Patient satisfaction with treatments for moderate-to-severe plaque psoriasis in clinical practice.

BACKGROUND: Treatment satisfaction among patients with moderate-to-severe psoriasis has not been studied and compared across treatments using a validated instrument. OBJECTIVES: To assess patient-reported satisfaction with systemic and phototherapy treatments for moderate-to-severe psoriasis in clinical practice and to correlate satisfaction with disease severity and quality-of-life measures. METHODS: This was a cross-sectional study of 1182 patients with moderate-to-severe psoriasis in the Dermatology Clinical Effectiveness Research Network in the U.S.A. Patients receiving either topical therapies only; monotherapy with oral systemic therapies, biologics or narrowband ultraviolet B phototherapy; or combination therapy with biologics and methotrexate completed the Treatment Satisfaction Questionnaire for Medication version II. RESULTS: Median unadjusted overall satisfaction scores were highest for patients receiving biologic monotherapies, biologic-methotrexate combinations, or phototherapy (83.3); scores were lowest for those receiving topical therapies only or acitretin (66.7). In fully adjusted models, compared with patients receiving methotrexate monotherapy, those receiving adalimumab, etanercept, ustekinumab, phototherapy or adalimumab with methotrexate had significantly higher median overall satisfaction scores by 7.2-8.3 points, while those receiving topical therapies only had significantly lower overall satisfaction by 8.9 points. Adjusted convenience scores were lowest for patients receiving topical therapies only or infliximab. Modest but significant correlations were found between the overall satisfaction subscale and both the Psoriasis Area and Severity Index (ρ = -0.36, P < 0.001) and the Dermatology Life Quality Index (ρ = -0.47, P < 0.001). CONCLUSIONS: Discernible differences were found in treatment satisfaction among therapies, particularly regarding treatment effectiveness and convenience. Further application of treatment satisfaction measures may inform treatment decisions and guideline development.

Cost-effective restoration for carbon sequestration across Brazil's biomes.

Tropical ecosystems are central to the global focus on halting and reversing habitat destruction as a means of mitigating carbon emissions. Brazil has been highlighted as a vital part of global climate agreements because, whilst ongoing land-use change causes it to be the world's fifth biggest greenhouse gas emitting country, it also has one of the greatest potentials to implement ecosystem restoration. Global carbon markets provide the opportunity of a financially viable way to implement restoration projects at scale. However, except for rainforests, the restoration potential of many major tropical biomes is not widely recognised, with the result that carbon sequestration potential may be squandered. We synthesize data on land availability, land degradation status, restoration costs, area of native vegetation remaining, carbon storage potential and carbon market prices for 5475 municipalities across Brazil's major biomes, including the savannas and tropical dry forests. Using a modelling analysis, we determine how fast restoration could be implemented across these biomes within existing carbon markets. We argue that even with a sole focus on carbon, we must restore other tropical biomes, as well as rainforests, to effectively increase benefits. The inclusion of dry forests and savannas doubles the area which could be restored in a financially viable manner, increasing the potential CO2e sequestered >40 % above that offered by rainforests alone. Importantly, we show that in the short-term avoiding emissions through conservation will be necessary for Brazil to achieve it's 2030 climate goal, because it can sequester 1.5 to 4.3 Pg of CO2e by 2030, relative to 0.127 Pg CO2e from restoration. However, in the longer term, restoration across all biomes in Brazil could draw down between 3.9 and 9.8 Pg of CO2e from the atmosphere by 2050 and 2080.

Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium.

