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Carriage of Candida species and C albicans biotypes in patients undergoing chemotherapy or bone marrow transplantation for haematological disease.

Six hundred and seventy four yeast isolates obtained from routine microbiological screening of 153 patients with haematological disease were identified and Candida albicans isolates biotyped over nine months to determine longitudinal and cross sectional patterns of yeast colonisation. A yeast microflora persisted in many patients despite the routine prophylactic use of oral antifungal agents. Analysis of the yeast species isolated on a cross sectional basis showed that C albicans accounted for 65% of yeasts isolated from the oral cavity but only 45% of the faecal yeast flora. Longitudinal changes in yeast flora occurred significantly more often in faecal samples than in oral samples and significantly less often in sites colonised with C albicans than in sites colonised with other species. No associations were found between the yeasts isolated and the nature of antifungal prophylaxis used, or the extent of a patient's stay in hospital.

Antifungal Agents↗

Evidence for longevity differences between left handed and right handed men: an archival study of cricketers.

STUDY OBJECTIVE: The aim was to examine the relationship between handedness and longevity. DESIGN: This was an archival (retrospective) survey of a cohort of adult men who had played 'first-class cricket'. SETTING: The United Kingdom PARTICIPANTS: The subjects consisted of all of the deceased players included in an encyclopedia of 'first-class cricket' whose bowling hand had been recorded (n = 3165). The study also considered a further 2314 players, born before 1951 but still alive at the time the book was published (1984). MEASUREMENTS AND MAIN RESULTS: Using the bowling hand as an indicator of handedness it was possible to compare the lifespans of 2580 right handed men and 585 left handed men. The average life spans of the two groups differed by 25 months (right = 65.62, left = 63.52), a highly significant difference (p = 0.006). An examination of cause of death (where noted) strongly indicated that the left handed men were more likely to die prematurely in accidents or in warfare. As a consequence, when these unnatural deaths were removed from the sample the longevity difference between the right handers and left handers was considerably reduced. There was no evidence that these results related to any longitudinal change in the proportion of right handers to left handers across the time course of the sample. CONCLUSION: The study found clear evidence that left handedness was associated with a decrease in longevity among a cohort of adult, athletic men. A major factor responsible for this result seemed to be a differential likelihood of accidental death or death during warfare.

Aged↗

Quantitative MRI of the wrist and nerve conduction studies in patients with idiopathic carpal tunnel syndrome.

OBJECTIVE: To correlate morphological findings of idiopathic carpal tunnel syndrome (CTS) with the function of the median nerve. METHODS: In this study, 105 wrists of 105 women patients with idiopathic CTS, and 36 wrists of 36 female volunteers were subjected to nerve conduction studies and MRI. Cross sectional area, signal intensity ratio, and the flattening ratio of the median nerve, carpal tunnel area, flexor tendon area, synovial area, and intersynovial space, and the palmar bowing of the transverse carpal ligament (TCL) were quantified by MRI and correlated with the severity of the disease determined by nerve conduction studies. RESULTS: Cross sectional areas of the median nerve, flexor tendons, and carpal tunnel, and the palmar bowing of the TCL of the CTS groups were greater than in the control group, but differences were not detected among the CTS groups for the area of the flexor tendons and the carpal tunnel. Enlargement, flattening, and high signal intensity of the median nerve at the distal radioulnar joint level were more significant in the advanced than in the earlier stages of the disease. Increase in palmar bowing of the TCL was less prominent in the most advanced group. Linear correlation between the area of the carpal tunnel and palmar bowing of the TCL was noted. CONCLUSION: Severity of the disease could be judged by evaluating not only longitudinal changes of signal intensity and configuration of the median nerve, but also palmar bowing of the TCL. Increased palmar bowing of the TCL was found to be associated with an increase in the area of the carpal tunnel.

Carpal Tunnel Syndrome↗

Decline in spirometric variables in grain workers from start of employment: differential effect of duration of follow up.

