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Biomedical subjects

S Halvorsen

Publications and source records attributed to S Halvorsen.

At least 19 recordsLinked to original sources

Physiology of erythropoietin during mammalian development.

UNLABELLED: Growth is a fundamental process of mammalian development. Several observations regarding regulation of erythropoiesis during growth are not easily explained by the hypoxia-erythropoietin (Epo) concept. This review focuses primarily on this aspect of the physiology of Epo. The question is raised of whether this regulation during growth is based on the hypoxia-Epo mechanism alone, or whether Epo acts in concert with general growth-promoting factors, particularly growth hormone (GH) and the insulin-like growth factors (IGF-I and -II). Supporting the latter hypothesis is the observation that the Epo and GH/IGF systems are activated by hypoxia and share similar receptors and pathways. Recent studies indicate that human fetal and infant growth is stimulated by GH, IGF-I and IGF-II. Epo, GH and IGFs are expressed early in fetal life. Although the rate of erythropoiesis in the fetus is high, serum Epo levels are low. The Epo response to hypoxia in the fetus and neonate is reduced compared with adults. Following delivery the Epo levels vary between species, probably related to the oxygen transport capacity of the hemoglobin (Hb) mass. IGF-I levels are low in the fetus and increase slowly following birth, except in preterm infants in whom the levels decline. In all mammals Hb declines following birth, giving rise to "early anemia". Except in the human, Epo levels increase proportionally with the fall in Hb, but there is a discrepancy between the curves for serum immunoreactive Epo (siEpo) and for erythropoiesis stimulating factors (ESF): the latter include other stimulatory factors in addition to Epo. Hypertransfusion of mice in the period of "early anemia" suppresses siEpo, but not ESF and erythropoiesis, as it does in adult mice. GH and IGF-I have direct effects on erythropoiesis in vitro and act particularly at the later stages of red cell differentiation. IGF-I acts synergistically with Epo, and its effects are most marked when Epo levels are low. Human recombinant (rhu) IGF-I stimulates erythropoiesis in neonatal rats, but not in newborn mice and lambs. In adult mice, in hypophysectomized rats and in mice with end-stage renal failure, however, a stimulatory effect of this growth factor was found on red cell production. RhuGH stimulates erythropoiesis in GH-deficient short children. CONCLUSION: Fetal and early postnatal erythropoiesis are dependent on factors in addition to Epo. The likely candidates are GH and IGF-I. The in vitro stimulating effects of these factors on erythropoiesis are convincing, but more data are needed on the in vivo effects.

Anemia↗

[Diagnoses and increased levels of troponin T among discharged patients].

BACKGROUND: New criteria for diagnosing acute myocardial infarction, in which the cardiac troponin T or I plays a central role, have recently been proposed. We wanted to estimate what an application of these criteria would have meant for the diagnoses given patients discharged from our hospital in 2000. MATERIAL AND METHODS: From the hospital data bases, 3,461 in-hospital patients were identified in whom troponin T levels in blood had been determined. Maximal troponin T levels and diagnoses on discharge were recorded. Only one diagnosis was used for each patient. The diagnoses were selected in a priority order favouring those diseases that are known most often to cause increased troponin T levels, starting with the codes for acute myocardial infarction. RESULTS: By applying the new criteria, the number of patients with myocardial infarction was estimated to increase 17%, 33% and 61% depending on the decision level for troponin T used, 0.20, 0.10 or 0.03 microgram/l, respectively. Congestive heart failure and atrial fibrillation were the most frequent cardiac diagnoses in patients with increased troponin T level without evidence of acute coronary syndromes. Other, non-cardiac diagnoses included renal diseases, sepsis, and acute lung diseases. INTERPRETATION: Application of the new diagnostic criteria will markedly increase the recorded incidence of acute myocardial infarction. The number of positive troponin T values in patients without acute coronary syndromes will increase progressively by lowering the diagnostic decision level of troponin T.

Atrial Fibrillation↗

Left ventricular function and infarct size 20 months after primary angioplasty for acute myocardial infarction.

