Quantitative assessment of driving performance in Parkinson's disease.

OBJECTIVES: The primary aim of this study was to determine how Parkinson's disease (PD) affects driving performance. It also examined whether changes in driver safety were related to specific clinical disease markers or an individual's self rating of driving ability. METHODS: The driving performance of 25 patients with idiopathic PD and 21 age matched controls was assessed on a standardised open road route by an occupational therapist and driving instructor, to provide overall safety ratings and specific driving error scores. RESULTS: The drivers with PD were rated as significantly less safe (p<0.05) than controls, and more than half of the drivers with PD would not have passed a state based driving test. The driver safety ratings were more strongly related to disease duration (r = -0.60) than to their on time Unified Parkinson's Disease Rating Scale (r = -0.24). Drivers with PD made significantly more errors than the control group during manoeuvres that involved changing lanes and lane keeping, monitoring their blind spot, reversing, car parking, and traffic light controlled intersections. The driving instructor also had to intervene to avoid an incident significantly more often for drivers with PD than for controls. Interestingly, driver safety ratings were unrelated to an individual's rating of their own driving performance, and this was the case for all participants. CONCLUSIONS: As a group, drivers with PD are less safe to drive than age matched controls. Standard clinical markers cannot reliably predict driver safety. Further studies are required to ascertain whether the identified driving difficulties can be ameliorated.

Comparison of driving performance of young and old drivers (with and without visual impairment) measured during in-traffic conditions.

PURPOSE: The aim of this study was to determine whether visual impairment and age affected driver performance and safety rated during in-traffic driving conditions. METHODS: Participants included 30 younger, 25 middle-aged, and 35 older subjects with normal vision and 47 older subjects with visual impairment. All subjects were legally eligible to drive. Driving performance was assessed during in-traffic conditions by a professional driving instructor and an occupational therapist using specific scoring criteria. RESULTS: Group allocation significantly affected driving performance as assessed by the driving instructor and occupational therapist (p < 0.05). The driving instructor and occupational therapist scores were highly correlated (r = 0.76). Of the drivers who were scored as being unsafe, all were older and the majority (75%) had visual impairment. DISCUSSION: Older drivers with or without visual impairment were rated as being less safe than the younger and middle-aged drivers with normal vision.

Production of cloned pigs from in vitro systems.

Here we describe a procedure for cloning pigs by the use of in vitro culture systems. Four healthy male piglets from two litters were born following nuclear transfer of cultured somatic cells and subsequent embryo transfer. The initiation of five additional pregnancies demonstrates the reproducibility of this procedure. Its important features include extended in vitro culture of fetal cells preceding nuclear transfer, as well as in vitro maturation and activation of oocytes and in vitro embryo culture. The cell culture and nuclear transfer techniques described here should allow the use of genetic modification procedures to produce tissues and organs from cloned pigs with reduced immunogenicity for use in xenotransplantation.

Comparison of the safety, vaccine virus shedding, and immunogenicity of influenza virus vaccine, trivalent, types A and B, live cold-adapted, administered to human immunodeficiency virus (HIV)-infected and non-HIV-infected adults.

Fifty-seven human immunodeficiency virus (HIV)-infected (CDC class A1-2) and 54 non-HIV-infected adults, not prescreened for influenza susceptibility, were randomized to receive trivalent live attenuated influenza vaccine (LAIV) or placebo intranasally. LAIV was safe and well tolerated with no serious adverse events attributable to vaccine. Reactogenicity rates were similar in LAIV and placebo recipients except that runny nose/nasal congestion was significantly more common in LAIV recipients regardless of HIV status. No prolonged shedding of LAIV was observed in HIV-infected participants. HIV RNA levels were not increased and CD4 counts were not decreased in HIV-infected LAIV recipients compared with placebo recipients after immunization. Shedding of LAIV and increases in antibody titers were infrequent, consistent with prior experience in unscreened adults. The data suggest that inadvertent vaccination with LAIV in relatively asymptomatic HIV-infected adults would not be associated with frequent significant adverse events.

Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial.

