Bassett Medical Center

BACKGROUND: Bronchiolitis is an acute, viral lower respiratory tract infection affecting infants and is sometimes treated with bronchodilators. OBJECTIVES: To assess the effects of bronchodilators on clinical outcomes in infants (0 to 12 months) with acute bronchiolitis. SEARCH METHODS: We searched CENTRAL 2013, Issue 12, MEDLINE (1966 to January Week 2, 2014) and EMBASE (1998 to January 2014). SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing bronchodilators (other than epinephrine) with placebo for bronchiolitis. DATA COLLECTION AND ANALYSIS: Two authors assessed trial quality and extracted data. We obtained unpublished data from trial authors. MAIN RESULTS: We included 30 trials (35 data sets) representing 1992 infants with bronchiolitis. In 11 inpatient and 10 outpatient studies, oxygen saturation did not improve with bronchodilators (mean difference (MD) -0.43, 95% confidence interval (CI) -0.92 to 0.06, n = 1242). Outpatient bronchodilator treatment did not reduce the rate of hospitalization (11.9% in bronchodilator group versus 15.9% in placebo group, odds ratio (OR) 0.75, 95% CI 0.46 to 1.21, n = 710). Inpatient bronchodilator treatment did not reduce the duration of hospitalization (MD 0.06, 95% CI -0.27 to 0.39, n = 349).Effect estimates for inpatients (MD -0.62, 95% CI -1.40 to 0.16) were slightly larger than for outpatients (MD -0.25, 95% CI -0.61 to 0.11) for oximetry. Oximetry outcomes showed significant heterogeneity (I(2) statistic = 81%). Including only studies with low risk of bias had little impact on the overall effect size of oximetry (MD -0.38, 95% CI -0.75 to 0.00) but results were close to statistical significance.In eight inpatient studies, there was no change in average clinical score (standardized MD (SMD) -0.14, 95% CI -0.41 to 0.12) with bronchodilators. In nine outpatient studies, the average clinical score decreased slightly with bronchodilators (SMD -0.42, 95% CI -0.79 to -0.06), a statistically significant finding of questionable clinical importance. The clinical score outcome showed significant heterogeneity (I(2) statistic = 73%). Including only studies with low risk of bias reduced the heterogeneity but had little impact on the overall effect size of average clinical score (SMD -0.22, 95% CI -0.41 to -0.03).Sub-analyses limited to nebulized albuterol or salbutamol among outpatients (nine studies) showed no effect on oxygen saturation (MD -0.19, 95% CI -0.59 to 0.21, n = 572), average clinical score (SMD -0.36, 95% CI -0.83 to 0.11, n = 532) or hospital admission after treatment (OR 0.77, 95% CI 0.44 to 1.33, n = 404).Adverse effects included tachycardia, oxygen desaturation and tremors. AUTHORS' CONCLUSIONS: Bronchodilators such as albuterol or salbutamol do not improve oxygen saturation, do not reduce hospital admission after outpatient treatment, do not shorten the duration of hospitalization and do not reduce the time to resolution of illness at home. Given the adverse side effects and the expense associated with these treatments, bronchodilators are not effective in the routine management of bronchiolitis. This meta-analysis continues to be limited by the small sample sizes and the lack of standardized study design and validated outcomes across the studies. Future trials with large sample sizes, standardized methodology across clinical sites and consistent assessment methods are needed to answer completely the question of efficacy.

