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Biomedical subjects

S Olsen

Publications and source records attributed to S Olsen.

At least 19 recordsLinked to original sources

A surgically induced hypoxic environment causes changes in the metastatic behaviour of tumours in vitro.

The use of laparoscopic techniques for curative resections of malignant tumours has been under scrutiny. The potential benefits to the patient in the form of earlier recovery and less immune paresis are countered by the reports of increased tumour recurrence. The biological sequelae of the hypoxic laparoscopic environment on tumour cells is unknown. Components of the metastatic cascade were evaluated under in vitro laparoscopic conditions using a human colonic adenocarcinoma cell line (SW1222). Exposure to the laparoscopic gases carbon dioxide and helium for 4 h, comparable to the duration of a laparoscopic colorectal resection, had no effect on cell viability. A cellular hypoxic insult was demonstrated by the induction of hypoxia inducible factor 1alpha (HIF-1alpha). Exposure also resulted in significant reduction in homotypic adhesion as well as to a variety of extracellular matrix components. These effects were recoverable under re-oxygenation. The changes were reflected at the molecular level by significant down regulation of adhesion molecules known to be involved in tumour progression (E-cadherin, CD44 and beta1 sub-unit). Modulation of adherence has significant implications for laparoscopic oncological surgery, demonstrating that tumours become potentially more friable and easier to disseminate in surgeons who are less experienced or where instrumentation is sub-optimal.

Adenocarcinoma↗

Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer.

PURPOSE: This randomized, controlled, multicenter, open-label, phase III study compared docetaxel versus paclitaxel in patients with advanced breast cancer that had progressed after an anthracycline-containing chemotherapy regimen. PATIENTS AND METHODS: Patients (n = 449) were randomly assigned to receive either docetaxel 100 mg/m2 (n = 225) or paclitaxel 175 mg/m2 (n = 224) on day 1, every 21 days until tumor progression, unacceptable toxicity, or withdrawal of consent. RESULTS: In the intent-to-treat population, both the median overall survival (OS, 15.4 v 12.7 months; hazard ratio [HR], 1.41; 95% CI, 1.15 to 1.73; P = .03) and the median time to progression (TTP, 5.7 months v 3.6 months; HR, 1.64; 95% CI, 1.33 to 2.02; P < .0001) for docetaxel were significantly longer than for paclitaxel, and the overall response rate (ORR, 32% v 25%; P = .10) was higher for docetaxel. These results were confirmed by multivariate analyses. The incidence of treatment-related hematologic and nonhematologic toxicities was greater for docetaxel than for paclitaxel; however, quality-of-life scores were not statistically different between treatment groups over time. CONCLUSION: Docetaxel was superior to paclitaxel in terms of OS and TTP. ORR was higher for docetaxel. Hematologic and nonhematologic toxicities occurred more frequently in the docetaxel group. The global quality-of-life scores were similar for both agents over time.

Adenocarcinoma↗

Conical intersection dynamics in solution: the chromophore of Green Fluorescent Protein.

We use ab initio results to reparameterize a multi-reference semiempirical method to reproduce the ground and excited state potential energy surfaces (PESs) for the chromophore of Green Fluorescent Protein (GFP). The validity of the new parameter set is tested, and the new method is combined with a quantum mechanical/molecular mechanical (QM/MM) treatment so that it can be applied in the solution phase. Solvent effects on the energetics of the relevant conical intersections are explored. We then combine this representation of the ground and excited state PESs with the full multiple spawning (FMS) nonadiabatic wavepacket dynamics method to simulate the photodynamics of the neutral GFP chromophore in both gas and solution phases. In these calculations, the PESs and their nonadiabatic couplings are evaluated simultaneously with the nuclear dynamics, ie. "on-the-fly". The effect of solvation is seen to be quite dramatic, resulting in an order of magnitude decrease in the excited state lifetime. We observe a correlated torsion about a double bond and its adjacent single bond in both gas and solution phases. This is discussed in the context of previous proposals about minimal volume isomerization mechanisms in protein environments.

Green Fluorescent Proteins↗

A finite element formulation and program to study transient swelling and load-carriage in healthy and degenerate articular cartilage.

The theory of poroelasticity is extended to include physico-chemical swelling and used to predict the transient responses of normal and degenerate articular cartilage to both chemical and mechanical loading; with emphasis on isolating the influence of the major parameters which govern its deformation. Using a new hybrid element, our mathematical relationships were implemented in a purpose-built poroelastic finite element analysis algorithm (u-pi-c program) which was used to resolve the nature of the coupling between the mechanical and chemical responses of cartilage when subjected to ionic transport across its membranous skeleton. Our results demonstrate that one of the roles of the strain-dependent matrix permeability is to limit the rate of transmission of stresses from the fluid to the collagen-proteoglycan solid skeleton in the incipient stages of loading, and that the major contribution of the swelling pressure is that of preventing any excessive deformation of the matrix.

