IL-6 levels in acute and post myocardial infarction: their relation to CRP levels, infarction size, left ventricular systolic function, and heart failure

BACKGROUND: Inflammatory mechanisms in heart disease are of great interest. The proinflammatory cytokine interleukin (IL) 6 has been linked to increased morbidity in unstable angina pectoris and depressed myocardial function in heart failure (HF). METHODS: We studied the relation of IL-6 levels to C-reactive protein (CRP), infarction size, left ventricular function, and HF in acute myocardial infarction (MI) and after hospital discharge in 31 consecutive patients (19 males, mean age 69+/-13 years). Blood sampling for IL-6 was performed on admittance, four times on day 1, twice on day 2, and once daily on days 3-5, and 6 and 12 weeks later. Clinical signs of HF were evaluated daily during hospitalization and after 6 and 12 weeks. Echocardiography was performed on day 3 and at 6 weeks. RESULTS: IL-6 showed a curved time course with elevated levels already on admittance (mean+/-S.D. 19.3+/-26.9 ng/l), thereafter increasing to a peak on days 1 and 2 (maximum 68.5+/-152.9 ng/l), and then declining rapidly to lower, although not normalized, levels during hospitalization and at 6 and 12 weeks. CRP showed a similar time pattern, but with a later peak and a seemingly less rapid decline in levels. Mean levels of IL-6 and CRP on days 1-5 correlated highly (r=0.794, p<0.0001). IL-6 and infarction size did not correlate. HF during hospitalization and at 6 weeks was not related to IL-6; however, patients with HF at 12 weeks had higher IL-6 levels, both at 6 and 12 weeks. Patients on ACE inhibitors or diuretics at discharge had higher IL-6 levels at 6 weeks. IL-6 during hospitalization was not related to LVF; yet, patients with depressed LVF in the hospital and at 6 weeks had higher IL-6 levels at 6 and 12 weeks. CONCLUSIONS: IL-6 in acute MI shows a curved time course and is highly correlated to CRP. It peaks on days 1 and 2 and remains elevated even after 12 weeks. Increased IL-6 levels after hospital discharge are associated with HF and depressed LVF. Whether anti-inflammatory agents will influence left ventricular dysfunction and outcome postacute MI has yet to be determined.     

Association between a functional polymorphism in the progesterone receptor gene and panic disorder in women

Although genetic factors are known to be important risk factors for panic disorder there is as yet no conclusive data regarding specific gene variants. Prompted by evidence supporting progesterone to influence the pathophysiology of panic disorder, polymorphisms in the progesterone receptor gene, a single nucleotide polymorphism (G331A) and an insertion/deletion polymorphism (PROGINS) were investigated in 72 patients with panic disorder and 452 controls. The frequency of the A-allele of the G331A polymorphism was higher in panic disorder patients than in controls (p = 0.01). When male and female patients were analyzed separately, the association was observed in female patients only (p = 0.0009), with an odds ratio of 3.5. No differences between groups were observed for the PROGINS polymorphism. In conclusion, these data suggest that the G331A polymorphism in the progesterone receptor gene may influence the risk for panic disorder in women.     

The pharmacokinetics of antiviral therapy in paediatric patients

Effective treatment requires administration of optimal drug dose. In paediatric patients this may be difficult to achieve due to lack of pharmacokinetic studies, administration of small doses, changes in body composition, continuous growth, and development and maturation of organs and systems. This article reviews the factors and misconceptions associated with determining optimal drug dose and route of administration in different paediatric populations. The pharmacokinetics, appropriate doses and preferred routes of administration for aciclovir, ganciclovir, famciclovir, foscarnet and cidofovir, for treating herpesvirus infections in the paediatric population, are discussed.     

Hypovolemia is a main factor behind disturbed perfusion and metabolism in the intestine during endotoxemia in cat

Disturbances in intestinal metabolism and perfusion during SIRS can be direct effects of toxic substances, and/or effects secondary to hypovolemia. An attempt to evaluate the significance of hypovolemia for intestinal disturbances during SIRS was made in the present study on feline by evaluating the degree to which the intestinal alterations following endotoxin infusion were restored by a clinically relevant volume infusion. The results were compared with control animals treated identically except that they were not given a volume infusion. We analyzed effects of a colloid infusion during endotoxemia on intestinal perfusion, and on the metabolites lactate, pyruvate, glucose, and glycerol in the intestinal wall, the latter by a microdialysis technique. Arterial and central venous blood pressures, and superior mesenteric artery blood flow were measured, and intestinal oxygen delivery and uptake were calculated. To evaluate to what extent a restoring effect of a colloid infusion was dependent on the type of colloid solution used, three different colloids with about the same volume expanding effects (6% albumin, 6% dextran 70 and 6% hydroxyethyl starch, n = 3 x 6) were tested randomly and blinded. Four hrs after start of endotoxin (1 mg/kg + 1 mg/kg/h), the colloid was infused at a rate of 5 mL/kg for 30 min followed by 2.5 mL/kg/h. Endotoxin caused a marked deterioration of perfusion and metabolic parameters. Most of these parameters turned towards normalization, though not fully reaching baseline values within 4 hrs after start of the colloid infusion. In the control experiments (n = 4), the endotoxin-induced deteriorations persisted or were aggravated during the corresponding time period. The results indicated that hypovolemia is an essential factor but not the only one behind alterations in metabolism and perfusion in the intestine during SIRS, and the alterations can be significantly reduced by adequate volume substitution. In this respect no differences could be seen between the three colloids tested.     