BACKGROUND: Recent studies have identified critical roles for microRNAs (miRNAs) in a variety of cellular processes, including regulation of cardiomyocyte death. However, the signature of miRNA expression and possible roles of miRNA in the ischemic heart have been less well studied. METHODS AND RESULTS: We performed miRNA arrays to detect the expression pattern of miRNAs in murine hearts subjected to ischemia/reperfusion (I/R) in vivo and ex vivo. Surprisingly, we found that only miR-320 expression was significantly decreased in the hearts on I/R in vivo and ex vivo. This was further confirmed by TaqMan real-time polymerase chain reaction. Gain-of-function and loss-of-function approaches were employed in cultured adult rat cardiomyocytes to investigate the functional roles of miR-320. Overexpression of miR-320 enhanced cardiomyocyte death and apoptosis, whereas knockdown was cytoprotective, on simulated I/R. Furthermore, transgenic mice with cardiac-specific overexpression of miR-320 revealed an increased extent of apoptosis and infarction size in the hearts on I/R in vivo and ex vivo relative to the wild-type controls. Conversely, in vivo treatment with antagomir-320 reduced infarction size relative to the administration of mutant antagomir-320 and saline controls. Using TargetScan software and proteomic analysis, we identified heat-shock protein 20 (Hsp20), a known cardioprotective protein, as an important candidate target for miR-320. This was validated experimentally by utilizing a luciferase/GFP reporter activity assay and examining the expression of Hsp20 on miR-320 overexpression and knockdown in cardiomyocytes. CONCLUSIONS: Our data demonstrate that miR-320 is involved in the regulation of I/R-induced cardiac injury and dysfunction via antithetical regulation of Hsp20. Thus, miR-320 may constitute a new therapeutic target for ischemic heart diseases.

The increased breast cancer risk in female night shift workers has been postulated to result from the suppression of pineal melatonin production by exposure to light at night. Exposure of rats bearing rat hepatomas or human breast cancer xenografts to increasing intensities of white fluorescent light during each 12-hour dark phase (0-345 microW/cm2) resulted in a dose-dependent suppression of nocturnal melatonin blood levels and a stimulation of tumor growth and linoleic acid uptake/metabolism to the mitogenic molecule 13-hydroxyoctadecadienoic acid. Venous blood samples were collected from healthy, premenopausal female volunteers during either the daytime, nighttime, or nighttime following 90 minutes of ocular bright, white fluorescent light exposure at 580 microW/cm2 (i.e., 2,800 lx). Compared with tumors perfused with daytime-collected melatonin-deficient blood, human breast cancer xenografts and rat hepatomas perfused in situ, with nocturnal, physiologically melatonin-rich blood collected during the night, exhibited markedly suppressed proliferative activity and linoleic acid uptake/metabolism. Tumors perfused with melatonin-deficient blood collected following ocular exposure to light at night exhibited the daytime pattern of high tumor proliferative activity. These results are the first to show that the tumor growth response to exposure to light during darkness is intensity dependent and that the human nocturnal, circadian melatonin signal not only inhibits human breast cancer growth but that this effect is extinguished by short-term ocular exposure to bright, white light at night. These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers.

Leukemia has been studied in two sets of identical two. One leukemic twin was irradiated with 850 r and the other with 1,140 r from Co/sup 60/ sources. Each was then given bone marrow from the respective normal twin. Successful transplantation of this isologous marrow was determined by the return of morrow function, evident after less than two weeks, and by a benign clinical course following radiation. Leukemia recurred after remissions of seven weeks in one case and 12 weeks in the other. From these two patients it was concluded that transplants of isopogous marrow are readily achieved in man; one thousand r of whole-body radiation does not produce troublesome acute radiation sickness in man when given at a rate of 20 to 40 r per hour; whole-body irradiation at the 1,000 r level produces a remission but not a cure of leukemia when followed by isologous marrow. (auth)

