This study focuses on endoscopic and pathologic alterations of gastrointestinal (GI) disorders of Iranian patients with common variable immunodeficiency (CVID). Nineteen of 39 CVID patients (48%) had GI complaints. The most common symptom was chronic diarrhea (28%). In endoscopic examination of small intestines, 15 patients had no abnormal finding. Duodenal biopsy revealed villous atrophy in eight and nodular lymphoid hyperplasia in three patients. There was no statistically significant difference between patients with and patients without duodenal villous atrophy regarding the presence of chronic diarrhea, anemia, and absolute CD4+T cells. In three patients, biopsies of the colon showed chronic noncrypt-destructive colitis. GI problems pose a high morbidity to CVID patients and are second only to respiratory complications. CVID patients are at increased risk of infectious and inflammatory conditions in the GI tract. Early diagnosis of these complications improves the quality of life and well-being of patients.

AbstractIntervertebral disc degeneration (IVDD) is one of the common causes of low back pain. Similar to many other multifactorial diseases, it is affected by environmental and genetic factors. Although not completely understood, genetic factors include a wide spectrum of variations, such as single nucleotide polymorphisms, which could play a significant role in the etiology of this disease. Besides, the interactions with environmental factors could make the role of genetic factors more complicated. Genetic variations in disc components could participate in developing degenerative disc disease through altering the normal homeostasis of discs. Gene polymorphisms in disc proteins (collagens I, II, III, IX, and XI), proteoglycans (aggrecan), cytokines (interleukins I, VI, and X), enzymes (matrix metalloproteinases II, III, and IX), and vitamin D receptor seem to play considerable roles in the pathology of this disease. There are also many other investigated genes that could somehow take part in the process. However, it seems that more studies are needed to clarify the exact role of genetics in IVDD.

As the severity of nonalcoholic fatty infiltration increases, the incidence of abnormal hepatic vein waveforms increases and hepatic artery resistance index decreases.

Background: X-linked agammaglobulinemia (XLA) is a hereditary immunodeficiency characterized by an early onset of recurrent bacterial infections, a profound deficiency of all immunoglobulin isotypes and a markedly reduced number of peripheral B lymphocytes. Eighty-five percent of the patients with this phenotype have mutations in Bruton’s tyrosine kinase (BTK) gene. Methods: To provide an informative outlook of clinical and immunological manifestations of XLA in Iran, 37 Iranian male patients with an age range of 1–34 years, followed over a period of 25 years, were studied. Twenty-four of the 37 patients were screened for BTK gene mutation using PCR-SSCP followed by direct sequencing. BTK protein expression assay was done by flow cytometry in 9 families. Results: All patients first presented with infectious diseases, the most common of which were respiratory tract infections. Eighteen different mutations were identified, 13 of which were novel: IVS1+5G>C, 1896G>A, 349delA, 1618C>T, 1783T>C, 2084A>G, 1346delT, 1351delGAG, 587A>G, IVS14–1G>A, IVS3+2T>C, 1482G>A, 1975C>A. Conclusion: The fact that we found a great number of novel mutations in a relatively limited number of patients underlines the heterogeneity of BTK mutations in the Iranian population. The large number of new mutations indicates that extended studies in this region would be rewarding.

Common variable immunodeficiency (CVID) is a heterogeneous group of disorders, characterized by hypogammaglobulinemia, defective specific-antibody production resulting in recurrent bacterial infections. Delay in diagnosis and inadequate treatment result in increased irreversible complications and mortality. To determine persistent morbidities, mortality rate and survival in Iranian patients with CVID, hospital records of 72 (39 males and 33 females) diagnosed CVID patients were reviewed. Probabilities of survival after diagnosis of CVID were estimated from Kaplan-Meier life tables. Studied patients were enrolled over a 20-year period (1984-2005). The most commonly observed complication was bronchiectasis (24 cases), followed by splenomegaly, intestinal villous atrophy (11 cases), and failure to thrive (10 cases). Post-diagnosis survival was estimated as 65% for the first 6.5 years, which remains the same until 14 years after diagnosis when the survival curve drops to nearly 45%. The mortality rate among patients who had no regular visits and did not receive periodical IVIG was more remarkable when compared with those who had been followed up timely (p-value = 0.001). The most common cause of death was respiratory failure. Based on our observation, it can be highlighted that all patients with CVID, even under regular immunoglobulin replacement, need close monitoring for early detection of complications and introduction of appropriate management.

