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Biomedical subjects

J Anderson

Publications and source records attributed to J Anderson.

At least 37 records · Page 2Linked to original sources

Passive stiffness is increased in soleus muscle of desmin knockout mouse.

The effects of an absence of desmin on passive stiffness of skeletal muscle were analyzed using soleus muscles from desmin knockout mice. Stiffness was evaluated by analyzing the passive tension induced by a ramp-and-hold extension test. This test showed that passive resistance to stretch was largely increased for muscles lacking desmin. This study could facilitate interpretation of changes in muscle mechanics observed in humans affected by desmin-related myopathies.

Animals↗

PAX3-FKHR induces morphological change and enhances cellular proliferation and invasion in rhabdomyosarcoma.

Alveolar rhabdomyosarcoma (ARMS) is consistently associated with the characteristic translocations t(2;13)(q35;q14) and t(1;13)(p36;q14), which encode for the PAX3-FKHR and PAX7-FKHR fusion oncoproteins respectively. We have investigated the relationship between PAX3-FKHR expression and ARMS histogenesis in primary tumors and cell culture systems. In a blinded histological review of discrepant primary tumors in which there was PAX3-FKHR expression but embryonal histology, we found small areas of alveolar histology in 6 of 11 cases. This suggests that histology alone may under-represent the association between PAX3-FKHR and ARMS, and we investigated this link by examining the effect of ectopic PAX3-FKHR expression on RMS cells. Two cell lines, RD and HX170C, were stably transfected with a PAX3-FKHR expression construct. In cloned transfectants derived from both lines, PAX3-FKHR expression resulted in increased proliferative rate in vitro and promoted cell growth in the absence of added growth factors. Tumors that formed as xenografts in immunodeficient mice were faster growing, more locally invasive, and had a denser, more pleomorphic architecture than untransfected or empty vector transfected tumors. The characteristic clefts and alveolar spaces of ARMS, however, were not seen. In contrast, tumors grown as xenografts from individual clones derived from ARMS cell lines showed all of the classical morphological features of ARMS suggesting divergence in vivo from precursor cells propagated in culture.

Animals↗

Human immunodeficiency virus and assisted reproduction: reconsidering evidence, reframing ethics.

OBJECTIVE: To review the advances in the treatment of human immunodeficiency virus (HIV) infection and revisit the medical, ethical, and legal issues surrounding infertility management in HIV-infected couples. DESIGN: Analytic review. RESULTS(S): HIV infection continues to be a serious public health and reproductive issue. However, present policies which allow for the categorical exclusion of HIV-infected individuals from infertility services should be reconsidered in light of improvements in the prognosis of infected individuals and a dramatic decrease in the risk of vertical transmission. An analysis of the ethical cogency of the arguments against the provision of services does not substantiate the exclusion of HIV-infected individuals; rather, the principle of justice requires that HIV-infected women be treated the same way as a woman who might have an increased risk of conceiving a child with a disability or a may have a decreased life expectancy due to a chronic illness such as diabetes. Ethical disagreement notwithstanding, with the precedents recently established by the Americans with Disabilities Act (ADA), discrimination based on HIV status would also likely be unlawful under most circumstances. CONCLUSIONS(S): With advances in the treatment of HIV infection, contextualized counseling and a respect for patients' decisions regarding infertility treatment should be adopted as public policy. It is neither ethically nor legally justifiable to categorically exclude individuals from infertility services on the basis of HIV infection.

Acquired Immunodeficiency Syndrome↗

Adenosarcoma in a patient with vaginal endometriosis.

BACKGROUND: Adenosarcoma in a patient with extraovarian endometriosis is a rare event and can be easily overlooked. CASE: A woman with a history of endometriosis underwent multiple resections of a vaginal mass and medical treatment for presumed recurrent endometriosis. Eventually, a vaginal adenosarcoma was diagnosed. CONCLUSION: The possibility of adenosarcoma should be considered if an enlarging mass occurs at the site of extraovarian endometriosis.

