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Biomedical subjects

R Christensen

Publications and source records attributed to R Christensen.

At least 19 recordsLinked to original sources
PubMed2006

Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival.

Bmi-1 is a polycomb group protein that was identified as c-myc cooperating oncogene in murine lymphomagenesis. The current study was undertaken to determine the role of Bmi-1 in human oral carcinogenesis. Bmi-1 protein and RNA expression levels were markedly enhanced in the cells of oral squamous cell carcinomas (OSCC) compared with that of normal human oral keratinocytes (NHOK). Enhanced-Bmi-1 expression was also detected in situ in the archived oral mucosal tissues with cancerous and precancerous histopathology, including that of mild epithelial dysplasia. Thus, Bmi-1 expression occurs at a very early stage in oral carcinogenesis. To determine the biological role of Bmi-1 in cell proliferation, endogenous Bmi-1 was knocked down in actively proliferating SCC4 cells and NHOK by RNA interference. After Bmi-1 knockdown, cell replication was severely retarded. However, the expression of p16(INK4A), a known cellular target of Bmi-1, was not changed in cells with or without Bmi-1 knockdown. Furthermore, Bmi-1 knockdown in HOK-16B-BaP-T cells, in which the p16(INK4A)/pRb pathway was abrogated, led to immediate arrest of replication and loss of viable cells. Thus, our data suggest that Bmi-1 may act through p16(INK4A)-independent pathways to regulate cellular proliferation during oral cancer progression.

Carcinoma, Squamous Cell↗
PubMed2006

Ultrasound guided electrocoagulation in patients with chronic non-insertional Achilles tendinopathy: a pilot study.

BACKGROUND: High resolution colour Doppler ultrasound shows intratendinous Doppler activity in patients with chronic Achilles tendinopathy. Treatment of this neovascularisation with sclerosing therapy seems to relieve the pain. However, the procedure often has to be repeated. OBJECTIVE: To investigate the effect of electrocoagulation of the neovessels on tendon pain and tendon vascularity in patients with chronic Achilles tendinopathy. METHODS: Colour Doppler ultrasound guided electrocoagulation was used on vessels in the ventral portion of the Achilles tendon in 11 patients (seven men, four women, mean age 41 years) with painful chronic mid-portion Achilles tendinosis. A unipolar coagulation device was used. RESULTS: One patient dropped out after two months (dissatisfied with the results). The remaining 10 patients (91%) were satisfied. These 10 patients were still satisfied at six months of follow up and had returned to their previous level of activity. All 10 patients were "cured" after one treatment. The patient who dropped out received two treatments because of lack of progress. There was significantly reduced pain (Likert pain scale, 0-10) during activity, from a median of 7 (range 4 to 10) at baseline to 0 (0 to 8) at six months' follow up (p<0.005); and at rest, from 1.5 (1 to 5) to 0 (0 to 8) (p = 0.005). In all patients, vascularisation was unchanged at the six months follow up, with no significant change in semiquantitative or quantitative colour scoring. CONCLUSIONS: Coagulation in the area with vessels entering the tendon appears to be effective treatment for painful chronic mid-tendinous Achilles tendinopathy. No effect on the intratendinous Doppler activity could be detected, suggesting that the effect is independent of changes in blood flow. Localisation of hyperaemia appears to be the key to the pathology and for targeting the treatment. One explanation could be that the effect is obtained by destruction of nerves accompanying the vessels.

Achilles Tendon↗
PubMed2006

Reproducibility and inter-reader agreement of a scoring system for ultrasound evaluation of hip osteoarthritis.

OBJECTIVE: To evaluate the intra-reader and inter-reader agreements of ultrasonographic assessments of hip joints in patients with hip osteoarthritis. DESIGN: Ultrasonography was performed on 100 patients with hip osteoarthritis at 14 MHz using a 8-15 MHz linear probe. Dynamic sweeps of the hip and representative still images were used for the analysis. A semiquantitative grading score was introduced in the evaluation of the ultrasound pictures and compared with an overall ultrasound evaluation. The evaluation was performed by a specialist in ultrasonography and a rheumatologist trained in musculoskeletal ultrasound examination. Clinical pain assessment and joint aspiration were obtained in parallel with the ultrasonography. RESULTS: Intraobserver agreement represented by intraclass correlation coefficients (ICC) (exact agreement in percentage; unweighted kappa values) showed good to excellent correlation, 0.8 with regard to the osteophyte score, 0.78 with regard to the femoral head score, 0.71 with regard to the fluid score and 0.69 with regard to the synovial profile score. Interobserver agreement was fair to good with corresponding ICC 0.65, 0.63, 0.45 and 0.6, respectively. In comparison, the ICC for the global osteoarthritis and synovial assessments were 0.7 and 0.72, respectively, for the intraobserver rating and 0.56 and 0.58, respectively, for the interobserver rating. CONCLUSIONS: This study suggests that ultrasound is a reproducible method for the assessment of changes in the osseous surface and synovium-related inflammation. The semiquantitative scoring system presented seemed to match the global assessment of a trained ultrasound investigator and might be used by less-trained investigators.

