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BACKGROUND: Intestinal adaptation after massive bowel resection in animal models is characterized by increased gut-mucosal growth and expression of nutrient transporters. Few data about these indexes exist in humans with short-bowel syndrome (SBS). OBJECTIVE: The objective was to compare small-bowel and colonic mucosal growth and expression of the peptide transporter PepT1 in adults with or without SBS. DESIGN: Mucosal biopsy specimens were obtained from the small bowel and colon of 33 control subjects with intact intestine and from 13 SBS patients dependent on parenteral nutrition because of chronic malabsorption. Gut-mucosal crypt depth, villus height, and villus width were measured, and expression of PepT1 was determined by Northern blotting, in situ hybridization, and immunohistochemistry. RESULTS: The indexes of small-bowel and colonic mucosal growth were not significantly different between the 2 groups. PepT1 expression was high in the apical region of duodenal, jejunal, and ileal villus epithelial cells; low in absorptive colonocytes; and not significantly different in the distal small intestine of the 2 groups. However, the abundance of PepT1 mRNA in the colon of SBS patients was more than 5-fold that in control subjects (P < 0.01). CONCLUSIONS: Gut adaptation in SBS patients does not appear to involve an increase in gut-mucosal crypt depth or villus size. PepT1 is abundant along the small-bowel brush border in humans; expression in the colon indicates that the large intestine has a mechanism for luminal di- and tripeptide transport. Up-regulation of colonic PepT1 in SBS may adaptively improve accrual of malabsorbed di- and tripeptides, independent of changes in the mucosal surface area. [ABSTRACT FROM AUTHOR]

Abstract Background To address dental workforce shortages in underserved areas in the United States, some States have enacted legislation to make it easier for foreign dental school graduates to become licensed dentists. However, the extent to which foreign dental school graduates will solve the problem of dental workforce shortages is poorly understood. Furthermore, the potential impact that foreign-trained dentists have on improving access to dental care for vulnerable patients living in dental Health Professional Shortage Areas (HPSAs) and those enrolled in public insurance programs, such as Medicaid, is unknown. The objective of this paper is to provide a preliminary understanding of the practice behaviors of foreign-trained dentists. The authors used Washington State as a case study to identify the potential impact foreign dental school graduates have on improving access to dental care for vulnerable populations. The following hypotheses were tested: a) among all newly licensed dentists, foreign-trained dentists are more likely to participate in the Medicaid program than U.S.-trained dentists; and b) among newly licensed dentists who participated in the Medicaid program, foreign-trained dentists are more likely to practice in dental HPSAs than U.S.-trained dentists. Methods The authors used dental license and Medicaid license data to compare the proportions of newly licensed, foreign- and U.S.-trained dentists who participated in the Medicaid program and the proportions that practiced in a dental HPSA. Results Using bivariate analyses, the authors found that a significantly lower proportion of foreign-trained dentists participated in the Medicaid program than U.S.-trained dentists (12.9% and 22.8%, respectively; P = 0.011). Among newly licensed dentists who participated in the Medicaid program, there was no significant difference in the proportions of foreign- and U.S.-trained dentists who practiced in a dental HPSA (P = 0.683). Conclusions Legislation that makes it easier for foreign-trained dentists to obtain licensure is unlikely to address dental workforce shortages or improve access to dental care for vulnerable populations in the United States. Licensing foreign dental school graduates in the United States also has ethical implications for the dental workforces in other countries.

In addition to malignancies, survivin (a member of the apoptosis inhibitor family) has been implicated in the pathogenesis of inflammatory disorders, including autoimmune and allergic diseases. Survivin is constantly expressed in the proliferating hematopoietic progenitor cells, and it is re-expressed in the mature cells of the innate and adaptive immunity, upon activation. Survivin enhances the expression of co-stimulatory molecules and MHC class II molecules in dendritic cells, and promotes the lifespan of macrophages, neutrophils, and eosinophils, while suppressing natural killer (NK) cell activity. Survivin has been implicated in T cell maturation, T cell expansion, effector CD4 + T cell differentiation, maintenance of memory CD4 + T and CD8 + T cells, as well as antibody production. Upregulated expression of survivin was indicated in the T cells as well as various samples collected from allergic patients. Survivin can contribute to the pathogenesis of allergic diseases via the promotion of the Th2 polarization, promoting IL-4 expression, compromising activation-induced cell death (AICD) in Th2 cells, and preventing apoptosis of eosinophils, as well as, amplification of eosinophilia. Moreover, survivin can interfere with clonal deletion of autoreactive T and B cells, as well as suppress Treg cell development and activity supporting the development of autoimmune diseases. This review discusses the role of survivin in immunity, allergy and autoimmunity as well as provides evidence that survivin may be considered as a novel therapeutic target for the treatment of allergic and autoimmune diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder more common in autosomal recessive (AR) than X-linked in Iran. This study aimed to assess whether having a child with AR-CGD would increase the likelihood of the next child being affected by CGD. Ninety-one families with at least one child affected by AR-CGD entered this study. Out of the 270 children, 128 were affected by AR-CGD. We used a cross tab for the odds ratio (OR) calculation, in which exposure to a previously affected child and the next child's status were evaluated. This study illustrated that the chances of having another child afflicted with AR-CGD are significantly increased if the previous child had AR-CGD (OR=2.77, 95% CI=1.35-5.69).Althoug h AR disorders affect 25% of each pregnancy, we showed that the chance that the next child would be affected by CGD, given that the previous child was affected, is 2.77 times greater than in families with a normal child. It is recommended to warn families with one or more affected children to evaluate the risk of CGD in their subsequent pregnancies with prenatal diagnosis.

