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PubMed2004

Distinct diagnostic criteria of fulminant type 1 diabetes based on serum C-peptide response and HbA1c levels at onset.

OBJECTIVE: Diagnostic criteria in fulminant type 1 diabetes, a novel subtype of type 1 diabetes, remain unclear. RESEARCH DESIGN AND METHODS: We analyzed basal and longitudinal changes of serum C-peptide levels during a 75-g oral glucose tolerance test (OGTT) in 125 consecutively recruited patients with type 1 diabetes including fulminant type 1 diabetes (n = 25) and acute-onset type 1 diabetes (n = 100). Discriminating criteria of fulminant type 1 diabetes were examined using receiver-operating characteristic curve analysis and multiple logistic regression analysis. RESULTS: The integrated values of serum C-peptide response during OGTT (SigmaC-peptide) in fulminant type 1 diabetes at onset, 1 year, and 2 years after onset were markedly lower than those in acute-onset type 1 diabetes. None of the patients with fulminant type 1 diabetes had improvement of C-peptide response to OGTT. Fasting C-peptide values at onset in fulminant type 1 diabetes were significantly lower than those in acute-onset type 1 diabetes. We established diagnostic criteria of serum C-peptide and HbA(1c) levels at onset that discriminate fulminant type 1 diabetes from acute-onset type 1 diabetes with high sensitivity and specificity: a criterion in which the levels of both the fasting C-peptide is <or=0.033 nmol/l and HbA(1c) is <or=8.0% or a criterion in which the levels of both the SigmaC-peptide is <or=0.540 nmol/l and HbA(1c) is <or=8.0%. CONCLUSIONS: Fulminant type 1 diabetes has extremely low beta-cell function at onset that rarely recovers after onset. Sensitive and specific diagnostic criteria were established for detection of fulminant type 1 diabetes based on serum C-peptide and HbA(1c) levels at onset.

Adolescent↗

PubMed2000

A longitudinal study of leptin during development in the male rhesus monkey: the effect of body composition and season on circulating leptin levels.

The objective of this study was to examine longitudinal changes in serum leptin concentrations during development and to correlate those changes with sexual development in male rhesus monkeys housed under natural environmental conditions. Blood samples were drawn from 8 control animals approximately every other month from 10 to 30 mo of age and thereafter monthly through 80 mo of age. Leptin levels declined through the juvenile period until the onset of puberty and were negatively correlated with body weight. Seven of the eight animals became sexually mature during the breeding season of their fourth year of life. Puberty was delayed in the other animal until the subsequent breeding season. There were no significant fluctuations in leptin levels prior to or in association with the pubertal rise in LH and testosterone (T) secretion. During the peripubertal period, levels of leptin varied between 2 and 3 ng/ml. The animal that exhibited delayed puberty had the lowest body weight and highest leptin levels during this period. With the achievement of sexual maturity, leptin levels varied seasonally, with peak levels in the late winter (Jan-Mar) and a nadir in the late summer (Aug-Sept). A late winter rise in leptin was also evident in most of the animals during Years 2 and 3, but not during Year 4. In the fall of Years 5 and 6, the seasonal rise in leptin concentrations lagged 3-4 mo behind the seasonal increase in LH and T. In the fall of Year 5, but not thereafter, leptin levels were positively related to percent body fat and negatively correlated with lean body mass. The data do not support the hypothesis that increasing leptin concentrations trigger the onset of puberty in the male rhesus monkey. During the juvenile period and after sexual maturation, but not during the peripubertal period, leptin secretion varied with season in the animals; but the environmental factors that cue or drive this rhythm remain to be determined.

Aging↗

PubMed1997

Synchronous decline of serum-soluble HLA class I antigen and beta-cell function in insulin-dependent diabetes mellitus.

