Serial prognostic capabilities of electrocardiographic indices of infarcted and hibernating myocardium in predicting short- and long-term outcome following coronary artery bypass surgery

Concentrations and ex vivo production of interleukin 1 beta (IL-1), tumour necrosis alpha (TNF), interleukin 6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and TNF soluble receptors (sTNF-receptors, P55 and P75) were measured in bronchoalveolar lavage (BAL) fluid and blood in 23 HIV-seropositive (HIV+) patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy HIV-seronegative (HIV-) controls and asymptomatic HIV+ subjects. Concentrations of the proinflammatory cytokine IL-1 beta were increased in BAL fluid of HIV+ patients with PCP (184 +/- 47 pg mL-1) compared with undetectable levels in healthy control subjects (P = 0.0001). In plasma of these patients higher concentrations of the anti-inflammatory cytokine IL-1RA were found during acute PCP than after recovery (2.1 +/- 0.7 vs. 0.5 +/- 0.2 ng mL-1, P = 0.01). No correlations could be found between cytokine concentrations and clinical severity of the infection. Corticosteroid treatment did not influence cytokine concentrations in BAL or blood, nor did it suppress the production in alveolar cells. In whole-blood cultures, however, lipopolysaccharide (LPS)-stimulated production was significantly suppressed for IL-1 (1.3 vs. 5.5 ng mL-1, P = 0.009) and for IL-6 (0.6 vs. 2.5 ng mL-1, P = 0.01). The overall data show that in HIV+ patients with PCP (similar to what we had found previously in HIV-patients with PCP) proinflammatory cytokines are more prominently present in BAL, whereas anti-inflammatory reaction is predominant in the circulation.     

Synchrony in telomere length of the human fetus

We measured serum tumour necrosis factor-alpha (TNF-alpha) as well as interleukin-1betta (IL-1beta) and GH concentrations in 15 children with isolated growth hormone deficiency (GHD), age range 5.1-13.9 years, before and 4 and 24h after the first GH injection (0.1 IU/kg s.c.). No differences were found in basal concentrations of serum TNF-alpha and IL-1beta between GHD children (10.01 +/- 1.55 pg/ml and 2.14 +/- .16 ng/ml respectively) and sex- and age-matched controls (11.57 +/- 2.16 pg/ml and 3.78 +/- 1.46 ng/ml respectively). In GHD children, serum TNF-alpha and IL-1beta values had significantly increased (P < 0.002) 4h (26.75 +/- 5.57 pg/ml and 2.99 +/- 0.21 ng/ml respectively) and decreased again 24 h after GH administration. Likewise, serum GH levels had significantly increased 4 h (from 1.29 +/- 0.69 to 48.71 +/- 13.35 ng/ml, P < 0.001) and decreased to basal values 24h after GH administration. A significant correlation was found between basal serum concentrations of GH and those of both TNF-alpha (P < 0.01) and IL-1beta (P < 0.05). However, no correlation was found between serum GH concentration and either TNF-alpha or IL-1beta levels 4 and 24h after GH administration. Our data suggest that GH plays a role in modulating TNF-alpha and IL-1beta release in humans.     

Serum levels of interleukin 1 and tumor necrosis factor alpha correlate with peritoneal adhesion grades in humans after major abdominal surgery

Peritoneal adhesions are a leading cause of potential morbidity and mortality. We undertook this prospective study to determine the clinical relevance of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) levels as biological markers for peritoneal adhesion formation in humans. Fifteen patients who had previous colectomies and were undergoing re-exploration for an elective vascular procedure were studied. Blood samples were collected from each patient preoperatively and 30 minutes after the abdominal incision was made. Serum levels of IL-1 and TNF-alpha were determined using enzyme-linked immunosorbent assay kits. Adhesions were graded using an adhesion scale of 0 (none), 1 (mild), 2 (moderate), and 3 (extensive, dense). Preoperative levels of IL-1 and TNF-alpha did not differ significantly among all patients (IL-1 level was 60 +/- 14 pg/mL, and TNF-alpha level was 45 +/- 11 pg/mL; mean +/- standard deviation). Significant correlation was observed between grades of adhesions and early intraoperative levels of IL-1 [101 +/- 36 pg/mL for grade 1 (n = 8) vs 298 +/- 73 pg/mL for grade 3 (n = 6); P < 0.01] and TNF-alpha (88 +/- 23 pg/mL for grade 1 vs 261 +/- 88 mL for grade 3; P < 0.02). We conclude that early elevations of IL-1 and TNF-alpha are reliable biological markers for postoperative adhesions in humans. Studies utilizing cytokines antibodies to these markers may further elucidate the efficacy of this method for prevention of peritoneal adhesions.     

