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Biomedical subjects

F Knudsen

Publications and source records attributed to F Knudsen.

At least 73 records · Page 4Linked to original sources

Three cases of factor I deficiency: the effect of treatment with plasma.

Three patients with congenital factor I deficiency associated with different clinical manifestations are described. Case 1 had one single episode of meningococcal disease, case 2 experienced four episodes of meningococcal disease and several other severe infections, whereas case 3, without known predisposition for infections, died from a subacute immune-complex mediated syndrome, resembling polyarteritis nodosa. Family studies in cases 1 and 2 revealed healthy individuals with factor I concentrations below the lower reference limit, indicating heterozygous carriers. The pedigree analyses were consistent with autosomal codominant inheritance. The estimated minimal frequency of the deficient gene was 0.002. Pedigree analysis was not performed in case 3 but the father and sister was found to be probable heterozygous carriers. Cases 2 and 3 were treated with infusions of freshly frozen plasma (FFP) (40 and 27 ml/kg bodyweight) during acute illness and the immunochemical complement profile was monitored. Following plasma infusion factor I was cleared from the circulation with a half-life of 29-45 h. The plasma infusions induced generation of C3d and C4d, increase in native factor B and C3 concentrations and disappearance of Ba split products. Native C3 and C4 increased to normal concentrations and remained normal till 16 days after the plasma infusions, whereas native factor B decreased to preinfusion levels 8 days after plasma infusion. It is concluded, that congenital factor I deficiency can present with different clinical manifestations and may be more prevalent than hitherto anticipated. Furthermore, infusion of blood products containing small amounts of functional factor I can partly normalize the complement profile, with a more prolonged effect on C3 and C4 than on factor B metabolism.

ABO Blood-Group System↗

Relationship between urinary prostaglandin E2 and F2 alpha excretion and plasma arginine vasopressin during renal concentrating and diluting tests in renal transplant recipients.

Urinary excretion of prostaglandin E2 (PGE2 and F2 alpha (PGF2 alpha) and plasma concentration of arginine vasopressin (AVP) were determined during urinary concentrating and diluting tests in renal transplant recipients and control subjects. During the concentrating test PGE2 and PGF2 alpha remained unchanged in the renal transplant recipients, whereas both PGE2 and PGF2 alpha were significantly reduced in the control subjects. During the diluting test PGE2 and PGF2 alpha increased in both groups but, contrary to PGF2 alpha, PGE2 was significantly higher in all periods in the transplant recipients compared to the controls. However, the prostaglandin excretion rates per kidney were significantly higher in the renal transplant recipients than control subjects, for all periods during both the concentrating and the diluting test. Arginine vasopressin was significantly higher in renal transplant recipients than control subjects during basal conditions, increased to a significantly higher level in the transplant recipients after thirst, but was reduced to the same levels in the two groups during the diluting test. It is concluded that the increased excretion of prostaglandins in renal transplant recipients may be a compensatory phenomenon representing an adaptation to a reduced renal mass in order to maintain adequate renal water excretion. Although a direct relationship between the prostaglandin excretions of PGE2 and PGF2 alpha and AVP does not seem to exist, it is possible that the higher prostaglandin excretion in the renal transplant recipients may be a counterbalancing mechanism to the higher AVP level, which most likely is secondary to a decreased responsiveness to vasopressin of the renal collecting ducts in the transplanted kidney.

Adult↗

Exaggerated natriuretic response to isotonic volume expansion in hypertensive renal transplant recipients: evaluation of proximal and distal tubular reabsorption by simultaneous determination of renal plasma clearance of lithium and 51Cr-EDTA.

In fourteen hypertensive and fourteen normotensive renal transplant recipients, and in a group of thirteen healthy controls, changes in natriuresis, glomerular filtration rate (GFR), and tubular reabsorption of sodium were determined in relation to intravenous infusion of 2 mmol isotonic sodium chloride per kg body weight. An exaggerated natriuresis was demonstrated in the hypertensive renal transplant recipients. This new finding indicates that the augmented natriuresis following plasma volume expansion, which is a characteristic finding in subjects with arterial hypertension, is not mediated by the renal nerves. Investigation of the tubular reabsorption rates of sodium by simultaneous determination of the renal clearance of 51Cr-EDTA and lithium showed that in the hypertensives the changes in tubular handling of sodium were different from those registered in the normotensive subjects. The increased sodium excretion in the hypertensive renal transplant recipients was caused by an increased output of sodium from the proximal tubules which was not fully compensated for by an increased distal reabsorption. Whether this increased delivery of sodium to the distal segments was caused by changes in GFR or in the proximal tubular reabsorption of sodium could not be clarified in the present study and warrants further investigations.

