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Biomedical subjects

J Davies

Publications and source records attributed to J Davies.

At least 37 records · Page 2Linked to original sources
PubMed2004

Restoration of flow following haemodialysis catheter thrombus. Analysis of rt-PA infusion in tunnelled dialysis catheters.

PROBLEM: Urokinase and streptokinase are commonly used thrombolytic agents for obstructed central venous catheters. Although proven to be efficacious, these agents have the potential to induce fibrin breakdown and streptokinase cannot be used repeatedly because of its allergenic nature. Published evidence suggests that Urokinase is safe and effective (>70% efficacy for catheter installation) and that Tissue-type plasminogen activator (rt-PA) can achieve as much as 98% success. OBJECTIVE: To describe our experience with and our protocol for the use of rt-PA as an alternative agent for catheter thrombolysis. DESIGN: Investigation of a cohort of haemodialysis patients with tunnelled central venous catheter (SPCVC) placed between December 2001 to August 2003 and who developed catheter thrombus (female, n = 8: male, n = 12). Each patient was given an infusion of between 1 and 2 mg rt-PA/h for 4 h. The dose was dependent on partial or total line obstruction. The technical success of rt-PA is defined as returning catheter blood flow to >250 mL/min for a 4-h period. FINDINGS: Twenty patients required 57 infusions in 38 lumens between 01/01/02 to 01/09/03. For completely blocked lines rt-PA was infused at 2 mg/h for 4 h achieving 85% success rate. For inadequate flow (<250 mL/min) rt-PA was infused at 1 mg/h for 4 h achieving an 88% success rate. CONCLUSION: Rt-PA administered at 2 mg/h for blocked lines effectively restores haemodialysis catheter patency, and at 1 mg/h for sluggish lines is also effective in restoring blood flow through catheters.

Catheterization, Central Venous↗
PubMed2004

Parathyroid hormone activates adhesion in bone marrow stromal precursor cells.

The ability of parathyroid hormone (PTH) to enhance bone formation has recently been exploited in the treatment of osteoporosis. However, the underlying mechanisms are unknown. Osteoblasts, the bone-forming cells, derive from multipotential bone marrow stromal precursors called colony-forming units-fibroblastic (CFU-F) upon culture ex vivo. Adhesion of such stromal precursors to bone is likely to be an early event in the anabolic response of bone to PTH. To test this, we measured the number of CFU-F that could be extracted from murine bone marrow after administration of an anabolic dose of PTH. We found that a very early response is a dramatic reduction, starting within 2 h, in the number of CFU-F that could be extracted from their bone marrow. We then tested whether PTH has the ability to activate adhesion of CFU-F in vitro. For this, bone marrow cells were incubated in PTH for varying times. Non-adherent cells were then removed, and the adherent cells were incubated in PTH-free medium for 14 days to assess, as colony formation, the number of CFU-F that had adhered in the preceding period. We found that incubation in PTH caused a substantial increase in the number of CFU-F that adhered within 24 h. This increase was abrogated by peptidic inhibitors of integrins. The increase did not seem to be mediated through a PTH-induced increase in interleukin-6, since interleukin-6 had no effect on CFU-F numbers when substituted for PTH. Similarly, adhesion was unaffected by incubation of bone marrow cells in dibutyryl cyclic AMP, nor by inhibitors or donors of nitric oxide. However, activation of CFU-F in vitro by PTH was strongly inhibited by indomethacin and mimicked by prostaglandin E(2), and indomethacin reversed the PTH-mediated reduction of CFU-F that could be extracted from mouse bone marrow. These results suggested that PTH rapidly activates adhesion of CFU-F to plastic or bone surfaces. This activation may represent an early event in the anabolic response of bone cells to PTH.

Animals↗
PubMed2003

How patients manage gastrointestinal symptoms after pelvic radiotherapy.

BACKGROUND: Approximately 13,000 patients undergo pelvic radiotherapy annually in the UK. It is not clear how frequently patients develop a permanent change in bowel habit after pelvic radiotherapy that affects their quality of life because the measures of gastrointestinal toxicity used in trials in the past have generally been inadequate. It has been suggested that patients who are symptomatic are only rarely referred to a gastroenterologist and it is not known how patients manage their symptoms. METHODS: Patients who had completed radiotherapy for pelvic cancer at least 1 year previously were invited to answer 30 structured questions in a face-to-face interview to determine the frequency of gastrointestinal symptoms and what orthodox, dietary and complementary therapies they used to deal with them. They were also asked to score the effectiveness of the measures they had taken. RESULTS: One hundred and seven patients were recruited [35 males; median age, 65 years (range, 35-80 years); 72 females; median age, 67.5 years (range, 31-87 years)]. Eight had been treated for a gastrointestinal primary tumour, 34 for a urological tumour and 65 for gynaecological tumours. Eighty-seven patients (81%) described new-onset gastrointestinal problems starting after radiotherapy. These symptoms affected the quality of life in 56 patients (52%). Significant effects on the quality of life were caused by diarrhoea or constipation (n = 53), faecal leakage (n = 19), abdominal, rectal or perineal pain (n = 14) and rectal bleeding (n = 6). Fifty-nine patients had seen a doctor for their symptoms (86% found this helpful), 12 had seen a dietician or nurse (50% found this helpful) and 14 had seen alternative practitioners (88% found this helpful). Dietary manipulation generally did not improve symptoms, except in a small group of patients (14/15) who avoided raw vegetables to great benefit. CONCLUSIONS: At least 1 year after pelvic radiotherapy, gastrointestinal symptoms which have an adverse effect on the quality of life may be more common than generally reported. Patients found that advice from doctors and alternative practitioners was equally valuable. Dietary manipulation was generally unhelpful for gastrointestinal symptoms after pelvic radiotherapy, although the role of eliminating raw vegetables may benefit from further evaluation.

