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Biomedical subjects

H Larsson

Publications and source records attributed to H Larsson.

At least 109 records · Page 6Linked to original sources

Should the exercise test (ET) be performed at discharge or one month later after an episode of unstable angina or non-Q-wave myocardial infarction?

The diagnostic and prognostic value of symptom limited exercise tests (ET) performed before discharge and after one month were compared in men admitted to hospital after an episode of unstable angina or a non-Q-wave myocardial infarction (MI). A 'Positive ET' was defined as either a maximal work load below 100 W or ST-depression greater than or equal to 0.1 mV in 1-2 leads below 130 W or ST-depression greater than or equal to 0.1 mV in more than 2 leads at any load at the ET. During follow-up, severe angina was the only indication for coronary angiography and revascularization. There were no significant differences in diagnostic findings between the tests--Positive ET in 47% and Negative ET in 25% at both ETs. The occurrence of MI or death and the need of revascularization were related to signs of ischemia at both ETs. There were no differences in prognostic value between the early and late tests regarding MI or death or future severe angina during the 11 months' follow-up after the one month ET. However, half (10%) of the overall event rate (20%) during the one year follow-up occurred during the first months. The risk of these events could be identified by the predischarge but, for obvious reasons, not by the one month ET. Therefore, the present study suggests that a symptom limited ET should be performed before discharge in men stabilized after an episode of unstable angina or non-Q-wave MI.

Angina, Unstable↗

Autonomic nervous system function in patients with primary obstructive sleep apnoea syndrome.

Ten patients with obstructive sleep apnoea syndrome cured by uvulopalatopharyngoplasty were compared to nine patients considered as surgical failures, using cardiovascular reflex tests--Valsalva manoeuvre, respiratory sinus arrhythmia, isometric handgrip and head-up tilt. Two patients had signs of moderate vagal dysfunction, but no case of definite autonomic nervous dysfunction was diagnosed. The overall results indicated sympathetic overreactivity, positively correlated to oxygen desaturation indices and remaining after successful treatment. Four patients did not exhibit bradycardia during sleep apnoea. Two of them had decreased respiratory sinus arrhythmia when awake, but two had normal values. This implies a difference in vagal responsiveness between the awake and sleeping states, or that other factors besides vagus function influence the bradycardia response to apnoea. The group mean values were all within normal limits. There was no significant difference between the two groups in any test. Autonomic nervous dysfunction therefore does not seem to contribute to surgical failure, nor to occur with increased incidence among patients with primary obstructive sleep apnoea syndrome.

Adult↗

Partial pronase digestion of rat gastric mucosa isolates cells undergoing replicative DNA synthesis.

A pronase digestion procedure for the isolation of gastric mucosal cells was evaluated for its usefulness in measuring unscheduled DNA synthesis (UDS). The method has been claimed to be suited for assessing the genotoxicity potential of compounds. Compounds were given orally to rats. After 13 h [3H]thymidine was injected and after another hour the animals were killed. The dissected stomachs were treated with pronase for 45 min and the incorporation of radioactivity into DNA was determined. Autoradiography was also performed both on the mucosa and on the isolated cell suspension. The cell suspensions were found to include cells undergoing normal replicative (S phase) DNA synthesis. Of all cells isolated, 4.8 +/- 0.6% consisted of S phase cells. The total amount of DNA recovered (corresponding to the number of cells isolated) was variable and ranged from 20 to 671 micrograms DNA, i.e. approximately 30-fold variation. Neither omeprazole (10, 30 and 80 mg/kg) nor ranitidine (215 mg/kg) had any effect on [3H]thymidine incorporation. The known carcinogen 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) increased incorporation. Refeeding of fasted animals increased incorporation of [3H]thymidine almost 4-fold, showing that animal feeding status influences incorporation. Hydroxyurea, the selective inhibitor of S phase DNA synthesis, inhibited [3H]thymidine incorporation in control and omeprazole-treated animals as well as that induced by MNNG by 92-98%. The results clearly show that the pronase digestion procedure used releases cells undergoing normal, replicative DNA synthesis and can therefore neither be used for measurements of UDS nor for the assessment of the genotoxic potential of drugs.

Administration, Oral↗

Studies on blood rheology in patients with primary pulmonary hypertension.

