Interleukin-6 release is higher across arm than leg muscles during whole-body exercise

Exercising muscle releases interleukin-6 (IL-6), but the mechanisms controlling this process are poorly understood. This study was performed to test the hypothesis that the IL-6 release differs in arm and leg muscle during whole-body exercise, owing to differences in muscle metabolism. Sixteen subjects (10 men and six women, with body mass index 24 ± 1 kg m(-2) and peak oxygen uptake 3.4 ± 0.6 l min(-1)) performed a 90 min combined arm and leg cycle exercise at 60% of maximal oxygen uptake. The subjects arrived at the laboratory having fasted overnight, and catheters were placed in the femoral artery and vein and in the subclavian vein. During exercise, arterial and venous limb blood was sampled and arm and leg blood flow were measured by thermodilution. Lean limb mass was measured by dual-energy X-ray absorbtiometry scanning. Before and after exercise, biopsies were obtained from vastus lateralis and deltoideus. During exercise, IL-6 release was similar between men and women and higher (P < 0.05) from arms than legs (1.01 ± 0.42 and 0.33 ± 0.12 ng min(-1) (kg lean limb mass)(-1), respectively). Blood flow (425 ± 36 and 554 ± 35 ml min(-1) (kg lean limb mass)(-1)) and fatty acid uptake (26 ± 7 and 47 ± 7 μmol min(-1) (kg lean limb mass)(-1)) were lower, glucose uptake similar (51 ± 12 and 41 ± 8 mmol min(-1) (kg lean limb mass)(-1)) and lactate release higher (82 ± 32 and -2 ± 12 μmol min(-1) (kg lean limb mass)(-1)) in arms than legs, respectively, during exercise (P < 0.05). No correlations were present between IL-6 release and exogenous substrate uptakes. Muscle glycogen was similar in arms and legs before exercise (388 ± 22 and 428 ± 25 mmol (kg dry weight)(-1)), but after exercise it was only significantly lower in the leg (219 ± 29 mmol (kg dry weight)(-1)). The novel finding of a markedly higher IL-6 release from the exercising arm compared with the leg during whole-body exercise was not directly correlated to release or uptake of exogenous substrate, nor to muscle glycogen utilization.     

Detection of IgA antibodies to cat, β-lactoglobulin, and ovalbumin allergens in human milk

Background: The relationship between the development of allergy during infancy and breast-feeding remains controversial. This controversy may be due to individual variations in the composition of human milk. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is still unknown. IgA antibodies to inhalant allergens have not been previously detected. Objective: Our purpose was to analyze secretory IgA antibody levels to cat, β-lactoglobulin, and ovalbumin allergens in colostrum and mature milk in relation to maternal allergy. Methods: Colostrum and samples of mature milk were obtained after 1 and 3 months of lactation from 53 nursing mothers (17 allergic and 36 nonallergic mothers) and were analyzed for total secretory IgA levels by ELISA and secretory IgA antibodies to cat, β-lactoglobulin, and ovalbumin by an enzyme-amplified ELISA. The specificity of the assays was confirmed by inhibition experiments. Results: Secretory IgA to cat, β-lactoglobulin, and ovalbumin allergens were detected in colostrum as well as mature milk. The levels of secretory IgA to ovalbumin were lower in colostrum from allergic mothers with P = .016, whereas the levels to β-lactoglobulin and cat were similar in the 2 groups. IgA antibodies to ovalbumin were detected in 94% of the colostrum samples from allergic and in all samples from nonallergic mothers, in 82% and 96%, respectively at 1 month, and 53% and 65% at 3 months. Fewer samples had detectable secretory IgA antibodies to β-lactoglobulin than to ovalbumin and cat, and only 33% and 10% of the samples from the allergic and nonallergic mothers, respectively, remained positive at 3 months. All the allergic mothers had detectable IgA to cat in colostrum, whereas 83% and 73% of the samples were positive at 1 and 3 months. The corresponding numbers were 93%, 81%, and 81% in the nonallergic mothers (not significant). Conclusion: Even a low level of exposure of the mucosa (eg, by inhalant allergens) can induce antibody secretion into the milk, both in allergic and nonallergic mothers. (J Allergy Clin Immunol 2000;105:1236-40.)     

Dose-Response Relations for Anal Sphincter Regarding Fecal Leakage and Blood or Phlegm in Stools after Radiotherapy for Prostate Cancer

