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Biomedical subjects

D Nielsen

Publications and source records attributed to D Nielsen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Rehabilitation of patients with chronic obstructive pulmonary disease. Exercise twice a week is not sufficient!

Several studies of chronic obstructive pulmonary disease (COPD) have shown that pulmonary rehabilitation, consisting of at least three training sessions a week, improves exercise performance and health status. This study investigates feasibility, effect and economic aspects of a rehabilitation programme consisting of two sessions a week for 8 weeks. Twenty-four patients with moderate COPD were randomized to rehabilitation and 21 to placebo. Patients were assigned to an 8-week programme of exercise plus education (Exercise group) or conventional community care (Placebo group). The rehabilitation program was carried out in a hospital outpatient setting and consisted of 16 h exercise and 13.5 h of education. The exercise group received physiotherapy and education twice a week. Seven patients did not complete the programme. The characteristics of the 38 COPD-patients at baseline were the following: (mean +/- SD) forced expiratory volume in 1 sec (FEV1) 1.1+/-0.4 1 (47% of predicted), 6-min walking distance (6MWD) 413+/-75 m, score of St. George's Respiratory Questionnaire (SGRQ) 44+/-21. Health-status, assessed by SGRQ and The Psychological General Well-being (PGWB) Index, did not improve. Rehabilitation resulted in an insignificant improvement in the 6MWD [29 m (95% confidence interval: -8 -66 m)]. We conclude that a rehabilitation program consisting of exercise and education twice a week for 8 weeks had no effect on exercise performance and well being in patients with moderate COPD.

Ambulatory Care↗
PubMed2000

Deaths due to disease of seafarers on board Singapore ships.

Based on records kept in the Singapore Mercantile Marine Office, the paper presents the results of a study on deaths due to disease of seafarers on board Singapore ships. Out of a total of 373 deaths, altogether 69 fatalities were attributed to diseases. More than 65% (n=45) of theses deaths were due to circulatory diseases commonly associated with life-style factors, but only 24 cases had a specific and 9 cases had an unspecific diagnosis confirmed by a medical, practitioner. A total of 32 seafarers (46.4%) died of a sudden death and were found dead by their shipmates whereas 17 seafarers (24.6%) died on board after a short illness. In only two cases was it reported that Radio Medical advice had been sought indicating either a lack of interest of the ship's management or a lack of knowledge or information on the availability of such services. Eight of the fatalities who died on board had seen a doctor and been declared fit to stay on board, pointing to deficiencies in the port medical services or pressures on port doctors to avoid a costly repatriation. The mean annual mortality rate for deaths due to all causes was 26.5 per 10,000 seafarers and due to disease was 4.9 per 10,000 seafarers.

Cause of Death↗
PubMed1999

Novel tests for marker-disease association using the Collaborative Study on the Genetics of Alcoholism data.

We applied several novel tests for association and linkage in the presence of association to the Genetic Analysis Workshop 11 Problem 1 data set. Our analyses included a Hardy-Weinberg test for association between a marker and a disease susceptibility locus, a Bayesian transmission/disequilibrium test, and a Bayesian case-control test. Positive results for each of these methods require the presence of population association between the marker and a disease susceptibility locus.

Alcoholism↗
PubMed1999

Localization of the locus causing Spider Lamb Syndrome to the distal end of ovine Chromosome 6.

Spider Lamb Syndrome (SLS) is a semi-lethal congenital disorder, causing severe skeletal abnormalities in sheep. The syndrome has now been disseminated into several sheep breeds in the United States, Canada, and Australia. The mode of inheritance for SLS is autosomal recessive, making the identification and culling of carrier animals difficult due to their normal phenotype. Two large pedigrees segregating for the SLS mutation were established, and a genome scan with genetic markers from previously published genome maps of cattle and sheep was used to map the locus causing SLS. Genetic linkage between SLS and several microsatellite markers, OarJMP8, McM214, OarJMP12, and BL1038, was detected, thereby mapping the SLS locus to the telomeric end of ovine Chromosome (Chr) 6. Alignment of ovine Chr 6 with its evolutionary ortholog, human Chr 4, revealed a positional candidate gene, fibroblast growth factor receptor 3 (FGFR3).

