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Biomedical subjects

S H Fox

Publications and source records attributed to S H Fox.

At least 19 recordsLinked to original sources
PubMed2005

Prevention of osteoporosis in glucocorticoid-treated neurology patients.

OBJECTIVES: Iatrogenic, including corticosteroid-induced osteoporosis is preventable with administration of osteoprotective biphosphonates. The best medical practice is published in the National Guidelines: UK Osteoporosis Consensus Group (1998, update 2002). We conducted an audit in prednisolone-treated general neurology patients, to assess compliance to national guidelines, raise awareness of osteoporosis prevention, and improve clinical practice in a tertiary neurology referral centre. METHODS AND RESULTS: Preintervention: Of the 48 cases (21 male) identified twenty-nine (61%) received osteoporosis prophylaxis. Nineteen (40%) were given biphosphonates, while 10 (21%) hormone replacement therapy or calcium and Vitamin D. INTERVENTION: Results were presented to the consultant body. Postintervention: Data were collected prospectively on 48 patients (30 male) in year 2001. Thirty-eight (79%) received prophylaxis: 35 (73%) were started on biphosphonates, while 3 (6%) on calcium and Vitamin D. This process was repeated 2 years later to assess sustainability. Of the 48 patients, 44 (92%) received prophylaxis: 41 (86%) were taking biphosphonates, while 3 (6%) calcium and Vitamin D. CONCLUSION: We present an original and complete audit on osteoporosis prophylaxis in a typical population of neurology patients. Though initial results were similar to previous reports, our audit led to significant improvement in clinical practice. National guidelines could not be followed meticulously, as our centre has no regular access to bone densitometry. Our patient population had other risk factors for osteoporosis apart from steroid use. Therefore, we recommend that neurologists in this setting use osteoporosis prophylaxis for all their patients on long-term corticosteroids.

Adult↗
PubMed2005

A writing device improves writing in primary writing tremor.

Primary writing tremor (PWT) is task-specific and interferes with handwriting. Several reports have shown a beneficial response of this disorder to stereotactic functional neurosurgery. Significant improvement with a writing device was demonstrated with blind rating of handwriting and spiral drawing samples collected before and during its use in nine patients with PWT, suggesting that this therapeutic modality should be tried before considering chronic pharmacotherapy or functional neurosurgery.

Adult↗
PubMed2003

Deep brain stimulation of the subthalamic nucleus: effectiveness in advanced Parkinson's disease patients previously reliant on apomorphine.

OBJECTIVES: To assess the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with advanced Parkinson's disease previously reliant on apomorphine as their main antiparkinsonian medication. METHODS: Seven patients with motor fluctuations despite optimal medical treatment given as predominantly apomorphine infusion (n=6), or intermittent apomorphine injections (n=1) underwent bilateral STN DBS using frameless stereotactic surgery. Standard assessments of parkinsonism and motor fluctuations, using Unified Parkinson's Disease Rating Scale (UPDRS) were performed before and six months after surgery. Assessments were performed both on and off medication, and postoperative with the stimulators switched on and off. RESULTS: Bilateral STN DBS improved motor scores (UPDRS III) by 61% when off medication (p<0.05). Clinical fluctuations (UPDRS IV items 36-39) were reduced by 46.2% (p<0.05). Total daily apomorphine dose was reduced by 68.9% (p<0.05) and apomorphine infusion via a pump was no longer required in four patients. There were no operative complications. Two patients required treatment for hallucinations postoperatively but there was no significant change in mini-mental state examination. CONCLUSIONS: In patients with advanced Parkinson's disease, previously reliant on apomorphine, bilateral STN DBS is an effective treatment to reduce motor fluctuations and enable a reduction in apomorphine use.

Aged↗
PubMed2001

Cannabinoids reduce levodopa-induced dyskinesia in Parkinson's disease: a pilot study.

The lateral segment of the globus pallidus (GPl) is thought to be overactive in levodopa-induced dyskinesia in PD. Stimulation of cannabinoid receptors in the GPl reduces gamma-aminobutyric acid (GABA) reuptake and enhances GABA transmission and may thus alleviate dyskinesia. In a randomized, double-blind, placebo-controlled, crossover trial (n = 7), the authors demonstrate that the cannabinoid receptor agonist nabilone significantly reduces levodopa-induced dyskinesia in PD.

Aged↗
PubMed2001

Neural mechanisms underlying peak-dose dyskinesia induced by levodopa and apomorphine are distinct: evidence from the effects of the alpha(2) adrenoceptor antagonist idazoxan.

