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Background: Femoral shaft fractures in children are common in low and middle income countries. In high-income countries, patient age, fracture pattern, associated injuries, child/family socioeconomic status, and surgeon preference dictate fracture management. There is limited literature on treatment patterns for pediatric femur fractures in resource-limited settings. This study surveys surgeons from low (LIC), lower-middle (LMIC), and upper-middle income (UMIC) countries regarding treatment patterns for pediatric femur fractures., Methods: Surgeons completed an electronic survey reporting surgeon demographics and treatment preference for pediatric femur fractures. Treatment preferences and indications for treatment were separated into 4 groups: infant (0 to 6 mo); toddler (7 mo to 4 y); child (5 to 12 y); adolescent (12 to 17 y). The survey was available in English, Spanish, and French. Analysis was completed with t test and χ test for continuous and categorical variables, respectively, and weighted Pearson correlation (P<0.05)., Results: Survey respondents consisted of 413 surgeons from 83 countries (20 LIC, 33 LMIC, 30 UMIC). The majority of respondents were fellowship trained (83%) most commonly in pediatrics (26%) and trauma (43%). Most treated >10 pediatric femur fractures per year (68%). Respondents reported treating infant femur fractures nonoperatively using Pavlik harness (19%), spica cast (60%), or traction with delayed spica cast (14%). Decreasing socioeconomic status was associated with higher nonoperative treatment rate in toddlers, children, and adolescents. Respondents commonly utilize bed rest and traction for child femur fractures in LICs (63%) and LMICs (65%) compared with UMICs (35%) (UMIC vs. LMIC P<0.001; UMIC vs. LIC P<0.001). Surgeries in children more commonly involve open reduction with internal fixation (UMIC 19%, LMIC 33%, LIC 40%; P<0.05 between UMIC-LMIC and UMIC-LIC)., Conclusion: This is one of the largest surveys describing treatment patterns for pediatric femur fractures in low and middle income countries. Differences are evident including lower operative treatment rate in younger children and lower intramedullary fixation rates in older children. Future studies should investigate the value of treatment options in resource-limited settings., Level of Evidence: Level II-prospective comparative study.

Study Design: Retrospective cohort study., Objective: Evaluate the effects of parity (number of births) on measures of sagittal posture in elderly women. The long-term objective of this study is to identify and mitigate factors contributing to age-related postural deformity in older adults., Summary of Background Data: Adult spinal deformity is a prevalent condition that often requires costly surgical management. Females are disproportionately represented in spinal deformity surgical cases with up to 90% of patients being women. The potential contributions of pregnancy on postural degeneration have only begun to be acknowledged and require further study., Methods: Two hundred eight women with standing lateral radiographs were selected from the TwinsUK register. Parity information was extracted from questionnaires. Sagittal balance measurements (thoracic kyphosis, lumbar lordosis [LL], pelvic incidence [PI]) were collected and PI-LL mismatch was calculated. One-way analysis of variance tests were done between three separate age categories for measures of sagittal balance and parity and stepwise multivariate regression was done for PI-LL., Results: Both age and PI-LL mismatch significantly differed between parity categories. PI-LL was on average 7.0° ± 2.5° greater in multiparous (3+ births) subjects than in nulliparous subjects (P < 0.01). Parity did not have an independent relationship with lumbar disc degeneration, lumbar bone mineral density, or any of the individual sagittal balance parameters (P > 0.05 for all), except for PI-LL. From a subanalysis of the effect of parity on sagittal alignment within twin pairs, we found that within pair differences in parity associate with within pair differences in thoracic kyphosis., Conclusion: This study established correlations between measures of spinal curvature in older women and parity for the first time. Longitudinal research is required to establish a causative relationship., Level of Evidence: 4.