Prospective study of 164 young men from the start of employment in grain elevators showed that of those seen at the initial evaluation of respiratory state only 30% were available for a complete four year follow up. The drop out of subjects could represent a health related selection leading to the underestimation of respiratory effects of exposure to grain dust as assessed in the survivor group. This hypothesis was examined by comparisons of longitudinal changes in lung function in four groups defined by the duration of follow up involving the initial examination and periodic evaluations after one, two, and four years of work. Sixty four men were tested only on the initial examination (group I), 18 underwent two (group II), 31 underwent three (group III), and 51 (group IV) all four examinations. The groups had similar mean ages (range: 19.4-20.1 years), mean duration of previous exposure to grain dust (range: 8-13 weeks), smoking habits, lung function, and prevalences of respiratory symptoms evaluated on the initial occasion. The average decline in lung function over the first year was associated with duration of follow up. The annual decline in FVC (ml) was 58 in group II, 41 in group III and -55 (increase) in group IV; the decline in FEV1 (ml) was 224, 130, and 70 respectively. The differences for the annual declines of FEV1, FEF25-759 Vmax509 and Vmax25 were significant between groups II and IV, and the FEF25-759 Vmax509 and Vmax25 differed significantly between groups II and III. The results show that the restriction of analysis to the survivors may underestimate the relation between work and respiratory impairment.

Adolescent↗

Lung function over six years among professional divers.

AIMS: To analyse longitudinal changes in pulmonary function in professional divers and their relation with cumulative diving exposure. METHODS: The study included 87 men at the start of their education as professional divers. At follow up one, three, and six years later, 83, 81, and 77 divers were reexamined. The median number of compressed air dives in the 77 divers over the follow up period was 196 (range 37-2000). A group of non-smoking policemen (n = 64) were subjected to follow up examinations in parallel with the divers. Assessment of lung function included dynamic lung volumes, maximal expiratory flow rates, and transfer factor for carbon monoxide (Tl(CO)). The individual rates of change of the lung function variables were calculated by fitting linear regression lines to the data, expressed as percent change per year. RESULTS: The annual reductions in forced vital capacity (FVC) and forced expired volume in one second (FEV(1)) were 0.91 (SD 1.22) and 0.84 (SD 1.28) per cent per year in divers, which were significantly higher than the reductions in the policemen of 0.24 (SD 1.04) and 0.16 (SD 1.07) per cent per year (p < 0.001). The annual reduction in the maximal expiratory flow rates at 25% and 75% of FVC expired (FEF(25%) and FEF(75%)) were related to the log(10) transformed cumulative number of dives in a multiple regression analysis (p < 0.05). The annual reductions in Tl(CO) were 1.33 (SD 1.85) and 0.43 (SD 1.53) per cent per year in divers and policemen (p < 0.05). CONCLUSIONS: FVC, FEV(1), maximal expiratory flow rates, and Tl(CO) were significantly reduced in divers over the follow up period when compared with policemen. The contrasts within and between groups suggest that diving has contributed to the reduction in lung function.

Accidents, Occupational↗

Recovery of the ciliated epithelium following acute bronchiolitis in infancy.

BACKGROUND: Little is known about the longitudinal changes in the ciliated respiratory epithelium of infants following viral bronchiolitis. A study was undertaken to investigate the time required for the ciliated epithelium to return to normal following bronchiolitis in infants treated with inhaled steroids or placebo. METHODS: Thirty one previously healthy term infants were studied as part of a clinical trial to determine the effect of 12 weeks of treatment with inhaled fluticasone (FP) or placebo via a spacer device (17 FP, 14 placebo). Nineteen healthy children aged 0-6 years previously studied in our department were used as controls. Nasal biopsy specimens were taken from infants with bronchiolitis and ciliary beat frequency (CBF) was measured before treatment and repeated 3, 6, 12, and 24 weeks later. The epithelial ultrastructure was examined by transmission electron microscopy and a normal errors mixed model based on normal controls was used to examine the time for cilia to return to normal in bronchiolitic infants. RESULTS: The mean CBF of infants with bronchiolitis (in Hz) at weeks 0, 3, 6, 12, and 24 were 0.5 (n = 4), 10.9 (n = 4), 12.0 (n = 9), 11.9 (n = 8), and 12.1 (n = 7) in the placebo group and 10.6 (n = 6), 11.4 (n = 9), 8.8 (n = 8), 10.9 (n = 4), and 13.2 (n = 7) in the FP group. The time for the epithelial ultrastructure to normalise was as follows: epithelial integrity score (13.1 weeks), % ciliated cells with loss of cilia (14.0 weeks), and % epithelial cells with abnormalities in projection (16.7 weeks) or mitochondria (15.9 weeks). Inhaled steroids had no significant effects on CBF or epithelial ultrastructure. CONCLUSION: Ciliary loss and epithelial abnormalities persist on average for 13-17 weeks following acute bronchiolitis in infancy.