CONTEXT: Influenza virus is a major cause of illness, disruption to daily life, and increased use of health care in all age groups. OBJECTIVE: To assess the safety and effectiveness of intranasally administered trivalent, live, attenuated influenza virus (LAIV) vaccine for reducing illness, absenteeism, and health care use among healthy, working adults. DESIGN: Randomized, double-blind, placebo-controlled trial conducted from September 1997 through March 1998. SETTING: Thirteen centers across the United States. PARTICIPANTS: A total of 4561 healthy, working adults aged 18 to 64 years recruited through health insurance plans, at work sites, and from the general population. INTERVENTION: Participants were randomized 2:1 to receive intranasally administered trivalent LAIV vaccine (n = 3041) or placebo (n = 1520) in the fall of 1997. MAIN OUTCOME MEASURES: Episodes of febrile illness, severe febrile illness, febrile upper respiratory tract illness, work loss, and health care use during the peak and total influenza outbreak periods, and adverse events. RESULTS: Recipients of LAIV vaccine were as likely to experience 1 or more febrile illnesses as placebo recipients during peak outbreak periods (13.2% for vaccine vs 14.6% for placebo; P=.19). However, vaccination significantly reduced the numbers of severe febrile illnesses (18.8% reduction; 95% confidence interval [CI], 7.4%-28.8%) and febrile upper respiratory tract illnesses (23.6% reduction; 95% CI, 12.7%-33.2%). Vaccination also led to fewer days of illness across all illness syndromes (22.9% reduction for febrile illnesses; 27.3% reduction for severe febrile illnesses), fewer days of work lost (17.9% reduction for severe febrile illnesses; 28.4% reduction for febrile upper respiratory tract illnesses), and fewer days with health care provider visits (24.8% reduction for severe febrile illnesses; 40.9% reduction for febrile upper respiratory tract illnesses). Use of prescription antibiotics and over-the-counter medications was also reduced across all illness syndromes. Vaccine recipients were more likely to experience runny nose or sore throat during the first 7 days after vaccination, but serious adverse events between the groups were not significantly different. The match between the type A(H3N2) vaccine strain and the predominant circulating virus strain (A/Sydney/05/97[H3N2]) for the 1997-1998 season was poor, suggesting that LAIV provided substantial cross-protection against this variant influenza A virus strain. CONCLUSION: Intranasal trivalent LAIV vaccine was safe and effective in healthy, working adults in a year in which a drifted influenza A virus predominated.

Filgrastim prevents severe neutropenia and reduces infective morbidity in patients with advanced HIV infection: results of a randomized, multicenter, controlled trial. G-CSF 930101 Study Group.

OBJECTIVE: To assess the effect of filgrastim treatment on the incidence of severe neutropenia in patients with advanced HIV infection, and the effect of initial filgrastim treatment on prevention of infectious morbidity. DESIGN: Randomized, controlled, open-label, multicenter study. SETTING: Outpatient centers and physician offices. PATIENTS: Men and women aged > 13 years, who were HIV antibody-positive, and had a CD4 cell count < 200 x 10(6)/l, absolute neutrophil count (ANC) 0.75-1.0 x 10(9)/l, and platelet count > or = 50 x 10(9)/l within 7 days of randomization were eligible. Two hundred and fifty-eight patients entered and 201 completed the study. INTERVENTION: Daily filgrastim (starting at 1 microg/kg daily, adjusted up to 10 microg/kg daily) or intermittent filgrastim (starting at 300 microg daily one to three times per week to a maximum of 600 microg daily 7 days weekly) was administered to maintain an ANC between 2 and 10 x 10(9)/l. Patients in the control group received filgrastim if severe neutropenia developed. MAIN OUTCOME MEASURES: Incidence of severe neutropenia (ANC < 0.5 x 10(9)/l) or death, incidence of bacterial and fungal infections, duration of hospitalization and intravenous antibacterial use, and safety. RESULTS: The primary endpoint of severe neutropenia or death was less frequent in patients who received daily (12.8%) or intermittent (8.2%) filgrastim compared with control patients (34.1%; P<0.002 and P<0.0001 for comparison with daily and intermittent groups, respectively). Filgrastim-treated patients developed 31% fewer bacterial infections and 54% fewer severe bacterial infections than control patients, required 26% less hospital days including 45% fewer hospital days for bacterial infections, and needed 28% fewer days of intravenous antibacterials. Filgrastim was not associated with an increase in HIV-1 plasma RNA level in a subset of patients in whom this was measured or any new or unexpected adverse events. CONCLUSION: Filgrastim was safe and effective in preventing severe neutropenia in patients with advanced HIV infection, and may reduce the incidence and duration of bacterial infections, incidence of severe bacterial infections, duration of hospital days for infections, and days of intravenous antibacterial agents.

