Upper esophageal sphincter (UES) metrics on high-resolution manometry (HRM) differentiate achalasia subtypes.

BACKGROUND: The upper esophageal sphincter (UES) reflexively responds to bolus presence within the esophageal lumen, therefore UES metrics can vary in achalasia. METHODS: Within consecutive patients undergoing esophageal high-resolution manometry (HRM), 302 patients (58.2±1.0 year, 57% F) with esophageal outflow obstruction were identified, and compared to 16 asymptomatic controls (27.7±0.7 year, 56% F). Esophageal outflow obstruction was segregated into achalasia subtypes 1, 2, and 3, and esophagogastric junction outflow obstruction (EGJOO with intact peristalsis) using Chicago Classification v3.0. UES and lower esophageal sphincter (LES) metrics were compared between esophageal outflow obstruction and normal controls using univariate and multivariate analysis. Linear regression excluded multicollinearity of pressure metrics that demonstrated significant differences across individual subtype comparisons. KEY RESULTS: LES integrated relaxation pressure (IRP) had utility in differentiating achalasia from controls (P<.0001), but no utility in segregating between subtypes (P=.27). In comparison to controls, patients collectively demonstrated univariate differences in UES mean basal pressure, relaxation time to nadir, recovery time, and residual pressure (UES-RP) (P≤.049). UES-RP was highest in type 2 achalasia (P<.0001 compared to other subtypes and controls). In multivariate analysis, only UES-RP retained significance in comparison between each of the subgroups (P≤.02 for each comparison). Intrabolus pressure was highest in type 3 achalasia; this demonstrated significant differences across some but not all subtype comparisons. CONCLUSIONS AND INFERENCES: Nadir UES-RP can differentiate achalasia subtypes within the esophageal outflow obstruction spectrum, with highest values in type 2 achalasia. This metric likely represents a surrogate marker for esophageal pressurization.

Nonalcoholic fatty liver disease (NAFLD) in the Veterans Administration population: development and validation of an algorithm for NAFLD using automated data.

BACKGROUND: In practice, nonalcoholic fatty liver disease (NAFLD) is diagnosed based on elevated liver enzymes and confirmatory liver biopsy or abdominal imaging. Neither method is feasible in identifying individuals with NAFLD in a large-scale healthcare system. AIM: To develop and validate an algorithm to identify patients with NAFLD using automated data. METHODS: Using the Veterans Administration Corporate Data Warehouse, we identified patients who had persistent ALT elevation (≥2 values ≥40 IU/mL ≥6 months apart) and did not have evidence of hepatitis B, hepatitis C or excessive alcohol use. We conducted a structured chart review of 450 patients classified as NAFLD and 150 patients who were classified as non-NAFLD by the database algorithm, and subsequently refined the database algorithm. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for the initial database definition of NAFLD were 78.4% (95% CI: 70.0-86.8%), 74.5% (95% CI: 68.1-80.9%), 64.1% (95% CI: 56.4-71.7%) and 85.6% (95% CI: 79.4-91.8%), respectively. Reclassifying patients as having NAFLD if they had two elevated ALTs that were at least 6 months apart but within 2 years of each other, increased the specificity and PPV of the algorithm to 92.4% (95% CI: 88.8-96.0%) and 80.8% (95% CI: 72.5-89.0%), respectively. However, the sensitivity and NPV decreased to 55.0% (95% CI: 46.1-63.9%) and 78.0% (95% CI: 72.1-83.8%), respectively. CONCLUSIONS: Predictive algorithms using automated data can be used to identify patients with NAFLD, determine prevalence of NAFLD at the system-wide level, and may help select a target population for future clinical studies in veterans with NAFLD.

Tetraaza analogues of lithium and sodium alums: synthesis and X-ray structures of the single strand polymer [Li(THF)2(Al[SO2(NtBu)2]2)] infinity and the contact ion pairs [Na(15-crown-5)][Al(SO2(NtBu)2)2] and ([Na(15-crown-5)][O2S(mu-NBn)2Al(mu-NBnSO2NBn)])2.

