Control Subjects Mean Research Articles

Vitamin D status in Egyptian euthyroid multinodular non-toxic goiter patients and its correlation with TSH levels

Background and aimAlthough the prevalence of MNG is widespread throughout the world, its pathogenesis is poorly understood, and the complex interactions of both genetic predisposition and the individuals’ environment are likely. However, to the best of our knowledge, it remains unknown whether there is a relationship between vitamin D status and prevalence or pathogenesis of euthyroid MNG. Therefore, the goal of the present study was determination of vitamin D status in euthyroid MNG as well as exploration of the correlation between vitamin D status & TSH levels. MethodsA total of 77 patients diagnosed with euthyroid MNG and 50 subjects without goiter were matched according to age, weight and BMI as control group in this case control study. ResultsWe found that patients with euthyroid MNG had statistically significant lower mean of [25(OH)D] (24.21±8.68ng/mL) in comparison with its mean in control subjects (28.37±10.91ng/mL, P value=0.019). The 28 sufficient vitamin D MNG patients had statistically significant lower level of TSH than 49 insufficient vitamin D MNG patients. Vitamin D and TSH levels correlate with vitamin D levels in MNG patients in Pearson correlation. Also 25 OH vitamin D was a significant independent predictor for TSH levels among euthyroid MNG patients in regression analysis. ConclusionsPatients with euthyroid MNG have lower levels of vitamin D and TSH levels correlate with vitamin D levels in euthyroid MNG patients. In addition, 25 OH vitamin D was a significant independent predictor for TSH levels among euthyroid MNG patients. We recommend hypovitaminosis D evaluation and correction in patients with MNG.

Vitamin D status in Egyptian euthyroid multinodular non-toxic goiter patients and its correlation with TSH levels

Background and aimAlthough the prevalence of MNG is widespread throughout the world, its pathogenesis is poorly understood, and the complex interactions of both genetic predisposition and the individuals’ environment are likely. However, to the best of our knowledge, it remains unknown whether there is a relationship between vitamin D status and prevalence or pathogenesis of euthyroid MNG. Therefore, the goal of the present study was determination of vitamin D status in euthyroid MNG as well as exploration of the correlation between vitamin D status & TSH levels. MethodsA total of 77 patients diagnosed with euthyroid MNG and 50 subjects without goiter were matched according to age, weight and BMI as control group in this case control study. ResultsWe found that patients with euthyroid MNG had statistically significant lower mean of [25(OH)D] (24.21±8.68ng/mL) in comparison with its mean in control subjects (28.37±10.91ng/mL, P value=0.019). The 28 sufficient vitamin D MNG patients had statistically significant lower level of TSH than 49 insufficient vitamin D MNG patients. Vitamin D and TSH levels correlate with vitamin D levels in MNG patients in Pearson correlation. Also 25 OH vitamin D was a significant independent predictor for TSH levels among euthyroid MNG patients in regression analysis. ConclusionsPatients with euthyroid MNG have lower levels of vitamin D and TSH levels correlate with vitamin D levels in euthyroid MNG patients. In addition, 25 OH vitamin D was a significant independent predictor for TSH levels among euthyroid MNG patients. We recommend hypovitaminosis D evaluation and correction in patients with MNG.

Serum liver enzyme pattern in birth asphyxia associated liver injury.

PurposeTo study temporal pattern of serum liver enzymes levels in newborns with hepatic injury associated with birth asphyxia (BA).MethodsSingleton term newborns with BA and ≤72 hours of age admitted to neonatal intensive care unit were prospectively enrolled. Term newborns with physiological jaundice and without BA were studied as controls. Serum liver enzymes were measured at <24 hours, 24-72 hours, and at 6-12 days of age for cases and at 1-6 days of age for controls. BA was defined by 1 minute Apgar score <7 or delayed or absent cry with hypoxic ischemic encephalopathy. BA-associated liver injury was defined as serum alanine aminotransferase (ALT) elevation beyond +2 standard deviation (ALT > +2 SD) above the mean of control subjects at any of the three time points.ResultsSixty controls and 62 cases were enrolled. Thirty-five cases (56%) developed BA-associated liver injury (ALT>81 IU/L). They had higher serum levels of ALT, aspartate aminotransferase, lactate dehydrogenase than the control infants, with peak at 24-72 hours. In controls, serum liver enzyme levels were significantly higher in appropriate-for-date (AFD) babies than small-for-date (SFD) babies. Serum enzyme pattern and extent of elevation were comparable between SFD and AFD babies. Degree of serum liver enzyme elevation had no relationship with severity of hypoxic encephalopathy.ConclusionSerum liver enzyme elevation is common in BA; it peaks at 24-72 hours followed by a sharp decline by 6-12 days of age. Pattern and extent of enzyme elevation are comparable between SFD and AFD babies.

