Biomedical subjects

P Kaufmann

Publications and source records attributed to P Kaufmann.

At least 73 records · Page 4Linked to original sources

PubMed1999

Relation of serial measurements of plasma-soluble intercellular adhesion molecule-1 to severity of acute pancreatitis.

OBJECTIVE: Acute pancreatitis remains a clinical challenge because it is difficult to predict whether, in a given patient, the disease will be mild or will run a severe course with a possibly fatal outcome. The aim of this study was to investigate whether circulating soluble intercellular adhesion molecule-1 (sICAM-1) as a marker of leukocyte activation is related to the severity of the disease. METHODS: The study included 29 consecutive adults admitted with acute pancreatitis. Plasma sICAM-1 levels were measured serially over a period of 6 days, and values and time courses were correlated with clinical severity. RESULTS: Our patients fell into four groups on the basis of the following measurements: 1) Decreasing sICAM- levels with maximal values of 446 +/- 90 ng/ml (mean +/- SEM) slightly above the upper limit of normal were associated with uncomplicated mild disease in seven patients. 2) In nine patients with sICAM-1 concentrations reaching a peak of 743 +/- 121 ng/ml after 3 days, severe pancreatitis was present in 11% and pancreatic necrosis occurred in 33%. 3) A second increase of sICAM-1 (maximal level: 993 +/- 169 ng/ml) after an initial decrease (relapsing pattern, 7 patients) was associated with a severe course of disease in 71% including pancreatic necrosis in 43% and nosocomial pneumonia in 42%. 4) A rapid increase of sICAM-1 reaching highest maximal values of 1738 +/- 104 ng/ml (p < 0.0001) indicated fulminant pancreatic necrosis and a fatal outcome in six patients. CONCLUSIONS: Serial plasma sICAM-1 levels in patients with acute pancreatitis within the first 6 days after admission fall into four different groups of severity according to the shape of the curves. This suggests that the time course of elevated plasma sICAM-1 concentrations reflects the risk of developing necrosis and clinical complications in acute pancreatitis.

Acute Disease↗

PubMed1999

Apoptosis cascade progresses during turnover of human trophoblast: analysis of villous cytotrophoblast and syncytial fragments in vitro.

Growth and survival of the trophoblast layer of the human placenta depends on continuous incorporation of villous trophoblast stem cells (cytotrophoblast), by syncytial fusion, into the syncytiotrophoblast. Descriptive studies suggest that this process may be intimately related to apoptosis. We have analyzed the expression and activation of initiator and execution caspases, critical effectors of apoptosis, in relation to trophoblast turnover (differentiation) in human placental villi. We used immunohistochemistry, caspase enzyme histochemistry, caspase activity assays, Western blots, and autoradiography techniques on placental tissue sections, trophoblast lysates, villous explants, and isolated trophoblast fragments (villous cytotrophoblast and mononuclear syncytial elements) in vitro. Our data demonstrate expression of initiator caspases 8 and 10 and activity of caspase 8 in villous cytotrophoblast. Proforms of the execution caspases 3, 6, and 7 were also expressed in villous cytotrophoblast, but activation of execution caspases 3 and 6 could only be demonstrated in the syncytiotrophoblast after syncytial fusion. Down-regulation of the general transcription level (reduced incorporation of [3H]uridine) as well as cleavage of the execution caspase substrates poly-(ADP-ribose)polymerase and lamin B was confined to syncytiotrophoblast and preceded the final events of apoptotic death (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling reactivity and nuclear collapse). Our data confirm that the apoptosis cascade in villous trophoblast is regulated in parallel with trophoblast differentiation, syncytial fusion, and trophoblast turnover.

Apoptosis↗

PubMed1999

[Trophoblast invasion in pre-eclampsia].

