Noninfectious Complications in B-Lymphopenic Common Variable Immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is considered the most symptomatic type of inborn errors of immunity in humans. Along with infectious complications, which have numerous consequences, noninfectious complications are a major challenge among CVID patients. METHODS: All CVID patients registered in the national database were included in this retrospective cohort study. Patients were divided into 2 groups based on the presence of B-cell lymphopenia. Demographic characteristics, laboratory findings, noninfectious organ involvement, autoimmunity, and lymphoproliferative diseases were evaluated. RESULTS: Among 387 enrolled patients, 66.4% were diagnosed with noninfectious complications and 33.6% with isolated infectious presentations. Enteropathy, autoimmunity, and lymphoproliferative disorders were reported in 35.1%, 24.3%, and 21.4% of patients, respectively. Some complications, including autoimmunity and hepatosplenomegaly, were reported to be significantly more frequent among patients with B-cell lymphopenia. As for organ involvement, the dermatologic, endocrine, and musculoskeletal systems were predominantly affected in CVID patients with B-cell lymphopenia. Among autoimmune manifestations, the frequency of rheumatologic, hematologic, and gastrointestinal autoimmunity was reported to be higher than that of other types of autoimmunity not associated with B cell-lymphopenia. Furthermore, hematological cancers, particularly lymphoma, were the most common type of malignancy. The mortality rate was 24.5%, and respiratory failure and malignancies were the most common causes of death, with no significant differences between the 2 groups. CONCLUSIONS: Considering that some of the noninfectious complications might be associated with B-cell lymphopenia, regular patient monitoring and follow-up with proper medication (in addition to immunoglobulin replacement therapy) are highly recommended to prevent sequelae and increase patient quality of life.

Non-Infectious Complications in B-Lymphopenic Common Variable Immunodeficiency.

BACKGROUND AND OBJECTIVE: Common variable immunodeficiency (CVID) is considered the most symptomatic type of inborn errors of immunity in humans. Along with infectious complications, which have numerous consequences, non-infectious complications are also a major challenge among CVID patients. METHODS: All registered CVID patients in the national database were included in this retrospective cohort study. Patients were divided into two groups based on the presence of B-cell lymphopenia. Demographic characteristics, laboratory findings, non-infectious organ involvements, autoimmunity, and lymphoproliferative diseases were evaluated. RESULTS: Among 387 enrolled patients, 66.4% were diagnosed with non-infectious complications; however, 33.6% had only infectious presentations. Enteropathy, autoimmunity, and lymphoproliferative disorders were reported in 35.1%, 24.3%, and 21.4% of patients, respectively. Some complications, including autoimmunity and hepatosplenomegaly, were reported to be significantly higher among patients with B-cell lymphopenia. Among organ involvement, dermatologic, endocrine and musculoskeletal systems were predominantly affected in CVID patients with B-cell lymphopenia. Among autoimmune manifestations, the frequency of rheumatologic, hematologic, and gastrointestinal autoimmunity was reported to be higher compared to other types of autoimmunity independent from the B cell-lymphopenia. Furthermore, hematological cancers, particularly lymphoma, were slightly introduced as the most common type of malignancy. Meanwhile, the mortality rate was 24.5%, and respiratory failure and malignancies were reported as the most common cause of death in our patients without significant differences between the two groups. CONCLUSION: Considering that some of the non-infectious complications might be associated with B-cell lymphopenia, therefore, regular patient monitoring and follow-up along with proper medications (besides immunoglobulins replacement therapy) are highly recommended to prevent further sequels and increase the patients' quality of life.

Infectious etiology of chronic diarrhea in patients with primary immunodeficiency diseases.