Serum B12 Levels In Children with Sickle Cell Disease Are Lower Than In Healthy Control Subjects

AbstractAbstract 1647Clinical B12 (cobalamin) deficiency occurs in sickle cell disease (SCD) but it is uncommon (NEJM 2003;348:2204). Several publications report lower serum B12 concentrations in SCD subjects than in controls (Acta Haematol 1984;71:299; J Intern Med 1995;237:551; J Nat Med Assoc 2006;98:352). However, other studies do not show these differences (Am J Hematol 2004;76:114; South Med J 2004;97:149; J Am Coll Nutr 2000;19:608). Serum transcobalamin concentrations are high in SCD (Scand J Haematol 1983;30:135; Acat Haematol 1989;81:117) so that one would expect higher than normal B12 levels in these patients. We measured serum B12 concentrations in 467 children and adolescents with SCD and in 69 control subjects matched for age, sex, and ethnicity. All subjects were enrolled in the PUSH protocol, a multicenter study for determining the prevalence and significance of pulmonary hypertension in children with SCD. The median serum B12 concentration in SCD was lower than in controls (960 vs. 1094 pg/ml, p=0.003). No patient had a serum B12 value lower than 227 pg/ml (3 SD below the mean of control subjects) and sickle genotype did not affect B12 concentration. Univariate analysis in children with the Hb SS genotype (N=343) showed that age, body mass index, serum creatinine (all three p=0.0001), and red cell MCV (p=0.025) were each inversely correlated with B12 levels, and this suggested the possibility that as children grow, their B12 requirements increase. In SS children higher leukocyte counts, serum AST, and serum ALT were all associated with higher B12 levels (p=0.005, p=0.0001, and 0.011, respectively), while blood Hb concentration, a-thalassemia status, Hb F %, platelet count, and hemolytic parameters were unrelated to serum B12. The median B12 level in SS children (941 pg/ml) remained significantly lower than that of controls even after adjustment for age and WBC. Children with Hb SS who were taking hydroxyurea had significantly lower median B12 levels (845 pg/ml, N=141) than SS children not on this drug (992 pg/ml, N=200 p=0.027) (Figure) but after adjustment for age and WBC this difference was no longer significant (p=0.5).These results suggest that (a) children with SCD have lower, though still normal, serum B12 concentrations than healthy subjects, (b) this difference is not explained by SCD leukocytosis so that it could represent increased B12 requirements, and (c) hydroxyurea treatment reduces B12 levels even further probably as a result of its lowering effect on leukocyte count. However, because hydroxyurea was not given in a randomized manner, we cannot exclude the confounding effect of age on B12 level in hydroxurea treated subjects. Since we and others (Acat Haematol 1989;81:117) show that in SCD serum B12 decreases with age, as is the case also in non-SCD individuals (Am J Clin Nutr 1997;66:741), it would seem prudent to monitor cobalamin levels in SCD adults, particularly in older subjects and in those taking hydroxyurea. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Plasma homovanillic acid in adolescents with bulimia nervosa

Dopaminergic abnormalities in bulimia nervosa have been reported in some studies, but results are not consistent across studies. In the present study, clinical characteristics, plasma level of homovanillic acid (pHVA) and two scales – the Eating Attitudes Test (EAT) and the Beck Depression Inventory (BDI) – were assessed in 36 adolescent bulimia nervosa patients (mean age16.3 years, S.D. 1.1) who were consecutively seen on an Eating Disorder Unit. Levels of pHVA were also measured in 16 healthy control adolescents from the general population. Patients had significantly higher mean pHVA than controls. Eighteen patients (50%) had a pHVA level equal to or higher than the mean of control subjects plus one standard deviation, and this group of patients had significantly higher mean BDI scores and non-significantly higher mean EAT scores, although they did not differ from the other patients in age, time elapsed since the onset of disorder, body mass index and number of binges or vomits. Moreover, in logistic regression analysis the BDI score proved to be an independent predictor of high pHVA. The level of pHVA is increased in bulimia nervosa patients with high scores on measures of depressive and eating symptomatology.

