Specific self-antigen-driven immune response in pericardial effusion as an isolated GVHD manifestation.

Pericardial effusion and cardiac tamponade have been described as GVHD manifestations in the post transplant period. Direct evidence of GVHD-related TCR or B-cell receptor clones in patients with pericardial effusion has never been described. Using several methods, including FACS and spectratyping analysis to assess T- and B-cell clonality and to quantify TCR excision circles to assess newly thymus-derived T cells, we were able to show expansion of oligoclonal T-cell populations and the possible presence of early/premature B cells in the pericardial effusion but not in peripheral mononuclear cells. This may explain the presentation of an isolated GVHD manifestation.

Vitamin D deficiency and insufficiency in Orthodox and non-Orthodox Jewish mothers in Israel.

BACKGROUND: The modest clothing that Orthodox Jewish women wear exposes very little of their skin to sunlight. Under these conditions they may develop vitamin D deficiency, even in sunny Israel. OBJECTIVES: To determine and compare the vitamin D nutritional status in Jewish orthodox mothers to that of non-orthodox mothers who live in the same metropolitan area in Israel. METHODS: 25-Hydroxyvitamin D was measured by competitive protein-binding radioassay in the sera of 341 Jewish Israeli mothers (156 orthodox and 185 non-orthodox). The sera were obtained 48-72 hours after childbirth during the late summer of 1998 and the spring of 1999. RESULTS: The mean (SD) serum concentration of 25-OHD was significantly (P < 0.002) lower (13.5 +/- 7.5 ng/ml) in the orthodox than in the non-orthodox mothers (18.6 +/- 9.6 ng/ml). Vitamin D deficiency (< 5 ng/ml) and insufficiency (< 10 ng/ml) were more common in the orthodox mothers (5.1% and 32.7% respectively) than in the non-orthodox mothers (2.7% and 13%, respectively). In subgroups of mothers supplemented with 400 units of vitamin D daily during pregnancy, vitamin D deficiency and insufficiency were less common (2.2% and 13%, respectively) in orthodox and non-orthodox mothers (0% and 8.1%, respectively). Vitamin D insufficiency was more common in the winter than in the summer only among non-orthodox mothers. CONCLUSIONS: The high prevalence of vitamin D deficiency and insufficiency in Israeli mothers raises the question whether vitamin D supplements should be given to pregnant women in Israel, at least to orthodox mothers.

Procalcitonin correlates with C-reactive protein as an acute-phase reactant in pediatric patients.

BACKGROUND: Previous reports on the behavior of procalcitonin blood levels in diverse clinical conditions suggest that it is part of the activation of cellular immunity and is another acute-phase reactant. OBJECTIVE: To compare procalcitonin with C-reactive protein, a well-known acute-phase reactant, in a series of acutely febrile pediatric patients and to review recent literature on procalcitonin. METHODS: Procalcitonin and CRP levels were evaluated in 38 blood samples of pediatric patients who were admitted to the Dana Children's Hospital for evaluation of unexplained fever or for sepsis work-up. RESULTS: The parallelism between procalcitonin and CRP was found to be highly significant (P < 0.01). CONCLUSION: The rise of procalcitonin blood levels in febrile pediatric patients suggests that it is part of the acute-phase reaction, parallel with the CRP reaction.

First generation cephalosporins as therapy for uncomplicated pyelonephritis in children. A retrospective analysis.

There is no consensus opinion for the optimal management of pyelonephritis in children. We summarized our experience with first generation cephalosporins by a retrospective analysis of 129 pediatric patients with pyelonephritis who were treated either by first generation cephalosporins (97 patients, group 1) or broad-spectrum antibiotics (32 patients, group 2). Group 1 patients were less likely to have reported previous urinary infections or anatomical urinary tract abnormalities (16.2% vs. 53.1%, p= 0.002) and pathogens other than E. coli (7.3% vs. 25%, p=0.02). Resistance to first generation cephalosporins was identified in 22.6% of pathogens cultured, however, only 7.5% of them had poor clinical responses and required alternative treatment replacement. Our findings show that first generation cephalosporins could be used in our region to treat pyelonephritis in an otherwise healthy child, and that they can provide therapeutic success even in the face of apparent bacterial resistance.

Effect of endothelin-1 on alpha-smooth muscle actin expression and on alveolar fibroblasts proliferation in interstitial lung diseases.

