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Biomedical subjects

J B Knudsen

Publications and source records attributed to J B Knudsen.

At least 37 records · Page 2Linked to original sources
PubMed1989

The Copenhagen case-control study of bladder cancer. V. Review of the role of urinary-tract infection.

During the years 1979-1981, a population-based study of 388 patients with bladder cancer, including papilloma, and of 790 controls was conducted in Greater Copenhagen. No pronounced difference between cases and controls of either sex was observed for bladder infection, kidney infection or bladder stones. Women with kidney stones had a significantly elevated relative bladder cancer risk (RR = 3.7; 95% CI = 1.2-12.1); the risk for bladder cancer was also increased (RR = 1.5), although not significantly so, in women who had ever had a 'kidney disease'. A review of the existing studies in humans and in animals of the association between bladder infection and cancer reveals a need for studies to determine whether urinary-tract infections increase either the true risk for bladder tumours or only complications of early bladder cancer before a clinical diagnosis has been made.

Adult↗
PubMed1988

Carcinoma of the urinary bladder after treatment with cyclophosphamide for non-Hodgkin's lymphoma.

We observed nine cases of transitional-cell carcinoma of the urinary bladder among patients who had had long-term treatment of other cancers with cyclophosphamide. Seven of the bladder carcinomas occurred within a cohort of 471 patients treated for non-Hodgkin's lymphomas. In this cohort the relative risk of bladder cancer was 6.8 (95 percent confidence interval, 3.2 to 14.2). The cumulative risk (mean +/- SE) was 3.5 +/- 1.8 percent 8 years after the start of treatment with cyclophosphamide and 10.7 +/- 4.9 percent after 12 years. Three of the nine patients were 50 years of age or younger; seven died with progressive bladder cancer. Subsequently, an additional patient had acute nonlymphocytic leukemia. Hemorrhagic cystitis was observed in 33 patients (cumulative risk, 11.8 +/- 2.1 percent after five years). Development of carcinoma of the urinary bladder was not related to previous hemorrhagic cystitis. The results caution against long-term treatment with cyclophosphamide for diseases with a favorable prognosis.

Adult↗
PubMed1988

The Copenhagen case-control study of renal pelvis and ureter cancer: role of smoking and occupational exposures.

Smoking habits and occupational exposures were investigated for 96 patients with cancer of the renal pelvis and ureter (including papilloma) and 294 hospital controls. In comparison with persons who never smoked, significantly increased relative risks were seen for smokers of cigarettes alone (RR = 2.6; 95% CI: 1.0-6.7) and in combination with other types of tobacco (RR = 3.8; 95% CI: 1.3-11.5). Non-significantly increased relative risks were observed for pipe smokers (RR = 2.2; 95% CI: 0.1-97) and for mixed pipe, cigar, and cigarillo smokers (RR = 6.5; 95% CI: 0.4-21.2). A strong dose-effect (p less than 0.001) relationship was seen between the lifetime total amount of tobacco smoked and the risk of pelvis-ureter tumors, with the heaviest smokers having an 8-fold risk. Comparison with the dose-effect relationship for a parallel study of bladder cancer indicated that the relationship with tobacco was stronger for pelvis-ureter tumors. Deep inhalation of cigarette smoke increased the risk (RR = 3.4; 95% CI: 1.9-6.1), while stopping smoking (RR = 0.6; 95% CI: 0.3-1.1) and use of filter cigarettes (RR = 0.5; 95% CI: 0.3-0.9) decreased the risk. Significantly increased risks emerged for employment in the chemical, petrochemical and plastics industries (RR = 4.0; 95% CI: 1.6-9.8), and for exposure to coal and coke (RR = 4.0; 95% CI: 1.2-13.6), asphalt and tar (RR = 5.5; 95% CI: 1.6-19.6). Cigarette smoking accounted for 56% of male and 40% of female pelvis and ureter tumors in eastern Denmark.

Adult↗
PubMed1988

Inhibition of platelet function by low-dose plain and micro-encapsulated acetylsalicylic acid.

The effect of two acetylsalicylic acid (ASA) formulations, plain (Magnyl) and micro-encapsulated (Globentyl), on platelet aggregation, thromboxane formation, and bleeding time was studied in 12 healthy volunteers in a randomized double-blind cross-over study. All subjects were treated with Magnyl and Globentyl (75 mg daily) in periods of 2 weeks, separated by a wash-out period of 2 weeks. Both drugs significantly depressed platelet aggregation and thromboxane formation and prolonged bleeding time without difference in mode of action of the drugs. It is concluded that significant inhibition of platelet activity may be achieved by low-dose ASA treatment with micro-encapsulated as well as with plain formulations.

Adult↗
PubMed1988

Differential effects of timolol and metoprolol on platelet function at rest and during exercise.

