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Biomedical subjects

U Karlsson

Publications and source records attributed to U Karlsson.

At least 19 recordsLinked to original sources

Historical pollution of seldom monitored trace elements in Sweden--Part B: sediment analysis of silver, antimony, thallium and indium.

Sediment cores from four boreal and remote lakes in a south to north transect in central Sweden were analysed for acid leachable silver, antimony, thallium and indium in the solid sediment phase and the corresponding porewater. Dating of the cores was made by their content of acid leachable lead and the (206)Pb/(207)Pb ratio, in one lake also by (210)Pb. The impact of diagenesis on element redistribution in the sediments was included and found to be minor except for thallium. The results show lowered concentrations towards the north and most intense accumulation after the Second World War, which is taken as evidence for atmospheric deposition being the primary source. Indium has declining concentrations in recent strata while silver and antimony increase. Thallium has lowered acid-leachable concentrations in recent strata. For all metals the impact of domestic industrialisation as well as the early industrialisation of central Europe is discernible. Only thallium appears to reach a geological background at depths that correspond to the late 18th century. For the other metals elevated levels are concluded.

Environmental Monitoring↗

Dysphagia following chemoradiation for locally advanced head and neck cancer.

BACKGROUND: To assess the prevalence, severity and morbidity of dysphagia following concurrent chemoradiation for head and neck cancer. PATIENTS AND METHODS: Patients who underwent chemotherapy and radiation for head and neck malignancies were evaluated for their ability to resume oral feeding following treatment. Modified barium swallow (MBS) studies were performed if the patients complained of dysphagia or if there was clinical suspicion of aspiration. The severity of dysphagia was graded on a scale of 1-7. If significant abnormalities were found, swallowing studies were repeated until resolution of dysphagia. RESULTS: Between March 1999 and May 2002, 55 patients with locally advanced head and neck cancer underwent concurrent chemotherapy and radiation. Aspiration pneumonia was observed in eight patients, three during treatment and five following treatment. Five patients died from pneumonia. Two patients developed respiratory failure requiring intubation as a complication of pneumonia. At a median follow-up of 17 months (range 6-48 months), 25 patients (45%) developed severe dysphagia requiring prolonged tube feedings for more than 3 months (22 patients) or repeated dilatations (three patients). Among 33 patients who underwent MBS following treatment, 12 patients (36%) had silent aspiration (grade 6-7 dysphagia). Thirteen patients (39%) developed grade 4-5 dysphagia which required prolonged enteral nutritional support to supplement their oral intake. Most patients had severe weight loss (0-21 kg) during treatment, likely due in part to mucositis in the orodigestive tube. CONCLUSIONS: Dysphagia is a common, debilitating and potentially life-threatening sequela of concurrent chemoradiation for head and neck malignancy. Physicians should be aware that the clinical manifestations of aspiration may be unreliable and insidious, because of the depressed cough reflex. Modified and traditional barium swallows should be performed following treatment to assess the safety of oral feeding and the structural integrity of the pharynx and esophagus. Patients with severe dysphagia may benefit from rehabilitation. Tube feeding should be continued for those with aspiration.

Adult↗

Concurrent interferon-alpha and radiation for head and neck melanoma.

Melanoma cells are resistant to radiation in part due to their capacity to repair sublethal damage. A large fraction dose is therefore often utilized. However, if the tumour is located close to critical structures with modest tolerance, high fraction doses increase the risk for late complications compared with standard fractionation, but using the latter alone risks the desired outcome. Concurrent systemic biotherapy with standard radiation fractions may therefore represent an acceptable compromise. The outcome of concurrent systemic interferon-alpha (IFNalpha) and radiation in three patients with head and neck melanoma was evaluated. Standard radiation fractions were used because of the radiosensitizing properties of IFNalpha. Acute toxicity was significant and required treatment interruptions. However, all side effects subsided following treatment. All three patients achieved local control at follow-up periods of 24, 18 and 19 months, respectively. One patient developed widespread distant metastases. The combination of IFNalpha with radiation is considered feasible in terms of outcome and should be investigated with a larger cohort of patients. Toxicity is significant, and the addition of radioprotectors could be desirable.

Aged↗

Glutamate-induced currents reveal three functionally distinct NMDA receptor populations in rat dorsal horn - effects of peripheral nerve lesion and inflammation.

