Biomedical subjects

D Ikle

Publications and source records attributed to D Ikle.

11 recordsLinked to original sources

PubMed2001

Circadian rhythm of core body temperature in subjects with chronic fatigue syndrome.

The pathophysiological basis for chronic fatigue syndrome (CFS) remains poorly understood. Certain symptoms of CFS, namely fatigue, neurocognitive symptoms and sleep disturbance, are similar to those of acute jet lag and shift work syndromes thus raising the possibility that CFS might be a condition associated with disturbances in endogenous circadian rhythms. In this study, we tested this hypothesis by examining the circadian rhythm of core body temperature (CBT) in CFS and control subjects. Continuous recordings of CBT were obtained every 5 min over 48 h in a group of 10 subjects who met the Center for Disease Control (CDC) definition of CFS and 10 normal control subjects. Subjects in the two groups were age, sex and weight-matched and were known to have normal basal metabolic rates and thyroid function. CBT recordings were performed under ambulatory conditions in a clinical research centre with the use of an ingestible radio frequency transmitter pill and a belt-worn receiver-logger. CBT time series were analysed by a cosinor analysis and by a harmonic-regression-plus-correlated-noise model to estimate the mean, amplitude and phase angle of the rhythm. The goodness of fit of each model was also compared using the Akaike Information Criterion (AIC) and sigma2. Average parameters for each group were compared by Student's t-test. By cosinor analysis, the only significant difference between CFS and control groups was in the phase angle of the third harmonic (P=0.02). The optimal harmonic-regression-plus-correlated-noise models selected were ARMA(1,1): control 7, CFS 6; ARMA(2,0): control 1, CFS 4; and ARMA(2,1): control 2 subjects. The optimal fit ARMA model contained two harmonics in eight of 10 control subjects but was more variable in the CFS subjects (1 harmonic: 5 subjects; 2 harmonics: 1 subject; 3 harmonics: 4 subjects). The goodness of fit measures for the optimal ARMA model were also better in the control than the CFS group, but the differences were not statistically significant. We conclude that, measured under ambulatory conditions, the circadian rhythm of CBT in CFS is nearly indistinguishable from that of normal control subjects although there was a tendency for greater variability in the rhythm. Hence, it is unlikely that the symptoms of CFS are because of disturbance in the circadian rhythm of CBT.

Adult↗

PubMed2000

Keratin immunohistochemistry detects clinically significant metastases in bone marrow biopsy specimens in women with lobular breast carcinoma.

Some patients with breast cancer currently undergo bone marrow biopsy to make clinical decisions regarding therapy; however, lobular carcinoma can be difficult to detect in routine histologic sections. The authors reviewed retrospectively all available bone marrow biopsies from patients with lobular carcinoma diagnosed between January, 1, 1989, and September, 25, 1997, at the City of Hope National Medical Center to identify useful morphologic features and to determine the utility of pan-keratin immunohistochemical (IHC) staining. A total of 65 biopsies from 54 patients were reviewed. Thirteen of the 65 biopsies were classified initially as containing metastatic tumor based on histologic features alone. With the addition of keratin IHC, seven additional cases of metastatic disease were detected. Forty of the 54 patients received stem cell replacement or autologous bone marrow transplantation. Disease-free survival after high-dose chemotherapy with stem cell replacement or autologous bone marrow transplantation was stratified into three groups based on hematoxylin and eosin (H&E) staining and IHC results. Two-year disease-free survival was 33% for the H&E-/IHC+ group versus 90% for the H&E-/IHC- group (p = 0.005) among patients clinically free of disease at the time of stem cell replacement or autologous bone marrow transplantation. Two-year disease-free survival was 0% in the H&E+/IHC+ group (p = 0.04, compared with the H&E-/ IHC+ group). The authors conclude that routine morphologic examination without the aid of keratin IHC is unreliable in detecting clinically relevant metastatic lobular carcinoma in bone marrow biopsies. These findings suggest that pan-keratin immunostaining may be indicated on bone marrow biopsy specimens from lobular carcinoma patients if the biopsy appears histologically negative for metastatic tumor on H&E sections.

Adult↗

PubMed1999

Predicting regional mutability in antibody V genes based solely on di- and trinucleotide sequence composition.