Adenosarcoma↗

Clinical and pathological features of posttransplant lymphoproliferative disorders: influence on survival and response to treatment.

PURPOSE: To review the clinical and pathological characteristics of patients with posttransplant lymphoproliferative disorders (PTLD) occurring after solid organ transplantation and determine the influence of these characteristics on response to treatment and survival. PATIENTS AND METHODS: Retrospective review of 32 patients. RESULTS: Overall five-year survival was 59%. Forty-five percent of patients diagnosed within the first year after transplant had advanced disease. Characteristics that were associated with poorer survival were diagnosis within the first year posttransplant, monoclonal tumors and presentation with an infectious mononucleosis-like syndrome. Six of eight patients treated with surgery are alive and disease-free. CONCLUSION: Patients with PTLD can achieve long-term survival. Surgery can play an important role in selected patients. Characteristics that may be associated with poorer survival are diagnosis within the first year after transplant, presence of a monoclonal tumor or an infectious mononucleosis-like presentation.

Adolescent↗

Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer.

PURPOSE: SIR-Spheres are radioactive yttrium90 microspheres (SIR-Spheres, Sirtex Medical Limited, Australia) used to selectively target high levels of ionising radiation to tumors within the liver. This trial was designed to measure any increased patient benefit by adding a single administration of SIR-Spheres to a regimen of regional hepatic artery chemotherapy (HAC) administered as a 12 day infusion of floxuridine and repeated at monthly intervals, vs. the same chemotherapy alone. PATIENTS AND METHODS: A phase III randomised clinical trial entering 74 patients was undertaken on patients with bi-lobar non-resectable liver metastases from primary adenocarcinoma of the large bowel. Patient benefit criteria assessed in the trial were tumor response, time to disease progression in the liver, overall survival, quality of life, and treatment related toxicity. Tumor response was measured by serial changes in both cross-sectional tumor areas and total tumor volumes, provided any response lasted not less than three months as well as changes in serum carcino-embryonic antigen (CEA). RESULTS: The partial and complete response rate (PR + CR) was significantly greater for patients receiving SIR-Spheres when measured by tumor areas (44%) vs. 17.6%, P = 0.01) tumor volumes (50% vs. 24%, P = 0.03) and CEA (72% vs. 47%, P = 0.004). The median time to disease progression in the liver was significantly longer for patients receiving SIR-Spheres in comparison to patients receiving HAC alone when measured by either tumor areas (9.7 vs. 15.9 months, P = 0.001), tumor volumes (7.6 vs. 12.0 months, P = 0.04) or CEA (5.7 vs. 6.7 months, P = 0.06). The one, two, three and five-year survival for patients receiving SIR-Spheres was 72%, 39%, 17% and 3.5%, compared to 68%, 29%, 6.5% and 0% for HAC alone. Cox regression analysis suggests an improvement in survival for patients treated with SIR-Spheres who survive more than 15 months (P = 0.06). There was no increase in grade 3-4 treatment related toxicity and no loss of quality of life for patients receiving SIR-Spheres in comparison to patients receiving HAC alone. CONCLUSION: The combination of a single injection of SIR-Spheres plus HAC is substantially more effective in increasing tumor responses and progression free survival than the same regimen of HAC alone.

Adenocarcinoma↗

Expression of the sodium iodide symporter and thyroglobulin genes are reduced in papillary thyroid cancer.

