Showing papers by "St Bartholomew's Hospital published in 2007"

Effects of Torcetrapib in Patients at High Risk for Coronary Events

Abstract: Background Inhibition of cholesteryl ester transfer protein (CETP) has been shown to have a substantial effect on plasma lipoprotein levels. We investigated whether torcetrapib, a potent CETP inhibitor, might reduce major cardiovascular events. The trial was terminated prematurely because of an increased risk of death and cardiac events in patients receiving torcetrapib. Methods We conducted a randomized, double-blind study involving 15,067 patients at high cardiovascular risk. The patients received either torcetrapib plus atorvastatin or atorvastatin alone. The primary outcome was the time to the first major cardiovascular event, which was defined as death from coronary heart disease, nonfatal myocardial infarction, stroke, or hospitalization for unstable angina. Results At 12 months in patients who received torcetrapib, there was an increase of 72.1% in high-density lipoprotein cholesterol and a decrease of 24.9% in low-density lipoprotein cholesterol, as compared with baseline (P<0.001 for both compari...

Venice Chart international consensus document on atrial fibrillation ablation.

Abstract: Venice Chart International Consensus Document on Atrial Fibrillation Ablation ANDREA NATALE, M.D.,∗ ANTONIO RAVIELE, M.D.,† THOMAS ARENTZ, M.D.,‡ HUGH CALKINS, M.D.,¶ SHIH-ANN CHEN, M.D.,∗∗ MICHEL HAISSAGUERRE, M.D.,†† GERHARD HINDRICKS, M.D.,‡‡ YEN HO, M.D.,¶¶ KARL HEINZ KUCK, M.D.,∗∗∗ FRANCIS MARCHLINSKI, M.D.,††† CARLO NAPOLITANO, M.D.,‡‡‡ DOUGLAS PACKER, M.D.,¶¶¶ CARLO PAPPONE, M.D.,∗∗∗∗ ERIC N. PRYSTOWSKY, M.D.,†††† RICHARD SCHILLING, M.D.,‡‡‡‡ DIPEN SHAH, M.D.,¶¶¶¶ SAKIS THEMISTOCLAKIS, M.D.,† and ATUL VERMA, M.D.,∗∗∗∗∗ for the Venice Chart members From the ∗Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, USA; †Department of Cardiology, Arrhythmologic Section, Umberto I Hospital, Venice-Mestre, Italy; ‡Arrhythmia Service, Herz-Zentrum, Bad Krozingen, Germany; ¶Department of Cardiology, The Johns Hopkins Hospital, Baltimore, USA; ∗∗Division of Cardiology, Department of Medicine, National Yang-Ming University School of Medicine and Taipei Veterans General Hospital, Taipei, Taiwan; ††Hospital du Haut Leveque, CHU Bordeaux, Bordeaux, France; ‡‡University Leipzig, Heart Center, Department of Cardiology, Leipzig, Germany; ¶¶National Heart and Lung Institute, Imperial College and Royal Brompton & Harefield Hospitals, London, UK; ∗∗∗Second Medical Department, St Georg General Hospital, Hamburg, Germany; †††Cardiovascular Division, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, USA; ‡‡‡Molecular Cardiology Laboratory, University of Pavia, Salvatore Maugeri Foundation, Pavia, Italy; ¶¶¶Department of Clinical Cardiac Electrophysiology and Internal Medicine, Mayo Clinic, Rochester, USA; ∗∗∗∗Department of Cardiology, Electrophysiology and Cardiac Pacing Unit, San Raffaele University Hospital, Milan, Italy; ††††St. Vincent Hospital and Health Care Center Program, Indianapolis, USA; ‡‡‡‡St. Bartholomew’s Hospital, London, UK; ¶¶¶¶Cardiology Cantonal Hospital of Geneva, Geneva, Switzerland; ∗∗∗∗∗University of Toronto, Toronto, Canada.

The endocrine system and ageing.

