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Biomedical subjects

K Nicholson

Publications and source records attributed to K Nicholson.

At least 19 recordsLinked to original sources
PubMed1999

Extrapyramidal side effects during chronic combined dopamine D1 and D2 antagonist treatment in Cebus apella monkeys.

Previous studies in non-human primates have shown that tolerance to dystonia occurs during chronic dopamine D1 (D1) but not D2 antagonism and induction/aggravation of oral dyskinesia (TD) during D2 but not D1 antagonism. We were therefore interested in determining the effects of combined chronic D1 + D2 antagonism on dystonia and dyskinesia. To this intent, 8 male Cebus apella monkeys were treated 10 weeks with gradually increasing doses of D1 antagonist (NNC 112) + a D2 antagonist (raclopride), followed by 2 weeks of treatment with the D2 antagonist alone. Due to previous neuroleptic exposure, 5 monkeys had TD and all were sensitized to dystonia. During the combined antagonist treatment, tolerance to dystonia occurred; the tolerance disappearing upon discontinuation of the D1 antagonist and continuation of the D2 antagonist alone. Parallel to these results, improvement of TD was seen during the combined antagonist treatment with worsening during the D2 antagonist alone. Both the combined antagonists and the D2 antagonist alone resulted in moderate/severe bradykinesia, with no tolerance. These findings indicate that supplementation of traditional D2 antagonism with a D1 antagonist would lessen the risk of dystonia and allow alleviation of preexisting TD, though parkinsonian side effects might still occur. The findings further indicate that separate dopaminergic mechanisms control dystonia/dyskinesia and parkinsonism.

Animals↗
PubMed1998

Effects of the common cold on mood and performance.

Previous research has shown that both experimentally-induced and naturally occurring upper respiratory tract illnesses (URTIs) influence mood and mental functioning. None of the previous studies of naturally occurring colds has conducted appropriate virological assays to determine the nature of the infecting agent. This is an essential methodological step in studies of malaise associated with URTIs. The aim of this research was to investigate the effects of naturally occurring colds on mood and objective measures of performance. This was done by first conducting a cross-sectional comparison of 37 healthy people and 158 volunteers with colds and then a longitudinal study in which 100 volunteers developed colds and 87 remained healthy. Virological techniques were used to identify infecting agents and comparisons made across the different groups. The results showed that having a cold was associated with reduced alertness and slowed reaction times. These effects were observed both for colds where the infecting virus was identified and those where it was not. Similar effects were obtained for both rhinovirus and coronavirus colds. One may conclude that upper respiratory tract illnesses lead to a reduction in subjective alertness and impaired psychomotor functioning. This was true for both illnesses where the infecting agent was identified and for those clinical illnesses where no virus was detected. It is now important to identify the mechanisms linking infection and illness with the behavioural changes. Similarly, the impact of these effects on real-life activities such as driving needs examining. Finally, methods of treatment need to be developed which not only treat the local symptoms of the illnesses but remove the negative mood and the performance impairments.

Adolescent↗
PubMed1995

[Abuse of Ecstasy (3,4-methylenedioxymethamphetamine). Pharmacological, neuropsychiatric and behavioral aspects].

Ecstasy (3,4-methylenedioxymethamphetamine) is a popular recreational drug, a "designer drug", which has been developed from the basic structure in amphetamine. Ecstasy has now reached the illegal drug market in Denmark via the US, Great Britain and Sweden. The drug is related to a certain youth culture from which it is estimated that many drug abusers have been recruited. The desired effects of ecstasy, namely enhanced openness, awareness and empathy, have previously been used in various therapeutic connections. In later years the drug has led to abuse which, in connection with certain cultural behaviour patterns (for example in discotheques), can cause dangerous psychiatric as well as somatic effects. The undesirable psychiatric effects range from fear through depression to actual psychoses, and the somatic effects vary from symptoms of increased sympathetic activity to malignant hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, renal failure, and lethal hepatotoxicity. The last mentioned symptoms occur in connection with prolonged physical activities such as exhausting dancing sessions. The article discusses the available treatments for conditions of abuse and stresses the need for prophylactic efforts in the form of information and awareness of the problem.

Brain Diseases↗
PubMed1995

Behavior and the basal ganglia.

