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Biomedical subjects

P King

Publications and source records attributed to P King.

At least 19 recordsLinked to original sources
PubMed2000

Radioimmunoguided surgery using indium-111 capromab pendetide (PROSTASCINT) to diagnose supraclavicular metastasis from prostate cancer.

A 59-year-old man presented with a Gleason score of 4 + 4 = 8 prostate cancer and with multiple bilateral pelvic nodes involved at open pelvic lymph node dissection. On indium-111 capromab pendetide (ProstaScint) scan, there was increased tracer deposition in the prostate, the mesenteric nodes, the right pulmonary hilum, and the left supraclavicular fossa. The ProstaScint injection was repeated, and the gamma probe was used to localize tissue that accumulated radiotracer. Two nodes were excised, one that exhibited increased uptake and one that did not. The radioactive lymph node contained metastatic prostate cancer. No malignancy was found in the second node.

Adenocarcinoma↗
PubMed2000

Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia.

Weight loss in cancer cachexia is attributable to decreased food intake and/or enhanced energy expenditure. We investigated the roles of the uncoupling proteins (UCPs) UCPI, -2, and -3 in a murine model of cachexia, the MAC16 adenocarcinoma. Weight fell to 24% below that of non-tumor-bearing controls (P < 0.01) 18 days after MAC16 inoculation, with significant reductions in fat-pad mass (-67%; P < 0.01) and muscle mass (-20%; P < 0.01). Food intake was 26-60% lower (P < 0.01) than in controls on days 17-18. Non-tumor-bearing mice, pair-fed to match MAC16-induced hypophagia, showed less weight loss (10% below controls, P < 0.01; 16% above MAC-16, P < 0.01) and smaller decreases in fat-pad mass (21% below controls, P < 0.01). Core temperature in MAC16 mice was significantly lower (-2.4 degrees C, P < 0.01) than in controls, and pair-feeding had no effect. MAC16 mice showed significantly higher UCP1 mRNA levels in brown adipose tissue (BAT) than in controls (+63%, P < 0.01), and pair-feeding had no effect. UCP2 and -3 expression in BAT did not differ significantly between groups. By contrast, UCP2 mRNA levels in skeletal muscle were comparably increased in both MAC16 and pair-fed groups (respectively, 183 and 163% above controls; both, P < 0.05), with no significant difference between these two groups. Similarly, UCP3 mRNA was significantly higher than controls in both MAC16 (+163%, P < 0.05) and pair-fed (+253%, P < 0.01) groups, with no significant difference between the two experimental groups. Overexpression of UCP1 in BAT in MAC16-bearing mice may be an adaptive response to hypothermia, which is apparently induced by tumor products; increased thermogenesis in BAT could increase total energy expenditure and, thus, contribute to tissue wasting. Increased UCP2 and -3 expression in muscle are both attributable to reduced food intake and may be involved in lipid utilization during lipolysis in MAC16-induced cachexia.

Adenocarcinoma↗
PubMed2000

Artificial skin reduces nutritional requirements in a severely burned child.

An 11 year old boy had 60% BSA burns excised and artificial skin (Integra(R)) applied. None of the burn wound was grafted. At 3 weeks post burn his serum biochemistry was normal, except for a low serum albumin. Mean energy intake for the first 3 weeks was half his non-burned requirement and mean protein intake was close to his non-burned requirement. This is the first report to show that a reduction in nutritional requirements may be observed using skin substitutes.

Blood Chemical Analysis↗
PubMed2000

Doppler ultrasound (pre- and post-contrast enhancement) for detection of recurrent stenosis in stented renal arteries: preliminary results.

The purpose of the present paper was to assess whether conventional renal Doppler ultrasound and the commonly used parameters of peak systolic velocity and renal aortic ratio may be an appropriate modality for the follow-up of renal artery stents. A total of 19 arteries in 15 patients was examined with both renal Doppler ultrasound and angiography for the presence or absence of recurrent renal artery stenosis. Disease was considered present on angiography if the arterial diameter was more than 60% stenotic. Doppler criteria for stenosis were either a peak systolic velocity of > 180 cm/s or a renal aortic ratio of > 3.0. Echo enhancement with Levovist (Schering, Berlin, Germany) was used if studies were technically unsuccessful or to improve diagnostic confidence. Renal Doppler ultrasound detected 100% of renal artery stenoses. The specificity was 75%, the positive predictive value was 67% and the negative predictive value was 100%. Echo enhancement improved the technical success rate from 89 to 95% and also increased diagnostic confidence in six examinations. The present limited study suggests that similar renal Doppler parameters as used for the study of unstented renal arteries may be applied to the examination of renal arteries with renal stents in situ. It therefore suggests that Doppler ultrasound may provide an adequate non-invasive means of renal artery stent follow-up, particularly when combined with echo-enhancing agents. Further study is warranted to confirm these initial conclusions.

