Trends in diagnoses after implementation of the Chicago classification for esophageal motility disorders (V3.0) for high-resolution manometry studies.

To determine trends in the diagnostic distribution of esophageal motility disorders after implementation of the Chicago Classification Version 3.0 (CC V3.0) for interpretation of high-resolution manometry (HRM) studies compared to non-Chicago Classification criteria. Retrospective trends analysis of patients with an HRM study conducted at a single center from January 1, 2013 to September 30, 2015. The implementation of the CC V3.0 for manometry interpretation occurred in September 2014. Patient charts were manually reviewed for data collection including demographics and HRM diagnoses. The prevalence and relative risks (RR) of CC V3.0 diagnostic categories (i.e. normal, indeterminate, achalasia, and EGJ outflow obstruction [EJGOO], and major and minor motility disorders) were calculated before and after CC V3.0 implementation. Four hundred sixty-five HRM studies were included in the study including 268 before and 179 after CC V3.0 implementation. The mean ± SD age was 54 ± 15.4 years and 59.8% were female (n = 278). The percentage with indeterminate diagnosis decreased from 35.3% before CC V3.0 implementation to 16.8% after implementation (adjusted RR 0.5, 95%CI 0.30-0.70, p < 0.001). The percentage with a major motility disorders decreased from 13.9% to 7.3% (adjusted RR 0.5, 95%CI 0.2-1.0, p < 0.001). The percentage with EJGOO and minor diagnoses increased from 1.4% to 14.5% and 11.9% to 22.9%, respectively. The percentage with achalasia and normal diagnosis did not change over the study period. Implementation of CCV3.0 was associated with changes in the distribution of esophageal motility diagnoses in clinical practice. The percentage of indeterminate and major diagnosis decreased and EGJOO and minor diagnoses increased. The decrease in the number of indeterminate studies suggests that the CC V3.0 may clarify the criteria for the interpreting physician. The increase in studies with a diagnosis of EGJ outflow obstruction may reflect the heterogeneity of disorders with clinically relevant outflow obstruction.

1st metatarso-phalangeal joint arthroplasty with ROTO-glide implant.

BACKGROUND: Total joint replacement of the 1st metatarso-phalangeal Joint (MTPJ) has been controversial as arthrodesis remains a good option for patients with end stage 1st MTPJ arthritis. We present a multi centre service evaluation of the ROTO-glide device METHODS: 33 ROTO-glide procedures were carried out in 30 patients across 7 sites within the UK. Exclusion criteria - hallux valgus and arthritis, age below 45 years and over 80 years, inflammatory joint disease. Patient assessed pre and post operatively with AOFAS and Oxford forefoot (MOXFQ) scores and plain radiographs. All patients carried out the same post operative protocol RESULTS: Average age at patients was 58.6 years (45-77). Follow up average was 16.9 months (12-29). Pre-op AOFAS scores average 41.4 (17-67) and post op average 76 (29-100) and the MOXFQ summary index decreased from an average of 43 (20-64) pre op to an average of 17 (0-51) post op. Average total range of motion pre operatively was 32° and post operatively was 61°. There were 2 post operative complications but no revisions were necessary. CONCLUSIONS: The early results of this multi centre service evaluation of the ROTO-glide 1st MTPJ replacement support its continued use and evaluation of the prosthesis further.

The inflammatory milieu and the insulin like growth factor axis in children with inflammatory bowel disease following recombinant human growth hormone treatment.

