Effects of a Rice Bran Dietary Intervention on the Composition of the Intestinal Microbiota of Adults with a High Risk of Colorectal Cancer: A Pilot Randomised-Controlled Trial

Rice bran exhibits chemopreventive properties that may help to prevent colorectal cancer (CRC), and a short-term rice bran dietary intervention may promote intestinal health via modification of the intestinal microbiota. We conducted a pilot, double-blind, randomised placebo-controlled trial to assess the feasibility of implementing a long-term (24-week) rice bran dietary intervention in Chinese subjects with a high risk of CRC, and to examine its effects on the composition of their intestinal microbiota. Forty subjects were randomised into the intervention group (n = 19) or the control group (n = 20). The intervention participants consumed 30 g of rice bran over 24-h intervals for 24 weeks, whilst the control participants consumed 30 g of rice powder on the same schedule. High rates of retention (97.5%) and compliance (≥91.3%) were observed. No adverse effects were reported. The intervention significantly enhanced the intestinal abundance of Firmicutes and Lactobacillus, and tended to increase the Firmicutes/Bacteroidetes ratio and the intestinal abundance of Prevotella_9 and the health-promoting Lactobacillales and Bifidobacteria, but had no effect on bacterial diversity. Overall, a 24-week rice bran dietary intervention was feasible, and may increase intestinal health by inducing health-promoting modification of the intestinal microbiota. Further larger-scale studies involving a longer intervention duration and multiple follow-up outcome assessments are recommended.     

Influence of α-tocopherol over the time course of experimental IgA nephropathy

 The present study investigated the pathogenesis and the time course of kidney injury in experimental IgA nephropathy. In order to determine an appropriate period in the course of experimental IgA nephropathy to study renal injury and repair, we examined proteinuria and IgA deposition in the renal mesangium after 4, 8, and 16 weeks of mucosal challenge by bovine gamma globulins (BGG) provided in the drinking water. The hallmark of IgA deposition in the mesangium was present after 4 weeks and 8 weeks of BGG inoculation, but by 16 weeks, the mesangial IgA deposition had resolved. In addition, we confirmed our previous report on the beneficial effects of α-tocopherol in reducing proteinuria in IgA nephropathy at 8 weeks, and extended this observation to investigate the effects of dietary supplementation of α-tocopherol at both 4 weeks and 16 weeks. Proteinuria resolved spontaneously at 16 weeks. There is oxidative stress, as suggested by the elevation in plasma and renal malondialdehyde content, and increased fibrogenic cytokine message, as suggested by elevated transforming growth factor β1 mRNA. These increases were clearly blunted by α-tocopherol at both 4 weeks and 8 weeks. Treatment with α-tocopherol was associated with a significant reduction in the severity of proteinuria. Thus, our data suggest that the period between 4 and 8 weeks of BGG vaccination could be relevant in designing an appropriate model to study the molecular biology of the pathogenesis of renal injury and the effects of treatment. The 16-week model may be useful in exploring gene expression involved with spontaneous resolution. Received: 17 February 1998 / Revised: 2 June 1998 / Accepted: 3 June 1998     

Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy.

PURPOSE: For cancer patients receiving cytotoxic chemotherapy, hepatitis B virus (HBV) reactivation is a well described complication resulting in varying degrees of liver damage. The objectives of this study were to assess the efficacy of the antiviral agent lamivudine in reducing the incidence of HBV reactivation and diminishing morbidity and mortality of cancer patients with chronic HBV infection during chemotherapy. PATIENTS AND METHODS: Two groups were compared in this nonrandomized study. The prophylactic lamivudine group consisted of 65 patients in a phase II study who were treated with lamivudine before and until 8 weeks after discontinuing chemotherapy. The historical controls consisted of 193 consecutive patients who underwent chemotherapy without prophylactic lamivudine. Significant prognosticators for the development of HBV reactivation were determined based on data from the controls. Potential confounding factors were identified between the two groups. The outcomes were compared. RESULTS: In the controls, lymphoma and anthracycline usage were factors identified to be associated with reactivation. The two groups were comparable in most baseline characteristics, although in the prophylactic lamivudine group, there were significantly more patients with lymphoma and receiving anthracyclines. In the prophylactic lamivudine group, there was significantly less HBV reactivation (4.6% v 24.4% in the controls; P <.001), fewer incidences of hepatitis (17.5% v 44.6%; P <.0001) that were less severe (4.8% v 18.7%; P =.0005), and less disruption of chemotherapy (15.4% v 34.6%; P =.0029). The reduction in overall mortality was not statistically different. CONCLUSION: Prophylactic lamivudine significantly reduced the incidence of HBV reactivation and the overall morbidity of cancer patients undergoing chemotherapy.     

Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: therapeutic monitoring with plasma Epstein-Barr virus DNA.

PURPOSE: To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. PATIENTS AND METHODS: Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. CONCLUSION This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC.     

Phase II study of Temodal in the treatment of patients with advanced nasopharyngeal carcinoma

Purpose: A single-institution phase II trial of Temodal (temozolomide, SCH52365) in Chinese patients with advance nasopharyngeal carcinoma was undertaken to determine the efficacy and safety of the drug in this population. Methods: A total of 14 patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma were entered into the study. One patient was unevaluable. Temodal was given at doses of 150 or 200 mg/m² daily on days 1–5 every 28 days. Results: In all, 30 cycles of Temodal were given with no significant toxicity. All 13 (100%) evaluable patients had progressive disease after 2 (84.6%) or 4 (15.4%) courses. Conclusion: Temodal given on this schedule has no activity in advanced nasopharyngeal carcinoma. Received: 9 January 1998 / Accepted: 4 February 1998     

Video-fluoroscopic study of swallowing in children with neurodevelopmental disorders

BACKGROUND: Children with neurodevelopmental disorders can have feeding problems. Malnutrition and recurrent aspiration pneumonia can increase the risk of morbidity and mortality. Video-fluoroscopic study of swallowing (VFSS) is essential in understanding the pathological mechanisms involved during swallowing. METHODS: The aim of the present study was to assess the role of VFSS in assessment and management of four children with various neurodevelopmental disorders in a multidisciplinary feeding team. We describe the team approach, with the participation of child neurologist, radiologist with the rehabilitation team including the speech therapist, occupational therapist and dietician, in the assessment and plan of management. RESULTS: Video-fluoroscopic study of swallowing had been useful in assessing the type of swallowing problems with treatment goals targeted to the basic underlying pathophysiological mechanism. CONCLUSION: A child neurologist should be involved in the multidisciplinary oromotor rehabilitation program for neurologically impaired children with feeding problems.     

Synthesis and evaluation of a 18F‐labeled 4‐phenylpiperidine‐4‐carbonitrile radioligand for σ1 receptor imaging

We report the design and synthesis of several 4‐phenylpiperidine‐4‐carbonitrile derivatives as σ₁ receptor ligands. In vitro radioligand competition binding assays showed that all the ligands exhibited low nanomolar affinity for σ₁ receptors (K_i(σ₁) = 1.22–2.14 nM) and extremely high subtype selectivity (K_i(σ₂) = 830–1710 nM; K_i(σ₂)/K_i(σ₁) = 680–887). [¹⁸F]9 was prepared in 42–46% isolated radiochemical yield, with a radiochemical purity of >99% by HPLC analysis after purification, via nucleophilic ¹⁸F^‐ substitution of the corresponding tosylate precursor. Biodistribution studies in mice demonstrated high initial brain uptakes and high brain‐to‐blood ratios. Administration of SA4503 or haloperidol 5 min prior to injection of [¹⁸F]9 significantly reduced the accumulation of radiotracers in organs known to contain σ₁ receptors. Two radioactive metabolites were observed in the brain at 30 min after radiotracer injection. [¹⁸F]9 may serve as a lead compound to develop suitable radiotracers for σ₁ receptor imaging with positron emission tomography.     

Management of drooling for children with neurological problems in Hong Kong

OBJECTIVES: To share our experience in the management of drooling in Hong Kong, to describe the clinical profile of children with this problem, and to report the clinical outcome of oro-motor training. METHODS: Children attending the Drooling Clinic of Alice Ho Miu Ling Nethersole Hospital, Hong Kong between January 2000 and June 2003 were included. Multidisciplinary assessment was performed to ascertain the medical condition, functional status and oro-motor difficulties of each child. Intervention might include optimization of medical condition, oro-motor training and surgery. Severity of drooling was rated by a 10-point visual analogue scale (VAS). The outcome of oro-motor training was assessed by the change in VAS from baseline. RESULTS: Eight children, with a mean age of 11.9 years, were included. Six children suffered from cerebral palsy and two had syndromal diagnoses. All had moderate or severe mental retardation. Poor lip closure, inadequate jaw control and delay in swallowing were common oro-motor difficulties. All children received oro-motor training. The mean duration of follow-up for seven children was 17 months. The mean baseline VAS was 7.1. When compared with the baseline, VAS rating during the training period decreased with a mean difference of 3.0. The difference remained at 1.9 at 4 months after training had stopped. Other functional gains, such as improved sucking and swallowing, were identified. Six caregivers declined surgery. One child improved and did not require surgery. CoNCLUSIONS: Short-term follow-up of oro-motor training suggested beneficial outcome.