Relationship between plasma levels of leukotriene E4 and arterial partial pressure of carbon dioxide in asthmatic patients

To examine whether plasma levels of leukotriene E₄ (LTE₄) are associated with arterial partial pressure of carbon dioxide (Paco₂), we measured the concentration of LTE₄ in the femoral artery of six asthmatic patients. Paco₂ was measured concomitantly. Six healthy male volunteers served as control subjects. Twenty milliters of blood was drawn from the femoral artery of the six patients during remission and during a wheezing attack treated without prednisolone. Leukotriene E₄ was detected by high-pressure liquid chromatography and radioimmunoassay. In the six asthmatic patients, mean LTE₄ levels were 11.3 ± 1.72 pg/ml and 30.9 ± 7.44 pg/ml during remission and wheezing, respectively. These levels were significantly different (P < 0.01). The mean LTE₄ level in the six control subjects was 10.8 ± 3.74 pg/ml. Mean Paco₂ values during remission and wheezing were 35.3 ± 5.24 mmHg and 45.3 ± 4.06 mmHg, respectively. Leukotriene E₄ levels were correlated with Paco₂ (r = 0.669; P < 0.05). We conclude that LTE₄ levels in arterial blood reflect the severity of asthmatic attacks.     

哮喘患儿外周血单个核细胞瘦素及Foxp3的表达

目的 探讨哮喘患儿瘦素及CD4⁺CD25⁺调节性T细胞(Treg)特异性转录因子叉头状转录因子P3(Foxp3)在外周血单个核细胞(PBMC)中的表达及意义。方法 选取2013年8月～2015年5月在沭阳县人民医院门诊及住院的28例哮喘患儿发作期(发作组),26例哮喘患儿缓解期(缓解组)及25例健康体检儿童(对照组),采用ELISA法检测各组血浆及PBMC培养上清液中的瘦素浓度,实时荧光定量PCR法测定PBMC中Foxp3的相对表达量,进行统计学分析。结果 发作组、缓解组和对照组三组血浆浓度(19.98±5.40 ng/ml,13.73±2.28 ng/ml,12.17±3.95 ng/ml)及PBMC培养上清液瘦素浓度(55.94±11.09 pg/ml,31.97±7.71 pg/ml,27.85±7.67 pg/ml)差异均有统计学意义(F=27.07,75.96,P均<0.01); 组间两两比较,发作组均高于缓解组与对照组(P均<0.01),而缓解组与对照组差异无统计学意义(P>0.05)。发作组、缓解组和对照组三组PBMC Foxp3相对表达量(2.70±0.48,3.84±0.45,3.77±0.38)差异有统计学意义(F=57.35,P<0.01); 组间两两比较,发作组低于缓解组与对照组(P<0.01),而缓解组与对照组差异无统计学意义(P>0.05)。发作组患儿PBMC培养上清液瘦素浓度与PBMC Foxp3相对表达量呈负相关(R=-0.730,P<0.01),而血浆瘦素浓度与PBMC Foxp3相对表达量无明显相关性(R=-0.367,P=0.550)。结论 哮喘患儿PBMC分泌瘦素增加,且分泌的瘦素抑制了Foxp3的表达。     

Plasma and urinary leukotrienes in sickle cell disease: possible role in the inflammatory process

Abstract. Sickle cell (HbSS) disease is associated with rheological and inflammatory stresses within the microcirculation. In order to determine the role of leukotrienes in the inflammatory processes in HbSS patients, we analysed plasma and urine levels of leukotrienes (LT); LTB₄, LTC₄, LTD₄, and LTE₄ as indicators of their in vivo metabolism. Plasma and urine level samples of 15 HbSS patients in steady-state and age-matched healthy, homozygous (HbAA) controls were extracted for leukotrienes and quantitated by HPLC. Control plasma level of leukotrienes (mean ± SEM, ng ml^-1) were: LTB₄, 8·95 ± 0·26; LTC₄, 7·24 ± 0·21; LTD₄, 11·42 ± 0·40; and LTE₄, 14·51 ± 0·50. Corresponding values for HbSS patients were: LTB₄, 6·15 ± 0·42; LTC₄, 13·61 ± 1·45; LTD₄, 6·44 ± 0·51 and LTE₄, 4·97 ± 0·37. The differences were significant at P < 0·05. Urine levels (mean ± SEM, ng mmol^-1 creatinine), for controls were: LTB₄, 10·60 ± 0·35; LTC₄, 360·0 ± 9·82. Values for HbSS urine were: LTB₄, 27·50 ± 3·33; LTC₄, 356·0 ± 17·87; LTD₄, 69·90 ± 14·51. LTD₄ was not detected in control urine. These results suggest that sickle cell patients may exhibit impaired ability to catabolize LTC₄ in plasma during steady state conditions. This altered metabolism may contribute to the persistent stress of the microcirculation, and is probably related to the abnormal microvascular rheology of sickle blood cells.     