Melatonin, as a new member of an expanding group of regulatory factors that control cell proliferation and loss, is the only known chronobiotic, hormonal regulator of neoplastic cell growth. At physiological circulating concentrations, this indoleamine is cytostatic and inhibits cancer cell proliferation in vitro via specific cell cycle effects. At pharmacological concentrations, melatonin exhibits cytotoxic activity in cancer cells. At both physiological and pharmacological concentrations, melatonin acts as a differentiating agent in some cancer cells and lowers their invasive and metastatic status through alterations in adhesion molecules and maintenance of gap junctional intercellular communication. In other cancer cell types, melatonin, either alone or in combination with other agents, induces apoptotic cell death. Biochemical and molecular mechanisms of melatonin's oncostatic action may include regulation of estrogen receptor expression and transactivation, calcium/calmodulin activity, protein kinase C activity, cytoskeletal architecture and function, intracellular redox status, melatonin receptor-mediated signal transduction cascades, and fatty acid transport and metabolism. A major mechanism mediating melatonin's circadian stage-dependent tumor growth inhibitory action is the suppression of epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) activity. This occurs via melatonin receptor-mediated blockade of tumor linoleic acid uptake and its conversion to 13-hydroxyoctadecadienoic acid (13-HODE) which normally activates EGFR/MAPK mitogenic signaling. This represents a potentially unifying model for the chronobiological inhibitory regulation of cancer growth by melatonin in the maintenance of the host/cancer balance. It also provides the first biological explanation of melatonin-induced enhancement of the efficacy and reduced toxicity of chemo- and radiotherapy in cancer patients.

BACKGROUND: The presence of a cardiovascular implantable electronic device has long been a contraindication for the performance of magnetic resonance imaging (MRI). We established a prospective registry to determine the risks associated with MRI at a magnetic field strength of 1.5 tesla for patients who had a pacemaker or implantable cardioverter-defibrillator (ICD) that was "non-MRI-conditional" (i.e., not approved by the Food and Drug Administration for MRI scanning). METHODS: Patients in the registry were referred for clinically indicated nonthoracic MRI at a field strength of 1.5 tesla. Devices were interrogated before and after MRI with the use of a standardized protocol and were appropriately reprogrammed before the scanning. The primary end points were death, generator or lead failure, induced arrhythmia, loss of capture, or electrical reset during the scanning. The secondary end points were changes in device settings. RESULTS: MRI was performed in 1000 cases in which patients had a pacemaker and in 500 cases in which patients had an ICD. No deaths, lead failures, losses of capture, or ventricular arrhythmias occurred during MRI. One ICD generator could not be interrogated after MRI and required immediate replacement; the device had not been appropriately programmed per protocol before the MRI. We observed six cases of self-terminating atrial fibrillation or flutter and six cases of partial electrical reset. Changes in lead impedance, pacing threshold, battery voltage, and P-wave and R-wave amplitude exceeded prespecified thresholds in a small number of cases. Repeat MRI was not associated with an increase in adverse events. CONCLUSIONS: In this study, device or lead failure did not occur in any patient with a non-MRI-conditional pacemaker or ICD who underwent clinically indicated nonthoracic MRI at 1.5 tesla, was appropriately screened, and had the device reprogrammed in accordance with the prespecified protocol. (Funded by St. Jude Medical and others; MagnaSafe ClinicalTrials.gov number, NCT00907361 .).

Light, including artificial light, has a range of effects on human physiology and behavior and can therefore alter human physiology when inappropriately timed. One example of potential light-induced disruption is the effect of light on circadian organization, including the production of several hormone rhythms. Changes in light-dark exposure (e.g., by nonday occupation or transmeridian travel) shift the timing of the circadian system such that internal rhythms can become desynchronized from both the external environment and internally with each other, impairing our ability to sleep and wake at the appropriate times and compromising physiologic and metabolic processes. Light can also have direct acute effects on neuroendocrine systems, for example, in suppressing melatonin synthesis or elevating cortisol production that may have untoward long-term consequences. For these reasons, the National Institute of Environmental Health Sciences convened a workshop of a diverse group of scientists to consider how best to conduct research on possible connections between lighting and health. According to the participants in the workshop, there are three broad areas of research effort that need to be addressed. First are the basic biophysical and molecular genetic mechanisms for phototransduction for circadian, neuroendocrine, and neurobehavioral regulation. Second are the possible physiologic consequences of disrupting these circadian regulatory processes such as on hormone production, particularly melatonin, and normal and neoplastic tissue growth dynamics. Third are effects of light-induced physiologic disruption on disease occurrence and prognosis, and how prevention and treatment could be improved by application of this knowledge.