Somatic mutations are not distributed randomly throughout Ab V region genes. A sequence-specific target bias is revealed by a defined hierarchy of mutability among di- and trinucleotide sequences located within Ig intronic DNA. Here we report that the di- and trinucleotide mutability preference pattern is shared by mouse intronic JH and Jkappa clusters and by human VH genes, suggesting that a common mutation mechanism exists for all Ig V genes of both species. Using di- and trinucleotide target preferences, we performed a comprehensive analysis of human and murine germline V genes to predict regional mutabilities. Heavy chain genes of both species exhibit indistinguishable patterns in which complementarity-determining region 1 (CDR1), CDR2, and framework region 3 (FR3) are predicted to be more mutable than FR1 and FR2. This prediction is borne out by empirical mutation data from nonproductively rearranged human VH genes. Analysis of light chain genes in both species also revealed a common, but unexpected, pattern in which FR2 is predicted to be highly mutable. While our analyses of nonfunctional Ig genes accurately predicts regional mutation preferences in VH genes, observed relative mutability differences between regions are more extreme than expected. This cannot be readily accounted for by nascent mRNA secondary structure or by a supplemental gene conversion mechanism that might favor nucleotide replacements in CDR. Collectively, our data support the concept of a common mutation mechanism for heavy and light chain genes of mice and humans with regional bias that is qualitatively, but not quantitatively, accounted for by short nucleotide sequence composition.

Animals↗

PubMed1999

Prediction of early-onset asthma in genetically at-risk children.

The W.T. Grant Foundation Asthma Risk Study was designed to prospectively examine children who were considered at a genetically increased risk for the development of asthma. The respective contributions of 11 potential risk factors, both environmental and biological, were assessed in order to determine their relative roles in affecting the early onset of asthma. This is a report of an inception cohort of children born to asthmatic mothers and followed for a 3-year period. All 150 families were recruited from the general community and living within 2 h of the National Jewish Center for Immunology and Respiratory Medicine (Denver, CO). Mothers in the index risk sample had been previously diagnosed with asthma and were recruited during their pregnancy through physician referrals and media solicitation. The index sample of 150 families was 92% Caucasian and predominantly middle class. The mean age of mothers was 29.3 years, and of fathers, 31.1 years. The main outcome was the determination of the early onset of asthma and its association with quantified risk factors. By age 3 years, 14 of the 150 children had developed asthma. Frequent illness, IgE levels at age 6 months, parenting difficulties, and early eczema were significantly associated with the onset of asthma (P = 0.003, P = 0.006, P = 0.01, and P = 0.03, respectively). Only frequent illness, elevated serum IgE levels, and parenting difficulties entered a predictive model where they were independently related to the development of asthma.

Age of Onset↗

PubMed1999

Fatal and near-fatal asthma questionnaire: prelude to a national registry.

BACKGROUND: Asthma mortality rates continue to be unacceptably high in the United States. As a follow-up to the initiatives proposed by the Asthma Mortality Task Force in 1987, the Committee on Asthma Mortality of the American Academy of Allergy, Asthma, and Immunology developed a questionnaire on fatal and near-fatal asthma. OBJECTIVE: This study assessed completeness of answers from participating physicians and described characteristics of patients with fatal and near-fatal asthma. METHODS: There were 111 survey items intended to characterize patients with fatal or near-fatal exacerbations of asthma. The questionnaire was sent to the members of the American Academy of Allergy, Asthma, and Immunology (approximately 3900), and a total of 143 usable questionnaires were received. RESULTS: Responding physicians had information on most items in the questionnaire; the mean number of responses was 120 of 143 possible, with a median of 128 and a range of 40 to 143. Patient demographics, description of the event, identification of overall risk for the event, use of medications, and characteristics of asthma management had the most complete responses (median response rates were 126-143). Presence of factors contributing to the event had fewer responses (range, 44-125). The physicians frequently had information on some psychologic characteristics (eg, 108 responses for depression and/or hopelessness and 127 responses for social support) but less information on several others (eg, 62 responses for family dysfunction). Statistical analysis of the completed surveys indicated that only 2 characteristics distinguished fatal from near-fatal asthma: progression in minutes (adjusted odds ratio, 4. 89; 95% confidence interval, 2.05-12.90) and absence of a past history of intubation (adjusted odds ratio, 3.55; 95% confidence interval, 1.55-8.97). CONCLUSIONS: There is a need to gather further data on patients with fatal and near-fatal events to design appropriate prospective studies on asthma morbidity and mortality rates. Physicians can contribute important information about these patients. Gathering such data would be enhanced by establishing a national registry on fatal and near-fatal asthma.