Detection of (1–3)-β-D-glucan in a rat model of aspergillosis

The G test containing factor G, fractioned from the Limulus lysate, was used to detect (1–3)-β-D -glucan in a rat model of aspergillosis. Aspergillus fumigatus strain MF-13, 1 × 10⁴ conidia, were inoculated transtracheally into rats treated with cortisone acetate (100 mg/kg) and fed a low-protein (8%) diet. Increased serum (1–3)-β-D -glucan was found on the sixth day after inoculation in concentrations of 370 ± 178 pg/ml (mean ±SD) in untreated controls, and 154 ± 43 pg/ml in rats treated with 0.5 mg/kg of amphotericin B. On day 11 (1–3)-β-D -glucan concentrations were 2,590 ± 2,940 pg/ml and 448 ± 442 pg/ml, respectively. The elevation in levels of (1–3)-β-D -glucan increased in correlation with the elevation of galactomannan antigen titers; (1–3)-β-D -glucan is thus measurable during experimental aspergillosis in rats.©1995 wiley-Liss, inc.     

Determination of the bioavailability of intranasal elcatonin in humans: Development of a sandwich transfer enzyme immunoassay for elcatonin

A sandwich transfer enzyme immunoassay for elcatonin (ECT) and its usability for the pharmacokinetic study are described. The anti-salmon calcitonin (SCT) antibody was used for the present assay. The assay procedure consisted of the reaction of ECT with 2,4-dinitrophenylbiotinyl anti-SCT IgG and anti-SCT Fab′-β-D -galactosidase conjugate, trapping onto (anti-2,4-dinitrophenyl bovine serum albumin) IgG-coated polystyrene balls, eluting with ϵN-2,4-dinitrophenyl-L-lysine and transferring to streptavidin-coated polystyrene balls and fluorometric detection of β-D -galactosidase activity. The practical detection limit of ECT was 0.15 pg (44 amol)/50 μl of sample and 3 pg/ml as the concentration. The application of this method has enabled us to directly estimate the bioavailability of ECT dosed intranasaly at a therapeutic level (100 IU, 17 μg) for its anti-osteoporotic effect as compared to an intramuscular dose (40 IU, 6.7 μg). The pharmacokinetic parameters of the intranasal ECT (n = 6) thus estimated were as follows: the area under the serum concentration-time curve (AUC) = 2,570 ± 1,650 (SD) pg × min/ml, and the maximal concentration (Cmax) = 60 ± 25 (SD) pg/ml with the maximal time (Tmax) = 17.5 ± 6.9 (SD) min, when the AUC for the intramuscular ECT (n = 9) = 9,460 ± 5,870 (SD) pg × min/ml and the Cmax = 165 ± 79 (SD) pg/ml with the Tmax = 16.1 ± 4.2 (SD) min. J. Clin. Lab. Anal. 12:356–362, 1998. © 1998 Wiley-Liss, Inc.     

Kinetics of 13CO2 elimination after ingestion of 13C bicarbonate: the effects of exercise and acid base balance

