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Biomedical subjects

J Ingerslev

Publications and source records attributed to J Ingerslev.

At least 91 records · Page 5Linked to original sources
PubMed1997

Is an ephedrine caffeine treatment contraindicated in hypertension?

OBJECTIVES: To examine how the slimming drug, Letigen, containing ephedrine (E) 20 mg and caffeine (C) 200 mg (E + C), affects blood pressure in normotensive and hypertensive patients treated with adrenergic beta-receptor blocking drugs and/or other antihypertensive agents, during a period of six weeks. DESIGN: A double-blind, randomised, placebo controlled study of five parallel groups of overweight patients from general practices. SUBJECTS: One hundred and thirty-six patients with Body Mass Index (BMI) > 25 kg/m2 were included consecutively by 25 general practitioners in Denmark and randomized into five groups: (1) Hypertensive patients treated with betablockers and E + C; (2) Hypertensive patients treated with antihypertensive agents other than betablockers, and E + C; (3) Normotensive patients treated with E + C; (4) Hypertensive patients under any antihypertensive treatment + placebo; and (5) Normotensive patients + placebo. All patients were instructed in a 1200 kcal (= 5040 kj) diet. RESULTS: Of a total of 136 patients aged 20-74 y, 112 completed the study protocol. Fluctuations in systolic and diastolic blood pressure were seen in all groups. The systolic blood pressure was reduced significantly (5.5 mmHg) in the patients treated with antihypertensive agents other than betablockers, plus E + C. In the other hypertensive groups the reduction in blood pressure was not significant. In normotensive patients treated with E + C, the systolic and the diastolic blood pressure declined significantly (4.4/3.9 mmHg). At the end of the treatment period heart rate had increased significantly (4.9 beats/min) in the group of normotensive patients treated with E + C. Blood pressure and heart rate measured by the patient at home showed similar fluctuations from baseline prior to and during treatment with E + C or placebo. A mean loss of weight of approximately 4 kg in 6 weeks was significant for all the groups. There was no significant difference between the groups during this short period of treatment. In 56% of the patients treated with E + C complaints/side-effects related to the medical treatment were found at questioning. Corresponding complaints occurred in 21% of the placebo treated patients. In the E + C treated group 7% dropped out due to side-effects. In the placebo group there were no drop-outs. CONCLUSIONS: This study does not support the assumption that E + C should cause rises in blood pressure, acutely or during shortterm treatment, in either normotensive or hypertensive obese patients. The antihypertensive effect of the betablockers was not reversed by E + C.

Adolescent↗
PubMed1997

Markers of haemostatic activation before and after blood donation and plasmapheresis.

BACKGROUND AND OBJECTIVES: Previous studies have reported signs of haemostatic activation after haemorrhage. The aim of this study was to measure sensitive markers for haemostatic activation after blood donation or plasmapheresis in healthy donors. MATERIALS AND METHODS: Blood samples were drawn before as well as 5 min and 1 h after donation in 40 male donors, of whom 29 gave 1 unit of blood and 11 underwent plasmapheresis. Standard assays were used. RESULTS: Plasma concentrations of the activation markers prothrombin fragment 1 + 2, thrombin-antithrombin complexes, and von Willebrand factor did not increase after blood or plasma donation. CONCLUSIONS: In our opinion, these procedures are safe.

Adult↗
PubMed1997

Acute von Willebrand factor secretion from the endothelium in vivo: assessment through plasma propeptide (vWf:AgII) Levels.

Elevated plasma concentrations of von Willebrand factor (vWf) are increasingly recognized as a cardiovascular risk factor, and are used as a marker of endothelial activation. However, the factors which determine the rate of vWf release from the endothelium in vivo have not been defined clearly. In addition, vWf plasma levels may also be influenced by adhesion of vWf to the vascular wall or to platelets, and by its rate of degradation. The propeptide of vWf (also called vWf:AgII) is stored and released in equimolar amounts with vWf. In the present study we attempted to determine whether this propeptide could be a more reliable marker of endothelial secretion than vWf itself. To accomplish this we developed an ELISA based on monoclonal antibodies. The propeptide levels in normal plasma were found to be 0.7 microgram/ml, more than 10 times lower than vWf itself. Administration of desmopressin (DDAVP) induced a rapid relative increase in propeptide (from 106 to 879%) and in vWf (from 112 to 272%). However, the increases in vWf and propeptide were equivalent when expressed in molar units. A time course study indicated a half-life of the propeptide of 3 h or less. In a baboon model of disseminated intravascular coagulation (DIC) induced by FXa, vWf increased by less than 100%, whereas the propeptide concentrations increased by up to 450%. In view of the massive thrombin generation (as assessed by fibrinogen depletion), the increases in vWf are small, compared to the strong secretory response to thrombin and fibrin previously observed in vitro. Our results suggest that due to its rapid turnover, the propeptide could provide a sensitive plasma marker of acute endothelial secretion.

