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PubMedDate not supplied

Calcium-sensing receptor gene polymorphisms in primary hyperparathyroidism.

The calcium-sensing receptor (CaR) polymorphism A986S has been found to be associated with higher serum calcium levels in normal subjects, suggesting that this amino acid change might decrease the inhibitory activity of the mutated receptor, render the parathyroid cells more prone to proliferate, and eventually increase the risk of developing primary hyperparathyroidism (PHPT). The aim of the present study was to investigate the frequency of this and other 2 known CaR polymorphisms (R990G and Q1011 E) in patients with PHPT and their effect on its phenotype. We studied 103 Italian patients with PHPT and 148 healthy Italian subjects and we compared the results in 50 pairs matched for sex, age and geographic provenience. A fragment of exon 7 of the CaR gene, containing the 3 polymorphic loci of interest (A986S, R990G, and Q1011E), was amplified by PCR and sequenced. Serum calcium and PTH levels, BMD and other biochemical and clinical parameters were evaluated. The frequency distribution of the A9865, R990G, and Q1011 E polymorphisms in the 103 PHPT patients was 39.8%, 5.8%, and 2.0%, respectively. There was no difference in the frequency of the 3 CaR polymorphisms in the 50 matched pairs of patients and controls. We found no significant difference in several clinical and biochemical parameters between PHPT patients carrying or not the 986S allele. Finally, no relationship was observed between the 986S genotype and total and ionized serum calcium in control subjects. The A986S CaR polymorphism is the most common in Italian PHPT patients and the allotype AS does not appear to play a relevant role in the pathogenesis of PHPT and its severity. The A986S polymorphism does not correlate with serum calcium levels in normal Italian subjects.

Adult↗
PubMed2003

Air pollution and children's health in São Paulo (1986-1998).

Air pollution in the conurbation of São Paulo, Brazil, with 17 million inhabitants, has been measured from air quality monitoring stations. In three contrasted sample areas, children's respiratory health parameters were collected to assess the role of air pollution in 1986. Twelve years later, in 1998, a similar study was undertaken to evaluate the impact of pollution control programs on the respiratory symptoms of children living in the same neighborhoods previously studied. Results indicated that pollution control programs were in part neutralized by increased number of cars and that the control of a single pollutant was not enough to protect children's health. In the area where both particulate matter and sulfur dioxide levels decreased, there was a reduction in the prevalence of respiratory symptoms.

Adolescent↗
PubMed1999

Is there a risk in being a good Samaritan?

It's Nursing Week and you are at a booth in a busy shopping mall. After spending a couple of hours talking with people, answering questions and taking blood pressure readings, you start to sip a well-earned cup of coffee. You glance down the mall and observe a middle-aged man suddenly clutch at his chest and fall to the floor. You alert your colleagues to call 911 as you run down the mall to do what you can. You reach the man, announce, "I know CPR," and initiate resuscitation. You have just spent an invigorating day on the ski slopes. As you drive home, you are horrified to see a car spin out of control and roll over into the ditch a couple of car lengths ahead of you. Suddenly you face a dilemma. You are an experienced nurse who wants to help and yet, lurking in the back of your mind, there is the nagging fear that you could be sued. You wonder if are you legally obligated to stop and assist. Could you be liable if you fail to do so?

Accidents, Traffic↗
PubMed2001

A comparative study of the effects of carbamazepine and the NMDA receptor antagonist remacemide on road tracking and car-following performance in actual traffic.