OBJECTIVE: To study changes in left ventricular function and infarct size during long-term follow-up after acute myocardial infarction treated with primary angioplasty. DESIGN: From 1996 to 1998, 100 consecutive patients were treated with primary angioplasty for acute ST-elevation myocardial infarction. Angioplasty was successful in 95% of the patients. Global left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography before discharge, after 6 weeks and after a mean follow-up time of 20 months. Infarct size was assessed by technetium 99m-tetrofosmin myocardial perfusion tomography (SPECT) at rest, performed at the same time intervals. RESULTS: Mean LVEF was 56% at discharge, 55% after 6 weeks and 57% after 20 months of follow-up. No significant improvement in LVEF was observed. Only 8% of the patients at follow-up had LVEF lower than 40%. After 1 week, a mean perfusion defect of 19% was measured by SPECT. After 6 weeks and 20 months of follow-up, the mean perfusion defects were reduced to 14% (p < 0.001) and 15%, respectively. CONCLUSION: Left ventricular function was well preserved with a mean LVEF of 57% 20 months after primary angioplasty for acute myocardial infarction. No significant change in LVEF was observed from 1 week after angioplasty to follow-up. Infarct sizes as assessed by SPECT imaging with tetrofosmin were reduced from 1 to 6 weeks, but did not change further during long-term follow-up. The reduction in the perfusion defects over time was probably due to gradual relief of stunning.

Angioplasty, Balloon, Coronary↗

Discrepancy between fibrinogen concentrations determined by clotting rate and clottability assays during the acute-phase reaction.

Assays based on clotting rate are commonly used as a routine method for determining the fibrinogen concentration in plasma. However, little is known about the influence of the acute-phase reaction on this assay. In order to disclose discrepancies between the fibrinogen concentrations obtained by a clotting rate assay (as described by Clauss) and a reference assay for total clottable protein (according to Jacobsson), we compared the fibrinogen concentrations determined by these two methods in plasma-samples collected preoperatively and on postoperative days 1, 3, and 5 in patients undergoing major elective surgery. The HMW (High Molecular Weight)-, LMW- and LMW'-fibrinogen fractions of the patient samples were also determined. In preoperative samples, good agreement between the two assays was found. In samples collected on postoperative days 1 and 3, the fibrinogen concentrations measured with the clotting rate assay were significantly higher than the concentrations measured with the total clottable protein assay (p=0.015 on both days). SDS-gel electrophoresis showed an increase in the median HMW-fraction from 69.7% (range 64.3-70.4) in preoperative samples to 85.8% (80.7-87.6) in samples drawn on day 3. The difference between fibrinogen concentrations obtained by the two methods was significantly correlated to the HMW-fraction of the samples. We conclude that during an acute-phase reaction, fibrinogen concentrations obtained by a clotting rate assay (as described by Clauss) are significantly higher than those measured by a total clottable protein assay (according to Jacobsson). The difference between the two methods correlates well with the relative HMW-fraction, indicating that the increase in HMW-fibrinogen is the main contributor to the observed discrepancy.

Acute-Phase Reaction↗

Fulminant meningococcal septicemia: dissociation between plasma thrombopoietin levels and platelet counts.

Thrombopoietin (TPO), interleukin (IL)-6, and platelets were measured serially in 9 patients with fulminant meningococcal septicemia and consumption coagulopathy. The results were compared with those of patients with meningococcal meningitis and mild meningococcemia (n=10) and with those of healthy control subjects (n=19). TPO levels in control subjects were below the detection limit (<63 pg/mL). In patients with fulminant meningococcal septicemia, the median TPO level on admission was 193 pg/mL (range, 133-401 pg/mL), and the level peaked within 3-7 days (median, 488 pg/mL; range, 239-1334 pg/mL). Platelet counts remained low, despite the elevated TPO levels. In patients with meningitis or meningococcemia, the median TPO level on admission was 112 pg/mL (range, <63-695 pg/mL), and the TPO level was not detectable within 48 h. Platelet counts for these patients remained within normal limits. Maximum IL-6 levels in patients with septicemia were observed on admission (median, 5317 pg/mL; range, 188-651,000 pg/mL) and increased earlier than TPO levels. In patients with fulminant septicemia, TPO level increases significantly whereas the level of circulating platelets does not.