Short-term recombinant human DNase in bronchiectasis. Effect on clinical state and in vitro sputum transportability.

We report a double blind placebo-controlled phase II study of the efficacy and safety of nebulized recombinant human DNase (rhDNase) administered for 14 d to adults with bronchiectasis not caused by cystic fibrosis. All were in a stable clinical state at the commencement of the study, and they received (1) rhDNase 2.5 mg twice daily, (2) rhDNase once daily, or (3) placebo (excipient only) inhalation. The outcome measures were spirometry, subjective quality of life/dyspnea, and safety. We also measured the ciliary transportability of the sputum expectorated before and after the treatment period, using the mucus-depleted bovine trachea. The drug was well tolerated, but it produced no significant change in any of the outcome variables or in sputum transportability. When the drug was incubated with bronchiectatic sputum in vitro, a fall in transportability was observed. We discuss possible explanations for the lack of a measurable benefit from rhDNase in this study population, which appears to contrast with the improvements shown in cystic fibrosis using studies of similar design.

Long-term physical functioning in persons with knee osteoarthritis from NHANES. I: Effects of comorbid medical conditions.

This study examined the effects of comorbid medical conditions (heart disease, pulmonary disease, hypertension and obesity) on the association of radiographic knee osteoarthritis (OA) with long-term difficulty in physical function. Data are from the National Health and Nutrition Examination Survey, 1971-1975 (NHANES I), a prospective epidemiologic cohort study, and the NHANES Epidemiologic Follow-up Study, 1982-1984 (NHEFS) and included 4059 persons who were 45-74 years old and participated in the detailed examination component of NHANES I. Knee OA was ascertained by anterior-posterior bilateral radiographs of the knee and self-report of knee pain, heart and pulmonary disease by self report of disease or symptoms, and hypertension and obesity by blood pressure and weight measurements. The presence of symptomatic knee OA at NHANES I was associated with reported difficulty at NHEFS 1982-84 in functions which used the lower extremity (ambulation and transfer). The presence of coexistent chronic conditions, particularly heart disease, pulmonary disease and obesity, increased the likelihood of subsequent disability. These findings suggest that knee OA is associated with long-term physical disability, and that the presence of coexistent chronic disease may increase the amount of long-term disability from knee OA.

Speed of memory scanning is not affected in early HIV-1 infection.

Thirty-seven nondemented HIV-seropositive and 17 seronegative control subjects were administered the Sternberg speed of memory scanning task, a procedure frequently employed to study mental slowing in patients with subcortical dementing disorders. Experimental and control subjects did not differ in speed of memory scanning, as indexed by the slopes of set size-reaction time functions, nor on mean 0-intercepts for the RT functions, which index stimulus detection and motor response time. Intercept values were significantly greater for subjects with a positive alcohol abuse history and for subjects with greater self-reported depression, but slopes were not significantly correlated with substance abuse history or psychological distress. Cognitive slowing in early HIV-1 infection is not a nonspecific effect observed across all measures of information processing speed. Underlying component functions measured must be carefully considered when selecting reaction time tasks for study with HIV-seropositive subjects. The term "subcortical" dementia may be too general a descriptor, and RT task performance may provide an alternative basis for classification of dementia types.

Knee osteoarthritis and physical functioning: evidence from the NHANES I Epidemiologic Followup Study.

Although osteoarthritis (OA) is common among adults, little is known about its long-term impact on physical function. Therefore, in a cohort of 2,884 adults aged 45 years or older, [National Health and Nutrition Examination Survey I (NHANES I 1971-1975)] we examined the association of baseline radiographic knee OA and difficulty in physical functioning 10 years later (NHANES I Followup Study 1982-1984). In sex specific analyses, after controlling for age, race and length of followup, persons with radiographic knee OA were more likely than persons without knee OA to report difficulty with physical functioning, particularly for activities involving mobility, transfer and instrumental activities of daily living. However, the association of knee OA with physical functioning was influenced by the radiographic grade of OA and knee pain at NHANES I, suggesting that disease severity and pain are important in anticipating difficulties with physical functioning in persons with knee OA.