Using quantitative RT-PCR in RNA from right ventricular (RV) endomyocardial biopsies from intact nonfailing hearts, and subjects with moderate RV failure from primary pulmonary hypertension (PPH) or idiopathic dilated cardiomyopathy (IDC), we measured expression of genes involved in regulation of contractility or hypertrophy. Gene expression was also assessed in LV (left ventricular) and RV free wall and RV endomyocardium of hearts from end-stage IDC subjects undergoing heart transplantation or from nonfailing donors. In intact failing hearts, downregulation of beta1-receptor mRNA and protein, upregulation of atrial natriuretic peptide mRNA expression, and increased myocyte diameter indicated similar degrees of failure and hypertrophy in the IDC and PPH phenotypes. The only molecular phenotypic difference between PPH and IDC RVs was upregulation of beta2-receptor gene expression in PPH but not IDC. The major new findings were that (a) both nonfailing intact and explanted human ventricular myocardium expressed substantial amounts of alpha-myosin heavy chain mRNA (alpha-MHC, 23-34% of total), and (b) in heart failure alpha-MHC was downregulated (by 67-84%) and beta-MHC gene expression was upregulated. We conclude that at the mRNA level nonfailing human heart expresses substantial alpha-MHC. In myocardial failure this alteration in gene expression of MHC isoforms, if translated into protein expression, would decrease myosin ATPase enzyme velocity and slow speed of contraction.

Temporal and Spatial Variances in Arterial Spin-Labeling Are Inversely Related to Large-Artery Blood Velocity.

BACKGROUND AND PURPOSE: The relationship between extracranial large-artery characteristics and arterial spin-labeling MR imaging may influence the quality of arterial spin-labeling-CBF images for older adults with and without vascular pathology. We hypothesized that extracranial arterial blood velocity can explain between-person differences in arterial spin-labeling data systematically across clinical populations. MATERIALS AND METHODS: We performed consecutive pseudocontinuous arterial spin-labeling and phase-contrast MR imaging on 82 individuals (20-88 years of age, 50% women), including healthy young adults, healthy older adults, and older adults with cerebral small vessel disease or chronic stroke infarcts. We examined associations between extracranial phase-contrast hemodynamics and intracranial arterial spin-labeling characteristics, which were defined by labeling efficiency, temporal signal-to-noise ratio, and spatial coefficient of variation. RESULTS: Large-artery blood velocity was inversely associated with labeling efficiency (P = .007), temporal SNR (P < .001), and spatial coefficient of variation (P = .05) of arterial spin-labeling, after accounting for age, sex, and group. Correction for labeling efficiency on an individual basis led to additional group differences in GM-CBF compared to correction using a constant labeling efficiency. CONCLUSIONS: Between-subject arterial spin-labeling variance was partially explained by extracranial velocity but not cross-sectional area. Choosing arterial spin-labeling timing parameters with on-line knowledge of blood velocity may improve CBF quantification.

Increased central arterial stiffness and altered cerebrovascular haemodynamic properties in South Asian older adults.

South Asians (SA) suffer from a higher burden of heart disease and stroke compared with White Caucasians (CA). We hypothesized that increased arterial stiffness in older adults of SA origin would be associated with greater cerebrovascular pulsatile pressure and flow characteristics compared with CA older adults. Forty-four SA and CA older adults, free of known cardiovascular and cerebrovascular diseases, were assessed. Vascular ageing was characterized by brachial-ankle pulse wave velocity, carotid pulse pressure, compliance coefficient (CC) and intima-media thickness (IMT). Duplex ultrasonography of the internal carotid arteries estimated anterior cerebral blood flow (aCBF) and cerebrovascular resistance (aCVR), and transcranial Doppler ultrasound quantified middle cerebral artery blood flow velocity, resistive index (RI) and pulsatility index (PI). Fasting blood samples were collected to assess glycaemic status, lipid profile and C-reactive protein. SA had higher carotid pulse pressure and lower CC indicating stiffer arteries compared with CA. Multiple regression analyses revealed that ethnic differences in arterial stiffness were associated with glycated haemoglobin level in SA. Among SA, an inverse association was observed between carotid CC and aCVR. In turn, aCVR was associated with a steeper reduction in aCBF in SA than in CA. IMT was strongly associated with greater PI and RI (r>0.81, P<0.001) in SA, whereas a weaker relationship for PI (r=0.46, P=0.03) and no significant relationship for RI were found in CA. The study found stronger associations between pulsatile cerebrovascular haemodynamics and structural and functional alterations in central arteries in SA that may underlie the elevated risk for cerebrovascular disease.