The rheologic properties of blood were studied in 6 patients with primary pulmonary hypertension (PPH) and compared with those of a control group of 10 healthy subjects. Blood viscosity was studied with a rotational viscometer and blood cell deformability with a filtrometer giving values for clogging particles (CP) and red cell transit time (RCTT). Blood viscosity at varying shear rates was found to be increased both at natural (p less than 0.025-0.005) and standardized hematocrit, 45% (p less than 0.05 at 40 s-1) in patients with PPH. Red cell deformability was reduced as indicated by a significant increase of RCTT (p less than 0.01). Increased values for hematocrit (p less than 0.001), hemoglobin concentration (p less than 0.001), and erythrocyte count (p less than 0.005) were found and decreased values for mean corpuscular hemoglobin concentration (MCHC) (p less than 0.025) and HDL cholesterol (p less than 0.005). Plasma viscosity, white cell deformability, white cell count, mean corpuscular volume (MCV), and plasma fibrinogen concentration did not significantly differ from the values found in the control group. It is concluded that patients with PPH have impaired blood rheology. The hemorheologic abnormalities in these patients may be of hemodynamic significance.

Adult↗

Long-time follow-up after UPPP for obstructive sleep apnea syndrome. Results of sleep apnea recordings and subjective evaluation 6 months and 2 years after surgery.

Fifty unselected consecutive patients with obstructive sleep apnea syndrome (OSAS) underwent uvulopalatopharyngoplasty (UPPP). The diagnosis was based on the patient's history and recording of respiration movements (Static Charge Sensitive Bed. SCSB) and oximetry, alone or combined with polysomnography. Renewed SCSB oximetry recordings were used to evaluate the success of the treatment. Six months postoperatively 40% of the patients were classified as non-responders, i.e. their oxygen desaturation indices (ODI) were reduced by less than 50% or were still above 20. The mean body mass index (BMI) was significantly higher in the non-responder group. A second recording with complete data was obtained in 45 patients after an average of 21 months. It was found that 9 patients who had been responders in the first postoperative recording had become non-responders. Only 18 of the patients with complete data could be verified as responders after 2 years. The patients who relapsed showed a significant increase in mean BMI between the first and second postoperative recordings compared to the patients who remained responders. There were no significant differences between responders and non-responders concerning age or preoperative severity of OSAS expressed as ODI, nadir SaO2 and percentage of obstructive periodic breathing. Of the non-responders, 47% in the first postoperative recording and 52% in the second reported complete recovery from excessive daytime sleepiness. This subjective improvement was not correlated to the objective results. The conclusions of this study are thus that one postoperative recording is not enough to estimate the outcome of UPPP and that statements of the patient's subjective recovery alone must not be used for this purpose.

Adult↗

Changes in the functional state of the erythrocyte membrane: significance for red cell filterability and blood viscosity.

Blood samples from nine healthy men were studied to determine the effect of ouabain and elevated serum calcium concentration on blood viscosity, measured by a rotational viscometer, and on red cell filterability by the St George's Filtrometer, giving values for clogging particles (CP) and red cell transit time (RCTT). Blood viscosity at a standardized haematocrit of 45% and red cell filterability was investigated in blood samples incubated for 1 h with Ringer's solution only (control), with ouabain (0.70 mmol/l) in plasma, or with serum calcium concentration increased by 3.0 mmol/l by addition of CaCl2. Incubation with ouabain significantly reduced erythrocyte K+ concentration and increased that of Na+. Ouabain caused a decrease in blood viscosity (p less than 0.05-0.005) compared to controls, although there was no decrease in red cell filterability parameters. When incubating with calcium, CP and RCTT increased significantly indicating 'stiffer' red cells, but there was no increase in blood viscosity. It is concluded that blood viscosity may be influenced by red cell factors not detected by CP or RCTT, which in turn appear to reflect red cell deformability with greater sensitivity and specificity than blood viscosity. It is concluded also that the functional state of the cell membrane may be of significance for the rheological properties of erythrocytes.

Adult↗

Treatment of severe colitis in Behçet's syndrome with thalidomide (CG-217).

