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Biomedical subjects

G Hamilton

Publications and source records attributed to G Hamilton.

At least 91 records · Page 5Linked to original sources
PubMed1995

Biomechanical properties of normal tendons, normal palmar aponeuroses, and tissues from patients with Dupuytren's disease subjected to elastase and chondroitinase treatment.

Normal tendons, normal palmar aponeuroses and palmar aponeuroses from patients with Dupuytren's disease were subjected to elastase or chondroitinase treatment. Young's modulus was derived from the linear portion of stress-strain graph. It showed the lowest value for the apparently normal palmar aponeuroses and the highest value for tendon samples. Elastase treatment caused an increase of extensibility and a reduction of Young's modulus of normal palmar aponeuroses and tendons, but not of contracture bands. In normal tendons, normal palmar aponeuroses and apparently normal palmar aponeuroses residual strain and hysteresis loop increased significantly as a linear function of the amount of digested elastin. In contrast these biomechanical parameters were not affected significantly in contracture bands. In normal and apparently normal areas incubation with chondroitinase ABC resulted in a significant increase of residual strain and, as opposed to elastase, a decrease of normalized hysteresis loop. In contracture bands, however, these biomechanical parameters remained unchanged. RELEVANCE: The increasing evidence of a correlation between morphological changes of palmar elastin and ground substance with the progress of Dupuytren's disease emphasizes the need to determine the relative importance of these connective tissue components for the pathogenesis of Dupuytren's disease.

Journal Article↗
PubMed1995

Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro.

Toxin A but not toxin B, appears to mediate intestinal damage in animal models of Clostridium difficile enteritis. The purpose of this study was to investigate the electrophysiologic and morphologic effects of purified C. difficile toxins A and B on human colonic mucosa in Ussing chambers. Luminal exposure of tissues to 16-65 nM of toxin A and 0.2-29 nM of toxin B for 5 h caused dose-dependent epithelial damage. Potential difference, short-circuit current and resistance decreased by 76, 58, and 46%, respectively, with 32 nM of toxin A and by 76, 55, and 47%, respectively, with 3 nM of toxin B, when compared with baseline (P < 0.05). 3 nM of toxin A did not cause electrophysiologic changes. Permeability to [3H]mannitol increased 16-fold after exposure to 32 nM of toxin A and to 3 nM of toxin B when compared with controls (P < 0.05). Light and scanning electron microscopy after exposure to either toxin revealed patchy damage and exfoliation of superficial epithelial cells, while crypt epithelium remained intact. Fluorescent microscopy of phalloidin-stained sections showed that both toxins caused disruption and condensation of cellular F-actin. Our results demonstrate that the human colon is approximately 10 times more sensitive to the damaging effects of toxin B than toxin A, suggesting that toxin B may be more important than toxin A in the pathogenesis of C. difficile colitis in man.

Actins↗
PubMed1994

Low-dose intra-arterial thrombolysis in the treatment of phlegmasia caerulea dolens.

Three patients with phlegmasia caerulea dolens treated successfully by low-dose intra-arterial thrombolysis are presented. In all patients a rapid improvement was observed and amputation avoided. The risk of pulmonary embolus was reduced by the use of a retrievable vena cava filter in one patient and thrombolytic therapy in the presence of a previously inserted cava filter in the other two.

Adult↗
PubMed1994

Dental infection in vascular surgical patients.

Seventy patients, 18 women and 52 men of mean age 68 (range 52-81) years, with vascular disease were studied using the Community Periodontal Index of Treatment Needs (CPITN). Twenty-six were edentulous and 44 dentate; 32 dentate patients were wearing partial dentures. All had occlusive peripheral arterial disease (ankle:brachial pressure index less than 0.9) or aortic aneurysm. No significant periodontal pathology was found in edentulous patients. Of the dentate patients, 28 were in the significant pathology range (CPITN 4) and 12 were in the moderate pathology group (CPITN 3); only four had no significant pathology (CPITN 0-2). As a proportion of prosthetic vascular graft infections may be due to dental sepsis, surgeons should consider referral for dental assessment before elective bypass grafting and patients should be warned about the importance of dental care after operation.

