bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroprotective effects of Nigella sativa on experimental spinal cord injury in rats
Authors: Kanter M , Coskun O , Kalayc M , Buyukbas S , Cagavi F
Published: March 2006

The aim of this study was to investigate the possible beneficial effects of Nigella sativa (NS) in comparison to methylprednisolone on experimental spinal cord injury (SCI) in rats. SCI was performed by placing an aneurysm clip extradurally at the level of T11-12. Rats were neurologically tested over 24 h after trauma and spinal cord tissue samples were harvested for both biochemical and histopathological evaluation. The neurological scores of rats were not found to be different in SCI groups. SCI significantly increased the spinal cord tissue malondialdehyde (MDA) and protein carbonyl (PC) levels, however SCI decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzyme activities compared to the control. Methylprednisolone and NS treatment decreased tissue MDA and PC levels and prevented inhibition of SOD, GSH-Px and CAT enzymes in the tissues. The most significant results were obtained when NS was given. In SCI and placebo groups, the neurons of spinal cord tissue became extensively dark and degenerated with picnotic nuclei. The morphology of neurons in methylprednisolone and NS-treated groups were well protected, however, not as well as the neurons of the control group. The number of neurons in the spinal cord tissue of the SCI and placebo groups was significantly less than the control, laminectomy, methylprednisolone and NS-treated groups. In conclusion, NS treatment might be beneficial in spinal cord tissue damage, and therefore shows potential for clinical implications.
Effectiveness and costs of acute day hospital treatment compared with conventional in-patient care
Authors: Priebe Stefan , Jones Gemma , McCabe Rosemarie , Briscoe Jane , Wright Donna , Sleed Michelle , Beecham Jennifer
Published: February 2006

Background

Data on effectiveness of acute day hospital treatment for psychiatric illness are inconsistent.

Aims

To establish the effectiveness and costs of care in a day hospital providing acute treatment exclusively.

Method

In a randomised controlled trial, 206 voluntarily admitted patients were allocated to either day hospital treatment or conventional wards. Psychopathology, treatment satisfaction and subjective quality of life at discharge, 3 months and 12 months after discharge, readmissions to acute psychiatric treatment within 3 and 12 months, and costs in the index treatment period were taken as outcome criteria.

Results

Day hospital patients showed significantly more favourable changes in psychopathology at discharge but not at follow-up. They also reported higher treatment satisfaction at discharge and after 3 months, but not after 12 months. There were no significant differences in subjective quality of life or in readmissions during follow-up. Mean total support costs were higher for the day hospital group.

Conclusions

Day hospital treatment for voluntary psychiatric patients in an inner-city area appears more effective in terms of reducing psychopathology in the short term and generates greater patient satisfaction than conventional in-patient care, but may be more costly.
Influence of age on outcome of psychological treatments in first-episode psychosis
Authors: Haddock Gillian , Lewis Shôn , Bentall Richard , Dunn Graham , Drake Richard , Tarrier Nicholas
Published: February 2006

Background

Psychological treatments have been shown to be effective in patients with psychosis. However, the studies published to date have included participants across wide age ranges, so few conclusions can be reached about the effectiveness of such treatments in relation to age.

Aims

To evaluate outcomes by age in a randomised controlled trial designed to evaluate the effectiveness of cognitive-behavioural therapy (CBT), supportive counselling and treatment as usual.

Method

Outcomes were evaluated in terms of symptoms, social functioning, insight and therapeutic alliance according to age at 3- and 18-month follow-up.

Results

Younger participants responded better to supportive counselling than to treatment as usual and CBTover 3 months. Older participants responded better to CBT than to supportive counselling over 18 months. Younger participants showed a greater increase in insight after CBT compared with treatment as usual and supportive counselling, and were more difficult to engage in therapy.

Conclusions

Young people may have different needs with regard to engagement in psychological treatments. Treatment providers need to take age-specific factors into account.
Rechallenge with clozapine following leucopenia or neutropenia during previous therapy
Authors: Dunk Louisa R. , Annan Linda J. , Andrews Christopher D.
Published: February 2006

Background

Further treatment with clozapine is contraindicated in any patient who has previously experienced leucopenia or neutropenia during clozapine therapy.

Aims

To investigate the results of such a rechallenge in 53 patients.

Method

An analysis was made of the demographic, haematological and outcome data of patients in the UK and Ireland who were rechallenged with clozapine following leucopenia or neutropenia during previous clozapine therapy.

Results

Of 53 patients who were rechallenged, 20 (38%) experienced a further blood dyscrasia. In 17 of these 20 patients (85%) the second blood dyscrasia was more severe(P<0.001), in 12(60%) it lasted longer (P=0.0368) and in 17 (85%) it occurred more quickly on rechallenge (P<0.001). Of the original 53 patients, 55% (29 patients) are still receiving clozapine.

Conclusions

No clear risk factor for repeat blood dyscrasias was identified. Despite this, after risks and benefits have been considered, rechallenge may well be justified in some patients.
Effect of a structured educational intervention on explanatory models of relatives of patients with schizophrenia
Authors: Das S. , Saravanan B. , Karunakaran K. P. , Manoranjitham S. , Ezhilarasu P. , Jacob K. S.
Published: February 2006

We examined the effect of a structured educational programme on explanatory models of illness among the relatives of people with schizophrenia, in a randomised controlled trial. Participants were assessed at baseline (n=100) and after 2 weeks (n=75) using a vignette from the Short Explanatory Model Interview. There was a reduction in non-biomedical causal explanatory models at follow-up among those who had completed the structured educational programme compared with the control group. There was no significant difference in non-biomedical treatment explanatory models between the two groups.
Violence in women with psychosis in the community: Prospective study
Authors: Dean Kimberlie , Walsh Elizabeth , Moran Paul , Tyrer Peter , Creed Francis , Byford Sarah , Burns Tom , Murray Robin , Fahy Tom
Published: February 2006

Background

Little is known about the determinants of violence in women with psychosis.