Endothelin-1 (ET-1) is a potent constrictor and mitogen peptide which is expressed in several pulmonary diseases. To elucidate the involvement of ET-1 in lung interstitial pathologic events, we assessed ET-1 secretion by alveolar macrophages (AM) and fibroblasts recovered from the bronchoalveolar lavage (BAL) of patients with idiopathic pulmonary fibrosis (IPF), sarcoidosis (SA) and from control subjects. We characterized in vitro alveolar fibroblasts of all subjects using monoclonal antibody specific to alpha-smooth muscle actin (alpha-SM actin) and human fibroblast marker. We also examined the effect of ET-1 on the fibroblasts' mitogenesis and on their cytoskeletal phenotype. The AM recovered from IPF patients showed increased spontaneous secretion of ET-1 compared with cells from SA and control subjects. The expression of alpha-SM actin in the fibroblasts from IPF patients was significantly higher than in SA fibroblasts and normal lung fibroblasts. Assessing alveolar fibroblasts purity revealed a negative staining for alpha-SM actin in all SA and control fibroblasts, while alveolar fibroblasts recovered from IPF were 100% positive for alpha-SM actin, a reliable differentiation marker of myofibroblastic cells. Exposure of SA alveolar fibroblasts to ET-1 resulted in an increased expression of alpha-SM actin. Addition of exogenous ET-1 to alveolar fibroblasts culture stimulated DNA synthesis and proliferation in all groups. Moreover, neutralization of ET-1 by monoclonal antibody was shown to decrease 3H-thymidine incorporation in fibroblasts cultured with AM supernatants. These results suggest possible interactions between AM, myofibroblasts and fibroblasts in interstitial lung diseases (ILD). By modulating alpha-SM actin expression and exertion of the mitogenic effect on alveolar fibroblasts, ET-1 might play an important role in the fibrogenesis of ILD.

Increased apoptosis in patients with major depression: A preliminary study.

Apoptosis is a programmed cell death that can be observed in normal cells. Major depression poses a combination of a depressed and destructive autoimmune reaction. We measured apoptosis in the PBLs of seven patients with major depression and in age- and sex-matched controls. We observed significantly increased apoptosis in the PBLs of depressive patients (p < 0.05). These preliminary results could contribute to an understanding of the interactions of the CNS with the immune system, which could lead to the increased vulnerability of the CNS in depressive disorders. Further studies are needed to establish these results.

Immune activation in non-treated suicidal major depression.

In the following study we have analyzed cytokine secretion of T-cells of suicidal and non-suicidal depressed patients and healthy controls. It was found that T-cells of suicidal depressed patients have Th1 characteristics, while T-cells of non-suicidal depressed patients have Th2 characteristics. Th1 environment is associated with most of autoimmune diseases. It is thus speculated that Th1 activation in suicidal depression may reflect a unique form of autoimmune suicide.

Immunologic responses of HIV-1-infected study subjects to immunization with a mixture of peptide protein derivative-V3 loop peptide conjugates.

V3 loop peptide sequences from several HIV-1 strains were covalently linked to purified protein derivative (PPD) of Mycobacterium tuberculosis. A mixture of PPD conjugates of V3 loop peptides from six different strains of HIV-1 induced a stronger antibody response than a single V3 peptide-conjugate administered to guinea pigs and humans. Sera from animals immunized with a PPD-six peptide-PPD conjugate neutralized multiple primary-isolate strains of HIV-1. Potent immune responses were noted only when animals were primed with bacillus Calmette-Guerin (BCG), PPD was covalently bound to the peptides, and PPD was used as the carrier protein. Based on these animal studies, an immunogen consisting of PPD-conjugated V3 loop peptides from five HIV-1 strains was tested in 7 HIV-1 seropositive PPD skin test positive study subjects. Vaccinees exhibited over time a uniform increase in neutralizing antibodies for both laboratory adapted and primary isolates of HIV-1, including strains from multiple clades. In 3 patients with baseline viral loads between 8000 and 12,000 RNA copies/ml, the viral load declined in 2 patients to <400 copies/ml and in 1 patient to 1200 copies/ml without concurrent administration of highly active antiretroviral therapy (HAART).

Complications of minocycline therapy for acne vulgaris: case reports and review of the literature.

In order to raise the awareness of the potential side effects that can be induced by minocycline, we report three adolescent girls who experienced serious adverse reactions to this therapy, which was prescribed for acne vulgaris.

Effects of inhaled corticosteroids and inhaled cromolyn sodium on urinary growth hormone excretion in asthmatic children.

