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A J Hughes

Publications and source records attributed to A J Hughes.

At least 19 recordsLinked to original sources
PubMed2005

Diagnosis of Mycobacterium tuberculosis infection using ESAT-6 and intracellular cytokine cytometry.

Diagnosis of infection with Mycobacterium tuberculosis (MTB) using tuberculin skin testing (TST) is often hampered by prior Bacille Calmette-Guérin (BCG) vaccination. ESAT-6 is a protein that is expressed by MTB but absent in BCG. It has been postulated that it might be useful in distinguishing MTB-specific immune responses. This study measured CD4 T cell responder frequencies specific for ESAT-6 and the TST reagent purified protein derivative (PPD) in patients with tuberculosis (n = 16), controls with non-tuberculous pneumonia (n = 8) and normal subjects (n = 7). Responses were identified using the intracellular cytokine staining technique and flow cytometry on whole blood samples, and performed blinded to the patient condition. Antigen-specific CD4 cells were defined by CD69 positivity and one or more cytokine [interleukin (IL)-2, IL-4, IL-10, interferon (IFN)-gamma] and/or CD40L positivity. With ESAT-6 stimulation it was found that TB patients had significantly higher frequencies of IFN-gamma and CD40L-positive CD4 T cells compared to the normal group, while no significant differences were measured with PPD stimulation. A responder frequency of 0.01% or higher for at least one of the measured cytokines/CD40L was defined as a positive response. Using this criterion to compare the two patient groups, PPD had 100% sensitivity but 0% specificity while ESAT-6 had 100% sensitivity and 88% specificity. Use of MTB-specific proteins such as ESAT-6 in combination with intracellular cytokine staining and flow cytometry has the potential to identify individuals with MTB infection.

Adult↗
PubMed2003

Lewy body cortical involvement may not always predict dementia in Parkinson's disease.

BACKGROUND: The presence of Lewy bodies (LB) in the neocortex and limbic system in patients with Parkinson's disease (PD) is commonly thought to be linked with cognitive impairment. The authors present here a series of patients with diagnosis of PD in life and no significant cognitive impairment who, at necropsy, satisfied the current neuropathological criteria for dementia with Lewy bodies (DLB). METHODS: Two hundred and seventy six brains with PD pathology were examined at the Queen Square Brain Bank in London between 1993 and 1999. The neuropathological diagnosis was PD, but 117 patients also had sufficient LB involvement above the brain stem to satisfy the current neuropathological criteria for DLB (50 patients had a neuropathological picture consistent with the limbic category of DLB and 67 with neocortical DLB). Forty eight cases were excluded who developed early cognitive impairment together with motor features of parkinsonism, 12 cases for lack of detailed clinical history, and 19 cases with coexistent features of advanced Alzheimer's disease changes. Thirty eight patients (13.8% of the total with PD pathology and 32.5 % of the total with DLB pathology) were found where there was no or very late cognitive impairment reported in the clinical records. RESULTS: Selected cases were 24 men and 14 women, with a mean (SD) age at onset of parkinsonian symptoms of 60.1 (10.1) years and a mean disease duration of 15.3 (5.5) years. At some time during the evolution of the disease 21 patients developed different degrees of cognitive impairment (after a mean disease duration of 12.2 (4.8) years). Clinical diagnosis at death was PD in 10 cases and PD with dementia in 11. In the remaining 17 patients no history of cognitive impairment was ever recorded in life and all of them had a clinical diagnosis of PD at death; in this subgroup, nine patients later revealed a neuropathological picture consistent with limbic (or transitional) category of DLB and eight with neocortical DLB. Interestingly, in all these patients the parkinsonian features including the response to dopaminergic drugs were indistinguishable from classic brain stem PD. CONCLUSIONS: The authors demonstrate that the classic pathology of DLB can commonly be seen outside the generally accepted clinical spectrum for DLB and that important factors other than the absolute number of LB in the neocortex and limbic system influence the development of cognitive impairment in PD. Furthermore, the pathology of PD may be indistinguishable from that reported in DLB, suggesting that the two clinicopathological syndromes may be attributable to the same biological abnormality.

