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Biomedical subjects

L Nielsen

Publications and source records attributed to L Nielsen.

At least 73 records · Page 4Linked to original sources

Improved outcome of coronary arterial bypass surgery in a small center after identification and modification of peroperative risk factors.

By uni- and multivariate analysis, predictors of surgical mortality and postoperative angina were identified retrospectively in 189 patients having had coronary arterial bypass surgery over the period 1978-1984. After modification of these risk factors, surgical outcome was followed up in another 178 patients undergoing operation from 1985 to 1987. The surgical mortality of 7% in the first series was closely associated with postoperative signs of acute myocardial injury. All deaths occurred in patients having at least 3 out of 5 pre- and peroperative risk factors: triple vessel/left main coronary arterial disease, incomplete revascularization, no propranolol treatment, Bretschneider cardioplegia other than "HTP"-solution with blood preperfusion and perioperative vasopressor support. The procedures of cardiac protection were modified. St Thomas multidose potassium cardioplegia and general hypothermia were introduced, perioperative propranolol treatment increased and bypass time decreased. Improved cardiac protection with this regime was seen in the patients operated in 1985-1987 when compared with the first series with regard to perioperative vasopressor support (8 vs 33%, P less than 0.001), spontaneous operative defibrillation (72 vs 52%, P less than 0.001), postoperative arrhythmias (20 vs 43%, P less than 0.001), peak levels of serum enzymes (P less than 0.001), myocardial infarction (7 vs 19%, P less than 0.001) and hospital mortality (2 vs 7%, P less than 0.05). The incidence of freedom from symptoms at 3 months was also increased in the patients undergoing operation from 1985 to 1987 (72 vs 61%, P less than 0.05). Even small centers can improve their surgical outcome by carefully analysing their own results and modifying the identified risk factors.

Angina Pectoris↗

GABA agonists and uptake inhibitors. Synthesis, absolute stereochemistry, and enantioselectivity of (R)-(-)- and (S)-(+)-homo-beta-proline.

The cyclic analogue of 4-aminobutyric acid (GABA), 3-pyrrolidineacetic acid (homo-beta-proline), is a potent agonist at GABAA receptors, it interacts effectively with GABA-uptake mechanisms, and it is a moderately potent inhibitor of GABAB receptor binding. (R)-(-)- (10) and (S)-(+)-homo-beta-proline (15) were synthesized via methyl (3S)-1-[(R)-1-phenylethyl]-5-oxo-3-pyrrolidinecarboxylate (5) and its 3R diastereomer (4), respectively. The mixture 3 consisting of 4 and 5 was synthesized via addition-cyclization reactions between (R)-1-phenylethylamine and itaconic acid (1). The diastereomers 5 and 4, which were separated chromatographically, were converted into (R)- (10) and (S)-homo-beta-proline (15), respectively. The absolute stereochemistry of 10 and 15 was established on the basis of an X-ray analysis of compound 5. The enantiomers 10 and 15 were shown to bind to GABAA and GABAB receptor sites with opposite stereoselectivity. Thus, (R)-homo-beta-proline (10) proved to be more than 1 order of magnitude more potent than the S enantiomer (15) as an inhibitor of GABAA receptor binding, whereas the GABAB receptor affinity of homo-beta-proline was shown to reside exclusively in (S)-homo-beta-proline (15). In contrast to the stereoselective receptor affinities of 10 and 15, these enantiomers were approximately equieffective as inhibitors of synaptosomal GABA uptake.

Animals↗

TMJ function and the effects on the masticatory system on 14-16-year-old Danish children in relation to orthodontic treatment.

The effect of orthodontic treatment on the functional status of the masticatory system was analysed in 706 children from three Danish communities. Three-hundred-and-eighty-eight (48 per cent) of the children were treated orthodontically and the 295 (37 per cent) of the total population had terminated the treatment and were included in the analysis. Fifty-seven cases (7.1%) of the total population were discontinued before the orthodontic treatment was considered finished by the orthodontist. Discontinuation did not, however, seem to influence the functional status. Increasing the orthodontic treatment frequency from 38 to 51 per cent did not decrease the functional problems of a young population. On the contrary, the community with the lowest treatment frequency (38 per cent) demonstrated fewer functional problems among the orthodontically treated subjects than did the two communities with higher treatment frequencies, indicating paradoxically that it may be a functional risk to treat the last 13 per cent with minor discrepancies. Tenderness on palpation of the musculature and the TMJ capsule were generally more prevalent among orthodontically treated subjects. Children who had their treatments performed by either orthodontist or paedodontist alone demonstrated more muscular problems than children who had been treated by a team of orthodontists and paedodontists. Related to the severity of the malocclusion these findings stress the importance of more consideration to establish a functionally satisfactory occlusion after orthodontic treatment. Functional status was not related to the type of orthodontic treatment, including extraction therapy, use of either fixed or removable appliances.

