RESUMO
Bioenergetic constraints are the ultimate determinant of the timing of reproduction, and seasonal breeding is consequently a widely observed trait. Consistent with this, attention has focused on plasticity in reproductive phenology conceptualized as a response to concomitant advances in the phenology of the environmental energy supply caused by climate change. Few studies, however, have directly compared timing of reproduction with energetic status in free-living wild animals. Here we demonstrate that neither body mass nor adiposity are strong proximate predictors of date of conception in wild reindeer (Rangifer tarandus). Weak coupling between energetic status and the phenology of reproduction accounts for the increasing discrepancy between the phenology of forage (energy supply) and the phenology of reproduction (energy demand) observed across the last 2-4 decades in two populations of this species. The results emphasise that phenological plasticity is not a passive response to changes in energy supply but derives from the way in which environmental factors interact with the core control mechanisms that govern timing. Central in this respect is integration, within the rheostatic centres of the hypothalamus, of information on nutritional status with the circannual life-history calendar.
Assuntos
Rena , Reprodução , Animais , Estações do Ano , Reprodução/fisiologia , Mamíferos , Animais Selvagens , Mudança ClimáticaRESUMO
Comprehensive multi-dimensional hyphenation of a thermogravimetry device (i.e. a thermobalance) to gas chromatography and single photon ionization-time-of-flight mass spectrometry (TG-GC×SPI-MS) has been used to investigate two crude oil samples of different geographical origin. The source of the applied vacuum ultraviolet radiation is an electron beam pumped rare gas excimer lamp (EBEL). The soft photoionization favors the formation of molecular ions. Introduction of a fast, rapidly modulated gas chromatographic separation step in comparison with solely TG-SPI-MS enables strongly enhanced detection especially with such highly complex organic matrices as crude oil. In contrast with former TG-SPI-MS measurements, separation and identification of overlying substances is possible because of different GC retention times. The specific contribution of isobaric compounds to one mass signal is determined for alkanes, naphthalenes, alkylated benzenes, and other compounds.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas/instrumentação , Petróleo/análise , Termogravimetria/instrumentação , Desenho de Equipamento , Cromatografia Gasosa-Espectrometria de Massas/economia , Fatores de TempoRESUMO
One of the pathways activated during liver fibrosis is the Rho kinase pathway, which regulates activation, migration, and contraction of hepatic stellate cells (HSC). Inhibition of this kinase by the Rho kinase inhibitor Y27632 [(+)-(R)-trans- 4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride] has been shown to reduce fibrosis in animal models. However, kinase expression is ubiquitous, so any inhibitor may affect many cell types. We hypothesize that cell-specific delivery of a kinase inhibitor will be beneficial. Therefore, we conjugated Y27632 to the carrier mannose-6-phosphate (M6P) human serum albumin (HSA), which is taken up specifically in activated HSC through the M6P/insulin-like growth factor II receptor. This conjugate decreased protein expression of phosphorylated myosin light chain 2 (pMLC2) and vinculin, downstream of Rho kinase, in activated primary HSC and decreased the migration and contraction of HSC. In an ex vivo model, free Y27632 decreased contractility of rat aortas, whereas the Y27-conjugate did not, showing that the Y27-conjugate does not affect nontarget tissue. In chronic CCl(4)-induced liver fibrosis, both free drug and conjugate reduced HSC activation; however, only the Y27-conjugate significantly reduced collagen deposition. Treatment with the Y27-conjugate, but not with free drug, reduced pMLC2 expression in livers 24 h after injection, demonstrating prolonged inhibition of the Rho kinase pathway. The Rho kinase inhibitor Y27632 can be specifically targeted to HSC using M6PHSA, decreasing its effects in nontarget tissues. The targeted drug effectively reduced fibrotic parameters in vivo via the inhibition of the Rho kinase pathway.
