Biomedical subjects

G Hamilton

Publications and source records attributed to G Hamilton.

At least 307 records · Page 17Linked to original sources

PubMedDate not supplied

In vitro uptake 153gadolinium and gadolinium complexes by hyaline articular cartilage.

This in vitro study evaluated whether Gadolinium (Gd) penetrates into hyaline cartilage and would be incorporated into vital chondrocytes. Hyaline joint cartilage of rabbits was exposed to radioactive 153GdCl3 and to a radioactive 153Gd-DTPA-BSA-complex (DTPA, diethylene-triaminepentaacetic acid; BSA, bovine serum albumine). In addition an exchange experiment with radioactive 153GdCl3 versus Gd-DTPA-di-N-methylglucamine (Magnevist) was performed. Incorporation of 153GdCl3 into neuroblastoma cells, connective tissue cells and chondrocytes was tested. The results showed that the depth and extent of incorporation of Gd depends on the molecular mass and time of exposure. 153Gd-DTPA-BSA complexes exhibited an incorporation rate of maximal 11% +/- 2.8% up to the middle third of the cartilage within 24 h with almost no incorporation (2 +/- 1.9%) for the deep layer. The exchange experiment revealed no uptake of Gd for the deep layer. The maximal incorporation rate of 153GdCl3 into vital chondrocytes was 6.3%. These data indicate that under the condition of MR-arthrography, Gd-DTPA-di-N-methylglucamine will not be absorbed into the deep layers of hyaline cartilage and will not be incorporated into vital chondrocytes.

Animals↗

PubMedDate not supplied

Objectives to direct the training of emergency medicine residents on off-service rotations: hand surgery.

This is the fifth article in a continuing series on objectives to direct the training of emergency medicine residents. The emergency physician frequently must deal with hand injuries. Often these may appear innocuous; recognition of these injuries requires certain technical skills and a working knowledge of these entities. Specific objectives presented provide guidance for the didactic content as well as skill mastery for the resident experience.

Emergency Medicine↗

PubMedDate not supplied

Objectives to direct the training of emergency medicine residents on off-service rotation in neurosurgery.

The off-service rotation in Neurosurgery is included in some programs training emergency medicine residents. It may also be offered as an elective. The experience on this rotation can lack opportunity and educational content if structured guidance is not available. We have addressed this problem by developing a written curricula containing subject content listing, objectives, and references for the Neurosurgery off-service rotation for emergency medicine residents. This is the 23rd in a series of objectives for off-service rotations for emergency medicine residents.

Curriculum↗

PubMedDate not supplied

Objectives to direct the training of emergency medicine residents on off-service rotation in cardiology, Part 1.

This article is the first of a two-part series outlining the objectives for emergency medicine residents on a cardiology rotation. Cardiology is offered as an off service rotation or an elective at some emergency medicine residency training programs. An organized core curriculum may provide a structured learning environment to help ensure that certain principles and objectives important to the practice of emergency medicine are learned. We have developed a written core curriculum containing a subject content list, learning objectives, and references for emergency medicine residents on cardiology services. This is the 28th in a series of objectives for off-service rotations for emergency medicine residents.

Cardiology↗

PubMedDate not supplied

Diagnosing depression in the medically ill: validity of a lay-administered structured diagnostic interview.

