An Rx for pills--and politics. What's hot this election year? Drug costs and a pair of thorny tax issues.
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Drug Costs↗
Biomedical subjects
D Thompson
Publications and source records attributed to D Thompson.
The Feds step up the pace. In the hot race to wrap up the human genome, government mappers say they're two-thirds home.
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Animals↗
Upper gastrointestinal tract safety profile of alendronate: the fracture intervention trial.
OBJECTIVES: To determine whether alendronate sodium treatment is associated with upper gastrointestinal (GI) tract adverse experiences (AEs)-particularly those of the stomach, duodenum, or esophagus-in the Fracture Intervention Trial, and to assess the relationship between alendronate use and upper GI tract events among women at increased risk for these outcomes. DESIGN: Randomized, double-blind, placebo-controlled trial with a mean follow-up of 3.8 years. Women were initially randomized to receive alendronate sodium, 5 mg/d, or placebo. After 2 years, the alendronate sodium dose was increased to 10 mg/d. PARTICIPANTS: A total of 6459 women aged 54 to 81 years recruited from 11 US clinical centers. All participants had low hip bone mineral density. Women with major upper GI tract disease (recent ulcers, upper GI tract bleeding, or use of daily medication for dyspepsia) were excluded. Regular nonsteroidal anti-inflammatory drug users were not excluded. MEASUREMENTS: Self-reported upper GI tract AEs were ascertained by interview every 3 months. Serious upper GI tract AEs were confirmed and classified by review of hospital records and endoscopy reports, if available. Upper GI tract AEs were further analyzed in 2 specified groups-gastroduodenal and esophageal-to examine events that might be related to upper GI tract mucosal irritation. Gastric and duodenal perforations, ulcers, and bleeding events were combined for analysis of these clinically important outcomes. RESULTS: The overall incidence of upper GI tract events was similar in the alendronate and placebo groups (47.5% vs. 46.2%; relative risk [RR], 1.02; 95% confidence interval [CI], 0.95-1.10). The incidence of gastroduodenal perforations, ulcers, and bleeding events was 1.6% in the alendronate group and 1.9% in the placebo group (RR, 0.86; 95% CI, 0.59-1.24). The incidence of nonspecific upper GI tract conditions, such as abdominal pain, dyspepsia, nausea, and vomiting, was also similar in the 2 groups. Esophageal events occurred in 10.0% and 9.4% of patients in the alendronate and placebo groups, respectively (RR, 1.06; 95% CI, 0.91-1.24). Esophagitis not reported as reflux was more common in the alendronate group (0.7%) than in the placebo group (0.4%), but not significantly so (RR, 1.71; 95% CI, 0.90-3.39). Alendronate use was not associated with a significant increase in upper GI tract events among women at increased risk for these events (those aged > or =75 years with previous upper GI tract disease or using nonsteroidal anti-inflammatory drugs). CONCLUSION: In these older women, upper GI tract complaints, particularly dyspepsia and abdominal pain, were common, but alendronate treatment was not associated with an increased incidence of upper GI tract events, even in high-risk subgroups.
Aged↗
The gene machine. To the consternation of his rivals, Craig Venter may have the human DNA 100% mapped by summer.
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Human Genome Project↗
An automated machine vision system for the histological grading of cervical intraepithelial neoplasia (CIN).