Summary: Background.Primary immunodeficiency diseases (PIDs) are life-threatening disorders, which manifest commonly with gastrointestinal (GI) signs, mainly as chronic diarrhea. Objective. To investigate and compare infectious etiology of chronic diarrhea in different PIDs. Patients and methods. Assessing clinical features, obtaining immunological profiles, as well as characterizing infectious etiology of diarrhea were performed in 38 PID patients with chronic diarrhea. Stool samples and/or biopsy specimens were checked using culture, microscopic examination, RT-PCR, and PCR, as appropriate. The patients were diagnosed to have common variable immunodeficiency (CVID), severe combined immunodeficiency (SCID), X-linked agammaglobulinemia (XLA), and hyper-IgM (HIgM) syndrome. Results. In 32 patients we identified 41 infectious agents including 16 parasitic (39.0%, the most common Giardia lamblia), 11 bacterial (26.8%, the most common salmonella spp), 8 viral (19.5%, the most frequent group A rotavirus), and 6 fungal organisms (14.7%, the most common Candida albicans). From 6 of the patients, no infectious agent was isolated. In CVID bacteria and parasites, in SCID bacteria and viruses, in XLA parasites, and in individuals with HIgM syndrome parasites were the leading causes of chronic diarrhea. Infection with giardia and cryptosporidium were more frequent in XLA and HIgM, respectively. Conclusion. The current study suggests considering both usual and unusual pathogens in laboratory investigation and in the empiric treatment of chronic diarrhea. Opportunistic pathogens should be taken into account when no other pathogen is identified, especially in patients on long-term treatment or prophylaxis with antifungals/antibiotics and in those from geographical locations that favor pathogenicity of these organisms.

Single nucleotide polymorphisms of the genes encoding IL-10 and TGF-Beta1 in Iranian children with atopic dermatitis

Background: Atopic dermatitis is an inflammatory skin disease in which both genetic and environmental factors interact to determine the susceptibility and severity of the disease. Objective: The aim of this study was to determine the association between atopic dermatitis and IL-10 and TGF-Beta1 gene polymorphisms. Methods: The allele and genotype frequencies of genes encoding for IL-10 and TGF-Beta1 were investigated in 89 patients with atopic dermatitis in comparison with 138 in the control group using the PCR-SSP method. Results: A significant increase was found in the frequency of the TGF-Beta1 codon 10/C allele among patients (p < 0.001, OR = 6.77), whereas a significant decrease was observed in the frequency of the T allele at the same position (p < 0.001, OR = 0.14). The frequency of the TGF-Beta1 codon 25/G allele in the control group was significantly higher than among patients (p < 0.001, OR = 0.08). A significant positive correlation was seen between CC (p < 0.001, OR = 15.10) and CG (p < 0.001) genotypes and AD at codons 10 and 25, respectively. The most frequent haplotypes among patients was TGF-Beta1 CG which was significantly higher than in the control subjects (50% in patients vs. 39.9% in controls, p = 0.042). A significant increase was found in the frequency of TGF-Beta CC (36% in patients vs. 7.6% in controls, p < 0.001) and TC (14% in patients vs. 0% in controls, p < 0.001) haplotypes among patients compared to controls. By contrast, the TGF-Beta1 TG haplotype was significantly lower in patients than controls (0% in patients vs. 52.5% in controls, p < 0.001). There were no significant differences in the frequency of alleles, genotypes and haplotypes of the IL-10 gene. Conclusions: We found a strong association between the polymorphisms of the TGF-Beta1 gene at codon 10 and codon 25 positions and atopic dermatitis (AU)

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Single nucleotide polymorphisms of the genes encoding IL-10 and TGF-ß1 in Iranian children with atopic dermatitis.

BACKGROUND: Atopic dermatitis is an inflammatory skin disease in which both genetic and environmental factors interact to determine the susceptibility and severity of the disease. OBJECTIVE: The aim of this study was to determine the association between atopic dermatitis and IL-10 and TGF-ß1 gene polymorphisms. METHODS: The allele and genotype frequencies of genes encoding for IL-10 and TGF-ß1 were investigated in 89 patients with atopic dermatitis in comparison with 138 in the control group using the PCR-SSP method. RESULTS: A significant increase was found in the frequency of the TGF-ß1 codon 10/C allele among patients (p<0.001, OR=6.77), whereas a significant decrease was observed in the frequency of the T allele at the same position (p<0.001, OR=0.14). The frequency of the TGF-ß1 codon 25/G allele in the control group was significantly higher than among patients (p<0.001, OR=0.08). A significant positive correlation was seen between CC (p<0.001, OR=15.10) and CG (p<0.001) genotypes and AD at codons 10 and 25, respectively. The most frequent haplotypes among patients was TGF-ß1 CG which was significantly higher than in the control subjects (50% in patients vs. 39.9% in controls, p=0.042). A significant increase was found in the frequency of TGF-ß CC (36% in patients vs. 7.6% in controls, p<0.001) and TC (14% in patients vs. 0% in controls, p<0.001) haplotypes among patients compared to controls. By contrast, the TGF-ß1 TG haplotype was significantly lower in patients than controls (0% in patients vs. 52.5% in controls, p<0.001). There were no significant differences in the frequency of alleles, genotypes and haplotypes of the IL-10 gene. CONCLUSIONS: We found a strong association between the polymorphisms of the TGF-ß1 gene at codon 10 and codon 25 positions and atopic dermatitis.