Adult↗
PubMed1996

Four novel mutations in deficiency of coagulation factor XIII: consequences to expression and structure of the A-subunit.

The characterization of naturally occurring mutations is one way to approach functionally significant domains of polypeptides. About 10 mutations have been reported in factor XIII (FXIII) A-subunit deficiency, but very little is known about the effects of the mutations on the expression or the structure of this enzyme. In this study, the recent crystallization of FXIII A-subunit and determination of the three-dimensional model were used for the first time to pursue the structural consequences of mutations in the A-subunit. The molecular analysis of four families from Sweden, Germany, and Denmark revealed four previously unreported point mutations. Three of the mutations were missense mutations, Arg326-->Gln, Arg252-->Ile, and Leu498-->Pro, and one was a nonsense mutation, a deletion of thymidine in codon for Phe8 resulting in early frameshift and premature termination of the polypeptide chain. In the case of the nonsense mutation, delT Phe8, the steady-state mRNA level of FXIII A-subunit was reduced, as quantitated by reverse transcriptase-polymerase chain reaction and solid-phase minisequencing. In contrast, none of the missense mutations affected mRNA levels, indicating the possible translation of the mutant polypeptides. However, by enzyme-linked immunosorbent analysis and immunofluorescence, all the patients demonstrated a complete lack of detectable factor XIIIA antigen in their platelets. In the structural analysis, we included the mutations described in this work and the Met242-->Thr mutation reported earlier by us. Interestingly, in the three-dimensional model, all four missense mutations are localized in the evolutionarily conserved catalytic core domain. The substitutions are at least 15 A away from the catalytic cleft and do not affect any of the residues known to be directly involved in the enzymatic reaction. The structural analyses suggest that the mutations are most likely interfering with proper folding and stability of the protein, which is in agreement with the observed absence of detectable FXIIIA antigen. Arg326, Arg252, and Met242 are all buried within the molecule. The Arg326-->Gln and Arg252-->Ile mutations are substitutions of smaller, neutral amino acids for large, charged residues. They disrupt the electrostatic balance and hydrogen-bonding interactions in structurally significant areas. The Met242-->Thr mutation is located in the same region of the core domain as the Arg252-->Ile site and is expected to have a destabilizing effect due to an introduction of a smaller, polar residue in a tightly packed hydrophobic pocket. The substitution of proline for Leu498 is predicted to cause unfavorable interatomic contacts and a disruption of the alpha-helix mainchain hydrogen-bonding pattern; it is likely to form a kink in the helix next to the dimer interface and is expected to impair proper dimerization of the A-subunits. In the case of all four missense mutations studied, the knowledge achieved from the three-dimensional model of crystallized FXIII A-subunit provides essential information about the structural significance of the specific residues and aids in understanding the biologic consequences of the mutations observed at the cellular level.

Adolescent↗
PubMed1996

Pain control after dental surgery: a double-blind, randomised trial of lornoxicam versus morphine.

Lornoxicam is a new non-steroidal anti-inflammatory drug of the oxicam class. This randomised, double-blind, placebo controlled trial compared the analgesic efficacy and tolerability of intramuscular (IM) injections of lornoxicam (4, 8, 16 and 20 mg) with morphine (10 and 20 mg) and placebo in 252 patients with mainly moderate to severe pain following surgical removal of an impacted mandibular third molar. Patients treated with lornoxicam or morphine experienced a significantly greater cumulative pain relief over the 4-h post-injection period (TOTPAR0-4) than placebo recipients. This effect appeared to be dose-dependent, with patients in the lornoxicam 4 mg or morphine 10 mg groups recording significantly lower TOTPAR0-4 scores than patients in the higher dosage groups of these drugs. No significant difference was detected between the morphine 20 mg group and the lornoxicam 8, 16 and 20 mg groups. Lornoxicam was well tolerated at all doses and was associated with a significantly lower incidence of adverse events than morphine 10 or 20 mg. Thus, the analgesic efficacy of IM lornoxicam at doses > or = 4 mg is superior to placebo, and doses > or = 8 mg are at least as effective as IM morphine 20 mg. Furthermore, lornoxicam possesses a more favourable tolerability profile than morphine and thus represents an attractive alternative for the treatment of moderate to severe acute pain.

Adolescent↗
PubMed1996

Growth hormone treatment of subfertile males.

