A phase II study on the efficacy and safety of procedural analgesia with fentanyl buccal tablet in cancer patients for the placement of indwelling central venous access systems.

BACKGROUND: Pain in cancer patients is often related to oncologic therapies and diagnostic procedures. The placement of fully implantable venous access systems is a very common procedure in oncology patients. Local anaesthesia is the method most commonly used to overcome pain related to this surgical procedure, but the local anaesthetic may be unable to completely eradicate all pain. This study investigates the effectiveness and safety of fentanyl buccal tablet (FBT), administered by OraVescent® technology, in reducing procedural pain related to the placement of indwelling central venous access systems (Ports) in opioid-naïve cancer patients. METHODS: Inpatients who required an indwelling vascular access (Port) were preoperatively assessed with a self-assessment questionnaire on anxiety and pain. A 100 µg FBT was administered 10 min before preparation of the operating field. A self-assessment scale for pain experienced during the procedure was administered at the end of the procedure. Vital signs and the presence of any side effects or bothersome symptoms were monitored during the procedure, at the end, and 4 h later. RESULTS: From October 2012 to June 2014, 65 patients were enrolled in the study. A total of 61 (93.9 %) patients perceived no or a little pain during the procedure. Four patients (6.2 %) reported a lot of pain. No patient reported very severe pain. This data is significant in terms of the lower than expected presence of pain (Fisher test p = 0.0018) as assessed in our previous experience without procedural analgesia. The most common side effects of FBT was drowsiness, experienced by 28 patients at the end of the procedure (43.1 %), significantly reduced (p < 0.01) to 8 patients after 4 h (12.5 %). Nausea was present in 6 cases at the end of the procedure (9.2 %) and in 7 cases 4 h later (10.9 %). Vomiting was present in 3 cases at the end (4.7 %) and in 2 other patients after 4 h (7.8 %). No significant change of vital parameters was observed between the baseline and the subsequent measurements in all patients studied. CONCLUSIONS: The significant improvement in the number of patients experiencing little or no pain, accompanied by a lower number of non-severe side effects, suggests that FBT is a valid, practical and safe method of procedural analgesia. It will be necessary to perform further studies, taking into account the need for standard antiemetic pre-medication to minimise the incidence of nausea and vomiting.

Blood pressure levels, left ventricular mass and function are correlated with left atrial volume in mild to moderate hypertensive patients.

Arterial hypertension is associated with an increased risk of atrial fibrillation (AF), and leads to a pronounced increase in morbidity and mortality. Left atrial volume (LAV) is an important prognostic marker in the older populations. The aim of our study was to identify the clinical and echocardiographic determinants of LAV in middle-aged (<70 years old) essential hypertensive patients.We evaluated cardiac structure and function in 458 patients, 394 treated and untreated mild to moderate essential hypertensives patients (mean+/-s.d. age 48.4+/-11.1 years) with no associated clinical condition and 64 normotensive control participants (age 45.7+/-12.8 years; P=0.12). A multivariate analysis was performed to calculate the relative weight of each of the variables considered able to predict LAV. The LAV index (LAVi) was significantly increased in the essential hypertensive group vs the control group and was significantly dependent on blood pressure levels (SBP and DBP, P<0.05 for both) and body mass index (BMI) (P<0.0001). Considering the left ventricular (LV) variables, the LV mass index (LVMI) (R(2)=0.19, P<0.001) and LAV were increased in essential hypertensive patients with left ventricular hypertrophy (LVH), and patients with enlarged LAV showed lower systolic and diastolic function and an increased LVMI. The LAVi is dependent on blood pressure levels and anthropometric variables (age and BMI). Further structural (LVMI) and functional (systolic and diastolic) variables are related to the LAVi; LVMI is the most important variable associated with LAV in mild to moderate essential hypertensive adult patients. These findings highlight the importance of left atrium evaluation in adult, relatively young, essential hypertensive patients.

Cognitive decline and low blood pressure: the other side of the coin.

