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Biomedical subjects

C Serra

Publications and source records attributed to C Serra.

At least 19 recordsLinked to original sources

Preventing occupational stress in healthcare workers.

BACKGROUND: Healthcare workers can suffer from occupational stress which may lead to serious mental and physical health problems. OBJECTIVES: To evaluate the effectiveness of work and person-directed interventions in preventing stress at work in healthcare workers. SEARCH STRATEGY: We searched the Cochrane Depression Anxiety and Neurosis Group trials Specialised Register, MEDLINE, PsychInfo and Cochrane Occupational Health Field database. SELECTION CRITERIA: Randomised controlled clinical trials (RCT) of interventions aimed at preventing psychological stress in healthcare workers. For work-directed interventions interrupted time series and prospective cohort were also eligible. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Meta-analysis and qualitative synthesis were performed where appropriate. MAIN RESULTS: We identified 14 RCTs, three cluster-randomised trials and two crossover trials, including a total of 1,564 participants in intervention groups and 1,248 controls. Two trials were of high quality. Interventions were grouped into 1) person-directed: cognitive-behavioural, relaxation, music-making, therapeutic massage and multicomponent; and 2) work-directed: attitude change and communication, support from colleagues and participatory problem solving and decision-making, and changes in work organisation. There is limited evidence that person-directed interventions can reduce stress (standardised mean difference or SMD -0.85; 95% CI -1.21, -0.49); burnout: Emotional Exhaustion (weighted mean difference or WMD -5.82; 95% CI -11.02, -0.63) and lack of Personal Accomplishment (WMD -3.61; 95% CI -4.65, -2.58); and anxiety: state anxiety (WMD -9.42; 95% CI -16.92, -1.93) and trait anxiety (WMD -6.91; 95% CI -12.80, -1.01). One trial showed that stress remained low a month after intervention (WMD -6.10; 95% CI -8.44, -3.76). Another trial showed a reduction in Emotional Exhaustion (Mean Difference or MD -2.69; 95% CI -4.20, -1.17) and in lack of Personal Accomplishment (MD -2.41; 95% CI -3.83, -0.99) maintained up to two years when the intervention was boosted with refresher sessions. Two studies showed a reduction that was maintained up to a month in state anxiety (WMD -8.31; 95% CI -11.49, -5.13) and trait anxiety (WMD -4.09; 95% CI -7.60, -0.58). There is limited evidence that work-directed interventions can reduce stress symptoms (Mean Difference or MD -0.34; 95% CI -0.62, -0.06); Depersonalization (MD -1.14; 95% CI -2.18, -0.10), and general symptoms (MD -2.90; 95% CI -5.16, -0.64). One study showed that the difference in stress symptom level was nonsignificant at six months (MD -0.19; 95% CI -0.49, 0.11). AUTHORS' CONCLUSIONS: Limited evidence is available for the effectiveness of interventions to reduce stress levels in healthcare workers. Larger and better quality trials are needed.

Health Personnel↗

Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors.

Pharmacological interventions that increase myofiber size counter the functional decline of dystrophic muscles. We show that deacetylase inhibitors increase the size of myofibers in dystrophin-deficient (MDX) and alpha-sarcoglycan (alpha-SG)-deficient mice by inducing the expression of the myostatin antagonist follistatin in satellite cells. Deacetylase inhibitor treatment conferred on dystrophic muscles resistance to contraction-coupled degeneration and alleviated both morphological and functional consequences of the primary genetic defect. These results provide a rationale for using deacetylase inhibitors in the pharmacological therapy of muscular dystrophies.

Animals↗

Protein kinase C theta co-operates with calcineurin in the activation of slow muscle genes in cultured myogenic cells.