Adult↗
PubMed2002

Parasitic worms of the central nervous system: an Australian perspective.

The diagnosis and management of parasitic diseases of the central nervous system (CNS) is difficult, even for infectious diseases physicians and neurologists. Furthermore, few overviews of the spectrum of causative helminths and clinical syndromes have been published. In the present study, we review the seven most common parasitic diseases of the CNS: (i) cysticercosis, (ii) neuroschistosomiasis, (iii) paragonimiasis, (iv) angiostrongyliasis, (v) hydatid disease, (vi) sparganosis and (vii) gnathostomiasis. Major syndromes of parasitic disease of the CNS and their differential causes are discussed, including: (i) cystic lesions, (ii) enhancing granulomas (with and without creeping subcutaneous eruptions), (iii) eosinophilic meningoencephalitis and (iv) spinal cord disease. Specific risk factors that predispose to these infections are also discussed and particular attention is drawn to the situation in Australia.

Angiostrongylus↗
PubMed2002

Polymyositis as a cause of total gut failure.

BACKGROUND: Gastrointestinal manifestations are seen in systemic sclerosis and mixed connective tissue disorders but are rare in pure polymyositis. CASE REPORT: A 44 year old woman with polymyositis who developed total gut failure requiring treatment with total parenteral nutrition is described. RESULTS: The patient's polymyositis is now fully controlled biochemically, but her gastrointestinal symptoms persist.

Colonic Pseudo-Obstruction↗
PubMed2001

Improved accuracy of clinical diagnosis of Lewy body Parkinson's disease.

The authors studied the accuracy of clinical diagnosis of idiopathic PD (IPD) in 100 consecutive clinically diagnosed cases that came to neuropathological examination. Ninety fulfilled pathologic criteria for IPD. Ten were misdiagnosed: multiple system atrophy (six), progressive supranuclear palsy (two), post-encephalitic parkinsonism (one), and vascular parkinsonism (one). Assessment of the clinical features suggests that an accuracy of 90% may be the highest that can be expected using current diagnostic criteria.

Adult↗
PubMed2001

Motor imagery in Parkinson's disease: a PET study.

We used positron emission tomography (PET) with 15O-labelled water to record patterns of cerebral activation in six patients with Parkinson's disease (PD), studied when clinically "off" and after turning "on" as a result of dopaminergic stimulation. They were asked to imagine a finger opposition movement performed with their right hand, externally paced at a rate of 1 Hz. Trials alternating between motor imagery and rest were measured. A pilot study of three age-matched controls was also performed. We chose the task as a robust method of activating the supplementary motor area (SMA), defects of which have been reported in PD. The PD patients showed normal degrees of activation of the SMA (proper) when both "off" and "on." Significant activation with imagining movement also occurred in the ipsilateral inferior parietal cortex (both "off" and when "on") and ipsilateral premotor cortex (when "off" only). The patients showed significantly greater activation of the rostral anterior cingulate and significantly less activation of the left lingual gyrus and precuneus when performing the task "on" compared with their performance when "off." PD patients when imagining movement and "off" showed less activation of several sites including the right dorsolateral prefrontal cortex (DLPFC) when compared to the controls performing the same task. No significant differences from controls were present when the patients imagined when "on." Our results are consistent with other studies showing deficits of pre-SMA function in PD with preserved function of the SMA proper. In addition to the areas of reduced activation (anterior cingulate, DLPFC), there were also sites of activation (ipsilateral premotor and inferior parietal cortex) previously reported as locations of compensatory overactivity for PD patients performing similar tasks. Both failure of activation and compensatory changes are likely to contribute to the motor deficit in PD.

Aged↗
PubMed2000

Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra.