Effects of cross-training on markers of insulin resistance/hyperinsulinemia

This study examined, through a randomized controlled trial, the effects of cross-training (combined resistance and endurance exercise) on markers of insulin resistance, (e.g., dyslipidemia, intra-abdominal obesity, hyperinsulinemia, and hypertension), body composition, and performance in hyperinsulinemic individuals. Sedentary adult males characterized as hyperinsulinemic (fasting insulin > 2 OuU.mL-1), randomly assigned to two groups (N = 8 each), completed 14 wk of training at 3 d.wk-1. An endurance-only (E) group performed both continuous cycle exercise and walking (30 min each at 60-70% heart rate reserve). A cross-training (C) group performed both endurance and resistance exercise (8 exercises, 4 sets/exercise, 8-12 repetitions/set) in a single session. Both E and C groups demonstrated similar increases in VO2max (25% and 27%) while only C demonstrated an increase in 1 RM bench press (19%) and leg press (25%). The changes induced by C training were significantly greater than those from E training alone in percent fat (6.9 +/- 1.3 vs 1.4 +/- 1.4), insulin concentration (8.5 +/- 2.7 vs 3.0 +/- 1.3 uU.mL-1), glucose levels (11.1 +/- 2.9 vs 5.9 +/- 2.6 mg.dL-1), HDL-C levels (5.1 +/- 1.3 vs 2.9 +/- 1.6 mg.dL-1), triglyceride concentration (43.8 +/- 13.6 mg.dL-1), and systolic blood pressure (14.6 +/- 5.5 vs 8.3 +/- 6.8 mm Hg). Results indicate that the addition of resistance training to an endurance training program will induce significantly greater differences in markers of insulin resistance and body composition in individuals with hyperinsulinemia than endurance training alone.     

Plasma endotoxin and cytokine levels in neutropenic and non-neutropenic bacteremic patients

Plasma endotoxin, tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 1 receptor antagonist (IL-1ra), and interleukin 6 (IL-6) concentrations in 69 bacteremic patients were compared with those in 54 nonbacteremic patients suffering from suspected bacterial infections. Only three (11%) of the 27 patients with gram-negative bacteremia showed detectable levels of endotoxin. TNF-alpha was detected in 6% of the bacteremic patients and in none of the nonbacteremic patients. Median IL-6 levels were significantly higher in bacteremic than in nonbacteremic patients (55 vs. 0 pg/ml, p = 0.0008). IL-6 concentrations were similar in neutropenic and non-neutropenic bacteremic patients (median 55 vs. 74 pg/ml). In contrast, neutropenic bacteremic patients had significantly lower concentrations of IL-1ra than non-neutropenic bacteremic patients (250 vs. 1,950 pg/ml, p < 0.0001). Patients with fatal bacteremia had significantly higher concentrations of IL-6 and IL-1ra than the survivors (median, 450 vs. 40, p = 0.012 and 7,600 vs. 420 pg/ml, p = 0.0075, respectively). Determinations of endotoxin or TNF-alpha in patients with suspected bacteremia failed to offer clinically relevant data on the prognosis of these patients. IL-6 levels correlated with both the presence of bacteremia and the risk of death. Granulocytopenic patients with bacteremia had lower levels of circulating IL-1ra than patients with normal granulocyte counts, and these levels correlated with poor outcome.     

Cytokine profile in chronic cardiac failure

Elevated tumour necrosis factor alpha (TNF-alpha) has been demonstrated in chronic cardiac failure (CCF) and may relate to severity of CCF and development of cachexia. We measured TNF receptor p55 in addition to TNF-alpha in an attempt to improve the detection rate of TNF-alpha activation, and simultaneously measured interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein. Thirty-four patients with CCF and 24 control subjects were studied. Only TNF receptor p55 [6.95 (0.77-42.3) vs. 5.52 (1.50-13.36) ng mL-1 (median (range)] and IL-6 [0.335 (0-9.79) vs. 0(0-14.71) pg mL-1) were significantly elevated in patients compared with control subjects (both P < 0.05). All inflammatory markers were more frequently elevated in patients, but none correlated with any of the clinical parameters studied. Reasons for inflammatory marker elevation in CCF are uncertain, but future studies should measure the p55 TNF receptor and IL-6 in addition to TNF-alpha, to improve detection of cytokine activity.     