Assuntos
Amidas/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , Amidas/química , Amidas/metabolismo , Animais , Aorta/efeitos dos fármacos , Portadores de Fármacos , Humanos , Fator de Crescimento Insulin-Like II/metabolismo , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Masculino , Manosefosfatos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/metabolismo , Piridinas/química , Piridinas/metabolismo , Ratos , Ratos Wistar , Albumina Sérica/metabolismo , Quinases Associadas a rho/metabolismoRESUMO
A comprehensive investigation of real-time temperature-induced resonance shift cancellation for silicon wire based biosensor arrays is reported for the first time. A reference resonator, protected by either a SU8 or SiO(2) cladding layer, is used to track temperature changes. The temperature dependence of resonators in aqueous solutions, pertinent to biosensing applications, is measured under steady-state conditions and the operating parameters influencing these properties are discussed. Real-time measurements show that the reference resonator resonances reflect the temperature changes without noticeable time delay, enabling effective cancellation of temperature-induced shifts. Binding between complementary IgG protein pairs is monitored over 4 orders of magnitude dynamic range down to a concentration of 20 pM, demonstrating a resolvable mass of 40 attograms. Reactions are measured over time periods as long as 3 hours with high stability, showing a scatter corresponding to a fluid refractive index fluctuation of ± 4 × 10(-6) in the baseline data. Sensor arrays with a SU8 protective cladding are easy to fabricate, while oxide cladding is found to provide superior stability for measurements involving long time scales.
Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Coloração e Rotulagem , Temperatura , Animais , Eletricidade , Imunoglobulina G/análise , Coelhos , Silício/química , Dióxido de Silício/química , Análise Espectral , Fatores de TempoRESUMO
A new interferometer-based optical sensing platform with nanostructured thin films of ZrO2 or TiO2 as sensing environment has been developed. With the application of an IC compatible Si(3)N(4) waveguide technology, Mach-Zehnder interferometer devices have been fabricated. The application of the glancing angle deposition technique allowed fabrication of nanostructured thin films as the optical sensing environment. Sensing ability of fabricated devices has been demonstrated through the refractive index measurement of a known gas. The transmission spectra and time response measurements have demonstrated a maximum phase shift of Delta phi=pi/10 and a |Delta P(out)|=0.65 dBm. Devices with TiO2 film on the sensing region performed much better than devices with ZrO2, with sensitivity twice as high.
Assuntos
Gases/análise , Interferometria/instrumentação , Membranas Artificiais , Nanoestruturas/química , Nanotecnologia/instrumentação , Refratometria/instrumentação , Transdutores , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Nanoestruturas/ultraestrutura , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
A method is developed for extracting the coupling and loss coefficients of ring resonators from the peak widths, depths, and spacings of the resonances of a single resonator. Although the formulas used do not distinguish which coefficient is coupling and which is loss, it is shown how these coefficients can be disentangled based on how they vary with wavelength or device parameters.
RESUMO
INTRODUCTION: Over 90% of hip fractures in older adults result from falls, and hospital patients are at especially high risk. Specific types of wearable hip protectors have been shown to reduce hip fracture risk during a fall by up to 80%, but user compliance has averaged less than 50%. We describe the development and evaluation of a "stick-on" hip protector (secured over the hip with a skin-friendly adhesive) for older patients in acute care. METHODS: An initial version of the product was evaluated with six female patients (aged 76-91) in a hospital ward, who were asked to wear it for one week. We subsequently refined the product through biomechanical testing and solicited feedback from 43 health professionals on a second prototype. RESULTS: The first prototype was worn by five of six patients for the full week or duration of their hospital stay. The second prototype (20 mm thick, surface area 19 × 15.5 cm) provided 36% force attenuation, more than common garment-based models (20-21%). Feedback from patients and health professionals highlighted usability, comfort, cost, and appearance. CONCLUSIONS: Our results from biomechanical and user testing support the need for further work to determine the value of stick-on hip protectors in acute care.
