Effect of controlled hypoglycaemia on sympathetic skin response in patients with Type 1 diabetes and control subjects.

AIM: To evaluate the quantity and mechanism of sudomotor function during euglycaemia and hypoglycaemia using sympathetic skin responses in patients with Type 1 diabetes and control subjects. METHODS: Sympathetic skin responses were measured in 16 patients with diabetes without neuropathy and in eight control subjects during euglycaemic and hypoglycaemic clamp. RESULTS: During hypoglycaemia, the number of repetitive synchronous sympathetic skin responses significantly increased in both groups (P<0.05), and this increase was significantly associated with the hypoglycaemia and sweating. CONCLUSIONS: During hypoglycaemia the number of repetitive synchronous sympathetic skin responses was related to increased sweating according to the hypoglycaemic symptom score. This is best explained by central nervous system reactions. The sympathetic skin responses of the patients with Type 1 diabetes had a weaker correlation with hypoglycaemia and its symptoms, which was possibly attributable to an adaptation or a dysfunction of the patients' sudomotor pathways.

Strategies for free flap transfer and revascularisation with long-term outcome in the treatment of large diabetic foot lesions.

OBJECTIVE/BACKGROUND: To analyse the impact of ischaemia and revascularisation strategies on the long-term outcome of patients undergoing free flap transfer (FFT) for large diabetic foot lesions penetrating to the tendon, bone, or joint. METHODS: Foot lesions of 63 patients with diabetes (median age 56 years; 70% male) were covered with a FTT in 1991-2003. Three groups were formed and followed until 2009: patients with a native in line artery to the ulcer area (n = 19; group A), patients with correctable ischaemia requiring vascular bypass (n = 32; group B), and patients with uncorrectable ischaemia lacking a recipient vessel in the ulcer area (n = 12; group C). RESULTS: The respective 1, 5, and 10 year amputation free survival rates were 90%, 79%, and 63% in group A; 66%, 25%, and 18% in group B; and 50%, 42%, and 17%, in group C. The respective 1, 5, and 10 year leg salvage rates were 94%, 94%, and 87% in group A; 71%, 65%, and 65% in group B; and 50%, 50%, and 50% in group C. In 1 year, 43%, 45%, and 18% of the patients in groups A, B, and C, respectively, achieved stable epithelisation for at least 6 months. The overall amputation rate was associated with smoking (relative risk [RR] 3.09, 95% confidence interval [CI] 1.8-5.3), heel ulceration (RR 2.25, 95% CI 1.1-4.7), nephropathy (RR 2.24, 95% CI 1.04-4.82), and an ulcer diameter of >10 cm (RR 2.08, 95% CI 1.03-4.48). CONCLUSION: Despite diabetic comorbidities, complicated foot defects may be covered by means of an FFT with excellent long-term amputation free survival, provided that a patent native artery feeds the ulcer area. Ischaemic limbs may also be salvaged with combined FFT and vascular reconstruction in non-smokers and in the absence of very extensive heel ulcers. Occasionally, amputation is avoidable with FFT, even without the possibility of direct revascularisation.

Excess of miRNA-378a-5p perturbs mitotic fidelity and correlates with breast cancer tumourigenesis in vivo.

BACKGROUND: Optimal expression and proper function of key mitotic proteins facilitate control and repair processes that aim to prevent loss or gain of chromosomes, a hallmark of cancer. Altered expression of small regulatory microRNAs is associated with tumourigenesis and metastasis but the impact on mitotic signalling has remained unclear. METHODS: Cell-based high-throughput screen identified miR-378a-5p as a mitosis perturbing microRNA. Transient transfections, immunofluorescence, western blotting, time-lapse microscopy, FISH and reporter assays were used to characterise the mitotic anomalies by excess miR-378a-5p. Analysis of microRNA profiles in breast tumours was performed. RESULTS: Overexpression of miR-378a-5p induced numerical chromosome changes in cells and abrogated taxol-induced mitotic block via premature inactivation of the spindle assembly checkpoint. Moreover, excess miR-378a-5p triggered receptor tyrosine kinase-MAP kinase pathway signalling, and was associated with suppression of Aurora B kinase. In breast cancer in vivo, we found that high miR-378a-5p levels correlate with the most aggressive, poorly differentiated forms of cancer. INTERPRETATION: Downregulation of Aurora B by excess miR-378a-5p can explain the observed microtubule drug resistance and increased chromosomal imbalance in the microRNA-overexpressing cells. The results suggest that breast tumours may deploy high miR-378a-5p levels to gain growth advantage and antagonise taxane therapy.

