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Biomedical subjects

P Arnold

Publications and source records attributed to P Arnold.

At least 55 records · Page 3Linked to original sources
PubMed1999

The N-terminal anchor sequences of 11beta-hydroxysteroid dehydrogenases determine their orientation in the endoplasmic reticulum membrane.

11beta-Hydroxysteroid dehydrogenase enzymes (11beta- HSD) regulate the ratio of active endogenous glucocorticoids to their inactive keto-metabolites, thereby controlling the access of glucocorticoids to their cognate receptors. In this study, the topology and intracellular localization of 11beta-HSD1 and 11beta-HSD2 have been analyzed by immunohistochemistry and protease protection assays of in vitro transcription/translation products. 11beta-HSD constructs, tagged with the FLAG epitope, were transiently expressed in HEK-293 cells. The enzymatic characteristics of tagged and native enzymes were indistinguishable. Fluorescence microscopy demonstrated the localization of both 11beta-HSD1 and 11beta-HSD2 exclusively to the endoplasmic reticulum (ER) membrane. To examine the orientation of tagged 11beta-HSD enzymes within the ER membrane, we stained selectively permeabilized HEK-293 cells with anti-FLAG antibody. Immunohistochemistry revealed that the N terminus of 11beta-HSD1 is cytoplasmic, and the catalytic domain containing the C terminus is protruding into the ER lumen. In contrast, the N terminus of 11beta-HSD2 is lumenal, and the catalytic domain is facing the cytoplasm. Chimeric proteins where the N-terminal anchor sequences of 11beta-HSD1 and 11beta-HSD2 were exchanged adopted inverted orientation in the ER membrane. However, both chimeric proteins were not catalytically active. Furthermore, mutation of a tyrosine motif to alanine in the transmembrane segment of 11beta-HSD1 significantly reduced V(max). The subcellular localization of 11beta-HSD1 was not affected by mutations of the tyrosine motif or of a di-lysine motif in the N terminus. However, residue Lys(5), but not Lys(6), turned out to be critical for the topology of 11beta-HSD1. Mutation of Lys(5) to Ser inverted the orientation of 11beta-HSD1 in the ER membrane without loss of catalytic activity. Our results emphasize the importance of the N-terminal transmembrane segments of 11beta-HSD enzymes for their proper function and demonstrate that they are sufficient to determine their orientation in the ER membrane.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

The optimal radiologic method for assessing spinal canal compromise and cord compression in patients with cervical spinal cord injury. Part II: Results of a multicenter study.

STUDY DESIGN: A multicenter, retrospective study using computed tomographic and magnetic resonance imaging data to establish quantitative, reliable criteria of canal compromise and cord compression in patients with cervical spinal cord injury. OBJECTIVES: To develop and validate a radiologic assessment tool of spinal canal compromise and cord compression in cervical spinal cord injury for use in clinical trials. SUMMARY OF BACKGROUND DATA: There are few quantitative, reliable criteria for radiologic measurement of cervical spinal canal compromise or cord compression after acute spinal cord injury. METHODS: The study included 71 patients (55 men, 16 women; mean age, 39.7 +/- 18.7 years) with acute cervical spinal cord injury. Causes of spinal cord injury included motor vehicle accidents (n = 36), falls (n = 20), water-related injuries (n = 8), sports (n = 5), assault (n = 1), and farm accidents (n = 1). Canal compromise was measured on computed tomographic scan and T1- and T2-weighted magnetic resonance imaging, and cord compression at the level of maximum injury was measured on T1- and T2-weighted magnetic resonance imaging. All films were assessed by two independent observers. RESULTS: There was a strong correlation of canal compromise and/or cord compression measurements between axial and midsagittal computed tomography, and between axial and midsagittal T2-weighted magnetic resonance imaging. Spinal canal compromise assessed by computed tomography showed a significant although moderate correlation with spinal cord compression assessed by T1- and T2-weighted magnetic resonance imaging. Virtually all patients with canal compromise of 25% or more on computed tomographic scan had evidence of some degree of cord compression on magnetic resonance imaging, but a large number of patients with less than 25% canal compromise on computed tomographic scan also had evidence on magnetic resonance imaging of cord compression. CONCLUSIONS: In patients with cervical spinal cord injury, the midsagittal T1- and T2-weighted magnetic resonance imaging provides an objective, quantifiable, and reliable assessment of spinal cord compression that cannot be adequately assessed by computed tomography alone.

Adolescent↗
PubMed1999

Bioavailability investigation of a new tilidine/naloxone liquid formulation compared to a reference formulation.