The reaction of an alkali metal aluminohydride MAlH4 (M = Li, Na) with N,N'-bis-(tert-butyl)sulfamide or N,N'-bis-(benzyl)sulfamide in THF produces the complex ions (Al[SO2(NR)2]2)- (R = tBu, Bn). The X-ray structures of [Li(THF)2(Al[SO2(NtBu)2]2)] infinity (1), [Na(15-crown-5)][Al(SO2(NtBu)2)2], (2) and ([Na(15-crown-5)][O2S(mu-NBn)2Al(mu-NBnSO2NBn)])2 (3.3THF) are reported. The two diazasulfate ligands [SO2(NtBu)2]2- are N,N' chelated to Al3+ in both 1 and 2. In the lithium derivative 1 the spirocyclic (Al[SO2(NtBu)2]2)- anions are bridged by the bis-solvated cations Li(THF)2+ to give a polymeric strand. In the sodium salt 2 the complex anion is O,O' chelated to Na+, which is further encapsulated by a 15-crown-5 ligand to give a monomeric ion-pair complex. By contrast, the benzyl derivative 3 forms a dimer in which the terminal [SO2(NBn)2]2- ligands are (N,N'),(O,O') bis-chelated to Al3+ and Na+, respectively, and the bridging ligands adopt a novel N,O-chelate, N'-monodentate bonding mode. The central core of 3 consists of two four-membered AlOSN rings bridged by two NtBu groups. Crystal data: 1, orthorhombic, Pna2(1), a = 20.159(5) degrees, b = 10.354(3) degrees, c = 15.833(4) degrees, alpha = beta = gamma = 90 degrees, V = 3304.7(15) A3, Z = 4; 2, monoclinic, P2(1)/n, a = 16.031(2) A, b = 9.907(2) A, c = 23.963(4) A, beta = 103.326(2) degrees, Z = 4; 3, triclinic, P1, a = 12.7237(11) A, b = 14.0108(13) A, c = 16.2050(14) A, alpha = 110.351(2) degrees, beta = 111.538(2) degrees, gamma = 97.350(2) degrees, Z = 1.

The polyurethane foam covering the Même breast prosthesis: a biomedical breakthrough or a biomaterial tar baby?

Because controversy continues to surround the implantation of the polyurethane foam-covered Même breast prosthesis, in vitro experiments were conducted to determine: (1) whether the polyurethane foam contains extractable toluene diamine isomers (TDAs), and (2) whether the polyurethane foam releases TDAs on exposure to mild hydrolytic conditions. Results confirmed the presence of extractable TDAs and other impurities in the foam covering the unused Même prosthesis, and that the concentrations of these impurities could be significantly reduced by washing the foam in a regular detergent. This washing step was omitted from the manufacturer's production process. Furthermore, on exposure to mild alkalis, the foam exhibited significant degradation, rapid fragmentation, loss of mechanical strength and physical integrity, as well as the release of additional TDAs. Because of the potential long-term risks associated with the release of TDAs in vivo, continued clinical use of the Même prosthesis containing this particular type of foam appears questionable.

Degradation of explanted polyurethane cardiac pacing leads and of polyurethane.

Polyurethane cardiac pacing leads explanted at autopsy and from reoperated patients were examined for degradation in the insulation. Scanning electron microscopy (SEM) analysis showed cracks on the polyurethane surface which were both parallel and perpendicular to the longitudinal axis of the lead. Surface analyses of leads were performed using Fourier-Transform Infra-red (FT-IR) spectrophotometry in the attenuated total reflectance mode. The FT-IR spectra of visibly deteriorated polyurethane from explanted lead sheaths were compared with that of unused polyurethane tubing used for such sheaths. Changes were most evident in the regions of 3000-2800, 1730 and 1368 cm-1. The observed alterations in the FT-IR spectra were consistent with a degradation mechanism involving oxidative chain cleavage in the polyurethane amorphous regions. New polyurethane tubing (Pellethane-Type 80A) was exposed to sodium hypochlorite to simulate a possible in-vivo process and generate reference material. Degradation with associated decreases in tensile strength and molecular weight was recorded. This study showed that polyurethane insulation used in pacing leads is susceptible to oxidative degradation.

Perfluorocarbon blood substitutes.

The salient physicochemical properties of the fluorocarbons are briefly reviewed, including their solubility for the physiologically important gases and their properties relevant to formulation (nonmiscibility with water). The preparations used to date are described, including their properties and compositions, with some comment about the available knowledge of the properties of the constituents. A critical review of the biological aspects and the possible uses of fluorocarbon emulsions constitutes the main body of the manuscript. Gas-transporting capabilities are considered quantitatively. The biological effects of these preparations are reviewed in in vivo, whole body systems, with some in vitro evidence where appropriate. The usefulness of these preparations investigated to date are reviewed under the broad headings of cardiovascular system, radiology, intoxications, and organ preservation. Finally, the shortcomings and potential usefulness are discussed, with recommendations for potential modifications.