Aged↗
PubMed1994

Endothelial seeding of compliant polyurethane vascular graft material.

Compliance was measured in a new compliant polyurethane vascular graft material and in polytetrafluoroethylene (PTFE) graft material using an ultrasonic device; attachment of indium-111 oxine-labelled human endothelial cells to both surfaces with a range of surface coatings was assessed. Compliant polyurethane was six to eight times more compliant than PTFE (P < 0.01) at all pressures in the range 50-120 mmHg, and endothelial cell attachment to uncoated polyurethane was three times better than to uncoated PTFE at times up to 90 min (P < 0.01). Attachment to polyurethane was also better after blood clot, collagen and fibronectin treatment at times up to 30 min (P < 0.05). Endothelial seeding of compliant graft material may provide a prosthetic vascular substitute with characteristics similar to those of autologous vein.

Aged↗
PubMed1994

Intracellular pH regulation of human colonic crypt cells.

In order to investigate the regulation of intracellular pH (pHi) in freshly isolated human colonocytes, we have used a newly developed technique for the rapid isolation and covalent attachment of these cells to glass surfaces and microspectrofluorimetric measurement of the pH-sensitive fluorescence of 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF)-loaded specimens in a perfusion chamber (37 degrees C). In N-2-hydroxyethylpiperazine-N'-2-ethanesulphonic-acid-(HEPES)-buffered Ringer solution (HBS) a baseline pHi of 7.35 +/- 0.03 (mean +/- SD; n = 42) was found for human colonocytes and in HBS, NH4Cl-prepulse-induced intracellular acidification in colonocytes is reversed rapidly by the ubiquitous amiloride-sensitive (1 mmol/l) Na+/H+ exchanger. Switching from HBS to HCO(3-)-buffered solution (BBS) led to a transient intracellular acification (7.29 +/- 0.09), followed by a recovery to a final resting pHi of 7.43 +/- 0.03. One-third of the acid extrusion in BBS is amiloridesensitive; the remaining two-thirds are caused by the dihydroderivative of 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (H2DIDS)-sensitive HCO(3-)-dependent mechanisms. The functional activity of an acid-extruding Na+/HCO3- cotransporter in human colonocytes was observed in response to the reintroduction of Na+ into amiloride-containing Na+/Cl(-)-free BBS. In addition, the mechanism leading to alkalinization (7.56 +/- 0.05) in Cl(-)-free BBS was identified as Na(+)-dependent Cl-/HCO3- exchange, by its H2DIDS sensitivity and the specific requirement for Cl- and Na+. The intrinsic buffering capacity (beta i) of the human colonocytes was calculated from pH changes induced by sequential NH4Cl-loading steps during blockage of acid/base transporters.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Inhibition of P-glycoprotein-mediated vinblastine transport across HCT-8 intestinal carcinoma monolayers by verapamil, cyclosporine A and SDZ PSC 833 in dependence on extracellular pH.