Abstract. In order to investigate the effects of muscular work and preceding exercise on the retention of exogenous labelled bicarbonate, we studied the effects of oral administration of [¹³C]bicarbonate (0·1 mg kg^-1) in five subjects at rest before exercise and during and after 1 h of treadmill walking at 73% VO_2max on three separate occasions. Elimination of CO₂ from labelled bicarbonate was 62·6±8·1% at rest, 103·6±11·3% during exercise (P<0·01) and 43·0±4·7% during recovery from exercise (P= 0·01). During exercise mean residence time (MRT) was shorter than at rest (35±7 min vs. 54±9min, P < 0·02) and CO₂ pool size was larger (998±160 ml CO₂kg^-1, vs. 194±28ml CO₂kg^-1, P < 0·001). Compared to values obtained at rest, during recovery from exercise, MRT and CO₂ pool size were reduced (34±5min, P < 0·05; 116±19 ml CO₂kg^-1, P < 0·02, respectively). In an additional five subjects acidosis and alkalosis were induced prior to administration of oral [¹³C]bicarbonate at rest. Elimination of bicarbonate was lower during acidosis (46·1±5·6%, P < 0·01) but was unaltered (50·9±5·6%, NS) during alkalosis, compared to the values obtained at resting pH. During acidosis MRT and CO₂ pool size decreased (37±3min, P<0·01 and 123±10ml CO₂kg^-1, P < 0·01, respectively) whereas in alkalosis MRT was unchanged (65±8 min NS) but CO₂ pool size was increased (230±23ml CO₂kg^-1, P < 0·05). The kinetics of elimination of ¹³CO₂ from administered bicarbonate after exercise are different to those at rest and resemble acidosis. The appropriate correction factor for sequestered ¹³C should be used in metabolic studies of the post-exercise state when using ¹³C tracers.     

Radioimmunoassay of Vasopressin in Unextracted Plasma

A radioimmunoassay (RIA) for arg₈-vasopressin (AVP) in unextracted human plasma was based on a sensitive anti-AVP rabbit antiserum, inhibition of enzymatic damage to [¹²⁵I]AVP and AVP, and the use of an individual plasma blank, to correct for interference of plasma factors with the RIA. Sensitivity was 0.4 pg of synthetic AVP detected, corresponding to 1.2 pg/ml of AVP in human plasma. Recovery of AVP added to pooled plasma was 94 ± 9.3% (mean± S.D.) in the low range (AVP, 2.8 pg/ml added) and 106 ± 11.7% in the high range (45.0 pg/ml added). In 26 healthy, ambulatory subjects on ad lib. water intake, plasma AVP concentration was 2.0 ± 1.22 pg/ml in the supine position and in 28 healthy subjects, 6.2 ± 4.3 pg/ml in the upright position. Water loading suppressed the plasma AVP concentration. Smoking caused increased plasma AVP in 3 subjects despite water loading.     

Pharmacokinetic comparison of oral and local action transcutaneous flurbiprofen in healthy volunteers

Flurbiprofen is a propionic acid–derived nonsteroidal anti–inflammatory drug (NSAID) used widely in the treatment of rheumatism and nonarthritic pain. The pharmacokinetics of topically and orally administered flurbiprofen were compared in a two–part, open study involving healthy adult volunteers. In the first (cross–over) part of the study, 12 Caucasians were randomized to receive either a single oral dose of 50 mg flurbiprofen or a single topical application of a novel 40 mg flurbiprofen–containing patch on the right wrist for 12 h. In the second part of the study, each subject applied a flurbiprofen–containing patch twice daily to the same wrist for 7 days. Plasma concentrations of flurbiprofen and urinary concentrations of the NSAID and its metabolites were measured by high–performance liquid chromatography assay, to enable comparison of the pharmacokinetic parameters for delivery of the drug by both routes. Maximum concentrations of the NSAID in plasma (C_max) were much lower after a single application of the topical 40 mg flurbiprofen patch than after a single oral dose of 50 mg of the NSAID (mean ± SD: 43 ± 16 ng/ml versus 5999 ± 1300 ng/ml, respectively). After repeated application of the topical patch, C_max increased only slightly to 103 ± 57 ng/ml. The mean relative bioavailability of flurbiprofen from the patch was 3–5 ± 1–7%, calculated from plasma area under the curve data and 4-4 ± 2–8% from urinary excretion data. The temporal profile of the appearance of flurbiprofen in the circulation also differed, with maximum concentrations occurring (T_max) 2 ± 1 h after the oral dose but not until 20 ± 6 h of applying the first patch, decreasing to 4 ± 3 h after repeated applications. Steady–state plasma concentrations were reached within 5 days of repeated patch applications; these exhibited intersubject variability ranging from 32 to 285 ng/ml. Percutaneous absorption of flurbiprofen from the patch into the systemic circulation was thus relatively slow and systemic concentrations of the drug achieved by this route were much lower than those obtained after oral intake of comparable doses. The systemic concentrations achieved via the topical route are likely to be insufficient to account for the demonstrable efficacy of the formulation in clinical trials, which is considered to depend on local enhanced topical delivery of flurbiprofen. Moreover, it might reasonably be supposed that the use of the flurbiprofen–containing patch as a localized treatment for musculoskeletal soft–tissue lesions will elicit a lower incidence of systemic adverse effects than occurs with the orally administered NSAID.     