Acute Disease↗

Health-related quality of life in patients with idiopathic pulmonary fibrosis: a systematic review.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) profoundly affects the quality of patients' lives. A systematic review was performed to evaluate critically the published literature and to examine what is known about health-related quality of life (HRQL) in patients with IPF. METHODS: The MEDLINE, EMBASE, Health and Psychosocial Instruments, and Cochrane Library databases were searched to 1 April 2004. Abstracts and bibliographies of published articles were scanned and contact was made with investigators. Included studies analysed HRQL (or quality of life) in at least 10 patients with IPF. Two reviewers independently selected studies, evaluated their quality according to predetermined criteria, and abstracted data on study design, patients' demographic and clinical characteristics, and quality of life outcome measures. RESULTS: Seven studies met the inclusion criteria. The studies enrolled 512 patients with IPF and used three different instruments to measure HRQL. All studies had important limitations in methodological quality; none measured longitudinal changes in HRQL over time. Patients reported substantially impaired HRQL, especially in domains that measured physical health and level of independence. Patients with IPF appear to have similar impairments in HRQL to those with chronic obstructive pulmonary disease. Measures of dyspnoea were moderately correlated with scores from domains that measured physical health (R2 = 0.03-0.66) and energy/fatigue/pep (R2 = 0.19-0.55), but measures of pulmonary function and gas exchange did not correlate as strongly with these and other domains. CONCLUSION: Studies of HRQL in patients with IPF suggest that, in addition to the obvious effect on physical health, general health, energy level, respiratory symptoms, and level of independence are also impaired. Variability in HRQL among patients is not fully explained by measures of dyspnoea or pulmonary function, suggesting that HRQL measures provide unique information. More research is needed to identify or design appropriate measurement instruments for patients with IPF and to examine changes in HRQL over time or in response to specific treatments.

Aged↗

Downregulated IRS-1 and PPARgamma in obese women with gestational diabetes: relationship to FFA during pregnancy.

Gestational diabetes mellitus (GDM) is associated with elevated postprandial free fatty acids (FFA) and insulin resistance; however, little is known about the cellular mechanisms underlying insulin resistance to suppress lipolysis during gestation. We evaluated the longitudinal changes in insulin suppression of FFA before pregnancy and in early (12-14 wk) and late (34-36 wk) gestation in obese subjects with normal glucose tolerance and in obese GDM subjects. Abdominal subcutaneous adipose tissue biopsies were also obtained during cesarean delivery from normal obese pregnant (Preg-Con), GDM, and nonpregnant obese control (Non-Preg-Con) subjects during gynecological surgery. GDM subjects had higher basal plasma FFA before pregnancy (P = 0.055). Insulin's ability to suppress FFA levels declined from early to late gestation in both GDM and Preg-Con subjects and was significantly less in GDM subjects compared with Preg-Con subjects over time (P = 0.025). Adipose tissue insulin receptor substrate (IRS)-1 protein levels were 43% lower (P = 0.02) and p85alpha subunit of phosphatidylinositol 3-kinase was twofold higher (P = 0.03) in GDM compared with Preg-Con subjects. The levels of peroxisome proliferator-activated receptor-gamma (PPARgamma) mRNA and protein were lower by 38% in Preg-Con (P = 0.006) and by 48% in GDM subjects (P = 0.005) compared with Non-Preg controls. Lipoprotein lipase and fatty acid-binding protein-2 mRNA levels were 73 and 52% lower in GDM compared with Preg-Con subjects (P < 0.002). Thus GDM women have decreased IRS-1, which may contribute to reduced insulin suppression of lipolysis with advancing gestation. Decreased PPARgamma and its target genes may be part of the molecular mechanism to accelerate fat catabolism to meet fetal nutrient demand in late gestation.

Adipose Tissue↗

Rate-dependent [K+](o) accumulation in canine right atria in vivo: electrophysiological consequences.