The importance of the N-methyl-D-aspartate (NMDA) receptor in various painful conditions is well established. The effects of peripheral nerve lesion or joint inflammation, as models of different pain states, on NMDA receptor-mediated currents and NMDA receptor subunit mRNA expression were therefore studied in acutely dissociated neurones from the rat spinal cord dorsal horn. In the neuronal population from control rats, all four NR2 subunits and both NR1 splice variants assayed were detected. A majority of neurones expressed mRNA for more than one NR2 subunit, and some neurones expressed all four NR2 subunits as well as both NR1 splice variants. The NR2B subunit was the most commonly expressed, while the NR2C was the rarest. Following nerve lesion, fewer neurones expressed NR2A compared to the control. The dose-response curve for glutamate-evoked NMDA receptor-mediated currents in the neurones was best described by a three-component fit, suggesting that three functionally distinct NMDA receptor populations are present in the dorsal horn. Minor changes in the dose-response curve after nerve lesion could not be ascribed with certainty to the lesion. Changes in other parameters of NMDA receptor-mediated currents were observed neither after nerve lesion nor after joint inflammation. In summary, the present work demonstrates that single dorsal horn neurones express mRNA for several NMDA receptor subunits. The glutamate dose-response curves indicate that there are three major types of NMDA receptors present in dorsal horn neurones. We also report a reduced expression of NR2A following peripheral nerve lesion.

Animals↗

Structure of the PPARalpha and -gamma ligand binding domain in complex with AZ 242; ligand selectivity and agonist activation in the PPAR family.

BACKGROUND: The peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors belonging to the nuclear receptor family. The roles of PPARalpha in fatty acid oxidation and PPARgamma in adipocyte differentiation and lipid storage have been characterized extensively. PPARs are activated by fatty acids and eicosanoids and are also targets for antidyslipidemic drugs, but the molecular interactions governing ligand selectivity for specific subtypes are unclear due to the lack of a PPARalpha ligand binding domain structure. RESULTS: We have solved the crystal structure of the PPARalpha ligand binding domain (LBD) in complex with the combined PPARalpha and -gamma agonist AZ 242, a novel dihydro cinnamate derivative that is structurally different from thiazolidinediones. In addition, we present the crystal structure of the PPARgamma_LBD/AZ 242 complex and provide a rationale for ligand selectivity toward the PPARalpha and -gamma subtypes. Heteronuclear NMR data on PPARalpha in both the apo form and in complex with AZ 242 shows an overall stabilization of the LBD upon agonist binding. A comparison of the novel PPARalpha/AZ 242 complex with the PPARgamma/AZ 242 complex and previously solved PPARgamma structures reveals a conserved hydrogen bonding network between agonists and the AF2 helix. CONCLUSIONS: The complex of PPARalpha and PPARgamma with the dual specificity agonist AZ 242 highlights the conserved interactions required for receptor activation. Together with the NMR data, this suggests a general model for ligand activation in the PPAR family. A comparison of the ligand binding sites reveals a molecular explanation for subtype selectivity and provides a basis for rational drug design.

Binding Sites↗

Human granulocytic ehrlichiosis--a clinical case in Scandinavia.

A clinical case of human granulocytic ehrlichiosis in Scandinavia is presented. The patient developed high fever, myalgia, headache and dyspnoea. Doxycycline treatment resulted in a dramatic improvement. Laboratory confirmation included a fourfold change in anti-Ehrlichia equi IFA titre and a positive PCR confirmed by gene sequence analysis.

Adult↗

Interferon-alpha combined with radiotherapy in the treatment of unresectable melanoma.

A case of recurrent and twice resected sinonasal melanoma is presented. The large recurrent tumor was found to regress by a concurrent combination of 6660 cGy photon radiation and subcutaneous interferon-alpha injections given for a period of 8 weeks. Possible mechanisms of potentiation between interferon and radiation are discussed. The unexpected result in this case report raises interesting questions about this treatment combination.

Antineoplastic Agents↗

A prospective 5-year study of fixed partial prostheses supported by implants with machined and TiO2-blasted surface.

