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Biomedical subjects

J Jacobsen

Publications and source records attributed to J Jacobsen.

At least 37 records · Page 2Linked to original sources

Management of anaphylactic shock evaluated using a full-scale anaesthesia simulator.

BACKGROUND: The diagnosis of an anaphylactic reaction during anaesthesia is not the first consideration for the anaesthetist and might be missed. The aim of this study was to describe anaesthetists' management of an anaphylactic reaction concerning diagnosing, treatment and application of anaesthesia crisis resource management (ACRM) in a full-scale anaesthesia simulator. METHODS: Forty-two anaesthetists in teams of two attended training sessions with a critical incident of anaphylactic shock in a full-scale simulator. Trained observers from the study group evaluated the medical treatment according to a treatment sequence developed from the literature and graded the ACRM performance on a five-point scale where 1 is bad and 5 is best. RESULTS: None of the teams made the correct diagnosis within 10 min and treatment according to the treatment sequence was not initiated. Only 6/21 teams considered the right diagnosis but first after hints from the instructor 15 min after the start of the incident. Evaluation of the use of the total ACRM concept (that is the use of all of the ACRM expressions seen in a total connection: called general impression) gave a median value of 2.0 with a range of (1-3). CONCLUSION: Anaphylactic shock was difficult to diagnose and no structured plans were used for the treatment in the simulated incident in this study.

Anaphylaxis↗

How do anaesthesiologists treat malignant hyperthermia in a full-scale anaesthesia simulator?

BACKGROUND: Clinical malignant hyperthermia (MH) is rare and usually occurs unexpectedly. Prompt diagnosis and correct treatment is crucial for survival of the patient developing fulminant MH. The aims of the present study were to investigate whether anaesthesiologists could make a correct diagnosis of MH and to evaluate their treatment of fulminant MH in a simulator. METHODS: Thirty-two teams (one anaesthesiologist/one nurse anaesthetist) were exposed to an event of clinical MH in a full-scale simulator. Their performance was videotaped for retrospective analysis of the treatment on the basis of the recommendations of the Danish Malignant Hyperthermia Register. RESULTS: All 32 teams asked the surgeon to terminate the surgery as fast as possible, switched off the vaporiser and administered 100% oxygen. Although all intended to hyperventilate the patient, only 14 teams actually managed to perform the hyperventilation. Most problems were found in teams that switched to manual ventilation. All teams treated the patient with dantrolene, and symptomatic treatment was initiated by all even though some elements of the full treatment were lacking, possibly due to the limited time available. CONCLUSION: All teams diagnosed MH in the simulator satisfactorily. The surprising negative finding was that more than half of the participants failed to hyperventilate the "patient" although they intended to do so. This investigation shows that the problem in these teams' treatment of MH was more a question of practical management of the resources than lack of theoretical knowledge.

Anesthesiology↗

Increased serum cortisol levels are associated with high tumour grade in patients with renal cell carcinoma.

Cortisol and dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) are the major steroid hormones produced by the human adrenal cortex. The serum levels of cortisol and DHEAS were analysed in 211 consecutive patients with renal cell carcinoma before initiation of therapy. Serum cortisol was significantly higher in patients with renal cell carcinoma compared with that in patients with benign cysts (p < 0.0001). Serum cortisol was independent of disease stage, but positively correlated to tumour diameter and grade. The serum levels of DHEAS were higher in men than in women, and decreased with age, but did not correlate with disease stage, tumour diameter or grade. The prognosis of patients with elevated serum cortisol tended to be poorer (p = 0.06) than the prognosis of those with lower levels. In a multivariate analysis, disease stage and tumour grade were independent predictors of prognosis. Age, gender and serum levels of cortisol and DHEAS were of limited value for prognosis.

Adult↗

Tumor associated trypsin inhibitor as a prognostic factor in renal cell carcinoma.