Interleukin-6 and tumor necrosis factor-alpha gene polymorphisms in chronic idiopathic urticaria

BACKGROUND: This study was performed to evaluate association of gene polymorphisms among proinflammatory cytokines and susceptibility to chronic idiopathic urticaria (CIU). METHODS: Ninety patients with prolonged urticaria more than 6 weeks were included as case group. Single nucleotide polymorphisms (SNPs) of IL-6 (G/C −174, G/A nt565) and TNF-α (G/A −308, G/A −238) were evaluated, using polymerase chain reaction (PCR); and the results were compared to the control group. RESULTS: Gallele was significantly higher in the patients at locus of −238 of promoter of TNF-α gene (p < 0.001). Frequency of following genotypes were significantly lower in patients with CIU, compared to controls: AG at −308 and GA at −238 of TNF-α gene (p < 0.05 and p < 0.001, respectively), CG at −174 and GG at +565 of IL-6 gene (p < 0.05). Additionally, following genotypes were more common among patients with CIU: GG at −308 and −238 of TNF-α gene (p < 0.05 and p < 0.001, respectively), GG at −174 and GA at +565 of IL-6 gene (p < 0.05). CONCLUSIONS: Pro-inflammatory cytokine gene polymorphisms can affect susceptibility to CIU. TNF-α promoter polymorphisms as well as IL-6 gene polymorphisms are associated with CIU

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Human papilloma virus and nasopharyngeal carcinoma: pathology, prognosis, recurrence and mortality of the disease.

BACKGROUND: One of the malignant tumors among head and neck cancers is nasopharyngeal carcinoma. Many studies consider human papilloma virus (HPV) as a cause for nasopharyngeal carcinoma. METHODS: 41 paraffin-wax-embedded block samples were examined to detect HPV DNA and its subtype's presence by polymerase chain reaction. The recurrence, prognosis and survival were evaluated for an average of 48 months. RESULTS: HPV DNA was positive in 9 patients (22%). The overall recurrence rate was 75% in HPV negative patients and 11% in HPV positive ones. The mortality rate in HPV negative and positive patients was 37.5% and 0%, respectively. CONCLUSION: HPV type 18 and 16 were the most common subtypes. Also, it can be implied that patients which are HPV positive had better prognosis and also less recurrence.

Association of single nucleotide polymorphisms of interleukin-1 family with atopic dermatitis

BACKGROUND: Interleukin-1 (IL-1) seems to have an important role in early reactions towards microbes, while its genetic variability could affect this role in atopic patients who have a distressed immunity towards dermatological infections. METHODS: Eighty-nine patients with atopic dermatitis (AD), who were referred to a main referral paediatric hospital, were enrolled in this study. Single nucleotide polymorphisms (SNP) of the following IL-1 cluster genes were assessed in this group of patients: IL-1α −889, IL-1β −511, IL-1β +3962, IL-1R Pst-I 1970, and IL-1RA Mspa-I 11100. The results were compared with a group of 140 healthy subjects from the same region. RESULTS: Fourteen percent of the controls had TT homozygous genotype in IL-1R at position Pst-I 1970, while only 2% of the patients with AD had this genotype (p = 0.005, OR: 0.14, 95%CI: 0.02-0.64). The CC homozygous genotype was the most common genotype in IL-1α position −889 and IL-1β at position +3962 in both groups of patients with AD and the controls, while the TC heterozygous genotype was the most common genotype in IL-1β at position −511 and IL-1R at position Pst-I 1970, with no significant difference between the two groups. CONCLUSIONS: This study showed a significant negative association in the IL-1R Mspa-I 11100 TT homozygous genotype in the patients with AD

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Interleukin-6 and tumor necrosis factor-alpha gene polymorphisms in chronic idiopathic urticaria.