It is generally accepted that insufficient invasion of trophoblast cells into the myometrial portions of the spiral arteries is thought to play a crucial role in the development of preeclampsia. As a consequence, uteroplacental vessels fail to undergo adaptive changes which are imperative to provide a sufficient blood supply to the placenta. Consecutive placental hypoxia is supposed to cause secretion/shedding of still unidentified placental metabolites resulting in different forms of pregnancy-induced hypertension. This review presents published data concerning the causes of insufficient trophoblast invasion in preeclampsia. Expression of HLA-G by extravillous trophoblast cells seems to be altered, resulting in activation of the maternal immune system. The pattern of integrin expression as well as the secretion of proteases is reported to be disturbed, which could lead to a reduced invasive potential of the trophoblast cells. Recent data indicate a pathophysiological role of NK-cells and macrophages in the altered trophoblast invasion. Also angiotensinogen Thr235 polymorphism seems to alter early physiologic changes in spiral arteries. In summary, preeclampsia seems to be induced by a multifactorial disturbance of trophoblast invasiveness which is characterized by reduced invasiveness of the trophoblast cells themselves and by an activated maternal immune response blocking the invasion by the semiallogenic trophoblast.

Female↗

PubMed1998

Increased fetoplacental angiogenesis during first trimester in anaemic women.

BACKGROUND: Epidemiological studies describe an association between relative size of the placenta at delivery and cardiovascular morbidity and mortality during adult life. Some determinants of placental size, such as maternal anaemia, have been acknowledged, but no plausible mechanism has been advanced to explain the initiation of postnatal disease. METHODS: Placental villous vascularisation in anaemic women (Hb<90 g/L) was assessed in the first and third trimesters of pregnancy by immunohistochemical identification of villous capillaries and compared with that of gestational age-matched groups of women with normal (Hb>110 g/L; control group) concentrations of haemoglobin, and an intermediate group (Hb 90-110 g/L). FINDINGS: Anaemia, especially in the first trimester, was associated with increased numbers of capillaries per villous cross section (mean 11.70 [SE 0.35] vs 4.14 [0.27]) located mainly in the outer third of the stroma beneath the trophoblast (94% [1.15] vs 67% [1.82]) and with increased numbers of villous macrophages and of proliferating MIB-1-positive cells compared with the control group. INTERPRETATION: Maternal anaemia in early pregnancy seems to influence the pattern of placental vascularisation. Such changes might alter placental vascular impedance during early fetal life, thereby exerting important effects on cardiovascular development.

Adult↗

PubMed1998

Percutaneous transluminal coronary angioplasty reverses vasoconstriction of stenotic coronary arteries in hypertensive patients.

BACKGROUND: Endothelial dysfunction of coronary arteries with impaired vasodilation has been reported in patients with arterial hypertension. However, the effect of dynamic exercise on coronary vasomotion of a stenotic vessel segment before and after PTCA has not yet been evaluated in these patients. METHODS AND RESULTS: Coronary vasomotion of a normal and a stenotic vessel segment was studied in 39 patients with coronary artery disease during supine bicycle exercise before and 9+/-3 months after PTCA. Luminal area changes were determined by biplane quantitative coronary arteriography. There were 21 normotensive and 18 hypertensive patients who did not differ with regard to clinical characteristics. Percent area stenosis decreased after PTCA from 90% to 39% (P<0.001) in normotensive and from 86% to 33% (P<0.001) in hypertensive patients. Exercise-induced vasomotion of the normal vessel segment was significantly different between normotensives and hypertensives before (+19% versus +1%, P<0.01) and after (+16% versus +3%, P<0.01) PTCA. In contrast, stenotic vessel segments showed vasoconstriction in both normotensive and hypertensive patients (Deltaexercise, -11% versus - 20%, P=NS), which was reversed after PTCA (+3% versus +2%, P=NS). CONCLUSIONS: Normal coronary arteries show reduced vasodilation during exercise in hypertensive patients that may be explained by the presence of endothelial dysfunction. Stenotic vessels demonstrate paradoxical vasoconstriction during exercise in both normotensive and hypertensive patients. PTCA reverses vasoconstriction by elimination of the flow-limiting stenosis and prevention of coronary stenosis narrowing during exercise in normotensive and hypertensive patients.

Adult↗

PubMed1998

[Diagnosis and indication for aortic valve replacement in asymptomatic and symptomatic patients with aortic regurgitation].

