Biomedical subjects

D N Iklé

Publications and source records attributed to D N Iklé.

13 recordsLinked to original sources

PubMed2003

Almonds vs complex carbohydrates in a weight reduction program.

OBJECTIVE: To evaluate the effect of an almond-enriched (high monounsaturated fat, MUFA) or complex carbohydrate-enriched (high carbohydrate) formula-based low-calorie diet (LCD) on anthropometric, body composition and metabolic parameters in a weight reduction program. DESIGN: A randomized, prospective 24-week trial in a free-living population evaluating two distinct macronutrient interventions on obesity and metabolic syndrome-related parameters during weight reduction. SUBJECTS: In total, 65 overweight and obese adults (age: 27-79 y, body mass index (BMI): 27-55 kg/m(2)). INTERVENTION: A formula-based LCD enriched with 84 g/day of almonds (almond-LCD; 39% total fat, 25% MUFA and 32% carbohydrate as percent of dietary energy) or self-selected complex carbohydrates (CHO-LCD; 18% total fat, 5% MUFA and 53% carbohydrate as percent of dietary energy) featuring equivalent calories and protein. MAIN OUTCOME MEASUREMENTS: Various anthropometric, body composition and metabolic parameters at baseline, during and after 24 weeks of dietary intervention. RESULTS: LCD supplementation with almonds, in contrast to complex carbohydrates, was associated with greater reductions in weight/BMI (-18 vs -11%), waist circumference (WC) (-14 vs -9%), fat mass (FM) (-30 vs -20%), total body water (-8 vs -1%) and systolic blood pressure (-11 vs 0%), P=0.0001-0.05. A 62% greater reduction in weight/BMI, 50% greater reduction in WC and 56% greater reduction in FM were observed in the almond-LCD as compared to the CHO-LCD intervention. Ketone levels increased only in the almond-LCD group (+260 vs 0%, P<0.02). High-density lipoprotein cholesterol (HDL-C) increased in the CHO-LCD group and decreased in the almond-LCD group (+15 vs -6%, P=0.05). Glucose, insulin, diastolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and LDL-C to HDL-C ratio decreased significantly to a similar extent in both dietary interventions. Homeostasis model analysis of insulin resistance (HOMA-IR) decreased in both study groups over time (almond-LCD: -66% and CHO-LCD: -35%, P<0.0001). Among subjects with type 2 diabetes, diabetes medication reductions were sustained or further reduced in a greater proportion of almond-LCD as compared to CHO-LCD subjects (96 vs 50%, respectively) [correction]. CONCLUSION: Our findings suggest that an almond-enriched LCD improves a preponderance of the abnormalities associated with the metabolic syndrome. Both dietary interventions were effective in decreasing body weight beyond the weight loss observed during long-term pharmacological interventions; however, the almond-LCD group experienced a sustained and greater weight reduction for the duration of the 24-week intervention. Almond supplementation of a formula-based LCD is a novel alternative to self-selected complex carbohydrates and has a potential role in reducing the public health implications of obesity.

Adult↗

PubMed1999

FMRP expression as a potential prognostic indicator in fragile X syndrome.

Absence or deficit of FMR1 protein (FMRP) resulting from methylation of full mutation genes is the fundamental defect in fragile X syndrome. We used FMRP immunocytochemistry and detailed phenotypic assessment to investigate the relationship between degree of FMRP expression and the broad clinical spectrum of impairment in 80 individuals affected with fragile X syndrome. FMRP expression correlated with IQ in mosaic males (P=0.043), males with a partially methylated full mutation (P=0.0005), and females with a full mutation (P=0.046). In the females, FMRP expression also correlated with the number of fragile X physical features (P=0.0003). Even modest deficits in FMRP result in some manifestations of fragile X syndrome. In this initial study of 53 males, FMRP expression testing had a very high positive predictive value (100%, confidence interval of 29-100%) for a nonretarded IQ among males with expression of FMRP in > or = 50% of lymphocytes (3 males), suggesting that FMRP expression may have potential as a prognostic indicator in males with fragile X syndrome.

