Search

Summary Primary hyperoxaluria (PH) is a rare autosomal recessive disorder of glyoxylate metabolism in humans. It is characterized by the accumulation of oxalate and subsequent precipitation of calcium oxalate crystals, primarily in the kidneys. Deficiencies in glyoxylate-metabolizing enzymes alanine-glyoxylate aminotransferase (AGXT) or glyoxylate reductase/hydroxypyruvate reductase (GRHPR) occur in 95% of PH cases. Seven Coton de Tulear puppies from four apparently unrelated litters were examined owing to sudden illness at the age of 3-4 weeks. A complete necropsy was performed. The typical finding was tubular necrosis with extensive oxalate crystal deposition. Based on history and necropsy findings, PH was suspected. Eight microsatellite loci flanking AGXT and GRHPR were analysed, and based on segregation results, AGXT was suspected as to be the candidate gene. AGXT exon sequencing revealed a single base change (c.996G>A) that changed one conserved residue (p.Gly102Ser). The mutation was tested in of 118 Finnish Coton de Tulear dogs, ten (8.5%) of which were revealed as carriers. This preliminary study reports PH as a cause of neonatal death in Finnish Coton de Tulear and suggests that genetic testing of dogs be carried out before breeding to prevent the birth of affected offspring. [ABSTRACT FROM AUTHOR]

Scand J Caring Sci; 2010; 24; 592–599 Effects of the implementation of the web-based patient support system on staff’s attitudes towards computers and IT use: a randomised controlled trial Utilisation of information technology (IT) in the treatment of people with severe mental health problems is an unknown area in Europe. Use of IT and guiding patients to relevant sources of health information requires that nursing staff have positive attitudes toward computers and accept IT use as a part of daily practises. The aim of the study was to assess the effects of the implementation of a web-based patient support system on staff’s attitudes towards computers and IT use on psychiatric wards. Hundred and forty-nine nurses in two psychiatric hospitals in Finland were randomised to two groups to deliver patient education for patients with schizophrenia and psychosis with a web-based system (n = 76) or leaflets (n = 73). After baseline nurses were followed-up for 18 months after the introduction of the system. The primary outcome was nurses’ motivation to utilise computers, and the secondary outcomes were nurses’ beliefs in and satisfaction with computers, and use of computer and internet. There were no statistically significant differences between study groups in attitudes towards computers (motivation p = 0.936, beliefs p = 0.270, satisfaction p = 0.462) and internet use (p = 0.276). However, nurses’ general computer use (p = 0.029) increased more in the leaflet group than in the IT intervention group. We can conclude that IT has promise as an alternative method in patient education, as the implementation of the web-based patient support system in daily basis did not have a negative effect on nurses’ attitudes towards IT. [ABSTRACT FROM AUTHOR]

Aim. This paper is a report of a study to describe nurses' experiences of information technology-based standardized patient education in inpatient psychiatric care. Background. Serious mental health problems are an increasing global concern. Emerging evidence supports the implementation of practices that are conducive to patient self-management and improved patient outcomes among chronically ill patients with mental health problems. In contrast, the attitude of staff towards information technology has been reported to be contradictory in mental health care. Method. After 1 year of using an Internet-based portal (Mieli.Net) developed for patients with schizophrenia spectrum psychosis, all 89 participating nurses were asked to complete questionnaires about their experiences. The data were collected in 2006. Fifty-six participants (63%) returned completed questionnaires and the data were analysed using content analysis. Findings. Nurses' experiences of the information technology-based standardized patient education were categorized into two major categories describing the advantages and obstacles in using information technology. Nurses thought that it brought the patients and nurses closer to each other and helped nurses to provide individual support for their patients. However, the education was time-consuming. Conclusion. Systematic patient education using information technology is a promising method of patient-centred care which supports nurses in their daily work. However, it must fit in with clinical activities, and nurses need some guidance in understanding its benefits. The study data can be used in policy-making when developing methods to improve the transparency of information provision in psychiatric nursing. [ABSTRACT FROM AUTHOR]