Adult↗

[Fibrinogen as a cardiovascular risk factor--marker or causal factor?].

Fibrinogen is an important determinant of blood haemostasis and viscosity. Several prospective studies have demonstrated plasma fibrinogen concentration to be an important predictor of cardiovascular disease, both in healthy subjects and in patients with coronary disease. Subjects with high plasma fibrinogen concentrations have a two to four-fold increased risk of developing cardiovascular disease compared to those with low fibrinogen. Whether fibrinogen is a causative factor for atherosclerosis or a marker of the inflammatory process of atherosclerosis remains to be proven.

Adult↗

Severe liver failure in exertional heat stroke.

Exertional heat stroke usually occurs in warm climates. Increased serum levels of liver enzymes is a common finding in this condition, whereas liver failure is a more rare event that carries a poor prognosis. Liver transplantation has been recommended as treatment in cases of severe liver failure, but no long-term survival after this procedure in exertional heat stroke has been described. We report the case of a 31-year-old man who had a heat stroke after running 5 km at 21 degrees C. He developed severe liver damage, with serum alanine aminotransferase (ALAT) activities increasing to 16,410 U/l (reference values, 10-50 U/l) after 48 h, concomitantly with a pronounced coagulation disturbance, with Normotest (NT) decreasing to 12% (international normalized ratio (INR) = 4.2) (reference values, 70%-130% for NT and 0.8-1.2 for INR). A liver biopsy on the 5th day after the incident showed extensive liver cell necrosis. The patient was referred to be considered for liver transplantation but recovered completely on conservative treatment. We conclude that exertional heat stroke is a diagnostic possibility also in temperate climates and that severe liver failure may ensue. The liver injury is reversible, and the indications for liver transplantation in this situation have not been clarified.

Adult↗

Prosthetic heart valve thrombosis during dicloxacillin therapy.

A 76-year-old woman receiving warfarin after aortic valve replacement experienced prosthetic valve thrombosis during dicloxacillin therapy. Successful thrombolysis was achieved with tissue plasminogen activator. The international normalized ratio (INR) on admission was reduced to 1.4 and an increased warfarin dosage was required for three weeks following discontinuation of dicloxacillin treatment in order to maintain therapeutic INRs. Careful monitoring of INRs and titration of the warfarin dosage is recommended when dicloxacillin is prescribed to patients receiving warfarin.

Aged↗

[Bilateral pulmonary infiltrations in patients admitted to an intensive care unit].

Diffuse pulmonary infiltrates are commonly found in hypoxic respiratory failure. We have reviewed 16 patients admitted to our medical intensive care unit over a period of 21 months, of whom seven died in hospital. Only patients requiring ventilatory support (CPAP or mechanical ventilation) for respiratory failure due to non-cardiogenic causes were included. All patients met the criteria for the diagnosis of ARDS. Three patients suffered from Wegener's granulomatosis, three from Pneumocystis carinii pneumonia, three from bacterial pneumonia, and two from pneumonia. Staphylococcal septicemia, SLE, sarcoidosis, cancer-associated hemolytic-uremic syndrome and ARDS of unknown etiology were each found in one patient. We discuss diagnosis and treatment of such patients on the basis of our experience.

Adult↗

Bioaccumulation of mercury in pelagic freshwater food webs.

Current paradigms regarding the bioaccumulation of mercury are rooted in observations that monomethyl mercury (meHg) biomagnifies along pelagic food chains. However, mechanisms regulating the formation of meHg, its initial incorporation at the base of pelagic food chains, and its subsequent trophic transfer remain controversial. Here we use field data from 15 northern Wisconsin lakes, equilibrium aqueous speciation modeling, and statistical modeling to revisit several hypotheses about the uptake, distribution, and fate of inorganic Hg (HgII) and meHg in aquatic biota. Our field data comprise determinations of total Hg (HgT) and meHg in surface waters, sediments, microseston, zooplankton, and small fish in each of the study lakes. For these lake waters, strong positive correlations between DOC and aqueous concentrations of mercury along with negative correlations between DOC and the seston-water partitioning of mercury indicate that organic ligands bind HgII and meHg strongly enough to dominate their apparent aqueous speciation. In the microseston, zooplankton and fish, meHg concentrations and bioaccumulation factors (BAFs) increased with increasing trophic level while biotic concentrations of HgII decreased--indicating that meHg was indeed the biomagnified species of mercury. For all trophic levels, meHg concentrations varied positively with the calculated aqueous concentration of meHg+ (free ion), especially when coupled with pH, or meHgOH (hydroxide) species but not with meHgCl0, the neutral chloride complex. These findings suggest that: (1) the passive uptake of meHg does not control bioaccumulation at the base of aquatic food webs in nature (i.e. phyto- and bacterioplankton); (2) correlation with pH and DOC largely reflect the supply and bioavailability of meHg to lower trophic levels; and (3) meHg concentrations at higher trophic levels reflect uptake at low trophic levels and other factors, such as diet and growth. Low concentrations of meHg in surficial sediments indicate that the fates of biotic HgII and meHg are different. Most biotic meHg is demethylated rather than buried in lake sediments.