Sudden increases in heart rate cause accumulation of K+ in the extracellular space. However, the exact relationship between rate and extracellular K+ concentration ([K+](o)) in vivo is unknown. We measured [K+](o) in right atria of anesthetized dogs by using K(+)-sensitive electrodes. Peak increase in [K+](o) ranged from 0.18 +/- 0.04 mM [means +/- SE; cycle length (CL) = 350 ms] to 0.80 +/- 0.09 mM (CL = 250 ms) above baseline (3.50 +/- 0.08 mM at CL = 380 ms; n = 5). During rapid pacing-induced atrial fibrillation, peak increase in [K+](o) averaged 0.80 +/- 0.07 mM (n = 5). Whole cell current-clamp measurements in single right atrial myocytes (n = 5) showed that raising [K+](o) from 3 to 5 mM in 1-mM steps progressively depolarized resting membrane potential and reduced both phase 0 action potential amplitude and maximal upstroke velocity. Multisite epicardial mapping (n = 4) demonstrated that sudden rate increases changed longitudinal conduction velocity (CV(L)) by -3.6 +/- 1.8% to -5.9 +/- 1.2% over a CL range of 330 to 250 ms. Our observations suggest that rate-related [K+](o) accumulation in vivo is of sufficient magnitude to modulate those cellular electrophysiological properties that determine atrial CV(L).

Action Potentials↗

In vivo measurement of total body magnesium and manganese in rats.

Mg and Mn are essential minerals in many biological processes. Thus knowledge of their absolute amounts and how those amounts may be altered is important. In the past the in vivo measurement of Mg in animals was limited by both the poor geometry of the counting system and the requirement for multiple counts of the animal over several hours. We have developed a neutron activation technique for the direct in vivo measurement of total body Mg and Mn in the rat. The counting system adapted for the technique has a response that is relatively invariant (+/- 2.5%) to differences in body size. A least-squares curve fitting technique was developed that requires only a single 5-min count of the animal. Our in vivo values for body Mg and Mn were in excellent agreement (+/- 2.0%) with the results of total carcass analysis using atomic absorption. Longitudinal changes in total body Mg and Mn were examined in vivo in two groups of animals maintained on test diets that contained different amounts of Mg.

Activation Analysis↗

Solute conductance of blood-gas barrier in hamsters exposed to hyperoxia.

Hamsters were exposed to greater than 95% O2 continuously for up to 5 days to determine longitudinal changes in the diffusive conductance of the alveolar epithelium and capillary endothelium as a result of hyperoxia. Permeability X surface area (PS, cm3/s X 10(-4)) was measured by isolated, perfused lung techniques. Alveolar epithelium PS for [14C]sucrose and 125I-bovine serum albumin (BSA) were determined at seven exposure times. Control PS (sucrose) and PS(BSA) averaged 1.00 and 0.022, respectively. Values were unchanged until 4.5 days, when significant increases in both, but especially PS(BSA), occurred. After 5 days, PS values were 4.69 and 0.691, respectively. Capillary endothelium PS for 125I-BSA and fluoresceinisothiocyanate dextran-150 (D-150) were measured at four exposure times. Control endothelium PS(BSA) and PS(D-150) averaged 0.232 and 0.048, respectively. These values were also unchanged after 4 days but increased to 0.440 and 0.131 after 5 days. Wet lung weight significantly increased after only 4 days. Hyperoxia thus increased both endothelium and epithelium PS, but epithelium changes were much greater. These functional changes do not occur for several days, occur simultaneously, and follow increases in lung wet weight.

Animals↗

The spatial-temporal redistribution of pulmonary blood flow with postnatal growth.

The pulmonary vascular tree undergoes remarkable postnatal development and remodeling. While a number of studies have characterized longitudinal changes in vascular function with growth, none have explored regional patterns of vascular remodeling. We therefore studied six neonatal pigs to see how regional blood flow changes with growth. We selected pigs because of their rapid growth and their similarities to human development with respect to the pulmonary vascular tree. Fluorescent microspheres of varying colors were injected into the pulmonary circulation to mark regional blood on days 3, 12, 27, 43, and 71 after birth. The animals were awake and in the prone posture for all injections. The lungs were subsequently removed, air dried, and sectioned into approximately 2-cm(3) pieces. Flow on each injection day was determined for each piece. Despite the increase in the hydrostatic gradient in the lung with growth, there was a strong correlation between blood flow to the same lung piece when compared on days 3 and 71 (0.73 +/- 0.12). Although a dorsal-ventral gradient of perfusion did not exist on day 3, blood flow increased more in the dorsal region by day 12 and then gradually became more uniform by day 71. Although most of the lung pieces did not show any discernable pattern of blood flow redistribution, there were spatial patterns of blood flow redistribution that were similar across animals. Our findings suggest that local mechanisms, shared across animals, guide regional changes in vascular resistance or vasoregulation during postnatal development. In the pig, these mechanisms act to produce more uniform flow in the normal posture for an ambulating quadruped. The stimuli for these changes have not yet been identified.