RESUMO
Rho kinase activity in hepatic stellate cells (HSCs) is associated with activation, transformation and contraction of these cells, leading to extracellular matrix production and portal hypertension in liver cirrhosis. Inhibition of rho kinase activity can reduce these activities, but may also lead to side effects, for instance systemic hypotension. This can be circumvented by liver-specific delivery of a rho kinase inhibitor to effector cells. Therefore, we targeted the rho kinase inhibitor Y27632 to the key pathogenic cells in liver fibrosis, i.e. myofibroblasts including activated HSCs that highly express the PDGFß-receptor, using the drug carrier pPB-MSA. This carrier consists of mouse serum albumin (MSA) covalently coupled to several PDGFßR-recognizing moieties (pPB). We aimed to create a prolonged release system of such a targeted construct, by encapsulating pPB-MSA-Y27632 in biodegradable polymeric microspheres, thereby reducing short-lasting peak concentrations and the need for frequent administrations. Firstly, we confirmed the vasodilating potency of PDGFß-receptor targeted Y27632 in vitro in a contraction assay using HSCs seeded on a collagen gel. We subsequently demonstrated the in vivo antifibrotic efficacy of pPB-MSA-Y27632-loaded microspheres in the Mdr2-/- mouse model of progressive biliary liver fibrosis. A single subcutaneous microsphere administration followed by organ harvest one week later clearly attenuated liver fibrosis progression and significantly suppressed the expression of fibrosis related genes, such as several collagens, profibrotic cytokines and matrix metalloproteinases. In conclusion, we demonstrate that polymeric microspheres are suitable as drug delivery system for the sustained systemic delivery of targeted protein constructs with antifibrotic potential, such as pPB-MSA-Y27632. This formulation appears suitable for the sustained treatment of liver fibrosis and possibly other chronic diseases.
Assuntos
Amidas/administração & dosagem , Portadores de Fármacos/administração & dosagem , Cirrose Hepática/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Animais , Linhagem Celular , Preparações de Ação Retardada/administração & dosagem , Feminino , Humanos , Cirrose Hepática/metabolismo , Camundongos Knockout , Microesferas , Membro 4 da Subfamília B de Transportadores de Cassetes de Ligação de ATPRESUMO
We demonstrate folded waveguide ring resonators for biomolecular sensing. We show that extending the ring cavity length increases the resonator quality factor, and thereby enhances the sensor resolution and minimum level of detection, while at the same time relaxing the tolerance on the coupling conditions to provide stable and large resonance contrast. The folded spiral path geometry allows a 1.2 mm long ring waveguide to be enclosed in a 150 microm diameter sensor area. The spiral cavity resonator is used to monitor the streptavidin protein binding with a detection limit of approximately 3 pg/mm(2), or a total mass of approximately 5 fg. The real time measurements are used to analyze the kinetics of biotin-streptavidin binding.
Assuntos
Técnicas Biossensoriais/instrumentação , Óptica e Fotônica/instrumentação , Fotometria/instrumentação , Mapeamento de Interação de Proteínas/instrumentação , Proteínas/química , Sítios de Ligação , Miniaturização , Ligação ProteicaRESUMO
Liver fibrogenesis is associated with excessive production of extracellular matrix by myofibroblasts that often leads to cirrhosis and consequently liver dysfunction and death. Novel protein-based antifibrotic drugs show high specificity and efficacy, but their use in the treatment of fibrosis causes a high burden for patients, since repetitive and long-term parenteral administration is required as most proteins and peptides are rapidly cleared from the circulation. Therefore, we developed biodegradable polymeric microspheres for the sustained release of proteinaceous drugs. We encapsulated the drug carrier pPB-HSA, which specifically binds to the PDGFßR that is highly upregulated on activated myofibroblasts, into microspheres composed of hydrophilic multi-block copolymers composed of poly(l-lactide) and poly ethylene glycol/poly(ϵ-caprolactone), allowing diffusion-controlled release. Firstly, we estimated in mice with acute fibrogenesis induced by a single CCl4 injection the half-life of I125-labeled pPB-HSA at 40 min and confirmed the preferential accumulation in fibrotic tissue. Subsequently, we determined in the Mdr2 −/− mouse model of advanced biliary liver fibrosis how the subcutaneously injected microspheres released pPB-HSA into both plasma and fibrotic liver at 24 h after injection, which was maintained for six days. Although the microspheres still contained protein at day seven, pPB-HSA plasma and liver concentrations were decreased. This reduction was associated with an antibody response against the human albumin-based carrier protein, which was prevented by using a mouse albumin-based equivalent (pPB-MSA). In conclusion, this study shows that our polymeric microspheres are suitable as sustained release formulation for targeted protein constructs such as pPB-HSA. These formulations could be applied for the long-term treatment of chronic diseases such as liver fibrosis.