Dyskinesia, secondary to dopamine replacement therapy, is the major complication of currently available therapies for Parkinson's disease. Alpha(2) adrenoceptor antagonists, such as idazoxan, can significantly reduce levodopa-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned, nonhuman primate model of Parkinson's disease and in human. This action of adrenoceptor antagonists may involve blockade of the actions of noradrenaline synthesised from levodopa. We hypothesise that, because dopamine receptor agonists, such as apomorphine, cannot be metabolised to produce noradrenaline, activation of adrenoceptors may not be involved in dyskinesia produced by such agents. If this were the case, idazoxan would not be expected to reduce apomorphine-induced dyskinesia. MPTP-lesioned marmosets with stable dyskinesia induced by prolonged levodopa therapy were given an acute challenge with apomorphine (0.3 mg/kg subcutaneously) or levodopa (8.0 mg/kg orally), these doses produced equivalent peak-dose dyskinesia. Idazoxan (2.5 mg/kg p.o.), or vehicle, was then administered with either apomorphine or levodopa. Idazoxan abolished levodopa-induced dyskinesia but did not affect apomorphine-induced dyskinesia (P < 0.05 and P > 0.05, respectively, Wilcoxon matched pairs test). Idazoxan also extended the anti-parkinsonian actions of levodopa but did not affect those of apomorphine. The pharmacological characteristics of the neural mechanisms underlying levodopa-induced dyskinesia and apomorphine-induced dyskinesia in parkinsonism thus appear to be distinct, at least with respect to the involvement of alpha(2) adrenoceptors. Specifically, levodopa, but not apomorphine-induced dyskinesia, involves activation of adrenoceptors. This finding may have major implications for understanding dyskinesia and should be borne in mind when designing clinical studies in which levodopa or dopamine receptor agonist challenges are employed to assess potential anti-dyskinetic properties of drugs.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Mu- and delta-opioid receptor antagonists reduce levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease.

Long-term treatment of Parkinson's disease with levodopa is complicated by the emergence of involuntary movements, known as levodopa-induced dyskinesia. It has been hypothesized that increased opioid transmission in striatal output pathways may be responsible for the generation of dyskinesia. In this study, we have investigated the effect of blockade of opioid peptide transmission on levodopa-induced dyskinesia in a primate model of Parkinson's disease-the MPTP-lesioned marmoset. Coadministration of nonselective and mu- or delta-subtype-selective opioid receptor antagonists with levodopa resulted in a significant decrease in dyskinesia. There was no attenuation of the anti-parkinsonian actions of levodopa. These data suggest that specific mu- or delta-opioid receptor antagonists might be applicable clinically in the treatment of levodopa-induced dyskinesia in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Antiparkinsonian action of a delta opioid agonist in rodent and primate models of Parkinson's disease.

The opioid peptides localized in striatal projection neurons are of great relevance to Parkinson's disease, not only as a consequence of their distribution, but also due to the pronounced changes in expression seen in Parkinson's disease. It has long been suspected that increased expression of enkephalin may represent one of the many mechanisms that compensate for dopamine (DA) depletion in Parkinson's disease. Here we demonstrate that a systemically delivered, selective delta opioid agonist (SNC80) has potent antiparkinsonian actions in both rat and primate models of Parkinson's disease. In rats treated with either the D2-preferring DA antagonist haloperidol (1 mg/kg) or the selective D1 antagonist SCH23390 (1 mg/kg), but not a combination of D1 and D2 antagonists, SNC80 (10 mg/kg) completely reversed the catalepsy induced by DA antagonists. In rats rendered immobile by treatment with reserpine, SNC80 dose-dependently reversed akinesia (EC(50) 7.49 mg/kg). These effects were dose-dependently inhibited (IC(50) 1.05 mg/kg) by a selective delta opioid antagonist (naltrindole) and by SCH23390 (1 mg/kg), but not by haloperidol (1 mg/kg). SNC80 also reversed parkinsonian symptoms in the MPTP-treated marmoset. At 10 mg/kg (ip), scores measuring bradykinesia and posture were significantly reduced and motor activity increased to levels comparable with pre-MPTP-treatment scores. Any treatment that serves to increase delta opioid receptor activation may be a useful therapeutic strategy for the treatment of Parkinson's disease, either in the early stages or as an adjunct to dopamine replacement therapy. Furthermore, enhanced enkephalin expression observed in Parkinson's disease may serve to potentiate dopamine acting preferentially at D1 receptors.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Traumatic experiences and the mental health of Senegalese refugees.

