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Biomedical subjects

M Holm

Publications and source records attributed to M Holm.

At least 73 records · Page 4Linked to original sources
PubMed1997

Epicardial right atrial free wall mapping in chronic atrial fibrillation. Documentation of repetitive activation with a focal spread--a hitherto unrecognised phenomenon in man.

BACKGROUND: Previous studies have shown that atrial fibrillation of recent onset in man is based on a varying number of simultaneously present activation waves reentering either themselves or each other. In the present study, right atrial activation during chronic atrial fibrillation in man was studied. METHODS AND RESULTS: In 16 patients with chronic atrial fibrillation multiple epicardial recordings of 8 s each were made at the right atrial posterior free wall and at the appendage using a 20 x 35 mm electrode array with 56 bipolar measurement points. The preferable activation pattern of each recording and the propagation direction, cycle length and conduction velocity of individual activation waves within each recording were determined. Activation was characterized by unorganised activation with several simultaneously present activation waves: inconsistent preferable activation pattern (n = 5), predominantly organised activation with either frequent episodes of uniform activation: consistent preferable activation pattern (n = 7) or frequent episodes of activation with focal spread; focal preferable activation pattern (n = 4). Random re-entry was frequently documented in recordings with the inconsistent preferable activation pattern and less frequently in recordings with the consistent and focal preferable activation pattern. Complete re-entry circuits were rarely documented. The median fibrillation cycle length was 146, 159 (P < 0.05) and 165 ms (not significant) and the mean conduction velocity during uniform activation was 64, 67 and 83 cm. s-1 (not significant) in recordings with the inconsistent, consistent and focal preferable activation pattern, respectively. CONCLUSIONS: During chronic atrial fibrillation in man, right atrial free wall activation ranges from disorganised activation with multiple co-existing activation waves to predominantly organised activation characterized by either uniform activation consistent with the presence of large re-entry circuits or repetitive activation of unknown mechanism and focal spread.

Aged↗
PubMed1997

Sympathetic and renin-angiotensin activation during graded hypovolemia in pigs: impact on mesenteric perfusion and duodenal mucosal function.

Sympathetic and angiotensinergic activation reduce splanchnic oxygen delivery during hypovolemia, which may lead to failure of the intestinal mucosal barrier and eventually multiple organ dysfunction. This study integrates sympathetic and angiotensinergic responses with splanchnic hemodynamics and duodenal mucosal function during hypovolemia and evaluates pharmacologic blockade of either system to ameliorate the impact of acute hypovolemia. Chloralose-anesthetized pigs subjected to 20 and 40% blood volume reductions were randomized to controls or administered guanethidine or enalaprilate to block sympathetic and angiotensinergic activation, as assessed by plasma norepinephrine spillover and angiotensin II levels, respectively. Mesenteric and hepatic oxygen delivery/consumption as well as duodenal mucosal alkaline secretion and potential difference were determined. Hypovolemia preferentially increased mesenteric sympathetic outflow and caused a vigorous angiotensinergic activation. Guanethidine and enalaprilate blocked effectively the sympathetic and angiotensinergic responses. Treatment with enalaprilate, but not guanethidine, prevented the reduction of mesenteric oxygenation and duodenal mucosal alkaline secretion and potential difference observed in control animals. The down-regulation of mesenteric oxygenation and duodenal mucosal function during hypovolemia can be prevented by administration of enalaprilate, whereas guanethidine is uneffective in this respect. Interference with the reninangiotensin system might be of clinical interest to support mesenteric perfusion and organ function in hypovolemia.

Angiotensin II↗
PubMed1997

Psychiatric morbidity in primary public health care: a multicentre investigation. Part II. Hidden morbidity and choice of treatment.