BACKGROUND: This study was performed to evaluate association of gene polymorphisms among proinflammatory cytokines and susceptibility to chronic idiopathic urticaria (CIU). METHODS: Ninety patients with prolonged urticaria more than 6 weeks were included as case group. Single nucleotide polymorphisms (SNPs) of IL-6 (G/C -174, G/A nt565) and TNF-α (G/A -308, G/A -238) were evaluated, using polymerase chain reaction (PCR); and the results were compared to the control group. RESULTS: G allele was significantly higher in the patients at locus of -238 of promoter of TNF-α gene (p<0.001). Frequency of following genotypes were significantly lower in patients with CIU, compared to controls: AG at -308 and GA at -238 of TNF-α gene (p<0.05 and p<0.001, respectively), CG at -174 and GG at +565 of IL-6 gene (p<0.05). Additionally, following genotypes were more common among patients with CIU: GG at -308 and -238 of TNF-α gene (p<0.05 and p<0.001, respectively), GG at -174 and GA at +565 of IL-6 gene (p<0.05). CONCLUSIONS: Pro-inflammatory cytokine gene polymorphisms can affect susceptibility to CIU. TNF-α promoter polymorphisms as well as IL-6 gene polymorphisms are associated with CIU.

Association of single nucleotide polymorphisms of interleukin-1 family with atopic dermatitis.

BACKGROUND: Interleukin-1 (IL-1) seems to have an important role in early reactions towards microbes, while its genetic variability could affect this role in atopic patients who have a distressed immunity towards dermatological infections. METHODS: Eighty-nine patients with atopic dermatitis (AD), who were referred to a main referral paediatric hospital, were enrolled in this study. Single nucleotide polymorphisms (SNP) of the following IL-1 cluster genes were assessed in this group of patients: IL-1α -889, IL-1ß -511, IL-1ß +3962, IL-1R Pst-I 1970, and IL-1RA Mspa-I 11100. The results were compared with a group of 140 healthy subjects from the same region. RESULTS: Fourteen percent of the controls had TT homozygous genotype in IL-1R at position Pst-I 1970, while only 2% of the patients with AD had this genotype (p=0.005, OR: 0.14, 95%CI: 0.02-0.64). The CC homozygous genotype was the most common genotype in IL-1α position -889 and IL-1ß at position +3962 in both groups of patients with AD and the controls, while the TC heterozygous genotype was the most common genotype in IL-1ß at position -511 and IL-1R at position Pst-I 1970, with no significant difference between the two groups. CONCLUSIONS: This study showed a significant negative association in the IL-1R Mspa-I 11100 TT homozygous genotype in the patients with AD.

Single-Nucleotide Polymorphisms of TNFA and IL1 in Allergic Rhinitis

Background: Allergic rhinitis is a complex polygenic disorder of the upper respiratory tract. Given that proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL) 1 seem to play a role in the development of allergic rhinitis, we evaluated the associations between various single-nucleotide polymorphisms (SNPs) of the TNF and IL1 genes in a case-control study. Methods: The study population comprised 98 patients with allergic rhinitis. Genotyping was performed using polymerase chain reaction with sequence-specific primers for 2 TNFA promoter variants (rs1800629 and rs361525), 1 variant in the promoter region of IL1A (rs1800587), 2 SNPs in the IL1B gene (rs16944 and rs1143634), 1 variant in the IL1 receptor (rs2234650), and 1 in IL1RA (rs315952). Results: Patients who were homozygous for the T allele of rs16944 in IL1B had an 8.1-fold greater risk of allergic rhinitis than those with the C allele. In TNFA, a significant relationship was also detected between rs1800629 and rs361525 and allergic rhinitis. Except for rs1800587 in IL1A and rs315952 in IL1RA, significant differences were found between the patient and control groups for all other SNPs. Conclusions: We found that allelic variants in the TNFA and IL1 genes were not only associated with the risk of developing allergic rhinitis, but also affected disease course and severity (AU)

