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Biomedical subjects

M Karlsson

Publications and source records attributed to M Karlsson.

At least 19 recordsLinked to original sources

DNA ploidy and S-phase fraction as prognostic factors in patients with uveal melanomas.

In 96 patients with uveal malignant melanomas the tumours were investigated by DNA flow cytometry. Thirty-eight per cent of the melanomas were aneuploid. By univariate analysis significant correlations with survival were found for histological type, tumour size, DNA ploidy, evidence of 'blind eye' and S-phase fraction. By multivariate analysis, significant prognostic variables were found to be histological type (P = 0.0008), tumour size (P < 0.0001) and DNA ploidy (P = 0.0038). Evidence of 'blind eye' was not significantly correlated with survival after adjustments for the other variables mentioned above. The S-phase fraction could be estimated in all 60 diploid tumours and in 12 of 36 aneuploid melanomas. By univariate analysis this variable was found to be a significant prognostic factor, but did not remain so after adjustment for ploidy, histological type and tumor size. We further conclude that patients with small DNA diploid uveal melanomas of spindle cell type have a rather favourable prognosis.

Adult

Cross-sectional study of risk factors for symptoms in the neck and shoulder area.

This study was performed in order to evaluate how individual characteristics, as well as ergonomic, organizational and psychosocial factors in the work situation are associated with early symptoms in the neck and shoulder area. Nine hundred randomly drawn subjects of the working population in a semi-rural community in Sweden were mailed a questionnaire comprising the Nordic questionnaire on musculoskeletal symptoms, questions on ergonomic, organizational and psychosocial work conditions, life style factors, and background factors. The total response rate was 73% (n = 637). Questions on ergonomic work conditions and on organizational and psychosocial work conditions provided the measures of exposure. Prevalence ratios (PR) were calculated for symptoms in the neck and shoulder area as reported by 303 subjects. Significant determinants for early symptoms were being a female and being an immigrant, as were repetitive movements demanding precision. High work pace, low work content and work role ambiguity were significant organizational risk factors while life style characteristics did not appear as risk factors. The results suggest that symptoms are signals not only of ergonomic deficiencies in the work situation, but in particular of work organizational conditions. Special attention should be given to the work conditions of women and immigrants in preventive interventions.

Adolescent

Invasion of the rat ventral root L5 by putative sympathetic C-fibers after neonatal sciatic nerve crush.

The present study examines the occurrence of C-fibers in lumbar ventral roots after sciatic nerve crush in neonatal and adult rats. Electron microscopic analysis showed that the number of C-fibers in the ventral root L5 increased significantly on the lesion side after neonatal but not adult sciatic nerve crush and that the number of C-fibers was higher in the ventral root L5 on the unoperated side compared to this root in normal control rats. In order to determine whether the new C-fibers in the L5 root on the lesion side are sensory or sympathetic we made immunohistochemical studies on roots from neonatally crushed rats. We found that there was no obvious lesion side/contralateral side or operated rat/control rat difference with respect to the occurrence and general configuration of axons with substance P-, calcitonin gene-related peptide- or vasoactive intestinal polypeptide-like immunoreactivity. However, the occurrence of axons with tyrosine hydroxylase-like immunoreactivity appeared clearly higher in the ventral root L5 on the lesion side compared to the unoperated side in neonatally crushed rats. Moreover, these axons seemed to be more numerous also in the ventral root L5 on the unoperated side compared to normal control rats. No lesion side/contralateral side or operated rat/control rat differences were seen in the ventral root L4. We propose that the ventral root L5 is invaded by putative sympathetic C-fibers after sciatic nerve crush lesions in newborn rats.

Age Factors

Complications after transpedicular stabilization of the spine. A survivorship analysis of 163 cases.