A total of 1,281 patients were examined during consultation with their GP in a Nordic multicentre study focusing on the prevalence of psychiatric illness, hidden psychiatric morbidity, treatment and pathways to specialized care. The methodology and prevalence were reported in an accompanying paper. The present paper presents results concerning the variables hidden psychiatric morbidity, treatment and pathways to specialized care. The GPs detected 44% of the psychiatric cases compared with the result of a diagnostic interview (PSE). The distinction between psychosis and non-psychosis did not influence the GPs' ability to detect a mental illness. According to the GPs' assessment the majority of patients suffering from a mental disorder consulted their GP about physical complaints. The GPs treated the patients themselves, and only a limited number of cases were referred to psychiatrists or psychologists.

Adolescent↗
PubMed1997

ANG II prolongs splanchnic nerve-mediated inhibition of duodenal mucosal alkaline secretion in the rat.

Hypovolemia inhibits duodenal mucosal alkaline (HCO-3) secretion by activation of sympathoadrenergic nerves. A possible involvement of the renin-angiotensin system was investigated. Experiments were performed on chloralose-anesthetized rats. The mucosal alkaline output by a duodenal segment was measured using in situ pH-stat titration equipment. A modest hypovolemia was induced by bleeding the animals approximately 10% of the total blood volume. This procedure decreased duodenal mucosal alkaline secretion to a sustained level of approximately 50% of baseline and reduced mean arterial pressure by approximately 20 mmHg. Intravenous pretreatment with the angiotensin-converting enzyme (ACE) inhibitor enalaprilate (0.7 mg/kg) or the angiotensin II-receptor antagonist losartan (10 mg/kg) altered the response to hypovolemia to a transient one, and alkaline secretion returned to the control level within 40-50 min. When exogenous angiotensin II was administered intravenously (0.25 and 0.75 microgram.kg-1.h-1), a hypovolemia-induced sustained depression of the secretion was observed even during ACE inhibition. Direct electrical stimulation (3 Hz, 5 V, 5 ms, bilaterally) of the peripheral splanchnic nerves decreased duodenal mucosal alkaline secretion to approximately 60% of the control level and increased mean arterial pressure by approximately 20 mmHg. However, in enalaprilate-pretreated animals, the inhibition of alkaline secretion due to splanchnic nerve stimulation was transient, a response that became sustained on angiotensin II substitution. These results suggest that the renin-angiotensin system prolongs the sympathoadrenergic inhibition of duodenal mucosal alkaline secretion and that angiotensin II, in this regard, acts mainly on the peripheral sympathetic efferents.

Angiotensin II↗
PubMed1996

[Results of radiotherapy of ureteral obstruction in invasive bladder cancer].

Retrospective evaluation of the records of 574 patients with muscle-invasive bladder cancer revealed 90 patients (16%) with ureteric obstruction; the obstruction was bilateral in 24%. The effect of radiotherapy was assessed in 55 patients with 68 obstructed kidneys. Six patients with eight obstructed kidneys required percutaneous nephrostomy or ureteric catheters in addition to radiotherapy. Drainage improved in only 20% of kidneys and the diverting catheter could be withdrawn permanently in only one (17%) of the diverted patients. The median survival was 11 months. Irradiation was followed by significant complications in 37 patients (67%). This raises doubts about the assumed beneficial effect of irradiation on ureteric obstruction due to muscle invasive bladder cancer. The short median survival of 11 months confirms that ureteric obstruction is a poor prognostic factor in muscle invasive bladder cancer.

Aged↗
PubMed1996

A new method for analysis of atrial activation during chronic atrial fibrillation in man.