Altered TUBB3 expression contributes to the epothilone response of mitotic cells.

BACKGROUND: Epothilones are a novel group of microtubule (mt) targeting cancer drugs that bind to the ß-subunit of the αß-tubulin dimer. Epothilones inhibit cell proliferation and induce cell death by interfering with the normal mt function. In this study, we examined the consequences of altered expression of human ß-tubulin isotypes in terms of the epothilone drug response in human lung and breast cancer cell lines. METHODS: The ß-tubulin isotypes TUBB2A-C, TUBB3 and TUBB were silenced or overexpressed in A549, A549EpoB40 and MCF7 cell lines in the presence or absence of epothilones. The drug effects on cell proliferation, mitosis and mt dynamics were determined using live cell microscopy and immunofluorescence assays. RESULTS: Loss of TUBB3 enhanced the action of epothilones. TUBB3 knockdown increased the severity of drug-induced mitotic defects and resulted in stabilisation of the mt dynamics in cells. Moreover, exogenous expression of TUBB3 in the epothilone resistant cell line conferred the response to drug treatments. In contrast, reduced levels of TUBB2A-C or TUBB had not apparent effect on the cells' response to epothilones. CONCLUSION: Our results show that the expression of TUBB3 contributes to the cellular response to epothilones, putatively by having an impact on the mt dynamics.

Estimating motor unit numbers from a CMAP scan: Repeatability study on three muscles at 15 centres.

OBJECTIVE: To assess the repeatability and suitability for multicentre studies of MScanFit motor unit number estimation (MUNE), which involves modelling compound muscle action potential (CMAP) scans. METHODS: Fifteen groups in 9 countries recorded CMAP scans twice, 1-2 weeks apart in healthy subjects from abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. The original MScanFit program (MScanFit-1) was compared with a revised version (MScanFit-2), designed to accommodate different muscles and recording conditions by setting the minimal motor unit size as a function of maximum CMAP. RESULTS: Complete sets of 6 recordings were obtained from 148 subjects. CMAP amplitudes differed significantly between centres for all muscles, and the same was true for MScanFit-1 MUNE. With MScanFit-2, MUNE differed less between centres but remained significantly different for APB. Coefficients of variation between repeats were 18.0% for ADM, 16.8% for APB, and 12.1% for TA. CONCLUSIONS: It is recommended for multicentre studies to use MScanFit-2 for analysis. TA provided the least variable MUNE values between subjects and the most repeatable within subjects. SIGNIFICANCE: MScanFit was primarily devised to model the discontinuities in CMAP scans in patients and is less suitable for healthy subjects with smooth scans.

Chipster: user-friendly analysis software for microarray and other high-throughput data.

BACKGROUND: The growth of high-throughput technologies such as microarrays and next generation sequencing has been accompanied by active research in data analysis methodology, producing new analysis methods at a rapid pace. While most of the newly developed methods are freely available, their use requires substantial computational skills. In order to enable non-programming biologists to benefit from the method development in a timely manner, we have created the Chipster software. RESULTS: Chipster (http://chipster.csc.fi/) brings a powerful collection of data analysis methods within the reach of bioscientists via its intuitive graphical user interface. Users can analyze and integrate different data types such as gene expression, miRNA and aCGH. The analysis functionality is complemented with rich interactive visualizations, allowing users to select datapoints and create new gene lists based on these selections. Importantly, users can save the performed analysis steps as reusable, automatic workflows, which can also be shared with other users. Being a versatile and easily extendable platform, Chipster can be used for microarray, proteomics and sequencing data. In this article we describe its comprehensive collection of analysis and visualization tools for microarray data using three case studies. CONCLUSIONS: Chipster is a user-friendly analysis software for high-throughput data. Its intuitive graphical user interface enables biologists to access a powerful collection of data analysis and integration tools, and to visualize data interactively. Users can collaborate by sharing analysis sessions and workflows. Chipster is open source, and the server installation package is freely available.