Low blood pressure has been found to be associated with cognitive decline and dementia in cross-sectional studies. Two mechanisms have been proposed to interpret this association: blood pressure levels decrease during the course of the dementia process, and low blood pressure induces or accelerates cognitive decline by lowering cerebral blood flow. Results of the prospective studies are contradictory. Low blood pressure and orthostatic hypotension have been found to predict cognitive impairment in the elderly population in some studies only. While hypotension may play a protective role in healthy elderly people, low blood pressure levels in frail elderly patients with associated diseases may cause cerebral hypoperfusion and accelerate cognitive decline.

Baroreflex sensitivity is impaired in essential hypertensives with central obesity.

Recently, much interest has focussed on the potential interaction between sympathetic nervous system and global cardiovascular risk. We investigated how baroreflex sensitivity (BRS), an index of autonomic function, interacts with central obesity (CO) in an essential hypertensive (EH) population. We selected 170 EHs and 43 normotensives (NT), (median age 47.3+/-11.3 and 49.1+/-13 years, respectively). Anthropometric parameters were measured for each and BRS was evaluated by a non-invasive method using Portapres TNO. The BRS evaluation was made using the sequences method. Systolic blood pressure (SBP) and heart rate were significantly higher in EH (P<0.001 and P=0.007, respectively). BRS was significantly greater in NT (P=0.02), and was associated inversely with waist circumference (WC) (P=0.005), but not with SBP or with other metabolic risk factors. Body mass index, total and high-density lipoprotein cholesterol, age and WC were not significantly different between the two groups. These results were confirmed by age pounded analysis. Finally, a separate analysis of the hypertensive group with CO (n=84) demonstrated a significantly lower BRS compared with the other hypertensive patients (n=86) (P<0.001). BRS is associated with WC but not with arterial pressure values and metabolic risk factors. Hypertensive subjects with CO show an impairment of BRS. Owing to its association with abdominal fat distribution and subsequently insulin resistance, BRS could represent a further and reliable index for evaluation of global cardiovascular risk in hypertensive patients.

Técnica e resultados do tratamento da procidência retal por vídeo-laparoscopia / Technique and results of the treatment of the rectal procidencia for video-laparoscopic

Um crescente número de publicações na literatura tem demonstrado que a correção cirúrgica por vídeo-laparoscopia de pacientes com procidência retal determina bons resultados funcionais, baixo índice de recidivas e morbi-mortalidade.No entanto, ainda existem limitações ao seu emprego devido à necessidade de equipamento específico e à longa curva de aprendizado deste procedimento quando se utiliza o acesso vídeo-laparoscópico. Neste artigo, os autores fazem uma breve revisão sobre a etiologia e investigação pré-operatória de adultos portadores de procidência retal, apresentam sua experiência pessoal com o tratamento laparoscópico e descrevem os principais aspectos técnicos envolvidos.

Resultados das operações com ressecção alargada em 46 pacientes com câncer colorretal / Results of the operations with extended resections in 46 patients with colorectal cancer

O objetivo deste estudo é conhecer os órgãos invadidos, a morbidade e as variáveis clínico-patológicas associadas ao prognóstico de pacientes submetidos ao tratamento cirúrgico de câncer colorretal(CCR) por operações com ressecção alargada. Pacientes e métodos: Avaliamos retrospectivamente 46 pacientes portadores de CCR que foram submetidos a operações com ressecção alargada, entre 1995 e 2002. Resultados: Ocorreram três (6,5por cento) complicações intra-operatórias, a taxa de complicações pós-operatórias foi de 30,4por cento e a mortalidade foi de 6,5por cento. As taxas de sobrevida global foram de 63por cento após dois anos e 18,5por cento após cinco anos. A sobrevida global após dois anos foi: 85por cento para pacientes com mais de 64 anos de idade e 46por cento para pacientes com menos de 64 anos de idade(p=0,016);de 100por cento para pacientes com tumores nos estágios I e II(estadiamento anátomo-patológico TNM-AJCC/UICC), de 38,5por cento nos estágios III e de 33por cento nos estágios IV(p=0,001). Conclusões: Não há evidente aumento da morbidade intra ou pós-operatória para operações colorretais com ressecção alargada para CCR; a suspeita de invasão neoplásica por contiguidade pode ser confirmada em mais de 60por cento dos casos e a sobrevida após tratamento cirúrgico para os pacientes operados com intenção radical esteve relacionada principalmente à idade e ao estadiamento do tumor.