Anti-Allergic Agents↗

PubMed1998

Early preferential stimulation of gamma delta T cells by TNF-alpha.

Although recent findings indicate that gamma delta T cells influence both early innate and Ag-specific adaptive host responses, it has remained unclear what triggers gamma delta T cell reactivity. Investigating very early T cell activation in mouse and human models of bacterial infection, we measured CD69 expression as an indicator of early cellular activation. Both murine alpha beta and gamma delta T cells responded polyclonally to systemic bacterial infections, and to LPS. However, gamma delta T cells responded more strongly to the bacteria and to LPS. In vitro LPS-stimulated human T cells showed a similar differential response pattern. We identified TNF-alpha as mediator of the early differential T cell activation, and of differential proliferative responses. The stronger response of gamma delta T cells to TNF-alpha was correlated with higher inducible expression levels of TNF-Rp75. Among unstimulated splenocytes, more gamma delta T cells than alpha beta T cells expressed CD44 at high levels. The data suggest that TNF-Rp75 determines the differential T cell reactivity, and that most gamma delta T cells in the normal spleen are present in a presensitized state. As TNF-alpha stimulates activated T cells, it may early preferentially connect gamma delta T cell functions with those of cells that produce this cytokine, including activated innate effector cells and Ag-stimulated T lymphocytes.

Animals↗

PubMed1994

A comparison of commercial jet nebulizers.

Seventeen commercially available jet nebulizers from 15 commercial sources were studied (Acorn-I, Acorn-II, AquaTower, AVA-NEB, Cirrhus, Dart, DeVilbiss 646, Downdraft, Fan Jet, MB-5, Misty Neb, PARI LC JET, PARI-JET, Salter 8900, Sidestream, Updraft-II, Whisper Jet). All nebulizers were filled with 2 ml of saline solution plus 0.5 ml of albuterol and powered with the same source (DeVilbiss PulmoAide). We compared total output (TO), time for total output (TTO), and percent output in respirable range (PORR). The TO was obtained by weighing before nebulization and at the point of eight-fold decline in output. The TTO was calculated from initiation of nebulization to the point of eightfold decline in output. The PORR was measured by a laser particle analyzer in continuous nebulization to the same point of abrupt drop in output. The TO varied from 0.98 To 1.86 ml (p < 0.0001) with the Acorn-I, Acorn-II, Updraft-II, and Sidestream, significantly greater than the others (p < 0.05). The TTO varied from 2.28 to 20.95 min (p < 0.0001). The AquaTower, PARI LC JET and PARI-JET, DeVilbiss, and Dart were significantly shorter than the others (p < 0.05). The PORR varied from 21.89 to 71.95 percent (p < 0.0001). The Sidestream was significantly greater than all others (p < 0.05). The PARI LC JET and PARI-JET were, in turn, significantly greater than the remaining models (p < 0.05). To combine these characteristics, we calculated respirable particle delivery rate (RPDR) by dividing TO by TTO and multiplying by PORR. The RPDR varied from 0.03 ml/min to 0.26 ml/min (p < 0.0001). The PARI LC JET (0.24 ml/min) and the PARI-JET (0.26 mg/min) had a RPDR that was significantly greater than the other models except the AquaTower, which, however, had a markedly variable performance. The Sidestream (0.19 mg/ml) did not differ significantly from the above group, nor from the DeVilbiss and Downdraft. All other models had significantly lower outputs (p < 0.05). We conclude that the output characteristics of commercial nebulizers vary greatly and will impact on the time required for treatment as well as the total amount of drug delivered to the lungs.

Aerosols↗

PubMed1991

Psychological change associated with theophylline treatment of asthmatic children: a 6-month study.

