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Biomedical subjects

M Holm

Publications and source records attributed to M Holm.

At least 37 records · Page 2Linked to original sources

[Six years of experiences from a department of geriatric psychiatry].

After a project period from 1994 to 1997, all hospital-based psychogeriatric services in the Norwegian county of Telemark have been located to one department in the central hospital. The department has three differentiated bed units and one out-patient unit. This article describes the psychogeriatric department before and after the project, and includes an evaluation of the quality of service. The changes following the reorganization have been evaluated with an internal analysis, questionnaires to primary health care personnel and an examination of medical and psychiatric records. In 1995 and 1997, questionnaires were sent to general practitioners and district nurses in Telemark County. An independent consultant examined 40 medical and psychiatric records in 1995 and 1997, evaluating them according to selected quality standards. The response rates among doctors were 59% in 1995 and 48% in 1997. The responses show that primary health care doctors and nurses make use of the department's services and that they are increasingly satisfied with the quality of these services. The examination of medical and psychiatric records shows insufficient documentation of psychiatric symptoms and activities of daily life in 1995, but significant improvements by 1997. There are drawbacks to the evaluation method employed. However, we find it warranted to conclude that the reorganization has been functional and that the quality of services has improved.

Aged↗

Dynamic cell cycle kinetics in vitro and in vivo in myelodysplastic syndromes with special reference to the influence of hematopoietic growth factors.

We have investigated the effect of HGF in vivo and in vitro in MDS using a recently developed FCM assay involving the simultaneous measurement of cell surface antigens, DNA content, and BrdUrd or IodUrd incorporation. This allows for the determination of the dynamic cell kinetic parameters: LI, T(s), and T(pot) and we observed that in vitro HGF stimulation resulted in a significant decrease in mean T(pot) values from 6.6 to 3.5 days. Importantly, we demonstrated that in vivo GM-CSF administration to patients with RAEB resulted in a shortening of T(pot) within the 2 first weeks of GM-CSF treatment.

Aged↗

Tonometric assessment of jejunal mucosal nitric oxide formation in anaesthetized pigs.

Nitric oxide (NO) in the gut has attracted increasing interest as a regulatory factor for a wide variety of intestinal functions. This study was performed to evaluate some methodological aspects and jejunal sources for NO synthesis. Bench side evaluations and an animal model using chloralose-anaesthetized pigs were used. Immunohistochemistry was performed on samples from pig intestine and direct measurements of intestinal NO formation were performed using intraluminal tonometry. Tonometric measurements were quantitatively accurate and with high reproducibility. A substantial NO formation was assessed which was markedly inhibited by luminal administration of the non-selective NOS inhibitor L-NAME. Intravenous administration of L-NAME also reduced jejunal NO formation but to a lesser extent. Immunohistochemistry revealed staining for the inducible type of NOS in the mucosal surface epithelium whereas endothelial and neuronal subtypes were located in deeper layers of the jejunal wall. The study argues for that the source of jejunal NO production, as measured by intraluminal tonometry, is located in close proximity with the intestinal mucosa. The NOS in this compartment is predominantly of the inducible type.

Anesthetics, Dissociative↗

Recording monophasic action potentials using a platinum-electrode ablation catheter.

AIMS: The monophasic action potential (MAP) is conventionally recorded using Ag-AgCl electrodes which are not suitable for delivering radiofrequency currents. To be able to use the sharp MAP upstroke for identifying the local activation, as a step towards the development of a MAP-guided catheter ablation technique, the possibility of recording MAP via platinum electrodes of an ordinary ablation catheter was explored. METHODS AND RESULTS: One hundred and forty-two MAP recordings from the endocardium were obtained via an ablation catheter in 40 patients undergoing electrophysiological study/catheter ablation. During sinus rhythm and pacing, 90% of the ventricular and 100% of the atrial MAPs had stable baselines. The amplitudes were 13 +/- 4.2 mV for ventricular and 2.4 +/- 0.8 mV for atrial MAPs. During mapping and ablation, MAPs and uni- and bipolar electrograms were recorded simultaneously using the same tip electrode in eight patients. The MAPs provided more distinct local activation than the electrograms. During 17 MAP recordings, additional MAPs were recorded simultaneously using an Ag-AgCl electrode catheter in the immediate vicinity of the ablation catheter. The MAPs taken with the ablation catheter had characteristics consistent with those taken with the Ag-AgCl catheter. CONCLUSIONS: (1) Platinum electrodes can be used for timely recording of MAPs in patients. (2) It is feasible to record MAPs and deliver radiofrequency currents via the same platinum-tip electrode. These findings suggest that MAP-guided catheter ablation is technically possible.