OBJECTIVES: The authors studied complications of transpedicular stabilization methods. SUMMARY OF BACKGROUND DATA: One hundred and sixty-three consecutive transpedicular stabilization procedures were performed between January 1987 and December 1991. The indications for stabilization were trauma (33 cases), metastatic spinal disorder (30 cases), spinal stenosis (33 cases), spondylolisthesis (27 cases), ankylosing spondylitis (6 cases), low back pain (22 cases), and miscellaneous (12 cases). METHODS: Patients records and the entire series of radiographs for each case were scrutinized by independent observers. All per- and postoperative complications, including implant loosening and fatigue, were recorded. Clinical and radiographic survivorship analyses of the implants were performed. RESULTS: Early complications were unusual and none were associated with permanent morbidity. The probability of not having the implant removed in the first postoperative year was 85%. There was a 40% risk of radiographic failure, defined as loosening or implant fatigue, at 6 months. The outcome was more favorable in cases in which anterior vertebral interbody fusion was also performed. CONCLUSIONS: Transpedicular fixation is a safe procedure with a low incidence of serious per- and early postoperative complications. The mechanical durability of transpedicular fixators used alone is a cause for concern.

Adolescent

Sensory C-fibers in rat ventral roots are capsaicin-insensitive and they do not mediate extravasation from pial vessels.

Mammalian ventral roots and pia mater contain sensory C-fibers, some of which exhibit a substance P- and/or calcitonin gene-related peptide (CGRP)-like immunoreactivity. At some locations, sensory axons containing these neuropeptides evoke peripheral plasma protein extravasation after antidromic electrical stimulation. Such axons usually disappear following treatment of neonatal rats with capsaicin. The purpose of the present study is to find out if afferent C-fibers in the rat ventral roots L4 and L5 are capsaicin-sensitive, and if antidromic stimulation of these fibers elicits extravasation in the root and/or the ventral pia mater. The results show (1) that the number of C-fibers in these ventral roots is unaffected by neonatal capsaicin treatment, as seen in the electron microscope; (2) that the occurrence and general configuration of axons with substance P- and CGRP-like immunoreactivity do not appear abnormal in neonatally capsaicin-treated rats, as revealed by fluorescence microscopy on longitudinal frozen sections; (3) that Evans blue albumin is not extravasated in the ventral root or pia mater after electrical ventral root stimulation or following systemic injection of capsaicin. We conclude, that ventral root afferents are functionally different from otherwise similar afferents at other locations.

Animals

Inhibition of soluble catechol-O-methyltransferase and single-dose pharmacokinetics after oral and intravenous administration of entacapone.

The inhibition of soluble catechol-O-methyl-transferase (S-COMT) in red blood cells (RBCs) by entacapone, and the pharmacokinetics of entacapone after single oral (5-800 mg) and i.v. (25 mg) doses have been examined in an open study in 12 healthy young male volunteers. Oral entacapone dose-dependently decreased the activity of S-COMT in RBCs with a maximum inhibition of 82% after the highest dose (800 mg). The inhibition of S-COMT in RBCs was reversible and the activity recovered within 4-8 h. Entacapone showed linear pharmacokinetics over the dose range studied: Cmax and AUC were correlated with the dose of the drug. Oral absorption of entacapone was fast, with a tmax ranging from 0.4 to 0.9 h, depending on the dose. Systemic availability of entacapone varied between 30 and 46%. Entacapone was rapidly eliminated by metabolism with a half-life of 0.27-0.30 h after oral doses of 5 to 50 mg. After doses from 100 to 800 mg the disposition was best described by two phases with a t1/2 alpha of 0.27-0.37 h and t1/2 beta of 1.59-3.44 h. Over the dose range studied, the single oral and i.v. doses of entacapone were well tolerated. No haematological, biochemical or haemodynamic adverse effects were seen. The results show that entacapone is an orally effective and reversible COMT inhibitor in man and has simple, linear pharmacokinetics.

Administration, Oral

Importance of collateral vessels in aortic coarctation: computer simulation at rest and exercise using transmission line elements.

Coarctation of the aorta causes arterial hypertension in the upper body and a low blood pressure downstream. Collateral blood vessels compensate by reducing the downstream pressure drop. To study the effect of various coarctation and collateral properties, we designed a computer model of the arterial circulation. The model contains a flow source and a library of subroutines for the lines and connectors. Distributed friction and wall viscoelasticity effects are included. Computer simulation was performed, using published values for vessel dimensions, in an arterial model with a coarctation and one lumped collateral. Rest and two levels of exercise (by increased heart rate) were studied. Without a collateral, we found the downstream pressure of the model was extremely dependent on the size of the coarctation. A collateral vessel reduced the pressure difference between the up- and downstream circulations. For a severe coarctation, the length and the diameter of the collateral were the main factors determining the downstream pressure and flow, whereas wall stiffness of the collateral had little influence. The relationship between mean pressure drop and cardiac output in coarctation was also dependent on the peripheral resistance in different flow beds, especially during exercise.