The binding of labeled free amino acids to liver and to purified protein by commonly used fixatives was investigated. Glutaraldehyde caused 25% of free leucine to be bound to serum albumin in solution, whereas formaldehyde bound only 0.5%. Liver slices were incubated for 2 min in the presence of labeled leucine and of puromycin, which permits absorption of leucine into the cell but inhibits incorporation into protein. Both counting and radioautographic techniques showed that glutaraldehyde bound 30 times, and osmic acid six times, as much free amino acid as did formaldehyde. By comparing liver slices incubated with and without puromycin for 2 min, it was calculated that in radioautographs prepared after fixation with glutaraldehyde, osmic acid, or formaldehyde 63, 25, and 4% respectively of the grains were due to binding of free amino acid. Formaldehyde, freshly prepared from paraformaldehyde, gives good preservation and is the recommended fixative for radioautography. When levels of free substrate in a tissue are high at the time fixative is added, the amount of binding of free substrate induced by the fixative should be included as a control in radioautographic experiments.

Few well-controlled diet studies have investigated the effects of reducing dietary saturated fatty acid (SFA) intake in premenopausal and postmenopausal women or in blacks. We conducted a multicenter, randomized, crossover-design trial of the effects of reducing dietary SFA on plasma lipids and lipoproteins in 103 healthy adults 22 to 67 years old. There were 46 men and 57 women, of whom 26 were black, 18 were postmenopausal women, and 16 were men > or =40 years old. All meals and snacks, except Saturday dinner, were prepared and served by the research centers. The study was designed to compare three diets: an average American diet (AAD), a Step 1 diet, and a low-SFA (Low-Sat) diet. Dietary cholesterol was constant. Diet composition was validated and monitored by a central laboratory. Each diet was consumed for 8 weeks, and blood samples were obtained during weeks 5 through 8. The compositions of the three diets were as follows: AAD, 34.3% kcal fat and 15.0% kcal SFA; Step 1, 28.6% kcal fat and 9.0% kcal SFA; and Low-Sat, 25.3% kcal fat and 6.1% kcal SFA. Each diet provided approximately 275 mg cholesterol/d. Compared with AAD, plasma total cholesterol in the whole group fell 5% on Step 1 and 9% on Low-Sat. LDL cholesterol was 7% lower on Step 1 and 11% lower on Low-Sat than on the AAD (both P<.01). Similar responses were seen in each subgroup. HDL cholesterol fell 7% on Step 1 and 11% on Low-Sat (both P<.01). Reductions in HDL cholesterol were seen in all subgroups except blacks and older men. Plasma triglyceride levels increased approximately 9% between AAD and Step 1 but did not increase further from Step 1 to Low-Sat. Changes in triglyceride levels were not significant in most subgroups. Surprisingly, plasma Lp(a) concentrations increased in a stepwise fashion as SFA was reduced. In a well-controlled feeding study, stepwise reductions in SFA resulted in parallel reductions in plasma total and LDL cholesterol levels. Diet effects were remarkably similar in several subgroups of men and women and in blacks. The reductions in total and LDL cholesterol achieved in these different subgroups indicate that diet can have a significant impact on risk for atherosclerotic cardiovascular disease in the total population.

The outcome of flourishing and its predictors have not been well documented among US children, especially those who face adversity. Using data for 2016 and 2017 from the National Survey of Children's Health, we determined the prevalence and predictors of flourishing among US children ages 6-17. A three-item index included indicators of flourishing: children's interest and curiosity in learning new things, persistence in completing tasks, and capacity to regulate emotions. The national prevalence of flourishing was 40.3 percent (29.9-45.0 percent across states). At each level of adverse childhood experiences, household income, and special health care needs, the prevalence of flourishing increased in a graded fashion with increasing levels of family resilience and connection. Across the sectors of health care, education, and human services, evidence-based programs and policies to increase family resilience and connection could increase flourishing in US children, even as society addresses remediable causes of childhood adversity.