Chronic volume overload is associated with dilatation and eccentric hypertrophy of the left ventricle (= ventricular remodeling). With the dilatation of the left ventricle and the shift of the pressure-volume-relationship to the right, the filling pressures can be kept normal despite severe regurgitation. Therefore, the patient with aortic regurgitation can remain asymptomatic over many years. Thus, the indication for aortic valve replacement in patients with severe aortic regurgitation is sometimes difficult and may lead to problems to choose the optimal time point for operation. As a general rule, symptomatic patients with severe aortic regurgitation should be operated as soon as possible. In asymptomatic patients with significant dilatation of the left ventricle and reduction of systolic pump function the therapy of choice is aortic valve replacement. Asymptomatic patients with normal left ventricular function have usually a good prognosis with a yearly mortality rate of approximately 0.04%. However, in the presence of significant dilatation of the left ventricle, i.e. enddiastolic chamber diameter more than 70 mm respectively endsystolic diameter more than 50 mm, patients have to be checked on a regular basis, i.e. in yearly intervals to detect left ventricular dysfunction in due time. According to the literature, asymptomatic patients with severe aortic regurgitation develop left ventricular dysfunction in a yearly rate of 4%. However, approximately 50% of all patients are even after 10 years asymptomatic. The indication for aortic valve replacement is given when the patient shows a deterioration of left ventricular function or becomes symptomatic. Valve replacement is also indicated in patients with an ejection fraction below 50% and/or endsytolic chamber diameter of more than 55 mm. Therapy of choice in symptomatic patients with severe aortic regurgitation is aortic valve replacement. In asymptomatic patients, operation depends on the degree of chamber dilatation respectively the severity of left ventricular dysfunction. In patients with severe aortic regurgitation but without clinical symptoms and moderate enlargement of the left ventricle regular check-ups in yearly intervals are indicated. In the presence of severe left ventricular dilatation check-ups should be performed on a half-year basis to prevent irreversible damage to the heart muscle.

Aortic Valve Insufficiency↗

PubMed1998

Near fatal anticholinergic intoxication after routine fundoscopy.

We describe a case of severe anticholinergic intoxication following the topical instillation of tropicamide-containing eyedrops. Tropicamide is a short-acting atropine-like derivative and has been regarded as an effective and safe mydriatic. Half an hour after routine fundoscopy, a 62-year-old man experienced two generalized seizures with respiratory arrest and required intubation and mechanical ventilation. The patient was treated with physostigmine and made a full recovery.

Antidotes↗

PubMed1998

Enhanced coronary vasoconstriction after PTCA in patients with acute ischemia.

UNLABELLED: Coronary vasoconstriction of the distal vessel segment has been reported after percutaneous transluminal coronary angiography (PTCA), which was explained by increased vasoconstrictor influences. In patients with acute ischemia these changes may be even enhanced. Thus, vasomotion of the epicardial coronary arteries was studied before and after PTCA in patients with acute ischemia due to unstable angina or acute infarction. METHODS: 52 patients were divided into 2 groups: Group 1 (controls) consisted of 31 patients who underwent elective (PTCA) and group 2 of 21 patients who underwent emergency PTCA for unstable angina or acute infarction. Coronary artery dimensions proximal and distal to the culprit lesion were determined by quantitative coronary angiography before and after PTCA as well as after 0.2 mg nitroglycerin i.c. at the end of the procedure. RESULTS: Stenosis severity was similar before and after PTCA in both groups (before, 91 +/- 8% in group 1 vs 90 +/- 9% in group 2; after, 28 +/- 9% vs 23 +/- 10%, resp.). Heart rate and mean blood pressure remained unchanged. In the group with acute ischemia no vasodilation of the proximal (2 +/- 3%) and distal vessel (-1 +/- 4%) occurred after PTCA, whereas in the control group significant vasodilation of both vessel segments (11 +/- 2% resp. 13 +/- 3%) was found. The response to nitroglycerin was maintained in both groups. In the control group there was a significant correlation between stenosis severity and percent diameter change of the distal vessel segment. However, in the acute ischemic group this relationship was shifted downwards suggesting an enhanced vasoconstrictor response in these patients. CONCLUSIONS: Epicardial coronary arteries in patients with acute ischemia show an enhanced vasoconstriction after PTCA. Nevertheless, the response to nitroglycerin is maintained suggesting that functional (endothelial dysfunction) rather than structural factors are responsible for this phenomenon.

