Kasra Moazzami

Comparison of pulmonary diseases in common variable immunodeficiency and X-linked agammaglobulinaemia

Background and objective:  Pulmonary disease is the most common complication in patients with common variable immunodeficiency (CVID) or X‐linked agammaglobulinaemia (XLA). Pulmonary disease may progress despite immunoglobulin replacement therapy. In this study pulmonary complications were compared in patients with CVID or XLA.

Neutropenia and Primary Immunodeficiency Diseases

Primary immunodeficiency diseases (PID) are a heterogeneous group of congenital disorders of the immune system leading to recurrent infections, autoimmunity, malignancies, and hematological disorders. This review focuses specifically on inherited disorders associated with neutropenia, which may occur in isolation or as a feature of more complex immune disorders. It has been known for a long time that defined immunodeficiency syndromes, such as CD40L deficiency, WHIM syndrome, or Chédiak Higashi syndrome, may be associated with neutropenia even though the mechanisms are poorly understood. In some PID, neutropenia may result from chronic viral infection or from autoimmunity. Recently, the identification of several novel genetic defects (e.g., p14-deficiency, HAX1-deficiency, AK2-deficiency) has shed light on the pathophysiology of congenital neutropenia. This review summarizes the clinical, immunological, and genetic features of congenital neutropenia syndromes.

Analysis of Switched Memory B Cells in Patients with IgA Deficiency

Background: Selective IgA deficiency (SIGAD) is the most common primary antibody deficiency, characterized by significant decreased serum levels of IgA in the presence of normal IgG and IgM. Despite several investigations into the nature of the disease, the exact pathophysiology of SIGAD is still unknown. Methods: In this study, switched memory B cells (CD19+/CD27+/IgD– cell population) of 28 patients with SIGAD and 28 matched healthy controls were investigated using flow cytometry. Results: The percentage of switched memory B cells in all healthy controls was more than 0.4%. In SIGAD patients, who were classified as group I, the percentage of switched memory B cells was less than 0.4% (0.34 ± 0.06) in 7 patients (25%). The remaining 21 patients were designated as group II (1.74 ± 0.12%). The mean concentration of IgG in group I was significantly lower than in group II (1,014 ± 278 vs. 1,388 ± 406 mg/dl, p = 0.028). Comparison of clinical features between the 2 groups revealed that episodes of pneumonia during the course of disease were significantly higher in group I than in group II (p = 0.002). Autoimmune diseases in group I (57.1%) were also significantly higher (p = 0.01) than in group II (23.8%). The prevalence of bronchiectasis was 57% in group I, while only 1 patient (4.7%) in group II developed bronchiectasis (p = 0.006). Specific antibody deficiency in group I was documented in 5 patients and in group II in 4 patients (p = 0.01). Conclusions: The classification of SIGAD patients by assessment of switched memory B cells could help physicians with the clinical prognosis for these patients, whereas the patients with reduced switched memory B cells are prone to severe phenotypes.

Maternal mobile phone exposure adversely affects the electrophysiological properties of Purkinje neurons in rat offspring

Electromagnetic field (EMF) radiations emitted from mobile phones may cause structural damage to neurons. With the increased usage of mobile phones worldwide, concerns about their possible effects on the nervous system are rising. In the present study, we aimed to elucidate the possible effects of prenatal EMF exposure on the cerebellum of offspring Wistar rats. Rats in the EMF group were exposed to 900-MHz pulse-EMF irradiation for 6h per day during all gestation period. Ten offspring per each group were evaluated for behavioral and electrophysiological evaluations. Cerebellum-related behavioral dysfunctions were analyzed using motor learning and cerebellum-dependent functional tasks (Accelerated Rotarod, Hanging and Open field tests). Whole-cell patch clamp recordings were used for electrophysiological evaluations. The results of the present study failed to show any behavioral abnormalities in rats exposed to chronic EMF radiation. However, whole-cell patch clamp recordings revealed decreased neuronal excitability of Purkinje cells in rats exposed to EMF. The most prominent changes included afterhyperpolarization amplitude, spike frequency, half width and first spike latency. In conclusion, the results of the present study show that prenatal EMF exposure results in altered electrophysiological properties of Purkinje neurons. However, these changes may not be severe enough to alter the cerebellum-dependent functional tasks.

Safety and efficacy of granulocyte-colony-stimulating factor administration following autologous intramuscular implantation of bone marrow mononuclear cells: a randomized controlled trial in patients with advanced lower limb ischemia.

BACKGROUND AIMS The aim was to investigate the therapeutic effect of granulocyte-colony-stimulating factor (G-CSF) administration following implantation of autologous bone marrow mononuclear cells (BM MNC) for patients with lower limb ischemia. METHODS The design was a randomized controlled trial. Fifteen patients with severe chronic limb ischemia were treated with autologous BM MNC [without G-CSF (MNC-G-CSF) or combined with G-CSF administration for 5 days following transplantation (MNC+G-CSF)]. RESULTS All clinical parameters, including ankle brachial index, visual analog scale and pain-free walking distance, showed a mean improvement from baseline, which was measured at 4 and 24 weeks after transplantation in both groups. However, in three (20%) patients, the clinical course did not improve and limb salvage was not achieved. No significant difference was observed among the patients treated in the MNC-G-CSF and MNC+G-CSF groups. No severe adverse reactions were reported during the study period. No relationship was observed between both the numbers of viable MNC or CD34+ cells and the clinical outcome. CONCLUSIONS Autologous transplantation of BM MNC into ischemic lower limbs is safe, feasible and efficient for patients with severe peripheral artery disease. However, the administration of G-CSF following cell transplantation does not improve the effect of BM MNC implantation and therefore would not have any beneficial value in clinical applications of such cases.