Background: Low-cost motion analysis systems (LCMASs) have emerged as easy and practical methods to measure the functional workspace (FWS). Thus, we ventured to apply an LCMAS, the Kinect2 gaming camera, to evaluate the FWS in patients with shoulder osteoarthritis (OA) and patients who underwent total shoulder arthroplasty (TSA) or reverse total shoulder arthroplasty (RTSA)., Methods: A cross-sectional study of participants with OA (n = 53), TSA (n = 70), and RTSA (n = 34) was performed. The FWS as measured by an LCMAS, the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form score, and the Patient-Reported Outcomes Measurement Information System (PROMIS) score were collected. For participants who underwent TSA or RTSA, the FWS was evaluated at 6, 12, and 24 months postoperatively. The correlation of the FWS with the ASES score and PROMIS score was determined. Significance was set at P < .05., Results: Patients who underwent TSA or RTSA had a significantly higher FWS than patients with shoulder OA at almost all time points. Patients who underwent TSA had a significantly higher FWS than patients who underwent RTSA at 24 months after surgery. PROMIS and ASES scores showed strong correlations with the FWS in patients who underwent TSA (R = 0.75 [P < .001] and R = 0.83 [P < .001], respectively) and RTSA (R = 0.84 [P < .001] and R = 0.73 [P < .001], respectively)., Conclusion: The FWS measured by an LCMAS is an easy and low-cost method to quantify the reachable space of the hand in patients and shows strong correlations with patient-reported outcome measures. This may be a useful tool to assess upper-extremity range of motion before and after shoulder arthroplasty., (Copyright © 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Clinical assessment of thumb motion is challenging, due to the complex anatomy and motion of the thumb. It is especially difficult to measure hand movement during activity, and to measure the effects of surgery that changes the morphology of the thumb. A three-dimensional model of the hand may enable clinicians to better assess prehension and thumb motion at baseline, and following surgical intervention., Methods: A kinematic model of the hand was developed to measure thumb and finger position during functional tasks, enabling the calculation of the volume of space in which prehension could occur. This method was validated by application to a mechanical model of the hand, and then applied to ten adult participants, using three-dimensional motion analysis with a marker array developed for the purpose of this study., Findings: This method can be used to accurately measure three-dimensional thumb joint range of motion (RoM) and predicted functional workspace during functional activities. The thumb carpometacarpal joint was predominantly responsible for thumb position during functional tasks. Predicted functional workspace is proportional to hand morphometric measurements., Interpretation: A kinematic model of the hand measures thumb RoM and predicts functional workspace during functional activities., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: To compare bipolar bone loss by evaluating the degree of glenoid bone loss, Hill-Sachs lesion size, and glenoid track in adolescents and adults with shoulder dislocations., Methods: We performed a retrospective review between 2012 and 2016 of surgical and nonsurgical patients with a history of anterior shoulder dislocations (primary or recurrent) who underwent magnetic resonance imaging of the affected shoulder. The exclusion criteria included multidirectional instability, prior surgery, and posterior dislocation. Patients were grouped into 2 groups: adolescents (aged 10-19 years) and adults (aged ≥20 years). The groups were compared regarding measures of glenoid bone loss (best-fit circle technique) and Hill-Sachs lesion size (medial margin of rotator cuff footprint to medial margin of Hill-Sachs lesion). If the medial margin of a Hill-Sachs lesion was within the glenoid track, it was defined as on track; if it was more medial than the glenoid track, it was defined as off track., Results: We identified 45 adolescents (mean age, 16.1 years) and 30 adults (mean age, 28.9 years) with anterior shoulder dislocations. There was no significant difference in percentage of bone loss between adolescents (mean, 8.4%) and adults (mean, 9.9%; P = .23). There was no significant difference in Hill-Sachs lesion size between adolescents (mean, 12.7 mm) and adults (mean, 9.9 mm; P = .12). There were 12 patients with off-track lesions. Off-track lesions were present in 11 of 45 adolescents (24.4%) and 1 of 30 adults (3.3%). Adolescents had an increased risk of having an off-track lesion (odds ratio, 9.38; 95% confidence interval, 1.14-77.1). A subgroup analysis identified multiple dislocations as an independent risk factor for an off-track lesion (odds ratio, 4.15; 95% confidence interval, 0.85-20.23)., Conclusions: This study shows that adolescence and a history of multiple dislocations are independent risk factors for a greater likelihood of glenoid off-track lesions. The findings support the use of bipolar assessment of shoulder dislocators, especially in adolescents and multiple dislocators., Level of Evidence: Level III, retrospective comparative study., (Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: The magnetic mini-mover procedure (3MP) uses magnetic force to gradually remodel pectus excavatum deformity. A magnet is implanted on the sternum and coupled with an external magnetic brace. Under Investigational Device Exemption and Institutional Review Board approval, we performed a pilot study of safety, probable efficacy, and cost-effectiveness of this new treatment of an orphan disease using an implantable pediatric device., Methods: Ten otherwise healthy patients, ages 8 to 14 years, with severe pectus excavatum (pectus severity index [PSI] > 3.5) underwent 3MP treatment (mean, 18.8 ± 2.5 months). Safety was assessed by postimplant and postexplant electrocardiograms and monthly chest x-rays. Efficacy was assessed by change in pectus severity index as measured using pretreatment and posttreatment computed tomographic scan. Cost of 3MP was compared with that of standard procedures., Results: The 3MP device had no detectable ill effect. Device weld failure or malpositioning required revision in 5 patients. Average wear time was 16 