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Biomedical subjects

G Hamilton

Publications and source records attributed to G Hamilton.

At least 109 records · Page 6Linked to original sources
PubMed1999

In vivo femoropopliteal arterial wall compliance in subjects with and without lower limb vascular disease.

OBJECTIVE: The purpose of this study was to further the development of a compliant vascular graft with a preliminary assessment of the elastic properties of the femoropopliteal artery in subjects with and without lower limb peripheral vascular disease. METHODS: This prospective controlled study was set in a university department of surgery. Using an ultrasound scan wall tracking system with the simultaneous measurement of brachial blood pressure, measurements of femoropopliteal artery wall motion were undertaken in 11 patients with peripheral vascular disease (group 1), in 11 older control subjects who were matched for blood pressure, age, and sex (group 2), and in 12 younger control subjects (group 3). Diametrical compliance and stiffness index were determined for the common femoral artery, the proximal superficial femoral artery, the distal superficial femoral artery (DSFA), and the midgenicular popliteal artery. RESULTS: All the arterial segments in group 1 showed a trend towards increased stiffness and less compliance than the group 2, age-matched control vessels, with significantly lower distensibility noted at the common femoral artery (mean compliance of 6.2% vs 14.1% mm Hg(-1) x 10(-2), respectively; P <.05) and the DSFA (mean compliance of 2.2% vs 1.9% mm Hg(-1) x 10(-2), respectively; P <.05). The popliteal artery segment in group 3 proved to be more compliant and less stiff than did the same vessel in group 2 (8.5% vs 4.7% mm Hg(-1) x 10(-2), respectively; P <.01). In all three study groups, the DSFA was consistently noted to be the least distensible vessel segment. CONCLUSION: Lower limb peripheral vascular disease is associated with a reduction in femoropopliteal artery elasticity. Age alone appears to have a minimal effect on the compliance of the proximal half of the femoropopliteal segment. The elastic properties of the femoropopliteal vessel are subject to marked variation along its course. To minimize compliance mismatch, the degree of elasticity engineered into a vascular graft must reflect that observed in vivo.

Adult↗
PubMed1999

Treatment of advanced pancreatic cancer with the long-acting somatostatin analogue lanreotide: in vitro and in vivo results.

Fourteen patients with metastatic pancreatic adenocarcinoma were treated with the long-acting somatostatin (SST) analogue lanreotide. No objective response was obtained, and the median survival was 4 months (range 1.8-7 months). Pancreatic cancer could not be visualized by means of SST-receptor (R) scintigraphy in our patients. In vitro data also demonstrated absence of SSTR2 expression, suggesting pancreatic cancer not to be a potential target for treatment with SST analogues.

Adenocarcinoma↗
PubMed1999

Modern management of pulmonary embolism.

BACKGROUND: Pulmonary embolism is a significant cause of morbidity and death after operation. The introduction of new technologies in the diagnosis, and thrombolysis in the treatment, of pulmonary embolism has led to a need to reappraise the management of this condition. METHODS: This review encompasses a comprehensive discussion of diagnostic modalities and therapeutic strategies used in the current management of pulmonary embolism. Relevant papers on the diagnosis and treatment of pulmonary embolism were identified from a Medline search for the period 1967-1998. Additional papers were derived from the reference lists of retrieved articles. Articles presenting prospectively gathered data have been referenced preferentially. RESULTS AND CONCLUSION: Algorithms for the diagnosis and treatment of pulmonary embolism are presented.

Algorithms↗
PubMed1999

Graduated compression stockings in the prevention of venous thromboembolism.