An iron-binding exochelin prevents restenosis due to coronary artery balloon injury in a porcine model.

Background- Vascular smooth muscle cell (VSMC) proliferation is a critical factor in the neointima formation that causes restenosis after coronary angioplasty (PTCA). Desferri-exochelin 772SM (D-EXO), a highly diffusible, lipophilic iron chelator secreted by Mycobacterium tuberculosis, inhibits proliferation of VSMCs in culture. We hypothesized that treatment with D-EXO would inhibit neointima formation in balloon-injured vessels in vivo. Methods and Results- We subjected 24 pigs to overstretch coronary artery injury with standard PTCA balloons and then administered intramural injections of either D-EXO (n=14) or vehicle (n=10) through an Infiltrator catheter. Treatments were randomized, and the investigators were blinded with regard to treatment group until data analysis was completed. One month later, we euthanized the pigs, excised the injured coronary segments, made multiple sections of each segment, and identified the site of maximal neointima formation. An injury score based on the degree of disruption of the internal or external elastic lamina or media was assigned. D-EXO reduced stenosis index (neointima area divided by the area within the internal elastic lamina), adjusted for injury score, by 47%. Neointima thickness was also reduced. Conclusions- D-EXO, injected intramurally, substantially inhibited formation of neointima in a porcine vascular injury model.

Aspirin impairs reverse myocardial remodeling in patients with heart failure treated with beta-blockers.

OBJECTIVES: We hypothesized that aspirin (ASA) might alter the beneficial effect of beta-blockers on left ventricular ejection fraction (LVEF) in patients with chronic heart failure. BACKGROUND: Aspirin blunts the vasodilation caused by both angiotensin-converting enzyme (ACE) inhibitors and beta-blockers in hypertensive patients and in patients with heart failure. Several studies suggest that ASA also blunts some of beneficial effects of ACE inhibitors on mortality in patients with heart failure. To our knowledge, there have been no data evaluating the possible interaction of ASA and beta-blockers on left ventricular remodeling in patients with heart failure. METHODS: We retrospectively evaluated patients entered into the Multicenter Oral Carvedilol Heart failure Assessment (MOCHA) trial, a 6-month, double-blind, randomized, placebo-controlled, multicenter, dose-response evaluation of carvedilol in patients with chronic stable symptomatic heart failure. Multivariate analysis was performed to determine if aspirin independently influenced the improvement in LVEF. RESULTS: Over all randomized patients (n = 293), LVEF improved 8.2 +/- 0.8 ejection fraction (EF) units in ASA nonusers and 4.5 +/- 0.7 EF units in ASA users (p = 0.005). In subjects randomized to treatment with carvedilol (n = 231), LVEF improved 9.5 +/- 0.9 EF units in ASA nonusers and 5.8 +/- 0.8 EF units in ASA users (p = 0.02). In subjects randomized to treatment with placebo (n = 62), LVEF improved 2.8 +/- 1.2 EF units in ASA nonusers and 0.5 +/- 1.4 EF units in ASA users (p = 0.20). Aspirin did not significantly affect the heart rate or systolic blood pressure response in either the placebo or carvedilol groups. The effect of ASA became more significant on multivariate analysis. The change in LVEF was also influenced by carvedilol dose, etiology of heart failure, baseline heart rate, EF and coumadin use. The detrimental effect of ASA on the improvement in LVEF was dose-related and was present in both placebo and carvedilol groups, although the effect was statistically significant only in the much larger carvedilol group. CONCLUSIONS: Aspirin significantly affects the changes in LVEF over time in patients with heart failure and systolic dysfunction treated with carvedilol. The specific mechanism(s) underlying this interaction are unknown and further studies are needed to provide additional understanding of the molecular basis of factors influencing reverse remodeling in patients with heart failure.

Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure.