Ten male patients suffering from stable angina pectoris were studied at rest and immediately after exercise during treatment either with timolol (a non-selective beta-blocker) or with metoprolol (a beta 1-selective blocker). Timolol induced a significant increase in platelet aggregation and a reduction in platelet cyclic AMP, and it also raised the plasma adrenaline at rest and during exercise as compared to the pre-treatment level. Metoprolol had none of these effects. Prior to medication and during metoprolol treatment, exercise led to an increase in the peripheral platelet count, whereas timolol was associated with a reduction of platelets during physical effort. Neither drug affected platelet thromboxane B2 at rest. During exercise, its level was not affected in the pre-treatment period or during metoprolol treatment but it was sharply increased by timolol therapy.

Adrenergic beta-Antagonists↗
PubMed1988

Radioimmunoassay for quantitative measurement of factor VIII-heavy chain.

An immunoassay has been developed for the measurement of factor VIII heavy chain (FVIII-HC). IgG from a human inhibitor plasma with specificity for FVIII-HC and FVIII-light chain (FVIII-LC) was coated to microplates with loose wells. After washing, the plates were incubated with sample and after another wash 125I-FVIII-HC was added so that the amount of bound tracer was dependent on the amount of FVIII-HC in sample. When EDTA was included in the assay buffer the assay response was increased 3-fold for normal human plasma. This indicated that the antibody was reactive with a determinant hidden in the FVIII-HC/FVIII-LC complex as EDTA splits the complex. The sensitivity of the assay was 0.004 units/ml (1 unit/ml in normal human plasma pool). Together with a previously published assay for FVIII-LC it has now become possible to measure the relative amounts of FVIII-HC and FVIII-LC in haemophilia A plasma and to study the separate expression of FVIII-HC and FVIII-LC by recombinant DNA technology. Patients with severe haemophilia A had FVIII-HC levels below 0.01 units/ml. However, inhibitor patients in high dose FVIII-treatment showed up to 50 times higher levels of FVIII-HC than FVIII-LC and FVIII:C, indicating the presence of FVIII/anti-FVIII-LC immune complexes. Thus, dependent on assay specificity plasma samples can show very variable content of FVIII:antigen.

Factor VIII↗
PubMed1988

Platelet function in classic migraine during attack-free periods.

It has been reported that migraine sufferers have an enhanced platelet activity, as well as an enhanced thromboembolic risk. In this study, 12 subjects with classic migraine were compared with 12 age- and sex-matched controls. The following parameters were tested: platelet aggregation; platelet content of ADP, ATP and cyclic-AMP (cAMP); plasma levels of cAMP, 6-keto-PGF1 alpha and thromboxane B2, serum levels of TxB2 and lipids. ADP- and adrenaline-induced platelet aggregation, platelet content of ADP, ATP and cAMP did not differ significantly between the groups. Platelets from migraine subjects, however, showed a decreased beta-adrenoceptor response to stimulation with isoprenaline when determined as platelet cAMP production in vitro. The prostacyclin metabolite 6-keto-PGF 1 alpha was significantly decreased in the migraine group. No difference were observed in TxB2. Plasma lipids were similar, except that the migraine cases had higher levels of LDL-cholesterol. These data do not confirm a general platelet malfunction in migraine patients, but suggest a decreased functional capacity of platelet beta-adrenoceptors and an altered metabolism of prostacyclin and LDL-cholesterol.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Operative treatment of recurrent cancer of the uterine cervix after radiotherapy.

During the period 1976-83, 47 women were operated on for recurrent or persistent cancer of the uterine cervix following initial radiation therapy. The operations performed were Wertheim's operation combined with dissection of the pelvic nodes, or some type of pelvic exenteration. With a 5-year survival of 31% in our material, surgical treatment of centrally located recurrences is a realistic possibility. We recommend an exenterative procedure as the operation is technically easier and the complications require less radical surgical treatment. The operation should only be done on narrow indications in the hope of achieving a cure, and the selection of patients must thus be stringent.

Aged↗
PubMed1988

Radical cystectomy for residual of recurrent tumour after definitive radiotherapy (salvage cystectomy).

The results of salvage cystectomy for persistent or recurrent tumour following definite radiotherapy in 47 patients are reviewed. The calculated five-year survival rate was 25% for all stages, with a significantly better survival for the low pathological stages. Operative mortality was 12.8%. It was concluded that salvage cystectomy is a suitable supplement in the treatment of bladder cancer in spite of the considerable operative mortality and complication rate.

Adult↗
PubMed1987

Continuous high-dose factor VIII for the induction of immune tolerance in haemophilia A patients with high responder state: a description of eleven patients treated.