Background: It is well established that upper and lower airways are often clumped together when diagnosing and treating a disease. This study was designed to determine the prevalence of upper and lower airway diseases and to assess the effect of sociodemographic factors on the prevalence and the comorbidity of these disorders. Methods: This cross-sectional population-based study included patients with ages ranging between 15 to 65 years, who were referred to allergy outpatient clinics in various provinces of Iran from April to September 2020. A modified global Allergy and Asthma European Network (GA2LEN) screening questionnaire was filled out by local allergists of the 12 selected provinces in Iran. Information about the patients and sociodemographic factors was also recorded. Statistical analysis was done by univariate statistical analyses and multiple logistic regressions in SPSS software Version 26. Results: Out of 4988 recruited patients, 1078 (21.6%) had the symptoms of allergic rhinitis (AR) and 285 (5.7%) met the criteria of asthma. The prevalence of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) was 21.6 % and 22%, respectively. The highest prevalence of AR and ARS was in Tehran with the arateof of 33.9% each. Asthma was more prevalent in Khuzestan (14.2%) and CRS in Baluchestan (57.5%). Our analysis showed that the patients with asthma were most likely to have other allergic diseases as well-CRS (OR = 4.8; 95% CI, 2.02- 5.82), AR (OR= 2.5, 95% CI, 2.10-3), ARS (OR = 1.8; 95% CI, 2.10-3), followed by eczema (OR = 1.4; 95% CI, 1.13-1.67).We found that those individuals with CRS were most likely to have painkiller hypersensitivity (OR= 2.1; 95% CI, 1.21-3.83). Furthermore, smoking has been found more than 1.5 folds in patients with ARS. After adjusting variables, there was no correlation between education, occupation, and ethnicity with the studied diseases. Conclusion: Rhinosinusitis is a common condition among Iranian patients. This study confirmed that inflammation of the upper and lower airways can occur simultaneously. Gender, education, occupation, and ethnicity were found to be irrelevant in the development of either AR, asthma, ARS, or CRS., Competing Interests: The authors declare that they have no competing interests., (© 2022 Iran University of Medical Sciences.)

Asthma is a common respiratory disease affecting humans. Helminth parasites, including Toxocara species, have been implicated as predisposing factors of asthma. However, various studies present different findings on asthma- Toxocara association. Herein, we investigated the association of asthma manifestations with Toxocara seropositivity in a case-control setting on 248 participants (147 women and 101 men), with 124 healthy individuals as the control group and 124 patients known to have asthma based on the medical records of asthma clinics of Kerman University of Medical Sciences. Consequently, we presented a scoping review of all previous studies carried out on this topic, summarizing current findings and existing knowledge on this issue. Of 248 participants, 31 (12.5%) were Toxocara -seropositive, of which 19 (15.3%) were in the patient group and 12 (9.7%) in the control group. A significant relationship was found between asthma severity and age in Toxocara -seropositive individuals ( P < 0.04). We found no significant relationship between asthma and Toxocara seropositivity. We identified 7,724 related records in three major scientific databases, NCBI PubMed, Scopus, and Google Scholar. The review of the literature showed that there are 80 published articles on asthma- Toxocara relationship with contradictory findings. More than half of the studies were performed in only four countries, namely, Brazil, the Netherlands, the United States, and Iran. The study population in 70% of the studies were children, and few studies investigated asthma- Toxocara association in adults. The most common study designs for investigating the association of asthma and Toxocara seropositivity were cross-sectional (35.0%), case-control (27.5%), and animal experimental (12.5%) studies. This study found no significant relationship between asthma manifestations and toxocariasis in a case-control setting. However, a scoping review of the current literature suggests that further experimental and field longitudinal cohort studies are required to elucidate the nature of asthma- Toxocara interaction in humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bazargan, Lari, Borhani and Fasihi Harandi.)

Background: Human echinococcoses are the infection caused by the larval stages of different species of the genus Echinococcus, mostly E. granulosus and E. multilocularis. There is no aggregated information on the nature and characteristics echinococcosis in patients with immunodeficiency. This study presents a systematic review of the current literature published on the status of echinococcosis in immunocompromised individuals., Methods: An electronic search of related articles in four major databases (PubMed, Scopus, Web of Science and Google Scholar) was performed up to November 2021. All related studies meeting the inclusion criteria were assessed for qualitative analysis. Data available on different characteristics of the diseases were extracted. The data were subsequently categorized into two subgroups: Cystic Echinococcosis (CE) and Alveolar Echinococcosis (AE)., Results: Twenty-eight articles related to the existence of echinococcosis in immunocompromised hosts were included. HIV/AIDS was found as the most frequent condition in immunocompromised CE patients. Most of the CE cases with immunodeficiency were female (66.4%). The dominant stages of the cysts were CE2 and CE3. Surgery was performed for 76.2% of the patients. A high mortality rate of 23.8% was recorded in CE patients. Malignancies was the dominant condition in AE patients., Conclusion: Findings of the present study can potentially improve our understanding of the impact of immunodeficiency syndromes on echinococcoses and contribute to an improved diagnosis, treatment and quality of care in immunocompromised patients suffering from cystic and alveolar echinococcosis., (Copyright © 2022. Published by Elsevier B.V.)