Understanding the validity of structured psychiatric diagnostic interviews in medically ill patients will advance the ability to conduct research into the treatment and management of these disorders in general medical settings. We compared the University of Michigan version of the CIDI (Composite International Diagnostic Interview) for major depression to a clinical gold standard, derived through Spitzer's Longitudinal, Expert, All Data (LEAD) criteria based on the SCID-III-R. A convenience sample of medical inpatients was administered the SCID-III-R and the CIDI for major depression in random order. A physician panel reviewed the SCID interview and other pertinent data and determined whether patients had a lifetime or current (past month) diagnosis of major depression. The CIDI was scored with and without hierarchical exclusions for mania, hypomania, substance use, or medical illness. When the UM-CIDI was scored for a lifetime diagnosis of major depression without hierarchical exclusions, agreement above chance (kappa) was very good (kappa = 0.67) between the CIDI and the physician panel and good (kappa = 0.46) when the UM-CIDI was scored with exclusions. Agreement above chance for diagnosis of a recent disorder was better for UM-CIDI scoring with exclusions (kappa = 0.51) compared to scoring without exclusions (kappa = 0.43). Predictive value-positive was excellent in both scoring versions for a lifetime diagnosis (82%) and good to very good for current depression (46% and 62%). In all cases predictive value-negative was very good to excellent (77-93%). Discordant cases were almost uniformly due to difficulties in attribution of symptoms to medical illnesses. We conclude that the CIDI can perform acceptably as a research instrument to diagnose major depression in medically ill patients, potentially supplemented by clinician review of cases identified by the CIDI with current disorder.

Adult↗

PubMedDate not supplied

Secondary prevention and referral of elderly patients to a cardiovascular lipid service.

The burden of cardiovascular disease in the elderly has increased interest in lipid profiles which retain associations with outcome except at extreme age and for which management has benefits at least in secondary prevention. The source, clinical and laboratory background of 90 male and 120 female consecutive referrals age >70 years to a specialist cardiovascular lipid service have been analysed. Main sources were vascular surgery 47%, cardiology 9% and general practice 41% with 6% referred through routine health checks. Presenting lipids (mM: mean+/-S.D.) were: males: cholesterol 6.9+/-1.7, triglycerides 2.3+/-1.5, HDL 1.2+/-0.3; females: cholesterol 7.8+/-1.4, triglycerides 2.1+/-1.3, HDL 1.5+/-0.5, consistent with greater awareness of lipid-related problems in males but significant vascular disease in females. Secondary lipemia was defined in 131/210, 62.3% of patients (83 recognised before clinic presentation, 48 found at follow-up, mainly diabetes). Significant vascular disease was identified in 166/210 patients, significant other risk factors in another 35 patients. Levels of lipoprotein(a) were widely distributed for all groups, but elevated against population profiles for all groups with vascular disease. Referrals were monitored and not routinely accepted: reassuringly most then accepted were justified through atheroma-related disease and opportunities for secondary prevention, with little additional burden through untargeted routine health checks. Recognition of and management of secondary lipemia and obesity were however incomplete.

Journal Article↗

PubMedDate not supplied

Endothelial progenitor cells and their potential clinical applications in peripheral arterial disease.

Endothelial progenitor cells (EPCs) were originally thought to be present only during embryonic development. New evidence suggests that they can persist into adult life, circulate in the peripheral blood and may play an important part in endothelial repair and replacement of dysfunctional endothelium. They may also play a role in the formation of new blood vessels (angiogenesis, vasculogenesis, and arteriogenesis) in ischemic tissues. In addition, EPCs have the potential to endothelialize small-diameter prosthetic vascular bypass grafts and generate a nonthrombogenic surface, thereby increasing the patency rate of these grafts. EPCs may also be used in the clinical assessment of risk of vascular disease. In this review, the authors discuss the potential use of EPCs in the management of peripheral arterial disease (PAD).

Blood Vessel Prosthesis↗

PubMedDate not supplied

Micronuclear DNA from Paramecium tetraurelia: serotype 51 A gene has internally eliminated sequences.

