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Biomedical subjects

A D Kay

Publications and source records attributed to A D Kay.

At least 19 recordsLinked to original sources
PubMed2003

Remodelling of cerebrospinal fluid lipoproteins after subarachnoid hemorrhage.

Lipoprotein particles (Lps) in normal human cerebrospinal fluid (CSF) are distinct from those found in plasma and include unique apolipoprotein E (apoE indicates protein; APOE, gene) containing lipoproteins rarely seen in human plasma. Less favourable neurological recovery after subarachnoid hemorrhage (SAH) has been observed in patients who possess the APOE epsilon4 allele raising the possibility that apoE influences neuronal survival after brain injury. We analysed Lps from control and SAH CSF testing the hypotheses that following brain injury CSF Lps undergo remodelling and apoE containing Lps are selectively depleted from brain injury CSF. Lipoproteins were fractionated using CSF from six control pools and six patients with SAH on a sepharose 6HR 10/30 size exclusion column. Fractions were assayed for total cholesterol (TC), free cholesterol (FC), phospholipid, triglyceride (TG), apoE, apolipoprotein B (apoB), and apolipoprotein AI (apoAI). Compared to control CSF there were significant (P<0.05) increases in TC, FC, TG, and apoAI in SAH CSF. Plasma sized apoB-containing lipoproteins and a very small apoAI-containing Lps were identified in the SAH CSF, which were not present in controls. However, despite the release of plasma lipoproteins into the subarachnoid space, there was no significant increase in CSF apoE. These data provide novel indirect evidence suggesting that after SAH CSF Lps undergo remodelling and apoE containing Lps are selectively reduced in brain injury CSF. The remodelling of CSF Lps and selective reduction of apoE containing lipoproteins may reflect an important response of the human brain to injury.

Adult↗
PubMed2002

Toxicity of myoglobin and haemoglobin: oxidative stress in patients with rhabdomyolysis and subarachnoid haemorrhage.

Haemolytic events, such as those following rhabdomyolysis and subarachnoid haemorrhage, often result in pathological complications such as vasoconstriction. Haem-protein cross-linked myoglobin and haemoglobin are generated by ferric-ferryl redox cycling, and thus can be used as markers of oxidative stress. We have found haem-protein cross-linked myoglobin in the urine of patients suffering from rhabdomyolysis and haem-protein cross-linked haemoglobin in the cerebrospinal fluid of patients following subarachnoid haemorrhage. These findings provide strong evidence that these respiratory haem proteins can be involved in powerful oxidation processes in vivo. We have previously proposed that these oxidation processes in rhabdomyolysis include the formation of potent vasoconstrictor molecules, generated by the myoglobin-catalysed oxidation of membranes, inducing nephrotoxicity and renal failure. Haem-protein cross-linked haemoglobin in cerebrospinal fluid suggests that a similar mechanism of lipid oxidation is present and that this may provide a mechanistic basis for the delayed vasospasm that follows subarachnoid haemorrhage.

Hemeproteins↗
PubMed2001

The head injured adult--who cares?

A prospective observational survey of 2957 adults admitted to acute general hospitals in Glasgow after head injury, enabled the features of patients managed in the general hospital 48 hours after head injury to be compared with those transferred to the regional neurosurgical unit and those discharged from hospital.

Adult↗
PubMed2001

Spinal cord stimulation--a long-term evaluation in patients with chronic pain.

Spinal cord stimulation (SCS) is an established treatment modality for chronic pain, angina pectoris, and peripheral vascular disease. This study evaluates experience with SCS over a 13-year period with emphasis on surgical complications, revisions and pain relief. It took the form of a retrospective study of medical/surgical records coupled with a postal/telephone questionnaire. The subjects consisted of seventy patients, aged from 21 to 76 years (mean 47; median 46), with severe, chronic pain refractory to conventional treatment, who underwent SCS implantation between 1984 and 1997. It investigated surgical revisions, complications and pain relief. There were 72 surgical revisions comprising electrode replacement/repositioning (32), generator replacement (22), cable failure (6) and implant removal (12). Half the devices were revised within 3 years (95% confidence interval: 2-5 years) of implantation. Six (8.6%) implants became infected. Sixty per cent of patients reported substantial relief of pain. This study shows that the majority of patients undergoing SCS derive significant benefit in terms of pain relief, but commonly require surgical revisions due to both technical and biological factors. These devices require systematic evaluation to determine optimal usage, clinical effectiveness and cost-benefit analysis.

