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Biomedical subjects

M Karlsson

Publications and source records attributed to M Karlsson.

At least 163 records · Page 9Linked to original sources

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↗

Phenyl-substituted prostaglandins: potent and selective antiglaucoma agents.

A series of phenyl-substituted analogues of prostaglandin F2 alpha (PGF2 alpha) were prepared and evaluated for ocular hypotensive effect and side effects in different animal models. In addition, the activity of the analogues on FP receptors was studied in vitro. The results were compared with those of PGF2 alpha and its isopropyl ester. The phenyl-substituted PGF2 alpha analogues exhibited good intraocular pressure reducing effect, were more selective, and exhibited a much higher therapeutic index in the eye than PGF2 alpha or its isopropyl ester. The analogues exhibited high activity on FP receptors in a stereoselective manner for the 15 alpha-hydroxyl group.

Animals↗

Routes of putative afferent axons in rat lumbosacral ventral roots and pia mater.

Unmyelinated sensory axons occur in mammalian ventral roots. On this basis the law of Magendie has been questioned. With few exceptions, the current ideas on the routes that these axons might follow have been based on electron microscopic examination of transverse sections, and evidence obtained through electrophysiological experiments or tracer studies. The purpose of the present study is to examine putative afferent rat ventral root axons, which have been visualized directly by immunohistochemical labelling. After immunolabelling of axons containing substance P or calcitonin gene-related peptide in longitudinal sections from the ventral roots L4-S1, and in wholemount pia mater-rootlet preparations, fluorescent fibres were searched for in the microscope. The results show that some immunolabelled axons end blindly in the root, while others shift to the pia mater, or make U-turns. Some axons make irregular 'zigzag' deviations or branch. No immunoreactive axons were seen entering the spinal cord via the ventral roots. These observations support the view that the law of Magendie is valid.

Animals↗

Myelography in the late postoperative period in patients subjected to anterior cervical decompression and fusion.

During a 13 year period, 286 patients with cervical disc herniation and/or spondylotic spurs, were subjected to anterior decompression and vertebral interbody fusion with autologous bone. Twenty patients were re-admitted in the late postoperative period due to recurrent radicular symptoms and/or signs of myelopathy. In these patients myelography was performed again. In 14 patients spinal cord compression and/or nerve root involvement at a new level was visualized. At the operated level, however, the myelograms demonstrated a smooth anterior wall in the spinal canal. The series confirms the safety, effectiveness and reliability of the Cloward procedure in achieving long term spinal cord and nerve root decompression, and a solid vertebral interbody fusion.

Cervical Vertebrae↗

Matching of electron and photon beams with a multi-leaf collimator.

Multi-leaf collimators (MLCs) are offered as an accessory to many accelerators for radiation therapy. However, beam edges generated with these collimators are not as smooth as can be achieved with individually made blocks. The clinical drawbacks and benefits of this ripple were evaluated both for single field treatments and for combined adjacent fields of different beam qualities. In this investigation the MLC-collimated beams of the MM50 racetrack microtron were studied. The distance between the field edge and the 90% isodose was measured at the reference depth for four beam qualities (20 MV photons and 10, 20 and 50 MeV electrons). This distance was found to vary from approximately 6 mm for straight beam edges (i.e., all collimator leaves aligned) to approximately 2 mm from the tip of the leaves for a saw-tooth shaped beam edge. The over- and under-dosage in the joint between combined adjacent fields was found to be typically +/- 10% in small volumes. Improved clinical techniques using adjacent photon and electron fields with the same isocentre and source position (without moving the gantry) have been developed. For treatments of the breast, including the mammary chain, a uniform dose distribution was created with special attention given to the irradiation of the heart and lung outside the target volume. A method for head and neck treatments was optimised to give uniform dose distribution in the joint between the photon and electron fields and a method of treating the mediastinum, including the chest wall in front of the left lung, was analysed with respect to dose uniformity in the tumour and shielding of the lung.

Breast↗

DNA ploidy and S-phase in primary malignant melanoma as prognostic factors for stage III disease.

In 82 patients with stage III malignant melanoma, the primary tumours were investigated by DNA flow cytometry. The tumours were classified as DNA diploid (n = 36), tetraploid (n = 11) and aneuploid (n = 35). By univariate analysis a significant correlation with post-recurrence survival was found for time to first metastasis, DNA-ploidy and S-phase fraction. By multivariate analysis, significant prognostic variables were found to be the time to first metastasis (P = 0.006), and ploidy (P = 0.011). Patients with diploid melanomas and a long recurrence-free interval had a median post-recurrence survival time of 45 months compared to 18 months in patients with DNA aneuploid tumours and an early recurrence. The S-phase could be estimated in 47 primary melanomas and was found to be a significant prognostic variable (P = 0.017). The median survival was 45 months for patients with melanomas with a S-phase fraction below 5%, and 19 months for melanomas with S-phase above 10%. The prognostic value of the S-phase remained significant even after adjustment for recurrence-free interval and DNA ploidy.

