A real-time measurement of general practice workload in the Republic of Ireland: a prospective study.

Background: Demand for GP services in the Republic of Ireland (RoI) is increasing, and the resultant escalation in workload demands is an issue of growing concern. Accordingly, the accurate measurement and description of GP workload is essential to inform future healthcare planning.

Aim: To provide a real-time measurement of GP workload with respect to hours worked and of proportional time expenditure on typical workload activities.

How does the introduction of free GP care for children impact on GP service provision? A qualitative study of GPs.

Background: Optimising child health in general practice is a key health service priority. In Ireland, where 23% of Ireland's population are aged under 16, GP consultations have historically involved a private fee or have been covered by Ireland's General Medical Services (GMS) scheme. In July 2015, this scheme was expanded so that free GP care was provided to all children aged under 6 years.

70,489 primary care encounters: retrospective analysis of morbidity at a primary care centre in Ireland.

Background: While considerable changes are happening in primary care in Ireland and considerable potential exists in intelligence derived from practice-based data to inform these changes, relatively few large-scale general morbidity surveys have been published.

Aims: To examine the most common reasons why people attend primary care, specifically 'reasons for encounter' (RFEs) among the general practice population and among specific demographic groups (i.e.

Does eliminating fees at point of access affect Irish general practice attendance rates in the under 6 years old population? A cross sectional study at six general practices.

With the introduction of free point of access GP care for children aged under six imminent, we sought to determine consultation rates among this group. We interrogated data from practice management systems at six general practices (total patient population 27080). A total of 1931 children aged under six were responsible for 5814 surgery consultations.

Are Irish adult general practice consultation rates as low as official records suggest? A cross sectional study at six general practices.

Accurate data on primary care activity is key to health services planning and reconfiguration. Official data estimate general practice adult consultation rates to be 3.2 visits annually, based on patient self reports.

Interleukin-1beta but not tumor necrosis factor-alpha potentiates neuronal damage by quinolinic acid: protection by an adenosine A2A receptor antagonist.

Quinolinic acid is an agonist at glutamate receptors sensitive to N-methyl-D-aspartate (NMDA). It has been implicated in neural dysfunction associated with infections, trauma, and ischemia, although its neurotoxic potency is relatively low. This study was designed to examine the effects of a combination of quinolinic acid and the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha).

Telomerase alone extends the replicative life span of human skeletal muscle cells without compromising genomic stability.

Continuous cycles of muscle fiber necrosis and regeneration are characteristic of the muscular dystrophies, and in some cases this leads to premature replicative senescence of myoblasts in vitro. The molecular mechanism of senescence in human myoblasts is poorly understood but there is evidence to suggest that telomeric attrition may be one of the ways by which this is achieved. We report here, for the first time, the extension of normal human skeletal muscle cell replicative life span by the reconstitution of telomerase activity.

Chronic fatigue syndrome: new evidence for a central fatigue disorder.

Considerable evidence points towards a prominent role for central nervous system (CNS) mechanisms in the pathogenesis of chronic fatigue syndrome (CFS), a disorder characterized chiefly by persistent, often debilitating, fatigue. We wished to characterize circulating profiles of putative amino acid modulators of CNS 5-hydroxytryptamine (5-HT; serotoninergic) and dopaminergic function in CFS patients at rest, as well as during symptom-limited exercise and subsequent recovery. Groups of 12 CFS patients and 11 age- and sex-matched sedentary controls, with similar physical activity histories, underwent ramp-incremental exercise to the limit of tolerance.

Muscle fibrillin deficiency in Marfan's syndrome myopathy.

Objective: To report a family with Marfan's syndrome in whom a myopathy was associated with respiratory failure; muscle biopsies from affected individuals were examined to determine whether there were abnormalities in fibrillin.

Methods: 21 family members underwent detailed clinical examination, including neurological and pulmonary assessment. Muscle biopsies in the most severely affected cases were immunostained using monoclonal antibodies to specific fibrillin components.

The role of kynurenines in the production of neuronal death, and the neuroprotective effect of purines.

The kynurenine metabolic pathway from tryptophan accounts for a large proportion of the metabolism of this amino acid in the brain. Although a major route for the generation of the essential co-factor nicotinamide adenine dinucleotide (NAD), two components of the pathway have marked effects on neurons. Quinolinic acid is an agonist at N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors, while kynurenic acid is an antagonist and, thus, a potential neuroprotectant.

Validation of a simple, rapid, and economical technique for distinguishing type 1 and 2 fibres in fixed and frozen skeletal muscle.

Aims: To produce a method of distinguishing between type 1 and 2 skeletal muscle fibres that would be more economical and reproducible than the standard ATPase method and be applicable to both fixed and frozen tissue. Because the ATPase method has been accepted as the basis for fibre identification for the past 50 years, the new method should not give significantly different results.

Methods: Isoforms of myosin correlate with isoforms of myofibrillar ATPase and an immunohistochemical (IHC) double labelling protocol was devised using monoclonal antibodies to fast and slow myosin.

Enhanced neuronal damage by co-administration of quinolinic acid and free radicals, and protection by adenosine A2A receptor antagonists.