Denopamine, a beta1-adrenergic agonist, prolongs survival in a murine model of congestive heart failure induced by viral myocarditis: suppression of tumor necrosis factor-alpha production in the heart

OBJECTIVES: This study was designed to examine the effects of denopamine, a selective beta1-adrenergic agonist, in a murine model of congestive heart failure (CHF) due to viral myocarditis. BACKGROUND: Positive inotropic agents are used to treat severe heart failure due to myocarditis. However, sympathomimetic agents have not been found beneficial in animal models of myocarditis. METHODS: In vitro: The effects of denopamine on lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) production was studied in murine spleen cells. In vivo: Four-week-old DBA/2 mice were inoculated with the encephalomyocarditis virus (day 0). Denopamine (14 micromol/kg), denopamine (14 micromol/kg) with a selective beta1-blocker metoprolol (42 micromol/kg), or denopamine (14 micromol/kg) with metoprolol (84 micromol/kg) was given daily, and control mice received the vehicle only. Survival and myocardial histology on day 14 and TNF-alpha levels in the heart on day 6 were examined. RESULTS: In the in vitro study, TNF-alpha levels in treated cells were significantly lower than in controls (p < 0.05). In the in vivo study treatment with denopamine significantly improved the survival of the animals (14 of 25 (56%) treated, vs 5 of 25 (20%) control mice), attenuated myocardial lesions, and suppressed TNF-alpha production (66.5+/-7.5 pg/mg of heart in treated mice vs 113.5+/-15.1 pg/mg of heart in control mice, mean+/-SE). There was a strong linear relationship between mortality and TNF-alpha levels (r=0.98, n=4, p < 0.05). These in vitro and in vivo effects of denopamine were significantly inhibited by metoprolol. CONCLUSIONS: These results suggest that denopamine may exert its beneficial effects, in part, by suppressing the production of TNF-alpha via beta1-adrenoceptors.     

Comparison of the Interplak and manual toothbrushes in a population with mental retardation/developmental disabilities (MR/DD)

A still debated question in the field of the cytokine network in psoriasis is represented by contrasting data reported on the local amount of IL-1 beta amounts, of IL-1 in this dermatosis. In fact previous studies have suggested that there were decreased Il-1 alpha amounts at the lesional level but increased nonfunctional IL-1 beta concentrations as compared to the non-lesional and normal epidermis. However, recent data suggest that IL-1 alpha and, to a lesser extent, IL-1 beta amounts, are both increased and biologically active in the epidermal cell suspension of lesional psoriatic skin as compared to those of normal skin. The data reported in the present paper show that IL-1 alpha levels are decreased in psoriatic lesional extracts of whole skin (mean 2.9 +/- 2 pg/mg) as compared to non-lesional (mean 6.7 +/- 6.2 mg/mg; p = 0.02) or normal skin (mean 13.8 +/- 9.4 pg/mg; p = 0.0002). IL-1 alpha concentrations were also significantly lower in the non-lesional skin than in normal skin (p = 0.02). In contrast, the IL-1 beta levels (mean 1.2 +/- 0.74 pg/mg were higher in the lesional samples than in the non-lesional ones (mean 0.5 +/- 0.4 pg/mg; p = 0.0004) or in normal skin (mean 0.4 +/- 0.2 pg/mg; p = 0.004). No differences in IL-1 beta levels were observed between non-lesional and normal skin (p = 0.3). In addition both IL-1 alpha and IL-1 beta are directly correlated with the disease severity and each other. Our data, extending the Il-1 determination to the whole skin, seem to confirm the previously reported findings at the epidermis level and provide new light on possible interpretation of literature discrepancies.     

Lack of correlation between the reduction of sevoflurane MAC and the cerebellar cyclic GMP concentrations in mice treated with 7-nitroindazole