Adult↗
PubMed2006

The management of osteoarthritis in the obese patient: practical considerations and guidelines for therapy.

Obesity and osteoarthritis (OA) co-exist in an increasing part of the population. The two diseases intertwine in several ways. The evolution in the population shows a tendency towards deterioration of both by increasing general age and weight. The two diseases share pathogenetic features and the development of one disease increases the risk of the other and may be the onset of a vicious circle. There is a link between treatments of these two diseases as well. There is now solid (gold) evidence that by treating effectively the obesity of patients with co-occurring OA, the functional status is dramatically ameliorated; the short-term results are equal to that of a joint replacement. The long-term efficacy of a weight loss remains to be shown. OA is definitely one of many diseases in which obesity must be taken seriously into account when planning a correct treatment of patients. The regimens used in the controlled studies of such patients are reviewed and it may be concluded that practical aspects of the dietary intervention in obese patients with OA are not different from general recommendations.

Comorbidity↗
PubMed2005

Intra-articular treatment of hip osteoarthritis: a randomized trial of hyaluronic acid, corticosteroid, and isotonic saline.

OBJECTIVE: Hyaluronic acid (HA) and corticosteroids are both widely used for intra-articular treatment of knee osteoarthritis (OA). We examined the effect of both drugs in intra-articular treatment for hip OA. METHODS: One hundred and one patients with hip OA were included in a prospective double blind study, using a randomized controlled trial with a three-armed parallel-group design. Three ultrasound-guided, intra-articular injections were given at 14 days interval. The primary outcome measure was 'pain on walking', registered on a visual analogue scale (VAS). Evaluation was performed at baseline and after 14, 28 and 90 days. The study adhered to the Consolidated Standards of Reporting Trials. All analyses were based on intention-to-treat analyses, and used 'mixed-procedures' with the baseline-observation as covariate. RESULTS: There were no significant interactions with respect to Treatment x Time for any of the analyzed outcome measures. There was a significant treatment effect for 'pain on walking' (P=0.044) due to a significant improvement following corticosteroid compared to saline with an effect-size of 0.6 (95% confidence interval: 0.1-1.1, P=0.021). By contrast, HA compared to saline had an effect size of 0.4 (-0.1 to 0.9; P=0.13). The peak-effect was obtained after 2 weeks. There was no difference between the treatment groups at endpoint. No significant side effects of the injections were observed. CONCLUSIONS: Patients treated with corticosteroids experienced significant improvement during the 3 months of intervention, with an effect size indicating a moderate clinical effect. Although a similar significant result following treatment with HA could not be shown, the effect size indicated a small clinical improvement. A higher number of patients in future HA studies would serve to clarify this point.

Adjuvants, Immunologic↗
PubMed2005

Weight loss: the treatment of choice for knee osteoarthritis? A randomized trial.