A method for the isolation of micronuclear DNA from Paramecium tetraurelia has been developed. After cell lysis, a low speed centrifugation at 1,000 g is used to remove all of the unbroken cells and macronuclei and approximately two thirds of the macronuclear fragments. Next a higher speed centrifugation of 9,000 g sediments the micronuclei and frees them from small particulates and soluble constituents. Advantage is then taken of the fact that micronuclei have a lower density than do macronuclear fragments in 45%-60% Percoll. Micronuclei float to the top during centrifugation at 24,000 g, while macronuclear fragments sediment. After several cycles of centrifugation in Percoll, the micronuclei, although heavily contaminated with cytoplasmic components, are essentially free of macronuclei and macronuclear fragments. Micronuclear DNA can then be extracted from the suspension. The whole procedure is very rapid and in about an hour micronuclear and macronuclear DNA can be separated. About 2 micrograms of micronuclear DNA can be obtained from 6 x 10(7) paramecia. We find that there are internal sequences in the micronuclear A gene DNA in wild type cells which are eliminated when the micronuclei develop into macronuclei. They yield unique restriction fragments for micronuclei and macronuclei. Therefore the purity of the preparations is easily monitored by probing Southern blots of restriction enzyme-digested DNA with the cloned A gene. No differences have been found between the micronuclear A gene in wild type and the d48 mutant.

Animals↗

PubMedDate not supplied

Short-term lipid-lowering treatment with atorvastatin improves renal function but not renal blood flow indices in patients with peripheral arterial disease.

Some studies have suggested that lipid lowering with statins exerts favorable effects on the progression of chronic kidney disease. Therefore, the authors assessed the effects of short-term atorvastatin treatment on biochemical markers of renal function and evaluated duplex indices of renal blood flow (RBF) in patients with peripheral arterial disease. Hyperlipidemic claudicants (n = 18), aged 44-85 years, were treated for 8 weeks with 20 mg/day atorvastatin. Blood tests at baseline and after 8 weeks included serum fasting lipids, creatinine, urate, and cystatin C (a sensitive indicator of renal function) levels. RBF was also assessed (n = 9) by measuring pulsatile and resistance duplex indices. As expected, there was a significant improvement in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. There was also a significant (p < 0.0001) fall in serum creatinine from 89 (58-125) to 79 micromol/L (54-119) and an increase in calculated creatinine clearance (CrCl) from 72 (40-129) to 80 mL/minute (47-138; p < 0.0001). Serum cystatin C values decreased significantly (p = 0.0002) from 1.04 (0.57-1.56) to 0.90 mg/L (0.47-1.47). There were no detectable changes in the RBF duplex indices. Treatment of stable claudicants with atorvastatin for 8 weeks was associated with improved renal function (as assessed by serum creatinine, cystatin C, and calculated CrCl) without changes in RBF. Further studies are required to identify the mechanisms involved in this phenomenon.

Adult↗

PubMedDate not supplied

Serum levels of vasoactive intestinal peptide (VIP) in patients with adenocarcinomas of the gastrointestinal tract.

BACKGROUND: VIP acts as a neuroendocrine mediator under physiological conditions, with an important role in water and electrolyte secretion in the gut. Recent findings suggest that VIP also promotes growth and proliferation of normal as well as malignant cells. We have investigated the VIP-serum levels in patients with pancreatic cancer and colonic adenocarcinoma as compared to healthy controls. This was accompanied by immunohistochemical investigations and in vitro experiments to further define the role of the peptide in pancreatic and colorectal cancer. MATERIALS AND METHODS: Serum levels of VIP were evaluated under standardized conditions in a total of 135 patients; 45 patients had metastatic colorectal cancer, 45 suffered from metastatic pancreatic cancer, and 45 healthy volunteers served as controls. Human pancreatic and colorectal carcinoma cell lines were incubated over 5 days with VIP in increasing concentrations. RESULTS: In healthy controls, a median VIP-serum level of 42.44 +/- 2.540 pg/ml (range, 12.9-98.5 pg/ml) was found, while patients with pancreatic cancer had a median level of 40.58 +/- 3.013 pg/ml (range, 6.9-102.4 pg/ml). In patients with cancer originating in the colon, however, a median serum level of 116 +/- 10.14 pg/ml (range, 51.6-487 pg/ml) was found. While no difference between healthy controls and patients with pancreatic cancer could be detected (p = 0.6381), a significant difference between patients with colorectal cancer and healthy controls (p < 0.0001) and patients with pancreatic cancer (p < 0.0001) was demonstrated. The median VIP-concentrations found in the patients sera for pancreatic and colonic tumor patient groups, 40 pg/ml and 115 pg/ml respectively, had no significant effect on the proliferation of PANC-1 and HT29, inhibited ASPC-1, BxPC3, COLO201 and HCT-15 cells, and stimulated the growth of one pancreatic (CAPAN-1) and one colonic (COLO320DM) cell line under these conditions. CONCLUSIONS: As opposed to pancreatic cancer and healthy controls, patients in our series had elevated serum VIP-levels. Further studies are warranted to evaluate whether VIP can be used as a tumor marker in this disease.