The ability of the multidrug resistance modifiers R- and R,S-verapamil (VPL), cyclosporine A (CsA) and its non-immunosuppressive derivative SDZ PSC 833 (PSC 833) to inhibit P-glycoprotein (P-gp)-mediated transepithelial flux of tritiated vinblastine was investigated using tight and highly resistant (R > 1,400 omega cm2) monolayer cultures of intestinal adenocarcinoma-derived HCT-8 cells grown on permeable tissue-culture inserts. Apical addition of these chemosensitizers inhibited drug flux (137 pmol h-1 cm-2; range, 133-142 pmol h-1 cm-2) in the basal to apical secretory direction at clinically relevant concentrations, with PSC 833 showing the highest activity, exhibiting inhibition at concentrations as low as 10 ng/ml (9 nM). Acidification of the modulator-containing apical compartment to an extracellular pH (pHo) of 6.8 had no influence on MDR reversal by CsA at 1 microgram/ml (0.9 microM; flux inhibition, 52%) or by PSC 833 at 100 ng/ml (0.09 microM; flux inhibition, 60%), in contrast to R,S- and R-VPL, which showed decreased inhibition and caused less accumulation of vinblastine in HCT-8 cells under this condition (flux inhibition of 35% and 23%, respectively, at pHo 6.8 vs 50% and 43%, respectively, at pHo 7.5). P-gp-mediated rhodamine 123 efflux from dye-loaded single-cell suspensions of HCT-8 cells as measured by flow cytometry was not impeded at pHo 6.8 in comparison with pHo 7.5 in standard medium, but at low pHo the inhibitory activity of R-VPL (29% vs 60% rhodamine 123 efflux inhibition) was diminished significantly, again without a reduction in the effect of PSC 833 (rhodamine 123 flux inhibition, 75%). In conclusion, drug extrusion across polarised monolayers, which offer a relevant model for normal epithelia and tumour border areas, is inhibited by the apical presence of R,S- and R-VPL, CsA and PSC 833 at similar concentrations described for single-cell suspensions, resulting in increased (2.2- to 3.7-fold) intracellular drug accumulation. Functional apical P-gp expression, the absence of paracellular leakage and modulator-sensitive rhodamine 123 efflux in single HCT-8 cells indicate a P-gp-mediated transcellular efflux in HCT-8 monolayers. In addition to its high MDR-reversing capacity, the inhibitory activity of PSC 833 is not affected by acidic extracellular conditions, which reduce the VPL-induced drug retention significantly. As far as MDR contributes to the overall cellular drug resistance of solid tumours with hypoxic and acidic microenvironments, PSC 833 holds the greatest promise for clinical reversal of unresponsiveness to the respective group of chemotherapeutics.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Comparison of laser Doppler perfusion imaging, laser Doppler flowmetry, and thermographic imaging for assessment of blood flow in human skin.

In this study we compared three non-invasive methods of measuring skin perfusion, thermographic imaging (TI), laser Doppler flowmetry (LDF) and the new technique of laser Doppler imaging (LDI). Seven normal volunteers were studied in a temperature-controlled room with an ambient temperature of 22 +/- 1 degree C. Images of the left hand were recorded using LDI followed by TI. LDF was then used on two standard locations on the fingers and back of the hand. The measurements were then repeated for a hot (37 degrees C) and then a cold (10 degrees C) challenge. A significant linear correlation (r = 0.960, p < 0.01, with 95% confidence limit of 0.35-0.77, n = 38) was found between LDF and LDI. However, LDF and LDI did not correlate well with TI (r = 0.577, p < 0.01, with 95% confidence limit of 0.32-0.76, n = 38). The LDI method was found to be highly reproducible (mean +/- 1 SD; 625 +/- 30, with coefficient of variation 5%). The blood flow and temperature distribution of skin of the hand was then recorded using TI and LDI in 10 patients (mean age +/- SD, 41.7 +/- 9.9) with scleroderma and eight normal volunteers (mean age +/- SD, 30.6 +/- 6.5). The overall mean blood flow and temperature in the hands of patients with scleroderma (mean +/- SD 444 +/- 265 flux, 29.3 +/- 3.3 degrees C) was significantly (p < 0.0001) lower compared with the normal volunteers (mean +/- SD, 912 +/- 390 flux, 34.0 +/- 3.2 degrees).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Outbreak of measles in a teenage school population: the need to immunize susceptible adolescents.

An outbreak of measles occurred in a community school and the surrounding area in Crowborough, East Sussex, UK, from December 1992 to February 1993. There were 96 suspected cases reported: 66 cases among 1673 students at one school and 30 community cases. The majority of suspected cases were in those aged 11-17 (78%), 2 cases occurred in infants < 1 year old and 8 cases in adults aged 18 years or over. Data collected on 60 (91%) of the 66 suspect school cases showed 56 (93%) had an illness which met a case definition of measles. Eighteen had confirmatory IgM measles antibody. Two cases were hospitalized. The local percentage uptake for measles immunization for the school age years affected varied between 64% and 84%. A survey of parents showed that approximately 74% of the students attending the school had a history of measles immunization. The immunization rates reported by parents for children who developed measles was 21%, (29% based on GP records) compared with 77% for those who remained well. Vaccine efficacy was estimated to be 92%. This outbreak, along with others recently reported in older unimmunized children in the UK, reinforces the need for catch-up immunization programmes to reach this susceptible group of adolescents.