An oral solution available as ethanol-free droplets of the fixed drug combination tilidine-HCl 50 mg/naloxone-HCl 4 mg (CAS 27107-79-5 and CAS 465-65-6, respectively; Tilidin-ratiopharm plus Tropfen) was investigated in 12 healthy volunteers together with an ethanol-containing reference preparation for comparable bioavailability. The study was conducted in an open, randomized, two-way cross-over design applying single doses of 20 droplets (equivalent to 50 mg tilidine-HCl/4 mg naloxone-HCl) of either formulation in the fasting state. The drug plasma profiles were monitored for a period of 48 h by means of LC-MS/MS for tilidine and its active metabolite nortilidine, whereas GC-MS was employed in order to determine naloxone and its phase I metabolite, 6-beta-naloxole. Maximum concentrations (Cmax) achieved were 22.28 ng/ml (tilidine) and 92.78 ng/ml (nortilidine) for the test preparation. Corresponding values for the reference preparation were 24.95 ng/ml (tilidine) and 100.73 ng/ml (nortilidine). The extent of drug absorption (AUC0-infinity) amounted to 38.83 ng h/ml and 467.63 ng h/ml for the prodrug tilidine and the metabolite nortilidine of the test preparation and corresponded well to 43.81 ng h/ml and 493.85 ng h/ml of the reference. Regarding the rate of drug absorption, essentially identical tmax and Rabs values for both tilidine and nortilidine of either preparation in addition pointed to well comparable liquid formulations and equipotent analgesia may be inferred from opioid pharmakokinetic profiles. Pharmacokinetics of the opioid antagonist naloxone and 6-beta-naloxole were also determined and resulted in well coinciding profiles for both preparations. Thus despite the fact that only minimum oral naloxone bioavailabilities were observed, plasma level monitoring of naloxone and 6-beta-naloxole allowed for demonstration of systemic exposure of opioid antagonistic compounds throughout a period of 2-3 h after oral drug administration. Due to the limited number of subjects involved, the primary aim of the study did not consist in demonstration of drug bioequivalence. Rather a comparable bioavailability between preparations was assumed if AUC and Cmax point estimators of 90% confidence intervals would be contained within a 0.80-1.20 range. The study outcome revealed that all four investigated analytes met this requirement, whilst nortilidine pharmacokinetic parameters even fulfilled commonly accepted bioequivalence criteria, i.e. inclusion of 90% confidence intervals of AUC- and Cmax-ratios within acceptance limits of 80% and 125%. Increased data variation observed with bioavailability parameters of tilidine, naloxone and 6-beta-naloxole prevented their bioequivalence demonstration based on only 12 study participants. In conclusion, single doses of two different tilidine/naloxone 50 mg/4 mg liquid formulations revealed well comparable bioavailability for all 4 analytes investigated. Both treatments were fairly well tolerated. Most frequently reported adverse events were dizziness, headache and nausea, which all recovered without sequelae and necessity of concomitant treatment.

Adult↗
PubMed1999

Nutritional secondary hyperparathyroidism in six cats.

Nutritional secondary hyperparathyroidism (NSH) was diagnosed in six cats during a three-year period, based on clinical, radiographic and laboratory findings. Clinical signs were attributable to severe osteopenia (n = 5) and hypocalcaemia (n = 4), which had resulted in spontaneous fractures of long bones, scapulae, pelvis, nasal bones, or spine, and in excitation, muscle twitching or seizures, respectively. Serum parathormone levels were markedly elevated, and 1,25(OH)2-vitamin D3 mildly elevated, whereas 25(OH)-vitamin D3 was mildly decreased compared to age-matched healthy cats. Treatment was limited to short-term parenteral calcium gluconate injections, as clinically indicated, a balanced diet and cage rest, which resulted in quick clinical recovery in four cases. The remaining two cats had to be euthanased because of progressive neurological deficits secondary to spinal fractures. At the time of writing, a multitude of commercial balanced diets is widely available and diseases secondary to dietary deficiencies have become rare. Nevertheless, NSH is still an important clinical entity, and should be considered in growing cats presenting with spontaneous fractures or seizures.

Animals↗
PubMed1999

Does classroom amplification aid comprehension?