Adult↗

PubMed1998

Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta.

Villous trophoblast in the human placenta consists of a population of proliferating stem cells which differentiate and individually fuse into the syncytiotrophoblast. We studied the apoptotic cascade in this complex epithelial layer by immunohistochemical localization of Fas, FasL, Bcl-2, Mcl-1, pro-caspase-3 and caspase-3, T-cell-restricted intracellular antigen-related protein (TIAR), poly(ADP-ribose) polymerase (PARP), lamin B, topoisomerase IIalpha, and transglutaminase II in cryostat and paraffin-fixed tissue sections from normal human first-trimester and term placental villi. The relationship between the apoptotic cascade and syncytial fusion was studied by coincubation of intact villi with FITC-coupled annexin-V, to detect the phosphatidylserine flip, and propidium iodide, to detect plasma membrane permeability. The final events of the apoptotic cascade were studied by the TUNEL reaction and ultrastructural appearance of the trophoblast. The phosphatidylserine flip was identified in some of the villous cytotrophoblastic cells, but the presence of both Bcl-2 and Mcl-1 proteins presumably prevented continuation of the apoptotic cascade. The syncytiotrophoblast demonstrated heterogeneous findings, suggesting variable progression along the apoptotic cascade. In some areas Bcl-2 and Mcl-1 predominated, with preservation of the nuclear proteins PARP, lamin B, and topoisomerase IIalpha; in other areas, especially in and around syncytial sprouts, Bcl-2 and Mcl-1 were absent, accompanied by loss of nuclear proteins, presence of phosphatidylserine flip, and TUNEL positivity. These data suggest that the apoptotic cascade is initiated in the villous cytotrophoblast, which in turn promotes syncytial fusion. Donation of anti-apoptotic proteins into the syncytium, such as Bcl-2 and Mcl-1, focally inhibits further progression along this cascade. Completion of the apoptotic cascade takes place in and around syncytial sprouts, providing further evidence that these are the sites of trophoblast shedding into the maternal circulation.

Apoptosis↗

PubMed1998

Immunohistochemistry of matrix metalloproteinases (MMP), their substrates, and their inhibitors (TIMP) during trophoblast invasion in the human placenta.

The invasion of extravillous trophoblast cells into the maternal endometrium is one of the key events in human placentation. The ability of these cells to infiltrate the uterine wall and to anchor the placenta to it as well as their ability to infiltrate and to adjust utero-placental vessels to pregnancy depends, among other things, on their ability to secrete enzymes that degrade the extracellular matrix. Most of the latter enzymes belong to the family of matrix metalloproteinases. Their activity is regulated by the tissue inhibitors of matrix metalloproteinases. We have studied the distribution patterns of matrix metalloproteinases-1, -2, -3, and -9 and their inhibitors TIMP-1 and TIMP-2 as compared to the distribution of their substrates along the invasive pathway of extravillous trophoblast of 1st, 2nd, and 3rd trimester placentas by means of light microscopy on paraffin and cryostat sections as well as at the ultrastructural level (only 3rd trimester placenta). The comparison of different methods proved to be necessary, since the immunohistochemical distribution patterns of these soluble enzymes are considerably influenced by the pretreatment of tissues. All three methods revealed immunoreactivities of both, proteinases and their inhibitors, not only intracellularly in the extravillous trophoblast but also extracellularly in its surrounding matrix, the distribution patterns depending on the stage of pregnancy and on the degree of differentiation of trophoblast cells along their invasive pathway. Within the extracellular matrix, immunolocalization of matrix metalloproteinases as well as their inhibitors showed a specific relation to certain extracellular matrix molecules.

Collagen↗

PubMed1998

The extent of trophoblast invasion in the preplacental vasculature of the guinea-pig.