PURPOSE: The aim of the present study was to evaluate whether there was a difference between machined and TiO(2)-blasted implants regarding survival rate and marginal bone loss during a 5-year observation period. MATERIALS AND METHODS: A total of 133 implants (Astra Tech Dental Implants; Astra Tech AB, Mölndal, Sweden) were placed in 50 patients at 6 centers in 4 Scandinavian countries. Forty-eight implants were installed in the maxilla and 85 implants in the mandible. A randomization and a stratification were done, so that each fixed partial prosthesis was supported by at least 1 machined and 1 TiO(2)-blasted implant. The implant-supported fixed partial prostheses (ISFPP) were fabricated within 2 months after postoperative healing. A total of 52 ISFPP (17 maxillary, 35 mandibular) were inserted. The patients were clinically examined once a year for 5 years. At the annual follow-up, biological as well as technical complications were recorded. RESULTS: Of the 133 implants placed, 3 were reported as failed after 5 years of follow-up, resulting in an overall cumulative survival rate of 97.6%. The cumulative implant survival rates were 100% for the TiO(2)-blasted implants and 95.1% for the machined implants. No significant difference in survival was, however, found between the machined and TiO(2)-blasted implants after 5 years. The mean marginal bone loss in the maxilla was 0.21 +/- 0.83 mm (SD) for the machined implants and 0.51 +/- 1.11 mm (SD) for the TiO(2)-blasted implants during the 5-year observation period. In the mandible, the mean marginal loss was 0.22 +/- 1.13 mm for the machined implants and 0.52 +/- 1.07 mm for the TiO(2)-blasted implants from baseline to the 5-year examination. No significant difference in marginal bone loss between the 2 surface groups was found during the 5-year observation period. CONCLUSIONS: The present study shows good 5-year results with small ISFPP in the mandible, as well as in the maxilla. No significant differences were found in failure rate and marginal bone loss around implants with a machined rather than a TiO(2)-blasted surface. J Prosthodont 2001;10:2-7.

Alveolar Bone Loss↗

Nonsubmerged implants in the treatment of the edentulous lower jaw: a 5-year prospective longitudinal study of ITI hollow screws.

BACKGROUND: Although most implant systems have been designed for a two-stage surgical technique, a one-stage surgical technique has always been advocated for the ITI Dental Implant System (Straumann AG, Waldenburg, Switzerland). A new generation of ITI implants was presented in 1988 and included a hollow cylinder, a hollow screw, and a solid screw. PURPOSE: The goal of this study was to evaluate the one-stage surgical technique in connection with the ITI hollow screw in a longitudinal study over 5 years. MATERIALS AND METHODS: Forty-six patients with edentulous lower jaws were supplied with ITI hollow-screw implants. Patients who requested an overdenture (n = 18) had four implants inserted; those who requested a fixed bridge (n = 28) had five to six implants. The patients have been followed annually for 5 years. There was a dropout of three patients (6.5%); one patient did not want to cooperate, one moved from the area, and one was deceased. The clinical examinations included bridge removal for evaluation of the individual implant stability in connection with the 1-, 3-, and 5-year examinations. Radiographic examinations were performed with intraoral radiographs and the long-cone technique. RESULTS: The survival rate after 5 years was 95.7%. The success rate (in which implants undergoing treatment of peri-implantitis were not counted as successes) was 91.4%. The mean marginal bone loss between the baseline and the 1-year examination was 0.1 mm and between the 1- and 5-year examinations was 0.1 mm. These changes in marginal bone level were not significant. CONCLUSIONS: The success rate of ITI hollow-screw implants in the edentulous mandible was 91.4% after a 5-year observation period. There was no significant change in mean bone level between the loading of the implants and the 5-year examination. Peri-implantitis was diagnosed in three patients with poor oral hygiene, and it affected six implants. Five of these failed in spite of treatment.

Adult↗

Disability and quality of life in individuals with postpolio syndrome.