Serum immunoglobulin A concentration in infancy, but not human milk immunoglobulin A, is associated with subsequent atopic manifestations in children and adolescents: a 20-year prospective follow-up study.

BACKGROUND: Serum and secretory IgA concentrations have been suggested to be inversely associated with allergic symptoms in children. Furthermore, low maternal milk IgA concentration has been suggested to be associated with the development of cow's milk allergy. OBJECTIVE: Our aim was to explore whether the serum IgA concentrations in infancy and the IgA concentration of maternal milk predict atopic manifestations in childhood and up to age 20 years. METHODS: A cohort of 200 unselected full-term newborns was prospectively followed up from birth to age 20 years with measurement of serum total IgA at ages 2 and 6 months. The mothers were encouraged to maintain exclusive breastfeeding for as long as possible. Total IgA concentration of maternal milk was measured at birth (colostrum, n=169) and at 2 (n=167) and 6 (n=119) months of lactation. The children were re-assessed at ages 5, 11 and 20 years for the occurrence of allergic symptoms, with skin prick testing and measurement of serum IgE. RESULTS: Children and adolescents with respiratory allergic symptoms and sensitization had a higher serum IgA concentration at age 2 months than the non-atopic subjects. Colostrum and breast milk IgA concentrations were not associated with the development of allergic symptoms in the recipient infant. However, maternal milk IgA concentration at 6 months of lactation was inversely associated with elevated serum total IgE and positive skin prick test to tree pollen in the offspring at age 20 years. CONCLUSIONS AND CLINICAL RELEVANCE: Increased serum IgA concentration at age 2 months is associated with the development of subsequent allergic symptoms and sensitization in childhood and adolescence. Maternal milk IgA concentrations are not associated with subsequent allergic symptoms in the recipient infant. The present study provides novel information on the role of IgA in the development of respiratory allergy and sensitization.

Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and is involved in regulating anaphase onset and late mitotic events.

We have investigated the function of p55CDC, a mammalian protein related to Cdc20 and Hct1/Cdh1 in Saccharomyces cerevisiae, and Fizzy and Fizzy-related in Drosophila. Immunofluorescence studies and expression of a p55CDC-GFP chimera demonstrate that p55CDC is concentrated at the kinetochores in M phase cells from late prophase to telophase. Some p55CDC is also associated with the spindle microtubules and spindle poles, and some is diffuse in the cytoplasm. At anaphase, the concentration of p55CDC at the kinetochores gradually diminishes, and is gone by late telophase. In extracts prepared from M phase, but not from interphase HeLa cells, p55CDC coimmunoprecipitates with three important elements of the M phase checkpoint machinery: Cdc27, Cdc16, and Mad2. p55CDC is required for binding Mad2 with the Cdc27 and Cdc16. Thus, it is likely that p55CDC mediates the association of Mad2 with the cyclosome/anaphase-promoting complex. Microinjection of anti-p55CDC antibody into mitotic mammalian cells induces arrest or delay at metaphase, and impairs progression of late mitotic events. These studies suggest that mammalian p55CDC may be part of a regulatory and targeting complex for the anaphase-promoting complex.

High insulin levels are positively associated with peripheral nervous system function.

