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Biomedical subjects

M S Hansen

Publications and source records attributed to M S Hansen.

At least 19 recordsLinked to original sources
PubMed2003

Prognostic importance of the oxidized product of catecholamines, adrenolutin, in patients with severe heart failure.

OBJECTIVES: The purpose of this study was to assess whether adrenolutin, the inert product of the highly reactive molecules aminochromes, is increased in severe chronic heart failure and whether it is associated with a poor prognosis. BACKGROUND: Experimental evidence suggests that oxidative products of catecholamines, aminochromes, are more cardiotoxic than unoxidized catecholamines and may be increased in heart failure. METHODS: Adrenolutin was measured at baseline and at 1 and 3 months in 263 patients with chronic New York Heart Association class III or IV heart failure and a left ventricular ejection fraction of 22% +/- 7%. Adrenolutin levels were compared with normal levels, and their relation to prognosis was evaluated. RESULTS: Baseline adrenolutin was increased (55 +/- 90 pg/mL vs 8.4 +/- 9.1 pg/mL for control, P <.02) and remained increased at 1 month (49 +/- 65 pg/mL). During a mean follow-up of 309 +/- 148 days (22-609 days), 57 patients died. Baseline adrenolutin levels correlated with mortality rates by univariate and multivariate analyses (relative risk 1.06, 95% CI 1.01-1.10 for each 17.9-pg/mL rise, P =.032). Left ventricular ejection fraction (P =.013) and New York Heart Association class (P =.009) were the only other variables associated with survival. Age, sex, plasma creatinine, plasma N-terminal atrial natriuretic peptide, and plasma norepinephrine levels were not retained in our model. Adrenolutin levels 1 month after random assignment were not significantly correlated with total mortality rate (P =.061) but were correlated with mortality rate from low output (relative risk 1.14, 95% CI 1.06-1.22, P =.002). CONCLUSIONS: Plasma adrenolutin is increased in patients with heart failure and correlates with a poor prognosis independent of other important predictors of survival. This finding has potentially important pathophysiologic, prognostic, and therapeutic implications.

Aged↗
PubMed2003

Neurohormones and oxidative stress in nonischemic cardiomyopathy: relationship to survival and the effect of treatment with amlodipine.

OBJECTIVES: The purpose of this study was to assess the effects of amlodipine on neurohormones and oxidative stress in nonischemic cardiomyopathy, and determine the relationship between baseline and posttreatment levels of these markers with survival. BACKGROUND: Neurohormones and oxidative stress are important in the pathophysiology of heart failure. Calcium-channel blockers are associated with poor outcomes in patients with heart failure, in part due to neurohormonal activation. In contrast, amlodipine, a second-generation dihydropyridine, has a more favorable clinical profile. METHODS: In the Prospective Randomized Amlodipine Survival Evaluation 2 (PRAISE-2) trial, a subset of 181 patients with nonischemic cardiomyopathy were randomized to amlodipine (10 mg/day) or placebo. Blood samples were evaluated at baseline, 2 weeks and 26 weeks for norepinephrine, epinephrine, angiotensin II, dopamine, N-terminal pro-atrial natriuretic peptide (Nt-pro-ANP), brain natriuretic peptide (BNP), adrenolutin and malondialdehyde. RESULTS: There was no difference in levels of neurohormones or oxidative stress markers between the amlodipine and placebo groups at the different times. Both Nt-pro-ANP and BNP decreased at 2 weeks and at 26 weeks. Baseline Nt-pro-ANP correlated with survival in multivariate analysis (P =.001). A strong relationship was found between a reduction in BNP at 26 weeks and survival, with a hazard ratio of 0.153 (95% CI 0.051-0.461, P =.017). No relationship was found between markers of oxidative stress and survival. CONCLUSIONS: We conclude that amlodipine does not affect circulating neurohormones and oxidative stress markers in patients with nonischemic cardiomyopathy treated with angiotensin-converting enzyme inhibitors, digoxin and diuretics. In addition, low circulating Nt-pro-ANP and a reduction in BNP over time confers a good prognosis.

Amlodipine↗
PubMed2003

Mental illness in new neurological patients.

