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Biomedical subjects

J Holm

Publications and source records attributed to J Holm.

At least 91 records · Page 5Linked to original sources
PubMed1994

Epidural anaesthesia prolonged into the postoperative period prevents stress response and platelet hyperaggregability after peripheral vascular surgery.

The occlusion rate of peripheral vascular grafts depends on technical as well as endogenous factors. Platelets play an integral part in graft failure and it has been suggested that anaesthesia may influence platelet function. In order to evaluate the influence of anaesthesia on stress response and platelet function in peripheral vascular surgery, patients (n = 18) were allocated to either general anaesthesia (GA; n = 9) followed by alleviation of postoperative pain with intramuscular analgesics or to lumbar epidural anaesthesia (EPI; n = 9) which was continued for 24 hours postoperatively. Before, during, as well as after vascular surgery of the lower extremity plasma levels of cortisol, glucose, serotonin (p-5HT), and urinary 5-hydroxyindole-3-acetic acid (5-HIAA) were analysed and platelet aggregability was determined. In the GA group surgery was accompanied by a significant stress response while in the EPI group this stress response was almost completely abolished. Platelet aggregability was reduced intraoperatively in both groups but in the postoperative period there was a marked hyperaggregability only in the GA group. P-5HT was increased preoperatively in both groups but was not affected by surgery. It is concluded that epidural anaesthesia, due to its effects on platelet aggregability, may be advantageous for peripheral vascular surgery.

Aged↗
PubMed1994

Folate receptor of human mammary adenocarcinoma.

Binding of 3H-folate to human mammary tumor homogenate was of a high-affinity type (K = 10(10) M-1) and displayed apparent positive cooperativity. Radioligand dissociation was slow at pH 7.4, but rapid at pH 3.5. As compared to methotrexate, 5-formyltetrahydrofolate acted as a strong inhibitor of radioligand binding. Gel chromatography of radioligand-labeled homogenate of tumor tissue revealed three peaks: a small > or = 110 kDa peak and two major peaks of folate-binding activity (M(r) approximately 25 kDa and M(r) approximately 100 kDa). Mammary tumor tissue showed immunostaining with rabbit antibodies against human milk folate binder. A parallel elevation in the concentrations of folate-binding protein and triglyceride in tumor tissue as compared to normal tissue adjacent to the tumor was compatible with the localization of folate-binding protein in the triglyceride-rich fraction of mammary gland homogenate.

Adenocarcinoma↗
PubMed1994

The high-affinity folate receptor of normal and malignant human colonic mucosa.

The hypothesis that folate depletion is a risk factor for development of colonic neoplasia prompted us to study the presence of a putative folate receptor in human colon mucosa. Binding of 3H-folate to normal and malignant mucosa studied by equilibrium dialysis was of high-affinity type (K = 10(10) L/mol) and displayed apparent positive cooperativity. Radioligand dissociation was slow at pH 7.4, but rapid at pH 3.5. As compared to methotrexate, 5-formyltetrahydrofolate was a potent inhibitor of binding. Gel filtration revealed a 25 kDa and a 100 kDa peak of folate-binding activity. Immunoreactivity studies were performed with rabbit antibodies against human 25 kDa milk folate-binding protein. Immunoblotting showed a single band at 65 kDa, and tissue sections exhibited immunostaining of mucosal areas. The present folate receptor with characteristics similar to those of other high-affinity folate-binding proteins may serve as a regulator of intracellular folate concentration in colon mucosa.

Carrier Proteins↗
PubMed1994

Folate deficiency in cerebrospinal fluid associated with a defect in folate binding protein in the central nervous system.