Adult skeletal muscle fibers can be divided into fast and slow twitch subtypes on the basis of specific contractile and metabolic properties, and on distinctive patterns of muscle gene expression. The calcium, calmodulin-dependent protein phosphatase, calcineurin, stimulates slow fiber-specific genes (myoglobin (Mb), troponin I slow) in cultured skeletal muscle cells, as well as in transgenic mice, through the co-operation of peroxisome-proliferation-activator receptor gamma co-activator 1alpha (PGC1alpha) myocyte enhancer factor 2 (MEF2), and nuclear factor of activated T cells (NFAT) transcription factors. Specific protein kinase C isoforms have been shown to functionally co-operate with calcineurin in different cellular models. We investigated whether specific protein kinase C isoforms are involved in calcineurin-induced slow skeletal muscle gene expression. By pharmacological inhibition or exogenous expression of mutant forms, we show that protein kinase C theta (the protein kinase C isoform predominantly expressed in skeletal muscle) is required and co-operates with calcineurin in the activation of the Mb promoter, as well as in the induction of slow isoforms of myosin and troponin I expression, in cultured muscle cells. This co-operation acts primarily regulating MEF2 activity, as shown by using reporter gene expression driven by the Mb promoter mutated in the specific binding sites. MEF2 activity on the Mb promoter is known to be dependent on both PGC1alpha and inactivation of histone deacetylases (HDACs) activity. We show in this study that protein kinase C theta is required for, even though it does not co-operate in, PGC1alpha-dependent Mb activation. Importantly, protein kinase C theta regulates the HDAC5 nucleus/cytoplasm location. We conclude that protein kinase C theta ensures maximal activation of MEF2, by regulating both MEF2 transcriptional complex formation and HDACs nuclear export.

Active Transport, Cell Nucleus↗

[Allograft-prosthesis composite arthroplasty for posttraumatic floating elbow].

Loss of bone stock in the elbow joint raises serious problems for reconstruction surgery. Total allograft-prosthesis composite arthroplasty is an attractive alternative to revision prosthesis and isolated osteoarticular allografts known to have many drawbacks. Use of this method is rather recent for revision procedures and tumor surgery and posttraumatic cases are rare (five reported cases). We report a case of posttraumatic floating elbow treated with this technique. At 75 months follow-up, the clinical result was excellent with the Mayo Clinic performance score at 100/100. Allograft-native bone fusion was complete and there were no complications, particularly no loosening. This composite technique is particularly well adapted for patients with major bone and joint loss. It can avoid the specific problems associated with each of the techniques used alone. The allograft reconstructs bone stock while the prosthetic component avoids the clinical expression of graft epiphyseal lysis.

Arthroplasty, Replacement↗

Acanthamoeba castellanii promotion of in vitro survival and transmission of coxsackie b3 viruses.

This work was undertaken to determine whether Acanthamoeba could play a role in the survival and transmission of coxsackieviruses and focused on in vitro interactions between Acanthamoeba castellanii and coxsackie B3 viruses (CVB-3). Residual virus titer evaluations and immunofluorescence experiments revealed a remarkable CVB-3 adsorption on amoeba surfaces and accumulation inside cells. The survival of viruses was independent of the dynamics of amoeba replication and encystment. In addition, our results indicated that virus-infected amoebas can release infectious viruses during interaction with human macrophages. On the basis of these data, Acanthamoeba appears to be a potential promoter of the survival of coxsackieviruses and their transmission to human hosts.

Acanthamoeba castellanii↗

Assessment of lifetime exposure to trihalomethanes through different routes.

OBJECTIVES: To evaluate lifetime exposure to trihalomethanes (THM) through ingestion, inhalation, and dermal absorption in a hospital based case-control study of bladder cancer conducted between 1998 and 2001 in five areas of Spain. The study base was comprised of subjects living in the catchment areas of the participating hospitals. METHODS: Individual information on water related habits was obtained from personal interviews of 1219 cases and 1271 controls: residential and occupational history, drinking water source at each residence and job, amount of water consumption, frequency and duration of showering, bathing, and swimming pool attendance. THM levels, water source history, and year when chlorination started in study areas were ascertained through measurements in drinking water samples and questionnaires to water companies and local authorities. Estimates of THM levels covered 79% of the subjects' person-years of exposure. RESULTS: Current and historical average THM levels in water were correlated. Control subjects reported that drinking water source in the last residence was municipal for 63%, bottled for 22%, private well for 2%, and other sources for 13%. For the time window between age 15 and the time of interview, average residential THM level was 32.2 mug/l. THM exposure through ingestion was 23.7 mug/day on average, and was correlated with the ingestion THM level in the workplace. Overall, 79% usually took showers, 16% usually took baths, and 13% had ever attended a swimming pool. Between 21% and 45% of controls unexposed to THM through ingestion were evaluated as moderately or highly exposed through showering or bathing, and 5-10% were exposed through swimming in pools. CONCLUSION: The importance of evaluating different routes is underscored by findings from experimental studies showing substantial differences in THM uptake and internal distribution by route.

Adult↗

Multiple sclerosis-associated retrovirus and optic neuritis.