It is unclear whether recombinant human growth hormone (rhGH) in inflammatory bowel disease (IBD) alters cytokine profile. The objective of this study is to evaluate changes in cytokines and systemic markers of the insulin growth factor axis following 6 months of rhGH treatment in children with IBD. In a six-month randomised control trial in children with IBD treated with rhGH at 0.067 mg/kg/day and controls (11 in each group), we measured pro-, anti-inflammatory cytokines and systemic markers of the IGF axis (total IGF-1, free IGF-1, total IGFBP-3, ALS, IGFBP-2) at baseline (T+0), and six months (T+6). Results expressed as median (range). In the rhGH group, TNFα was 3.1pg/ml (2.9, 100.6) and 3.6pg/ml (3.1, 5.3) at T+0 and T+6, respectively (p=0.85), whereas in the controls this was 3.3pg/ ml (2.7, 4.0) and 3.1pg/m l (2.7, 4.7), respectively (p=0.79). In the rhGH group, IL1ß was 18.0pg/ml (5.0,716.7) and 18.0pg/ml (1.7, 52.2) at T+0 and T+6 respectively(p=0.90), whereas in the controls this was 19.8pg/ml (4.1, 27.1) and 19.1pg/ml (2.4,77.3), respectively (p=0.65). None of the twenty-eight other cytokines analysed was different at T+6 in either group. Despite increase in total IGF1 in the rhGH group (p=0.03), free IGF1, IGFBP3, ALS and IGFBP2 did not change in either group at T+6. Percentage change in IGFBP3, was significantly associated with percentage change in IL2 (r=0.77, p=0.009) and IL4 (r=0.58, p=0.01). Percentage change in ALS was significantly associated with percentage change in IL2 (r=0.90, p less than 0.0001) and IL4 (r=0.63, p=0.04). Although changes in markers of the GH/IGF-1 axis do show an association with cytokines (IL-2, IL-4) in pediatric IBD, six months of rhGH treatment was not associated with any significant changes in levels of a range of pro and anti-inflammatory cytokine. Careful evaluation of disease process is required in future trials of rhGH in paediatric IBD.

Lunar gravity analysis from long-term effects.

The global lunar gravity field was determined from a weighted least squares analysis of the averaged classical element of the five Lunar Orbiters.The observed-minus-computed residuals have been reduced by a factor of 10 from a previously derived gravity field.The values of the second-degree zonal and sectorial harmonics are compatible with those derived from libration data.

Mariner 9 celestial mechanics experiment: gravity field and pole direction of Mars.

Analysis of the Mariner 9 radio-tracking data shows that the Martian gravity field is rougher than that of Earth or the moon, and that the accepted direction of Mars's rotation axis is in error by about 0.5 degrees . The new value for the pole direction for the epoch 1971.9, referred to the mean equatorial system of 1950.0, is right ascension alpha= 317.3 degrees +/- 0.3 degrees , declination delta = 52.6 degrees +/- 0.2 degrees . The values found for the coefficients of the low-order harmonics of Mars's gravity field are as follows: J(2)=(1.96+/-0.01)x10(-3), referred to an equatorial radius of 3394 kilometers; C(22) = -(5 +/- 1) x 10(-5); and S(22) = (3 +/- 1) x 10(-5). The value for J(2) is in excellent agreement with the result from, Wilkins' analysis of the observations of Phobos. The other two coefficients imply a value of (2.5 +/- 0.5) x 10(-4) for the fractional difference in the principal equatorial moments of inertia; the axis of the minimum moment passes near 105 degrees W.

Rhesus incompatibility as a risk factor for schizophrenia in male adults.

BACKGROUND: Rhesus (Rh) incompatibility is a cause of hemolytic disease of the fetus and newborn. Hemolytic disease results from the transplacentally transmitted maternal antibodies against Rh factor D and can cause permanent neurological damage in the affected newborn. This study examines the hypothesis that Rh incompatibility may be a risk factor for schizophrenia. METHODS: A sample of 1867 male subjects was divided into two groups, 535 Rh incompatible and 1332 Rh compatible, and compared on rate of schizophrenia. RESULTS: The rate of schizophrenia was significantly higher in the Rh-incompatible group (2.1%) compared with the Rh-compatible group (0.8%) (P < .03). In addition, since the risk for Rh hemolytic disease increases with second and later Rh incompatible pregnancies, it is noteworthy that the second- and later-born incompatible offspring exhibited a significantly higher rate of schizophrenia than second- and later-born compatible offspring (P < .05). Also, as predicted, the rate of schizophrenia among firstborn incompatible subjects was not significantly different from that of firstborn compatible subjects (1.1% vs 0.7%). CONCLUSION: Rh incompatibility may be a risk factor for schizophrenia.