Adult↗
PubMed2000

The RNA-binding protein HuD is required for GAP-43 mRNA stability, GAP-43 gene expression, and PKC-dependent neurite outgrowth in PC12 cells.

The RNA-binding protein HuD binds to a regulatory element in the 3' untranslated region (3' UTR) of the GAP-43 mRNA. To investigate the functional significance of this interaction, we generated PC12 cell lines in which HuD levels were controlled by transfection with either antisense (pDuH) or sense (pcHuD) constructs. pDuH-transfected cells contained reduced amounts of GAP-43 protein and mRNA, and these levels remained low even after nerve growth factor (NGF) stimulation, a treatment that is normally associated with protein kinase C (PKC)-dependent stabilization of the GAP-43 mRNA and neuronal differentiation. Analysis of GAP-43 mRNA stability demonstrated that the mRNA had a shorter half-life in these cells. In agreement with their deficient GAP-43 expression, pDuH cells failed to grow neurites in the presence of NGF or phorbol esters. These cells, however, exhibited normal neurite outgrowth when exposed to dibutyryl-cAMP, an agent that induces outgrowth independently from GAP-43. We observed opposite effects in pcHuD-transfected cells. The GAP-43 mRNA was stabilized in these cells, leading to an increase in the levels of the GAP-43 mRNA and protein. pcHuD cells were also found to grow short spontaneous neurites, a process that required the presence of GAP-43. In conclusion, our results suggest that HuD plays a critical role in PKC-mediated neurite outgrowth in PC12 cells and that this protein does so primarily by promoting the stabilization of the GAP-43 mRNA.

Animals↗
PubMed1999

Comparable changes in synaptic dopamine induced by methylphenidate and by cocaine in the baboon brain.

Though the blockade of dopamine transporters (DAT) is associated with cocaine's and methylphenidate's reinforcing effects, it is the stimulation of dopamine (DA) receptors, achieved by increases in synaptic DA, that enables these effects to occur. Positron emission tomography (PET) and [11C]raclopride were used to assess the levels of occupancy of DA D2 receptors by dopamine achieved by doses of cocaine or methylphenidate previously documented to block over 70% of DAT. Studies were performed in five baboons using a paired scan protocol designed to measure DA D2 receptor availability (Bmax/Kd) at baseline conditions and after intravenous administration of either cocaine or methylphenidate. Cocaine (1-2 mg/kg) or methylphenidate (0.5 mg/kg) administered 5 min prior to [11C]raclopride decreased Bmax/Kd by 29+/-3% and 32 + 4%, respectively. Smaller reductions in Bmax/Kd (13% for cocaine given 30 min before [11C]raclopride and 25+/-10% for methylphenidate given 40 min before [11C]raclopride) were seen with longer periods between drug and radioligand. These observations are consistent with the slower striatal clearance kinetics of [11C]methylphenidate than [1C]cocaine observed in previous PET experiments and with the approximately twofold higher potency of methylphenidate than cocaine in in vitro experiments. Though the elevation of synaptic DA induced by >70% occupancy of DAT by these drugs lead to a modest increase in occupancy of D2 receptors (25-30%), further studies are required to assess if this is an underestimation because of differences in D2 receptor binding kinetics between raclopride and DA.

Animals↗
PubMed1999

Euglycaemic hyperinsulinaemia does not affect gastric emptying in type I and type II diabetes mellitus.

Hyperglycaemia slows gastric emptying in both normal subjects and patients with diabetes mellitus. The mechanisms mediating this effect, particularly the potential role of insulin, are uncertain. Hyperinsulinaemia has been reported to slow gastric emptying in normal subjects during euglycaemia. The purpose of this study was to evaluate the effect of euglycaemic hyperinsulinaemia on gastric emptying in Type I (insulin-dependent) and Type II (noninsulin-dependent) diabetes mellitus. In six patients with uncomplicated Type I and eight patients with uncomplicated Type II diabetes mellitus, measurements of gastric emptying were done on 2 separate days. No patients had gastrointestinal symptoms or cardiovascular autonomic neuropathy. The insulin infusion rate was 40 mU x m(-2) x min(-1) on one day and 80 mU x m(-2) x min(-1) on the other. Gastric emptying and intragastric meal distribution were measured using a scintigraphic technique for 3 h after ingestion of a mixed solid/liquid meal and results compared with a range established in normal volunteers. In both Type I and Type II patients the serum insulin concentration had no effect on gastric emptying or intragastric meal distribution of solids or liquids. When gastric emptying during insulin infusion rates of 40 mU x m(-2) x min(-1) and 80 mU x m(-2) x min(-1) were compared the solid T50 was 137.8+/-24.6 min vs. 128.7+/-24.3 min and liquid T50 was 36.7+/-19.4 min vs. 40.4+/-15.7 min in the Type I patients; the solid T50 was 94.9+/-19.1 vs. 86.1+/-10.7 min and liquid T50 was 21.8+/-6.9 min vs. 21.8+/-5.9 min in the Type II patients. We conclude that hyperinsulinaemia during euglycaemia has no notable effect on gastric emptying in patients with uncomplicated Type I and Type II diabetes; any effect of insulin on gastric emptying in patients with diabetes is likely to be minimal.