Animals↗

Ethanol treatment in ethylene glycol poisoned patients.

Two otherwise healthy 16-y-old female patients were treated with sodium bicarbonate and ethanol after the ingestion of unknown quantities of ethylene glycol. Patient 2 was admitted twice for ethylene glycol poisoning in unrelated events. In patient 1, the maximum levels of ethylene glycol and glycolate in plasma were 14 mmol/L (0.9 g/L) and 8.2 mmol/L (0.5 g/L), respectively. In patient 2, the maximum levels of ethylene glycol in plasma during the 2 admissions were 18 mmol/L (1.1 g/L) and 45 mmol (2.8 g/L), respectively. In patient 1, a blood ethanol concentration between 130-140 mg/dL (28-30 mmol/L) was reached 3 h after the start of ethanol administration and maintained for 22 h. During this period, ethylene glycol metabolism was effectively inhibited as indicated by S-glycolate levels and that 88% of the eliminated ethylene glycol was accounted for in the urine. This suggests that ethanol therapy alone may be sufficient for patients admitted early with low serum ethylene glycol concentrations. During the admissions of patient 2, the blood ethanol concentrations were presumed to effectively inhibit ethylene glycol metabolism as judged from normal acid/base parameters. However, during the second admission the bolus infusion of ethanol was associated with respiratory arrest. During both admissions for patient 2, hemodialysis constituted the major route of ethylene glycol elimination.

Adolescent↗

Effect of low and moderate doses of recombinant human erythropoietin on the haematological response in premature infants on a high protein and iron intake.

UNLABELLED: There is no consensus regarding protein intake and the doses of recombinant human erythropoietin (r-HuEpo) and iron in the treatment of anaemia of prematurity (AOP). This open, randomized study has compared the effectiveness of 50 IU r-HuEpo/kg with that of 100 IU/kg, both given subcutaneously thrice weekly. In addition, two different protein supplements have been compared; lyophilized human milk protein and a commercial cow's milk product. Total protein intake was 3 g/kg per day. Daily iron dose was 18-36 mg. "Healthy" preterm infants (n = 32, birth weight: 800-1400 g, gestational age < or = 31 weeks) were studied from age 3 to 8 weeks. The two protein regimens yielded no differences in body growth, reticulocyte count or Hb concentration. In both r-HuEpo dose groups increased number of reticulocytes followed start of treatment; higher levels were, however, found in the group receiving 100 IU/kg. Mean Hb concentration plateaued at 12 g/dl for infants receiving 100 IU/kg, at 11 g/dl in the 50 IU/kg group. Even though serum levels of ferritin and transferrin saturation indicated no iron deficiency, soluble transferrin receptor increased in both groups, more rapidly and to higher levels in the 100 IU/kg group. In addition, the number of infants having more than 8% hypochromic red cells increased in both groups. CONCLUSIONS: Commercial cow's milk protein added to human milk was as good as human milk protein supplementation in supporting growth and erythropoiesis. Fifty IU/kg r-HuEpo thrice weekly during AOP stimulated erythropoiesis significantly, but less so than 100 IU/kg. Even when using high oral doses of iron to preterms receiving r-HuEpo, our data suggested a certain degree of iron deficient erythropoiesis.

Anemia, Neonatal↗