OBJECTIVE: To study spermatogenesis and sperm motility during GH therapy in infertile men. DESIGN: Prospective open study. Each patient was treated with GH for 12 weeks and followed for a total of 36 weeks with sampling of blood and semen. SETTING: Outpatients studied at a clinical research unit of a university hospital. PATIENTS: Nine oligozoospermic (<5 x 10(6) sperm/mL) males and nine asthenozoospermic (percentage motile sperm <30 and >15 x 10(6) sperm/mL) males. The patient groups had a significantly lower GH response to an arginine GH stimulation test as compared with a control group. RESULTS: Serum insulin-like growth factor I (IGF-I) and serum IGF-binding protein 3 (IGFBP-3) levels increased significantly during GH treatment, as did seminal IGF-I. Serum E2, T, PRL, FSH, LH, and GH-binding protein were unchanged during the study. Sperm motility was increased significantly during GH treatment in both patient groups. There was no difference in sperm count during the treatment. There were three pregnancies in the nine couples from the asthenozoospermic group and no pregnancies in the oligozoospermic group. CONCLUSION: The biologic and clinical results in this study encourage the initiation of double-blind, placebo-controlled trials.

Adult↗
PubMed1996

Major surgery in haemophilic patients with inhibitors using recombinant factor VIIa.

In the haemophilic patient, development of antibodies that inhibit the function of the missing coagulation factor causes several delicate problems. Most importantly, antibodies will block the function of the specific coagulation factor, and often the antibody activity is so fierce that effective substitution therapy is outruled. In consequence, alternative measures must be adopted to control bleeding. Amongst those most commonly employed, like factor IX concentrates, activated prothrombin complex concentrates, and factor VIII of porcine origin, a new recombinant activated factor VII molecule has been evaluated clinically for some years with promising results. The aim of the present paper was to present a series of patients suffering from haemophilia A or B in whom inhibitors have complicated the clinical picture, and in whom a surgical procedure was indicated. As part of a compassionate use program devised by the producer of this genetically engineered factor VIIa, 12 patients underwent life-saving or essential surgery where the recombinant factor VIIa product was used to promote haemostasis in 13 surgical procedures. Due to a short in vivo half-life of activated factor VIIa, frequent administration was scheduled, injecting factor VIIa every 2-3 h for up to 2 days after which dosage intervals were prolonged. In one case, a global evaluation of the end treatment result was not reported, but in all of the other 12 cases the end result were considered excellent (n = 11) or efficient (n = 1). In none of the cases was other types of coagulation factor treatment modalities necessary. In conclusion, recombinant factor VIIa seems a tempting alternative to traditional treatment of the haemophilic patient with inhibitors, in whom surgery is called for. With other types of haemostatic agents, surgery in haemophilic inhibitor patients has only been studied rarely, and operations have generally been restricted to life-threatening situations.

Adolescent↗
PubMed1996

Two mutations in exon XII of the protein S alpha gene in four thrombophilic families resulting in premature stop codons and depressed levels of mutated mRNA.

Sixteen Danish unrelated thrombophilic families with plasma protein S deficiency of type 1 (or III) are currently under investigation in our laboratory for defects in the protein S alpha gene. The present paper describes a part of this work, which deals with the identification and phenotypical presentation of two unique mutations in exon XII of the protein S alpha gene in four of these families. The mutations were identified by SSCP screening followed by nucleotide sequence analysis or by direct nucleotide sequence analysis. The mutation found in one family (D) is a novel deletion of an A in either the codon for Gly448 (GGA) or Ile449 (ATI) resulting in a frameshift and a premature stop codon at position 454. The other mutation shared by three families (F, G and J) is a previously reported C-->T transition within a hypermutable CG dinucleotide sequence converting Arg410 (CGA) to Stop (TGA). All affected individuals are heterozygotes for their mutation and in each family the protein S genotype, the plasma protein S phenotype (not shown for Family J) and the clinical phenotype cosegregate. The two mutations can fully explain the abnormal protein S phenotype since premature stop codons are known to disrupt gene function of the mutated allele. Analysis of protein S mRNA from platelets showed that both mutations result in a marked reduction in the amount of protein S mRNA from the mutated alleles indicating that the mutations exert their deleterious effects on gene expression at the transcriptional level. The Arg410-->Stop mutation in Families F, G and J is in all instances linked to a G at the site of a common neutral dimorphism in the codon for Pro626 (CCA/G) in exon XV. This indicates that the mutation in these families could have arisen in a common ancestor. The Arg410 (CGA)-->Stop (TGA) mutation is also seen in exon XII of the normal protein S alpha gene. This gives rise to the speculation as to whether the mutation in the protein S alpha gene is the result of an interaction with the protein S beta gene leading to double homologous unequal crossing-over or gene conversion of a short DNA sequence. However, this is unlikely since none of the 7 other protein S beta-specific nucleotides are present in the mutated exon XII sequence of the protein S alpha gene. The common Arg506-->Gln Leiden mutation in coagulation factor V is not an additional risk factor for thrombosis in any of the four families studied.

