Predictors of gastric emptying in Parkinson''s disease

Predictors of gastric emptying (GE) in patients with idiopathic Parkinson's disease (PD) of a solid and liquid meal are not well defined. For measurement of GE 80 patients with PD were randomly assigned to receive either a solid meal (250 kcal) containing 13C-octanoate (n = 40) or a liquid meal (315 kcal) with 13C-acetate (n = 40). All patient groups were off medication affecting motility and were matched for age, gender, body mass index, disease duration and severity, using Unified Parkinson's Disease Rating Scale (UPDRS). Gastric emptying was compared with a healthy control group (n = 40). Multiple regression analysis was used to determine predictors of gastric emptying. Exactly 88% and 38% of PD patients had delayed GE of solids and liquids respectively. Solid and liquid emptying was similar in women and men. There were no differences in GE in PD patients < 65 years of age when compared with patients > or = 65 years. Multiple regression analysis showed that motor handicaps such as rigour and action tremor are independent predictors of solid GE (r = 0.68, P < 0.001). The severity of motor impairment, but not any other neurological symptom, as assessed by UPDRS is associated with gastroparesis in PD and solid emptying is more likely to be delayed.     

Inhibin and renin in follicular fluids of patients with one or two ovaries stimulated with a GnRH agonist and gonadotrophins

Follicular fluids from eight patients with one ovary and from ten patients with two ovaries were investigated for bioactive inhibin, total renin, oestradiol (E2) and progesterone (P4) concentrations. Four follicular fluids were pooled per patient before assessment. All women had been stimulated similarly using a protocol including a GnRH agonist, HMG and HCG. Renin levels were significantly lower and P4 significantly higher in pools of follicular fluid from patients with one ovary, whereas inhibin and E2 concentrations were similar in both patient groups. A significant negative correlation was found in the pools of follicular fluid between inhibin and E2 in both groups. These results suggest a role for inhibin and renin in the paracrine and autocrine control of stimulated follicular development.     

Increased plasma cathepsin D concentration in hepatic carcinoma and cirrhosis but not in breast cancer

Using a sandwich enzyme-linked immunoassay, plasma total cathepsin D concentration was assayed in 40 breast cancer patients and 84 patients with various liver diseases and compared to that of 52 normal subjects. There were no significant variations found in breast cancer patients related to tumor size, node invasiveness or metastases. In normal women, cathepsin D levels were slightly but not significantly increased in the luteal phase and in pregnancy. By contrast, plasma cathepsin D concentration was significantly increased in 70-75% of patients with liver disease (cirrhosis, hepatocarcinoma, hepatitis), but not in those with liver steatosis. Cathepsin D was independent of most of the plasma hepatic function tests and was correlated with alpha-fetoprotein in cirrhosis and with alpha-fucosidase in primary hepatocellular carcinoma. We conclude that plasma cathepsin D is not a useful marker in breast cancer. However, since the cellular level of this protease is associated with risk of metastasis in breast cancer, clinical follow-up will be required to test whether high cathepsin D plasma concentration has any prognostic value in liver cirrhosis and primary hepatocarcinoma.     

One‐ and two‐stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint

Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single‐ordered categorical endpoint. The sample size requirements for one‐stage and two‐stage designs are derived, based on an approach similar to that of Dunnett. Detailed computations are prepared for an illustrative example concerning a study in stroke. Allowance for early stopping for futility is made. Simulations are used to verify that the specified type I error and power requirements are valid, despite certain approximations used in the derivation of sample size. The advantages and disadvantages of the different designs are discussed, and the scope for extending the approach to different forms of endpoint is considered. Copyright © 2008 John Wiley & Sons, Ltd.     

Flow cytometry analysis of platelet antibodies

We have devised assays to detect both circulating alloantibodies to platelets (indirect assay) and platelet-association IgG and IgM (direct assay) using a flow cytometric technique. A variety of patients with immune thrombocytopenia were studied. Employment of a confocal lens in the flow cytometer increased the discrimination power of the instrument. Patients with autoimmune thrombocytopenia (idiopathic thrombocytic purpura [ITP], systemic lupus erythematosus (SLE), lymphoma, leukemia, and drug-induced thrombocytopenia showed a significant increase in platelet-associated antibody. Circulating antibodies to platelets (alloantibodies) were demonstrated in cases of platelet refractoriness and neonatal isoimmune purpura. Day-today precision of the assays ranged from 3% to 6% (coefficient of variation). No interference was shown in the presence of hemoglobin (5 g/L), triglycerides (10 g/L), or polyclonal and monoclonal immunoglobulinemia (50 g/L: IgG, IgA, IgM). The sensitivity of the direct assay was 500 attograms of IgG or IgM platelet.     