Eleven severely affected haemophilia A patients (aged 6-42 y) with F VIII:C inhibitor (high responders) were treated with high-dose F VIII in order to eliminate the inhibitors. The patients comprise Danish high responder patients treated during the period 1977-1985. In all patients the inhibitors decreased significantly. In six, the inhibitor apparently disappeared (detection limit 0.4 Bethesda Units per ml) (BU/ml), in four patients a low level inhibitor of 0.4-1.4 BU/ml persisted. One patient is still on high-dose schedule. The duration of high-dose treatments ranged from less than one month up to 18 months. In all patients the tendency to spontaneous bleedings vanished when a measurable VIII:C level appeared in the post-infusion sample. The inhibitor suppression has allowed for extensive physical training and rehabilitation orthopaedic surgery. The patients are now able to conduct a normal haemophilic life on self-administered prophylactic doses of F VIII.

Adolescent↗
PubMed1987

The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations.

We have studied the activation of human blood platelets by the inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin. The effect of thapsigargin was compared with other common agonists (calcium ionophore A23187, phorbol ester TPA and thrombin). Platelet aggregation, serotonin release, raised cytoplasmic free calcium level and phosphorylation of platelet proteins was examined in platelet-rich plasma and washed platelet suspension. In contrast to A23187 and thrombin, the platelet activation induced by thapsigargin developed slowly, with maximal response obtained after 2-3 min. Both the thapsigargin- and the A23187-induced serotonin releases were synergistically increased by TPA. Studies of the phosphorylation of platelet proteins revealed that thapsigargin and A23187 equally well induced a selective phosphorylation of two proteins with apparent molecular masses of 20 kDa and 47 kDa. These proteins, which are substrates of myosin light-chain kinase and protein kinase C respectively, are known to be involved in platelet activation. The thapsigargin-induced platelet aggregation and serotonin release was completely inhibited by class I (nimodipine), class II (verapamil) and class III (diltiazem) calcium-channel blockers. The inhibitory activity of nimodipine was abolished by the corresponding 1,4-dihydropyridine calcium-channel agonist, BAY K 8644. These results shows that the thapsigargin-induced platelet activation is mediated by an increase in the cytoplasmic free calcium level, presumably obtained by stimulation of the passive calcium transport through specific channels. These thapsigargin-sensitive channels should predominantly be located in the membranes of intracellular calcium stores rather than in the plasma membrane, because removal of extracellular calcium by EGTA had only an insignificant effect on the thapsigargin-induced rise in cytoplasmic free calcium level.

Blood Platelets↗
PubMed1987

The Copenhagen case-control study of bladder cancer: role of smoking in invasive and non-invasive bladder tumours.

A population based study of 388 cases of bladder cancer including papillomas and 787 controls in Greater Copenhagen confirmed the role of smoking in the aetiology of bladder cancer. Significantly increased relative risks were found for persons who had smoked only cigarettes (RR = 2.9; both sexes combined) and for mixed smokers including cigarettes (RR = 3.6; both sexes combined). Multiple logistic regression analysis showed significant influences of the amount (pack years) of cigarettes smoked and a reduced risk among persons who had stopped smoking. No significant effects of smoking pipe or cigars/cigarillos were apparent, and the present study does not confirm previous suggestions of associations between the smoking of cigars/cigarillos and bladder cancer in Denmark. Only a slight increase in relative risk with the amount smoked was found. The influence of smoking on bladder cancer risk was similar for tumours in stages T1 and T2-4 at diagnosis and also for tumours of grades 1-2 and grades 3-4 at diagnosis.

Aged↗
PubMed1987

The Copenhagen case-referent study on bladder cancer. Risks among drivers, painters and certain other occupations.

Occupational risk of bladder cancer (including papilloma) was investigated as part of a case-referent study in Copenhagen. Occupational histories were obtained on 389 cases and 790 referents drawn at random from the general population of the study area. When persons with missing information were excluded, a total of 371 cases (280 men, 91 women) and 771 referents (577 men, 194 women) were left for analysis. After adjustment for tobacco smoking, age, and sex, significantly increased relative risks were observed for occupation in land transport, in particular bus, taxi, or truck driving. A statistically significant trend was seen with duration of employment in these trades. Based on a logistic regression analysis, a relative risk (RR) of 1.3 was determined for 10 years of employment in the trade. An association was also found for employment in trades undertaking painting (RR = 1.4 for 10 years' employment), and a significant trend emerged for duration of employment. A positive association with employment in the textile and leather industry disappeared after adjustment for tobacco smoking, and no association with duration of employment emerged. No association was found with employment in the chemical, rubber, iron and metal industries or in health services.

Automobile Driving↗
PubMed1987

Platelet survival, platelet factor-4 and bleeding time in myeloproliferative disorders.

In 27 patients with myeloproliferative disorders observations on thrombohaemorrhagic complications, platelet function tests and spleen size were made. Sixteen patients had thrombotic or haemorrhagic episodes. All 27 patients had elevated platelet factor-4 and 25 patients had a shortened platelet survival. Patients with myelofibrosis had a significantly shorter platelet survival than patients with polycythaemia vera (p less than 0.05). Seven out of 23 patients investigated had prolonged bleeding time. The observed abnormalities of platelet function tests were not related to thrombohaemorrhagic complications or spleen size.

Adult↗