Adolescent↗

A community-wide outbreak of hepatitis A in a religious community: impact of mass administration of immune globulin.

Community-wide outbreaks of hepatitis A are frequently prolonged and difficult to control. An extensive outbreak of hepatitis A in a religious community provided an opportunity to assess the effect of mass administration of immune globulin on the course of the outbreak. Between July 1, 1988 and May 30, 1989, 204 cases occurred among 3,500 residents (58/1,000), with persons aged 5-19 years having the highest attack rate. It was found that 89% of persons older than age 19, but no persons under age 20, had evidence of prior hepatitis A infection. During a 5-day campaign, immune globulin (0.02 ml/kg) was administered to 2,287 (65%) of the 3,500 residents. The cost of vaccine and syringes was less than $3,500. New cases among immune globulin recipients virtually stopped 2 weeks after the campaign, and the incidence of hepatitis in the community decreased from 9.6/week to 1.9/week. Among persons younger than age 20 years, the efficacy of immune globulin was 88.9% (95% confidence interval 77.9-94.5) for seven months. Although the authors cannot be sure that the outbreak will not recur, they believe that mass administration of immune globulin appears to have been partially effective at controlling this community-wide outbreak.

Adolescent↗

Screening for functional disorders of the masticatory system among teenagers.

This study evaluated the efficiency of a questionnaire as compared to a brief clinical examination for identification of clinically assessed craniomandibular disorder cases. 706 Danish children 14-16 yr old answered a self-administered questionnaire concerned with dysfunction symptoms and oral habits. In addition they were subjected to a clinical examination of signs of dysfunction from the masticatory system. Based on the present study a self-administered questionnaire for screening purposes used in an a priori healthy population of teenagers cannot be recommended. The answers to the questionnaire showed a low reproducibility and their ability to predict clinically assessed signs of dysfunction was inadequate. The most favorable combinations of single questions were calculated in order to optimize sensitivity, specificity, and predictive value of the questionnaire. A maximum of 65% of the clinically diseased subjects were identified by the questionnaire and only 41% of the test positive subjects had their subjective diagnoses confirmed at the clinical examination. The brief clinical screening procedure succeeded in identifying 92% of children with severely disturbed function. The subjects testing positively according to the brief clinical examination were children with either moderate or severe disturbances except for only one case. Based on a cost to benefit consideration a brief clinical examination is preferred to a self-administered questionnaire as a routine procedure for detection of craniomandibular disorders.

Adolescent↗

Serum sensitivity of a diversity of Escherichia coli antigenic reference strains. Correlation with an LPS variation phenomenon.

One hundred and ninety-four E. coli O, K and H antigen reference strains and some strains of certain O:K types were examined for resistance to the bactericidal effect of normal human serum by the method of Olling. A strain was defined as serum-resistant when less than 50% and serum-sensitive when greater than 90% bacteria were killed. Fifty-seven reference strains were serum-sensitive, 21 of them produced K antigens which apparently had no protective role. Thirty-seven reference strains were serum-resistant, and 13 of these produced no K antigen; thus the O antigens might by themselves be protective in these cases. K- mutants of the serum-resistant O8:K87 strains were serum-sensitive, and the O9:K9 strain changed from being serum-resistant to being partly resistant when the K antigen was lost; mutants of the O6:K13 strain with no or a small amount of K13 were less resistant than the original K+ strain; similar mutants of the O22:K13 reference strain did not show any decrease in serum resistance. Strongly related to 022 is 083, and results with several 083 strains pointed to the importance of this O antigen for serum resistance. In an O83:K14 strain a spontaneous variation occurred in LPS from a few to many repeating units; this variation was accompanied by a change from serum sensitivity to serum resistance.

Antigens, Bacterial↗

Identification, synthesis and immunogenicity of cuticular collagens from the filarial nematodes Brugia malayi and Brugia pahangi.

