Long-term follow-up of ninety eight Iranian patients with primary immune deficiency in a single tertiary centre

PURPOSE: The aim was to describe the clinical manifestations, complications and long-term outcome of a cohort of Iranian patients with primary immune deficiency (PID). METHOD: We retrospectively studied the demographic, clinical and immunological characteristics of the PID patients in a single tertiary centre, from January 1989 to July 2014. The patients were classified according to the International Union of Immunological Societies Expert Committee on PID. RESULTS: 98 patients were diagnosed with and followed-up for 15 disorders. The mean age at onset and diagnosis and the diagnostic delay were 8±10, 14.2±13.1 and 6.1±7 years, respectively. Parental consanguinity rate was 57%. Predominantly Antibody Deficiency was the most common diagnosis (n=63), followed by congenital defects of phagocytes (n=16), combined immunodeficiencies (n=12), well defined syndromes (n=4) and defects in innate immunity (n=3). Recurrent sinopulmonary infection was the most common presentation. Active infections were treated appropriately, in addition to prophylactic therapy with IVIG and antimicrobials. Not all the patients were compliant with prophylactic regimens due to cost and unavailability. One SCID patient underwent successful bone marrow transplantation. The total mortality rate was 19% during the follow-up period (7.8±7.6 years). The mean age of living patients at the time of study was 23±11.7 years. CONCLUSIONS: Physicians awareness of PID has been rising dramatically in Iran, ensuring an increasing number of patients being diagnosed and treated. More effective treatment services, including health insurance coverage and drug availability are needed to improve the outcome of PID patients

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Long-term follow-up of ninety eight Iranian patients with primary immune deficiency in a single tertiary centre.

PURPOSE: The aim was to describe the clinical manifestations, complications and long-term outcome of a cohort of Iranian patients with primary immune deficiency (PID). METHOD: We retrospectively studied the demographic, clinical and immunological characteristics of the PID patients in a single tertiary centre, from January 1989 to July 2014. The patients were classified according to the International Union of Immunological Societies Expert Committee on PID. RESULTS: 98 patients were diagnosed with and followed-up for 15 disorders. The mean age at onset and diagnosis and the diagnostic delay were 8±10, 14.2±13.1 and 6.1±7 years, respectively. Parental consanguinity rate was 57%. Predominantly Antibody Deficiency was the most common diagnosis (n=63), followed by congenital defects of phagocytes (n=16), combined immunodeficiencies (n=12), well defined syndromes (n=4) and defects in innate immunity (n=3). Recurrent sinopulmonary infection was the most common presentation. Active infections were treated appropriately, in addition to prophylactic therapy with IVIG and antimicrobials. Not all the patients were compliant with prophylactic regimens due to cost and unavailability. One SCID patient underwent successful bone marrow transplantation. The total mortality rate was 19% during the follow-up period (7.8±7.6 years). The mean age of living patients at the time of study was 23±11.7 years. CONCLUSIONS: Physicians awareness of PID has been rising dramatically in Iran, ensuring an increasing number of patients being diagnosed and treated. More effective treatment services, including health insurance coverage and drug availability are needed to improve the outcome of PID patients.

What do we need to eradicate rubella in the Islamic Republic of Iran?

To evaluate the need for congenital rubella syndrome prevention in our national health programme we aimed to determine the rate of anti-rubella positivity in umbilical cord blood samples 8 years after measles-rubella mass vaccination in the Islamic Republic of Iran. In a cross-sectional study we tested umbilical cord blood samples for anti-rubella IgG and IgM by ELISA in 154 deliveries at a university hospital in Tehran. Overall 72.7% of umbilical cord blood samples were positive for anti-rubella lgG and 27.3% were negative. All of the samples were negative for anti-rubella IgM. In the samples with a history of mothers' rubella vaccination, only 87.5% were positive for anti-rubella IgG. The results suggest the need for another mass vaccination for rubella in women of child-bearing age and continuation of routine vaccination of infants, plus consideration of obligatory anti-rubella IgG testing before pregnancy in women who were not vaccinated and vaccination of women before marriage.

A unified approach for detection of induced epileptic seizures in rats using ECoG signals.

