Motor function of the proximal stomach and visceral perception in gastro-oesophageal reflux disease

Oxytocin (OT) is present in the mammalian testis and has been shown to play a role in the modulation of seminiferous tubule contractility and steroidogenesis. However, stage-specific effects of the peptide have not been previously investigated. In this study, computer-assisted analysis and time-lapse videomicrography were used to investigate basal contractility and the response to OT of seminiferous tubules at specific stages of the spermatogenic cycle. Adult rat testes were placed in fresh oxygenated DMEM F12 medium, decapsulated, and the tubules gently teased apart. Stages were identified by transillumination and a 10 mm section of tubule at each of stages IV-V, VII-VIII and XIII-I was placed in a microslide chamber and perifused with medium. After a control period of 3 h, OT (2 nM) was given for 1 h, followed by another control period of 1 h. The experiment was repeated using tubules from different rats and data were analysed to give arbitrary units of tubule contractility. Contractility was observed in all the tubules studied and the contractile activity was shown to vary depending on the stage of the spermatogenic cycle. Mean basal contractility at stages VII-VIII, the time when sperm are shed from the epithelium, was significantly lower than that at stages IV-V and XIII-I. The response of the tubules to OT was also stage-dependent, with the peptide producing the largest increases in contractile activity at stages VII-VIII and having no effect at stages IV-V. We postulate that these stage-specific differences in basal and OT-stimulated contractility may be important in co-ordinating the movement of developing germ cells towards the lumen of the seminiferous epithelium and in the process of spermiation.     

Predicting the development of late-life late-onset drinking problems: a 7-year prospective study

There has been little empirical study of risk factors for the development of late-life late-onset drinking problems. In the current prospective study, we compare two groups of older adults who, at a baseline assessment, were nonproblem drinkers: individuals who developed drinking problems over the course of the next 7 years (n = 77) and those who did not (n = 197). Late-onset problem drinkers reported mild to moderate drinking problems and spontaneous remission rates were high. Compared with stable nonproblem drinkers, late-onset problem drinkers at baseline were more likely to report incipient problems, heavier alcohol consumption, greater friend approval of drinking, more reliance on avoidance coping strategies, were more likely to smoke, and were less likely to have acute medical conditions that could potentially be complicated by alcohol consumption. Contrary to expectation, life stressors did not predict drinking problem onset. However, compared with stable nonproblem drinkers, late-onset problem drinkers were more likely to have a history of responding to stressors and negative affect with increased alcohol consumption.     

Effect of oral acyclovir or ganciclovir therapy after preemptive intravenous ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus seropositive renal and liver transplant recipients receiving antilymphocyte antibody therapy

BACKGROUND: Organ transplant recipients who are seropositive for cytomegalovirus (CMV) and who are treated with antilymphocyte antibody (ALA) therapy have a high rate of symptomatic CMV disease. The intravenous administration of ganciclovir therapy once daily during ALA therapy decreased the incidence from 24% to 10% in patients receiving ALA as an induction therapy and from 64% to 22% in those treated for rejection. The present study was undertaken to determine whether a more intensive and sustained antiviral regimen could be more effective. METHODS: From April 1995 to December 1997, all CMV seropositive renal and liver transplant recipients who received ALA therapy were treated with intravenously administered ganciclovir (5 mg/kg/day with dose adjusted for renal dysfunction) for the length of ALA therapy and then with orally administered acyclovir (400 mg three times/day) or ganciclovir (1 gm twice/day) for 3 to 4 months. The incidence of CMV viremia and of CMV disease was determined during the 6 months after completion of ALA therapy. RESULTS: Forty-one patients (35 renal and 6 liver transplant recipients) were studied. CMV disease occurred in 2 patients (4.9%), both of whom were treated for rejection; it occurred in 1 of 21 patients (4.8%) treated with orally administered acyclovir, and in 1 of 20 patients (5%) treated with orally administered ganciclovir. The only patient who developed CMV disease in the ganciclovir group had received only 26 days of oral antiviral therapy. No CMV disease was documented in the group of patients receiving ALA therapy as induction therapy. CMV viremia occurred in three patients in the acyclovir group (14.3%) and in one patient in the ganciclovir group (5%). Among renal transplant recipients only, 1 of 35 patients developed CMV disease (2.9%) and no case of CMV disease was documented in patients treated with orally administered ganciclovir. All six patients receiving two courses of ALA therapy each were free of CMV disease. Toxicity of the regimen was minimal, and antiviral resistance did not develop. CONCLUSIONS: Preemptive antiviral therapy with intravenously administered ganciclovir during ALA therapy and then orally administered ganciclovir for 3 to 4 months provides virtually complete protection against the excessive rate of CMV disease that occurs in CMV seropositive allograft recipients receiving ALA therapy.     

Reliability of phase-velocity measurements of tibial bone

BACKGROUND AND PURPOSE: The Bone Stiffness Measurement Device-Swing is capable of measuring the propagation velocity of flexural waves in human tibial bone, which relates to bending stiffness. If the interrater and intrarater reliability of measurements obtained with the device are established, it can be used with confidence in assessing changes in bone. The purposes of this study were to detect potential sources of measurement error and to establish the interrater and intrarater reliability of measurements taken with the device. SUBJECTS AND METHODS: In the first part of the study, a random-effects design was used to obtain phase-velocity measurements in subjects without known orthopedic or neurological impairments. The second part of the study consisted of possible applications of the device with mixed designs on subjects with spinal cord injuries. By means of generalizability theory, multiple sources of error (eg, occasion, clinician, repetition) were estimated. For the clinical trial, 17 persons with spinal cord injuries not older than 5 weeks were tested. RESULTS: The standard error of measurement (SEM) for intrarater reliability measurements ranged from 7.3 to 9.8 m x s(-1) . The SEMs for interrater reliability measurements ranged from 5.7 to 9.5 m x s(-1). The SEMs for measurements obtained by a single clinician in a clinical population ranged from 11.9 to 39.7 m x s(-1). CONCLUSION AND DISCUSSION: The reproducibility of measurements obtained with the device is suitably high for the device to be used for evaluation in clinical and research settings.     