Adult↗
PubMed2003

The DNA sequence and analysis of human chromosome 6.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Animals↗
PubMed2003

Unusual intestinal sequelae after operations for Ascaris lumbricoides infestation.

Two children with severe bowel sequelae distal to the site of an Ascaris lumbricoides bowel obstruction are reported. It is postulated that these resulted from inflammatory reaction to toxic decomposition products of disintegrating worms. Surgery should be modified in the presence of bowel-wall injury distal to the site of ascarid worm - bolus obstruction.

Animals↗
PubMed2003

Further delineation of the sequences required for the expression and physiological regulation of the vasopressin gene in transgenic rat hypothalamic magnocellular neurones.

We have introduced transgenes into rats with a view to defining genomic regions that mediate the cell-specific and physiological regulation of the vasopressin gene. These transgenes consist of the rat vasopressin structural gene with a reporter inserted into exon III, flanked by different lengths of upstream and downstream sequences. 11-VCAT-3 is flanked by 11 kbp of upstream sequences and 3 kbp of downstream sequences. The previously described 5-VCAT-3 is flanked by 5 kbp of upstream and 3 kbp of downstream sequences. 3-VCAT-3 has 3 kbp of upstream and 3 kbp of downstream sequences, and 3-VCAT-0.2 is flanked by 3 kbp of upstream and 0.2 kbp of downstream sequences. All four transgenes elicit the same expression patterns; low basal expression is seen in the magnocellular supraoptic and paraventricular nuclei, and is negligible in the suprachiasmatic nucleus. Expression increases markedly in vasopressin magnocellular cells following dehydration. The sequences responsible for the cell-specific expression and physiological regulation of our transgenes thus reside within the confines of the smallest construct studied, 3-VCAT-0.2.

Animals↗
PubMed2002

Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating capacity in hypopituitary adults with GH deficiency.

OBJECTIVES: Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro-atherogenic state associated with adult GHD. DESIGN AND PATIENTS: In a randomized, double-blind, placebo-controlled study we investigated the effects of GH replacement on low-density lipoprotein (LDL) oxidation and neutrophil superoxide (O(-)(2)) generating capacity in 32 GHD adults (19 males, 13 females; age range 19-64 years) over 3 months. Thirty age- and sex-matched healthy controls were also studied. MEASUREMENTS: Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper-catalysed lag phase of LDL oxidation. Neutrophil O(-)(2)- generating capacity was assessed by a lucigenin-based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis. RESULTS: Compared to controls, GHD subjects had higher LDL cholesterol (4.0 +/- 0.8 vs. 3.5 +/- 0.9 mmol/l, P < 0.01) and higher triglyceride concentrations (2.3 +/- 1.5 vs. 1.1 +/- 0.7 mmol/l, P < 0.001) but lower HDL cholesterol (1.1 +/- 0.3 mmol/l vs. 1.4 +/- 0.4 mmol/l, P < 0.01), lower levels of HPOs (0.72 +/- 0.35 vs. 0.92 +/- 0.20 microm, P < 0.01) and lower basal (2.5 +/- 1.5 vs. 4.5 +/- 2.3 mV/5 x 10(5) neutrophils, P < 0.01) and peak post-activation levels (23.2 +/- 11.1 vs. 34.4 +/- 15.6 mV/5 x 10(5) neutrophils, P < 0.01) of neutrophil O(-)(2)- generation. GH replacement resulted in an increase in HPOs from 0.70 +/- 0.39 to 0.86 +/- 0.19 microm (P < 0.05), although there was no change in the lag time of LDL oxidation. Neutrophil O(-)(2)- generating capacity was enhanced with a rise in basal O(-)(2)- generation from 2.8 +/- 1.4 to 5.4 +/- 4.6 mV/5 x 10(5) neutrophils (P < 0.05) and in peak post-activation O(-)(2)- generation from 21.9 +/- 9.5 to 35.8 +/- 21.7 mV/5 x 10(5) neutrophils (P < 0.05). LDL cholesterol was reduced from 4.1 +/- 0.8 mmol/l to 3.5 +/- 0.8 mmol/l (P < 0.01). No significant changes in measured parameters occurred in the placebo group. CONCLUSIONS: Adult GHD is associated with reduced lipid peroxidation and impaired neutrophil O(-)(2)- generating capacity, both of which are reversible with GH replacement. Our data suggest that: (i) that oxidative stress is not a major feature of the pro-atherogenic state in hypopituitary adults with GHD and (ii) a role for GH in modulating neutrophil function and leucocyte-lipoprotein interactions.