Adult↗
PubMed2000

A clinical audit of the Hakim programmable valve in patients with complex hydrocephalus.

The objective of the investigation was to determine the pattern of use of the Hakim (Medos) programmable valve implanted in patients with complex hydrocephalus and their clinical outcome. A prospective audit of patients with complex hydrocephalus undergoing Hakim programmable valve implantation between 1989 and 1994 in the United Kingdom and Ireland, was followed-up for a minimum of 5 years. Surgical practice and complications were audited together with clinical outcome. One-hundred-and-thirty-nine patients (80 male, 59 female; mean age 43.4 years; median 47 years; range 1 month-84 years) with complex hydrocephalus due to a wide range of aetiologies were implanted with the Hakim programmable valve. Eighty-eight (63%) had large or massive ventricles prior to implantation; seven (5%) were slit. Fifty-five (40%) had previously been shunted with a fixed pressure system. One-hundred-and-thirty-one (94%) of the Hakim programmable shunts were ventriculoperitoneal; four (3%) ventriculoatrial; two (1.4%) cystoperitoneal; and two (1.5%) lumboperitoneal. The initial opening pressure selected ranged from 50 to 200 mmH2O (median 120). Valves were reprogrammed on average 1.7 times with 143 reprogrammings in the first year after implantation; 67 in the second; 19 in the third; three in the fourth; two in the fifth. Forty-nine (36%) valves were never reprogrammed after implantation. During the 5 years audit period, there were 70 (50%) shunt revisions, 40 of which were performed within 1 year of implantation. Thirty-six (27%) shunts were removed. There were 24 (18%) shunt infections. Subdural collections were identified in 37(27%) patients after Hakim programmable valve implantation; 10 (27%) required surgical drainage. Five (3.7%) patients developed symptomatic slit ventricles after Hakim programmable valve implantation. Headache was improved following reprogramming in 27(71%) of the 38 patients with refractory headache. After Hakim programmable valve implantation, patients underwent an average of 4.6 CT scans (range 1-25); 0.3 MRI (range 1-5) and 1.8 skull radiographs (range 1-20). The mean hospital stay per patient over 5 years was 26 days (range 1-110 days). Five years after implantation, the Glasgow Outcome scale was favourable in 64% of patients. The Hakim programmable valve is useful in the management of patients with complex hydrocephalus and may reduce the need for shunt revision for headache. Non-haemorrhagic, post-shunting, subdural collections identified on routine postoperative CT may be treated by reprogramming.

Adolescent↗
PubMed1988

Cerebrospinal fluid somatostatin and neuropeptide Y. Concentrations in aging and in dementia of the Alzheimer type with and without extrapyramidal signs.

Cerebrospinal fluid somatostatin and neuropeptide Y concentrations were measured in 26 healthy normal subjects, 27 patients with dementia of the Alzheimer type (DAT), and seven patients with DAT with extrapyramidal signs (EDAT). In healthy normal subjects, there was no significant correlation between age and either somatostatin or neuropeptide Y concentration. However, the concentrations of both peptides correlated significantly with each other. In patients with DAT and EDAT, the concentrations of somatostatin (17.5 +/- 5.0 and 16.4 +/- 5.0 pg/mL, respectively) were significantly reduced relative to age-matched control subjects (23.1 +/- 8.2 pg/mL) but were unrelated to dementia severity and did not change significantly during the progression of the disease. Neuropeptide Y concentrations did not differ significantly between the age-matched control, DAT, and EDAT groups (38.2 +/- 12.8, 37.0 +/- 12.3, and 30.3 +/- 7.8 pg/mL, respectively). These results suggest that in DAT, dysfunction of cortical somatostatin but not neuropeptide Y transmitter systems is reflected by reduced cerebrospinal fluid concentrations.

Adult↗
PubMed1988

Cerebrospinal fluid cholinesterases in aging and in dementia of the Alzheimer type.