Adenocarcinoma↗

PubMedDate not supplied

Ciclosporin monitoring in kidney-transplanted children: high-performance liquid chromatography versus radioimmunoassay.

Due to large individual differences in absorption, utilization and metabolism of the predominantly used drug ciclosporin (CsA) for selective immunosuppression in kidney graft recipients, therapeutic blood levels (immunosuppression/toxicity) can be maintained only by frequent measurements of the CsA concentrations in blood samples and dosage readjustments. The purpose of the present study was to investigate the usefulness of a high-performance liquid chromatography (HPLC) method for native CsA and a radioimmunoassay (RIA) method for CsA and metabolites measuring simultaneously using both HPLC and RIA and creatinine serum levels (Crea) in whole blood samples from 19 kidney-transplanted children over a 3-year observation period. By comparison of the results of HPLC, RIA and Crea determinations (n = 1,284) we found a highly variable metabolization rate (RIA/HPLC ratio) of 5.25 +/- 2.33 (range 1.37-12.9). No direct correlation was found between changes in RIA/HPLC ratios and kidney function, rejection and infection periods. Dosage/HPLC and dosage/RIA showed no significant correlation. A higher correlation between HPLC, Crea and nephrotoxicity was found than between RIA and Crea. Because of rapid and large variations of CsA metabolization rates in young allograft recipients, we recommend measurements of CsA blood concentrations with any HPLC method specific for unchanged drug, since CsA metabolites detected by RIA, at least those which are most abundant, have less immunosuppressive and toxic effects.

Adolescent↗

PubMedDate not supplied

Neopterin and interferon gamma serum levels in renal allograft recipients.

In the follow-up of children receiving renal allografts the early differential diagnosis of infections and rejection episodes is the main problem. Serum levels of neopterin (N), a pteridine released from stimulated macrophages, was determined by radioimmunoassay. Also interferon-gamma (IF) serum levels, a marker of T lymphocyte activity, were determined with an immunoradiometric assay in 19 kidney-transplanted children. Both, infections and rejection episodes, are accompanied by distinct increases in N. The IF are elevated 1-3 days earlier than N, the median values during infections being significantly (p less than or equal to 0.001) higher than those during rejection crises. The routine measurement of N and IF allow the simple, quick and reliable monitoring of the immune status, which seems to be of a high relevance for the daily monitoring of transplant recipients.

Adolescent↗

PubMedDate not supplied

In vitro antiproliferative effects of albumin-doxorubicin conjugates against Ewing's sarcoma and peripheral neuroectodermal tumor cells.