The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. In humans, production of IFN-gamma is associated with the control of infection in children infected by Leishmania chagasi. In visceral leishmaniasis, an impairment in IFN-gamma production and high IL-4 and IL-10 levels (Th2 cytokines) are observed in antigen-stimulated peripheral blood mononuclear cells (PBMC). Moreover, IL-12 restores IFN-gamma production and enhances the cytotoxic response. IL-10 is the cytokine involved in down-regulation of IFN-gamma production, since anti-IL-10 monoclonal antibody (mAb) restores in vitro IFN-gamma production and lymphoproliferative responses, and IL-10 abrogates the effect of IL-12. In cutaneous and mucosal leishmaniasis, high levels of IFN-gamma are found in L. amazonensis-stimulated PBMC. However, low or absent IFN-gamma levels were observed in antigen-stimulated PBMC from 50% of subjects with less than 60 days of disease (24 +/- 26 pg/ml). This response was restored by IL-12 (308 +/- 342 pg/ml) and anti-IL-10 mAb (380 +/- 245 pg/ml) (P < 0.05). Later during the disease, high levels of IFN-gamma and TNF-alpha are produced both in cutaneous and mucosal leishmaniasis. After treatment there is a decrease in TNF-alpha levels (366 +/- 224 pg/ml before treatment vs 142 +/- 107 pg/ml after treatment, P = 0.02). Although production of IFN-gamma and TNF-alpha might be involved in the control of parasite multiplication in the early phases of Leishmania infection, these cytokines might also be involved in the tissue damage seen in tegumentary leishmaniasis.     

Testosterone and IL-6 requirements for human C-reactive protein gene expression in transgenic mice

In vitro, IL-6 is the main inducer of the human C-reactive protein (CRP) gene, and IL-1 and steroids can enhance this effect. However, in mice, IL-6 is necessary but not sufficient for induction of the human CRP transgene, and testosterone is required for its constitutive expression by males. To examine the relative contributions of testosterone and IL-6 in the regulation of CRP gene expression, we produced CRP-transgenic (CRPtg), IL-6-deficient (IL-6-/-) mice. Male CRPtg/IL-6-/- mice expressed CRP constitutively, but CRP levels were not increased after injection of LPS. However, acute-phase CRP levels were attained after injection of IL-6. In contrast, female CRPtg/IL-6-/- mice did not express CRP constitutively or after administration of LPS, IL-6, IL-1, or IL-6 plus IL-1. Like males, testosterone-treated CRPtg/IL-6-/- females expressed CRP constitutively, and their transgene responded to injection of IL-6. The endogenous acute-phase protein serum amyloid P (SAP) was expressed constitutively equally by male and female IL-6-/- mice, responded minimally to LPS, and did not respond to either IL-6 or IL-1 alone. Acute-phase levels of SAP were induced in IL-6-/- mice by injection of IL-6 together with IL-1 or LPS. We conclude that in vivo, both constitutive and IL-6-dependent acute-phase expression of the CRP transgene require testosterone. In contrast, testosterone is not required for expression of the SAP gene, which requires IL-1 plus IL-6 for acute-phase induction.     

The Stomatology Information Retrieval (Reference) System]

BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by monoclonal proliferation of activated Langerhans cells. Neither etiology nor pathomechanism of this disorder is presently known. However, despite monoclonality LCH might represent a reactive clonal disorder induced by immune dysfunction rather than a malignant process. To investigate a putative cytokine dysregulation in the pathogenesis of this disorder and searching for parameters of both disease activity and prognosis, serum concentrations of proinflammatory and T-cell derived cytokines were evaluated in LCH patients. MATERIALS AND METHODS: Serum levels of IL-1 beta, IL-2, sIL-2R and TNF-alpha were determined by ELISA in seven children with different types of LCH: Three children (aged 6, 10 and 14 years, respectively) with single system/single bone disease; one child (11 years) with recurrent single system/multiple bone disease and three children (1, 2 and 2 years, respectively) with multisystem disease. RESULTS: sIL-2R was elevated at diagnosis in seven children as compared to healthy adults (mean +/- SEM: 5,256 +/- 3,751 U/ml vs. 73 +/- 5.5 U/ml; P < 0.005) or healthy children (mean +/- SEM: 10,195 +/- 2,798 pg/ml vs. 2,638 +/- 156 pg/ml; P < 0.01). A positive correlation between serum levels of sIL-2R and extent of the disease could be observed. During remission, sIL-2R levels declined. IL-1 beta, IL-2, and TNF-alpha remained within the normal range during the study period. CONCLUSIONS: Elevated sIL-2R levels seem to correlate positively with both extent and activity of LCH, thus indicating a pathological T-cell activation as a pathogenetic factor. sIL-2R level is a promising parameter to monitor disease activity in LCH and may also be of prognostic relevance.     

