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Biomedical subjects

J Holm

Publications and source records attributed to J Holm.

At least 145 records · Page 8Linked to original sources
PubMed1990

Transcobalamin II deficiency presenting with methylmalonic aciduria and homocystinuria and abnormal absorption of cobalamin.

An infant with deficiency of transcobalamin II (TCII) presented with virtually complete failure to thrive and life-threatening pancytopenia. Methylmalonic acid and homocystine were found in the urine. The concentration of B12 in the serum was 26 pg/ml. Fibroblasts derived from the patient failed to take up labeled cobalamin in the absence of a source of TCII. Uptake was normal in the presence of TCII. Treatment with parenteral cobalamin reversed the clinical and hematological manifestations of the disease but she developed glossitis when the interval between injections was lengthened. Intestinal absorption of 57Co-cobalamin was less than 1% and remained abnormal when highly purified human intrinsic factor was given along with the labeled B12. Absorption improved when the labeled B12 was given together with rabbit TCII. The data suggest that TCII as well as intrinsic factor is required for transport of cobalamin from the intestine to the blood.

Failure to Thrive↗
PubMed1990

A high-affinity folate binding protein in human amniotic fluid. Radioligand binding characteristics, immunological properties and molecular size.

The presence of a folate binding protein of high-affinity type (affinity constant 5.10(9) M-1, maximum folate binding 3 nM) in human amniotic fluid was demonstrated in equilibrium dialysis experiments (37 degrees C, pH 7.4) with the radioligand 3H-folate. Dissociation of 3H-folate from the binding protein was slow at pH 7.4 but rapid at pH 3.5. By use of rabbit antibodies against low molecular weight folate binding protein from human milk we determined the concentration of folate binding protein in 5 amniotic fluids (range 1.5-2.3 nM) in an Enzyme-Linked Immunosorbent Assay (ELISA). Ultrogel AcA 44 chromatography of amniotic fluid showed that immunoreactive and radioligand bound folate binding protein coeluted in two peaks: a major one (Mr approximately 25,000) and a minor one (Mr approximately 100,000).

Amniotic Fluid↗
PubMed1990

Cellular and immunologic features of carotid artery disease in man and experimental animal models.

A better understanding of the pathogenesis of atherosclerosis and of post surgical intimal hyperplasia can be obtained by analysis of the cellular composition of the lesions using immunohistochemical techniques. In the present study, we have compared human atherosclerotic plaques obtained as endarterectomy specimens from the carotid artery, with lesions induced by mechanical injury and cholesterol feeding in rats and rabbits. Antibodies to cell type-specific antigens were used to identify cells, and visualisation was with enzyme-conjugated second antibodies. Our data show that the lipid core region of the human plaque is dominated by macrophages. Such cells also dominate the lesions of cholesterol-fed rabbits. In contrast, intimal lesions induced by balloon catheters in rats consist almost entirely of vascular smooth muscle cells, with a small inflammatory infiltrate of monocytes and T lymphocytes. This situation resembles that in the fibrous cap region of the human plaque. However, the human lesion contains a much higher proportion of T lymphocytes and macrophages than the experimental one. In all types of lesions, class II major histocompatibility antigens were induced on the cells, suggesting that an immune reaction with activation of T lymphocytes may be taking place. Finally, different subpopulations of smooth muscle cells were observed, possibly representing different degrees of differentiation or a response to immune mediators. In conclusion, our studies demonstrate that different experimental models resemble the human disease in various aspects. The choice of experimental model will therefore depend on the problem to be studied. The balloon catheter model should be ideally suited for studies of intimal hyperplasia after surgery and also for studies of fibrous cap formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Acute embolic lower limb ischaemia is associated with decreased red cell deformability.