Many classrooms are noisy and this interferes with listening and teaching. FM soundfield (FM) amplification systems have been developed which provide a uniform soundfield throughout the classroom and increase the speech-signal:noise ratio. The effect on comprehension of such a system was investigated. Forty-nine pupils (comprising the two top classes of a mainstream primary school) participated in this study, with a mean age of 9.92 years (range 8.58-11.42 years). The Neale Analysis of Reading Ability (Neale, 1988a, b) was modified and administered as a spoken comprehension test. Tests of nonverbal intelligence, auditory memory and a questionnaire were given. The passages spoken though the FM amplification system were understood better than the comparable unamplified passages. Auditory memory, sex and non-verbal intelligence had no effect on improved comprehension. FM amplification significantly improved comprehension and could be considered for use in other schools.

Amplifiers, Electronic↗
PubMed1999

Neurocytoma of the cauda equina. Case report.

A case of a neurocytoma involving a nerve root of the cauda equina in a 46-year-old woman is reported. The patient presented with a 2-month history of progressive left lower-extremity weakness and pain and decreased ability to walk, as well as complaints of incomplete voiding. A magnetic resonance image revealed a 7-mm oval mass that was located intrathecally and extended from T-12 to L-1 and was adjacent to a nerve root. No lesions were identified at higher vertebral levels. The mass was excised. On histological examination it was found to have classical features of a neurocytoma. To the best of the authors' knowledge, this is the first report of a neurocytoma occurring in that region. A detailed histological description of this case and review of the pertinent literature are provided.

Cauda Equina↗
PubMed1998

Impaired endothelium-dependent relaxation in large, but not small arteries in rats after coronary ligation.

Vascular responses were studied in both large and small arteries of rats following 8 weeks of heart failure produced by coronary ligation. Responses to noradrenaline, acetylcholine and sodium nitroprusside were studied in isolated thoracic aorta and mesenteric arteries. In the aorta, concentration-response curves for noradrenaline were similar between heart failure and sham animals and unaffected by the nitric oxide synthase inhibitor, NG-nitro-L-arginine (L-NOARG). Relaxation by acetylcholine was impaired in heart failure rats (EC50-6.79 log M heart failure vs. -7.15 log M sham). In the presence of L-NOARG, relaxation by acetylcholine was completely abolished in rings from sham rats, whereas constriction was observed in rings from heart failure rats. Relaxation by sodium nitroprusside was not different between sham and heart failure rats. In mesenteric arteries, responses to noradrenaline, acetylcholine and sodium nitroprusside were not different between heart failure and sham rats. L-NOARG reduced the maximum response to acetylcholine in both heart failure (82% to 50%) and shams (89% to 49%) by a similar magnitude, with no effect on relaxation to sodium nitroprusside. These data suggest that acetylcholine-induced relaxation is impaired in the aorta, but not mesenteric arteries in rats with heart failure. The mechanism is not solely due to impaired nitric oxide release and may be due to acetylcholine-induced contraction.

Acetylcholine↗
PubMed1998

[Review of the results of the ARO multicenter study].

The ARO multicenter study intended to show clinical and radiological differences with regard to different systems of fixation and designs of the prothesis in total hip replacement in patients with hip dysplasia, osteoarthritis and rheumatoid arthritis. In 1987 and 1988 5255 total hip prothesis were implanted by the 24 hospitals which took part in the study. 3133 prothesis (95.6%) were clinically and radiologically examined. The follow-up period averaged 6.9 years. The results of the Aro multicenter-study showed that despite difficult preoperative conditions especially in cases of rheumatoid arthritis the satisfaction rate improved remarkably. During the operation less complications arose in comparison to patients with hip dysplasia and osteoarthritis. Regarding the rate of infection after operation there were no differences between the 3 groups. Only the rate of post-operative luxation concerning rheumatoid patients turned out to be twice the number of the others. In our opinion this is due to the fact that these rheumatics were operated by posterior approach. Patients with rheumatoid arthritis were satisfied most with their surgeries. Results of rheumatic patients according to Harris hip score were slightly worse than the results of the two other groups. This was due to systemic involvement and bad preoperative function of the hip. As a result of the study there were no differences in using cemented or cementless techniques for rheumatic hip replacement. The decision for the method of fixation should depend on the patient's ability to relief the prothesis after operation. The study has shown that cementless implantation can also be used for young rheumatics provided that a suitable design of prothesis will be selected.

Arthritis, Rheumatoid↗
PubMed1998

[Radiologic results of the ARO multicenter study].

We present the radiological results of 2286 total hip replacements (THR) from the multicenter study. Concerning the acetabular component the analysis showed that socket migration and radiolucent lines were much more dependent on the specific design of the socket than on the primary diagnosis. A similar results was found for the femoral stems: rheumatoid arthritis did not cause a higher percentage of stem subsidence, radiolucent lines or bone remodeling. Within a mid-term follow-up period the reduced bone quality in rheumatoid arthritis is not associated to premature failure of a cemented or cementless prosthesis. THR failure seems to be more dependent on specific construction features of the individual socket and stem.