Brain-derived neurotrophic factor (BDNF) has potent effects on survival and morphology of dopaminergic neurons and thus its loss could contribute to death of these cells in Parkinson's disease (PD). In situ hybridization revealed that BDNF mRNA is strongly expressed by dopaminergic neurons in control substantia nigra pars compacta (SNpc). In clinically and neuropathologically typical PD, SNpc BDNF mRNA expression is reduced by 70% (P = 0.001). This reduction is due, in part, to loss of dopaminergic neurons which express BDNF. However, surviving dopaminergic neurons in the PD SNpc also expressed less BDNF mRNA (20%, P = 0.02) than their normal counterparts. Moreover, while 15% of control neurons had BDNF mRNA expression >1 SD below the control mean, twice as many (28%) of the surviving PD SNpc dopaminergic neurons had BDNF mRNA expression below this value. This 13% difference in proportions (95% CI 8-17%, P < or = 0.000001) indicates the presence of a subset of neurons in PD with particularly low BDNF mRNA expression. Moreover, both control and PD neurons displayed a direct relationship between the density of BDNF mRNA expression per square micrometer of cell surface and neuronal size (r(2) = 0.93, P </= 0.00001) which was lost only in PD neurons expressing the lowest levels of BDNF mRNA. If BDNF is an autocrine/paracrine factor for SNpc dopaminergic neurons, loss of BDNF-expressing neurons may compromise the well-being of their surviving neighbors. Moreover, neurons expressing particularly low levels of BDNF mRNA may be those at greatest risk of injury in PD and possibly the trigger for the degeneration itself.

Aged↗
PubMed1998

Apomorphine-induced penile erections in Parkinson's disease.

Penile erections were regularly induced by intermittent subcutaneous injections of apomorphine in five patients with Parkinson's disease (PD) complicated by motor fluctuations. Four of the patients reported erectile dysfunction before beginning apomorphine and two of these report a significant improvement in their sexual function resulting from apomorphine use. Animal studies suggest central D2-type dopamine receptor stimulation and oxytocin release from the paraventricular nucleus of the hypothalamus mediate the effect. Erections reported with other dopamine agonists and levodopa are probably mediated by the same mechanism. Apomorphine-induced erections in PD are probably more common than previously thought. The benefit of apomorphine on sexual function in some patients suggests a possible role in the treatment of impotence in PD.

Adult↗
PubMed1998

Gait analysis in patients with Parkinson's disease and motor fluctuations: influence of levodopa and comparison with other measures of motor function.

Although clinical rating scales and simple timed tests of motor function are widely used to assess motor response to therapy, gait analysis may provide an alternative measure of this response. We studied 15 patients with PD complicated by motor fluctuations, first to determine changes in temporal and spatial gait parameters following levodopa, secondly to assess the stability of repeated gait measures and timed tests in "off" and "on" states, and thirdly to determine the use of gait analysis in the assessment of the dopaminergic response. Gait analysis (velocity, stride length, cadence, and double limb support), clinical rating scales (modified Webster scale and Hoehn and Yahr stage), and timed tests of motor function (hand tapping and stand-walk-sit time) were performed before ("off") and after ("on") a levodopa challenge. Stride length and gait velocity increased following medication whereas cadence and double limb support did not. Most gait measures and the stand-walk-sit time were stable over three consecutive trials in both "off" and "on" states. Of the gait measures, only cadence in the "off" state changed significantly whereas the tapping count improved with repeated trials in both "off" and "on" states. Changes in stride length, gait velocity, and tapping count following levodopa correlated with changes in clinical rating scales following treatment. Measurement of gait parameters provides a reliable, objective alternative to rating scales and timed tests in assessing the dopaminergic response in patients with PD and motor fluctuations.

Aged↗
PubMed1998

Hyperbaric oxygen in the treatment of refractory haemorrhagic cystitis.

Haemorrhagic cystitis is a common and often debilitating complication of chemotherapy for which treatment is frequently unsatisfactory. With over 80 cases reported of radiation-induced cystitis treated successfully with hyperbaric oxygen, attention is now turning to the treatment of chemotherapeutic agent-induced cystitis. We report a case of haemorrhagic cystitis occurring after autologous peripheral blood stem cell transplantation for multiple myeloma. The patient had received cyclophosphamide and busulfan and had BK and adenoviruria. The haemorrhage was refractory to multiple conventional treatments but resolved after a course of hyperbaric oxygen.

