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Biomedical subjects

M D Taylor

Publications and source records attributed to M D Taylor.

At least 19 recordsLinked to original sources

Survey of the prevalence, diagnosis and treatment of dermatological conditions in small animals in general practice.

A survey was made of the prevalence, diagnosis and treatment of dermatological conditions in small animals in general practice in the UK. Out of 3707 small animal consultations in general practice that were observed and recorded, 795 (21.4 per cent) involved animals that had a dermatological problem. In dogs and exotic species, pruritus was the most common presenting sign, accounting for 30 to 40 per cent of the dermatological consultations. In cats, cutaneous swellings were the most common presentation (36 per cent). A diagnosis or recommendation for treatment was made on the basis of the presenting clinical signs and physical examination alone in 576 (72 per cent) of the cases, and various diagnostic tests were performed in the other cases. In dogs, parasitic infestations, bacterial infections and neoplasia accounted for the majority of the diagnoses. In cats, parasites and bacterial infections were the most common. In exotic species, parasites accounted for over 80 per cent of the dermatological diagnoses. In dogs, the most common final diagnoses were otitis, pyoderma, anal sac impaction, flea infestation and atopic dermatitis. In cats, abscesses, flea infestation, and otitis were the most common diagnoses. In exotic species, the most common diagnosis was an unspecified mite infestation. Systemic antibiotics were prescribed in 196 cases (25 per cent), systemic glucocorticoids were prescribed in 162 cases (20 per cent) and treatment with an ectoparasiticide was prescribed in 167 cases (21 per cent).

Animals↗

Childhood IQ and all-cause mortality before and after age 65: prospective observational study linking the Scottish Mental Survey 1932 and the Midspan studies.

OBJECTIVES: The objective was to investigate how childhood IQ related to all-cause mortality before and after age 65. DESIGN: The Midspan prospective cohort studies, followed-up for mortality for 25 years, were linked to individuals' childhood IQ from the Scottish Mental Survey 1932. METHODS: The Midspan studies collected data on risk factors for cardiorespiratory disease from a questionnaire and at a screening examination, and were conducted on adults in Scotland in the 1970s. An age 11 IQ from the Scottish Mental Survey 1932, a cognitive ability test conducted on 1921-born children attending schools in Scotland, was found for 938 Midspan participants. The relationship between childhood IQ and mortality risk, adjusting for adulthood socio-economic confounders, was analysed. The effect of adjustment for childhood IQ on the relationship between established risk factors (blood pressure, smoking, height and respiratory function) and mortality was also investigated. RESULTS: For deaths occurring up to age 65, there was a 36% increased risk per standard deviation decrease (15 points) in childhood IQ which was reduced to 29% after adjusting for social class and deprivation category. There was no statistically significant relationship between childhood IQ and deaths occurring after the age of 65. Adjustment for childhood IQ attenuated the risk factor-mortality relationship in deaths occurring up to age 65, but had no effect in deaths occurring after age 65. CONCLUSIONS: Childhood IQ was significantly related to deaths occurring up to age 65, but not to deaths occurring after age 65.

Adolescent↗

Creatine phosphate administration preserves myocardial function in a model of off-pump coronary revascularization.