Action Potentials↗

Intragastric CO2 and nitric oxide participate in the regulation of peptone-induced gastrin release in humans.

BACKGROUND: Moderate acidification of the gastric lumen inhibits peptone-induced gastrin release. The aim of the present study was to investigate if the gastric acid neutralization products CO2 (from secreted HCO3) and NO (from reduced salivary nitrite) could act as intermediate messengers between luminal acidity and the inhibition of peptone-induced gastrin release. METHODS: Fourteen healthy volunteers (mean age, 27 years; range, 20-39 years; 3 women) participated in the study. Intragastric perfusion with saline or peptone was performed on the healthy volunteers. Venous blood samples were analyzed for serum gastrin concentrations. Intragastric NO was measured by chemiluminescence. RESULTS: Basal serum gastrin ranged between 11 and 23 pmol/l. Peptone in Sörensen's phosphated buffer (pH 6.9, PCO2 0 mmHg) increased serum gastrin by 83% +/- 23%, whereas acidified peptone (pH 2.0) did not stimulate gastrin release. Acidified peptone buffered with NaHCO3 to neutrality (pH 6.9, PCO2 approximately 600 mmHg) increased serum gastrin by 166% +/- 29%. Low intragastric NO levels were obtained by deviation of saliva. During such salivary depletion, acidified peptone (pH 2.0) stimulated gastrin release to a level of about 40% of the control response (pH 6.9). This peptone-induced gastrin response during salivary deviation was inhibited by addition of nitrite to the perfusate. CONCLUSIONS: Acid-induced inhibition of peptone-stimulated gastrin release is partly dependent on intraluminal NO formed in the reaction between salivary nitrite and gastric acid. In addition, the gastric acid neutralization product CO2 seems to potentiate the effect of peptone on gastrin release.

Adult↗

Hospitalization due to Pasteurella multocida-infected animal bite wounds: correlation with inadequate primary antibiotic medication.

Over a 10-y period, patients hospitalized with Pasteurella-induced cat or dog bite-associated wound infection were analysed retrospectively with regard to preceding antibiotic medication. In 10/14 cases, hospitalization was necessitated in spite of prophylactic or therapeutic administration of oral antibiotics. In 1 case, phenoxymethylpenicillin and flucloxacillin had been prescribed. The other patients received flucloxacillin (7 patients), erythromycin, or cefadroxil (1 patient each), agents that are not consistently active against Pasteurella. In conclusion, hospitalization due to Pasteurella-induced animal bite-associated wound infection seemed to be related to the prescription of suboptimal oral antibiotic therapy at a preceding medical consultation.

Adolescent↗

Management and monitoring of recombinant activated factor VII.

Recombinant factor VIIa (rFVIIa) has recently been introduced as a new 'bypassing' agent to improve haemostasis in haemophilia patients with inhibitors to factor (F) VIII or FIX. In noninhibitor patients, levels of circulating FVIII or FIX can be used to assess the quality of substitution therapy. In contrast, laboratory monitoring of haemostatic efficacy in patients treated with rFVIIa has proved more complex. Evaluation of patient samples saved during rFVIIa treatment have revealed some correlation between FVII:C levels and improved haemostasis, while whole blood elasticity, as determined by thromboelastography, has been shown to improve following rFVIIa treatment. The investigation aimed to study the efficacy of rFVIIa in activating FX:C and in shortening the whole blood clotting time (WBCT) using the newly-developed roTEG coagulation instrument. Results indicated a substantial and apparently dose-dependent activation of FX:C by rFVIIa. In addition, the presence of FIX appeared to influence FX:C activation. In-vitro and ex-vivo roTEG thromboelastograph measurements showed that FVIIa shortened WBCT, although normalization did not occur. The results presented here are based on a small number of observations in a few patients and further studies should be planned to test the efficacy of these monitoring principles in clinical treatment practice with rFVIIa.

Bleeding Time↗

[Prophylactic contralateral orchiopexy in patients with testicular torsion].