An adult male patient of Dutch ancestry has a slowly progressive neurological disease characterised by a cerebellar syndrome, distal spinal muscular atrophy, pyramidal tract dysfunction, and perceptive hearing loss. A severe folate deficiency state was found in CSF in combination with a normal serum and red cell folate state. Two unknown abnormal metabolites were present in CSF. The concentration of immunoreactive folate binding protein in CSF was unusually low, whereas the concentration of the protein measured with radioligand (3H-folate) binding was unusually high. The transfer of folate over the choroid plexus seems to be disturbed, potentially reflecting a defect in the choroid plexus folate binder.

Adolescent↗
PubMed1994

Microalbuminuria in 411 untreated individuals with established hypertension, white coat hypertension, and normotension.

We compared urinary albumin excretion in normotensive subjects and patients with white coat and established hypertension. The study involved prospective comparison of office blood pressure, daytime ambulatory blood pressure, and urinary albumin excretion in consecutive patients (n = 284) who were selected from general practice with newly diagnosed mild to moderate hypertension before the institution of pharmacologic antihypertensive therapy. All patients had a diastolic office blood pressure above 90 mm Hg; 173 had a consistently elevated diastolic blood pressure (established hypertension), and 111 had an average daytime ambulatory blood pressure below 90 mm Hg (white coat hypertension). A sample of 127 subjects drawn from the Danish national register served as a normotensive control group. The main outcome measure was the ratio of early morning urinary albumin to creatinine. This ratio differed significantly among the three groups, being (on a molar basis) 21 +/- 69 x 10(-6) in the normotensive subjects, 22 +/- 39 x 10(-6) in the white coat hypertensive patients, and 51 +/- 177 x 10(-6) in patients with established hypertension. The difference remained significant after correction for covariables. The ratio of early morning urinary albumin to creatinine was weakly but significantly correlated to blood pressure, was more pronounced for ambulatory than for office measurements, was more pronounced for systolic than for diastolic pressure, and was more pronounced for hypertensive than for normotensive individuals. The ratio was as reproducible a measure as 24-hour albumin excretion. We conclude that white coat hypertensive patients have less renal involvement than patients with established hypertension but more than a normotensive control group.

Adult↗
PubMed1994

Retinopathy in type II diabetes mellitus associated with above-normal urinary excretion of RBP.

We performed a cross-sectional study on the urinary excretion profiles of albumin (a marker of glomerular dysfunction) and retinol-binding protein (a low molecular mass protein marker of renal proximal tubular dysfunction) in non-insulin dependent (Type II) diabetics, with or without retinopathy. The urinary excretion of both proteins, in particular retinol-binding protein, was significantly higher in patients with background/proliferative retinopathy compared to patients without retinopathy. The degree of retinopathy correlated to the urinary excretion of albumin (P < 0.005) and retinol-binding protein (P < 0.0001). Retinopathy occurred at a higher frequency in patients with above-normal urinary excretion of retinol-binding protein, both in the absence or presence of micro/macroalbuminuria. The frequency of retinopathy among micro/macroalbuminuric patients with a normal urinary excretion of retinol-binding protein did not differ significantly from that observed in patients with a normal urinary excretion of both proteins. We cannot explain the association between retinopathy and proximal tubular dysfunction in Type II diabetes. However, it is possible that both phenomena are related to a common pathogenetic factor.

Aged↗
PubMed1993

Investigation of roe deer--criteria for use as a bioindicator in specimen banking.

Some results are given for a 5-year study to establish standard operation procedures for roe deer (Capreolus capreolus). The criteria for bioindication of roe deer are listed for three forestry districts in the east of Lower Saxony (Braunschweig, Fallersleben, Lappwald). The organs investigated for use are liver, kidney, kidney fat, brain and were collected from animals with an intact abdomen and were packed in Teflon bags after being shot. The fresh samples are kept at +4 degrees C and prepared in a laboratory within 24 h. The organs were investigated for 20 organic and 15 inorganic constituents. Twenty-two detectable contaminants from different collections are evaluated by using a personal computer (PC) with a Statistical Package of Social Science (SPSS) program. The results show that liver is a good accumulating organ; organ size and the regular distribution of the contaminants throughout the organ are an advantage. Significant variations in concentrations of contaminants are observed in May until August; levels stabilize in September to November. Animals < 18 months of age should be selected from rather narrow and uniform biotopes for specimen banking during the periods of autumn to winter or May. Pooling of the samples is not recommended.

