Search PubMed⌕ Search

Biomedical subjects

M G Davies

Publications and source records attributed to M G Davies.

At least 19 recordsLinked to original sources
PubMed2004

Pemphigus foliaceus: an adverse reaction to lisinopril.

Lisinopril is an angiotensin converting enzyme inhibitor used in the treatment of cardiovascular disease. We report a case of pemphigus foliaceus in a 66-year-old male treated with lisinopril for hypertension and a previous myocardial infarction. The drug-induced variant of pemphigus is caused by a wide variety of drugs and is most frequently associated with captopril and penicillamine. It has not previously been reported in this commonly used drug.

Aged↗
PubMed2003

Airway surface pH in subjects with cystic fibrosis.

The cystic fibrosis (CF) transmembrane conductance regulator protein can transport bicarbonate and may therefore regulate airway surface (AS) pH. Disturbances of AS pH could contribute to the pathophysiology of CF lung disease. Five studies were carried out including the following: study 1) nasal pH measurements were made in 25 CF and 10 non-CF adults using an antimony pH probe. Mean nasal pH was significantly lower in the CF group. Nasal potential difference may have been a confounding factor; study 2) in a fresh cohort of CF and non-CF subjects, no significant difference was found between the two groups using a gold pH probe; study 3) simultaneous nasal pH measurements were made in 15 CF and 15 non-CF adults using both probes. In the CF group, there was a trend for the antimony probe to read lower than the gold probe. In the non-CF group, the antimony probe read higher. The pH difference noted in study 1 related to technical factors; study 4) the effect of acute changes in serum acid/base balance on nasal pH was assessed in five non-CF adults. Nasal pH was not altered by either acute respiratory acidosis or alkalosis; study 5) nasal and lower airway pH was measured in five CF and six non-CF children. No difference was found between the groups. There was a correlation between nasal and lower airway pH. The authors conclude that airway surface pH does not differ between cystic fibrosis and noncystic fibrosis subjects and therefore, cystic fibrosis transmembrane conductance regulator may not play a major role in airway surface pH in vivo.

Adolescent↗
PubMed2001

Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43.

Dominant transmission of multiple uterine and cutaneous smooth-muscle tumors is seen in the disorder multiple leiomyomatosis (ML). We undertook a genomewide screen of 11 families segregating ML and found evidence for linkage to chromosome 1q42.3-q43 (maximum multipoint LOD score 5.40). Haplotype construction and analysis of recombinations permitted the minimal interval containing the locus, which we have designated "MCUL1," to be refined to an approximately 14-cM region flanked by markers D1S517 and D1S2842. Allelic-loss studies of tumors indicated that MCUL1 may act as a tumor suppressor. Identification of MCUL1 should have wide interest, since this gene may harbor low-penetrance variants predisposing to the common form of uterine fibroids and/or may undergo somatic mutation in sporadic leiomyomata.

Chromosome Mapping↗
PubMed2001

External beam irradiation for inhibition of intimal hyperplasia following prosthetic bypass: preliminary results.

To determine whether external beam irradiation delivered immediately after graft implantation can inhibit anastomotic intimal hyperplasia (IH) 1 month following polytetrafluoroethylene (PTFE) bypass in a sheep carotid artery model, 23 sheep underwent bilateral bypass of the ligated common carotid artery with 8-mm PTFE immediately followed by a single dose of irradiation (15, 21, or 30 Gy) to one side. The 15 animals with bilaterally patent grafts were euthanized at 1 month and graft-arterial anastomoses harvested. Using computer-aided image analysis, IH areas and thicknesses were measured. Graft patency in this model was 83% at 1 month and did not differ according to treatment administered. In the control animals, IH was greatest at mid-anastomosis, but minimal within the native vessel. All three radiation doses markedly inhibited mid-anastomotic IH area and thickness. At the proximal anastomosis, 30 Gy reduced the IH area 20-fold, from 2.06 to 0.14 mm2 (p < 0.0001 by ANOVA), and IH thickness 70-fold, from 29.0 to 0.4 micron (p < 0.0002); similar effects were seen at the distal anastomosis. No adverse effects of radiation treatment were observed. External beam irradiation in doses of 15 to 30 Gy delivered in a single fraction immediately after operation markedly inhibits development of intimal hyperplasia 1 month following end-to-side anastomosis with PTFE in sheep.