Aged↗

Fractionated irradiation and late changes in rat parotid gland: effects on the number of acinar cells, potassium efflux, and amylase secretion.

Irradiation of head- and neck cancer commonly results in oral dryness and discomfort for the patients due to salivary gland damage. The exact mechanisms behind the inherent radiosensitivity of salivary glands remain to be elucidated. In the present study, we used different in vitro secretory models and quantitative morphological characterization of rat parotid gland following fractionated unilateral irradiation to one gland on a 5-day fraction schedule (Monday-Friday) with 6 MV photons (total dose 30, 35, 40 and 45 Gy) or a two-fractions regimens in 5 days (Monday and Friday) with total dose of 24 and 32 Gy. The contralateral shielded gland served as control, and parallel analyses of irradiated and control glands were performed 180 days following the last irradiation treatment. The relative noradrenaline stimulated electrolyte secretion (86rubidium tracer for potassium) was decreased in the irradiated compared with control glands. The noradrenaline-stimulated exocytotic amylase release was not significantly affected by irradiation, but the gland content of amylase was decreased dose-dependently. The quantitative morphological analysis revealed a dose-dependent decline in the number of acinar cells, whereas the other parenchymal cells (intercalated, striated- and excretory duct cells) were unaffected by the irradiation compared with control glands.

Amylases↗

The effect of catechol-O-methyl transferase inhibition by entacapone on the pharmacokinetics and metabolism of levodopa in healthy volunteers.

We studied the effect of inhibiting the enzyme catechol-O-methyltransferase (COMT) by a novel COMT inhibitor, entacapone, on the pharmacokinetics and metabolism of levodopa in 12 healthy male volunteers. Single increasing oral doses of entacapone (50-400 mg) were administered concomitantly with a single oral dose of levodopa/carbidopa (100/25 mg). The subjects were treated with carbidopa (100 mg t.i.d.) for 1 day prior to the administration of study drugs. Plasma concentrations of levodopa; its metabolites 3-O-methyldopa (3-OMD), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA); as well as carbidopa and entacapone were determined for pharmacokinetic calculations. Entacapone dose-dependently increased the area under the plasma concentration-time curve (AUC) of levodopa; the increase was 65% after the 400 mg dose of entacapone. Neither Cmax nor Tmax of levodopa was statistically significantly influenced by entacapone. Entacapone dose-dependently decreased the AUC of 3-OMD, maximally by 58%. The AUC of DOPAC was statistically significantly increased but no change in the AUC of HVA was observed after entacapone. No drug-related adverse events or hemodynamic effects were observed. The in vivo biochemical effects of entacapone indicate that it is an orally active COMT inhibitor and that it may improve the therapeutic efficacy of levodopa in Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗

A sequence-specific function for the N-terminal signal-like sequence of the TonB protein.

TonB is a proline-rich protein which provides a functional link between the inner and outer membranes of Gram-negative bacteria. TonB is anchored to the inner membrane via an N-terminal signal-like sequence and spans the periplasm, interacting with transport receptors in the outer membrane. We have investigated the role of the N-terminal signal-like peptide in TonB function. Replacement of the N-terminal sequence with heterologous sequences indicates that it has at least three distinct roles in TonB function: (i) to facilitate translocation of TonB across the cytoplasmic membrane; (ii) to anchor TonB to the cytoplasmic membrane; (iii) a sequence-specific functional interaction with the ExbBD proteins.

Amino Acid Sequence↗

ExbB acts as a chaperone-like protein to stabilize TonB in the cytoplasm.

The TonB protein is required to transduce energy from the cytoplasmic membrane to outer membrane transport proteins of Gram-negative bacteria. Two accessory proteins, ExbB and ExbD, are required for TonB function and it has been suggested that TonB and ExbBD form a complex in the membrane. In this paper we demonstrate that there are two spatially distinct, functional interactions between ExbBD and TonB. First, there is an interaction between ExbBD and the N-terminal signal-like peptide of TonB, probably the formation of a stable complex in the membrane. Second, ExbB interacts with TonB in the cytoplasm. This interaction involves the domain of TonB that is normally periplasmic. Thus, this is a transient interaction which occurs during the synthesis and/or localization of TonB, implying a chaperone-like role for ExbB. The transmembrane topology of ExbB was shown to be consistent with this role.

Amino Acid Sequence↗