Comparison between enzyme-linked immunosorbent assay and cytotoxic cross-match procedures for detecting IgG anti-donor antibodies

BACKGROUND: Disadvantages inherent to complement-dependent cytotoxicity cross-match (CDC XM) methods are the requirements for complement and viable target cells, detection of antibodies (Abs) against non-HLA antigens, and subjective scoring. Cross-Stat (SangStat Medical Corp., Menlo Park, CA), a recently developed enzyme-linked immunosorbent assay XM procedure for the detection of IgG anti-donor HLA Abs, is theoretically devoid of these flaws. METHODS: We compared results of Cross-Stat and our standard anti-human globulin (AHG)-enhanced CDC XM procedure on 524 sera from 230 transplant candidates, which were evaluated against 51 cadaveric donors. RESULTS: There was a significant correlation between AHG-CDC IgG XM and Cross-Stat results (P<0.001). For false negative sera, repeat AHG-CDC IgG XMs were still positive after platelet absorption, indicating that the Abs present were either non-HLA Abs or anti-HLA class II. Flow cytometry testing of false positive sera usually (42/62) substantiated Cross-Stat results, indicating that the discrepancy with AHG-CDC IgG XM is caused by greater sensitivity of Cross-Stat. Relative to the AHG-CDC XM, the sensitivity of Cross-Stat was 100%, the specificity was 93%, the positive predictive value was 73%, and the negative predictive value was 100%. A technical shortcoming of the Cross-Stat assay is that the frequency of indeterminate samples in the assays was 15%. Among 49 Cross-Stat negative vs. 13 Cross-Stat positive primary cadaveric renal allograft recipients (all AHG-CDC IgG-XM negative), there was no statistical difference in overall graft survival. CONCLUSION: Given the important theoretical advantages of enzyme-linked immunosorbent assay-based XM methods over the CDC XM, however, further testing of the clinical relevance of the Cross-Stat is warranted.     

Pattern formation in chick feather development: distribution of beta 1-integrin in normal and scaleless embryos

We have examined the immunolocalization of beta 1-integrin during feather development in the spino-lumbar tract of the backskin from normal and scaleless chick embryos. beta 1-integrin appears during early feather development in three distinct phases which correspond to important developmental events. The first phase (5-5 1/2 days of incubation; Hamburger and Hamilton [H.H.] stage 27) represents the period prior to the formation of dermis. During this phase, beta 1-integrin antiserum labels mesenchymal cells located in the central region of the spino-lumbar tract where the initiation site for feather development is located. The second phase (5 1/2-7 1/2 days of incubation; H.H. stages 28-32) corresponds to the period during which dermis is formed. The cells that make up the dermis are readily distinguished by their lack of beta 1-integrin immunostaining. The third phase (7 1/2-10 days of incubation; H.H. stages 33-36) begins with the sudden appearance of beta 1-integrin in the central and lateral regions of the dermis. The pattern of beta 1-integrin immunostaining in scaleless backskin becomes different from that of normal backskin during this phase. In normal backskin the dermal condensations of feather germs are not labeled with the beta 1-integrin antiserum. This produces a heterogeneous immunostaining pattern very similar to the pattern seen for Type I collagen (Mauger et al. [1982] Dev. Biol. 94:93-105). In contrast, homogeneous immunostaining is observed in the dermis of scaleless backskin. The initial time of appearance, manner of appearance, and pattern of integrin expression in the third phase suggest that beta 1-integrin may be involved in the stabilization of the feather pattern. We also observed the appearance of beta 1-integrin on the epidermal basal cells during the time of feather follicle formation. The beta 1-integrin antiserum reacts strongly with the baso-lateral surfaces of normal basal cells, yet the basal surfaces of the scaleless basal cells are unstained. This lack of immunostaining along the basal surfaces of the scaleless basal cells may relate to the abnormal adhesion between the epidermis and dermis in scaleless backskin.     

Dietary modulation of human platelet phenolsulphotransferase activity

1. The mammalian phenolsulphotransferase enzymes are known to play a major role in both the detoxification and possibly the activation of pre-carcinogenic phenols and aromatic amines. 2. Vegetable cytosol preparations were tested in vitro for their ability to affect the sulphation of two reference compounds (rho-nitrophenol and dopamine, which are selective substrates for the phenol and monoamine forms of phenolsulphotransferase respectively), and to act as substrates for the enzymes in comparison with the same reference compounds. 3. The majority of cytosols greatly decreased (> 80%) the sulphation of either or both the reference compounds. This effect may have been due to either enzyme inhibition or substrate binding. 4. Whereas some of the cytosols were sulphated under the assay conditions, most were not. Additionally, it was found that a cytosol that decreased the sulphation of the two reference compounds was not necessarily poorly sulphated itself. 5. It is concluded that dietary factors have the potential to play a major role in modulating the sulphation detoxification pathway, and have wide ranging implications with regard to adverse drug reactions.