To further clarify the mechanisms maintaining chronic atrial fibrillation (CAF), a method identifying preferable activation patterns of the atria during fibrillation, by time averaging of multiple discrete excitation vectors, was developed. Repeated recordings, each of 56 atrial bipolar electrograms simultaneously acquired during 8 s, were made at multiple sites in the right atrial free wall and the left atrial appendage in 16 patients with CAF using a 2.17 x 3.54 cm electrode array. The local activation times (LAT's) in each recording were estimated as the median activation time at the respective measurement point. By calculating the time difference between the LAT's at adjacent measurement points in two spatial dimensions, a direction vector was created for each activation wave passing each set of measurement points, a total of 42 sets. By time averaging of the individual direction vectors (typically n = 55) at each set of measurement points, preferable activation patterns were determined. Three types of activation patterns were found: 1) inconsistent activation (n = 5), 2) consistent activation with preferential propagation directions (n = 7) and 3) consistent activation with impulses originating from a localizable site within the recording area (n = 4). All activation patterns were reproducible and the two latter patterns were proven significant using statistical tests. We conclude that this new method is useful in further clarification of the mechanisms involved in the maintenance of atrial fibrillation.

Aged↗
PubMed1996

The bone-marrow infiltration pattern in B-cell chronic lymphocytic leukemia is not an important prognostic factor. Danish CLL Study Group.

In a multicentre study of 635 consecutive newly diagnosed patients with B-CLL, the histological bone marrow (BM) specimens were reviewed independently by each of 3 pathologists and found evaluable for BM infiltration pattern in 575 patients, 404 of whom had a CD5+, mainly FMC7-, faint surface-membrane immunoglobulin (SIg) fluorescence-intensity ppenotype. In these 404 patients the following BM infiltration patterns were found: mixed nodular-interstitial (30%), moderate interstitial (44%), heavy interstitial (20%) and diffuse packed (6%). In univariate survival analysis, significant differences were found according to BM pattern (p < 0.05), the presence of nodules being a favorable prognostic sign. In multivariate survival analysis in a model including age, clinical stage, BM pattern, BM lymphocytosis, WBC and sex, only age and stage but not BM pattern or BM lymphocytosis had independent prognostic significance. In stage A, progression-free survival was significantly longer in patients with nodular than in patients with non-nodular bone-marrow pattern. The overall survival of these patients, however, did not differ, possibly owing to the prompt and prolonged treatment given to most patients at the time of progression to stage B or C. We conclude that in CD5+, SIg(faint), mainly FMC7-B-CLL, bone-marrow histology may predict unstable disease in early clinical stage but is not important for treatment decisions, when these are based on clinical stage.

Age Factors↗
PubMed1996

Ion transport mechanisms in native rabbit nasal airway epithelium.

Net ion transports in rabbit nasal airway epithelium (RNAE) were estimated from unidirectional fluxes of 22Na+, 36Cl-, and 86Rb+ (K+ tracer), short-circuit current (Isc), and epithelial conductance (Gt) under short-circuit conditions in excised parallel RNAE from the two sides of the nasal septum mounted in Ussing chambers at 37 degrees C. Net Na+ absorption (JNa; 76 nmol.min-1.cm-2) was nearly equal to the net charge flux (Jnet), equivalent to the control Isc of 137 microA/cm2 (Jnet = Isc/zF = 85 neq.min-1.cm-2). Secretions of Cl- (9 nmol.min-1.cm-2) and K+ (Rb+) (1.2 nmol.min-1.cm-2) were small. Intra-animal variations between right- and left-side Isc values were small compared with large interanimal variations, suggesting long-term regulation of JNa. Serosal ouabain (10(-4) M) abolished Isc. Mucosal amiloride (10(-4) M) maximally inhibited Isc by 68% and JNa by 78%, abolished K+ (Rb+) secretion, increased Cl- secretion slightly (to 16 nmol.min-1.cm-2), and decreased control Gt (13.4 mS/cm2) by 26%. Amiloride-insensitive JNa was inhibited approximately 50% by mucosal hydrochlorothiazide (10(-4) M) but not by mucosal bumetanide, phloridzine, or ethoxzolamide. The Cl- secretion was abolished by serosal bumetanide (10(-4) M) and also by mucosal diphenylamine-2-carboxylate (2.5.10(-4) M) or bumetanide (10(-4) M). Serosal Ba2+ (2 mM) inhibited JNa and increased K+ (Rb+) secretion. The latter was blocked by mucosal Ba2+. Passive Cl- (but not Na+) fluxes varied proportionally with Gt and were approximately four times higher than passive Na+ fluxes, suggesting 1) significant anion selectivity of a low-resistance paracellular pathway and 2) separate routes for paracellular Cl- and Na+ fluxes. We conclude that RNAE is a suitable model organ for studies of regulation of JNa in native human airway epithelia.

