Cytokines and tumor markers in potentially malignant disorders and oral squamous cell carcinoma: a pilot study.

OBJECTIVE: To evaluate serum levels of interleukin (IL)-1, IL-6, IL-8, IL-10, soluble IL-2 receptor (sIL-2R), squamous cell carcinoma antigen (SCCA), tissue polypeptide-specific antigen (TPS) and vascular endothelial growth factor (VEGF) in patients with potentially malignant disorders (PMD), oral squamous cell carcinoma (OSCC), or status-post (SP) OSCC. SUBJECTS AND METHODS: Blood was collected from 47 patients, either controls or diagnosed with PMD, OSCC, or SPOSCC. Levels of cytokines and tumor marker were evaluated by ELISAs. Normal levels were based on previous studies and pathology determined by chi-square and Fisher's exact tests. P ≤ 0.05 was considered statistically significant. RESULTS: Above normal levels of SCCA were found for OSCC and dysplasia patients (33.3% and 11.1%, respectively) and high range of normal (upper 20% of the normal range) for lichen planus, SPOSCC, and dysplasia patients (6.67%, 33.3%, and 22.2%, respectively), differences that approached statistical significance (P = 0.055). No differences were found between groups for other tested markers. A progression was seen for SCCA from high range of normal in SPOSCC to a mixture of high normal and elevated in dysplasia to elevated in active OSCC, suggesting that SCCA may be correlated with cancer progression. CONCLUSION: Higher levels of serum SCCA may serve as a marker for dysplasia and progression to oral carcinogenesis.

Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression.

BACKGROUND AND AIMS: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thrombosis, obstetric complications and the presence of anti-phospholipid antibodies such as anti-ß2GPI-Abs. These antibodies may set off the coagulation cascade via several mechanisms, including the induction of tissue factor (TF) expression. Vitamin D has recently emerged as an immunomodulator that might exert an anti-thrombotic effect. Therefore, we studied serum vitamin D levels in a cohort of APS patients, as well as the effect of vitamin D in an in vitro model of APS-mediated thrombosis. METHODS: Serum vitamin D levels were measured in 179 European APS patients and 141 healthy controls using the LIAISON chemiluminescent immunoassay, and the levels were evaluated in conjunction with a wide spectrum of clinical manifestations. In an vitro model, anti-ß2GPI antibodies were purified from four patients with APS to evaluate the expression of TF in activated starved human umbilical vein endothelial cells. The effect of vitamin D (1,25-dihydroxyvitamin D, 10 nm) on anti-ß2GPI-Abs mediated TF expression was analysed by immunoblot. RESULTS: Vitamin D deficiency (serum level ≤15 ng/ml) was documented in 49.5% of our APS patients versus 30% of controls (p<0.001) and was significantly correlated with thrombosis (58% vs 42%; p<0.05), neurological and ophthalmic manifestations, pulmonary hypertension, livedo reticularis and skin ulcerations. In vitro vitamin D inhibited the expression of TF induced by anti-ß2GPI-antibodies. CONCLUSIONS: Vitamin D deficiency is common among APS patients and is associated with clinically defined thrombotic events. Vitamin D inhibits anti-ß2GPI-mediated TF expression in vitro. Thus, vitamin D deficiency might be associated with decreased inhibition of TF expression and increased coagulation in APS. Evaluation of vitamin D status and vitamin D supplementation in APS patients should be considered.

Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D?

BACKGROUND: Low serum vitamin D concentrations have been reported in several autoimmune disorders. OBJECTIVE: To assess whether low serum vitamin D concentrations are related to disease activity of patients with systemic lupus erythematosus (SLE). METHODS: 378 patients from several European and Israeli cohorts were pooled and their disease activity was measured by two different methods: 278 patients had SLE disease activity-2000 (SLEDAI-2K) scores and 100 patients had European Consensus Lupus Activity Measurement (ECLAM) scores. In order to combine the two systems the scores were converted into standardised values (z-scores), enabling univariate summary statistics for the two variables (SLEDAI-2K and ECLAM). The commercial kit, LIAISON 25-OH vitamin D assay (310900-Diasorin) was used to measure serum concentration of 25-OH vitamin D in 378 patients with SLE. RESULTS: A significant negative correlation was demonstrated between the serum concentration of vitamin D and the standardised values (z-scores) of disease activity scores as measured by the SLEDAI-2K and ECLAM scales (Pearson's correlation coefficient r=-0.12, p=0.018). CONCLUSIONS: In a cohort of patients with SLE originating from Israel and Europe vitamin D serum concentrations were found to be inversely related to disease activity.