OBJECTIVE: We wanted to assess the effect of rapid diet-induced weight loss on the function of obese, knee osteoarthritis (OA) patients. METHODS: Eighty patients with knee OA, 89% women (n=71), were recruited. Mean (SD) body-mass index (BMI) was 35.9 (5.1) kg/m(2) and age 62.6 (11.1) years. Patients were randomized to either a low-energy diet (LED 3.4MJ/day), or a control diet (5MJ/day). The LED group had weekly dietary sessions, whereas the control group was given a booklet describing weight loss practices. Changes in body weight and body composition were examined as independent predictors of changes in knee OA symptoms. Symptoms were monitored by the Western Ontario and McMaster Universities' (WOMAC) OA index. RESULTS: The LED and control group lost a mean (SE) of 11.1 (0.6)% and 4.3 (0.6)%, respectively, with a mean difference being 6.8% (95% confidence interval (CI): 5.5 to 8.1%; P<0.0001). The decrease in body fat percent was higher in the LED group, 2.2% (1.5 to 3.0%; P<0.0001). The total WOMAC index improved in the LED group (P<0.0001), but not in the control group (P=0.12), mean difference: -219.3mm (-369.2 to -69.4mm; P=0.005). The 'Number Needed to Treat (NNT)' to ensure an improvement in WOMAC>/=50% was 3.4 (2.1 to 8.8) patients. Changes in total WOMAC index were best predicted by the reduction of body fat percent, with a 9.4% (4.8 to 13.9%) improvement in WOMAC for each percent of body fat reduced (P=0.0005). CONCLUSIONS: In our patients with knee OA, a weight reduction of 10% improved function by 28%. LED might be of advantage to control diet because of the rapidity of weight loss and a more significant loss of body fat.

Adipose Tissue↗
PubMed2005

Learning effect of isokinetic measurements in healthy subjects, and reliability and comparability of Biodex and Lido dynamometers.

The aim of this study was to examine the learning effect during a set of isokinetic measurements, to evaluate the reliability of the Biodex System 3 PRO dynamometer, and to compare the Biodex System 3 PRO and the Lido Active dynamometers on both extension and flexion over the elbow and the knee at 60 degrees s(-1). Thirteen (nine women, four men) healthy participants were measured five times using the Biodex and once using the Lido dynamometer. The intervals between the first four tests were 20 min, and 1 week between tests 4 and 5. Between Biodex and Lido measurements there was a 20 min time interval. When comparing the first five measurements (Biodex), no systematic effect over time and an excellent reliability were found with respect to elbow and knee flexion and extension. No difference in muscle strength (Nm) between the Biodex and Lido was observed for knee flexion (P = 0.59), knee extension (P = 0.18) and elbow extension (P = 0.63). However, elbow flexion showed a 14.8% (95% CI: 11.2-18.4%; P = 0.0001) higher peak torque on Biodex. In conclusion, no learning effect was observed and the Biodex proved to be a highly reliable isokinetic dynamometer. A difference was observed when comparing Biodex and Lido on elbow flexion, but the difference did not outrange the expected variation found with a typical isokinetic measurement, which is why both sets of equipment seem applicable in clinical practice.

Adolescent↗
PubMed2005

Effect of static stretching of quadriceps and hamstring muscles on knee joint position sense.

OBJECTIVES: To evaluate if a stretch regimen consisting of three 30 second stretches would alter joint position sense (JPS). METHODS: A blinded, randomised, cross over design with a washout time of 24 hours was used with 20 healthy volunteers. JPS was estimated from the ability to reproduce the same position in one knee (target versus estimated angle) expressed as the difference between target and estimated angle (constant error, CE). Measurements were repeated three times in a sitting and a prone position on the dominant leg measured before and immediately after the static stretch. The static stretch consisted of a 30 second stretch followed by a 30 second pause, repeated three times. RESULTS: At baseline, the mean (SD) CE was -2.71 (3.57) degrees in the sitting position. No difference (p = 0.99) in CE between stretching and control was observed (0.00; 95% confidence interval -0.98 to 0.99). At baseline, the CE was -3.28 (4.81) degrees in the prone position. No difference (p = 0.89) in CE between stretching and control was observed (0.12; 95% confidence interval -1.52 to 1.76). CONCLUSION: A static stretch regimen had no effect on JPS in healthy volunteers.

Adult↗
PubMed2004

Clinical features and epidemiology of septicaemia and meningitis in neonates due to Streptococcus agalactiae in Copenhagen County, Denmark: a 10 year survey from 1992 to 2001.