Assuntos
Portadores de Fármacos/administração & dosagem , Cirrose Hepática/metabolismo , Polímeros/administração & dosagem , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Albumina Sérica/administração & dosagem , Animais , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Portadores de Fármacos/farmacocinética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microesferas , Polímeros/farmacocinética , Albumina Sérica/farmacocinéticaRESUMO
We demonstrate a 50-channel high-resolution arrayed waveguide grating microspectrometer with a 0.2 nm channel spacing on a silicon-on-insulator (SOI) platform. The chip size is 8 mm x 8 mm. High channel density and spectral resolution are achieved using high aspect ratio 0.6 mum x 1.5 mum waveguide apertures to inject the light into the input combiner and to intercept different spectral channels at the output combiner focal region. The measured crosstalk is <-10 dB, the 3 dB channel bandwidth is 0.15 nm, and the insertion loss is -17 dB near the central wavelength of lambda = 1.545 mum.
RESUMO
Health-seeking patterns of persons with tuberculosis (TB) before reporting at the Directly Observed Treatment Short-course (DOTS) clinic for diagnosis and treatment were analysed. A total of 221 persons registered in the DOTS programme in 12 randomly selected rural and urban Local Government Areas in southern Nigeria were interviewed using a semi-structured questionnaire. Perceived causes of TB influenced first choice of treatment. Patients re-evaluated initial choices and shop for alternatives in persistent TB. Chemists were the first port of call for most patients. Those with unscientific causative theories of tuberculosis such as witchcraft engaged more in multiple health-seeking than those who indicated bacterial infection (P < 0.0001). The respondents had a median diagnostic-delay of 90 days. Delay in commencement of DOTS treatment was attributable to ignorance among patients and poor attitude of health workers. In conclusion, delay exists between recognition of symptoms and initiation of treatment in DOTS clinics partly because of ignorance among patients. Health workers' attitude to patients reporting at health clinics also discouraged the use of DOTS facilities. Consequently, it is recommended to address such delay through social mobilization of communities and through engaging Chemists in TB service delivery in this area.
Assuntos
Comportamento de Escolha , Serviços de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde , Tuberculose , Adulto , Terapia Diretamente Observada , Feminino , Humanos , Masculino , Nigéria/epidemiologia , Observação , Inquéritos e Questionários , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/fisiopatologia , Tuberculose/terapiaRESUMO
Injectable sustained release drug delivery systems are an attractive alternative for the intravenous delivery of therapeutic proteins. In particular, for chronic diseases such as fibrosis, this approach could improve therapy by reducing the administration frequency while avoiding large variations in plasma levels. In fibrotic tissues the platelet-derived growth factor receptor beta (PDGFßR) is highly upregulated, which provides a target for site-specific delivery of drugs. Our aim was to develop an injectable sustained release formulation for the subcutaneous delivery of the PDGFßR-targeted drug carrier protein pPB-HSA, which is composed of multiple PDGFßR-recognizing moieties (pPB) attached to human serum albumin (HSA). We used blends of biodegradable multi-block copolymers with different swelling degree to optimize the release rate using the model protein HSA from microspheres produced via a water-in-oil-in-water double emulsion evaporation process. The optimized formulation containing pPB-HSA, showed complete release in vitro within 14days. After subcutaneous administration to mice suffering from renal fibrosis pPB-HSA was released from the microspheres and distributed into plasma for at least 7days after administration. Furthermore, we demonstrated an enhanced accumulation of pPB-HSA in the fibrotic kidney. Altogether, we show that subcutaneously administered polymeric microspheres present a suitable sustained release drug delivery system for the controlled systemic delivery for proteins such as pPB-HSA.