h/d. Pectus severity index improved in patients in the early or mid puberty but not in patients with noncompliant chest walls. Average cost for 3MP was $46,859, compared with $81,206 and $81,022 for Nuss and Ravitch, respectively., Conclusion: The 3MP is a safe, cost-effective, outpatient alternative treatment for pectus excavatum that achieves good results for patients in early and midpuberty stages., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Previously we demonstrated the safety and patency of a magnetic compression anastomosis (magnamosis). We present the further development of this technique, with specific focus on optimizing device design for minimally invasive magnamosis., Study Design: The magnamosis device was designed to incorporate 3 features: 2 convex-concave radially symmetric halves that magnetically self-align, a central channel for immediate patency, and specially engineered radial topography of the mating surfaces to promote gradual remodeling. Each symmetrical half consists of a ring-shaped neodymium-iron-boron magnet encased in polycarbonate casing. Twenty-one young adult pigs underwent either magnetic gastrojejunostomy (n = 13) or jejunojejunostomy (n = 8). Animals were euthanized at 1, 2, 4, and 6 weeks after operation. Anastomoses were studied with contrast radiography, burst pressure, and histology., Results: Gastrojejunostomy: In all animals with successful placement of magnets, anastomoses were patent by contrast fluoroscopy, well healed by histologic examination, and showed excellent burst strength. Jejunojejunostomy: All animals had uneventful clinical courses, indicating that the magnamosis with immediate patency functioned properly without device dislodgement. At sacrifice, all magnamoses were patent, well healed by histology, and had burst strengths that equaled or exceeded that of traditional stapled anastomoses., Conclusions: Minimally invasive placement of a custom magnetic device in the stomach and jejunum allows intraluminal self-alignment and subsequent compression anastomosis over 3 to 10 days. The magnamosis is immediately patent and develops strength equal to or greater than that of hand-sewn or stapled anastomoses. Magnamosis is effective in the pig model, and may be a safe, effective, and minimally invasive alternative to current anastomotic strategies in humans., (Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The Magnetic Mini-Mover Procedure (3MP) uses a magnetic implant coupled with an external magnet to generate force sufficient to gradually remodel pectus excavatum deformities. This is an interim report of the evolution of the 3MP during a Food and Drug Administration-approved clinical trial., Methods: After obtaining Institutional Review Board approval, we performed the 3MP on 10 otherwise healthy patients with moderate to severe pectus excavatum deformities (age, 8-14 years; Haller index >3.5). Operative techniques evolved to improve ease of implantation. Patients were evaluated monthly by a pediatric surgeon and orthotist. Electrocardiograms were performed pre- and postoperatively. Sternal position was documented by pre- and postprocedure computed tomographic scan, interval chest x-ray, depth gauge, and interval photographs., Results: There was no detectable effect of the static magnetic field on wound healing or cardiopulmonary function. No detectable injuries and minimal skin changes resulted from brace wear. Operative techniques evolved to include a custom sternal punch and a flexible guide wire to guide the posterior plate into position behind the sternum, reducing outpatient operating time to one-half hour. In 9 patients, the procedure was performed as an outpatient basis; and 1 patient was observed overnight. Three patients required evacuation of retained pleural air postoperatively, and 2 required an outpatient revision. A custom-fitted orthotic brace (Magnatract) was extensively modified to increase user friendliness and functionality while incorporating several novel functions: a screw displacement mechanism so patients can easily self-adjust magnetic force, a miniature data logger to measure force and temperature data every 10 minutes, and an interactive online Web portal for remote patient evaluation. All attempts to quantitate sternal position (radiographic, fluid volume, and depth gauge) were inadequate. Visual assessment remains the best indicator., Conclusions: In this interim report, the 3MP appears to be a safe, minimally invasive, outpatient, cost-effective alternative treatment of pectus excavatum. Outcomes will be reported upon the completion of this phase II clinical trial., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study is to evaluate the effect of prenatal steroid treatment in fetuses with sonographically diagnosed congenital cystic adenomatoid malformations (CCAMs)., Methods: This was an institutional review board-approved retrospective review of 372 patients referred to the University of California, San Francisco (UCSF), for fetal CCAM. Inclusion criteria were (1) a predominately microcystic CCAM lesion sonographically diagnosed at our institution, (2) maternal administration of a single course of prenatal corticosteroids (betamethasone), and (3) no fetal surgery. CCAM volume-to-head ratio (CVR), presence of hydrops, mediastinal shift, and diaphragm eversion were assessed before and after administration of betamethasone. The primary end points were survival to birth and neonatal discharge., Results: Sixteen patients with predominantly microcystic CCAMs were treated with prenatal steroids. Three were excluded because of lack of follow-up information. All remaining fetuses (13/13) survived to delivery and 11/13 (84.6%) survived to neonatal discharge. At the time of steroid administration, all patients had CVR greater than 1.6, and 9 (69.2%) also had nonimmune hydrops fetalis. After a course of steroids, CVR decreased in 8 (61.5%) of the 13 patients, and hydrops resolved in 7 (77.8%) of the 9 patients with hydrops. The 2 patients whose hydrops did not resolve with steroid treatment did not survive to discharge., Conclusion: In high-risk fetal patients with predominantly microcystic CCAM lesions, betamethasone is an effective treatment. This series is a pilot study for a prospective randomized trial comparing treatment of CCAM with betamethasone to placebo., (Copyright 2010 Elsevier Inc. All rights reserved.)