Adaptation, Physiological↗

Current understanding of in-stent restenosis and the potential benefit of drug eluting stents.

Percutaneous transluminal coronary angioplasty has revolutionized the management of patients with coronary artery disease. Unfortunately, the procedure's utility is limited by a frequent complication: restenosis. Coronary stenting prevents the elastic recoil and negative remodeling that can occur after angioplasty but, by inciting varying degrees of intimal expansion, it can also produce arterial renarrowing, known as in-stent restenosis (ISR). The precise mechanisms involved in the pathogenesis of ISR are incompletely understood. The recent introduction of drug-eluting stents (DESs) may help prevent ISR. However, DESs have not been universally successful, and they may introduce new complications that require further refinement. This review summarizes the current understanding of the pathogenesis of ISR and provides an objective overview of DESs.

Angioplasty, Balloon, Coronary↗

A finite element analysis methodology for representing the articular cartilage functional structure.

Recognising that the unique biomechanical properties of articular cartilage are a consequence of its structure, this paper describes a finite element methodology which explicitly represents this structure using a modified overlay element model. The validity of this novel concept was then tested by using it to predict the axial curling forces generated by cartilage matrices subjected to saline solutions of known molality and concentration in a novel experimental protocol. Our results show that the finite element modelling methodology accurately represents the intrinsic biomechanical state of the cartilage matrix and can be used to predict its transient load-carriage behaviour. We conclude that this ability to represent the intrinsic swollen condition of a given cartilage matrix offers a viable avenue for numerical analysis of degenerate articular cartilage and also those matrices affected by disease.

Animals↗

Timing of postexercise protein intake is important for muscle hypertrophy with resistance training in elderly humans.

1. Age-associated loss of skeletal muscle mass and strength can partly be counteracted by resistance training, causing a net synthesis of muscular proteins. Protein synthesis is influenced synergistically by postexercise amino acid supplementation, but the importance of the timing of protein intake remains unresolved. 2. The study investigated the importance of immediate (P0) or delayed (P2) intake of an oral protein supplement upon muscle hypertrophy and strength over a period of resistance training in elderly males. 3. Thirteen men (age, 74 +/- 1 years; body mass index (BMI), 25 +/- 1 kg m(-2) (means +/- S.E.M.)) completed a 12 week resistance training programme (3 times per week) receiving oral protein in liquid form (10 g protein, 7 g carbohydrate, 3 g fat) immediately after (P0) or 2 h after (P2) each training session. Muscle hypertrophy was evaluated by magnetic resonance imaging (MRI) and from muscle biopsies and muscle strength was determined using dynamic and isokinetic strength measurements. Body composition was determined from dual-energy X-ray absorptiometry (DEXA) and food records were obtained over 4 days. The plasma insulin response to protein supplementation was also determined. 4. In response to training, the cross-sectional area of m. quadriceps femoris (54.6 +/- 0.5 to 58.3 +/- 0.5 cm(2)) and mean fibre area (4047 +/- 320 to 5019 +/- 615 microm(2)) increased in the P0 group, whereas no significant increase was observed in P2. For P0 both dynamic and isokinetic strength increased, by 46 and 15 %, respectively (P < 0.05), whereas P2 only improved in dynamic strength, by 36 % (P < 0.05). No differences in glucose or insulin response were observed between protein intake at 0 and 2 h postexercise. 5. We conclude that early intake of an oral protein supplement after resistance training is important for the development of hypertrophy in skeletal muscle of elderly men in response to resistance training.

Aged↗

Renal function and structure in albuminuric type 2 diabetic patients without retinopathy.