Animals↗
PubMed2001

Reduction in wound morbidity rates following endoscopic saphenous vein harvest.

To determine whether less-invasive saphenous vein harvest reduces morbidity in patients undergoing infrainguinal bypass, we retrospectively compared 61 patients undergoing endoscopic harvest (ENDO) with 49 patients undergoing conventional harvest (OPEN) over the past 13 months. Patients were classified as potential short-stay if adjunctive suprainguinal inflow procedures or foot amputations were not required and the patient was ambulatory prior to elective operation. Mean endoscopic harvest time was 50+/-18 (range 25-90) min, and no more than three 5-cm incisions were required in 87% of cases. Szilagyi class II or III wound complications occurred after 1 of the 61 (2%) ENDO procedures and 7 of the 49 (14%) OPEN (p < 0.01), and any complication occurred in 13 (21%) vs. 25 (51%) of ENDO and OPEN procedures, respectively (p < 0.002). Mean postoperative length of stay was significantly shorter in the 24 short-stay ENDO (4.0+/-2.4 days) vs. 25 short-stay OPEN (6.0+/-3.2 days) patients (p < 0.02). Thirty-day patency rates between the two groups were not different. Endoscopic saphenous vein harvest is associated with a reduced incidence of serious wound complications and, in selected patients, shortened postoperative hospital stay.

Aged↗
PubMed2001

G-protein expression and intimal hyperplasia after arterial injury: a role for Galpha(i) proteins.

PURPOSE: Guanine nucleotide binding protein (G-protein) coupled receptors are involved in smooth muscle cell proliferation, but the role of G-proteins in arterial intimal hyperplasia has not been defined. This study examines the expression of G-proteins in the developing intimal hyperplasia after balloon injury of the rat carotid artery and specifically tests the hypothesis that the pertussis toxin sensitive G(i) G-protein subunit plays a role in the initiation of intimal hyperplasia. METHODS: In vitro responses to serum stimulation (10% fetal bovine serum) were examined in the presence and absence of pertussis toxin (PTx). After a standard balloon injury in male Sprague-Dawley rats, the expression of G-protein subunits (alpha(o), alpha(i), alpha(q), alpha(s), and betagamma) was determined by means of Western blotting in the first 28 days. Thereafter, a second set of animals was allocated to control and PTx-treated (a Galpha(i) inhibitor; 500 ng/mL in an externally applied 30% pluronic gel) groups. Smooth muscle cell proliferation was estimated by means of thymidine analogue 5-bromo-2' deoxyuridine incorporation 2 days after injury, and vessel dimensions were determined by means of videomorphometry 14 days after injury. RESULTS: There was inhibition of DNA synthesis and smooth muscle cell proliferation in response to serum with an IC(50) of 100 ng/mL. Three days after balloon injury, there was an increase in Galpha(i3) expression, which decreased at days 7, 14, and 28, compared with the uninjured carotid. Galpha(q) expression increased in a time-dependent manner. There was a marked time-dependent increase in Gbetagamma in the 28 days. Galpha(i2) and Galpha(s) isoforms (45 and 52 kDa) did not change significantly with time. There was no major change in Galpha(i1) and Galpha(o) in the study period. At 14 days, PTx treatment reduced intimal hyperplasia by 52% (63 +/- 4 microm vs. 30 +/- 5 microm, control vs. PTx; P <.001). Medial smooth muscle cell proliferation at day 2 was decreased in the PTx group, compared with that in the gel-coated group (15% +/- 2% and 26% +/- 3%; P = .02). CONCLUSION: After balloon injury, there is a time-dependent increase in G-protein expression, which is subunit specific. Activation of PTx sensitive G-proteins (Galpha(i)) is involved during the initiation of intimal hyperplasia after arterial injury, and their inhibition results in a decrease in early medial cell proliferation. This acute interruption of G(i) signaling produces a long-term decrease in intimal hyperplasia.

Animals↗
PubMed2001

Local treatment with recombinant tissue factor pathway inhibitor reduces the development of intimal hyperplasia in experimental vein grafts.