AIM: Off pump coronary artery bypass grafting (OPCAB) involves, and is occasionally impaired by obligatory regional myocardial ischemia, particularly with the use of proximal coronary in-flow occlusion techniques. Intracoronary shunts do not guarantee absence of distal ischemia given their small inner diameter and the presence of proximal coronary stenosis. Additional adjunctive measures to provide short-term myocardial protection may facilitate OPCAB. High-energy phosphate supplementation with creatine phosphate prior to ischemia may attenuate ischemic dysfunction. METHODS: In a rodent model of a transient coronary occlusion and myocardial ischemia, 36 animals underwent preischemic intravenous infusion of either creatine phosphate or saline, 10 minutes of proximal left anterior descending (LAD) occlusion, and 10 minutes of reperfusion. Rats underwent continuous intracavitary pressure monitoring and cellular ATP levels were quantified using a luciferin/luciferase bioluminescence assay. RESULTS: Within 2 minutes of ischemia onset, creatine phosphate animals exhibited statistically significant greater preservation of myocardial function compared to controls, an augmentation which persisted throughout the duration of ischemia and subsequent reperfusion. Furthermore, significantly greater cellular ATP levels were observed among creatine phosphate treated animals (344+/-55 nMol/g tissue, n=5) compared to control animals (160+/-9 nMol/g tissue, n=5)(p=0.014). CONCLUSIONS: A strategy of intravenous high-energy phosphate administration successfully prevented ischemic ventricular dysfunction in a rodent model of OPCAB.

Adenosine Triphosphate↗

Childhood IQ and cardiovascular disease in adulthood: prospective observational study linking the Scottish Mental Survey 1932 and the Midspan studies.

This study investigated the influence of childhood IQ on the relationships between risk factors and cardiovascular disease (CVD), coronary heart disease (CHD) and stroke in adulthood. Participants were from the Midspan prospective cohort studies which were conducted on adults in Scotland in the 1970s. Data on risk factors were collected from a questionnaire and at a screening examination, and participants were followed up for 25 years for hospital admissions and mortality. 938 Midspan participants were successfully matched with their age 11 IQ from the Scottish Mental Survey 1932, in which 1921-born children attending schools in Scotland took a cognitive ability test. Childhood IQ was negatively correlated with diastolic and systolic blood pressure, and positively correlated with height and respiratory function in adulthood. For each of CVD, CHD and stroke, defined as either a hospital admission or death, there was an increased relative rate per standard deviation decrease (15 points) in childhood IQ of 1.11 (95% confidence interval 1.01-1.23), 1.16 (1.03-1.32) and 1.10 (0.88-1.36), respectively. With events divided into those first occurring before and those first occurring after the age of 65, the relationships between childhood IQ and CVD, CHD and stroke were only seen before age 65 and not after age 65. Blood pressure, height, respiratory function and smoking were associated with CVD events. Relationships were stronger in the early compared to the later period for smoking and FEV1, and stronger in the later compared to the earlier period for blood pressure. Adjustment for childhood IQ had small attenuating effects on the risk factor-CVD relationship before age 65 and no effects after age 65. Adjustment for risk factors attenuated the childhood IQ-CVD relationship by a small amount before age 65. Childhood IQ was associated with CVD risk factors and events and can be considered an important new risk factor.

Adolescent↗

The Scottish mental survey 1932 linked to the Midspan studies: a prospective investigation of childhood intelligence and future health.

The Scottish mental survey of 1932 (SMS1932) recorded mental ability test scores for nearly all children born in 1921 and at school in Scotland on 1 June 1932. The Collaborative and Renfrew/Paisley studies, two of the Midspan studies, obtained health and social data by questionnaire and a physical examination in the 1970s. Some Midspan participants were born in 1921 and may also have taken part in the SMS1932, so there was a possibility that their mental ability data from childhood would be available. The 1921 born Midspan participants were matched with the computerized SMS1932 database, and in total, 1032 of 1251 people (82.5%) were matched successfully. Of those matched, 938 (90.9%) had a mental ability test score recorded. The mean score of the matched sample was 37.2 (standard deviation (SD) 13.9) out of a possible score of 76. The mean (SD) for the boys and girls was 38.3 (14.2) and 35.7 (13.9), respectively. This compared with 38.6 (15.7) and 37.2 (14.3) for boys and girls in all of Scotland. Graded relationships were found between mental ability in childhood, and social class and deprivation category of residence in adulthood. Being in a higher social class or in a more affluent deprivation category was associated with higher childhood mental ability scores, and the scores reduced with increasing deprivation. Future plans for the matched data include examining associations between childhood mental ability and other childhood and adult risk factors for disease in adulthood, and modelling childhood mental ability, alongside other factors available in the Midspan database, as a risk factor for specific illnesses, admission to hospital and mortality.