OBJECTIVES: We sought to assess the effects of combined oral positive inotropic and beta-blocker therapy in patients with severe heart failure. BACKGROUND: Patients with severe, class IV heart failure who receive standard medical therapy exhibit a 1-year mortality rate >50%. Moreover, such patients generally do not tolerate beta-blockade, a promising new therapy for chronic heart failure. Positive inotropes, including phosphodiesterase inhibitors, are associated with increased mortality when administered over the long term in these patients. The addition of a beta-blocker to positive inotropic therapy might attenuate this adverse effect, although long-term oral inotropic therapy might serve as a bridge to beta-blockade. METHODS: Thirty patients with severe heart failure (left ventricular ejection fraction [LVEF] 17.2+/-1.2%, cardiac index 1.6+/-0.1 liter/min per m2) were treated with the combination of oral enoximone (a phosphodiesterase inhibitor) and oral metoprolol at two institutions. Enoximone was given at a dose of < or = 1 mg/kg body weight three times a day. After clinical stabilization, metoprolol was initiated at 6.25 mg twice a day and slowly titrated up to a target dose of 100 to 200 mg/day. RESULTS: Ninety-six percent of the patients tolerated enoximone, whereas 80% tolerated the addition of metoprolol. The mean duration of combination therapy was 9.4+/-1.8 months. The mean length of follow-up was 20.9+/-3.9 months. Of the 23 patients receiving the combination therapy, 48% were weaned off enoximone over the long term. The LVEF increased significantly, from 17.7+/-1.6% to 27.6+/-3.4% (p=0.01), whereas the New York Heart Association functional class improved from 4+/-0 to 2.8+/-0.1 (p=0.0001). The number of hospital admissions tended to decrease during therapy (p=0.06). The estimated probability of survival at 1 year was 81+/-9%. Heart transplantation was performed successfully in nine patients (30%). CONCLUSIONS: Combination therapy with a positive inotrope and a beta-blocker appears to be useful in the treatment of severe, class IV heart failure. It may be used as a palliative measure when transplantation is not an option or as a bridge to heart transplantation. Further study of this form of combined therapy is warranted.

Low-dose enoximone improves exercise capacity in chronic heart failure. Enoximone Study Group.

OBJECTIVES: This study was designed to evaluate the effects of low-dose enoximone on exercise capacity. BACKGROUND: At higher doses the phosphodiesterase inhibitor, enoximone, has been shown to increase exercise capacity and decrease symptoms in heart failure patients but also to increase mortality. The effects of lower doses of enoximone on exercise capacity and adverse events have not been evaluated. METHODS: This is a prospective, double-blind, placebo-controlled, multicenter trial (nine U.S. centers) conducted in 105 patients with New York Heart Association class II to III, ischemic or nonischemic chronic heart failure (CHF). Patients were randomized to placebo or enoximone at 25 or 50 mg orally three times a day. Treadmill maximal exercise testing was done at baseline and after 4, 8 and 12 weeks of treatment, using a modified Naughton protocol. Patients were also evaluated for changes in quality of life and for increased arrhythmias by Holter monitoring. RESULTS: By the protocol-specified method of statistical analysis (the last observation carried-forward method), enoximone at 50 mg three times a day improved exercise capacity by 117 s at 12 weeks (p = 0.003). Enoximone at 25 mg three times a day also improved exercise capacity at 12 weeks by 115 s (p = 0.013). No increases in ventricular arrhythmias were noted. There were four deaths in the placebo group and 2 and 0 deaths in the enoximone 25 mg three times a day and enoximone 50 mg three times a day groups, respectively. Effects on degree of dyspnea and patient and physician assessments of clinical status favored the enoximone groups. CONCLUSIONS: Twelve weeks of treatment with low-dose enoximone improves exercise capacity in patients with CHF, without increasing adverse events.

Cold denaturation of CheY.