Abstract: Complex changes occur within the endocrine system of ageing individuals This article explores the changes that occur in the metabolism and production of various hormones and discusses the resulting clinical consequences As individuals age there is a decline in the peripheral levels of oestrogen and testosterone, with an increase in luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin Additionally there is a decline in serum concentrations of growth hormone, insulin-like growth factor-I and dehydroepiandrosterone and its sulphate-bound form Even though there are complex changes within the hypothalmo-pituitary-adrenal/thyroid axis, there is minimal change in adrenal and thyroid function with ageing The clinical significance of these deficiencies with age are variable and include reduced protein synthesis, decrease in lean body mass and bone mass, increased fat mass, insulin resistance, higher cardiovascular disease risk, increase in vasomotor symptoms, fatigue, depression, anaemia, poor libido, erectile deficiency and a decline in immune function For each endocrine system, studies have been carried out in an attempt to reverse the effects of ageing by altering the serum hormonal levels of older individuals However, the real benefits of hormonal treatment in older individuals are still being evaluated

Myeloablative Therapy With Autologous Bone Marrow Transplantation for Follicular Lymphoma at the Time of Second or Subsequent Remission: Long-Term Follow-Up

Abstract: Purpose The aim of this retrospective analysis was to determine the outcome of patients with follicular lymphoma who received myeloablative therapy supported by autologous bone marrow transplantation as consolidation of second or subsequent remission, with a minimum follow-up of 12 years. Patients and Methods One hundred twenty-one adults received cyclophosphamide (CY) and total-body irradiation (TBI) supported by autologous bone marrow transplantation, with the marrow mononuclear cell fraction having been treated with monoclonal antibodies and complement. Data from St Bartholomew's Hospital and Dana-Farber Cancer Institute were combined for the purpose of this analysis because the patients were treated in an identical manner. Results Fifty-seven patients are alive, 41 without progression between 9 and 19 years; 64 patients have died, 20 without progression. With a median follow-up of 13.5 years, 60 patients have developed recurrent lymphoma. There is an apparent plateau on the remission duration curve at 48% at 12 years. Survival of patients treated in second remission was significantly longer than the survival of patients treated later in the course of the illness. Both remission duration and overall survival were also significantly longer for patients treated in second remission compared with an age-matched, remission-matched group of patients treated at St Bartholomew's Hospital before the introduction of this treatment. However, use of CY+TBI was associated with a significant risk of secondary myelodysplasia and secondary acute myeloblastic leukemia, resulting in 15 patient deaths. Conclusion These mature data confirm that prolonged freedom from recurrence may be achieved with myeloablative therapy and that a plateau on the curve seems to emerge with long follow-up.

Predictive markers in breast cancer--the present.

Abstract: Breast cancer is a heterogeneous disease and there is a continual drive to identify markers that will aid in predicting prognosis and response to therapy. To date, relatively few markers have established prognostic power. Oestrogen receptor (ER) is probably the most powerful predictive marker in breast cancer management, both in determining prognosis and in predicting response to hormone therapies. Progesterone receptor (PR) is also a widely used marker, although its value is less well established. HER-2 status has also become a routine prognostic and predictive factor in breast cancer. Given the importance of these biological markers in patient management, it is essential that assays are robust and quality controlled, and that interpretation is standardized. Furthermore, it is important to be aware of the limitations in their predictive power, and how this may be refined through addition of further biological markers. The aim of this review is to provide an overview of the established role of ER, PR and HER-2 in patient management, the current standards for assessing these markers, as well as highlighting the controversies that still surround their use and methods of assessment.