PURPOSE: We analyzed the prognostic significance of pretreatment serum tumor associated trypsin inhibitor in renal cell carcinoma. MATERIALS AND METHODS: Serum samples were obtained before surgery from 188 patients who underwent radical nephrectomy for renal cell carcinoma. Median followup of living patients was 8.5 years. Serum tumor associated trypsin inhibitor was measured by a time resolved immunofluorometric assay. Statistical analysis was performed using the Kaplan-Meier method, log rank and stratified log rank tests. RESULTS: Preoperatively serum tumor associated trypsin inhibitor was elevated with a cutoff 16 microg/l in 48% of the patients with normal serum creatinine. The concentration in patients with cancer was significantly higher than in controls (p <0.0001). The serum level correlated with clinical stage and nuclear grade. Patients with an elevated level had significantly shorter survival time than those with a normal level (p = 0.005). Stratified log rank test demonstrated that tumor associated trypsin inhibitor was a prognostic factor independent of stage and grade in all patients as well as in those with nonmetastatic disease. CONCLUSIONS: Increased preoperative serum tumor associated trypsin inhibitor was associated with poor survival in renal cell carcinoma. The serum level was an independent prognostic variable. Preoperative serum tumor associated trypsin inhibitor appears to be a useful predictive factor that may be used to identify patients at increased risk of aggressive disease.

Adult↗

The MHC class II-associated chicken invariant chain shares functional properties with its mammalian homologs.

The nucleotide sequence of chicken invariant chain (Ii) was determined, and the amino acid sequence similarity with human Ii is 61%. Certain regions important for the biological function of human Ii are highly conserved between chicken and mammals. The cytoplasmic tail of chicken Ii fused to the plasma membrane reporter molecule neuraminidase relocated the protein to endosomes. Moreover, like the mammalian orthologs, the cytoplasmic tail was found to contain two independent leucine-based endosomal sorting signals. Chicken Ii was found to interact with human Ii and crosslinking studies also indicate that chicken Ii assembles as a trimer. The chicken Ii can furthermore bind the human MHC class II (HLA-DR1). Many of the functional properties between the chicken Ii and its mammalian orthologs are thus maintained in spite of their sequence differences.

Animals↗

Outcome of sulcus fixation of dislocated posterior chamber intraocular lenses using temporary externalization of the haptics.

OBJECTIVE: This study evaluated the visual outcome and complications of repositioning and sulcus fixation of a dislocated posterior chamber intraocular lens (PC IOL) using a technique in which the haptics of the IOL are temporarily externalized for suture placement. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Seventy-eight patients with a dislocated PC IOL. INTERVENTION: All patients underwent surgery to fixate the PC IOL using this technique. MAIN OUTCOME MEASURES: Patients were evaluated for visual acuity, refractive error, and surgical complications associated with the procedure. RESULTS: The average visual acuity before surgery was 20/205 (range, 20/20 to light perception), with a median refractive error of -1.00 diopters (D; range, -7.25-+15.00 D). After surgery, the average visual acuity improved to 20/72 (range, 20/20 to no light perception), with a median refractive error of -0.75 D (range, -5.50-+3.50 D). Patients were observed for a median of 15.5 months (range, 6-57 months). Twenty patients had postoperative cystoid macular edema (26%), 7 patients had an epiretinal membrane (ERM) (9%), and 5 patients had a retinal detachment (6%). Eight patients (10%) experienced iris capture of the sutured IOL, and in three patients (4%) the PC IOL dislocated again after surgery. CONCLUSIONS: This technique is an effective method for securing a dislocated PC IOL.

Adult↗

Vascular endothelial growth factor as prognostic factor in renal cell carcinoma.

PURPOSE: Vascular endothelial growth factor (VEGF) has been recognized as an important constituent of vascularization and growth of solid tumors. Serum VEGF levels were evaluated and correlated to clinicopathologic findings and clinical outcome in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: Serum samples were collected before surgery in 164 patients with RCC. Levels of VEGF165 protein in sera were measured using a quantitative ELISA. Univariate and multivariate analyses were performed. RESULTS: The VEGF165 level in serum was significantly increased (p = 0.0001) in patients with RCC (median 343.4 pg./ml.) compared with the control patients (median 103.8 pg./ml.). The level of VEGF165 in serum correlated to clinical stage and histopathological grade. Patients with VEGF165 levels below median value had significantly longer survival time than patients with higher levels (p = 0.0001). This was also shown when VEGF165 was analyzed in univariate Cox regression (p = 0.0001). The impact of VEGF165 on survival was especially shown in patients having tumors with vein invasion (pT3b-c N0 M0) and in patients with clinical stages I - III (p = 0.0240 and p = 0.0023, respectively). When using multivariate analysis, only tumor stage and grade remained as independent prognostic variables. CONCLUSIONS: In RCC, serum VEGF165 level was significantly correlated to tumor stage and grade. Increased levels were correlated to adverse survival. Although, VEGF did not remain as an independent prognostic factor in multivariate analysis the levels of VEGF165 in serum was found useful for the identification of patients with potentially progressive disease especially for those with vein invasion.