OBJECTIVE: The aim of this study was to analyze peripheral nervous system (PNS) function in overweight and obese individuals. MATERIALS AND METHODS: Forty-four adult non-diabetic overweight individuals were recruited. Peroneal motor nerve conduction and radial, sural, and medial plantar sensory nerve conduction were studied. Insulin and glucose levels were determined twice (over a 2- to 3-year period) with an oral glucose tolerance test (OGTT). Multiple stepwise linear regression models adjusted for age, height, weight, and skin temperature were used to analyze the data. RESULTS: Analysis revealed that baseline insulin levels measured 120 min after an OGTT explained 18% of the variation in peroneal F-wave minimum latency, 8% of peroneal F-wave maximum latency variation, 15% of sural sensory latency variation, 13% of sural sensory nerve conduction velocity (NCV) variation, and 10% of the variation in medial plantar sensory NCV. DISCUSSION AND CONCLUSION: Our study shows that serum insulin levels measured 120 min after an OGGT are positively associated with PNS function. High insulin levels without notably high glucose levels appear to be beneficial for the function of the PNS.

Compressive sensing in electrical impedance tomography for breathing monitoring.

OBJECTIVE: Electrical impedance tomography (EIT) is a functional imaging technique in which cross-sectional images of structures are reconstructed based on boundary trans-impedance measurements. Continuous functional thorax monitoring using EIT has been extensively researched. Increasing the number of electrodes, number of planes and frame rate may improve clinical decision making. Thus, a limiting factor in high temporal resolution, 3D and fast EIT is the handling of the volume of raw impedance data produced for transmission and its subsequent storage. Owing to the periodicity (i.e. sparsity in frequency domain) of breathing and other physiological variations that may be reflected in EIT boundary measurements, data dimensionality may be reduced efficiently at the time of sampling using compressed sensing techniques. This way, a fewer number of samples may be taken. APPROACH: Measurements using a 32-electrode, 48-frames-per-second EIT system from 30 neonates were post-processed to simulate random demodulation acquisition method on 2000 frames (each consisting of 544 measurements) for compression ratios (CRs) ranging from 2 to 100. Sparse reconstruction was performed by solving the basis pursuit problem using SPGL1 package. The global impedance data (i.e. sum of all 544 measurements in each frame) was used in the subsequent studies. The signal to noise ratio (SNR) for the entire frequency band (0 Hz-24 Hz) and three local frequency bands were analysed. A breath detection algorithm was applied to traces and the subsequent error-rates were calculated while considering the outcome of the algorithm applied to a down-sampled and linearly interpolated version of the traces as the baseline. MAIN RESULTS: SNR degradation was generally proportional with CR. The mean degradation for 0 Hz-8 Hz (of interest for the target physiological variations) was below ~15 dB for all CRs. The error-rates in the outcome of the breath detection algorithm in the case of decompressed traces were lower than those associated with the corresponding down-sampled traces for CR ⩾ 25, corresponding to sub-Nyquist rate for breathing frequency. For instance, the mean error-rate associated with CR = 50 was ~60% lower than that of the corresponding down-sampled traces. SIGNIFICANCE: To the best of our knowledge, no other study has evaluated the applicability of compressive sensing techniques on raw boundary impedance data in EIT. While further research should be directed at optimising the acquisition and decompression techniques for this application, this contribution serves as the baseline for future efforts.

Serum cholesterol level in infancy is inversely associated with subsequent allergy in children and adolescents. A 20-year follow-up study.

BACKGROUND: Previous studies suggest an association between an altered lipoprotein profile and atopy. The association has been hypothesized to be due to alterations in the dietary fat intake, a factor possibly contributing to the increase of allergic diseases in industrialized countries. OBJECTIVE: We aimed at assessing whether there is an association between the serum lipid levels in infancy and subsequent development of allergic symptoms in childhood and adolescence. METHODS: A cohort of 200 unselected newborns was prospectively followed up from birth to age 20 years (from 1981 to 2002) with repeated measurements of total cholesterol from birth and throughout the first year of life. The subjects were re-examined at the ages of 5, 11 and 20 years, with assessment of the occurrence of allergic symptoms, skin prick testing (SPT) and measurement of total IgE and of the total, high- and low-density lipoprotein cholesterol. RESULTS: Children and adolescents with allergic symptoms, SPT positivity and an elevated IgE had lower total cholesterol levels in infancy and childhood than the non-atopic subjects. The difference was not detectable in cord blood, but became significant from age 2 months onward. CONCLUSION: The inverse association between the cholesterol level in infancy and subsequent manifestations of atopy seems not to be due to atopy-related dietary alterations, because it was already present in early infancy, when virtually all the infants were on a similar diet, i.e. on exclusive breastfeeding.