Serum-soluble HLA class I molecules (sHLA) have immunomodulatory functions and their serum levels correlate with the HLA class I phenotype. We studied longitudinal changes of serum sHLA levels in insulin-dependent diabetes mellitus (IDDM). A total of 198 serum samples were obtained from 40 IDDM patients before and after IDDM onset. sHLA was assayed by a sandwich ELISA. sHLA levels in IDDM patients at the initiation of insulin therapy (IDDM onset) were markedly reduced compared with those in normal controls (334.2 +/- 26.3 ng/ml vs 492.4 +/- 55.5 ng/ml, mean +/- SEM, P = 0.0038). They fell sharply during 6 months before and after the onset of IDDM. The dynamic profile of sHLA and the time course of beta-cell loss were different between IDDM patients with and without HLA-A24. In those with HLA-A24, sHLA became significantly lower than normal controls with HLA-A24 at IDDM onset. Recovery of their sHLA values occurred at 3 years from IDDM onset. On the other hand, in those without HLA-A24, sHLA levels began to decrease since the onset of IDDM and became significantly lower than normal controls without HLA-A24 at 4 years after the onset. Recovery of sHLA occurred at more than 6 years from the onset. An early (within 18 months), complete loss of beta-cell function occurred in 5 of 13 IDDM patients with HLA-A24 compared with 1 of 14 of those without HLA-A24 (P = 0.077). A late (more than 36 months after the onset of IDDM), complete loss of beta-cell function occurred in 7 of 14 IDDM patients without HLA-A24 but in none of 13 of those with HLA-A24 (P = 0.0058). These results indicate that the decline of sHLA is synchronous with massive beta-cell destruction, and that these events occur during a short period in IDDM patients with HLA-A24, whereas they occur during a relatively long period in those without HLA-A24.

Adolescent↗

PubMed1994

A longitudinal study of bacterial vaginosis during pregnancy.

OBJECTIVE: To determine the longitudinal changes in the incidence of vaginosis in pregnancy. DESIGN: A prospective study of women during pregnancy. SETTING: A District General Hospital in North-West London. SUBJECTS: Seven hundred and eighteen pregnant women attending antenatal clinics. At their first attendance and subsequently, Gram-stained vaginal smears were examined and Mycoplasma hominis and Gardnerella vaginalis were sought by culture. RESULTS: Initially, 87 (12%) women had bacterial vaginosis diagnosed on Gram-stained reading of the vaginal smears. Examination of further smears, obtained from 176 women at 36 weeks of gestation, showed that those whose vaginal flora was normal initially, and who went to term, rarely developed vaginosis (three of 127, 2.4%). Samples were obtained at 36 weeks gestation from 32 women who had bacterial vaginosis initially, and went to term. In almost 50% (15 of 32) of these a normal lactobacillus-dominated flora had regenerated. Thirty-five women (5%) had initial vaginal smears graded as intermediate. From this group, six of the 17 (35%) women from whom samples were obtained at 36 weeks gestation still had flora of an intermediate pattern; 10(59%) now had normal flora and only one (6%) had developed bacterial vaginosis. Women with bacterial vaginosis were more likely to be culture-positive for M. hominis than those with normal flora (34/78 versus 10/563, odds ratio 42.73 (18.9 to 102.3) P < 0.001), or to be culture-positive for G. vaginalis than those with normal flora (35/78 versus 21/563, odds ratio 21.0 (10.75 to 41.2) P < 0.001). CONCLUSION: Pregnant women do not commonly develop bacterial vaginosis after 16 weeks gestation, and if present, it remits spontaneously in approximately half of those who reach term. As bacterial vaginosis is associated with increased rates of second trimester miscarriage and preterm delivery, any treatment aimed at its eradication in pregnancy should be given no later than the beginning of the second trimester of pregnancy.

Adult↗

PubMed1999

Alterations in bone turnover and impaired development of bone mineral density in newly diagnosed children with cancer: a 1-year prospective study.