Influence of antidepressants on whole gut and orocaecal transit times in health and irritable bowel syndrome

Abstract: SUMMARY Background: Antidepressants are used in the treatment of irritable bowel syndrome but it is unclear whether any symptomatic improvement is due solely to correction of an associated affective disorder, or whether these drugs have effects on bowel function which may be of therapeutic benefit. Intestinal transit is known to be abnormal in some irritable bowel syndrome patients. Methods: We have studied the effects of imipramine, a tricyclic antidepressant with mixed pharmacological properties, and paroxetine, a selective 5-hydroxy-tryptamine re-uptake inhibitor, on intestinal transit times. Results: Median (range) whole gut transit time was lower in 10 diarrhoea-predominant irritable bowel syndrome patients, 22.2 (3.6–51.6) h, compared to 28 control subjects 39.6 (7.2–68.4) h, (P < 0.05). Similarly, orocaecal transit time was shorter at 55 (30–90) min in diarrhoea-predominant irritable bowel syndrome patients compared to 75 (40–150) min in controls, (P < 0.05). Four days’administration of imipramine increasing to a daily dose of 100 mg prolonged both orocaecal and whole gut transit times in 12 control subjects and six diarrhoea-predominant irritable bowel syndrome patients. In contrast, 30 mg paroxetine daily for 4 days reduced orocaecal transit time in ten controls and eight irritable bowel syndrome patients, but had no effect on whole gut transit time. Conclusion: Short-term administration of antidepressants alters intestinal transit, but the selective 5-hydroxytryptamine re-uptake inhibitor, paroxetine, has different effects to the tricyclic drug, imipramine. These effects on transit precede any effects on mood. Although there is a high prevalence of affective disorder in irritable bowel syndrome clinic patients, these drugs may have additional therapeutic actions on the gut. These actions might be taken into account when prescribing antidepressants in irritable bowel syndrome.

Transformation of follicular lymphoma to diffuse large B-cell lymphoma proceeds by distinct oncogenic mechanisms.

Abstract: This study was undertaken to further elucidate the biological mechanisms underlying the frequent event of transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL). The gene expression profiles of 20 paired lymph node biopsies, derived from the same patient pre- and post-transformation, were analysed using the Lymphochip cDNA microarray. TP53 mutation analysis was performed and copy number alterations at the c-REL and CDNK2A examined. Immunohistochemistry was performed on an independent panel of paired transformation paraffin-embedded samples. Transformed follicular lymphoma was predominantly of the germinal centre B-like phenotype both at the mRNA and protein level. Despite this homogeneity, transformation proceeded by at least two pathways. One mechanism was characterised by high proliferation, as assessed by the co-ordinately expressed genes of the proliferation signature. This group was associated with the presence of recurrent oncogenic abnormalities. In the remaining cases, proliferation was not increased and transformation proceeded by alternative routes as yet undetermined. Genes involved in cellular proliferation prevailed amongst those that were significantly increased upon transformation and T cell and follicular dendritic-associated genes predominated amongst those that decreased. t-FL is a germinal centre B (GCB)-like malignancy that evolves by two pathways, one that is similar in proliferation rate to the antecedent FL and the other that has a higher proliferation rate and is characterised by the presence of recognised oncogenic abnormalities.

Patients discharged from medium secure forensic psychiatry services: reconvictions and risk factors

Abstract: Background Treatment within medium secure forensic psychiatry services is expected to reduce risk to the public. Aims To measure the period prevalence and incidence of offending following discharge and identify associated risk factors. Method Follow-up of patients from 7 of 14 regional services in England and Wales who spent time at risk ( n =1344) for a mean of 6.2 years. Outcome was obtained from offenders index, hospital case-files and the central register of deaths. Results One in 8 men and 1 in 16 women were convicted of grave offences. Incidence rates indicated low density and most patients were not subsequently convicted. Offence predictors included gender, younger age, early-onset offending, previous convictions and a comorbid or primary diagnosis of personality disorder. Longer in-patient stay and restriction on discharge were protective. Conclusions Risks of reoffending remain for a subgroup of discharged patients. Future research should aim to improve their identification and risk management following discharge.

Polymeric nutrition as the primary therapy in children with small bowel Crohn's disease.