Early results of autologous chondrocyte implantation in the talus.

Autologous chondrocyte implantation (ACI) has been used most commonly as a treatment for cartilage defects in the knee and there are few studies of its use in other joints. We describe ten patients with an osteochondral lesion of the talus who underwent ACI using cartilage taken from the knee and were prospectively reviewed with a mean follow-up of 23 months. In nine patients the satisfaction score was 'pleased' or 'extremely pleased', which was sustained at four years. The mean Mazur ankle score increased by 23 points at a mean follow-up of 23 months. The Lysholm knee score returned to the pre-operative level at one year in three patients, with the remaining seven showing a reduction of 15% at 12 months, suggesting donor-site morbidity. Nine patients underwent arthroscopic examination at one year and all were shown to have filled defects and stable cartilage. Biopsies taken from graft sites showed mostly fibrocartilage with some hyaline cartilage. The short-term results of ACI for osteochondral lesions of the talus are good despite some morbidity at the donor site.

Thyroid-stimulating autoantibodies usually contain only lambda-light chains: evidence for the "forbidden clone" theory.

Burnet's "forbidden clone" theory would predict that in patients with Graves' disease the pathogenic thyroid-stimulating autoantibody (TSab)-secreting clones arise by somatic mutation. Because each lymphocyte and its progeny are permanently committed to producing antibodies of a single light chain type, a clone arising by somatic mutation occurring in a single cell would be expected to produce autoantibodies of exclusively kappa or exclusively lambda type in an individual patient. Using affinity chromatographic techniques and monoclonal antibodies, we investigated the light chain type of TSab in 11 patients with Graves' disease. In all patients tested, TSab activity was confined to a single light chain type, confirming the recent work of Zakarija who used affinity chromatography with polyclonal antisera, but contrasting with earlier studies which used immuno-precipitation methods. Furthermore, the light chain type was lambda in 10 of the 11 patients. These observations provide support for the forbidden clone theory. In addition, the marked preponderance of patients producing TSab of the lambda-light chain type indicates that TSab are more likely to arise from the lambda repertoire of clones than from the kappa repertoire and suggests that immunoglobulin light chain V genes may be genetic determinants for susceptibility to Graves' disease.

Autoantibodies to acetylcholine receptor in myasthenia gravis: light chains.

We studied the light chain type of autoantibodies to acetylcholine receptor (AChR) by affinity chromatography with monoclonal anti-kappa and anti-lambda antibodies. The autoantibodies in four of eight myasthenic patients were of a single light chain type; the others comprised both types. In Graves' disease and cold-reactive hemolytic anemia, the pathogenic autoantibodies are confined to a single light chain type in individual patients, and in other diseases, doubtfully pathogenic autoantibodies are invariably mixtures of both light chain types. AChR antibodies may comprise both pathogenic and nonpathogenic types of autoantibody.

Luminescent visualization of antigens on blots.

Proteins separated by SDS gel electrophoresis and transferred to a nitrocellulose sheet can be visualised by 'probing' with peroxidase-linked reagents which are detected by luminescence. A modified luminescent substrate is described containing 4-methylumbelliferone which enhances light emission four-fold. Using the modified substrate, luminescent detection was found to be more sensitive than chromogenic detection of peroxidase using 4-chloro-1-napthol. The new technique was used in conjunction with the immunoblot method to demonstrate antigenic differences between rat and mouse erythrocytes.

Antigenicity of rat erythrocyte glycophorins.

