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Biomedical subjects

H Laurell

Publications and source records attributed to H Laurell.

34 records · Page 2Linked to original sources

Molecular cloning of the murine substance K and substance P receptor genes.

The peptides substance K and substance P evoke a variety of biological responses via distinct, guanosine-nucleotide-binding-regulatory-protein-coupled receptors. We have screened a murine genomic cosmid library using oligonucleotide probes and have isolated, cloned and characterized the substance K receptor and the substance P receptor genes. The coding portion of the substance K receptor gene consists of five exons distributed over 13 kbp. The substance P receptor gene is considerably larger than that of substance K (more than 30 kbp), however, the boundaries of the four exons that have been characterized in the substance P receptor gene correspond exactly to the homologous exons in the substance K receptor gene. To verify the identity of the isolated genes, we have cloned the corresponding cDNA by means of the polymerase chain reaction and we have expressed these cDNA species in Xenopus laevis oocytes. The ligand binding characteristics determined in this system pharmacologically confirm the identity of the two receptors. The deduced amino acid sequence of the mouse substance K receptor is 94% identical to the rat sequence and 85% identical to the bovine and human sequences. The mouse substance P receptor amino acid sequence is 99% identical to the rat sequence. The cloning of the murine substance K and substance P receptor genes should contribute substantially to the generation of in vivo models for the detailed analysis of the functional significance of these receptors.

Amino Acid Sequence↗

Acute and hang-over effects of alcohol on simulated driving performance.

The aim was to study hang-over effects from alcohol in simulated driving. The driving task was to negotiate 20 km in as short time as possible. The road had many curves, horizontal and vertical, with ice friction at irregular intervals. 24 healthy volunteers, aged 22-46, with valid driving licenses, all screened as moderate drinkers, participated as subjects in a repeated measurements design. In the acute intoxicated state (average BAC 150 mg%), driving performance was severely impaired. Performance was also impaired, but to a much lesser degree, in the morning after the alcohol consumption when average BAC was just below 40 mg%. Later during the day no significant differences were demonstrated. After another night's sleep, all effects were gone. An issue raised in a previous study on hang-over effects, whether the subjects were treated exactly alike in the hang-over and the control conditions the night before testing (with the exception for the alcohol consumption in the first case), that is attended a party and stayed overnight at the research institute in both conditions, or whether they did so only in the hang-over condition, did not seem to matter for the estimated hang-over effect.

Adult↗

Acute and carry-over effects of brotizolam compared to nitrazepam and placebo in monotonous simulated driving.

Eighteen healthy volunteers of both sexes, aged 20-35 years, were tested in the morning after three nights of medication with brotizolam 0.25 mg, nitrazepam 5 mg or placebo on a monotonous simulated driving task. The effect measures were subsidiary auditory reaction time and time outside road. Measurements of self-rated alertness were carried out as well. No effects were demonstrated from treatments on either measure. Nitrazepam however tended to score worst on all measures, except time outside road which could not be analysed with respect to statistical significance because of an insufficient number of subjects leaving the road. Twelve of the subjects were also tested immediately after drug intake on the first night of each medication period. Reaction time decrement was observed in both active drugs conditions with no difference between the two. The other measures, however non-significant, pointed in the same direction with the greatest decrement for nitrazepam.

Adult↗

Dextromethorphan: polymorphic serum pattern of the O-demethylated and didemethylated metabolites in man.

1. The interindividual differences in serum concentrations of dextromethorphan (DM) and its metabolites were studied in 29 healthy subjects given 120 mg orally. They were also phenotyped according to the urinary ratio of debrisoquine and 4-hydroxy-debrisoquine. 2. Four (14%) subjects were found to be poor metabolizers (PM) with a dextromethorphan/dextrorphan metabolite ratio in plasma of 3.6 or more compared with extensive metabolizers (EM) with a ratio of 0.11 or less. Significant levels of 3-hydroxymorphinan were measurable in all individuals except two, both of whom were PMs. This subdivision corresponded to the phenotype determined by the metabolic ratio of debrisoquine (r = 0.92). 3. Twelve of the 29 subjects reported adverse drug reactions after dextromethorphan administration compared with none after placebo.