Adult↗

[Secondary prevention of ischemic heart disease. A questionnaire study and suggestions to improved cooperation between hospitals and general practice].

The aim of the present study was to examine the extent of secondary prophylaxis in patients following hospitalization under the diagnosis of ischaemic heart (IHD). Our data were based on hospital records and questionnaires sent to patients admitted to the Cardiological Department, Frederiksberg Hospital, under the diagnosis of IHD during the first six months of 1996. One hundred and twenty-five patients were included, of these 106 answered the questionnaire. We found that overall patients were insufficiently treated with aspirin, beta-blockers and antilipidaemic agents. Measures to reduce smoking and to increase physical exercise were sparse. We concluded that secondary intervention instituted from the Cardiological Department in question was not up to generally agreed standards. Suggestions to improve secondary prophylaxis in patients with IHD are presented. The importance of increased co-operation between hospital, general practitioner and patient is emphasized. A patient-born record designed for this purpose is presented.

Adult↗

Macular hole surgery with internal-limiting membrane peeling and intravitreous air.

OBJECTIVE: To examine the results of macular hole surgery using pars plana vitrectomy, internal-limiting membrane peeling, and intravitreous air in a series of consecutive patients. DESIGN: A retrospective, interventional, noncomparative case series. PATIENTS: Fifty consecutive patients (58 eyes) with full-thickness macular holes. INTERVENTION: All eyes underwent a pars plana vitrectomy with internal-limiting membrane peeling and intravitreous air, and patients were asked to position face-down for only 4 days. MAIN OUTCOME MEASURES: Status of macular holes, visual acuity, and associated findings and complications. RESULTS: All patients had postsurgical follow-up of 6 months or greater. Eight eyes (14%) presented with stage-2 macular holes, 48 eyes (83%) with stage-3 macular holes, and 2 eyes (3%) with stage-4 macular holes. Only 26 eyes (45%) had a macular epiretinal membrane seen before surgery. Fifty-three (91 %) of the 58 macular holes were closed with 1 operation, and 55 (95%) had closure of the macular holes with subsequent operations. Five (9%) of 58 eyes had an initial visual acuity of 20/50 or better, and 31 eyes (53%) had a final visual acuity of 20/50 or better. Of the 45 eyes with symptoms of less than 6 months' duration, 44 (98%) had macular holes that were closed with 1 operation and 27 (60%) had a final visual acuity of 20/50 or better. Of the 13 eyes with symptoms of 6 months' duration or longer, 9 (69%) had macular holes that were closed with 1 operation and 4 (31 %) had a final visual acuity of 20/50 or better. Complications attributed to the operation included retinal tears, retinal detachments, postoperative macular puckers, and macular light toxicity. CONCLUSIONS: The anatomic and visual results in this series are good. The current technique is similar to that of conventional macular hole surgery except for the use of intravitreous air, internal-limiting membrane peeling in all eyes, and only 4 days of postoperative positioning. This study would suggest that peeling of the internal-limiting membrane is an important adjuvant for successful closure of macular holes.

Adult↗

Pars plana vitrectomy without scleral buckle for pseudophakic retinal detachments.