AIM: To elucidate the clinical and biochemical features, and to estimate the incidence and outcome of invasive culture-verified group B streptococcal (GBS) septicaemia/meningitis in neonates in Denmark. METHODS: Clinical microbiology laboratory records in patients 0-3 mo of age were searched for culture-verified GBS during 1992-2001 in Copenhagen County. Clinical records at the neonatal intensive care unit were reviewed retrospectively. Selected clinical and biochemical parameters were evaluated. RESULTS: 61 neonates had culture-verified GBS septicaemia/meningitis. The mean annual incidence was 0.76 cases per 1000 livebirths (range 0.0-1.91). A significant decrease in incidence was observed in the latest 3 y. The male:female ratio was 1.3:1. Eighty percent of the neonates had early-onset GBS within 24 h, 57% with symptoms at birth. Predominant initial symptoms were respiratory (72%), cardiovascular (69%) and neurological (63%). Only 4% developed GBS by day 7-90. Seventy-five percent had maternal or neonatal risk factors for early-onset GBS disease; 21% had clinical asphyxia, 37% of the mothers had premature rupture of membranes and 31% of the mothers were febrile. Initial C-reactive protein (CRP) was low, but increased significantly after more than 12 h duration of symptoms in 82% of patients. Leucopenia was an important initial haematological marker. CONCLUSION: The incidence of early-onset GBS has decreased significantly in Denmark, probably because of preventive measures in pregnancy and during birth. Respiratory symptoms are early signs of early-onset GBS. Initial leucopenia and a late (12-48 h) increase in CRP are valuable markers for invasive GBS.

C-Reactive Protein↗
PubMed2001

Influence of ethanol on thermoregulation: mapping quantitative trait loci.

The genetic basis for the effects of ethanol on thermoregulation was investigated by utilizing recombinant inbred mouse strains from C57BL/6J and DBA/2J progenitor strains. Changes in core body temperature (T(c)) and the degree of fluctuation of T(c) were monitored in male mice following the administration of ethanol in an environment with cyclic changes in ambient temperature (T(a)). Changes in T(c) were utilized to assess ethanol-induced effects on regulated T(c), whereas fluctuations in T(c) were utilized to assess thermoregulatory disruption. Ethanol was administered intraperitoneally at 1.5, 2.5, and 3.5 g/kg for all strains. Change in T(c) and increase in tail temperature were also evaluated at 2.5 g/kg ethanol in a constant T(a) of 26 degrees C. Associations between the measured physiological responses and previously mapped genetic markers were used to identify quantitative trait loci (QTLs). This established probable chromosome locations for a number of genes for the responses. To our knowledge, this is the first report of QTLs that underlie changes in regulation as well as the disruption of a physiological regulatory system.

Animals↗
PubMed2001

Data augmentation priors for Bayesian and semi-Bayes analyses of conditional-logistic and proportional-hazards regression.

Data augmentation priors have a long history in Bayesian data analysis. Formulae for such priors have been derived for generalized linear models, but their accuracy depends on two approximation steps. This note presents a method for using offsets as well as scaling factors to improve the accuracy of the approximations in logistic regression. This method produces an exceptionally simple form of data augmentation that allows it to be used with any standard package for conditional-logistic or proportional-hazards regression to perform Bayesian and semi-Bayes analyses of matched and survival data. The method is illustrated with an analysis of a matched case-control study of diet and breast cancer.

Algorithms↗
PubMed2001

Immediate neurocognitive effects of methylphenidate on learning-impaired survivors of childhood cancer.

PURPOSE: To test if methylphenidate (MPH) has an objective beneficial effect on immediate performance on tests of neurocognitive functions among learning-impaired survivors of childhood acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT). PATIENTS AND METHODS: From July 1, 1997 through December 31, 1998, 104 long-term survivors of childhood ALL or a malignant BT completed neurocognitive screening for learning impairments and concurrent problems with sustained attention. Eligibility criteria for the MPH trial included an estimated intelligence quotient greater than 50, academic achievement in the 16(th) percentile or lower for age in reading, math, or spelling, and an ability to sustain attention on a computerized version of the Conners' Continuous Performance Test (CPT) in the 16(th) percentile or lower for age and sex. Of the 104, 32 (BT, n = 25; ALL, n = 7) were eligible on the basis of these a priori criteria for a randomized, double-blinded, placebo-controlled trial of MPH. The patients ingested a placebo (lactose) or MPH (0.6 mg/kg; 20 mg maximum) and repeated selected portions of the screening battery 90 minutes later. RESULTS: Compared to the 17 patients randomized to the placebo group, the 15 patients randomized to the MPH group had a significantly greater improvement on the CPT for sustained attention (errors of omission, P =.015) and overall index (P =.008) but not for errors of commission (indicative of impulsiveness) nor reaction times. A trend for greater improvement in the MPH group on a measure of verbal memory failed to reach statistical significance. No trend was observed for MPH effectiveness in improving learning of a word association task. No significant side effects from MPH were observed. CONCLUSION: MPH resulted in a statistically significant improvement on measures of attention abilities that cannot be explained by placebo or practice effects.