Clinical performance of a novel textile interface for neonatal chest electrical impedance tomography.

OBJECTIVE: Critically ill neonates and infants might particularly benefit from continuous chest electrical impedance tomography (EIT) monitoring at the bedside. In this study a textile 32-electrode interface for neonatal EIT examination has been developed and tested to validate its clinical performance. The objectives were to assess ease of use in a clinical setting, stability of contact impedance at the electrode-skin interface and possible adverse effects. APPROACH: Thirty preterm infants (gestational age: 30.3 ± 3.9 week (mean ± SD), postnatal age: 13.8 ± 28.2 d, body weight at inclusion: 1727 ± 869 g) were included in this multicentre study. The electrode-skin contact impedances were measured continuously for up to 3 d and analysed during the initial 20-min phase after fastening the belt and during a 10 h measurement interval without any clinical interventions. The skin condition was assessed by attending clinicians. MAIN RESULTS: Our findings imply that the textile electrode interface is suitable for long-term neonatal chest EIT imaging. It does not cause any distress for the preterm infants or discomfort. Stable contact impedance of about 300 Ohm was observed immediately after fastening the electrode belt and during the subsequent 20 min period. A slight increase in contact impedance was observed over time. Tidal variation of contact impedance was less than 5 Ohm. SIGNIFICANCE: The availability of a textile 32-electrode belt for neonatal EIT imaging with simple, fast, accurate and reproducible placement on the chest strengthens the potential of EIT to be used for regional lung monitoring in critically ill neonates and infants.

Human inhibitor of apoptosis protein (IAP) survivin participates in regulation of chromosome segregation and mitotic exit.

A signaling cascade termed the "spindle checkpoint" monitors interactions between the kinetochores of chromosomes and spindle microtubules to prevent precocious separation of sister chromatids. We have investigated the role of human inhibitor of apoptosis protein (IAP) surviving in regulation of cell division. We demonstrate that HeLa and PtK1 cells transfected or microinjected with surviving anti-sense oligonucleotides produce significantly more polyploid and micronucleated progeny cells and show abortive mitosis when treated with spindle poisons. Furthermore, perturbation of surviving function in HeLa and PtK1 cells with anti-surviving antibodies at the beginning of mitosis affects the normal timing of separation of sister chromatids and disturbs the 3F3/2 phosphoepitope-recognized tension sensing mechanism of the spindle checkpoint. This leads to premature separation of sister chromatids, which results in an uneven distribution of chromosomes between the newly formed progeny cells-an event associated with tumor formation in many cell types. Finally, cells injected with anti-surviving antibody exit mitotic block induced with microtubule drugs. Our data suggest that surviving protein may function within the spindle checkpoint pathway.

Cholesterol and its precursors in human milk during prolonged exclusive breast-feeding.