The estrous cycle affects cocaine self-administration on a progressive ratio schedule in rats

Although it has been demonstrated that many of the behavioral responses to psychomotor stimulants are gender dependent and hormonally sensitive, few studies have examined the possibility that the estrous cycle interacts with drug reinforcement in laboratory animals. The present experiment assessed the effect of the estrous cycle on two aspects of cocaine self-administration behavior: the breaking point on a progressive ratio (PR) schedule and the rate of cocaine intake on a fixed ratio one (FR1) schedule. On the PR schedule, the first lever response produced a drug infusion. Subsequent response requirements escalated with each injection until the behavior extinguished. Breaking points were defined as the final ratio completed. On a FR1 schedule, the estrous cycle had no effect on the rate of drug intake. On a PR schedule, female rats reached higher breaking points during estrus than during other stages of the estrous cycle. Furthermore, female rats displayed higher breaking points than male rats. It appears that the estrous cycle influences an animal's motivation to self-administer cocaine.     

Is endoscopic one‐piece mucosal resection essential for early gastric cancer?

Background: Endoscopic mucosal resection (EMR) is widely accepted as a minimally invasive treatment for early gastric cancer (EGC) in Japan. However, the criteria for EMR must be strictly adhered to otherwise patients will miss the chance for additional therapy. We assess the important factor in expanding the indication of EMR. Methods: We investigated 1101 EGCs that had been resected by EMR at the National Cancer Center Hospital (NCCH), Tokyo, Japan, according to the indication recommended by Japanese Gastric Cancer Association (JGCA) and the expanded indication proposed by NCCH. Curability and local recurrence of the EMRs were assessed related to the applied indication and the number of resected specimens. Results: The recurrence rate of non‐evaluable resection was higher than that of evaluable resection (P < 0.0001). Eighty‐three lesions among 772 lesions in the JGCA group were non‐evaluable. Thirty‐seven leisons among 329 lesions in the NCCH group were non‐evaluable. There was no difference in the rate of non‐evaluable resection between JGCA and NCCH groups (P = 0.8329). However, the rate of curative resection was lower in the NCCH group than in the JGCA group (P = 0.0009). In piecemeal resection, there was no difference in the rate of non‐evaluable resection between JGCA and NCCH groups (P = 0.0527). In one‐piece resection, the rate of non‐evaluable resection was lower in the NCCH group than the JGCA group (P = 0.0137). Conclusion: Based on our series of cases, we propose one‐piece resection as a gold standard for EMR because it enables accurate histological evaluation, even in the EMR, according to the expanded indication.     

The pH of Exhaled Breath Condensate of Patients with Allograft Rejection After Lung Transplantation

Endogenous airway acidification, as assessed by the condensate pH, has been implicated in the pathophysiology of inflammatory airway diseases such as cystic fibrosis and asthma. The aim of this study was to investigate the pH of condensate in patients after lung transplantation (LTX). From the cohort of transplanted patients at our center, 83 patients (9 heart-lung transplantation, 48 double-lung transplantation, 26 single-lung transplantation) were recruited and analyzed in a cross-sectional manner: 26 patients were diagnosed with chronic rejection or bronchiolitis obliterans syndrome (BOS), 7 patients were diagnosed with acute rejection (AR) while 50 patients had no evidence of rejection according to the International Society for Heart and Lung Transplantation criteria. The condensate pH was significantly reduced in patients with BOS and AR when compared to patients without rejection and control subjects (5.8 +/- 0.5 and 6.2 +/- 0.4 versus 6.6 +/- 0.4 and 6.5 +/- 0 .4, respectively; p < 0.05). Moreover, there was a significant correlation between condensate pH levels and the BOS grade (r =-0.62; p < 0.01), the FEV(1) (r = 0.39; p < 0.01) and the total cell and neutrophil count in bronchoalveolar lavage fluid (r =-0.39 and r =-0.56, respectively; p < 0.01). Airway acidification occurs in BOS and may directly or indirectly reflect airway inflammation in patients with allograft rejection after LTX. Measuring condensate pH might thus be a new tool for the evaluation of rejection in lung transplant patients.     

Circulating filarial antigen in cats infected with Brugia pahangi is indicative of the presence of adult worms

Using counterimmunoelectrophoresis with rabbit antisera raised against soluble extracts of adult females of Brugia pahangi parasite antigen was detected in the serum of all cats repeatedly infected with B. pahangi. Antigen was never detected in uninfected cats. The antigen was associated with the presence of adult worms. Antigen was detected consistently in a cat that was amicrofilaraemic but at autopsy harboured only two or three adult worms. Conversely, some cats showed slowly declining numbers of microfilariae and, in these, circulating antigen declined before the number of microfilariae. Eventually no antigen was detectable in circulation whereas microfilariae, although in diminishing numbers, were still present. At autopsy no adult worms were found in these cats. Antigen also appeared in several cats before they became microfilaraemic.