Aortic Coarctation

Pharmacokinetics and pharmacodynamics of simendan, a novel calcium sensitizer, in healthy volunteers.

OBJECTIVE: To assess pharmacokinetics and correlation of pharmacokinetics and pharmacodynamics of simendan, a new calcium-sensitizing compound aimed at the treatment of congestive heart failure, in healthy volunteers. METHODS: Simendan was administered to eight healthy subjects in seven different doses, and its concentrations in plasma and proportions of enantiomers (levosimendan and dextrosimendan) were determined. Hemodynamic effects were measured by M-mode echocardiography. RESULTS: The area under the plasma concentration time-curve increased linearly and correlated with dose (p < 0.001). The volumes of distribution were small (mean VC, 8.5 to 14.1 L; VSS, 12.8 to 28.4 L) and elimination fairly fast (mean t1/2 beta, 0.83 to 1.77 hours). There were only minor differences between the pharmacokinetic profiles of the enantiomers of simendan. The increase in maximal ejection fraction (EF) correlated significantly with the plasma concentrations of simendan (p < 0.01; r2 = 0.33). However, the correlation coefficient was higher between estimated concentrations of simendan in peripheral compartment and ejection fraction; r2 was 0.79 (p < 0.01) and 0.94 (p < 0.001) after 2 and 5 mg doses, respectively. One subject after 5 mg simendan and one subject after 10 mg simendan had transient vasovagal reactions consisting of decreases in heart rate and blood pressure. CONCLUSIONS: Simendan has favorable and predictable hemodynamic actions. The pharmacokinetic profile facilitates rapid dose adjustments during intravenous administration.

Adult

DNA ploidy and S-phase fraction in primary melanomas and their regional metastases.

Flow cytometric analysis of DNA ploidy and S-phase fraction was performed on the primary melanomas and the first metastases from 55 melanoma patients with regional lymph node metastases or in transit metastases. The frequency of aneuploidy was significantly higher in metastases than in the primary tumour (p = 0.009), suggesting a higher growth potential in melanoma metastases than in the primary tumours. In 18 patients with reliable S-phase determinations from both primary tumour and metastasis there was no significant difference in mean S-phase fraction between primary melanomas and metastases. Skin metastases localized in dermis and subcutis had a significantly (p = 0.012) higher mean S-phase fraction than lymph node metastases.

Adult

A multileaf delineator system for a radiotherapy simulator.

Multileaf collimators are offered as an accessory to many accelerators for conformal radiotherapy and the dose planning systems are capable of calculating multileaf collimated beams. There is further a frequent desire to verify the radiation fields on a radiotherapy simulator prior to the actual treatment. For this purpose, an accessory to the simulator was developed (the multileaf delineator). With this unit the front end of the individual leaves are indicated both on the skin of the patient and in the x-ray image. All anatomical structures both outside and inside the field edge are, however, still fully visible.

Biophysical Phenomena

Serological follow-up after treatment of patients with erythema migrans and neuroborreliosis.

