Listening to patients' needs to improve their subjective quality of life

BACKGROUND: Subjective quality of life has gained a crucial role as a global measure of outcome in mental health care. This study aimed to investigate the impact of meeting needs for care, as assessed by both patients and mental health professionals, to improve the subjective quality of life in a sample of patients receiving community-based psychiatric care. METHOD: The study was conducted using a 4-year prospective longitudinal design. A cohort of patients from the South-Verona Community-based Mental Health Service (CMHS) was assessed at baseline and follow-up using, among other social and clinical measures, the Camberwell Assessment of Need (both staff and patient versions) and the Lancashire Quality of Life Profile. Predictors of changes of subjective quality of life were explored using block-stratified multiple regression procedures. RESULTS: Improvement in patients' clinical conditions as well as the reduction in patient-rated unmet needs in the social domain predicted an increase in subjective quality of life over 4 years; changes in staff-rated needs did not show any association with changes in subjective quality of life. CONCLUSIONS: Meeting self-perceived social needs, beyond symptoms reduction, seems to be of particular importance for ensuring a better quality of life for people with mental disorders. If the main goal of mental health care is to improve the quality of life of users, a policy of actively addressing patient-rated needs should be implemented.     

Acute dopamine/noradrenaline reuptake inhibition enhances human exercise performance in warm, but not temperate conditions

Nine healthy endurance-trained males were recruited to examine the effect of a dual dopamine/noradrenaline reuptake inhibitor on performance, thermoregulation and the hormonal responses to exercise. Subjects performed four trials, ingesting either a placebo (pla) or 2 × 300 mg bupropion (bup), prior to exercise in temperate (18°C) or warm (30°C) conditions. Trials consisted of 60 min cycle exercise at 55% W _max immediately followed by a time trial (TT). TT performance in the heat was significantly improved by bupropion (pla: 39.8 ± 3.9 min, bup: 36.4 ± 5.7 min; P = 0.046), but no difference between treatments was apparent in temperate conditions (pla: 30.6 ± 2.2 min, bup: 30.6 ± 1.9 min; P = 0.954). While TT power output was consistently lower in the heat when compared to temperate conditions, this decrement was attenuated by bupropion. At the end of the TT in the heat, both core temperature (pla 39.7 ± 0.3°C, bup 40.0 ± 0.3°C; P = 0.017) and HR (pla 178 ± 7 beats min⁻¹, bup 183 ± 12 beats min⁻¹; P = 0.039), were higher in the bupropion trial than in the placebo. Circulating pituitary and adrenal hormone concentrations increased throughout exercise in all trials. Circulating serum prolactin was elevated above temperate levels during exercise in a warm environment ( P < 0.001). These data indicate that performance in warm conditions is enhanced by acute administration of a dual dopamine/noradrenaline reuptake inhibitor. No such effect was apparent under temperate conditions. It appears that bupropion enabled subjects to maintain a greater TT power output in the heat with the same perception of effort and thermal stress reported during the placebo trial, despite the attainment of a higher core temperature.     

Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus

PSORS1, near HLA-C, is the major genetic determinant of psoriasis. We present genetic and structural evidence suggesting a major role for the HCR gene at the PSORS1 locus. Genotyping of 419 families from six populations revealed that coding single-nucleotide polymorphisms of HCR formed a conserved allele HCR*WWCC that associated highly significantly with psoriasis and with the HLA-Cw6 allele in all populations. Because of strong linkage disequilibrium between HLA-Cw6 and HCR*WWCC, the two genes could not be genetically distinguished by this sample size. However, the variant HCR allele was predicted to differ in secondary structure from the wild-type protein. HCR protein expression in lesional psoriatic skin differed considerably from that observed in normal skin. These results provide strong evidence for the HCR*WWCC allele as a major genetic determinant for psoriasis, probably by a mechanism impacting on keratinocyte proliferation.     