Arthritis, Rheumatoid↗
PubMed1998

[Implant failure after total hip replacement. Comparison of patients with primary coxarthrosis, rheumatoid arthritis and dysplastic coxarthrosis].

The analysis of THR-failures showed that the acetabular component still is the main problem of total hip replacement. The acetabular cup fails more often than the stem. In the midterm analysis the failure rate is a little bit higher in cementless than in cement fixed cups. The known effect that the failure rate of cups fixed with cement increases exponentially 8 to 10 years after implantation, could of course not be seen in this study. The success of the cementless fixation was negatively influenced by the diagnosis rheumatoid arthritis, age over 70 and the fixation manner: the failure rate of threaded cups was higher than the one of press-fit cups although the Zweymüller-cup as well as the Link type V-cup showed good results. The midterm results of the stem were very good for the cementless as for the cemented technique. Some implants showed compared to others significantly worse results. The further implantation should be thought of, what partially has already happened. The results of cementless stem fixation in patients with rheumatoid arthritis, osteoarthrosis and dysplastic osteoarthritis is comparable, so that cementless fixation should be thought of in case of adequate conditions (ability of partial weight bearing for some weeks, age under 60).

Aged↗
PubMed1998

[Patellar resurfacing. Results of a prospective randomized study].

The mid-term results of this prospective randomized study illustrate why it is difficult to define a clear position concerning the issue of patellar resurfacing in total knee arthroplasty. In both groups of 20 patients typical complications for the respective procedures have occurred. One patient from group A with patellar resurfacing had to be revised for loosening of the patellar implant. In group B without resurfacing 3 patellae subluxated, 2 having been revised. Furthermore 4 patients complained about mild to moderate anterior knee pain. The Knee and Function Scores of the patients without revision were not significantly different except for the parameter pain (Knee Score Gr. A:84.8, Gr. B:77.8; pain Gr. A:46.9, Gr. B:41.9; Function Score Gr. A:78.5, Gr. B:71.9; climbing stairs Gr. A:38.5, Gr. B:33.8). The radiological measurements found the patellae with resurfacing significantly less tilted with 3.8 degrees than the patellae without resurfacing with 6.4 degrees. With the correct implantation technique patellar resurfacing guarantees a good clinical result within the first 5 years. Leaving the patella unresurfaced was associated with a higher rate of anterior knee pain and revision in our study.

Aged↗
PubMed1998

Memory for faces and objects by deaf and hearing signers and hearing nonsigners.

The memory of 11 deaf and 11 hearing British Sign Language users and 11 hearing nonsigners for pictures of faces of and verbalizable objects was measured using the game Concentration. The three groups performed at the same level for the objects. In contrast the deaf signers were better for faces than the hearing signers, who in turn were superior to the hearing nonsigners, who were the worst. Three hypotheses were made: That there would be no significant difference in terms of the number of attempts between the three groups on the verbalizable object task, that the hearing and deaf signers would demonstrate superior performance to that of the hearing nonsigners on the matching faces task, and that the hearing and deaf signers would exhibit similar performance levels on the matching faces task. The first two hypotheses were supported, but the third was not. Deaf signers were found to be superior for memory for faces to hearing signers and hearing nonsigners. Possible explanations for the findings are discussed, including the possibility that deafness and the long use of sign language have additive effects.

Adolescent↗
PubMed1998

[Imported hepatozoonosis in the dog: 3 cases].

Canine hepatozoonosis is presented with 3 cases. The most common signs are: fever, anorexia, weight loss, diarrhea and vomiting, muscle weakness, lymphadenopathy, anemia and purulent discharge from the nose and the eyes. Because an infection with H. canis in the dog is often associated with other infectious diseases such as leishmaniasis, ehrlichiosis and babesiosis, the clinical picture may be dominated by these diseases. The diagnosis is made with the typical inclusions in neutrophilic granulocytes and monocytes. Only short remissions may be obtained with the presently available medications.

Animals↗
PubMed1998

[Solar glossitis in sled dogs].

In a colony of sledge dogs, an increased incidence of ulcerative glossitis was diagnosed. Several facts indicate that the lesions were directly caused by UV light. The presence of signs coincided with the use of the dogs of the glacier. The lesions were localized on the first part of the tongue. The histologic changes were consistent with a phototoxic reaction and other causes of glossitis were ruled out.

Animals↗