In the present study, longitudinal changes in bone mineral density, bone turnover, and bone hormonal metabolism were evaluated in newly diagnosed children with cancer. Lumbar spine (L2-L4) and femoral neck bone mineral densities (grams per cm2) were measured by dual energy x-ray absorptiometry in 28 children (age, 2.9-16.0 yr; median, 8.0 yr; 10 acute lymphoblastic leukemias, 18 solid tumors) at diagnosis and after a 1-yr follow-up. Apparent volumetric density (grams per cm3) was calculated to minimize the effect of bone size on BMD. Serum levels of osteocalcin (OC), type I collagen carboxyl-terminal propeptide (PICP), and type I collagen carboxyl-terminal telopeptide were measured serially during the study. Serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, insulin-like growth factor I (IGF-I), and IGF-binding protein-3 were analyzed at diagnosis and at 1-yr follow-up. A significant decrease in femoral bone mineral density and apparent volumetric density was observed during the year after diagnosis [(mean (SD), -10.1% (8.8%) and -11.3% (8.1%) respectively; P < 0.01], whereas age- and sex-matched controls showed annual increments of +5.4% (7.7%; P < 0.01) and +0.7% (5.7%; P = NS) respectively. The markers of bone formation (PICP and OC) were significantly decreased at diagnosis. By the end of the follow-up, PICP and OC were normalized, whereas the marker of bone resorption (type I collagen carboxyl-terminal telopeptide) was significantly increased. Reduced levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and IGF-binding protein-3 were observed during the study. To conclude, increased bone resorption and impaired development of femoral bone density were observed in children with cancer during chemotherapy. Deficient accumulation of bone mass may lead to impaired development of peak bone mass and predispose children with cancer to increased risk of osteoporosis and diminished skeletal resistance to fractures later in life.

Absorptiometry, Photon↗

PubMed2006

Changing times: a longitudinal analysis of international firearm suicide data.

We investigated changes in the proportion of firearm suicides in Western countries since the 1980s and the relation of these changes to the change in the proportion of households owning firearms. Several countries had an obvious decline in firearm suicides: Norway, United Kingdom, Canada, Australia, and New Zealand. Multilevel modeling of longitudinal data confirmed the effect of the proportion of households owning firearms. Legislation and regulatory measures reducing the availability of firearms in private households can distinctly strengthen the prevention of firearm suicides.

Australia↗

PubMed2005

Risk factors for declining ankle-brachial index in men and women 65 years or older: the Cardiovascular Health Study.

BACKGROUND: An ankle-brachial index (ABI) of less than 0.9 is a noninvasive measure of lower extremity arterial disease and a predictor of cardiovascular events. Little information is available on longitudinal change in ABI or on risk factors for declining ABI in a community-based population. METHODS: To assess risk factors for ABI decline, we studied 5888 participants in the Cardiovascular Health Study cohort (men and women 65 years or older). We measured ABI in 1992-1993 and again in 1998-1999. At baseline, we excluded individuals with an ABI less than 0.9, ABI greater than 1.4, or confirmed symptomatic lower extremity arterial disease (n = 823). The group with ABI decline included 218 participants with decline greater than 0.15 and to 0.9 or less. The comparison group comprised the remaining 2071 participants with follow-up ABI. RESULTS: The percentage of participants with ABI decline was 9.5% over 6 years of follow-up. The mean +/- SD decline was 0.33 +/- 0.12 in cases of ABI decline and 0.02 +/- 0.13 in non-cases. Independent predictors of ABI decline, reported as odds ratios, were age, 1.96 (95% confidence interval [CI], 1.42-2.71) for 75 to 84 years and 3.79 (95% CI, 1.36-10.5) for those older than 85 years compared with those younger than 75 years; current cigarette use, 1.74 (95% CI, 1.02-2.96); hypertension, 1.64 (95% CI, 1.18-2.28); diabetes, 1.77 (95% CI, 1.14-2.76); higher low-density lipoprotein cholesterol level, 1.60 (95% CI, 1.03-2.51), and lipid-lowering drug use 1.74 (95% CI, 1.05-2.89). CONCLUSION: Worsening lower extremity arterial disease, assessed as ABI decline, occurred in 9.5% of this elderly cohort over 6 years and was associated with modifiable vascular disease risk factors.

Aged↗

PubMed2001

The effects of age on rate of progression of Alzheimer disease and dementia with associated cerebrovascular disease.