Background: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations., Methods: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data., Results: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity., Conclusions: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease., (© 2021 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Blastocystis is a parasite that colonizes in the human intestine. Its clinical features include diarrhea, abdominal pain, or urticarial and irritable bowel syndrome (IBS). Spite of being significant genetic diversity and numerous subtypes within the genus there were no associations between its subtypes and symptomatology., Materials and Methods: Aim of this project was subtyping of the protozoa in 184 Iranian people with history of IBS/IBD (n = 74) or chronic urticaria (n = 59) and individuals referred to general clinic (n = 51). Microscopic and molecular examinations used for identifying and subtyping of Blastocystis., Results: Overall, frequency of the parasite was 24.46% while, 29.41% of people who referred to general clinic, 20.27%, and 25.42% of IBS/IBD and urticarial cases were infected, respectively. Subtyping result showed that 28.89% of all people were infected with Blastocystis sp. while the prevalence of ST3, ST2 and ST1 were 22.22%, 22.22%, and 17.78%, respectively. Blastocystis sp., was identified in most IBS/IBD cases (46.7%) followed with ST2 and ST3 (13.3 and 13.3, respectively). Whereas, in chronic urticaria group ST2(33.3%) was the major subtype and most individuals in control group were infected with ST3 (33.3%). Pearson's Chi Square test showed no significant differences between the parasite or subtype prevalence and diseases (p > 0.05)., Conclusion: Given significant factors have effect on clinical signs including host or parasite genetics, microbiota, as well as environmental factors, it seems that further studies are needed to find out different markers of host susceptibility to diverse parasite genotypes in patients with irritable bowel syndrome or urticaria.

Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

One of the components of NADPH oxidase is p47-phox, encoded by NCF1 gene. This study aims to find new genetic changes and clinical features in 38 Iranian patients with autosomal recessive chronic granulomatous disease (AR-CGD) caused by NCF1 gene defect. Patients who had abnormal NBT and DHR-1,2,3 assay with loss of p47-phox in Western blotting were included in this study. After recording demographic and clinical data, PCR amplification was performed followed by direct sequencing for all exons and exon-intron boundaries. The most common form of CGD in Iran was AR-CGD due to consanguinity marriages. Among patients with AR-CGD, NCF1 deficiency was found to be more common than other forms. Cutaneous involvements (53%), pulmonary infections (50%) and lymphadenopathy (29%) were more prevalent than other clinical manifestations of CGD. Mutation analysis of NCF1 gene identified five different mutations. Homozygous delta GT deletion (c.75&#95;76delGT) was the most frequent mutation and was detected in more than 63% of families. Six families had a nonsense mutation in exon 7 (c.579G > A). Two novel mutations were found in exon 4 in two families, including a missense mutation (c.328C > T) and a nine-nucleotide deletion (c.331&#95;339delTGTCCCCAC). Genetic detection of these mutations may result in early diagnosis and prevention of possible complications of the disease. This could be useful for timely decision-making for haematopoietic stem cell transplantation and for carrier detection as well as prenatal diagnosis of next children in the affected families. Our findings might help to predict outcomes, raise awareness and help effective treatment in these patients., (© 2019 The Foundation for the Scandinavian Journal of Immunology.)

Background: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses., Objective: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings., Methods: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID., Results: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 μ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with μ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with μ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008)., Conclusions: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Asthma as a chronic disease may affect the growth process. The aim of this study was to investigate the anthropometric indices in 2-18 years old children with asthma and compare them with the control group., Patients and Methods: In a case-control study, 150 asthmatic children with age of 2-18 years as case group and 300 age- and sex-matched healthy children as control group were randomly included. The height, weight, and body mass index (BMI) of both group measured by the standard method and Z score was calculated. Data were analyzed using SPSS, chi-square and analysis of variance., Results: Totally, 290 boys (64.4%) and 160 girls (35.6%) with mean age of 6.58±2.82 years were evaluated. Case group had significantly lower height compared to the healthy control group (117.00±0.17 cm vs. 121.00±0.15 cm respectively, P=0.025). No significant differences were detected in weight (23.13±9.75 kg vs. 24.62±10.36 kg, P=0.145) and BMI (16.32±3.10 kg/m 2 vs. 16.28±3.16 kg/m 2 , P=0.900) between case and control groups, respectively. There were no significant relationships between normal and abnormal Z scores of height, weight and BMI in case and control group (P>0.05)., Conclusion: Despite 4 cm difference between the age of two groups, no differences in height, weight ad BMI between two groups may be due to good control of the disease in the case group or lack of significant growth related effect of asthma., Competing Interests: COMPETING INTERESTS Authors have declared that no competing interests exist.

Background: The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders., Method: The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013-2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing., Results: Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort., Conclusions: During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.

Background: The imbalance between Th2 and Treg cells plays fundamental role in the pathogenesis of allergic asthma. The current study aimed at assessing the expression of some Th2 and Treg cell-related parameters in patients with allergic asthma., Material and Methods: The serum and peripheral blood mononuclear cell (PBMC) samples were collected from 30 patients with asthma and 36 healthy subjects. The serum levels of transforming growth factor (TGF)-β, interleukin (IL)-4, as well as the expression levels of GATA3 and FOXP3 genes in PBMCs were determined by the enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR), respectively. The PBMCs were cultured for 48 hours with/without phytohemagglutinin (PHA) stimulation. The TGF-β and IL-4 levels in supernatants were also determined., Results: The serum levels of IL-4, the expression level of GATA3 , and GATA3/FOXP3 ratio in patients with asthma were significantly higher than healthy subjects (P <0.002, P <0.001, and P <0.004, respectively). The FOXP3 expression did no differ between the two groups. The serum level of TGF-β as well as its secretion profile in non-stimulated and stimulated PBMCs isolated from patients with asthma were significantly higher than those of the controls (P <0.03, P <0.001, and P <0.001, respectively). The serum TGF-β levels in severe asthma were significantly higher than moderate asthma; whereas the TGF-β secretion by PHA-stimulated PBMCs isolated from moderate asthma was higher than that of severe pattern of the disease (P <0.001 and P <0.05, respectively). The GTAT3/FOXP3 expression ratio in moderate asthma was significantly higher than severe form (P <0.04)., Conclusion: The results confirmed a Th2 cell-biased pattern and possible contribution of TGF-β in allergic asthma. TGF-β may have different expression patterns in moderate and severe asthma and the two forms of the disease may have differences in some main immunological parameters., Competing Interests: Conflict of interest The authors have no any conflict of interest.