RATIONALE: Antiepileptic drugs are known to produce side effects which may impair driving performance. Performance effects, however, may differ substantially between individual antiepileptic drugs. OBJECTIVE: To compare the effects of carbamazepine, remacemide, and placebo on actual driving performance during a 12-day incremental dosing regimen. METHODS: Twenty-two healthy volunteers participated in a three-way, double-blind, cross-over driving study. Treatment effects were assessed in two actual driving tests carried out on days 8, 10, and 12 of each treatment period. The Road Tracking Test involved driving an instrumented vehicle at a constant speed and steady lateral position between the delineated lane boundaries. Standard deviation of lateral position (SDLP) was measured to indicate precision of road tracking control. The Car-Following Test involved driving the same vehicle behind a leading car and maintaining that distance while the latter executed a series of deceleration/acceleration maneuvers. Time to speed adaptation (TSA) and brake reaction time were the primary measures. RESULTS: Remacemide did not affect the subjects' driving performance. Carbamazepine increased SDLP throughout treatment and lengthened TSA on day 8. Changes in SDLP relative to placebo were comparable to those previously seen in drivers conducting the same test with blood alcohol concentrations of 0.05 g/dl. CONCLUSION: Remacemide, at the given dose regimen, does not affect driving performance. Carbamazepine, at the given dose regimen, can produce mild but sufficient impairment to put epileptic patients at risk when driving, at least during initiation therapy.

Acetamides↗
PubMed2006

Phenobarbital regulates nuclear expression of HNF-4alpha in mouse and rat hepatocytes independent of CAR and PXR.

Phenobarbital is a lipophilic molecule used as a sedative and antiepileptic drug that elicits a multitude of effects in the liver, including gross liver enlargement, hepatocyte hypertrophy, and induced expression of drug-metabolizing enzymes and other liver-specific genes. The constitutive androstane receptor (CAR; NR1I3) and to a lesser extent the pregnane X receptor (PXR; NR1I2) are responsible for mediating induction of many phenobarbital-responsive genes. However, CAR-mediated transcriptional control of some genes is critically dependent on hepatocyte nuclear factor 4 alpha (HNF-4alpha; NR2A1), which itself regulates multiple liver-specific genes involved in hepatic growth, metabolism, and differentiation. We studied the effects of phenobarbital on HNF-4alpha expression in hepatocytes and provide evidence that HNF-4alpha nuclear expression is regulated in response to phenobarbital. Real-time polymerase chain reaction analyses revealed that HNF-4alpha mRNA is modestly up-regulated by phenobarbital. In addition, nuclear expression of HNF-4alpha protein is significantly elevated 3 hours after the administration of phenobarbital in wild-type, CAR-/-, and CAR-/-/PXR-/- mice. In vitro analysis revealed that phenobarbital-induced HNF-4alpha expression is both time- and dose dependent. In addition, the phosphatase inhibitor okadaic acid and the Ca2+/calmodulin-dependent protein kinase II inhibitor KN62 block nuclear induction of HNF-4alpha by phenobarbital. Furthermore, HNF-4alpha nuclear expression is enhanced by inhibition of cyclic AMP-dependent protein kinase A. In conclusion, induced nuclear expression of HNF-4alpha and CAR is an integral part of the phenobarbital response, aimed at coordinated regulation of genes involved in drug metabolism and detoxification as well as maintenance of liver function.

Animals↗
PubMed2006

[The role of urotensin II in airway remodeling of asthma].