Aims

To identify predictors of violence in a community sample of women with chronic psychosis.

Method

The 2-year prevalence of physical assault was estimated for a sample of 304 women with psychosis. Baseline socio-demographic and clinical factors were used to identify predictors of assault.

Results

The 2-year prevalence of assault in the sample was 17%. Assaultive behaviour was associated with previous violence (OR=5.87, 95% CI 2.42–14.25), non-violent convictions (OR=2.63, 95% CI 1.17–5.93), victimisation (OR=2.46, 95% CI 1.02–5.93), African–Caribbean ethnicity (OR=2.24, 95% CI 1.02–4.77), cluster B personality disorder (OR=2.66, 95% CI 1.11–6.38) and high levels of unmet need (OR=1.17, 95%C11.01–1.35). An interaction between African–Caribbean ethnicity and cluster B personality disorder was identified in relation to violent outcome. Violent women were found to be more costly to services.

Conclusions

Nearly a fifth of community-dwelling women with chronic psychosis committed assault over a period of 2 years. Six independent risk factors were found to predict violence.
Risk for coronary heart disease in people with severe mental illness
Authors: Osborn David P. J. , Nazareth Irwin , King Michael B.
Published: February 2006

Background

Despite concern about the incidence of coronary heart disease (CHD) in people with severe mental illness (SMI), there is little systematic research on CHD risk factors in this population.

Aims

To compare the main risk factors for CHD in people with and without SMI in primary care, to investigate the role of socio-economic variables, and to examine any association between antipsychotic medication and CHD risk.

Method

Cross-sectional screening.

Results

In total, 75 of 182 general practice patients with SMI and 150 of 313 such patients without SMI attended the interview. SMI was associated with: raised 10-year CHD risk scores (OR= 1.8, 95% CI 1.0–3.1); high-density-lipoprotein (HDL)-cholesterol levels <l.0 mmol/l (OR=4.0, 95% CI 1.5–10.7); raised cholesterol/HDL-cholesterol ratios (OR=1.8, 95% CI 1.0–3.2); diabetes mellitus (OR=3.8, 95% CI 1.1–13.3) and smoking (OR=3.0, 95% CI 1.7–3.4). These associations varied significantly with age. Adjustment for unemployment did not fully explain the associations.

Conclusions

Excess risk factors for CHD are not wholly accounted for by medication or socio-economic deprivation. There is an urgent need for CHD screening and for relevant interventions for smoking cessation and diabetes, as well as advice on diet and exercise, in patients with SMI.
Life events, first depression onset and the serotonin transporter gene
Authors: Wilhelm Kay , Mitchell Philip B. , Niven Heather , Finch Adam , Wedgwood Lucinda , Scimone Anna , Blair Ian P. , Parker Gordon , Schofield Peter R.
Published: February 2006

Background

A relationship between the serotonin transporter gene, adverse events and onset of major depression has been reported.

Aims

To replicate a gene × environment interaction in a cohort with longitudinal data for life events, experience of depression, parental bonding and neuroticism.

Method

Atthe 25-year follow-up, genomic DNA was obtained from 127 cohort members (mean age 48 years) to determine the genotype of the serotonin transporter gene-linked promoter region (5-HTTLPR). Associations were investigated between the 5-HTTLPR genotype, positive and adverse life events and the gene × environment interaction, and also between the 5-HTTLPR genotype and risk factors for depression.

Results

No relationship was found between 5-HTTLPR genotype and either risk factors for depression or positive life events. Adverse life events had a significantly greater impact on the onset of depression for individuals with the s/s genotype.

Conclusions

The 5-HTTLPR genotype is a significant predictor of onset of major depression following multiple adverse events. This is one of the more robust findings concerning specific biological risk factors for depression.
Painful symptoms in depression: Under-recognised and under-treated?
Authors: Peveler Robert , Katona Cornelius , Wessely Simon , Dowrick Christopher
Published: February 2006

Current diagnostic systems maintain an artificial division between ‘physical’ and ‘psychological’ disorders. This is exemplified by the way in which pain symptoms are dealt with in the context of depressive illness. The consequences of this are discussed, and ways to enhance the clinical care of patients with depression and pain are suggested.
Children with learning disabilities and related needs placed out of borough: parents' perspective
Authors: Shuwa Amma , Fitzgerald Brian , Clemente Carmen , Grant Denny
Published: February 2006

Aims and Method

To investigate parental experience of children with learning disability being placed out of borough. The parents of 70 children were interviewed.

Results

Parents would prefer in-borough provision but 90% were satisfied with the current school. The main problems experienced in-borough were poor advice, delays, lack of information and family stress. After out-of-borough placement there was a reported increase in the use of speech and language therapy, occupational therapy and sensory facilities and a decrease in the use of paediatric services, social services, and mental health services.