OBJECTIVE: Epileptic seizure detection is a key step for epilepsy assessment. In this work, using the pentylenetetrazole (PTZ) model, seizures were induced in rats, and ECoG signals in interictal, preictal, ictal, and postictal periods were recorded. The recorded ECoG signals were then analyzed to detect epileptic seizures in the epileptic rats. METHODS: Two different approaches were considered in this work: thresholding and classification. In the thresholding approach, a feature is calculated in consecutive windows, and the resulted index is tracked over time and compared with a threshold. The moment the index crosses the threshold is considered as the moment of seizure onset. In the classification approach, features are extracted from before, during, and after ictal periods and statistically analyzed. Statistical characteristics of some features have a significant difference among these periods, thus resulting in epileptic seizure detection. RESULTS: Several features were examined in the thresholding approach. Nonlinear energy and coastline features were successful in epileptic seizure detection. The best result was achieved by the coastline feature, which led to a mean of a 2-second delay in its correct detections. In the classification approach, the best result was achieved using the fuzzy similarity index that led to Pvalue<0.001. CONCLUSION: This study showed that variance-based features were more appropriate for tracking abrupt changes in ECoG signals. Therefore, these features perform better in seizure onset estimation, whereas nonlinear features or indices, which are based on dynamical systems, can better track the transition of neural system to ictal period. SIGNIFICANCE: This paper presents examination of different features and indices for detection of induced epileptic seizures from rat's ECoG signals.

Intensive Care Unit nosocomial sinusitis at the Rasoul Akram Hospital: Tehran, Iran, 2007-2008.

BACKGROUND: Nosocomial rhino sinusitis causes major problems in all Intensive Care Units (ICUs). OBJECTIVE: To describe incidence, epidemiologic, clinical manifestations, and microbiologic findings in ICUs admitted cases with nosocomial sinusitis. METHODS#ENTITYSTARTX00026; MATERIALS: A prospective, cross sectional study done in Pediatric & Adult ICUs in Rasoul Akram Hospital; Tehran Iran (2007-2008). Para-nasal sinus computed tomography (CT) was performed in all adults with fever of unknown origin (FUO) within 48h of admission and repeated thereafter (4-7 days). Infectious sinusitis was diagnosed by microbiological analysis of sinus fluid aspirates. RESULTS: Acute bacterial nosocomial sinusitis proved in 82% (51/ 63) of all cases. Head trauma was the most common cause; (n = 22, 45%) of cases. The results of culture were positive for 45 cases (82%). Of 45 culture positives, 19 yielded Gram negative organisms (41%) and 9 (22%) gave Gram positives (S. aureous, Streptococus spp). The remainders (n = 17, 37%) consisted of mixed aerobic/anaerobic bacteria. Seven cases, were positive in gram staining of sinus drainage and these were positive in culture for S. pneumonia (n = 5), Hemophilus influenza (n = 2). The type of organisms were not related to Glasgow Coma Scale in cases (P = 0.3). CONCLUSION: Nosocomial organisms isolated were quite different from community acquired rhino sinusitis cases. Investigation of CT scan and drainage of Para-nasal sinuses would be helpful in undiagnosed FUO cases, especially in traumatic patients. Optimal treatment usually consists of removal of the tubes, mobilizing the patient, and administration the broad-spectrum antibiotics.

Immunoasssay chromatographic antigen test for rapid diagnosis of Group A beta hemolytic Streptococcus pharyngitis in children: A cross/ sectional study.

BACKGROUND AND OBJECTIVE: Group A beta-hemolytic streptococcus (GABHS) is an important pharyngotonsillitis etiologic agent in children. The objective of this study was diagnosis of streptococcal pharyngitis based on rapid antigen detection test and conventional pharyngeal culture. MATERIALS AND METHODS: The rapid GABHS antigen detection test was compared to culture on blood agar, the gold standard for the diagnosis of this etiologic agent. RESULTS: Streptococcal antigen was detected in pharyngeal specimens of 34.5% of cases by rapid strip test. We detected group A Streptococcus in 17.2% of pharyngeal culture. There was no agreement between two methods ( PV < 0.1). The negative pharyngeal culture results are probably due to antibiotic usage in 43.2% of patients. Positive rapid test results in pharyngeal swab was age dependent ( P < 0.05). There was good correlation between observing the "petechia in pharynx of patients" and positive rapid test in pharyngeal swab (P < 0.004). Throat culture results were relatated to previous antibiotic usage ( P < 0.03). CONCLUSION: The rapid test in pharyngeal swab is helpful for rapid diagnosis and treatment of GABHS pharyngitis. Diagnosis of GABHS pharyngitis based on soley clinical findings is misleading in the majority of cases. Petechia observed in pharynx of the cases was highly predictive of streptococcal pharyngitis.