OBJECTIVE: To determine the prevalence of psychiatric disorders in new neurological inpatients and outpatients, and examine whether they are recognised, treated, or referred to psychiatric consultation. METHODS: 198 consecutive patients referred for the first time to a neurologist were studied using a two phase design. ICD-10 psychiatric diagnoses were established by means of the SCAN (Schedules for Clinical Assessment in Neuropsychiatry). RESULTS: The overall prevalence of current mental disorders was 55.1% (95% CI: 46.2 to 63.8), and 65.0% (95% CI: 56.1 to 73.0) had at least once in their life had a psychiatric disorder. The most frequent current diagnoses were somatoform disorders (33.8%, (95% CI: 25.9 to 42.7%)), followed by phobias (21.8%; 95% CI: 15.3 to 30.0), substance use disorders (13.3%; 95% CI: 8.3 to 20.6) and depression/dysthymia (14.4; 95% CI: 9.1 to 21.8). The psychiatric morbidity markedly declined with increasing age. Compared with 63.5% of the women, 46.4% of the men had a psychiatric disorder. Substance use disorders were more frequent in men than women (p=0.002). Patients with a psychiatric disorder were more frequently seen in the outpatients' clinic than those without. The neurologists detected 14%-40% of the cases, 16.9% were in treatment, and only 4.6% were referred to mental health care. CONCLUSION: Psychiatric disorders, in particular somatoform disorders, are extremely common in neurological patients, especially in young and middle aged patients, outpatients, and women. The results call for more research on mental illness' impact on care and outcome in neurological patients.

Ambulatory Care↗
PubMed2001

[Antithrombotic treatment of atrial fibrillation in hospital].

BACKGROUND: In clinical guidelines regarding atrial fibrillation, oral anticoagulation is recommended for patients over the age of 65 or with additional risk factors. The aim of the present study was to investigate how these recommendations are followed in clinical practice. MATERIAL AND METHODS: A retrospective study was conducted among patients hospitalized for atrial fibrillation at Tromsø University Hospital from 1995 to 1998. Data were obtained from hospital files. RESULTS: 362 patients with atrial fibrillation (57% men), mean age 68.4 years (range 24-96), were included. 23.5% had their first atrial fibrillation event. 224 (62%) patients experienced successful cardioversion during hospitalization(s), while 138 (38%) were discharged from hospital with chronic atrial fibrillation. 97 (70%) of these patients were given warfarin at discharge. Previous stroke and atrial fibrillation were significant predictors for warfarin prescription. Prescription did not increase with age. 28 (20%) of patients with chronic atrial fibrillation received acetylsalicylic acid, while 16 (12%) were not given antithrombotic treatment. INTERPRETATION: This study indicates a high degree of implementation of guidelines for antithrombotic treatment of patients with chronic atrial fibrillation in hospital practice.

Adult↗
PubMed2001

Mental disorders among internal medical inpatients: prevalence, detection, and treatment status.

OBJECTIVE: To determine the prevalence of ICD-10 mental disorders among internal medical inpatients, the relation between mental disorder, age, and gender, and the recognition and referral of the disordered patients. METHOD: 294 consecutive medical inpatients were examined with a two-phase design using the SCAN (Schedules for Clinical Assessment in Neuropsychiatry) for ICD-10 psychiatric diagnoses. Information from questionnaires and interviews with patients, doctors, nurses, and from medical records. RESULTS: The prevalence of current mental disorders was 38.7%, being heavily increased in young patients. Main diagnoses were somatoform disorders (17.6%), phobias (12.9%), substance use disorders (10.9%), and depression (8.3%). Psychiatric consultations were very few. About 38-56% of the cases were recognized by medical doctors and nurses, and only about 20% were in mental health treatment. CONCLUSION: The prevalence of mental disorders among internal medical inpatients is high and increased in young patients and women. Detection and referral are low, and few are treated.

Adult↗
PubMed2001

A quantitative assay for HIV DNA integration in vivo.

Early steps of infection by HIV-1 involve entry of the viral core into cells, reverse transcription to form the linear viral DNA, and integration of that DNA into a chromosome of the host. The unintegrated DNA can also follow non-productive pathways, in which it is circularized by recombination between DNA long-terminal repeats (LTRs), circularized by ligation of the DNA ends or degraded. Here we report quantitative methods that monitor formation of reverse transcription products, two-LTR circles and integrated proviruses. The integration assay employs a novel quantitative form of Alu-PCR that should be generally applicable to studies of integrating viruses and gene transfer vectors.

Anti-HIV Agents↗
PubMed2000

[Magnetic resonance imaging as a marker of inflammation, destruction and prognosis in rheumatoid arthritis wrists].

To evaluate MRI for assessment of inflammation, destruction and prognosis in rheumatoid arthritis (RA), 26 RA patients, randomized to disease-modifying anti-rheumatic drug (DMARD) therapy alone or in combination with oral prednisolone, were followed for one year with contrast-enhanced MRI of the dominant wrist (months zero, three, six and 12), conventional radiography and clinical and biochemical examinations. Significant synovial membrane volume reductions were observed in both groups, earliest in the DMARD + prednisolone group. The rate of erosive progression on MRI was highly correlated with baseline and area-under-curve (AUC)-values of synovial membrane volume, but not with baseline or AUC-values of local or global clinical or biochemical parameters, nor with +/- prednisolone. MRI was more sensitive than radiography as regards detection of progressive bone destruction (22 versus 12 new bone erosions). MRI may prove valuable as marker of joint disease activity and destruction and, perhaps, prognosis in RA.