Altered expression of the gene encoding the sodium iodine symporter (NIS) may be an important factor that leads to the reduced iodine accumulation characteristic of most benign and malignant thyroid nodules. Both up- and down-regulation of NIS gene expression have been reported in thyroid cancer using several different methods. The goal of the present study was to accurately identify alterations in NIS gene expression in benign and malignant thyroid nodules using an accurate real-time quantitative RT-PCR assay system. Total RNA was prepared from 18 benign thyroid nodules, 20 papillary thyroid cancers, and 23 normal thyroid samples from 38 subjects. Quantitative RT-PCR was used to measure NIS and thyroglobulin (TG) mRNA expression in normal thyroid tissue and in each nodular tissue sample. Papillary thyroid cancer samples had significantly lower NIS mRNA expression (72 +/- 41 picogram equivalents [pg Eq]), than did benign nodules (829 +/- 385 pg Eq), or normal tissues (1907 +/- 868 pg Eq, P = 0.04). Most important, in the paired samples, NIS gene expression was decreased in each papillary thyroid cancer compared with normal tissue (69% median decrease; range, 40-96%; P = .013). Eleven of the 12 benign nodules also demonstrated lower NIS gene expression than the normal tissue (49% decrease; range, 2-96%; P = .04). Analysis of the paired samples demonstrated that Tg mRNA expression was significantly lower in each of the thyroid cancer samples than in corresponding normal tissue (759 +/- 245 pg Eq vs. 1854 +/- 542 pg Eq, P = .03). We have demonstrated a significant decrement in NIS gene expression in all papillary thyroid cancers and in over 90% of benign nodules examined compared with adjacent normal thyroid tissue, using a highly accurate quantitative RT-PCR technique. Similarly, thyroid cancers demonstrated significantly lower TG mRNA expression than corresponding normal thyroid. Reduced NIS expression may be an important factor in the impairment of iodine-concentrating ability of neoplastic thyroid tissues.

Antisense Elements (Genetics)↗

Waveform optimization for internal atrial defibrillation: effects of waveform rounding, phase duration, and voltage swing.

The aim of this study was to compare the efficacy of internal atrial defibrillation by conventional truncated exponential biphasic waveforms with and without waveform rounding (1-2 phases) and to determine optimal duration for this novel double rounded waveform. Atrial fibrillation, induced by rapid electrical stimulation, was converted by internal shocks through defibrillation catheters (lateral right atrium and coronary sinus) in anesthetised sheep. Rounding the leading edges of the conventional biphasic waveform (Ventritex HVS-02; settings 100/-50 V, 150/-70 V, and 200/-100 V; n = 8) reduced delivered peak and trough voltages, currents, and energy (by > or = 21 %, P < 0.001; for double (both phases) rounded) without decreasing cardioversion success. At 100/-50 V the efficacy of single (first phase) rounded (53 +/- 13%; mean +/- SEM) and double rounded (59 +/- 11%) shocks was similar to the conventional waveform (56 +/- 14%). Double rounded waveform (phase durations 1-20 ms) efficacy was optimum at 6-10 ms phase duration (100% success at 10-ms phase duration; 1.52 +/- 0.04 J delivered energy; n = 6). Successful cardioversion by conventional, single rounded, and double rounded biphasic waveforms (duration 6 ms each phase), conventional monophasic, rounded monophasic (duration 12 ms), and a damped sine waveform correlated strongly with peak-to-trough voltage swing within the waveform (r = 0.882; P < 0.01; n = 8). For internal atrial defibrillation, rounding both phases of the conventional biphasic waveforms, the double rounded waveform, permits similar efficacy to the conventional truncated exponential biphasic waveform at reduced peak voltage, current, and delivered energy. Optimum phase duration is 6-10 ms (tested range 1-20 ms).

Animals↗

Vancomycin-resistant enterococci colonization in patients at seven hemodialysis centers.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are increasing in prevalence at many institutions, and are often reported in dialysis patients. We studied the prevalence of and risk factors for VRE at seven outpatient hemodialysis centers (three in Baltimore, MD, USA, and four in Richmond, VA, USA). METHODS: Rectal or stool cultures were performed on consenting hemodialysis patients during December 1997 to April 1998. Consenting patients were recultured during May to July 1998 (median 120 days later). Clinical and laboratory data and functional status (1 to 10 scale: 1, normal function; 9, home attendant, not totally disabled; 10, disabled, living at home) were recorded. RESULTS: Of 478 cultures performed, 20 (4.2%) were positive for VRE. Among the seven centers, the prevalence of VRE-positive cultures varied from 1.0 to 7.9%. Independently significant risk factors for a VRE-positive culture were a functional score of 9 to 10 (odds ratio 6.9, P < 0.001), antimicrobial receipt within 90 days before culture (odds ratio 6.1, P < 0.001), and a history of injection drug use (odds ratio 5.4, P = 0.004). CONCLUSIONS: VRE-colonized patients were present at all seven participating centers, suggesting that careful infection-control precautions should be used at all centers to limit transmission. In agreement with previous studies, VRE colonization was more frequent in patients who had received antimicrobial agents recently, underscoring the importance of judicious antimicrobial use in limiting selection for this potential pathogen.