BACKGROUND: Relatively little is known about how cerebrovascular disease affects progression of dementia. Previous studies have found no differences in progression of Alzheimer disease and vascular dementia, but these studies have not specifically examined age effects. OBJECTIVE: To test whether the rate of cognitive decline is different in Alzheimer disease compared with dementia with associated cerebrovascular disease in clinical and autopsy patient series. PATIENTS AND METHODS: We studied the longitudinal course of cognitive function as measured by the Mini-Mental State Examination (MMSE) in patients with clinically and neuropathologically diagnosed conditions evaluated through a university Alzheimer disease center. Clinical patients were grouped according to possible Alzheimer disease without stroke (n = 37), probable Alzheimer disease without stroke (n = 181), and dementia with stroke (n = 50). Autopsy cases were categorized into Alzheimer disease (n = 78) and dementia with vascular disease (n = 13). Data were analyzed using random-effects modeling of longitudinal change. RESULTS: There was a significant interaction between age and diagnosis in determining rate of change on the MMSE scores for both the clinical and autopsy samples. Rate of change decreased slightly with advancing age for Alzheimer disease groups, but increased with age for dementia with cerebrovascular disease groups. CONCLUSIONS: Dementia with cerebrovascular disease declined faster in patients 80 years and older compared with Alzheimer disease without associated cerebrovascular pathological conditions, but showed slower decline in patients younger than 80 years. This effect most likely reflects combined Alzheimer and vascular pathological conditions in older patients with cerebrovascular disease.

Adult↗

PubMed1991

Effective head and neck tumor markers. The continuing quest.

To evaluate the clinical value of two serologic tumor markers, squamous cell carcinoma-associated antigen and plasma lipid-bound sialic acid, for identifying cancers of the head and neck, plasma specimens were obtained from patients receiving care for untreated newly diagnosed cancers of the head and neck, routine surveillance for recurrence, or treatment for chronic nonmalignant otolaryngologic conditions. Using identical methods at two institutions, levels of both markers were determined blind to diagnoses for patients with biopsy-proven cancers of the head and neck (n = 134) and for those defined as cancer free based on clinical evaluation for 6 months (n = 140). Disease status was determined blind to tumor marker level results. Cancer prevalence was 48.9%. Applying standard normal limits used alone, plasma lipid-bound sialic acid test sensitivity was 63.4% and specificity was 77.9%. For squamous cell carcinoma-associated antigen alone, test sensitivity was 27.6% and specificity was 85.0%. Neither test alone appears sensitive enough to effectively detect early cancers of the head and neck. When the results of both tests in series combination were positive, sensitivity was 18.7% and specificity was 95.0%. If either was positive in parallel combination, sensitivity was 72.4% and specificity was 68.0%. Further evaluation is required that applies different definitions of normal and determines longitudinal changes with disease status.

Antigens, Neoplasm↗

PubMed1989

Serum alkaline phosphatase and serum zinc concentrations in preterm infants with rickets and fractures.

This study aimed to determine the longitudinal changes in serum zinc concentrations and the relationship between serum alkaline phosphatase (AP) activity and serum zinc concentrations in small preterm infants. The total serum AP and serum zinc concentrations were determined serially at 3, 6, 9, and 12 months in 72 infants with mean (+/- SEM) birth weights of 1000 +/- 29 g and gestational ages of 28.6 +/- 0.3 weeks. Twenty-four of 72 infants had radiographic evidence of rickets and/or fractures (R/F). In infants with R/F, group mean (+/- SEM) serum AP (371 +/- 42 U/L) and serum zinc (12.5 +/- 1.0 mumol/L) concentrations were significantly higher at 3 months compared with infants in the non-R/F group (193 +/- 12 U/L and 9.6 +/- 0.3 mumol/L, respectively). During the study, the serum AP concentrations decreased, and the serum zinc concentrations increased; both stabilized after 6 months. The serum AP concentrations were not related to the serum zinc concentrations. We speculate that in preterm infants, an increased bone turnover and a release of tissue (bone) zinc may contribute to the higher group mean serum AP and serum zinc concentrations at the time of diagnoses in infants with R/F compared with those infants without R/F.

Alkaline Phosphatase↗

PubMed1999

Longitudinal clinical and functional pulmonary follow-up after megatherapy, fractionated total body irradiation, and autologous bone marrow transplantation for metastatic neuroblastoma.