Absorption↗

In vitro effect of etomidate and thiopental on granulocyte migration.

An increased mortality has been reported during long-term etomidate infusion. Inhibition of adrenal corticosteroid synthesis has been incriminated - but other factors related to host defence cannot be excluded. Using an under-agarose assay, we investigated the effect of etomidate on in vitro granulocyte migration. Unlike thiopental (50 micrograms/ml), etomidate (4-32 micrograms/ml) did not affect either spontaneous or directed migration. Impaired granulocyte migration is an unlikely cause of morbidity during long-term etomidate infusion.

Cell Movement↗

The ability of uremic serum to induce neutrophil chemotaxis in relation to hemodialysis.

The ability of serum to attract normal neutrophil granulocytes was investigated in 11 uremic patients before and after hemodialysis using a modified assay system for granulocyte migration under agarose. The chemotactic responses towards serum from the uremic patients were significantly decreased (p less than 0.01) prior to hemodialysis compared to control serum from a healthy individual. Hemodialysis acutely normalized the depressed chemotactic responses. It is concluded that hemodialysis improves the ability of uremic serum to attract neutrophils, and it is suggested that this improvement might be due to removal of granulocyte inhibitory factors from the sera.

Chemotaxis, Leukocyte↗

Defective protein C in uraemia.

Protein C activity and antigen levels were determined in 10 haemodialysis patients and 10 healthy controls matched for age and sex. Markedly decreased protein C activity was found whereas protein C antigen level was normal in uraemics. This finding, together with our recent observation that plasma protein C activity is partly normalised during haemodialysis, lead us to suggest the presence of one or more inhibitors of protein C activity in plasma from patients with uraemia.

Adult↗

Assessment of complement activation during extracorporeal circulation by measurement of complement split C3d.

The present report summarizes our previous experience with the effect of various dialyzer membranes on leukocyte count, plasma C3d and C5a/C5ades-Arg, and total hemolytic complement. A relationship between the formation of C5a/C5ades-Arg within the dialyzer and hemodialysis leukopenia was demonstrated by comparing different membranes. Arterial plasma C3d was found to be a useful cumulative marker of complement activation during hemodialysis. C3d was shown to be generated in the artificial kidney with kinetics resembling the formation of C5a/C5ades-Arg. Total hemolytic complement transitorily decreased with all membranes, but did not reflect dialyzer biocompatibility. It is suggested that determination of complement-split C3d outdates previous more elaborate estimates of complement activation during hemodialysis.

Complement Activation↗

Angiotensinogen is an acute-phase protein in man.

Accumulating information concerning the structure of angiotensinogen suggests a resemblance of this component of the renin-angiotensin system to the acute-phase protein alpha 1-antitrypsin. Compared to a group of age- and sex-matched controls without signs of infection, markedly elevated levels of angiotensinogen (increase in median value: 70%), alpha 1-antitrypsin (102%), caeruloplasmin (76%), haptoglobin (261%), and orosomucoid (162%) were found in plasma from 14 patients with acute inflammatory disease. This finding indicates that angiotensinogen should be included in the list of acute-phase proteins in man, and raises the question whether angiotensinogen is involved in the regulation of the renin-angiotensin system during inflammation and tissue injury.

Acute Disease↗

Biocompatibility of a new polycarbonate dialysis membrane.

The present report summarizes our experience with a new polycarbonate (PC)-based dialysis membrane (Gambro Lundia PRO-5) compared with a cuprophan (CP)-based membrane (Gambro Lundia 10-5N). Platelet count decreased during dialysis with CP, but was unchanged with PC membranes. Platelet injury, reflected by decreased platelet aggregation and increase in plasma beta-thromboglobulin, occurred equally with both membranes. Complement activation (C3d and C5a), leukopenia and release of granulocyte-derived elastase was more extensive with CP than with PC membranes. The new membrane represents an improvement of biocompatibility with respect to the complement-leukocyte system, whereas the effect on platelets resembles the injury caused by CP membranes.

Adenosine Diphosphate↗

Effect of exercise on plasma concentrations of arginine vasopressin, angiotensin II and aldosterone in hypertensive and normotensive renal transplant recipients.