Clinical Implications

Specialist services should be helpful and reduce family burden by keeping children in-borough.
Mill Hill Emergency Hospital: 1939–1945
Authors: Hilton Claire
Published: February 2006

Have you ever wondered why the well-known Mill Hill Vocabulary Scale was named after a suburb of North London? Little known to most psychiatrists or to local people in Mill Hill, a major part of the Maudsley Hospital was evacuated there from central London during the Second World War. Mill Hill School had been evacuateden masseto St Bees in Cumberland. The vacant buildings were requisitioned by the Emergency Medical Service for the Maudsley Hospital. Much innovative psychiatric treatment and research took place there throughout the war with a star-studded cast, including some outstanding clinicians and researchers. This brief review of historical sources aims to give a flavour of the clinical work of the Mill Hill Maudsley.
Systemic thinking in practice: a remedy for trainees' team-working dilemmas?
Authors: Ingrassia Antonina
Published: February 2006

The training of junior doctors is one of the priorities of the Royal College of Psychiatrists. An essential part of this training happens in multidisciplinary teams, and the ability to work effectively as a member of a clinical team is one of the core attributes of our professional identity as psychiatrists.
Reducing hypnotic use on two older adult functional wards: an effective audit?
Authors: Caswell Lucy , Hoosen Imthiaz , Vassilas Christopher A. , Haque Sayeed
Published: February 2006

Aims and Method

We undertook an audit of hypnotic use on two functional older adult wards, followed by an educational intervention to all nursing staff and junior doctors. We then repeated the audit.

Results

Our pre-intervention audit showed a hypnotic use of 48%. This decreased to 26% for the first month following the educational intervention. Usage increased gradually in proportion to time from intervention. However, over the 4-month post-intervention period hypnotic use remained significantly lower than pre-intervention throughout the time period studied.

Clinical Implications

As the study is an audit there is no control group, but our results suggest regular staff education is needed to sustain a reduction in hypnotic use.
What's in a name? Views on psychiatric services for older people
Authors: Kelly Fionnuala , Reidy Julianne , Swanwick Gregory
Published: February 2006

Aims and Method

The aim of this study was to provide a name for a psychiatric service for older people in Dublin. A total of 296 individuals (167 doctors, 129 workshop attendees) were surveyed regarding their views on a name for the service.

Results

‘Age-related psychiatry’ was a universally popular term. It was chosen by 43% of general practitioners, 56% of hospital doctors and 44% of the workshop attendees, as one of their top three choices. ‘Psychiatry of old age’, ‘geriatric psychiatry’ and ‘psychogeriatrics' were unpopular with all three groups.

Clinical Implications

Names can gradually become stigmatising over time. This applies to the terms for ‘old’ and ‘psychiatry’. In this survey all groups surveyed rejected some of the terms in widespread clinical use.
Phase III Study of Two Different Dosing Schedules of Erythropoietin in Anemic Patients With Cancer
Authors: Steensma David P. , Molina Roy , Sloan Jeff A. , Nikcevich Daniel A. , Schaefer Paul L. , Rowland Kendrith M. , Dentchev Todor , Novotny Paul J. , Tschetter Loren K. , Alberts Steven R. , Hogan Thomas F. , Law Amy , Loprinzi Charles L.
Published: February 2006

Purpose

To compare maintenance epoetin alfa administered once every 3 weeks with continued weekly epoetin alfa for patients with cancer-associated anemia.

Patients and Methods

Eligible patients were randomly assigned at enrollment to receive three weekly doses of epoetin alfa 40,000 U subcutaneously (SC), followed by either standard weekly epoetin alfa (40K arm) or 120,000 U of epoetin alfa (120K arm) SC every 3 weeks for 18 additional weeks.

Results

Three hundred sixty-five patients were enrolled. One hundred eighty-three patients were assigned to the 40K arm, and 182 were assigned to the 120K arm. There was no difference in the proportion of patients requiring transfusions during the study (23% in 40K arm and 18% in 120K arm, P = .22) or specifically during the maintenance phase (13% in 40K arm v 15% in 120K arm, P = .58). Patients randomly assigned to the 40K arm were more likely to have a ≥ 2 or ≥ 3 g/dL hemoglobin (Hb) increment, were more likely to have a drug dose held because of high Hb, and had higher mean end-of-study Hb levels. Toxicities, including thromboembolism, and overall survival were similar. Patients in the 40K arm had a higher global quality of life (QOL) at baseline for unclear reasons, whereas patients in the 120K arm had a greater global QOL improvement during the study, so end-of-study QOL was equivalent.

Conclusion

After three weekly doses of epoetin alfa 40,000 U, a dose of 120,000 U can be administered safely once every 3 weeks without increasing transfusion needs or sacrificing QOL. The Hb increment is somewhat greater with continued weekly epoetin alfa. Lack of blinding as a result of different treatment schedules may have confounded results.
Addition of Epirubicin As a Third Drug to Carboplatin-Paclitaxel in First-Line Treatment of Advanced Ovarian Cancer: A Prospectively Randomized Gynecologic Cancer Intergroup Trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group and the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens
Authors: du Bois Andreas , Weber Beatrice , Rochon Justine , Meier Werner , Goupil Alain , Olbricht Sigrid , Barats Jean-Claude , Kuhn Walther , Orfeuvre Hubert , Wagner Uwe , Richter Barbara , Lueck Hans-Joachim , Pfisterer Jacobus , Costa Serban , Schroeder Willibald , Kimmig Rainer , Pujade-Lauraine Eric
Published: February 2006

Purpose

Despite the progress that has been achieved, long-term survival rates in patients with advanced ovarian cancer are still disappointing. One attempt to improve results could be the addition of non–cross-resistant drugs to platinum-paclitaxel combination regimens. Anthracyclines were among the candidates for incorporation as a third drug into first-line regimens.

