Autologous haematopoietic stem-cell transplantation in multiple sclerosis: benefits and risks

Autologous haematopoietic stem-cell transplantation has been evaluated over the last years as a possible new therapeutic strategy in severe forms of multiple sclerosis unresponsive to the approved therapies. Up to now, more than 400 patients have been treated and numerous are the phase I and phase II studies which addressed the feasibility of this treatment, the efficacy, side effects and transplant-related mortality. The clinical response is strongly related to the intensity of the conditioning regimen utilized as well as to the phase of the disease course in which the therapy is carried out. Rapidly evolving multiple sclerosis with a relapsing–remitting clinical course and MRI signs of activity are the cases that can take more advantage. The risk of mortality, which dropped in the last years to 2–3%, is still the main problem of this powerful therapy.     

Exercise training improves autonomic function and inflammatory pattern in women with polycystic ovary syndrome (PCOS)

Background Polycystic ovary syndrome (PCOS) is a common female reproductive‐age endocrine disease predominantly characterized by chronic anovulation, hyperandrogenism, insulin‐resistance and low‐grade inflammatory status. Exercise training (ET) favourably modulates cardiopulmonary function and insulin‐sensitivity markers in PCOS women. The present study investigated the effects of ET on autonomic function and inflammatory pattern in PCOS women. Study design Prospective baseline uncontrolled clinical study. Methods One‐hundred and eighty five PCOS women referred to our department were screened for the inclusion into the study protocol from March 2004 to July 2007. One‐hundred and twenty four PCOS women met the criteria for the inclusion into the study protocol and were subdivided into two groups each composed of 62 patients: PCOS‐T (trained) group underwent 3‐month ET program, whereas PCOS‐UnT (untrained) group did not. At baseline and at 3‐month follow‐up, hormonal and metabolic profile, cardiopulmonary parameters, autonomic function (as expressed by heart rate recovery, HRR) and inflammatory pattern [as expressed by C‐reactive protein (CRP) and white blood cells (WBCs) count] were evaluated. Results PCOS‐T showed a significant (P < 0·05) improvement in maximal oxygen consumption (VO_2max) and in post‐exercise HRR, and a significant (P < 0·001) decrease in CRP and WBCs; whereas no statistically significant changes of the same parameters were observed in PCOS‐UnT. Multiple linear regression analysis showed that 3‐month HRR is linearly related to the inclusion in training group (β = 0·316, P < 0·001), VO_2max (β = 0·151, P = 0·032) and the ratio between glucose and insulin area under curve (AUC) (β = 0·207, P = 0·003), and inversely related to body mass index (β = –0·146, P = 0·046), insulin AUC (β = –0·152, P = 0·032), CRP (β = –0·165, P < 0·021), and WBCs count (β = –0·175, P = 0·039). Conclusions Exercise training improves autonomic function and inflammatory pattern in PCOS women.     

Exposure to ambient black carbon derived from a unique inventory and high-resolution model

Black carbon (BC) is increasingly recognized as a significant air pollutant with harmful effects on human health, either in its own right or as a carrier of other chemicals. The adverse impact is of particular concern in those developing regions with high emissions and a growing population density. The results of recent studies indicate that BC emissions could be underestimated by a factor of 2–3 and this is particularly true for the hot-spot Asian region. Here we present a unique inventory at 10-km resolution based on a recently published global fuel consumption data product and updated emission factor measurements. The unique inventory is coupled to an Asia-nested (∼50 km) atmospheric model and used to calculate the global population exposure to BC with fully quantified uncertainty. Evaluating the modeled surface BC concentrations against observations reveals great improvement. The bias is reduced from −88% to −35% in Asia when the unique inventory and higher-resolution model replace a previous inventory combined with a coarse-resolution model. The bias can be further reduced to −12% by downscaling to 10 km using emission as a proxy. Our estimated global population-weighted BC exposure concentration constrained by observations is 2.14 μg⋅m⁻³; 130% higher than that obtained using less detailed inventories and low-resolution models.Black carbon (BC), or soot, emitted from incomplete combustion of carbonaceous fuels is an air pollutant which also plays an important role in climate change (1). BC is an indicator of air particulate pollution and BC in ambient air has an impact on human health (2). In a recent study in China, it was found that the effects of BC on morbidity appear to be more robust than the effects of fine particles in general (3, 4).However, global atmospheric aerosol models often underestimate the concentration of BC at the surface, particularly over Asia, by a factor that typically ranges from 2 to 10 (5–7). In one study, the observed BC surface concentration for China could only be reproduced by doubling the emissions prescribed to a transport model (8). It is often argued that the underestimation is due to a low bias in BC emission inventories, suggesting a need to revisit these previous inventories (9).In a bottom-up approach, BC emission is estimated based on the amount of fuel consumed and an emission factor (EF_BC, defined as the amount of BC emitted per unit mass of fuel consumed) for each of various combustion sources. For previous inventories, the lack of EF_BC measurements in developing countries led to high uncertainty in estimating the total emissions (10). In addition, the use of fuel data at the national level is likely to distort the geographical distribution of emissions within large countries such as China and India (11). Recently, a 0.1° × 0.1° fuel database with 64 types of combustion has been developed based on local or national fuel consumption statistics. This database improves the resolution of the spatial distribution of emissions for large countries (12). To fill the data gap in developing countries, a set of EF_BC values has been compiled for various residential solid fuel combustion devices and vehicles (13–20). In addition to the problems with the emission inventories, the coarse resolution of existing global aerosol models also hinders our ability to capture detailed spatial variation, leading to poor agreement between model prediction and observations (7).In this study we develop and evaluate a unique global BC emission inventory using a zoomed aerosol model, and estimate the global population’s exposure to BC with a focus on Asia. The influence of model resolution and the use of an updated emission inventory on the calculated BC concentration are evaluated against field observations.     