Serum inflammatory cytokines, complement components, and soluble interleukin 2 receptor in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic cholestatic autoimmune liver disease characterized by selective destruction of the intrahepatic bile ducts and highly specific serum anti-mitochondrial autoantibodies (AMA). Several studies have attempted to determine the cytokine pattern characterizing PBC, yet no definitive data have been gathered. The present study was designed to evaluate pro-inflammatory cytokines (IL-1beta, IL-6, TNFalpha), soluble IL-2 receptor (sIL-2R, e.g. soluble CD25), and complement components (C1q, C3, factor B, properdin) levels in sera from 84 patients with PBC and 41 controls. PBC was characterized by significantly higher levels of all pro-inflammatory cytokines when compared to controls; these included IL-1beta (433.3 +/- 13.2 vs. 316.6 +/- 14.7 pg/ml, P < 0.001), IL-6 (701 +/- 17.4 vs. 158 +/- 22.5 pg/ml, P < 0.001), TNFalpha (3.38 +/- 0.6 pg/ml vs. undetectable, P = 0.001), and sIL-2R (1527.1 +/- 106 vs. 566.4 +/- 28.7 U/ml, P < 0.001). Similarly, all complement components were also significantly higher in PBC compared to control sera. In conclusion, PBC sera manifest higher levels of sIL-2R and complement components and this may reflect a perpetuated immune activation. As expected, we also report that all major pro-inflammatory cytokine levels are enhanced in PBC. Further longitudinal analyses could demonstrate a correlation between these markers and disease stage or inflammatory activity, to predict histological staging, disease activity, and response to treatment.

Prognostic role of serum cytokeratin 19 fragments in advanced non-small-cell lung cancer: association of marker changes after two chemotherapy cycles with different measures of clinical response and survival.

Prognostic implication of serum cytokeratin 19 fragments (CYFRA 21-1) was explored in 60 advanced NSCLC patients, whereas in 45 patients assessable for serological response a >or=35% CYFRA 21-1 decline after two chemotherapy cycles was strongly associated with non-progression (NP), defined as a sum of objective response (OR)+stable disease (P<0.0001) and survival (P=0.0002). Association of OR with survival was not significant. In multivariate survival analysis, >or=35% marker decline and radiological NP status were found as major determinants of prolonged survival with RR: 0.37 (P=0.01) and 0.63 (P=0.01), respectively. In advanced NSCLC patients, NP reflects therapeutic efficacy better than traditional OR. CYFRA 21-1 >or=35% decline seems to be a reliable surrogate marker of treatment efficacy in terms of survival.

Plasma vascular endothelial growth factor level is a predictor of the severity of postoperative capillary leak syndrome in neonates undergoing cardiopulmonary bypass.

Capillary leak syndrome (CLS), characterized by extravascular fluid accumulation and significant organ dysfunction, is a serious complication in children undergoing cardiopulmonary bypass (CPB). We examined the relationship between plasma vascular endothelial growth factor (VEGF) levels and severity of CLS. The kinetics of VEGF in the plasma of 11 neonates and 7 older children undergoing CPB were investigated, correlating plasma VEGF levels and CLS clinical presentation. The degree of postoperative CLS was quantified by measuring parameters of extracellular volume and end-organ dysfunction. A chest-wall soft-tissue-width index (CSTWI) was designed in order to standardize the extracellular fluid accumulation. Most CLS parameters were significantly more prominent in the neonatal patients. Low plasma VEFG levels (>35 pg/ml) were found in 3 neonatal control patients and all but, sample from the older group patient. The neonates had significantly higher preoperative VEGF plasma levels (684.4 +/- 559.1 pg/ml, P = 0.02), which decreased during the operation to levels below 35 pg/ml and increased again 24 h postoperatively to levels significantly higher than in the older patients (484 +/- 270.3 pg/ml, P = 0.001). Multilinear regression analysis found preoperative VEGF levels to independently correlate with CLS as represented by CSTWI (P < 0.01, r = 0.726). Both the occurrence of post-CPB CLS and plasma VEGF levels pre- and postoperatively were thus higher in neonates than in children. Plasma VEGF level is a predictor of the severity of postoperative CLS.