A 35-year-old male patient, known in our department since 1979 on account of a severe and complete Behçet's syndrome, was treated with thalidomide (CG-217) as a final pharmacological measure to avoid colectomy during a severe attack of Behçet colitis. Prior to the administration of thalidomide, the patient had been treated for 7 weeks with full parenteral nutrition and high doses of steroids intravenously without a satisfactory effect on the colitis. Treatment with sulphasalazin was unsuccessful because of a decreasing number of platelets on this drug. After a few days on thalidomide, 300 mg given once daily at bedtime, the patient's stools were normalized and without reaction for blood, his oral ulcers and pleural effusion disappeared, and his steroid doses could be reduced. Gradually he was put on oral nutrition again, and his rectal mucosa became normalized. The dose of thalidomide was reduced to 200 mg, and then to 100 mg daily when the patient was discharged from hospital, less than 3 weeks after institution of the drug treatment. After 5 months as an out-patient his condition is still satisfactory and without symptoms of his former disease. Thalidomide has previously been reported to be of value in treatment of Behçet's syndrome, but to my knowledge never with such a dramatic effect on a severe colitis as reported in this case.

Adult↗

The role of gastric mucosal histamine in acid secretion and experimentally induced lesions in the rat.

The role played by histamine from enterochromaffin-like (ECL) cells and mast cells in gastric acid secretion and in the development of ethanol-induced gastric lesions was studied in the rat. This was done by examining the effects of inhibition of the histamine-producing enzyme histidine decarboxylase (HDC) with alpha-fluoromethylhistidine (alpha-FMH) and the effects of degranulation of the mucosal mast cells with dexamethasone. A single dose of alpha-FMH (50 mg/kg p.o.) inhibited the HDC activity by 94% but did not affect histamine levels in the gastric mucosa 2 h after dose. Repeated treatment resulted in an almost complete inhibition of HDC activity and in a reduction of histamine levels by 75%. Pentagastrin failed to stimulate acid secretion after 4 days treatment with alpha-FMH, whereas the acid response to histamine was unaffected in chronic gastric fistula rats. Ethanol failed to induce gastric lesions in rats pretreated for 4 days with dexamethasone whereas 4 days pretreatment with alpha-FMH did not influence ethanol-induced lesion formation. The present results show that histamine synthesis is required for pentagastrin-stimulated gastric acid secretion and that mucosal mast-cell histamine plays a role in the development of ethanol-induced gastric lesions.

Animals↗

Tritiated thymidine incorporation into DNA in rat gastric mucosal cells.

The parietal cell acid pump inhibitor, omeprazole, has undergone numerous genotoxicity studies, the conclusions of which have all been negative. A recent report by Burlinson described a method which is claimed to measure unscheduled DNA synthesis (UDS) in gastric mucosa, based on the incorporation of tritiated thymidine (3H-TdR) into DNA. In a subsequent letter it was concluded that omeprazole induces a significant increase in UDS, and it was suggested that 'for omeprazole, a genotoxic action cannot be discounted'. The Burlinson method of measuring UDS relies upon selective separation of non-dividing oxyntic mucosal surface cells from the stem cells located in the proliferative zone. These stem cells undergo normal cell division, subsequently migrate to the top and bottom of the gland, differentiating into the various specialized cells of the gland such as surface, parietal and chief cells. In the oxyntic mucosa the majority of stem cells are located at a level corresponding to one fifth of the mucosal thickness from the surface. The purpose of this study was to evaluate the Burlinson method, which depends upon the selective isolation of non-dividing surface cells by pronase digestion. The fraction used for measurement was investigated in terms of 3H-TdR uptake, the cellular distribution of 3H-TdR by autoradiography, the number of parietal cells and the sensitivity of 3H-TdR uptake for hydroxyurea (an inhibitor of normal, scheduled DNA synthesis). The results show that pronase digestion did not selectively isolate surface epithelial cells and that the digest contained both parietal cells (15 +/- 1.5%) and glandular fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A limited diagnostic investigation for obstructive sleep apnea syndrome. Oximetry and static charge sensitive bed.

A simplified sleep apnea investigation consisting of combined oximetry and respiration movement monitoring was compared with conventional polysomnography. These two types of recordings were performed simultaneously during one night in 77 patients with suspected obstructive sleep apnea syndrome (OSAS). A static charge sensitive bed (SCSB) was used in the simplified recording because it provides a comfortable and reliable means of recording respiration movements. Periods of obstructive apneas gave a diamond-shaped periodic respiration movement pattern in the SCSB, usually accompanied by repetitive oxygen desaturations. The average number of desaturations greater than or equal to 4 percent per sleeping hour was termed the oxygen desaturation index (ODI) and compared with the apnea index (AI). In the whole population they were well correlated (p less than 0.0001, R2 = 0.41), but in individual cases there were considerable discrepancies. Patients with periodic respiration movements less than 18 percent of total sleeping time and ODI less than 2 never had AI greater than or equal to 5, whereas patients with periodic respiration greater than 45 percent and ODI greater than 6 always had AI greater than or equal to 5. Fifty-one of the 77 patients fulfilled these criteria. A bradycardia response to apneas was absent in 29 percent of patients with AI greater than or equal to 5. A combination of respiration movement and oximetry recording thus seems to give sufficient information to confirm or negate a diagnosis of OSAS in a majority of patients with clinical symptoms. In borderline patients, further investigations should be performed.