The aim of the study was to examine the recommendations for prophylactic contralateral orchiopexy in patients presenting with unilateral testicular torsion in Denmark. A questionnaire was mailed to the 61 surgical departments treating acute urological patients. Prophylactic contralateral orchiopexy was performed in 60 of the 61 departments. Twenty-eight departments routinely performed a combined ipsilateral and contralateral operation. In 20 departments the contralateral procedure was performed immediately in the case of a vital ipsilateral testis, but delayed a median of five (3-12) weeks in the case of a necrotic testis. In seven departments the contralateral orchiopexy was routinely performed a median of 10 (2-12) weeks after the ipsilateral operation, and in the remaining five departments the time of the contralateral procedure was determined by the surgeon. In conclusion prophylactic contralateral orchiopexy was widely used in patients with unilateral testicular torsion, but the timing of the procedure varied.

Denmark↗

Preconditions of language development in deaf children.

The harmful effects of childhood hearing impairment are given little thought by many people because hearing loss is largely an invisible handicap. An infant with a hearing impairment is generally healthy-looking and develops relatively normally during the first year of life. Hearing impairment in infants interferes with the normal development of spoken language. We are biologically programmed to develop certain skills in response to certain inputs. Language learning is one such skill which must be gained very early in life. Hearing is the most important basis for normal language acquisition and language is the keystone of modern society. Hearing loss must be identified as early as possible in the first years of life, especially a child with profound or severe hearing loss must be identified in the first year of life. If not, the child has missed an irreversible sensitive phase for learning of speech and language.

Deafness↗

AML and Ets proteins regulate the I alpha1 germ-line promoter.

The immunoglobulin heavy chain (IgH) class switch recombination of B lymphocytes preferentially targets unrearranged IgH genes that have already been rendered transcriptionally active. Transcription of the germ-line IgH genes is controlled by intervening (I) regions upstream of their switch regions. The I alpha1 promoter activates transcription of the human germ-line C alpha1 gene for IgA1 and mediates the transforming growth factor (TGF)-beta1 responsiveness of this locus. Here we show that the I alpha1 promoter contains several binding sites for the AML/PEBP2/CBF family of transcription factors and that AML and Ets proteins are major regulators of the basal and TGF-beta-inducible promoter activity. Our data constitute a starting point for studies to elucidate the molecular mechanism by which TGF-beta regulates IgA production.

Animals↗

Screening for somatization and hypochondriasis in primary care and neurological in-patients: a seven-item scale for hypochondriasis and somatization.

The aim of this study was to investigate the internal and external validity of the Whiteley Index as a screening instrument for somatization illness. A 14-item version of the Whiteley Index for hypochondriacal traits was given to 99 of 191 consecutive primary care patients, aged 18-65 years, and to 100 consecutive patients, aged 18-60 years, admitted for the first time to a neurological ward. The primary care sample was, in addition, interviewed by means of the SCAN (Schedules for Clinical Assessment in Neuropsychiatry) psychiatric interview. The GPs and the neurologists were asked to rate various characteristics of the patients that might indicate somatization. The internal validity of the Whiteley Index was tested by means of latent structure analysis. On this basis, a reduced seven-item scale (Whiteley-7 scale) and two subscales (i.e., an Illness Conviction and Illness Worrying scale, each with three items) were constructed. All three had a high internal validity fitting into the very restricted Rasch statistical model (p>0.05) and an acceptable transferability between most of the subpopulations investigated. In the primary care population, the Whiteley-7 and the Illness Conviction scales at cut-point 0/1 showed 1.00 and 0.87 sensitivity and 0.65 and 0.87 specificity, respectively, using as "gold standard" the fulfillment of criteria for at least one ICD-10 somatoform disorder, and 0.71 and 0.63 sensitivity and 0.62 and 0.87 specificity, respectively, as gold standard for the fulfillment of criteria for at least one DSM-IV somatoform disorder, excluding the NOS diagnostic group. The Illness Worrying subscale showed less impressive performance in this respect. The agreement between the Whiteley-7 scale including the two subscales and neurologists' rating and the GPs' rating and the somatization subscale on the SCL-90 was modest or worse. It may be concluded that the Whiteley-7 scale and the Illness Conviction subscale had acceptable psychometric profiles, and both seem to be promising screening tools for not only hypochondriasis but also for somatoform disorders in general.

Adolescent↗

Structural organization and interactions of COP1, a light-regulated developmental switch.