BACKGROUND: In type 2 diabetic patients without retinopathy the cause of albuminuria is heterogeneous and our knowledge of the relationship between kidney structure and function in these patients is limited. Therefore, a long-term study evaluating the structural-functional relationship in albuminuric type 2 diabetic patients without retinopathy was performed. METHODS: Mesangial volume of total glomerular volume (Vv (mes/glom)), fractional area of focal interstitial fibrosis and tubular atrophy of cortical area (FF) and percentage of sclerosed glomeruli (S/G) were measured on kidney biopsies from 49 type 2 diabetic patients without retinopathy. Glomerular filtration rate (GFR) was determined at least 3 times (median 8 (range 3-20)) in each patient. Patients were followed for 7.0 (1.1-17) years. Albuminuria and blood pressure were measured every 3-6 months. RESULTS: Biopsies revealed diabetic glomerulopathy (DG-group) in 69% of the patients (27 male/7 female) and normal glomerular structure (n=9) or glomerulonephritis (n=6) were found in 31% (13 male/2 female) (NDG-group). In the DG-group GFR decreased from 97+/-5 to 66+/-5 ml/min/1.73 m(2) (mean+/-SE) (P<0.001), with a rate of decline in GFR of 5.3+/-0.8 ml/min/year and in the NDG-group from 93+/-7 to 74+/-11 ml/min/1.73 m(2) (P<0.01), with a rate of decline in GFR of 3.2+/-0.9 ml/min/year, P=0.09 between groups. Mean arterial blood pressure decreased from 109+/-2 to 100+/-2 mm Hg (P<0.001) (DG-group) and remained unchanged in the NDG-group. An association between Vv (mes/glom) and rate of decline in GFR was revealed mainly in the NDG-group (DG-group; r=0.31, P=0.07 and NDG-group; r=0.74, P<0.01). Furthermore, the rate of decline in GFR seemed to be associated with FF in the NDG group (r=0.48, P=0.07). Percentage of S/G was not associated with the rate of decline in GFR. Vv (mes/glom) was associated with mean albuminuria during follow-up in the DG group; r=0.38, P<0.03 (NDG group; r=0.51, P=0.09). Albuminuria was an independent predictor of the rate of decline in GFR in both groups (DG-group; r=0.40, P<0.05 and NDG-group; r=0.61, P<0.01). CONCLUSIONS: Our study revealed a tendency to a faster rate of decline in GFR in the DG-group compared to the much smaller NDG-group, characterized by marked heterogeneity of the underlying kidney lesions and rate of GFR loss. A large mesangial volume fraction was associated with increased albuminuria and loss in GFR. Albuminuria acted as a progression promoter in both groups.

Albuminuria↗

The effectiveness of active head restraint in preventing whiplash.

BACKGROUND: Whiplash injury claims have increased for two decades and manual head restraints are often incorrectly adjusted. A Self-Aligning Head Restraint (SAHR) was designed to move upward and forward by occupant motion in a rear crash providing earlier neck support, even when the head restraint is positioned low. This study determines its field effectiveness. METHODS: Insurance records were analyzed for consecutive Saab rear crashes in Sweden over 18 months. The Saab 9000/900 had standard head restraints and Saab 9-5/9-3 had SAHR. A questionnaire was mailed to the occupants, insurance and medical records were reviewed, and phone interviews were conducted. RESULTS: SAHR reduced whiplash injury risks by 75 +/- 11% from an 18 +/- 5% incidence in 85 occupants with standard head restraints to 4 +/- 3% in 92 occupants with SAHR. No SAHR seat required repair or replacement after the crashes. CONCLUSION: SAHR is effective in reducing whiplash injury in rear crashes and is a passive public-health approach that works irrespective of manual head-restraint adjustment.

Accidents, Traffic↗

Field validation of the use of RB51 as antigen in a complement fixation test to identify calves vaccinated with Brucella abortus RB51.

In order to confirm the efficiency of an experimental RB51-based complement fixation (CF) test in identifying cattle vaccinated with Brucella abortus strain RB51, 831 sera from 110 vaccinated and 48 unvaccinated Hereford heifers of Iowa, collected for studies conducted in different years, were sent to Italy without coding to be tested in a CF test using RB51 as antigen. Most of the calves, aged from 3 to 10 months, were vaccinated subcutaneously with the recommended dosage of 10(10) CFU of RB51 commercial vaccine, while only six calves received 10(9) CFU of the same vaccine. Serum samples for serologic testing, collected until 16 postinoculation weeks (PIW), were also tested by routine surveillance tests for brucellosis such as rose bengal plate and CF tests performed with B. abortus smooth strain 99 as control antigen. RB51 CF test results obtained by testing sera from cattle vaccinated in 1999 indicate that the sensitivity of the reaction is 97% at 2 to 3 PIW and 90% until 8 PIW and decreases to 65% at 12 PIW, the specificity remaining at 100%. Collectively, the results of this study confirm that serologic standard tests fail to detect antibodies to RB51 while the RB51-based CF test is able to monitor antibody responses to RB51 until 15 to 16 PIW with a specificity of 100%. In addition, unlike the RB51-based dot blot assay, which is the only test currently used to monitor antibody responses to RB51, the CF test also detected specific responses following vaccination with 10(9) CFU of RB51, although seroconversion was only 50% at 8 PIW. In conclusion, because of high specificity and sensitivity, the CF test described here can be used to efficaciously monitor serologic responses following RB51 vaccination in cattle and could also be employed to detect RB51 infection in humans exposed to this strain.

Animals↗

Causes of albuminuria in patients with type 2 diabetes without diabetic retinopathy.