The kinetics of leptin in Meigs' syndrome.

OBJECTIVE: The aim of this study was to assess the kinetics and possible role of leptin in the pathophysiology of Meigs' syndrome. METHODS: We report on a 62-year-old patient admitted for a large ovarian tumor, hydrothorax, and ascites. The patient underwent abdominal hysterectomy and bilateral adnexectomy revealing a benign ovarian fibroma and no evidence of malignant cells in the pleural or peritoneal fluids. Analysis of serum, peritoneal, and pleural fluids from this patient was performed before, during, and after the operation. RESULTS: Preoperatively, the patient had low levels of leptin in the serum, peritoneal, and pleural fluids. Serum levels increased after removal of the ovarian tumor along with the resolution of ascites and hydrothorax. CONCLUSION: Leptin levels inversely correlate to tumor burden, third space fluid accumulation, and clinical status in Meigs' syndrome. These findings suggest the involvement of leptin in the pathophysiology of this syndrome.

Soluble ICAM-1 and E-selectin levels correlate with clinical and biological aspects of severe ovarian hyperstimulation syndrome.

OBJECTIVE: To assess the potential involvement of the soluble endothelial cell-leukocyte adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1) in the pathophysiology of capillary hyperpermeability in the ovarian hyperstimulation syndrome (OHSS). DESIGN: Controlled clinical study. SETTING: Women hospitalized for severe OHSS after ovulation induction for IVF at two tertiary medical centers. PATIENT(S): Eleven patients with severe OHSS undergoing IVF and 20 controls who had received a similar ovulation induction regimen and did not develop OHSS. INTERVENTION(S): Serial serum samples were obtained from all patients with OHSS from admission until discharge. Ascitic fluid was obtained from all patients by therapeutic paracentesis. Serum was obtained from all controls 4-8 days after ET. MAIN OUTCOME MEASURE(S): Samples were assayed for soluble E-selectin and soluble ICAM-1 by using enzyme-linked immunosorbent assay and results were correlated with clinical and biological aspects of OHSS. RESULT(S): Compared with controls, patients with severe OHSS had higher levels of soluble ICAM-1 and lower levels of soluble E-selectin detected in serum and ascites. Serum levels of soluble ICAM-1 decreased, while soluble E-selectin levels increased along with clinical and biological improvement. Serum soluble ICAM-1 showed significant positive correlation and serum soluble E-selectin showed significant negative correlation with clinical and biological aspects of severe OHSS. CONCLUSION(S): Soluble ICAM-1 and soluble E-selectin seem to be involved in the pathophysiology of capillary hyperpermeability in severe OHSS.

The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines.

Sambucus nigra L. products - Sambucol - are based on a standardized black elderberry extract. They are natural remedies with antiviral properties, especially against different strains of influenza virus. Sambucol was shown to be effective in vitro against 10 strains of influenza virus. In a double-blind, placebo-controlled, randomized study, Sambucol reduced the duration of flu symptoms to 3-4 days. Convalescent phase serum showed a higher antibody level to influenza virus in the Sambucol group, than in the control group. The present study aimed to assess the effect of Sambucol products on the healthy immune system - namely, its effect on cytokine production. The production of inflammatory cytokines was tested using blood - derived monocytes from 12 healthy human donors. Adherent monocytes were separated from PBL and incubated with different Sambucol preparations i.e., Sambucol Elderberry Extract, Sambucol Black Elderberry Syrup, Sambucol Immune System and Sambucol for Kids. Production of inflammatory cytokines (IL-1 beta, TNF-alpha, IL-6, IL-8) was significantly increased, mostly by the Sambucol Black Elderberry Extract (2-45 fold), as compared to LPS, a known monocyte activator (3.6-10.7 fold). The most striking increase was noted in TNF-alpha production (44.9 fold). We conclude from this study that, in addition to its antiviral properties, Sambucol Elderberry Extract and its formulations activate the healthy immune system by increasing inflammatory cytokine production. Sambucol might therefore be beneficial to the immune system activation and in the inflammatory process in healthy individuals or in patients with various diseases. Sambucol could also have an immunoprotective or immunostimulatory effect when administered to cancer or AIDS patients, in conjunction with chemotherapeutic or other treatments. In view of the increasing popularity of botanical supplements, such studies and investigations in vitro, in vivo and in clinical trials need to be developed.

