Marine n-3 polyunsaturated fatty acids and coronary heart disease: Part II. clinical trials and recommendations.
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Angina Pectoris↗
Biomedical subjects
L H Rasmussen
Publications and source records attributed to L H Rasmussen.
[Anticoagulant therapy].
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Administration, Oral↗
[Abciximab (ReoPro) in the treatment of acute coronary syndromes].
Platelet activation plays a major role in the pathophysiology of acute coronary syndromes (ACS). Inhibition of platelet function is the basic pharmacological treatment of ACS. Platelet membrane glycoprotein IIb/IIIa inhibitors, a new class of potent antiplatelet agents, have been used in the treatment of ACS and in the prevention of complications after percutaneous coronary interventions (PCI). Several large clinical trials have demonstrated the effectiveness of this class of agents. The first of these agents to show beneficial effects after coronary interventions was the mouse/human chimeric Fab fragment antibody c7E3 abciximab (ReoPro). The purpose of this article is to describe the pharmacology of abciximab and to review the results of the clinical trials carried out with the drug in patients with ACS, treated either with or without acute/elective PCI.
Angioplasty, Balloon, Coronary↗
Dramatic improvement of severe acute disseminated encephalomyelitis after treatment with intravenous immunoglobulin in a three-year-old boy.
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Brain↗
[Clinical studies on glycoprotein IIb/IIIa receptor antagonist].
Platelet activation plays a major role in the pathophysiology of acute coronary syndromes (ACS), and inhibition of platelet function is the basic pharmacological treatment of ACS. Platelet membrane glycoprotein IIb/IIIa inhibitors, a new class of potent antiplatelet agents, have been used in the treatment of ACS, as well as in the prevention of complications after percutaneous coronary interventions. The aim of this article is to describe the potential possibilities of platelet inhibition and to review the pharmacology of glycoprotein IIb/IIIa inhibitors, the results of the clinical trials with these agents, and their current use in the pharmacological treatment of ACS and in relation to percutaneous coronary intervention.
Controlled Clinical Trials as Topic↗
[Parvovirus B19 infection as the cause of hepatitis and neutrophil granulocytosis in a 20-year old woman].
A case of Parvovirus B19 infection (erythema infectiosum) in a 20 year old woman is presented. The patient presented with fever, arthritis in one knee, neutrophil granulocytosis and biochemical evidence of hepatitis. Serological evidence of Parvovirus B19 infection was found as the only explanation of the clinical picture. Hepatitis was due to Parvovirus B19 infection as there was no serological evidence of EBV or CMV reactivation. Neutrophil granulocytosis and thrombocytosis were found and were probably due to an active bone marrow in the recovery phase of bone marrow aplasia.
Adult↗
Dose response profiles of human growth hormone in subcutaneous wound chambers in rats.
OBJECTIVE: To investigate dose response profiles of human growth hormone in soft connective tissue healing when it is given locally in subcutaneous wound chambers. DESIGN: Placebo controlled parallel study. SETTING: Institute of Medical Anatomy, Denmark. MATERIAL: 36 male Sprague Dawley rats, in three group of 12. INTERVENTIONS: Stainless steel wire mesh cylinders 7 mm in diameter and 20 mm long were implanted subcutaneously in pairs in the upper and lower back on either side of the midline in three groups of male Sprague Dawley rats. Two groups were each given two different doses of growth hormone (group 1, 0.2 and 0.7 IU; and group 2, 0.02 and 2 IU) in two cylinders and vehicle alone in the two cylinders on the opposite side. Group 3 were given vehicle alone in two cylinders and needle puncture (sham) on the opposite side. Injections of growth hormone or vehicle (placebo) were given every three days for 16 days. MAIN OUTCOME MEASURES: Body weight, weight of granulation tissue, and concentrations of hydroxyproline and aminoterminal propeptide of procollagen type III. RESULTS: The dose response curves for weight of granulation tissue and deposition of collagen were upward convex (ANOVA p < 0.001 and 0.001, respectively). Growth hormone in doses of 0.2 and 0.7 IU stimulated formation of granulation tissue to means of 180% (95% confidence interval (Cl) 149% to 210%) and 174% (95% Cl 148% to 200%) more than in the placebo treated cylinders (group 3) (p < 0.05 and < 0.01, respectively). Doses of 0.2 and 2 IU, however, had less effect. The placebo cylinders in animals in groups 1 and 2 contained a mean of 157% (95% Cl 137% to 177%) more granulation tissue than the cylinders in group 3, indicating that locally applied growth hormone also had a systemic effect. CONCLUSION: The clinical use of topical growth hormone in wound healing may be complicated by the relatively narrow therapeutic interval.
Animals↗
Evaluation of recombinant human growth hormone for wound management.
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Animals↗
Influence of human growth hormone on granulation tissue formation, collagen deposition, and the aminoterminal propeptide of collagen type III in wound chambers in rats.