Calcium loss in sweat does not stimulate PTH release: A study of Bikram hot yoga

It has been hypothesized that sweat loss during exercise causes a disruption in calcium homeostasis that activates bone resorption and over time leads to low bone mineral density. The purpose of this small pilot study was to determine whether dermal calcium loss from a bout of excessive sweating during light intensity physical activity triggers an increase in biomarkers of bone resorption. Biochemical markers related to bone homeostasis were measured before and after a 90 min Bikram hot yoga practice performed in a room heated to 105 °F with 40 % humidity. Participants were five females with a mean age of 47.4 ± 4.7 years. Nude body weight, serum total calcium (Ca²⁺), free ionized calcium, albumin, parathyroid hormone (PTH) and CTX-I were measured before and after a Bikram hot yoga practice. Mean estimated sweat loss was 1.54 ± 0.65 L, which elicited a 1.9 ± 0.9 % decrease in participant’s body weight. Mean Ca²⁺ concentration in sweat was 2.9 ± 1.7 mg/dl and the estimated mean total calcium lost was 41.3 ± 16.4 mg. Serum ionized Ca²⁺ increased from 4.76 ± 0.29 mg/dl to 5.35 ± 0.36 mg/dl after the Bikram hot yoga practice (p = 0.0118). Serum PTH decreased from pre- 33.9 ± 3.3 pg/ml to post- 29.9 ± 2.1 pg/ml yoga practice (p = 0.0015) when adjusted for hemoconcentration (PTH_ADJ), implying a decrease in PTH secretion. We conclude that calcium loss in sweat during 90 min of Bikram hot yoga did not trigger an increase in PTH secretion and did not initiate bone resorption.     

Progressive central hypovolaemia in man—resulting in a vasovagal syncope?

Summary. Hypotensive functional haemorrhage induced by venous pooling of blood in the legs has been reported to be characterized by a vasovagal reaction. In the present study these observations were extended by determination of the hormonal profile developed during progressive central hypovolaemia and an emotionally induced vasovagal syncope. In six subjects venous pooling resulted in normotensive central hypovolaemia, in one subject hypotensive central hypovolaemia was induced, and one subject experienced an emotionally induced vasovagal syncope. During normotensive central hypovolaemia heart rate increased from 58 ± 4 to 76 ± 4 beats min^-1 (P<0·05) and cardiac output fell from 6·1 ± 0·4 to 4·1 ± 0·21 min^-1. Pulse pressure and central venous pressure decreased from 64 ± 4 to 53 ± 4 mmHg, and from 8 ± 2 to 3 ± 2 mmHg, respectively. Adrenalin and noradrenalin increased from 87 ± 10 to 120 ± 20 pg/ml and from 196 ± 33 to 370 ± 50 pg/ml, respectively. Angiotensin II increased from 13 ± 4 to 36 ± 6 pg/ml and aldosterone from 63 ± 9 to 180 ± 27 pg/ml. In hypotensive central hypovolaemia the decrease in mean arterial pressure was accompanied by a decrease in heart rate and increments in the plasma concentrations of pancreatic polypeptide, indicating increased vagal activity and β-endorphin, while plasma noradrenalin was unchanged. In emotionally induced syncope heart rate decreased to cardiac arrest for 13 s, associated with increments in the plasma concentrations of pancreatic polypeptide and β-endorphin. It is concluded (1) that normotensive functional haemorrhage in man is associated with increased sympathetic activity and (2) that the qualitatively similar observations obtained during an emotionally and a hypovolaemic-induced hypotensive episode indicate that the hypotensive functional haemorrhage is characterized by a vasovagal reaction.     