BACKGROUND: The estimation of the parameters that describe the dose-response relations of anal sphincter regarding the clinical endpoints of fecal leakage and blood or phlegm in stools is important in the optimization of prostate cancer radiotherapy. Also, the validity of the relative seriality model for this clinical case needs to be examined by associating the clinical follow-up results with the predicted complication rates. PATIENTS AND METHODS: In this study, 65 patients who received radiation therapy for clinically localized prostate adenocarcinoma are analyzed. The clinical treatment outcome and the three-dimensional dose distribution delivered to anal sphincter were available for each patient. A questionnaire was used for assessing the clinical bowel and urinary symptoms. A maximum likelihood fitting was performed to calculate the best estimates of the parameters used by the relative seriality model. The clinical utilization of the calculated parameters in predicting anal sphincter complication probabilities was illustrated by applying the best estimate of the parameters to a subset of the patient population. RESULTS: The estimated values of the parameters for the two clinical endpoints are D (50) = 70.2 Gy, gamma = 1.22, s = 0.35 for fecal leakage and D (50) = 74.0 Gy, gamma = 0.75, s approximately 0 for blood or phlegm in stools. The standard deviations of the parameters were also calculated together with the confidence intervals of the dose-response curves. The analysis proved that the treatment outcome pattern of the patient material can suitably be reproduced by the relative seriality model (probability of finding a worse fit = 60.2%, the area under the receiver operating characteristic curve = 0.72 and 0.69 and chi(2)-test = 0.97 and 0.86, respectively). CONCLUSION: Fecal leakage is characterized by a medium relative seriality whereas blood or phlegm in stools was found to have strong volume dependence (low relative seriality). Diminishing the biologically effective uniform dose to anal sphincter < 40-45 Gy may significantly reduce the risk of fecal leakage or blood or phlegm in stools for patients irradiated for prostate cancer.     

Absolute quantification of human liver metabolite concentrations by localized in vivo 31P NMR spectroscopy in diffuse liver disease

Phosphorus-31 NMR spectroscopy using slice selection (DRESS) was used to investigate the absolute concentrations of metabolites in the human liver. Absolute concentrations provide more specific biochemical information compared to spectrum integral ratios. Nine patients with histopathologically proven diffuse liver disease and 12 healthy individuals were examined in a 1.5-T MR scanner (GE Signa LX Echospeed plus). The metabolite concentration quantification procedures included: (1) determination of optimal depth for the in vivo measurements, (2) mapping the detection coil characteristics, (3) calculation of selected slice and liver volume ratios using simple segmentation procedures and (4) spectral analysis in the time domain. The patients had significantly lower concentrations of phosphodiesters (PDE), 6.3±3.9 mM, and ATP-, 3.6±1.1 mM, (P<0.05) compared with the control group (10.0±4.2 mM and 4.2±0.3 mM, respectively). The concentrations of phosphomonoesters (PME) were higher in the patient group, although this was not significant. Constructing an anabolic charge (AC) based on absolute concentrations, [PME]/([PME] + [PDE]), the patients had a significantly larger AC than the control subjects, 0.29 vs. 0.16 (P<0.005). Absolute concentration measurements of phosphorus metabolites in the liver are feasible using a slice selective sequence, and the technique demonstrates significant differences between patients and healthy subjects.     

Cellular uptake of radioiodine delivered by trastuzumab can be modified by the addition of epidermal growth factor

Purpose The purpose of this study was to analyse whether non-radiolabelled epidermal growth factor (EGF) can modify the cellular uptake of ¹²⁵I when delivered as [¹²⁵I]trastuzumab. ¹²⁵I was used as a marker for the diagnostically and therapeutically more interesting isotopes ¹²³I (SPECT), ¹²⁴I (PET) and ¹³¹I (therapy).Methods The cell-associated radioactivity was measured in squamous carcinoma A431 cells following addition of [¹²⁵I]trastuzumab. Different concentrations of [¹²⁵I]trastuzumab and unlabelled EGF were used, and the total, membrane-bound and internalised radioactivity was measured. We also analysed how EGF and trastuzumab affected the cell growth. Results It was generally found that the cellular ¹²⁵I uptake was decreased by the addition of EGF when [¹²⁵I]trastuzumab was added for short incubation times. However, if the incubation times were longer, EGF increased the ¹²⁵I uptake. This shift came earlier when higher [¹²⁵I]trastuzumab concentrations were applied. The addition of EGF also influenced cell proliferation, and concentrations above 10 ng/ml reduced cell growth by approximately 20% after 24 h of incubation.Conclusion By adding unlabelled EGF, it was possible to modify the cellular uptake of [¹²⁵I]trastuzumab. This points towards new approaches for the modification of radionuclide uptake in EGFR- and HER2-positive tumours.     

Atenolol in Migraine Prophylaxis a Double-blind Cross-over Multicentre Study

SYNOPSIS
The prophylactic anti-migraine effect of atenolol was compared to placebo in a multicentre study on 63 patients with classical and/or common migraine. The study design was double-blind cross-over and patients were given atenolol 100 mg o.d. or matching placebo during a study treatment period of 24 weeks. The effect of atenolol was significantly better than that of placebo: integrated headache values were reduced in 70% of the patients (p = 0.004) and the proportion of days with headache was reduced in 59% of the patients (p = 0.010). Few side effects were reported with both atenolol and placebo. This study shows atenolol to be safe and effective in the prophylactic treatment of migraine.     