The major structural proteins of the cuticle of the filarial nematode parasites Brugia malayi and Brugia pahangi were identified by extrinsic iodination and sensitivity to clostridial collagenase. At least 16 acidic components were identified in adult worms by 2-dimensional electrophoresis, with molecular weights ranging from 35,000 to 160,000. These proteins appear to be cross-linked by disulphide bonds, and localised in the basal and inner cortical layers of the cuticle. The outer cortex, containing the epicuticle, is insoluble in 1% sodium dodecyl sulphate and 5% 2-mercaptoethanol, and can be isolated free of cellular material. Despite their inaccessibility to the immune system in intact worms, antibodies to the cuticular collagens are provoked in humans infected with a variety of filarial parasites. Immunological cross-reactivity was demonstrated between a 35 kDa component and human type IV (basement membrane) collagen. Autoantibodies to type IV collagen were detected in a number of individuals with lymphatic filariasis, although no correlation could be drawn with observed pathology. Synthesis of cuticular collagens is discontinuous, occurs at negligible levels in mature adult male worms, and does not appear to involve the production of small molecular weight precursors, in contrast to Caenorhabditis elegans. Hybridisation with a heterologous cDNA probe coding for the alpha 2 chain of chicken type 1 collagen suggests that they are encoded by a multigene family.

Animals↗

Ultrasonically guided 125iodine seed implantation with external radiation in management of localized prostatic carcinoma.

Thirty-three patients with localized prostatic carcinoma (16 poorly differentiated) were treated with transperineal 125Iodine seed implantation (160 Gy) guided by transrectal ultrasonography and subsequent external beam irradiation (47.4 Gy). The observation time was six to sixty-eight months with a median follow-up of thirty-five months. Median change in prostatic volume was a reduction of 35 percent. Re-biopsy or transurethral resection of the prostate was performed in 25 patients after one to two years, revealing still malignant histology in 12 (48%). Development of distant metastases occurred in 14 patients (44%), and 8 have died of prostatic cancer. Fourteen patients suffered from late complications of which surgical intervention was indicated in 3 cases.

Aged↗

GABA receptors on the somatic muscle cells of the parasitic nematode, Ascaris suum: stereoselectivity indicates similarity to a GABAA-type agonist recognition site.

1. The gamma-aminobutyric acid (GABA) receptors on the somatic muscle cells of Ascaris, which mediate muscle cell hyperpolarization and relaxation, have been characterized by use of intracellular recording techniques. 2. These receptors are like mammalian GABAA-receptors in that the response is mediated by an increase conductance to chloride ions. The GABAA-mimetic, muscimol, has a relative potency of 0.40 +/- 0.02 (n = 3) compared to GABA. 3. The stereoselectivity of the GABA receptor on Ascaris is identical to that for the mammalian GABAA-receptor, as determined from the relative potency of three pairs of enantiomers of structural analogues of GABA. 4. The most potent agonist is (S)-(+)-dihydromuscimol which is 7.53 +/- 0.98 (n = 5) times more potent than GABA. 5. The Ascaris GABA receptor is not significantly blocked, at concentrations below 100 microM by the potent, competitive GABAA-receptor antagonist, SR95531. 6. The Ascaris GABA receptor does not recognise agents that are known to block the GABA gated chloride channel in mammalian preparations such as t-butylbicyclophosphorothionate (TBPS, 10 microM, n = 2) or the insecticide dieldrin (100 microM, n = 3). 7. GABAergic responses in Ascaris are not potentiated by pentobarbitone (100 microM, n = 3) or flurazepam (100 microM, n = 3). 8. The potencies of various GABA-mimetics in the Ascaris preparation have been compared with their potency at displacing GABAA-receptor binding in mammalian brain. Excluding the sulphonic acid derivatives of GABA, the correlation coefficient (r) between the potencies of compounds in the two systems is 0.74 (P less than 0.01). The significance of this correlation is discussed. 9. The pharmacology of the Ascaris GABA receptor is discussed in relation to other invertebrate systems and the mammalian subclassification of GABA receptors.

Animals↗

Prevalence, interrelation, and severity of signs of dysfunction from masticatory system in 14-16-year-old Danish children.