B-type natriuretic peptide as an indicator of right ventricular dysfunction in acute pulmonary embolism

Objective: B‐type natriuretic peptide (BNP) is a neurohormone secreted from cardiac ventricles in response to ventricular strain. The aim of present study was to evaluate the role of BNP in the diagnosis of the right ventricular (RV) dysfunction in acute pulmonary embolism (PE). Methods: BNP levels were measured in patients with acute PE as diagnosed by high probability lung scan or positive spiral computed tomography. All patients underwent standard echocardiography and blood tests during the second hour of the diagnosis. Results: Forty patients diagnosed as acute PE (mean age, 60.4 ± 13.2 years; 62.5% women) were enrolled in this study. Patients with RV dysfunction had significantly higher BNP levels than patients without RV dysfunction (426 ± 299.42 pg/ml vs. 39.09 ± 25.22 pg/ml, p < 0.001). BNP‐discriminated patients with or without RV dysfunction (area under the receiver operating characteristic curve, 0.943; 95% CI, 0.863–1.022). BNP > 90 pg/ml was associated with a risk ratio of 165 (95% CI, 13.7–1987.2) for the diagnosis of RV dysfunction. There was a significant correlation between RV end‐diastolic diameter and BNP (r = 0.89, p < 0.001). Sixteen patients (40%) were diagnosed as having low‐risk PE, 19 patients (47.5%) with submassive PE and five patients (12.5%) with massive PE. The mean BNP was 39.09 ± 25.2, 378.4 ± 288.4 and 609.2 ± 279.2 pg/ml in each group respectively. Conclusion: Measurement of BNP levels may be a useful approach in diagnosis of RV dysfunction in patients with acute PE. The possibility of RV dysfunction in patients with plasma BNP levels > 90 pg/ml should be strongly considered.     

Perfusion heterogeneity does not explain excess muscle oxygen uptake during variable intensity exercise

The association between muscle oxygen uptake (VO₂) and perfusion or perfusion heterogeneity (relative dispersion, RD) was studied in eight healthy male subjects during intermittent isometric (1 s on, 2 s off) one‐legged knee‐extension exercise at variable intensities using positron emission tomography and a‐v blood sampling. Resistance during the first 6 min of exercise was 50% of maximal isometric voluntary contraction force (MVC) (HI‐1), followed by 6 min at 10% MVC (LOW) and finishing with 6 min at 50% MVC (HI‐2). Muscle perfusion and O₂ delivery during HI‐1 (26 ± 5 and 5·4 ± 1·0 ml 100 g^?1 min^?1) and HI‐2 (28 ± 4 and 5·8 ± 0·7 ml 100 g^?1 min^?1) were similar, but both were higher (P<0·01) than during LOW (15 ± 3 and 3·0 ± 0·6 ml 100 g^?1 min^?1). Muscle VO₂ was also higher during both HI workloads (HI‐1 3·3 ± 0·4 and HI‐2 4·1 ± 0·6 ml 100 g^?1 min^?1) than LOW (1·4 ± 0·4 ml 100 g^?1 min^?1; P<0·01) and 25% higher during HI‐2 than HI‐1 (P<0·05). O₂ extraction was higher during HI workloads (HI‐1 62 ± 7 and HI‐2 70 ± 7%) than LOW (45 ± 8%; P<0·01). O₂ extraction tended to be higher (P = 0·08) during HI‐2 when compared to HI‐1. Perfusion was less heterogeneous (P<0·05) during HI workloads when compared to LOW with no difference between HI workloads. Thus, during one‐legged knee‐extension exercise at variable intensities, skeletal muscle perfusion and O₂ delivery are unchanged between high‐intensity workloads, whereas muscle VO₂ is increased during the second high‐intensity workload. Perfusion heterogeneity cannot explain this discrepancy between O₂ delivery and uptake. We propose that the excess muscle VO₂ during the second high‐intensity workload is derived from working muscle cells.     

Comparison between Wako-WB003 and Fungitec G tests for detection of (1→3)-β-D-glucan in systemic mycosis