Pregnancy-induced structural changes in spiral arteries seem to be a prerequisite for successful fetal outcome in humans. It is unknown whether these changes also occur in other preplacental vessels (radial and arcuate arteries) in normal pregnancies. Since the radial and arcuate arteries need to dilate in order to accommodate the increase in placental blood flow during pregnancy, it is expected that they are also invaded by trophoblast and respond with structural changes. The objective of the present study was to evaluate the extent of trophoblast invasion in the guinea-pig preplacental vasculature and its effect on the vascular structure of mesometrial, myometrial and arcade arteries. Under general anaesthesia the vascular system of non- (n = 4), mid- (n = 4) and late- (n = 8) pregnant guinea-pigs was fixed by immersion or perfusion. Cross-sections of immersion-fixed mesometrial and arcade arteries were stained with toluidine blue. Cross-sections of perfusion-fixed mesometrial, myometrial and arcade arteries were stained with haematoxylin-eosin, Elastica van Gieson staining and antibodies against alpha-smooth-muscle-actin (ASMA), cytokeratin and factor VIII, to detect vascular smooth muscle, trophoblastic, and endothelial cells, respectively. In addition, the external and internal vascular circumference of sections from perfusion-fixed tissue was determined. All cross-sections were evaluated by light microscopy. In the course of pregnancy, progressive endothelial swelling, disappearance of the elastic lamina interna and disarrangement of the tunica media were observed in the myometrial and throughout the mesometrial arteries up to the junction with the arcade arteries. These changes coincided the migration of keratin-positive staining giant cells. It is concluded that in normal guinea-pig pregnancy, structural changes occur in the entire mesometrial artery and at least a part of the myometrial artery, although such changes were not seen in the arcade artery.

Actins↗

PubMed1998

Immunohistochemical identification of the receptor for urokinase plasminogen activator associated with fibrin deposition in normal and ectopic human placenta.

The receptor for urokinase plasminogen activator (uPAR) is a key molecule in cell surface-directed plasminogen activation. uPAR binds urokinase plasminogen activator (uPA) and thereby focuses plasminogen activation on the cell surface. Plasmin dissolves fibrin deposits and facilitates cell migration during tissue repair processes by degrading the extracellular matrix. During human implantation and placental development, plasmin is considered important for both trophoblast migration/invasion and for fibrin surveillance. This study examined the expression of uPAR in normal and ectopic human placentae by immunohistochemistry. In first and third trimester normal placentae as well as in tubal ectopic placental tissues, a high uPAR expression was seen in the trophoblast associated with deposits of fibrin-type fibrinoid. Extravillous trophoblast of the basal plate, of the cell islands, and of the cell columns was also positive for uPAR in the first trimester whereas at term the expression of the protein was decreased. Moreover, uPAR immunostaining was observed in decidual cells throughout normal gestation and in endometrial tissues of patients with ectopic pregnancies. These findings suggest that uPAR participates in placental development and in trophoblast invasion particularly in the first trimester of pregnancy and that uPAR is involved in repair mechanisms of the trophoblast and fibrin surveillance.

Adult↗

PubMed1998

Cardiac risk after mediastinal irradiation for Hodgkin's disease.