Tryptophan depletion in SSRI-recovered depressed outpatients

RATIONALE: Recently, a number of studies have challenged the finding that acute tryptophan depletion (TD) increases depressive symptoms in medicated, formerly depressed patients. The present study examined the effects of acute nutritional TD on remitted depressed patients currently treated with selective serotonin reuptake inhibitors. In an attempt to clarify conflicting earlier findings, the effects of a number of clinical variables on outcome were also investigated. METHODS: Ten patients underwent TD in a double-blind, controlled, balanced crossover fashion. The control session followed the procedure of Krahn et al. (1996 Neuropsychopharmacology 15:325-328). Sessions were 5-8 days apart. RESULTS: TD was significantly related to increased scores on clinician-rated depression and anxiety scales, and on self-rated depression, anxiety, and somatic symptoms. The control challenge had no effect, despite the fact that the reductions in plasma tryptophan during the control session were unexpectedly high. Some evidence was found for a threshold in the relationship between reduction of plasma tryptophan and mood response. CONCLUSIONS: The mood effect of TD in medicated, formerly depressed patients was confirmed. A threshold may exist for mood effects following TD, implying that recent negative findings may have been caused by insufficient depletion. No other predicting or mediating factors were identified, although the variable "history of response pattern to medication" deserves further study.     

Prevalence and Clinical Features of Known Type 2 Diabetes in the Elderly: A Population-based Study

In a large population-based survey, 1947 Type 2 diabetic subjects aged 40 yr and over were identified, with high ascertainment (91%). Age-specific prevalence increased from 2.48% in the age group 40–64 to 5.62% in the age group ≤65 yr; 35% of subjects were 65 yr and over at the onset of the disease. Elderly diabetic subjects showed a significantly (p < 0.001) lower frequency of family history of diabetes (26% vs 42%), obesity at diagnosis (62% vs 70.6%) and fasting plasma glucose (FPG) (8.3 ± 2.4 vs 8.1 ± 2.8 mmol I^?1). Elderly diabetic subjects were more commonly managed by general practitioners (GPs) (29.7% vs 21.5%). Elderly patients attending only the GPs differed in FPG, which was significantly lower (7.9 ± 2.1 nmol I^?1 vs 8.5 ± 2.6 mmol I^?1). Good metabolic control (FPG <6.6 mmol I^?1) was found in 17.5% of subjects in the age group 40–64 and in 22.9% in the age group ≥65 yr. Poor metabolic control was more commonly seen in those attending the diabetic clinic. HBA_1c measurement was available in 32.0% of the elderly attending the diabetic clinic and in only 10.7% of those in the care of GPs. Fundal examination was available in 48.2% and in 36.5%, respectively, of diabetic subjects in the age groups 40–64 and ≥65 yr, without differences between those attending and those not attending the diabetic clinic. In conclusion, this survey showed a higher prevalence of diabetes in the elderly in an Italian population with some peculiar characteristics: low degree of obesity, poor metabolic control, high prevalence of hypertension and low use of insulin therapy.     

ErbB3-dependent motility and intravasation in breast cancer metastasis

A better understanding of how epidermal growth factor receptor family members (ErbBs) contribute to metastasis is important for evaluating ErbB-directed therapies. Activation of ErbB3/ErbB2 heterodimers can affect both proliferation and motility. We find that increasing ErbB3-dependent signaling in orthotopic injection models of breast cancer can enhance intravasation and lung metastasis with no effect on primary tumor growth or microvessel density. Enhanced metastatic ability due to increased expression of ErbB2 or ErbB3 correlated with stronger chemotaxis and invasion responses to heregulin beta1. Suppression of ErbB3 expression reduced both intravasation and metastasis. A human breast cancer tumor tissue microarray showed a significant association between ErbB3 and ErbB2 expression and metastasis independent of tumor size. These results indicate that ErbB3-dependent signaling through ErbB3/ErbB2 heterodimers can contribute to metastasis through enhancing tumor cell invasion and intravasation in vivo and that ErbB-directed therapies may be useful for the inhibition of invasion independent of effects on tumor growth.     

Management of patients with non-functioning gastroentero-pancreatic neuroendocrine tumours

The Authors examine the feasibility of diagnosing non-functioning gastroentero-pancreatic neuroendocrine tumours preoperatively or intraoperatively, with particular reference to laboratory examinations and octreoscan scintigraphy, which are capable of conditioning the surgical treatment and subsequent follow-up. Of the 4 cases reported here: three presented multiple intestinal localizations, and in only one case the origin of the primitive carcinoma was undefined. The suspicion of a non-functioning neuroendocrine tumour must be considered when yellowish or ochre-coloured intestinal lesions are found intraoperatively. Determination of specific markers and octreoscan scintigraphy must be performed without awaiting histological confirmation. Surgery plays a fundamental role in the debulking of these carcinomas. However, medical therapy with the aid of specific laboratory examinations and octreoscan scintigraphy may improve the long-term survival.     

Assessment and management of surgical wounds in clinical practice

Successful nursing care of surgical wounds is dependent on the nurse's knowledge and understanding of normal wound healing physiology, the type of surgery performed, the method of closure and the optimal treatment of the resultant wound. Using this knowledge, nurses can provide a systematic and holistic patient assessment, and consider any potential wound-related complications.