Context: Self-myofascial release (SMR) is a technique used to treat myofascial restrictions and restore soft-tissue extensibility., Purpose: To determine whether the pressure and contact area on the lateral thigh differ between a Multilevel rigid roller (MRR) and a Bio-Foam roller (BFR) for participants performing SMR., Participants: Ten healthy young men and women., Methods: Participants performed an SMR technique on the lateral thigh using both myofascial rollers. Thin-film pressure sensels recorded pressure and contact area during each SMR trial., Results: Mean sensel pressure exerted on the soft tissue of the lateral thigh by the MRR (51.8 +/- 10.7 kPa) was significantly (P < .001) greater than that of the conventional BFR (33.4 +/- 6.4 kPa). Mean contact area of the MRR (47.0 +/- 16.1 cm2) was significantly (P < .005) less than that of the BFR (68.4 +/- 25.3 cm2)., Conclusion: The significantly higher pressure and isolated contact area with the MRR suggest a potential benefit in SMR.

The diarrhea observed in patients with cholera is known to be related to secretion of water and electrolytes into the intestinal lumen. However, the exact mechanisms involved in these secretory processes have remained unclear. Although it is clear that purified toxin acts on epithelial cell metabolism, its activity on Na+ transport across intestinal mucosa is equivocal: reported either to prevent net Na+ absorption or to cause net secretion of Na+ from serosa to mucosa. Since total transmural Na+ fluxes across "leaky" epithelia involve very significant movement via a paracellular shunt pathway, we studied the effects of cholera toxin on the cellular and paracellular pathways of Na+ movement. Unidirectional Na+ fluxes were examined as functions of applied potential in control tissues and in tissues from the same animal treated with purified cholera toxin. Treatment of rabbit ileum in vitro with toxin simulated the cellular component of serosa-to-mucosa Na+ flux (from 2.41 +/- 0.49 muequiv./h per cm2 under control conditions to 4.71 +/- 0.43 muequiv./h per cm2 after treatment with toxin, P less than 0.01). The effect of cholera toxin on Na+ movement through the cells from mucosa to serosa appeared to be insignificant. Finally, a marked decrease in the Na+ permeability (P less than 0.01) and no detectable significant changes in transference number for Na+ of the paracellular shunt pathway were observed following treatment with cholera toxin. These results provide direct evidence for the hypothesis that purified cholera toxin stimulates active sodium secretion but has minimal effect on sodium absorption.