Cross Infection↗

A prospective study of vascular access infections at seven outpatient hemodialysis centers.

Vascular access infections are a major cause of morbidity and mortality in hemodialysis patients, and the use of antimicrobials to treat such infections contributes to the emergence and spread of antimicrobial-resistant bacteria. To determine the incidence of and risk factors for vascular access infections, we studied hemodialysis patients at 7 outpatient dialysis centers (4 in Richmond, VA, and 3 in Baltimore, MD) during December 1997 to July 1998. Vascular access infections were defined as local signs (pus or redness) at the vascular access site or a positive blood culture with no known source other than the vascular access; and hospitalization or receipt of an intravenous (IV) antimicrobial. A total of 796 patients were followed for 4,134 patient-months. The vascular access infection rate was 3.5/100 patient-months, ie, patients had a 3.5% risk of infection each month. Independent risk factors were the specific dialysis unit where the patient was treated (relative hazard varying from 1.0 to 4.1 among the 7 centers), catheter access (relative hazard, 2.1 v implanted access), albumin level (relative hazard, 2.4 for lowest v highest quartile), urea reduction ratio (relative hazard, 2.2 for lowest v highest quartile), and hospitalizations during the previous 90 days (relative hazard, 4.9 for >/=6 v zero hospitalizations). These data confirm that vascular access infections are common in hemodialysis patients and that infection rates differ substantially among different centers. Catheter use should be minimized to reduce these infections. Additionally, the possibility that improved serum albumin and urea reduction ratio could reduce vascular access infections should be evaluated.

Aged↗

Presence and usability in shared space virtual conferencing: a participatory design study.

The use of teleconferencing as an alternative to taking part in expensive or impractical traditional meetings is becoming more and more popular. However, there are limitations to both audio and video conferencing, such as lack of presence and involvement. These can potentially be avoided by the use of virtual shared space conferencing. This paper describes a three-phase study intended to investigate the issues of presence and usability with respect to this alternative form of conferencing. The first phase involved informal tests to establish a suitable starting point for the second phase, which employed a participatory design methodology whereby users of a prototype system contributed to its development toward an optimally usable and well-featured design, both for the meeting environment and for the user interface to it. The third phase involved further user trials to assess and refine the conclusions indicated by the second phase. The results of the study indicate a number of requirements for optimal design of shared space conferencing systems. These requirements include (1) the need to be selective about the degree of realism in different aspects of the system, (2) the importance of view control and avatar animation in support of talker identification, (3) the desire of users for flexibility and freedom with regard to turn-taking and gesture control, and (4) the benefits of symbolic acting when certain important considerations for its implementation are respected. Finally, the results also show that, following a short period of user habituation, shared space conferencing can induce a strong sense of involvement and presence for users.

Communication↗

Women and coronary heart disease.

Coronary heart disease (CHD) is the leading cause of death in men and women in the United States. The incidence of CHD during midlife is lower in women than men, but the gap narrows with each decade. Because women have a longer life span than men, the absolute numbers of CHD deaths are roughly equal. Effective diagnosis of CHD in women requires the recognition of gender differences in presentation and pathogenesis. Women present with atypical symptoms and are less likely to have adequate primary prevention. This article discusses the differences between men and women in CHD and examines the assessment, diagnosis, and clinical management of CHD in women.