When viewed as a whole, these basal ganglia-thalamo-cortical circuits appear to play a modulating role in a wide range of behaviors. At the cortical level, given convergence upon specified regions within the frontal lobes, the behaviors in question would be those dependent upon SMA, premotor, frontal eye fields, dorsolateral, and orbitofrontal outflow targets. Broadly speaking, processes such as the generation, maintenance, switching, and blending of motor, mental, or emotional sets would be involved. Accordingly, in basal ganglia disease, the planning and the execution of the above behavioral domains can be affected. Given the diversity and complexity of activity within the basal ganglia, the consequences of disruption depend largely upon lesion site and the associated interplay of neurochemical factors. For example, in the motor domain, damage to various striatal circuitry levels can result in either hypo- or hyperkinetic disorders of movement. Following this analogy, it might also be said that diverse lesions, depending on site, can result in problems with the development and maintenance of behavioral sets ("hypophrenic") versus problems in relinquishing preferential sets ("hyperphrenic"). These contrasting patterns are best represented in PD and OCD, respectively. In the latter case, however, the "hyperphrenic" pattern would only apply to those behaviors which are part of the obsessional rituals. This suggests that procedural system "overdrive" remains domain-specific as is the case for most operations within the procedural system. To return to the broad principle of habituation, a process first described in the context of the visual system and its connections with the tail of the caudate nucleus, it would be tempting to view PD and OCD as disorders of "under" and "over" habituation to behavioral routines. Unfortunately, the situation has proven to be more complex in view of recent neuropsychological findings (Nicholson et al., in preparation). Using a variety of problem-solving and other cognitive tasks, both PD and OCD patients were found to require more practice and/or the provision of external guidelines to facilitate habit formation. Thus, in both cases, as in other disorders of the basal ganglia, the establishment of useful heuristics by which to direct adaptive behavior suffers. OCD patients therefore appear to have at least two compartmentalized types of basal ganglia dysfunction: the ritualistic compulsions and obsessions as well as the heuristic inefficiency (i.e., poor procedural mobilization). PD patients would also suffer a similar fate as it is known that the degrees of motor versus nonmotor (i.e., procedural) deficit are poorly correlated (42).(ABSTRACT TRUNCATED AT 400 WORDS)

Affect↗
PubMed1994

Prognosis in cystic fibrosis treated with continuous flucloxacillin from the neonatal period.

All newborn infants in East Anglia are screened for cystic fibrosis by blood immunoreactive trypsin assay at 7 days. Thirty eight infants with cystic fibrosis were randomised to treatment with either continuous oral flucloxacillin 250 mg/day (group P, n = 18) or with episodic antimicrobials as clinically indicated (group E, n = 20). Their progress was monitored from diagnosis to 24 months by a nurse coordinator who visited all infants regularly, at home and in hospital, to collect anthropometric, dietary, clinical, and microbiological data. Mean (range) age of confirmation of diagnosis was 5.7 weeks (1-14 weeks). There was no significant difference in birth weight, genotype, immunoreactive trypsin concentration, neonatal history, symptoms at diagnosis, pancreatic enzyme supplementation, or parental smoking history between the groups. Infants in group E had more frequent cough and a greater number of Staphylococcus aureus isolates than infants in group P. More infants of group E were admitted to hospital, had higher admission rates during the second year (19 v 5), for longer periods (6.4 v 2.2 days), despite receiving more than double the number of courses of antibiotics than group P infants (in addition to flucloxacillin). Continuous prophylactic flucloxacillin from early diagnosis of cystic fibrosis is associated with improved clinical progress during the first two years of life.

Bacterial Infections↗
PubMed1993

Primary diagnosis predicts prognosis of lung transplant candidates.

Optimal timing for consideration of lung transplantation remains unknown. This study examined survival in patients with end-stage lung disease awaiting transplantation. Primary disease group and relevant indicators were evaluated. Ninety-three patients who met selection criteria for lung transplantation were included in this retrospective review. Of this total, 31% underwent transplantation, 38% remain waiting, and 31% died. Results demonstrate that the six-month actuarial survival rate was 89% for Eisenmenger's syndrome, 81% for emphysema, 74% for cystic fibrosis, 60% for primary pulmonary hypertension, and 38% for interstitial lung disease. Parameters found to be significant included a higher mean right atrial pressure in primary pulmonary hypertension patients who died awaiting transplantation, and lower forced expiratory volume in one second and forced vital capacity measurements in cystic fibrosis patients who died awaiting transplantation. We conclude that primary disease significantly affects survival in candidates awaiting transplantation. Reliable indicators predictive of survival are not available. Earlier referral for consideration of lung transplantation is recommended.

Adolescent↗
PubMed1993

Cystic fibrosis identified by neonatal screening: incidence, genotype, and early natural history.