Administration, Oral↗
PubMed2001

Cutaneous gene therapy--an update.

In this paper we review various strategies for gene transfer into the skin, their applications and show some of our own examples. The skin is the most accessible somatic tissue. Inherited skin diseases, such as epidermolysis bullosa and ichthyosis, and various systemic metabolic disorders are under investigation as potential candidate diseases for cutaneous gene transfer. Research is directed against genetic therapy of wounds and malignancies as well. So far, cutaneous gene transfer only has been used experimentally, but several clinical trials are under preparation.

Gene Transfer Techniques↗
PubMed2001

The development of the distal femur Less Invasive Stabilization System (LISS).

Fractures around the knee typically require operative fixation to achieve an acceptable, functional outcome. The idea behind the Less Invasive Stabilization System (LISS) was to combine the advantages of both interlocked intramedullary nailing techniques and the early advances of the so-called biological plating technique into one system. This paper introduces the mechanical concept of a locked internal fixator and details some important aspects of the anatomical and biomechanical development of the LISS.

Bone Screws↗
PubMed2001

Invasive radiology for pediatric trauma.

Interventional radiology has assumed an expanded role in the management of the pediatric trauma patient. Transcatheter endovascular embolization for the polytraumatized and bleeding patient has proven to be effective and potentially life saving. Nonvascular interventional techniques can be applied to the pediatric trauma patient with curative or temporizing effects. The minimally invasive nature and rapidity of these procedures allows their emergent use in both the unstable and stable pediatric trauma patient.

Angiography↗
PubMed2001

Adherence to antiretroviral therapy among HIV-positive children: examination of the role of caregiver health beliefs.

This study examined the association between two components of the Health Belief Model (perceived vulnerability and barriers) and adherence to antiretroviral therapy (ART) among children who are HIV-infected. The parents/caregivers of 30 children (mean age = 5.21, SD = 3.18) who were HIV-infected and who were on active ART were surveyed to assess current methods of adherence assessment and educational efforts within the institution. All participants (except one) were African American and reported low monthly family incomes (M = $869.45, SD = $832.63). Assessment instruments included measures of perceived vulnerability, caregiver-reported adherence and perceived barriers, and objective measures of adherence (clinical pill count; electronic measurement). The results failed to demonstrate a significant relationship between parental perceived vulnerability, perceived barriers and adherence to antiretroviral medications. Methods of assessing adherence provided significantly discrepant estimates of adherence. Results are discussed in terms of implications for patient care and for future research in this area. The addition of behavioural and motivational components to traditional educational approaches may positively impact treatment results.

Adolescent↗
PubMed2001

Elevated expression of hTERT is associated with dysplastic cell transformation during human oral carcinogenesis in situ.

PURPOSE: Telomerase is a ribonucleoprotein complex composed of the catalytic protein subunit (human telomerase reverse transcriptase or hTERT) and the RNA template. This enzyme activity is a necessary and rate-limiting step of cellular immortalization and could provide a unique marker of aberrant cells, which may selectively be targeted. The current study was undertaken to quantitatively determine the degree of telomerase activation during multistage oral carcinogenesis using paraffin-embedded tissue samples. EXPERIMENTAL DESIGN: hTERT expression level was quantitatively compared between normal and cancerous oral tissues by real-time reverse-transcription-PCR (RT-PCR). Also, the presence of hTERT transcript in individual cells was surveyed in the biopsy specimens with varying degrees of histopathology by in situ RT-PCR. RESULTS: Low level of hTERT amplification was detected by real-time RT-PCR in most (11/13) normal human oral mucosa. hTERT expression was also detected in the majority (11/12) of squamous cell carcinoma tissues, and the level was significantly (P < 0.05) elevated, on the average, by a factor >6.9. By in situ RT-PCR, hTERT expression was not noted in normal epithelium (0/10) nor in mild dysplasia (0/7) but was detected in moderate dysplasia (4/5) and in those tissues with a higher grade of histopathology: severe dysplasia (3/3) and invasive carcinoma (4/4). CONCLUSIONS: These results indicate that enhanced expression of telomerase activity occurs early during human oral carcinogenesis and support the critical role of telomerase in the development of human oral cancer.

Adult↗