OBJECTIVE: To observe the change of urotensin II (U-II) expression in airways of rat asthmatic models, and of patients with asthma, and therefore to investigate the role of U-II in the pathogenesis of asthma and airway remodeling. METHODS: Twenty Wistar rats were divided into a control group (10 rats) and an asthmatic group (10 rats). The animal model of asthma was established by ovalbumin intraperitoneal injection and aerosolization. The internal perimeter of bronchi (Pi), bronchial wall area (WA) and the area of bronchial smooth muscle (WAm) were measured by a computerized image analyzer, and the WA/Pi and WAm/Pi were calculated to express airway remodeling. Autopsy lung tissues from 5 patients with asthma and 5 normal human controls died of car accident were collected, stained with hematoxylin and eosin stain, and the streptavidin peroxidase method. The expression level of U-II and the percentage of positive U-II cell in the airways of rats and patients with asthma were measured. RESULTS: Rats exposed to ovalbumin developed asthma and airway remodeling: the WA/Pi and WAm/Pi [(24.1 +/- 2.4) microm(2)/microm, (5.3 +/- 1.9) microm(2)/microm] were increased, as compared with the normal group [(16.5 +/- 1.7) microm(2)/microm, (3.8 +/- 1.2) microm(2)/microm], the difference being significant (t = 3.892, 3.785, all P < 0.01). The expression level of U-II in asthmatic rats was 2.46 +/- 0.15, while in the control group was 1.26 +/- 0.11, the difference being significant (t = 6.236, P < 0.01). There was a positive correlation between the level of U-II and WAm/Pi (r = 0.712, P < 0.01). The percentage of positive U-II cells in the asthmatic rats was (82 +/- 8)%, while in the control rats was (22 +/- 8)%, the difference being significant (t = 19.102, P < 0.01). The expression level of U-II in patients with asthma was 2.61 +/- 0.19, while in the control group was 1.36 +/- 0.12, the difference being significant (t = 7.374, P < 0.01). The percentage of positive U-II cells in patients with asthma was (75 +/- 9)%, while in the controls was (27 +/- 7)%, the difference being significant (t = 16.236, P < 0.01). CONCLUSION: The expression of U-II is increased in airways of rat asthmatic models and of patients with asthma. It may play an important role in the pathogenesis of asthma and airway remodeling.

Adult↗
PubMed2003

Driver sleepiness and risk of car crashes in Shenyang, a Chinese northeastern city: population-based case-control study.

OBJECTIVE: To estimate the association of driver sleepiness with the risk of car crashes. METHODS: A population-based case-control study was conducted in Shenyang, a northeastern city in China, between November 2001 and July 2002. The case group comprised 406 car drivers involved in crashes, and 438 car drivers recruited at randomly selected sites, and on the day of week, and the time of day when they were driving on highways in the study region during the study period were used as control groups. Face-to-face interviews with drivers were conducted according to a well-structured questionnaire covering the circumstances of their current trip and their background information. Stanford sleepiness scale and Epworth sleepiness scale were used to quantify acute sleepiness and chronic sleepiness respectively. RESULTS: There was a strong association between chronic sleepiness and the risk of car crash. Significantly increased risk of crash was associated with drivers who identified themselves as sleepy (Epworth sleepiness score > or = 10 vs < 10; adjusted odds ratio 2.07, 95% confidence interval 1.30 to 3.29), but no increased risk was associated with measures of acute sleepiness. CONCLUSIONS: Chronic sleepiness in car drivers significantly increases the risk of car crash. Reductions in road traffic injuries may be achieved if fewer people drive when they are sleepy.

Accidents, Traffic↗
PubMed1984

Psychomotor seizures.

A 30-year-old woman presented to the emergency department after an episode of "dizziness" that caused her to lose control of her car. During the preceding 12-month period she had had recurrent "dizzy" spells and abdominal pains for which she was evaluated by several physicians in various emergency departments. Physical and general neurological examination on presentation was within normal limits. Outpatient CT scan was normal, and an EEG revealed a right temporal lobe spike with slow wave pattern suggestive of temporal lobe focus. Since begun on therapeutic doses (300 mg per day of phenytoin), the patient has not experienced further spells or abdominal pains. This report emphasizes the need to be cognizant of an underlying seizure disorder as a possible etiologic agent responsible for a traumatic incident.

Abdomen↗
PubMed2001

The delivery of preventive services for patient symptoms.

BACKGROUND: Although data are available on rates of delivery of preventive services by primary care physicians, the proportion of services delivered because of related symptoms or signs, rather than for primary or secondary prevention of disease is not known. METHODS: Research nurses directly observed 4454 consecutive visits to 138 practicing family physicians. Direct observation was used to identify delivery of 36 different services recommended by the U.S. Preventive Services Task Force and to assess whether delivery of these services was associated with related signs or symptoms. RESULTS: One or more preventive services were delivered in 33% of visits, with rates ranging from 0.2% (HIV prevention) to 19.9% (tobacco counseling). In contrast to pure prevention, services were frequently performed for assessment or care of symptoms or signs, with the ratio ranging from 0% (eye examination; car seat, poison control, and HIV prevention counseling) to 66.7% (hearing test). Physicians varied considerably in the frequency at which their delivery of recommended preventive services was associated with patient symptoms, from 0% to 100% for screening services and from 0% to 100% for counseling services. CONCLUSIONS: Because of the illness focus of most primary care visits, preventive service delivery is often associated with related signs or symptoms. Care of illnesses appears to present an important impetus and perhaps teachable moments for providing preventive care. Clinician variability in preventive service delivery for patient symptoms shows an opportunity to improve the primary and secondary prevention focus of practice to meet public health prevention goals.