Animal Diseases↗
PubMed1999

Identification of four variants in the tryptophan hydroxylase promoter and association to behavior.

One of the most replicated findings in biological psychiatry is the observation of lower 5-hydroxyindoleacetic acid concentrations, the major metabolite of serotonin, in the brain and cerebrospinal fluid of subjects with impulsive aggression. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin, however functional variants have not been reported from the coding sequence of this gene. Therefore, we screened the human TPH promoter (TPH-P) for genetic variants which could modulate TPH gene transcription. The TPH-P (2093 nucleotides) was screened for sequence variation by SSCP analysis of 260 individuals from Finnish, Italian, American Caucasian, and American Indian populations. Four common polymorphisms were identified: -7180T>G, -7065C>T, -6526A>G, and -5806G>T (designated as nucleotides upstream of the translation start site). In the Finns, the four polymorphisms had a minor allele frequency of 0.40 and in this population linkage disequilibrium between the four loci was complete. In the other populations the minor allele frequencies ranged from 0.40 to 0.45. TPH -6526A>G genotype was determined in 167 unrelated Finnish offenders and 153 controls previously studied for the TPH IVS7+779C>A polymorphism. A significant association was observed between -6526A>G and suicidality in the offenders. TPH -6526A>G and the previously reported intron seven polymorphism, TPH IVS7+779C>A, exhibited a normalised linkage disequilibrium of 0.89 in Finns. Normalized linkage disequilibrium was reduced in other populations, being 0.49 and 0.21 in Italians and American Indians, respectively. In conclusion, four TPH-P variants were identified which can be used for haplotype-based analysis to localize functional TPH alleles influencing behavior.

Adult↗
PubMed1999

Combined field block and i.p. instillation of ropivacaine for pain management after laparoscopic sterilization.

We have studied the effect of ropivacaine for combined port site and mesosalpinx infiltration, and peritoneal instillation on pain, nausea and vomiting after laparoscopic sterilization, in a double-blind, placebo-controlled study in 80 patients. The total dose of ropivacaine was 285 mg. All patients received intra- and postoperative NSAID in fixed doses. Abdominal and shoulder pain, nausea and vomiting were recorded during the first 8 h after operation and in a diary for 3 days. In the ropivacaine group, abdominal pain scores were lower during the first 4 h (P < 0.00001), additional use of morphine was less (P < 0.001) and fewer patients had nausea or vomiting during the first 72 h (five vs 14; P < 0.05). There were no signs of local anaesthetic toxicity.

Adult↗
PubMed1999

Combined epidural-spinal opioid-free anaesthesia and analgesia for hysterectomy.

Postoperative nausea and vomiting (PONV) are major problems after gynaecological surgery. We studied 40 patients undergoing total abdominal hysterectomy, allocated randomly to receive opioid-free epidural-spinal anaesthesia or general anaesthesia with continuous epidural bupivacaine 15 mg h-1 or continuous bupivacaine 10 mg h-1 with epidural morphine 0.2 mg h-1, respectively, for postoperative analgesia. Nausea, vomiting, pain and bowel function were scored on 4-point scales for 3 days. Patients undergoing general anaesthesia had significantly higher nausea and vomiting scores (P < 0.01) but significantly lower pain scores during rest (P < 0.05) and mobilization (P < 0.01). More patients undergoing general anaesthesia received antiemetics (13 vs five; P < 0.05), but fewer received supplementary opioids on the ward (eight vs 16; P < 0.05). We conclude that opioid-free epidural-spinal anaesthesia for hysterectomy caused less PONV, but with less effective analgesia compared with general anaesthesia with postoperative continuous epidural morphine and bupivacaine.

Adult↗
PubMed1999

Genetics of suicide in depression.

Evidence is mounting that genetic factors may be included in the many determinants of suicide. Clinical studies of psychiatric patients have suggested that risk of suicidal behavior is increased by the presence of family history of suicidality, a claim that is also supported by findings of twin and adoption studies. In addition, molecular genetic studies have reported polymorphisms in the tryptophan hydroxylase gene that is involved in the synthesis of serotonin. The genetic susceptibility to suicide, however, tends to affect individuals only in association with stress or psychiatric illness.