PURPOSE: To evaluate the risk of cardiac lesions after conventionally fractionated irradiation (Rt) of the mediastine with or without chemotherapy (Ct) in patients with Hodgkin's disease (HD) and to relate them to known cardiovascular risk factors. PATIENTS AND METHODS: Between 1964 and 1992, 352 (total group) patients with HD were treated with curative intention using Rt with or without Ct including the mediastine and had a follow-up of at least 1 year. More than 96% of the patients had a complete follow-up. One hundred forty-four patients (64% of the living patients, heart study group) have regular follow-up in our department and had a special heart examination including rest and exercise ECG, echocardiography and myocardial perfusion scintigraphy (112 patients). Doses per fraction in the anterior heart region were between 1.3 and 2.1 Gy. Total doses were between 30.0 and 42.0 Gy in 93% of cases. The mean length of follow-up was 11.2 years (range 1.0-31.5 years). Other cardiovascular risk factors evaluated were body mass index, blood pressure, smoking history, diabetes mellitus, hypercholesterolemia and history of coronary artery disease before Rt. RESULTS: In the total group, the risk of fatal cardiac ischemic events and/or of sudden unexpected death was significantly higher than expected with a relative risk of 4.2 for myocardial infarction and 6.7 for myocardial infarction or sudden death. In female patients and in patients without other cardiovascular risk factors, the risk of fatal or non-fatal ischemic cardiac events was not significantly different from the expected value. In the subgroup with no cardiovascular risk factors and treatment without Ct, there was no ischemic or other major cardiac event. Echocardiography showed valvular thickenings in a large amount of the patients (the cumulative risk after 30-year follow-up was above 60%) but mostly without hemodynamic disturbance. In patients without hypertension and without coronary artery disease, findings of perfusion scintigraphy and echocardiographic evaluation of systolic and diastolic function were normal. Treatment with Ct was not a significant risk factor for cardiac events but the number of patients whose treatment included adriamycin and with a follow-up exceeding 10 years is to low for a definitive evaluation. CONCLUSIONS: In patients without the usual cardiovascular risk factors (smoking, hypertension, obesity, hypercholesterolemia, diabetes mellitus) the risk of serious cardiac lesions after conventionally fractionated irradiation of the mediastinum with an intermediate total dose between 30 and 40 Gy is low. Also the cardiac risk of the combination of this irradiation with Ct including adriamycin with a total dose between 200 and 300 mg/m2 seems low but further long-term observation is necessary.

Adolescent↗

PubMed1998

Influence of the culprit lesion on clinical symptoms of coronary artery disease, with special emphasis on exercise data.

BACKGROUND: Clinical symptoms have been found to correlate only poorly with the severity of the culprit lesion in coronary artery disease. The purpose of the present study was to evaluate the influence of the culprit lesion and its change during exercise on clinical symptoms in patients with this condition. METHODS: Minimal luminal area was determined using biplane quantitative coronary angiography in 42 patients (aged 53 +/- 8 years) with coronary artery disease. Percent diameter stenosis and minimal luminal area and its change during exercise were assessed in all patients and compared with clinical symptoms judged according to the functional classification of the New York Heart Association (NYHA). Coronary dimensions were determined with the patient at rest, during supine bicycle exercise and after sublingual administration of 1.6 mg glyceryl trinitrate. RESULTS: Exercise-induced vasoconstriction of the culprit lesion was found in all patients (-14.0% at 102 W), but there was exercise-induced vasodilatation in the normal vessel segments (+13.0%). However, only minimal vasoconstriction was found in groups 1 (NYHA I: -0.5%, NS) and 2 (NYHA II: -4.7%, NS), but significant constriction in groups 3 (NYHA II-III: -18.0%, P < 0.01) and 4 (NYHA III: -31.4, P < 0.01). Vasodilatation of the normal vessel segments was similar in the four groups. The observed inverse relationship between exercise-induced changes in minimal luminal area and NYHA classification was stronger than the relationship between NYHA and minimal luminal area when the patient was at rest. There was no correlation between glyceryl trinitrate-induced vasodilatation and NYHA classification. CONCLUSIONS: The more severe the culprit lesion, the more pronounced the exercise-induced vasoconstriction. This effect of the culprit lesion was reflected by the clinical symptoms: the greater the exercise-induced vasoconstriction, the higher the NYHA classification. Thus the anatomy of the lesion (= severity) and the functional integrity of the endothelium (= exercise-induced vasomotion) are two major determinants of clinical symptoms.

Cardiac Catheterization↗

PubMed1998

Neopterin plasma concentrations predict the course of severe acute pancreatitis.

In a prospective, descriptive study in 25 patients with acute pancreatitis neopterin plasma concentrations were found to be associated with the severity of the disease, which was assessed using weights of the worst 17 physiological abnormalities of the APACHE-III score over a 24 h-period after hospital admission. Neopterin concentrations were higher in severe pancreatitis (n = 10) compared to mild disease, and there existed a positive exponential correlation between neopterin and the Acute Physiology Score (r = 0.66). Higher neopterin concentrations were associated with the development of multiple organ failure (p = 0.012) and death (p = 0.019). At a cut-off concentration of 12 nmol/l the sensitivity (80%) and specificity (100%) of neopterin for the discrimination between mild and severe clinical course of pancreatitis was more accurate than C-reactive protein at a risk threshold of 1.2 g/l (70% and 87%). Development of pancreatic necrosis was associated with higher neopterin concentrations than edematous pancreatitis (p < 0.001).