Introduction: Allergic rhinitis (AR) is a common airway disease. In order to study the prevalence of AR in high school students in Kerman, the Score for Allergic Rhinitis (SFAR) was used and the quality of life in the students affected by rhinitis was evaluated using the SF-36 questionnaire., Materials and Methods: This was a cross-sectional, analytical, descriptive study, based on the SFAR scale. Quality of life in students with AR was evaluated using the SF-36 questionnaire., Results: From 1511 students who completed the SFAR questionnaire, 291 (52.6%, girls; 47.4%, boys) had AR. Domestic dust was the most common cause of the disease. The most common symptoms of AR were rhinorrhea (76.6%), epiphora (76.3%), nasal congestion (64.3%), and itching (54.3%). According to the ARYA scale, (Allergic Rhinitis and its Impact on Asthma), 41.9% of students had moderate-to-severe rhinitis and 58.1% had mild rhinitis. A total of 43.1% of patients with moderate-to-severe rhinitis had a persistent condition and 56.9% had an intermediate condition. Results of the SF-36 questionnaire among students with AR showed a significant difference in physical functioning and bodily pain in comparison with healthy students., Conclusion: The results of this study show that the prevalence of AR among Kerman high school students is 19.3%. Because of the effect of this disease on the life quality of high school students in terms of both physical functioning and bodily pain, efforts should be made to reduce allergen levels as far as possible.

Background: Chronic granulomatous disease (CGD) is a rare immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. We studied CGD inheritance forms (autosomal recessive (AR) or X-linked (XL)) and AR-CGD subtypes in Iran., Methods: Clinical and functional investigations were conducted in 93 Iranian CGD patients from 75 families., Results: Most of the patients were AR-CGD (87.1%). This was related to consanguineous marriages (p = 0.001). The age of onset of symptoms and diagnosis were lower in XL-CGD compared with AR-CGD (p < 0.0001 for both). Among AR-CGD patients, p47phox defect was the predominant subtype (55.5%). The most common clinical features in patients were lymphadenopathy (65.6%) and pulmonary involvement (57%). XL-CGD patients were affected more frequently with severe infectious manifestations., Conclusions: Although XL-CGD is the most common type of the disease worldwide, only 12 patients (12.9%) were XL-CGD in our study. The relatively high frequency of AR-CGD is probable due to widely common consanguineous marriages in Iran.

Objective: Carotenoids, vitamin A, and tocopherols serve important roles in many key body functions. However, availability of these compounds may be decreased in patients with short bowel syndrome (SBS) due to decreased oral intake of fruits and vegetables and/or decreased intestinal absorption. Little information is available on serum concentrations of carotenoids, vitamin A, and tocopherols during chronic parenteral nutrition (PN) or during PN weaning. The aim of this study was to prospectively examine serum concentrations of a wide variety of carotenoids, vitamin A, and tocopherols in patients with SBS undergoing an intensive 12-wk intestinal rehabilitation program., Methods: Twenty-one PN-dependent adult patients with SBS were enrolled in a 12-wk intestinal rehabilitation program, which included individualized dietary modification, multivitamin supplementation, and randomization to receive subcutaneous placebo (n = 9) or human growth hormone (0.1 mg . kg(-1) . d(-1); n = 12). PN weaning was initiated after week 4 and advanced as tolerated. Serum concentrations of carotenoids, vitamin A, and tocopherols were determined at baseline and at weeks 4 and 12., Results: A significant percentage of subjects exhibited low serum concentrations for carotenoids and alpha-tocopherol at study entry, and a few subjects had low concentrations of retinol (5%). Carotenoid and vitamin A valves did not improve over time, while alpha-tocopherol levels rose. Serum alpha-tocopherol concentration was negatively associated with PN lipid dose (r = -0.34, P < 0.008)., Conclusion: Patients with SBS are depleted in diet-derived carotenoids despite oral and intravenous multivitamin supplementation and dietary adjustment during intestinal rehabilitation and PN weaning. Reduction of PN lipid infusion may improve serum alpha-tocopherol concentrations.

Background: Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients., Methods: This was a double-blind, randomized, controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine-free amino acids (STD-PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN-PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge., Results: Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN-PN. GLN-PN did not alter infection rates after pancreatic necrosis surgery (17 STD-PN and 15 GLN-PN patients). In nonpancreatic surgery patients (12 STD-PN and 15 GLN-PN), GLN-PN was associated with significantly decreased total nosocomial infections (STD-PN 36 vs GLN-PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram-negative bacteria (each P < .05)., Conclusions: Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.

