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Biomedical subjects

Z Spirer

Publications and source records attributed to Z Spirer.

At least 19 recordsLinked to original sources

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.

Acute-Phase Reaction↗

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).

AIDS Vaccines↗

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.

Adult↗

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.

Cytokines↗

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.

Actins↗

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.

Administration, Inhalation↗

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.

Acute Disease↗

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.

Home Care Services↗

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.

Child↗

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.

Cell Division↗

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.

Cilia↗

Localized fibromyalgia in a child.

A 14-year-old male was investigated because of a limp and a localized sharp pain in the right lumber paravertebral region radiating to the lower abdomen and the medial aspect of the thigh, which started following forced physical activity. With the diagnosis of fibromyalgia the patient received two perifacetal injections of local anaesthetics with steroids followed by transcutaneous electrical nerve stimulation (TENS). Following the injections, pain intensity dropped dramatically, disability was reduced and muscle swelling resolved. The possible association of symptoms to sport activity raises the question of sport-induced fibromyalgia, and the excellent response to treatment may suggest a facet joint irritation as possible aetiology.

Adolescent↗

Low-dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids.

The aim of the present study was to examine the use of low-dose ACTH-(1-24) stimulation for assessment of adrenal function and the detection of mild adrenal insufficiency. The criteria for normal response to ACTH-(1-24) are a peak cortisol level of more than 500 nmol/L (18.1 micrograms/dL) and an increment of the cortisol level above the basal one of more than 200 nmol/L (7.2 micrograms/dL). These criteria were satisfied by 32 of 33 healthy children and adults subjected to an ACTH-(1-24) dose 500 times lower (0.5 micrograms/1.73 m2) than the dose of 250 micrograms in the standard test. At 20 min, the peak cortisol level was the same in the low-dose test [(621 +/- 28 nmol/L) (22.5 +/- 1.0 microgram/dL)] as in the standard ACTH test [(654 +/- 31 nmol/L) (23.7 +/- 1.1 microgram/dL)]. Of 46 asthmatic patients who had been treated with inhaled beclomethasone dipropionate (482 +/- 42 micrograms/m2 daily; n = 32) or budesonide (507 +/- 62 micrograms/m2 daily; n = 14) for over 6 months, 16 (35%) failed to reach a cortisol peak of more than 500 nmol/L (18.1 micrograms/dL) following stimulation with 0.5 micrograms ACTH-(1-24)/1.73 m2. Of these, 11 (24%) showed a cortisol increment of less than 200 nmol/L (7.2 micrograms/dL). These 16 patients, showing insufficient response to low-dose ACTH-(1-24), also had a significantly lower (P < 0.01) mean 24-h urinary free cortisol excretion [(71 +/- 10 nmol/m2.24 h) (25.7 +/- 3.6 micrograms/m2.24 h)] than patients who responded normally [(118 +/- 11 nmol/m2.24 h) (42.8 +/- 4.0 micrograms/m2.24 h). Nonetheless, all but one of the poor responders to a 0.5 microgram ACTH showed normal stimulation with the standard 250 micrograms ACTH test. Therefore, it appears that a low-dose ACTH test is capable of revealing mild adrenal insufficiency, which is not detected by the standard high-dose ACTH test.

Administration, Inhalation↗

Amniotic fluid and plasma levels of parathyroid hormone-related protein and hormonal modulation of its secretion by amniotic fluid cells.

Parathyroid hormone-related (PTHrP), the major mediator of humoral hypercalcemia of malignancy, may also regulate placental calcium flux, uterine contraction and fetal tissue development. In the present study, we demonstrated that the mean immunoreactive PTHrP concentrations in amniotic fluid at mid-gestation (21.2 +/- 3.7 pmol/l) and at term (19.0 +/- 2.7 pmol/l) were 13-16-fold higher than levels measured in either fetal (1.6 +/- 0.1 pmol/l) or maternal plasma (1.4 +/- 0.3 pmol/l) at term and equal to levels found in plasma of patients with humoral hypercalcemia of malignancy. In vitro studies pointed to three possible sources of PTHrP in amniotic fluid: cultured amniotic fluid cells, cells derived from the amniotic membrane overlying the placenta and placental villous core mesenchymal cells. Treatment of cultured amniotic fluid cells with human prolactin, human placental lactogen (hPL) or human growth hormone (100 micrograms/l) increased PTHrP secretion after 24 h by 43%, 109% and 90%, respectively. Insulin-like growth factors I and II (100 micrograms/l), insulin (100 micrograms/l) and epidermal growth factor (EGF) (10 micrograms/l) increased PTHrP secretion by 53%, 46%, 68% and 118%, respectively. The stimulation of PTHrP secretion by EGF or by hPL was both time- and dose-dependent. In contrast, calcitriol and dexamethasone (10 nmol/l) decreased PTHrP secretion by 32% and 75%, respectively. Estradiol, progesterone, dihydrotestosterone and human chorionic gonadotropin had no effect on PTHrP secretion. These findings support the notion that PTHrP may play a physiological role in the uteroplacental unit and demonstrate that human amniotic fluid cells could be a useful model for studying the regulation of PTHrP production and secretion by hormones and growth factors.

Amniotic Fluid↗

Long-term follow-up and outcome of infants with non-organic failure to thrive.

Sixty-one children diagnosed as having non-organic failure to thrive during infancy were reviewed at an average of 5 years after their initial presentation, and were compared to a control group matched for age, sex, social class, and ethnic affiliation. Children with a previous history of failure to thrive were found to be shorter and, in particular, to gain less weight. Birthweight percentile and maternal height of children with failure to thrive were lower than those of matched children from the control group. They also had more learning difficulties and evidenced developmental delay. The degree of growth retardation and the duration of follow-up had no significant effect on the outcome. In contrast, birthweight, maternal height, and social status and, to a lesser extent, paternal parameters were good predictors of catching-up capabilities of these infants in terms of weight and height. Children who caught up faster had better school performances and came from families of higher socioeconomic status. Failure to thrive is a multifactorial process involving biological, nutritional, and environmental factors. All these components should be considered in long-term follow-up and management.

Anthropometry↗

A survey of current Israeli practices and approach to partially treated meningitis in children.

Children with partially treated (PT) meningitis present diagnostic and therapeutic dilemmas. Since the approach to these children is not uniform, both in the literature and in daily practice, we conducted a survey among leading Israeli pediatricians from various hospitals to learn about their opinions and practices relating to this problem. Twenty-eight of 30 senior pediatricians responded to a questionnaire encompassing the various aspects of PT meningitis. The results of the survey highlighted the confusion and lack of clear policy regarding the definition, diagnostic approach and treatment of these children. Fifty percent of the pediatricians stated that even one dose of an antimicrobial agent, regardless of the type of drug, is sufficient for the definition of PT meningitis; 43% of the responders did not require any threshold parameter in CSF findings for the definition of probable bacterial meningitis among PT children and 52% did not think that a second lumbar puncture was useful as a diagnostic aid in PT meningitis. Epidemiological circumstances played a role in the diagnostic and therapeutic approach of infectious disease specialists mainly, but less so in the other groups of pediatricians. Finally, more than half the responders did not use throat cultures to identify potential carriers among PT meningitis patients and did not consider the use of prophylactic treatment in close contacts. These data clearly indicate the need for guidelines regarding the various aspects of PT meningitis.

Anti-Bacterial Agents↗