Vitamin E as an antioxidant/free radical scavenger against amyloid beta-peptide-induced oxidative stress in neocortical synaptosomal membranes and hippocampal neurons in culture: insights into Alzheimer's disease

Amyloid beta-peptide (Abeta), the major constituent in senile plaques in Alzheimer's disease (AD) brain, is thought by many researchers to be central to neurotoxicity in AD brain. Increasing evidence from many laboratories indicates that AD brain is under oxidative stress, with strong evidence of protein oxidation, lipid peroxidation, and peroxynitrite damage. A link between the central role of Abeta and oxidative stress in AD brain may be Abeta-associated free radical oxidative stress. If so, antioxidants such as vitamin E should modulate Abeta-induced oxidative damage and neurotoxicity in brain cells. This review summarizes studies of Abeta-associated free radical oxidative stress and its inhibition by vitamin E in cortical synaptosomal membranes and hippocampal neuronal cells in culture. Taken together with the recent report that vitamin E slows the progression of AD, this review strongly supports a central role of Abeta-associated free radical oxidative stress in neurotoxicity in AD brain.     

Primary liposarcoma of the orbit: a clinicopathological study

Primary liposarcoma of the orbit is a rare tumour. There are very few cases of orbital liposarcoma reported in the literature, mostly of the myxoid variety. In this paper, the authors report the clinical presentation, histopathological features, results of diagnostic studies and management of a case of orbital low grade myxoliposarcoma with local recurrence, together with a review of the literature.     

Pre-emptive analgesia with epidural morphine or morphine and bupivacaine

Studies of preemptive analgesia in humans have shown conflicting results. The study design, patient population and the duration of assessment of postoperative pain are important in the evaluation of preemptive analgesia. We carried out a prospective, randomized, double-blind controlled study in 80 patients of physical status ASA 1-3 undergoing upper abdominal and thoracic surgery. Patients received two epidural injections, one 20 minutes before induction and the other at the end of surgery. Study solution was either morphine (50 micrograms/kg), with or without 0.1% bupivacaine in 10 ml of normal saline, or normal saline alone. The study groups (Pre M, Pre MB) were given either morphine or morphine-bupivacaine before induction and saline at the end of surgery. The control groups (Post M, Post MB) were given saline before induction and morphine or morphine-bupivacaine at the end of surgery. Postoperative pain was assessed with a Visual Analogue Scale (VAS) during coughing and deep breathing at six-hourly intervals for five days. Epidural morphine was given if the VAS exceeded 4. Pre MB compared to Post MB had a significantly increased interval between the analgesic top-ups (P < 0.01) and decreased total postoperative morphine requirements (P < 0.0001) and number of top-ups (P < 0.001). Pre M and Post M were comparable. Pre MB compared to Pre M had significantly decreased total postoperative morphine requirements (P < 0.0001) and number of top-ups (P < 0.0001). Epidural morphine plus bupivacaine is effective as a preemptive analgesic. Morphine plus bupivacaine has better efficacy than morphine given alone before the induction of anaesthesia.     

Retroperitoneoscopic excision of phaeochromocytoma--haemodynamic events, complications and outcome

Over a period of 15 months, 11 patients with phaeochromocytoma underwent retroperitoneoscopic excision of their tumours. Five patients had bilateral tumours. All patients underwent thorough preoperative evaluation and preparation with alpha- and beta-blockade. In the majority of the patients a hypertensive response was seen during generation of pneumoretroperitoneum. However, the period of tumour dissection and excision was devoid of large haemodynamic fluctuations. The average time taken was 3.5 to 4 hours per gland. Blood loss in successful laparoscopic excision averaged 240 ml (range 120 to 700 ml). In these patients satisfactory postoperative analgesia could be provided with intramuscular pethidine or intramuscular diclofenac sodium. In three patients the procedure had to be converted to open laparotomy due to haemorrhage. All three patients had preoperative radiological evidence of inferior vena cava and aortic involvement. Patient selection plays an important role in a successful outcome.     

External laryngocele

Laryngocele is an extremely rare condition. A case of external laryngocele is being reported along with a brief review on its pathogenesis, clinical presentation and management.     

The pancreatic ductal epithelium serves as a potential pool of progenitor cells

Abstract:  With the increasing success of islet transplantation, β-cell replacement therapy has had renewed interest. To make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin-producing cells must become readily available. The most promising sources are stem cells, whether embryonic or adult stem cells. Clearly identifiable adult pancreatic stem cells have yet to be characterized. Although considerable evidence suggests their possibility, recent lineage-tracing experiments challenge their existence. Even in light of these lineage-tracing experiments, we suggest that evidence for neogenesis or new islet formation after birth remains strong. Our work has suggested that the pancreatic duct epithelium itself serves as a pool for progenitors for both islet and acinar tissues after birth and into adulthood and, thus, that the duct epithelium can be considered 'facultative stem cells'. We will develop our case for this hypothesis in this perspective.     