The thermal stability of the bacterial chemotaxis protein CheY from Salmonella typhimurium has been examined by thermal denaturation at pH 7.0 in the presence of guanidine-HCl and urea. For both denaturants, thermal denaturation monitored by circular dichroism spectropolarimetry consists of transitions both above and below 25 degrees C, which is strong evidence for a heat capacity change that is > or = 1500 cal/(mol K) upon unfolding. While many data for chemical and thermal denaturation are consistent with data for CheY from Escherichia coli, the observation of cold denaturation for S. typhimurium CheY is inconsistent with the small heat capacity change, 600 to 850 cal/(mol K), reported for denaturation of the E. coli protein.

Correlated motions in native proteins from MS analysis of NH exchange: evidence for a manifold of unfolding reactions in ovomucoid third domain.

Native-state amide hydrogen exchange monitored by NMR spectroscopy and mass spectrometry (MS) has the potential to provide detailed residue-level information regarding correlated motions occurring on the microseconds to seconds timescale. To expand the applicability of MS to these studies, a new algorithm has been developed to interpret MS data for exchange occurring between the EX2 and EX1 kinetic limits. Re-interpretation of MS data for ovomucoid third domain reveals multiple unfolding or partial unfolding reactions.

Microsecond to minute dynamics revealed by EX1-type hydrogen exchange at nearly every backbone hydrogen bond in a native protein.

A previous comprehensive analysis of the pH dependence of native-state amide hydrogen (NH) exchange in turkey ovomucoid third domain (OMTKY3) yielded apparent opening and closing rate constants (k(op) and k(cl)) at 14 NH groups involved in global conformational changes. This analysis has been extended to 18 additional slowly exchanging NH groups. Quench-flow experiments were performed to monitor NH exchange in native OMTKY3 from neutral to very alkaline pH ( approximately 12) conditions. Above pH 10 the mechanism of exchange switched from one governed by a rapid equilibrium preceding the chemistry of exchange (i.e. EX2 exchange), to one where exchange was limited by the rate of opening (i.e. EX1 exchange). Kinetics of solvent exposure are now known for nearly all backbone NH groups in native OMTKY3, yielding rate constants that span five orders of magnitude, 0.004 to 200 s(-1).

Defining protein ensembles with native-state NH exchange: kinetics of interconversion and cooperative units from combined NMR and MS analysis.

Previous studies of native-state peptide hydrogen atom (NH) exchange in turkey ovomucoid third domain (OMTKY3) yielded the thermodynamics and kinetics of unfolding and folding for the 14 slowest-exchanging peptide hydrogen atoms (NHs). Unfolding rate constants and free energies for nine of the NHs are very similar, suggesting that these NHs exchange during a single cooperative unfolding event. Electrospray ionization mass spectrometry (ESI-MS) has been used to test this hypothesis. ESI-MS data and MS peak simulations suggest that this hypothesis is incorrect: in spite of the similarity in their unfolding rate constants, only three to five of the nine residues exchange in a cooperative manner. Thus, residues with similar thermodynamics and kinetics of exchange are probably involved in multiple conformational equilibria. Overall, combined NMR and MS analysis of NH exchange provides a rich and complex picture of the ensemble properties of native proteins.

Solution structure of turkey ovomucoid third domain as determined from nuclear magnetic resonance data.

The solution structure of the 56 amino acid residue turkey ovomucoid third domain was determined by n.m.r. methods. Of the 661 distance constraints used in the calculations, 120 were determined by quadratic approximation of the cross-relaxation rates. The remaining constraints were crudely estimated from a more standard analysis of NOESY spectra. Additionally, 29 torsion angle constraints, 17 hydrogen bonds, and three disulfide bridges were used in the structure calculations. Stereospecific assignments were accomplished for 24 beta-methylene groups and six isopropyl methyl groups (43% chiral assignments). The addition of more accurate distance constraints to the distance geometry/simulated annealing approach resulted in a significant reduction in the dispersion of calculated backbone torsion angles and root-mean-square deviations between structures. Detailed comparisons have been made between the n.m.r. structures of OMTKY3 and published X-ray structures of the same protein and of closely related avian ovomucoid third domains. The refinement with more accurate distance constraints reduced differences between families of the n.m.r. and the X-ray structures.