Adult↗

The carry-over effects of triazolam compared with nitrazepam and placebo in acute emergency driving situations and in monotonous simulated driving.

Eighteen healthy volunteers of both sexes, aged 20-34, were tested in the morning while undertaking real car driving avoidance manoeuvres and during monotonous simulated driving after 1 and 3 nights of medication with triazolam 0.25 mg, nitrazepam 5 mg or placebo. The study was a double-blind, randomized, cross-over study, where a minimum of 7 days wash-out separated the 3 treatment periods. Nitrazepam was found to impair performance in the simulated task after 1 but not after 3 nights of medication. Performance in the triazolam condition was not significantly different from the other conditions on this task on either day. However, after one night of medication triazolam tended to score worse than placebo but better than nitrazepam. In real car driving a tendency was noted for nitrazepam to score worst, whereas the difference between placebo and triazolam was hardly noticeable. The same tendency appeared on both days.

Automobile Driving↗

Different composition of the eosinophilic bone marrow pool in reactive eosinophilia and eosinophilic leukaemia.

The composition of the eosinophilic cell series in the bone marrow has been analysed in 10 patients with a pronounced reactive eosinophilia (RE) and in 2 with eosinophilic leukaemia (EL). An imparied differentiation of the eosinophils was found in the EL patients compared with the RE group. Thus the ratio of eosinophilic promyelocytestmyelocytes: segmented eosinophils was 9.2 and 9.1, respectively, in the patients with EL and 0.1--3.1 (average 1.3) in the RE patients. It is suggested that EL is characterized by an impaired differentiation of the eosinophilic bone marrow cells and that the recognition of this abnormality is of value in the diffential diagnosis between EL and RE.

Adult↗

Driving vigilance simulator test.

Drivers suffering from sleepiness at the wheel run the risk of being involved in car accidents. To evaluate whether objective data of driving performance can be assessed in patients with excessive tendency of falling asleep at the wheel, two test versions of a computerized driving program were created to fit an advanced driving simulator. For the evaluation 15 male drivers with habitual sleep spells whilst driving were selected among patients with the clinical features of the sleep apnoea syndrome. The brake reaction time and the deviations from straight road-line were significantly increased when compared to the performance of 10 matched controls. Irrespective of test version, the driving simulator with the program used was found to be a sensitive method to ascertain driving vigilance impairment in quantitative terms. It would also be a valuable method to evaluate the efficiency of treatment in selected patients.

Accidents, Traffic↗

Why do surgeons miss malignancies in patients with acute abdominal pain?

BACKGROUND: The aim of this study was to characterize patients seeking medical advice for acute abdominal pain who were later diagnosed with an intra-abdominal malignancy. PATIENTS AND METHODS: Patients with acute abdominal pain were registered between 1997 and 2000, employing a detailed schedule comprising 111 parameters. The diagnoses (n=2395 patients) were re-evaluated one year later. RESULTS: A total of 66 patients (2.8%) were found to have an intra-abdominal malignancy at follow-up, of whom 37 cases had been undetected at discharge. Malignancy of the liver, biliary tract and pancreas constituted 30% and colorectal cancer 32% of the tumours undetected at discharge. Constipation, intestinal obstruction and non-specific abdominal pain (NSAP) were the most common preliminary diagnoses in patients among whom abdominal malignancy was later detected. CONCLUSION: Except for age and pain duration, the history and clinical investigation provide few clues to suggest an abdominal malignancy in patients with acute abdominal pain. NSAP, of unknown or known etiology, including constipation, should be suspected as a possible sign of abdominal malignancy in all patients over 50 years of age.

Abdominal Neoplasms↗