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Biomedical subjects

B Lund

Publications and source records attributed to B Lund.

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

Phase I trial with weekly EO9, a novel bioreductive alkylating indoloquinone, by the EORTC Early Clinical Study Group (ECSG).

PURPOSE: EO9 is a new synthetic bioreductive alkylating indoloquinone, with preferential activity against solid tumors and higher antitumor activity under anaerobic conditions compared with aerobic conditions. In preclinical models EO9 demonstrated no major organ toxicity. The aim of the present phase I study was to determine the toxicities and the maximal tolerated dose (MTD) of EO9 administered as a 5-min i.v. infusion weekly to patients with solid cancers. METHODS: Twenty-eight patients entered the study. The dose was escalated from 2.7 mg/m2 according to a Fibonacci-like schedule. RESULTS AND CONCLUSION: The dose-limiting toxicity was proteinuria. No other major toxicities were detected and in particular there was no significant increase in serum creatinine. This was in contrast to findings in a previous phase I trial using EO9 in a 3-weekly schedule, where a number of patients experienced severely decreased kidney function. The MTD in the present study was 15.0 mg/m2 weekly and the recommended dose for phase II studies was 12.0 mg/m2 weekly. Compared with 3-weekly EO9, the dose intensity could be increased from 22 mg/m2 to 36 mg/m2 with the weekly administration. Phase II studies have been performed by the EORTC Early Clinical Study Group in advanced breast, gastric, colorectal, pancreatic, and non-small-cell lung cancer.

Adult↗
PubMed2000

Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group.

The purpose of this randomized, double-masked, placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis. The study was conducted at 80 study centers in Europe and Australia. Postmenopausal women (n = 1226) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo; all subjects also received elemental calcium 1000 mg/day, and up to 500 IU/day vitamin D if baseline levels were low. The study duration was 3 years; however, the 2.5 mg group was discontinued by protocol amendment after 2 years. Lateral spinal radiographs were taken annually for assessment of vertebral fractures, and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals. Risedronate 5 mg reduced the risk of new vertebral fractures by 49% over 3 years compared with control (p<0.001). A significant reduction of 61% was seen within the first year (p = 0.001). The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years. The risk of nonvertebral fractures was reduced by 33% compared with control over 3 years (p = 0.06). Risedronate significantly increased bone mineral density at the spine and hip within 6 months. The adverse-event profile of risedronate, including gastrointestinal adverse events, was similar to that of control. Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis, reducing the incidence of vertebral fractures and improving bone density in women with established disease.

Absorptiometry, Photon↗
PubMed2000

Impact on human intestinal microflora of an Enterococcus faecium probiotic and vancomycin.

The aims of this study were to evaluate the impact of a fermented milk product containing viable Enterococcus faecium on human intestinal microflora and to evaluate any risk of development of vancomycin-resistant enterococci (VRE). Twenty Danish and 20 Swedish healthy volunteers were given 150 ml of the fermented milk product once daily, equivalent to a daily dose of 4.5 x 10(9) to 7.5 x 10(9) CFU E. faecium, for 10 d. Half of the volunteers also received 125 mg vancomycin orally q.i.d. for 10 d. Faecal samples were collected on day 0 before intake, on day 10 directly after end of intake and on day 31, 3 weeks after the end of the experiment. There was a significant increase in the total number of enterococci on day 10 (p < 0.01) in the group receiving only the E. faecium supplement, but 3 weeks later the level was as before intake. In the vancomycin group, the total number of enterococci was reduced on day 10 (p < 0.01) but had increased on day 31 (p < 0.01) in relation to day 0. In none of the Swedish and 4 of the Danish volunteers, VRE were sporadically detected, but without relation to intake of the probiotic or vancomycin. In healthy young Danish individuals the VRE carrier rate tended to be higher than previously found.

Adult↗
PubMed2000

Phase I study of single, escalating doses of a superantigen-antibody fusion protein (PNU-214565) in patients with advanced colorectal or pancreatic carcinoma.