One prognostic factor for early multiple sclerosis (MS) patients to develop a definite MS may be the presence of the MS-associated retrovirus (MSRV) in the cerebrospinal fluid (CSF). We designed a specific study on a cohort of optic neuritis (ON) patients to evaluate the MSRV-dependent conversion to MS relative to the prediction conferred by magnetic resonance imaging (MRI) and CSF abnormalities. At follow-up, 33.3% MSRV+ and 0% MSRV- ON patients developed MS (P = 0.03). The prediction value is lower than that given by CSF and MRI abnormalities (42.3%). This intriguing finding is discussed in the light of the abundant discrepancies observed in the MSRV literature. Multiple Sclerosis 2006; 12: 357-359. www.multiplesclerosisjournal.com

Adolescent↗

Vesiculous prurigo pigmentosa in a 13-year-old girl: good response to isotretinoin.

Prurigo pigmentosa is a rare inflammatory disease of unknown origin, first reported from Japan, with only 33 cases described in non-Japanese patients. We describe a 13-year-old girl with a pruriginous symmetrical eruption of papules and vesicles affecting her back, neck and chest of 1 month duration. She remembered a similar, but lighter eruption, 2 months before. As the initial diagnosis was of a vesiculobullous form of Darier disease, treatment with isotretinoin 40 mg/day was started with good response. Histological study showed a superficial perivascular and interstitial dermatitis composed predominantly of lymphocytes. The epidermis was spongiotic, with exocytosis of lymphocytes and some neutrophils and necrotic keratinocytes. All these findings were consistent with prurigo pigmentosa. The lesions resolved leaving a light brown reticulate hyperpigmentation. Prurigo pigmentosa has never been reported in prepubescent patients, the vesiculobullous forms are unusual, and the only treatments used previously are sulphonamides, tetracyclines and macrolides. We report a 13-year-old Caucasian girl with vesiculobullous prurigo pigmentosa successfully treated with isotretinoin.

Administration, Cutaneous↗

Zollinger-Ellison syndrome. Diagnosis and therapy.

Zollinger-Ellison syndrome (ZES) is characterised by refractory peptic ulcer disease, severe diarrhoea and gastric acid hypersecretion associated with an islet-cell tumor of the pancreas (gastrinoma). ZES is sporadic in 62-80% of cases and in 20-38% of cases is associated with multiple endocrine neoplasia type 1 (MEN 1). The diagnosis of ZES is certain when the plasma gastrin is >1000 pg/mL and the basal acid output is >15 mEq/h in patients with an intact stomach, >5 mEq/h in gastrectomised patients, or when the hypergastrinemia is associated with a pH <2. Treatment is based on the control of gastric acid hypersecretion and of the malignant tumor and its possible metastases. Proton pump inhibitors are the most effective antisecretory drugs and can be administered at high dosages without drug-related adverse effects. All sporadic, localised gastrinomas should be excised if possible. When liver metastases are also present, their debulking may improve symptoms and survival, and facilitate medical treatment. There is some controversy as to the surgical approach for gastrinomas associated with MEN 1. Somatostatin analogues can be useful in reducing gastric acid hypersecretion, serum gastrin and gastric enterochromaffin-like cells, and can thus contribute to treating the disease more effectively. Their antiproliferative effect can be used in treating liver metastases. Chemotherapy and/or interferon are indicated only in patients with malignant progressive disease. Embolisation and chemoembolisation are effective in controlling clinical symptoms; however, they do not seem to improve survival.

Biomarkers↗

Chemotherapy versus best supportive care for extensive small cell lung cancer.

BACKGROUND: Combination chemotherapy has been the mainstay of treatment for extensive stage small cell lung cancer (SCLC) over the last 25 years even though it only gives a short prolongation in median survival time. The main goal for these patients, if their survival prognosis is limited, should be adequate palliation with the aim of improving their quality of life. OBJECTIVES: To evaluate the effectiveness of chemotherapy in extensive SCLC compared with best supportive care (BSC) or placebo treatment. SEARCH STRATEGY: Medline (1966-Jan 2003), Embase (1974-Jan 2003), Cancerlit (1993-Jan 2003) and the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 4, 2002) were searched. In addition experts in the field were contacted to identify further studies not found by electronic searches. SELECTION CRITERIA: Randomised controlled trials in which any chemotherapy treatment was compared with a placebo group or best supportive care in patients with extensive stage SCLC. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were undertaken independently by two reviewers and disagreements were resolved by a third author. Additional information on the included studies was obtained from the author of the original studies. MAIN RESULTS: Only two studies (the first published in 1977 and the second in 1982) met the inclusion criteria of the review. A total of 65 patients with extensive disease (33 in the first study and 32 in the second) were randomised to received either placebo treatment or ifosfamide. In the second study a third arm of comparison included ifosfamide plus CCNU. Ifosfamide gave an extra 78.5 days survival (mean survival time) compared with the placebo group. Partial tumour response was greater with the active treatment. Toxicity was only seen in the chemotherapy group. Pooled analysis was not possible because only mean survival time was reported in both studies for patients with extensive disease. REVIEWER'S CONCLUSIONS: Chemotherapeutic treatment prolongs survival in comparison with placebo in patients with advanced SCLC. Nevertheless the impact of chemotherapy on quality of life and in patients with poor prognosis is unknown. Well-designed, controlled trials are needed to further evaluate the risks and benefits of different chemotherapeutic schedules in patients with advanced small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Drugs for preventing lung cancer in healthy people.