S-Nitrosylation of Calcium-Handling Proteins in Cardiac Adrenergic Signaling and Hypertrophy

RATIONALE The regulation of calcium (Ca(2+)) homeostasis by β-adrenergic receptor (βAR) activation provides the essential underpinnings of sympathetic regulation of myocardial function, as well as a basis for understanding molecular events that result in hypertrophic signaling and heart failure. Sympathetic stimulation of the βAR not only induces protein phosphorylation but also activates nitric oxide-dependent signaling, which modulates cardiac contractility. Nonetheless, the role of nitric oxide in βAR-dependent regulation of Ca(2+) handling has not yet been explicated fully. OBJECTIVE To elucidate the role of protein S-nitrosylation, a major transducer of nitric oxide bioactivity, on βAR-dependent alterations in cardiomyocyte Ca(2+) handling and hypertrophy. METHODS AND RESULTS Using transgenic mice to titrate the levels of protein S-nitrosylation, we uncovered major roles for protein S-nitrosylation, in general, and for phospholamban and cardiac troponin C S-nitrosylation, in particular, in βAR-dependent regulation of Ca(2+) homeostasis. Notably, S-nitrosylation of phospholamban consequent upon βAR stimulation is necessary for the inhibitory pentamerization of phospholamban, which activates sarcoplasmic reticulum Ca(2+)-ATPase and increases cytosolic Ca(2+) transients. Coincident S-nitrosylation of cardiac troponin C decreases myocardial sensitivity to Ca(2+). During chronic adrenergic stimulation, global reductions in cellular S-nitrosylation mitigate hypertrophic signaling resulting from Ca(2+) overload. CONCLUSIONS S-Nitrosylation operates in concert with phosphorylation to regulate many cardiac Ca(2+)-handling proteins, including phospholamban and cardiac troponin C, thereby playing an essential and previously unrecognized role in cardiac Ca(2+) homeostasis. Manipulation of the S-nitrosylation level may prove therapeutic in heart failure.

T-Wave Alternans as an Arrhythmic Risk Stratifier: State of the Art

Microvolt level T-wave alternans (MTWA), a phenomenon of beat-to-beat variability in the repolarization phase of the ventricles, has been closely associated with an increased risk of ventricular tachyarrhythmic events (VTE) and sudden cardiac death (SCD) during medium- and long-term follow-up. Recent observations also suggest that heightened MTWA magnitude may be closely associated with short-term risk of impending VTE. At the subcellular and cellular level, perturbations in calcium transport processes likely play a primary role in the genesis of alternans, which then secondarily lead to alternans of action potential morphology and duration (APD). As such, MTWA may play a role not only in risk stratification but also more fundamentally in the pathogenesis of VTE. In this paper, we outline recent advances in understanding the pathogenesis of MTWA and also the utility of T-wave alternans testing for clinical risk stratification. We also highlight emerging clinical applications for MTWA.

ENT manifestations in Iranian patients with primary antibody deficiencies

OBJECTIVE One hundred and nine patients with primary antibody deficiencies were selected in order to determine the frequency of ENT complications. METHOD Demographic information and ENT medical histories were collected for each patient. Duration of study for each patient was divided into two periods of before diagnosis and after diagnosis and the initiation of treatment. RESULTS Eighty-two of 109 patients (75.2 per cent) experienced ENT infections during the course of the disease (63: otitis media, 75: sinusitis and nine: mastoiditis). At the time of diagnosis, 52 (47.7 per cent) out of 109 patients presented with an ENT symptom. The frequencies of episodes were 27 for sinusitis and 25 for otitis media (one complicated with mastoiditis). After immunoglobulin replacement therapy the incidence of otitis media was reduced from 1.75 before treatment to 0.39 after treatment per patient per year (p = 0.008). The incidence of sinusitis also significantly decreased from 2.38 to 0.78 (p value = 0.011). CONCLUSION ENT infections are common medical problems in primary antibody deficiency patients. Persistent and recurrent ENT infections should be suspected as originating from a possible underlying immunodeficiency.

Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 pyramidal neurons in rat offspring.

Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology. Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques.

Oral metronidazole as antibiotic prophylaxis for patients with nonperforated appendicitis

Background The rate of wound infection after appendectomy without antibiotic prophylaxis is 10%–30%. The role of prophylactic antibiotic therapy in nonperforated appendicitis is still controversial. Metronidazole is against anaerobic organisms and its bioavailability after oral and parenteral administration has been shown to be similar. The objective of the present study is to compare the infective complications rate after open appendectomy for nonperforated appendicitis receiving either oral or intravenous metronidazole as prophylaxis. Methods and Materials From June 2007 to July 2009 in a randomized controlled trial, 204 patients with nonperforated appendicitis underwent an open appendectomy; 122 male and 82 female with mean age of 25 years. Among these, 102 (case group) received oral metronidazole and in 102 (control group) metronidazole was administered intravenously before surgery. The rate of wound infection and duration of the postoperative hospital stay was studied in the two groups. Results The rate of wound infection was not significantly different in the two groups. (6% and 4% in study and control group, respectively, P = 0.861). Also the hospital stay was equal in two groups (2.3 days and 2.7 days in study and control group, respectively, P = 0.293). Conclusion Single dose of oral metronidazole prior to operation can provide a sufficient prophylaxis for nonperforated appendicitis; so, it can be substitute the parental route of antibiotic administration.