Patients and Methods

We performed a prospectively randomized phase III study comparing carboplatin-paclitaxel (TC; area under the curve 5/175 mg/m2, respectively) with epirubicin 60 mg/m2 added to the same combination (TEC) in previously untreated patients with advanced epithelial ovarian cancer. All drugs were administered intravenously on day 1 of a 3-week schedule for a planned minimum of six courses.

Results

Between November 1997 and February 2000, 1,282 patients were randomly assigned to receive either TC (635 patients) or TEC (647 patients), respectively. Grade 3/4 hematologic and some nonhematologic toxicities (nausea/emesis, mucositis, and infections) occurred significantly more frequently in the TEC arm. Accordingly, quality-of-life analysis showed inferiority of TEC versus TC. Median progression-free survival time was 18.4 months for the TEC arm and 17.9 months for the TC arm (hazard ratio [HR], 0.95; 95% CI, 0.83 to 1.07; P = .3342). Median overall survival time was 45.8 months for the TEC arm and 41.0 months for the TC arm (HR, 0.93; 95% CI, 0.81 to 1.08; P = .3652). Similar nonsignificant differences were observed when strata were analyzed separately.

Conclusion

Addition of epirubicin to TC did not improve survival or time to treatment failure in patients with advanced epithelial ovarian cancer; therefore, it cannot be recommended for clinical use in this population.
Phase I Study of Antisense Oligonucleotide Against Vascular Endothelial Growth Factor: Decrease in Plasma Vascular Endothelial Growth Factor With Potential Clinical Efficacy
Authors: Levine Alexandra M. , Tulpule Anil , Quinn David I. , Gorospe Gerardo , Smith D. Lynne , Hornor Laurie , Boswell William D. , Espina Byron M. , Groshen Susan G. , Masood Rizwan , Gill Parkash S.
Published: March 2006

Purpose

Vascular endothelial growth factor antisense (VEGF-AS) is an antisense oligonucleotide that targets VEGF, inhibiting angiogenesis and tumor cell proliferation. This study established the safety, biologic effects, and pharmacokinetics of VEGF-AS in 51 patients with advanced malignancies.

Methods

VEGF-AS was administered as a 2-hour infusion daily for 5 consecutive days for only one cycle on the first four dose levels, and then administered daily for 5 days every other week for up to 4 months on subsequent levels. Pharmacokinetics, tumor response, and the effect on plasma VEGF levels were determined.

Results

The maximum-tolerated dose was 200 mg/m2. Dose-limiting toxicities included grade 4 fever, and pulmonary embolism in one patient each at 250 mg/m2. Mild anemia, fever, fatigue, and gastrointestinal complaints were the most common adverse events. VEGF-AS t1/2β (beta-phase terminal half-life of drug concentration) was 2.25 hours (range, 1.97 to 2.95 hours). Mean plasma VEGF-A (P = .002) and VEGF-C (P = .01) levels decreased 24 hours postinfusion, with a trend towards greater decreases at higher dose levels. At the maximum-tolerated dose, five of six patients demonstrated reductions in plasma VEGF. Clinical responses included complete remission in one patient with AIDS-Kaposi's sarcoma, a mixed but dramatic response in one patient with cutaneous T-cell lymphoma, and prolongation of progression-free survival compared with that obtained on the immediate prior regimen in six patients (12%) with renal cell, bronchoalveolar, small cell lung, thyroid, and ovarian carcinomas, and chondrosarcoma, respectively.

Conclusion

VEGF-AS was well tolerated, with biologic effects and preliminary evidence of clinical efficacy.
Serum Circulating Human mRNA Profiling and Its Utility for Oral Cancer Detection
Authors: Li Yang , Elashoff David , Oh Myungshin , Sinha Uttam , St John Maie A.R. , Zhou Xiaofeng , Abemayor Elliot , Wong David T.
Published: February 2006

Purpose

The purpose of this study is to explore the presence of informative RNA biomarkers from human serum transcriptome, and evaluate the serum transcriptome diagnostics for disease detection. Oral squamous cell carcinoma (OSCC) was selected as the proof-of-concept disease.

Patients and Methods

Blood samples were collected from patients (n = 32) with primary T1/T2 OSCC and matched healthy patients (n = 35). Circulating RNA was isolated from serum and linearly amplified using T7 polymerase. Microarrays were applied for profiling transcriptome in serum from 10 cancer patients and controls. The differential gene expression was analyzed by combining the present calls, t tests, and fold-change statistics. Quantitative polymerase chain reaction (PCR) was used to validate the selected candidate RNA markers identified by microarray. Receiver operating characteristic curve and classification models were exploited to evaluate the diagnostic power of these markers for OSCC.

Results

Human serum circulating mRNAs were presented by reverse transcriptase PCR. Microarray identified 2,623 ± 868 probes assigned present calls in OSCC (n = 10) versus 1,792 ± 165 in healthy patients (n = 10), indicating a higher complexity of serum transciptome in OSCC patients (P = .002, Wilcoxon test). Three hundred thirty-five serum RNAs exhibited significantly differential expression level between the two groups (P < .05, t test; fold ≥ 2). Five cancer-related gene transcripts were consistently validated by quantitative PCR on serum from OSCC patients (n = 32) and controls (n = 35). The best combination of biomarkers yielded a receiver operating characteristic curve value of 88%, sensitivity (91%), and specificity (71%) in distinguishing OSCC.