Antecedentes: La rinitis alérgica es una alteración poligénica compleja de las vías respiratorias. El TNF y la familia de la IL-1, como citoquinas proinflamatorias, parecen jugar un papel en el desarrollo de la rinitis alérgica. En este estudio de casos y controles, se evalúan las posibles asociaciones de diferentes polimorfismos de nucleótidos simples (SNPs) de los genes que regulan TNF- α e IL1. Métodos: Se estudiaron 19 pacientes con rinitis alérgica, los cuales fueron genotipados mediante PCR para primeras especie-específicos, para dos variantes del promotor del TNF- α (rs1800629 y rs361525), uno en el receptor de IL1 (rs2234650), dos SNPs en el gen de IL1ß (rs16944 y rs1143634), uno en el receptor de IL1 receptor (rs2234650) y IL1RA (rs315952). Resultados: En cuanto a los resultados obtenidos, los pacientes homicigotos para el alelo T de rs16944 en IL1ß mostraron un riesgo 8.1 veces mayor de tener rinitis alérgica que los que presentaban el alelo C. Con respecto al TNF- α, se observó una relación significativa entre los dos SNPs rs1800629 y rs361525 con la presentación de una rinitis alérgica. Excepto rs1800587, en IL1 α, y rs315952 en IL1RA, encuentran una diferencia significativa entre el grupo control y el de pacientes para el resto de los SNPs. Algunos SNPs se asociaron con el curso y con la gravedad de la enfermedad. Conclusiones: En conclusión, encontramos variantes genéticas de TNF-α y IL1 que se asocian con el riesgo de desarrollar una rinitis alérgica, y que también afectan al curso y gravedad de la enfermedad (AU)

Association between the interleukin 6 genotype at position -174 and atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic skin disorder of unknown origin that usually manifests for the first time in early infancy. Different types of genetic predisposition and environmental factors seem to be associated with the disease. METHODS: This study was performed to evaluate the frequency of alleles, genotypes, and haplotypes of interleukin (IL) 6 single-nucleotide polymorphisms (SNPs) at positions -174 and nt565 in 89 Iranian children with AD and 139 healthy controls. RESULTS: The G allele was significantly more frequent at position -174 in IL6 in atopic patients than in the healthy controls (P < .001; OR, 2.82). Genotype GG was found at the same position in 71% of the patients; this frequency was significantly higher than the frequency of 30% recorded in the controls (P < .001; OR, 5.60). The GG haplotype of IL6 (-174, nt565) was significantly more frequent in the atopic patients than in the healthy controls (P < .001; OR, 2.99). CONCLUSIONS: A significant increase in the frequency of the G allele and GG genotype at position -174 of IL6 was found in patients with AD, thus suggesting that production of this cytokine is greater in atopic patients.

Association Between the Interleukin 6 Genotype at Position –174 and Atopic Dermatitis

Antecedentes: La dermatitis atópica (DA) es una alteración crónica de la piel de origen desconocido, que habitualmente comienza en la infancia. Diferentes predisposiciones y factores ambientales se asocian a esta enfermedad. Métodos: Este estudio se realizó en 89 niños iraníes con DA para evaluar la frecuencia de alelos, genotipos y haplotipos de polimorfismos genéticos simples (SNPs) de la IL6 en las posiciones 174 y nt565 en comparación con 139 controles sanos. Resultados: Observamos un incremento significativo del alelo G de la IL6 en la posición –174 en los pacientes con DA comparado con el grupo control (p<0.001, OR=2.82). El genotipo GG de la misma posición se encontró en el 71% de los pacientes frente al 30% en los controles (p<0.001, OR=5.60). También se observa un incremento significativo en el haplotipo GG de la IL6 (-174, nt565) en los pacientes con DA comparados con los controles sanos (p<0.001, OR=2.99). Conclusiones: En conclusión observamos un aumento significativo del alelo Gallele y del genotipo GG en la posición -174 de la IL6 en pacientes con DA, lo que podría sugerir un aumento de la producción de esta citocina en los pacientes con DA (AU)