Na and Cl fluxes and short-circuit current (Isc) in rabbit ileum have been studied as a function of ionic concentrations in HCO3-free solutions. Both net Na flux (JNanet) and Isc show similar saturation functions of [Na] at fixed [Cl]. They show no significant difference between zero and 112 mM Na but at 140 mM Na Isc is significantly greater than the JNanet. Net Cl transport, secretion, is observed only at 140 mM Na and is approximately equivalent to the difference between the Isc and JNanet. The transcellular mucosa-to-serosa Na fluxes measured at 140 and 70 mM Na do not differ significantly from the corresponding Isc. The net Cl flux varies with [Cl] at fixed [Na] while Isc is virtually not affected by [Cl]. These results suggest that the absorptive Na transport process is electrogenic and responsible for the Isc and that the secretory fluxes of Na and Cl are coupled, require high [Na], vary with [Cl], and do not contribute to Isc. K-free solution abolishes the Isc after a prolonged lag. Finally, the effect of a low resistance shunt pathway on active Na absorption is examined with a four-compartment model.

The four unidirectional fluxes of alanine across the mucosal and serosal borders of rabbit ileum were evaluated as functions of the alanine concentration on a single piece of tissue using a method previously described (Naftalin, R.J. and Curran, P.F. (1974) J. Membrane Biol. 16, 257-278). The effects of Na+ removal and of ouabain on these fluxes were investigated. Alanine was actively transported across the mucosal membrane under control conditions; Na+ removal or ouabain inhibited this process as a result of a decrease in flux from the mucosal solution to the cell and an increase in the flux in the opposite direction. The results concerning mucosal efflux of alanine are apparently inconsistent with the carrier model for alanine transport at this border. Alanine transfer across the serosal membrane appeared to involve a facilitated transfer mechanism. Alanine movement at the serosal side of the cell was not influenced by Na+.

The apparent affinities of various amino acids for the neutral amino acid transport system in rabbit ileum were determined by measuring the inhibition of L-methionine-(14)C influx across the brush border membrane. The apparent affinity was very low for compounds lacking an alpha-amino group, compounds with the alpha-hydrogen substituted by a methyl group, D-compounds, compounds with tertiary branching in the side chain, compounds with either a positive or negative charge in the side chain, and in most cases, compounds with a hydrophilic moiety in the side chain. High apparent affinities were exhibited by compounds with unbranched carbon or carbon-sulfur side chains. Branched compounds such as valine and leucine exhibited affinities which correlate with binding of only the linear portion of the side chain. The calculated change in free energy of binding is 370 cal/mol/CH(2) group which suggests the binding region for the side chain is partially hydrophobic. The affinities of families of analogues, derivatives of cysteine, methionine, serine, alanine, valine, and phenylalanine, correlate with their calculated octanol/water partition coefficients and are also correlated with apparent structural and electronic differences between families. The data permit a preliminary description of the functional geometry of the neutral amino acid transport site. The site contains a region for binding the alpha-amino group, alpha-carboxyl group, and side chain. The regions about the alpha-amino group and alpha-hydrogen are quite sterically limited. The side chain binding region is hydrophobic in nature and appears to be shallow, binding only the linear portion of branched or ring compounds.