Red cell deformability is an important determinant of peripheral blood flow. In this study the red cell filtration rate (RFR) was measured in 17 patients admitted for acute embolic lower limb ischaemia. The severity of the limb ischaemia on admission was scored from 0 to 6 depending on the degree of pain, and loss of motor and sensibility functions in the ischaemic extremity. Patients who presented with very severe ischaemia on admission underwent early embolectomy whereas those with less severe ischaemia (range from 0 to approximately 3 in ischaemic score) initially were treated conservatively with heparin. Red cell filtration rate was assessed with a standard microfiltration method and expressed in microliters/sec. On admission the RFR averages 30 +/- 5 microliters/sec (mean +/- S.D.), significantly lower than the corresponding value in a normal population of similar age (50 +/- 5 microliters/sec). There was an inverse relationship (r = 0.74, P less than 0.001 by use of linear regression analysis) between the ischaemic score and the RFR on admission, with low RFR values being related to high ischaemic scores. Forty-eight hours after revascularisation, the RFR had improved significantly in the patients having undergone successful revascularisation, whereas it was unchanged in conservatively treated patients. It is concluded that patients with acute embolic lower limb ischaemia have an impaired red cell filtration rate suggesting decreased red cell deformability, the impairment being related to the severity of the ischaemia. A poor red cell filtration rate on admission is related to increased risk of postoperative gangrene and/or cardiac death. Successful revascularisation, but not conservative heparin treatment is associated with increasing deformability.

Aged↗
PubMed1990

A stable prostacyclin analogue (iloprost) in the treatment of ischaemic ulcers of the lower limb. A Scandinavian-Polish placebo controlled, randomised multicenter study.

The clinical efficacy of the prostacyclin analogue iloprost was studied during a 2 week treatment and 6 month follow-up period in 103 patients with ischaemic ulcers who were randomised to receive active treatment or placebo. Responders were defined as those patients who achieved healing of at least one third of the ulcer area during the study period. The overall responder rate was 41.3%, compared with 25% for the control group (P = 0.086). Side effects including flushing and headache, were common. The study population had a mortality of 23% during the 6 month period, the amputation rate was 43.5% for iloprost and 50% for placebo treated patients. In this severely diseased population of patients a treatment period limited to 2 weeks did not sufficiently improve ulcer healing.

Adult↗
PubMed1990

Cardiac output in patients with acute lower limb ischaemia of presumed embolic origin--a predictor of severity and outcome?

Cardiodynamic studies using a non-invasive computerised thoracic electrical bioimpedance (TEB) equipment were performed in 35 patients presenting with acute lower limb ischaemia of presumed embolic origin, and in 36 age-matched control patients without emboli. Patients who presented with imminent gangrene were promptly operated upon, whereas those who had less severe ischaemia were treated initially with heparin only. In the former group, cardiac output and myocardial contractility were very low on admission, while systemic vascular resistance was high. Cardiac output was further decreased when measured immediately after revascularisation, whereas it had become normal 2 days later. In patients with less severe acute ischaemia, cardiac output and myocardial contractility values on admission were similar to those of control patients, and no changes were observed after 2 days of conservative treatment. Overall, cardiac output on admission was significantly related to the simultaneously observed severity of the limb ischaemia. A low cardiac output (less than 1.7 l/min m2) on admission was found to predict severe cardiac complications (60% mortality within 10 days), whereas clinical assessment of cardiac failure on admission was poorly related to outcome. We conclude that patients with acute lower limb ischaemia of presumed embolic origin often have unrecognised poor cardiac function, which is related to the severity of the limb ischaemia and to outcome. By routine non-invasive TEB cardiodynamic measurements, high risk patients can rapidly be identified and proper treatment regimes be instituted in each individual patient.

Aged↗
PubMed1990

Cardiac output determinations in the pig--thoracic electrical bioimpedance versus thermodilution.

The accuracy of transthoracic electrical bioimpedance (TEB) for continuous, noninvasive measurement of cardiac output (Qt) in pigs was assessed in comparison with the thermodilution (TD) technique. Using the TEB technique, the different thoracic habitus of the pig had to be corrected for A good correlation with the TD technique was obtained (r = .87; p less than .001; n = 86) using thoracic length value (the measured value plus 25%) in an NCCOM3-R6 cardiodynamic computer for Qt values ranging from 2.9 to 9.8 L/min in pigs weighing from 40 to 75 kg. However, the Qt values given by the NCCOM3 were systematically 11% to 15% higher over the full range of values than the average of NCCOM-3 and TD Qt values. On the basis of the good agreement in the present study between the TEB and TD techniques over a broad range of Qt values, we conclude that TEB offers a valuable continuous, noninvasive alternative to TD for Qt determinations in experimental porcine models.

Animals↗
PubMed1990

Diabetic retinopathy related to degree of albuminuria and tubular (low molecular weight) proteinuria in insulin-dependent (type I) diabetes mellitus.