Abstract: SUMMARY Background: Recent studies in adults have shown that polymeric (whole protein) diets are as effective as semi-elemental and elemental formulae for the induction of remission in small bowel Crohn's disease. Whole protein diets are more palatable and cheaper. There have been no studies confirming efficacy in children. Patients and Methods: We report our experience with seven children with active small bowel Crohn's disease given a casein-based, polymeric feed rich in TGF-SbT2 (Specific Polymeric Diet; Nestl–Clintec; Vevey, Switzerland) as complete nutrition for 8 weeks. Results: Initial and follow-up assessments were performed. All children showed a significant improvement in disease activity, with C-reactive protein returning to normal, an increase in serum albumin and a good weight gain. Initial and follow-up ileal biopsies were assessed and showed reduced mucosal inflammation in six of seven children, with complete healing in two. Conclusion: In an uncontrolled descriptive study we have shown that a polymeric (whole protein) diet is a therapeutic option for small bowel Crohn's disease in children. By comprehensive follow-up we have demonstrated clinical and biochemical remission, with an improved endoscopic appearance and a reduction of mucosal inflammation in the terminal ileum.

Evaluation of endometrial carcinoma on magnetic resonance imaging

Abstract: Our aims were to assess diagnostic performance of T2-weighted (T2W) and dynamic gadolinium-enhanced T1-weighted (T1W) magnetic resonance imaging (MRI) in the preoperative assessment of myometrial and cervical invasion by endometrial carcinoma and to identify imaging features that predict nodal metastases. Two radiologists retrospectively reviewed MR images of 96 patients with endometrial carcinoma. Tumor size, depth of myometrial and cervical invasion, and nodal enlargement were recorded and then correlated with histology. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the identification of any myometrial invasion (superficial or deep) were 0.94, 0.50, 0.93, 0.55 on T2W and 0.92, 0.50, 0.92, 0.50 on dynamic T1W, and for deep myometrial invasion were 0.84, 0.78, 0.65, 0.91 on T2W and 0.72, 0.88, 0.72, 0.88 on dynamic T1W. The sensitivity, specificity, PPV and NPV for any cervical invasion (endocervical or stromal) were 0.65, 0.87, 0.57, 0.90 on T2W and 0.50, 0.90, 0.46, 0.92 on dynamic T1W, and for cervical stromal involvement were 0.69, 0.95, 0.69, 0.95 on T2W and 0.50, 0.96, 0.57, 0.95 on dynamic T1W. Leiomyoma or adenomyosis were seen in 73% of misdiagnosed cases. Sensitivity and specificity for the detection of nodal metastases was 66% and 73%, respectively. Fifty percent of patients with cervical invasion on MRI had nodal metastases. In conclusion, MRI has a high sensitivity for detecting myometrial invasion and a high NPV for deep invasion. MRI has a high specificity and NPV for detecting cervical invasion. Dynamic enhancement did not improve diagnostic performance. MRI may allow accurate categorization of cases into low- or high-risk groups ensuring suitable extent of surgery and adjuvant therapy.

The performance of magnetic resonance imaging in early cervical carcinoma: a long-term experience