BACKGROUND: A prospective follow-up was undertaken to document longitudinal changes in lung function in children with neuroblastoma treated with the Lyon-Marseille-Curie-East of France Group protocol, consisting of high-dose chemotherapy schedules in combination with total body irradiation (TBI) and autologous bone marrow transplantation (ABMT), to determine the extent and timing of any changes seen and to describe late clinical and functional pulmonary sequelae. PROCEDURES: Eighteen children (1.5-6.9 years of age at TBI) performed pulmonary function tests (PFTs). These included measurement of functional residual capacity (FRC) to assess lung growth and dynamic lung compliance (CLdyn) and lung transfer factor for CO (TLCO) for evaluation of distal bronchi and/or interstitial abnormalities. RESULTS: The clinical follow-up showed that bronchopulmonary symptoms occurred in 12 children. Three of them were clinically severely incapacitated. Serial PFTs showed an initial decrease of all mean values 6 months after TBI, with improvement in mean values of FRC and TLCO at 1 year. Thereafter, a significant decrease of mean FRC and CLdyn was observed from 2 years to 4 years after TBI with preservation of TLCO, suggesting restrictive ventilatory defects rather than pulmonary fibrosis. Individual analysis showed PFT defects in 100% of children 4 years after TBI. There was a higher incidence of lung pathology after two blocks of high-dose chemotherapy than after one block (100% versus 40%) and more severe sequelae. However these children had residual disease present after induction associated with lower baseline PFT. CONCLUSIONS: PFT defects were found in all children 4 years after TBI-ABMT, but they remained within acceptable limits except in very young children.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

Cross-validation of six short forms of the WAIS-R in a healthy geriatric sample.

A number of methods have been developed in recent years to estimate full-scale IQ scores from abbreviated versions of the revised Wechsler Adult Intelligence Scale (WAIS-R), including Silverstein's (1982) two- and four-subtest short forms, Reynolds, Willson, and Clark's (1983) four-subtest short form, and Brooker and Cyr's (1986) two-, three- and four-subtest short forms. Short forms are of particular interest to the clinician and researcher who need a brief screening scale of cognitive abilities for the elderly, but their effectiveness with a normal aging sample has not been established. The present study examines the accuracy of six methods of estimating full-scale IQs from abbreviated versions of the WAIS-R in a middle-aged to elderly nonpsychiatric sample of 28 healthy males. Although all six methods were found to yield scores that were correlated highly with full scale scores, the method of Reynolds et al. (1983) resulted in short-form IQ estimates that were significantly different statistically from full-scale IQ scores. Although most of the six short-form methods appear to be useful screening measures for cognitive functioning and longitudinal changes in intellectual functions in the elderly, their use for classification purposes is not supported in the present study.

Achievement↗

PubMed2004

Suicidality in terminally ill Japanese patients with cancer.

BACKGROUND: The risk of suicide is higher in patients with cancer than in the general population, making end-of-life care of suicidal terminal patients with cancer critical. To identify factors and longitudinal changes associated with suicidality among terminally ill Japanese patients with cancer, a prospective cohort study was performed. METHODS: Consecutive outpatients with cancer who registered with a palliative care unit participated. Structured interviews (e.g., Structured Clinical Interview for DSM- III-R [SCID]) were conducted to assess patient suicidal ideation (Ideation) and interest in requesting euthanasia (Interest) as main outcome measures of suicidality. Possible correlated factors also were investigated. The authors analyzed the data from 140 terminally ill patients with cancer at initial study participation (baseline) whose subsequent survival time was < 6 months. Of these 140 patients, 57 (40.7%) completed the follow-up assessment after admission to the unit. RESULTS: At baseline, 8.6% of the patients had Ideation and 5.0% had Interest. Self-reported anxiety and depression was significantly associated with Ideation (P= 0.003). Changes in Ideation and Interest occurred in 38.6% and 15.8% of the patients, respectively. Ideation was more likely to change than Interest (P = 0.006). The current study did not identify factors that predict changes and occurrences of suicidal ideation and interest in requesting euthanasia. CONCLUSIONS: Suicidality can change even in terminally ill patients. End-of-life care that focuses on the psychologic distress of dying individuals may be a way of preventing suicide.

Adult↗

PubMed2001

A confocal study of spinal interneurons in living larval zebrafish.