To investigate the duration and kinetics of immunoglobulin M (IgM) and IgG antibodies against Borrelia burgdorferi in serum after treatment of Lyme borreliosis, consecutive serum samples from 30 seropositive patients with erythema migrans and 91 seropositive patients with neuroborreliosis were analyzed with a capture IgM enzyme-linked immunosorbent assay (ELISA) and an indirect IgG ELISA, both using B. burgdorferi flagella as the antigen. All the patients improved after treatment: 97 patients had a complete clinical recovery, while 24 patients had sequelae. The results showed that patients with erythema migrans and early neuroborreliosis more often initially had highly elevated IgM optical density (OD) values and low IgG OD values against B. burgdorferi, while the opposite was found in patients with late neuroborreliosis. During follow-up, the majority of patients had developed negative or significantly declining IgM ODs after 1 to 1.5 years but persistently positive IgM ODs were found up to 17 months after treatment of erythema migrans and 3 years after treatment of neuroborreliosis. IgG antibody levels declined more slowly and remained elevated to a larger extent, but more than half of the patients had developed negative IgG ODs within 5 years after therapy. However, positive IgG OD values were found after 9 to 10 years for patients treated for neuroborreliosis as well as erythema migrans. Both IgM and IgG antibodies against B. burgdorferi may persist for months to years after successful treatment of Lyme borreliosis. Consequently, a single serum sample with antibodies against B. burgdorferi must always be carefully evaluated and correlated to clinical symptoms.

Adult

Case-control study of risk factors for disease in the neck and shoulder area.

A case-control study was performed to elucidate the strength of the relation between musculoskeletal disorders in the neck and shoulders and physical, organisational, and psychosocial aspects of the work environment. Cases were identified as those persons who consulted a physician in a community in southern Sweden for new musculoskeletal disorders in the neck and shoulders during a study period from August 1988 to the end of October 1989. One hundred and nine cases were collected and clinically examined. The cases also answered the Nordic questionnaire on symptoms as well as a questionnaire on work conditions and background factors. Controls were drawn as a random sample of the working population in the community where the cases appeared. A total of 637 controls answered the same questionnaires as the cases. Odds ratios (ORs) were calculated by logistic regression. The odds ratios were 11.4 for women, 4.9 for immigrant background, and 3.7 for current smoking. To exercise rarely, compared with often, appeared as a preventive factor with an OR of 0.3. The ORs for various determinants of physical work load were 7.5 for repetitive movements demanding precision, 13.6 for light lifting, 3.6 for uncomfortable sitting positions, 4.8 for work with lifted arms, and 3.5 for a rushed work pace. Regarding work organisational determinants, the ORs were 16.5 for ambiguity of work role (uncertainty whether the person could manage the work) 2.6 for low quality work, and 3.8 for high demands on attention. Several of the determinants showed a significant dose-response relation with disease. It seems that work organisation and psychosocial work conditions are as important determinants for disease in the neck and shoulders as are the physical work conditions.

Adolescent

Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis.

To compare the efficacy of oral doxycycline and IV penicillin G for the treatment of neuroborreliosis, we randomized consecutive patients with Lyme neuroborreliosis to receive either IV penicillin G (3 g q 6 h) or oral deoxycycline (200 mg q 24 h) for 14 days. All patients had antibodies against Borrelia burgdorferi in serum, CSF, or both, or had a positive CSF culture. Twenty-three patients randomized to penicillin G and 31 patients to doxycycline were included in the study. All patients improved during treatment, and there were no significant differences between the two treatment groups in patient scoring, CSF analysis, or serologic and clinical follow-up during 1 year. There were no treatment failures, although one patient in each treatment group was re-treated because of residual symptoms. In conclusion, oral doxycycline is an adequate and cost-effective alternative to IV penicillin for the treatment of Lyme neuroborreliosis.

Administration, Oral

Long-term results of fracture of the scaphoid. A follow-up study of more than thirty years.

Fifty-six patients who had had a fracture of the scaphoid from January 1950 through December 1959 were interviewed, re-examined, and had radiographs made of both hands an average of thirty-six years (range, thirty-one to forty years) later. The average age at the time of the treatment was twenty-eight years (range, fifteen to forty-five years). Fifty-two of the fifty-six patients were treated at the time of the fracture; the other four had a non-union when first seen. The rate of non-union for the fresh fractures at the most recent follow-up examination was 10 per cent (five of fifty-two). Dorsal intercalated-segment instability was found in three of the fifty-six patients; all three had a pseudarthrosis and manifest radiocarpal osteoarthrosis. Marked radiocarpal osteoarthrosis developed in only one (2 per cent) of the forty-seven patients who had a healed fracture; it was far more common in the group that had a pseudarthrosis, in which the prevalence was five of nine patients. Manifest osteoarthrosis also seemed to be associated with pain or weakness: it had developed in only three (6 per cent) of the forty-nine patients who did not have any symptoms at the re-examination, compared with three of the seven who had symptoms.

