Dysplasia severity is associated with poor quality of life in patients with Barrett's esophagus referred for endoscopic eradication therapy.

Limited data exist regarding patient-reported outcomes and quality of life (QOL) experienced by patients with Barrett's esophagus (BE) referred for endoscopic eradication therapy (EET). Specifically, the impact of grade of dysplasia has not been explored. The purpose of this study is to measure patient-reported symptoms and QOL and identify factors associated with poor QOL in BE patients referred for EET. This was a prospective multicenter study conducted from January 2015 to October 2017, which included patients with BE referred for EET. Participants completed a set of validated questionnaires to measure QOL, symptom severity, and psychosocial factors. The primary outcome was poor QOL defined by a PROMIS score >12. Multivariable logistic regression analysis was performed to identify factors associated with poor QOL. In total, 193 patients participated (mean age 64.6 years, BE length 5.5 cm, 82% males, 92% Caucasians) with poor QOL reported in 104 (53.9%) participants. On univariate analysis, patients with poor QOL had lower use of twice daily proton pump inhibitor use (61.5% vs. 86.5%, P = 0.03), shorter disease duration (4.9 vs. 5.9 years, P = 0.04) and progressive increase in grade of dysplasia (high-grade dysplasia: 68.8% vs. 31.3%, esophageal adenocarcinoma: 75.5% vs. 24.5%, P < 0.001). Multivariate analysis demonstrated that high-grade dysplasia was independently associated with poor QOL (OR: 5.57, 95% CI: 1.05, 29.5, P = 0.04). In summary, poor QOL is experienced by the majority of patients with BE referred for EET and the degree of dysplasia was independently associated with poor QOL, which emphasizes the need to incorporate patient-centered outcomes when studying treatment of BE-related dysplasia.

Infections associated with ventricular assist devices: epidemiology and effect on prognosis after transplantation.

BACKGROUND: Ventricular assist devices (VADs) can be used as a bridge to orthotopic heart transplantation (OHT) in people with severe congestive heart failure. Although they can be inserted for an indefinite time period (unlike balloon pumps), they do carry a substantial risk of infection. We studied the epidemiology, microbiology, and consequences of infection in patients with VADs who ultimately had cardiac transplantation. METHODS: Records of VAD-supported patients at our institution between January 1995 and January 2005 were identified by ICD-9 code. Infection was classified as driveline infection, pocket infection, mediastinitis, or VAD endocarditis in increasing severity of illness. RESULTS: Of 73 patients identified by ICD-9 code, 60 had charts available for review. Of these 60, 72% had a VAD infection: 13 had VAD endocarditis; 3, mediastinitis; 25, pocket infection; and 29, driveline infection. The only association of infection (43 patients, 72%) and demography or underlying disease was that of endocarditis with older age (median age 59 vs. 53 years; P=0.02) and diabetes mellitus (13 patients, 30%; risk ratio 3.4; P=0.01). The duration of VAD support was longer in infected patients (median 125 days) vs. uninfected ones (25 days). Median survival measured from the time of VAD placement (although also true from the time of transplantation) was shorter in patients with VAD endocarditis (120 days) and pocket infection (350 days) vs. no infection (>2400 days) with a significant P=0.017 for endocarditis. Four patients had infections after transplantation that were caused by the same organism as their VAD infection. The predominant pathogens in VAD infection were Staphylococcus and Enterococcus spp. CONCLUSION: VAD use as a bridge to cardiac transplantation is associated with a large number of device-related infections. Patients with infected VADs, on average, wait longer for transplantation than patients with uninfected VADs, and patients with VAD endocarditis have a shorter survival than patients with no VAD infection or simple driveline infection.

Effect of prior nucleoside use on the two-year virological response to an initial protease inhibitor regimen in HIV-infected patients.

PURPOSE: This retrospective study investigates the effect of prior nucleoside (nucleoside reverse transcriptase inhibitor [NRTI]) experience on 2-year virologic response to an initial protease inhibitor-highly active antiretroviral therapy (PI-HAART) regimen. METHOD: 152 patients who started a PI (excluding saquinavir hard gel capsule [hgc] as a sole PI) with two NRTIs between January 1996 and May 1998 at two HIV treatment sites were included. RESULTS: 109 patients (71%) were NRTI experienced. 106 patients received two new NRTIs, and 32 received one new NRTI. Overall, 51% of patients had a virologic response (HIV viral load <400 copies/mL); the mean follow-up was 28 months. Virologic response was associated with the use of at least one new NRTI (relative risk [RR] 2.1; p =.031) but not with prior NRTI experience (p =.19). A complete virologic response was most likely to occur when two new NRTIs were used (RR 2.3) rather than one new NRTI (RR 1.8), but this was not significant (p =.12). CONCLUSION: This study suggests that prior nucleoside experience is not a key predictor of 2-year virologic response in patients who receive at least one new NRTI in an initial PI-HAART regimen.

The T lymphocyte structure CD60 contains a sialylated carbohydrate epitope that is expressed on both gangliosides and glycoproteins.