Arabidopsis seedling development follows contrasting patterns depending on ambient light conditions, photomorphogenesis in the light and skotomorphogenesis or etiolation in darkness. COP1 is a limiting or regulatory component in mediating repression of photomorphogenesis in the absence of light. COP1 acts within the nucleus in the dark, directly interacts and regulates specific transcription factors that are required for promoting photomorphogenesis. Light abrogates COP1 action and results in progressive nuclear depletion of COP1 with increasing light stimuli. COP1 contains multiple structural modules, which are responsible for interacting with distinct cellular factors and play specific functional roles. We review the most recent progress in understanding the COP1 action and propose specific models based on the recent studies.

Animals↗

Differentiation of the peptidergic vasoregulatory response to standardized splanchnic hypoperfusion by acute hypovolaemia or sepsis in anaesthetized pigs.

This study was performed to integratively investigate the vasoregulatory response during standardized splanchnic hypoperfusion in pigs. Splanchnic perfusion was reduced to 50% of baseline by: haemorrhage by 20 and 40% of the estimated total blood volume; femoral venous infusion of live E. coli to establish sepsis of systemic origin; portal venous infusion of live E. coli to establish sepsis of splanchnic origin. Invasive haemodynamic monitoring and radioimmunoassay analyses of arterial plasma concentrations of angiotensin II, endothelin-1 and atrial natriuretic peptide were carried out. Acute hypovolaemia reduced systemic and splanchnic vascular resistances following transient increases and increased angiotensin II levels (+587%), whereas endothelin-1 and atrial natriuretic peptide levels did not change significantly. Systemic sepsis following femoral venous infusion of E. coli resulted in increased splanchnic vascular resistance and increased levels of angiotensin II (+274%), endothelin-1 (+134%) and atrial natriuretic peptide (+185%). Infusion of E. coli via the portal venous route induced an increase in splanchnic vascular resistance associated with particularly elevated levels of angiotensin II (+1770%) as well as increased endothelin-1 (+201%) and atrial natriuretic peptide (+229%) concentrations. Hypovolaemia and sepsis, although standardized with a predefined level of splanchnic hypoperfusion, elicited differentiated cardiovascular and vasopeptidergic responses. Sepsis, particularly of portal origin, notably increased splanchnic vascular resistance related to increased production of the vasoconstrictors angiotensin II and endothelin-1. The role of atrial natriuretic peptide as a vasodilator seems to be of subordinate importance in hypovolaemia and sepsis.

Acute Disease↗

Dynamic cell cycle kinetics of normal CD34+ cells and CD38+/- subsets of haemopoietic progenitor cells in G-CSF-mobilized peripheral blood.

Using a recently developed flow cytometric assay for the simultaneous measurement of cell surface antigens, DNA content and bromodeoxyuridine incorporation, we have for the first time determined the labelling index (LI), the duration of the S-phase (Ts) and the potential doubling time (Tpot) of purified CD34+ cells mobilized by G-CSF from 10 normal donors. Although CD34+ cells were not actively cycling immediately following purification, up to 5% could nevertheless traverse cell cycle without exogenous stimulation during the first 24 h of culture. In addition, it was possible to induce CD34+ cells to enter cycling by stimulation with haemopoietic growth factors (IL-3, IL-6 and SCF), resulting in median Tpot values of 18.2 d at 21 h, 7.7 d at 29 h, and 4.5 d at 37 h. Importantly, stimulation of CD34+ cells was seen almost exclusively within the CD38+ subset (mean Tpot value 2.8 d), whereas CD38- cells were not recruited into cycle (mean Tpot value 35.9 d). In conclusion, although cell cycle entry and progression can easily be induced in differentiated CD34+/CD38+ cells, immature CD34+/CD38- cells will remain dormant in most of the clinical and laboratory stimulation protocols hitherto employed. This assay can be used to obtain detailed cell cycle kinetics in leucocyte subsets in health and disease.

ADP-ribosyl Cyclase↗

Solution properties of the free and DNA-bound Runt domain of AML1.