1 This double-blind, cross-over, placebo-controlled study on six healthy male volunteers was designed to evaluate the effects ofα2-adrenoceptor antagonism on cardiac parasympathetic regulation.2 The subjects received atipamezole intravenously as a three-step infusion, which aimed at steady-state serum concentrations of 10, 30 and 90 ng ml−1 at 50-min intervals.3 Drug effects were assessed with repeated recordings of blood pressure and electrocardiogram, in which the high-frequency (0.15–0.40 Hz) R-R interval variation is supposed to reflect cardiac parasympathetic efferent neuronal activity.4 At the end of the three steps of the infusion, the mean (±SD) concentrations of atipamezole were 10.5 (3.9), 26.8 (5.6) and 81.3 (21.1) ng ml−1.5 Within this concentration range, atipamezole appeared to reduce slightly the high-frequency R-R interval fluctuations, indicating a minor vagolytic effect in the heart.6 Atipamezole increased systolic and diastolic arterial pressure, on average by 20 and 14 mmHg (maxima at the second step of the infusion), which evidently reflects an overall sympathetic augmentation. [ABSTRACT FROM AUTHOR]

The article focuses on epilepsy in mentally retarded patients. Carbamazepine (CBZ) is currently used in the treatment of various epileptic disorders in all age groups. It is as effective as phenobarbital, phenytoin or primidone in the prevention of generalized tonic-clonic seizures, but significantly more effective than the others in the treatment of complex partial seizures. In a steady-state situation, the half-life of CBZ becomes shorter and the fluctuations in serum concentrations of the drug become more pronounced than in the beginning of the treatment, since CBZ induces its own metabolism.

1. Single doses (10, 30 and 100 mg) of atipamezole (MPV-1248), a new potent and selective imidazole-type alpha 2-adrenoceptor antagonist, and saline placebo were administered as 20 min intravenous infusions to six healthy male volunteers in a randomized double-blind, cross-over phase I study. Later, 100 mg atipamezole was given orally to the same subjects in an open fashion. 2. The i.v. doses resulted in linearly dose-related concentrations of atipamezole in plasma. Pharmacokinetic calculations revealed an elimination half-life of 1.7-2.0 h, an apparent volume of distribution of 3.0-3.5 l kg-1 and a total plasma clearance of 1.1-1.5 l h-1 kg-1. No atipamezole could be detected in plasma after oral dosing. 3. Subjective drug effects were seen mainly after the largest i.v. dose and included increased alertness and nervousness, coldness and sweating of hands and feet, tremor and shivering, motor restlessness, and increased salivation. Salivation was also quantitated using dental cotton rolls, with dose-related increases produced by the i.v. doses. 4. The 100 mg i.v. dose increased plasma noradrenaline concentrations on average by 484 +/− 269 (s.d.)%, and also elevated both systolic and diastolic blood pressure (mean increases 17 +/− 7/14 +/− 2 mm Hg). The 30 mg dose had minor and the 10 mg dose no effects on these variables. Adrenaline and cyclic AMP levels in plasma were increased only after the largest dose. No drug effects were observed after oral dosing. 4. Plasma C-peptide and blood glucose levels were not markedly influenced by the drug, and cortisol secretion was not stimulated. 5. The observed effects are compatible with the presumed alpha 2-adrenoceptor antagonistic action of atipamezole and are in general concordance with the reported results of other alpha 2- adrenoceptor antagonists (yohimbine and idazoxan). 6. Although not orally active, atipamezole may prove to be a useful agent in studies of alpha 2-adrenoceptor function in man. [ABSTRACT FROM AUTHOR]