The influence of growth hormone on granulation tissue formation was investigated in wire mesh cylinders implanted subcutaneously in rats. Two groups of 10 rats (study 1) and 1 group of 12 rats (study 2) were used for the investigation. Growth hormone, 0.02 and 0.2 IU (study 1), 0.05 and 0.2 IU (study 2), or vehicle only, was injected into the cylinders every third day for 16 days. In study 2, wound fluid was aspirated before injection of growth hormone and saved for later analysis of the aminoterminal propeptide of collagen type III. In both studies, growth hormone significantly increased the formation of granulation tissue and of total collagen content dose-dependently, whereas the relative amount of collagen was unaffected by growth hormone treatment. Wound fluid aminopropeptide increased significantly after implantation of the cylinders until day 7, before declining slightly, with no difference between the groups. We conclude that growth hormone stimulated granulation tissue formation and collagen deposition dose-dependently in the wound cylinders when injected every third day. The results suggest that growth hormone treatment does not cause excessive collagen deposition in newly formed granulation tissue.
Journal Article↗
The reference range for complexed alpha 2-macroglobulin human plasma: development of a new enzyme linked in immunosorbent assay (ELISA) for quantitation of complexed alpha 2-macroglobulin.
Purified alpha 2-macroglobulin was complexed by reaction with methylamine and used to raise monoclonal murine antibodies. A four-step enzyme linked immunosorbent assay (ELISA) was developed to determine the antibody-specificity of the produced monoclonal murine antibodies towards human native and complexed alpha 2-macroglobulin. Two monoclonal antibodies were selected, H11A11 (specific towards complexed alpha 2-macroglobulin) and 1CG4 (recognizes both forms of the molecule), and purified by affinity chromatography on protein G. The purified antibodies were used to develop a fast three-step ELISA for exact quantitation of complexed and total alpha 2-macroglobulin in human plasma. The intra-assay coefficient of variation (CV) for measurement of complexed alpha 2-macroglobulin is 2.2-9.9%, whereas the inter-assay CV was determined to be 3.7-10.5% and the recovery of the assay is 93-108%. The assay for total alpha 2-macroglobulin has an intra-assay CV of 3.0-15.5%, an interassay CV of 5.1-21.2% and a recovery of 91-116%. Citrated plasma samples from 139 healthy blood donors were examined, resulting in a reference range for complexed alpha 2-macroglobulin of 13.5-31.1 mg 1(-1) with a median value of 21.7 mg 1(-1). The concentration of total alpha 2-macroglobulin was measured by the same assay using the monoclonal antibodies 1CG4. For total alpha 2-macroglobulin we determined the reference range to be 1.12-3.54 g 1(-1) with a median value of 2.14 g 1(-1). Based on these results the reference range for complexed alpha 2-macroglobulin as a percentage of total alpha 2-macroglobulin was calculated to be 0.8-1.9% with a median value of 1.0%.
Adult↗
Effect of meal frequency on blood glucose, insulin, and free fatty acids in NIDDM subjects.
OBJECTIVE: We studied the effects of meal frequency on blood glucose, serum insulin, and FFAs in 12 NIDDM subjects. RESEARCH DESIGN AND METHODS: Subjects were assigned in random order to two 8-hr observation periods after an overnight fast. They received isocaloric diets with similar composition either as six small or as two large meals. At the end of each study period, an IVGTT was given. RESULTS: Two large meals induced an 84% greater maximum amplitude of glucose excursions than six small meals (6.1 +/- 0.5 vs. 3.3 +/- 0.5 mM, P < 0.005) and higher insulin responses (P < 0.03). The Kg response to an IVGTT did not differ in the two situations. The average FFA level was lowest in response to frequent meals (P < 0.02). CONCLUSIONS: A higher meal frequency acutely subdues glucose excursions and reduces insulin and FFA levels during the daytime in older NIDDM subjects.
Blood Glucose↗
[Growth hormone and surgery].
Development of biosynthetic human growth hormone (b-hGH) may be a beneficial supplement in the treatment of surgical patients with major traumas in future. As a result of its anabolic actions, b-hGH has proved to be protein conserving in patients who have undergone major gastrointestinal operations with a net decrease in urinary protein excretion, increased fat oxidation and preservation of grip strength and lean body mass. In addition, animal experiments have shown a pronounced stimulatory effect on the healing of tibial fractures in both young and old rats and in the healing of colon anastomoses, as evaluated from the biomechanical properties of the tissues. Experimental skin wounds have also been shown to benefit from b-hGH treatment but only in the early phases of the healing process. Studies on woundhealing in humans have revealed beneficial effects of b-hGH on donor-site healing in skin grafting of patients with severe burns on systemic administration and on healing of chronic leg ulcers on topical application. Further studies in humans with characterization of patients who may benefit from the treatment and the dose-response relations are required to evaluate possible employment of growth hormone in surgical practice.
Animals↗
Collagen types I and III propeptides as markers of healing in chronic leg ulcers. A noninvasive method for the determination of procollagen propeptides in wound fluid--influence of growth hormone.