Theophylline has been associated with a variety of behavioral side effects in asthmatic children. This study was a 6-month investigation of the relationship between theophylline treatment and psychological changes in 8 to 16 year old asthmatic children. Included were a group receiving theophylline (n = 19), a control group not receiving theophylline (n = 44), and a nonasthmatic control group (n = 24). The three groups had similar age, socioeconomic status, and IQ. The two groups of children with asthma demonstrated greater emotional dysfunction, characterized by tendency toward withdrawal and depression, than the nonasthmatic control group. Each of five assessment appointments (baseline and 1 week, 1 month, 3 months, and 6 months after beginning theophylline treatment) included measures of pulmonary function, attention, impulsivity, memory, fine motor control, activity level, self-reported mood, and parental observation of difficult behavior. Pulmonary functions were lower in the theophylline group at baseline but improved significantly after commencement of theophylline therapy. Over the 6-month interval, children in the theophylline group demonstrated improved scores on a laboratory measure of attention, while their parents reported increased conduct problems and hyperactivity. On the whole, psychological score changes were subtle, and no other between-group differences emerged in the remaining laboratory measures.

Affective Symptoms↗

PubMed1990

Diagnosis of adolescent hypertension on initial screening by the use of height age.

The tremendous variability in growth and maturation during adolescence makes body mass a better determinant of blood pressure (BP) than chronologic age (CA). To evaluate whether two accepted indicators of body mass, height age (HA), and weight age (WA) could accurately predict hypertension on initial screening, 1426 healthy adolescents had their BP, height, and weight measured and Tanner stage assessed. The mean of three BP measurements were compared to eight published nomograms which correlate BP with height, weight, or CA. Patients with an initial elevated BP (greater than 95 percentile for height, weight or CA) were reevaluated to verify persistent hypertension. Eighty-seven (6.1%) initially appeared to be hypertensive with 0.84% persistently hypertensive. The diagnosis of hypertension varied considerably when the BP measurements were reevaluated based on HA or WA. Height age was the most sensitive (100%) and specific (62.6%) criteria for the diagnosis of hypertension and can be used for initial BP screening in this age group.

Adolescent↗

PubMed1977

A simple ultrasonic method for evaluating liver size.

By measuring the liver area (maximum section) and plotting this against intra-abdominal area at the same level, one can calculate tolerance levels for 80% of the population (63 normal patients) with a 95% confidence. This provides a simple semiquantitative index in relating liver size of a specific patient to the normal range. Its use in 14 patients with liver disease was demonstrated.

Humans↗

PubMedDate not supplied

Combined effects of tamoxifen and a chimeric humanized single chain antibody against the type I IGF receptor on breast tumor growth in vivo.

Proliferative and anti-apoptotic actions of IGFs are mediated by the IGF-I receptor (IGF-IR), to which both IGF-I and -II bind with high affinity. We previously reported that alphaIGF-IR scFv-Fc (scFv-Fc) consisting of the alphaIGF-IR scFv and human IgG (1) Fc domain retained general characteristics of the parental 1H7 monoclonal antibody, and significantly suppressed MCF-7 tumor growth. We proposed IGF-IR down-regulation as a possible mechanism for inhibition of MCF-7 tumor growth. To further determine the therapeutic potentials of this approach, in vivo effects of this antibody on breast tumor growth were evaluated in the absence or presence of tamoxifen (Tam) using a T61 human breast tumor model. T61 xenograft growth in athymic mice was compared under five conditions, PBS, scFv-Fc, Tam, scFv-Fc+Tam, and control antibody. While treatment with PBS and control antibody did not affect T61 tumor growth, scFv-Fc, Tam, and scFv-Fc+Tam treatments significantly suppressed the tumor growth during the first two weeks of treatment. Although the growth inhibitory effect of scFv-Fc during the first two weeks was significant, the tumor grew as rapidly as PBS-treated tumors thereafter. This rapid tumor growth was suppressed when scFv-Fc was combined with Tam. Throughout four weeks, the combined Tam+scFv-Fc treatment was more effective in inhibiting the T61 tumor growth than scFv-Fc or Tam treatment alone. scFv-Fc treatment down-regulated IGF-IR which appears to contribute to tumor growth inhibition. This study provides evidence that simultaneous targeting of IGF-IR and the estrogen receptor may enhance the therapeutic effect.

Animals↗