A clinical evaluation of the functional status of the masticatory system was performed on 706 14-16-yr-old children who had received a minimum of 9 yr regular dental care and had only natural teeth. Applying a classification system developed for this specific age group, 19% were assigned to the group with moderate and 11% to the group with severe disturbances. An analysis of the association between the signs of dysfunction revealed that TMJ clicking was always associated with some but not necessarily numerous palpatory findings. The localizations of the TMJ clickings were related to specific signs of dysfunction from the masticatory system. Restriction of movement capacity of 2 standard deviations was frequently found as an isolated phenomenon, whereas restriction of 3 standard deviations was always associated with either palpatory findings or sounds from the joints.

Adolescent↗

Zidovudine treatment of AIDS and ARC in Denmark 1987.

In 1987, a total of 138 Danish patients (94 AIDS and 44 ARC) received treatment with zidovudine, a total observation period of 572 treatment months. 15 AIDS and 1 ARC patient died after a median of 70 days (range 2-295). In the ARC group 4 patients developed AIDS (3 Pneumocystis carinii pneumonia, 1 Kaposi's sarcoma). Among the AIDS patients 38 new opportunistic infections were reported. 24 of these opportunistic infections occurred within 6 weeks after treatment initiation. 79 patients were observed for more than 3 months, 25 of these had their daily dose zidovudine reduced, usually from 1,200 mg to 600 mg, 9 others were temporarily off drug. HIV antigen was analyzed in serum samples from 93 patients. Of these, 28 (52%) of 54 initially HIV antigen-positive became antigen-negative, 7 (18%) of 39 initially HIV antigen-negative became antigen-positive within the first 8 weeks of zidovudine treatment. In 57 patients the total count of CD4+ cells were evaluated. A significant increase in the number of CD4+ cells was observed during treatment. In nearly all patients an increase in MCV and a decrease in neutrophil count was observed. 44 of the patients received a total of 307 blood transfusions on 94 occasions and 19 (14%) patients required multiple transfusions. The mortality among the AIDS patients was significantly lower compared to historical controls. In our experience zidovudine treatment is reasonably well tolerated and the side effects are manageable.

AIDS-Related Complex↗

Nerve growth factor enhances antigen and other secretagogue-induced histamine release from rat peritoneal mast cells in the absence of phosphatidylserine.

The effects of 2.5S nerve growth factor (NGF) and epidermal growth factor (EGF), isolated from mouse submaxillary glands, on histamine release from rat peritoneal mast cells (PMCs) were studied. In the absence of phosphatidylserine, NGF (1 ng/ml to 1 microgram/ml) did not cause histamine release from PMCs isolated from normal rats and those infected with the nematode Nippostrongylus brasiliensis. However, when PMCs (greater than 97% pure) were preincubated with NGF and then challenged with worm antigen (Ag), there was a marked enhancement of histamine release (approximately twofold with a maximum effect at 10 ng/ml of NGF [3.8 X 10(-10) mol/L]) compared with the release induced by Ag alone. EGF (1 ng/ml to 1 microgram/ml) neither produced histamine release from PMCs in the presence of phosphatidylserine nor enhanced Ag-induced histamine release. This suggests that NGF acts directly on PMCs by activation of cell-surface receptors. The early kinetics of Ag-induced histamine release were altered by NGF that increased the initial rate at 15 seconds but did not prolong the overall duration of histamine release. Simultaneous addition of Ag and NGF did not cause enhanced histamine release; thus, some preincubation time with NGF (5 minutes or less) was required for the activation of PMCs. Moreover, after PMCs were activated by NGF, that state persisted for 1 hour, even when unbound NGF was removed by washing, and thereafter subsided gradually. Further studies revealed that NGF enhanced histamine release induced by concanavalin A, compound 48/80, and ionophore A23187. These results suggest that NGF might be an important molecule in inflammatory responses through the regulation of mediator release from mast cells.

Animals↗

Clinical classification of 14-16-year-old Danish children according to functional status of the masticatory system.

The high prevalence of functional disturbances in the masticatory system and the tendency to increasing severity with duration stresses the necessity for a reproducible index. Clinical examination of the masticatory system was performed in 14-16-yr-old children. The sequence of examination, TMJ-muscles-opening capacity was chosen in order to minimize the bias. For the same reason, information on symptoms and occlusal conditions was not available for the examiner. According to the amount and character of the signs of dysfunction, the children were classified into three groups. Both single traits of dysfunction and the classification of the subjects were tested for reproducibility. The reproducibility of the compound clinical index was high. The ability to differentiate between children with moderate/severe signs and without signs was higher but the highest value was reached when differentiation was made between children with no/moderate signs and children with severe signs.