Adult↗
PubMed2000

Going virtual with quicktime VR: new methods and standardized tools for interactive dynamic visualization of anatomical structures.

Continuing evolution of computer-based multimedia technologies has produced QuickTime, a multiplatform digital media standard that is supported by stand-alone commercial programs and World Wide Web browsers. While its core functions might be most commonly employed for production and delivery of conventional video programs (e.g., lecture videos), additional QuickTime VR "virtual reality" features can be used to produce photorealistic, interactive "non-linear movies" of anatomical structures ranging in size from microscopic through gross anatomic. But what is really included in QuickTime VR and how can it be easily used to produce novel and innovative visualizations for education and research? This tutorial introduces the QuickTime multimedia environment, its QuickTime VR extensions, basic linear and non-linear digital video technologies, image acquisition, and other specialized QuickTime VR production methods. Four separate practical applications are presented for light and electron microscopy, dissectable preserved specimens, and explorable functional anatomy in magnetic resonance cinegrams.

Anatomy, Cross-Sectional↗
PubMed2000

The reliability of balance tests performed on the kinesthetic ability trainer (KAT 2000).

The Kinesthetic Ability Trainer (KAT 2000) is a balance platform designed for training and functional testing of the neuromuscular control system. Forty healthy and sports-active persons were tested and 1 month later retested to investigate the reliability of the KAT 2000 testing "one-leg static balance" and "two-leg dynamic balance". A significant improvement at retesting on the same day was seen in both tests; furthermore the dynamic test result improved significantly with retesting 1 month later. The data obtained made it possible to calculate the 95% confidence limits for an unchanged test result for a single person and a group of persons. The results show a clear learning effect when the persons are retested, especially in the dynamic test. The KAT 2000 can be used as a tool for testing groups of persons both in short- and long-term studies, but it cannot be used for testing single persons due to the great variance in the test results. Further investigations involving injured persons are needed to determine the range of improvement after intervention.

Adolescent↗
PubMed2000

Retroviral cDNA integration: stimulation by HMG I family proteins.

To replicate, a retrovirus must synthesize a cDNA copy of the viral RNA genome and integrate that cDNA into a chromosome of the host. We have investigated the role of a host cell cofactor, HMG I(Y) protein, in integration of human immunodeficiency virus type 1 (HIV-1) and Moloney murine leukemia virus (MoMLV) cDNA. Previously we reported that HMG I(Y) cofractionates with HIV-1 preintegration complexes (PICs) isolated from freshly infected cells. PICs depleted of required components by treatment with high concentrations of salt could be reconstituted by addition of purified HMG I(Y) in vitro. Here we report studies using immunoprecipitation that indicate that HMG I(Y) is associated with MoMLV preintegration complexes. In mechanistic studies, we show for both HIV-1 and MoMLV that each HMG I(Y) monomer must contain multiple DNA binding domains to stimulate integration by HMG I(Y)-depleted PICs. We also find that HMG I(Y) can condense model HIV-1 or MoMLV cDNA in vitro as measured by stimulation of intermolecular ligation. This reaction, like reconstitution of integration, depends on the presence of multiple DNA binding domains in each HMG I(Y) monomer. These data suggest that binding of multivalent HMG I(Y) monomers to multiple cDNA sites compacts retroviral cDNA, thereby promoting formation of active integrase-cDNA complexes.

DNA, Complementary↗
PubMed1999

Lamellarin alpha 20-sulfate, an inhibitor of HIV-1 integrase active against HIV-1 virus in cell culture.

HIV-1 integrase is an attractive target for anti-retroviral chemotherapy, but to date no clinically useful inhibitors have been developed. We have screened diverse marine natural products for compounds active against integrase in vitro and found a series of ascidian alkaloids, the lamellarins, that show selective inhibition. A new member of the family named lamellarin alpha 20-sulfate (1), the structure of which was determined from spectroscopic data, displayed the most favorable therapeutic index. The site of action of lamellarin alpha 20-sulfate on the integrase protein was mapped by testing activity against deletion mutants of integrase. Inhibition of isolated catalytic domain was detectable though weaker than inhibition of full length integrase; possibly lamellarin alpha 20-sulfate binds a site composed of multiple integrase domains. Lamellarin alpha 20-sulfate also inhibited integration in vitro by authentic HIV-1 replication intermediates isolated from infected cells. Lamellarin alpha 20-sulfate was tested against wild type HIV using the MAGI indicator cell assay and found to inhibit early steps of HIV replication. To clarify the inhibitor target, we tested inhibition against an HIV-based retroviral vector bearing a different viral envelope. Inhibition was observed, indicating that the HIV envelope cannot be the sole target of lamellarin alpha 20-sulfate in cell culture. In addition, these single round tests rule out action against viral assembly or budding. These findings provide a new class of compounds for potential development of clinically useful integrase inhibitors.