Adolescent↗
PubMed2000

Efficient light harvesting through carotenoids.

We review the factors that control the efficiency of carotenoid-chlorophyll excitation transfer in photosynthetic light harvesting. For this we summarize first the recently developed theory that describes electronic couplings between carotenoids and chlorophylls and we outline in particular the influence of length of conjugated system and of symmetry breaking on the couplings. We focus hereby on the structurally solved lycopene-BChl system of LH 2 from Rhodospirillum molischianum and the peridinin-Chl a system of PCP from Amphidinium carterae. In addition, we review recent spectroscopic data for neurosporene, spheroidene and lycopene, three carotenoids with different lengths of conjugated systems. On the basis of the measured energies, emission lineshapes, solution and protein environment lifetimes for their 2A ( g ) (-) and 1B ( u ) (+) states as well as of the theoretically determined couplings, we conclude that the transfer efficiencies from the 2A ( g ) (-) state are controlled by the Car(2A ( g ) (-) )-BChl(Q(g)) electronic couplings and the 2A ( g ) (-) --> 1A ( g ) (-) internal conversion rates. We suggest that symmetry breaking and geometry rather than length of conjugated system dominate couplings involving the 2A ( g ) (-) state. Differences in transfer efficiencies from the 1B ( u ) (+) state in LH 2 and PCP are found to be dominated by the differences in spectral overlap. The role of the 1B ( u ) (+) state is likely to be influenced by a lower-lying (in longer polyenes), optically forbidden 1B ( u ) (-) state.

Journal Article↗
PubMed2006

Conductance of a biomolecular wire.

Carotenoids (Car) act as "wires" that discharge unwanted electrons in the reaction center of higher plants. One step in this "side-path" electron conduction is thought to be mediated by Car oxidation. We have carried out direct measurements of the conductance of single-Car molecules under potential control in a membrane-mimicking environment, and we found that when Car are oxidized conductance is enhanced and the electronic decay constant (beta) is decreased. However, the neutral molecule may already be conductive enough to account for observed electron transfer rates.

Carotenoids↗
PubMed1999

Expression of the primary coxsackie and adenovirus receptor is downregulated during skeletal muscle maturation and limits the efficacy of adenovirus-mediated gene delivery to muscle cells.

Skeletal muscle fibers are infected efficiently by adenoviral vectors only in neonatal animals. This lack of tropism for mature skeletal muscle may be partly due to inefficient binding of adenoviral particles to the cell surface. We evaluated in developing mouse muscle the expression levels of two high-affinity receptors for adenovirus, MHC class I and the coxsackie and adenovirus receptor (CAR). The moderate levels of MHC class I transcripts that were detected in quadriceps, gastrocnemius, and heart muscle did not vary between postnatal day 3 and day 60 adult tissue. A low level of CAR expression was detected on postnatal day 3 in quadriceps and gastrocnemius muscles, but CAR expression was barely detectable in adult skeletal muscle even by reverse transcriptase-polymerase chain reaction. In contrast, CAR transcripts were moderately abundant at all stages of heart muscle development. Ectopic expression of CAR in C2C12 mouse myoblast cells increased their transducibility by adenovirus at all multiplicities of infection (MOIs) tested as measured by lacZ reporter gene activity following AVCMVlacZ infection, with an 80-fold difference between CAR-expressing cells and control C2C12 cells at an MOI of 50. Primary myoblasts ectopically expressing CAR were injected into muscles of syngeneic hosts; following incorporation of the exogenous myoblasts into host myofibers, an increased transducibility of adult muscle fibers by AVCMVlacZ was observed in the host. Expression of the lacZ reporter gene in host myofibers coincided with CAR immunoreactivity. Furthermore, sarcolemmal CAR expression was markedly increased in regenerating muscle fibers of the dystrophic mdx mouse, fibers that are susceptible to adenovirus transduction. These analyses show that CAR expression by skeletal muscle correlates with its susceptibility to adenovirus transduction, and that forced CAR expression in mature myofibers dramatically increases their susceptibility to adenovirus transduction.