The histological grading of cervical intraepithelial neoplasia (CIN) remains subjective, resulting in inter- and intra-observer variation and poor reproducibility in the grading of cervical lesions. This study has attempted to develop an objective grading system using automated machine vision. The architectural features of cervical squamous epithelium are quantitatively analysed using a combination of computerized digital image processing and Delaunay triangulation analysis; 230 images digitally captured from cases previously classified by a gynaecological pathologist included normal cervical squamous epithelium (n=30), koilocytosis (n=46), CIN 1 (n=52), CIN 2 (n=56), and CIN 3 (n=46). Intra- and inter-observer variation had kappa values of 0.502 and 0.415, respectively. A machine vision system was developed in KS400 macro programming language to segment and mark the centres of all nuclei within the epithelium. By object-oriented analysis of image components, the positional information of nuclei was used to construct a Delaunay triangulation mesh. Each mesh was analysed to compute triangle dimensions including the mean triangle area, the mean triangle edge length, and the number of triangles per unit area, giving an individual quantitative profile of measurements for each case. Discriminant analysis of the geometric data revealed the significant discriminatory variables from which a classification score was derived. The scoring system distinguished between normal and CIN 3 in 98.7% of cases and between koilocytosis and CIN 1 in 76.5% of cases, but only 62.3% of the CIN cases were classified into the correct group, with the CIN 2 group showing the highest rate of misclassification. Graphical plots of triangulation data demonstrated the continuum of morphological change from normal squamous epithelium to the highest grade of CIN, with overlapping of the groups originally defined by the pathologists. This study shows that automated location of nuclei in cervical biopsies using computerized image analysis is possible. Analysis of positional information enables quantitative evaluation of architectural features in CIN using Delaunay triangulation meshes, which is effective in the objective classification of CIN. This demonstrates the future potential of automated machine vision systems in diagnostic histopathology.
Female↗
Exercise-based rehabilitation for coronary heart disease.
BACKGROUND: The burden of cardiovascular disease world-wide is one of great concern to patients and health care agencies alike. Circulatory diseases, including myocardial infarction (MI) and stroke, kill more people than any other disease. Cardiac rehabilitation aims to restore patients who have suffered myocardial infarction to optimal health through exercise only based rehabilitation or comprehensive cardiac rehabilitation (eg. smoking cessation advice, diet and counselling as well as exercise). Data from two published and widely cited meta-analyses (Oldridge 1988, O'Connor 1989) of over 4,000 patients each have demonstrated that patients randomised to exercise-based cardiac rehabilitation after MI have a statistically significant reduction in all-cause and cardiac mortality of about 20 to 25% compared to patients receiving conventional care. However, the trials included were small and often of poor methodological quality. Incomplete literature review methods may have resulted in publication bias thereby resulting in an over-estimate of the benefit of cardiac rehabilitation. The randomised controlled trials used in the reviews have focused almost exclusively on low-risk, middle-aged males post MI, thereby excluding women and the elderly. OBJECTIVES: To determine the effectiveness of exercise only rehabilitation and exercise in addition to other rehabilitation interventions (termed comprehensive cardiac rehabilitation) compared with usual care on the mortality, morbidity, health-related quality of life (HRQoL) and modifiable cardiac risk factors of patients with coronary heart disease. SEARCH STRATEGY: Electronic databases were searched for randomised controlled trials, using standardised trial filters, from the earliest date available to December 31st 1998. SELECTION CRITERIA: Men and women of all ages, in both hospital-based and community-based settings, who have had myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, or who have angina pectoris or coronary artery disease defined by angiography have been included. Studies involving participants following heart transplant, heart valve surgery or heart failure have been excluded. Follow up periods of less than 6 months were excluded. DATA COLLECTION AND ANALYSIS: Studies were selected independently by two reviewers, and data extracted independently. Authors were contacted where possible to obtain missing information. MAIN RESULTS: The current systematic review has allowed analysis of an increased number of patients from approximately 4500 in the earlier meta-analyses to 7683 (2582 in exercise only and 5101 in the comprehensive cardiac rehabilitation group). The quality of reporting overall was poor, with generally high losses to follow up. The pooled effect