BACKGROUND: Surveys still show a wide variation in routine use of deep vein thrombosis (DVT) prophylaxis despite its established place in current patient management. This article reviews the mechanism of action, efficacy and complications of stockings in preventing DVT. METHODS: Relevant publications indexed in Medline (1966-1998) and the Cochrane database were identified. Appropriate articles identified from the reference lists of the above searches were also selected and reviewed. RESULTS AND CONCLUSION: Graduated compression stockings reduce the overall cross-sectional area of the limb, increase the linear velocity of venous flow, reduce venous wall distension and improve valvular function. Fifteen randomized controlled trials of graduated compression stockings alone were reviewed. Stockings reduced the relative risk of DVT by 64 per cent in general surgical patients and 57 per cent following total hip replacement. The effect of stockings was enhanced by combination with pharmacological agents such as heparin; the combination is recommended in patients at moderate or high risk of DVT. Knee-length stockings are as effective and should replace above-knee stockings. Complications are rare and avoidable.

Bandages↗
PubMed1999

Vascular surgical society of great britain and ireland: thrombelastography can differentiate ischaemic from haemorrhagic stroke

BACKGROUND: Thrombolysis could be a major step forward in the treatment of acute ischaemic stroke. Early treatment is essential to maximize therapeutic benefit. Imaging by computed tomography (CT) or magnetic resonance imaging is mandatory to exclude haemorrhagic stroke before initiation of therapy. Thrombelastography (TEG), a test of global haemostasis, produces a characteristic tracing over 15-30 min. The potential of TEG to differentiate patients with ischaemic from haemorrhagic stroke was investigated. METHODS: Fifteen patients with a clinical diagnosis of acute stroke were studied. Fibrinogen levels and lipid profiles were measured, and CT of the brain, coagulation screens and TEG were performed. The CT scans were interpreted by a single radiologist. TEG data were classified as normal (index less than 2), hypercoagulable (index 2-3) or profoundly hypercoagulable (index greater than 3). RESULTS: There was no correlation between any of the parameters studied other than TEG with CT findings. Both patients with a haemorrhagic stroke showed normal findings on TEG. Eleven of the 12 patients with ischaemic stroke were hypercoagulable or profoundly hypercoagulable. CONCLUSION: TEG is capable of differentiating haemorrhagic from ischaemic stroke. It has the potential to target thrombolytic therapy for those patients most likely to benefit.

Journal Article↗
PubMed1999

Vascular surgical society of great britain and ireland: caval filters are an underexploited therapy for acute pulmonary embolism

BACKGROUND: Inferior vena caval filters are a recognized intervention for recurrent pulmonary embolism (PE). Filter utilization in the UK is considerably less than in Europe; this may partly be due to omission of referral of appropriate patients. METHODS: A cohort with the prospect of benefit from caval filter insertion was identified by retrospective study of inpatients who died within 30 days of a positive ventilation-perfusion (V/Q) scan over 2 years. The number of actively managed patients in this group who fulfilled the recognized criteria for caval filter insertion was determined. RESULTS: Fifty-two of 606 patients died within 30 days of scanning. Information was available on 38 (73 per cent) of 52 who had 39 scans (14 positive, 22 negative, three indeterminate). Six of 14 patients (two men and four women, aged 46-84 years) with a positive scan had strong indications for caval filter deployment including contraindication to anticoagulation (three), recurrent PE despite adequate anticoagulation (two) and complications arising from anticoagulation (one). All six died following continuing embolism or complications from anticoagulation. CONCLUSION: Six of 14 patients who died following acute PE required caval filtration but were not offered this intervention. Failure to refer patients who would benefit from filtration may partially account for the disparity in utilization of caval filters between the UK and Europe. Furthermore, because of the choice of death as outcome marker, this study underestimated the value of caval filter utilization.

Journal Article↗
PubMed1999

Building community for the long-term: an intergenerational commitment.

Intergenerational visitation programs have demonstrated advantages for the young and old, but few programs last more than a year or two. Weaving long-term intergenerational programs into the fabric of both school curricula and community cultural life was the goal of a project launched in 1988 in Phoenix, Arizona. Classrooms of children visit weekly or biweekly with nearby nursing home residents, developing friendships while pursuing educational activities. Carefully planned and widespread community support through board participation, donations, and publicity has allowed the program to continue to expand, while the budget has decreased. Materials are available which facilitate program replication.

Aged↗
PubMed1999

Cross-education of muscle strength is greater with stimulated than voluntary contractions.