Adolescent↗
PubMed1994

Intermittent claudication due to spinal stenosis in a vascular surgical practice.

Intermittent claudication can be due to spinal canal stenosis. In order to define the frequency with which this condition presents to a vascular surgeon a review of 271 patients referred with claudication was carried out. Twenty-one (8%) were ultimately diagnosed as having spinal stenosis. There were no significant differences with regard to age or sex between these patients and those with true vascular claudication. There was, however, a significantly lower number of smokers in the spinal stenosis group. When the presenting features of the spinal stenosis group were analysed 62% (13/21) reported sensory symptoms such as numbness or parasthesiae, 38% (8/21) back pain and 67% (14/21) true pain in the legs on walking. In 71% (15/21), symptoms were reported as being bilateral and 29% (6/21) had reduced Doppler pressures. It is stressed that vascular surgeons need to maintain a high index of suspicion for spinal stenosis especially as the condition may coexist with vascular disease, making diagnosis difficult.

Adult↗
PubMed1994

Diminished platelet yield and enhanced platelet aggregability in platelet-rich plasma of peripheral vascular disease patients.

Centrifugation of citrated whole blood (cit-WB) for platelet rich plasma (PRP) preparation resulted in a significantly diminished platelet yield compared to when blood was collected in citrate + aspirin (acetylsalicylic acid; ASA) or EDTA anticoagulants in both apparently healthy young subjects and peripheral vascular disease (PVD) patients. The loss in platelets was significantly greater in PVD patients than in young apparently healthy subjects when using cit-WB. Median platelet volume (MePV) of PRP preparations was not different between PVD patients and apparently healthy subjects. The MePV of EDTA-PRP preparations was significantly bigger than cit-PRP and cit + ASA-PRP in both PVD patients and apparently healthy subjects. Citrate and citrate + ASA-PRP of patients was significantly more aggregable to adrenaline. In EDTA-PRP, adrenaline-induced aggregation did not occur. These findings indicate that platelet hyperactivity occurs in PVD even in the presence of ASA. Furthermore, studies involving the use of PRP may not be representative in PVD due to the significant loss of platelets during centrifugation. The methodology described here can be used by those who do not have facilities designed specifically for platelet research.

Aged↗
PubMed1994

Ischaemia of the small intestine in patients with systemic sclerosis: Raynaud's phenomenon or chronic vasculopathy?

We investigated duodenal and gastric mucosal blood flow by endoscopic laser Doppler flowmetry (LDF) in ten patients with systemic sclerosis (SSc) and in ten healthy volunteers. In addition, we tested for the presence of small bowel bacterial overgrowth by jejunal aspiration. Jejunal aspiration and LDF were done consecutively, via a gastroscope, using a flexible catheter and laser Doppler probe. Following these procedures, two duodenal biopsies were obtained for light and electron microscopy. Mean duodenal and gastric blood flow were significantly lower in patients with SSc than in normal subjects (516 flux units vs. 240, 521 vs. 202, both p < 0.001). There was no correlation between age and blood flow in patients or volunteers. Four of the ten patients had evidence of significant bacterial overgrowth on jejunal aspiration (> 10(5) colony-forming units/ml). These findings support the hypothesis that within the small intestine of patients with SSc, factors independent of bacterial overgrowth may be responsible for malabsorption. The observed reduction in small-intestine mucosal blood flow may play an important contributory role. Further studies are required to determine whether this represents reversible or chronic progressive ischaemia, and its effect on nutrient absorption.

Adult↗