estimate for total mortality for the exercise only intervention shows a 27% reduction in all cause mortality (random effects model OR 0.73 (0.54, 0.98)). Similarly, comprehensive cardiac rehabilitation reduced all cause mortality compared to usual care, but to a lesser degree (OR 0.87 (0.71, 1.05)). Total cardiac mortality was reduced by 31% (random effects model OR 0.69 (0.51, 0.94)) and 26% (random effects model OR 0.74 (0.57, 0.96)) in the exercise only and comprehensive cardiac rehabilitation intervention groups respectively when compared to usual care. Neither intervention had any effect on the ocurrence of non-fatal myocardial infarction. There was a significant net reduction in total cholesterol in the comprehensive cardiac rehabilitation group (pooled WMD random effects model -0.57 mmol/l (-0.83, -0.31)), but not the exercise only rehabilitation group. Similarly, LDL was significantly reduced in the comprehensive cardiac rehabilitation group (pooled WMD random effects model -0.51 mmol/l (-0.82, -0.19). The effect of exercise only rehabilitation or comprehensive cardiac rehabilitation interventions on revascularisation rates, blood pressure or smoking behaviour could not be determined by this meta-analysis due to the small number of trials reporting these outcomes and heterogeneity between trials. It was not possible to combine the data from studies reporting HRQoL as an outcome. Eighteen different instruments were used to assess HRQoL in the 11 studies reporting it as an outcome. The data are presented qualitatively, only one trial reporting significant improvements with the intervention. REVIEWER'S CONCLUSIONS: Exercise-based cardiac rehabilitation appears to be effective in reducing cardiac deaths but the evidence base is weakened by poor quality trials. It is not clear from this review whether exercise only or a comprehensive cardiac rehabilitation intervention is more beneficial. The population studied in this review is still predominately male, middle aged and low risk. Identification of the ethnic origin of the participants was seldom reported. (ABSTRACT TRUNCATED)
Coronary Disease↗
A study of EEG, electroretinogram, visual evoked potential, and eye movements in classical lissencephaly.
EEG, flash electroretinogram (ERG), and visual evoked potential (VEP) findings are described in eight children with classical lissencephaly (six girls, two boys), with a mean age of 17.6 months (range 2 to 60 months). The EEG shows typically high-voltage activity. Eye movements were formally recorded in two patients, and both showed features associated with oculomotor apraxia. The ERG and VEP to flash stimulation were normal in all cases. Two subjects had pattern reversal stimulation, and their pattern VEPs were within normal limits. Some patients with lissencephaly may appear to have delayed visual maturation on first presentation, and EEG and eye movement studies are valuable in indicating neurological deficiency at an early stage in these subjects.
Apraxias↗
Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin.
PURPOSE: To evaluate the toxicity, response rate and short-term survival associated with the chemotherapy combinations of docetaxel plus cisplatin or carboplatin when used for the treatment of patients with metastatic carcinoma of unknown primary site. PATIENTS AND METHODS: Twenty-six patients were treated with docetaxel 75 mg/m2 i.v. and cisplatin 75 mg/m2 i.v. given every three weeks (study A) and subsequently, 47 patients were treated with docetaxel 65 mg/m2 and carboplatin (AUC dose = 6) every three weeks (study B). Stable or responding patients received a maximum of eight courses of therapy. Patients who were known to be in treatable subset groups were excluded from these trials. The majority of patients had two or more sites of metastasis; about 45% had adenocarcinoma and 50% poorly differentiated carcinoma. RESULTS: In study A, 6 of 23 (26%) assessable patients had a major response to therapy. The median survival was eight months and one-year survival 42%. Seven patients were removed from the study early for grade 3 or 4 nausea and vomiting. In study B, 9 of 40 assessable patients (22%) had a major response to therapy. Median survival was eight months and one-year survival 29%. Toxicity associated with this regimen was predominantly myelosuppression. Comparisons of the two sequential trials showed no differences in response rates or survivals (P = 0.75). CONCLUSIONS: Docetaxel and cisplatin (study A) is an active combination in carcinoma of unknown primary site, but associated with substantial gastrointestinal toxicity. A combination of docetaxel plus carboplatin (study B) is better tolerated and produced a similar response rate, median survival and one-year survival. Comparative phase III trials will be necessary to unequivically prove a survival advantage for any form of therapy in these patients. However, the survival for patients with carcinoma of unknown primary site receiving docetaxel-based chemotherapy is comparable to the survivals for several other groups of advanced cancer patients, such as non-small cell lung cancer, receiving various types of chemotherapy.