Conclusion

The utility of serum transcriptome diagnostics is successfully demonstrated for OSCC detection. This novel concept could be developed as an adjunctive tool for disease diagnosis.
Hepatic Arterial Infusion Versus Systemic Therapy for Hepatic Metastases From Colorectal Cancer: A Randomized Trial of Efficacy, Quality of Life, and Molecular Markers (CALGB 9481)
Authors: Kemeny Nancy E. , Niedzwiecki Donna , Hollis Donna R. , Lenz Heinz-Josef , Warren Robert S. , Naughton Michelle J. , Weeks Jane C. , Sigurdson Elin R. , Herndon James E. , Zhang Chunfeng , Mayer Robert J.
Published: February 2006

Purpose

Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome.

Methods

In a multi-institutional trial, 135 patients were randomly assigned to receive HAI versus systemic bolus fluorouracil and leucovorin. The primary end point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost, and the influence of molecular markers.

Results

Overall survival was significantly longer for HAI versus systemic treatment (median, 24.4 v 20 months; P = .0034), as were response rates (47% and 24%; P = .012) and time to hepatic progression (THP; 9.8 v 7.3 months; P = .034). Time to extrahepatic progression (7.7 v 14.8 months; P = .029) was significantly shorter in the HAI group. Quality-of-life measurements showed improved physical functioning in the HAI group at the 3- and 6-month follow-up assessments. Toxicity included grade ≥ 3 neutropenia (2% and 45%; P < .01), stomatitis (0% and 24%; P < .01), and bilirubin elevation (18.6% and 0; P < .01) in the HAI and systemic treatment groups, respectively. A greater proportion of men versus women receiving HAI experienced biliary toxicity (37% and 15%, respectively; P = .05). For HAI patients with thymidylate synthase levels in tumor less than or ≥ 4, the median survival was 24 and 14 months, respectively (P = .17).

Conclusion

HAI therapy increased overall survival, response rate, THP, and was associated with better physical functioning compared with systemic therapy. Additional studies need to address the overall benefit and cost of new chemotherapy agents versus HAI alone or the combination of HAI with new agents.
Clinical and Molecular Studies of the Effect of Imatinib on Advanced Aggressive Fibromatosis (desmoid tumor)
Authors: Heinrich Michael C. , McArthur Grant A. , Demetri George D. , Joensuu Heikki , Bono Petri , Herrmann Richard , Hirte Hal , Cresta Sara , Koslin D. Bradley , Corless Christopher L. , Dirnhofer Stephan , van Oosterom Allan T. , Nikolova Zariana , Dimitrijevic Sasa , Fletcher Jonathan A.
Published: February 2006

Purpose

To determine the clinical efficacy of imatinib in patients with advanced aggressive fibromatosis (AF) and to identify the molecular basis of response/nonresponse to this agent.

Patients and Methods

Nineteen patients with AF were treated with imatinib (800 mg/d) as part of a phase II clinical study. Tumor specimens were analyzed for mutations of KIT, PDGFRA, PDGFRB, and CTNNB1 (beta-catenin). Tumor expression of total and activated KIT, PDGFRA, and PDGFRB were assessed using immunohistochemistry and immunoblotting techniques. We also measured plasma levels of PDGF-AA and PDGF-BB in patients and normal patient controls.

Results

Three of 19 patients (15.7%) had a partial response to treatment, with four additional patients having stable disease that lasted more than 1 year (overall 1 year tumor control rate of 36.8%). No mutations of KIT, PDGFRA, or PDGFRB were found. Sixteen of 19 patients (84%) had mutations involving the WNT pathway (APC or CTNNB1). However, there was no correlation between WNT pathway mutations and clinical response to imatinib. AF tumors expressed minimal to null levels of KIT and PDGFRA but expressed levels of PDGFRB that are comparable with normal fibroblasts. However, PDGFRB phosphorylation was not detected, suggesting that PDGFRB is only weakly activated. AF patients had elevated levels of PDGF-AA and PDGF-BB compared with normal patient controls. Notably, the plasma level of PDGF-BB was inversely correlated with time to treatment failure.

Conclusion

Imatinib is an active agent in the treatment of advanced AF. Imatinib response in AF patients may be mediated by inhibition of PDGFRB kinase activity.
Fulvestrant in Women With Advanced Breast Cancer After Progression on Prior Aromatase Inhibitor Therapy: North Central Cancer Treatment Group Trial N0032
Authors: Ingle James N. , Suman Vera J. , Rowland Kendrith M. , Mirchandani Deepu , Bernath Albert M. , Camoriano John K. , Fishkin Paul A.S. , Nikcevich Daniel A. , Perez Edith A.
Published: February 2006

Purpose

Fulvestrant is an antiestrogen that leads to estrogen receptor degradation and has demonstrated efficacy in breast cancer patients who have had disease recurrence or progression after tamoxifen. This study was designed to examine the efficacy and toxicity of fulvestrant in patients with disease progression on a third-generation aromatase inhibitor (AI).

Patients and Methods

A one-stage phase II trial was conducted in postmenopausal women with measurable disease by Response Evaluation Criteria in Solid Tumors criteria who experienced disease progression after treatment with a third-generation AI and, at most, one additional hormonal agent. Tumors must have been estrogen receptor and/or progesterone receptor positive. The primary end point was objective response rate, and secondary end points were time to disease progression, survival, duration of response, and toxicity.

Results

Eighty patients were enrolled, and three were ineligible. Characteristics of the 77 eligible patients included median age of 68 years, performance score of 0 or 1 in 91% of patients, visceral dominant disease in 88% of patients, two prior hormonal treatments in 73% of patients, and prior chemotherapy for metastatic disease in 32% of patients. Eleven patients (14.3%) achieved a partial response, and 16 patients (20.8%) had stable disease for at least 6 months, for a clinical benefit rate of 35%. Antitumor activity seemed to be higher in women with prior treatment with AI alone compared with women whose prior treatment also included tamoxifen. Median time to progression was 3 months, and median survival time was 20.2 months. Fulvestrant was well tolerated.