Abstract: We report our long-term experience of performance of magnetic resonance imaging (MRI) in localizing cervical tumor, assessing tumor size, staging, and lymph node infiltration in patients with early cervical cancer. MRI of 150 patients with early carcinoma between 1995-2005 was retrospectively reviewed. Tumor location, size, tumor distance from internal os, parametrial invasion, myometrial invasion, lymph node size, and location were documented. All patients underwent surgery, pelvic lymphadenectomy, and histological correlation of MRI findings. For staging, MRI and histopathology had kappa value of 0.89. For parametrial invasion, MRI had specificity, negative predictive value (NPV) of 97% and 100%, respectively. For tumor size, MRI and histology had mean difference of -0.9 mm with 95% limits of agreement between -12.6 to +13 mm. In tumors greater than 10 mm, mean difference was 0.3 mm and limits of agreement were -7.5 to +7.9 mm. For internal os involvement sensitivity, specificity, positive predictive value (PPV) and NPV were 90%, 98%, 86%, 98%. respectively. For myometrial invasion sensitivity, specificity, NPV, and PPV were 100%, 99%, 88%, 100%, respectively. Incidence of nodal metastases was 2.9%. On a per-patient basis, sensitivity, specificity for nodal involvement was 37% and 92% and on node-by-node basis, sensitivity and specificity of MRI was 27% and 99%, respectively. Our study confirms MRI is highly accurate in localizing cervical tumor, excluding parametrial invasion, confirming myometrial and internal os invasion. MRI is therefore useful in selecting patients for surgery and mandatory in patients for fertility-preserving surgery. Using accepted size criteria for nodal involvement, MRI is insensitive and currently will not avoid need for pelvic lymphadenectomy.

Personality disorder and cardiovascular disease: Results from a national household survey

Abstract: Objective: Little is known about the physical health of personality-disordered people. This study investigated associations between personality disorder and cardiovascular disease in a large, nationally representative sample from Great Britain.Method: A random sample of 8580 adults aged 16 to 74 years, living in England, Wales, and Scotland in 2000 was screened for the presence of personality disorders using the screening questionnaire of the Structured Clinical Interview for DSM-IV Axis II Personality Disorders. Self-reported stroke or ischemic heart disease was ascertained. Age, sex, social class (by occupation), self-reported hypertension or diabetes smoking history, and alcoholism were entered into regression models as potential confounding/mediating factors.Results: Participants screening positive for any personality disorder were more likely to report experiencing a stroke and ischemic heart disease (age- and sex-adjusted odds ratios [ORs] were 2.1 [95% CI, 1.2 to 3.8] and 1.5 [95% CI, 1.1 to 2.1], respectively). After adjusting for potential confounders, significant associations were found between any personality disorder and stroke (OR=1.9; 95% CI, 1.0 to 3.5) and any personality disorder and ischemic heart disease (OR=1.4; 95% CI, 1.0 to 1.9). After adjustment, avoidant (OR=4.0; 95% CI, 1.2 to 13.3), obsessive-compulsive (OR=2.9; 95% CI, 1.3 to 6.6), and borderline personality disorders (OR=8.5; 95% CI, 1.0 to 72.8) were significantly associated with stroke. Ischemic heart disease was significantly associated with avoidant (OR=2.2; 95% CI, 1.1 to 4.5), paranoid (OR=2.1; 95% CI, 1.0 to 4.3), schizotypal (OR=3.6; 95% CI, 1.5 to 8.6), schizoid (OR=1.6; 95% CI, 1.1 to 2.4), and borderline personality disorders (OR=7.2; 95% CI, 2.1 to 24.3).Conclusion: People at risk for personality order are also at increased risk for cardiovascular disease. This increased risk is not explained by differences in socioeconomic status or lifestyle. Dysfunctional personality traits may have a direct role in the etiology of cardiovascular disease.

Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy

Abstract: Chronic fatigue syndrome (CFS, also called myalgic encephalomyelitis/encephalopathy or ME) is a debilitating condition with no known cause or cure. Improvement may occur with medical care and additional therapies of pacing, cognitive behavioural therapy and graded exercise therapy. The latter two therapies have been found to be efficacious in small trials, but patient organisations' surveys have reported adverse effects. Although pacing has been advocated by patient organisations, it lacks empirical support. Specialist medical care is commonly provided but its efficacy when given alone is not established. This trial compares the efficacy of the additional therapies when added to specialist medical care against specialist medical care alone. 600 patients, who meet operationalised diagnostic criteria for CFS, will be recruited from secondary care into a randomised trial of four treatments, stratified by current comorbid depressive episode and different CFS/ME criteria. The four treatments are standardised specialist medical care either given alone, or with adaptive pacing therapy or cognitive behaviour therapy or graded exercise therapy. Supplementary therapies will involve fourteen sessions over 23 weeks and a 'booster session' at 36 weeks. Outcome will be assessed at 12, 24, and 52 weeks after randomisation. Two primary outcomes of self-rated fatigue and physical function will assess differential effects of each treatment on these measures. Secondary outcomes include adverse events and reactions, subjective measures of symptoms, mood, sleep and function and objective measures of physical activity, fitness, cost-effectiveness and cost-utility. The primary analysis will be based on intention to treat and will use logistic regression models to compare treatments. Secondary outcomes will be analysed by repeated measures analysis of variance with a linear mixed model. All analyses will allow for stratification factors. Mediators and moderators will be explored using multiple linear and logistic regression techniques with interactive terms, with the sample split into two to allow validation of the initial models. Economic analyses will incorporate sensitivity measures. The results of the trial will provide information about the benefits and adverse effects of these treatments, their cost-effectiveness and cost-utility, the process of clinical improvement and the predictors of efficacy.

Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myeloma.

Abstract: Adverse prognostic factors in multiple myeloma include advanced age, number of prior therapies, and higher International Staging System (ISS) disease stage. In the international, randomised, phase-3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study, bortezomib demonstrated significantly longer time to progression (TTP), higher response rates and improved survival compared with high-dose dexamethasone in patients with relapsed multiple myeloma following one to three prior therapies. In this APEX subgroup analysis, efficacy of bortezomib and dexamethasone was compared in elderly (age > or =65 years) and high-risk (>1 prior line of therapy; ISS stage II/III; refractory to prior therapy) patients. Bortezomib demonstrated substantial clinical activity in these patients. Response rate (34-40% vs. 13-19%), including complete response rate (5-8% vs. 0-1%), was significantly higher with bortezomib versus dexamethasone in all four subgroups. Similarly, median TTP was significantly longer with bortezomib versus dexamethasone, and 1-year survival probability was significantly higher in all subgroups. As in the total APEX population, rates of grade 3/4 adverse events were higher in bortezomib- versus dexamethasone-treated patients aged > or =65 years and with >1 prior line, while rates of serious adverse events were similar; toxicities generally proved manageable. Bortezomib should be considered an appropriate treatment for elderly and high-risk patients with relapsed multiple myeloma.

Wilms' tumour 1 mutations are associated with FLT3-ITD and failure of standard induction chemotherapy in patients with normal karyotype AML

Abstract: Wilms' tumour 1 mutations are associated with FLT3-ITD and failure of standard induction chemotherapy in patients with normal karyotype AML

The Proteasome Inhibitor Bortezomib Acts Independently of p53 and Induces Cell Death via Apoptosis and Mitotic Catastrophe in B-Cell Lymphoma Cell Lines

Abstract: Bortezomib is a proteasome inhibitor with proven efficacy in multiple myeloma and non-Hodgkin's lymphoma. This study reports the effects of bortezomib in B-cell lymphoma cell lines with differing sensitivity to bortezomib to investigate factors that influence sensitivity. Bortezomib induced a time- and concentration-dependent reduction in cell viability in five lymphoma cell lines, with EC(50) values ranging from 6 nmol/L (DHL-7 cells) to 25 nmol/L (DHL-4 cells) after 72 h. Bortezomib cytotoxicity was independent of p53 function, as all cell lines exhibited mutations by sequence analysis. The difference in sensitivity was not explained by proteasome or nuclear factor-kappaB (NF-kappaB) inhibition as these were similar in the most and least sensitive cells. NF-kappaB inhibition was less marked than that of a specific NF-kappaB inhibitor, Bay 11-7082. Cell cycle analysis showed a marked G(2)-arrested population in the least sensitive DHL-4 line only, an effect that was not present with Bay 11-7082 treatment. Conversely, in DHL-7 cells, bortezomib treatment resulted in cells moving into an aberrant mitosis, indicative of mitotic catastrophe that may contribute to increased sensitivity to bortezomib. These studies show that although bortezomib treatment had similar effects on apoptotic and NF-kappaB signaling pathways in these cell lines, different cell cycle effects were observed and induction of a further mechanism of cell death, mitotic catastrophe, was observed in the more sensitive cell line, which may provide some pointers to the difference in sensitivity between cell lines. An improved understanding of how DHL-7 cells abrogate the G(2)-M cell cycle checkpoint may help identify targets to increase the efficacy of bortezomib.