The CD60 antigen is expressed on a majority of T cells in autoimmune lesions, and anti-CD60 can activate T lymphocytes. CD60 has been defined as the GD3 ganglioside, and subsequently as the 9-O-acetylated form of GD3. However, other evidence suggests that anti-CD60 recognizes a glycoprotein or family of glycoproteins expressed by T lymphocytes. The current studies were undertaken to better define the identity of the CD60 antigen on both T cells and non-T cells. Treatment of intact cells with neuraminidases of various specificities confirmed that detection of the CD60 epitope depends on expression of an alpha2, 8-disialic acid carbohydrate linkage, as is found in GD3 and related gangliosides. However, the sialicacid polymer colominic acid inhibited anti-GD2 and anti-GD3, but not anti-CD60 from binding to cell surfaces. Expression of CD60 did not correlate with expression of GD3 on a variety of cell lines and T cell populations. Expression of CD60 and 9-O-acetyl-GD3 was roughly parallel on some non-T cell lines such as melanoma cells, but on T cells expression of CD60 was consistently greater. Antibodies to GD2, GD3 and 9-O-acetyl-GD3 were ineffective at inhibiting binding of anti-CD60 to CD60+ cells. Activation responses of T cells to anti-CD60 were inducible in either the presence or absence of a response to anti-GD3. A novel inhibitor of glucosyl ceramide synthesis, D-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (D-t-P4) reduced expression of GD3 much more than CD60 on activated T lymphocytes. Following biotinylation of HUT78 T cells, anti-CD60 immunoprecipitated a 70 kDa antigen. Taken together, the present data and previous findings suggest that anti-CD60 can recognize both a modified form of the GD3 ganglioside and a carbohydrate-dependent complex epitope present on one or more glycoproteins. This glycoprotein epitope may be the more abundant and functionally significant CD60 antigen on T lymphocytes, while 9-O-acetyl-GD3 is likely to be the principal structure recognized by anti-CD60 on melanoma cells. These findings emphasize the complexity of understanding the functional roles of carbohydrate epitopes in cell activation.

The new commitment to patient satisfaction.

CheckUp helps dentists measure and increase patient satisfaction through easy, inexpensive patient surveys. The CheckUp survey is endorsed by the American Dental Association (ADA) and several state dental associations. This article discusses the importance of committing to and maintaining the highest possible level of patient satisfaction not only as a practice management strategy, but also as a source of pride in one's reputation as a professional.

Evidence of a locus for schizophrenia and related disorders on the short arm of chromosome 5 in a large pedigree.

We attempted to identify a locus for schizophrenia and related disorders in 24 nuclear families of schizophrenic probands using a predefined classification system for affected cases that included those disorders most clearly identified as sharing a genetic relationship with schizophrenia--schizoaffective disorder and schizotypal personality disorder. Initially, we evaluated 8 markers on chromosome 5 on the first 12 families with available genotyping and diagnostic assessments and, assuming autosomal dominant transmission, found a lod score of 2.67 for the D5S111 locus (5p14.1-13.1) in one large nuclear family (no. 17; sibship: n = 12; schizophrenia: n = 3; schizotypal personality disorder: n = 2); the other 11 families were much smaller, less complete, and provided little additional information. Other branches of no. 17 were then assessed and the 2-point lod score for family 17 rose to 3.72; using multipoint analysis the lod score in 17 was 4.37. When only schizophrenia was used to define affectedness, the positive evidence for linkage to D5S111 was greatly reduced. Sensitivity analysis indicated that the lod score is heavily dependent upon the predefined diagnostic criteria. Our studies of other families of schizophrenic probands eventually totalled 23, but linkage to D5S111 in these yielded a -2.41 lod score. The results provide evidence for genetic linkage of the D5S111 locus to schizophrenia and related disorders in one family. It may be of interest that over several generations, almost all the ancestors of family 17 could be traced back to a small, relatively isolated, hill region of Puerto Rico.

Characterization of the oligosaccharide structures on bee venom phospholipase A2.

The N-linked oligosaccharide structures on bee venom phospholipase A2 were investigated. The oligosaccharides on purified phospholipase A2 were released by hydrazinolysis and labeled in vitro by reduction with NaB3H4. Following purification, the labeled oligosaccharides were characterized by size exclusion chromatography in combination with digestion with specific glycosidases. Linkage positions were determined by methylation analysis. Four types of structures were identified on the molecule, all of which were of truncated high-mannose type and none of which contained any alpha-(1-->2)-linked mannose residues. The majority of the structures were Man3 oligosaccharides with (43%) or without (38%) a fucose residue linked alpha-(1-->6) to the reducing N-acetylglucosamine. The remaining 19% of the oligosaccharides on the molecule were identified as a Man5 oligosaccharide without core fucose (9.6%) and a core-fucosylated Man4 structure (9.2%).

Isolation and expression of a cDNA clone encoding a bovine UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase.