Objectives: Little data are published on the habitual home oral diet of patients with short bowel syndrome (SBS)., Methods: We assessed nutrient intake from oral food and beverages in 19 stable patients with severe SBS who live in the southeastern United States. Intestinal absorption of energy, fat, nitrogen (N), and carbohydrate (CHO) was determined in a metabolic ward., Results: We studied 12 women and 7 men, age 48 +/- 3 y of age (mean +/- SE) receiving parenteral nutrition for 31 +/- 8 mo following massive small bowel resection (118 +/- 25 cm residual small bowel). The patients demonstrated severe malabsorption of energy (59 +/- 3% of oral intake), fat (41 +/- 5%), N (42 +/- 5%) and CHO (76 +/- 3%). Oral energy intake was 2656 +/- 242 kcal/d (39 +/- 3 kcal/kg/d) and oral protein intake was 1.4 +/- 0.1 g/kg/d. Food/beverage intake constituted 49 +/- 4% of total (enteral plus parenteral) daily fluid intake, 66 +/- 4% of total daily kcal and 58 +/- 5% of total daily N intake. Oral fat intake averaged 92 +/- 11 g/day ( approximately 35% of total oral energy). Oral fluid intake averaged 2712 +/- 240 ml/d, primarily from water, soft drinks, sweet tea and coffee. Simple sugars comprised 42 +/- 3% of oral CHO intake. Usual dietary intake of multiple micronutrients were below the Recommended Dietary Allowances (RDA) in a large percentage of patients: vitamin A (47%), vitamin D (79%), vitamin E (79%), vitamin K (63%), thiamine (42%), vitamin B6 (68%), vitamin B12 (11%), vitamin C (58%), folate (37%), iron (37%), calcium (63%), magnesium (79%) and zinc (68%). Only seven patients (37%) were taking oral multivitamin-mineral supplements and only six subjects (32%) were taking oral iron and calcium supplements, respectively., Conclusion: In these SBS patients, an oral diet provided a significant proportion of daily nutrient intake. The types of foods and fluids consumed are likely to worsen malabsorption and thus increase PN requirements. Oral intake of essential micronutrients was very low in a significant proportion of these individuals.

Background: Glutamine (Gln) may become conditionally indispensable during critical illness. The short-term metabolic effects of enteral versus parenteral Gln supplementation are unknown in this clinical setting., Objectives: We studied metabolic effects of intravenous (i.v.) alanyl-Gln dipeptide (AG) supplementation and enteral (e.n.) AG supplementation on plasma Gln concentration, antioxidant status, plasma lymphocyte subset number, gut permeability and nitrogen balance in adult critically ill patients requiring tube feeding compared to a control group not receiving Gln supplementation., Methods: In a double-blind, pilot clinical trial, 44 medical and surgical ICU patients received identical Gln-free tube feedings 24 h/day and were randomized to either isonitrogenous control (n=15), e.n. AG (n=15) or i.v. AG (n=14) groups (AG). Twelve patients were discontinued from the study. The goal AG dose was 0.5 g/kg/day. Biochemical and metabolic endpoints were measured at baseline and on day 9 (plasma Gln, antioxidant indices, lymphocyte subsets; serum IGF-1 and IGF-binding protein-3; intestinal permeability). Nitrogen balance was determined between study days 6 and 8., Results: Illness severity indices, clinical demographics, enteral energy and nitrogen intake and major biochemical indices were similar between groups during study. Plasma Gln was higher in the i.v. AG (565+/-119 microM, mean+/-SEM) vs the e.n. AG (411+/-27 microM) group by day 9 (p=0.039); however, subjects in the i.v. AG group received a higher dose of AG (i.v. AG 0.50 versus e.n. AG 0.32+/-0.02 g/kg/day; p<0.001). E.n. AG subjects showed a significant increase in plasma alpha-tocopherol levels over time and maintained plasma gamma-tocopherol concentrations. There were no differences between groups for plasma concentrations of vitamin C, glutathione, malondialdehyde (MDA), T-lymphocyte subsets, intestinal permeability or nitrogen balance., Conclusions: This study showed that alanyl-Gln administration by enteral or parenteral routes did not appear to affect antioxidant capacity or oxidative stress markers, T-lymphocyte subset (CD-3, CD-4, CD-8) number, gut barrier function or whole-body protein metabolism compared to unsupplemented ICU patients requiring enteral tube feeding. Enteral Gln appeared to maintain plasma tocopherol levels in this pilot metabolic study.

Gut barrier dysfunction may occur in short bowel syndrome (SBS). We hypothesized that systemic exposure to flagellin and lipopolysaccharide (LPS) in SBS might regulate specific immune responses. We analyzed serial serum samples obtained from parenteral nutrition (PN)-dependent patients with SBS versus non-SBS control serum. Serum from 23 adult SBS patients was obtained at baseline and 4, 8, 12, 16, 20, and 24 wk in a trial of modified diet with or without growth hormone. Control serum was obtained from 48 healthy adults and 37 adults requiring PN during critical illness. Serum flagellin was detected by an ELISA recognizing an array of gram-negative flagellins, and LPS was detected by limulus assay. Serum flagellin- and LPS-specific immunoglobulin levels (IgM, IgA, and IgG) were determined by ELISA. Serum flagellin and LPS were undetectable in control subjects. In contrast, serum flagellin, LPS, or both were detected in 14 SBS patients (61%) during one or more time points [flagellin alone, 5/23 (22%); LPS alone, 6/23 (26%); or flagellin + LPS, 3/23 (13%)]. Flagellin-specific serum IgM, IgA, and IgG levels were markedly increased in SBS patients compared with both control populations and remained elevated during the 6-mo study period. LPS-specific IgA was significantly higher in SBS patients compared with healthy controls; LPS-specific IgM, IgA, and IgG levels each decreased over time in association with PN weaning. We conclude that adults with PN-dependent SBS are systemically exposed to flagellin and LPS, presumably from the gut lumen. This likely regulates innate and adaptive immune responses to these specific bacterial products.