Bone marrow stromal dysfunction in mice administered cytosine arabinoside.

OBJECTIVE: The aim of the study was to investigate ex-vivo the bone marrow (BM) stroma of mice under conditions of low- and high-dose cytosine arabinoside (Ara-C), a cycle-specific drug (S-phase) and to assess possible stromal damage, apart from the killing of hematopoietic cells. Stroma consists of mesenchymal elements generally not in the cell cycle; therefore it could not be a target for the killing effect of Ara- C. MATERIALS AND METHODS: The stromal function was studied by the following: the incidence of stromal stem cells, i.e. CFU-F; formation of stromal layers under growth conditions of long-term culture (LTC) followed by irradiation and overlayering of test cells in contact and non-contact co-cultures; subsequent culture of the test cells in a semi-solid medium to assay the incidence of hyperproliferative potential cells (HPPC); production of GM-CSF, IL-3, IL-4, IL-6 and IFNgamma in the conditioned medium (CM) of confluent stromal layers. All tests and assays were carried out on BM specimens, 1-4 d after Ara-C administration and on controls. RESULTS: Low-dose Ara-C induces a marked decrease of CFU-F, compensated by cycle induction of pre-CFU-F, young-type stromal stem cells. High-dose Ara-C causes a CFU-F decrease to almost zero level. The time length to layer confluency is normal after low-dose Ara-C ( approximately 10 d) and prolonged after a high dose ( approximately 30 d). The confluent layers from mice receiving low- or high-dose Ara-C support hematopoiesis adequately. Among the growth factors and cytokines assayed, only IL-6 is detected in CM layers. IL-6 decreases after a low dose of Ara-C and increases after a high dose. The cause of IL-6 fluctuations is yet to be investigated. It is, however, evident that IL-6 is not an essential factor in support of hematopoiesis. CONCLUSIONS: Taken together, the current study in mice indicates that Ara-C administration, in particular a high dose, induces bone marrow stromal damage and/or disfunction. The long period of time to reach layer confluency after a high Ara-C dose might reflect the in-vivo situation of slow stromal regeneration.

Markedly elevated levels of vascular endothelial growth factor, fibroblast growth factor, and interleukin 6 in Meigs syndrome.

Analysis of serum and peritoneal and pleural fluid from a patient with Meigs' syndrome revealed high levels of vascular endothelial growth factor, fibroblast growth factor, and interleukin 6. Serum levels declined after removal of the ovarian tumor, along with resolution of ascites and hydrothorax. These findings suggest the involvement of these vasoactive factors in ascites and pleural fluid formation in Meigs' syndrome.

Ex vivo expansion of CD56+ cytotoxic cells from human umbilical cord blood.

The immune-mediated effect of natural killer (NK) and cytotoxic T cells against residual tumor cells previously was shown to prevent relapse and reinduce remission after bone marrow transplantation. Human umbilical cord blood is a rich source of cytotoxic CD56+ cells including fetal NK cells (CD16(-)CD56+1) with high lytic capabilities upon activation with interleukin-2 (IL-2). Cord blood transplantations are reported to be associated with lower risk of graft-vs-host disease, which may jeopardize the graft-vs-leukemia effect. Therefore, our goal was to expand and amplify, ex vivo, cord blood-derived CD56+ cell-mediated cytotoxic activity. Cord blood-derived CD56+ cells were separated using anti-CD56 monoclonal antibody and immunomagnetic beads. The cells were expanded in the presence of irradiated feeder cells and various concentrations of IL-2. Maximal fold expansion (152 +/- 29) was achieved on day 22 by culturing the cells in the presence of irradiated autologous lymphocytes. Irradiated murine stromal cells yielded 42 +/- fourfold expansion (p < 0.05). FACS analysis at the peak of expansion revealed that the cells were 96% +/- 1% CD56+. Interferon-gamma levels significantly decreased throughout the culture period (from 1,034 +/- 34 pg/mL to 21 +/- 8 pg/mL) as did IL-6 levels (from 11,535 +/- 1,452 pg/mL to 323 +/- 161 pg/mL) whereas tumor necrosis factor-alpha levels did not change. The expanded cells manifested potent lytic capabilities against K562 and Colo-205 cell lines (70.9% +/- 2.0% and 48.2% +/- 4.0%, respectively) (n = 5) (effector-to-target ratio 25:1). Coculturing the expanded NK cells with fresh ALL blasts resulted in 85% +/- 1% inhibition of colony growth in methylcellulose (n = 2). In addition, the CD56+ expanded cells induced 44% +/- 7.5% apoptosis of K562 target cells (n = 3). It is possible to effectively expand cord blood-derived CD56+ cells, ex vivo, while maintaining their antileukemic capablilities.