Amiloride↗
PubMed1996

Clinical experience with recombinant factor VIIa in patients with thrombocytopenia.

Platelets play a central role in primary hemostasis. The role of the coagulation mechanism during early stages of hemostasis is less clear, although increasing evidence is emerging indicating the ultimate importance of the factor VII (FVII)-tissue factor-dependent coagulation system in providing the first thrombin molecules necessary for the platelet activation to occur. Supporting this, early fibrin formation has been reported to occur within the bleeding time wound and infusion of recombinant FVIIa (rFIIa) has been shown to shorten the bleeding time in rabbits. We have investigated whether infusion of rFVIIa would enhance fibrin formation in bleeding time wounds in patients with thrombocytopenia as reflected by a shortening of the bleeding time. A reduction of the bleeding time was found in 55/105 cases (52%). The decrease was significantly more pronounced when the platelet count exceeded 20 x 10(9)/l. With the exception of an anaphylactoid reaction in 1 patient, no major adverse reactions related to the study drug were observed. Nine infusions of rFVIIa were given to 8 thrombocytopenic patients with overt bleeding. One patient received two infusions. Bleeding decreased in all patients and stopped in 6 patients.

Adolescent↗
PubMed1996

A pilot study of rehabilitation at home after stroke: a health-economic appraisal.

This study aimed at describing the health-economic implications and organisational issues of rehabilitation at home in south-west Stockholm of 15 acute stroke patients, mean age 68.2, male:female ratio 9:6, independent in feeding and continent one week after their stroke. Average patient satisfaction with different dimensions of care was 92%. Perceived dysfunction, by means of the Sickness Impact Profile, 3 months after stroke was highest for Recreation-and-Pastime, Home Management and Ambulation. Between 3-12 months after stroke, functional improvement was particularly seen in Home Management, Recreation-and-Pastime and Emotional Behaviour. Three fourths of the patients received help with different ADL tasks from a family caregiver and 1/5 from home service assistants. According to the scores for subjective health of the spouses and time used to help the patient, the burden that the programme put on the patient's family was modest, temporary and in accordance with preferences reported by the elderly in Sweden. The mean duration of hospital stay for patients under rehabilitation at home was 14 days and for a selected comparison group with similar ADL-grade, 27 days. The mean number of therapy sessions at home was 11. Each home visit took 3.2 hours, 60% of which were direct patient time. In the selected comparison group, 1/3 was referred to other departments for rehabilitation and care, and 40% had contacts with day-care and paramedical professionals after discharge from the hospital. During the first year after stroke, the average, direct, per capita cost for rehabilitation at home amounted to SEK 127,730 divided between hospital care (50%), followed by contribution by family caregivers (18%), rehabilitation at home (10%), out-patient visits to physicians and nurses (8.8%), home-help service (7%), auxiliary equipment (2%), medication (1.5%), home adaptation (1%) and transportation service (0.3%). This organisational model of home-based rehabilitation of stroke patients constitutes a feasible, possibly less expensive alternative and complement to current rehabilitation in hospital and primary care, which could be further developed and evaluated.

Aged↗
PubMed1995

Regression of media-to-lumen ratio of human subcutaneous arteries and left ventricular hypertrophy during treatment with an angiotensin-converting enzyme inhibitor-based regimen in hypertensive patients.