OVER a period of ten years the laboratory responsible for the identification of miscellaneous types of bacteria at the Communicable Disease Center received 63 strains of Actinobacillus actinomycetemcomitans and 83 strains of Haemophilus aphrophilus. The cultural and serologic studies of 67 of these strains have been the subject of a previous report.1 These organisms are seldom encountered and infrequently identified even when isolated. Although seemingly unrelated by generic designation, they are in fact closely related and frequently confused. It is unlikely that any physician would be able to collect a comparable number of cases of either infection to report. For . . .

Abstract A 24-residue peptide, called the fragment, has been isolated from a peptic digest of bovine serum albumin. This peptide has the same terminal sequence, Asp-Thr-, as does bovine serum albumin, and will similarly bind a single ion of copper(II) at its terminal α-amino group. Spectral and titrimetric data are reported which suggest that the Cu(II)-binding site for both albumin and peptide is a chelate locus involving multiple nitrogenous ligands in the neutral pH range. Addition of copper(II) to the peptide decreases the slope of its titration curve in the pH range, 6 to 7, and decreases its catalytic effect on the hydrolysis of p-nitrophenyl acetate. These effects lead to the proposal that a histidyl residue occupies position 3 in the peptide chain and that the unique binding site for Cu(II) in both the Asp fragment and intact albumin is the amino-terminal sequence, Asp-Thr-His-. The bulk of the albumin molecule has relatively little influence on the properties of this site.

1.The incorporation of CY-leucine into serum albumin from various fractions of rat liver cells is reported as a function of time after leucine injection in vivo.

The growth of rat hepatoma 7288CTC in vivo is stimulated by the uptake of linoleic acid (LA) and its metabolism to 13-hydroxyoctadecadienoic acid (13-HODE), an important mitogenic signaling molecule within this tumor. Conversely, the growth of a variety of experimental cancers in vivo is inhibited by either physiological or pharmacological levels of the pineal gland hormone melatonin, although the mechanism(s) are unknown. We tested the hypothesis that the mechanism of melatonin's anticancer action in vivo involves the inhibition of tumor LA uptake and metabolism to 13-HODE in hepatoma 7288CTC. Tumor uptake of LA and release of 13-HODE, measured in tissue-isolated rat hepatoma 7288CTC at 4-h intervals over a 24-h period, were highest during the light phase and lowest during the mid-dark phase, when plasma melatonin levels were lowest and highest, respectively. Pinealectomy eliminated this rhythm of tumor LA uptake and 13-HODE production, indicating that it was driven by the circadian melatonin rhythm. Perfusion of tissue-isolated tumors in situ with melatonin (1 nM) rapidly and reversibly inhibited the uptake of plasma fatty acids (FAs), including LA, and its metabolism to 13-HODE. These inhibitory effects of melatonin on tumor FA uptake and 13-HODE release were completely reversed by perfusion of tumors in situ with melatonin receptor antagonist S-20928, pertussis toxin, forskolin, or 8-bromo-cAMP. Perfusion of tumors in situ with melatonin also decreased tumor [3H]thymidine incorporation and DNA content; these effects on DNA synthesis were also prevented by the coperfusion of tumors with melatonin and S-20928, pertussis toxin, forskolin, 8-Br-cAMP, or 13-HODE. Pinealectomy stimulated tumor growth, LA uptake and metabolism to 13-HODE, and FA storage in hepatoma 7288CTC, whereas melatonin administration (200 microg/day) was inhibitory in vivo. Northern blot analysis revealed that, compared with normal liver tissue, hepatoma 7288CTC overexpressed mRNA transcripts for a plasma membrane-associated FA transport protein (FATP). FATP mRNA expression was unaffected by the treatment of tumor-bearing rats with daily afternoon melatonin injections or exposure to constant light. These results support a novel mechanism of tumor growth inhibition by melatonin involving a melatonin receptor-mediated suppression of cAMP levels, resulting in diminished tumor FA transport, possibly via decreased FATP function. The inhibition of these signal transduction events by melatonin culminates in the suppression of LA uptake, LA metabolism to the mitogenic signaling molecule 13-HODE, and cancer growth.

