Search PubMed⌕ Search

Biomedical subjects

D O'Mahony

Publications and source records attributed to D O'Mahony.

At least 19 recordsLinked to original sources
PubMed1995

Pathophysiology of carotid sinus hypersensitivity in elderly patients.

Carotid sinus hypersensitivity (CSH) is recognised in up to 45% of elderly patients with syncope, falls, and dizziness that may not be attributed to specific myocardial sinus node dysfunction, various diseases that affect pacemaker activity, cardiac output and blood supply to the brain. The pathophysiology of CSH is unclear but it is associated with ageing, hypertension, and ischaemic heart disease. CSH is potentially treatable with dual chamber pacing for prolonged sinus arrest (cardio-inhibitory CSH) but therapy for the more prevalent hypotension (vasodepressor CSH) is unsatisfactory. However, hypersensitivity of the carotid sinus is not consistent with the known blunting effects of senescence and hypertension on baroreflex sensitivity. The present hypothesis proposes that CSH in elderly patients results from up-regulation of brainstem postsynaptic alpha-2 adrenoceptors. Reduced carotid sinus compliance in elderly arteriosclerotic hypertensive patients will reduce afferent impulse traffic in the baroreflex pathway. Such relative deafferentation may be expected to cause baroreflex postsynaptic hypersensitivity, mediated by up-regulation of the dominant postsynaptic receptor population in the baroreflex pathway, ie, alpha-2 adrenoceptors. Vigorous carotid sinus stimulation, eg, massage, could thus cause an overshoot baroreflex efferent response, resulting in profound hypotension and bradycardia. Hypotension and bradycardia are compounded by the effects of age, hypertension, ischaemic heart disease and arteriosclerosis on rapid cardiovascular compensation, resulting in cerebral hypoperfusion and syncope. Thus CSH in elderly patients should be considered as a clinical marker of widespread arteriosclerotic disease, rather than as a distinct disease entity. If correct, this hypothesis has potentially important implications for the pharmacotherapy of hypotension-related symptoms in elderly arteriosclerotic patients.

Afferent Pathways↗
PubMed1994

Cellular activation of thromboxane receptors.

Thromboxane A2 is an abundant and potent product of arachidonic acid metabolism in human platelets. Its clinical importance is highlighted by the efficacy of aspirin, which, due to its irreversible inhibition of the enzyme PGG/H synthase, selects the anucleate platelet as a particular target for extended duration of action. A single thromboxane receptor gene has been identified by southern blot; sequence polymorphism in the gene sequence has been identified. The recombinant receptor is also subject to posttranslational modifications, which may modify its affinity for natural ligands. Pharmacological studies have suggested some heterogeneity among thromboxane receptors. These observations have been rendered more interesting by the discovery of an F prostaglandin isomer, 8-epi-PGF2 alpha, which exerts its biological effects through a thromboxane (or closely related) receptor. This isomer can be generated in a free radical-catalyzed or cyclooxygenase-dependent manner.

Animals↗
PubMed1994

Primary auditory pathway and reticular activating system dysfunction in Alzheimer's disease.

Patients with Alzheimer's disease (AD) have pathologic involvement of several important components of the primary auditory pathway, including the inferior colliculus, medial geniculate body, primary auditory cortex, and secondary auditory cortex. The main components of the brainstem auditory evoked response (BAER) and middle latency response (MLR) reflect the function of portions of the primary auditory pathway, including those affected pathologically in AD. The amplitude of the P1 component of the MLR reflects the degree of neuronal activity of midbrain portions of the ascending reticular activating system (ARAS) with cortical cholinergic projections. To determine whether there is dysfunction of the primary auditory pathway and ARAS in AD, we compared simultaneous BAER and MLR component latency and amplitude measurements in patients with mild-moderate AD (n = 35) and age-matched healthy elderly controls (n = 34). There were significant latency delays in brainstem transmission time (BAER I-V interpeak latency; p < 0.05) and in primary auditory cortex evoked potential generation (MLR Pa latency; p < 0.05) in the AD group compared with controls. In addition, there was a significant reduction in the P1 component amplitude of the MLR in the AD group (p < 0.01). These results indicate dysfunction of the primary auditory pathway and ARAS in patients with mild-moderate AD and support the hypothesis that impairment of auditory function and of arousal are intrinsic features of AD.

Aged↗
PubMed1994

The discriminant value of semiquantitative SPECT data in mild Alzheimer's disease.