Evaluation of an interferon-gamma release assay in young contacts of active tuberculosis cases.

In a cross-sectional study in a hospital in Tehran in 2006-08 the QuantiFERON-TB interferon-gamma release assay (QTB) was compared with the tuberculin skin test (TST) in 59 young people (aged < 20 years) with close contact with immunocompetent cases of proven pulmonary tuberculosis. After 1 year follow-up 10 subjects had progressed to tuberculosis disease and received treatment; TSTwas positive in 30% and QTB in 100%. Of the 49 non-progressive subjects, TST was positive in 10.4% and QTB in 16.3%. The agreement between TST and QTB assay in non-progressive subjects was poor (K = 0.43). False positive and false negative rates for TST were 40.0% and 9.3% respectively; positive and predictive values were 60.0% and 90.7%. We suggest adding the interferon assay to the skin test in the decision to perform chest X-ray or to start chemoprophylaxis at least in younger subjects (aged < 20 years).

Viral infections detected by serology and PCR of perilymphatic fluid in children with idiopathic sensorineural hearing loss.

The etiology of sensorineural hearing loss (SNHL) in children may be viral. This cross-sectional study aimed to determine the role of viral infectious agents in children with idiopathic SNHL. Of 119 children with SNHL aged 3-168 months undergoing cochlear implant surgery at a hospital in Tehran, no cause could be established in 18 cases (15.1%). Cytomegalovirus (CMV) and herpes simplex virus (HSV) active infections (detected by DNA-PCR, confirmed by serology) were found in the perilymphatic fluid of 16.7% (3/18) cases of idiopathic SNHL. Serology was performed on blood samples from 11 of these cases: specific antibodies against CMV, Toxoplasma spp., HSV and rubella were determined in all cases; acute T. gondii infection was detected in 7 cases and rubella IgG was found in only 1 case. Neonatal screening for CMV, HSV and T gondii may be helpful in the Islamic Republi of Iran.

Viral infections detected by serology and PCR of perilymphatic fluid in children with idiopathic sensorineural hearing loss

The etiology of sensorineural hearing loss [SNHL] in children may be viral. This cross-sectional study aimed to determine the role of viral infectious agents in children with idiopathic SNHL Of 119 children with SNHL aged 3-168 months undergoing cochlear implant surgery at a hospital in Tehran, no cause could be established in 18 cases [15.1%]. Cytomegalovirus [CMV] and herpes simplex virus [HSV] active infections [detected by DNA-PCR, confirmed by serology] were found in the perilymphatic fluid of 16.7% [3/18] cases of idiopathic SNHL Serology was performed on blood samples from 11 of these cases: specific antibodies against CMV, Toxoplasmo spp., HSV and rubella were determined in all cases; acute T. gondii infection was detected in 7 cases and rubella IgG was found in only 1 case. Neonatal screening for CMV, HSV and T. gondii may be helpful in the Islamic Republic of Iran

Evaluation of an interferon-gamma release assay in young contacts of active tuberculosis cases

In a cross-sectional study in a hospital in Tehran in 2006-08 the QuantiFERON[Registered]-TB interferon-gamma release assay [QTB] was compared with the tuberculin skin test [TST] in 59 young people [aged<20 years] with close contact with immunocompetent cases of proven pulmonary tuberculosis. After 1 year follow-up 10 subjects had progressed to tuberculosis disease and received treatment; TST was positive in 30% and QTB in 100%. Of the 49 non-progressive subjects, TST was positive in 10.4% and QTB in 16.3%. The agreement between TST and QTB assay in non-progressive subjects was poor [Kappa=0.43]. False positive and false negative rates for TST were 40.0% and 9.3% respectively; positive and predictive values were 60.0% and 90.7%. We suggest adding the interferon assay to the skin test in the decision to perform chest X-ray or to start chemoprophylaxis at least in younger subjects [aged<20 years]

The role of adenosine A(1) receptors in mediating the inhibitory effects of low frequency stimulation of perforant path on kindling acquisition in rats.