The PEA15 gene is overexpressed and related to insulin resistance in healthy first-degree relatives of patients with type 2 diabetes

Overexpression of the gene encoding phosphoprotein enriched in astrocytes 15 (PEA15), also known as phosphoprotein enriched in diabetes (PED), causes insulin resistance and diabetes in transgenic mice and has been observed in type 2 diabetic individuals. The aim of this study was to investigate whether PEA15 overexpression occurs in individuals at high risk of diabetes and whether it is associated with specific type 2 diabetes subphenotypes. We analysed PEA15 expression in euglycaemic first-degree relatives (FDR) of type 2 diabetic subjects. The expression of PEA15 in peripheral blood leucocytes (PBLs) paralleled that in fat and skeletal muscle tissues. In PBLs from the FDR, PEA15 expression was two-fold higher than in euglycaemic individuals with no family history of diabetes (control subjects), both at the protein and the mRNA level (p < 0.001). The expression of PEA15 was comparable in FDR and type 2 diabetic subjects and in each group close to one-third of the subjects expressed PEA15 levels more than 2 SD higher than the mean of control subjects. Subjects with IFG with at least one type 2 diabetes-affected FDR also overexpressed PEA15 (p < 0.05). In all the groups analysed, PEA15 expression was independent of sex and unrelated to age, BMI, waist circumference, systolic and diastolic BP, and fasting cholesterol, triacylglycerol and glucose levels. However, in euglycaemic FDR of type 2 diabetic subjects, PEA15 expression was inversely correlated with insulin sensitivity (r = -557, p = 0.01). We conclude that PEA15 overexpression represents a common defect in FDR of patients with type 2 diabetes and is correlated with reduced insulin sensitivity in these individuals.

Quantitative analysis of cytokine mRNA expression in hearts from patients with nonischemic dilated cardiomyopathy (DCM).

There is increasing evidence that inflammatory cytokines play an important role in the development of heart failure. To evaluate the role of cytokines in nonischemic DCM, we analyzed the relative quantity of cytokine mRNA expression in the hearts from DCM patients with refractory heart failure, using the ABI PRISM7700 real-time PCR system. We used heart tissues resected from 32 DCM patients at the time of elective partial ventriculectomy (PLV), and five biopsy specimens with normal histological findings as control. Interleukin (IL)-1beta, IL-10, and Tumor Necrosis Factor (TNF)-alpha mRNA were expressed at low levels in all normal hearts. The number of IL-10-positive DCM cases was significantly smaller than normal controls (P = 0.0036). One (10%) of 10 DCM patients with IL-10 mRNA expression died after PLV, and 10 (45%) of 22 DCM patients without IL-10 mRNA expression died. IL-1beta mRNA was overexpressed (over twice the mean of control subjects) in 15 of 32, and TNF-alpha mRNA in 10 of 32 patients. We propose the classification of DCM patients into subgroups on the basis of cytokine mRNA expression. Anticytokine therapy or cytokine therapy may have potential in improving the condition of heart failure in certain subgroups of DCM patients. We suggest that DCM patients with heart failure deteriorate without IL-10 mRNA expression in the myocardium. The classification of DCM patients into subgroups on the basis of cytokine mRNA expression may have great value in considering the treatment of this heterogeneous disease state.

Steroid-Naive Adolescents with Mild Intermittent Allergic Asthma Have Airway Hyperresponsiveness and Elevated Exhaled Nitric Oxide Levels