Adult↗

Psychosocial factors and diabetes-related outcomes following diagnosis of Type 1 diabetes in adults: the Edinburgh Prospective Diabetes Study.

AIMS: To examine prospectively the relationships between psychosocial variables and diabetes-related outcomes in adults with newly diagnosed Type 1 diabetes. METHODS: A total of 84 adults (48 male) with a median (range) age of 30.8 (17-51) years with newly diagnosed Type 1 diabetes were recruited for the study. Shortly after initial diagnosis each participant's personality, cognitive ability, and recent psychiatric distress were assessed. At 4 months (n = 69) and at 12 months (n = 66) after diagnosis diabetes-related outcomes were measured, including each respondent's knowledge of diabetes, satisfaction with diabetes treatment and diabetes-related quality of life. Glycated haemoglobin (HbA1c) was recorded at each clinic attendance. RESULTS: Social class (Spearman's correlation r = -0.30 and -0.28, respectively, P < 0.05) and scores on the National Adult Reading Test (r = 0.38 and 0.36, respectively, P < 0.01) were consistently associated with knowledge of diabetes at 4 months and at 12 months after diagnosis. Hierarchical regression revealed that alcohol consumption recorded at diagnosis and knowledge of diabetes at 4 months were independent predictors of glycaemic control at 12 months (adjusted r2 = 0.16). Total scores on the Diabetes Treatment Satisfaction Questionnaire (DTSQ) at 12 months were significantly predicted by age at diagnosis (adjusted r2 = 0.08). High neuroticism at diagnosis was consistently associated with poorer self-reported diabetes quality of life at 4 months and at 12 months after diagnosis (rs between -0.30 and -0.39, P < 0.05). CONCLUSIONS: Long-standing psychosocial factors have a significant influence on self-reported outcomes during the 12 months following diagnosis of Type 1 diabetes but may not be reliable predictors of glycaemic control. Further follow-up is necessary to determine the longer-term predictors of objective (e.g. glycaemic control) and subjective (e.g. quality of life) indicators of coping in people with diabetes.

Adaptation, Psychological↗

Muscle-derived neurotrophin-3 reduces injury-induced proprioceptive degeneration in neonatal mice.

During perinatal development, proprioceptive muscle afferents are quite sensitive to nerve injury. Here, we have used transgenic mice that overexpress neurotrophin-3 (NT-3) in skeletal muscle (myo/NT-3 mice) to explore whether NT-3 plays a neuroprotective role for perinatal muscle afferents following nerve injury. Measurements of NT-3 mRNA using RT-PCR revealed that levels of endogenous NT-3 mRNA in wild-type muscles remained constant during the first postnatal week following nerve crush or nerve section on postnatal day (PN) 1. In comparison, myo/NT-3 mice had significantly elevated levels of NT-3 mRNA that were maintained or increased following injury. To assess whether muscle-derived NT-3 could prevent injury-induced neuronal death, neuron survival in the DRG was analyzed in mice 5 days after sciatic nerve crush on PN3. Retrograde prelabeling of muscle afferents and parvalbumin immunocytochemistry both revealed that overexpression of NT-3 in muscle significantly reduced neuronal loss following injury. Similar neuroprotective effects of NT-3 were observed in wild-type mice injected with exogenous NT-3 in the gastrocnemius muscles. To test whether NT-3 could prevent muscle spindle degeneration, spindle number and morphology were assessed 3 weeks after sciatic nerve crush or section on PN1. No spindles were present in either wildtype or myo/NT-3 muscles after nerve section, demonstrating that NT-3 overexpression cannot maintain spindles following complete denervation. Moreover, NT-3 overexpression could not prevent moderate spindle loss in muscle and did not stimulate new spindle formation following nerve crush. Our results demonstrate that in addition to its early actions on sensory neuron generation and naturally occurring cell death, NT-3 has important neuroprotective effects on muscle afferents during postnatal development.