Over the past few years there has been an increasing awareness that asthma is a chronic inflammatory airways disease. The current therapeutic strategies for treating asthma focus on suppressing the inflammatory process by using cromones or inhaled corticosteroids (ICS). The beneficial effects of ICS in asthma are now well known, but its detrimental effect on linear growth remains a controversial issue. The aim of this open label, nonrandomized, cross-sectional, one-time study was to determine the influence of these drugs on urinary growth hormone (U-GH) levels in prepubertal asthmatic children. U-GH levels were measured in 47 prepubertal asthmatic children who had been treated for at least 6 months with either ICS (beclomethasone or budesonide at a mean daily dose of 360 microg) or with 80 mg daily dose of cromolyn sodium (CrS). There were also nine healthy children who served as a control. These three groups of children were matched for age and gender ratio. The mean level of U-GH in the CrS-treated group was 2.94 +/- 0.96 ng/night; this was significantly higher compared to the mean level of the ICS-treated group (1.99 +/- 0.83 ng/night; P < 0.001) and to the mean level of the control group (1.98 +/- 0.39 ng/night; P < 0.006). There was no significant difference between the mean level of U-GH in the group treated by ICS and the controls (P < 0.9). These results show that the mean levels of U-GH secretion of the children who were treated by CrS for 6 months was significantly increased, compared to the mean U-GH level of the ICS-treated group and the controls. The mean U-GH levels in the last two groups showed no statistically significant difference.

High-dose intravenous immunoglobulin in transient neonatal myasthenia gravis.

A preterm newborn had transient neonatal myasthenia gravis and was mechanically ventilated for 9 days. In addition to the usual supportive care, she was treated with neostigmine and underwent two exchange transfusions. High-dose intravenous immunoglobulin therapy (2 gm/kg) was used for the first time in transient neonatal myasthenia gravis to the best of our knowledge. The clinical and laboratory responses are presented.

Home monitoring for infants at high risk for the sudden infant death syndrome.

The rate of sudden infant death syndrome (SIDS) In Israel is relatively low (0.5-0.9:1,000). Home cardiorespiratory monitoring (HM) is an accepted practice in infants at high risk for SIDS. We report our experience with 261 infants who were referred to our SIDS prevention program. They included: 52 preterm infants with apneas and bradycardias, 83 SIDS siblings (3 twins), 22 infants of drug-addicted mothers, and 104 infants after an idiopathic apparent life-threatening event (ALTE). HM was performed in 40 of 52 preterms, 38 of 83 SIDS siblings, all 22 infants of addicted mothers and 67 of 104 post-ALTE. All received 24 h/day medical and technical backup as well as emotional support, and were closely followed until 15 months of age. None of the 261 infants died. Five infants experienced six ALTEs that required resuscitative measures; another 28 infants had monitor alarms judged as real by the caregivers. The average duration of HM was 3.2 months (range 1-7). In 8 of 167 cases the parents stopped HM earlier than recommended, and in 34 of 167 cases (20%), parents continued HM beyond the time when discontinuation was recommended by the medical personnel. Among the caregivers, 85% found HM to be reassuring and stated that it helped them to conduct a normal life. We suggest that in our population, HM may have a favorable effect on family life. With close backup and support, most families will benefit from HM and will gain reassurance that will enable them to conduct normal life.

Periodic syndromes of childhood.

Periodic syndromes of childhood comprise a large group of disorders that require long-term follow-up to be diagnosed. Several disorders have fixed rhythmicity and are therefore identified more easily. Other disorders are usually diagnosed after a prolonged follow-up and exclusion of other more common childhood diseases. In general, most of the periodic fever syndromes have a benign prognosis, and their symptomatology tends to improve in the long term. Periodic syndromes without fever or chronic pain syndromes constitute not only a diagnostic dilemma but also a therapeutic challenge. A general diagnostic approach to the periodic syndromes is outlined in Figure 1.

Familial nasal acilia syndrome.

Mucociliary dysfunction can be caused by the absence of cilia or by abnormalities in their ultrastructure. A family in which some members were suffering from respiratory morbidity due to lack of cilia is described.

Effect of IL-6 on alveolar fibroblast proliferation in interstitial lung diseases.

Alveolar macrophage-fibroblast interaction may be involved in the pathogenesis of interstitial lung diseases (ILD). Herein, we compared IL-6 secretion from alveolar macrophages (AM) and alveolar fibroblasts (AFb) recovered from patients with sarcoidosis (SA) and with diffuse interstitial fibrosis (DIF). Moreover, we evaluated the effect of IL-6 on the in vitro AFb proliferation in both diseases. AM and AFb from SA patients showed increased spontaneous secretion of IL-6 compared with cells from DIF subjects. Tumor necrosis factor-alpha (TNFalpha) and interleukin-1 (IL-1) enhanced IL-6 secretion and IL-6 mRNA transcription in AFb of SA patients. Addition of anti-IL-6 MoAbs increased AFb proliferation capacity in SA, but suppressed it in DIF. These results show that only SA AM and AFb secrete high levels of IL-6 which have suppressive effect on AFb proliferation. This may indicate a potential role of IL-6 in the fibrogenesis of ILD.