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Biomedical subjects

D King

Publications and source records attributed to D King.

At least 91 records · Page 5Linked to original sources
PubMed1998

Depletion of dopamine in the prefrontal cortex decreases the basal electrophysiological activity of mesolimbic dopamine neurons.

One hypothesis regarding the etiology of schizophrenia proposes that disruption of the dopaminergic innervation of the prefrontal cortex leads to an increase in dopamine (DA) transmission in subcortical regions. In the present study, we examined the effect of 6-hydroxydopamine lesions of the medial prefrontal cortex (mPFC) dopamine innervation on the spontaneous electrophysiological activity of ventral tegmental DA neurons recorded in vivo. DA cell activity was assessed along three dimensions: (1) the relative proportion of DA neurons exhibiting spontaneous activity, (2) their basal firing rate, and (3) the mean percentage of spikes fired in bursts. In lesioned rats, DA neurons in the ventral tegmental area (VTA) exhibited a significantly slower mean firing rate, as well as a significant reduction in the percentage of spikes fired in bursts relative to controls. In contrast, depletion of DA in the mPFC did not have a significant effect on the relative proportion of VTA DA neurons exhibiting spontaneous activity. We suggest that by reducing the basal electrophysiological activity of VTA DA neurons, mPFC DA depletion may lead to an increase in the level of responsivity of the system to excitatory stimuli. Thus, the magnitude of increase in action potential-dependent DA release that occurs in response to a challenge may be augmented in lesioned rats.

Action Potentials↗
PubMed1998

Biogeographic origins of goannas (Varanidae): a molecular perspective.

This project aims to clarify the phylogenetic relationships among the extant species of Varanus in order to elucidate the origins of Varanidae, using DNA sequences. Results obtained for a minimum of 662 nucleotides of 12S rRNA sequence data from each of 21 extant species of Varanus indicate that the Australian varanids form a single monophyletic clade and also suggest that within the Australian varanids, members of the subgenus Odatria (pygmy monitors) may from a clade separate from those in the subgenus Varanus (large monitors). The Asian species appear to be sister taxa to the Australian species, while the two African species investigated were most divergent, suggesting that the Varanidae are not Gondwanic in origin. Hypothesis testing analyses were performed and involved constraining the 12S sequence data according to previously described topologies and testing the difference using parametric and nonparametric statistics. The phylogeny generated using 12S sequence data was statistically different from previously described morphological trees, while there was some support for topologies based on chomosomal and immunological datasets. Overall, our results suggest that the Australian species may be derived from an Asian source and are, therefore, in agreement with the hypothesis based on the fossil record suggesting that Varanidae may be Asian in origin.

Animals↗
PubMed1998

Confirmation of FWT1 as a Wilms' tumour susceptibility gene and phenotypic characteristics of Wilms' tumour attributable to FWT1.

A susceptibility gene for Wilms' tumour (WT), designated FWT1, was previously mapped to chromosome 17q12-q21 by linkage analysis of a single family. We now confirm the existence of this gene by analysis of additional cases in the original family (3-point LOD score=5.69), and by detecting strong evidence of linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score=2.56). Analysis of 11 smaller WT families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT.

Chromosomes, Human, Pair 17↗
PubMed1998

Processing/activation of caspases, -3 and -7 and -8 but not caspase-2, in the induction of apoptosis in B-chronic lymphocytic leukemia cells.

Chlorambucil and prednisolone, two commonly used drugs in the treatment of chronic lymphocytic leukemia (CLL), induce apoptosis in CLL cells. We have investigated the involvement in this apoptotic cell death of caspases, which cleave critical cellular substrates thereby acting as the executioners of the apoptotic process. Induction of spontaneous or chlorambucil/prednisolone-induced apoptosis of freshly isolated B-CLL cells in culture resulted in the activation of the 'effector' caspases, -3 and -7, but generally not of caspase-2. Activation of caspases-3 and -7 was accompanied by the proteolysis of the DNA repair enzyme, poly (ADP-ribose) polymerase. Induction of apoptosis was also accompanied by the processing of caspase-8, the extent of which varied between patients. Induction of apoptosis and processing of all the caspases was inhibited by the cell permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone (Z-VAD.fmk). Our results demonstrate a key role for the activation and processing of caspases in the execution phase of apoptosis in CLL cells. Apoptosis of CLL cells resulted in the selective activation of some but not all caspases. Our results suggest that the dysregulation of apoptosis observed in CLL may be due to the signalling leading to the activation of caspases rather than a deletion of pro-caspases. High levels of caspase-8 in CLL cells in conjunction with low levels of CD95 receptor may offer new therapeutic opportunities for the treatment of CLL.