Adult↗
Persistent vomiting in patients with diabetes.
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Adult↗
A randomized controlled trial of psychotherapy in patients with chronic functional dyspepsia.
BACKGROUND & AIMS: This study aimed to determine whether brief psychodynamic-interpersonal (PI) psychotherapy is more efficacious than a psychological control for patients with chronic, intractable functional dyspepsia (FD), and whether patients with abnormal gastric function respond differently than those with normal gastric function. METHODS: Ninety-five consecutive patients with chronic symptoms of FD who had failed to respond to conventional pharmacologic treatments were approached. Thirty-seven received PI psychotherapy, and 36 the control condition (supportive therapy). Patients completed self-report questionnaires before and after treatment and 12 months later. The patients' gastroenterologists, who were blind to the study groups, conducted independent ratings before and after treatment. Forty-nine patients also underwent a radioisotope gastric emptying study. An intention-to-treat analysis was used with baseline scores as covariates. RESULTS: At the end of treatment, there were significant advantages for PI psychotherapy compared with controls for the gastroenterologists' (P = 0.002) and patients' total symptom score (P = 0.015). One year after treatment, the symptomatic scores were similar. However, a subanalysis showed that PI therapy was superior to the control condition at 1 year, when patients with severe heartburn were excluded. There was no difference in outcome between patients with normal and abnormal gastric emptying. CONCLUSIONS: PI therapy may have both short- and long-term effects in patients with dyspepsia, but further evaluation is required. Its cost-effectiveness needs to be determined.
Adult↗
Serological analysis of a cryptosporidiosis epidemic.
BACKGROUND: A cryptosporidiosis epidemic occurred among residents and visitors to Collingwood, Ontario, during March 1996. Fifty-five per cent of 36 confirmed cases were Collingwood visitors and 57% of Collingwood resident cases were under 10 years of age. The low level of reported diarrhoeal illness among adult Collingwood residents caused government officials and physicians to question whether an epidemic had occurred in Collingwood. METHODS: To better evaluate the extent of the epidemic, anonymous surplus sera from 89 adult Collingwood residents, collected for routine tests prior to, during and after the epidemic, and from 80 adult Toronto residents were tested using a Western blot assay for IgG antibody response to two Cryptosporidium antigen groups (15/17-kDa and 27-kDa). RESULTS: For sera collected from 1 January 1996 to 17 June 1996, a higher fraction of Collingwood residents had a detectable serological response (P < 0.002) and the mean intensity of serological responses was higher for Collingwood than Toronto residents (P < 0.001). The mean intensity of serological responses for Collingwood residents was higher in specimens drawn during the 8 weeks following the initial case reports compared to those drawn before or after this period (15/17-kDa, P < 0.02; 27-kDa, P < 0.10). CONCLUSIONS: These elevated serological responses indicate that Cryptosporidium infections among Collingwood residents likely occurred more commonly than illness reports suggested, consistent with a community-wide cryptosporidiosis epidemic. Similar studies should be considered in future suspected cryptosporidiosis epidemic investigations.
Adult↗
The impact of long-term acute-care facilities on the outcome and cost of care for patients undergoing prolonged mechanical ventilation.