A total of 25 patients with newly diagnosed or poorly controlled essential hypertension were randomly selected from a larger group referred to hospital. Treatment was initiated with perindopril (4-8 mg orally). If normotension was not achieved, isradipine (5-10 mg orally) was added and, if necessary, hydralazine was added. Before treatment and at the end of a 9-month period of normotension (diastolic blood pressure < or = 90 mm Hg), 24-hour blood pressure and echocardiographic measurements were performed and resistance artery structure was determined. A total of 20 age- and sex-matched normotensives were used as controls. During antihypertensive treatment, mean blood pressure was reduced from 128 +/- 11 to 103 +/- 6 mm Hg. Left ventricular mass was reduced from 300 +/- 76 to 198 +/- 54 g. The media:lumen ratio of the resistance arteries decreased from 9.8 +/- 2.6% to 7.8 +/- 1.9%; control subjects exhibited a media:lumen ratio of the same magnitude (7.9 +/- 2.0%). Results indicate that a perindopril-based regimen is extremely efficient in normalizing resistance artery and cardiac ventricular structures within one year of treatment. The impact of these findings on the excess cardiovascular morbidity and mortality in arterial hypertension still remains to be demonstrated.

Analysis of Variance↗
PubMed1995

The relation between peripheral vascular structure, left ventricular hypertrophy, and ambulatory blood pressure in essential hypertension.

The relations between left ventricular mass (LVM), peripheral resistance artery structure, and ambulatory BP were studied in 83 patients with previously untreated or poorly regulated essential hypertension and 20 healthy controls of similar age and sex. LVM was assessed by echocardiography. Signs of left ventricular hypertrophy (LVH) were present in 67 (81%) of the patients and in none of the controls. Peripheral resistance arteries were isolated from surgical gluteal skin biopsies and mounted in a Mulvany-Halpern isometric small vessel myograph, and their media:lumen ratio, media thickness, and media cross-sectional area were determined under standardized conditions. Mean (+/- SD) ambulatory BP was 122 +/- 9 mm Hg among patients and 96 +/- 8 mm Hg among controls (P < .001). LVM was 327 +/- 99 g among patients and 197 +/- 37 g among controls (P < .001). Media thickness of resistance arteries was 21.0 +/- 4.2 microns among hypertensives and 16.2 +/- 2.6 microns among controls (P < .001). The media:lumen ratio of arteries from patients was 10.2 +/- 2.6% v 7.9 +/- 2.0% in arteries of similar internal diameter from controls (P < .01). Both LVM index (LVMI) and media/lumen ratio correlated significantly with BP. There was significant correlation between media:lumen ratio and LVMI among hypertensive patients (r = 0.45, P < .001), but if patients were subdivided according to the presence of LVH this correlation was found only among patients with LVH (r = 0.60 P< .001) and not among patient without LVH nor controls. Multiple regression analyses of age, body surface area, media/lumen ratio, and BP on LVM or LVMI revealed independent contributions of media/lumen ratio and BP. Age had no influence in the models. Similar results were obtained when casual BP was replaced with ambulatory BP in these analyses. No correlation was found between LVMI and media cross-sectional area. A minor subset of patients with complete absence of nocturnal BP drop had particularly great LVM and media:lumen ratio. The study suggests that cardiac and arteriolar tissue undergo parallel structural remodeling in essential hypertension.

Adult↗
PubMed1995

Psychiatric morbidity in primary public health care: a Nordic multicentre investigation. Part I: method and prevalence of psychiatric morbidity.

The prevalence of mental illness in five different Scandinavian primary care populations was investigated in this study. Patients consecutively consulting their general practitioner a particular week-day were included in the study. Initially the SCL-25 was applied and next the high scores and a sample of the low scores were interviewed by the PSE. In the analysis the screening procedure was first validated. The internal validity of the SCL was tested by means of Rasch latent structure analysis and the external validity tested by ROC/QROC analysis. Based on this, a short 8-item version of the SCL was developed. The prevalence of mental illness in all centres was 0.26 with a minimum of 0.14 in Nacka and a maximum of 0.34 in Turku.

Adolescent↗
PubMed1995

Normalization of structural cardiovascular changes during antihypertensive treatment with a regimen based on the ACE-inhibitor perindopril.