OBJECTIVE: To report the anatomic and visual results of primary pars plana vitrectomy (PPV) without scleral buckling to repair primary rhegmatogenous retinal detachments in pseudophakic eyes. DESIGN: Nonrandomized, prospective, comparative clinical trial. PARTICIPANTS: Two hundred eighty-three consecutive patients (294 eyes) with pseudophakia, peripheral retinal tears, and new rhegmatogenous retinal detachments were treated according to the surgery protocol. INTERVENTION: Patients underwent PPV with fluid-gas exchange and endolaser to repair the retinal detachment. Two hundred sixty-four patients (275 eyes) were followed from 6 months to 6 years and 8 months with an average follow-up of 19 months. MAIN OUTCOME MEASURES: Reattachment of the retina and visual outcome were compared to previously published studies. RESULTS: Of 97 eyes with a macula-attached rhegmatogenous retinal detachment, 88 eyes (91%) were reattached with a single operation, and of the 178 eyes with a macula-detached retinal detachment, 153 (86%) eyes were reattached with a single operation. In 241 (88%) of 275 eyes, the retina was reattached with a single operation, and in 265 (96%) of 275 eyes, the retina was ultimately reattached with subsequent operations. The median initial visual acuity was 20/300, and the median final visual acuity was 20/40. The rate of reattachment with one operation was similar for eyes with an anterior chamber intraocular lens (91%) and for eyes with a posterior chamber intraocular lens (88%). Refractive error measurements obtained in 81 eyes were essentially unchanged. The mean change in refractive error was -0.15 diopter. Seventeen eyes (6%) developed macular puckers requiring surgery, 46 eyes (17%) developed cystoid macular edema, and 6 eyes (2%) developed full-thickness macular holes. CONCLUSION: Primary PPV with fluid-gas exchange and laser is a safe, effective method to repair primary pseudophakic retinal detachments. The anatomic reattachment rate and the visual acuity obtained with this technique appear to be at least as good as those reported in the literature for scleral buckling, PPV with scleral buckling, and pneumatic retinopexy.

Fluorocarbons↗

Cyclodextrin inclusion complexes of antimycotics intended to act in the oral cavity--drug supersaturation, toxicity on TR146 cells and release from a delivery system.

The dissolution rate, the toxicity and the release from chewing gum of miconazole and econazole cyclodextrin products and complexes were investigated. The dissolution rate studies showed that an amorphous miconazole hydroxypropyl-beta-cyclodextrin product gave drug supersaturation, whereas drug supersaturation was not present during dissolution rate testing of an econazole hydroxypropyl-beta-cyclodextrin product. The miconazole hydroxypropyl-beta-cyclodextrin product and genuine cyclodextrin inclusion complexes of miconazole, econazole and clotrimazole were toxic on a human TR146 buccal cell culture model. The toxicity was probably due to drug supersaturation, thereby increasing the bioavailability of the antimycotics. The econazole hydroxypropyl-beta-cyclodextrin product and physical mixtures of miconazole or econazole and beta-cyclodextrin did not give supersaturation and were not as toxic as the above-mentioned compounds. Neat econazole and miconazole, a genuine econazole beta-cyclodextrin complex and the miconazole hydroxypropyl-beta-cyclodextrin product were incorporated in chewing gum. The miconazole hydroxypropyl-beta-cyclodextrin gum had a much higher drug release in vitro than the neat miconazole gum. The genuine econazole beta-cyclodextrin complex only increased the drug release moderately when compared with the release from the neat econazole gum. The release studies were performed on a mastication device.

2-Hydroxypropyl-beta-cyclodextrin↗

Filter-grown TR146 cells as an in vitro model of human buccal epithelial permeability.

Use of a cell culture model of a specific epithelium requires documentation of its differentiation. This study reports permeability of mannitol concurrent with a profile of differentiation markers of filter-grown TR146 cells, a cell line originating from a human buccal carcinoma, cultivated submerged or at the air-liquid interface for 23 to 31 d. A multilayered squamous epithelial-like tissue was found. The maximal permeability barrier and the most distinct stratification were obtained at day 23, when cultured submerged (apparent permeability coefficient 4.08 +/- 0.15 (x 10(-6)) cm/s; transepithelial electrical resistance 102 +/- 5 omega x cm2). The profile of differentiation markers demonstrated similarities to normal human buccal epithelium by expression of K4, K10, K13, K16, and K19 keratins, plasma membrane-associated transglutaminase, involucrin, and epidermal growth factor receptor. Uniform expression of K5, K8 and K18 was consistent with the carcinogenic origin of TR146 cells. Identical profiles of differentiation markers were obtained irrespective of method or time of culture. Karyotyping proved the human origin of TR146 cells. Three different passages had near triploid (3n+-) chromosome compliments and consistent occurrence of four marker chromosomes [mar4, mar5, mar9, and add(5)(p)], while differences between them defined them as subclones. The results indicate that a submerged filter-grown TR146 cell culture at day 23 of culture has the potential to model the human buccal epithelial barrier for permeation of drugs.

Antigens, Differentiation↗

Cyclodextrin inclusion complexes of miconazole and econazole--isolation, toxicity on human cells, and confirmation of a new interpretation of the drug supersaturation phenomenon.