Interleukin-18 binding protein in acute graft versus host disease and engraftment following allogeneic peripheral blood stem cell transplants.

Dysregulation of the cytokine network plays an important role in graft-versus-host disease (GVHD). Interleukin-18 (IL-18) is an obligatory cytokine for interferon-gamma (IFN-gamma) production and IFN-gamma and sIFN-gammaR are elevated in patients with GVHD. Because IL-18 binding protein (IL-18BP) is an inhibitor of IL-18-mediated IFN-gamma production, we evaluated IL-18BP levels in patients undergoing allogeneic peripheral blood stem cell transplantation (PBSCT). IL-18BP levels were assessed in 14 patients on day -10 (before conditioning), on the day of transplant, on the day of engraftment, and during transplant-related complications. A comparison of the kinetics of IL-18BP and soluble(s) IL-6R, sIFN-gammaR, IL-18 serum levels was performed. IL-18BP levels were assessed by specific monoclonal antibodies in a double-sandwich enzyme-linked immunosorbent assay (ELISA). In all patients IL-18BP levels decreased during conditioning and increased in parallel with engraftment (p < 0.05). Accordingly, during rejection, IL-18BP serum levels remained low and similar to pretransplant levels. The mean elevation of IL-18BP detected in association to acute GVHD was significantly higher in comparison to normal engraftment (p < 0.05). A correlation between IL-18BP, sIFNgammaR, and sIL-6R serum levels was found in all patients. No correlation between IL-18 and IL-18BP serum levels was found in patients undergoing uneventful PBSCT and rejection, whereas a marked increase in both IL-18 and IL-18BP levels was detected during acute GVHD (p < 0.01). Our data suggest that the dysregulation of IL-18 and IL-18BP may be important in the pathophysiology of transplant-related complications. Furthermore, because preliminary data from our group show that IL-18 blockage ameliorates GVHD in murine models, it is inferred that these cytokines may represent potential targets in the development of new therapeutic strategies in acute GVHD.

Comparison of the attitudes of Israeli therapists and lay persons to ethical dilemmas in psychotherapy.

The issues of confidentiality and boundaries cause ethical dilemmas for psychotherapists. We investigated whether therapists have ethical attitudes to confidentiality and boundaries that are unique to their professional group compared with lay persons and whether gender or professional characteristics are associated with these attitudes. Clinical vignettes capturing ethical dilemmas regarding confidentiality and boundaries were presented to 93 psychotherapists of different professional backgrounds (professional group) and 55 staff and students from the fields of law and the humanities (lay group). In general, the lay group showed a greater tendency to maintain confidentiality than the professional group. Regarding boundaries, the majority of psychotherapists were against initiating any sexual relationship with current patients, former patients, students, or supervisees; the differences between the groups in this area were statistically significant. The vast majority of therapists (96.7%) disapproved of accepting money in advance compared with only 54.4% of the lay group. Analysis of the psychotherapists by professional background revealed that for the majority of the vignettes, there was no difference in attitude to confidentiality and boundaries between psychiatrists, psychologists, and social workers. The present study shows that therapists have different ethical codes from nontherapists regarding the issues of boundaries and the treatment contract. Therapists are stricter than nontherapists regarding issues of boundaries but less strict regarding issues of confidentiality, and there are some minor differences in the attitudes to these issues among different types of therapists.

High oxygen concentration exacerbates cardiopulmonary bypass-induced lung injury.