Although atopic asthma symptoms often seem to disappear around puberty, subjects in this age group may experience unexpected, often severe, asthma attacks. This may be related to persistence of untreated airway hyperresponsiveness/inflammation in a life period characterized by low perceptiveness of disease-related symptoms. This study was designed to evaluate the prevalence and the severity of bronchial hyperreactivity and the exhaled nitric oxide (FENO) levels in a group of steroid-naive asthmatic adolescents. Fifty-two patients with mild-intermittent asthma were studied, ages 12 to 16, sensitized to house dust mites; 22 age-matched controls, were also studied. Asthma patients showed FEV1, FEF25–75%, and FVC values not significantly different from controls, (p>0.05, each comparison). By contrast, although none of the control subjects showed bronchial hyperreactivity, increased airway responsiveness to methacholine (MCh) was demonstrated in the majority of the patients and found to be severe in 36.5% (MCh PD20 ≥ 400 µg or accumulative dose ≤1220 µg) and moderate in 32.7% (MCh PD20 400–1400 µg or accumulative dose 1220–4620 µg). In addition, FENO concentrations were significantly higher in asthmatics, as compared with controls (20.4 ± 5.3 ppb and 4.4 ± 0.7 ppb, respectively; p<0.01) and 83% of the patients had FENO levels higher than 8.9 ppb (i.e., >2 standard deviations of the mean in control subjects). A positive, statistically significant correlation was found between FEF25–75% values and MCh PD20 (r = 0.358; p<0.01) or MCh accumulative dose (r = 0.355; p<0.05). No correlations were demonstrated between MCh responsiveness and FVC or FEV1 values or FENO levels and between FENO levels and pulmonary function parameters (p>0.05). The high incidence of bronchial hyperresponsiveness to MCh and of airway inflammation (as demonstrated by the elevated FENO levels) in adolescents with mild asthma suggests the need for more accurate evaluation and, possibly, for early intervention with antiinflammatory drugs in a significant proportion of patients in this age group.

Inspiratory Muscle Strength in Acute Asthma

Study objectivesThe aim of this study was to measure inspiratory pressure-generating capacity in patients presenting with acute asthma, as it has been suggested that inspiratory muscle fatigue may contribute to breathlessness and acute respiratory failure. DesignDescriptive study. SettingEmergency departments of two inner-city hospitals. PatientsFifty-one patients with acute asthma, and 45 patients without respiratory disease who served as control subjects. Measurements and resultsMaximum inspiratory pressure-generating capacity was measured soon after presentation by the sniff nasal inspiratory pressure (SNIP) method. The mean (SD) SNIP was 110 cm H2O (23 cm H2O) in men with asthma (mean for control subjects, 126 cm H2O [25 cm H2O]; p < 0.05) and 80 cm H2O [24 cm H2O] in women with asthma (mean for control subjects, 105 cm H2O (26 cm H2O); p < 0.01). In a second study of simultaneous SNIP and intrathoracic pressure measurements in a group of patients with acute asthma (n = 10) and control subjects (n = 11), the effect of airways obstruction on SNIP was assessed. The measurement of sniff esophageal pressure was more negative than SNIP by approximately 16% in asthmatic patients and by 4% in control subjects. Taking account of the likely effect of airways obstruction on SNIP, the reduction in inspiratory pressure-generating capacity that was observed in these patients with moderately severe acute asthma was minor and was consistent with the modest hyperinflation observed. ConclusionsThis study did not find evidence of inspiratory muscle weakness or fatigue in patients with moderately severe acute asthma presenting to the emergency department.

Whole blood ionized magnesium: age-related differences in normal values and clinical implications of ionized hypomagnesemia in patients undergoing surgery for congenital cardiac disease

Objectives: We sought to (1) determine reference values for whole blood ionized magnesium concentrations in newborns, children, and young adults and (2) evaluate the frequency and clinical implications of ionized hypomagnesemia in patients undergoing surgery for congenital heart disease. Method: We prospectively measured ionized magnesium concentrations in 299 subjects (113 control subjects and 186 patients undergoing surgery for congenital heart disease). Subjects were categorized by age. In the surgical group blood samples were obtained before bypass, during bypass (cooling and rewarming), after bypass, and during admission to the intensive care unit. Ionized hypomagnesemia was defined as ionized magnesium level 2 standard deviations below the mean of control subjects in the same age group. Patients were analyzed, controlling for cardiopulmonary bypass time. Results: In the control group ionized magnesium concentrations differed by age. Neonates and adults showed lower ionized magnesium concentrations compared with those of other age groups. Infants exhibited the highest ionized magnesium concentration. In the surgical group patients older than 1 month showed a higher proportion of ionized hypomagnesemia compared with that found in neonates at baseline ( P < .001), after bypass ( P = .03), and at admission to the intensive care unit ( P = .02). Controlling for cardiopulmonary bypass time, patients older than 1 month who were hypomagnesemic during bypass showed longer intubation time ( P = .001) and longer intensive care stay ( P = .01) and tended to have a higher pediatric severity of illness score on intensive care admission ( P = .14) compared with patients without ionized hypomagnesemia. Conclusions: There are age-related differences in normal ionized magnesium concentrations. Ionized hypomagnesemia is a common and clinically relevant occurrence among patients older than 1 month of age undergoing surgery for congenital heart disease. (J Thorac Cardiovasc Surg 2000;119:891-8)

Increase in gamma/delta T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease.