Untreated essential hypertension is associated with left ventricular hypertrophy (LVH) and structural changes in resistance vessels. The aim of this study was to establish the effect of perindopril based antihypertensive therapy on media thickness to lumen diameter (media:lumen) ratio of peripheral resistance vessels and left ventricular mass in essential hypertension. Twenty-five patients with newly diagnosed or poorly regulated essential hypertension were treated with perindopril. Insufficient treatment response (DBP > 90 mmHg) led to addition of isradipine, and hydralazine was used as a tertiary drug if necessary. Gluteal subcutaneous biopsies were taken surgically at baseline and after 9 months of successful treatment. Two small resistance arteries were isolated and mounted in a small vessel myograph, and media:lumen ratio (%) was measured under standardized conditions. Left ventricular mass was determined by echocardiography. Mean (SD) media:lumen ratio decreased from 9.8 (2.6) % to 7.8 (1.9) % (p < 0.05), while left ventricular mass decreased from 299 (75) g to 199 (53) g (p < 0.001). Correlation was found between changes in left ventricular mass index and media:lumen ratio (r = 0.62, p < 0.01). It is concluded that a perindopril based regimen efficiently normalizes resistance artery structure and left ventricular hypertrophy in essential hypertension within one year of treatment. The impact of these findings on the excess cardiovascular morbidity and mortality in arterial hypertension remains to be investigated.

Adult↗
PubMed1995

Intervention design for rehabilitation at home after stroke. A pilot feasibility study.

This study aimed at identifying the characteristics and feasibility of rehabilitation at home for acute stroke patients in south-west Stockholm. A population-based systematic sample of 16 patients, fulfilling defined criteria, was selected from approximately 1/3 of the stroke patients having been in hospital for one week or more at a neurology department, and offered early discharge in combination with home-based rehabilitation as an alternative to sustained rehabilitation in hospital. Fifteen patients, mean age 68.2 years, male/female ratio 9/6, independent in feeding and continent one week after acute stroke, participated in the study. The most important components of the home-based rehabilitation programme were that: 1) one therapist was selected as case-manager using the other therapists on a consultant basis; 2) the training sessions consisted of different task-specific activities, based on the patients' personal interest; 3) education and individual counselling were offered to all spouses; and 4) adherence to structured training between therapy sessions was promoted. The length of such programmes varied from 4 to 19 weeks after discharge and the mean number of home visits was 11. Reported time for training between therapy sessions for 14 patients was mean 1.2 hours per day. The patients' lifestyle activities, personal and instrumental ADL, and motor capacity at 3, 6 and 12 months after stroke, assessed by validated and reliable methods, followed patterns similar to those reported for other stroke patients. The mean time in hospital for patients in the study was 14 days; for patients with similar ADL capacity but not included in the study it was 27 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1994

Calcium/calmodulin inhibition of basic-helix-loop-helix transcription factor domains.

The ubiquitous Ca(2+)-binding protein calmodulin (CaM) is a key protein in Ca2+ homeostasis and activation of eukaryotic cells. CaM is the molecular link between free Ca2+ in the cell and the inhibition, or activation, of numerous enzymes. Many nuclear functions are under Ca2+/CaM control, and some transcriptional activators are known to be Ca2+ modulated indirectly through Ca2+/CaM-dependent protein kinases. But Ca2+/CaM has not yet been found to directly modulate any transcription factor or other DNA-binding protein. Transcription factors of the basic-helix-loop-helix (bHLH) group are important regulators in numerous systems. Here we report that binding of Ca(2+)-loaded CaM to the bHLH domains of several bHLH proteins directly inhibits their DNA binding. Other bHLH proteins are either less sensitive or resistant. Ca2+ ionophore selectively inhibits transcriptional activation by Ca2+/CaM-sensitive bHLH proteins in vivo, implying that Ca2+ can directly influence transcription through differential CaM inhibition of bHLH domains.

Animals↗