Adolescent↗

PubMed1999

Survivors of neonatal extracorporeal membrane oxygenation at school age: unusual findings on intelligence testing.

Data are presented on 17 children who received extracorporeal membrane oxygenation (ECMO) in the neonatal period for persistent pulmonary hypertension (PPHN). These children are being followed as part of a larger program of follow-up research on children who have been treated for PPHN with several treatment methods. On intelligence testing at ages 5 to 8 years, these 17 children had unusual patterns of results. A higher-than-predicted percentage of the ECMO survivors had discrepancies between their Verbal and Performance IQ and a much-higher-than-predicted percentage had areas of unusual strength or weakness on their IQ subtest scores. Also, there was a significant correlation between the amount of time a child received ECMO and the child's Performance IQ: the longer the child received ECMO, the higher the Performance IQ. While findings of unusual weaknesses or deficits on intelligence testing at school age in children who have been severely ill in the neonatal period are not unusual, findings of high scores and areas of strength are not easily explained, particularly when these findings seem to relate to an invasive treatment like ECMO. Similar findings have been reported in two other small studies, which suggest that the impact of ECMO on the developing infant brain may not be purely detrimental.

Child↗

PubMed1999

Can chest CT be used to exclude aortic injury?

PURPOSE: To determine whether chest computed tomography (CT) can be used to exclude aortic injury. MATERIALS AND METHODS: Patients in whom there was very high suspicion of traumatic aortic injury were examined with aortography only. Other patients were examined with contrast material-enhanced CT. Follow-up aortography was performed in all patients with moderate to high suspicion of traumatic aortic injury and in all patients with CT scans that were positive for traumatic aortic injury. CT scans were regarded as positive when they showed mediastinal hematoma or direct findings of aortic injury. During a 4 1/2-year period, 1,009 patients (263 female, 746 male; age range, 3-90 years) were evaluated for possible traumatic aortic injury. RESULTS: Of the 207 patients who underwent aortography directly without CT, 10 had traumatic aortic injury. Of the 802 patients who were examined with CT, 382 underwent follow-up aortography. In this group, there were 10 true-positive and no false-negative CT scans. CT had 100% sensitivity and a 100% negative predictive value for the detection of traumatic aortic injury.

Adolescent↗

PubMed1999

Effect of oxygen on lung superoxide dismutase activities in premature baboons with bronchopulmonary dysplasia.

We investigated the effects of gestational age and oxygen exposure on superoxide dismutase (SOD) activities in distal fetal lung tissue in primate models of bronchopulmonary dysplasia. During the final third of fetal life, lung coppper-zinc SOD (Cu,ZnSOD) specific activity decreased, whereas lung manganese SOD (MnSOD) specific activity tended to increase. In the premature newborn (140 days, 78% of term gestation), lung total SOD and Cu,ZnSOD specific activities decreased after 6-10 days of ventilation with as needed [pro re nada (PRN)] or 100% oxygen compared with fetal control animals. Neither Cu,ZnSOD mRNA nor protein expression changed after either oxygen exposure at this gestation (140 days) relative to fetal control animals. At this age (6-10 days), lung MnSOD specific activity did not change in oxygen-exposed relative to fetal control animals, even though lung expression of MnSOD mRNA and protein increased after PRN or 100% oxygen exposure. In the very premature 125-day newborn (69% of term), lung Cu,ZnSOD specific activity and protein decreased, whereas Cu,ZnSOD mRNA increased, after 6-10 days of ventilation with PRN oxygen compared with fetal control animals. In fetal lung explants, hyperoxia also decreased expression of SOD activity acutely (16-h exposure, 125 and 140 days gestation). To conclude, expression of SOD activity in the premature primate lung did not increase in response to elevated oxygen tension, apparently due to effects occurring subsequent to the expression of these mRNAs.

Animals↗

PubMed1999

Pro-inflammatory and T cell inhibitory cytokines are secreted at high levels in tumor cell cultures of human renal cell carcinoma.