It is well established that active sodium-ion transport and water flow across isolated toad bladder are increased by antidiuretic hormone (ADH) and by cAMP. These agents were also observed in previous studies to cause changes in the amount of radioactive phosphate in a specific protein in the toad bladder. This protein, found by SDS-polyacrylamide gel electrophoresis of toad bladder epithelial preparations, had an apparent molecular weight of 49,000 daltons. In the present study, a correlation was found between the ability of a variety of substances to affect the amount of radioactive phosphate in this 40,000-dalton protein and their ability to alter the rate of sodium transport. Thus several agents (ADH, cAMP, theophylline, adenine, prostaglandin E1, and Mn Cl-2) caused a decrease in the amount of radioactive phosphate in the 49,000-dalton protein and also stimulated active sodium transport across the bladder. Conversely, ZnCl-2 produced an increase in the amount of radioactive phosphate in this protein and an inhibition of sodium transport. With each of these agents, the time-course of change in phosphorylation of this protein was, in general, similar to that for sodium transport. A second phosphoprotein, with an apparent molecular weight of about 42,000 daltons, showed changes in parallel with, but less extensive than, those observed in the 49,000 dalton protein. There was no consistent relationship between changes in level of phosphorylation of either in the 49,000- or 42,000- dalton protein and changes in osmotic water permeability. The results are compatible with the possibility that regulation by ADH and by cAMP of sodium transport in the toad bladder epithelium may be mediated through regulation of the amount of phosphate in a specific protein.

Sodium flux from serosa to mucosa, J(sm) (Na) in rabbit ileum in vitro has been studied as a function of applied electrical potential at equal sodium concentrations in the bathing solutions. The results indicate that J(sm) (Na) involves two pathways, a diffusional flux through a paracellular shunt pathway and a flux that is independent of applied potential and presumably involves a transcellular pathway. The latter pathway comprises approximately 25 % of J(sm) (Na) in Ringer's solution containing 10 mM glucose and 25 mM bicarbonate. It is stimulated significantly by theophylline unaffected by removal of glucose or addition of ouabain but is reduced to negligible values by anoxia, dinitrophenol, and replacement of all chloride and bicarbonate by isethionate. Thus this component of J(sm) (Na) has a number of characteristics consistent with involvement in a specific secretory process mediating an electrically neutral secretory transport of sodium plus anion from serosa to mucosa. In addition to stimulating this process, theophylline significantly reduced the permeability of the paracellular shunt pathway to sodium.

Na transport by the isolated toad colon has been studied by measuring transmural Na fluxes and by direct measurement of the Na influx across the mucosal border. Net Na transport accounts for 88% of the short circuit current in the presence and in the absence of exogenous aldosterone. Na influx across the mucosal border appears to consist of two components. One component is highly correlated with short circuit current, is a saturable function of mucosal Na concentration, and is inhibited by lithium ions in the mucosal medium. The second component is a linear function of mucosal Na concentration, is unaffected by lithium, and is apparently not related to net Na transport by the tissue.

Calcium added to the solution bathing the outside of isolated frog skin caused a reversible decrease in net sodium transport across the skin. At constant sodium concentration, the inhibition of transport increased with increasing calcium concentration, but approached a limiting value. This maximum degree of inhibition was found to depend on sodium concentration; sodium transport could be inhibited by 60 per cent at 96 mM sodium, but by only 18 per cent at 19 mM sodium. The relative effectiveness of a given calcium concentration was also greater the higher the sodium concentration. The unidirectional flux of chloride across the short-circuited skin was decreased by calcium to approximately the same degree as active sodium transport. The results have been interpreted in terms of a relatively non-specific decrease in permeability of the outward facing membrane of the transporting cells. The resulting decrease in sodium permeability apparently causes a decrease in active sodium transport by reducing the availability of sodium to the transporting system.