The 3-5 year survival rates of patients with disseminated Ewing's sarcoma (ES) or the closely related peripheral primitive neuroectodermal tumors (PNET) remain low, even under aggressive treatment involving highly toxic multidrug chemotherapeutic regimens. ES and PNET are sensitive to doxorubicin, but may escape treatment by expression of the multidrug-resistant phenotype and/or other mechanisms. In this study, we have identified albumin as growth supporting factor for ES and PNET cells in IGF-I-supplemented serum-free tissue culture medium. To investigate the specificity and toxicity of albumin-based drug conjugates, doxorubicin was coupled to bovine serum albumin (BSA) by either a two step glutaraldehyde or carbodiimide-C4-spacer technique, yielding monomeric DOX-albumin conjugates with conjugation numbers ranging from 3-20 moles DOX/mole BSA. Cellular uptake of fluorescein-isothiocyanate-(FITC)-labeled albumin and DOX-albumin conjugates could be demonstrated by flow cytometric measurements of cell-associated fluorescence and confocal microscopy. The cytostatic activity of these conjugates against ES/PNET cell lines, a neuroblastoma (LAN-1) and prostate cancer carcinoma cell line (PC-3) and normal lymphoblasts was tested in short-term proliferation assays (48 h). The results show a high selectivity of the DOX-albumin conjugates for ES/PNET cell lines, with highest growth inhibition by conjugates with low DOX conjugation numbers (n = 3) in serum-supplemented medium (17-32 fold loss of activity compared to free DOX), followed by 20-DOX-C4-albumin in serum-free medium and low activity of the other conjugates. In conclusion, DOX-albumin conjugates inhibit the growth of ES/PNET cell lines selectively, showing low activity against the unrelated carcinoma line PC-3 and sparing normal lymphoblasts. The inverse correlation of activity and conjugation number demonstrates a low cytotoxic activity of DOX in acid-stable binding to monomeric albumin, pointing to a selective cytostatic activity of the modified albumin against ES and PNET cells, even in the presence of a 100 fold excess of unmodified serum albumin.

Carbodiimides↗

PubMedDate not supplied

The multidrug-resistance modifiers verapamil, cyclosporine A and tamoxifen induce an intracellular acidification in colon carcinoma cell lines in vitro.

In this study we have investigated the effects of the multidrug-resistance (MDR) modifiers verapamil (VPM), cyclosporin A (CsA) and tamoxifen (TMX) on the intracellular pH(pHi) of four colon carcinoma-derived cell lines with low P-glycoprotein expression (CaCo-2, HT-29, SW 620 and SW 480). Addition of VPM (1 mu M), CsA (1 microgram/ml) or TMX (2 microM) in HEPES- or bicarbonate/CO2-buffered Ringer's solution was followed by dose-dependent and reversible decreases of the pHi (0.1-0.3 units) of all cell lines, as measured ratiometrically by the changes in the pH-dependent fluorescence of bis(carboxyethyl)carboxyfluorescein (BCECF). Testing the effects of the resistance modifiers on the Na+/H+ antiporter and bicarbonate trans-porters under appropriate buffer conditions and addition of inhibitors (amiloride, DIDS) revealed that the chemomodulator-induced acidification does not interfere with the function of these major pHi-regulating acid-base transporters. The induction of changes in pHi shows no correlation with MDR-reversing activity of the drugs and our data do not support the P-gp-inhibition-mediated accumulation of acidic substrates as underlying mechanism. In addition to the P-gp-directed MDR-reversal, chemomodulator-induced intracellular acidification may enhance the chemosensitivity of the cells especially under alkaline extracellular conditions, and contribute to the decreased efficacy of MDR-modifiers in acidic extracellular environments and to the chemosensitising effect of VPM in P-gp-negative cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Effect of naftidrofuryl and aspirin on platelet aggregation in peripheral vascular disease.

Platelet aggregation in whole blood (WB) was assessed in healthy subjects and in patients with peripheral vascular disease (PVD) using a WB-free platelet counting (WB-FPC) method. Aggregation induced by stirring and platelet agonists was significantly enhanced in PVD patients. WB-FPC aggregation induced by 5-HT was diminished significantly by incubation with naftidrofuryl (NAF) in WB of PVD patients. In contrast, aspirin (acetylsalicylic acid; ASA), added in vitro, did not significantly affect 5-HT or stirring-induced WB-PFC aggregation in PVD patients. Furthermore, 5-HT-induced WB-FPC was inhibited by NAF in blood collected from PVD patients that were taking low dose aspirin. These findings suggest that NAF may be of benefit to patients with hyperaggregable platelets and elevated plasma 5-HT concentrations, factors thought to predispose to thrombotic complications.