NH2-terminal amino acid sequence obtained from a UDP-GalNAc:polypeptide N-acetylgalactosaminyl-transferase (GalNAc-transferase) isolated from bovine colostrum was used for the construction of synthetic oligonucleotide primers. Subsequent polymerase chain reaction and library screenings of a bovine intestine cDNA library produced seven positive clones. The largest clone had a 2294-base pair insert that contained an open reading frame coding for a protein composed of 559 amino acids with a predicted polypeptide molecular mass of 64,173 Da. The cloned molecule has no significant sequence homology to previously reported cloned glycosyltransferases, but appears to have a similar domain structure. It is a type II membrane protein with a 23-amino acid putative transmembrane region starting 8 amino acids from the NH2 terminus. The transmembrane segment of the molecule is immediately followed by a sequence rich in proline residues. The molecule contains three consensus sequences for N-linked glycosylation and five predicted sites for O-glycosylation. Northern blot analysis of poly(A+) mRNA isolated from Madin-Darby bovine kidney cells, bovine mammary tissue, and eight human tissues demonstrated the expression of two transcripts differing in size by approximately 1 kilobase. The cloned DNA was expressed in insect cells using a baculovirus vector. This resulted in an almost 100-fold increase in GalNAc-transferase activity in lysates prepared from cells infected with virus containing the GalNAc-transferase gene compared to cells infected with virus containing DNA coding for an unrelated molecule or uninfected cells. Immunoprecipitation from lysates prepared from infected cells labeled in vivo with [35S] methionine showed a large increase in the recovery of an approximately 67-kDa protein.

High temperature fluorescence cell for laser spectroscopy of Na in noble gas atmospheres: design and performance.

The design and performance of a simple fluorescence cell for laser-spectrometric studies of metal vapors at elevated temperatures (T

Antithymocyte gamma globulin, low-dosage cyclosporine, and tapering steroids as an immunosuppressive regimen to avoid early kidney failure in heart transplantation.

Cyclosporine is a powerful immunosuppressive agent that unfortunately has significant renal toxicity. Two risk factors associated with a high incidence of kidney failure in patients receiving cyclosporine have been described in the literature. In an effort to decrease the possibility of renal toxicity with the use of cyclosporine, we use low-dosage cyclosporine, antithymocyte gamma globulin, and tapering dosages of steroids as an immunosuppressive regimen. Twenty-one patients had orthotopic heart transplants from January 1985 to January 1986. Sixteen of 21 patients or 70% had at least one high risk factor for kidney failure. There were no episodes of acute kidney failure, and the blood urea nitrogen and creatinine levels that were recorded over an average of 8.5 months per patient did not increase significantly from preoperative values. Seventeen of 21 or 81% of the patients are alive and functioning fully. The incidence of rejection per patient was 0.9, and there were no biopsy-proven severe rejections. One patient died at 5 months; the autopsy showed generalized moderate rejection. There were 0.24 episodes of infection per patient, with one patient who died from Pneumocystis pneumonia. With this immunosuppression protocol, early postoperative kidney dysfunction was avoided. The incidences of rejection and infection were within acceptable range, and the quality of life in the 17 survivors is excellent.

[Serum testosterone response to chorionic gonadotropin (HCG) injection in normal and cryptorchid children (author's transl)]. / Respuesta de la testosterona sérica in la inyección de gonadotrofina coriónica (HCG) en niños normale y con criptorquídia.

Plasma testosterone (ng/ml) was measured in a group of prepuberal children with intrascrotal testes (n = 15) and in a group of prepuberal cryptorchid children (7 unilateral and 3 bilateral; n = 10) before and after stimulus with 3000IU of HCG (Group A) and with 5000IU (Group B). The serum testosterone before HCG stimulus was similar in normal (Group A: 1.10 +/- 0.03: Group B: 1.18 +/- 0.31) as well as in those of the cryptorchid children (Group A: 1 +/- 0.28; Group B: 1.19 +/- 0.36). The stimulus with 3000IU of HCG did not significantly raise the plasma testosterone in both normal (2.42 +/- 1.09) and cryptorchid children (1.70 +/- 0.5). The stimulus with 5000IU of HCG increased the plasma testosterone to 3.52 +/- 1 in normal children and 3.26 +/- 1.2 in cryptorchid children (p less than 0.05 with respect to the pre HCG values), with no difference in the response between the normal and the cryptorchid children.

Visually monitored postrotary nystagmus in seven autistic children.

Therapists who evaluate the sensorimotor functions of autistic children have become increasingly interested in monitoring their responses to vestibular stimulation. In this study, the duration of the nystagmus reflex is visually monitored and then measured by means of a stop-watch. Each of 7 autistic subjects received 18 sessions (36 trials) of horizontal semicircular canal stimulation during a period of 25 days. In each trial a graduated acceleration in a hand operated rotating chair preceded an abrupt stop, with a rapid deceleration from 180 degrees/second to 0 degree/second. Although subject option (intentional response) imposes limitations on the data interpretation, inspection of the nystagmus functions over time suggests the following: substantial trial-to-trial variability; substantial subject-to-subject variability; greater scores following trials to the subjects' left (the direction of the second trial in each session) than to the right (the direction of the first); and no evidence of consistent change for most subjects in nystagmus duration across the 36 trials. Implications for clinical evaluation of nystagmus are discussed.