The limulus factor G reacts with (1→3)-β-D-glucan, a major structural component of fungal cell walls. The Fungitec G test is a colorimetric assay that measures the concentration of (1→3)-β-D-glucan and is used as a serodiagnostic test for deep mycosis. Wako-WB003 is another assay for (1→3)-β-D-glucan that determines the change in turbidity of the gelatin reaction of limulus factor G with (1→3)-β-D-glucan. In five rabbits inoculated intravenously with 1 × 10⁷ CFU of Candida albicans, the concentration of (1→3)-β-D-glucan measured by the fungitec G test increased gradually reaching a peak of 660.9 ± 427.9 pg/ml (mean ± SD) 4 days after inoculation, but to 42.225 ± 41.275 ng/ml on day 6 in the Wako-WB003 test. In one rabbit challenged intravenously with 5 × 10⁶ CFU of C. albicans, (1→3)-β-D-glucan increased to 101.5 pg/ml on day 4 on the fungitec G test, whereas the level remained below the detection limit of the Wako-WB003 test throughout the course of the disease. We also detected high concentrations of (1→3)-β-D-glucan in 11 patients with candidemia, 4 with suspected candidemia, 1 with invasive pulmonary aspergillosis, and 12 patients with aspergilloma. The concentration of (1→3)-β-D-glucan measured by the Fungitec G test was > 150, > 1006.8, 312.1, and 55.6 ± 37.4 pg/ml (range, 20.1–138.0 pg/ml), and by the Wako-WB003 test > 153.000, > 17.70, 153.000 and 2.645 ± 7.248 ng/ml (range, < 25.20 ng/ml) in these patients, respectively. In contrast, the concentration of (1→3)-β-D-glucan in 9 patients with pulmonary cryptococcosis and 6 with superficial candida colonization ranged from < 13.2 and < 15.3 pg/ml in the Fungitec G test and < 0.53 and < 0.12 ng/ml in Wako-WB003 test. There was a weak relationship between the concentration of (1→3)-β-D-glucan measured by the Fungitec G test and Wako-WB003 test (r = 0.521). Our results indicate that the sensitivity of the Wako-WB003 test is lower than that of the Fungitec G test. J. Clin. Lab. Anal. 11:73–77. © 1997 Wiley-Liss, Inc.     

Quantitative determination of prostaglandins in human gastric juice by radioimmunoassay

Prostaglandins in human gastric juice and human saliva were determined by radioimmunoassay after extraction and chromatography on silicic acid columns. Basal levels in gastric juice were found to be 443.8 ± 49.0 pg/ml prostaglandin E₂ and 153.7 ± 23.6 pg/ml prostaglandin A₂. Prostaglandin F_2α was below 50 pg/ml in most cases.The prostaglandin A₂ found seems to be secreted as prostaglandin E₂ which is dehydrated after secretion at the low pH of gastric juice. Some of the prostaglandin A₂ might also come from saliva. Pentagastrin stimulation of gastric secretion did not significantly change the concentrations of prostaglandins in gastric juice, but tended to increase the total output of prostaglandins concomitantly with the increase in volume of gastric secretion.     

Exercise significantly increases plasma adrenaline and oxidized low-density lipoprotein in normal healthy subjects but not in persons with spinal cord injury

Mitsui T, Nakamura T, Ito T, Umemoto Y, Sakamoto K, Kinoshita T, Nakagawa M, Tajima F. Exercise significantly increases plasma adrenaline and oxidized low-density lipoprotein in normal healthy subjects but not in persons with spinal cord injury.ObjectivesTo compare plasma concentrations of oxidized low-density lipoprotein (oxLDL) and adrenaline during exercise between persons with spinal cord injury (SCI) and able-bodied (AB) individuals.DesignRandomized controlled study.SettingHuman laboratory at a medical university.ParticipantsPersons with SCI (n=7) and AB individuals (n=9).InterventionTwo-hour arm crank ergometer exercise at 60% maximum oxygen consumption.Main Outcome MeasuresPlasma oxLDL and adrenaline levels.ResultsExercise significantly increased plasma adrenaline levels in AB persons (mean ± SD: rest, 45.4±32.2pg/mL; exercise, 200.9±113.7pg/mL; P<.05) and persons with SCI; however; the magnitude of the increase in those with SCI was attenuated (mean ± SD: rest, 45.4±14.0pg/mL; exercise, 83.0±55.8pg/mL; P<.05). Exercise also significantly increased plasma oxLDL levels in AB persons (mean ± SD: rest, 102.2±30.2U/L; exercise, 179.7±60.0U/L; P<.05), but not in persons with SCI (mean ± SD: rest, 124.3±66.0U/L; exercise, 138.9±59.5U/L).ConclusionsThe results suggest that increases in plasma adrenaline levels during exercise contribute to the increase in plasma oxLDL levels.     

Is endotoxin and cytokine release related to a decrease in gastric intramucosal pH after hemorrhagic shock?