Concentrations of cholesterol and its precursors were investigated in human milk from 88 mothers at 2 mo, 28 mothers at 6 mo, and 6 mothers at 9 mo of lactation. These mothers, who were exclusively breast-feeding their infants, collected fore- and hindmilk samples at every feeding over a 24-h period. Samples were analyzed by gas-liquid chromatography and mass spectrometry. Mean (+/- SD) cholesterol concentrations were 0.41 +/- 0.094, 0.46 +/- 0.094, and 0.49 +/- 0.10 mmol/L, respectively. The following cholesterol precursors were identified: squalene, lanosterol, dimethylsterol, delta 8.24-methostenol, lathosterol, and desmosterol. Mean concentrations were 0.04 +/- 0.11, 0.35 +/- 0.13, and 0.29 +/- 0.012 mmol/L for desmosterol, 0.0094 +/- 0.0027, 0.012 +/- 0.0039, and 0.011 +/- 0.0039 mmol/L for squalene, and from 0.0011 to 0.0027 mmol/L for all the other precursors. The precursors' equally low concentrations, except for desmosterol and squalene, and the significant correlations with each other suggest that the mammary gland synthesizes cholesterol from lanosterol by preserving the side-chain double bond and that the rate-limiting step may be the conversion of desmosterol to cholesterol.

Adverse long-term effects of brain radiotherapy in adult low-grade glioma patients.

OBJECTIVE: To study the long-term effects of radiotherapy on cognitive function in adult patients operated on for low-grade glioma. METHODS: A cohort of 160 patients who underwent surgery for low-grade gliomas of cerebral hemisphere between 1980 and 1992 in a single institution serving a defined population was studied. At a mean follow-up time of 7 years, 28 of the 101 patients who had postoperative irradiation (and no second surgery or chemotherapy) were still alive and eligible for MRI and neuropsychological study. Twenty-three of 59 patients who did not have radiotherapy, second surgery, or chemotherapy were alive and eligible at a mean of 10 years. RESULTS: The group that had postoperative irradiation performed significantly worse than the group that did not in cognitive tests. This difference was not accounted for by histologic diagnosis; location, extent of removal, or progression of the tumor; or any patient factor. Leukoencephalopathy was more severe in the group that had postoperative irradiation than in the group without radiotherapy, and correlated to poor memory performances only in the postoperative radiotherapy group. Average Karnofsky performance scale score was significantly lower in the group that had postoperative irradiation than in the group that did not. CONCLUSION: In adults with low-grade glioma, postoperative radiotherapy poses a significant risk of long-term leukoencephalopathy and cognitive impairment.

Serum C-reactive protein, erythrocyte sedimentation rate, and white blood cell count in acute hematogenous osteomyelitis of children.

OBJECTIVE: The aim of this prospective study was to compare the clinical value of the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell (WBC) count in diagnosis and follow-up of acute hematogenous osteomyelitis in children. DESIGN: Forty-four children aged 2 weeks to 14 years with bacteriologically confirmed acute hematogenous osteomyelitis were examined. Staphylococcus aureus was responsible in 39 cases (89%), Haemophilus influenzae type b in 3 cases (7%), pneumococcus in 1 case (2%), and a microaerophilic streptococcus in 1 case (2%). ESR was measured at the time of admission and on days 3, 5, 7, 10, 14, 19, and 29 of treatment, and CRP was measured on the same days as ESR but also on days 2, 9, 12, 17, and 23. WBC count was examined at the time of admission and on days 5, 10, 19, and 29. RESULTS: ESR was elevated (> or = 20 mm/h) initially in 92% of the cases; the mean value was 45 mm/h, and the peak values (mean 58 mm/h) were reached on days 3 to 5. After this the levels slowly returned to normal in approximately 3 weeks (mean 18 days). CRP was elevated (> 19 mg/L) at the time of admission in 98% of the cases, the mean value being 71 mg/L. The peak CRP value was reached on day 2 (mean 83 mg/L). The decrease was very rapid, normal values being reached within a week (mean 6.9 days). The WBC count was a poor indicator of acute hematogenous osteomyelitis, since only 35% of the children had leukocytosis (WBCs > 12 x 10(9)/L) at the time of admission. CONCLUSIONS: In patients with acute hematogenous osteomyelitis, CRP increased and especially decreased significantly faster than ESR, reflecting the effectiveness of the therapy given and predicting recovery more sensitively than ESR or WBC count.

Exclusive breast-feeding and weaning: effect on serum cholesterol and lipoprotein concentrations in infants during the first year of life.