Assuntos
Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Fibrose/tratamento farmacológico , Nefropatias/tratamento farmacológico , Polímeros/química , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Albumina Sérica Humana/química , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Fibrose/metabolismo , Humanos , Nefropatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroesferasRESUMO
OBJECTIVE: This study aimed to compare the effectiveness of two different breast pump suction patterns (BPSP) during the initiation of lactation in mothers of term, late preterm and preterm infants. METHODS: Breast pump-dependent mothers (n=130) of term (n=19), late preterm (n=44) and preterm (n=67) infants were assigned to either a standard or irregular-BPSP after birth until the onset of secretory activation. Both groups used the same standard maintenance BPSP thereafter. Time to secretory activation, time to full milk production and daily milk output were compared between the standard and I-BPSP groups, and between the term, late preterm and preterm groups. RESULTS: Mothers using the irregular-BPSP demonstrated significantly greater daily milk output and established secretory activation significantly earlier. This effect was observed in mothers of term, late preterm and preterm infants. CONCLUSION: The irregular-BPSP mimicking sucking of healthy newborns is more effective at achieving secretory activation and an earlier adequate milk supply than the standard-BPSP. The irregular-BPSP can be used successfully for mothers of preterm up to term infants who are breast pump dependent during the establishment of lactation.
Assuntos
Extração de Leite/instrumentação , Leite Humano/metabolismo , Nascimento Prematuro , Nascimento a Termo , Aleitamento Materno , Feminino , Humanos , Recém-Nascido , Lactação/fisiologia , Países BaixosRESUMO
The rate of proton extrusion by whole cells of Rhodospirillum rubrum is constant on a bacteriochlorophyll basis only above cellular bacteriochlorophyll concentrations of about 10 nmol bacteriochlorophyll per mg cell protein. At specific bacteriochlorophyll cellular levels below this value, the rate of proton extrusion per bacteriochlorophyll increases. Correspondingly, membrane preparations isolated from these cells exhibit increases in the rate of proton uptake on a pigment basis. Concomitant with variations in the rates of proton extrusion by whole cells, light energy fluxes for saturating this process also vary. A fair proportionality between maximum rates of proton extrusion of whole cells and the bacteriochlorophyll cellular levels above 10 nmol per mg protein indicates that the degree of continuity of intracytoplasmic membranes and of the cytoplasmic membrane remains largely constant.
Assuntos
Fotossíntese , Rhodospirillum rubrum/metabolismo , Bacterioclorofilas/metabolismo , Concentração de Íons de Hidrogênio , Cinética , LuzRESUMO
In order to assess hepatic glycogen stores in patients with noninsulin dependent diabetes mellitus (NIDDM) after a 3-day fast, the incremental glucose response to 1.0 mg iv glucagon (glucose area under the curve, glucoseAUC) was assessed in 19 obese diabetic subjects after an overnight (14 h) fast and again after a 3-day (64 h) fast. Results were compared to those of lean (n = 6) and obese (n = 15) nondiabetic subjects. During the fast, plasma glucose fell significantly in the lean (4.9 +/- 0.2 to 3.9 +/- 0.2 mmol/L), obese (5.1 +/- 0.1 to 4.2 +/- 0.2 mmol/L), and diabetic (14.7 +/- 0.7 to 10.3 +/- 1.0 mmol/L) subjects. However, in contrast to the fall in glucoseAUC observed in the lean (92.4 +/- 15.4 to 39.9 +/- 8.1 mmol min-1 L-1, P less than 0.02) and obese (64.4 +/- 11.1 to 48.4 +/- 9.4 mmol min-1 L-1) subjects, the glucoseAUC increased in diabetic subjects from 81.6 +/- 8.6 to 103.9 +/- 8.8 mmol min-1 L-1 during the fast, and was significantly greater than that of either the lean (P less than 0.001) or obese (P less than 0.001) nondiabetic subjects after the 64-h fast. Evidence that the glucose response to glucagon after a 64-h fast represents glycogenolysis and not gluconeogenesis was provided by studies in 10 additional subjects (5 obese nondiabetic subjects and 5 patients with NIDDM). Overall hepatic glucose output calculated from glucose kinetic data [( 3-3H]glucose) increased in diabetic and nondiabetic subjects