Conclusion

Fulvestrant is a well-tolerated treatment and has efficacy against breast cancers that have progressed after therapy with a third-generation AI.
Venous Thromboembolism in Patients With Colorectal Cancer: Incidence and Effect on Survival
Authors: Alcalay Allison , Wun Ted , Khatri Vijay , Chew Helen K. , Harvey Danielle , Zhou Hong , White Richard H.
Published: February 2006

Purpose

To describe the incidence and outcomes associated with venous thromboembolism (VTE) among patients with colorectal cancer.

Methods

This was a retrospective analysis of all colorectal cancer patients diagnosed in California between 1993 and 1995 and 1997 to 1999. Principal outcomes were incident symptomatic VTE events and death. Associations between specific risk factors and principal outcomes were analyzed using Cox proportional hazards models.

Results

Among 68,142 colorectal cancer patients, 50% were women, mean age was 70 ± 15 years, and approximately 70% underwent a major operation. The 2-year cumulative incidence of VTE was 2,100 patients (3.1%), with an incidence rate that decreased significantly over time from 5.0% (events/100 patient-years) in months 0 to 6 to 1.4% during months 7 to 12 to 0.6% during the second year. Significant predictors of VTE included metastatic stage (hazard ratio [HR] = 3.2; 95% CI, 2.8 to 3.8) and three or more comorbid conditions (HR = 2.0; 95% CI, 1.7 to 2.3). The risk of VTE was significantly reduced among Asians/Pacific Islanders (HR = 0.4; 95% CI, 0.3 to 0.5.) and patients who underwent an abdominal operation (HR = 0.4; 95% CI, 0.3 to 0.4). In risk-adjusted models, VTE was a significant predictor of death within 1 year of cancer diagnosis among patients with local- (HR = 1.8; 95% CI, 1.4 to 2.3) or regional-stage disease (HR = 1.5; 95% CI, 1.3 to 1.8) but not among patients with metastatic disease (HR = 1.1; 95% CI, 1.0 to 1.2).

Conclusion

The incidence of VTE among colorectal cancer patients was highest in the first 6 months after diagnosis and decreased rapidly thereafter. Metastatic disease and the number of medical comorbidities were the strongest predictors of VTE. Incident VTE reduced survival among patients with local or regional disease, suggesting that, in these patients, VTE may reflect the presence of a biologically more aggressive cancer.
Randomized Dose-Escalation Study Evaluating Peginterferon Alfa-2a in Patients With Metastatic Malignant Melanoma
Authors: Dummer Reinhard , Garbe Claus , Thompson John A. , Eggermont Alexander M. , Yoo Kisook , Maier Tanja , Bergstrom Bengt
Published: February 2006

Purpose

A pegylated interferon, peginterferon alfa-2a (PEG-IFNα-2a; 40 kd), has the potential for improved tumor response and survival with lower toxicity than IFNα. This open-label, randomized study evaluated the safety, tolerability, and efficacy of subcutaneous PEG-IFNα-2a in patients with metastatic malignant melanoma (stage IV American Joint Committee on Cancer staging system).

Patients and Methods

PEG-IFNα-2a was administered subcutaneously at 180 (n = 48), 360 (n = 53), or 450 μg (n = 49) once weekly for 24 weeks, with maintenance therapy for responders. Efficacy was assessed by the proportion of patients with complete response (CR) or partial response (PR).

Results

The major response rate (CR or PR) was 6% in the 180-μg group (CR, 2%; PR, 4%), 8% in the 360-μg group (CR, 2%; PR, 6%), and 12% in the 450-μg group (CR, 6%; PR, 6%). The times to achieve a major response, duration of major response, rate of disease progression, and 12-month survival were similar between groups, although overall median survival was significantly different among the three groups (P = .0136). More patients required dose adjustment for safety reasons in the higher dose groups, but PEG-IFNα-2a was generally well tolerated, with few withdrawals because of adverse events (6%, 19%, and 16% in the 180-, 360-, and 450-μg groups, respectively). The most common adverse events were fatigue, pyrexia, and nausea.

Conclusion

PEG-IFNα-2a at doses up to 450 μg once weekly has shown good tolerability and similar efficacy to conventional IFNα and monochemotherapy in stage IV metastatic melanoma.
Use of Cigarette-Smoking History to Estimate the Likelihood of Mutations in Epidermal Growth Factor Receptor Gene Exons 19 and 21 in Lung Adenocarcinomas
Authors: Pham DuyKhanh , Kris Mark G. , Riely Gregory J. , Sarkaria Inderpal S. , McDonough Tiffani , Chuai Shaokun , Venkatraman Ennapadam S. , Miller Vincent A. , Ladanyi Marc , Pao William , Wilson Richard K. , Singh Bhuvanesh , Rusch Valerie W.
Published: February 2006

Purpose

Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers.

Methods

EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit ≥ 1 year ago), or current smokers (quit < 1 year ago).

Results

We detected EGFR mutations in 34 (51%) of 67 never smokers (95% CI, 38% to 64%), 29 (19%) of 151 former smokers (95% CI, 13% to 27%), and two (4%) of 47 current smokers (95% CI, 1% to 16%). Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P < .001) or stopped smoking less than 25 years ago (P < .02) compared with individuals who never smoked. The number of smoking pack-years and smoke-free years predicted the prevalence of EGFR mutations (areas under receiver operating characteristic curve = 0.78 and 0.77, respectively).