OBJECTIVES: To compare the 6-month mortality rate of chronically ventilated patients treated either exclusively in a traditional acute-care hospital or transferred during hospitalization to a long-term acute-care facility. To analyze the hospital cost of care and estimate the amount of uncompensated care incurred by acute-care hospitals under the Medicare prospective payment diagnostic related groups system. DESIGN: Retrospective chart review and questionnaire. SETTING: Fifty-four acute-care referral hospitals and 26 longterm acute-care institutions. PATIENTS: A total of 432 ventilated patients selected from 3,266 patients referred but not transferred to a study long-term acute-care facility and 1,702 ventilated patients from 4,174 patients referred and then subsequently transferred to the long-term acute-care facility. Six-month outcomes were determined for the subgroup of patients > or =65 yrs old (279 and 1,340 patients, respectively). Hospital charges were available for 192 of the 279 nontransferred patients who were > or =65 yrs old and 1,332 of the 1,340 transferred patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 6-month mortality rate was 67.4% for the 279 nontransferred patients and 67.2% for the 1,340 transferred patients. On multiple regression analysis, variables associated with the 6-month mortality rate included initial admitting diagnosis, age, the acute physiology score, and presence of decubitus ulcer. After controlling for these variables, there was no significant difference in 6-month mortality rate, but admission to the long-term acute-care facility was associated with a longer mean survival time. Average total hospital costs for the 192 nontransferred patients was $78,474, and estimated Medicare reimbursement was $62,472, resulting in an average of $16,002 of uncompensated care per patient. Estimated costs for the long-term acute-care facility admissions were $56,825. CONCLUSIONS: Patients undergoing prolonged ventilation have high hospital and 6-month mortality rates, and 6-month outcomes are not significantly different for those transferred to long-term acute-care facilities. These patients generate high costs, and acute-care hospitals are significantly underreimbursed by Medicare for these costs. Acute-care hospitals can reduce the amount of uncompensated care by earlier transfer of appropriate patients to a long-term acute-care facility.
Aged↗
Growth factor-independent proliferation of erythroid cells infected with Friend spleen focus-forming virus is protein kinase C dependent but does not require Ras-GTP.
Interaction of erythropoietin (Epo) with its cell surface receptor activates signal transduction pathways which result in the proliferation and differentiation of erythroid cells. Infection of erythroid cells with the Friend spleen focus-forming virus (SFFV) leads to the interaction of the viral envelope glycoprotein with the Epo receptor and renders these cells Epo independent. We previously reported that SFFV induces Epo independence by constitutively activating components of several Epo signal transduction pathways, including the Jak-Stat and the Raf-1/mitogen-activated protein kinase (MAPK) pathways. To further evaluate the mechanism by which SFFV activates the Raf-1/MAPK pathway, we investigated the effects of SFFV on upstream components of this pathway, and our results indicate that SFFV activates Shc and Grb2 and that this leads to Ras activation. While studies with a dominant-negative Ras indicated that Ras was required for Epo-induced proliferation of normal erythroid cells, the Epo-independent growth of SFFV-infected cells can still occur in the absence of Ras, although at reduced levels. In contrast, protein kinase C (PKC) was shown to be required for the Epo-independent proliferation of SFFV-infected cells. Further studies indicated that PKC, which is thought to be involved in the activation of both Raf-1 and MAPK, was required only for the activation of MAPK, not Raf-1, in SFFV-infected cells. Our results indicate that Ras and PKC define two distinct signals converging on MAPK in both Epo-stimulated and SFFV-infected erythroid cells and that activation of only PKC is sufficient for the Epo-independent proliferation of SFFV-infected cells.
Adaptor Proteins, Signal Transducing↗
Erythroid cells rendered erythropoietin independent by infection with Friend spleen focus-forming virus show constitutive activation of phosphatidylinositol 3-kinase and Akt kinase: involvement of insulin receptor substrate-related adapter proteins.