Cross-education enhances the performance of muscles not directly involved in the chronic conditioning of the muscles in a remote limb. Substantial cross-education occurs after training with eccentric contractions or with contractions evoked by electromyostimulation (EMS). Since during EMS and eccentric contractions, skin and muscle afferents are activated that have excitatory effects on contralateral homologous muscles, it was hypothesized that exercise training with stimulated vs. voluntary eccentric contractions would lead to greater cross-education. Thirty-two women were randomly assigned to a voluntary (Vol), an EMS, or remote EMS (rEMS) exercise group and performed 840 voluntary or stimulated eccentric contractions over 6 weeks. All subjects, including nonexercising controls (Con), were tested pre- and posttraining for maximal voluntary and stimulated isometric and eccentric quadriceps strength. Ipsilateral voluntary and stimulated forces increased in all groups. Changes in EMG activity paralleled those in voluntary force in each limb. No changes occurred in grip strength. The great contra- and ipsilateral strength gains after EMS training were most likely related to an additive effect of EMS and muscle lengthening.

Adult↗
PubMed1999

Bacteroides fragilis toxin 2 damages human colonic mucosa in vitro.

BACKGROUND: Strains of Bacteroides fragilis producing a 20 kDa protein toxin (B fragilis toxin (BFT) or fragilysin) are associated with diarrhoea in animals and humans. Although in vitro results indicate that BFT damages intestinal epithelial cells in culture, the effects of BFT on native human colon are not known. AIMS: To examine the electrophysiological and morphological effects of purified BFT-2 on human colonic mucosa in vitro. METHODS: For resistance (R) measurements, colonic mucosa mounted in Ussing chambers was exposed to luminal or serosal BFT-2 (1.25-10 nM) and after four hours morphological damage was measured on haematoxylin and eosin stained sections using morphometry. F actin distribution was assessed using confocal microscopy. RESULTS: Serosal BFT-2 for four hours was four-, two-, seven-, and threefold more potent than luminal BFT-2 in decreasing resistance, increasing epithelial 3H-mannitol permeability, and damaging crypt and surface colonocytes, respectively (p<0.05). Confocal microscopy showed reduced colonocyte F actin staining intensity after exposure to BFT-2. CONCLUSIONS: BFT-2 increases human colonic permeability and damages human colonic epithelial cells in vitro. These effects may be important in the development of diarrhoea and intestinal inflammation caused by B fragilis in vivo.

Actins↗
PubMed1999

Effects of substance P on human colonic mucosa in vitro.

Previous studies indicated that the peptide substance P (SP) causes Cl--dependent secretion in animal colonic mucosa. We investigated the effects of SP in human colonic mucosa mounted in Ussing chamber. Drugs for pharmacological characterization of SP-induced responses were applied 30 min before SP. Serosal, but not luminal, administration of SP (10(-8) to 10(-6) M) induced a rapid, monophasic concentration and Cl--dependent, bumetanide-sensitive short-circuit current (Isc) increase, which was inhibited by the SP neurokinin 1 (NK1)-receptor antagonist CP-96345, the neuronal blocker TTX, the mast cell stabilizer lodoxamide, the histamine 1-receptor antagonist pyrilamine, and the PG synthesis inhibitor indomethacin. SP caused TTX- and lodoxamide-sensitive histamine release from colonic mucosa. Two-photon microscopy revealed NK1 (SP)-receptor immunoreactivity on nerve cells. The tyrosine kinase inhibitor genistein concentration dependently blocked SP-induced Isc increase without impairing forskolin- and carbachol-mediated Isc increase. We conclude that SP stimulates Cl--dependent secretion in human colon by a pathway(s) involving mucosal nerves, mast cells, and the mast cell product histamine. Our results also indicate that tyrosine kinases may be involved in this SP-induced response.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

DOTA-lanreotide: a novel somatostatin analog for tumor diagnosis and therapy.