Conclusion

The likelihood of EGFR mutations in exons 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 25 years ago. These data can assist clinicians in assessing the likelihood of exon 19 and 21 EGFR mutations in patients with lung adenocarcinoma when mutational analysis is not feasible.
Differential Cell Cycle–Regulatory Protein Expression in Biliary Tract Adenocarcinoma: Correlation With Anatomic Site, Pathologic Variables, and Clinical Outcome
Authors: Jarnagin William R. , Klimstra David S. , Hezel Michael , Gonen Mithat , Fong Yuman , Roggin Kevin , Cymes Karina , DeMatteo Ronald P. , D'Angelica Michael , Blumgart Leslie H. , Singh Bhuvanesh
Published: February 2006

Purpose

Biliary tract adenocarcinomas (BTAs), although anatomically related, arise through ill-defined and possibly different location-related pathogenetic pathways. This clinicopathologic study characterizes differences in cell cycle–regulatory protein expression across the spectrum of BTA.

Methods

Tissue microarrays were prepared from paraffin-embedded surgical specimens with triplicate cores of BTA and benign tissue. Immunohistochemical expression of p53, cyclin D1, p21, Bcl2, p27, Mdm2, and Ki-67 was assessed, and the results were correlated with pathologic variables and survival. Hierarchical clustering was used to partition the data based on protein expression, and then the data were analyzed according to anatomic location.

Results

Tissue from 128 surgical patients (1992 to 2002) was obtained. Tumor sites of origin were intrahepatic cholangiocarcinoma (IH; n = 23), hilar cholangiocarcinoma (Hilar; n = 54), gallbladder (GB; n = 32), and distal bile duct (Distal; n = 19). p27 expression decreased progressively from proximal to distal in the biliary tree and correlated with location-related differences in outcome; cyclin D1 and Bcl2 overexpression also varied according to anatomic site. Aberrant p53 staining and cyclin D1 overexpression were lower in papillary tumors compared with the more common sclerosing tumors. The expression profiles of GB and Hilar were more similar to each other than either was to IH or Distal (86% clustering in the first partition). After an R0 resection, overexpression of Mdm2 (P = .0062) and absent p27 expression (P = .0165) independently predicted poor outcome.

Conclusion

BTAs differentially express cell cycle–regulatory proteins based on tumor location and morphology. Prognostic roles were identified for Mdm2 and p27. Overlap in the pathogenesis of GB and Hilar tumors was suggested.
Phase III Comparison of Depomedroxyprogesterone Acetate to Venlafaxine for Managing Hot Flashes: North Central Cancer Treatment Group Trial N99C7
Authors: Loprinzi Charles L. , Levitt Ralph , Barton Debra , Sloan Jeff A. , Dakhil Shaker R. , Nikcevich Daniel A. , Bearden James D. , Mailliard James A. , Tschetter Loren K. , Fitch Tom R. , Kugler John W.
Published: February 2006

Purpose

Vasomotor hot flashes are a common problem in menopausal women. Given concerns regarding estrogen and/or combined hormonal therapy, other treatment options are desired. Prior trials have confirmed that progestational agents and newer antidepressants effectively reduce hot flashes. This current trial compared a single intramuscular dose of medroxyprogesterone acetate (MPA), depot preparation, versus daily oral venlafaxine as treatment for hot flashes.

Methods

Women with bothersome hot flashes were entered onto this trial, were randomly assigned to treatment, and then had a baseline week where hot flash scores were recorded without treatment. They were then treated and observed for 6 weeks; daily diaries were used to measure hot flash frequencies and severities. There were 109 patients per each arm randomly assigned to receive MPA 400 mg intramuscularly for a single dose versus venlafaxine 37.5 mg per day for a week, then 75 mg per day.

Results

During the sixth week after random assignment, hot flash scores were reduced by 55% in the venlafaxine arm versus 79% in the MPA arm (P < .0001). In an intention-to-treat analysis, 46% of venlafaxine patients (50 of 109) compared with 74% of the MPA patients (81 of 109) had a decrease in hot flashes by more than 50% from baseline (P < .0001). Less toxicity was reported in the MPA arm.

Conclusion

A single MPA dose seems to be well tolerated and more effectively reduces hot flashes than does venlafaxine.
Psychiatry: Role of Risperidone in Children with Autism Spectrum Disorder
Authors: Chavez Benjamin , Chavez-Brown Mapy , Rey Jose A
Published: March 2006

Objective:

To review the clinical trials investigating the efficacy and safety of risperidone in the treatment of children with autism spectrum disorder (ASD).

Data Sources:

Searches of MEDLINE/PubMed (1992–February 2006) were conducted, as well as an extensive manual review of journals, using the key words autism and risperidone.

Study Selection and Data Extraction:

Only double-blind, placebo-controlled trials were included for review.

Data Synthesis:

ASD is the most common of the pervasive developmental disorders. The main characteristics (core symptoms) of autism are impairment in social skills, problems communicating, and stereotypical movements. Behavioral manifestations or maladaptive behaviors include aggression, irritability, hyperactivity, inattention, impulsivity, tantrums, and self-injurious behavior.

Conclusions:

Based on the data examined, risperidone appears efficacious and safe for treating certain behavioral aspects of autism including irritability, aggression, hyperactivity, and stereotypy. It does not appear to be as effective for the treatment of the core symptoms of autism.
Hepatic Veno-Occlusive Disease Associated with Immunosuppressive Cyclophosphamide Dosing and Roxithromycin
Authors: Beltinger Johannes , Haschke Manuel , Kaufmann Priska , Michot Marc , Terracciano Luigi , Krähenbühl Stephan
Published: March 2006

Objective:

To report on a patient developing hepatic veno-occlusive disease while being treated with immunosuppressive doses of cyclophosphamide (≤2 mg/kg).