Animals↗
PubMed1999

Integration complexes derived from HIV vectors for rapid assays in vitro.

Of three enzymes encoded by HIV-reverse transcriptase, protease, and integrase-only the first two have been exploited clinically as inhibitor targets. Efforts to develop inhibitors of purified integrase protein have yielded many compounds, but none with clinical utility. A different source of integration activity for studies in vitro is provided by replication intermediates isolated from HIV-infected cells. These preintegration complexes (PICs) can direct integration of the endogenously synthesized viral cDNA into an added target DNA in vitro. Despite their authentic activities, assays of PICs have not been widely used due to technical obstacles, particularly the requirement for handling large amounts of infectious HIV. Here, we describe greatly improved methods for producing PICs using HIV-based vectors that are capable of establishing an integrated provirus but not a spreading infection. We also report the development of a PIC integration assay using DNA-coated microtiter plates, which speeds assays of PIC integration in vitro. We used this method to screen a library of chemicals related to known integrase inhibitors and found a new compound, quinalizarin sulfate, that displayed enhanced activity against PICs.

Anti-HIV Agents↗
PubMed1997

Human immunodeficiency virus type 2 preintegration complexes: activities in vitro and response to inhibitors.

We have established an assay for the function of preintegration complexes (PICs) of human immunodeficiency virus type 2 (HIV-2) to investigate the integration mechanism and to develop additional methods for screening candidate integration inhibitors. We partially purified HIV-2 PICs and found that they were competent to integrate viral cDNA into target DNA in vitro. Analysis of the structure of integration products on Southern blots revealed forms consistent with those expected for authentic integration products and circular forms containing one and two long terminal repeats. To determine whether in vitro products had the detailed structure expected of integration products formed in vivo, we recovered product molecules and analyzed junctions between viral DNA and target DNA. In the integration junctions of all nine molecules examined, we observed the 5-bp duplication of target sequence characteristic of integration in vivo. We investigated the possible role in integration of Vpx, a protein present in HIV-2 but not HIV-1 and known to be present in viral cores. Although association of Vpx with viral cDNA was detectable, our studies revealed no obvious role of Vpx in integration since the activities of PICs from Vpx- virions were indistinguishable from those of wild type. We have also investigated the use of HIV-2 PICs as tools to screen candidate HIV inhibitors. Assays with HIV-2 PICs, like assays with HIV-1 PICs, were less sensitive to many small molecule inhibitors than were reactions with purified integrase only. Comparing results of assays with PICs from HIV-1 and HIV-2 may be particularly useful, since inhibitors active against both may be more widely useful and less vulnerable to escape mutants.

Anti-HIV Agents↗
PubMed1996

Clozapine eligibility: the effect of stringent criteria on ethnic, gender and age subgroups of schizophrenic patients.

1. The purpose of this retrospective chart review study was to determine whether broad and stringent criteria differentially impact clozapine eligibility in ethnic, gender, and age subgroups of schizophrenic patients. 2. 505 patients charts were selected from a random cluster sample of mental health patients known to the city and county of San Francisco. Information related to clozapine eligibility was abstracted by trained non-clinical personnel. The impact of subgroup membership on eligibility was examined using logistic regression procedures. 3. Even under the broadest interpretation of FDA requirements for clozapine use, Asian patients were less likely to be eligible, since fewer Asian patients met clozapine treatment requirements. Under more stringent eligibility criteria, older patients were more likely to be excluded from eligibility when TD does not automatically satisfy treatment criteria, and younger patients were more likely to lose eligibility if the number of required adequate medication trials increases to three. 4. Broad eligibility criteria tend to differentially exclude Asian patients while more stringent criteria differentially exclude younger and older patients.

Adolescent↗
PubMed1995

Unexpected hepatotoxicity after priming and treatment with molgramostim (rhGM-CSF) in acute myeloid leukemia during induction chemotherapy.

The effect of supplementing induction chemotherapy with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was studied in a randomized trial of 18 patients with acute myeloid leukemia (AML). Ten patients received rhGM-CSF, starting on day one to three before chemotherapy and continued for a maximum of 21 days after the start of induction treatment. Unexpected adverse effects of rhGM-CSF and chemotherapy combination included a transient decline in plasma coagulation factors II, VII, and X (5 of 5 patients) and an increased transcapillary escape rate of albumin (in 3 of 3 patients tested). The decline in coagulation factors was prevented in subsequent patients by prophylactic treatment with vitamin K. Although the small number of patients studied may not allow a definite conclusion, caution with regard to liver function should be shown in combining rhGM-CSF with intensive chemotherapy.

Adult↗