Ammar K. Daoud

Diagnostic Markers for Neonatal Sepsis: Comparing C‐reactive Protein, Interleukin‐6 and Immunoglobulin M

This clinical study was conducted to evaluate the diagnostic value of C‐reactive protein (CRP), interlekin‐6 (IL‐6) and immunoglobulin M (IgM) in the early diagnosis of neonatal sepsis. The diagnostic values of each marker separately or in combinations were evaluated. The optimal cut‐off values of each marker in the diagnosis of neonatal sepsis were defined. Between December 2004 and March 2005, a total of 78 neonates at different ages with different diagnoses in a neonatal intensive care unit in North Jordan were enrolled. Patients were classified into ‘sepsis’ group, ‘probable sepsis’ group and ‘no sepsis’ group. Blood samples were collected for CRP, IL‐6 and IgM determination. A CRP value of 5 mg/l was the best among the three parameters with 95% sensitivity and 98% negative predictive value. Combination between parameters was helpful in enhancing the ability to diagnose sepsis. The best combination was CRP ≥ 5 mg/l and/or IgM of ≥20 mg/dl. We conclude that CRP, IL‐6 and IgM are helpful in the early diagnosis of Gram‐negative neonatal sepsis. However, CRP continues to be the best single test. The use of both CRP and IgM in combination was the most helpful in predicting Gram‐negative neonatal sepsis. We speculate a significant role of this combination in making decisions regarding antibiotics treatment and upgrading the level of medical care and observation in a setting where Gram‐negative micro‐organisms are causing the majority of neonatal infections.

Effects of diabetes mellitus vs. in vitro hyperglycemia on select immune cell functions

Diabetes mellitus (DM), one of the commonest metabolic disorders, can impair the function of cells involved in cellular and/or humoral immunity. This study sought to define potential effects upon cell-mediated immune cells due to an acute hyperglycemic state (in vitro) for comparison against those that might be attributable to a diabetic phenotype itself. Peripheral blood mononuclear cells (PBMC) were isolated from ten diabetic patients (5 with Type I disease and 5 with Type II) and 10 healthy controls. The cells were then challenged with 1 of 3 different mitogens (concanavalin A, phytohemagglutinin, pokeweed mitogen) in the presence of differing glucose concentrations (0, 100, 200, 400, or 800 mg/dl), and proliferative responses assessed. Neutrophils (PMNC) from the blood samples, exposed to the same experimental conditions, were analyzed for respiratory burst activity using nitroblue tetrazolium. The results indicated that there was significant inhibition of the proliferative responses to mitogens among the stimulated PBMC and in respiratory burst activity among the PMNC obtained from the diabetic patients. However, these effects were not affected by either the added presence of increasing amounts of exogenous glucose, the type of diabetes the patients had, the length of time the patient had had the disease, or whether or not the patients had been receiving insulin treatments. In contrast, the PBMC from healthy individuals appeared to display dose-trend decreases in responsiveness to mitogens; interestingly, similar effects on their PMNC were not evident. It was thus concluded that in situ ongoing repeated hyperglycemic states caused changes in cells of the immune system that could have been caused by repeated “continuous” exposures to excess sugar. Further studies are needed to more clearly identify hyperglycemia (sugar)-sensitive targets on/in these cells that could contribute to the appearance of the diabetic immunodeficiency in these types of patients.

Minocycline treatment results in reduced oral steroid requirements in adult asthma

The tetracycline antibiotics have pleiotropic anti-inflammatory properties that may explain their therapeutic benefit in rheumatoid arthritis and acne. As these agents suppress both cellular and humoral immune responses, they may be of benefit in treating asthma and other allergic disorders. The purpose of this study was to determine whether minocycline therapy of asthma has steroid sparing effects beyond its inherent antibiotic properties. Adult asthmatic patients (n = 17) were treated with minocycline 150 mg p.o. twice daily or placebo for 8 weeks in a randomized, double-blind, placebo-controlled crossover study. Patients were evaluated for clinical improvement in oral steroid requirements, spirometry, and symptom scores (Asthma Quality of Life Questionnaire). They underwent assessment for preexisting infection (CT facial sinuses, Chlamydia pneumoniae nasopharyngeal culture, and C. pneumoniae and Mycoplasma pneumoniae serology). Minocycline use was associated with a 30% reduction in mean daily prednisone use compared with placebo (8.8 mg versus 14.4 mg, respectively; p = 0.02). Pulmonary function testing showed improvement in forced vital capacity (FVC; percent predicted; p = 0.03) and improvement in actual FVC and forced expiratory volume in 1 second (percent predicted) approached statistical significance (p = 0.05 and 0.08, respectively). Minocycline treatment was associated with significant improvement in asthma symptoms brought on by environmental triggers (p = 0.01). This preliminary study of minocycline therapy showed oral steroid-sparing properties for those with moderate persistent and severe persistent asthma.