Adipose Tissue↗
PubMed1993

Ligand-induced conformation change in folate-binding protein.

C.d. and fluorescence spectroscopy have been used to investigate the effect of ligand binding on the structure and stability of folate-binding protein (FBP) from cow's whey. The c.d. spectrum of unligated FBP predicts the following secondary structure: 22% helix, 25% antiparallel beta-strand, 5% parallel beta-strand, 17% turn and 31% random-coil structure. Folate binding to FBP results in significant changes in the c.d. spectrum. Analysis of the spectrum shows a 10% decrease in antiparallel beta-strand as a result of ligand binding. Folate binding also leads to strong quenching of FBP tryptophan fluorescence. The magnitude of the quench is proportional to ligand binding. The guanidinium chloride-induced unfolding of FBP is shown to be a multistate process. Detection by c.d. and fluorescence spectroscopy lead to non-identical transitions. Modelling studies are consistent with the existence of a stable folding intermediate. Ligand binding to FBP increases the apparent folding stability of the molecule. Simultaneous detection by c.d. and fluorescence indicate that the apparent increased folding stability is derived from ligand-induced aggregation of FBP.

Animals↗
PubMed1993

Cardiac risk and peripheral vascular surgery: new approach based on a multifactorial risk index.

An inexpensive approach to stratification of patients admitted for arterial surgery into groups of high and low cardiac risk has been prospectively evaluated in 235 consecutive patients. The Goldman and Detsky indices, assessed by a nurse the day before surgery, both identified patient groups with increased risk of lethal or potentially lethal (myocardial infarction, pulmonary oedema) cardiac events within 30 days after peripheral vascular surgery. The Goldman index was the more sensitive predictor of cardiac death (overall frequency 3.1 per cent) while the Detsky index was superior for prediction of non-lethal cardiac events (overall frequency 5.9 per cent). The simplest and yet most effective stratification into high and low cardiac risk was achieved using a Detsky score of 10 as the cut-off. It is concluded that multifactorial risk index-based preoperative screening can identify low-risk patients (Detsky score < or = 10), who may be accepted for vascular surgery (aortic aneurysm surgery excluded) without additional cardiac testing.

Aged↗
PubMed1993

High-affinity folate binding in human mammary gland.

High-affinity 3H-folate binding in Triton X-100 solubilized human mammary gland tissue displayed characteristics, e.g. apparent positive cooperativity and increasing affinity with decreasing concentration of folate binding protein, shown to be typical of specific folate binding. Radioligand dissociation was slow at pH 7.4. A major fraction of the bound radioligand dissociated rapidly at pH 3.5, while a residual binding of 20% persisted even after prolonged dialysis at pH 3.5. Gel chromatography revealed two major folate binding proteins (M(r) approximately 100 kDa and 25 kDa). However, only one single band was detectable on SDS-PAGE immunoblotting. The highest folate binding activity per g protein was associated with the upper triglyceride-containing layer of the 1000 g supernatant of the homogenate. The folate binding protein extracted from this layer had a low cross-reactivity (< 5%) with rabbit antibodies against 25 kDa human milk folate binding protein. The folate binding protein in the 1000 g pellet and the aqueous phase of the 1000 g supernatant was present at a low concentration and had a cross-reactivity of 100%.

Breast↗
PubMed1993

High-affinity folate binding in human prostate.