Background: Atopic dermatitis (AD) is a chronic skin disorder of unknown origin that usually manifests for the first time in early infancy. Different types of genetic predisposition and environmental factors seem to be associated with the disease. Methods: This study was performed to evaluate the frequency of alleles, genotypes, and haplotypes of interleukin (IL) 6 single-nucleotide polymorphisms (SNPs) at positions –174 and nt565 in 89 Iranian children with AD and 139 healthy controls. Results: The G allele was significantly more frequent at position –174 in IL6 in atopic patients than in the healthy controls (P<.001; OR, 2.82). Genotype GG was found at the same position in 71% of the patients; this frequency was significantly higher than the frequency of 30% recorded in the controls (P<.001; OR, 5.60). The GG haplotype of IL6 (–174, nt565) was significantly more frequent in the atopic patients than in the healthy controls (P<.001; OR, 2.99). Conclusions: A significant increase in the frequency of the G allele and GG genotype at position –174 of IL6 was found in patients with AD, thus suggesting that production of this cytokine is greater in atopic patients (AU)

Single-nucleotide polymorphisms of TNFA and IL1 in allergic rhinitis.

BACKGROUND: Allergic rhinitis is a complex polygenic disorder of the upper respiratory tract. Given that proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL) 1 seem to play a role in the development of allergic rhinitis, we evaluated the associations between various single-nucleotide polymorphisms (SNPs) of the TNF and IL1 genes in a case-control study. METHODS: The study population comprised 98 patients with allergic rhinitis. Genotyping was performed using polymerase chain reaction with sequence-specific primers for 2 TNFA promoter variants (rs1800629 and rs361525), 1 variant in the promoter region of IL1A (rs1800587), 2 SNPs in the IL1B gene (rs16944 and rs1 143634), 1 variant in the IL1 receptor (rs2234650), and 1 in IL1RA (rs315952). RESULTS: Patients who were homozygous for the T allele of rs16944 in IL1B had an 8.1-fold greater risk of allergic rhinitis than those with the C allele. In TNFA, a significant relationship was also detected between rs1800629 and rs361525 and allergic rhinitis. Except for rs1800587 in IL1A and rs315952 in IL1RA, significant differences were found between the patient and control groups for all other SNPs. CONCLUSIONS: We found that allelic variants in the TNFA and IL1 genes were not only associated with the risk of developing allergic rhinitis, but also affected disease course and severity.

Pediatric patients with common variable immunodeficiency: long-term follow-up.

BACKGROUND: Common variable immunodeficiency (CVID) is the most common form of symptomatic primary immunodeficiency disease. It is characterized by hypogammaglobulinemia, increased predisposition to infections, autoimmunity, and cancer. OBJECTIVES: This study was performed to evaluate the clinical and immunological features of a group of pediatric patients with CVID. METHODS: The study population comprised 69 individuals with CVID diagnosed during childhood. RESULTS: The patients were followed up for a mean (SD) period of 5.2 (4.3) years. The mean diagnostic delay was 4.4 (3.6) years, which was significantly lower in patients who were diagnosed recently. Children were classified according to 5 clinical phenotypes: infections only (n=39), polyclonal lymphocytic infiltration (n=17), autoimmunity (n=12), malignancy (n=7), and enteropathy (n=3). Postdiagnosis survival (10-year) was 71%. CONCLUSIONS: The high percentages of pediatric patients with CVID in Iran may be due to the considerable prevalence of parental consanguinity in the region and an underlying genetic background.

Correlation between peripheral and central venous pressures in children with congenital heart disease.

Central venous pressure (CVP) measurement is a reliable method for evaluating intravascular volume status and cardiac function, but it is an invasive method that results in some complications such as arterial puncture, pneumothorax, and development of infection. The current study was performed to compare CVP measurements between central and peripheral catheters in infants and children with congenital heart disease referred for right-sided heart catheterization. The CVP and peripheral venous pressure (PVP) in 45 patients were measured simultaneously. The mean difference between CVPs measured from the central and peripheral catheters was 8 +/- 4 cm H(2)O. The linear regression equation showed that CVP = 0.32 PVP + 3.8 (r = 0.67; p < 0.005). There was no difference in CVP measurements depending on the intravenous cannula and chest diameters, arm diameter, arm length, body surface area, patient's age (< or =10 years and >10 years), and type of congenital heart disease (cyanotic or noncyanotic). In conclusion, although CVP measured from a peripheral intravenous catheter in infants and children with congenital heart disease is not as accurate as the measurement in adults, the aforementioned linear regression equation based on measurement of PVP gives a reliable estimate of CVP.