Polymorphisms of pro-inflammatory cytokine genes could take part in IVDD pathophysiology as the result of alteration in their expression levels or structures. The current study indicated significant roles of TNF-α -308 G/A and TNF-α -238 G/A SNPs with IVDD among Iranian patients. However, this study did not show any significant association between IVDD and either of SNPs of IL-1 and IL-6 genes.

Major causes of olfactory disorders are sinonasal disease, viral upper respiratory tract infection, head trauma and old age. Olfactory testing is an important part of objective assesment of the severity of the disease in chronic rhinosinusitis and nasal polyposis. The aim of this study was to correlate results of objective smell testing with subjective scores on olfaction and other nasal symptoms in different subgroups of patients with smell impairment.Data were extracted from questionnaires filled by patients sent to smell testing by the ENT specialist. For the analysis data were divided in subgroups: 20 with chronic rhinosinusitis (CRS), 24 patients operated for nasal polyps, 7 patients with nasal polyps on medical treatment, 7 with hyposmia after common cold, 4 with anosmia and 11 controls with no smell impairment. Smell testing was done by using the Sniffin Sticks 12 complete odorant. This test is based on the assessment of odor identification abilities for 12 standard odors with forced choice. Subjective scores on (0-4) were taken for olfaction, nasal obstruction, hypersecretion and headache.The correlation between subjective score for olfaction and olfactometry score was significant for the whole group (r 0.682), and was similar when anosmic and controls were excluded. Subjective olfaction and olfactometry score did not correlate with any other symptom. Comparing correlation coefficients between the subgroups, it seems that patients with CRS and nonoperated nasal polyp patients have better correlation between subjective and objective smell assesment than patients operated for nasal polyps and those who had olfactory lesion following viral infection.Although correlation between subjective and objective smell assesment is significant, some subgroups of patients overrate their ability to recognize odors. STRESS EFFECTS ON ALLERGIC INFLAMMATION OF THE AIRWAYS Pontus Stierna and Susanna GeorenDepartment of Otorhinolaryngology, Karolinska University Hospital, Stockholm, SwedenWe have used a mouse model to investigate the effects of endogenous GC synthesis and GC receptor inhibition, as well as acute stress, and different doses of exogenous administered GCs on inflammatory cells in different cellular compartments in allergic airway inflammation. including nerve growth factor (NGF) in the airways, during allergic inflammation.First we investigated the effects of endogenous GCs on eosinophilic airway inflammation. Inhibition of GC release with metyrapone (ME) induced an increase of bone marrow eosinophilia and when the ME treatment was combined with a GC receptor antagonist (RU 486) the allergen-induced bone marrow eosinophilia was further enhanced.The second study was focused on the effects of timing of a short acute stress on allergic airway inflammation in upper and lower airways. Short stress applied before an allergen challenge decreased the allergen-induced eosinophilia in bronchoalveolar lavage fluid and lungs and also the inflammation in the nasal tissue. No effects on eosinophilia or inflammation were seen...

Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis caused by loss-of-function mutations in the ECM1 gene, and previous studies have noted phenotypic variability. In this study, we examined 12 patients representing three Iranian families for clinical manifestations and genotyped them for mutations in ECM1. LP was diagnosed with characteristic mucocutaneous and neurologic manifestations. Five patients were also subjected to magnetic resonance imaging (MRI)/computed tomography (CT) scan of the central nervous system. DNA was isolated from peripheral blood from patients and their clinically unaffected relatives, and mutations in ECM1 were sought by PCRbased amplification of all exons and flanking intronic sequences, followed by bidirectional Sanger sequencing. Significant phenotypic variability in this multisystem disorder, including presence of convulsions and epilepsy in about half of the patients was noted. In most cases, this was associated with calcifications in the brain detected by MRI/CT scans. Genotyping of the affected individuals in three families from the central region of Iran revealed presence of homozygous c.507delT mutation in ECM1, reflecting the observed consanguinity in these families. This large cohort revealed extensive phenotypic variability in individuals with the same mutation in ECM1. This observation suggests a role for genetic and epigenetic as well as environmental modulation of the phenotype. Identification of mutations allows screening of unaffected individuals for presence or absence of this mutation in extended LP families, with implications for genetic counseling.