OBJECTIVES: The objectives of this study were to assess cytokine secretion in human renal cell carcinoma (RCC) and to identify cytokines contributing to the immunomodulatory effect of tumor cells. METHODS: Cytokine secretion in the supernatant of primary tumor cell cultures (PTCC) and corresponding cell lines (CL) was assayed using ELISA. Tumor cells were characterized by morphology, immunocytochemistry, and flow-cytometric analysis. Tumor-cell-induced T cell activation was determined by coculture of gamma delta and alpha beta T cell clones with tumor CL. RESULTS: We assessed the cytokine secretion of tumor cells from 27 PTCC and their corresponding CL (3/27) of RCC. We found that RCC predominantly produced both pro-inflammatory and T-cell-inhibitory cytokines, such as IL-8, IL-6, GM-CSF, TNF-alpha, IL-10 and TGF-beta 1. CL were adapted to serum-free medium which may prove as a useful tool in future studies of cytokine secretion in RCC. In addition, we used gamma delta and alpha beta T cell clones to assess the immunomodulatory effect of tumor cells from RCC and found that predominantly gamma delta T cells were activated by RCC. CONCLUSIONS: Our data suggest that RCC produce large amounts of both pro-inflammatory and T-cell-inhibitory cytokines that potentially could influence the immune response of the host, especially tumor-specific cytotoxic T cells.

Biomarkers, Tumor↗

PubMed1998

Neuropsychological and behavioral changes in asthmatic children treated with beclomethasone dipropionate versus theophylline.

OBJECTIVE: Results from previous investigations that examined the psychological side effects of theophylline have been inconsistent, and none have reported about inhaled corticosteroids. The objective of this study was to assess the relative psychological side effects of theophylline and beclomethasone in asthmatic children. METHODS: This was a multicenter, randomized, double-blind, parallel-groups study in which 102 asthmatic patients were assigned to one of two treatments: beclomethasone three times daily or theophylline twice daily. At baseline, 1 month, and 1 year, parents completed standardized behavioral questionnaires while the children received psychometric testing of attention and concentration, memory and learning, and problem-solving. RESULTS: Although power was sufficient to detect meaningful mean score changes, no consistent differential treatment effects were observed. Two significant treatment-by-period interactions were discordant, with one suggesting slightly better attention in the theophylline group, whereas the other indicated a small advantage in attention scores in the beclomethasone group. Numerous significant period effects revealed that behavior and cognitive test performance improved over the 1-year period, regardless of treatment, and confirmed a well established practice effect resulting from repeated administrations of such tests. CONCLUSIONS: Neither theophylline nor beclomethasone should be avoided out of concern for significant psychological side effects. The possibility remains that a subset of asthmatic children may be susceptible to such medication-induced changes; investigators have suggested that preschool children may be at particular risk, although no controlled studies with this age group have been conducted. Parental perceptions of medication side effects can be influenced by temporary effects present at initiation of treatment or by erroneous attribution of the psychological effects of the chronic illness. Reports of psychological changes in response to asthma medications must be addressed respectfully but objectively, with due consideration of available evidence and an awareness of other potential explanations.

Administration, Inhalation↗

PubMed1997

Retention of asthmatic patients in a longitudinal clinical trial.