Adenoviridae↗
PubMed2002

Development and validation of virtual driving simulator for the spinal injury patient.

We developed a virtual reality (VR) driving simulator in order to safely evaluate and improve the driving ability of spinal injury patients. The simulator is composed of an actual car, a beam projector, and a large screen. For the interface of our driving simulator, an actual car was adapted and then connected to a computer. We equipped the car with hand control driving devices especially adapted for spinal injury patients. A beam projector was used so that the subjects could see the virtual scene on a large screen set up in front of them. The virtual environment (VE) consisted of 18 sections (e.g., a speed-limited road, a straight road, a curved road, a left turn) and each section was linked naturally to the next. The subjects selected for this trial were 10 normal drivers with valid driving licenses and 15 patients with thoracic or lumbar cord injuries who had prior driving experience. For evaluation, five driving skills were measured, including average speed, steering stability, centerline violations, traffic signal violations, and driving time in various road conditions such as straight and curved roads. The normal subjects manipulated the gas pedal and the brake with their feet, while the patients manipulated a hand control with their hands. After they finished driving the whole course, the participants answered the questions such as "How realistic did the virtual reality driving simulator seem to you?" and "How much was your fear reduced?" In this study, we found that the difference in manipulation method (i.e., the patient group's hand control versus the normal driver's foot controls) does not seem to influence relative performance in the VR driving simulator, though training to improve the use of hand controls in the VR driving simulator would be useful to reduce the fear that the patients feel while driving.

Adult↗
PubMed1998

Enhancing effect of N-dodecyl-2-pyrrolidone on the percutaneous absorption of 5-fluorouracil derivatives.

The enhancing effects of N-dodecyl-2-pyrrolidone (NDP) on the percutaneous absorption of doxifluridine (DOX), 5-fluorouracil (5-FU), tegafur (TEG) and carmofur (CAR) were examined using an in vitro penetration technique and rat skin. Phosphate buffered isotonic saline (PBS), propylene glycol (PG) and PG containing 0.4M NDP (PGNDP) were applied as the donor solution. The correlation between the n-octanol/water partition coefficients and the permeability coefficients of DOX, 5-FU and TEG was investigated using both logarithmic plots. It was determined that the permeability coefficients are significantly correlated with their n-octanol/water partition coefficients on PBS. This result suggested that the non-polar stratum corneum lipid lamella in the skin might act as a rate limiting step on the skin penetration of DOX, 5-FU and TEG. The permeability coefficient of DOX, 5-FU and TEG was increased on PGNDP. The enhancing effect of NDP on the permeability coefficient was more effective at higher hydrophilic drugs, the values of the permeability coefficient had almost the same values on PGNDP and the dependency of the permeability coefficient on the n-octanol/water partition coefficient disappeared in the presence of NDP. These results indicated that the enhancing effect of NDP on the percutaneous absorption of DOX, 5-FU and TEG might be closely related to the perturbation of stratum corneum lipid lamella. Since it has been well recognized that CAR is decomposed into 5-FU in neutral and alkaline solution, the decomposition rate of CAR was measured using PBS solution and was found to be very rapid (Kd = 3.17 h-1, t1/2 = 13.1 min). The total concentrations of CAR plus 5-FU in the acceptor compartment were used to determine the permeability coefficient of CAR. The obtained value of the permeability coefficient of CAR on PG was almost the same as that of TEG on PG (CAR: 1.11 x 10(-3) cm/h, TEG: 1.24 x 10(-3) cm/h), while that of CAR on PGNDP was smaller than that of TEG on PGNDP (CAR: 6.06 x 10(-3) cm/h, TEG: 1.24 x 10(-2) cm/h). To determine the lipophilic property of CAR, the lipophilic index (log k') was measured by HPLC. The value of the lipophilic index of CAR was 92 times higher than that of TEG. These results indicated that CAR is a higher lipophilic compound, and the smaller value of the permeability coefficient of CAR compared with that of TEG on PGNDP might be caused by the strong binding of CAR to the rat skin (dermis). The dermis might act as a rate limiting step on the skin penetration of CAR, and the percutaneous absorption of CAR might be controlled by both the stratum corneum and the dermis.