The total serum cholesterol concentration of infants was investigated at birth (n = 193) and at the ages of 2 (n = 192), 4 (n = 192), 6 (n = 190), 9 (n = 188), and 12 months (n = 196). Concentrations of cholesterol--very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein-2 (HDL2), HDL3--and apoprotein B were analyzed in 36 infants at 2, 6, 9, and 12 months of age. Serum cholesterol concentration rose significantly more slowly in the weaned infants compared with exclusively breast-fed infants. The mean difference in total serum cholesterol value between the exclusively breast-fed and weaned infants was largest at ages 2 (0.9 mmol/L, P less than .001), 4 (0.6 mmol/L, P less than .01), and 6 months (0.5 mmol/L, P less than .01). The LDL cholesterol concentration was lower in weaned infants compared with exclusively breast-fed infants at age 2 and 6 months; the mean difference in LDL cholesterol value was 0.9 mmol/L at age 2 months (P less than .001) and 0.7 mmol/L at age 6 months (P less than .025). Also, the apoprotein B concentration was lower in weaned infants; the mean difference was 24 mg/dL at age 2 months (P less than .01) and 30 mg/dL at age 6 months (P less than .05). The apoprotein B-LDL cholesterol ratio was stable and similar in both feeding groups through the year. The HDL2 cholesterol concentration was lower in the formula-fed than in breast-fed infants at 2 months of age while the VLDL and HDL3 cholesterol concentrations were independent of the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Tracking of serum cholesterol and lipoprotein levels from the first year of life.

OBJECTIVE: To examine the development of tracking of serum cholesterol concentration from birth to childhood. DESIGN: In a longitudinal study of healthy children, concentrations of total serum cholesterol and triglyceride were determined at birth (n = 193); at 2 (n = 192), 4 (n = 192), 6 (n = 190), 7.5 (n = 118), 9 (n = 188), and 12 months (n = 196); and at 5 years of age (n = 162). Concentrations of cholesterol--very-low-density lipoprotein, low-density lipoprotein, high-density lipoprotein-2 (HDL2), and HDL3--were determined at 2, 6, 9, and 12 months (n = 36) and at 5 years (n = 162). RESULTS: The correlation coefficients of total cholesterol levels during the first year of life with the level at 5 years of age were as follows: at birth .04, at 2 months .36 (P < .001), at 4 months .26 (P < .001), at 6 months .28 (P < .001), at 7.5 months .25 (P < .001), at 9 months .35 (P < .001), and at 12 months .48 (P < .001). The correlation for exclusively breast-fed children between 6 months and 5 years of age was r = .37, P < .001, while that for children receiving partially breast milk, formula, or solid foods was r = .12, P = not significant (NS), and between 9 months and 5 years r = .38, P < .01, and r = .28, P < .05, respectively. The correlation coefficients of the lipoprotein levels between ages 12 months and 5 years were as follows: low-density lipoprotein cholesterol .58 (P < .001), total HDL cholesterol .30 (P < .05), HDL2 cholesterol .34 (P < .05), HDL3 cholesterol .17 (P = NS), very-low-density lipoprotein cholesterol .24 (P = NS), total triglyceride .37 (P < .05), and triglyceride-very-low-density lipoprotein .37 (P < .05). Of the children whose total serum cholesterol level was above the 90th percentile at birth, or at 2, 4, 6, 7.5, 9, or 12 months, 6%, 35%, 29%, 30%, 31%, 33%, and 45%, respectively, were above the 90th percentile at 5 years of age. In retrospect, 45% of the children whose serum cholesterol level was above the 90th percentile at 5 years were above the 90th percentile at the age of 12 months and 80% were in the highest quartile. CONCLUSIONS: The results indicate that tracking of serum cholesterol concentration during the first year of life is stronger when examining children who are receiving a relatively homogenous diet, such as exclusive breast-feeding, and weaker as children are weaned to formula and solid foods. After the weaning process is completed, children's relative serum cholesterol levels have become established and the tracking of serum cholesterol is of the same magnitude as for older children and adolescents.