To develop a T-cell-based therapy for carcinomas, the superantigen staphylococcal enterotoxin A (SEA) was supplied with tumor specificity by means of a recombinant fusion of the Fab fragment of the monoclonal antibody C242 recognizing human colorectal (CRC) and pancreatic carcinomas (PC). Using this Fab-SEA fusion protein (PNU-214565), potent cytotoxicity by activation of T cells can be obtained in the targeted area. Twenty-one patients with CRC and 3 with PC were treated with single, escalating doses of PNU-214565 to establish the maximum tolerated dose (MTD) and to define toxicities. The doses ranged from 0.01 ng/kg to 4.0 ng/kg with three patients at each dose level, except for the dose of 1.5 ng/kg with which six patients were treated because of dose-limiting toxicity. Adverse events (AE) were transient: 13 patients experienced mild to moderate fever. In one patient, a grade 3 fever was followed by a grade 2 hypotension. Other mild or moderate AEs were fatigue, nausea, vomiting, diarrhea, and abdominal pain. No significant hematological toxicity occurred. Immune activation was highly variable with strong activity in peripheral blood seen only in two patients at the dosage level 1.5 ng/kg. They showed pronounced elevations of interleukin-2 (IL-2), IL-6, tumor necrosis factor-alpha, and interferon-gamma, 3-5 hours after the start of infusion. In one patient, IL-2 and IL-6 increased substantially (2,925 U/mL and 32,000 U/mL) concomitantly with grade 3 fever and transient grade 2 neutropenia, grade 2 lymphopenia, and grade 2 monocytopenia. In conclusion, a single 3-hour infusion of PNU-214565 could be safely administered up to 4 ng/kg. MTD was not determined. Instead, a repeat-dose trial was initiated starting at 0.5 ng/kg, considered safe in this trial, with the objective of defining the MTD.

Adult↗
PubMed2000

Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer.

PURPOSE: To determine the side effects and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer. PATIENTS AND METHODS: Patients were randomly allocated to receive paclitaxel 175 mg/m(2) intravenously as a 3-hour infusion followed by either cisplatin 75 mg/m(2) or carboplatin (area under the plasma concentration-time curve of 5), both on day 1. The schedule was repeated every 3 weeks for at least six cycles. Women allocated to paclitaxel-cisplatin were admitted to the hospital, whereas the carboplatin regimen was administered to outpatients. RESULTS: A total of 208 eligible patients were randomized. Both regimens could be delivered in an optimal dose and without significant delay. Paclitaxel-carboplatin produced significantly less nausea and vomiting (P: <.01) and less peripheral neurotoxicity (P: =.04) but more granulocytopenia and thrombocytopenia (P: <.01). The overall response rate in 132 patients with measurable disease was 64% (84 of 132 patients), and in patients with elevated CA 125 levels at start, it was 74% (132 of 178 patients). With a median follow-up time of 37 months, the median progression-free survival time of all patients was 16 months and the median overall survival time was 31 months. The small number of patients entered onto the study caused wide confidence intervals (CIs) around the hazards ratio for progression-free survival of paclitaxel-carboplatin compared with paclitaxel-cisplatin (hazards ratio, 1.07; 95% CI, 0.78 to 1.48) and did not allow conclusions about efficacy. CONCLUSION: Paclitaxel-carboplatin is a feasible regimen for outpatients with ovarian cancer and has a better toxicity profile than paclitaxel-cisplatin.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Coenzyme Q10 administration increases antibody titer in hepatitis B vaccinated volunteers--a single blind placebo-controlled and randomized clinical study.

Persons involved in the study, 21 per treatment arm, were consuming ubiquinone (Q10), 90 mg/day, 180 mg/day or placebo, for two weeks prior to hepatitis B vaccination. After 30 days this vaccination was repeated. Q10 was given as soft gelatin capsules containing 30 mg each. The consumption was continued throughout the study conducted for 90 days. Clinical observations and laboratory tests were performed throughout the study and no adverse effects were observed in any of the groups. Already after 30 days the two groups receiving Q10 showed a slightly titer of antibodies to hepatitis B surface antigen then the placebo group. This difference escalated and the immunopotentiating effect of Q10 was even more clear-cut in the residual part of the study. In addition, a dose response did also seem to be present when comparing the 90 mg group with the 180 mg group. Statistics revealed that Q10 in the dose 180 mg/day is able to increase antibody response in vivo in humans vaccinated against hepatitis B with up to 57% (p = 0.011).