Two strange cases of hypereosinophilia and child's relapsing angio-oedema.

Two patients aged two and four years came to our observation with "angio-oedema" and relapsing hypodermitis. Atopic diseases were present in both family histories. The clinical examination of both children revealed a good nutritional status, the presence of angio-oedema with fleeting (48 hours max length) and localized hypodermic infiltrations. Amongst laboratory investigations, the blood cells count and the total count of Immunoglobulins showed hypereosinophilia and increased IgE levels over ten times the normal values. Prick tests for the most common inhalant and nutritive allergens were negative. A strong positivity of ELISA for Taenia Solium metacestodes on both sera samples suggested a diagnosis of human cysticercosis.

Pulse rate in childhood: reference limits.

BACKGROUND AND AIM: Systematic quantitative resting pulse rate measurements may represent an additional parameter for the study of cardiovascular risk factors in youth as well as in adulthood. The aim of this study was to evaluate resting pulse rate and its distribution curve in order to define reference limits in a sample of adolescents from Turin, Italy. METHODS AND RESULTS: The study population consisted of 2230 children aged 12-18 years, who were randomly enrolled from Turin Junior High Schools. All of the participants underwent pulse rate, blood pressure and height measurements. The 5th and 95th percentiles of the pulse rate in boys and girls are reported by age and height. The pulse rate was higher in the girls, but progressively decreased with age and somatic growth in both genders. CONCLUSIONS: The present study provides reference blood pressure values by age, gender and height in a sample of male and female adolescents.

Human herpesvirus 6.

The development of techniques for the culture of lymphoid cells and the isolation of viruses that infect these cells led to the discovery of human herpesvirus (HHV) 6 in 1986. At the time, HHV-6 was the first new human herpesvirus to be discovered in roughly a quarter of a century, and its isolation marked the beginning of an era of discovery in herpesvirology, with the identification of HHV-7 and HHV-8 (Kaposi's sarcoma-associated herpesvirus) during the following decade. Like most human herpesviruses, HHV-6 is ubiquitous and capable of establishing a lifelong, latent infection of its host. HHV-6 is particularly efficient at infecting infants and young children, and primary infection with the virus is associated with roseola infantum (exanthem subitum) and, most commonly, an undifferentiated febrile illness. Viral reactivation in the immunocompromised host has been linked to a variety of diseases, including encephalitis, and HHV-6 has been tentatively associated with multiple sclerosis. This article discusses the major properties of HHV-6, its association with human disease, and the pathobiological significance of viral reactivation.

Celiac plexus block: injectate spread and pain relief in patients with regional anatomic distortions.