Plasma concentrations of angiotensin II (A II), aldosterone (Aldo) and arginine vasopressin (AVP), and serum osmolality (Sosm) were determined before and after gradually increasing exercise loads on a bicycle ergometer in 10 hypertensive (group I) and 10 normotensive renal transplant recipients (group II), and in 15 healthy control subjects (group III). Working capacity was reduced in groups I and II. The A II, Aldo, AVP, Sosm increased in all groups after exercise. The A II was higher in group I than II and the percentage changes were significantly lower in groups I and II than in group III. There were no significant differences in Aldo between the groups either before or after exercise. The AVP was the same in groups I and II, and AVP in these groups was higher than in group III. The Sosm and AVP were significantly correlated in all groups. Neither A II, Aldo nor AVP were significantly correlated to systolic blood pressure (BP). Alterations in AVP, but not in A II or Aldo, were correlated to the degree of exercise load. It can be concluded that the renin-angiotensin-aldosterone system and the osmoregulatory system are stimulated during exercise in renal transplant recipients. The A II is elevated in post-renal transplant hypertension, but the responsiveness is reduced in both hypertensive and normotensive recipients. The alterations in AVP are probably secondary to changes in Sosm, and the higher AVP levels in recipients could be due to a decreased responsiveness of the renal tubules to AVP. Our findings are in good agreement with the hypothesis that hypertension after renal transplantation is angiotensin II-dependent.

Adult↗

Post-renal-transplant hypertension. Urine volume, free water clearance and plasma concentrations of arginine vasopressin, angiotensin II and aldosterone before and after oral water loading in hypertensive and normotensive renal transplant recipients.

Urine volume (V), free water clearance (CH2O) and plasma concentrations of arginine vasopressin (AVP), angiotensin II (A II) and aldosterone (Aldo) were determined before and three times during the first 5 h after an oral water load of 20 ml/kg body wt in 19 patients with post-renal-transplant hypertension (group I), in 13 normotensive renal transplant recipients (group II) and in 20 control subjects (group III). Both V and CH2O increased significantly in all groups, but considerably less in groups I and II than in group III. When CH2O was related to glomerular filtration rate no differences existed between patients and control subjects. Basal AVP was the same in groups I (3.3 pmol/l, median) and II (3.0 pmol/l), but significantly (p less than 0.01) higher than in group III (1.9 pmol/l). Basal A II was significantly (p less than 0.01) elevated in group I (18 pmol/l) when compared to both groups II (10 pmol/l) and III (11 pmol/l), and the level was independent of the presence of native kidneys. Basal Aldo was the same in all groups. During loading, AVP was reduced in all groups, A II was almost unchanged, and Aldo was increased in groups I and II and reduced in group III depending on alterations in serum potassium. Thus urinary diluting ability is reduced in renal transplant recipients due to a reduced glomerular filtration rate. The enhanced A II in hypertensive renal transplant recipients gives further evidence for the point of view that hypertension is angiotensin-dependent in most of these patients.

Adult↗

Urinary excretion of albumin and beta-2-microglobulin in hypertensive and normotensive renal transplant recipients during urinary diluting and concentrating tests.

Urinary excretion of albumin and beta-2-microglobulin was measured in nine hypertensive and nine normotensive renal transplant recipients and 10 healthy control subjects before and after an oral water load of 20 ml (kg body weight)-1 (study 1) and in eight hypertensive and 11 normotensive renal transplant recipients and 11 healthy control subjects during 24-h water deprivation (study 2). In both studies 1 and 2 urinary albumin excretion was significantly higher (p less than 0.01) in the hypertensive renal transplant recipients that in the normotensive patients and the control subjects (levels before loading; hypertensives: 23.9 micrograms/min (median), range 7.5-58.7; normotensives: 3.4 micrograms/min, range 1.0-49.3; controls: 2.9 micrograms/min, range 1.3-10.3). Urinary albumin excretion was significantly positive correlated to both systolic, diastolic and mean blood pressure (for mean blood pressure: rho = 0.625, n = 18, p less than 0.01) in transplanted patients. Albumin excretion tended to increase after water loading and to decrease during water deprivation in all groups. Beta-2-microglobulin excretion was approximately the same in all groups in both studies 1 and 2 and was not correlated to blood pressure. During a follow-up period of at least 18 months, none of the renal transplant recipients developed signs of chronic graft failure. Increased urinary albumin excretion in hypertensive renal transplant recipients thus appears to be caused by increased glomerular permeability that may be due to glomerular damage induced by arterial hypertension corresponding to the findings in essential hypertension.

Adult↗

Profound accidental hypothermia treated with peritoneal dialysis.

In five women and two men, profound accidental hypothermia--core temperature on admission 24-28 degrees C--was treated with peritoneal dialysis. In two cases 16 gauge intravenous catheters were used, without difficulty, for the dialysis. Six of the seven patients were intoxicated by hypnotics, and four also by alcohol. Two patients died--one 38 hours after admission due to acute myoglobinuric renal failure arising from gangrene of an arm, and the other after 71 hours, due to cerebral herniation. The remaining five patients recovered without cerebral sequelae. Peritoneal dialysis is a useful procedure for rewarming patients with profound accidental hypothermia.

Adolescent↗