Initial response to portoenterostomy determines long-term outcome in patients with biliary atresia

PURPOSE: The aim of this study was to assess the efficacy of portoenterostomy in biliary atresia and determine factors that predict outcomes. METHODS: The outcomes after portoenterostomy for biliary atresia from 1976 to 1996 were graded into 3 defined groups: G (good, jaundice free); I (intermediate, progressive liver disease with liver transplant if needed after 3 years of age); P (poor, liver transplant or death at less than 3 years of age). RESULTS: Twenty-seven of 49 children (55%) who underwent portoenterostomy responded. Of these, 13 (26%) were jaundice free (G). Of 14 children (28%) in I, 6 underwent liver transplant after 3 years of age. Of 22 children (44.8%) in P, 14 (28%) died before 3 years and 8 underwent liver transplant before 3 years. Thus, 42% of the children in this series are surviving with native liver. Age at operation in P was significantly different compared with G. Preoperative values of bilirubin and alanine transaminase were comparable in the 3 groups. Postoperative values of bilirubin and alanine transaminase were lower in G and I compared with P Complications were significantly lower in group G. CONCLUSIONS: Portoenterostomy alone in biliary atresia is beneficial in 40% of cases. Factors associated with the outcome include age at operation, postoperative cholangitis, and change in values of bilirubin and alanine transaminase. A classification based on decline of bilirubin and enzyme levels 3 months after portoenterostomy is proposed to predict the long-term outcome of an individual case of biliary atresia. It is particularly relevant in the intermediate group in which timing of referral may preclude or compromise liver transplant.     

Patient's quality of life and hearing outcomes after stapes surgery

Objectives: To determine the quality of life (QOL) after stapes surgery and whether audiological parameters for hearing correlate with specific QOL factors. Design: A retrospective cross‐sectional study. Setting: A tertiary referral centre. Participants: A series of 35 patients who underwent stapes surgery of which three were excluded because they were <18 years of age, chronically or mentally ill, or in a dependant relationship. Response rate was 93% (30/32). Nine were further excluded because they had revision or bilateral surgery, or missing data. Twenty‐one patients were included in this study. Main outcome measures: The Glasgow Benefit Inventory (GBI) was used to evaluate general QOL and the Hearing Disability and Handicap Scale (HDHS) was used as a disease‐specific measure. The Belfast Rule of Thumb and Glasgow Benefit Plot assessed hearing outcomes. Results: Operative success was 86% using the Belfast Rule of Thumb and 95% had closure of the air–bone gap to within 20 dB. 81.8% of patients reported a better overall QOL as surgery. Glasgow Benefit Inventory Social and GBI Physical scores correlated positively with the HDHS speech component (P < 0.05). The duration of hearing loss correlated inversely with the average HDHS score (P < 0.05). Conclusion: The majority of patients report a better QOL as undergoing stapes surgery. Speech impacts on people's physical and social QOL of patients. Quality of life tools, in addition to objective audiologic measurements can provide clinicians with patients’ subjective perspective that helps guide clinical decision‐making and counselling.     

Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

PURPOSE: The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.     

Towards an effective social care model for arrest referral: Implications for criminal justice interventions for problem drug users

Aims: To assess an operational model for arrest-referral schemes that successfully facilitates the entry of highly entrenched and chaotic problem drug users into specialist drug-treatment services. Methods: (1) An examination of case records from a voluntary arrest-referral service (SMART CJS) based across the Thames Valley region of the UK during 2002-2003; (2) Probablistic database linkage of agency case records with the National Drug Treatment Monitoring System (NDTMS); (3) participant observation and semi-structured interviews with agency staff.

Findings: Over half of problem drug users (58%) maintained contact with the scheme following initial contact in police custody. Referrals were made to a wide range of social-care services in addition to specialist drug treatment to include prison-based services, housing support and primary care. This model was able to demonstrate very high levels of specialist drug treatment uptake (53%) following referral. There was a close relationship between the average length of time a problem drug user entered treatment following contact in police custody and the average length of an active case file. Such an approach was considered essential to maintain motivation with clients.

Discussion: This social care model has operational validity in ensuring treatment uptake of recidivist problem drug-using offenders. Continuity of care alongside referrals addressing wider community harms including social exclusion and public health should be encouraged.