OBJECTIVE: To investigate the effect of ventilation with 100% oxygen on lung injury associated with surgery involving cardiopulmonary bypass (CPB). DESIGN: A prospective randomized study. SETTING: University hospital. PARTICIPANTS: Thirty patients undergoing coronary artery bypass graft surgery with CPB. INTERVENTIONS: Patients were randomized to receive 100% oxygen (Oxygen group) or 50% oxygen (Air group) throughout surgery. During CPB, patients' lungs in the Air group were flushed with air and in the Oxygen group with 100% oxygen. MEASUREMENTS AND MAIN RESULTS: Lung injury was evaluated by arterial oxygen tension-inspired oxygen concentration (PaO2-FIO2) ratio and cytokine levels (tumor necrosis factor-alpha and interleukin-8) in blood and bronchoalveolar lavage fluid measured before and after CPB. The lowest PaO2-FIO2 value was observed after 40 minutes following the completion of CPB in both groups. PaO2-FIO2 values 6 hours after CPB were not different from baseline in the Air group but remained lower (359+/-63 mmHg and 298+/-78 mmHg; p = 0.013) in the Oxygen group. Blood cytokine levels rose during surgery in both groups. Bronchoalveolar lavage levels of interleukin-8 did not change, whereas tumor necrosis factor-alpha increased only in the Oxygen group (p = 0.035). CONCLUSIONS: A significant decrease of oxygenation was observed in the early post-CPB period in both groups of patients, with delay in recovery in patients treated with 100% oxygen. A larger increase of the proinflammatory cytokines was found in patients treated with 100% oxygen. High oxygen concentrations during surgery with CPB should be used only when specifically required.

Short-term systemic effects of head and neck irradiation.

BACKGROUND: Various localized side effects which accompany head and neck irradiation [IR] have been widely reported. However, systemic side effects/have been only sparsely reported in the short-term period post-IR in an animal model. The potential modulatory role of zinc-desferrioxamine [Zn-DFO] on IR effects was examined because of its known ability to protect against the damage induced by free radicals which are mediated by redox-active metal ions. MATERIALS AND METHODS: We used three groups of male Wistar rats: a] sham irradiated controls b] irradiated [15 Gy]; c] irradiated and treated with Zn-DFO [20 mg/k] one hour prior to IR. During the first two weeks post-IR, body weight and food and water intake were monitored daily, while lymphocytes, segmented neutrophils and white blood cells [WBC] were counted at 10 minutes 4 and 16 hours and 1, 3, 7 and 14 days. Serum TNF-a and IL-6 were obtained at 10 minutes and 7 days. RESULTS: On day 7 post-IR, body weight and food and water intake were reduced by 84% 96% and 85% [p < 0.01], respectively in the above mentioned three groups of rats. This resulted in the death of 22% of the animals and was followed by recovery towards the end of the second week. At all time points examined between 10 minutes and 14 days, WBC were reduced by 52-74%. On the 7th day, Zn-DFO demonstrated a 33% protective effect against the WBC reduction. At 10 mins post-IR, a 84.8-fold [p < 0.01] increase of TNF-alpha, but not IL-6, was noted. However, on the 7th day post-IR, both TNF-alpha and IL-6 levels were increased by 48.5-fold and 102.5-fold [0.01], respectively. CONCLUSION: The data presented delineate the severe short-term systemic effects of head and neck IR in a rat model. We suggest considering the severe cachectic and immunocompromised status of the animals when performing various short-term studies with this model. During this period nutritional and immunological support for the examined animals is recommended. Further evaluation of the underlying mechanisms of IR-induced leukopenia and cachexia in animals and the possible implications for humans is warranted.

Perception of ill spouse and dyadic relationship in couples with affective disorder and those without.

BACKGROUND: This study compares the perception of spouses and the quality of the dyadic relationship of patients with severe affective disorders in remission with healthy couples. METHOD: The sample included spouses of patients between the ages of 20 and 65 who had been hospitalized with severe affective illness and who were currently in remission (depressive, n=23; bipolar, n=11) and a control group matched by socioeconomic status. Both groups completed three instruments measuring the quality of the dyadic relationship, attributed characteristics of the spouse and non-formal social support. RESULTS: The spouses of patients, as compared to spouses of controls, scored lower on consensus, unity and expressions of affection in their marital relationship, ranked their ill spouses lower on the positive qualities and higher on the negative qualities and reported receiving less emotional and practical support. LIMITATIONS: The limitations of the study are the small sample size and cross sectional design. CONCLUSIONS: The results suggest that severe affective disorders are associated with marital dysfunction, even during periods of symptom remission.

Increased levels of basic fibroblast growth factor are found in the cross-clamped heart during cardiopulmonary bypass.