The Runt domain is responsible for specific DNA and protein-protein interactions in a family of transcription factors which includes human AML1. Structural data on the Runt domain has not yet become available, possibly due to solubility and stability problems with expressed protein fragments. Here we describe the optimization and characterization of a 140-residue fragment, containing the Runt domain of AML1, which is suitable for structural studies. The fragment of AML1 including amino acids 46-185 [AML1 Dm(46-185)] contains a double cysteine-->serine mutation which does not affect Runt domain structure or DNA-binding affinity. Purified AML1 Dm(46-185) is soluble and optimally stable in a buffer containing 200 mm MgSO4 and 20 mm sodium phosphate at pH 6.0. Nuclear magnetic resonance and circular dichroism spectroscopy indicate that the Runt domain contains beta-sheet, but little or no alpha-helical secondary structure elements. The 45 N-terminal residues of AML1 are unstructured and removal of the N-terminal enhances sequence-specific DNA binding. The NMR spectrum of AML1 Dm(46-185) displays a favorable chemical shift dispersion and resolved NOE connectivities are readily identified, suggesting that a structure determination of this Runt domain fragment is feasible. A titration of 15N-labelled AML1 Dm(46-185) with a 14-bp cognate DNA duplex results in changes in the 15N NMR heteronuclear single quantum coherence spectrum which indicate the formation of a specific complex and structural changes in the Runt domain upon DNA binding.

Base Sequence↗

Effect of cardiac exposure by median sternotomy on atrial fibrillation cycle length.

BACKGROUND: Epicardial mapping is a powerful tool that has enabled us to gain insight into the electrical phenomena perpetuating atrial fibrillation and has guided the design of surgical and catheter-based therapeutic strategies. However, epicardial data are acquired during abnormal physiological conditions; the patients are anaesthetized, their chests opened, dislocating the heart and exposing it to air of room temperature, and the autonomic tone is modulated due to the surgery. The effect of intra-operative conditions on atrial electrophysiological properties have not been investigated before. Thus in the present study we assessed the atrial cycle length, shown to be an index of atrial refractoriness, and the ventricular rate before and during open-heart surgery in 10 patients with chronic atrial fibrillation and an underlying heart disease. METHODS AND RESULTS: Using a newly introduced and validated ECG method known as frequency analysis of fibrillatory ECG (FAF-ECG), the atrial cycle length and the ventricular rate were determined just before surgery. After anaesthesia and median sternotomy, epicardial mapping of the entire right atrial free wall was performed. The mean ventricular rate as well as the dominant atrial fibrillation cycle length consistently increased, the former from 71 to 92 beats x min(-1) (mean of all patients, P<0.05) and the latter from 156 to 172 ms (P<0.05). CONCLUSIONS: Atrial fibrillation cycle length, an index of atrial refractoriness, is increased as an effect of anaesthesia and heart exposure during open-heart surgery in patients with chronic atrial fibrillation, implying that atrial activation might be altered, which must be considered when interpreting data from epicardial conduction analysis.

Aged↗

The optimal oesophageal pacing technique--the importance of body position, interelectrode spacing, electrode surface area, pacing waveform and intra-oesophageal local anaesthesia.

In order to improve the technique of transoesophageal atrial stimulation (TAS), the effects of body position, interelectrode spacing and electrode surface area on pacing threshold were assessed in two substudies. The effects of intra-oesophageal local anaesthesia and of two different pacing wave configurations on pacing threshold and discomfort were also assessed. Substudy I comprised 16 subjects (3 patients with a history of paroxysmal supraventricular tachycardia and 13 healthy volunteers) and substudy II comprised 16 healthy volunteers. TAS was performed using a hexapolar luminal prototype oesophageal electrode catheter. In substudy I bipolar pacing was performed in the semi-supine and left decubitus body positions for different pulse durations (20, 10, 6 and 2 ms), interelectrode pole distances (10 to 24 mm) and electrode pole surface areas (0.22 to 0.66 cm2). In substudy II TAS was performed with square wave and triangular waveform pulses after intra-oesophageal saline and lidocaine 20 mg/ml. These solutions were given in random order. Neither the interelectrode distance nor electrode surface areas had any significant influence on pacing thresholds. Stimulation thresholds were not affected by body position. Intraoesophageal lidocaine did not affect the discomfort experienced. Peak pacing thresholds using a triangular waveform were significantly higher than thresholds using a square waveformn (p < 0.001). The optimal pacing technique for TAS remains to be defined. The TAS-induced pain is probably not generated from the oesophageal mucous membrane. There is a significant difference in pacing thresholds between triangular and square waveforms.

Adult↗