Animals↗

Delayed disease progression after allogeneic cell vaccination in hormone-resistant prostate cancer and correlation with immunologic variables.

PURPOSE: There are a significant number of patients with asymptomatic hormone-resistant prostate cancer who have increasing prostate-specific antigen (PSA) levels but little or no evaluable disease. The immunogenicity and minimal toxicity associated with cell-based vaccine therapy makes this approach attractive for these patients. EXPERIMENTAL DESIGN: We have evaluated a vaccine comprising monthly intradermal injection of three irradiated allogeneic prostate cell lines (8 x 10(6) cells each) over 1 year. The first two doses were supplemented with bacille Calmette-Guérin as vaccine adjuvant. Twenty-eight hormone-resistant prostate cancer patients were enrolled. Patients were assessed clinically and PSA levels were measured monthly. Radiologic scans (X-ray, computed tomography, and bone scan) were taken at baseline and at intervals throughout the treatment period. Comprehensive monthly immunologic monitoring was undertaken including proliferation studies, activation markers, cytokine protein expression, and gene copy number. This longitudinal data was analyzed through predictive modeling using artificial neural network feed-forward/back-propagation algorithms with multilayer perceptron architecture. RESULTS: Eleven of the 26 patients showed statistically significant, prolonged decreases in their PSA velocity (PSAV). None experienced any significant toxicity. Median time to disease progression was 58 weeks, compared with recent studies of other agents and historical control values of around 28 weeks. PSAV-responding patients showed a titratable T(H)1 cytokine release profile in response to restimulation with a vaccine lysate, while nonresponders showed a mixed T(H)1 and T(H)2 response. Furthermore, immunologic profile correlated with PSAV response by artificial neural network analysis. We found predictive power not only in expression of cytokines after maximal stimulation with phorbol 12-myristate 13-acetate, but also the method of analysis (qPCR measurement of IFN-gamma > qPCR measurement tumor necrosis factor-alpha > protein expression of IFN-gamma > protein expression of interleukin 2). CONCLUSIONS: Whole cell allogeneic vaccination in hormone-resistant prostate cancer is nontoxic and improves the natural history of the disease. Longitudinal changes in immunologic function in vaccinated patients may be better interpreted through predictive modeling using tools such as the artificial neural network rather than periodic "snapshot" readouts.

Aged↗

Understanding Ageing. An evaluation of research designs for assessing the interdependence of ageing-related changes.

BACKGROUND: Cross-sectional studies of samples varying widely in age have found moderate to high levels of shared age-related variance among measures of cognitive and physiological capabilities, leading researchers to posit common factors or common causal influences for diverse age-related phenomenon. OBJECTIVE: The influence of population average changes with age on cross-sectional estimates of association has not been widely appreciated in developmental and ageing research. Covariances among age-related variables in cross-sectional studies are highly confounded in regards to inferences about associations among rates of change within individuals since covariances can result from a number of sources including average population age-related differences (fixed age effects) in addition to initial individual differences and individual differences in rates of ageing (random age effects). Analysis of narrow age-cohort samples may provide a superior analytical basis for testing hypotheses regarding associations between rates of change in cross-sectional studies. CONCLUSIONS: The use of age-heterogeneous cross-sectional designs for evaluating interdependence of ageing-related processes is discouraged since associations will not necessarily reflect individual-level correlated rates of change. Typical cross-sectional studies do not provide sufficient evidence for the interdependence of ageing-related changes and should not serve as the basis for theories and hypotheses of ageing. Reanalyzing existing cross-sectional studies using a sequential narrow-age cohort approach provides a useful alternative for evaluating associations between ageing-related changes. Longitudinal designs, however, provide a much stronger basis for inference regarding associations between rates of ageing within individuals.

Adult↗

The quality circle: how to improve the outcome of paediatric diabetes care.

Most multicentre studies demonstrate that the outcome of diabetes therapy falls below the targets set up in recent guidelines. Applying quality control methodology may provide one means better to achieve such targets. Before setting up a quality circle, objective, standardized documentation of relevant quality indicators is necessary. Based on internal (for example longitudinal changes over time) and external quality control (comparison with other institutions), both favourable and unfavourable results achieved by each institution are identified. Such data provide the basis for intensive discussion among the members of diabetes care teams on how to remedy such deficits. In Germany, the working group on paediatric diabetology set up a system for external quality assessment in 1995: For 6 continuous years, quality indicators are compared twice yearly, and regional quality circles for more open discussions have been established, in addition to yearly nationwide meetings among all participants.