UNLABELLED: In most semiquantitative SPECT studies, overlap between groups of patients with Alzheimer's disease (AD) and age-matched elderly controls is such that single posterior cortical perfusion measurements lack sensitivity. In the present study, the value of a combination of semiquantitative temporoparietal SPECT parameters was examined. METHODS: Supratentorial transaxial perfusion measurements were obtained in frontal, anterior temporal, posterior temporoparietal and occipital cortical areas in both hemispheres, in a baseline population of 10 healthy elderly controls and 30 mild to moderately impaired AD patients, as well as in a prospective group of 15 patients with mild cognitive impairment, 12 patients with a diagnosis of probable AD and individual cases of multi-infarct dementia, dementia-frontal type and paranoid psychosis. A linear discriminant function (LDF) was calculated from the baseline subjects' data to classify control and AD subjects individually. RESULTS: Highly significant hypoperfusion was noted in both the anterior temporal and posterior temporoparietal regions of interest in the AD group compared with controls, but with significant overlap. Using an LDF incorporating these perfusion measurements in both hemispheres, 10/10 (100%) controls and 26/30 (87%) AD baseline subjects were correctly classified. Using the baseline LDF in the prospective 15 mildly impaired cases, 11/12 new mild AD cases and none of the 3 non-AD cases were classified in the AD group. CONCLUSION: These results support the use of a combination of semiquantitative SPECT perfusion estimates from cortical areas with predictable pathological involvement in AD in a linear discriminant format in the clinical assessment of patients with suspected AD.

Aged↗
PubMed1993

Coordinated decreases in rRNA gene transcription factors and rRNA synthesis during muscle cell differentiation.

rRNA synthesis decreases significantly during the differentiation of rat L6 myoblasts to myotubes. Nuclear run-on assays demonstrated that the decrease was attributable to decreased rates of rRNA gene transcription. Immunoblot analysis indicated a marked reduction in amounts of the RNA polymerase I transcription factors UBF1 and UBF2 (upstream binding factors 1 and 2, respectively). The levels of these factors dropped in parallel with the down-shift in rRNA gene transcription. The amount of UBF does not fall due to a general decrease in cellular protein, as myosin heavy-chain protein accumulates markedly during this same time. RNA blots of total RNA isolated from myoblasts and differentiating myotubes showed a decrease in the mRNA for UBF, at the same time the mRNA for myogenin was accumulating. The down-shift in UBF mRNA levels preceded the decrease in the protein levels for UBF. There have been reports that the acute response of the rRNA gene transcription system to physiological signals in many systems involves an RNA polymerase I-associated factor. However, our results imply that the regulation of rRNA gene DNA transcription in response to physiological processes, such as differentiation, may involve multiple regulatory pathways.

Adenosine Triphosphate↗
PubMed1993

Parkinson's dementia and Alzheimer's dementia: an evoked potential comparison.

Auditory endogenous event-related potentials (ERPs) and flash visual evoked potentials (VEPs) were recorded in 26 elderly patients with idiopathic Parkinson's disease (PD), 14 with dementia and 12 non-demented, 16 elderly patients with Alzheimer dementia (AD) and 15 cognitively intact controls. ERP P3 and flash-VEP N2, P2 and delta (P2-P1) latency measures were significantly increased in the demented PD group compared with controls. The ERP P3 latency was also significantly delayed in the AD group compared with controls, but the differences in the flash-VEP measures from controls were not significant. No significant differences were noted between the PD groups, except for a significantly shorter flash-VEP N1 latency in the demented PD group; this was also the only significant evoked potential difference between the AD and PD dementia groups, which were otherwise electrophysiologically similar.

Aged↗
PubMed1993

Suitable screening tests for cognitive impairment and depression in the terminally ill--a prospective prevalence study.

Although confusional states and depression are common accompaniments of advanced cancer, few objective data are available concerning the prevalence of these clinical states or what methods are most suitable for their accurate detection. We decided that a 10-question Abbreviated Mental Test Score (AMTS) and a semistructured application of modified DSMIII-R (Diagnostic and Statistical Manual of Mental Disorder, third edition-revised) criteria for a major depressive illness were the most suitable screening tests for a terminally ill population. Thirty of 87 patients (34%) displayed significant cognitive impairment. The AMTS rating declined with approaching death and also correlated negatively with age. Of 81 patients, 21 (26%) were depressed when screened using DSMIII-R criteria for depression. One-third of patients with impaired AMTS scores also satisfied DSMIII-R criteria for depression. Of cognitively impaired patients, 90% had at least two possible causes for their confused state. We have found that both the AMTS and semistructured interview using DSMIII-R criteria for depression are useful routine screening tests in the terminally ill.