Adult↗
PubMed1995

Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).

Blotting, Southern↗
PubMed1995

Plasma levels of von Willebrand factor in non-insulin-dependent diabetes mellitus are influenced by dietary monounsaturated fatty acids.

We have previously demonstrated a lowering effect on von Willebrand Factor (vWF) of a diet rich in monounsaturated fatty acids (MUFA) as compared with a high-carbohydrate diet. In the present study 16 non-insulin dependent diabetic (NIDDM) subjects participated in a cross-over experiment on an out-patient basis comparing the effects on vWF of three weeks treatments with two diets similar in carbohydrate and protein content, one rich in MUFA (30 energy %) and one rich in polyunsaturated fatty acids (PUFA) (30 energy %). Before and on the last day of the two diets, the levels of vWF, fibrinogen, fibronectin and alpha 2-macroglobulin were measured. After 3 weeks diet intervention vWF levels were lower after the MUFA regimen compared with the PUFA diet (mean +/- SD) (1.15 +/- 0.36 vs 1.32 +/- 0.42 U/ml, p = 0.003). Similar and unchanged levels of fibrinogen, fibronectin and alpha 2-macroglobulin were seen. In conclusion, three weeks on a diet rich in MUFA lowers vWF as compared with a PUFA rich diet, suggesting a beneficial effect of MUFA on the endothelium in NIDDM patients.

Cross-Over Studies↗
PubMed1995

Detection of ten new mutations by screening the gene encoding factor IX of Danish hemophilia B patients.

Hemophilia B is caused by a wide range of mutations. In order to characterize the mutations among patients in Denmark, we have systematically screened the entire coding region, the promoter region and exon flanking sequences of the gene encoding factor IX using single strand conformation and heteroduplex analyses. Patients from 32 different families were examined, and point mutations (23 different) were found in all of them. Ten of the mutations have not been reported by others; they include a splice site mutation, a single base pair deletion, and missense mutations. Notably, the study contains a female patient and a previously described Leyden mutation. In ten families with sporadic cases of hemophilia B, all 10 mothers were found to be carriers. The origin of two of these mutations was established.

Base Sequence↗
PubMed1994

[Coagulation factor VII--new physiopathological and therapeutic aspects].

Factor VII (FVII) is a vitamin K dependent coagulation factor that is synthesized in the liver, where clearance of the unactivated protein also takes place. It is a glycoprotein that following activation plays an important role in initiating coagulation after complex formation with tissue factor. A revised hypothesis of blood coagulation implicating the requirement of intact extrinsic and intrinsic pathways is presented. Increased activity of factor VII is associated with atherogenesis, and FVII deficiency may cause bleeding disorders. Recombinant FVIIa (rFVIIa) may be used in the treatment of haemophilic patients with antibodies against factor VIII or factor IX, utilizing its direct action in activation of factor X. Ongoing studies are investigating whether rFVIIa can shorten the bleeding time in patients with thrombocytopenia.

Blood Coagulation↗
PubMed1994

[Hemangiopericytoma. A rare vascular tumor with complicated operative and postoperative course].

Haemangiopericytoma (HPC) is a rare soft-tissue vascular neoplasm that may arise in almost all parts of the body. This report describes a 62-year-old man with one of the largest retroperitoneal HPC ever described weighing 950 grams. The surgical excision was followed by severe haemorrhages demanding several operations. The postoperative course was very complicated and prolonged. The geriatric rehabilitation was successful.

Hemangiopericytoma↗
PubMed1994

Decrease in von Willebrand factor levels after a high-monounsaturated-fat diet in non-insulin-dependent diabetic subjects.