The incidence of cystic fibrosis over the last 10 years in East Anglia (a region of the United Kingdom with a population of 2.1 million) has halved. This has happened during the establishment of a neonatal screening programme, which has enabled early diagnosis, genetic counselling, and lately the option of prenatal diagnosis in subsequent pregnancies. One hundred and seven children were born with cystic fibrosis between 1981 and 1990, eight of whom were siblings. The Guthrie blood spots of 82 infants detected by neonatal immunoreactive trypsin screening between 1981 and 1990 were examined for the presence of the most common cystic fibrosis gene mutation (delta F508). It was present in 135 (82%) of the 164 cystic fibrosis genes analysed with 54 (66%) cases being homozygous and 27 (33%) heterozygous. Sixty nine per cent of infants were symptomatic at the time of diagnosis regardless of genotype. No association was found between the early clinical or biochemical features of the disease and homozygosity or heterozygosity for this mutation. Screening for cystic fibrosis using the blood immunoreactive trypsin assay alone remains an effective method of identifying infants with the disease soon after birth, thereby allowing early therapeutic intervention. Genetic counselling and prenatal diagnosis have contributed to a reduction in the number of children born with cystic fibrosis, but may not entirely explain the decreasing incidence of the disease.

Cystic Fibrosis↗
PubMed1993

Influenza immunisation: policies and practices of general practitioners in England, 1991/92.

A large questionnaire survey of general practices in England to determine the most recent policies, perceptions, and procedures for influenza immunisation, and the extent to which individual practice characteristics were related to levels of vaccine distribution, was conducted during January and February 1992. The results indicate that the proportion of practices with influenza immunisation policies has increased considerably since the mid 1980s. However, some notable shortcomings remain and practice characteristics appear to have little influence on vaccine delivery, suggesting that other factors may also be important.

Aged↗
PubMed1991

High-grade T-cell lymphoma following treatment with cyclosporin A.

A 47-year-old man with persistent severe oropharyngeal ulceration developed a high-grade T-cell lymphoma soon after commencing treatment with cyclosporin A. Using Southern blotting to identify T-cell beta-chain gene rearrangements, evidence of clonal restriction was found both in blood and lymph node DNA samples. Two BamH1 rearranged bands were demonstrated in both samples. In the blood a 16 Kb band predominated, with a weaker 28 kb band. In the lymph node sample this pattern was reversed. The findings suggest that a bi-clonal population of T-lymphocytes or clonal evolution of an existing T-cell monoclone had developed, and that cyclosporin contributed to the emergence of a high-grade T-cell lymphoma.

Antigens, CD↗
PubMed1984

Purified chick embryo cell (PCEC) rabies vaccine for human use: clinical trials.

The purpose of the study was the clinical evaluation of the new PCEC-Rabies-Vaccine. In 620 healthy volunteers mild local side-reactions could be observed in less than 2% of the vaccinations. No relevant general reactions have been reported or seen after the 2200 injections apart three cases of urticaria. All the 218 volunteers tested developed neutralising rabies antibodies of the IgG-type between day 0 and day 30 after the first vaccination dose. In 45 patients the PCEC-Rabies-Vaccine, applied together with human rabies immunoglobulin in a postexposure vaccination, afforded protection against rabies after contact with a proven rabid animal. The clinical trials are proof that the compatibility and efficacy of the PCEC-Rabies-Vaccine match the high standards established by the HDC-Rabies-Vaccine.

Adolescent↗
PubMed1977

Immunity to attenuated influenza virus WRL 105 infection induced by heterologous, inactivated influenza A virus vaccines.

Groups of student volunteers were immunized with one of five different inactivated influenza virus vaccines. The concentration of virus in the various vaccines differed by both the international unitage test and by the concentration of haemagglutinin, as measured by the single radial diffusion test; the results of the two methods of standardization showed no correlation. The serum HI response to immunization was variable; volunteers given A/England/72 showed a 16.6-fold increase in homologous serum antibody titre whilst volunteers given A/Hong Kong/68 vaccine showed a 4.2-fold increase. The variable response of volunteers to immunization could not be explained by the varied concentration of virus in the vaccines, as measured by either test, the titres of serum HI antibody present before immunization, or a combination of these two factors.The ability to infect volunteers with WRL 105 virus 4 weeks after immunization with heterologous, inactivated virus vaccine was directly related to the degree of cross-reactivity between the haemagglutinins of this vaccine virus and WRL 105 virus. Thus, the greatest number of infections by the challenge virus were seen in volunteers given A/Hong Kong/68 vaccine, less were observed in volunteers given A/England/72 vaccine, and least were found in groups given A/Port Chalmers/73 or A/Scotland/74 vaccine. However, compared with the incidence of infection in volunteers given B/Hong Kong/73 vaccine, all the heterologous influenza A vaccine gave some immunity to challenge infection.

Antibodies, Viral↗