Textile arterial prostheses: is water permeability equivalent to porosity?

Porosity and water permeability are two distinct terms that describe different characteristics of vascular prostheses. The porosity is a measure of the void fraction within the prosthesis wall and is believed to give a rough prediction of the capacity of the graft to anchor newly formed surrounding tissue after implantation, whereas the water permeability indicates the rate at which water can flow through the prosthesis wall and, when measured under physiological pressure conditions, provides the surgeon with information about the need for preclotting prior to implantation. The literature has not always clearly distinguished between these two terms, and some authors in fact have suggested that they both refer to the same property of a prosthesis. In an attempt to clarify the issue, porosity and water permeability measurements were made on 34 commercial vascular prostheses having different textile constructions. Linear regression analysis demonstrated that these two characteristics are only weakly related (r = 0.59). It is therefore recommended that the current draft standards for such devices reference both properties: porosity and water permeability.

Chemically fixed human umbilical cord vein grafts as arterial substitutes: potential and limits.

In spite of reported successes, synthetic fabric grafts and microporous and plain synthetic conduits have proven unsuitable for aorto-coronary bypasses and showed weaknesses below the knee. Readily available and uniform diameter vascular substitutes with biological and mechanical properties comparable to human vessels would be of paramount interest. Following reported successes with chemically fixed human umbilical veins (HUV), we have attempted to develop smaller diameter blood conduits and have improved the currently prevalent techniques of fixation, preparation and storage to generate more convenient surgical products. In vitro assessment of the processed HUV demonstrated that the HUV can be easily processed to make an arterial substitute that can be preserved either in a liquid medium or as a dry product. However, the in vivo implantations in dogs led to disappointing results for liquid-preserved or albuminated veins. Critical-point dried grafts gave better results, unfortunately they do not heal and they can only degrade after implantation.

Aggregation of insulin, containing surfactants, in contact with different materials.

The aggregation of insulin and of insulin protected with surfactants was studied by shaking at 37 degrees C in glass, in polypropylene and polystyrene vials, and in CPI and Auto-Syringe insulin syringes and infusion sets. Surfactants such as Pluronic 17R8 and 25R5 hastened the aggregation, whereas Pluronic F68 was effective in preventing it. Furthermore, there was no change in the immunoreactivity of insulin containing Pluronic F68 even after 8 days of shaking. Unprotected insulin aggregated in all the vials. There appears to be little problem with the commercial syringes tested, but the infusion sets could cause aggregation of insulin if used over an extended period of time. Although Pluronic F68 prevented insulin aggregation in situ, it extracted more impurities from the contacting plastics. Further development in materials and design of insulin sets and insulin containers appears necessary.

Polyester prostheses as substitutes in the thoracic aorta of dogs. II. Evaluation of albuminated polyester grafts stored in ethanol.

In an attempt to find an alternative procedure to the preclotting of porous textile vascular prostheses, the feasibility of an albumin coating and ethanol preservation technique has been evaluated by implanting albuminated polyester prostheses as substitutes in the thoracic aorta of dogs. Nine different grafts representing woven, knitted, and velour constructions were implanted for periods ranging from 4 h to 6 months. At the sacrifice, the grafts were excized for measurement of the thrombogenicity of the flow surface, for pathological examination by light microscopy and SEM, and for quantifying the changes in the textile structure during implantation. Also the kidneys were removed and examined for infarcts caused by trapped circulating emboli. The healing characteristics of the nine different grafts proved similar and followed the same sequence of events as preclotted control grafts. The albumin coating and ethanol preservation resulted in a somewhat slower rate of healing. Yet, given sufficient time, a more completely healed graft was achieved as evidenced by the presence of endothelial-like cells throughout the length of the graft. In addition, the albumin is believed to reinforce the textile structure by reducing the tendency to stretch and dilate in vivo.

Preliminary findings on used cervical caps.

Rubber cervical caps (Lambert-Dalston), used for periods of time ranging from 1 month to 3 years, were collected and assessed for deterioration and contamination as part of a product safety and efficacy study. Examination at magnification of 10 to 30 times as well as evaluation of surface damage and bulk mechanical properties revealed significant deterioration on all caps used consistently for more than one year. Changes were also evident on caps worn for shorter periods. Potential for adverse reaction from rubber degradation products and contamination adsorbed from disinfecting agents does not appear negligible. This problem, in combination with the inability to satisfactorily clean the caps after use, further limits their clinical value. A rethinking of cap design and the choice of better cap materials appears necessary to minimize long-term user problems and to mitigate product-related aesthetic deficiencies of this fertility control method.