We used confocal microscopy to examine the morphology of spinal interneurons in living larval zebrafish with the aim of providing a morphological foundation for generating functional hypotheses. Interneurons were retrogradely labeled by injections of fluorescent dextrans into the spinal cord, and the three-dimensional morphology of living cells was reconstructed from confocal optical sections through the transparent fish. At least eight types of interneurons are present in the spinal cord of larval zebrafish; four of these are described here for the first time. The newly discovered cell types include classes of commissural neurons with axons that ascend, descend, and bifurcate in the contralateral spinal cord. Our reexamination of previously described cell types revealed functionally relevant features of their morphology, such as undescribed commissural axons, as well as the relationships between the trajectories of the axons of interneurons and the descending Mauthner axons. In addition to describing neurons, we surveyed their morphology at multiple positions along the spinal cord and found longitudinal changes in their distribution and sizes. For example, some cell types increase in size from rostral to caudal, whereas others decrease. Our observations lead to predictions of the roles of some of these interneurons in motor circuits. These predictions can be tested with the combination of functional imaging, single-cell ablation, and genetic approaches that make zebrafish a powerful model system for studying neuronal circuits.

Animals↗

PubMed2025

Association Analysis of the Circulating Proteome With Sarcopenia-Related Traits Reveals Potential Drug Targets for Sarcopenia.

BACKGROUND: Sarcopenia severely affects the physical health of the elderly. Currently, there is no specific drug available for sarcopenia. This study aims to identify pathogenic proteins and druggable targets for sarcopenia through Mendelian randomization (MR)-based analytical framework. METHODS: A sequential stepwise screening method that includes two-sample MR, Steiger filtering test and colocalization (MRSC) was applied to identify causal proteins associated with sarcopenia-related traits. In the MR analyses, 4372 circulating proteins with valid instrumental variables (IVs) from eight proteomic genome-wide association studies were utilized as exposures, and nine sarcopenia-related traits were utilized as outcomes. IVs were classified into cis-protein quantitative trait loci (pQTLs) and trans-pQTLs based on their positions. We conducted cis-only MRSC analyses and cis + trans MRSC analyses using cis-pQTLs and cis + trans pQTLs as IVs, respectively. Post-MRSC analyses were conducted on the prioritized findings of MRSC, including annotation of protein-altering variants (PAVs), assessment of overlap between pQTLs and expression quantitative trait loci (eQTLs), protein-protein interaction (PPI) analysis, pathway enrichment analysis and annotation of drug targets. Utilizing data from the UK Biobank, we performed an observational study to explore the associations between baseline circulating protein levels and the longitudinal changes in nine sarcopenia-related traits. RESULTS: A total of 181 causal associations for 65 proteins were prioritized by the cis-only MRSC analyses and 227 associations for 91 proteins were prioritized by the cis + trans MRSC analyses. Among the prioritized proteins, the majority of them employed non-PAVs as IVs and most of their cis-pQTLs overlapped with corresponding eQTLs and exhibited consistent directionality, with only one trans-pQTL overlapping with an eQTL. The PPI network of cis-only MRSC-prioritized proteins (p = 4.04 × 10-4) and cis + trans MRSC-prioritized proteins (p = 8.76 × 10-5) showed significantly more interactions than expected. Reactome, KEGG and GO pathway enrichment analyses for cis-only MRSC-prioritized proteins identified 52, 12 and 79 enriched pathways, respectively (adjusted p < 0.05). For proteins identified by cis + trans MRSC analyses, only 15 pathways were enriched through the GO pathway enrichment analyses. In the observational study, 197 circulating proteins were identified to be associated with one or more sarcopenia-related traits (p < 0.05/2923). Among them, the significant associations of CTSB (negative association) and ASGR1 (positive association) with sarcopenia-related traits were observed to have consistent directional associations in both MR-based studies and observational studies. Drug target annotations suggested that 52 MRSC-prioritized proteins and 145 biomarkers are drug targets or druggable. CONCLUSIONS: This study identified 89 potential pathogenic proteins and 197 candidate biomarkers for sarcopenia, providing valuable clues for the development of therapeutic drugs for sarcopenia.

Humans↗

PubMed2006

Course of psychological distress and its predictors in advanced non-small cell lung cancer patients.