Adult↗
PubMed1999

Fluoride release of glass ionomer-based luting cements in vitro.

STATEMENT OF PROBLEM: There is considerable variation in generic formulation and in reported fluoride release from resin-modified glass ionomer luting cements. PURPOSE: This study compared fluoride release from 2 generically similar resin-modified glass ionomer luting cements (Vitremer and Advance) with release from 2 conventional glass ionomer luting cements (Ketac-Cem and Fuji I). MATERIAL AND METHODS: Ten specimen disks of each of the 4 luting cements were fabricated and immersed in deionized water in individual polystyrene jars. The jars were stored in a humidor at 37 degrees C between test periods. At the same time each day, for 28 days, fluoride release from each specimen disk was measured in parts per million by testing the storage water. RESULTS: The 4 luting cements tested showed an initial high concentration of fluoride release during the first week, followed by a gradual decrease over the study period. Vitremer luting cement demonstrated the greatest mean cumulative fluoride release in parts per million over the study period (198), followed by Fuji I (140), Ketac-Cem (110), and Advance (99) luting cements. CONCLUSIONS: Resin-modified glass ionomer luting cements showed fluoride release comparable to the conventional glass ionomer luting cements. Vitremer luting cement released more fluoride over the 28-day period than the other cements.

Analysis of Variance↗
PubMed1999

The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones.

The antihypertensive agent moxonidine, an imidazoline Ii-receptor agonist, also induces hypophagia and lowers body weight in the obese spontaneously hypertensive rat, but the central mediation of this action and the neuronal pathways that moxonidine may interact with are not known. We studied whether moxonidine has anti-obesity effects in the genetically-obese and insulin-resistant fa/fa Zucker rat, and whether these are mediated through inhibition of the hypothalamic neuropeptide Y (NPY) neurones. Lean and obese Zucker rats were given moxonidine (3 mg kg(-1) day(-1)) or saline by gavage for 21 days. Moxonidine decreased food intake throughout by 20% in obese rats (P<0.001) and by 8% in lean rats (P<0.001), and reduced weight gain that final body weight was 15% lower in obese (P<0.001) and 7% lower in lean (P<0.01) rats than their untreated controls. Plasma insulin and leptin levels were decreased in moxonidine-treated obese rats (P<0.01 and P<0.05), but unchanged in treated lean rats. Uncoupling protein-1 gene expression in brown adipose tissue was stimulated by 40-50% (P< or =0.05) in both obese and lean animals given moxonidine. Obese animals given moxonidine showed a 37% reduction in hypothalamic NPY mRNA levels (P = 0.01), together with significantly increased NPY concentrations in the paraventricular nucleus (P<0.05), but no changes in the arcuate nucleus or other nuclei; this is consistent with reduced NPY synthesis in the arcuate nucleus and blocked release of NPY in the paraventricular nucleus. In lean animals, moxonidine did not affect NPY levels or NPY mRNA. The hypophagic, thermogenic and anti-obesity effects of moxonidine in obese Zucker rats may be partly due to inhibition of the NPY neurones, whose inappropriate overactivity may underlie obesity in this model.

Adipose Tissue↗
PubMed1999

Divergent effects of intracerebroventricular and peripheral leptin administration on feeding and hypothalamic neuropeptide Y in lean and obese (fa/fa) Zucker rats.