The relationship between rat red blood cell (RBC) glycophorins and the antigens recognised by anti-rat RBC antibodies was examined. Initially, murine monoclonal antibodies specific for surface epitopes on whole rat RBCs were tested for their reactivity with RBC membranes on Western blots and two were found which reacted with blotted antigens. These antibodies recognised two bands corresponding to the major PAS-stainable bands of rat RBC membranes (i.e., the glycophorins) and a number of minor bands, thus demonstrating that the bands are antigenically related. This band-pattern was remarkably similar to that obtained with mouse anti-rat RBC serum. Digestion with neuraminidase altered the electrophoretic mobility of most of the bands, providing additional evidence that they are sialoglycoproteins, although sialic acid was shown not to contribute to their antigenicity. The glycophorin nature of the major antigens was verified by reelectrophoresis and blotting of bands excised from SDS gels, which showed that they were interconvertible monomeric and dimeric forms of the same polypeptide chain. It is suggested that rat RBC glycophorins are a related family of sialoglycoproteins with the high molecular weight members being formed by dimerization of five lower molecular weight polypeptide chains in various combinations.

Identification of an erythrocyte autoantigen using monoclonal autoantibodies induced by immunization of mice with rat erythrocyte.

An erythrocyte autoantigen has been identified by means of monoclonal autoantibodies raised by immunizing mice with rat red blood cells (RBC). The autoantibodies reacted with intact rat and mouse RBC as judged by a cellular radioimmunoassay, and with a 52K band on western blots of rat and mouse RBC. They did not react with intact sheep RBC or blotted sheep erythrocyte membranes. Although anti-rat erythrocyte antibodies did react with bands in the molecular weight region of 50-55 K (on blots of rat erythrocyte membranes), these bands were susceptible to neuraminidase digestion, thus distinguishing them from the 52 K band recognized by monoclonal autoantibodies. The implications of the above results for the known autoantibody specificity of suppression is discussed, and it is suggested that they favour the existence of autoantigen-specific suppressor cells.

World standards for surgical implants: an American perspective.

Working cooperation among surgeons, manufacturers and scientists, working in many countries, over the last forty years has arrived at minimal standards. These standards are for both the materials to be used in the manufacture of surgical implants and for the design and performance of the implants themselves. An account is given here of the development of the standards writing procedure in the United States and the International Standards Organization in Geneva. The important contributions of all the working groups to write the present standards is underline. This process has been set up within the European countries, the United States of America, Canada and other nations, to make sure that materials are adequately investigated prior to their use for the manufacture of surgical implants. In addition the implants themselves must satisfy design requirements which have been set up by consensus, this allows for the expression of all interests. This is an account of what has been going on in standards writing and continues to take place in the writing of standards.

Scenarios for a viral etiology of schizophrenia.

Recent discoveries in the field of virus receptors have revolutionized our concepts of viral pathogenesis. The lysis of cells resulting from virus infection or immune recognition of infected cells is seen as merely one facet of a spectrum of pathogenic mechanisms which may be subtle and complex. This is particularly relevant to the central nervous and immune systems which share cell-surface receptors for various neuropeptides and neurotransmitters. A number of viruses are now known to share receptors for such endogenous ligands; indeed, some viruses (e.g., human immunodeficiency virus and vaccinia) may themselves be structural analogs of these ligands. There is, therefore, considerable scope for interference by viruses in the normal functioning of the brain and neuroendocrine systems. Brief reactive psychoses are occasionally reported as acute sequels to viral infections, but generally these are regarded as unrelated to schizophrenia. An opposite viewpoint is presented in the article: i.e., that the only reason these reactive psychoses do not progress to schizophrenia is that the majority of individuals affected are not predisposed genetically to schizophrenia. Conceivably, therefore, the genetic predisposition to schizophrenia may be attributable to genes which determine idiosyncratic differences in immune responsiveness to common viral pathogens.

Many spinal cord cells transiently express low molecular weight forms of glutamic acid decarboxylase during embryonic development.