Objectives: (a) To investigate the relationship between gut ischemia parameters (gastric intramucosal pH [pHi], mucosal–arterial carbon dioxide difference [PCO₂-gap]), and endotoxin or cytokine release during hemorrhagic shock; (b) to compare the predictive value of pHi, PCO₂-gap and arterial lactate concentrations. Design: Prospective study. Setting: Surgical intensive care unit of a university hospital. Patients: 20 multiple trauma patients with severe hemorrhagic shock. Interventions: Intramucosal measurements and blood samples were obtained on admission to the emergency room and repeatedly over 48 h. Measurements and results: Endotoxin was measured using a chromogenic limulus amoebocyte assay. Cytokine [tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6)] values were evaluated by immunoradiometric assays. Only 3 patients had positive blood cultures but endotoxins were detected at least once in all patients. Endotoxin levels were similar in survivors and nonsurvivors over the study period and were not related to pHi or PCO₂-gap. Initially, high levels of IL-6 were observed in both nonsurvivors and survivors [median 1778 pg/ml (range 435–44 540) vs 2068 pg/ml (range 996–92 300)]. IL-6 levels progressively decreased in the survivors but not significantly. On admission, TNFα concentrations were similar in nonsurvivors and survivors (42 ± 35 vs 46 ± 27 pg/ml). From the 24th h, TNFα values were higher in the nonsurvivors than in the survivors (24 h: 72 ± 38 vs 34 ± 17 pg/ml, p < 0.05). The greatest IL-6 levels were found for a pHi < 7.20 (28.5 ± 36.5 vs 1.8 ± 1.3 ng/ml, p < 0.05) or a PCO₂-gap > 7.5 mmHg (1 kPa) (32.5 ± 37.5 vs 1.7 ± 1.3 ng/ml, p < 0.01). With the same pHi threshold, no difference was found in endotoxin levels. The lactate concentrations were predictive for outcome from the 12th h (9.5 ± 5.9 vs 3.6 ± 2.3 mmol/l, p < 0.05). Conclusions: During severe hemorrhagic shock, endotoxin translocation from the gut was a common phenomenon that seemed independent of both pHi values and outcome. It could not explain IL-6 and TNFα release. In severe hemorrhagic shock, neither pHi nor PCO₂-gap provides additional information to the lactate measurements. Received: 17 February 1997 Accepted: 7 August 1997     

Rituximab preserves vision in ocular mucous membrane pemphigoid

Objective: To study the effectiveness and safety of anti-CD20 B-cell antibody rituximab (RTX) in the treatment of ocular mucous membrane pemphigoid (MMP).

Methods: Retrospective analysis of six MMP patients receiving RTX with or without concomitant immunosuppression. RTX was administered as a high dose regimen (1000 mg/infusion, day 0 and day 14/cycle). Five patients received more than one cycle. Main outcome measure was the treatment response, defined as complete remission (CR) or partial remission (PR), monitored at 16 and 24 weeks. As secondary outcome measure, drug-related adverse events were evaluated.

Results: All patients responded within 16 weeks. Initial treatment response vanished in five of six patients at a mean of 10 months (± 4.4 standard deviation [SD]). A second cycle was initiated thereafter (interval 12 months ± 6.4 SD) resulting in CR in two of five and PR in three of five patients. One patient stabilized only when additional immunosuppression was initiated. Mean follow up was 22 months (± 8.2 SD).Two individuals experienced infusion reactions.

Conclusions: Our study adds long-term data to the very limited experience with biologicals in MMP, indicating that RTX is a promising option for patients with advanced disease. We report for the first time the high dose regimen of RTX applied in a consecutive series.     

Changes in plasma erythropoietin and interleukin-6 concentrations in patients with septic shock after hemoperfusion with polymyxin B-immobilized fiber