Amidines↗

Postnatal regulation of limb proprioception by muscle-derived neurotrophin-3.

To investigate the effects of neurotrophin-3 (NT-3) on postnatal proprioceptive neurons and their targets, transgenic mice were generated that use the myosin light chain 1 (mlc) promoter to overexpress NT-3 in skeletal muscle. Ribonuclease protection assays revealed that NT-3 overexpression in hindlimb skeletal muscle began at embryonic day 14 (E14) and continued throughout adulthood. Overexpression of NT-3 during late embryogenesis resulted in increased numbers of large sensory and small fusimotor axons. Within a week of birth, mlc/NT-3 mice retract their limbs to the torso when lifted by the tail. Footprint analysis revealed that mlc/NT-3 mice had significant abnormalities in their gait compared with wild-types. Beam walking and rotorod analysis confirmed the poor limb control by mlc/NT-3 mice. These locomotive deficits progressively worsened with age and were likely related to the formation of morphologically abnormal muscle spindles. The most common spindle anomaly was the presence of excessive intrafusal bag fibers within individual muscle spindles. To assess the role of NT-3 in recovery from nerve injury, sciatic nerve crushes were performed in young adult mice. Two days after injury, mlc/NT-3 mice displayed significantly improved sciatic functional indexes and a significant increase in muscle spindles that remained associated with axons. The latter finding suggests that excess NT-3 in muscle may retard the degeneration of proprioceptive axons after nerve crush. Long-term survival after nerve injury in mlc/NT-3 mice did not induce further changes in spindle number or morphology. These findings demonstrate that, in addition to promoting embryonic proprioceptive neuron survival, postnatal overexpression of NT-3 in muscle leads to abnormal spindle formation and deficits in locomotive control. However, our results also show that NT-3 may be therapeutic for proprioceptive axons immediately after nerve injury by delaying axon degeneration.

Animals↗

L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure.

This study was designed to determine the efficacy and tolerability of increasing doses of L-threo-dihydroxyphenylserine (L-threo-DOPS) in treating symptomatic orthostatic hypotension associated with multiple system atrophy (MSA) and pure autonomic failure (PAF). Following a one-week run-in, patients (26 MSA; 6 PAF) with symptomatic orthostatic hypotension received increasing doses of L-threo-DOPS (100, 200 and 300 mg, twice daily) in an open, dose-ranging study. Incremental dose adjustment (after weeks two and four of outpatient treatment) was based on clinical need until blood pressure (BP), and symptoms improved. Final dosage was maintained for six weeks. With L-threo-DOPS, systolic BP decrease was reduced during orthostatic challenge (-22+/-28 mm Hg reduction from a baseline decrease of 54.3+/-27.7 mm Hg, p = 0.0001, n = 32; supine systolic BP at final visit was 118.9+/-28.2 mm Hg). By the end of the study, 25 patients (78%) improved, and in 14 patients (44%) orthostatic hypotension was no longer observed. Decreased orthostatic systolic BP decrease occurred in 22% (7/32), 24% (6/25) and 61% (11/18) of patients treated with 100, 200, and 300 mg L-threo-DOPS twice daily, respectively. An improvement occurred in symptoms associated with orthostatic hypotension, such as light-headedness, dizziness (p = 0.0125), and blurred vision (p = 0.0290). L-threo-DOPS was well tolerated, with the 2 serious adverse events reported being a possible complication of the disease under study, and with no reports of supine hypertension. In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF.

Adolescent↗

Cadmium in soil solutions from a transect of soils away from a fertiliser bin.