Long acting somatostatin-14 (SST) analogs are used clinically to inhibit tumor growth and proliferation of various tumor types via binding to specific receptors (R). We have developed a 111In-/90Y-labeled SST analog, DOTA-(D)betaNal1-lanreotide (DOTALAN), for tumor diagnosis and therapy. 111In-/90Y-DOTALAN bound with high affinity (dissociation constant, Kd, 1-12 nM) to a number of primary human tumors (n = 31) such as intestinal adenocarcinoma (n = 17; 150-4000 fmol/mg protein) or breast cancer (n = 4; 250-9000 fmol/mg protein). 111In-/90Y-DOTALAN exhibited a similar high binding affinity (Kd, 1-15 nM) for the human breast cancer cell lines T47D and ZR75-1, the prostate cancer cell lines PC3 and DU145, the colonic adenocarcinoma cell line HT29, the pancreatic adenocarcinoma cell line PANC1, and the melanoma cell line 518A2. When expressed in COS7 cells, 111In-DOTALAN bound with high affinity to hsst2 (Kd, 4.3 nM), hsst3 (Kd, 5.1 nM), hsst4 (Kd, 3.8 nM), and hsst5 (Kd, 10 nM) and with lower affinity to hsst1 (Kd, approximately 200 nM). The rank order of displacement of [125I]Tyr11-SST binding to hsst1 was: SST (IC50, 0.5 nM) >> DOTALAN (IC50, 154 nM) > lanreotide (LAN) approximate to Tyr3-octreotide (TOCT) approximate to DOTA-Tyr3-octreotide (DOTATOCT) approximate to DOTA-vapreotide (DOTAVAP; IC50, >1000 nM); that to hsst2 was: DOTATOCT approximate to TOCT approximate to DOTALAN approximate to SST approximately LAN approximate to DOTAVAP (IC50, 1.4 nM); that to hsst3 was: SST (IC50, 1.2 nM) > DOTALAN = LAN (IC50, 15 nM) approximate to TOCT (IC50, 20 nM) approximate to DOTAVAP (IC50, 28 nM) > DOTATOCT (IC50, 73 nM); that to hsst4 was: SST (IC50, 1.8 nM) approximate to DOTALAN (IC50, 2.5 nM) > LAN (IC50, 22 nM) >> DOTATOCT approximate to DOTAVAP approximate to TOCT (IC50, >500 nM); and that to hsst5 was: DOTALAN (IC50, 0.45 nM) > SST (IC50, 0.9 nM) > TOCT (IC50, 1.5 nM) > DOTAVAP (IC50, 5.4 nM) >> LAN (IC50, 21 nM) > DOTATOCT (IC50 260 nM). In Sprague Dawley rats (n = 10), 90Y-DOTALAN was rapidly cleared from the circulation and concentrated in hsst-positive tissues such as pancreas or pituitary. Taken together, our results indicate that 111In-/90Y-DOTALAN binds to a broad range of primary human tumors and tumor cell lines, probably via binding to hsst2-5. We conclude that this radiolabeled peptide can be used for hsst-mediated diagnosis (111In-DOTALAN) as well as systemic radiotherapy (90Y-DOTALAN) of human tumors.

Adenocarcinoma↗
PubMed1999

Resveratrol pretreatment desensitizes AHTO-7 human osteoblasts to growth stimulation in response to carcinoma cell supernatants.