Parameters that influence the precipitation of the beta-cyclodextrin (beta-CD) inclusion complexes of the antimycotics miconazole and econazole were investigated. The mechanistic reason for the superior antimycotic activity of the miconazole inclusion complex was studied. The toxicity of the complex was estimated. The temperature, the buffer strength, and the effect of the addition of hydrotropic agents on the CD solubility diagrams for the antimycotics were estimated. The miconazole and the CD dissolution rate for the complex was measured. The hemolytic activity of the miconazole inclusion complex, the physical mixture, miconazole, and the nitrate salt were compared. The toxicity on TR146 oral cell layers was measured. Lowering the temperature meant that both complexes precipitated at lower CD concentrations. Addition of hydrotropic agents and variation of the buffer strength affected the solubility diagrams. The dissolution medium was supersaturated with miconazole. The supersaturation was not disclosed by the traditional method to analyze for drug supersaturation. The miconazole complex was more toxic to erythrocytes than the physical mixture. On the other hand, the toxic effects of the two products on the TR146 cell layers were similar. Lowering the temperature eased the isolation of genuine CD inclusion complexes of miconazole and econazole. The miconazole supersaturation is likely to be the reason for the superior antimycotic activity of the complex. The complex and the physical mixture had about the same toxicity on TR146 cell layers.

Antifungal Agents↗

Molecular screening for proximal 15q abnormalities in a mentally retarded population.

Paternal or maternal deletions in the 15q11.2-q13 region are known to result in Prader-Willi syndrome (PWS) or Angelman syndrome (AS), respectively. Maternal duplications in 15q11.2-q13 have been found in patients with autism. A population of adults with moderate to profound mental retardation was studied to examine the usefulness of PCR based molecular methods in screening for proximal chromosome 15 abnormalities. Two hundred and eighty-five subjects were initially screened at five microsatellite markers with average heterozygosity values of 0.74 (range 0.54-0.82). Of these subjects, four had a single allele at all five loci, suggestive of a deletion or uniparental isodisomy. The four samples were further screened with additional markers located within 15q11.2-q13 as well as markers telomeric to this region. One subject had uniparental disomy (UPD) and three subjects had a deletion. To determine the parental origin of the 15q11-q13 region containing the single haplotype, samples were analysed with a newly developed methylation specific PCR technique at the SNRPN locus. Each of the four subjects showed presence of the paternal allele and absence of the maternal allele. All cases had a phenotype consistent with Angelman syndrome as expected for the level of mental retardation, but the subject with UPD was distinct from the other subjects with an absence of a history of seizures and presence of bilateral undescended testes and Parkinsonism. Although Angelman syndrome has an estimated population prevalence of 0.008%, at least 1.4% of the moderately to profoundly mentally retarded subjects screened were found to have Angelman syndrome.

Adult↗

REM-sleep motor disorder in children.

In 1986, Schenck and coworkers described REM-sleep behavior disorder as a treatable parasomnia affecting older males. This disorder is characterized by intermittent loss of the muscle atonia, which normally characterizes the rapid eye movement (REM) sleep state. Complex motor behaviors occur that are often injurious and are associated with dreaming. We have identified five children who meet the criteria for REM-sleep behavior disorder and describe the clinical and polysomnographic characteristics of these patients, along with corresponding polysomnographic characteristics of matched comparison subjects.

Child↗

Treatment of ventricular fibrillation during anaesthesia in an anaesthesia simulator.

BACKGROUND: To evaluate treatment of ventricular fibrillation (VF) occurring during anaesthesia and the use of a full-scale simulator, 80 anaesthetists in teams of two were attending a training session in the simulator Sophus. METHODS: The sessions were recorded on videotape and reviewed with the anaesthetists afterwards. Time of treatment and the sequence were registered. RESULTS: Onset time for VF was the starting point. Most of the subjects changed respiratory settings. Four teams did not change inspiratory oxygen and 17 teams did not turn off the vaporiser. Cardiac compression was initiated by all teams. DC-defibrillation was not used by two teams, with 38 of 40 teams defibrillating once, 37 twice and 29 teams three times. Adrenaline was administered by 30 of 40 teams. CONCLUSION: There was very little consistency among the teams regarding treatment for VF according to accepted algorithms. An anaesthesia simulator could be a tool for training and it is a safe way of demonstrating for the anaesthetist that certain treatment algorithms and behaviour during critical incidents are the most effective.

Anesthesia↗