Child↗

Fluorodeoxyglucose PET scan in pulmonary sarcoidosis during treatment with inhaled and oral corticosteroids.

The objective was to investigate longitudinal changes in fluorodeoxyglucose PET scan (FDG-PET) in a patient with pulmonary sarcoidosis prior to and during treatment with inhaled corticosteroids followed by systemic corticosteroids. The patient was a 41-year-old man presenting with stage I pulmonary sarcoidosis (hilar adenopathy), which had progressed to stage II (pulmonary infiltrates) 19 months later. FDG-PET was performed at 19, 29 and 33 months after presentation. No treatment was given prior to the 1st PET. Subsequently, before the 2nd PET, the patient was treated with inhaled beclomethasone (QVAR Autohaler) 0.8 mg/day for 8 months. Finally, prior to the 3rd PET, the patient was treated with oral prednisolone 30 mg/day for 3 months. The 1st PET showed a high FDG uptake in the hilar and mediastinal lymph nodes and a high focal uptake in the peripheral parts of the lungs. The 2nd PET showed a slight uptake in a few mediastinal lymph nodes and an unchanged high focal uptake in the peripheral parts of the lungs and the pleura. The 3rd PET showed no abnormal uptake at all. In conclusion, as assessed by FDG-PET, inhaled beclomethasone had no recognizable influence on sarcoid inflammatory activity. Treatment with oral prednisolone depressed the inflammatory activity to such a degree that it was undetectable by PET. The results are in accordance with clinical studies on pulmonary sarcoidosis, showing a marginal effect of inhaled corticosteroids and a marked effect of systemic corticosteroids.

Administration, Inhalation↗

Intra- and extrauterine maturation of amplitude-integrated electroencephalographic activity in preterm infants younger than 30 weeks of gestation.

OBJECTIVE: To prospectively investigate the longitudinal changes of amplitude-integrated electroencephalographic (aEEG) activity in preterm infants <30 weeks gestational age (GA). METHODS: Infants (GA <30 weeks) without evidence of neurological abnormalities had weekly aEEG recordings performed. The relative duration of the three aEEG patterns (discontinuous low voltage, discontinuous high voltage and continuous) was determined and the influence of GA and postnatal age (PNA) on the occurrence of each pattern was assessed. RESULTS: Ninety-eight infants (median GA 26 weeks; range 23-29 weeks) were studied. With higher GA (OR 1.68, 95% CI 1.33-2.13) and PNA (OR 1.91, 95% CI 1.53-2.38), the likelihood for the occurrence of continuous activity increased. The discontinuous low-voltage pattern was less likely to occur with increasing GA (OR 0.68, 95% CI 0.55-0.83) and PNA (OR 0.70, 95% CI 0.61-0.81). CONCLUSION: Maturation of aEEG activity in preterm infants is influenced by both GA and PNA.

Aging↗

Simple fasting methods to assess insulin sensitivity in childhood.

The 'gold standard' techniques used to measure insulin sensitivity in children are the hyperinsulinaemic-euglycaemic clamp and Bergman's minimal model. Although precise, these techniques are complex, invasive and time consuming. Alternative indirect measures of insulin sensitivity have been developed that utilize fasting glucose and insulin data in algorithms or computer programs. These methods include homeostatic model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI) and the glucose to insulin ratio (G:I). Each of these three fasting techniques has been developed and validated in adults, with little or no validation in children. Increasingly, HOMA and QUICKI are being used in childhood studies to assess insulin sensitivity. In a group of 79 pre-pubertal children, we found that the correlation between the minimal model and RHOMA (r = -0.4) was no better than that between the minimal model and fasting insulin (r = 0.4), with an even weaker correlation between the minimal model and QUICKI (r = 0.2). In addition, neither HOMA nor QUICKI were able to detect a reduction in insulin sensitivity with obesity or during growth hormone therapy, unlike the minimal model. In children with normal glucose levels, neither HOMA nor QUICKI was superior to fasting insulin. Validation of the derivation formulae for these methods in children is needed before they are more widely used. The potential benefits of these simple fasting techniques is that they are useful in large field studies. However, if the study groups are small or longitudinal changes in insulin sensitivity are sought, more precise techniques such as the clamp or minimal model should be used.

Adolescent↗