Objectives: Antioxidant depletion is common in critically ill patients. This study was designed to determine the effects of parenteral nutrition (PN), with or without glutamine (Gln) supplementation, on systemic antioxidant status in adult patients after major surgery who required PN in the surgical intensive care unit (SICU) setting., Methods: Fifty-nine patients in the SICU who required PN after pancreatic surgery or cardiac, vascular, or colonic (non-pancreatic) surgery were randomized in a double-blinded study to receive standard PN (Gln-free) or Gln-supplemented PN (Gln-PN) in which Gln was provided as alanyl-Gln dipeptide. Conventional PN vitamin and mineral doses were administered to all subjects. Plasma concentrations of the antioxidant glutathione (GSH) and the antioxidant nutrients alpha-tocopherol, vitamin C, and zinc were determined at baseline (initiation of study PN) and again after 7 d of study PN. Data were analyzed for the total study cohort and within the pancreatic surgery and non-pancreatic (cardiac, vascular, and colonic) surgery patient subgroups., Results: Mean plasma antioxidant concentrations were within or slightly below the normal ranges at baseline. However, a larger percentage of patients demonstrated below-normal baseline plasma concentrations of GSH (59%), vitamin C (59%), and zinc (68%), respectively. A smaller percentage of patients exhibited below-normal plasma alpha-tocopherol levels (21%). Study PN significantly improved plasma zinc levels in the entire study group and in each surgical subgroup. Gln-PN significantly improved the change in plasma levels of reduced GSH from baseline to day 7 in the non-pancreatic surgery patients (PN -0.27 microM versus Gln-PN +0.26 microM, P < 0.03)., Conclusion: Low plasma levels of key antioxidants were common in this group of patients in the SICU despite administration of PN containing conventional micronutrients. Compared with standard PN, Gln-supplemented PN improved plasma GSH levels in patients in the SICU after cardiac, vascular, or colonic operations.

Sensitive biomarkers for intestinal absorptive function would be clinically useful in short bowel syndrome (SBS). Citrulline (Cit) is a product of the metabolism of glutamine (Gln) and derived amino acids by enterocytes. Cit is produced almost exclusively by the gut, which is also a major site of Gln metabolism. The goals of this study were to examine whether plasma Cit and Gln concentrations are biomarkers of residual small intestinal length and nutrient absorptive functions in adult SBS patients followed prospectively. We studied 24 stable adults with severe SBS receiving chronic parenteral nutrition (PN) in a double-blind, randomized trial of individualized dietary modification +/- recombinant human growth hormone (GH). During a baseline week, intestinal absorption studies (% absorption of fluid, kcal, nitrogen, fat, carbohydrate, sodium, phosphorus, and magnesium) were performed and concomitant plasma Cit and Gln concentrations determined. Individualized dietary modification and treatment with subcutaneous injection of placebo (n = 9) or GH (0.1 mg/kg daily x 21 days, then 3 times/week; n = 15) were then begun. PN weaning was initiated after week 4 and continued as tolerated for 24 weeks. Repeat plasma amino acid determination and nutrient absorption studies were performed at weeks 4 and 12. Residual small bowel length at baseline was positively correlated with baseline plasma Cit (r = 0.467; p = .028). However, no significant correlations between absolute Cit or Gln concentrations and the percent absorption of nutrient substrates at any time point were observed. Similarly, no correlation between the change in Cit or GLN concentration and the change in % nutrient absorption was observed (baseline vs weeks 4 and 12, respectively). By weeks 12 and 24, 7 and 13 subjects were weaned completely from PN, respectively. However, baseline plasma Cit or Gln did not predict PN weaning at these time points. We concluded that plasma Cit (but not Gln) concentrations appeared to be an indicator of small intestinal length in adult SBS. However, neither plasma Cit nor Gln was a biomarker for intestinal absorptive function in this cohort of patients with SBS.

Background: Patients with short bowel syndrome (SBS) have a high prevalence of metabolic bone disease due to nutrient malabsorption and potential effects of parenteral nutrition (PN). Human growth hormone (hGH) has been shown in some studies to have anabolic effects on bone, but hGH effects on bone in patients with SBS are unknown., Methods: Adults with PN-dependent SBS underwent a 7-day period of baseline studies while receiving usual oral diet and PN and then began receiving modified diets designed to improve nutrient absorption and daily oral calcium/vitamin D supplements (1500 mg elemental calcium and 600 IU vitamin D, respectively). Subjects were randomized to receive in a double-blind manner either subcutaneous (sc) saline placebo as the control or hGH (0.1 mg/kg/d for 3 weeks, then 0.1 mg/kg 3 days a week for 8 subsequent weeks). Open-label hGH was given from week 13 to week 24 in subjects who required PN after completion of the 12-week double-blind phase. Markers of bone turnover (serum osteocalcin and urinary N-telopeptide [NTX]), vitamin D nutriture (serum calcium, 25-hydroxyvitamin D [25-OH D] and parathyroid hormone [PTH] concentrations), and intestinal calcium absorption were measured at baseline and at weeks 4 and 12. Dual x-ray absorptiometry (DXA) of the hip and spine was performed to determine bone mineral density (BMD) at baseline and weeks 12 and 24., Results: The majority of subjects in each group exhibited evidence of vitamin D deficiency at baseline (25-OH D levels<30 ng/mL; 78% and 79% of control and hGH-treated subjects, respectively). Subjects treated with hGH demonstrated a significant increase from baseline in serum osteocalcin levels at 12 weeks (+62%; p<.05). The levels of NTX were increased over time in the hGH-treated group; however, this did not reach statistical significance. Both NTX and osteocalcin remained unchanged in control subjects. BMD of the spine and total hip was unchanged in subjects treated with placebo or hGH at 24 weeks. However, femoral neck BMD was slightly but significantly decreased in the placebo group at this time point but remained unchanged from baseline in the hGH-treated subjects., Conclusions: hGH therapy significantly increased markers of bone turnover during the initial 3 months of therapy and stabilized femoral neck bone mass over a 6-month period in patients with severe SBS undergoing intestinal rehabilitation.