Adoption↗
PubMed1999

Loop diathermy or laser excisional conization for cervical intraepithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) can be managed by ablative or excisional procedures. We have compared the excision time, effectiveness, and safety of loop diathermy (loop) against laser conization. METHODS: In a prospective study in two hospital departments 222 women were randomized to loop or laser conization. Data were collected by questionnaires after operation and at two follow-up examinations. RESULTS: At department A (122 women), two physicians performed 27% of the loop and 35% of the laser excisions; at department B (100 women), the corresponding figures were 69% and 59%. Loop was quicker than laser conization in both departments (median 3-4 min versus 10-20 min), while laser conization was more time consuming in department A (median A/B = 20/10 min). Peroperative bleeding dominated during the laser procedure in both departments and complicated the loop procedure more frequently in department A. Postoperative bleeding occurred with equal frequency in the four groups (41.8%, 52.7%, 59.2%, 64.7%). At both departments, bleeding for more than two weeks was reported twice as often after laser conization (A:13.8%, B:24.2%), when compared to loop excision (A:7.1%, B:13.7%). Residual CIN was found in all of three re-conizations and in one of eight hysterectomy specimens. CONCLUSIONS: Loop was quicker than laser excision, per- and postoperative bleeding diminished, and the success rates were comparable. Physicians mastered Loop excision after a few attempts. However, the results improved, when performed by a restricted number of physicians. Histological incomplete excision indicates close colposcopic and cytologic follow-up to identify residual CIN.

Adult↗
PubMed1998

P-glycoprotein expression in Ehrlich ascites tumour cells after in vitro and in vivo selection with daunorubicin.

Fluctuation analysis experiments were performed to assess whether selection or induction determines expression of P-glycoprotein and resistance in the murine Ehrlich ascites tumour cell line (EHR2) after exposure to daunorubicin. Thirteen expanded populations of EHR2 cells were exposed to daunorubicin 7.5 x 10(-9) M or 10(-8) M for 2 weeks. Surviving clones were scored and propagated. Only clones exposed to daunorubicin 7.5 x 10(-9) M could be expanded for investigation. Drug resistance was assessed by the tetrazolium dye (MTT) cytotoxicity assay. Western blot was used for determination of P-glycoprotein. Compared with EHR2, the variant cells were 2.5- to 5.2-fold resistant to daunorubicin (mean 3.6-fold). P-glycoprotein was significantly increased in 11 of 25 clones (44%). Analysis of variance supported the hypothesis that spontaneous mutations conferred drug resistance in EHR2 cells exposed to daunorubicin 7.5 x 10(-9) M. At this level (5 log cell killing) of drug exposure, the mutation rate was estimated at 4.1 x 10(-6) per cell generation. In contrast, induction seemed to determine resistance in EHR2 cells in vitro exposed to daunorubicin 10(-8) M. The revertant EHR2/0.8/R was treated in vivo with daunorubicin for 24 h. After treatment, P-glycoprotein increased in EHR2/0.8/R (sevenfold) and the cell line developed resistance to daunorubicin (12-fold), suggesting that in EHR2/0.8/R the mdr1 gene was activated by induction. In conclusion, our study demonstrates that P-glycoprotein expression and daunorubicin resistance are primarily acquired by selection of spontaneously arising mutants. However, under certain conditions the mdr1 gene may be activated by induction.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer.