Adult↗
PubMed1992

'Pseudo-Alzheimer's' and primary brain tumour.

Primary brain tumour may present in the elderly purely as a dementing illness before the onset or detection of sensorimotor neurological symptoms or signs. Although neurological examination may indicate no definite signs, close attention to accepted DSM-IIIR and NINCDS-ADRDA diagnostic criteria for primary degenerative dementia and 'probable' Alzheimer's disease respectively will suggest a process other than a degenerative one. This was the case in two patients with primary brain tumour presenting clinically with dementing illness similar to but distinct from Alzheimer's disease.

Aged↗
PubMed1990

Down syndrome and autoimmune chronic active hepatitis: satisfactory outcome with therapy.

A case of autoimmune chronic active hepatitis (C.A.H.) in a 12-year old Down Syndrome child is described. This represents the second only documented case of autoimmune C.A.H. occurring in Down Syndrome; the first well-described case died from the disease. The patient described below had a satisfactory response to steroid therapy with restoration of normal liver histological appearances and function despite severe disease at presentation. Chronic hepatitis in Down Syndrome, although more usually of hepatitis B viral aetiology, may also be autoimmune in nature and resolve satisfactorily with appropriate therapy.

Autoimmune Diseases↗
PubMed1990

Characterization of factors that direct transcription of rat ribosomal DNA.

The protein components that direct and activate accurate transcription by rat RNA polymerase I were studied in extracts of Novikoff hepatoma ascites cells. A minimum of at least two components, besides RNA polymerase I, that are necessary for efficient utilization of templates were identified. The first factor, rat SL-1, is required for species-specific recognition of the rat RNA polymerase I promoter and may be sufficient to direct transcription by pure RNA polymerase I. Rat SL-1 directed the transcription of templates deleted to -31, the 5' boundary of the core promoter element (+1 being the transcription initiation site). The second factor, rUBF, increased the efficiency of template utilization. Transcription of deletion mutants indicated that the 5' boundary of the domain required for rUBF lay between -137 and -127. Experiments using block substitution mutants confirmed and extended these observations. Transcription experiments using those mutants demonstrated that two regions within the upstream promoter element were required for optimal levels of transcription in vitro. The first region was centered on nucleotides -129 and -124. The 5' boundary of the second domain mapped to between nucleotides -106 and -101. DNase footprint experiments using highly purified rUBF indicated that rUBF bound between -130 and -50. However, mutation of nucleotides -129 and -124 did not affect the rUBF footprint. These results indicate that basal levels of transcription by RNA polymerase I may require only SL-1 and the core promoter element. However, higher transcription levels are mediated by additional interactions of rUBF, and possibly SL-1, bound to distal promoter elements.

Animals↗
PubMed1990

Partial lipodystrophy in coeliac disease.

The association of coeliac disease and partial lipodystrophy is described. The patient also had deficiencies of serum IgA and C3 complement (the latter associated with partial lipodystrophy). In addition, there was subclinical dermatitis herpetiformis confirmed by skin biopsy. The facial wasting of fully developed partial lipodystrophy may be misinterpreted as a sign of malabsorption but the facial, upper limb, and truncal lipodystrophy contrasts with normal pelvic and lower limb appearances.

Adolescent↗
PubMed1990

Severe oxprenolol poisoning: the importance of glucagon infusion.

We describe a case of severe oxprenolol poisoning (8 g overdose) where restoration of normal blood pressure depended critically on high-dose glucagon infusion after several bolus injections of glucagon had failed. We stress the importance of infusion delivery of glucagon in severe beta-blocker poisoning.

Adult↗
PubMed1989

Group B streptococcal infection as a pyrexia of unknown origin.

Group B Streptococcal bacteraemia seldom behaves as a pyrexia of unknown origin (PUO) except in the context of infective endocarditis. Scleroderma is not known to predispose to Group B streptococcal infection. We report a case of Group B streptococcal bacteraemia presenting as a PUO in a patient with probable scleroderma in whom there was no evidence of endocarditis.

Aged↗
PubMed1989

Fulminant severe retinopathy in a newly diagnosed diabetic without risk factors.

The authors describe a 26-year-old female developing severe proliferative retinopathy within 2 weeks of diagnosis of insulin-dependent diabetes mellitus. The patient presented with profound diabetic ketoacidosis, but had no other risk factors for retinopathy. She had marked bilateral myopia which did not protect her from retinopathy. Nine months after diagnosis of diabetes, she has profound visual impairment despite correction for myopia, and has also developed marked autonomic neuropathy and diabetic nephropathy.

Adult↗