Adolescent↗

In vivo 1H spectroscopy of the human brain at 1.5 tesla. Preliminary experience at a clinical installation.

In vivo localized water suppressed proton spectroscopy of human brain was carried out on 15 healthy volunteers and 2 patients suffering from a brain tumour and an infarction, respectively. The measurements were performed on a whole body MR system, operating at 1.5 tesla using the stimulated echo technique. Our preliminary results indicate that it is possible to detect a number of metabolites in the brain within a total measurement time of one hour. The dominant peaks in the spectra from healthy volunteers are N-acetyl aspartate, choline and creatine/phosphocreatine. The spectra obtained from the brain tumour and the infarct, respectively, differed very much from those obtained in healthy brain tissue. Our preliminary results indicate that localized proton spectroscopy may contribute to non-invasive brain tumour classification and possibly also to the differentiation between tumours and infarcts in clinically doubtful cases.

Adult↗

Omeprazole and ranitidine, antisecretagogues with different modes of action, are equally effective in causing hyperplasia of enterochromaffin-like cells in rat stomach.

Female rats were treated for 28 days with high doses of the gastric acid secretion inhibitors omeprazole and ranitidine. Omeprazole, which is long-acting, was given orally once daily. Ranitidine, which is short-acting, was given by continuous infusion (via osmotic minipumps, implanted subcutaneously). The aim was to produce a similar degree of acid inhibition with the two drugs. The inhibition of acid secretion over the day and night was more pronounced in the omeprazole-treated rats (maximal inhibition 100%, minimum 85%) than in those receiving ranitidine (mean 70%). In both groups, there was a great increase in plasma gastrin, somewhat greater after omeprazole than after ranitidine. The gastrin concentration in the antrum was almost doubled by both treatments and there was a moderate increase in the number of antral gastrin cells in the omeprazole-treated rats. The number of enterochromaffin-like (ECL) cells (per visual field) increased in the oxyntic mucosa to the same extent (greater than 100%) in the ranitidine- and omeprazole-treated rats. Apart from the gastrin cells in the antrum and the ECL cells in the corpus no other gastric endocrine cell type seemed to respond to treatments with antisecretagogues. We conclude that, regardless of the type of antisecretagogue used, effective and long-term suppression of gastric acid secretion results in sustained hypergastrinemia and increased number of ECL cells. Conceivably therefore, the ECL cell hyperplasia reflects the trophic effect of gastrin.

Animals↗

Gamma-interferon-mediated down-regulation of electrolyte secretion by intestinal epithelial cells: a local immune mechanism?

Active chloride (Cl-) secretion by intestinal crypt enterocytes is the central pathophysiological disturbance in most cases of acute diarrhoea. We examined monolayers of the human intestinal cell line T84 mounted in Ussing chambers to see whether the T-cell lymphokine gamma interferon (IFN-gamma) might affect the Cl- secretory properties of these cells, which morphologically and functionally resemble native crypt enterocytes. Pretreatment of T84 cell layers with IFN-gamma for 24 h (but not for 3 h) markedly decreased the Cl- secretory response to vaso-active intestinal polypeptide (VIP) and to cholera toxin and carbachol without appreciably affecting the overall morphology, electrical resistance, or cyclic AMP response of the T84 cell monolayer. The IFN-gamma treatment, however, did induce subtle changes in the T84 cell membrane protein composition which might have affected ion channels regulating Cl- secretion. Our results may indicate a possible novel 'cell-mediated' immune mechanism through which activated gut T cells could modulate the extent of intestinal electrolyte and fluid secretion in, for example, enteric infections.

Carbachol↗

Omeprazole and cimetidine versus pentagastrin in canine ex vivo gastric chamber.