BACKGROUND: Tissue factor (TF)-initiated thrombin generation has been implicated in the development of intimal hyperplasia after arterial injury. An increase in intimal TF expression has been shown to precede the development of intimal hyperplasia in vein grafts. This study examines the effects of local treatment with recombinant human tissue factor pathway inhibitor (rTFPI) in experimental vein grafts. METHODS: Thirty-six male New Zealand white rabbits underwent bypass grafting of the carotid artery by use of the reversed ipsilateral jugular vein and were divided into four groups. Twenty animals had ex vivo incubation with rTFPI treatment (50 microg x mL(-1); n = 10) or placebo vehicle (control; n = 10). Sixteen animals received both ex vivo incubation and in vivo gel treatment with rTFPI (50 microg. mL(-1); n = 8) or without rTFPI (gel-control; n = 8). After operation, vein grafts were harvested at 3 days for immunohistochemical and Western analyses and at 28 days for histomorphologic study. RESULTS: Western analysis demonstrated a 6.2-fold reduction in the expression of TF protein with rTFPI treatment in comparison to without rTFPI treatment. CD-18 leukocyte staining was diminished, whereas Tie-2 endothelial staining was increased in all rTFPI-treated vein grafts, compared with control and gel-control vein grafts. Intimal thickness was reduced by 21% with ex vivo rTFPI treatment compared with placebo (69 +/- 4 versus 87 +/- 5 microm; P <.05) and by 30% with the addition of rTFPI in vivo compared with gel-control (60 +/- 4 versus 86 +/- 5 microm; P <.01). CONCLUSION: Local administration of rTFPI exerts early beneficial effects and limits the development of intimal hyperplasia in vein grafts. Therefore blocking TF-mediated pathway may offer new therapeutic options to reduce vein graft failure.

Animals↗
PubMed2001

Percutaneous transluminal revascularization for renal artery stenosis: Veterans Affairs Puget Sound Health Care System experience.

PURPOSE: The safety and efficacy of percutaneous transluminal intervention for renal artery stenosis is improving. This study evaluates the immediate and long-term anatomic and functional outcomes of percutaneous transluminal angioplasty and stenting for atherosclerotic renal artery stenosis in a Veterans Affairs population. METHODS: We performed a retrospective analysis of records from patients who underwent renal artery angioplasty with or without stenting at the Veterans Affairs Puget Sound Health Care System between January 1990 and June 1999. Indications for intervention included hypertension (78%) and rising serum creatinine (78%). Seventy-six patients (74 men, average age of 67 years, range 42-83 years) underwent 88 attempted interventions. Seventy-two percent of contralateral kidneys had significant disease (47% had a >60% stenosis; 16% were nonfunctioning or absent). RESULTS: Of the 88 planned interventions, 86 were successfully performed with placement of 46 stents (52%). Technical success (defined by <30% residual stenosis) was achieved in 78 vessels (89%). The procedure-related complication rate was 5%. Patient mortality by life table analysis was 49% at 5 years. Assisted primary patency rate at 5 years was 100%. Primary and secondary restenosis rates were 37% +/- 8% and 31% +/- 8% at 5 years, respectively. Sixty-eight percent of patients treated for hypertension demonstrated clinical benefit (improved or cured hypertension). This clinical benefit was maintained in 52% of the patients at 5 years, as measured by life table analysis. Serum creatinine was lowered or maintained in 88% of the patients, but this clinical benefit was only maintained in 25% of patients at 5 years. CONCLUSIONS: Transluminal intervention for clinically symptomatic atherosclerotic renal artery stenosis is technically successful and safe. There are excellent assisted-patency and low restenosis rates. There is immediate clinical benefit for most patients, as evidenced by improved control of hypertension and preservation of renal function. However, within 5 years the benefit is not maintained for either hypertension (50%) or renal function (20%). Therefore, although technically successful, functional outcomes after endoluminal intervention are not maintained in the long term.

Adult↗
PubMed2001

Why oral calcium supplements may reduce renal stone disease: report of a clinical pilot study.