Clinical Trials as Topic↗

Evaluation of a latex agglutination kit (Virogen Rotatest) for detection of bovine rotavirus in fecal samples.

The performance of the Virogen Rotatest latex agglutination test (LAT) was evaluated for detection of bovine rotavirus antigen. Sixty-three fecal samples from diarrheic calves were collected from November 1999 to May 2000 and screened by LAT, the Rotazyme II enzyme-linked immunosorbent assay (ELISA), and virus isolation (VI) followed by an anti-rotavirus fluorescent-antibody (FA) test to detect the presence of group A rotavirus antigen. Of the 63 samples screened by VI-FA, 33 (58%) tested positive for rotavirus antigen. When the results from the LAT were compared to those from VI-FA, the "gold standard" for detection of bovine rotavirus in fecal samples, the sensitivity and specificity were found to be 87.8 and 73.3%, respectively. Latex agglutination compared with ELISA (the reference method) showed 100% sensitivity and 96.3% specificity, and when ELISA was compared with VI, the sensitivity was 84.8% and the specificity was 73.3%. Latex agglutination is easy to perform in a short time and does not require expensive equipment or skilled personnel, and the reagents have long shelf lives. These factors make the LAT suitable and highly efficient for use in a clinical laboratory as a rapid screening test for bovine rotavirus.

Animals↗

Effect of power Doppler and digital subtraction techniques on the comparison of myocardial contrast echocardiography with SPECT.

OBJECTIVE: To compare the accuracy and feasibility of harmonic power Doppler and digitally subtracted colour coded grey scale imaging for the assessment of perfusion defect severity by single photon emission computed tomography (SPECT) in an unselected group of patients. DESIGN: Cohort study. SETTING: Regional cardiothoracic unit. PATIENTS: 49 patients (mean (SD) age 61 (11) years; 27 women, 22 men) with known or suspected coronary artery disease were studied with simultaneous myocardial contrast echo (MCE) and SPECT after standard dipyridamole stress. MAIN OUTCOME MEASURES: Regional myocardial perfusion by SPECT, performed with (99m)Tc tetrafosmin, scored qualitatively and also quantitated as per cent maximum activity. RESULTS: Normal perfusion was identified by SPECT in 225 of 270 segments (83%). Contrast echo images were interpretable in 92% of patients. The proportion of normal MCE by grey scale, subtracted, and power Doppler techniques were respectively 76%, 74%, and 88% (p < 0.05) at > 80% of maximum counts, compared with 65%, 69%, and 61% at < 60% of maximum counts. For each technique, specificity was lowest in the lateral wall, although power Doppler was the least affected. Grey scale and subtraction techniques were least accurate in the septal wall, but power Doppler showed particular problems in the apex. On a per patient analysis, the sensitivity was 67%, 75%, and 83% for detection of coronary artery disease using grey scale, colour coded, and power Doppler, respectively, with a significant difference between power Doppler and grey scale only (p < 0.05). Specificity was also the highest for power Doppler, at 55%, but not significantly different from subtracted colour coded images. CONCLUSIONS: Myocardial contrast echo using harmonic power Doppler has greater accuracy than with grey scale imaging and digital subtraction. However, power Doppler appears to be less sensitive for mild perfusion defects.

Aged↗

A multicenter study of bacterial vaginosis in women with or at risk for human immunodeficiency virus infection.