The purpose of our study was to conduct a preliminary investigation into the experiences and mental health of Senegalese refugees. Although research has established that refugees are more prone to psychiatric illnesses than the general population, little has been written about West African refugees. Our focus was on adult refugees (18 years of age and older) from the Casamance region of Senegal. A total of 80 participants (39 women, 41 men) were randomly selected from refugee camps in The Gambia. The Harvard Trauma Questionnaire and the Hopkins Symptom Checklist-25 were used to assess levels of traumatization and mental health status. Typical of refugees of war, participants reported suffering a large number of various traumas. High prevalence rates of anxiety, depression, and posttraumatic stress disorder were also found in this group. A substantial mental health problem exists within the Senegalese refugee population that may signify a potential human crisis.

Adolescent↗
PubMed2000

5-HT(2C) receptor antagonists enhance the behavioural response to dopamine D(1) receptor agonists in the 6-hydroxydopamine-lesioned rat.

Non-dopaminergic therapies are of potential interest in the treatment of Parkinson's disease given the complications associated with current dopamine-replacement therapies. In this study we demonstrate that SB 206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3, 5-tetrahydropyrrol[2,3-f]indole) (20 mg/kg) enhanced the actions of the dopamine D(1) receptor agonist, SKF 82958 ((+)-6-chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide) (1 mg/kg), in eliciting locomotion in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease. This action was only seen following prior priming with L-DOPA (L-3, 4-dihydroxyphenylalanine). SB 206553 had no effect on rotational behaviour when given alone. 5-HT(2C) receptor antagonists may have potential as a means of reducing reliance on dopamine replacement in the treatment of Parkinson's disease.

Animals↗
PubMed2000

5-HT2C receptor binding is increased in the substantia nigra pars reticulata in Parkinson's disease.

The involvement of abnormalities in nondopaminergic transmitter systems in Parkinson's disease is noteworthy because of the complications, such as dyskinesia, associated with long-term dopamine replacement therapy. The output regions of the basal ganglia, the substantia nigra pars reticulata, and the medial segment of the globus pallidus are overactive in Parkinson's disease but underactive in dyskinesia. 5-HT2C receptors are localized in these regions and are excitatory. A 5-HT2C receptor binding assay using [3H]-mesulergine and SB 200646A to define nonspecific binding was applied to postmortem tissue from patients with Parkinson's disease and from age-matched control patients. [3H]-mesulergine binding was increased in the substantia nigra pars reticulata by 108% in Parkinson's disease tissue as compared with control tissue. These data suggest abnormalities of 5-HT2C transmission in the basal ganglia of patients with Parkinson's disease.

Aged↗
PubMed2000

Antiparkinsonian actions of ifenprodil in the MPTP-lesioned marmoset model of Parkinson's disease.

Dopamine-replacement strategies form the basis of most symptomatic treatments for Parkinson's disease. However, since long-term dopamine-replacement therapies are characterized by many side effects, most notably dyskinesia, the concept of a nondopaminergic therapy for Parkinson's disease has attracted great interest. To date, it has proved difficult to devise a nondopaminergic therapy with efficacy comparable to that of dopamine replacement. In animal models of Parkinson's disease, loss of striatal dopamine leads to enhanced excitation of striatal NR2B-containing NMDA receptors. This is responsible, in part at least, for generating parkinsonian symptoms. Here we demonstrate that, in the MPTP-lesioned marmoset, monotherapy with the NR2B-selective NMDA receptor antagonist, ifenprodil, administered de novo, has antiparkinsonian effects equivalent to those of l-DOPA (administered as its methyl ester form). In MPTP-lesioned marmosets, median mobility scores, following vehicle-treatment were 12.5/h (range 6-21), compared to 61/h (range 26-121) in normal, non-MPTP-lesioned animals. Following ifenprodil (10 mg/kg) treatment in MPTP-lesioned marmosets, the median mobility score was 66/h (range 34-93), and following l-DOPA (10 mg/kg i.p.) treatment 89/h (range 82-92). The data support the proposal that NR2B-selective NMDA receptor antagonists have potential as a nondopaminergic monotherapy for the treatment of parkinsonian symptoms when given de novo.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

The Sierra Leonean refugee experience: traumatic events and psychiatric sequelae.