Aged↗
PubMed1998

Using the SARs to add policy value to household projections.

"Household projections are at the centre of the debate about future housing requirements in England. The Census of Population Sample of Anonymised Records offers actual and potential opportunities to ¿add value' to traditional projections. This article gives examples of such added value, including testing definitional sensitivity of projection outcomes, assisting further detailed disaggregation of projected components, assisting the matching of household projections to dwelling supply, and offering scope to explore via data linkage the relationships between household projections and ¿backlog' housing needs, affordability, dwelling size, and tenure."

Data Collection↗
PubMed1998

An emergency department tackles bed management and home-based care.

Ipswich Hospital Emergency Department played a vital role in the Post Acute Treatment in the Home Program (PATH) of West Moreton District Health Service. PATH used two strategies to reduce the district reliance on acute hospital beds: a short-stay unit for rapid assessment, treatment and early discharge of patients with simple conditions; and a hospital-in-the-home program utilising community health services to treat acute conditions. The program enhanced existing services to create a new treatment stream for acute patients and to promote a cultural shift from fragmented care to district responsibility for total episode of patient care.

Chest Pain↗
PubMed1998

The puzzle of Fran: home healthcare in a hurricane.

A natural disaster in the form of Hurricane Fran resulted not only in stories of ingenuity and compassion, but in a major performance improvement (PI) process for the entire agency. Through this PI process we learned about ourselves as a home health agency and discovered ways to improve our performance. More importantly we discovered ways to improve patient tracking and care during a disaster.

Community Health Nursing↗
PubMed1998

Vascular compromise and amputation after intramedullary nailing of a tibia fracture.

A case is presented of a fifty-three-year-old man with a displaced tibia-fibula fracture that was treated with an intramedullary nail. The morning after surgery pulses were absent and did not improve after fasciotomies. The patient was transferred to our institution, where an arteriogram showed tapering of the anterior tibial and peroneal vessels in the mid-calf and occlusion of the posterior tibial artery at the level of the ankle. Vascular status did not improve after heparinization and arteriogram thrombolysis. The patient ultimately underwent below-the-knee amputation and subsequent revision to above-the-knee amputation.

Amputation, Surgical↗
PubMed1998

Magnetic resonance imaging and temporal lobe epilepsy.

Surgical treatment is a well established option for patients with medically refractory temporal lobe epilepsy. Magnetic resonance imaging (MRI) has revolutionized the evaluation of these patients. New techniques can identify structural, metabolic and functional abnormalities associated with the epileptogenic zone. Mesial temporal sclerosis is the most common pathological finding and presents as hippocampal atrophy, which can be detected by visual inspection in most cases. Volumetric analysis of medial temporal structures offers the advantage of detecting bilateral abnormalities. Magnetic resonance spectroscopy can detect metabolic abnormalities associated with the epileptogenic focus. Functional MRI allows for the non-invasive evaluation of cognitive function, allowing for the localization of the neuroanatomic substrate of motor, sensory and cognitive functions. Intraoperative MRI-based image guided systems are a useful adjunct in the surgical treatment of this epileptic syndrome.

Central Nervous System↗
PubMed1998

Characteristics of patients with shingles admitted to a district general hospital.

Little is known about why some patients with shingles are admitted to hospital. We reviewed 72 case notes from a list of 80 patients admitted to hospital with shingles over a six-year period. Pain was the main complaint of the patients admitted, most of whom were elderly and lived alone. The commonest site of involvement in hospital admissions was the eye (herpes zoster ophthalmicus). Diagnosis of shingles was made after admission in 12 patients, eight of whom had originally been diagnosed as having an acute medical or surgical condition. We conclude that the prodromal phase of shingles may lead to misdiagnosis.

Aged↗
PubMed1998

The natural history of untreated lower urinary tract symptoms in middle-aged and elderly men over a period of five years.