Local allergic reaction in food-hypersensitive adults despite a lack of systemic food-specific IgE

BACKGROUND: Objective tools are lacking for the diagnosis of local gastrointestinal inflammatory reactions in skin prick test (SPT)-negative and serum IgE antibody (s-IgE Ab)-negative patients with suspected food allergy. OBJECTIVE: The purpose of this investigation was to evaluate the presence of eosinophils, T cells, local IgE-bearing cells, IL-4, and IFN-gamma in small intestinal biopsy specimens from adult SPT-negative/s-IgE Ab-negative patients with food allergy during symptomatic and nonsymptomatic periods. METHODS: Fourteen patients with food allergy-related gastrointestinal symptoms confirmed by double-blinded, placebo-controlled food challenge (DBPCFC) were investigated. Eleven of the patients were SPT-negative and s-IgE Ab-negative. Sex- and age-matched healthy volunteers were used as controls. Duodenal biopsies were studied with immunostaining through use of a panel of mouse monoclonal antibodies specific for eosinophils, CD3, CD4, CD8, IgE, IL-4, and IFN-gamma. RESULTS: Significant increases in numbers of MBP+ eosinophils, IgE-bearing cells, and T cells were found in the duodenal mucosa of the patients when they were symptomatic in comparison with when they were asymptomatic and in comparison with healthy controls. Numbers of IL-4+ cells were increased and numbers of IFN-gamma+ cells were reduced in the patients when they were symptomatic in comparison with when they were asymptomatic and in comparison with the controls. There were no differences in total s-IgE levels between any of the groups. CONCLUSION: A significant correlation was found between the appearance of symptoms of food hypersensitivity and the duodenal presence of IgE-bearing cells, activated eosinophils, and T cells in patients with negative SPT results and negative s-IgE Ab to the offending food. We suggest that a localized IgE-mediated response caused the gastrointestinal symptoms seen in these patients.     

Visualisation of the normal adrenals at SPET examination with <Superscript>111</Superscript>In-pentetreotide

On single-photon emission tomography (SPET) examinations with indium-111 pentetreotide, we have often observed a small "hot" spot close to the upper portion of the left kidney. While it was initially believed that this represented a tumour in the tail of the pancreas or in the left adrenal, we now understand that it represents normal adrenal uptake. Since the adrenals have not been described as normally visualised, this uptake may interfere with the interpretation of the examination. We have studied how often the normal adrenals are visualised at such examinations. One hundred consecutive clinical (111)In-pentetreotide examinations in adults including SPET of the abdomen and with normal findings were studied. All examinations with a hot spot attributable to the adrenals were, when available, compared with computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen performed on clinical grounds within 3 months before or at any time after the scintigraphy. In 11 patients both adrenals were visualised. In 27 patients only the left and in one only the right adrenal was visualised. CT or MRI examinations were available for comparison in 25 of these 39 patients. Two of these showed a pathological finding in the left adrenal. A conservative interpretation is that the normal adrenal is visualised on one or both sides in at least one-quarter of adults at SPET examination with (111)In-pentetreotide.     

Syncope--an unusual presentation of ventricle dysfunction in a patient with Fontan circulation

We report a case of recurrent syncope in association with moderate ventricular dysfunction and mild AV-valve regurgitation in an 18-year-old girl, 4 years after she underwent total cavopulmonary connection surgery. Cardiac catheterization revealed a transpulmonary gradient of 1-2 mmHg. During exercise, a dramatic fall in blood pressure and blood oxygenation was observed, paralleled by an increase in heart rate and central venous pressure. Although a slight increase in pulmonary vascular resistance could not be excluded, the reaction was interpreted in terms of an extremely low transpulmonary gradient in association with ventricular dysfunction. Five months after heart transplantation, the patient has been completely free from syncope. Fontan circulation usually involves a delicate haemodynamic situation which may necessitate haemodynamic re-evaluations, including dynamic measurements of the central venous pressure during exercise. Also a moderate ventricular dysfunction may result in compromised pulmonary circulation which in turn may lead to syncope during exercise as a result of insufficient systemic circulation.