At early developmental stages in the rat spinal cord (embryonic day 13), when neuronal progenitors are still proliferating, most differentiating neurons express truncated forms of glutamic acid decarboxylase (GAD) (approximately 25 kDa) which are the products of alternative splicing of the GAD67 gene. These truncated proteins do not appear to synthesize gamma-aminobutyric acid (GABA). The amino acid is detected in cells only after alternative splicing of the GAD67 gene generates a full-length, 67 kDa enzymatically active form of GAD. Both the 67 kDa GAD and GABA colocalize and appear diffusely distributed in the cytoplasm of embryonic neurons. GABA does not appear associated with synaptic vesicles until after birth, when its intracellular distribution becomes punctate and it colocalizes with synaptophysin. At this time, it also colocalizes with an immunologically distinct 65 kDa GAD protein encoded by a second GAD gene (GAD65). Expression of different GAD-related proteins with distinct intracellular distributions during development suggests that GABA, the product of these enzymes, may have trophic or metabolic roles during spinal cord differentiation.

Diabetic foot ulcers.

Neuropathic and vascular changes in patients with diabetes mellitus put them at risk for developing chronic foot wounds after minor trauma or after pressure has caused a breakdown in the integrity of the skin. Accurate diagnosis of the underlying cause is the first step toward a successful treatment plan, and in patients with severe ischemia, vascular reconstruction may be needed. Neuropathic ulcers respond well to less-invasive procedures, particularly when combined with reducing the pressure that caused the ulcer. When pressure is relieved by means of total contact casting, necrotic materials are removed, and protection is secured with a hydrocolloid dressing, these wounds have been found to heal, on an outpatient basis, after approximately 6 weeks. All diabetic foot ulcers are contaminated with a variety of organisms, but antibiotic treatments are usually unnecessary. When signs of a clinical infection are present and/or bone is exposed, osteomyelitis should be suspected. In these patients, aggressive surgical debridement, systemic antibiotics, and meticulous wound care regimens to restore the body's own bacterial barrier will often prevent amputation, the most serious complication of these wounds.

The development and complications of diabetic foot ulcers.

Neuropathy and ischemia, two common complications of diabetes mellitus, are the primary underlying risk factors for the development of foot ulcers and their complications. The presence of symmetric distal polyneuropathy, encompassing motor, sensory, and autonomic involvement, is one of the most important factors in the development of diabetic foot ulcers. Perhaps one third of diabetic foot ulcers have a mixed neuropathic and ischemic etiology. Although neuropathy and ischemia are the primary predisposing factors in the formation of diabetic foot ulcers, an initiating factor, such as physical or mechanical stress, is required for an ulcer to develop. Ischemic ulcers develop as a result of low perfusion pressure in a foot with inadequate blood supply, whereas neuropathic ulcers result from higher pressures in a foot with adequate blood supply but loss of protective sensation. In addition to increasing the risk of ulceration, diabetes mellitus also increases the risk of infection by impairing the body's ability to eliminate bacteria. The processes by which ulcers develop are reviewed here.

The role of the plaster bed after spinal fusion.

Between 1974 and 1983, 40 patients underwent intertransverse lumbar fusion at the Royal Free Hospital, London. Nine of these were managed after operation on a plaster bed for 12 weeks and the rest were mobilized within 2 weeks. A satisfactory radiologic fusion rate of 75% was achieved in the first group and of 70% in the second group. There was no significant difference between these two groups, (chi 2 test). The results do not support the use of the plaster bed after lumbar fusion.

Medial calcaneal osteotomy for relapsed equinovarus deformity. Long-term study of the results of Frederick Dwyer.

In the 1950s Frederick Dwyer evolved the concept of treating resistant and relapsed clubfoot by osteotomy of the calcaneum. He published the results of his medial opening wedge procedure in 1963 with a mean follow-up of five years. We present the structured, radiographic and functional results at a mean elapsed time of 27 years of 36 feet (26 patients) all operated on by Dwyer. Their mean Laaveg and Ponseti (1980) grading was 83.7%. In 94% the heel was in neutral or valgus and 86% of the feet were plantigrade. A good range of movement was present in the ankle and subtalar joints in 83%.

Neuropathic foot ulceration treated by total contact casts.

Ulceration of the insensitive foot continues to cause great morbidity in diabetic patients. We treated 46 patients with neuropathic ulceration by applying total contact casts. Most neuropathic ulcers healed within six weeks but ischaemic ulcers did not heal. One patient developed gangrene and required partial amputation of the foot.