This study investigated longitudinal changes and predictive factors for psychological distress among 85 newly diagnosed advanced non-small cell lung cancer (NSCLC) patients. Whereas tension-anxiety after diagnosis (T1) was significantly reduced at two months (T2) and six months (T3) after diagnosis and depression-dejection at T1 was significantly reduced at T2, other forms of psychological distress, including anger-hostility, vigor, fatigue, and confusion, did not show significant changes. Total mood disturbance did not show significant change. Only a higher total mood disturbance at T1 was a significant predictor of total mood disturbance at T3. These findings demonstrate that most types of psychological distress experienced by advanced NSCLC patients is likely to persist during the subsequent clinical course. The findings also suggest that initial psychological distress itself after cancer diagnosis is the most important predictor for subsequent psychological distress and that early intervention beginning immediately after the disclosure of a diagnosis of cancer is one way to prevent and/or reduce subsequent psychological distress in advanced NSCLC patients.

Adult↗

PubMed2002

Assessment of a low-cost home monitoring spirometer for children.

Electronic devices are now available to measure and store lung function parameters in the home. Before adopting a device for clinical or research use, it is important to validate it in the target patient group. The aim of this study was to assess a low-cost, portable, logging spirometer, the VM Plus (VM), against a standard laboratory Jaeger spirometer (JS) for use in children with respiratory disease. Seventy children with stable asthma or cystic fibrosis performed spirometry on the two devices, and results for peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV(1)) were compared. Comparison was made both using the two devices separately (separate method) and with the devices connected in series (series method). Reproducibility of the VM measurements was also assessed. Correlation between measurements was close (R values: separate, PEF, 0.91; FEV(1), 0.94; series, PEF, 0.97, FEV(1), 0.99), but PEF readings on the VM Plus were substantially higher than with the JS (mean difference: separate, 54.8 L/min; series, 28.2 L/min). This reflects well-reported differences in PEF measurements between the Mini-Wright PEF meter, on which the VM Plus spirometer is based, and conventional spirometers. Limits of agreement (series method) were: PEF, -13.2 to +69.6 L/min; FEV(1), -0.03 to +0.19 L. Reproducibility of VM Plus measurements was acceptable: coefficient of variation for PEF was 4%; for FEV(1), 4.3%; coefficient of reproducibility for PEF, 39 L/min; for FEV(1), 0.26 L. The VM Plus provides reasonably accurate, reproducible measurements of PEF and FEV(1), but intrinsic bias, particularly in PEF measurement, needs to be taken into account. Its potential to document longitudinal changes in lung function in children with respiratory disease at home merits further study.

Adolescent↗

PubMed2006

Plasma concentrations of soluble CTLA-4, CD28, CD80 and CD86 costimulatory molecules reflect disease severity of acute asthma in children.

Recent studies have demonstrated an elevation of plasma soluble costimulatory molecules B7.1 (CD80) and B7.2 (CD86), and their T lymphocyte counter receptors cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and CD28 in asthmatic patients. We hypothesized that these costimulatory molecules may reflect the severity of asthma and investigated the longitudinal changes of these soluble costimulatory molecules, and their clinical significance in children with an asthmatic exacerbation. Sixteen children hospitalized for asthmatic exacerbation were recruited and treated with systemic corticosteroid (CS) for 5 days. Plasma total Immunoglobulin E (IgE) and eosinophil cationic protein (ECP) concentrations were measured by microparticle immunoassay and fluorescence enzyme immunoassay, respectively. Soluble CTLA-4 (sCTLA-4), sCD28, sCD80, and sCD86 concentrations in plasma were measured by enzyme-linked immunosorbent assay, and their relationships with asthma severity, total IgE, ECP concentrations, and blood eosinophil count were analyzed. Plasma sCTLA-4, sCD28, sCD80, and sCD86 concentrations in patients were highest during the acute attack. They decreased significantly with a parallel increase of peak expiratory flow rate (PEFR) after CS treatment (all P < 0.05). Plasma sCTLA-4, sCD28, and sCD86 concentrations of patients at recruitment were inversely correlated with PEFR, whereas plasma sCD28 and sCD86 concentrations correlated positively with eosinophil count and plasma ECP concentration (all P < 0.05). Although there was no such correlation with IgE concentration, sCD28 was correlated very significantly with eosinophil count (r = 0.83, P < 0.0001). In conclusion, plasma sCTLA-4, sCD28, sCD86, and sCD80 concentrations may reflect the severity of acute asthma and more studies on larger cohorts are needed to assess whether these markers are useful for assessing asthmatic exacerbation in children.

Acute Disease↗