Leptin inhibits feeding and decreases body weight. It may act partly by inhibiting hypothalamic neurons that express neuropeptide Y, a powerful inducer of feeding and obesity. These neuropeptide Y neurons express the Ob-Rb leptin receptor and are overactive in the fatty (fa/fa) Zucker rat. The fa mutation affects the extracellular domain of the leptin receptor, but its impact on leptin action and neuropeptide Y neuronal activity is not fully known. We compared the effects of three doses of leptin given intracerebroventricularly and three doses of leptin injected intraperitoneally on food intake and hypothalamic neuropeptide Y mRNA, in lean and fatty Zucker rats. In lean rats, 4-h food intake was reduced in a dose-related fashion (P<0.01) by all intracerebroventricular leptin doses and by intraperitoneal doses of 300 and 600 microg/kg. Neuropeptide Y mRNA levels were reduced by 28% and 21% after the highest intracerebroventricular and intraperitoneal doses respectively (P<0. 01 for both). In fatty rats, only the highest intracerebroventricular leptin dose reduced food intake (by 22%; P<0. 01). Neuropeptide Y mRNA levels were 100% higher in fatty rats than in lean animals, and were reduced by 18% (P<0.01) after the highest intracerebroventricular leptin dose. Intraperitoneal injection had no effect on food intake and neuropeptide Y mRNA. The fa/fa Zucker rat is therefore less sensitive to leptin given intracerebroventricularly and particularly intraperitoneally, suggesting that the fa mutation interferes both with leptin's direct effects on neurons and its transport into the central nervous system. Obesity in the fa/fa Zucker rat may be partly due to the inability of leptin to inhibit hypothalamic neuropeptide Y neurons.

Animals↗
PubMed1999

Long-term survival characteristics of 832 resin-retained bridges and splints provided in a post-graduate teaching hospital between 1978 and 1993.

The clinical performance of 832 resin-retained bridges and splints provided in the adult fixed prosthodontic clinic of a post-graduate teaching hospital was reviewed. Recall data was available for 58.4% of cases and the median survival was 7 years and 10 months. Analysis of clinical variables influencing survival revealed that the design and retainer coverage were significant factors. The experience of the operator carrying out treatment also had a pronounced effect which was not readily explained in terms of the distribution of other significant factors. Resin-retained restorations made with minimal tooth preparation are shown to be capable of extended clinical service and their failure rarely resulted in adverse consequences for the patient. Patient satisfaction with their treatment was reportedly high.

Adolescent↗
PubMed1999

Decreased plasma leptin levels in lean and obese Zucker rats after treatment with the serotonin reuptake inhibitor fluoxetine.

Leptin inhibits feeding, stimulates thermogenesis and decreases body weight. Serotonin reduces food intake when injected into the hypothalamus and may interact with other neurotransmitters in the control of appetite. We therefore investigated the effects of the serotonergic drug fluoxetine, which inhibits serotonin reuptake, on food intake and plasma leptin levels in lean and obese Zucker rats. Fluoxetine significantly reduced food intake in lean and obese rats, both acutely after a single injection (10 mg/kg) and during continuous subcutaneous infusion (10 mg/kg/day for 7 days). Plasma leptin levels were reduced after both 4 hours and 7 days of fluoxetine administration in lean and after 7 days in fatty rats (all p<0.01). We have previously suggested that serotonin may decrease food intake by inhibiting neuropeptide Y neurones, and we further suggest that it also inhibits leptin, possibly by an effect on white adipose tissue.

Animals↗
PubMed1999

Using Doppler sonography to reveal renal artery stenosis: an evaluation of optimal imaging parameters.

OBJECTIVE: The aim of this study was to determine the accuracy of direct and indirect parameters for the diagnosis of renal artery stenosis and to determine the most useful thresholds for these parameters. SUBJECTS AND METHODS: One hundred twenty-five arteries in 63 patients were examined with renal Doppler sonography and angiography for the presence or absence of renal artery stenosis. Arteries were considered stenosed on angiography if there was a diameter reduction of greater than 60%. Renal Doppler sonographic measures of peak systolic velocity, renal aortic ratio, acceleration time, and acceleration were recorded and compared with the angiographically determined presence or absence of disease. RESULTS: Doppler examination was technically successful in 87% of kidneys and 76% of patients. Receiver operating characteristic analysis showed the optimal peak systolic velocity threshold to be 180 cm/sec and the optimal renal aortic ratio threshold to be 3.0. An acceleration time greater than 70 msec and an acceleration less than 300 cm/sec2 yielded sensitivities of 41% and 56%, respectively, and specificities of 85% and 62%, respectively. Combining a renal aortic ratio of greater than 3.0 or peak systolic velocity greater than 180 cm/sec provided the best combination of parameters with a sensitivity and sensitivity at 85% and 76%, respectively. CONCLUSION: The most accurate use of parameters was found to be a combination of either peak systolic velocity greater than 180 cm/sec or renal aortic ratio greater than 3.0. Indirect parameters were not found to be useful in predicting the presence or absence of renal artery stenosis.

Angiography, Digital Subtraction↗