during the first 30 min after glucagon administration and fell progressively thereafter. However, no increase in alanine gluconeogenesis (14C-alanine incorporation into glucose) was observed after glucagon administration in either subject group. The paradoxical accumulation of glycogen in the patients with NIDDM during the fast occurred despite basal rates of hepatic glucose output on the third day of the fast which were greater than those of obese nondiabetic subjects (9.0 +/- 1.2 vs. 5.6 +/- 0.5 mumol kg-1 min-1, P less than 0.05). A glycogen sparing action of increased gluconeogenesis is proposed as the explanation for the preservation of liver glycogen in patients with NIDDM.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus/metabolismo , Jejum , Glicogênio Hepático/metabolismo , Adulto , Glicemia/metabolismo , Peptídeo C/sangue , Peptídeo C/metabolismo , Feminino , Glucagon/sangue , Glucagon/metabolismo , Glucose/metabolismo , Humanos , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Masculino , Obesidade/metabolismo , Valores de ReferênciaRESUMO
While it is widely recognized that the manner in which organisms adjust their timing of reproduction reflects evolutionary strategies aimed at minimizing offspring mortality or maximizing reproductive output, the conditions under which the evolutionarily stable strategy involves synchronous or asynchronous reproduction is a matter of considerable discord. A recent theoretical model predicts that whether a population displays reproductive synchrony or asynchrony will depend on the relative scales of intrinsic regulation and environmental disturbance experienced by reproducing individuals. This model predicts that, under conditions of negligible competition and large-scale environmental perturbation, evolution of a single mixed strategy will result in asynchronous reproduction. We tested this prediction using empirical data on large-scale climatic fluctuation and the annual timing of reproduction by three species of flowering plants covering 1300-population-years and four degrees of latitude in Norway. In agreement with model predictions, within populations of all three species reproductive asynchrony increased with the magnitude of large-scale climatic perturbation, but bore no relation to the strength of local density dependence. These results suggest that mixed evolutionarily stable strategies can arise from the interplay of combinations of agents of selection and the scale at which they operate; hence it is fruitless to associate synchronous versus asynchronous timing with particular single factors like climate, competition, or predation.
Assuntos
Meio Ambiente , Magnoliopsida/crescimento & desenvolvimento , Modelos Biológicos , Clima , Magnoliopsida/genética , Magnoliopsida/fisiologia , Noruega , Reprodução/fisiologiaRESUMO
OBJECTIVE: As neonatal discharge before 24 hours of life becomes commonplace, the rejection of congenital hypothyroidism (CH) screening specimens obtained too early has created the need for numerous additional tests. We sought to determine whether the specimens obtained before 24 hours could be used safely. METHODS: During a 31-day period we measured thyrotropin in all thyroid-screening specimens that had been obtained before 24 hours. We also examined the early specimens from every infant diagnosed in New Jersey with CH during 1993 or 1994. RESULTS: Among the 663 specimens, those obtained at or before 12 hours and those from infants with birth weights less than 2500 g had too many low thyroxine results to be useful. Among the 515 specimens obtained at more than 12 to 24 hours from newborns weighing 2500 g or more, 37 (7%) had low thyroxine levels and 12 (2.3%) had thyrotropin levels of 20 microIU/mL (mU/L) or higher. Four hundred seventy-one of the 515 infants had subsequent specimens obtained at more than 24 hours, and none of the results were abnormal. There was no child weighing more than or equal to 2500 g who was diagnosed with CH in 1993 and 1994 whose specimen obtained at 24 hours or less was normal. CONCLUSIONS: Accepting specimens obtained at more than 12 to 24 hours from infants weighing 2500 g or more would have resulted in more than the usual number of false-positive results but no false-negative results. This would have decreased the requests for additional specimens by more than 90%.