David Gitlin

The turnover of amniotic fluid protein in the human conceptus

Abstract The amniotic fluid turnover of specific plasma proteins and protein hormones was studied in 19 pregnant women at 34 to 40 weeks of gestation. Seventeen of the women had normal pregnancies; of these, 6 were in labor during the study, and 11 were not. In the 2 remaining women, the fetuses were dead. Purified human serum albumin, serum γG, serum γA, chorionic gonadotropin, and growth hormone were labeled with either 131 I or 125 I, and the labeled proteins were then injected intra-amniotically singly or in pairs. Aliquots of amniotic fluid were obtained before the injection, 15 minutes after the injection, and at irregular intervals thereafter during the study period which lasted from 3½ hours to 13 days. Maternal and neonatal sera and urines were also obtained. All fluids were assayed for labeled protein as well as endogenous serum albumin, transferrin, γG, and γA. It was found that: (1) all 5 labeled proteins were cleared from amniotic fluid at similar rates, despite the marked differences in the molecular weights and metabolic functions of these proteins; (2) on the average, two thirds or more of the amniotic fluid volume was cleared of protein per day in the presence of a living fetus, over 80 per cent of this apparently by fetal swallowing, and the daily clearance of amniotic fluid averaged 342 ml. in the absence of labor and 554 ml. during labor, or 0.24 and 0.30 Gm. of amniotic fluid protein per kilogram of fetal weight, respectively; (3) fetal urine was the apparent source of a large fraction of the γG found in amniotic fluid, but fetal urine contributed less than 5 per cent of the albumin, less than 2 per cent of the transferrin, and little or none of the γA present in amniotic fluid; (4) amniotic fluid volume could change markedly in a matter of days—over a period of 5 days, it doubled in one normal patient and fell to half in another; (5) the volume of amniotic fluid swallowed by the fetus tended to vary directly with the volume of fluid in the amniotic cavity, a relation which, among other things, would serve to stabilize amniotic fluid volume.

Patient- and Practice-Related Determinants of Emergency Department Length of Stay for Patients With Psychiatric Illness

STUDY OBJECTIVE To identify patient and clinical management factors related to emergency department (ED) length of stay for psychiatric patients. METHODS This was a prospective study of 1,092 adults treated at one of 5 EDs between June 2008 and May 2009. Regression analyses were used to identify factors associated with ED length of stay and its 4 subcomponents. Secondary analyses considered patients discharged to home and those who were admitted or transferred separately. RESULTS The overall mean ED length of stay was 11.5 hours (median 8.2 hours). ED length of stay varied by discharge disposition, with patients discharged to home staying 8.6 hours (95% confidence interval 7.7 to 9.5 hours) and patients transferred to a hospital outside the system of care staying 15 hours (95% confidence interval 12.7 to 17.6 hours) on average. Older age and being uninsured were associated with increased ED length of stay, whereas race, sex, and homelessness had no association. Patients with a positive toxicology screen result for alcohol stayed an average of 6.2 hours longer than patients without toxicology screens, an effect observed primarily in the periods before disposition decision. Diagnostic imaging was associated with an average 3.2-hour greater length of stay, prolonging both early and late components of the ED stay. Restraint use had a similar effect, leading to a length of stay 4.2 hours longer than that of patients not requiring restraints. CONCLUSION Psychiatric patients spent more than 11 hours in the ED on average when seeking care. The need for hospitalization, restraint use, and the completion of diagnostic imaging had the greatest effect on postassessment boarding time, whereas the presence of alcohol on toxicology screening led to delays earlier in the ED stay. Identification and sharing of best practices associated with each of these factors would provide an opportunity for improvement in ED care for this population.