Case Summary:

A 66-year-old woman with autoimmune hemolytic anemia developed hepatic veno-occlusive disease while being treated with immunosuppressive cyclophosphamide 100 mg/day in combination with roxithromycin (total dose 600 mg/day). After all drugs were stopped, the patient recovered within 2 weeks. The Naranjo probability scale indicated a probable relationship between veno-occlusive disease and treatment with cyclophosphamide in this patient.

Discussion:

Since roxithromycin inhibits CYP3A4, which is involved with cyclophosphamide metabolism, a drug-drug interaction could have been responsible. In addition, roxithromycin is an inhibitor of the drug transporter P-glycoprotein, possibly leading to accumulation of cyclophosphamide in endothelial cells. Alternatively, since cyclophosphamide has been reported to induce apoptosis, roxithromycin could have rendered endothelial cells more vulnerable for apoptosis.

Conclusions:

In specific patients, cyclophosphamide can be associated with hepatic veno-occlusive disease at immunosuppressive doses.
Allele Dropout in PCR-Based Diagnosis of Wilson Disease: Mechanisms and Solutions
Authors: Lam Ching-Wan , Mak Chloe M
Published: February 2006

Background: We investigated the mechanisms leading to allele dropout—the nonamplification of 1 of the alleles—in PCR-based diagnosis of Wilson disease (WD).

Methods: We extracted genomic DNA from blood samples from 6 WD patients (P1–P6) with allele dropouts detected in a previous study of WD in a Hong Kong Chinese population. We amplified the ATP7B gene by PCR and performed direct DNA sequencing of all exons of the ATP7B gene. To support the proposed mechanism of allele dropout, we used proofreading DNA polymerase, primer design avoiding single-nucleotide polymorphism sites, and duplex PCR.

Results: Patients P1–P4 were all apparently homozygous for a known disease-causing mutation, c.2975C>T (p.P992L) in exon 13. Patient P5 was apparently homozygous for a novel mutation, c.2524G>A, and patient P6 was apparently homozygous for another known mutation, c.522_523insA (p.K175K-fs). In all cases, we determined that the patients were actually heterozygous for these mutations.

Conclusion: Our results confirm that allele dropout is the mechanism causing apparent homozygosity of heterozygous mutations in these WD patients.
A Taxonomy of the Pricing Practices of Exporting Firms: Evidence from Austria, Norway, and the United States
Authors: Solberg Carl Arthur , Stöttinger Barbara , Yaprak Attila
Published: February 2006

In this qualitative study, the authors offer a framework through which they examine the information use, strategic approach, and managerial control behavior in the export pricing practices of 24 firms based in Austria, Norway, and the United States. They offer propositions about export pricing behavior and suggestions for empirical research in the field.
Recent advances in physiological calcium homeostasis
Authors: Ramasamy Indra
Published: March 2006

A constant extracellular Ca
A selectivity study of reaction of the carbonate radical anion with methyl β-d-cellobioside and methyl β-d-glucoside in oxygenated aqueous solutions
Authors: Carlsson Magnus , Lind Johan , Merényi Gábor
Published: March 2006

In the presence of oxygen, radiolytically generated carbonate radical anions, CO3
•–, were reacted with methyl β-D-cellobioside and methyl β-D-glucoside. From the ensuing product pattern, it was concluded that CO3
•– abstracts hydrogen atoms predominantly from glucosidic C1–H bonds. This high intramolecular selectivity was rationalised mainly in terms of a polar effect on the transition state of the hydrogen abstraction reaction. The present findings are in sharp contrast to the relative inertness of CO3
•– towards glucosidic C1–H bonds previously observed in cotton linters. The reasons for this discrepancy are discussed in light of a possible future role of CO3
•– as a bleaching agent for pulp.
The effect of molecular composition of xylan extracted from birch on its assembly onto bleached softwood kraft pulp
Authors: Westbye Peter , Svanberg Christer , Gatenholm Paul
Published: March 2006

The effect of the molecular structure of xylan on its assembly onto softwood kraft pulps was investigated. Various xylan-rich fractions were isolated from birch wood chips by different mild treatments using water (H2O), acetic acid (HAc) and sulfur dioxide (SO2). The isolation involved prehydrolysis followed by alkaline extraction, with only the time, temperature and medium in the prehydrolysis step varied. After separation, the fractions were neutralised (pH 7) and some material agglomerated and became insoluble. Dynamic light scattering measurements revealed differences in aggregate size among the different fractions. The fractions that agglomerated to the greatest extent contained less glucuronic acid and a higher amount of lignin. Such fractions adsorbed to a significantly higher extent (25.5% compared to 5.0% for the lowest soluble fraction) onto bleached softwood kraft pulps in experiments performed in autoclaves. The adsorption was carried out with fixed process parameters (100°C, pH 10, 120 min). The adsorption of various xylan fractions resulted in different surface morphology on cellulose microfibrils, as observed by AFM. Pulps treated with xylans that were soluble at pH 7 showed small differences from the control sample, which was treated in an autoclave without the addition of xylan. Pulps treated with xylans that agglomerated at pH 7 showed a greater difference in the amount of nanosized aggregates covering the surface. ESCA analysis of the chemical surface composition indicated that samples containing more lignin showed a greater shift towards carbon-carbon bonds. A novel sequence for a pulping process is suggested.