The urinary excretion of albumin (a marker of glomerular damage) and retinol binding protein (a low molecular weight protein marker of tubular dysfunction) was determined by sensitive immunochemical methods in 110 insulin-dependent (Type I) diabetic patients. We observed a statistically significant correlation between the urinary excretion levels of both proteins, in particular albumin, and the degree of retinopathy. The incidence of macroalbuminuria and tubular proteinuria was significantly higher in patients with manifest background retinopathy and proliferative retinopathy as compared to patients with no or slight retinopathy. The duration of diabetes was significantly correlated to the degree of retinopathy, but not to the urinary excretion of albumin and retinol binding protein.

Adolescent↗
PubMed1990

Arterial blood pressure related to degree of albuminuria and low-molecular-weight proteinuria in IDDM.

Urinary excretion of albumin and retinol-binding protein (a marker of tubular proteinuria that results from impaired proximal tubular reabsorption of low-molecular-weight proteins) was determined in 110 insulin-dependent diabetic (IDDM) subjects. A statistically significant correlation between the urinary excretion of both proteins, in particular the retinol-binding protein, and the height of arterial blood pressure (systolic and diastolic) was observed. Correlation was weak, i.e., factors other than incipient nephropathy could be of greater importance for the development of arterial hypertension in diabetes.

Adolescent↗
PubMed1990

Pain control in the surgical debridement of leg ulcers by the use of a topical lidocaine--prilocaine cream, EMLA.

The analgesic effect of EMLA 5% cream for surgical cleansing of leg ulcers was investigated in an open study and in a double-blind comparison with placebo. Eighty patients with ulcers of venous or arterial origin participated. The cream was applied under occlusion and removed before cleansing. Plasma concentrations of lidocaine and prilocaine were assessed. The maximum individual concentrations were 0.8 microgram/ml for lidocaine and 0.08 microgram/ml for prilocaine. Pain was assessed according to a verbal rating scale and on a 100 mm visual analogue scale. The median VAS pain scores for EMLA and placebo were 18.5 and 84 mm (p less than 0.01). There were no severe adverse reactions. The results show that there is a need for pain control in surgical debridement of leg ulcers and that EMLA cream gives satisfactory analgesia for this procedure.

Administration, Topical↗
PubMed1990

A porcine model for acute distal aortic occlusion.

Periarterial and intramural nerves and lymphatics as well as the vascular endothelium may influence pathophysiologic responses to acute arterial occlusion. For study of such pathophysiologic patterns, experimental models resembling the clinical situation are therefore preferable. In this porcine study acute distal aortic occlusion was mimicked by use of a balloon catheter introduced via a vascular graft anastomosed to the lateral aortic wall. Peripheral circulatory disturbance was assessed by measurements of femoral vein blood flow, skin blood flow in the hind foot and oxygen tension in the calf muscle, which verified the degree of ischemia. During the 4-hour ischemic period, repeated arterial and venous blood gas analyses showed increasing acidosis in effluent venous blood from the hind limbs, which after reperfusion slowly normalized. As highly reproducible conditions are achievable with the present experimental model, it can be used for studies of pathophysiologic responses to acute distal aortic occlusion.

Animals↗
PubMed1989

[A prospective evaluation of transvaginal ultrasonic scanning in the initial assessment of suspected pelvic masses].

Eighty-six patients with suspected pelvic masses were evaluated with transvaginal sonography in connection with pelvic examination. The scans were performed by gynecologists with a limited experience in sonography. Sixty-nine cases could be verified by operation, laparoscopy, autopsy or by clinical follow-up. The predictive value of positive and negative findings were 97.6 and 87.5%, respectively. In 73% of the positive cases, a correct pathoanatomical diagnosis was made. The procedure was readily accepted by the patients. It is concluded that transvaginal sonography may easily be introduced in a gynecological department as a rapid and accurate aid in the evaluation of patients with suspected pelvic masses.

Adolescent↗
PubMed1989

A high-affinity folate binding protein in human urine. Radioligand binding characteristics, immunological properties and molecular size.