OBJECTIVES: To describe changes in untreated lower urinary tract symptoms (LUTS), levels of bothersomeness and interference in selected living activities arising from LUTS in a cohort of men followed up for a period of 5 years. METHODS: 1,994 men aged 40-79 years registered in four health centres in Scotland completed a urinary symptom questionnaire in the community. 1,177 (71% of original eligible participants) were followed up at 5 years. RESULTS: The mean level of LUTS and the level of bothersomeness they caused increased universally between baseline and 5 years. The largest increases in mean symptom levels occurred for straining, hesitancy, incomplete emptying, weak stream and nocturia, and for mean levels of bothersomeness, i.e. dribbling, incomplete emptying, weak stream, frequency, nocturia and intermittency. The increase in mean interference level in selected living activities arising from LUTS was less marked. The progression of LUTS over time in individual men was very variable; however, the overall trend was one of continuing deterioration. CONCLUSION: If left untreated, overall levels of middle-aged and elderly mens' LUTS, bothersomeness and interference in selected activities caused by these symptoms will increase over time.

Adult↗
PubMed1998

Gender affects renal vasoconstrictor response to Ang I and Ang II.

This study tested the hypothesis that gender affects the pressor and renal vasoconstrictor responses to angiotensin (Ang) I and Ang II in salt-replete normotensive subjects. Ang I and Ang II were infused in graded doses into 9 men and 8 women in a randomized, single-blind, crossover study. There were no differences between genders in baseline blood pressure, heart rate, sodium excretion, renal plasma flow, angiotensin-converting enzyme (ACE) genotype, ACE activity, plasma renin activity, aldosterone, or Ang II levels. Although pressor responses to Ang I and Ang II were similar in men and women, there was a negative relationship between the change in mean arterial pressure and the change in heart rate during Ang I and II infusion in women only. The half-time of the pressor response after discontinuation of Ang I but not Ang II infusion was greater in men than in women (9.5+/-2.2 versus 4.3+/-2.1 minutes, P<.05). This difference in duration did not result from gender differences in the metabolism of Ang I because Ang II levels measured during Ang I infusion were identical in men and women. In contrast, the renal vasoconstrictor response to Ang I and Ang II was significantly increased in women compared with that in men (Ang I, -243+/-31 versus -138+/-13 U/1.73 m2; Ang II, -233+/-25 versus -175+/-18 U/1.73 m2; P<.03). These data suggest an effect of gender on baroreflex reactivity during angiotensin infusion. Moreover, in the setting of similar Ang II concentrations, the dramatic difference in the renal vasoconstrictor responses to Ang I and Ang II between salt-replete men and salt-replete women suggests gender differences at a pharmacodynamic level.

Adult↗
PubMed1998

Functional MRI lateralization of memory in temporal lobe epilepsy.

OBJECTIVE: To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). BACKGROUND: Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. METHODS: fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. RESULTS: Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. CONCLUSIONS: fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery.

Adolescent↗
PubMed1998

Asthma diagnosis by spirometry. Sensitive or specific?

Spirometry is the recommended first-line investigation for diagnosing asthma, with greater than 15% improvement in FEV1 considered diagnostic. However, evidence suggests a majority of asthmatics may go undetected at 15%, thus a lower diagnostic value may be preferred.

Asthma↗
PubMed1998

Laparoscopic resection of a benign true cyst of the spleen with the harmonic scalpel producing high levels of CA 19-9 and carcinoembryonic antigen.

Primary true cysts of the spleen constitute 10 per cent of all nonparasitic cysts of the spleen. These cysts have been managed with total or partial splenectomy or marsupialization. Previous series reported elevated serum levels of CA 19-9 and carcinoembryonic antigen (CEA). A 16-year-old male presented with left upper quadrant pain and was found to have a mass on palpation. An ultrasound and a CT scan of the abdomen showed a 20-cm cystic lesion in the spleen. The CA 19-9 and CEA serum levels were 1264 units/ml (nl <33 units/ml) and 7.5 ng/ml (nl <3.1 ng/ml), respectively. Laparoscopic resection of the cyst using the harmonic scalpel was performed. The pathology showed a benign true epithelial cyst of the spleen, with strongly immunoperoxidase stains for keratin, CA 19-9, and CEA. Levels of CA 19-9 and CEA in the cystic fluid were 48,275 units/ml and 96.6 ng/ml, respectively. This is the first case reported in the literature of a true benign splenic cyst producing high levels of CEA and CA 19-9 in serum and cystic fluid. The patient was discharged home on the 1st postoperative day without problems and returned to his normal daily activities with the 1st week after surgery. The CA 19-9 and CEA serum levels returned to normal levels.

Adolescent↗