Adult↗
PubMed2002

Autophagy in hypothalamic neurones of rats expressing a familial neurohypophysial diabetes insipidus transgene.

We have tested the hypothesis that familial neurohypophysial diabetes insipidus (FNDI) is initiated by a process of autophagy. FNDI is a dominant, progressive inherited disorder characterized by pronounced drinking and urination caused by loss of secretion of antidiuretic hormone (vasopressin). In rats expressing an FNDI mutant transgene (Cys67stop) in vasopressin magnocellular neurones, the mutant protein fails to enter the regulated secretory pathway, and accumulates in a swollen and distended endoplasmic reticulum (ER) that also contains wild-type, endogenous vasopressin. Transmission electron microscopy suggested that these are autophagic vesicles. We have now examined the expression of vesicular markers in our transgenic rats, and demonstrate that activation of autolysosomal processes is a consequence of the expression of Cys67stop. Swollen vesicles containing Cys67stop are immunoreactive for cathepsin D (a lysosomal protease), endolyn (a marker of late endosomes) and lysosomal associated membrane protein 1, suggesting that they may be degradative autolysosomes. In addition, there is an up-regulation of lysosomal markers specifically in cells expressing Cys67stop. The expression of Cys67stop affects neither the trans-Golgi network nor early endosomes. These data support the proposal that Cys67stop mutant protein aggregates within the ER, which is targeted for lysosomal degradation by autophagy.

Animals↗
PubMed2002

Organophosphate poisoning complicated by a tachyarrhythmia and acute respiratory distress syndrome in a child.

A 9-year-old child presented with documented organophosphate insecticide poisoning. His course was initially complicated by a tachyarrhythmia with QT-interval prolongation that responded promptly to intravenous magnesium. However, following partial recovery, he developed progressive acute respiratory distress syndrome characterized by irreversible fibrosis and obliteration of the lung parenchyma.

Child↗
PubMed2002

Congenital solitary intestinal fibromatosis.

Neonatal intestinal obstruction due to a tumour is rare. We report a six-day-old male neonate who presented with abdominal distension and vomiting. Laparotomy revealed colonic obstruction caused by a stenosing fibrotic lesion in the proximal transverse colon. Histopathological examination of the resected specimen confirmed fibromatosis. We believe this represents the third reported case of solitary colonic fibromatosis. The literature on neonatal intestinal fibromatosis is reviewed.

Colectomy↗
PubMed2001

The Na(+)/H(+) exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction. Results of the evaluation of the safety and cardioprotective effects of eniporide in acute myocardial infarction (ESCAMI) trial.

OBJECTIVES: We conducted an international, prospective, randomized, double-blind, placebo-controlled phase 2 trial in patients undergoing thrombolytic therapy or primary angioplasty for acute ST-elevation myocardial infarction (MI) to investigate the effect of eniporide on infarct size and clinical outcome. BACKGROUND: Experimental studies suggest that the activity of the Na(+)/H(+) exchange (NHE) plays an important role in the unfavorable sequels of myocardial ischemia and reperfusion. Eniporide specifically inhibits the NHE-1 isoform and has been shown to limit infarct size in experimental models. METHODS: The primary efficacy end point was the infarct size measured by the cumulative release of alpha-hydroxybutyrate dehydrogenase (alpha-HDBH) (area under the curve [AUC] 0 to 72 h). In stage 1, 50, 100, 150 or 200 mg eniporide given as a 10-min infusion before start of reperfusion therapy were compared with placebo in 430 patients, and in stage 2, 100 and 150 mg eniporide were compared with placebo in 959 patients. RESULTS: In stage 1, the administration of 100 mg and 150 mg eniporide resulted in smaller infarct sizes (mean alpha-HBDH AUC in U/ml x h, placebo: 44.2, 100 mg eniporide: 40.2, 150 mg eniporide: 33.9), especially in the angioplasty group. In contrast, in stage 2 there was no difference in the enzymatic infarct size between the three groups (placebo: 41.2, 100 mg eniporide: 43.0, 150 mg eniporide: 41.5). Overall there was no effect of eniporide on clinical outcome (death, cardiogenic shock, heart failure, life-threatening arrhythmias). However, there was a significant reduction of the incidence of heart failure in patients reperfused late (>4 h). CONCLUSIONS: In this large study administration of the NHE-1 inhibitor eniporide, before reperfusion therapy in patients with acute ST elevation MI, did not limit infarct size or improve clinical outcome.

Adult↗