This study determined the incidence and concentration of methane-producing bacteria in tap water enema samples of 130 individuals taken before sigmoidoscopy. The number of subjects classified in five major colonic groups were as follows: normal colon 36, diverticulosis 57, inflammatory bowel disease 11, colon polyps 34, and colon cancer 11. Some patients were placed in more than one category. Ninety four of the subjects or 72% had methanogenic bacteria ranging in concentration from 6 to about 3 X 10(10)/g dry weight of faeces. The predominant methanogen in all groups was Methanobrevibacter smithii. Chi-square analysis showed that the incidence of methanogens in concentrations of 10(7)/g dry weight of faeces or greater in patients with diverticulosis (58%) was significantly greater than in normal patients (25%). High methanogen concentrations are associated with excretion of methane in the breath.

Incidence of and risk factors for aminoglycoside-associated nephrotoxicity (AAN) were evaluated in 1489 patients prospectively monitored with individualized pharmacokinetic monitoring (IPM). Incidence of AAN was 7.9% with individual (univariate) risk factors including advanced age, decreased albumin, poor nutritional status, pneumonia, concurrent furosemide, amphotericin B, vancomycin, cephalosporin, or piperacillin, intensive care unit treatment, leukemia, rapidly fatal illness, liver or renal disease, reduced aminoglycoside clearance, elevated initial steady-state trough concentration (Cminss), volume of distribution or half-life, duration of therapy, total dose, fever, male gender, shock, pleural effusion, and ascites. Multiple logistic regression revealed that Cminss, concurrent clindamycin, vancomycin, piperacillin, or cephalosporin, ascites, advanced age, male gender, decreased albumin, duration of therapy, and leukemia were significant independent risk factors for AAN. Positive predictive value of the model was 30.8%; negative predictive value was 91.7%. No identifiable risk factor alone or in combination was of sufficient sensitivity to reliably predict AAN, but use of IPM may lower the incidence of AAN.

Background: The aim of this meta-analysis was to assess the risks and incidence of nephrotoxicity and electrolyte abnormalities in patients receiving programmed cell death protein 1 (PD-1) inhibitors. Methods: We conducted a meta-analysis of clinical trials that monitored electrolyte levels and kidney functions during treatment with nivolumab or pembrolizumab by searching MEDLINE, EMBASE and the Cochrane Database from inception through April 2017. Our protocol is registered with International Prospective Register of Systematic Reviews; no.CRD42017060579. Results: A total of 48 clinical trials with a total of 11 482 patients were included. The overall pooled risk ratios (RR) of all acute kidney injury (AKI) and all electrolyte abnormalities in patients treated with PD-1 inhibitors were 1.86 [95% confidence interval (CI) 0.95-3.64] and 1.67 (95% CI 0.89-3.12), respectively. Compared with non-nephrotoxic controls, the pooled RR of AKI in patients treated with PD-1 inhibitors was 4.19 (95% CI 1.57-11.18). Prespecified subgroup analyses demonstrated a significant association between PD-1 inhibitors and hypocalcemia with a pooled RR of 10.87 (95% CI 1.40-84.16). The pooled estimated incidence rates of AKI and hypocalcemia in patients treated with PD-1 inhibitors were 2.2% (95% CI 1.5-3.0%) and 1.0% (95% CI 0.6-1.8%), respectively. Among patients who developed AKI with PD-1 inhibitors, the pooled estimated rate of interstitial nephritis was 16.6% (95% CI 10.2-26.0%). Conclusions: Treatment with PD-1 inhibitors is associated with a higher risk of AKI compared with non-nephrotoxic agents. It will be important to characterize the AKI patients to better understand the etiology behind the event. In addition, treatment with PD-1 inhibitors is associated with an increased risk of hypocalcemia. This study highlights a rare but serious adverse event of anti-PD-1 antibodies and we recommend, in addition to electrolytes panel, routine calcium monitoring.