Binding of 3H-folate in Triton X-100 solubilized human prostate homogenate was of a high-affinity type and displayed apparent positive cooperativity typical of specific folate binding. Radioligand dissociation was slow at pH 7.4, but rapid at pH 3.5. Gel chromatography revealed two major folate binding proteins (M(r) approximately 100 and 25 kDa), but only one single band (M(r) approximately 65-70 kDa) was detectable on SDS-PAGE and immunoblotting with rabbit-anti human milk folate binding protein. Concentration of folate binding protein in prostate homogenate expressed as maximum 3H-folate binding was 1.10 nmol/g protein, and the cross-reactivity with rabbit-anti human milk folate binding protein serum was 15% as determined by an enzyme-linked immunosorbent assay (median values; n = 6).

Carrier Proteins↗
PubMed1993

Cardiac risk screening of peripheral arterial surgical patients by the use of combined simple clinical and non-invasive cardiodynamic parameters.

Arterial surgical patients have a poor long-term survival and suffer significant risks of experiencing perioperative cardiac events, mainly due to a high incidence of coronary atherosclerosis impairing left ventricular function. The perioperative cardiac risk can be assessed by use of clinical cardiac risk indices, which are inexpensive but may have suboptimal sensitivity, or by more extensive cardiac tests. In this study the efficacy of a combined, non-invasive and inexpensive technique of risk assessment was prospectively evaluated in 195 patients undergoing peripheral arterial surgery (aortic aneurysms not included). All patients were preoperatively examined by a nurse registering the Detsky cardiac risk index score (DRI) and performing resting computerised bioimpedance cardiodynamic measurements (CM). Cardiac deaths (CD, n = 6), potentially lethal cardiac complications (PLC, n = 11) within 30 days and long-term survival during 20 +/- 12 (S.D.) months of follow-up were identified. CD was best predicted by combining CM and DRI, while PLC was best predicted by combining DRI and the haemoglobin concentration of the blood (Hb). A group without CD containing 88% of the cases was identified. Furthermore, the combination of DRI < or = 10 and Hb > 120 g/l identified a low risk group (57% of all cases) with no PLC or CD. Using CM, DRI and Hb in combination, patient groups with long-term survival from 0-90% were identified. We conclude that this inexpensive cardiac risk screening both identifies low risk vascular surgical patients, for whom more sophisticated preoperative cardiac testing can be omitted, and predicts long-term survival.

Aged↗
PubMed1993

Low-dose warfarin decreases coagulability without affecting prothrombin complex activity.

OBJECTIVES: To assess the efficacy of a fixed, low dose of warfarin in lowering factor VII coagulant activity (FVII:C) and to investigate the effects on the plasma coagulation cascade. DESIGN: An open pilot study with two dose levels of warfarin: 1.25 and 2.5 mg day-1 during two consecutive 4-week periods. All subjects received aspirin 75 mg day-1. Prothrombin fragment 1 + 2 (F(1 + 2)), protein C, protein S, FVII:C, factor X and P-prothrombin complex activity (P-PT) were measured at baseline, at 2-week intervals and 4 weeks after end of treatment. Coagulation activation peptide F(1 + 2) was used as a marker of thrombin formation. SUBJECTS: Twelve male patients with a history of myocardial infarction. Inclusion was made through a written questionnaire. RESULTS: Warfarin 1.25 mg day-1 lowered FVII:C from 113 U dl-1 to 107 U dl-1 (P = 0.025) and F(1 + 2) from 1.60 nmol l-1 to 1.27 nmol l-1 (P = 0.013) but had no effect on protein C or P-PT. A dose of 2.5 mg day-1 induced further lowering of FVII:C (91 U dl-1, P = 0.0042), and also of protein C from 116% to 99% (P = 0.034) and P-PT from 107% to 81% (P = 0.0096) mean values. CONCLUSION: Warfarin 1.25 mg day-1 seems to exert an anticoagulant effect without reduction in PT or the natural anticoagulant protein C and is suggested, in combination with aspirin, to be a safe and simple therapy against arterial thrombotic disease, making regular PT controls unnecessary.

Adult↗