BACKGROUND: Some studies have suggested a protective effect of antioxidant nutrients on lung cancer. Observational epidemiological studies suggest an association between higher dietary levels of fruits and vegetables containing beta carotene and a lower risk of lung cancer. OBJECTIVES: To determine whether vitamins, minerals and other potential agents, alone or in combination, reduce incidence and mortality from lung cancer in healthy people. SEARCH STRATEGY: The electronic databases MEDLINE (1966-july 2001), EMBASE (1974-july 2001) and the Cochrane Controlled Trial Register (CENTRAL, Issue 3/2001) and bibliographies were searched. In addition authors of included studies were contacted to identify potentially eligible published and unpublished trials. SELECTION CRITERIA: Included studies were randomised controlled clinical trials comparing different supplements or comparing supplements with placebo, administered to healthy people with the aim of preventing lung cancer. DATA COLLECTION AND ANALYSIS: Three reviewers independently selected the trials to be included in the review and assessed the methodological quality of each trial, and two extracted data using a standardised form. For each study, relative risk and 95% confidence limits were calculated for dichotomous outcomes. MAIN RESULTS: Four studies were eligible for inclusion. All were population based trials, including a total of 109,394 participants. Two studies included smokers, one included workers exposed to asbestos and two studies were carried out in health professionals. A group of participants with no known risk factors for lung cancer was included in the study sample of two trials. Beta-carotene was evaluated in all trials, alone or combination with alpha-tocopherol or retinol, and one study tested alpha-tocopherol alone. Duration of treatment varied from 2 to 12 years and follow-up was from two to five years. All trials had a placebo group. For people with risk factors for lung cancer no reduction in lung cancer incidence or mortality was found in those taking vitamins alone compared with placebo (incidence of lung cancer: RR 0.98, 95% CI 0.81-1.19; lung cancer mortality: RR 0.93, 95% CI 0.73-1.19). For people with no known risk factors of lung cancer, none of the vitamins or their combinations appeared to have any effect. Combined data from three studies showed a non-statistically significant increased risk of lung cancer incidence (RR 1.11, 95% CI 0.94-1.33) and mortality (RR 1.05, 95% CI 0.87-1.28) for beta-carotene alone at pharmacological doses in groups with risk factors for lung cancer. When beta-carotene was combined with retinol, data from a single study showed that there was a statistically significant, increased risk of lung cancer incidence (RR 1.42, 95% CI 1.13-1.80) and mortality (RR 1.75, 95% CI 1.29-2.38) in people with risk factors for lung cancer who took both vitamins compared with those who took placebo. Data from also from one study showed that the combination of beta-carotene with alpha-tocopherol in people with risk factors for lung cancer was associated with a non-statistically significant increased risk of lung cancer incidence (RR 1.16, 95% CI 0.96-1.39) and mortality (RR 1.15, 95% CI 0.91-1.45). No effect was observed for total cancer incidence, mortality or all-cause mortality. REVIEWER'S CONCLUSIONS: There is currently no evidence to support recommending vitamins such as alpha-tocopherol, beta-carotene or retinol, alone or in combination, to prevent lung cancer. A harmful effect was found for beta-carotene with retinol at pharmacological doses in people with risk factors for lung cancer (smoking and/or occupational exposure to asbestos). More research from larger trials and with longer follow-up is needed to analyse the effectiveness of other supplements.

Dietary Supplements↗

Transgenic mice with dominant negative PKC-theta in skeletal muscle: a new model of insulin resistance and obesity.