Blood flow limitation in vivo of small solute transfer during peritoneal dialysis in rats

The aim of this study was to determine whether or to what extent transperitoneal flux of small solutes is reduced at low blood flows during peritoneal dialysis (PD) in rats. Peritoneal blood flow reductions were achieved by bleeding anesthetized (300 g) rats by 25% of their blood volume. After bleeding, a 2 h PD dwell was started using standard PD fluid. The permeability-surface area product (PS) for (51)Cr-EDTA and glucose were assessed, as well as the transperitoneal clearance (Cl) of albumin. Control animals were not bled. After bleeding, peritoneal blood flow declined from 145 +/- 17 perfusion units (PU) to 59 +/- 12 PU (P = 0.001). Concomitant with this reduction, PS for (51)Cr-EDTA fell from 0.284 +/- 0.01 ml/min to 0.216 +/- 0.01 ml/min (P = 0.006) and PS for glucose from 0.338 +/- 0.02 ml/min to 0.294 +/- 0.01 ml/min (P = 0.046). Mean arterial BP (MAP) dropped from 133 +/- 4 mmHg to 61 +/- 5 mmHg (P = 0.008). Cl of albumin fell largely in proportion to the estimated capillary hydrostatic pressure drop, i.e., from 6.1 +/- 0.7 microl/min to 2.3 +/- 0.3 microl/min (P = 0.001). The results demonstrate that the transperitoneal clearances of small solutes are blood flow limited during PD, when peritoneal perfusion is markedly reduced. The level of flow limitation was, however, much lower than expected and observed in other tissues. Albumin transport, which is not blood flow limited, was reduced largely in proportion to the calculated capillary hydrostatic pressure decrease.     

Mobility provocation radiostereometry in anterior cervical spine fusions

This study aimed to evaluate the use of mobility-provocation radiostereometry (RSA) in anterior cervical spine fusions and compare the results to deformation studies on the same patients and plain flexion-extension radiographs. Mobility-provocation RSA was used to evaluate anterior cervical spine fusions in 45 patients. The motions recorded at 3 and 12 months postoperatively were compared to RSA measurements of deformation of the fusion over time and to plain flexion-extension radiographs in the same patients taken 3 months postoperatively. Studies of rotations from right to left revealed ten cases with significant motion at 3 months, and three at 12 months. With motion from flexion to extension, ten cases showed significant motion at 3 months and three at 12 months. In only three cases was the mobility-provocation RSA considered to add any information on the stability of the fusions compared to that obtained with the deformation studies. In 37 patients mobility-provocation radiography in flexion-extension using conventional technique was done to evaluate the accuracy. The mean difference between angular motions recorded on plain radiographs and rotations around the transverse axis in flexion to extension recorded with RSA was 1.6° (range 0.04°–8.04°, SD 2.1°). The corresponding 95% and 99% confidence limits for the difference between the two methods were 5.8° and 7.2°. The study showed that the use of mobility-provocation RSA did not add any information over that obtained by deformation RSA studies. Conventional radiography is too inaccurate to measure inducible displacement in this patient population.     

Lactobacilli attenuate bacteremia and endotoxemia associated with severe intra-abdominal infection

BACKGROUND: Systemic administration of antibiotics or selective decontamination is frequently used in the prophylaxis and treatment of infections originating from the gastrointestinal flora. In this study, we wanted to compare the protective effect of enteral administration of lactobacilli to gentamicin against severe intra-abdominal infection. METHODS: Male Sprague-Dawley rats underwent cecal ligation and puncture (CLP). Rats were pretreated with saline, Lactobacillus R2LC, and gentamicin. Bacterial growth and endotoxin levels in the blood, reticuloendothelial system (RES)-function, and intestinal transit were determined up to 24 hours after CLP. RESULTS: CLP-provoked bacteremia was significantly reduced by 48% and 55% in lactobacilli- and gentamicin-treated rats, respectively. Notably, CLP-induced endotoxemia was abolished at 12 hours, and reduced by 47% at 24 hours, in rats pretreated with lactobacilli. Gentamicin reduced endotoxin levels provoked by CLP by 86% at 12 hours, but had no effect at 24 hours. Lactobacilli had no effect on the clearance of Escherichia coli (E coli) from the blood, whereas intestinal transit was increased in lactobacilli-treated animals, suggesting that the beneficial effect of Lactobacillus R2LC is not related to an increase of phagocytic capacity but may rather be partly attributable to an enhanced intestinal motility. CONCLUSION: Enteral administration of Lactobacillus R2LC attenuates bacteremia and endotoxemia associated with intra-abdominal infection in rats.     

Endometrial carcinoma: Current concepts and future perspectives

Endometrial carcinoma is increasing worldwide and, in most of western Europe and the U.S., it is now the most common malignancy in the female pelvis.

The most common parameters in deciding therapy are staging, according to the International Federation of Gynecologists and Obstetricians (FIGO) and histopathological grading, and evaluation of myometrial invasion.

The treatment results in terms of a 5-year survival rate, are about 90% for well and moderately differentiated stage I to II endometrial carcinomas, whereas that for poorly differentiated ones is about 70%.²⁹ The latter figures point towards the need for further prognostic parameters to identify subgroups with a fatal form of the disease.

One such parameter might be the concentration of steroid receptors and promising results have been published recently⁷¹ but still better prognostic parameters have been proposed recently.

It is known that the DNA content in individual tumor cells is a prognostic parameter. Due to the development of flow cytometry such determinations are rapid and more precise, and the prognostic significance has been proved to be superior to the more commonly used parameters.^98,100