The effects of high inputs of phosphate fertiliser on Cd concentrations were studied in soil solutions extracted from topsoils. Soils were sampled along a transect at distances of 1-100 m away from a fertiliser bin. The transect was sampled four times during 1 year. Soil solutions were analysed for Cd, pH, major cations and anions, and other heavy metals (As, Cr, Cu, Pb). For one of the transect samplings, soil total Cd, Cr, Cu, Pb and P were also measured. Cd speciation in the soil solutions was calculated by the GEO-CHEM-PC computer program. Chemical composition varied substantially along the transect, and also between samplings, indicative of seasonal effects and the influence of a fresh application of superphosphate fertiliser during the year. Application of fertiliser decreased soil solution pH and increased the levels of heavy metals in soil solution. Generally, soil total Cd, Cr, Cu, Pb, and P decreased with increasing distance from the fertiliser bin. Correlations between P and the four heavy metals were: P and Cd (R2 = 0.978), P and Cr (R2 = 0.712), P and Pb (R2 = 0.538), P and Cu (R2 = 0.267). Less than 1% of the total Cd in the soil samples was found in the soil solution. The free metal ion Cd2+ accounted for 55-90% of solution Cd. Of the complexed species of Cd, the chloride and sulphate complexes were usually the most important, even when nitrate and phosphate concentrations were relatively high. The presence of As, Cr, Cu and Pb had no effect on Cd speciation.

Cadmium↗

Cip/Kip cell-cycle inhibitors: a neuro-oncological perspective.

The cell cycle is a precisely controlled cellular program that ensures normal cellular proliferation and development. The cyclin-dependant kinases (CDK) are molecules central to the continued progression through the cell-cycle checkpoints and as such are regulated by various mechanisms including cyclin levels, phosphorylation/dephosphorylation and cyclin-dependant kinase inhibitors (CKI). The CKIs are grouped into two families based on their structure and function, four lnk4 CKIs and three Cip/Kip CKIs. Abnormalities in these proteins can give rise to developmental defects and cancer. In this review, we will discuss the biochemistry and cell biology of the each of the Cip/Kip CKIs, their role in development as evidenced by targeted mutations in mice, and their role as possible tumor suppressor genes.

Animals↗

Molecular genetics of pineal region neoplasms.

A large variety of mass lesions have been reported in the region of the pineal gland. Pineal parenchymal tumors and germ cell tumors (GCTs) are especially characteristic of this region. Despite their rarity, a number of excellent studies on the cytogenetics and molecular genetics of pineal parenchymal tumors and pineal region GCTs have been published. These studies draw attention to a number of distinct genomic regions recurrently involved in the various subtypes of malignancies of the pineal gland. Outcomes for tumors in this location vary widely between patients and among differing histologies. Development of novel therapies for patients with poor prognoses will depend on the acquisition of a more detailed understanding of the molecular basis associated with the etiopathogenesis of these neoplasms. We review the literature on cytogenetics, familial syndromes, animal models and molecular genetics of pineal region neoplasms.

Animals↗

Overexpression of neurotrophin-3 in skeletal muscle alters normal and injury-induced limb control.

Transgenic overexpression of neurotrophin-3 (NT-3) in mice increases the number of surviving proprioceptive sensory components, including primary sensory neurons, gamma motoneurons and muscle spindles. The numbers of surviving alpha motoneurons are not affected by NT-3 overexpression (Wright et al., Neuron 19: 503-517, 1997). We have assessed the consequences NT-3-stimulated increase in the proprioceptive sensory system by measuring locomotive abilities of mice that overexpress NT-3 in all skeletal muscles (myo/NT-3 mice). In adulthood, one myo/NT-3 transgenic line continues to express NT-3 at high levels in muscle and maintains a hypertrophied proprioceptive system (high-OE myo/NT-3 mice). Compared to wildtypes, high-OE myo/NT-3 mice have nine times the amount of NT-3 protein in the medial gastrocnemius at six weeks of age. Although appearing normal during ordinary activity, high-OE myo/NT-3 mice display a distinct clasping phenotype when lifted by the tail. High-OE myo/NT-3 mice show severe locomotor deficits when performing beam walking and rotorod testing. These mice also demonstrate aberrant foot positioning during normal walking. However, following sciatic nerve crush, overexpression of NT-3 prevents further abnormalities in paw positioning, suggesting NT-3 may attenuate sensorimotor deficits that occur in response to sciatic nerve injury. Our results suggest that increases in proprioceptive sensory neurons, spindles and gamma motoneurons, along with continued postnatal NT-3 overexpression in muscle significantly disrupt normal locomotor control. Importantly, however, NT-3 may lessen initial deficits and thus improve functional recovery after peripheral nerve injury, suggesting these mice may serve as a good model to study NT-3's role in neuroprotection of proprioceptive afferents.