High levels of von Willebrand factor (vWF) have been reported in diabetics with vascular complications, suggesting a role for this protein in the development of cardiovascular complications in non-insulin-dependent diabetes mellitus (NIDDM). Recently, a diet rich in monounsaturated fatty acids (MUFA) has been found to improve glycemic control and decrease diurnal blood pressure as compared with a high-carbohydrate (H-CHO) diet in NIDDM subjects. To study the impact of MUFA on the hemostatic system, we compared the levels of vWF, fibrinogen, fibronectin, and alpha 2-macroglobulin before and after 3 weeks on a high-MUFA (H-MUFA) diet and on an isocaloric H-CHO diet in 15 NIDDM subjects. In a crossover study, the patients were randomly assigned to a H-CHO diet (50% carbohydrate, 30% fat [10% MUFA]) or a H-MUFA diet (30% carbohydrate, 50% fat [30% MUFA]). Before and on the last day of the two diets, vWF, fibrinogen, fibronectin, and alpha 2-macroglobulin levels were measured. The H-MUFA diet caused a decrease in vWF from 1.31 +/- 0.08 to 1.13 +/- 0.08 U/mL (P < .004), whereas an unchanged level was observed after a H-CHO diet (1.19 +/- 0.11 v 1.25 +/- 0.11 U/mL, NS). The relative changes in vWF during 3 weeks on a H-MUFA and on a H-CHO diet attained -12.5% +/- 3.2% versus 5.7% +/- 3.5%, respectively (P < .0001). Furthermore, unchanged levels of fibrinogen, fibronectin, and alpha 2-macroglobulin were seen after usage of the two diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-Over Studies↗
PubMed1994

Mild haemophilia A in Iceland: clinical genetic studies of three families with the same mutation.

OBJECTIVES: The aim of the study was to define the phenotype in three families with mild haemophilia A and to determine restriction fragment length polymorphisms (RFLP), which could support a hypothesis of a common progenitor of the families. DESIGN: Family survey. SETTING: Index cases were identified in and outside hospital and a family survey for symptoms and signs of bleeding in family members and sampling for coagulation and RFLP studies were mostly carried out in the field. SUBJECT: Family members with and without symptoms of bleeding were selected for investigation and normal spouses and unrelated individuals were investigated for control. INTERVENTIONS: Medical advice regarding affected family members were given to the families and their physicians. MAIN OUTCOME MEASURES: Bleeding time, factor VIII activity, quantification of factor VIII:Ag, von Willebrand factor (vWF) Ag and vWF ristocetin assay. Typing of RFLP polymorphisms for genetic homogeneity. RESULTS: Bleeding manifestations are present in both sexes in the three families although more frequent and more severe in the males. The level of factor VIII activity is between 10 and 20% in most affected males whereas 35-60% is found approximately in 2/3 of female carriers and in 1/3 of them factor VIII activity is within the normal range. It is suggested that screening for this mild haemophilia A gene by a molecular genetic method would be of clinical value now, its mutation having been detected. CONCLUSIONS: Transmission of mild haemophilia A through six to seven generations is demonstrated by the study. The mild haemophilia A type described is the most prevalent of haemophilia A types in Iceland (population 260,000, 1992). The founder effect was confirmed by studies of RFLP polymorphisms.

Adolescent↗
PubMed1993

[Hereditary protein S deficiency and familial thrombosis. A review with description of a Danish family with protein S deficiency].

Protein S is approximately 69,000 Da polypeptide that acts as a co-factor in conjunction with activated protein C, in the natural anticoagulant system of protein C which irreversibly cleaves activated coagulation factors Va and VIIIa on the cell surface. Although synthesis of protein S takes place in several tissues, the hepatic production of protein S is presumably the most important. It has been established that heterozygous deficiency of protein S may be found in families with increased tendency to thrombosis (thrombophilia). The protein S gene, located on chromosome No. 3, consists of a translated gene, denoted PS alpha, and homologous untranslated region, designated PS beta. In inherited protein S deficiency deletions in PS alpha and PS beta have been detected. The present report deals with a Danish family with highly increased tendency to thrombosis, the propositus of which is a male who developed a large deep-vein thrombosis at the age of 18 months. In this family, nine cases with a plasma level of total protein S close to 50% of normal were identified, six of which had experienced one or more incidents of thrombosis in the past. We recommend that young patients who develop spontaneous arterial or venous thrombosis should be tested for the presence of inherited abnormalities of natural anticoagulants like antithrombin-III and proteins S and C.

Adolescent↗
PubMed1993

[Fatal hemostatic complications following erroneous thrombolytic therapy in patients with suspected acute myocardial infarction].

This report describes the fate of two young men wrongly treated with thrombolysis for suspected myocardial infarction. Both had electrocardiographic changes upon admission. Correct diagnoses of aortic dissection and haemorrhagic pericarditis was obtained within a few hours, but, due to the prolonged disturbance of haemostasis, appropriate therapy could not be instituted, and outcome was fatal for both patients. These cases underline the importance of rigid ST criteria, and procedures for neutralization of thrombolysis are proposed.

Adult↗