Reversible G(1) arrest by dimethyl sulfoxide as a new method to synchronize Chinese hamster cells

Dimethyl sulfoxide (DMSO), a well-known differentiation inducer in several myeloid cells, also induces a reversible G(1) arrest in many cell lines. We recently showed that DMSO induces a G(1) phase arrest in Chinese hamster ovary (CHO) cells, by restoring contact inhibition and preventing high density-dependent apoptosis. CHO cells are frequently used in cell biology and mutagenesis studies due to their good growth capacity and ease of manipulation but are very difficult to synchronize by serum starvation since they detach from monolayers when they reach confluence. In this study we investigated the possibility of using DMSO to reversibly synchronize CHO cells in the G(1) phase of the cell cycle and analysed whether toxic effects follow the arrest using growth curve, sister chromatid exchange and micronuclei assays. We carried out a kinetic analysis of the arrest by DMSO and re-entry into the cell cycle after drug release by cytofluorimetric analysis of DNA content and bromodeoxyuridine incorporation. We show that CHO cells are efficiently and reversibly arrested in G(1) by DMSO in concentrations ranging between 1 and 2%. In our experiments, >90% of cells grown for 96 h in presence of the drug were arrested in G(1) and synchronously re-entered S phase approximately 8-12 h after release. Furthermore, expression levels of p27 were down-regulated during G(1) progression and cyclin D3 and E expression patterns were similar to those observed after serum starvation. No detectable cytotoxicity or genetic damage were induced in G(1) released cells as revealed by the tests employed. Our results show that DMSO is a very powerful inducer of G(1) synchronization in CHO cells without detectable cytotoxic or genetic effects in cell populations released from G(1) arrest. DMSO synchronization represents a model system in which to analyse protein activities regulating G(1) progression and investigate the response of G(1) cells to mutagen treatments.     

Biological properties associated with the enhanced lung-colonizing potential in a B16 murine melanoma line grown in a medium conditioned by syngeneic Corynebacterium parvum-elicited macrophages

A previous study by our laboratory showed that the peritoneal murine Corynebacterium parvum-elicited macrophages released into their growth medium an activity which enhanced the ability of B16-F10 melanoma cells to form experimental metastases in the lung of syngeneic mice. In the present study, we used a clone of B16-F10 line (F10-M3 cells) to investigate whether the increase in lung-colonizing potential due to the pro-clonogenic activity released by C. parvum-elicited macrophages was associated with biological properties characteristic of a metastatic phenotype. We have found that the pulmonary retention, growth rate in lung parenchyma, invasiveness through Matrigel, adhesiveness to IL-1-activated endothelium and MHC class I expression were increased in F10-M3 cells stimulated by the macrophage pro-clonogenic activity. By using an in vitro experimental protocol, the enhancement of lung-colonizing potential in the stimulated melanoma cells turned out to be a transient phenomenon as was the increase of invasiveness through Matrigel and the higher expression of MHC class I antigens. In conclusion, the melanoma cells stimulated by the pro-clonogenic activity released by C. parvum-elicited macrophages showed changes in biological parameters which are relevant to metastatic diffusion. These changes appeared as a temporary phenomenon which sustains the view that the metastatic phenotype represents a transient biological character influenced by host factors. This revised version was published online in July 2006 with corrections to the Cover Date.     

Extraskeletal myxoid chondrosarcoma: multimodal diagnosis and identification of a new cytogenetic subgroup characterized by t(9;17)(q22;q11)

Extraskeletal myxoid chondrosarcoma is a rare malignant soft tissue tumour that can be difficult to diagnose correctly, especially preoperatively. We describe four cases of extraskeletal myxoid chondrosarcoma of the extremities diagnosed by a multimodal approach. The cytological examination of fine-needle aspirates showed small and round, mildly pleomorphic cells lying in sheets and cords, but also dispersed within a myxoid and metachromatic intercellular substance. Histological, electron microscopic and immunocytochemical examination also yielded findings compatible with the diagnosis of extraskeletal myxoid chondrosarcoma. Cytogenetic analysis demonstrated a t(9;22)(q22;q12) in two tumours and a t(9;17)(q22;q11) in the third and fourth. The translocation t(9;22)(q22;q12) has been described repeatedly in extraskeletal myxoid chondrosarcoma but never in other tumours; hence, the detection of this pathognomonic chromosome abnormality in short-term cultured cells from fine-needle aspirates verified the diagnosis in two of the cases. The t(9;17)(q22;q11) found in the last two cases probably represents a new cytogenetic subgroup of extraskeletal myxoid chondrosarcoma as it, too, is unknown in other contexts. The multimodal approach taken in these four cases enabled a definite diagnosis of a rare malignant tumour whose cytological and histological features alone are usually not sufficiently distinct to rule out other differential diagnostic possibilities. Received: 16 March 1999 / Accepted: 1 June 1999     

Human respiratory coronavirus HKU1 versus other coronavirus infections in Italian hospitalised patients.