MULTIPLE SERUM PROTEIN DEFICIENCIES IN CONGENITAL AND ACQUIRED AGAMMAGLOBULINEMIA

The absence of serum y-globulins in patients afflicted with severe recurring bacterial infections has been reported (1, 2). Three forms of this metabolic disturbance, agammaglobulinemia, have been described (3): 1) a physiologic or transient form occurring in infants, 2) a congenital form which is inherited as a sex-linked recessive characteristic occurring in males, and 3) an acquired form, occurring in both sexes, with the onset of infections in adolescence or adulthood. The congenital and acquired forms of the disease are due to an absence of plasma cells in the tissues of these patients (3-5) with a consequent deficiency of y-globulin and failure of antibody synthesis (4); the plasma cells appear to be the site of antibody synthesis (6). Unlike the transient form, the failure of y-globulin synthesis in the congenital and acquired groups, once established, seems to be permanent. Using rabbit and horse antisera against human y-globulin in the quantitative precipitin reaction, it had been demonstrated that the failure of y-globulin synthesis in these patients was usually not complete and that small amounts of y-globulin were often present in their sera, less than 25 mg. per cent in the congenital form and less than 100 mg. per cent in the acquired form (3). In this report, it will be shown that at least two other plasma proteins in addition to y-globulin are either absent or markedly deficient in these two forms of the disease.

Hospital Variability in Emergency Department Length of Stay for Adult Patients Receiving Psychiatric Consultation: A Prospective Study

STUDY OBJECTIVE We ascertain the components of emergency department (ED) length of stay for adult patients receiving psychiatric evaluation and to examine their variability across 5 hospitals within a health care system. METHODS This was a prospective study of 1,092 adults treated between June 2008 and May 2009. Research staff abstracted length of stay and clinical information from the medical records. Clinicians completed a time log for each patient contact. Main outcomes were median times for the overall ED length of stay and its 4 components, or time from triage to request for psychiatric evaluation, request to start of psychiatric evaluation, start to completion of psychiatric evaluation with a disposition decision, and disposition decision to discharge from the ED. RESULTS The overall median length of stay was more than 8 hours. Median times for the components were 1.8 hours from triage to request, 15 minutes from request to start of psychiatric evaluation, 75 minutes from start of psychiatric evaluation to disposition decision, and nearly 3 hours from disposition decision to ED discharge. The median disposition decision to discharge time was substantially shorter for patients who went home (40 minutes) than for patients who were admitted (2.5 hours) or transferred for psychiatric admission at other facilities (6.3 hours). When adjustments for patient and clinical factors were made, differences in ED length of stay persisted between hospitals. CONCLUSION ED length of stay for psychiatric patients varied greatly between hospitals, highlighting differences in the organization of psychiatric services and inpatient bed availability. Findings may not generalize to other settings or populations.

Protein Binding by Specific Receptors on Human Placenta, Murine Placenta, and Suckling Murine Intestine in Relation to Protein Transport across These Tissues

Human, rat, and mouse placentas and rat and mouse intestines were homogenized in buffered saline, and fraction consisting primarily of cell membranes was separated from each of the homogenates by differential centrifugation. Human, bovine, and guinea pig IgG, and human IgE, Bence-Jones protein, serum albumin, insulin, and growth hormone were labeled with (131)I or (125)I, and the binding of these proteins by the cell membrane fractions was investigated. Rat and mouse sucklings were given labeled proteins intragastrically, and the amount of each protein absorbed after a given interval of time was determined. It was found that the degree and specificity of protein binding by the cell membrane fractions from human and murine placentas strikingly paralleled the relative rate and specificity of protein transport from mother to fetus in the respective species at or near term. Similarly, the degree and specificity of protein binding by the cell membrane fractions from suckling rat and mouse intestines tended to parallel the rate and specificity of protein absorption from the gastrointestinal tract in these animals. However, some discordance between protein binding and protein transport was also observed. The data suggest that: (a) the binding of a protein by specific receptors on cell membranes may be a necessary first step in the transcellular transport of the protein; (b) specific protein binding by cell receptors does not ensure the transport of that protein across the tissue barrier; and (c) specific transport mechanisms other than or in addition to specific cell membrane receptors are involved in the active transport of proteins across the human or murine placenta or the suckling murine intestine.

Cellular distribution of serum alpha-foetoprotein in organs of the fetal rat.