BACKGROUND: Prevention of study patient attrition and assessment of its impact on outcome data are problems that receive little attention despite their obvious importance in asthma research. OBJECTIVE: The medical, demographic, and psychologic characteristics of asthmatic children and adults who dropped out of a yearlong medication trial were assessed to determine whether this group differed from those who completed the study, potentially introducing bias into the data set and interfering with completion of the study's objectives. METHODS: Profiles of 362 adult and pediatric asthmatic patient dropouts from the multicenter trial were contrasted with profiles of those who completed the study. Despite a 1-month prerandomization screening, 24% of patients failed to complete the trial for varied reasons, which largely included noncompliance and treatment dissatisfaction. RESULTS: Although attrition rates were equal among adults and children, dropout-completer differentiation was not. Adult completers did not differ from dropouts in any variables. However, pediatric dropouts were more likely than completers to be female (67% and 36%, p = 0.008) and to have more reactive airways (PD20, 2.29 +/- 1.32 and 5.2 +/- 1.23, p = 0.05), to have reduced scores on tests of intelligence (Full Scale IQ, 102.2 +/- 2.6 and 112.5 +/- 1.6, p = 0.002) and problem solving (Wisconsin Card Sorting Test Error Scores, 39.8 +/- 4.1 and 29.1 +/- 2.0, p = 0.01), and to have increased behavioral problems (Child Behavior Checklist Total Problem Score, 60.7 +/- 2.5 and 53.6 +/- 1.1, p = 0.003). CONCLUSION: These findings demonstrate the potential of patient attrition to bias outcome in clinical trials and underscore the necessity of: (1) preventing its occurrence, (2) correctly assessing its causes, and (3) determining its ultimate impact on study results. Strategies for each of these three tasks should be implemented at the study's initial planning stages.

Adolescent↗

PubMed1995

Natural killer cell ontogeny in the athymic rat. Relationship between functional maturation and acquired resistance to E1A oncogene-expressing sarcoma cells.

Newborn nude rats are NK cell deficient and highly susceptible to tumor induction by NK-susceptible, E1A oncogene-expressing, BHK-21 sarcoma cells, whereas adults have normal NK activity and are tumor resistant. This model of NK cell-related tumor rejection was used to characterize age-related functional maturation of NK cells during nude rat ontogeny. Small numbers of cytolytic incompetent, NKR-P1+ cells were detected in the spleens of newborns. During the first month of life, there was an age-related increase in the numbers of splenic NK cells, followed by a stepwise maturation in their cytolytic competence. Three functional stages in NK cell cytolytic activity were apparent. A nonlytic newborn stage was followed by a transitional stage, during which absent or relatively weak spontaneous cytolytic activity was augmented by prolonged NK cell exposure to susceptible target cells. In the final stage, both spontaneous and augmented cytolytic activity increased toward the adult level that was attained by 4 wk of age. The data suggest the existence of a transient stage in NK cell ontogeny when triggering through the NKR-P1 molecule is functionally immature, and confirm the importance of a cytolytic competent, NK cell response for nude rat rejection of E1A oncogene-expressing tumor cells.

Adenovirus E1A Proteins↗

PubMed1993

Efficacy and safety of low-dose troleandomycin therapy in children with severe, steroid-requiring asthma.

BACKGROUND: Troleandomycin (TAO), a macrolide antibiotic, was studied as an alternative treatment in 18 children with severe, steroid-requiring asthma. METHODS: In this investigation three treatment arms were used in randomized, double-blind, parallel fashion: combination TAO and methylprednisolone (MPn), combination TAO and prednisone, and MPn alone. RESULTS: All groups tolerated a considerable reduction in glucocorticoid dose over the 12 weeks of the study: 80% +/- 6% for TAO-MPn, 55% +/- 8% for TAO-prednisone, and 44% +/- 14% for MPn alone. These reductions are all statistically significant (p < 0.05) within groups, and the differences between groups were statistically significant between the TAO-MPn and MPn alone groups. The concentration of methacholine required to induce a 20% decrease in forced expiratory volume in 1 second and pulmonary function were not significantly improved in any treatment group. Safety parameters including blood chemistry and hematology, adrenal function assessment; bone densitometry, and muscle strength testing, were not altered significantly. Two patients who received TAO had elevated liver enzyme levels; one required discontinuation of TAO and one experienced spontaneous resolution without intervention. Lack of statistically significant changes in the efficacy parameters were likely a result of small sample size and effects of the glucocorticoid dose taper. CONCLUSIONS: TAO is safe and may be a reasonable treatment alternative in a limited trial for patients who are unable to tolerate tapering of their glucocorticoid dosage. Therapy should be guided by the goal of treatment, that is, glucocorticoid dose reduction or improvement of pulmonary function with appropriate monitoring of pulmonary function and adverse effects.

Adolescent↗

PubMed1992

Studies on the role of tumor necrosis factor in adult respiratory distress syndrome.