1 The roles of the hepatic blood flow and the drug oxidizing enzyme system in eliminating oral propranolol and sotalol were studied in twelve subjects with biopsy proven liver parenchymal disease. 2 The apparent plasma clearance of propranolol was closely related both to the in vivo (antipyrine test) and in vitro (cytochrome P-450) indices of the activity of the hepatic mixed function oxidase system. 3 Propranolol clearance had also a clear relationship to the estimated liver blood flow. Altered flow was, however, suggested to be a minor factor when compared with changes in the enzyme system. 4 The elimination rate of sotalol had no correlation to the indices of hepatic drug metabolism or to the estimated liver blood flow. 5 It is concluded that both the deteriorated sinusoidal perfusion and the decreased mass of drug metabolizing enzymes may be responsible for the impaired elimination of oral propranolol in subjects with parenchymal liver disease. [ABSTRACT FROM AUTHOR]

Background: There is sparse information about postoperative pain after short stay surgery. We explored the incidence of immediate postoperative pain and its relationship with persistent pain or opioid use 2 weeks after surgery., Methods: This was a subgroup analysis of prospective and controlled data from adult patients (n = 931) who underwent short-stay surgery in a tertiary care hospital. Data comprised patient demographics, surgical category, pain scores and analgesic management during the recovery unit stay, before discharge on the postoperative morning after surgery and again 2 weeks after surgery., Results: Half of the patients had severe dynamic pain in the recovery unit. It was commonest after orthopaedic (70% of patients), followed by gynaecological (54%), gastrointestinal (51%) and spine surgery (49%). Multimodal pain management was used for most patients (n = 811, 87%) with opioid use predominant. The median oxycodone dose during short-stay was the highest after orthopaedic surgery (39 mg). The first individual dynamic pain score after surgery was associated with follow-up pain score at rest (OR = 1.37), dynamic pain (OR = 1.35) and pain interference (OR = 1.34) at 2 weeks after surgery. Maximum dynamic pain reported in the recovery unit was associated with pain at rest (OR = 1.56), dynamic pain (OR = 1.65) and pain interference (OR = 1.45) at 2 weeks after surgery. Pain scores at 2 weeks were highest and analgesic use greatest in those patients who underwent spinal surgery., Conclusions: Intense postoperative pain remains common after short-stay surgery in some surgical categories including orthopaedic surgery and is associated with a greater likelihood of pain at 2 weeks., (© 2022 Acta Anaesthesiologica Scandinavica Foundation.)

Background: The delays in transferring patients from emergency department (ED) to intensive care unit (ICU) are known to be linked with several adverse events, including prolonged ICU stay and increased hospital mortality. The factors associated with delayed ICU admission include shortage of ICU beds, organizational factors, ED overcrowding, and patient-related factors, including sepsis as admission diagnosis. The aim of this study was to examine ED-related factors associated with prolonged ED stay., Methods: The study population consisted of adult patients admitted (n = 479) from ED to ICU between 31 May 2016 and 19 March 2017 in Oulu University Hospital. A patient's ED length of stay (LOS) exceeding 180 minutes was considered delayed., Results: Most of the patients (380, 79.3%) were admitted to the ICU within 3 hours of hospital admission. In a logistic regression analysis, odds ratios (ORs) for ED LOS > 180 minutes were as follows: for Glasgow Coma Scale score > 9, 2.73 (1.39-5.32); for thrombocytes < 100 × 10 9 /mmol, 6.69 (2.32-19.26); for absence of pre-arrival notification, 5.27 (3.04-9.14); and for radiological examination, 3.95 (1.72-9.10). Trauma and intoxicated patients had shorter ED LOS while patients with medical conditions had more often prolonged admissions., Conclusion: The delays in ICU admissions were linked to therapeutic and diagnostic procedures and absence of pre-arrival notification. Patients were admitted to the ICU on the basis of diagnosis instead of clinical risk. However, the delays were not associated with worsening outcome, which indicates that sufficient care can be provided at the ED while the ICU admission is pending., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Aim: To determine the absolute bioavailability of extravascularly administered dexmedetomidine, a novel a2-adrenoceptor agonist, in healthy subjects., Methods: Single 2 microg x kg-1 doses of dexmedetomidine were given intravenously, intramuscularly, perorally and buccally (where the solution is not swallowed) to 12 healthy male subjects. The drug concentration-time data were analysed using linear one-compartment (buccal and peroral data), or two-compartment modelling (intravenous data), or noncompartmental methods (intramuscular data)., Results: Mean (95% CI) absolute bioavailability after peroral, buccal and intramuscular administration was 16% (12-20%), 82% (73-92%) and 104% (96-112%), respectively., Conclusion: Dexmedetomidine is well absorbed systemically through the oral mucosa, and therefore buccal dosing may provide an effective, noninvasive route to administer the drug.