A jejunal biopsy specimen from an asymptomatic 35 year old man was studied because of a low serum titre of reticulin antibody and the finding of coeliac disease in his son. In this specimen villous structure was quite normal as was the total number of intraepithelial lymphocytes, but the number of gamma/delta T cell receptor bearing lymphocytes was 10 times higher than the mean in control subjects. Two years later a further biopsy specimen was obtained because of clinical symptoms and an increased titre of reticulin antibody. This specimen showed villous atrophy with crypt hyperplasia and increased infiltration of intraepithelial lymphocytes compatible with coeliac disease. A control biopsy specimen taken during gluten free diet showed normalisation of the villous architecture. Latent coeliac disease may be characterised by an increase in gamma/delta positive cells similar to that seen in established coeliac disease.

Serum Glutathione Reductase and Cystic Fibrosis

Extract: Serum glutathione reductase (NADPH:GSSG oxidoreductase, EC. 1.6.4.2 (GR)) has been examined in cystic fibrosis subjects (CF), obligate CF heterozygotes, and control subjects. Serum protein concentration was similar in the three groups. Regardless of the units used to express activity (milligrams of protein or milliliters of serum) or whether or not samples were dialyzed against water or phosphate buffer, mean serum GR in CF was greater than in control subjects (P ≤ 0.002) in all series over several years. Under the above assay conditions no difference in serum GR between control subjects and carriers was detected. Calculated and assayed values of combined control and CF sera agreed as did expected and observed 50% activity in 1:2 sera dilutions in CF, control subjects, and carriers. Addition of FAD to incubation media did not effect enzyme activity in the three groups. Differences between CF and control subjects persisted after dialysis in membranes permitting passage of molecules of approximately 12,000 mol wt or less. These findings would tend to exclude the effect of extraneous serum factors in explaining the differences between CF and control subjects. The percentage of initial GR activity after four days storage (0-4°) was significantly greater in CF than in control subjects (P < 0.025). The effect of heparin on serum GR was recorded as the percentage of activity after incubation with heparin vs. activity in the standard assay for individual subjects. The effect of incubation with 5 μg/ml heparin on serum GR activity was greater in control subjects than in carriers (P < 0.0005) and CF (P < 0.0005). Mean serum GR activity in CF and carriers was unaffected by heparin, whereas mean activity in control subjects was decreased. In no control was the percentage of initial activity with heparin greater than the mean of CF and carrier groups. Only 3 of 20 CF and 4 of 20 carrier individuals had percentages lower than the control mean. The CF and carrier distributions were clearly different from the control distribution. Serum GR was determined in seven non-CF individuals with chronic obstructive pulmonary disease (COPD). Activity in the COPD was different from CF and no different from control subjects. In none of these controls or COPD was serum GR as great as the CF mean. Serum GR in no CF was as low as the mean of control subjects or COPD. It is concluded that serum GR activity is greater in CF than in control subjects, carriers, and non-CF COPD subjects; that the difference in activity is not attributable to an extraneous serum factor, that the activity difference is not secondary to chronic respiratory disease; that in comparison with control subjects, GR from CF serum behaves differently after storage; and that serum GR from CF and carriers behaves differently from control GR in the presence of heparin.Speculation: Abnormal activity of glutathione reductase may be fundamentally related to the pathogenesis of cystic fibrosis.

Determination of 3-Methoxy-4-Hydroxyphenylethylene Glycol, a Noradrenaline Metabolite, in Cerebrospinal Fluid and Urine

Abstract We describe a sensitive, accurate method for quantitative determination of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) in cerebrospinal fluid and urine. The method entails enzymatic hydrolysis of conjugated MHPG, acetylation of the phenolic group, thin-layer chromatographic purification, and estimation of total MHPG as the acetyl heptafluorobutyryl derivative by gas—liquid chromatography with electron capture detection and with use of aldrin as internal standard. Results obtained by this method compare favorably with those by other published procedures. Precision, calculated as the mean ± SD of the percentage differences between duplicate estimations, was 8.4 ± 8.0% for cerebrospinal fluid (3 ml) or 6.9 ± 6.6% for urine (2 ml). Total MHPG in lumbar cerebrospinal fluid specimens from 49 individuals ranged from 6.1 to 19.7 ng/ml, with no significant difference between the mean for control subjects and that for patients with affective disorders.