The relation between unidirectional influxes of Na and amino acids across the mucosal border of rabbit ileum was studied under a variety of conditions. At constant Na concentration in the mucosal bathing solution, amino acid influx followed Michaelis-Menten kinetics permitting determination of maximal influx and the apparent Michaelis constant, K(t). Reduction in Na concentration, using choline as substitute cation, caused an increase in K(t) for alanine but had no effect on maximal alanine influx. The reciprocal of K(t) was a linear function of Na concentration. Similar results were obtained for valine and leucine and these amino acids competitively inhibited alanine influx both in the presence and in the absence of Na. These results lead to a model for the transport system which involves combination of Na and amino acid with a single carrier or site leading to penetration of both solutes. The model predicts that alanine should cause an increase in Na influx and the ratio of this extra Na flux to alanine flux should vary with Na concentration. The observed relation agreed closely with predicted values for Na concentrations from 5 to 140 mM. These results support the hypothesis that interactions between Na and amino acid transport depend in part on a common entry mechanism at the mucosal border of the intestine.

Studies have been carried out on the movement of salt and water across the small intestine of the rat. Segments of the ileum of anesthetized rats have been perfused in vivo with unbuffered NaCl solutions or isotonic solutions of NaCl and mannitol. Kinetic analysis of movements of Na(24) and Cl(36) has permitted determination of the efflux and influx of Na and Cl. Net water absorption has been measured using hemoglobin as a reference substance. Water was found to move freely in response to gradients of osmotic pressure. Net water flux from isotonic solutions with varying NaCl concentration was directly dependent on net solute flux. The amount of water absorbed was equivalent to the amount required to maintain the absorbed solute at isotonic concentration. These results have been interpreted as indicating that water movement is a passive process depending on gradients of water activity and on the rate of absorption of solute. The effluxes of Na and Cl are linear functions of concentration in the lumen, but both ions are actively transported by the ileum according to the criterion of Ussing (Acta Physiol. Scand., 1949, 19, 43). The electrical potential difference between the lumen and plasma has been interpreted as a diffusion potential slightly modified by the excess of active Cl flux over active Na flux. The physical properties of the epithelial membrane indicate that it is equivalent to a membrane having negatively charged uniform right circular pores of 36 A radius occupying 0.001 per cent of the surface area.

The interaction between Na transfer and alanine transfer across the mucosal border of rabbit ileum has been studied further by examining the effect of alanine on Na movement. Studies on strips of mucosa treated with ouabain showed that net Na movements against a Na concentration difference could be caused by a concentration difference of alanine. Na extrusion from mucosal cells was demonstrated when cellular alanine concentration exceeded that in the external medium. Conversely, the cells took up Na against a concentration difference when external alanine concentration was greater than cellular concentration. Unidirectional Na efflux from the cells toward the mucosal solution was increased by loading the cells with alanine. The relation between the increment in Na efflux and alanine efflux was approximately that predicted by the model of Curran et al. (reference 2) for the Na-alanine interaction at the mucosal border of the cells. The results offer further indication that the transport system is reversible and symmetrical.

A method has been developed for determining unidirectional Na fluxes across the two faces of the transporting cells in the frog skin. The method has been used to investigate the location of the sites at which Ca and anti-diuretic hormone act to alter the rate of active Na transport across the skin. The results have indicated that the primary effect of both agents is on the Na permeability of the outward facing membrane of the cells. Ca decreases and the hormone increases permeability of this barrier. Neither agent appears to have a direct effect on the active transport system itself assuming that it is located at the inner membrane of the cells. The rate of active Na transport is altered as a result of changes in the size of the Na pool in the cells which occur because of changes in the rate of Na entry through the outer membrane. Thus, the results indicate that the Na permeability of the outer membrane plays an important role in controlling the rate of net active Na transport across the skin.