Modulation of glucocorticoid metabolism by the growth hormone - IGF-1 axis.

Abstract: The growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis plays an important role in modulating the peripheral metabolism of glucocorticoids mainly through its effect on the isoenzyme 11 beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) which, in vivo, functions as a reductase catalysing the conversion of cortisone to cortisol. Several in vivo and ex vivo studies have shown that the GH-IGF-I system inhibits the expression and activity of 11beta-HSD1 in adipose tissues and the liver resulting in reduced local regeneration of cortisol. This interaction has clinically significant implications as it may at least partly explain the phenotypes of acromegaly and adult GH deficiency and the effects that treatment of these conditions has on body composition. In addition, by accelerating the peripheral metabolism of cortisol, GH therapy may precipitate adrenal insufficiency in susceptible hypopituitary patients, and endocrinologists should be mindful of this phenomenon when starting hypopituitary patients on GH replacement therapy.

Endocrine manifestations in Langerhans cell histiocytosis.

Abstract: Langerhans cell histiocytosis is a rare, multisystem disease that shows a particular predilection for hypothalamo-pituitary axis involvement. Diabetes insipidus is the most frequent permanent consequence of Langerhans cell histiocytosis, developing in around a quarter of patients. Although the exact prevalence of anterior pituitary hormone deficiencies is not known, it is probably high and is almost always associated with diabetes insipidus. Established pituitary hormone deficiencies are mostly permanent and require prompt diagnosis and treatment, whereas continuous follow-up is needed to detect deficiencies that might evolve later during the course of the disease. Involvement of endocrine tissues other than the pituitary has also been described but is relatively rare. Further studies are needed to evaluate the effect that endocrine deficiencies exert on the overall prognosis of patients with Langerhans cell histiocytosis.

Radioimmunotherapy for B-cell lymphoma: Y90 ibritumomab tiuxetan and I(131) tositumomab.

Abstract: Radioimmunotherapy, targeting the CD20 antigen, in B-cell lymphoma has clearly demonstrated efficacy and tolerability over the preceding 15 years. As a result, two products are available with Food and Drug Administration approval for marketing - Y(90) ibritumomab tiuxetan and I(131) tositumomab, given as the Zevalin and Bexxar therapeutic regimens, respectively. Both demonstrate high-response rates and durability of remission in the relapsed/refractory disease setting. Data are emerging regarding their utility as initial therapy, and furthermore, they are been investigated for use sequentially with chemotherapy, and in the myeloablative setting. As yet however, how to best use these agents in the clinical disease course remains uncertain.

The effect of treatment on lymphokine-secreting cells in the intestinal mucosa of children with Crohn's disease.

Abstract: SUMMARY Background: Recent studies have shown both interleukin 2 (IL-2) and interferon gamma (IFN) to be elevated in patients with active Crohn's disease compared to ulcerative colitis or non-inflammatory bowel disease controls. However the effect of treatment on these lymphokines has not been studied. Patients and methods: Using a reverse haemolytic plaque assay the percentage of lymphokine-secreting cells was determined in the intestinal mucosa of children with Crohn's disease before and after 8 weeks of treatment with either enteral nutrition, cyclosporin or steroids. Results: Before treatment, a high percentage of cells isolated from mucosal biopsies secreted IL-2 or interferon-gamma. Eight weeks’treatment with the immunosuppressive agents cyclosporin, or with corticosteroids, produced a significant reduction in the percentage of IL-2 secreting cells, although only for the former was there also a reduction in interferon-gamma secreting cells. Enteral nutrition however, produced a reduction in lymphokine-secreting cells equivalent to cyclosporin and produced the best histological and clinical improvement. Conclusion: Enteral nutrition and cyclosporin can down-regulate lymphokine secretion in the gut in Crohn's disease.