The effects of acid inhibitory doses of omeprazole were compared with equieffective doses of cimetidine in the canine ex vivo stomach model (n = 30). Systemic blood pressure, temperature, stomach fluid and ion fluxes, potential difference, blood flow rates, and arterial and venous blood gases were monitored during each of nine 30-min periods. Two resting periods preceded seven periods of pentagastrin stimulation. During the last four of these, the drug effect was recorded (cimetidine 1.2 or 4.8 mumol.kg-1.h-1; omeprazole 0.3, 0.6, or 1.2 mumol/kg). Omeprazole (1.2 mumol/kg) produced 100% inhibition of stimulated acid efflux, no significant decrease in total gastric blood flow (venous outflow), 90% return of potential difference (PD) toward resting values, and a 55% reduction in stimulated oxygen consumption. Omeprazole also showed a dose-dependent K+ efflux at the two lower doses. Cimetidine (4.8 mumol.kg-1.h-1) given during pentagastrin stimulation showed a 70% decrease in total gastric blood flow, a 40% return of PD toward resting, and a 77% reduction in stimulated oxygen consumption. Neither drug showed significant changes in mucosal blood flow from resting values, thus supporting the principle that changes in gastric acid secretion and changes in blood flow are not necessarily correlated.

Animals↗

Correlation between inhibition of gastric acid secretion, plasma gastrin, and oxyntic mucosal histidine decarboxylase activity in the rat.

Female rats were treated for 1 week with ranitidine (125-1700 mumol/kg.day, given subcutaneously by means of osmotic minipumps), the proton pump inhibitor omeprazole (10-400 mumol/kg.day orally), or vehicle. Acid secretion, plasma gastrin levels, and oxyntic mucosal histidine decarboxylase (HDC) activity were determined. Both compounds dose-dependently inhibited maximally stimulated gastric acid secretion and caused a parallel increase in plasma gastrin levels. There was very good correlation between plasma gastrin levels and HDC activity for both compounds, although higher oxyntic mucosal HDC activity was found during ranitidine treatment. The higher HDC activity in the ranitidine-treated rats indicated the presence of a histamine H2-receptor on the ECL cells. It is concluded that, regardless of what kind of antisecretory agent is used, a dose-dependent inhibition of gastric acid secretion results in a parallel increase in plasma levels of gastrin, and as a consequence the HDC activity in the rat oxyntic mucosa is increased.

Animals↗

Slow and rapid electrical pulses in the caval vein at pain-evoked leg contraction in the rat.

Previous in vivo experiments in rats have shown that pulsed nerve stimulations of 20-50 mV require "external" electrical communication over vessels. This indicates that potential differences also should occur in associated vessels, at physiologic muscle contractions. Pinching toes of the hind leg of anaesthetized rats in the present study caused the animals to spontaneously pull the leg. This resulted in electric potential differences over two intracaval electrodes, as well as high frequency spikes. The slow potential pulses and high frequency spikes could be recorded dominantly in the vena cava compared with the extravascular tissue fluid. The electrical prerequisites and the previous experiments support the view that the vascular-interstitial fluid represents an "external" low resistant communication route of a closed circuit over the nerve cell bodies, the axons and the muscle fibers. A closed electrical circuit evidently increases our possibilities for explaining various structural and chemical events of the synaptic membranes.

Animals↗

Studies on blood viscosity during the menstrual cycle and in the postmenopausal period in healthy women.

Blood viscosity was measured in 14 healthy, menstruating women, aged 17-51 years and in 10 healthy, postmenopausal women, aged 55-64 years. The fertile women were studied once a week during a normal menstrual cycle and the postmenopausal women twice with an interval of 2 weeks. Blood viscosity was measured at natural hematocrit as well as at hematocrit 45%. In the postmenopausal women no changes in blood viscosity were found. In the fertile women, blood viscosity at hematocrit 45% was lowest at the start of the menstrual bleeding and increased to a peak at day 7 (p less than 0.01), with a similar pattern when measured at natural hematocrit. Plasma viscosity also had its lowest value at the onset of menstrual bleeding, increasing to a maximum at day 21. Changes in plasma triglycerides, but not in fibrinogen or cholesterol, seemed to contribute to this increase. Plasma factors only partly explained the variations in blood viscosity, and changes in red cell properties were also found to be of importance. The clinical significance of these rheological changes remains to be established, but at least theoretically there may be an increased risk for thromboembolism, e.g. at surgery, during days 5-15 of the cycle. In studies on blood flow and rheological conditions in fertile women, it seems advisable to standardize for time in the menstrual cycle.

Adult↗