Sheep trophoblast in monolayer cell culture.

Methods are described for the preparation and maintenance of ovine trophoblast in monolayer cell culture, and for the preparation of cultured cells for ultrastructural examination. Monolayers grown from dispersed and explanted primary cultures were maintained in consecutive subcultures for periods of 12 to 16 weeks. Towards the end of the first week of incubation high concentrations as the cultured developed. In the second week of incubation small binucleate cells were seen in cultures prepared for electron microscopy. By the 14th day larger binucleate cells were visible at the outer edges of the developing monolayer, and by the third to fourth week 25 to 40 per cent of the cells in culture were in binucleate form. Mature binucleate cells seeded in primary dispersed cultures did not survive beyond the 14th day. The result suggest that (a) the binucleate cells which first appear in monolayers of cultured trophoblast during the second week of incubation are formed by nuclear division of uninucleate cells and not from mature binucleate cells seeded in primary dispersed cultures; and (b) there may be a correlation between the numbers of binucleate cells present in the monolayer and the rate of production of ovine placental lactogen. Monolayer cultures of sheep trophoblast may well provide a useful and relatively inexpensive experimental system for the study of binucleate cells and the mechanisms of placental hormone production.

Ultrastructural changes in the placenta of the ewe after long-term intravascular infusion of 2-bromo-alpha-ergocryptine (CB154) into mother or fetus.

The fine structural appearance of the placenta of the ewe has been examined following long-term infusion of CB154 into either the fetus or the pregnant ewe. Binucleate cells which usually contain aggregations of spherical membrane-bound electron-dense inclusions, are a characteristic component of the chorionic epithelium of the sheep. Following CB154 infusion into either the fetus or ewe at 111 to 137 days of gestation, binucleate cells were partially or completely depleted of the droplets which are present in binucleate cells of control animals at a similar gestational age. No obvious changes in the maternal epithelial syncytium were observed after CB154 administration. Infusion of CB154 into the fetus alone was also followed by degenerative changes in some binucleate cells which ranged from condensation of nuclei to complete cell fragmentation. Either a direct or an indirect action of CB154 on binucleate cells is suggested by these observations. Hypoprolactinaemia followed CB154 infusion in all treated animals; its possible influence on binucleate cell activity is discussed.

Ultrastructural studies of the equine uterus and placenta following parturition.

Post-partum placentae and uterine biopsy samples from mares after normal and abnormal foalings are described. After normal delivery there is little damage to fetal or maternal tissues. The villous epitheliochorial palcenta separates cleanly at the maternal-fetal interface and the afterbirth consists almost exclusively of fetal tissue. Uterine involution is well advanced by the 3rd and 4th days post partum and the changes are usually complete by the oestrus 7--10 days after parturition. Placental separation and involution of the uterus appear to proceed normally in malpresented foals and in otherwise viable foals with musculoskeletal defects. In aborted, stillborn or dysmature foals there are obvious signs of damage to both fetal and maternal tissues. It is generally accepted that the growth and development of the fetus is dependent upon a placenta of adequate functional capabilities. The observations suggest that the placenta is similarly dependent upon its association with a normal healthy fetus.

Ultrastructural changes in the placenta of the ewe after fetal pituitary stalk section.

Binucleate cells are a normal component of the ovine chorionic epithelium, but are usually separated from the fetal-maternal interface by a thin layer of cytoplasm derived from the principal or uni-nucleate cells of the trophoblast. They are distinguished not only by two distinct and separate nuclei, but also by conspicuous membrane-bound cytoplasmic inclusions in the form of haloed droplets. After fetal pituitary stalk section binucleate cells move up to and participate in the formation of the fetal-maternal interface; furthermore they extend clear blunt-ended pseudopodia into the maternal epithelial syncytium. These activities do not appear to be supppressed by fetal infusion of cortisol or ACTH. The apparent motility of binucleate cells, together with the presence of haloed droplets within the maternal epithelial syncytium, suggests that after fetal pituitary stalk section binucleate cells invade the uterine syncytium, lose their limiting membranes and discharge their contents into the syncytial cytoplasm. Large molecules such as ovine placental lactogen may be transported from fetal to maternal tissues by this mechanism.