Interrelationships between metabolism, NaCl transport, and water transport have been studied in an in vitro preparation of rat ileum. When glucose is present in the mucosal solution, Na and Cl both appear to be actively transported from mucosa to serosa while water absorption is passive and dependent on net solute transport. Removal of glucose from the mucosal solution or treatment with dinitrophenol, monoiodoacetate, or anoxia inhibits active salt transport and as a result, water absorption is also inhibited. The dependence of water absorption on metabolism can be explained as a secondary effect due to its dependence on active salt transport. The relationship between salt and water transport has been discussed in terms of a model system.

The eflect of glucose and galactose on transport of alanine by rabbit ileum has been investigated. Transmural transport and cellular ac cumulation of the amino acid were in hibited by the sugars, but alanine in flux across the mucosal border of the cells was unaltered.

A combination of the methods described by Schultz et al. (6) and by Ussing and Zerahn (9) was used to measure directly the unidirectional uptake of sodium from the outside solution into the frog skin, under short-circuit conditions. The sodium uptake was determined at six sodium concentrations ranging from 3.4 to 114 mM. NaCl was replaced by choline chloride in the solutions bathing both sides of the skin. Sodium uptake is not a linear function of sodium concentration but appears to be composed of two components, a saturating one and one that varies linearly with concentration. The sodium uptake is inhibited by the addition of lithium to the outside solution. The effect appears to be primarily on the saturating component and has the characteristics of competitive inhibition. In addition, lithium uptake by the skin is inhibited by sodium. The effects of lithium cannot be ascribed to changes in electrical potential difference. Measurements with microelectrodes indicate that under short-circuit condition there is no change in the intracellular potential when lithium chloride is added to the outside solution.

Active Na transport across frog skin was separated from passive Na movement utilizing urea influx as a measure of passive (shunt) permeability. In this manner, the response of the overall active Na transport system to an applied potential was determined over a range from +200 mV to -100 mV. Active Na transport displays saturation as a function of applied potential, and both the level of saturation and the potential at which it is achieved are functions of the Na concentration in the external solution. The saturation with potential appears to involve a different step in the transport process than the saturation of Na flux as a function of external Na concentration. The observations can be qualitatively described by either a one-barrier or two-barrier model of the Na transport system.

Glutamate and aspartate influxes across the brush border of rabbit intestine are saturable processes that are subject to competitive inhibition and are markedly influenced by the Na concentration in the mucosal solution. Lowering the Na concentration increases the amino acid concentration needed to elicit a half-maximal influx but does not significantly affect the maximal influx. The interaction between Na and anionic amino acid influx can be described by the same kinetic model that has been applied to the influxes of neutral amino acids and lysine. Comparison of the kinetic parameters for anionic, neutral, and cationic amino acids suggests that amino acid charge influences (a) the stability of the binary (amino acid-site) complex and (b) the affinity of this binary complex for the subsequent binding of Na. A mechanistic interpretation of these interactions is proposed.

Phosphorylation of a specific protein was decreased in intact toad bladders by exposure to either antidiuretic hormone or monobutyryl cyclic AMP. The decrease in phosphorylation caused by these agents preceded the change in electrical potential difference (an indicator of the rate of sodium ion transport) observed in response to the same compounds. The addition of cyclic AMP to homogenates of toad bladder led to a decrease in phosphorylation of the same, or a similar, protein. In subcellular fractionation studies, the effect of cyclic AMP on the phosphorylation of this protein was observed in those fractions rich in membrane fragments, but not in the nuclear or cell-sap fractions. These and other results are compatible with the possibility that the regulation by vasopressin and cyclic AMP of sodium and/or water transport in toad bladder may be mediated through regulation of the phosphorylation of this specific protein.