Low frequency stimulation (LFS) has an inhibitory effect on rapid perforant path kindling acquisition. In the present study the role of adenosine A(1) and A(2A) receptors in mediating this inhibitory effect was investigated. Rats were kindled by perforant path stimulation using rapid kindling procedures (12 stimulations per day). LFS (0.1 ms pulse duration at 1 Hz, 200 pulses, and 50-150 muA) was applied to the perforant path immediately after termination of each rapid kindling stimulation. 1,3-Dimethyl-8-cyclopenthylxanthine (CPT; 50 muM), a selective A(1) antagonist and ZM241385 (ZM, 200 muM), a selective A(2A) antagonist were daily microinjected into the lateral ventricle 5 min before kindling stimulations. LFS had an inhibitory effect on kindling development. Pretreatment of animals with CPT reduced the inhibitory effect of LFS on kindling rate and suppressed the effects of LFS on potentiation of population EPSP during kindling acquisition. In addition, CPT was able to antagonize the effects of LFS on kindling-induced increase in early (10-50 ms intervals) and late (300-1000 ms intervals) paired pulse depression. ZM pretreatment had no effect on antiepileptogenic effects of LFS in kindling acquisition. In addition, LFS prevented the kindling-induced elevation of cyclic AMP (cAMP) levels in kindled animals. Based on these results, we suggest that the antiepileptogenic effects of LFS on perforant path kindling might be mediated through activation of adenosine A(1), but not A(2A) receptors. Moreover, modulation of cAMP levels by LFS may potentially be an important mechanism which explains the anticonvulsant effects of LFS in kindled seizures.

Sensorineural hearing loss due to Toxoplasma gondii in children: a case-control study.

OBJECTIVE: Sensorineural hearing loss (SNHL) can follow congenital toxoplasmosis. Treatment in the first year of life is associated with diminished occurrence of this sequel. In various parts of Iran, the prevalence of antibodies to Toxoplasma gondii ranges from 24% to 57.7%. We evaluate the possible role of Toxoplasma gondii infection on the occurrence of SNHL in children. DESIGN AND SETTING: This case-control study was performed in a tertiary care center in Tehran between 2002 and 2003. This study was carried out based on diagnostic parameters of the American Academy of Otolaryngology criteria for SNHL and a healthy control group. MAIN OUTCOME MEASURES: We compared the specific Toxoplasma gondii antibodies (IgM & IgG) measured by ELISA in 95 blood samples of infants with SNHL and 63 healthy matched infants. RESULTS: Acute (IgM) and previous (IgG) immunity to Toxoplasma gondii was found in 12 and 21.2% of SNHL children, respectively. Most cases with previous infections (IgG positive) were children aged less than 1 year old (i.e. maternal immunity), but acute infection (IgM positive) was higher in 3-5 year old age group. Acute infection (IgM) was significantly more frequent in the SNHL group, and previous immunity was higher in the controls (CI 95%, P-value = 0.01; 0.01). CONCLUSION: With respect to seropositive children, as we were unable to differentiate congenital from acquired cases, we recommend prevention of congenital toxoplasmosis by treatment of Toxoplasma infection in pregnant women and treatment of acquired Toxoplasma gondii infection after birth to minimise the risk of SNHL in children.

The role of galanin receptors in anticonvulsant effects of low-frequency stimulation in perforant path-kindled rats.

Low-frequency stimulation (LFS) has antiepileptogenic effects on kindled seizures. In the present study, the role of galanin receptors in the inhibitory effect of LFS on perforant path kindling acquisition was investigated in rats. Animals were kindled by perforant path stimulation in a rapid kindling manner (six stimulations per day). LFS (0.1 ms pulses at 1 Hz, 600 pulses, and 80-150 microA) was applied immediately after termination of each kindling stimulation. M35 (0.5 and 1.0 nM per site), a nonselective galanin receptor antagonist and M871 (1.0 microM per site), a selective galanin receptor type 2 (GalR2) antagonist, were daily microinjected into the dentate gyrus before starting the stimulation protocol. The expression of GalR2 in the dentate gyrus was also investigated using semi-quantitative RT-PCR. Application of LFS significantly retarded the kindling acquisition and delayed the expression of different kindled seizure stages. In addition, LFS significantly reduced the increment of daily afterdischarge duration during kindling development. Intra-dentate gyrus microinjection of both M35 and M871 significantly prevented the inhibitory effects of LFS on kindling parameters. During the focal kindled seizure stages (1-3) M871 had no significant effect. However, during generalized seizure stages (4 and 5), M871 had the same effect as M35. Semi-quantitative RT-PCR also showed that after kindling acquisition, the GalR2 mRNA level decreased in the dentate gyrus but application of LFS prevented this decrease. Obtained results show that activation of galanin receptors by endogenous galanin has a role in mediating the inhibitory effect of LFS on perforant path-kindled seizures. This role is exerted through GalR1 during focal- and through GalR2 during generalized-kindled seizures.