AIMS: To investigate whether increasing the daily baseline of gut calcium can cause a gradual downregulation of the active intestinal transport of calcium via reduced parathyroid hormone (PTH) mediated activation of vitamin D, and to discuss why such a mechanism might prevent calcium oxalate rich stones. To demonstrate the importance of seasonal effects upon the evaluation of such data. METHODS: Within an intensive 24 hour urine collection regimen, daily calcium supplementation (500 mg) was given to five stone formers for a 10 week period during a six month crossover study. In a further population of patients on follow up for previous renal stone disease, observations were made on 1066 24 hour urine samples collected over five years in respect of seasonal effects relevant to the interpretation of the study. RESULTS: In the group of patients on calcium supplements the following results were found. During calcium supplementation, the proportion of urine calcium to oxalate was higher (increased calcium to oxalate molar ratio), the 24 hour urine product of calcium and oxalate did not rise, and urine oxalate was lower during the first six weeks of supplementation. Twenty four hour urine calcium was 10.2% higher than baseline in the final four weeks of the 10 weeks of supplementation. Twenty four hour urine phosphate was 11.4% lower during the first six weeks of supplementation, but then rose while the patients were still on supplementation; renal tubular reabsorption of phosphate (TmP/GFR) mirrored the urine phosphate changes inversely. PTH was higher after stopping supplementation, but 1,25-(OH)2-cholecalciferol changes were not detected. In the 1066 urine samples collected over five years the following results were found. Calcium and oxalate excretion correlated positively and not inversely. Urine calcium and phosphate excretion were 5.5% and 2.5% higher, respectively, in "light" months of the year compared with "dark" months. A post summer decline in both urine calcium and urine phosphate was relevant to the interpretation of the study. CONCLUSIONS: Regular calcium supplementation does not raise the product of calcium and oxalate in urine and the proportion of oxalate to calcium is reduced. The underlying mechanisms of the changes seen in phosphate, calcium, and PTH and the observations on 1,25-(OH)2-cholecalciferol are not clear. Observed changes in phosphate could possibly be part of a calcium regulating feedback loop operating over a period of weeks. In evaluating these mechanisms background seasonal effects are important. It is possible that "programming" of the gut mucosa in terms of calcium transport is a major determinant of the relation between calcium and oxalate concentrations in urine and their relative abundance. Increased oral calcium, in association with a reduction of the relative proportion absorbed, may be pertinent to the prevention of calcium oxalate rich stones.

Administration, Oral↗
PubMed2000

Effect of platelet-derived growth factor receptor-alpha and -beta blockade on flow-induced neointimal formation in endothelialized baboon vascular grafts.

The growth of neointima and neointimal smooth muscle cells in baboon polytetrafluoroethylene grafts is regulated by blood flow. Because neointimal smooth muscle cells express both platelet-derived growth factor receptor-alpha and -beta (PDGFR-alpha and -beta), we designed this study to test the hypothesis that inhibiting either PDGFR-alpha or PDGFR-beta with a specific mouse/human chimeric antibody will modulate flow-induced neointimal formation. Bilateral aortoiliac grafts and distal femoral arteriovenous fistulae were placed in 17 baboons. After 8 weeks, 1 arteriovenous fistulae was ligated, normalizing flow through the ipsilateral graft while maintaining high flow in the contralateral graft. The experimental groups received a blocking antibody to PDGFR-alpha (Ab-PDGFR-alpha; 10 mg/kg; n=5) or PDGFR-beta (Ab-PDGFR-beta; 10 mg/kg; n=6) by pulsed intravenous administration 30 minutes before ligation and at 4, 8, 15, and 22 days after ligation. Controls received carrier medium alone (n=8). Serum antibody concentrations were followed. Grafts were harvested after 28 days and analyzed by videomorphometry. Serum Ab-PDGFR-alpha concentrations fell rapidly after day 7 to 0, whereas serum Ab-PDGFR-beta concentrations were maintained at the target levels (>50 microg/mL). Compared with controls (3.7+/-0.3), the ratio of the intimal areas (normalized flow/high flow) was significantly reduced in Ab-PDGFR-beta (1.2+/-0.2, P<0.01) but not in Ab-PDGFR-alpha (2.2+/-0.4). Ab-PDGFR-alpha decreased significantly the overall smooth muscle cell nuclear density of the neointima (P<0.01) compared with either the control or Ab-PDGFR-beta treated groups. PDGFR-beta is necessary for flow-induced neointimal formation in prosthetic grafts. Targeting PDGFR-beta may be an effective pharmacological strategy for suppressing graft neointimal development.

Animals↗