Calcitriol modulates in vivo and in vitro cytokine production: a role for intracellular calcium

Calcitriol modulates in vivoand in vitro cytokine production: A role for intracellular calcium. Background. Several immunomodulatory properties of calcitriol are currently known, however, only little information is available regarding the in vivo and in vitro effects of calcitriol on cytokine production in chronic renal failure. Methods. To study the in vitro effect of calcitriol on lipopolysaccharide (LPS)-induced cytokine production, peripheral blood mononuclear cells (PBMC, 2.5 ml/ml) from 12 chronic dialytic (HD), 15 undialyzed chronic renal failure (CRF) patients and 10 normal subjects (N) were incubated at 37 degrees for 12 hours with 100 ng of LPS (E. coli and P. maltofilia). Increasing doses of calcitriol from 10-10 to 10-9 M were added and cell associated TNF-alpha and IL-1beta were determined by immunoreactive tests after three freeze-thaw cycles. The intradialytic TNF-alpha and IL-1beta production were evaluated in vivo in 12 HD patients before and after three months of intravenous calcitriol treatment (6 microgram/week). Intracellular calcium [Ca++]i was determined on PBMC with a cytofluorimetric assay using FLUO-3 AM as the indicator. Results. In vitro, TNF-alpha increased from 3.6 +/- 1.9 pg/cell to 1797 +/- 337 in N, from 4.5 +/- 1.7 to 1724 +/- 232 in CRF and from 3.4 +/- 2.3 to 1244 +/- 553 in HD after the LPS stimulus. The production of TNF-alpha was inhibited by calcitriol in a dose-dependent manner [LPS + Vit.D3 100 ng, 2.9 +/- 2.1 in N, 3.7 +/- 1.9 in CRF and 3.4 +/- 1.7 in HD; LPS + Vit.D3 50 ng, 263 +/- 296 (N), 6.73 +/- 11 (CRF), 38 +/- 28 (HD); LPS + Vit.D3 25 ng = 873 +/- 583 (N), 325 +/- 483 (CRF), 588 +/- 507 (HD); LPS + Vit.D3 12.5 ng, 954 +/- 483 (N), 912 +/- 510 (CRF), 875 +/- 527 (HD)]. Comparable data were observed on IL-1beta production. In vivo, the intradialytic TNF-alpha increase (from 8.5 +/- 2.3 to 19 +/- 5.6 pg/2.5 x 106 cell) during hemodialysis was markedly reduced after calcitriol therapy (from 6.6 +/- 3.1 to 11 +/- 4.7). [Ca++]i decreased from 105 +/- 25 to 72 +/- 18 nM (P < 0.05) and a positive correlation between cytokine levels and [Ca++]i was found (r = 0.79; P < 0.001). Conclusions. The in vitro increase of cell-associated cytokine after LPS challenge was inhibited by calcitriol in a dose-dependent manner. These data suggest a possible in vivo modulatory effect of calcitriol therapy on cytokine production in hemodialysis.     

Soluble interleukin-1 receptor antagonist serum levels in smokers and nonsmokers with Graves' ophthalmopathy undergoing orbital radiotherapy

Interleukin-1 (IL-1) plays an important role in the pathogenesis of Graves' ophthalmopathy (GO). Impaired antagonism of the proinflammatory cytokine IL-1 by the naturally occurring IL-1 receptor antagonist (IL-1RA) has been implicated in the initiation and perpetuation of various autoimmune diseases and may play a role in the evolution of GO. Cigarette smoking appears to adversely affect the course of GO. We have evaluated the course of IL-1 alpha, IL-1 beta, and soluble IL-1RA (sIL-1RA) serum levels in smokers and nonsmokers with GO undergoing orbital radiotherapy (OR). We prospectively studied the eye status of 27 randomly selected patients (mean age 47.3 +/- 11.0 yr; 20 females; 18 smokers) with active, moderately severe GO before and 3 and 6 months following OR, respectively. None had received any previous treatment for GO, and all patients were kept euthyroid on carbimazole. Serum concentrations of IL-1 alpha, IL-1 beta, and sIL-1RA were measured using highly sensitive enzyme linked immunosorbent assay systems. Baseline sIL-1RA levels were negatively correlated with the number of cigarettes smoked before and following OR (P < 0.0001). Patients with no or minor therapeutic response to OR (n = 8), all of whom were smokers, revealed mean baseline sIL-1RA levels of 114 +/- 85 pg/mL, which increased to 172 +/- 103 pg/mL at 3 months and 149 +/- 96 pg/mL at 6 months after initiation of OR, respectively. By contrast, patients with a good clinical response (n = 19, 9 nonsmokers), revealed significantly higher baseline sIL-1RA levels at 294 +/- 148 pg/mL (P = 0.004), which increased to 845 +/- 668 pg/mL at 3 months (P = 0.01) and 634 +/- 337 pg/mL at 6 months (P < 0.001), respectively, following initiation of OR. Serum concentrations of IL-1 alpha IL-1 beta were below 3.9 pg/mL in all patients with GO who were studied, and were not correlated with gender, age, smoking status, clinical course, or outcome. Low baseline levels and impaired surge of sIL-1RA serum levels following OR were strongly correlated with smoking status and a less favorable therapeutic outcome in patients with active, moderately severe GO. Measurement of sIL-1RA may contribute to predict the therapeutic response to OR in patients with active, moderately severe GO. Strategies designed to raise local or systemic concentrations of sIL-1RA may be of benefit to patients with GO.     