Although a number of studies address the mental health status of refugees from a variety of regions in the world, there are no studies of the mental health status of West African refugees. It was the purpose of this study to determine the prevalence of various traumatic events to which a sample of Sierra Leonean refugees have been exposed as well as psychiatric sequelae associated with such exposure. A procedure of probability sampling was used to identify and assess a sample of 55 Sierra Leonean refugees residing in a UNHCR-sponsored camp in The Gambia, West Africa. The Harvard Trauma Questionnaire and the Hopkins Symptom Checklist-25 served as survey instruments. The findings clearly indicate the presence of disturbingly high prevalence rates for various traumatic experiences and psychiatric sequelae. It appears that a significant mental health problem exists that begs to be addressed.

Adult↗
PubMed2000

Four multidetector-row helical CT: image quality and volume coverage speed.

PURPOSE: To evaluate the imaging performance characteristics of four multidetector-row helical computed tomography (CT) and assess improvement in volume coverage speed over that with single multidetector-row helical CT. MATERIALS AND METHODS: The section-sensitivity profile and image noise of a four multidetector-row scanner were measured with phantom scans and compared with predictions from theoretic models. Nominal section thickness ranged from 1.25 to 10.00 mm, beam collimation from 1.25 to 5.00 mm, and table speed from 3.75 to 30.00 mm per rotation. Image artifacts with four and single multidetector-row helical CT were compared in both a phantom study and a subjective rating analysis of clinical images. RESULTS: Compared with single multidetector-row helical CT, the volume coverage speed of four multidetector-row helical CT (range, 3.75-30.00 mm per rotation) is at least twice as fast as that with single multidetector-row helical CT (1.0-10.0 mm per rotation) with fully comparable image quality or, in many cases, three times as fast with diagnostically comparable image quality. CONCLUSION: Compared with single multidetector-row helical CT, four multidetector-row helical CT provides a two- to threefold improvement in volume coverage speed with comparable diagnostic image quality.

Adult↗
PubMed2000

Juvenile offenders and accurate perception of time.

In the present study, 72 juvenile offenders and 24 high school boys with no criminal history were tested on how accurately they could estimate the passage of 15-, 30-, 60-, and 120 sec. periods of time. Hypotheses predicted significant differences between the accuracy of time estimations by juvenile offenders and high school students across and among all four trials and also between trials of time estimation by 24 violent juvenile offenders and 24 nonviolent juvenile offenders across and among the trials. Analysis indicated that these mostly Hispanic juvenile offenders produced significantly less accurate time estimations than nonoffending high school students, but no significant differences were found between estimates by violent juvenile and nonviolent juvenile offenders. The results are consistent with previous research indicating that deficits in ego functioning may be associated with the presence of maladaptive and antisocial behavior.

Adolescent↗
PubMed1999

The alpha2-adrenergic receptor antagonist idazoxan reduces dyskinesia and enhances anti-parkinsonian actions of L-dopa in the MPTP-lesioned primate model of Parkinson's disease.

Dopamine replacement therapy in patients with Parkinson's disease is plagued by the emergence of abnormal involuntary movements known as L-dopa-induced dyskinesias. It has been demonstrated that yohimbine can reduce L-dopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease. Yohimbine is, among other things, an alpha-adrenergic receptor antagonist. In this study, we demonstrate that the selective and potent alpha2-adrenergic receptor antagonist idazoxan reduces L-dopa-induced dyskinesia in the MPTP-lesioned marmoset model of Parkinson's disease. The alpha2-adrenergic receptor antagonists rauwolscine and yohimbine also reduce L-dopa-induced dyskinesia. Furthermore, we demonstrate that coadministration of idazoxan with L-dopa can provide an anti-parkinsonian action more than twice the length of that seen with L-dopa alone. However, idazoxan as a monotherapy displayed no anti-parkinsonian actions. We propose that idazoxan in combination with L-dopa may provide a novel approach to the treatment of Parkinson's disease that will not only reduce the dyskinetic side effects, but extend the anti-parkinsonian actions of L-dopa. Idazoxan, as an adjunct to dopamine replacement, may prove useful in the treatment of parkinsonian patients at all stages of disease progression.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1999

Strategies to prevent organ failure.

The gastrointestinal tract and the generalized inflammatory response initiated by severe injury or infection have been implicated in the pathophysiology of multiple-organ system failure. Once multiple-organ system failure has occurred, treatment focuses on supporting end-organ function. Recent studies have shown, however, that it may be possible to reduce the incidence and prevalence of multiple-organ system failure by controlling the reperfusion injury cascade, normalizing gastrointestinal blood flow and preserving the integrity of the gastrointestinal immune barrier.

Journal Article↗