Protein kinase C theta (PKC-theta) is the PKC isoform predominantly expressed in skeletal muscle, and it is supposed to mediate many signals necessary for muscle histogenesis and homeostasis, such as TGFbeta, nerve-dependent signals and insulin. To study the role of PKC-theta in these mechanisms we generated transgenic mice expressing a "kinase dead" mutant form of PKC-theta (PKC-thetaK/R), working as "dominant negative," specifically in skeletal muscle. These mice are viable and fertile, however, by the 6-7 months of age, they gain weight, mainly due to visceral fat deposition. Before the onset of obesity (4 months of age), they already show increased fasting and fed insulin levels and reduced insulin-sensitivity, as measured by ipITT, but normal glucose tolerance, as measured by ipGTT. After the 6-7 months of age, transgenic mice develop hyperinsulinemia in the fasting and fed state. The ipGTT revealed in the transgenic mice both hyperglycemia and hyperinsulinemia. At the molecular level, impaired activation of the IR/IRS/PI3K pathway and a significant decrease both in the levels and in insulin-stimulated activation of the serine/threonine kinase Akt were observed. Taken together these data demonstrate that over-expression of dominant negative PKC-theta in skeletal muscle causes obesity associated to insulin resistance, as demonstrated by defective receptor and post-receptorial activation of signaling cascade.

Animals↗

Gender-related differences in clinical and pathological characteristics and therapy of bladder cancer.

OBJECTIVE: To confirm the very high male:female ratios previously observed among Spanish bladder cancer patients and to assess gender differences in tumoral characteristics, diagnostic procedures, and treatment in a large series of consecutive bladder cancer patients. PATIENTS AND METHODS: All newly diagnosed bladder cancer patients (n=615) in 17 Spanish hospitals, between 1997-2000, were included. Information was collected both through personal interviews to patients and from medical records using a structured form. RESULTS: Seventy-six percent of tumours were superficial. The male:female ratio was 6.7 and it was similar for superficial and infiltrating tumours. Women were older than men at the diagnosis of bladder cancer (68.2+/-9.4 years versus 65.7+/-9.7 years, p=0.01). Ten percent of superficial tumours in women, versus 3% in men, were classified as "other histological types" (p=0.008). T1GIII tumours were more frequent among men (17% versus 7%, p=0.047). On the other hand, women were more likely to present with 0a-stage tumours (48.6% versus 35.5%, p=0.04), multiple tumours (50% versus 29%, trend test: 0.005), multi-centric tumours (54% versus 38%, p=0.019), and larger infiltrating masses (5.2 cm versus 3.8 cm, p=0.03) than men. Among 0a-stage tumours, only 23% of women compared to 54% of men received transurethral resection (TUR) alone (p=0.002). Women were almost five-fold more likely to receive additional therapies to TUR (p=0.004) after adjusting for age, geographical area, stage, tumoral size, nuclear grade, and multiplicity. CONCLUSION: The study confirms the very high male:female ratio of bladder cancer in Spain. We found substantial differences in the pathological characteristics of tumours from men and women. There was a tendency for women to receive more frequently non-standard, more aggressive, therapy than men.

Adult↗

Multiple sclerosis-associated retrovirus and MS prognosis: an observational study.

MS-associated retrovirus (MSRV) in the CSF may have gliotoxic properties and could be associated with a more disabling MS. The authors tested this hypothesis in 15 untreated patients with MS: 6 MSRV- and 9 MSRV+ at the time of CSF withdrawal. After a 3-year mean follow-up, MSRV- patients showed a stable MS course, whereas MSRV+ patients had a progressive course (p = 0.01).

Adolescent↗

Multiple sclerosis-associated retrovirus (MSRV) in Sardinian MS patients.

Blood and CSF of Sardinian patients with MS and neurologic control subjects were tested for MS-associated retrovirus (MSRV). CSF detection in MS was 50% at clinical onset, increasing with temporal disease progression, and 40% in control subjects. In blood, MSRV was detected in all MS patients, in most patients with inflammatory neurologic diseases, and rarely in healthy blood donors. MSRV may represent a marker of neurologic diseases of inflammatory origin.

Adult↗

Scratching the sporocyst surface: characterisation of European Aggregata species by atomic force microscopy.

The application of atomic force microscopy to the understanding of surface structure and atomic-scale measurements on the sporocyst of European Aggregata species, intracellular coccidia of the cephalopods Octopus vulgaris and Sepia officinalis, is presented here. Using the roughness mean surface (RMS) as an index, we reveal texture to be a key parameter for characterisation of the sporocyst surface properties, which resolve the historical synonymy within the European Aggregatidae. Roughness measurements from RMS algorithms may also be an important diagnostic taxonomic character for the differentiation of Aggregata species in the future.

Algorithms↗