BACKGROUND: The success of the neurolytic celiac plexus block, despite different approaches and methods used, depends on adequate spread of the injectate in the celiac area. This retrospective study was conducted to evaluate the patterns of alcohol spread and pain relief in patients with cancer or therapy-related anatomic distortion of the celiac area. METHODS: From 177 cancer patients who underwent computed tomography (CT)-guided single-needle neurolytic celiac plexus block via an anterior approach, a radiologist, blind to the aim of the study, retrospectively selected 105 patients with abnormal anatomy of the celiac area as judged by CT images obtained before the block. To evaluate CT patterns of neurolytic (mixed with contrast) spread, the celiac area was divided on the frontal plane into four quadrants: upper right and left and lower right and left, as related to the celiac artery. Results were expressed as the number of quadrants into which contrast spread, ie., four, three, two, or one quadrants with contrast. The patterns of contrast spread according to the number of quadrants with anatomic distortion were analyzed. Patient assessment by visual analog scale was reviewed to evaluate the degree of pain relief. Pain relief 30 days after block was considered long-lasting. Pain relief at 30 days after block was analyzed according to the number of quadrants with contrast. RESULTS: Overall, four, three, two, and one quadrants with contrast were observed in 9 (8%), 21 (20%), 49 (47%), and 26 (25%) patients, respectively. An inverse correlation was observed between the number of quadrants with anatomic distortion and the number of quadrants with contrast (P < 0.001). Long-lasting pain relief was noticed in nine of nine patients (100%; 95% confidence interval, 66-100) with contrast in four-quadrants, and in 10 of 21 patients (48%; 95% confidence interval, 26-70) with contrast in 3 quadrants (P < 0.01). None of the 75 patients with contrast in two quadrants or one quadrant experienced long-lasting pain relief. CONCLUSIONS: These findings suggest that, using the single-needle anterior approach, the neurolytic spread in the celiac area is highly hampered by the regional anatomic alterations. It also appears that only a complete (four quadrants) neurolytic spread in the celiac area can guarantee long-lasting analgesia, and that this picture may be obtained in a very limited fraction of patients with regional anatomic alterations.

Two distinct nucleosome alterations characterize chromatin remodeling at the Saccharomyces cerevisiae ADH2 promoter.

Glucose depletion derepresses the Saccharomyces cerevisiae ADH2 gene; this metabolic change is accompanied by chromatin structural modifications in the promoter region. We show that the ADR6/SWI1 gene is not necessary for derepression of the wild type chromosomal ADH2, whereas the transcription factor Adr1p, which regulates several S. cerevisiae functions, plays a major role in driving nucleosome reconfiguration and ADH2 expression. When we tested the effect of individual domains of the regulatory protein Adr1p on the chromatin structure of ADH2, a remodeling consisting of at least two steps was observed. Adr1p derivatives were analyzed in derepressing conditions, showing that the Adr1p DNA binding domain alone causes an alteration in chromatin organization in the absence of transcription. This alteration differs from the remodeling observed in the presence of the Adr1p activation domain when the promoter is transcriptionally active.

In vitro 1H and 31P NMR spectroscopic evidence of multiple aberrant biochemical pathways in murine trisomy 16 brain development.

Nuclear magnetic resonance (NMR) spectroscopy was used to evaluate cytosolic compounds and membrane phospholipids simultaneously in trisomy 16 (Ts16) and euploid (control) murine brain at fetal day 15 in order to examine the cellular biochemistry that underlies the neurodevelopmental consequences of chromosome triplication in this model of Down syndrome (DS). Proton NMR spectroscopic analysis of brain tissue extracts demonstrated decreased levels of choline and increased levels of myo-inositol (MI) in Ts16 brains compared with control. These data are consistent with the cholinergic deficits and elevated MI levels previously described in Ts16. Compared with euploid brains. Ts16 brains also possess higher levels of creatine, adenosine, and tyrosine. Increased levels of MI and creatine, compounds that are localized to glia, imply abnormalities in the trophic environment of Ts16 brain. Phosphorus NMR spectroscopic analysis of extracts further revealed elevated levels of anionic phospholipid membrane components, such as phosphatidylinositol (PtdIno) and phosphatidylethanolamine, in Ts16 brains. Since these compounds are confined to the inner leaflet of the membrane, the findings suggest that membrane composition is altered specifically in the cytosolic bilayer at this stage. Together our proton and phosphorus NMR spectroscopic results indicate that multiple biochemical pathways are affected in Ts16 brain development. Understanding the effects of these aberrations may elucidate the processes that lead to neural dysfunction and Alzheimer's disease (AD) neuropathology in DS individuals.

Pathfinders: a self-care and health education program for older widows and widowers.

Recent studies suggest that the loss of a spouse can be disruptive to the survivor's self-care and health promotion practices, especially for those who lack the knowledge and skills to successfully engage in these behaviors. Pathfinders is a theoretically and research-based self-care and health education program for recently widowed persons aged 50 and older. This article describes the program's structure, content, and recruitment methods. Preliminary evaluation data suggest that the program is achieving many of the intended outcomes. Issues pertaining to replication as well as limitations are discussed.