Adolescent

Serological follow-up after treatment of Borrelia arthritis and acrodermatitis chronica atrophicans.

To study the serological response to Borrelia burgdorferi after treatment of late Lyme borreliosis, consecutive serum samples from 20 patients with Borrelia arthritis and 21 with acrodermatitis chronica atrophicans were analysed with capture IgM ELISA and indirect IgG ELISA, both using B. burgdorferi flagella as antigen. Seven patients had positive IgM OD values, whereas all 41 had positive IgG OD values before therapy. In the majority, highly elevated IgG OD values were seen. All patients improved after antibiotic therapy, 32 recovering completely, while 9 had sequelae. At follow-up after 6 months to 5 years, 4/7 patients became negative IgM ELISA, whereas 3 still had slightly elevated IgM OD values 6 months, 1 year and 4.5 years, respectively, after therapy. Only one patient became negative in IgG ELISA during follow-up, although a significant decline in IgG OD values was seen in 22 of the remaining 40 initially IgG-positive patients. The serological response after successful treatment of Borrelia arthritis and acrodermatitis chronica atrophicans may persist for several years even with highly elevated IgG OD values in patients who have recovered completely.

Acrodermatitis

Closed treatment of Jones fracture. Good results in 40 cases after 11-26 years.

40 patients with transversal or short oblique fractures of the proximal shaft of the fifth metatarsal bone (Jones fracture) were treated with full weight bearing with or without elastic bandage in 39 cases and plaster cast immobilization in one. 24 cases were acute traumatic fractures, 14 stress fractures and 2 refractures. After 17 (11-26) years, 33 of the fractures had healed primarily, evidence of refracture or delayed union was found in 7 and there were no non-unions. All but one of the patients were free of symptoms.

Adolescent

Comparison of information sources for case-referent data.

OBJECTIVES: Exposure assessment and the ascertainment of cases are topics of main concern in epidemiologic research. To investigate validity aspects of this kind practically, a comparative evaluation was performed of information sources for case-referent data. METHODS: Cases of Hodgkin's disease and non-Hodgkin's lymphoma diagnosed in 1975-1984 were collected from the Regional Cancer Register in Linköping. The study population was restricted to men 20-80 years of age at diagnosis. Living cases included in a previous case-referent study and the complementary cases from the register were compared with regard to the exposures indicated by job title and industrial branch, as given in the National Population Census in 1975. Furthermore, questionnaire-based exposure information from the case-referent study was compared with exposures derived from census information. RESULTS: Only 21% of all of the cases in the study base had been included in the questionnaire-based case-referent study. No major differences in the distribution of exposure were found for the two case series, except that fewer subjects were economically inactive in the previous case-referent study. No clear relations appeared between survival and particular exposures. Risk estimates derived from the present cancer register study were compared with corresponding estimates from the previous case-referent study. With restriction to only economically active cases, the risk estimates approached those of the case-referent study. CONCLUSIONS: This comparison showed that incomplete ascertainment of cases in a case-referent study was not an important source of bias, at least not in relation to what could be achieved by more complete case ascertainment through register linkage.

Adult

Jones fracture. Surgical versus nonsurgical treatment.

Sixty-three patients with 66 transverse and short oblique fractures of the proximal shaft of the fifth metatarsal bone (Jones fracture) were evaluated an average of five years (range, one to ten years) after the injury. There were 27 acute fractures and 39 chronic, or stress, fractures. The primary treatment was surgical for one third of the injuries and nonsurgical for the others. Surgical treatment consisted of the insertion of medullary screws. Nonsurgical treatment consisted of the application of either a plaster cast or an elastic bandage. Almost one fourth of the fractures treated nonsurgically later had to be treated surgically because of delayed unions or refractures. Late surgery was required in 12% of acute fractures and in 50% of chronic fractures with sclerosis narrowing the medullary canal. Irrespective of the primary treatment, all the patients had full function at the time of the follow-up evaluation, and no nonunions were diagnosed.

Adolescent