Regional cerebral arterial transit time hemodynamics correlate with vascular risk factors and cognitive function in men with coronary artery disease.

BACKGROUND AND PURPOSE: Arterial transit time is the time needed for blood to travel from large arteries to capillaries, as estimated from arterial spin-labeling MR imaging. The purpose of this study was to determine whether vascular risk factors and cognitive performance are related to regional differences in cerebral arterial transit time in patients with coronary artery disease who are at risk for cognitive decline. MATERIALS AND METHODS: Arterial transit time was estimated from multiple postlabel delay pseudocontinuous arterial spin-labeling images obtained from 29 men with coronary artery disease. Tests of memory, attention, processing speed, and executive function were administered. Principal component analysis was used to create separate models of cognition and vascular risk, which were related to brain regions through voxelwise analyses of arterial transit time maps. RESULTS: Principal component analysis identified 2 components of vascular risk: 1) "pressor" (age, systolic blood pressure, and pulse pressure) and 2) "obesity" (body fat percentage and body mass index). Obesity was inversely related to arterial transit time in the posterior cingulate, precuneus, lateral occipital cortices, middle temporal gyrus, and frontal pole (P corrected < .05), whereas pressor was not significant. Cognitive scores were factored into a single component. Poor performance was inversely related to precuneus arterial transit time (P corrected < .05). The average arterial transit time in regions identified by obesity was associated with poorer cognitive function (r(2) = 0.21, t = -2.65, P = .01). CONCLUSIONS: Altered cerebral hemodynamics, notably in nodal structures of the default mode network, may be one way that vascular risk factors impact cognition in patients with coronary artery disease.

Some thermodynamic implications for the thermostability of proteins.

An analysis of the thermodynamics of protein stability reveals a general tendency for proteins that denature at higher temperatures to have greater free energies of maximal stability. To a reasonable approximation, the temperature of maximal stability for the set of globular, water-soluble proteins surveyed by Robertson and Murphy occurs at T* approximately 283K, independent of the heat denaturation temperature, T(m). This observation indicates, at least for these proteins, that thermostability tends to be achieved through elevation of the stability curve rather than by broadening or through a horizontal shift to higher temperatures. The relationship between the free energy of maximal stability and the temperature of heat denaturation is such that an increase in maximal stability of approximately 0.008 kJ/mole/residue is, on average, associated with a 1 degrees C increase in T(m). An estimate of the energetic consequences of thermal expansion suggests that these effects may contribute significantly to the destabilization of the native state of proteins with increasing temperature.

Thermodynamics of unfolding for turkey ovomucoid third domain: thermal and chemical denaturation.

We have used thermal and chemical denaturation to characterize the thermodynamics of unfolding for turkey ovomucoid third domain (OMTKY3). Thermal denaturation was monitored spectroscopically at a number of wave-lengths and data were subjected to van't Hoff analysis; at pH 2.0, the midpoint of denaturation (Tm) occurs at 58.6 +/- 0.4 degrees C and the enthalpy of unfolding at this temperature (delta Hm) is 40.8 +/- 0.3 kcal/mol. When Tm was perturbed by varying pH and denaturant concentration, the resulting plots of delta Hm versus Tm yield a mean value of 590 +/- 120 cal/(mol.K) for the change in heat capacity upon unfolding (delta Cp). A global fit of the same data to an equation that includes the temperature dependence for the enthalpy of unfolding yielded a value of 640 +/- 110 cal/(mol.K). We also performed a variation of the linear extrapolation method described by Pace and Laurents, which is an independent method for determining delta Cp (Pace, C.N. & Laurents, D., 1989, Biochemistry 28, 2520-2525). First, OMTKY3 was thermally denatured in the presence of a variety of denaturant concentrations. Linear extrapolations were then made from isothermal slices through the transition region of the denaturation curves. When extrapolated free energies of unfolding (delta Gu) were plotted versus temperature, the resulting curve appeared linear; therefore, delta Cp could not be determined. However, the data for delta Gu versus denaturant concentration are linear over an extraordinarily wide range of concentrations. Moreover, extrapolated values of delta Gu in urea are identical to values measured directly.