Genome-wide detection of recurring sites of uniparental disomy in follicular and transformed follicular lymphoma

Abstract: Single-nucleotide polymorphism (SNP) array analysis was performed using the 10K GeneChip array on a series of 26 paired follicular lymphoma (FL) and transformed-FL (t-FL) biopsies and the lymphoma cell lines SCI-1, DoHH2 and RL2261 Regions of acquired homozygosity were detected in 43/52 (83%) primary specimens with a mean of 17 and 30 aberrations in the FL and t-FL, respectively A notable feature was the occurrence of recurring sites of acquired uniparental disomy (aUDP) on 6p, 9p, 12q and 17p in cell lines and primary samples Homozygosity of 9p and 17p arose predominantly in t-FL and in three cases rendered the cell homozygous for a pre-existing mutation of either CDKN2A or TP53 These data suggest that mutation precedes mitotic recombination, which leads to the removal of the remaining wild-type allele In all, 18 cases exhibited abnormalities in both FL and t-FL samples In 10 cases blocks of homozygosity were detected in FL that were absent in the subsequent t-FL sample These differences support the notion that FL and t-FL may arise in a proportion of patients by divergence from a common malignant ancestor cell rather than by clonal evolution from an antecedent FL

Raman spectroscopic analysis of breast cancer tissues: identifying differences between normal, invasive ductal carcinoma and ductal carcinoma in situ of the breast tissue

Abstract: A relatively non-destructive method employing Raman spectroscopy for the analysis of histopathological specimens is described. Raman spectroscopy has allowed qualitative analysis of the same specimen used for histopathological evaluation. Breast cancer tissues have been analysed to demonstrate the feasibility of the chemical changes taking place in the biological tissue, which can be identified precisely, and the results are reproducible. Raman analysis of tissue sections provides distinct spectra that can be used to distinguish between the nuclear grades of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. Sixty cases of breast carcinoma including DCIS and IDC and seven cases of normal breast tissues were studied employing the Raman spectroscopic technique. This study reports for the first time spectral differences between DCIS grades. It is concluded that Raman spectroscopy can objectively distinguish between DCIS and IDC grades and is non-destructive and reproducible. It should become possible in future to use Raman spectroscopy as an informative and quantitative method suitable for classification of grades and diagnosis of breast carcinoma. Copyright © 2007 John Wiley & Sons, Ltd.

Comparison of Noncontact and Electroanatomic Mapping to Identify Scar and Arrhythmia Late After the Fontan Procedure

Abstract: Background— The right atrium late after the Fontan procedure is characterized by multiple complex arrhythmia circuits. We performed simultaneous electroanatomic and noncontact mapping to assess the accuracy of both systems to identify scar and arrhythmia. Methods and Results— Mapping was performed in 26 patients aged 26.8±8.9 years, 18.7±4.4 years after Fontan surgery. The area and site of abnormal endocardium defined by electroanatomic mapping (bipolar contact electrogram <0.5 mV) were compared with those defined by noncontact mapping during sinus rhythm and by dynamic substrate mapping. Contact and reconstructed unipolar electrograms at a known distance from the multielectrode array, recorded by the noncontact system simultaneously at 452 endocardial sites, were compared for morphological cross correlation, timing difference, and amplitude. Mapping of arrhythmias was performed with both systems when possible. The median patient abnormal endocardium as defined by electroanatomic mapping covered 38.0% (ra...