High-affinity binding of [3H]folate in human urine displayed characteristics, e.g. apparent positive cooperativity, which are typical of specific folate binding. By means of a two-site enzyme-linked immunosorbent assay (ELISA) with rabbit antibodies against the low molecular weight folate binding protein from human milk, we measured folate binding protein concentrations in the range of 0.51 to 4.13 nM in urine samples from 16 apparently healthy individuals. Ultrogel AcA 44 chromatography of the urine showed that immunoreactive and radioligand bound folate binding protein coeluted in one large peak (Mr approximately 25,000).

Carrier Proteins↗
PubMed1989

Excretion of hippuric acid during sodium benzoate therapy in patients with hyperglycinaemia or hyperammonaemia.

In patients with non-ketotic hyperglycinaemia and two patients with urea cycle disorders treated with varying doses of sodium benzoate there was linear correlation between intake of benzoate and excretion of hippurate. Patients with non-ketotic hyperglycinaemia excreted significantly more benzoate in the form of hippurate than patients with urea cycle disorders (74 +/- 7.0 vs 41 +/- 3.6%). The plasma concentration of glycine decreased following benzoate treatment only in the patients with non-ketotic hyperglycinaemia. The observed difference between the two groups in the excretion of hippurate seems to support the concept that glycine availability may be limiting in benzoate therapy for some patients.

Amino Acid Metabolism, Inborn Errors↗
PubMed1989

The effect of various thermal processes on the glycemic response to whole grain wheat products in humans and rats.

The effects of different thermal processes used to produce ready-to-eat cereals on the glycemic response to whole grain wheat were investigated in rats. The metabolic response to drum dried flour, which constitutes the major component in instant gruel and porridge, was also studied in healthy human subjects. Boiled flour was used for comparison. The degree of starch gelatinization and rate of starch hydrolysis in vitro were also measured. Incompletely gelatinized steam flaked and dry autoclaved products were digested more slowly in vitro and elicited lower glucose responses in rats compared with completely gelatinized drum dried, extrusion cooked or boiled samples. The initial glycemic response in rats was closely related to the rate of starch hydrolysis in the pepsin/alpha-amylase assay (r = 0.91, P less than 0.04). When pepsin was omitted, no significant correlation was obtained. The peak glucose, insulin and C-peptide responses in humans after breakfast meals of porridge prepared from drum dried flour and from boiled flour were similar, whereas the rate of depression of the glucose curve was more rapid after consuming drum dried porridge. It is concluded that the glycemic response to wheat products is affected by the processing conditions used. The more severe the processing conditions, the more rapid the digestion of starch.

Adult↗
PubMed1989

Continuous conjunctival oxygen tension (PcjO2) monitoring for assessment of cerebral oxygenation and metabolism during carotid artery surgery.

The clinical value of noninvasive continuous monitoring of conjunctival oxygen tension for assessment of cerebral perfusion during carotid endarterectomy performed under general anaesthesia has been evaluated. The patients (n = 17; mean age 62.5 +/- 1.7 years) were monitored as follows: conjunctival oxygen tension (PcjO2); internal jugular venous oxygen tension at the skull base level (PcijvO2); arterial blood pressure; arterial and internal jugular venous blood gases; acid-base data and lactate, pyruvate levels; end-tidal CO2 concentration. The mean preanaesthetic PcjO2 level of 4.86 +/- 0.40 kPa was significantly lower than PaO2(PcjO2)/PaO2 ratio of 0.48). Following anaesthesia, a larger PcjO2-PaO2 gradient (ratio 0.32) was seen in spite of the hyperoxic situation (FiO2 = 0.40) due to vasoconstriction induced by slight hypocapnia (reduction of PaCO2 from 5.13 +/- 0.08 to 4.64 +/- 0.10 kPa). The carotid artery crossclamping resulted in a rapid and pronounced decrease of PcjO2, while PcijvO2 remained unchanged. No relationship between PcjO2 and stump pressure was found, while a significant correlation (P less than 0.02) between PcjO2 and lactate in effluent venous blood from the brain was demonstrable. It is concluded that PcjO2 monitoring seems a clinically useful trend indicator of cerebral perfusion in the individual patient. Due to large interindividual variations in basal PcjO2 readings and in PcjO2 changes during carotid artery clamping, however, transconjunctival oxygen tension monitoring does not seem to allow early and accurate recognition of impending cerebral ischaemia during carotid endarterectomy, and its routine use therefore seems of limited value.

Adult↗