Primary immunodeficiency diseases (PIDs) are rare but include severe conditions found predominantly in children, Most PIDs have cutaneous manifestations that may be important as early diagnostic features. The purpose of this study was to determine the frequency and nature of cutaneous alterations associated with PIDs. This article is a cross-sectional study at the department of allergy and clinical immunology of children's medical center conducted between December 5, 2001 and April 20, 2002. The subjects included pediatric patients with a diagnosis of PID and dermatological diagnoses were made by a dermatologist. Two hundred and ten patients were studied They consisted of 68 cases of humoral deficiency, 22 cases of cellular and combined deficiencies, 57 cases of phagocytic defects and 63 cases of other PIDs. In 67 cases (31.8%) the cutaneous alterations preceded and were the basis for clinical immunological diagnosis. Overall cutaneous alterations were infections in 99 cases and eczematous dermatitis in 27 cases. Our findings support the results of other studies that most PIDs have cutaneous features which being their typical aspects are highly suggestive for the diagnosis of PIDs.

Primary immunodeficiency disorders include a variety of diseases that render patients more susceptible to infections. To determine the percentage of different primary immunodeficiency disorders diagnosed in the Children's Medical Center Hospital affiliated to Tehran University of Medical Sciences in Iran, we retrospectively reviewed the charts of the patients being referred to our hospital for immunologic evaluation of recurrent infections during a 20 year period. Among these patients, antibody deficiencies were the most frequent ones and were found in 52.6% of patients (n = 130). T-cell disorders, phagocytic disorders and complement deficiencies were found to be present in 24.69% (n = 61). 22.2% (n = 55) and 0.4% (n = 1) respectively. On the whole, common variable immunodeficiency was the most frequent disorder (n = 65), followed by ataxia telangiectasia (n = 39), X-linked agammaglobulinemia (n = 33), chronic granulomatous disease (n = 29) and selective IgA deficiency (n = 20). This study reveals that antibody deficiencies are the most common type of disorders as shown in other studies. A comparative study shows some differences between our results and other registries. This article also indicates that immunodeficiency disorders should be considered in patients with recurrent infections.

Neutropenia is characterized by decrease in the absolute number of circulating neutrophils and an increase susceptibility to infections. The current study was performed in order to explain the clinical and laboratory findings of patients with antibody deficiency disorders associated neutropenia. The patients' records of 19 neutropenic cases out of 207 patients with antibody deficiencies, who had been referred to Children's Medical Center and enrolled in Iranian primary immunodeficiency registry, were reviewed. Nineteen cases (14 male and 5 female), with a mean age of 10.7+/-5.7 years, were associated with neutropenia (9.2%). The disorders with associated neutropenia were Hyper IgM syndromes (3 of 8), Common variable immunodeficiency (13 of 109), and X-linked agammaglobulinemia (3 of 45). The median age for the onset of disease and diagnosis age were 15 months (1-134) and 3.8 years (6 months-13 years), respectively. The most common infections during the course of illness were pneumonia (13 cases), diarrhea (12 cases), oral candidiasis (9 cases), otitis media (6 cases), sinusitis (6 cases), cutaneous infections (5 cases), and abscess (5 cases). Other less frequent infections were: conjunctivitis, oral ulcers, meningitis, and osteomyelitis. Three neutropenic patients died because of recurrent infections. Neutropenia may occur in any of the primary immunodeficiency disorders. Persistent or severe infections always pose a supposition, which deserves further evaluation for detecting an underlying immune deficiency syndrome and neutropenia, since a delay in diagnosis may result in a serious organ damage or even death of the patient.

Chronic Granulomatous Disease (CGD) represents a group of inherited disorders of phagocytic system, manifesting recurrent infections at different sites. The present study was accomplished in order to determine the gastrointestinal manifestations of CGD patients. Fifty-seven patients (38 males and 19 females) with CGD, who had been referred to three immunodeficiency referral centers in Iran, were studied during a 24-year period (1980-2004). The median age at the time of study was 14.5 years old (1-56 years). The median onset age of symptoms was 5 months (1 month- 13.75 years), and that of diagnostic age was 5 years (2 months- 54.1 years), with a diagnostic delay of 33 months, on average. Seven patients were presented with acute diarrhea, 3 with oral candidiasis, and 2 with liver abscesses as the first chief complaints. Twenty-four cases (42.1%) had been complicated by gastrointestinal manifestations during their course of the disease. Of those, 12 cases (21.1%) had diarrhea, 7 (12.3%) oral candidiasis, 5 (8.8%) hepatitis, 4 (7.0%) hepatic abscess, and 2 cases (3.5%) gastric outlet obstruction. Also, failure to thrive was detected in 6 patients (10.5%). Four patients died (7%). CGD should be excluded in any patient with gastrointestinal manifestations especially chronic diarrhea, hepatic abscess, and gastric outlet obstruction.

Primary immunodeficiencies (PID) are a group of disorders, characterized by an unusual susceptibility to infections. Delay in diagnosis results in increased morbidity and mortality in affected patients. The purpose of this study was to determine the mortality rate of Iranian immunodeficient patients referred to Children Medical Center Hospital affiliated to Tehran University of Medical Sciences over a period of 20 years.In this study, records of 235 (146 males, 89 females) patients with immunodeficiency who were diagnosed and followed in our center, during 22 years period (1979-2001) were reviewed. The diagnosis of immunodeficiency was based on the standard criteria. The cause of death was determined by review of death certificates.Antibody deficiency was the most common diagnosis made in our patients. The overall five-year survival rate was 22.7% in our studied patient group; this was greatest in antibody deficiency. During the 22 year period of study, 32 patients died. As some of the patients could not be located, the true mortality rate ranged between 13.6% and 17.5%. The main leading cause of death were lower respiratory tract involvement in 14 cases (44%). The most common pathogenic microorganisms causing fatal infections were psudomonas and staphylococcus in 9 cases (28.1%) followed by E. coli in 7 (21.9%), tuberculosis in 13 (40.6%) and salmonella in 1 (3.1%).Based on our study, delay in diagnosis in patients with PID results in tissue and organ damage and several complications. Mortality and morbidity are increased in undiagnosed patients.