Analysis of Variance↗
PubMed1999

Preoperative bone mineral density of the proximal tibia and migration of the tibial component after uncemented total knee arthroplasty.

Twenty-two patients with primary osteoarthrosis of the knee all operated on with insertion of an uncemented total knee arthroplasty had a preoperative measurement of bone mineral density (BMD) in the coronal plane of the proximal tibia performed by dual-photon absorptiometry. Postoperatively and with follow-up after 6 weeks (n = 21), 1 year (n = 22), and 3 years (n = 19), radiographs suitable for radiostereometric analysis of the tibial component migration were obtained. One year postoperatively, stress examinations were performed with the aim of measuring inducible displacement of the tibial component. Most of the migration, expressed as maximal total point motion (MTPM), occurred during the first year with an average migration of approximately 1 mm. Regression analysis showed a positive relation between BMD and MTPM after 6 weeks (P = .03, r = .47), 1 year (P = .0005, r = .68), and 3 years (P = .02, r = .54). Inducible displacement did not reveal any significant relation to BMD. MTPM between 1 and 3 years, which is the clinically most important parameter with respect to later loosening of the tibial component, showed a negative relation to BMD (P = .04, r = -.47). Thus, tibial components of knees with preoperative high tibial BMD showed less continuous migration.

Aged↗
PubMed1999

Advanced epithelial ovarian cancer: 1998 consensus statements.

BACKGROUND: During an international workshop held in September 1998, a group of specialists in the field of ovarian cancer reached consensus on a number of issues with implications for standard practice and for research of advanced epithelial ovarian cancer. METHODS: Five groups of experts considered several issues which included: biologic factors, prognostic factors, surgery, initial chemotherapy, second-line treatment, the use of CA 125, investigational drugs, intra-peritoneal treatment and high-dose chemotherapy. The group attempted to arrive at answers to questions such as: Are there prognostic factors, which help to identify patients who will not do well with current therapy? What is the current best therapy for advanced ovarian carcinoma? What directions should research take in advanced ovarian cancer? These issues were discussed in a plenary meeting. RESULTS: One of the major conclusions drawn by the consensus committee was that in previously untreated advanced ovarian cancer, cisplatin plus paclitaxel has been shown to be superior to previous standard therapy with cisplatin plus cyclophosphamide (level I evidence). However, for many patients, carboplatin plus paclitaxel is a reasonable alternative because of toxicity and convenience considerations. Most participants felt that the benefits in terms of toxicity for the paclitaxel-carboplatin are such that its widespread adoption at this stage is justified. Until mature survival data are available a minority of investigators would recommend continued use of cisplatin plus paclitaxel, specifically for those patients with advanced disease with the best prognostic characteristics. For future clinical research in this area, new end points for randomised clinical trials, together with a new Trials Network, are proposed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Hereditary long QT syndrome].

The Long QT Syndrome (LQTS) is a hereditary disease, characterized by a prolonged QT-interval on the electrocardiogram and a high risk of syncope and sudden death due to ventricular arrhythmias. LQTS must be suspected in apparently healthy children and young people with syncope after emotional or physical stress. Untreated symptomatic patients have a high mortality, which is markedly reduced by sympathetic block. The knowledge of the diagnostic criteria for the LQTS, a detailed history including a family history and an ECG-recording with measurement of the QT-interval in every patient with inexplicable syncope will advance the diagnosis of the LQTS and improve the survival of these patients after proper therapy. The current knowledge on the molecular genetics, epidemiology, mechanisms of arrhythmias and therapy are presented with special emphasis on the defects in the control of ionic transport over the cell membrane caused by mutations in ion channels.

Adolescent↗
PubMed1998

[Arrhythmogenic right ventricular cardiomyopathy].

Arrhythmogenic right ventricular dysplasia is a rare cardiomyopathy, but a frequent cause of ventricular tachyarrhythmia and sudden cardiac death among young otherwise healthy individuals. This article contains a review of the current knowledge on epidemiology, diagnosis, symptoms and signs as well as theories on etiology and pathogenesis, prognosis and treatment. The aim is to draw attention to the disease as a cause of syncope, ventricular tachycardia and sudden cardiac death.

Arrhythmogenic Right Ventricular Dysplasia↗
PubMed1998

[From paroxysmal to chronic atrial fibrillation].