Aims: The purpose of this study was to characterize the dose relationship of selegline and desmethylselegiline pharmacokinetics within the selegiline dose range from 5 to 40 mg., Methods: Eight female subjects, of whom four were using oral contraceptives, ingested a single dose of 5 mg, 10 mg, 20 mg or 40 mg of selegiline HCl in an open four-period randomized study. Concentrations of selegiline and desmethlylselegiline in serum were measured by gas chromatography for 5 h. As it became evident that the use of oral steroids had a drastic effect on selegiline concentrations, the pharmacokinetic analyses were performed separately for oral contraceptive users and those not receiving any concomitant medication., Results: The total AUC and Cmax of selegiline were 10-to 20-fold higher in those subjects taking oral steroids compared with subjects with no concomitant medication; this finding was consistent and statistically significant at all the four dose levels. The dose linearity of selegiline pharmacokinetics failed to be demonstrated in both groups. The AUC and Cmax of desmethylselegiline were only moderately higher (about 1.5-fold; P=NS at each dose level) in the subjects taking oral steroids than in those not receiving concomitant medication. The AUC values of desmethylselegiline increased in a dose linear manner in subjects with no concomitant medication, but not in the oral steroid group. The metabolic ratio (AUC(desmethylselegiline)/AUC(selegiline)) was several-fold lower in the group receiving oral steroids compared with the no-concomitant-medication group (P<0.005 at all the four dose levels)., Conclusions: Concomitant use of oral contraceptives caused a drastic (20-fold) increase in the oral bioavailability of selegiline. The highly significant difference in the metabolic ratio between the groups provides evidence that the mechanism of the interaction between selegiline and female sex steroids involves reduced T-demethylation of selegiline. The present results suggest that concomitant use of selegiline with exogenous female sex steroids should be avoided or the dosage of selegiline should be reduced in order to minimize the risks of selegiline related adverse drug reactions.

Selegiline is readily absorbed from the gastrointestinal tract. It is distributed rapidly into the tissues, including the brain. It is the L-form of selegiline that is an active MAO-B inhibitor, the D-(+)-form being 25 times less active. Selegiline is metabolised into L-(-)-desmethylselegiline (DES), L-(-)-amphetamine (A) and L-(-)-methamphetamine (MA), mainly in the liver. We measured the steady state concentrations of the metabolites in the serum and cerebrospinal fluid (CSF) of patients with Parkinson's or Alzheimer's diseases who were on continuous selegiline therapy. The mean concentrations in serum and CSF were similar, and were not affected by the addition of levodopa. The mean concentrations of patients with Alzheimer's or Parkinson's disease were 6.5 +/- 2.5 ng/ml for A, 14.7 +/- 6.5 ng/ml for MA and 0.9 +/- 0.7 ng/ml for DES. The metabolites of selegiline were excreted in urine, and the recovery as metabolites was 87%. Due to the stereospecificity and the low CSF concentrations of the (-)amphetamine metabolites during the therapy with 10 mg selegiline, these metabolites do not seem to contribute significantly to the clinical efficacy of selegiline.