BACKGROUND: High concentrations of fibroblast growth factors (FGFs) are found in the heart. Even higher levels are measured during ischemia. Exogenous administration of FGF to ischemic myocardium promotes synthesis of collateral coronary circulation and induces local myocardial hypertrophy. The kinetics and the contribution of the heart and lungs to circulating basic FGF (bFGF) levels during cardiac surgery were characterized. PATIENTS AND METHODS: Plasma bFGF levels were measured in seven adults undergoing coronary artery bypass operations and 11 neonates undergoing congenital cardiac anomaly repair during cardiopulmonary bypass. RESULTS: In both the adult and the neonatal groups, bFGF plasma levels increased significantly immediately after removal of the aortic cross-clamp (adult group 15.43+/-6.3 aorta cross-clamped versus 29+/-4.1 after release, P=0.011; neonatal group 17.09+/-9.43 aorta cross-clamped versus 43.55+/-14.25 after release, P=0.004) and declined thereafter. In the adult group, higher levels of bFGF were recorded in blood recovered from the coronary sinus than in the aortic root during aortic cross-clamping (63.14+/-14.42 versus 43.86+/-12.05, P=0.011), and in both, levels were significantly higher than the peripheral measurements. CONCLUSIONS: Plasma bFGF levels increase during cardiopulmonary bypass. The source of this elevation is the lungs and heart.

Neoplastic cell activation and proliferative response to CD40-ligand characterize recurrent leukemic bouts in an unusual case of low grade lymphoma.

Spontaneous fluctuations in activity of low-grade B cell lymphomas are common but not understood. An explanation may be offered by studying an atypical SLL/CLL case characterized by recurrent cycles of leukemic phase alternating with spontaneous remission (1). During remissions, residual IgMkappa+ leukemic cells exhibited resting phenotype, low proliferative response to CD4O-ligand and delayed apoptosis. In contrast, the acute phase counterparts were phenotypically activated, underwent rapid apoptosis in culture and proliferated extensively in response to membrane-anchored CD40-ligand. Transient bursts of serum TNFalpha and IL-10 preceded the acute phases, which were characterized by the co-existence of CD40-ligand+ T lymphocytes and lymphoma cells in the bone marrow. Based on ex-vivo and in-vitro data, we suggest that changes in the lymphoma milieu affect the neoplastic cell activation status, rate of proliferation in response to activated T cells and rate of apoptosis. These responses may underlie both the induction and spontaneous regression of the acute phases in this unique lymphoma. Our findings raise the possibility that part of this mechanism may have evolved during transformation of indolent common CLL to its more aggressive form.

Specific in vitro proliferative immune responses and lymphokine production in Ethiopian children with and without tuberculosis.

UNLABELLED: We investigated the profile of some in vitro parameters of cellular immune responses in non-HIV-infected Ethiopian children and young adults with and without tuberculosis (TB) as compared to healthy Ethiopian and non-Ethiopian controls. The in vitro proliferative responses of peripheral blood mononuclear cells (PBMC) to purified protein derivative (PPD) were determined in 15 Ethiopian children and young adults with TB, 12 healthy Ethiopian children who were contacts of TB patients, 20 Ethiopian children without contact with TB and ten non-Ethiopian controls. All TB patients and contacts had a positive Mantoux skin test. The PBMC proliferative response to PPD of the Ethiopian children with TB was significantly higher than that of the Ethiopian children without TB, while all Ethiopian children demonstrated stronger proliferative response as compared to non-Ethiopian healthy controls. Interleukin 2 (IL-2), interferon gamma (IFN-gamma), interleukin 4 (IL-4) and interleukin 6 (IL-6) were measured by ELISA assays performed on the supernatant of PPD-stimulated and non-stimulated PBMC cultures of seven Ethiopian children with TB, ten Ethiopian children without TB and eight non-Ethiopian controls. IFN-gamma and IL-4 were undetectable and IL-2 levels in unstimulated supernatants were low in all groups. PPD stimulation induced a significant rise in IL-2 levels in Ethiopians with TB as compared to all other groups. There was no increase above baseline in IL-6 levels in any group studied. CONCLUSIONS: Ethiopian children with TB exhibit a strong cellular immune response as expressed by Mantoux tests and lack of stimulation of IL-4 and IL-6 production. This pattern suggests a Th1 type effective cellular immune response to mycobacteria in a cohort of young Ethiopians with TB.