Chronic atrial fibrillation is by definition always preceded by paroxysmal atrial fibrillation. The electropathophysiological mechanisms underlying paroxysmal atrial fibrillation are reviewed: atrial electrophysiological inhomogeneity, atrial ectopic activity, and cardiac autonomic dysfunction. Safe and effective interventions that prevent the progression from paroxysmal into chronic atrial fibrillation have not yet been developed. Such developments should be given high priority, as the consequences of chronic atrial fibrillation--stroke and heart failure--are unacceptable.

Atrial Fibrillation↗
PubMed1998

Recovery of beat-to-beat variations of QRS.

There is a growing interest in the analysis of beat-to-beat variations of the morphology (BBM) of cardiac waves in electrocardiograms (ECG). Such analyses are confronted with the low BBM-to-noise ratio. An ECG clustering technique is introduced that brings the benefits of signal averaging to BBM analysis and recovers the beat-to-beat pattern of BBM. ECG clustering aligns waves and sorts them into clusters. The precision of the alignment was enhanced by sub-sample alignment. Kohonen's self-organising neural networks identified the clusters of the cardiac waves during training. The subsequent clustering of a wave results in a label for the closest cluster, a distance to the cluster and optimal alignment. Furthermore, ECG clustering avoids base-line variations and amplitude modulation sufficiently to be applied to the QRS wave in the raw ECG. The technique is demonstrated on 14 subjects with coronary heart disease and no myocardial infarction, myocardial infarction, or inducible ventricular tachycardia. ECG clustering is a general-purpose technique for beat-to-beat analysis, where the variations are cyclic as in the sinus rhythm. Results show that beat-to-beat variations in the QRS morphology are in general cyclic, with a main period of about four cardiac cycles. All calculations were performed with the Cardio software.

Coronary Disease↗
PubMed1998

Long-term results from a phase II study of single agent paclitaxel (Taxol) in previously platinum treated patients with advanced ovarian cancer: the Nordic experience.

BACKGROUND: Owing to the wide spread perception of a possible benefit from paclitaxel in the second-line situation the Nordic Gynecologic Oncology Group (NGOG) conducted two prospective phase II studies of paclitaxel single agent treatment (175 mg/m2, three-hour i.v. infusion with standard pre-medication every third week) in patients with relapsing or progressing epithelial ovarian cancer following platinum. PATIENTS AND METHODS: Between 1992-1994 138 patients in total were enrolled of whom 136 received paclitaxel and were included in the toxicity and survival analysis, while 112 were evaluable for response. RESULTS: The overall response rate (CR + PR) was 28% with 16 patients achieving a CR (14%). The estimated median (range) time to progression was 4.1 (0.7-60.7) months. The projected four-year overall survival was 7%, with a median (range) of 9.6 (0.3-60.7) months. A multivariate logistic regression analysis showed that platinum resistance, and WHO performance status at baseline, independently correlated with survival at all three time points (median survival time 9.6, 18, and 24 months). Patients with platinum sensitive tumors and WHO performance status 0 had a median survival of 25.6 months compared to 7.0 months for the rest of the patients (P < or = 0.0001). No serious toxicity was registered. CONCLUSION: Paclitaxel could safely be administered in an outpatient setting using this schedule. Patients with platinum sensitive tumors and a good performance status were most likely to survive. However, these patients are also most likely to respond to re-treatment with a platinum compound. With reference to the reasonably good tumor control and limited toxicity observed in this study, we conclude that paclitaxel single agent therapy is a viable option in the salvage situation, which in some patients can give long-lasting responses. However, although responses can be induced in a significant number of patients, the survival figures remain poor.

Adult↗
PubMed1998

A double-blind, randomized, placebo-controlled study of efficacy and tolerance of meloxicam treatment in patients with osteoarthritis of the knee.