Tumor necrosis factor (TNF), rapidly becoming recognized as a mediator of inflammation, may be important in the pathogenesis of acute lung injury. Its role in the development of the adult respiratory distress syndrome (ARDS) in humans, however, has been difficult to clarify. To determine if TNF could be important early in the development of acute lung injury from multiple causes, we enrolled 103 patients within 8 h of meeting the criteria for an at-risk illness (sepsis, aspiration of gastric contents, severe pancreatitis, hypertransfusion, abdominal trauma, chest trauma, multiple fractures) and obtained multiple frequent blood samples for TNF measurements. Using five methods of TNF analysis, we were unable to find an association between TNF and the development of ARDS. However, we found significant differences in TNF measurements depending on the methods of analysis used, which could, at least in part, account for the inconsistencies in the published literature regarding the relationship between TNF and disease processes.

Adult↗

PubMed1992

Hypogammaglobulinemia in asthmatic patients.

We measured quantitative immunoglobulins (IgG, IgA, IgM, and IgG subclasses) in 101 unselected asthmatic patients. We identified hypogammaglobulinemia in 12 patients primarily involving IgG (dose-related) without a strong prediction for any IgG subclass. IgA and IgM were also suppressed but to a lesser extent. This prevalence of hypogammaglobulinemia (.12 +/- standard error of .03) is significantly greater than that seen in the normal population (approximately .025 +/- .017, P = .01). Hypogammaglobulinemia was strongly associated with use of systemic corticosteroids (P = .0001). A cumulative steroid dose of greater than or equal to 5 mg/day for at least 2 years was found in 10/12 patients with hypogammaglobulinemia compared with 37/89 patients without hypogammaglobulinemia (P = .024). No significant increase in the number of infectious episodes was seen in the hypogammaglobulinemic patients. To assess the significance of hypogammaglobulinemia in asthmatics, we assessed responses to tetanus and pneumococcal vaccine in three groups of asthmatics: (1) those with total IgG less than 400 mg/dL who had been on chronic oral steroids, (2) those with total IgG between 855 and 1199 mg/dL who were currently receiving oral steroids, and (3) those with total IgG between 855 and 1199 mg/dL who were not receiving oral steroids. All patients responded normally to tetanus vaccine, but three of eight patients in the hypogammaglobulinemic group showed impaired responses to pneumococcal vaccine. Patients with impaired pneumococcal responses were not clearly distinguishable on the basis of sinus disease or pneumonia. We conclude that although many patients with severe, steroid-dependent asthma experience repeated episodes of bronchitis or exacerbations of sinusitis, these problems are rarely associated with an impairment in specific antibody production. IgG subclass deficiencies are not common in this patient population. A very small subgroup of patients manifest a more severe hypogammaglobulinemia (IgG less than 400 mg/dL) or an inordinate frequency of infectious episodes. Given that bronchitis or sinusitis can be attributed to factors other than hypogammaglobulinemia in these patients, an assessment of specific antibody production in response to pneumococcal vaccination is warranted. A small but significant percentage of such patients will demonstrate impaired responses. These patients should be considered at increased risk for bacterial infections and should, therefore, be monitored closely for infectious episodes.

Adolescent↗

PubMedDate not supplied

Comparison of cytogenetics, cytokine secretion, and oncogene expression in primary cultures of renal carcinoma cells.

We compared the cytogenetic pattern of 20 different primary tumor cell cultures (PTCC) of renal cell carcinoma (RCC) to their cytokine secretion and oncogene expression. High secretion of IL-6 (gene locus on chromosome 7p21-p14) was correlated with the gain of an additional chromosome 7. Structural changes involving chromosome 5q22, the site of the GM-CSF gene, were matched with the high secretion of GM-CSF in PTCC. No such association was found for beta 2-microglobulin, TGF-beta 1, TNF-alpha, IL-8, and oncogenes, such as c-fos, c-myc, and pan-ras. Our approach may be useful in simultaneously analyzing several factors contributing to tumor progression and may contribute to understanding the multistep development of RCC.

Adult↗