PURPOSE: To evaluate the influence of cumulative dose, dose-intensity, single-dose level, and schedule of epirubicin on the risk of developing congestive heart failure (CHF) in patients with advanced breast cancer. PATIENTS AND METHODS: Four hundred sixty-nine consecutive anthracyline-naive patients with metastatic breast cancer were included. Only patients with cardiac failure according to New York Heart Association (NYHA) function class II or more were recorded as having CHF. For each patient, the following were calculated: the cumulative dose of epirubicin, mean dose-intensity (cumulative dose of epirubicin/duration of treatment), and single-dose level (cumulative dose of epirubicin/number of injections). RESULTS: Thirty-four patients (7.2%) developed CHF. The cumulative risk of cardiotoxicity was 4% at 900 mg/m2 and increased exponentially to 15% at 1,000 mg/m2. Irradiation against the mediastinum and thoracic spine increased the risk of CHF (P=.025), but dose-intensity, single-dose level, and schedule had no influence on the risk of developing CHF. Age, previous adjuvant irradiation (to the left or right hemithorax), and previous chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF]) were not risk factors. The median time to onset of CHF following the last dose of epirubicin was 57 days (range, 0 to 853). Among patients with CHF, 13 (38.2%) died of cardiac failure. The median survival time for all patients with CHF was 162 days (range, 0 to +1,957). Previous irradiation directly against the heart increased the risk of death due to cardiac failure and decreased the median survival time to 125 days (range, 0 to 336). CONCLUSION: The present large retrospective study of 469 patients substantiates previous results concerning the cardiotoxicity of epirubicin. A significantly increasing risk of CHF in patients who receive cumulative doses greater than 950 mg/m2 was established. The future recommended maximum cumulative dose of epirubicin should be 900 mg/m2 in patients with metastatic breast cancer. Previous irradiation against the heart leads to an increased risk of developing CHF with an accelerated course to death, which indicates an additive cardiotoxic effect of irradiation and epirubicin.

Adult↗
PubMed1997

ATPase activity of P-glycoprotein related to emergence of drug resistance in Ehrlich ascites tumor cell lines.

We have characterized the ATPase activity of a sensitive and five progressively daunorubicin resistant Ehrlich ascites tumor cell lines passaged in mice. For the nine different modulators of drug resistance that we have studied, the ATPase activity first rose with the modulator concentration and then declined. We analyzed the ATPase activity profiles in terms of an activation constant and an inhibition constant for each of the nine drugs and six cell lines. In this series of cell lines, the drug-stimulatable ATPase activity was directly proportional to the amount of P-glycoprotein. Pumping of daunorubicin was also correlated with the amount of P-glycoprotein, except that, for a highly passaged line more daunorubicin was pumped than could be accounted for by the content of P-glycoprotein. Between the 12th and the 36th passage an additional source of resistance emerged, which was not correlated with P-glycoprotein. Pumping of daunorubicin was negatively correlated with the cell volume for the different lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Breaking bad news--experience and attitude of young physicians].

This survey reports the attitude among second year medical doctors towards giving patients bad news. The questionnaire contained a mixture of open and closed questions. The questionnaire was returned by 88/119 (74%). All doctors felt that a patient who suffers from a serious, incurable disease has the right to be told the diagnosis, 98% of the doctors had broken bad news-most of them had done it several times. More than 90% of the doctors judged that their knowledge concerning breaking bad news, communication and crisis- and grief-reactions was average or above, but less than 10% thought that their knowledge was adequate. All the responders wanted instructions on how to break bad news, but only 45% had received some.

Adult↗
PubMed1997

CO2 laser treatment of traumatic pulpal exposures in dogs.

BACKGROUND AND OBJECTIVE: Successful non-devitalizing treatment of localized pulpal lesions in mature teeth is not ensured using conventional endodontic techniques. The objective of this study was to evaluate CO2 laser surgical treatment of pulpal exposures in canine patients. STUDY DESIGN/MATERIALS AND METHODS: 17 permanent teeth with pulpal exposures of < or = 48 h duration received localized laser pulp surgery. Laser Parameters: pulse duration: 0.01 s, pulse interval: 1.0 s, spot size: 0.004 cm2, fluence: 276 J/cm2. Exposures were dressed with CaOH and Glass ionomer. Clinical and radiographic evaluations were performed by one blinded clinician 24 and 52 weeks after treatment. RESULTS: 15/17 laser-treated teeth assessed over > or = 1 year post-treatment remained clinically and radiographically healthy. CONCLUSION: These results demonstrate the feasibility of using the CO2 laser for localized pulp surgery. Further studies must optimize laser parameters and identify the range of clinical pathologies which can be treated using this modality.

Animals↗
PubMed1997

Quality of life after cardiac surgery complicated by multiple organ failure.