Detection of human herpesvirus 6 by reverse transcription-PCR.

The role of human herpesvirus 6 (HHV-6) in disease beyond primary infection remains unclear. We have developed and validated a new reverse transcription-PCR (RT-PCR) assay for HHV-6 that can determine the presence of HHV-6 in clinical specimens and differentiate between latent and replicating virus. Peripheral blood mononuclear cells from 109 children were evaluated for HHV-6 by RT-PCR, DNA PCR, and viral culture. Of these samples, 106 were suitable for analysis. A total of 20 samples were positive for HHV-6 by culture and DNA PCR, of which 19 were positive by RT-PCR (sensitivity, 95%). All 28 samples from children that were negative by viral culture, but positive by DNA PCR, were negative for viral transcripts by our RT-PCR assay. One positive RT-PCR result was observed in 56 samples that were negative by tissue culture and DNA PCR. This indicates a low rate of false-positive results (1.2%) and a specificity of 98.8%. This RT-PCR assay can reliably differentiate between latent and actively replicating HHV-6 and should allow insight into the pathogenesis of this ubiquitous virus.

Acidos graxos de cadeia curta e doenças colorretais / Short-chain fatty acids and colorectal diseases

O cólon humano contribui de maneira importante para a fermentaçäo de polissacárides näo absorvidos, produzindo ácidos graxos de cadeia curta (AGCC). Este artigo analisa a importância fisiológica dos AGCC para os colonócitos e as perspectivas de sua utilizaçäo clínica no tratamento das doenças colorretais. Diversos efeitos benéficos säo atribuídos ao processo de fermentaçäo e à subsequente produçäo de AGCC, como a contribuiçäo às necessidades energéticas, à manutençäo da integridade e funçäo da mucosa colônica e implicaçöes no metabolismo nitrogenado, de lipídes e glicídios. Além disso, diversas afecçöes colorretais tem sido relacionadas a deficiência de AGCC, como a colite por desuso, colite ulcerativa, bolsite pós-proctocolectomia com anastomose íleo-anal e câncer colorretal. Por este motivo, o fornecimento de AGCC diretamente à mucosa intestinal ou por via intravenosa tem sido preconizado em diversas condiçöes clínicas

In vitro proton and phosphorus NMR spectroscopic analysis of murine (C57Bl/6J) brain development.

We report for the first time in vitro proton and phosphorus NMR spectroscopic analyses of murine brain development from fetal to adult stages. Chloroform-methanol extracts from C57B16/J mouse brain, at ages ranging from 15 days in utero (F15) to adult, permitted the simultaneous investigation of both cytosolic and membrane phospholipid compartments. The protein content of murine brain was determined and used for quantitation of individual metabolite levels. Proton NMR spectroscopy revealed that NAA, considered a neuronal marker, is undetectable at F15. Glutamate, GABA and creatine, however, are present at this time. All four compounds reach maximum levels at 21 days postnatal (P21). Choline and alanine levels are at their peak in fetal brain and progressively fall as the brain develops. Phosphorus NMR spectroscopy shows that phosphatidylcholine, phosphatidylinositol, sphingomyelin, and phosphatidylserine increase steadily from F15 to P21.

Older women's feelings about exercise and their adherence to an aerobic regimen over time.

Sedentary, overweight women aged 60-70 years were assigned either to a 16-week health education group (n = 70) in which they were instructed to exercise aerobically on their own three times per week or to a 16-week exercise group (n = 76) that consisted of three supervised aerobic sessions per week. Regression analyses performed at post-test and at 3-, 6-, and 18-months follow-up revealed that exercise frequency was not explained by group membership, but often was negatively associated with placing a greater value on exercising with peers. Those who were exercising more often at 6- and 18-months follow-up, however, valued the perceived benefits of exercise more highly. The findings of this study suggest the importance of emphasizing strategies that stress the intrinsically motivating benefits of exercise, as well as building into programs those aspects of exercise valued by the participants.