Adenoviruses, Human↗
PubMed1997

Response of parkinsonian swallowing dysfunction to dopaminergic stimulation.

OBJECTIVES: To determine the degree of dopaminergic response of swallowing dysfunction in Parkinson's disease. METHODS: Fifteen patients with idiopathic Parkinson's disease and symptomatic dysphagia were studied. All had motor fluctuations in response to long term levodopa therapy. On two separate days, after overnight withdrawal of all antiparkinsonian medication, a modified barium swallow using cinefluoroscopy and different food consistencies was performed before and after administration of oral levodopa and subcutaneous apomorphine. RESULTS: Despite all patients having an unequivocal motor response to both agents, there were few significant responses in any of the quantitative or qualitative criteria of swallowing dysfunction assessed. The oral preparatory phase, generally considered a more voluntary component of swallowing, showed a response, but not with all consistencies. In a subgroup of patients the pharyngeal phase time also improved. CONCLUSIONS: These findings suggest that parkinsonian swallowing dysfunction is not solely related to nigrostriatal dopamine deficiency and may be due to an additional non-dopamine related disturbance of the central pattern generator for swallowing in the pedunculopontine nucleus or related structures in the medulla.

Aged↗
PubMed1997

Clinicopathological aspects of Parkinson's disease.

Clinicopathological studies have shown that the accuracy of a clinical diagnosis of Parkinson's disease (PD) is less than 80%. More selected diagnostic criteria can increase the proportion of true PD cases identified to more than 90%. However, by using these criteria almost a third of pathologically confirmed cases may be rejected. Awareness of the high misdiagnosis rate and refinements in the clinical diagnostic criteria for other conditions that may present with parkinsonism seem to have led to an improvement in the accuracy of diagnosis to 84%. Cortical Lewy bodies, often in small numbers, are seen in almost all patients with PD. This has prompted intense efforts to clarify both the clinical and pathological criteria for diffuse Lewy body disease. The nomenclature of conditions with plentiful numbers of Lewy bodies in the neocortex and the relevance of associated pathology has become confusing and the subject of intense nosological debate. A recent consensus paper has suggested clinical and pathological diagnostic criteria for what has been termed 'dementia with Lewy bodies'. This new term awaits general acceptance while the proposed diagnostic criteria remain to be validated. The neuropathological substrate of dementia in PD continues to receive a lot of attention with suggestions that additive deficits from pathology in both cortical and subcortical structures probably explain most of the dementia seen in PD.

Brain↗
PubMed1997

Drug treatment of Parkinson's disease in the 1990s. Achievements and future possibilities.

Advances in the medical treatment of Parkinson's disease have improved the disability related to complications of long term levodopa therapy, including motor fluctuations, dyskinesias and neuropsychiatric toxicity. A range of new dopamine agonists are in various stages of preclinical and clinical development. Cabergoline appears to be effective in improving moderate motor fluctuations, and a number of dopamine partial agonists that can act as either agonists or antagonists depending on the degree of denervation and receptor sensitivity are being investigated. Apomorphine represents a significant advance in the treatment of well developed motor fluctuations in selected patients who are able to master the technique of subcutaneous administration. The catecholamine-O-methyl transferase inhibitors are proving useful in phase III studies in the management of patients with moderate motor fluctuations. A role for glutamate antagonists is supported by animal and early clinical data, although the poor therapeutic index associated with the currently available nonselective, noncompetitive glutamate antagonists has prompted a search for more selective antagonists with less toxicity. The management of levodopa-induced dyskinesias remains a major therapeutic challenge. Some reports of dopamine partial agonists, selective D2 receptor antagonists and atypical antipsychotics being useful await confirmation. Neuropsychiatric toxicity probably remains the major dose-limiting adverse effect of levodopa and is a major reason for parkinsonian patients being admitted to nursing homes. The development of new atypical antipsychotics with improved therapeutic indices, along with the possible use of serotonergic antagonists, may improve management of this difficult problem. The challenge will be to fit these new forms of treatment into our present range of available drugs and to assess their relative role within the emerging framework of functional neurosurgery for parkinsonian disability.

Antiparkinson Agents↗