Background: Although long-term intravenous immunoglobulin infusion is an effective treatment for children with antibody deficiencies, it can be complicated by systemic adverse reactions., Objective: To evaluate the adverse reactions of intravenous immunoglobulin therapy in patients with primary immunodeficiency., Methods: Seventy-one immunodeficient patients receiving intravenous immunoglobulin were evaluated during a 7-year period (1995-2002) at Children's Medical Center in Tehran, Iran. Immunological diagnoses were as follows: common variable immunodeficiency (31 patients), X-linked agammaglobulinemia (25 patients), IgG subclass deficiency (5 patients), hyper-IgM syndrome (2 patients), and ataxia-telangiectasia (8 patients)., Results: One hundred fifty-two cases (12.35%) of adverse reactions occurred following 1,231 infusions in 35 patients. The most frequent immediate adverse reactions were mild reactions (131 infusions), including chills, fever, flushing, muscle pains, nausea, headache, and anxiety. Moderate reactions, such as vomiting, chest pain, and wheezing, occurred in 19 infusions. Two patients experienced severe adverse reactions. The highest proportion (23.06%) of reaction to injection was in patients with common variable immunodeficiency., Conclusions: Intravenous immunoglobulin is a well tolerated medical agent for patients with antibody deficiency. However, to prevent occurrence of immediate adverse reactions during infusion in these patients, physicians should perform a detailed history and proper physical examination and check the titer of anti-IgA.

Long-term intravenous immunoglobulin (IVIG) infusion is an effective treatment for children with humoral immunodeficiencies, already be complicated by systemic adverse effects. In order to determine the adverse effects of intravenous immunoglobulin in patients with antibody deficiency, 45 immunodeficient patients receiving intravenous immunoglobulin were studied during a 36 month period at Children's Medical Center. The investigated group included 25 patients with common variable immunodeficiency, 14 patients with X-linked agammaglobulinemia and 6 patients with IgG subclass deficiency. A total of fifty adverse effects occurred through 955 infusions (5.2%). The most frequent immediate adverse effects were mild (40 infusions out of 955) in 22 cases, including: chills, flushing, fever, nausea and headache. Three patients experienced moderate effects (10 infusions out of 955) such as rash, severe headache, joint pain and chest tightness. None of the effects was anaphylactic type. It can be concluded that intravenous immunoglobulin is generally a well-tolerated medical agent for patients with antibody deficiency, but all patients should be monitored by a physician who is familiar with its indications, risks, adverse effects and their appropriate management.

Primary complement deficiencies are rare and two related patients are reported here. The first patient is a 41- year- old man with eighteen episodes of pneumococcal meningitis and other purulent infections. The serum C3 level was checked at three separate times, showing that this was a primary C3 deficient case; other immunological tests were however normal. This patient now takes prophylactic antibiotics and the meningitis has not recurred, but he does have glomerulonephritis. The second case is a 40 - year-old woman with repeated episodes of orofacial and laryngeal edema and dyspnea. The serum C1INH levels were 4.3 to 7 mgldL which were very low compared with normal healthy subjects (C1INH was 40-50 mg/dL in ten normal controls) and C4 was lower than normal but other immunological tests were normal. Other causes of angioederna such as lymphoproliferative disorders were excluded. She had hereditary angioedema without a family background. The condition may be due to genetic mutation. The angioedema was controlled with Danazol and Stanasol. As our patients are related, this may suggest a genetic relationship between these two disorders.

Admission hyperglycemia has been associated with increased hospital mortality in critically ill patients; however, it is not known whether hyperglycemia in patients admitted to general hospital wards is associated with poor outcome. The aim of this study was to determine the prevalence of in-hospital hyperglycemia and determine the survival and functional outcome of patients with hyperglycemia with and without a history of diabetes. We reviewed the medical records of 2030 consecutive adult patients admitted to Georgia Baptist Medical Center, a community teaching hospital in downtown Atlanta, GA, from July 1, 1998, to October 20, 1998. New hyperglycemia was defined as an admission or in-hospital fasting glucose level of 126 mg/dl (7 mmol/liter) or more or a random blood glucose level of 200 mg/dl (11.1 mmol/liter) or more on 2 or more determinations. Hyperglycemia was present in 38% of patients admitted to the hospital, of whom 26% had a known history of diabetes, and 12% had no history of diabetes before the admission. Newly discovered hyperglycemia was associated with higher in-hospital mortality rate (16%) compared with those patients with a prior history of diabetes (3%) and subjects with normoglycemia (1.7%; both P < 0.01). In addition, new hyperglycemic patients had a longer length of hospital stay, a higher admission rate to an intensive care unit, and were less likely to be discharged to home, frequently requiring transfer to a transitional care unit or nursing home facility. Our results indicate that in-hospital hyperglycemia is a common finding and represents an important marker of poor clinical outcome and mortality in patients with and without a history of diabetes. Patients with newly diagnosed hyperglycemia had a significantly higher mortality rate and a lower functional outcome than patients with a known history of diabetes or normoglycemia.