[Venous homografts as femoro-popliteal bypasses or as vascular access routes in chronic hemodialysis]. / Les homogreffes veineuses comme pontages fémoro-poplités ou comme abords vasculaires pour l'hémodialyse itérative.

Saphenous vein homografts preserved by freezing at 40 degrees C in the presence of antibiotics for periods of as much as six months were implanted as part of a clinical evaluation program. Candidates included one requiring femoro-popliteal reconstruction with two separate bypass procedure and reoperations for thrombosis and false aneurysm in the left limb as well as 23 maintenance hemodialysis patients (32 arteriovenous blood access shunts for a total of 424 patient-months). Explanted veins used as femoro-popliteal bypasses were examined after collection incidental to reoperations and autopsy. In-vivo dwell time varied between 7 and 51 months. The femoro-popliteal by-passes exhibited calcification and sclerosis. The dialysis access shunts had average service lives of about a year; 21 were replaced because of thrombosis, 10 were stenosed, 7 had aneurysms and necrosis was present in six. Although this implant provides a workable alternative approach to vascular reconstruction, the rapid degeneration of such veins in vivo is a limitation.

Polyester prostheses as substitutes in the thoracic aorta of dogs. I. Evaluation of commercial prostheses.

Using canine models, a representative selection of polyester or Dacron vascular prostheses, including woven, knitted, and velour types, were evaluated for their relative healing characteristics and for their structural changes during implantation. Following residence periods ranging from 4 h to 6 months at the site of the thoracic aorta, the dogs were sacraficed, and the grafts were excized for measurement of the thrombogenicity of the flow surface and for pathological examination by light microscopy and SEM. The kidneys were also removed and examined for infarcts caused by any trapped circulating emboli. The extent of healing, the presence of embolizing nuclei, and the thrombogenicity and morphology of the lumen surface were also assessed. The healing characteristics of each type of device proved similar. Velour fabrics exhibited more extensive encapsulation, but frequently their internal capsules failed to incorporate all the fibers. In all cases, cellular development on the lumen was limited to areas contiguous to the anastomoses. The initial porosity of the devices as measured by water permeability did not appear to influence the healing sequence to a significant extent. The grafts did exhibit differences in structural stability depending on whether they were of a knitted or woven construction. We suggest that users consider these different mechanical and structural properties when making their choice of a graft. Despite these differences, we believe that the healing process is far more host dependent than graft dependent.

[Glutaraldehyde - fixed human umbilical cord vein as a small diameter arterial substitute. Experimentation on the monkey]. / La veine ombilicale humaine traitée au glutaraldéhyde comme substitut artériel de petit diamètre. Expërimentation sur le singe.

Autologous saphenous veins, the preferred substitute material for aorto-coronary, femoro-popliteal and femoro-tibial by-pass, are usable in only 70% of individuals in need of such procedures. The development of small diameter substitute arteries is therefore essential to broaden the pool of patients who could benefit from this class of cardiovascular surgery. Existing substitutes, however, present major difficulties and have had limited success. In this laboratory, an attempt has been made to develop a vessel of 3 millimetres or less in diameter derived from human umbilical cord processed in glutaraldehyde. This substitute can be stored in 45% ethanol or dessicated by critical point drying. This device had been implanted as a segment of abdominal aorta in eight primates (Macaca fascicularis). Preliminary results are disappointing. The indicate that retention of a patency for more than a year post-implantation is difficultly achievable and that connective tissue hyperplasia leading to occlusion at the anastomoses is a major problem. Similar but larger diameter by-passes in the order of 6-8 millimetres should be investigated in greater detail, in order to better establish the "in-vivo" behavior of this class of tissue prosthesis. This would address the more fundamental issues pertaining to the clinical usefulness of fixed biological tissue by-pass devices.

New alternatives in the preparation of chemically fixed human umbilical veins as arterial substitutes.

Following reports of the successful use of chemically processed human umbilical veins as medium and small diameter arterial substitutes, the development of new and improved techniques for the preparation, fixation and storage of these bioprostheses has been attempted. A series of physical and "in vitro" tests was undertaken to predict the "in vivo" performance of these devices. The results indicate that the new techniques are not only technically feasible but may provide a more convenient, versatile and effective surgical product.