The erythroleukemia-inducing Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein which allows erythroid cells to proliferate and differentiate in the absence of erythropoietin (Epo). In an effort to understand how SFFV causes Epo independence, we have been examining erythroid cells rendered factor independent by SFFV infection for constitutive activation of signal-transducing molecules. Previous studies from our laboratory showed that various signal-transducing molecules known to be activated by Epo, including Stat proteins and components of the Raf-1/MAP kinase pathway, are constitutively activated in SFFV-infected erythroid cells in the absence of Epo. Since another signal transduction pathway involving activation of phosphatidylinositol 3-kinase (PI 3-kinase) after Epo stimulation plays an important role in erythroid cell proliferation and differentiation, we carried out studies to determine if this pathway was also activated in SFFV-infected cells in the absence of Epo. Our studies show that PI 3-kinase is constitutively activated in erythroid cells rendered factor independent by infection with SFFV and that PI 3-kinase activity, but not Epo receptor tyrosine phosphorylation, is required for the proliferation of these cells in the absence of Epo. We further show that in SFFV-infected erythroid cells grown in the absence of Epo, PI 3-kinase associates with the insulin receptor substrate (IRS)-related adapter molecules IRS-2, Gab1, and Gab2, which are constitutively tyrosine phosphorylated in SFFV-infected cells. Finally, Akt, a protein kinase that is one of the downstream effectors of PI 3-kinase, and SHIP, a lipid phosphatase that is important for Akt activation through PI 3-kinase, are both tyrosine phosphorylated in SFFV-infected cells grown in the absence of Epo. Our results indicate that induction of Epo independence by SFFV requires the activation of PI 3-kinase and suggest that constitutive activation of this kinase in SFFV-infected cells may occur primarily through interaction of PI 3-kinase with constitutively phosphorylated IRS-related adapter molecules.
Enzyme Activation↗
Vertical or asymmetric nystagmus need not imply neurological disease.
AIM: To indicate that congenital idiopathic nystagmus (CIN) and sensory defect nystagmus (SDN) can be vertical or asymmetric in some children. METHODS: Of 276 children presenting with nystagmus for electrophysiological testing, 14 were identified as having CIN or SDN, yet had a nystagmus which was either vertical (n=11) or horizontal asymmetric (n=3). Flash electroretinograms and flash and pattern visual evoked potentials (VEPs) were recorded in all patients. Eye movement assessment, including horizontal optokinetic nystagmus (OKN) testing, was carried out in 11/14 patients. RESULTS: Eight patients (seven with vertical, one with asymmetric horizontal nystagmus) had congenital cone dysfunction. One patient with vertical and another with asymmetric nystagmus had cone-rod dystrophy. One patient with vertical upbeat had congenital stationary night blindness. Two patients (one downbeat, one upbeat nystagmus) had normal electrophysiological, clinical, and brain magnetic resonance imaging findings and were classified as having CIN. One patient with asymmetric nystagmus showed electrophysiological and clinical findings associated with albinism. Horizontal OKN was present in 80% of patients tested, including the three cases with horizontal asymmetric nystagmus. This is atypical in both CIN and SDN, where the OKN is usually absent. CONCLUSIONS: Vertical and asymmetric nystagmus are most commonly associated with serious intracranial pathology and its presence is an indication for neuroimaging studies. However, such nystagmus can occur in children with retinal disease, albinism, and in cases with CIN. These findings stress the importance of non-invasive VEP/ERG testing in all cases of typical and also atypical nystagmus.
Child, Preschool↗
Testing the impact attenuation of loose-fill playground surfaces.
OBJECTIVES: Our objective was to measure the impact attenuation performance of five types of loose-fill playground surfaces at a variety of drop heights, material depths, and conditions. METHODS: In a laboratory setting, an instrumented head form was dropped on varying depths of loose-fill materials at one foot height increments until critical deceleration values were exceeded. The effects of test box size, material temperature, and compression were also studied. RESULTS: Data suggest that a larger test box size influences test results. Uncompressed materials performed quite unexpectedly, that is, resilience did not necessarily increase with increasing depth of material and temperature did not have uniform effects. Compression before testing improved consistency of results. CONCLUSION: The current standard test procedure (ASTM F1292) appears problematic for loose-fill materials. Our results indicate that (1) shredded rubber was the best performer; (2) there was little difference between sand, wood fibers, and wood chips; and (3) pea gravel had the worst performance, making it a poor choice for playground surfacing.
Accidental Falls↗
Expression of pi-class glutathione S-transferase: two populations of high grade prostatic intraepithelial neoplasia with different relations to carcinoma.