Objective: To find out whether polymyxin B-immobilized fiber (PMX-F) treatment affects the clinical parameters and plasma concentrations of erythropoietin (EPO) and interleukin (IL)-6. Design: A prospective case series study. Setting: Intensive care unit of the Department of Internal Medicine, Misato Junshin Hospital, Saitama, and Koto Hospital, Tokyo, Japan. Patients: 17 consecutive patients (10 men, 7 women; mean age 54.6 years) with clinically defined septic shock and 20 healthy volunteers (12 men, 8 women; mean age 52.2 years). Main results: Of the 17 patients with septic shock, 9 (53 %) survived. The systolic blood pressure increased significantly from 78 ± 6 to 106 ± 8 mm Hg 2 h after PMX-F treatment in patients with septic shock. Plasma endotoxin levels decreased significantly after treatment, from 40 ± 6 to 12 ± 4 pg/ml. The pretreatment plasma concentrations of EPO and IL-6 were significantly higher in the 8 nonsurviving patients with septic shock (EPO: 400 ± 36 mlU/ml; IL-6: 6260 ± 1180 pg/ml) than in the 9 surviving patients (EPO: 120 ± 22 mlU/ml; IL-6: 680 ± 138 pg/ml) and the 20 control subjects (EPO, 12 ± 6 mlU/ml; IL-6, 8 ± 2 pg/ml). Plasma concentrations of EPO and IL-6 in patients with septic shock decreased significantly after PMX-F treatment (EPO, nonsurviving: 320 ± 28 mlU/ml, p < 0.05; survivors: 26 ± 8 mlU/ml, p < 0.001; IL-6, nonsurviving: 3860 ± 840 pg/ml, p < 0.01; survivors: 84 ± 20 pg/ml, p < 0.001). Conclusions: Plasma concentrations of EPO and IL-6 may be prognostic indicators in patients with septic shock: PMX-F treatment may be effective in reducing the plasma concentrations of EPO and IL-6 in patients with septic shock. Received: 11 February 1998 Accepted: 5 October 1998     

Day‐to‐day variation in oxygen consumption at submaximal loads during ergometer cycling by adolescents

The day‐to‐day variation in oxygen consumption (V˙O₂) during ergometer cycling by 20 healthy adolescents, 10 females and 10 males, was measured using indirect calorimetry. The two sets of measurements were performed on two consecutive days. Great care was taken to minimize possible disturbing factors. Cycling started at 50 and 100 W for female and male adolescents, respectively. The load was increased at a rate of 5 W 30 s^?1. In order to reach steady state, the load was kept constant for 3·5 min twice during the cycling session, at 100 and 130 W for the females and at 130 and 160 W for the males. Cycling continued until exhaustion. The maximal loads were 196 W (mean) and 271 W (mean) for females and males, respectively. At the maximal loads the day‐to‐day variation (±2 SD) in oxygen consumption (V˙O₂) was ±330 ml min^?1 for females and 390 ml min^?1 for males. At the submaximal loads the day‐to‐day variation in heart rate (HR) was 9·3 beats min^?1 (±2 SD) (coefficient of variation, CV=3·4% at 130 W) for both sexes. The day‐to‐day variation in oxygen consumption (V˙O₂) was ±199 ml min^?1 (±2 SD) at the different submaximal loads and did not differ between female and male adolescents (CV=5·7% at 130 W). This natural day‐to‐day variation must be taken into consideration when using a submaximal ergometer cycling test for the evaluation of physical capacity in the two sexes.     

Good transfer of tebipenem into middle ear effusion conduces to the favorable clinical outcomes of tebipenem pivoxil in pediatric patients with acute otitis media

Tebipenem pivoxil, an oral carbapenem antibiotic for pediatric use, exhibits excellent clinical effects on acute otitis media (AOM). The present study was conducted to assess the pharmacokinetic profile of tebipenem in middle ear effusion and to examine the clinical efficacy of tebipenem pivoxil by calculating the values of the pharmacokinetic-pharmacodynamic parameters (AUC/MIC, C _max/MIC, and T > MIC) of tebipenem at the site of action. Twenty-three pediatric outpatients diagnosed with AOM were enrolled. Ear discharge or nasopharyngeal swabs collected before the onset of oral administration were used to conduct bacteriological examinations, and subjects were then treated by twice-a-day oral administration of tebipenem pivoxil 6 mg/kg. The clinical isolates of Streptococcus pneumoniae and Haemophilus influenzae were obtained from 10 and 19 pediatric patients (8 overlapped), respectively. On day 2 of administration, blood and middle ear effusion were collected from 20 pediatric patients to measure plasma and middle ear concentrations of tebipenem. Consequently, the C _max and the AUC_0–∞ in plasma were 5.3 ± 1.6 μg/ml (mean ± SD) and 7.9 ± 0.2 μg h/ml, respectively. The C _max in middle ear effusion of tebipenem was 1.2 ± 0.1 μg/ml, exceeding its MIC for these pathogens. The ratio of AUC_0–∞ in middle ear effusion to AUC_0–∞ in plasma was 0.36, showing the good transfer of tebipenem into the effusion; this result corroborated the known high rate of clinical efficacy of tebipenem pivoxil for patients with AOM and the low incidence of recurrence in them as manifested by the healing rate of 94.1 % (16/17).