Effects of season and illness on the dietary intake of weanlings during longitudinal studies in rural Bangladesh.

Longitudinal, quantitative studies of the dietary intake of 70 weanlings between five and 30 months of age from two Bangladeshi villages have been analyzed to determine the effects of season and illness on dietary intake. During 1014 days of observation, all foods consumed by the children were weighed by a field worker present in the home; 24-hour breast milk intake was estimated from 12-hour test weighings. Inter-individual differences explained 29% to 50% of the variance in consumption of selected nutrients and foods during 632 studies conducted when children were free from diarrhea and fever. Multiple linear regressions controlling for inter-individual differences indicated that 60-day seasonal periods explained a significant proportion of the variation in intake. Average energy consumption (kcal/kg/d) was approximately one-third greater during the post-harvest periods than during the pre-harvest monsoon period. Breast milk intake varied similarly even after controlling for age-related decreases. Consumption of rice and wheat, the major non-breast milk sources of energy and protein, had distinct seasonal patterns, thus limiting the overall seasonal variability in cereal intake. Older children, particularly boys, benefited more from the post-harvest relative abundance of food. The intake of most nutrients was significantly depressed by approximately 10% during febrile illnesses. Minor decreases in intake with other illnesses were not statistically significant.

Bone mineral density changes during lactation: maternal, dietary, and biochemical correlates.

The objectives of this study were to characterize the effects of lactation and weaning on maternal bone mineral density (BMD) and on biochemical markers of bone turnover, and to determine the effects of dietary intake, milk output, and other maternal factors on changes in BMD. Twenty-six fully lactating and eight nonlactating women were followed longitudinally through 7 mo postpartum; the lactating women were followed through postweaning. Maternal dietary and supplement intake data, infant milk intake measurements, blood and urine samples, and midradius and L2-L4 vertebral BMD measurements were obtained 0.5, 3, 5, and 7 mo postpartum. Biochemical analyses included measurements of calciotropic hormones, 24-h urinary excretion of calcium, markers of bone formation and resorption, estradiol, and prolactin. Estimated maternal demands for calcium excretion in milk were met by a combination of high calcium intake (from diet and supplements, 1500 +/- 460 mg/d at 0.5 mo for lactating women) and a decline of approximately 4% in vertebral BMD between 0.5 and 3 mo postpartum. Postweaning BMD (n = 15) at this site approximated initial values. Two factors were positively associated with vertebral BMD, estradiol (P < 0.001) and calcium intake (P = 0.03), whereas two factors were negatively associated, parity (P = 0.03) and protein intake (P = 0.01). In these well-nourished women, the results suggest that the extent of bone loss associated with lactation and its recovery postweaning are negatively influenced by parity. The results also suggest that the bone loss may be attenuated by a generous dietary ratio of calcium to protein.

Arm muscle indicators and creatinine excretion in children.

The ability of anthropometric measurements, including arm muscle area calculated from arm circumference and triceps skinfold thickness, to estimate creatinine excretion as an index of muscle mass was tested in 14 fully active children, 2 to 6 yr of age in a residential care facility. The children were placed on a meat and fish-free diet for 36 to 48 h before the determination of mean creatinine excretion during three 24-h urinary collections. Results indicated highly significant correlations between mean creatinine excretion and height (r = 0.71), weight (r = 0.69), and arm circumference (r = 0.63). However, arm muscle area had the highest correlation with creatinine excretion (r = 0.86) of any anthropometric variable used. Step-wise multiple-regression analysis indicated that including height or weight with arm muscle area did not significantly improve the estimation of creatinine excretion, but that weight for height added significantly to improve the estimation of creatinine excretion, but that arm muscle area can provide a useful index of body muscle as reflected in urinary creatinine excretion in young children.