Abstract The effects of protein depletion and repletion on the rate of albumin synthesis and on the levels of albumin in hepatic subcellular particles were measured in intact rats. A second serum protein of hepatic origin, transferrin, was measured simultaneously for comparison. A method capable of assaying albumin synthesis within a 16-min interval was developed in order to permit detection of rapid changes in rates of synthesis; in this procedure the total 14C-albumin content of intrahepatic albumin was divided by the integrated specific radioactivity of intrahepatic free 14C-l-leucine from the time of injection to the time of measurement. This method gave good agreement with measurements based on the circulating 14C-albumin at 2 hours after injection of the tracer. A 10-day period of protein depletion caused a 60 to 70% fall in rate of both albumin and transferrin synthesis, and a 40% fall in the quantities of these proteins bound in hepatic microsomes. Upon refeeding a complete mixture of amino acids by gavage, the level of microsomal albumin increased detectably within 15 min, and the rates of albumin and transferrin synthesis rose 50% within 30 min. This response was not inhibited by actinomycin D. These observations demonstrate the close control of albumin and transferrin synthesis by the amino acid supply in vivo. The amount of albumin in the intracellular albumin pool was observed to reach its normal level even before the circulating albumin level was restored, signifying that hypoalbuminemia can elicit increased synthesis without maintaining a decrease in the intracellular pool.

Abstract The incorporation of l-[14C]leucine was measured during a 16-min time interval in rats under various physiological conditions. Rates of albumin and liver protein formation in control rats 5 to 7 weeks of age were 3.13 and 28.8 mg/100 g of body weight per hour, respectively. The half-time of replacement of liver protein was 18 hours, appreciably faster than half-times obtained from measurements of catabolism of labeled liver protein. When synthesis of protein was inhibited by cycloheximide, loss of albumin from hepatic microsomal particles continued at its previously existing rate until the cells were nearly depleted of albumin. Rates of secretion measured in this manner were 0.34 and 0.74 mg per g of liver per hour in adult rats and young nephrotic rats, respectively; corresponding rates of synthesis determined with [14C]leucine were 0.34 and 0.77 mg per g of liver per hour. The agreement between the results obtained with these independent techniques adds some confidence to the use of the [14C]leucine method. The rate of albumin synthesis was unchanged when measured at 10 p.m. compared to 10 a.m. in rats on a 12-hour light-dark cycle. Fasting for 18 hours caused a 40% reduction. In adult rats the rate of albumin synthesis was 34% and that of liver protein 52% of the rates in control rats. No significant increase in albumin synthesis was detected in the presence of nephrosis caused by puromycin aminonucleoside, even when a supplement of protein plus hydrocortisone was given. The dynamics of the transport of albumin and its release from the cytoplasmic particles were similar in all of the conditions studied. The amount of albumin in hepatic microsomes, however, varied directly with the rate of albumin production over a 4-fold range. It is suggested that the stimulus for increased secretion is a small increase in the quantity of albumin in the microsomal particles.

To determine whether high prepregnant body mass index (BMI) is associated with later onset of lactogenesis II (LGII) and shorter duration of breastfeeding, we questioned 151 women about their demographic and psychosocial characteristics during pregnancy and about the onset of LGII during days 1 to 5 postpartum. Compared to women with earlier (< 72 hours) onset of LGII, those with later onset had a higher BMI (P < .05), a higher proportion of primiparity (P < .01), and a lower infant score on the Mother-Baby Assessment (P < .05). Prepregnant BMI (P < .04) and primiparity (P < .005) were each associated with later onset of LGII, but only primiparity remained significant when both factors were considered simultaneously. These results suggest that, in addition to those who have just delivered their first infant, those with higher prepregnant BMI values also warrant extra support to decrease their risk of early discontinuation of breastfeeding.