Single whisker experience started on postnatal days 0, 5 or 8 changes temporal characteristics of response integration in layers IV and V of rat barrel cortex neurons.

Neonatal single whisker experience changes the response properties of spared barrel neurons to deflections of principal and adjacent whiskers. However little is known about the temporal characteristics of the paired whisker inputs. To address this issue we used computer controlled mechanical displacement of paired whiskers in control and plucked animals (plucking of all whiskers but D2 started at 0, 5 and 8 postnatal days). The principal whisker (PW) and its caudal adjacent whisker (AW) were deflected simultaneously or serially at different inter-stimulus intervals (10, 20, 30, 50 and 100 ms). Neuronal responses were recorded in D2 spared barrel both in layers IV and V. In the control group, combined deflection of AW prior to PW led to suppression of ON and OFF responses to PW deflection both in layers IV and V. The magnitude of this suppression was strongly dependent on the inter-stimulus intervals (ISIs). At almost all tested ISIs, whisker plucking from P0, P5 and P8 weakened suppressive interactions in layers IV and V barrel neurons for both ON and OFF responses. The most decrease in inhibitory interactions was observed in P5 plucked animals. Principal whisker-evoked ON responses were increased only in P0 plucked animals both in layers IV and V. AW-evoked ON responses are decreased in P5 plucked animals in layer IV. The available data suggest that sensory experience can modulate temporal aspects of response integration and receptive field properties of layers IV and V neurons in barrel cortex. These changes have different critical periods.

Effects of GABAergic inhibition on neocortical long-term potentiation in the chronically prepared rat.

Long-term potentiation (LTP) is a form of activity-dependent synaptic plasticity that is a candidate cellular mechanism for some forms of learning and memory. Although GABAergic synaptic inhibition plays a critical role in regulating of synaptic plasticity, there is still little known about the GABAergic modulation on LTP induction in chronic preparation. In the present study we examined the effect of GABA(A) agonist, diazepam (DZM), and antagonist, picrotoxin (PTX) on the induction of LTP in the somatosensory cortex of freely moving rats for a long-term period. In adult rats a bipolar stimulating and recording electrode were implanted into corpus callusom and somatosensory cortex, respectively. Two weeks after the surgery, evoked field potential responses were recorded before, during (12 days), and after (1 month) induction period of LTP by high-frequency stimulation. The LTP characteristics were compared between control, DZM and PTX groups during the time course of recording in each rat. Administration of DZM prior to train, blocked the induction of neocortical LTP, while the PTX increased the development of LTP making the highest differential levels of LTP about 12 days after the initiation of LTP induction. Our findings suggest that the augmentation of LTP by PTX can be explained by an interaction between excitatory and inhibitory pathways. Suppression of neocortical inhibitory inputs by PTX causes enhancement in LTP induction. These results suggest that GABAergic system has an important role in synaptic plasticity and long-term modification of somatosensory cortex in freely moving rat.

Effects of neonatal C-fiber depletion on discrimination of principal and adjacent whisker stimulation within rat individual cortical barrels.

Controlled mechanical displacement was used to stimulate single whiskers in normal and C-fiber depleted rats to quantitatively examine the role of C-fibers in the response properties of barrel cortical cells. C-fiber depletion using neonatal capsaicin treatment increased the barrel single-unit response magnitude to deflection of both principal and adjacent whiskers while there was not any significant difference in the barrel cells' spontaneous activity. Capsaicin treatment increased the neural response duration of adjacent whisker stimulation but did not change that to the principal whisker deflection. There was no difference in response latencies of principal or adjacent whisker displacement between the normal and C-fiber-depleted groups. The efficiency of neural code for differentiation of principal and adjacent whiskers was measured by ROC analysis, which reflects the performance of an ideal observer in this discrimination using cells' firing rate. No significant difference was found in the performance of neurons in capsaicin-treated and control groups in distinguishing principal and adjacent whisker deflections from each other. These results suggest that neonatal C-fiber depletion causes an expansion of barrel cells receptive field but it does not affect the discrimination of individual whisker stimulation by the barrel cells.