OBJECTIVE: To evaluate quality of life after prolonged multiple system intensive care treatment in cardiac surgical patients. DESIGN: A case-control study. SETTING: Adult 12-bed thoracic intensive care unit (ICU) at a university teaching hospital. PATIENTS: Forty-seven patients surviving multiple organ failure requiring intensive care treatment for > or = 5 days (ICU group). Patients with a completely uncomplicated postoperative course were matched to the study group with respect to gender, age, and type and date of surgery. The Nottingham Health Profile was used to assess quality of life at least 1 yr after complicated cardiac surgery. INTERVENTIONS: Quality of life measures were collected at least 1 yr after discharge from the ICU. MEASUREMENTS AND MAIN RESULTS: Seventy-five percent of the patients in the ICU group suffered from multiple organ failure involving at least three organ systems, with a mean stay in the ICU of 9.0 +/- 1.2 (SEM) days. Quality of life was considerably reduced in the ICU group, with a higher total mean score of all dimensions of quality of life (22.7 +/- 2.6) compared with the control group (13.2 +/- 2.4 [SEM])(p < .01). The Nottingham Health Profile score was higher in three of six dimensions of health--i.e., energy (p < .05), physical mobility (p < .05), and emotional reactions (p < .05)--compared with the control group. A higher percentage of patients reported problems in three of six important activities of daily life--housework (p < .05), hobbies (p < .01), and sex life (p < .01)--compared with the control group. CONCLUSION: Patients treated with prolonged multiple system intensive care after heart surgery have a poor outcome with respect to quality of life measured at least 1 yr after discharge from the ICU.

Adult↗
PubMed1996

Cellular resistance to anthracyclines.

The antracyclines induce multiple intracellular effects; however, inhibition of the nuclear enzyme topoisomerase II (TOPO II) is the main mechanism of action. Resistance to anthracyclines in tumor cells is multifactorial. The main mechanisms are: (1) the classic multidrug resistance (MDR) phenotype, which is due to the presence of P-glycoprotein (PGP) in plasma membrane, that is, a "pump" that can extrude a wide range of anticancer drugs. Membrane-active drugs (e.g., verapamil) have been found in vitro to reverse this phenotype. Most clinical studies including chemosensitizers have, however, been disappointing. (2) Non-PGP-mediated MDR: this phenotype is characterized by expression of other proteins in the plasma membrane which are also able to extrude anticancer drugs. (3) Changes in the intracellular distribution of drug: this mechanism has been demonstrated in several cell lines, most often in combination with PGP or non-PGP-mediated resistance. (4) Glutathione transferases (GST) and detoxification mechanisms: these represent a multigene family of enzymes that conjugate glutathione to chemically reactive groups. Direct evidence for a causative role of GST in anthracycline resistance is missing. (5) Alterations in TOPO II (at-MDR): DNA topoisomerases are involved in several aspects of DNA metabolism, in particular genetic recombination, DNA transcription, and chromosome segregation. Low levels of expression or alterations in TOPO II are associated in vitro with resistance. (6) Increased DNA repair: in several cell lines, an increase in the efficacy of DNA repair has been associated with resistance to doxorubicin (DOX). So far, only classic MDR has been shown to contribute to resistance in clinical conditions, whereas evidence for the other mechanisms of resistance is still missing.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Tumor markers cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen for monitoring metastatic breast cancer during first-line chemotherapy and follow-up.

We investigated whether model systems integrating stochastic variation into criteria for marker assessment could be used for monitoring metastatic breast cancer. A total of 3989 serum samples was obtained from 204 patients receiving first-line chemotherapy and from 112 of these patients during follow-up. Each sample was analyzed for cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen. The efficiency for identifying progression and nonprogression was 94% during therapy and 85% during follow-up, with no false-positive marker results for progressive disease. At clinical progressive disease, the median positive lead time was 35 days during therapy and 76 days during follow-up. Tumor marker assessment may document that a therapy is effective and ought to be continued in spite of adverse toxic effects, and that a treatment is ineffective and should be stopped to prevent unnecessary toxicity. Marker information may also be useful in studies investigating whether early treatment during follow-up will alter the prognosis of metastatic breast cancer.

Adult↗