A noninvasive method allowing measurements of the propeptides of collagen type III (PIIINP) and type I (PICP) in ulcer washings was developed. The response to topical human growth hormone was examined. Fourteen patients with venous ulcers were treated sequentially with human growth hormone (0.1, 0.25, and 1 IU/cm2/day), each dose for 1 week, followed by 1 week washout. On alternate days, three and two times during treatment and washout periods, respectively, the ulcers were washed and incubated for 30 minutes with sterile water. No changes in healing rates in relation to growth hormone application were observed. In contrast, PIIINP increased significantly to 168% (154% to 184%) (mean, 95% confidence interval) and 195% (179% to 218%) 5 and 9 days, respectively, after start of treatment, (p < 0.01). Propeptides of collagen type I reached a significant increase, to 196% (172% to 232%), in the fourth week, (p < 0.01). The areas under the curves of PICP and PIIINP correlated significantly with the healing rates (r = 0.57, p = 0.04; and r = 0.64, p = 0.01, respectively). The authors conclude that propeptide measurements may be useful markers of healing in clinical studies.
Administration, Topical↗
[Chronic meningococcemia. A review and a report of 4 cases].
Four cases of chronic meningococcacemia (CM) are described. The diagnosis was based on recurring fever, exanthema, arthralgia/arthritis and positive blood culture with Neisseria meningitidis. The meningococcal antibody-test (MAT) was positive in all of the three patients tested. None of the patients had positive throat culture for Neisseria meningitidis. All patients had leucocytosis during the febrile periods. The symptoms lasted for 5-150 days before the diagnosis was made. These findings are discussed in relation to the literature.
Adult↗
Risk of bilateral testicular germ cell cancer in Denmark: 1960-1984.
The incidence of a second primary testicular germ cell cancer among 2850 (96.6% of eligible) men with a histologically verified first primary germ cell cancer diagnosed in the period 1960-1979 in Denmark was established. Of these 2850 men, 73 (2.6%) developed a contralateral testicular cancer. In five of these patients (0.18%), the tumors were synchronous. The cumulative risk of developing a contralateral cancer 25 years after diagnosis of the first testicular germ cell cancer was 5.2% according to a Kaplan-Meier estimate. It was higher among men with a nonseminoma as the first tumor (8.4%) than among men with a seminoma as the first tumor (3.6%). Of the second tumors, 12% were stage II and 17% were stage III at the time of diagnosis. Based on 24,588 person-years at risk and 68 nonsimultaneously occurring bilateral testicular germ cell cancers, the overall relative risk (RR) of developing a second primary cancer in the contralateral testicle following a first germ cell cancer was found to be 24.8 (95% confidence interval = 19-38). Among men with a nonseminoma, the risk was higher (RR = 27.1) than among men with a seminoma (RR = 22.5). The excess risk was not affected by age at diagnosis, calendar period, or time since diagnosis. Close surveillance by screening for and treatment of carcinoma in situ of the remaining testicle in testicular cancer patients are advised.
Adult↗
[Acute severe polyneuropathy in hepatic porphyria].
Two cases of acute polyneuropathy in patients with latent hepatic porphyria are presented. Porphyric neuropathy is a rare, serious, life-threatening disease. Since most cases are induced by drugs, early diagnosis is essential for the treatment and prognosis. Porphyria should always be considered in acute polyneuropathy.
Acute Disease↗
Protein kinase C subtypes in human neutrophils.
Protein kinase C from rat brain and human neutrophils was chromatographically separated on a hydroxylapatite column connected to a high-performance liquid chromatography (HPLC) system. Protein kinase C from rat brain was separated into three peaks (types I, II, and III). In contrast, only two types were obtained from human neutrophils matching type II and type III in brain. In cell membranes from unstimulated human neutrophils type III was predominant, but mainly type II was translocated to the membranes upon stimulation with phorbolmyristatacetate (PMA). Both types were equivalently activated by phosphatidylserine, diolein, and magnium and presented identical Km for ATP.
Animals↗
Injury and repair of smaller muscular and elastic arteries. Immunohistochemical demonstration of fibronectin and fibrinogen/fibrin and their degradation products in rabbit femoral and common carotid arteries following a dilatation injury.
Indirect immunoperoxidase staining for fibrinogen/fibrin and fibronectin was performed on normal and healing arterial tissue of muscular and smaller elastic arteries. Fibronectin was observed in the wall of the normal arteries, whereas fibrinogen/fibrin could not be demonstrated. Fibronectin was observed in the intima as well as the media deposited in a similar fashion in the femoral and carotid artery during repair. Apart from the early occurrence of fibrin/fibrinogen in the media of both arteries the distribution of fibrinogen/fibrin and degradation products differed. In the femoral artery a progressively weakening positive reaction for fibrinogen/fibrin and degradation products towards the lumen was observed in the intima and the media 7 and 14 days after the lesion. By 28 days the reaction in the media was negative. No thrombus formation was observed. In contrast, all the specimens examined from the common carotid arteries were obliterated by luminal thrombi 28 days after the lesion. The thrombus as well as the damaged intimal thickening and the compressed media were loaded with fibrinogen/fibrin and degradation products. The deposition of fibronectin, fibrinogen, and degradation products in the carotid artery was similar to that previously reported in experimental aortic arteriosclerosis in rabbits as well as in giant cell arteritis.
Animals↗