Adolescent↗

Diuresis renography in patients with reduced renal function.

Diuresis renography was performed twice at an interval of one week in 13 uraemic patients without hydronephrosis. In five of the patients, the 51Cr-EDTA clearance was below 10 ml/min x 1.73 m2 for the individual kidney, in eight of the patients between 10 and 25. During the renographies, respectively, 0.5 and 7.5 mg/kg of frusemide was given I.V. at 20 min. Compared with the data from eight normal control patients, the effect of frusemide on the renography curve was very poor and varied much in both groups. Our results suggest that diuresis renography gives no conclusive information about the upper urinary tract in kidneys with a 51Cr-EDTA clearance below 25 ml/min x 1.73 m2, even when the dose of frusemide is increased to 7.5 mg/kg.

Diuresis↗

Distinct localizations of urokinase-type plasminogen activator and its type 1 inhibitor under cultured human fibroblasts and sarcoma cells.

We studied the immunocytochemical localization of urokinase-type plasminogen activator (u-PA) and the type 1 plasminogen activator inhibitor (PAI-1) in human fibroblasts and sarcoma cells, using both polyclonal and monoclonal antibodies. The u-PA was found to be located at discrete cell-substratum contact sites, and also at areas of cell-cell contacts, whereas PAI-1 was distributed as a homogeneous carpet excluding strialike areas on the substrate under the cells. To confirm the extracellular localization of u-PA and PAI-1, we stained the cells live at 0 degree C before fixation. A double-labeling experiment showed different distribution of u-PA and PAI-1 under the cells, and especially their peripheral parts. The staining pattern of u-PA and PAI-1 resisted treatment with 0.2% saponin followed by mechanical removal of cells, a method previously reported to isolate focal contact membranes of fibroblasts. We further demonstrated the deposition of u-PA to the contact areas of cells obtained by saponin treatment by zymography, and that of PAI-1 by metabolic labeling, reverse zymography, immunoblotting, and immunoprecipitation. Fibronectin was also present in the preparations. The deposition of both PAI-1 and fibronectin by the sarcoma cells was enhanced, after treating the cells with 10(-6) M dexamethasone. The confinement of u-PA to discrete contact sites and the more uniform distribution of PAI-1 on the cell substratum may explain how cells producing large amounts of enzyme inhibitors can produce PA-mediated focal proteolysis.

Cell Line↗

Hemodynamic effects of high frequency ventilation superimposed on intermittent positive pressure ventilation in dogs.

The hemodynamic effects of high frequency ventilation (HFV) superimposed on intermittent positive pressure ventilation (IPPV) in seven dogs before and after thrombin infusion were investigated. HFV was superimposed on a Servo 900 B ventilator by a Siemens Elema HFV prototype unit. Mean arterial blood pressure, heart rate, central venous pressure, pulmonary artery pressure, cardiac output, right and left ventricular pressures, pleural pressure, arterial blood gases, and right and left ventricular ejection fractions were recorded. Measurements were done during IPPV alone and during HFV superimposed on IPPV. The HFV frequencies were 5, 15, and 20 Hz at a constant minute volume of 5 1. When HFV was started, the IPPV minute volume was reduced to one third of the initial volume. No significant changes in the measured parameters were observed during the different ventilatory modes either before or after thrombin infusion which doubled the pulmonary vascular resistance. It is concluded that high frequency ventilation superimposed on IPPV might be a ventilatory mode that offers cardiovascular stability and reduces the risk of barotrauma.

Animals↗

Peroperative cefuroxime v. long-term ampicillin and metronidazole in high-risk biliary and gastric surgery. A multicentre trial.

Randomization to cefuroxime in a two-dose peroperative regimen or to combined peroperative and postoperative (4 days) ampicillin and metronidazole was performed in a series of 418 high-risk patients undergoing biliary or gastric surgery. Postoperative wound infection appeared in 9 of the 210 patients who received ampicillin and metronidazole and in 2 of the 208 given cefuroxime (p less than 0.05). Four intraabdominal abscesses occurred in the former group and one in the latter. Three of these abscesses probably were attributable to complications of surgery as such, leaving one intraabdominal abscess in each group. Peroperative cefuroxime is concluded to be more effective than longer administration of ampicillin/metronidazole as protection against wound infection in high-risk patients undergoing biliary or gastric surgery.

Adult↗