BACKGROUND: The causes of albuminuria in patients with type 2 diabetes are heterogeneous and are scantily investigated, particularly if the patient has a lack of diabetic retinopathy. Therefore, we evaluated the structural background of albuminuria in a large consecutive group of Caucasian patients with type 2 diabetes without retinopathy. METHODS: Three hundred forty-seven consecutive patients with type 2 diabetes with persistent albuminuria (>300 mg/24 h) were recorded. Fundus photo (80%) and ophthalmoscopy were performed. Ninety-three (27%) had no retinopathy, and a kidney biopsy was performed in 52 (56%) of these patients. An insufficient tissue sample was obtained in one patient. The biopsies were evaluated by three masked nephropathologists. RESULTS: The biopsies revealed diabetic glomerulopathy in 69% of the patients (28 males and 7 females), while the remaining 31% (95% CI, 18 to 44) had either nondiabetic glomerulopathies such as glomerulonephritis (N = 7, 6 males and 1 female, 13%) or normal glomerular structure (N = 9, 7 males and 2 females, 18%). No significant differences in sex, age (56 +/- 8 vs. 53 +/- 10 years, mean SD), body mass index (30 +/- 4 vs. 31 +/- 8 kg/m2), known duration of diabetes (6 +/- 6 vs. 4 +/- 3 years), GFR (95 +/- 29 vs. 89 +/- 31 mL/min/1.73 m2), albuminuria (1304 +/- 169 to 4731 vs. 1050 +/- 181 to 5176 mg/24 hours), blood pressure (150/87 +/- 16/9 vs. 145/89 +/- 16/9 mm Hg), prevalence of hypertension (89 vs. 100%), hemoglobin A1c (8.2 +/- 1.6% vs. 9.0 +/- 2.5%), and serum total cholesterol (7.1 +/- 2.4 vs. 6.3 +/- 1.6 mmol/L) were found between patients with and without diabetic glomerulopathy. CONCLUSIONS: Albuminuric patients with type 2 diabetes without diabetic retinopathy have a prevalence of biopsies with normal glomerular structure or nondiabetic kidney diseases of approximately 30%. A separation between diabetic and nondiabetic glomerular lesions was not possible based on demographic, clinical, or laboratory data. Consequently, such patients may require further evaluation, including a kidney biopsy.

Adult↗

Validation of the fluorescence polarization assay and comparison to other serological assays for the detection of serum antibodies to Brucella abortus in bison.

A number of serological tests were compared for the detection of antibodies to Brucella abortus in bison (Bison bison). The performance of the fluorescence polarization assay (FPA) in both the preliminary evaluation and a subsequent blind validation indicated that this test was the most suitable for serological diagnosis of brucellosis in bison. The sensitivity and specificity in the preliminary evaluation were 92.1% and 99.4%, respectively. The sensitivity and specificity in a subsequent blind study were 96.3% and 97.6%, respectively. In a double blind study conducted on bison vaccinated with B. abortus strain 19, the data suggests that the FPA can differentiate bison infected with B. abortus from bison vaccinated with B. abortus strain 19. Both the indirect immunoassay (IELISA) and the competitive immunoassay (CELISA) performed nearly as well as the FPA. The buffered antigen plate agglutination test (BPAT) and the complement fixation test (CFT) did not perform as well as the FPA, CELISA or the IELISA in both studies. The FPA is a homogeneous assay eliminating the washing steps and reducing incubation to minutes rather than hours saving on time, equipment, materials, reagents and cost. These attributes, together, with its excellent sensitivity and specificity make the FPA an attractive test for the detection of serum antibodies to Brucella abortus in bison.

Agglutination Tests↗

[Renal biopsy in connection with long-term treatment of psoriasis with cyclosporine].

Renal biopsies were performed in 30 psoriatics during long-term low-dose cyclosporin (CSA) therapy (range 2.5-6 mg/kg/day) of from six months to eight years. The study included pretreatment biopsies in 25 of the patients. After two years all biopsies shared features consistent with CSA nephropathy despite completely normal pretreatment morphology in 18 of the 25 patients. The severity of the findings, which consisted of arteriolar hyalinosis, focal interstitial fibrosis and sclerotic glomeruli, increased with length of therapy. Mild renal lesions were seen during the first two years. After four years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of 11 patients. At the same time glomerular sclerosis had become significant. A decrease in glomerular filtration rate (GFR) correlated with the severity of the fibrosis. GFR studied in 14 patients six months to seven years after discontinuation of CSA was still significantly decreased in relation to baseline prior to therapy. The data from our study together with experiences from cardiac-transplanted patients indicate that patients with psoriasis, after two years therapy with CSA, should be rotated to other treatments or be followed carefully by GFR and sequential renal biopsies.

Adult↗