Resveratrol, a natural phytoestrogen, has been reported to promote differentiation of murine MC3T3-E1 osteoblasts and to inhibit proliferation of prostate cancer cell lines. In the present study we tested the effects of resveratrol on the increased proliferation of human AHTO-7 osteoblastic cell line induced by conditioned media (CM) from a panel of carcinoma cell lines. This compound was found to modulate AHTO-7 proliferation in a tamoxifen-sensitive mechanism at lower concentrations, but failed to induce the osteoblast differentiation marker alkaline phosphatase (ALP) in contrast to vitamin D3. The proliferative response of AHTO-7 cells to conditioned media from carcinoma cell lines was diminished (30-71.4% inhibition) upon pretreatment with 0.5 microM resveratrol. Highest inhibition was demonstrated for pancreas (BxPC3, Panc-1), breast (ZR75-1) and renal (ACHN) carcinoma cell line supernatants whereas the effect on colon carcinoma (SW620, Colo320DM) cell CM and prostate cancer (PC3, DU145 and LNCaP) CM was less pronounced. Direct addition of resveratrol affected only supernatants of cell lines (<25% inhibition) exhibiting growth stimulatory activity for normal WI-38 lung fibroblasts. Resveratrol inhibited proliferation of DU145 and LNCaP cells in concentrations exceeding 5 microM, altered cell cycle distribution of all prostate cancer cell lines in concentrations as low as 0.5 microM, but did not inhibit the production of osteoblastic factors by these lines. In conclusion, resveratrol failed to induce ALP activity as marker of osteoblast differentiation in human osteoblastic AHTO-7 cells, however, inhibited their response to osteoblastic carcinoma-derived growth factors in concentrations significantly lower than those to reduce growth of cancer cells, thus effectively modulating tumor - osteoblast interaction.

Alkaline Phosphatase↗
PubMed1998

Multicellular spheroids as an in vitro tumor model.

Multicellular spheroids (MCS) have been used as an in vitro model system of micrometastases and avascular tumor regions for studying cell adhesion-dependent resistance to cytotoxic drugs and possible reversal by chemosensitizers and adhesion-reversing agents. Multicellular drug resistance has been linked to limited accessibility of cell subpopulations, active drug efflux, quiescence of cells in deeper layers due to cell contact inhibition and adverse microenvironmental conditions like acidic extracellular pH, hypoxia and nutritional depletion. The shortcomings of MCS as a tumor model include limited knowledge of the mechanisms leading to necrosis/apoptosis of core cells, the production of an extracellular matrix (ECM) by tumor cells instead of intratumoral normal cell populations and the complex relationship of MCS parameters like size, growth regulation, synthesis of ECM components and others on the origin and pretreatment of the tumor cells and specific culture conditions.

Animals↗
PubMed1998

Somatostatin receptor subtype specificity and in vivo binding of a novel tumor tracer, 99mTc-P829.

Recent data suggest that somatostatin receptors (SSTRs) are expressed on various tumor cells. High-level expression of SSTR on the tumor cell surface provides the basis for the successful clinical use of radiolabeled ligands for the in vivo localization of tumor sites. We have characterized the in vitro binding properties of the novel SSTR ligand 99mTc-P829 using primary human tumors (carcinoids, breast cancers, intestinal adenocarcinomas, pheochromocytomas, small cell and non-small cell lung cancer, and melanomas; n = 28), various tumor cell lines, and COS7 cells transfected with the human SSTR (hSSTR) subtypes 1, 2, 3, 4, and 5. 99mTc-P829 bound to primary tumor cells and tumor cell lines with high affinity and high capacity. The dissociation constants (Kd) ranged between 1 and 20 nM. 99mTc-P829 also bound with high affinity to the transfected hSSTR2 (Kd, 2.5 nM), hSSTR5 (Kd, 2 nM), and hSSTR3 (Kd, 1.5 nM). Binding of 99mTc-P829 to hSSTR3 was found to be displaceable by unlabeled P829/([ReO]-P829), SST-14, and vasoactive intestinal peptide (VIP; IC50, 2 nM) and, less effectively, by Tyr3-octreotide (IC50, 20 nM). In contrast, the binding of 99mTc-P829 to hSSTR2 and hSSTR5 could be displaced by P829/([ReO]-P829) and Tyr3-octreotide but not by VIP. 99mTc-P829 scintigraphy revealed in vivo binding to primary or metastatic tumor sites in seven of eight patients with breast cancer and six of six patients with melanoma. In summary, our data show that 99mTc-P829 binds with high affinity to many different types of primary and cloned tumor cells. Furthermore, our data identify hSSTR2, the VIP acceptor hSSTR3, and hSSTR5 as the respective target receptors. Because these receptors are frequently expressed at high levels on primary tumor cells, 99mTc-P829 appears to be a promising novel peptide tracer for tumor imaging.

Animals↗