Safety and efficacy of pulse and daily calcitriol in patients on CAPD: a randomized trial

BACKGROUND: Calcitriol therapy is the mainstay of therapy for the treatment of secondary hyperparathyroidism. Oral administration of calcitriol is necessary in CAPD patients, but no studies have directly compared different routes of administration in this patient population. METHODS: To determine if the peak serum calcitriol level (pulse therapy) is more important than the total delivered dose, we randomized CAPD patients with mild to moderate secondary hyperparathyroidism to receive either pulse (3.0 microg twice a week, n = 10) or daily (0.75 microg a day, n = 8) oral calcitriol in comparable weekly doses. The main comparison was the rate of decline of serum intact parathyroid hormone (PTH) levels to reach the desired end-point of 100 pg/ml. The patients were dialysed with low-calcium dialysate and received only calcium-containing phosphate binders. RESULTS: Pharmacokinetic analysis after a single dose of 3.0 microg (pulse) vs 0.75 microg (daily) revealed 1,25(OH)2-vitamin D levels to be higher in the pulse group at 3 and 6 h, but equivalent by 12 h. The area under the curve for 1 week of daily and 1 week of pulse therapy was equal. The patients in the 2 arms had equivalent basal serum levels of PTH (pulse = 562 +/- 291 vs daily = 454 +/- 113 pg/ml), calcium (pulse = 2.32 +/- 0.20 vs daily = 2.32 +/- 0.12 mmol/l) and phosphorus (pulse = 1.32 +/- 0.52 vs daily = 1.35 +/- 0.26 mmol/l). The time required for the PTH to decrease to 100 pg/ml and the rate of decline in PTH were similar (time: pulse = 14.2 +/- 6.8 weeks, daily = 12.2 +/- 7 weeks; rate: pulse = 7.4 +/- 4.2 vs daily = 8.4 +/- 4.2% PTH/week; P = NS). The serum calcium increased similarly in both groups. Hypercalcaemia (> 2.9 mmol/l) was rare (pulse = 3, daily = 2 episodes). CONCLUSIONS: This study demonstrates that pulse and daily calcitriol are similarly effective and safe for the treatment of mild to moderate secondary hyperparathyroidism in CAPD patients despite higher peak levels of 1,25(OH)2-vitamin D with pulse therapy.     

The mouse homolog of the human Miller-Dieker chromosomal region (MDCR) maps to mouse chromosome 11 in close proximity to Mov9 and D11Nds1

Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 have been shown to stimulate the synthesis of acute-phase proteins; however, few studies have examined the effect of these cytokines on gluconeogenesis. We investigated the effects of these cytokines on gluconeogenesis in primary cultures of rat hepatocytes. Incubation of hepatocytes for 24 hours with TNF-alpha or IL-1 alpha did not affect gluconeogenesis. Hepatocytes incubated with 100 pmol/L and 1 nmol/L IL-6 had a dose-dependent increase (P < .05) in gluconeogenesis (2.6 +/- 0.1 and 3.2 +/- 0.1 pmol/10(6) cells/min, respectively) as compared with controls (2.0 +/- 0.1).     

Aggressive treatment of childhood asthma with local steroids. Good or bad?