Protein concentration and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were assayed in the cerebrospinal fluid (CSF) of 26 healthy normal subjects (20-86 years old), 27 patients with dementia of the Alzheimer type (DAT), and 10 patients with dementia of the Alzheimer type with extrapyramidal signs (EDAT). In normal subjects, there was an age-related increase in CSF protein and AChE activity and a significant correlation (p less than 0.001) between CSF protein and BChE activity. In the DAT and EDAT groups, CSF AChE activities (mean +/- SD = 17.5 +/- 3.6 and 15.3 +/- 4.4 nmol/min/ml, respectively) were significantly lower (p less than 0.05) than in 13 age-matched control subjects (21.5 +/- 5.6 nmol/min/ml). In contrast, neither CSF protein concentration, BChE activity, nor the ratio of AChE/BChE differed significantly between groups. In patients with DAT, CSF AChE activity was significantly lower (p less than 0.05) in subjects with an early onset compared to those with a late onset (16.4 +/- 3.4 and 19.7 +/- 2.8 nmol/min/ml, respectively), and activity in the latter group did not differ significantly from control values. CSF AChE activity was not related to dementia severity and did not change significantly over an 18-month period. Although these results confirm a cholinergic deficit in patients with DAT, the considerable overlap of CSF AChE activity between groups and the nonsignificant correlation between AChE activity and dementia severity limit the usefulness of CSF AChE as a diagnostic marker of this disorder.

Acetylcholinesterase↗
PubMed1988

Cerebrospinal fluid monoamine markers are decreased in dementia of the Alzheimer type with extrapyramidal features.

We measured monoamine metabolites and biopterin in the CSF of 37 patients with dementia of the Alzheimer type (DAT), with or without extrapyramidal signs, and in 14 age-matched healthy controls. Compared with concentrations in DAT and controls, the concentrations of homovanillic acid (HVA) and biopterin were significantly decreased in DAT with extrapyramidal signs (EDAT). CSF 3-methoxy-4-hydroxy-phenethyleneglycol and 5-hydroxyindoleacetic acid did not differ significantly among these groups. Age at onset of dementia was positively correlated with CSF HVA (r = 0.49, p less than 0.05). The two dementia groups did not differ significantly in the extent of ventricular dilation as measured by quantitative CT, but EDAT patients had lower Mini-Mental State Examination scores than did DAT patients. When patients were matched for age and dementia severity, CSF HVA and biopterin concentrations remained significantly lower in EDAT than in DAT patients. These results indicate that EDAT patients form a distinct subgroup of DAT with evidence of central monoamine dysfunction.

Aged↗
PubMed1987

Urethral pressure profilometry in mares.

A technique was developed for recording urethral pressure profiles (UPP) in mares. Profiles were obtained from 12 clinically normal mares and from 3 mares with urinary incontinence. Variables measured on the profile included intravesicular pressure and maximal urethral closure pressure. The mean maximal urethral closure pressure of the incontinent mares was significantly less (P less than or equal to 0.001) than that of the normal mares. The technique is simple and reliable for objectively evaluating urethral pressures in mares.

Animals↗
PubMed1987

Cerebrospinal fluid monoaminergic metabolites are elevated in adults with Down's syndrome.

Under conditions of rest and a low monoamine diet, brain monoamine activity was examined in young (less than 35 years) and old (greater than 35 years) adults with Down's syndrome and in control subjects by measuring the cerebrospinal fluid (CSF) and plasma concentrations of the neurotransmitter norepinephrine, and of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy 4-hydroxyphenylglycol (MHPG), the respective metabolites of the neurotransmitters serotonin, dopamine, and norepinephrine. There were no age-related differences in metabolite concentrations in either the Down's syndrome or control subjects. CSF concentrations of 5-HIAA, HVA, and norepinephrine were significantly higher in young subjects with Down's syndrome as compared with young controls, and CSF concentrations of 5-HIAA and norepinephrine were significantly higher, by twofold or more, in old subjects with Down's syndrome as compared with older controls. The results suggest that monoamine turnover and brain functional activity involving monoamines is elevated in Down's syndrome, and that the early neuropathological changes in the disorder are not associated with a monoamine deficit.

Adult↗
PubMed1987

Cerebrospinal fluid monoamines in Down's syndrome adults at different ages.

Markers of monoamine metabolism in lumbar cerebrospinal fluid (CSF) and plasma were determined in nine young, healthy adults with trisomy 21 Down's syndrome (DS), 21-34-years-old, and in three DS subjects over 45 years, two of whom were demented, as well as in two groups of age-matched controls. Test scores of general intelligence, visuospatial ability, visual discrimination and verbal intelligence were reduced significantly in the old as compared to the young DS subjects. Dementia in DS was evident from a history of mental deterioration, disorientation and hallucinations. In the young DS adults, as compared to the controls, CSF 5-HIAA and norepinephrine were significantly elevated but plasma levels were unchanged. HVA, MHPG and biopterin did not differ between the DS groups and age-matched controls, or with relation to age in the DS or control subjects. These results suggest an increased turnover of monoamines in young adults with DS but that alterations in monoamine metabolism are unrelated to the cognitive decline with age in DS.