BACKGROUND/AIMS: Patients with high grade prostatic intraepithelial neoplasia of the transition zone appear to be at increased risk of developing prostatic carcinoma, although not to the same degree as patients with high grade prostatic intraepithelial neoplasia of the peripheral/central zone. Previous investigations have shown loss of expression of pi-class glutathione S-transferase (GST-pi; an enzyme that protects against electrophilic carcinogens) in prostatic carcinoma and in high grade prostatic intraepithelial neoplasia. The aim of this study was to compare the expression of GST-pi in high grade prostatic intraepithelial neoplasia of the transition zone with that in high grade prostatic intraepithelial neoplasia of the peripheral/central zone (that is, non-transition zone). METHODS: Immunostaining with the anti-GST-pi antibody was performed on 20 high grade prostatic intraepithelial neoplasia samples of the transition zone, either isolated or associated with prostatic carcinoma (groups 1 and 2, respectively; 10 cases each) and on 20 high grade prostatic intraepithelial neoplasia samples of the non-transition zone, either isolated or associated with prostatic carcinoma (groups 3 and 4, respectively; 10 cases each). This study also included six samples of high grade prostatic intraepithelial neoplasia simultaneously present in the transition and non-transition zones and not associated with prostatic carcinoma (group 5). The presence of immunostaining, staining intensity, and the distribution of immunostaining were evaluated in the high grade prostatic intraepithelial neoplasia lesions and in the normal tissue and cancer areas. RESULTS: The GST-pi antibody stained the cytoplasm of the cells lining the ducts and acini of normal prostate tissue. Staining was stronger and more diffuse in the basal cell layer than in the luminal (or secretory) cell layer. Immunohistochemical staining with anti-GST-pi antibodies failed to detect the enzyme in all prostatic carcinoma foci but one. Two patterns were detected in high grade prostatic intraepithelial neoplasia. One was represented by GST-pi staining similar to that of the normal tissue (pattern A). The other deviated from it and was characterised by absence of GST-pi expression in the secretory cells and abundant expression in scattered basal cells (pattern B). Pattern A staining was seen more frequently in the transition than in the non-transition zone. Pattern B staining was seen mainly in high grade prostatic intraepithelial neoplasia of non-transition zone associated with cancer. CONCLUSIONS: The differential expression of GST-pi in the transition and non-transition zones indicates the existence of two populations with the morphological appearance of high grade prostatic intraepithelial neoplasia that might have different associations with carcinoma.
Aged↗
Management of choroid plexus tumours in children: 20 years experience at a single neurosurgical centre.
OBJECTIVE: Tumours of the choroid plexus are rare tumours of neuro-ectodermal origin, accounting for less than 1% of all intracranial tumours. Most cases present in children less than 2 years of age. While choroid plexus carcinomas (CPC) are reported to have an extremely poor prognosis, choroid plexus papillomas (CPP) are generally regarded as benign tumours with a very favourable long-term outcome. Management dilemmas are associated with the choice of surgical procedure, tumour vascularity, the treatment of hydrocephalus and the value of adjuvant therapy. The objective of this study was to review our experience with this rare tumour over a 20-year period. METHODS: Patients were identified from the Great Ormond Street Neurosurgical Brain Tumour Database. Over a 20-year period (1979-1999), 34 children were identified with a choroid plexus tumour. There were 25 cases of CPP and 9 cases of CPC. A retrospective review of case notes, radiological imaging, operation reports and pathology was performed. RESULTS: The median age at presentation was 17 months (1-138) for CPP and 13 months (2-102) for CPC. There was no sex difference for CPP. However, 8 of the 9 CPCs were male (89%). A complete surgical resection was achieved in all 25 cases of CPP and in 3 cases of CPC (33%). The median survival for CPPs was 75.5 months (2-228), with a median follow-up of 73.5 months (2-228). The median survival for CPCs was 6 months (1-90), with a median follow-up of 6 months (1-90). CONCLUSION: With modern neurosurgical practise, a cure should be the aim for all children with CPP. There is no evidence that adjuvant therapy has any role in the primary management of these children. However, CPC still has an extremely poor prognosis, and the efficacy of adjuvant therapy remains to be established.
Age of Onset↗