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID), with a favourable ratio of inhibition of cyclooxygenase-2 (COX-2)/cyclooxygenase-1 (COX-1), giving the drug the potential to produce few gastric adverse effects. The aim of this study was to investigate the efficacy and safety of meloxicam in patients with osteoarthritis (OA) of the knee. Five hundred and thirteen patients were treated in a double-blind trial comparing once-daily meloxicam 7.5 mg, 15mg, 30mg, or placebo (140, 134, 102 and 137 patients, respectively). Outcome measures included scores on Visual Analogue Scales (VAS) for pain on movement (primary endpoint) and pain at rest in the target joint as well as global efficacy. Lesquesne's index of severity and paracetamol consumption were also measured. Global tolerability and the occurrence of adverse events were monitored. Both meloxicam 7.5 mg and 15 mg were significantly more effective than placebo with respect to pain on movement (p < 0.01 and p < 0.03, respectively). Both doses of meloxicam compared favourably with placebo with respect to pain of the target joint at rest, although only the 15 mg dose achieved statistical significance (p < 0.02). Global efficacy showed a significant difference for both doses of meloxicam (p < 0.05 and p < 0.002 for 7.5 mg and 15 mg doses, respectively). Once daily meloxicam 7.5 and 15 mg is effective and well tolerated in the short term symptomatic treatment of OA of the knee.

Administration, Oral↗
PubMed1998

Docetaxel and cisplatin in metastatic urothelial cancer: a phase II study.

PURPOSE: Docetaxel and cisplatin has documented single-agent activity and different toxicity profiles in patients with metastatic urothelial cancer. We performed a phase II study in which docetaxel was combined with cisplatin to evaluate response rate, toxicity, and survival. PATIENTS AND METHODS: Eligibility criteria included performance status (World Health Organization [WHO]) less than 3; normal bone marrow, liver, and renal function; and no concurrent malignancy or symptomatic peripheral neuropathy. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Paris, France) 75 mg/m2 was combined with cisplatin 75 mg/m2 every third week. Patients received premedication with prednisolone and clemastine. RESULTS: A total of 25 patients were assessable for response and toxicity. Median age was 64 years; five patients had locoregional disease only and 20 had metastatic disease. Response was achieved in 15 patients (60%; 95% confidence interval [CI], 39% to 79%), including seven patients (26%) who achieved a complete response. Overall median survival time was 13.6 months (range, 1.5 to 26.4+). The most frequent toxicity was nausea and vomiting (80% of patients). Neutropenia grade 3 or 4 was observed in 56% of patients, but only one had febrile neutropenia. Mucositis and diarrhea were encountered in 13% of cycles, mostly grade 1 or 2. Peripheral neuropathy and skin changes grade 1 and 2 were observed in 76% and 36%, respectively. Fluid retention and hypersensitivity reactions were infrequent and mild. CONCLUSION: The combination of docetaxel and cisplatin is effective and feasible in patients with metastatic urothelial cancer with a manageable safety profile.

Aged↗
PubMed1998

Effect of nasal salmon calcitonin on post-traumatic osteopenia following ankle fracture. A randomized double-blind placebo-controlled study in 24 patients.

With the aim of preventing postfracture osteopenia, we randomized 24 patients with internally fixed ankle fractures to 3 months of treatment with placebo or 200 IU nasal salmon calcitonin (sCT) in a prospective, double-blind design. 3 patients were excluded, leaving 11 patients in the placebo group and 10 in the sCT group for study. Bilateral measurements of bone mineral content (BMC) in the coronal plane of the proximal tibia were performed by dual photon absorptiometry (DPA) postoperatively within 7 days of the fracture and after 1.5, 3 and 6 months. 3 months after the fracture, BMC in the injured legs had decreased by 14% in the placebo group and 2.1% in the sCT group. This difference was not statistically significant. In the healthy legs, a statistically significant intergroup difference was seen 6 weeks after the fracture, caused by a tendency towards a decrease in BMC of 4.6% in the placebo group, while BMC in the sCT group had increased by 7.4%. Nasal sCT may to some extent, but in this study not significantly, reduce postfracture osteopenia, and cause a significant effect on BMC in the healthy leg.

Absorptiometry, Photon↗
PubMed1998

Dysplasia epiphysealis hemimelica (Trevor's disease) of the distal radius.

The authors report a rare case of dysplasia epiphysealis hemimelica (DEH) or Trevor's disease of the radius in an Eskimo from Greenland. DEH is indistinguishable microscopically from osteochondroma, however its epiphyseal site of origin differentiates it from the osteochondroma, which characteristically originates in the metaphysis.

Aged↗