Animals↗

Awake craniotomy for removal of intracranial tumor: considerations for early discharge.

UNLABELLED: We retrospectively reviewed the anesthetic management, complications, and discharge time of 241 patients undergoing awake craniotomy for removal of intracranial tumor to determine the feasibility of early discharge. The results were analyzed by using univariate analysis of variance and multiple logistic regression. The median length of stay for inpatients was 4 days. Fifteen patients (6%) were discharged 6 h after surgery and 76 patients (31%) were discharged on the next day. Anesthesia was provided by using local infiltration supplemented with neurolept anesthesia consisting of midazolam, fentanyl, and propofol. There was no significant difference in the total amount of sedation required. Overall, anesthetic complications were minimal. One patient (0.4%) required conversion to general anesthesia and one patient developed a venous air embolus. Fifteen patients (6%) had self-limiting intraoperative seizures that were short-lived. Of the 16 patients scheduled for ambulatory surgery, there was one readmission and one unanticipated admission. It may be feasible to discharge patients on the same or the next day after awake craniotomy for removal of intracranial tumor. However, caution is advised and patient selection must be stringent with regards to the preoperative functional status of the patient, tumor depth, surrounding edema, patient support at home, and ease of access to hospital for readmission. IMPLICATIONS: It may be feasible to perform awake craniotomies for removal of intracranial tumor as an ambulatory procedure; however, caution is advised. Patient selection must be stringent with respect to the patient's preoperative functional status, tumor depth, surrounding edema, patient support at home, and ease of access to hospital for readmission.

Adolescent↗

Medulloblastoma in a child with Rubenstein-Taybi Syndrome: case report and review of the literature.

Although medulloblastoma is usually sporadic, there are a number of uncommon predisposing germline mutation syndromes, including: Gorlin's Syndrome, Turcot's Syndrome and Li-Fraumeni Syndrome. Patients with Rubenstein-Taybi Syndrome secondary to mutation/deletion of the CBP gene on chromosome 16 are predisposed to a variety of developmental anomalies as well as cancer. We report a child with Rubenstein-Taybi syndrome who developed a cerebellar medulloblastoma and review the literature on Rubenstein-Taybi Syndrome and pediatric medulloblastoma. As the product of the CBP gene functions in a variety of signaling pathways, we discuss the molecular implications of findings a medulloblastoma in a child with Rubenstein-Taybi Syndrome.

Abnormalities, Multiple↗

Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease.

Lentiviral delivery of glial cell line-derived neurotrophic factor (lenti-GDNF) was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease (PD). We injected lenti-GDNF into the striatum and substantia nigra of nonlesioned aged rhesus monkeys or young adult rhesus monkeys treated 1 week prior with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Extensive GDNF expression with anterograde and retrograde transport was seen in all animals. In aged monkeys, lenti-GDNF augmented dopaminergic function. In MPTP-treated monkeys, lenti-GDNF reversed functional deficits and completely prevented nigrostriatal degeneration. Additionally, lenti-GDNF injections to intact rhesus monkeys revealed long-term gene expression (8 months). In MPTP-treated monkeys, lenti-GDNF treatment reversed motor deficits in a hand-reach task. These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients.

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