BACKGROUND: Human respiratory coronavirus (hCoV) HKU1 infections were reported for the first time in 2005 in Hong Kong. OBJECTIVE: To investigate epidemiological, clinical, and diagnostic features of HKU1 infections. STUDY DESIGN: Longitudinal, prospective study from November 2005 through May 2006 in a hospitalised patient population. RESULTS: Overall, 48/426 (11.3%) patients were found to be infected by hCoV acute respiratory tract infections (ARTI). Of these, 10 (19.2%) were caused by HKU1 (6 single infections and 4 coinfections) during the period January-May 2006. Diagnosis was made by using RT-PCR for all four hCoVs, and in parallel, in-house developed group-specific monoclonal antibodies (MAbs) for HKU1 and 229E. HKU1-specific MAb was able to retrospectively identify 8 of 10 HKU1 strains detected by RT-PCR. Phylogenetic analysis showed that four HKU1 strains were genotype A and six genotype B. In HKU1-infected patients, the predominant clinical symptom was rhinorrhea (nine patients). Within group II hCoV, HKU1-infected patients had a significantly lower rate of lower ARTI compared to OC43-infected patients. CONCLUSION: HKU1 hCoV strains circulated in northern Italy during the winter-spring season 2005-2006. Both HKU1 genotypes were detected. HKU1-specific MAb may contribute to the rapid diagnosis of HKU1 infections currently performed by RT-PCR.     

Exhaled breath condensate cysteinyl leukotrienes are increased in children with exercise-induced bronchoconstriction

BACKGROUND: It is recognized that airway inflammation has a central role in the pathogenesis of asthma, but how it relates to exercise-induced bronchoconstriction (EIB) is not completely understood. OBJECTIVE: The aim of our study was to investigate the relationship between EIB and baseline concentrations of cysteinyl leukotrienes (Cys-LTs) and other inflammatory markers in exhaled breath condensate (EBC). METHODS: EBC was collected, and the fraction of exhaled nitric oxide (FE NO ) was measured in a group of 19 asthmatic children, after which they performed a treadmill exercise test. Fourteen healthy children were enrolled as control subjects. RESULTS: The asthmatic children were divided into the EIB group (decrease in FEV 1 , > or =12%) and the non-EIB group. The EBC was analyzed for the presence of Cys-LTs, leukotriene B 4 , and ammonia. Asthmatic patients with EIB (mean FEV 1 decrease, 23% +/- 3%) had higher Cys-LT concentrations than either asthmatic patients without EIB or control subjects (42.2 pg/mL [median] vs 11.7 pg/mL and 5.8 pg/mL; P < .05 and P < .001, respectively). Ammonia concentrations were lower in both the EIB and non-EIB groups than in control subjects (253.2 microM and 334.6 microM vs 798.4 microM; P < .01 and P < .05, respectively). No difference in EBC leukotriene B 4 levels was found among the 3 groups. Both asthmatic groups had higher FE NO levels than control subjects ( P < .001). EBC Cys-LT ( P < .01; r = 0.7) and FE NO ( P < .05; r = 0.5) values both correlated significantly with the postexercise FEV 1 decrease. CONCLUSION: this study shows that EBC Cys-LT values are higher in asthmatic children with EIB and correlate with the decrease in FEV 1 after exercise. These findings suggest that the pathways of both Cys-LT and nitric oxide are involved in the pathogenesis of EIB.     

Diltiazem impairs maturation and functions of human dendritic cells

The aim of this study was to define the effects of diltiazem, a calcium antagonist drug used in cardiology and in clinical transplantation, on the differentiation and maturation of human dendritic cells (DC). Herein, we demonstrate that diltiazem, in association with granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), induces monocytes to differentiate into cells with many of the characteristic of DC. However, diltiazem-induced DC express high levels of mannose receptor and Fc gamma RII and, consequently, manifest a higher endocytic activity compared with GM-CSF+IL-4-induced DC. Importantly, diltiazem-induced DCs have an impaired responsiveness to lipopolysaccharide and CD40 ligand because they produce decreased levels of IL-12 and reveal a reduced ability to stimulate alloreactive T-cell responses as well as in inducing interferon-gamma producing Th1 cells. These effects may contribute to a decreased DC-dependent T-cell activation and may help to explain the immunoregulatory function of diltiazem and its effectiveness in preventing transplant rejection.