value is added by nuclear testing in all patient subgroups, a testing strategy incorporating nuclear testing proved to be cost-effective only in the groups with an intermediate to high likelihood of coronary artery disease before scanning.     

Occurrence of transcranial Doppler high-intensity transient signals in patients with potential cardiac sources of embolism. A prospective study

BACKGROUND AND PURPOSE: Cerebral emboli can be recognized by typical "high-intensity transient signals" (HITS) in the transcranial Doppler (TCD) spectral curves. Patients with potential cardiac sources of embolism are at higher risk for stroke. METHODS: We examined the frequency of HITS in the left middle cerebral artery (MCA) with TCD over periods of 30 minutes in 100 patients having potential cardiac sources of embolism, as indicated by transthoracic or transesophageal echocardiography. RESULTS: Thirty-six (36%) of the patients presented with HITS. Sex, age, sufficient anticoagulation level, antiplatelet therapy, neurological symptoms, and a history of thrombosis had no influence on the prevalence and number of HITS. The patients with a single echocardiographic diagnosis were separated into eight echocardiographically defined groups: patients with (1) atrial fibrillation, (2) coronary artery disease plus ejection fraction of more than 30% including at least three wall segments of hypokinesia/akinesia, (3) coronary artery disease with less than 30% ejection fraction, (4) dilated cardiomyopathy, (5) infectious endocarditis, (6) aortic stenosis, (7) mitral stenosis, and (8) patent foramen ovale. A significant difference in HITS occurrence could not be found in any of the defined groups. Only patients with infectious endocarditis showed a tendency for a higher HITS prevalence. CONCLUSIONS: HITS are common phenomena in patients with potential cardiac sources of embolism. The clinical relevance of these HITS remains unclear.     

Onset of action of eformoterol by dry powder inhaler: objective and subjective measures

Fluorescence microscopy of caudal epididymal spermatozoa stained with 3, 3' dihexyloxacarbocyanine iodide (DiOC6(3)) showed intense fluorescence along the concave surface of the apical hook of spermatozoa of Rattus species and along the upper concave margin of the sperm head in Mus musculus. In the spermatozoa of Hydromys chrysogaster, Melomys cervinipes, and Pseudomys australis, the two ventral processes also fluoresced brightly. In P. australis, fluorescence in the apical hook of sperm heads was largely localized to its upper and lower surfaces. The sperm of N. alexis did not show consistent positive fluorescence. The localization of fluorescence in these spermatozoa after staining with DiOC6(3) was mainly restricted to regions where a large accumulation of perinuclear theca material lies beneath the plasmalemma. The reason for this remains to be determined, but DiOC6(3) may be useful for quickly demonstrating areas of abundant perinuclear thecal material in sperm heads of eutherian mammals by light microscopy.     

Injury prevention strategies to promote helmet use decrease severe head injuries at a level I trauma center

Head injuries (HIs) remain a major contributor to trauma mortality, with many deaths occurring despite optimal use of available therapy. Injury prevention is vital to decrease the impact of HIs. Helmets can decrease the severity of HIs in both bicycle crashes (BCs) and motorcycle crashes (MCCs). A major challenge is to increase helmet use. A mandatory motorcycle helmet law in 1990 and information campaigns aimed at bicyclists have increased the percentage of riders wearing helmets in Washington State. We hypothesized that there would be an associated decrease in the proportion of severe HIs in BC and MCC admissions to the state's only level I trauma center. We analyzed injury region and outcomes for all 466 BC and 992 MCC instate admissions from 1986 to 1993. For BCs, the proportion of severe HIs (Abbreviated Injury Scale score of 4 or 5) declined from 29% in 1986 to 11% in 1993 (p = 0.02). BC trends paralleled helmet use in observations on 8,860 bicycle riders in the area, in which the percentage of helmeted riders rose from 5% in 1987 to 62% in 1993 (p < 0.001). For MCCs, severe HIs declined from 20% before passage of the helmet law to 9% afterward (p < 0.001). Mortality decreased for BCs and MCCs (p < 0.05), and length of hospital stay and ICU stay decreased for BCs (p < 0.05). The percentage of helmeted BC admissions rose from 0% to 32% (p = 0.009), and helmeted MCC admissions rose from 41% to 80% (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation of fecundability and serum estradiol after danazol treatment in patients with advanced endometriosis

OBJECTIVE: To examine the relationship between pregnancy incidence and the level of serum E2 during danazol therapy. DESIGN: Danazol was given by 200 mg four times daily for 3 months. Serum E2 level was checked after completing the therapy, but before stopping medication. Patients then were advised to conceive at the appropriate time over a 6-month period. SETTING: Reproductive and Endocrine Laboratory of the Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan. PATIENTS: Infertile women with invasive endometriosis receiving conservative surgery and danazol treatment. INTERVENTIONS: Serum E2 is checked before medication and at the end of danazol therapy, but before stopping medication. MAIN OUTCOME MEASURES: Whether pregnancy is related to the change of serum E2 caused by danazol therapy. RESULTS: There were 24 pregnancies in 38 patients with invasive endometriosis after treatment. Pregnant patients had significantly lower serum E2 levels as compared with the nonpregnant patients. CONCLUSIONS: After conservative surgery for invasive endometriosis associated with infertility, the therapeutic period of danazol treatment could be shortened to 3 months. Because there is significant correlation of fecundability and serum E2 after danazol medication, serum E2 could be a guideline for predicting pregnancy or for prolonging or changing of treatment after danazol therapy.