Vitamin D deficiency and level of asthma control in women from North of Jordan: a case–control study

Abstract Introduction: Reduced vitamin-D levels in patients with asthma have been associated with impaired lung function, increased airway hyper-responsiveness, and reduced glucocorticoid responsiveness. Nationwide studies revealed a considerable prevalence of vitamin-D deficiency (VDD) in Jordanian women. Objective: A case–control study was conducted to determine the relationship between serum vitamin A and D levels and asthma among women in North of Jordan. Methods: Sixty-eight asthmatics, age range between 14 and 65 years and 77 healthy women, age range between 19 and 51 years, were enrolled. Asthma severity was classified using Global Initiative for Asthma (GINA) guidelines and Asthma Control Test (ACT) questionnaire. Serum vitamin-A and 25-hydroxyvitamin-D (25(OH)D3) levels were measured using high-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods, respectively. Results: The prevalence of VDD (<15 ng/ml) was higher but not statistically significant for women with asthma compared with controls (95.6% vs. 87.0%; p = 0.070). The severity of VDD correlated with the number of asthma medications (p = 0.020). 25(OH)-D3 serum levels directly correlated with asthma control level using ACT score (p = 0.012) and GINA classification (p = 0.046). After adjusting for age, the odds of having VDD for asthmatic women were 35.9 times higher than that for women with no asthma. There was no difference in serum vitamin-A level between healthy and asthmatic women (p = 0.214) and none had vitamin-A deficiency (<200 µg/dl). Conclusions: VDD is prevalent in women with asthma in northern Jordan. The severity of VDD correlated with poor asthma control and a need for more medications to control asthma. There was no association between vitamin-A and asthma.

The association between metabolic syndrome and coronary artery disease in Jordan

Background: Previous studies in Jordan showed a considerably high prevalence of metabolic syndrome (MeS) and its individual components. However, data about the association between MeS and coronary artery disease (CAD) in Jordan are lacking. Therefore, this study aimed to determine the association between MeS and CAD among Jordanians. Methods: This case-control study included 269 patients diagnosed with CAD and 1026 subjects without CAD. Data collected from cases and controls included socio-demographic and clinical characteristics and anthropometric measurements. Patients were diagnosed with MeS based on the criteria of the National Cholesterol Education Program (NCEP) adult treatment panel (ATP) III. Results: MeS was present in 65.1% of patients with CAD and in 44.0% of those with no CAD (p<0.0005). After adjusting for the important variables in the multivariate analysis, those with MeS were twice more likely to have CAD (OR = 1.94, 95% CI: 1.29, 2.93, p = 0.002) compared to those without MeS. The number of metabolic abnormalities was significantly associated with CAD, when it substituted MeS in the regression model, with a higher number of MeS components led to greater odds for CAD. Conclusions: The MeS, which occurs very frequently in the general population, is associated with CAD in Jordan. The identification of subjects with the MeS is conceivably useful from a clinical standpoint, as it can be anticipated that these individuals should benefit from interventions aimed at reducing cardiovascular risk.

The association of HLA-DQB1*0602 but not HLA-DRB1*15 with obstructive sleep apnea

PURPOSE Obstructive sleep apnea (OSA) is a sleep breathing disorder with unclear multifactorial pathogenesis. This study aimed to investigate the association between OSA and two human leukocyte antigens (HLA) alleles; DQB1*0602 and DRB1*15. METHODS Forty patients with OSA and 40 control subjects were enrolled in the study. OSA diagnosis was made utilizing the Apnea-Hypopnea Index (AHI)≥5 in overnight polysomnography (PSG). AHI was also used to determine OSA severity. Controls were randomly selected from healthy volunteers who had a low risk for OSA, utilizing the Berlin Questionnaire. Polymerase chain reaction (PCR) using Sequence Specific Primers (PCR-SSPs) was used to determine the association between HLA (HLA-DQB1*0602 and HLA-DRB1*15) and OSA, then statistical analyses of the results were performed. RESULTS HLA-DQB1*0602 allele was found in 85% of all OSA patients and 50% of controls (P< 0.001). In patients with severe OSA, HLA-DQB1*0602 was present in the 92.9% compared with 66.7% in non-severe OSA (P=0.05). HLA-DRB1*15 allele was found in 15% of OSA patients and 20% of controls, with no difference between the two groups (P=0.556). No statistical difference was found in HLA-DRB1*15 between severe and non-severe OSA (P=0.499). After adjusting for gender, HLA-DQB1*0602 allele was associated with increased odds of OSA (OR = 6.17, 95% CI 1.87-20.3, p = 0.003), but HLA-DRB1*15 allele was not associated with OSA (OR 0.45, 95% CI 0.12-1.73, p = 0.242). CONCLUSIONS The presence of HLA-DQB1*0602 allele, but not HLA-DRB1*15 allele, was significantly associated with OSA.

Frequency of three common mutations of CARD15/NOD2 gene in Jordanian patients with Crohn's disease.

Background and Aims: CARD15/NOD2 is recognized as a major susceptibility gene for Crohn’s disease. Several mutations of CARD15/NOD2 have been reported in different racial groups. We aimed to investigate the frequency of three common CARD15/NOD2 mutations in a Jordanian Original Research Article Jadallah et al.; BJMMR, 7(2): 93-105, 2015; Article no.BJMMR.2015.312 94 Crohn’s disease cohort. Methodology: Fifty one unrelated Crohn’s disease patients and fifty one ageand sex-matched healthy controls were recruited at two hospitals in Jordan. Demographic and phenotypic characteristics of patients were ascertained. Allele frequencies for three CARD15/NOD2 mutations (G2722C, C2104T, 3020insC) were determined by PCR-RFLP, ARM-PCR, and direct sequencing using allele specific primers. Results: The frequencies of G2722C alleles in Crohn’s disease patients were higher but not statistically significant as compared to healthy controls (5.9% vs. 1.9%; P = 0.32). On the other hand, C2104T and 3020insC mutations have not been detected in Crohn’s disease patients or healthy controls. Conclusion: Our findings indicate that common mutations of CARD15/NOD2 gene in White patients with Crohn’s disease are not associated with Crohn’s disease in the Jordanian population. Further studies are needed to ascertain the effect of these and other mutations on Crohn’s disease susceptibility and behavior in our population.