OBJECTIVES: Lipoprotein(a) consists of an LDL-particle attached to apolipoprotein(a), which is made by the liver. Diterpenes present in boiled coffee raise serum levels of LDL cholesterol and of the liver enzyme alanine aminotransferase in man. We investigated the association between intake of boiled coffee and serum levels of lipoprotein(a). DESIGN, SETTING AND SUBJECTS: Healthy Norwegians 40-42 years of age, who habitually consumed five or more cups of boiled coffee per day (n = 150) were compared with matched filter coffee consumers (n = 159) in a cross-sectional study, as part of the Norwegian National Health Screening in 1992. RESULTS: The median lipoprotein(a) level was 13.0 mg dL-1 (10th and 90th percentile: 2.5 and 75.0 mg dL-1, respectively) on boiled and 7.9 mg dL-1 (10th and 90th percentile: 1.9 and 62.5 mg dL-1, respectively) on filter coffee (P = 0.048). Means +/- SE were 25.8 +/- 2.4 mg dL-1 and 19.6 +/- 2.0 mg dL-1, respectively (P = 0.04). Although not statistically significant, subjects consuming nine or more cups of coffee per day had higher lipoprotein(a) levels than those drinking five to eight cups per day in both coffee groups. CONCLUSION: Chronic consumers of unfiltered, boiled coffee have higher serum levels of lipoprotein(a) than filter coffee drinkers.     

Gene therapy with bilirubin-UDP-glucuronosyltransferase in the Gunn rat model of Crigler-Najjar syndrome type 1

PURPOSE: The purpose of this study was to investigate the relationship between training-induced alterations in plasma volume (PV) and changes in fluid and electrolyte regulatory hormones during prolonged exercise. METHODS: Seven male subjects (VO2peak 49.2 +/- 2.4 mL.kg-1.min-1, X +/- SE) performed a cycling test before (C) and after (T) 6 d of training and after 6 d of detraining (DT). Training was conducted for 2 h.d-1 at 68% VO2peak at a room temperature between 26-28 degrees C. The 60-min exercise challenge included 20 min at 50%, 65%, and 75% VO2peak workloads. RESULTS: Training resulted in a calculated 13.8 +/- 1.6% PV expansion (P < 0.05) which recovered to C levels with DT (1.8 +/- 2.3%, P > 0.05). Compared with that at C, training resulted in a reduction of aldosterone (ALDO) concentration at all exercise intensities (P < 0.05) which normalized to C levels with DT. With T, epinephrine (EPI) concentrations were reduced at the highest power output only (365 +/- 51 vs 113 +/- 22 pg.mL-1; P < 0.05) and returned to C levels with DT. Arginine vasopressin (AVP) concentrations were also reduced at the highest workload only (20.2 +/- 3.2 pg.mL-1 vs 10.4 +/- 0.7 pg.mL-1; P < 0.05) and remained depressed after DT (11.8 +/- 1.3 pg.mL-1; P < 0.05). Atrial natriuretic factor (ANF) and norepinephrine (NOREPI) were not affected by T or DT. CONCLUSIONS: The results suggest that concentrations of ALDO, and to a lesser extent EPI, during exercise are related to PV levels, whereas ANF and NOREPI concentrations are not. AVP concentrations are related to other adaptive factors, the effects of which persist for a longer time course than do PV changes.     

Cytokine expression in a rat model of Staphylococcus aureus endophthalmitis

PURPOSE: To examine the ability of viable Staphylococcus aureus to induce the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, cytokine-induced neutrophil chemoattractant (CINC), and interferon (IFN)-gamma after intravitreal injection. METHODS: Experimental rat eyes were injected with a 25-microl volume of approximately 80 colony-forming units of viable S. aureus; control eyes received sterile saline. Eyes were graded daily for signs of clinical inflammation and were removed 6, 24, 48, and 72 hours after injection. One group was prepared for histologic analysis, and vitreous was removed from the other group for cytokine analysis, using standard enzyme-linked immunosorbent assay procedures. RESULTS: TNF-alpha, IL-1beta, CINC, and IFN-gamma were detected in experimental vitreous samples at increased levels that peaked at 24 hours. TNF-alpha, IL-1beta, and CINC declined at 48 hours, but IFN-gamma remained elevated. At 72 hours, levels returned to baseline. Statistically significant elevations of TNF-alpha, IL-1beta, and CINC were detected in experimental samples at 24, but not at 6 and 48 hours compared with levels in saline control samples (P < 0.03). A statistically significant increase in IFN-gamma was detected at 24 and 48 hours compared with control levels (P < 0.03). In experimental animals, clinical inflammation and inflammatory cells peaked at 24 hours, persisted at 48 hours, and began to decline thereafter. Neutrophils were the predominant inflammatory cell detected at 24 (72.3% of cells) and 48 (60.1%) hours. By 72 hours, the total number of inflammatory cells had decreased by 75.0%, and the cellular infiltrate had changed so that neutrophils equaled monocytes-macrophages. CONCLUSIONS: S. aureus induced the expression of TNF-alpha, IL-1beta, CINC, and IFN-gamma. The time course of these cytokine levels could account for the clinical inflammatory responses and the entry and decline of vitreous cells in this model of bacterial endophthalmitis.     