THE mammalian foetus synthesizes a serum α-globulin, called α-foetoprotein, which is not found in the adult of the species1–7. Although interspecies structural differences among the α-foetoproteins have been noted4–7, the protein of each species appears to be a homologue of foetuin, or bovine α-foetoprotein5,7. Synthesis of serum α-foetoprotein has been shown to occur in the liver in both the rat foetus8,9 and the human embryo9, and in the yolk sac of the rat9. The cells responsible for this synthesis are not known, however, and it has been suggested that the haematopoietic tissue of the liver may be the site of synthesis8. In the present investigation, the cellular distribution of α-foetoprotein in organs of the rat foetus was investigated by means of the fluorescent antibody method.

X-rays Affect the Incorporation of 5-Iododeoxyuridine into Deoxyribonucleic Acid

When labeled with iodine-131, 5-iododeoxyuridine, an analogue of thymidine, is useful in estimating the effect of x-radiation on deoxyribonucleic acid metabolism. Although this compound is readily incorporated into deoxyribonucleic acid in the absence of ionizing radiation, we find that whole-body exposure to as little as 10 r will significantly inhibit its incorporation.

On the mechanisms of maternofetal transfer of human albumin and γG globulin in the mouse

Abstract Human serum albumin and human γG globulin were labeled with 131I, and the labeled proteins were then mixed with different amounts of the respective unlabeled protein. These mixtures were injected intravenously into pregnant mice near term, and the amounts of protein-bound radioactivity present in the fetuses and in maternal serum 24 hr later were determined. The concentration of human albumin found in the fetus was proportional to the maternal serum concentration of this protein over the maternal range studied, from 0.03 to 935 mg/100 ml. On the other hand, the fetal concentration of human γG first increased rapidly as the maternal concentration increased to approximately 200 mg/100 ml and then decreased as the maternal concentration continued to increase above this level; however, as the maternal human γG level increased above approximately 1100 mg/100 ml, the fetal concentration again increased and became proportional to the maternal concentration. The data suggest that maternofetal transfer of human γG in the mouse may be mediated by two processess; one of these, as with the transfer of human albumin, appears to be first order in relation to the maternal serum concentration, and the other appears to be consistent with a carrier or enzymatic process that is directly or indirectly inhibited at high maternal serum levels.

DISTRIBUTION DYNAMICS OF CIRCULATING AND EXTRAVASCULAR I131 PLASMA PROTEINS

The use of radioiodine, specificaliy of 1131, as a label Tor plasma proteins has provided a tool for the study of plasina protein metabolisni that for the following 5 reasons is unique: ( i ) the label is relatively inexpensive; (2) it is easily incorporated into a plasma protein that has been isolatcd and purified independently ; ( 3 ) it can be given safely to human beiiigs ; (4) the labeled protein behaves and is handled by the body in a manner inclistitiguishable froin that of the hative protein, at least up to the process of degradation; and ( 5 ) here the departure of behavior from tliat of the iiative protein is likewise advantageous, since the labeled products of degradation are not reincorporated, but are excreted. Moreover, Ils1 labeling can be used in conjunction with another tool that has proved very useful in the study of the metabolisni of plasma proteins ; naniely, itnmunocliernistry. Witli suitable antisera, specific plasma proteins may be estimated easily and accurately, supplenienting the quantitative data obtained with P1 tracers. This paper is a discussion of sonie aspects of the metabolisni of plasma proteins that have been studied throiigh a comhination of iininunochemistry and labeling of specific plasma proteins.

Maternofoetal transfer of gamma G immunoglobulins.

BRAMBELL has suggested that the mechanisms which underlie the transmission of antibodies and other plasma proteins from mother to foetus are similar to those which operate in the catabolism of these proteins1. This concept was supported by the observation that maternofoetal transfer of homologous and heterologous γG globulins in the rabbit decreased with the half lives of these proteins1; the species order of decreasing maternofoetal transmission2 arid decreasing half life3 in the rabbit was rabbit > man > ginea-pig > horse > bovine. In this study, the maternofoetal transfer of γG globulin was examined in the mouse, rat and guinea-pig.