Adult↗

PubMedDate not supplied

[Compliance: a fundamental biomechanical property in the maintenance of an arterial reconstruction?].

The widespread use of graft replacement material led to complications inherent to these prostheses with increasing frequency. The discussion is still open on identifying those inherent features of vascular grafting that could contribute to long term success or short term failure. The search has been prompted for better arterial substitutes, among others, for repair particularly of lesions of smaller arteries. The ideal graft should have an innately blood-compatible flow surface with fixed endothelium and basement membrane and innately physiological mechanical properties. There are a number of biological and plastic materials competing for this goals. All plastic materials studied in clinical trials so far stimulate an uncontrollable proliferative response in host arteries behind or in the distal anastomosis; such causes failure of grafts when of small caliber. This distal anastomotic subintimal hyperplasia (SIH) is an ubiquitous pathologic entity in late graft occlusion. The cause of SIH has been the subject of much investigation. The role of compliance mismatch between host artery and vascular grafts in the development of SIH is discussed in this paper. While compliance may, in fact, be an important parameter in determining the results of bypass grafting, the dominant influence of hemodynamic and thrombogenic factors has continued to mask what is probably a very subtle effect. Summarizing the current knowledge it is likely that match or mismatch between the anisotropic behavior of the host artery and the linear respectively nonlinear response to varying blood pressure of the graft influences patency results. Any mismatch in tubular compliance in a quantitative manner will contribute to the long-term results but in a lesser degree. Disturbance of the biomechanical properties of the arterial tree due to an vascular anastomosis seems to be of utmost importance to the outcome, but up to now we were not able to demonstrate a link conclusively between compliance mismatch and the occurrence of subintimal hyperplasia. The present results imply a major impact on future graft design and the development of better anastomotic techniques, because compliance is a critical parameter for maintenance of arterial reconstructions.

Anastomosis, Surgical↗

PubMedDate not supplied

Atherosclerotic renal artery stenosis.

Atherosclerotic renal artery stenosis is a relatively common cause of hypertension and renal impairment in the elderly. We review its clinical features and the investigations and management options available.

Angioplasty, Balloon↗

PubMedDate not supplied

Biotransformation of topotecan in the isolated perfused rat liver: identification of three novel metabolites.

This study evaluates the metabolism of the anticancer drug topotecan (TPT) in the isolated perfused rat liver of male Wistar-rats. Using a sensitive high-performance liquid chromatography method, in bile TPT, its ring-opened hydroxycarboxylate form and three new metabolites could be quantified. Enzymatic hydrolysis of the metabolites with beta-glucuronidase and mass spectroscopy revealed the existence of glucuronidated TPT as well as unconjugated and glucuronidated bidesmethyl TPT. Biliary secretion of glucuronidated N-bidesmethyl TPT was fast reaching a maximum already after 15 min(30.6 +/- 15.1 pmol/g liver.min), whereas secretion of TPT, topotecan glucuronide and N-bidesmethyl TPT was delayed (maximum at 30 min: 431 +/- 19, 6.4 +/- 2.1 and 12.7 +/- 2.7 pmol/g liver.min, respectively). No release of TPT metabolites into the perfusate was detected. The amount of TPT, TPT glucuronide, N-bidesmethyl TPT and N-bidesmethyl TPT glucuronide excreted into bile during 60 min of perfusion was 2.10 +/- 0.483%, 0.031 +/- 0.006%, 0.058 +/- 0.013% and 0.108 +/- 0.012% of TPT cleared from the perfusate over 60 min, respectively. In conclusion we could identify three novel TPT metabolites, however, their overall metabolism in the rat liver is low.

Animals↗