Correlation of inflammatory cytokines with arthroscopic findings in patients with temporomandibular joint internal derangements

PURPOSE: The goal of this study was to evaluate the presence of the inflammatory cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) within the superior temporomandibular joint (TMJ) space in patients with internal derangements and to compare these values with the pathologic findings seen arthroscopically. PATIENTS AND METHODS: Thirty patients with symptomatic TMJ dysfunction and clinical and imaging evidence of internal derangements of the TMJ were evaluated. Before entering the superior joint space with the arthroscope, 2 mL sterile saline was injected and, after 30 seconds of equilibration, was aspirated for analysis. The surgeon then performed diagnostic arthroscopy. The degree of synovitis, degeneration, percent condylar roofing, and any pathologic changes, such as perforations, were recorded. The level of total protein in each sample was ascertained, as well as the levels of IL-1 beta, IL-6, and TNF-alpha. RESULTS: Of 30 samples tested, three were discarded because of failure to gain access into the superior joint space. Of the 27 remaining samples, IL-6 showed the closest correlation with the level of acute synovitis demonstrated arthroscopically. Two of the higher IL-6 levels (167 and 324 pg/microg protein) were seen with patients with a significant disc perforation. In patients with a high degree of vascularity, IL-6 was found to be between 0 to 581 pg/microg protein with an average of 80 pg/microg protein and a median value of 43 pg/mg. These values significantly correlated with the degree of vascularity (P < or = .02). This is in comparison with the 10 remaining patients, who showed significantly fewer vascular changes arthroscopically. In these patients, the range of IL-6 was 0 to 35 pg/microg protein, with an average of 19 pg/microg protein and a median value of 14.5 pg/microg. These values significantly correlated with the smaller degree of vascularity (P < or = .02). In seven patients, the role of nonsteroidal antiinflammatory drug (NSAID) use resulted in decreased levels of IL-6, which has been noted in previous studies. In patients with higher rated redundancy of the synovial tissue, the average IL-6 level was 92 pg/microg protein, whereas the median value was 44 pg/microg protein. In patients with little or no redundant synovial tissue, an average IL-6 level of 22 pg/microg protein was present. The median value in these same joints was 15 pg/microg protein. These IL-6 values significantly correlated with the degree of redundancy (P < or = .03). The degree of degenerative change (chondromalacia, fibrillation), disc displacement (roofing), and the presence or absence of adhesions did not significantly affect the levels of IL-6 within the patients studied. The presence of IL-1 beta and TNF-alpha was not found to correlate with the arthroscopic findings in the superior joint space. CONCLUSIONS: The presence of IL-6 correlated with the degree of acute synovitis. IL-1 beta and TNF-alpha were not found in significant levels within the superior joint space. These findings correlated with those reported by other investigators. The production of IL-6 by synovial cells and its role in TMJ disease warrants further investigation.     

Serum interleukin-6 in relation to acute-phase reactants and survival in patients with renal cell carcinoma

Patients with malignancies often present with signs of inflammatory reactions such as elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Since interleukin-6 (IL-6) is a possible regulator of these reactions and has been proposed as a predictor of prognosis, the aim of the study was to analyse its clinical significance in patients with renal cell carcinoma. Serum samples were collected from 196 patients before any treatment. IL-6 was analysed by an enzyme-linked immunoassay and compared with tumour grade, stage, acute-phase reactants and survival. Patients with renal cell carcinoma had significantly higher IL-6 levels (mean 28.1 +/- 63.4 ng/l; median 8.3 ng/l) compared with controls (mean 1.7 +/- 2.6 ng/l; median 0.5 ng/l; P < 0.001). Serum IL-6 levels in patients with distant metastases were significantly higher than for patients with tumours confined to the kidney (P = 0.02). This difference was more pronounced when serum IL-6 levels in patients with poorly differentiated tumours were compared with well-differentiated tumours (P < 0.001). A significant correlation between the acute-phase reactants CRP, ESR and IL-6 levels was found. Survival time was significantly shorter (P = 0.001) for patients with IL-6 levels above the median serum level compared with patients with lower levels. Similar significant prognostic results were obtained in the group of patients with metastatic disease, but not in group of patients with stage I-III. Serum levels of IL-6 correlated to tumour stage, grade and acute-phase reactants. Increased levels were related to the presence of metastases and adverse survival. Serum IL-6 proved univariate prognostic information but this prognostic significance was lost using a multivariate analysis.