BACKGROUND: Bacterial vaginosis is a common gynecologic infection that has been associated with a variety of gynecologic and obstetric complications, including pelvic inflammatory disease, postabortal infection and premature delivery. Recent studies suggest that bacterial vaginosis may increase a woman's risk for human immunodeficiency virus (HIV). We undertook this study to assess whether the prevalence and characteristics of bacterial vaginosis differed according to HIV status in high-risk US women. METHODS: Prevalence of bacterial vaginosis was assessed by Gram's stain and clinical criteria for 854 HIV-infected and 434 HIV-uninfected women enrolled in the HIV Epidemiology Research (HER) Study. Multiple logistic regression techniques were used to determine whether HIV infection independently predicted bacterial vaginosis. RESULTS: Almost half (46%) the women had bacterial vaginosis by Gram's stain. The prevalence of bacterial vaginosis was 47% in the HIV-positive women compared with 44% in the HIV-negative women; this difference was not statistically significant (p = 0.36). After adjustment for other covariates, HIV-positive women were more likely than HIV-negative women to have bacterial vaginosis (odds ratio (OR) 1.31; 95% confidence interval (CI) 1.01-1.70) by Gram's stain but not by clinical criteria (OR 1.16; CI 0.87-1.55). Among HIV-positive women, use of antiretroviral drugs was associated with a lower prevalence of bacterial vaginosis (adjusted OR 0.54; Cl 0.38-0.77). CONCLUSIONS: In this cross-sectional analysis of high-risk US women, HIV infection was positively correlated with bacterial vaginosis diagnosed by Gram's stain.

AIDS-Related Opportunistic Infections↗

Quality of life aspects of treatment options for localized and locally advanced prostate cancer.

Quality of life considerations are becoming increasingly important in prostate cancer management, particularly with the trend for patients to be diagnosed at an earlier age and at an earlier stage of disease. A rising serum prostate-specific antigen (PSA) level in the absence of symptoms can cause anxiety to many patients. Patients in this situation must weigh the benefits of treatment, such as delay in time to progression and increased time without pain, against the onset of adverse events that may affect quality of life. Traditionally, the active treatment options for locally advanced disease, following either new diagnosis or failure of treatment of primary curative intent, are radiotherapy and castration (medical or surgical). Radiotherapy may affect sexuality and bowel functioning, and castration is particularly associated with loss of libido and sexual dysfunction. Studies have shown that treatment-associated side effects extending over many years are of great concern to many patients. Therefore, for treatments with similar outcomes in terms of survival or time to progression, there is good reason to consider introducing new measures of efficacy based on quality of life endpoints. Data from two large studies of bicalutamide ('Casodex') therapy in patients with locally advanced prostate cancer show that this non-steroidal antiandrogen is not only associated with comparable survival outcomes but significant health-related quality of life benefits, compared with castration. In addition, a large early prostate cancer trial has demonstrated that bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, significantly reduces the risk of disease progression in patients with localized or locally advanced prostate cancer. Moreover, bicalutamide treatment was associated with fewer adverse events relating to sexual function. The risk of treatment-related side effects or influence on the total quality of life must be considered carefully for each individual patient in order to assess the most appropriate treatment option.

Androgen Antagonists↗

Antisense inhibition of macrophage inflammatory protein 1-alpha blocks bone destruction in a model of myeloma bone disease.

We recently identified macrophage inflammatory protein 1-alpha (MIP-1alpha) as a factor produced by multiple myeloma (MM) cells that may be responsible for the bone destruction in MM (1). To investigate the role of MIP-1alpha in MM bone disease in vivo, the human MM-derived cell line ARH was stably transfected with an antisense construct to MIP-1alpha (AS-ARH) and tested for its capacity to induce MM bone disease in SCID mice. Human MIP-1alpha levels in marrow plasma from AS-ARH mice were markedly decreased compared with controls treated with ARH cells transfected with empty vector (EV-ARH). Mice treated with AS-ARH cells lived longer than controls and, unlike the controls, they showed no radiologically identifiable lytic lesions. Histomorphometric analysis demonstrated that osteoclasts (OCLs) per square millimeter of bone and OCLs per millimeter of bone surface of AS-ARH mice were significantly less than in EV-ARH mice, and the percentage of tumors per total bone area was also significantly decreased. AS-ARH cells demonstrated decreased adherence to marrow stromal cells, due to reduced expression of the alpha(5)beta(1) integrin and diminished homing capacity and survival. These data support an important role for MIP-1alpha in cell homing, survival, and bone destruction in MM.

Animals↗