PURPOSE: The purpose of the study is to investigate disability and quality of life in individuals with the characteristic symptoms of postpolio syndrome. METHOD: Disability is assessed by means of the self-report activities of daily living instrument, and quality of life by means of Kaasa's questionnaire and the quality of life profile. RESULTS: The 39 subjects have on average lived with polio sequelae for 52 years. Their main difficulties are with moving, lifting and carrying. This means restricted mobility, sedentary activities and a need to prioritize. Half of them feel that polio has lessened their possibilities in life, and a quarter have still not accepted the limitations polio has involved. Nevertheless the majority report a high level of psychosocial well-being, and almost a quarter say that living with polio has meant personal development and strength. We found a significant correlation between on the one hand disability with regard to ambulation, arm strength and finger strength on the self-report ADL, and on the other hand the number of negative problems on the quality of life profile (0.33-0.45). CONCLUSION: The latter instrument needs further testing before its validity can be determined with certainty.

Activities of Daily Living↗

Combined preoperative chemotherapy and radiation for locally advanced rectal carcinoma.

To determine the efficacy of combined preoperative chemotherapy and radiation therapy for locally advanced rectal carcinoma and the rate of sphincter conservation, a retrospective survey of 39 patients with locally advanced rectal carcinoma treated with various 5-fluorouracil- and leukovorin-based chemotherapy regimens and radiation prior to surgery in a single institution was reviewed. Toxicity, local control and survival were evaluated and compared to previous studies with similarly staged patients. Long-term follow-up was available on 35 patients. The actuarial local failure was 5.7% while the actuarial 5-year survival was 87%. The mortality rate was low (2.5%) and the rate of long-term serious complications acceptable (11.4%). Combined preoperative chemotherapy and radiation provided excellent local regional control despite the poor prognostic factors associated with size, fixation, and the initial advanced tumor stage with acceptable morbidity. In addition, patients with tumors located in the lower third of the rectum may be able to undergo sphincter-sparing surgery. Although the median follow-up is relatively short (32.4 months), the results are in accordance with previous studies of neoadjuvant combined chemotherapy and radiation for locally advanced rectal carcinoma in terms of local and distant control.

Anal Canal↗

Nonsubmerged implants in the treatment of the edentulous upper jaw: a prospective clinical and radiographic study of ITI implants--results after 1 year.

BACKGROUND: A new generation of ITI implants, including a hollow cylinder, a hollow screw, and a solid screw, was described in 1988. Currently, the solid screw is the main alternative. PURPOSE: The aim of this study was to gain further clinical documentation of ITI solid-screw implants used in the edentulous upper jaw. This is a report 1 year after loading. MATERIALS AND METHODS: Twenty-eight patients with edentulous upper jaws (mean age, 57 yr) were supplied with four to eight ITI solid-screw implants in the upper jaw. In total, 167 implants (3.3 and 4.1 mm in diameter) were inserted. The implants were loaded about 7 months postoperatively. All patients were supplied with fixed screw-retained bridges. RESULTS: Twelve implants failed: 10 prior to loading and 2 after. Overall implant survival rate was 92.8%. Three of the five patients with implant loss were smokers. Signs of peri-implantitis were found in seven patients, affecting 12 implants. Mean marginal bone level at the loading of the implants (7 months after insertion) was situated 4.7 mm from the reference point of the implant. There was no significant change between loading and the 1-year examination. However, at several implants, the bone level at baseline was situated far apical of the reference point, indicating a bone loss before loading. CONCLUSIONS: The ITI screw implants, used in the edentulous upper jaw, had a survival rate of 92.8%. Mean bone loss between loading and the 1-year examination was 0.1 mm. Some implants had a bone level indicating a significant bone loss before loading. Peri-implantitis was found at about 7.2% of the implants inserted and at 25% of the failing implants.

Adult↗

Heterogeneous presynaptic Ca2+ channel types triggering GABA release onto medial preoptic neurons from rat.