Adult↗
PubMed1986

Cerebrospinal fluid neuron-specific enolase is reduced in Alzheimer's disease.

Neuron-specific enolase (NSE), a glycolytic enzyme enolase found in brain, was examined in the cerebrospinal fluid and serum of 30 patients with presumptive Alzheimer's disease (AD) and of 13 healthy controls and evaluated as a measure of neuronal functional activity associated with AD. The cerebrospinal fluid NSE levels of patients with AD were significantly reduced and serum NSE levels were significantly increased from controls. Cerebrospinal fluid NSE levels may be representative of central nervous system cell loss or a decrease in neuronal functional activity associated with AD.

Aged↗
PubMed1986

Cerebrospinal fluid biopterin is decreased in Alzheimer's disease.

Tetrahydrobiopterin is the cofactor in the hydroxylation of phenylalanine, tyrosine, and tryptophan leading to the eventual synthesis of the monoaminergic neurotransmitters, dopamine, norepinephrine, and serotonin, respectively. Total biopterin (90% of which is in the tetrahydro form) was measured in cerebrospinal fluid (CSF) and plasma of 30 patients with Alzheimer's disease and of 19 healthy controls. Plasma and CSF biopterin concentrations were not significantly correlated, but the mean CSF biopterin concentration in patients with Alzheimer's disease was significantly less than in age-matched controls, 13.5 pmol/mL as compared with 18.9 pmol/mL. The CSF biopterin concentration was not correlated with ventricular volume, as estimated by quantitative computed tomography, nor with the severity of dementia, as measured by various cognitive tests. The results suggest that a central biopterin deficiency exists in Alzheimer's disease.

Adult↗
PubMed1986

What causes falls? A logical diagnostic procedure.

Any fall in the elderly may signal impending major illness. Falls may be caused by any acute or chronic illness that causes weakness or dizziness. MI, stroke, or GI bleeding may well present with falls. A fall can be the first sign of urinary tract, respiratory, or gallbladder infection. Avoid open-ended questions, such as "What happened?" Patients often state they slipped or tripped--possibly not the true reason for the fall. Direct questions about symptoms ("Did you have difficulty in walking?" or "Did you feel dizzy?") elicit more specific information.

Accidental Falls↗
PubMed1985

Evaluation of zimeldine in Alzheimer's disease. Cognitive and biochemical measures.

Neuropsychological and neurochemical effects of zimeldine, a relatively specific serotonin reuptake blocker, were examined in four patients with clinically diagnosed Alzheimer's disease, in a double-blind, placebo-controlled, crossover study. Individualized doses of zimeldine were administered to achieve target plasma zimeldine concentrations of approximately 50 (low) to 100 (high) ng/mL. Overall, there was no significant effect of zimeldine on memory or reaction time measures as compared with placebo. The drug significantly reduced (by up to 38%) 5-hydroxyindoleacetic acid concentrations in the cereobrospinal fluid and almost abolished (90% reduction) platelet serotonin uptake. Cerebrospinal fluid concentrations of 3-methoxy-4-hydroxy-phenylglycol, a major metabolite of norepinephrine, and homovanillic acid, the major metabolite of dopamine, were not altered. Our findings indicate that alterations in central and peripheral serotoninergic function by a serotonin reuptake blocker (zimeldine) are unaccompanied by measurable changes in memory and/or reaction time in patients presumed to have Alzheimer's disease.

Aged↗
PubMed1985

Clinical history, brain metabolism, and neuropsychological function in Alzheimer's disease.

Data concerning 7 patients with a diagnosis of presumptive Alzheimer's disease (mean age, 65.6 years) are presented in detail in relation to the patients' regional cerebral metabolic rates for glucose. Rates were measured by positron emission tomography with fluorine 18-labeled fluoro-2-deoxy-D-glucose under conditions of reduced visual and auditory stimulation. A relationship was found between severity of dementia and brain metabolism. In patients with mild to moderate Alzheimer's disease, memory and intellectual deficits were evident without major reductions in absolute metabolic rates, while ratios of regional to whole brain metabolism revealed reductions in regions of the parietal lobes. In the late, severe form of the disease, brain metabolic rates were consistently and significantly reduced. The findings suggest that memory and intellectual deficits are reflected in reductions of brain metabolism in some brain regions in mild to moderate forms of Alzheimer's disease and that, in the late, severe form of the disease, reductions occur consistently throughout the brain.

Aged↗