Animals↗
PubMed1999

Teaching biomedical applications to secondary students.

Certain aspects of biomedical engineering applications lend themselves well to experimentation that can be done by high school students. This paper describes two experiments done during a six-week summer internship program in which two high school students used electrodes, circuit boards, and computers to mimic a sophisticated heart monitor and also to control a robotic car. Our experience suggests that simple illustrations of complex instrumentation can be effective in introducing adolescents to the biomedical engineering field.

Adolescent↗
PubMed1987

Acquired brain damage and driving: a review.

Five issues in evaluating driving ability after brain damage were addressed through a review of the literature. Some preliminary conclusions were reached: (1) about half of all subjects studied still hold a valid driver's license; (2) brain-damaged drivers could not, in general, be seen as risky drivers, although some individuals show decreased driving skill and risky behavior in traffic; and (3) statistics show no increase in traffic violations or accidents in groups of neurologic patients with acquired brain lesions or diseases. Frequently noted problems of brain-damaged drivers include poor judgment of traffic situations, impulsivity, and visuospatial impairments. Traditional psychologic tests have insufficient predictive value regarding fitness to drive. It is suggested that new techniques be developed to enable more valid statements about the skills needed for safe traffic participation. These assessment techniques should emphasize the higher cognitive levels in driving, ie, the tactical and strategic levels. At the moment, driver training programs in rehabilitation focus mainly on the operational level, with emphasis on handling the car, use of controls and mirrors, and technical adaptation of the vehicle.

Activities of Daily Living↗
PubMed1977

A critical evaluation of bronchial hygiene in pediatric pulmonary disease.

The variables inherent in analyzing the effectiveness of modalities used to achieve bronchial hygiene are numerous. Treatments may be given in a variety of settings, including intensive-care units, pediatric wards, respiratiory therapy departments, physical therapy departments, chronic-care hospitals, special education centers, and patient homes. Treatments are administered by a variety of medical professionals, allied health personnel, and lay volunteers. Motivation of the care providers as well as of the patients may vary greatly. Also, efforts are needed to study patients at comparable stages in their growth and development and in the progression of their particular diseases. Rather than perpetuating the unquestioning use of these various treatments, a series of carfully constructed and controlled studies done in collaborative fashion need to be performed. Until that time, the recommendations we have outlined dealing with each of the various segments of bronchial hygiene may serve as useful guidelines.

Aerosols↗
PubMed1981

Vehicle fingertip reach controls--human factors recommendations.

Interviews were conducted with 405 drivers of cars equipped with fingertip reach controls. A high percentage of finding problems was reported when the horn was mounted on a stalk and also when the turn signal was on a right stalk. Drivers of configurations with two left stalks had a large percentage of inadvertent operation problems for the turn signal and for the headlight beam selector. A laboratory experiment was conducted to evaluate modes of operation for the wiper on/off, wiper speed and washer on/off functions. Subjects performed best when the wiper on/off and speed control were actuated by a rotating had switch. Subjects' reactions to stalk mounted controls were much faster than their reactions to dash mounted controls. Recommendations to eliminate finding and inadvertent operation problems associated with fingertip reach controls are given.

Journal Article↗