1. Voltage-dependent Ca2+ channels triggering GABA release onto neurons from the medial preoptic nucleus of rat were investigated. Acutely dissociated neurons with adherent functional synaptic terminals were investigated by tight-seal whole-cell recordings from the postsynaptic cells. 2. Spontaneous current events similar to miniature postsynaptic currents were recorded. They were blocked by bicuculline (100 microM), showed a roughly unimodal amplitude distribution and a reversal potential consistent with a Cl- current, and were therefore attributed to GABAA receptors activated by synaptically released GABA. 3. Application of 140 mM KCl, expected to depolarize presynaptic terminals, evoked currents that were ascribed to a more massive release of GABA. The KCl-induced synaptic currents were abolished in Ca2+-free solutions and showed a roughly hyperbolic relation to external Ca2+ concentration with half-saturation at 0.15 mM. They further depended on the concentration of applied KCl in a way expected for high-threshold Ca2+ channels. 4. The KCl-evoked synaptic currents were completely blocked by 200 microM Cd2+, but only partially blocked by 200 microM Ni2+. The KCl-evoked synaptic currents were insensitive to the L-type Ca2+ channel blocker nifedipine (10 microM). However, the synaptic currents were sensitive to either 1 microM omega-conotoxin GVIA, 25 nM omega-agatoxin IVA or 1 microM omega-conotoxin MVIIC. 6. It was concluded that, in many presynaptic terminals, the Ca2+ influx triggering GABA release onto medial preoptic neurons is mainly mediated by one predominant type of high- threshold Ca2+ channel that may be either of N-, P- or Q-type. 7. It was further concluded that terminals with similar predominant channel types often were clustered on the same postsynaptic cell.

Animals↗

A 2-year report on maxillary and mandibular fixed partial dentures supported by Astra Tech dental implants. A comparison of 2 implants with different surface textures.

In 50 partially edentulous patients, 133 (48 maxillary; 85 mandibular) Astra Tech dental implants of 2 different surface textures (machined; TiO-blasted) were alternately installed, supporting 52 fixed partial dentures (FPDs). Before abutment connection 2 machined implants (1 mandibular; 1 maxillary) were found to be non-osseointegrated and were replaced. Another implant could not be restored due to a technical complication. Two FPDs were remade because of technical complications, both because of abutment fractures. Thus, after 2 years in function, the cumulative survival rates were 97.7% and 95.7% for implants and prostheses, respectively. There was no statistically significant difference in survival rate between the 2 types of implants, 100% (TiO-blasted) vs 95.3% (machined), P = 0.24. After 2 years in function, when both jaw and type of implants were combined, the mean (SD) marginal bone loss was 0.24 (0.69) mm. No statistically significant difference in bone loss was found between the 2 types of implant after 2 years of loading, 0.04 (0.82) mm, P > 0.30.

Alveolar Bone Loss↗

Currents evoked by GABA and glycine in acutely dissociated neurons from the rat medial preoptic nucleus.

The responses of acutely dissociated medial preoptic neurons to application of GABA, and glycine were studied using the perforated-patch whole-cell recording technique under voltage-clamp conditions. GABA, at a concentration of 1 mM, evoked outward currents in all cells (n = 33) when studied at potentials positive to -80 mV. The I-V relation was roughly linear. The currents evoked by GABA were partially blocked by 25-75 microM picrotoxin and were also partially or completely blocked by 100-200 microM bicuculline. Glycine, at a concentration of 1 mM, did also evoke outward currents in all cells (n = 12) when studied at potentials positive to -75 mV. The I-V relation was roughly linear. The currents evoked by glycine were largely blocked by 1 microM strychnine. In conclusion, the present work demonstrates that neurons from the medial preoptic nucleus of rat directly respond to the inhibitory transmitters GABA and glycine with currents that can be attributed to GABAA receptors and glycine receptors respectively.

Animals↗

Glutamate-evoked currents in acutely dissociated neurons from the rat medial preoptic nucleus.

Membrane currents evoked by glutamate were investigated in acutely dissociated neurons from the medial preoptic nucleus (MPN) of rat. Rapid application of glutamate induced a fast current component in all neurons studied. In addition, in > 50% of the neurons, a slow current component was elicited. The fast and the slow current components were selectively blocked by the AMPA-receptor antagonist NBQX and by the NMDA-receptor channel blocker MK-801, respectively. Rapid application of AMPA induced, in all neurons tested, currents with properties similar to the fast component of the glutamate-evoked currents whereas rapid application of NMDA induced, in approximately 75% of the neurons, currents similar to the slow component of the glutamate-evoked currents. The NMDA-evoked currents showed a marked outward rectification that was attributed to a potential-dependent block by extracellular Mg2+. The NMDA-evoked currents also required the presence of extracellular glycine in the micromolar range. In conclusion, the results show that MPN neurons respond to glutamate with currents that can be attributed to activation of ionotropic glutamate receptors of the AMPA-receptor type as well as of the NMDA-receptor type.

Animals↗