1. Quinolinic acid may be an important endogenous excitotoxin, but its concentrations in brain are low. We have therefore attempted to determine whether its neurotoxicity can be increased by the simultaneous presence of free radicals.

Antiviral pathway activation in patients with chronic fatigue syndrome and acute infection.

Gene expression of key enzymes in 2 antiviral pathways (ribonuclease latent [RNase L] and RNA-regulated protein kinase [PKR]) was compared in 22 patients with chronic fatigue syndrome (CFS), 10 patients with acute gastroenteritis, and 21 healthy volunteers. Pathway activation in the group of patients with infections differed significantly from that of the other 2 groups, in whom there was no evidence of upregulation. Therefore, assay of activation is unlikely to provide the basis for a diagnostic test for CFS.

Possible mediation of quinolinic acid-induced hippocampal damage by reactive oxygen species.

Several differences exist between quinolinic acid and N-methyl-D-aspartate (NMDA) in the potency and pharmacology of their neurotoxic actions in the brain, suggesting that quinolinic acid may act by mechanisms additional to the activation of NMDA receptors, possibly involving lipid peroxidation. In the present review, studies are considered which have attempted to determine whether free radicals might contribute to the neuronal damage induced by quinolinic acid. Following Injections into the hippocampus of anaesthetised rats, quinolinic acid induced damage is prevented by melatonin, by an action not blocked by the melatonin receptor blocker luzindole.

Muscle changes in the neuroleptic malignant syndrome.

Aims: To characterise the skeletal muscle changes in the neuroleptic malignant syndrome (NMS).

Methods: Detailed light and ultrastructural examination was carried out on skeletal muscle from three cases of NMS, two associated with recreational drugs (3,4-methlenedioxymethylamphetamine (MDMA, Ecstasy) and lysergic acid diethylamide (LSD)) and one with antipsychotic drugs (fluoxetine (Prozac) and remoxipride hydrochloride monohydrate (Roxiam)).

Results: The muscles were grossly swollen and oedematous in all cases, in one with such severe local involvement that the diagnosis of sarcoma was considered.

Role of kynurenines in the neurotoxic actions of kainic acid.

The neurotoxic actions of kainic acid can be partly suppressed by antagonists acting at N-methyl-D-aspartate (NMDA) receptors. The present study examined the possible role of endogenous components of the kynurenine pathway to this phenomenon. Administration of kainate (2 nmols) into the hippocampus of anaesthetized rats produced damage in the CA1 and CA3 regions.

Oxidative stress as a mechanism for quinolinic acid-induced hippocampal damage: protection by melatonin and deprenyl.

1. There are differences between the excitotoxic actions of quinolinic acid and N-methyl-D-aspartate (NMDA) which suggest that quinolinic acid may act by mechanisms additional to the activation of NMDA receptors. The present study was designed to examine the effect of a potent antioxidant, melatonin, and the potential neuroprotectant, deprenyl, as inhibitors of quinolinic acid-induced brain damage.

Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome.

Patients with the chronic fatigue syndrome (CFS) complain consistently of delay in recovery of peripheral muscle function after exercise. The purpose of this study was to try to confirm this observation. A fatiguing exercise test was carried out on the quadriceps muscle group of ten patients and ten control subjects.

Genomic and template RNA transcription in a model of persistent enteroviral infection.

Enteroviruses have been implicated in persistent infections of the nervous system and in certain paralytic motor neuron syndromes. Enteroviral persistence may depend on defective transcription, resulting in the abnormal production of equal amounts of genomic and template RNA strands rather than the normal ratio of 60-100:1. An in vitro model of a persistent coxsackie virus in human skeletal muscle cells was investigated using in situ hybridisation and a semiquantitative parallel, complementary, reverse transcriptase polymerase chain reaction.

Adenocarcinoma of the anal glands.

Adenocarcinoma of the anal glands is very rare but it is an important lesion to recognise as with early diagnosis, it has an excellent prognosis. Because it involves the submucosa widely and penetrates the mucosa late, it can be mistaken for metastatic gastrointestinal carcinoma, or tumour arising in sinuses and fistulae. Two cases, in a 44 year old man and a 73 year old woman, which illustrate the typical features are reported, in one of which the diagnosis was missed originally.

Search for picornaviruses at onset of inflammatory myopathy.

Picornaviruses may not play a role as persistent agents in the inflammatory myopathies, but it is still thought likely that they may act as triggers of an autoimmune process. Forty one muscle biopsy specimens, taken from three weeks to six months (mean four months) after onset, were examined using three different picornaviral primers and PCR. Moderate to severe disease activity was evident in all specimens.

Mouse inoculation studies reveal no transmissible agent in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) resembles the spongiform encephalopathies in its dual pattern of inherited and sporadic cases, its uniform prevalence in different populations, its late onset (suggestive of a long incubation period) and its pathological picture of neuronal degeneration without inflammation. There is a well-established protocol for primary transmission of scrapie and related diseases to mice. Using this, we inoculated four longlived, inbred, mouse strains with cord material fresh-frozen within three hours of death, from a case of ALS or a control case.