Adult↗

PubMed1998

Flow-dependent vasodilation in the coronary circulation: alterations in diseased states.

Flow-dependent vasodilation has been recognized to play an important role in the perfusion of the myocardium and the occurrence of myocardial ischaemia. In the past few years, the role of the endothelium in the regulation of coronary artery dimensions has gained a lot of attraction. Changes in coronary artery size are caused through the contraction and relaxation of the smooth musculature within the vessel wall. Vasoactive substances released from the endothelium play a crucial role in the regulation of vessel size and coronary vasomotor tone. During physiologic exercise, normal coronary arteries dilate, whereas stenotic arteries constrict. This abnormal behaviour of the stenotic artery has been associated with the occurrence of myocardial ischaemia, and has been thought to be either due to: endothelial dysfunction with reduced release or production of the endothelial derived relaxant factor (EDRF); an increased sympathetic stimulation during exercise; enhanced platelet aggregation with release of thromboxane A2 and serotonin; and/or a passive collapse of the disease-free vessel segment within the stenosis when blood-flow velocity increases during exercise. Thus, a diseased coronary endothelium may have a dramatic effect on the function of the coronary arteries, and may cause or contribute to the occurrence of myocardial ischaemia under high-demand situations, e.g. physical exercise or mental stress. Changes in flow-dependent vasodilation have been described in various disease states, e.g. hypercholesterolaemia, hypertension, diabetes mellitus, but also in valvular heart disease, heart failure and transplantation. Most of these alterations are due to functional changes of the endothelium, but vascular remodelling of the coronary arteries with thickening of the intima and an enlargement of the artery may affect these functional changes importantly.

Coronary Circulation↗

PubMed1998

Recommended dietary allowances (RDA) in the dietary management of children and adolescents with IDDM: an unfeasible target or an achievable cornerstone?

A diet in line with RDAs is seldom achieved by IDDM patients. High post-prandial glucose levels are often attributed to food excess rather than to inadequate insulin doses. Lower dietary CHO with greater fat (in particular SFA) and protein are progressively scheduled instead of increasing insulin units. We studied 194 IDDM patients (1-23 yr) on a diet conforming to RDAs with a restriction of sucrose and without a quantitative approach and exchange lists of food for one year. The diet consisted of a high intake of starchy foods and vegetables and a restricted amount of animal products. HbA1c mean values of the year were used as an indicator of metabolic control. The mean daily insulin dose was 0.53 U/kg in patients with diabetes duration (DD) < 2 yr and 0.81 U/kg in those with DD > 2 yr. Mean annual HbA1c was 7.1 +/- 0.9%. The prevalence of obesity was low (5.7%). Adolescent females were more obese than males. A dietary approach in line with RDA requirements, that may help prevent any complications related to an inappropriate diet pattern, coupled with a dynamic insulin adjustment, is the first-line intervention to prevent complications in IDDM patients.

Adolescent↗

PubMed1997

[Anemia and heart function].

Anemia typically leads to a state of hyperkinetic circulation with tachycardia, reduced peripheral resistance, increased stroke volume chamber dilatation, and finally to the development of left ventricular hypertrophy. These changes are usually well tolerated by patients with a healthy heart. In patients with heart diseases, however, anemia may lead to deterioration of ventricular performance and to increased morbidity and mortality respectively. Specific changes in cardiac function may arise depending on the causes of anemia such as myocardial iron deposition and dilatative cardiomyopathy in hemolytic anemia or alterations of homeostasis and reduction of cardiac function in renal anemia. With respect to cardiac function the cause of anemia must be corrected as far as possible and hemoglobin kept over a level of 10 g/dl. As far as renal anemia is concerned this goal can be reached by regular administration of erythropoietin and/or iron respectively.

Anemia↗