Increased mean corpuscular haemoglobin concentration: artefact or pathological condition?

INTRODUCTION: In daily practice in haematology laboratories, spurious increased MCHC induces an analytical alarm and needs prompt corrective action to ensure delivery of the right results to the clinicians. The aim of this study was to establish a 'decision tree' using the new parameters red blood cells (RBC-O) and haemoglobin (HGB-O) from the Sysmex XN-10 RET obtained by flow cytometry to deliver appropriate results. METHODS: From 128 unknown patients with MCHC > 365 g/L, all erythrocyte parameters including reticulocyte parameters were measured and analysed in parallel with blood smears, chemistry index and osmolarity. Differences between optical parameters (RBC-O, HGB-O) and usual parameters (RBC, HGB) obtained by impedance and photometry were reported also. RESULTS: Four groups were defined from observations: -RBC agglutination (n = 22); -optical interference (n = 17); -RBC disease (n = 18); and -others (n = 71). The use of RBC-O and HGB-O permitted efficient correction of the abnormalities when RBC agglutination and/or optical interference were present in 36 of 39 patients. Reticulocyte parameters permitted to elaborate an RBC score that allowed a highly sensitive detection of RBC disease patients (17/18). CONCLUSION: Based on new parameters, we propose a 'decision tree' that delivers time savings and supports biological interpretation in case of elevated MCHC.

Improving the quality of mental health care in multiple sclerosis.

OBJECTIVE: An exploratory study of mental health treatment of people with multiple sclerosis (MS) to identify hypotheses for future testing. METHODS: We mailed surveys to 8750 MS patients in four geographically distributed MS Centers; 3384 completed the survey. We used a modified version of the Experience of Care and Health Outcome Survey™ to assess mental health problems and experiences with mental health treatment and the Kessler 6 scale to identify serious mental illness. RESULTS: In the year before the survey, sixty percent of patients reported mental health problems. Less than one half of these individuals received mental health treatment, either from their MS care provider or a mental health professional in the MS Center or the community. Patients generally had good mental health treatment experiences, and felt helped by their treatment, but gave less positive reports about how long it took to be seen, receiving information about treatment options and managing their condition, and phone contact. Care experiences were more positive among those who received care from mental health professionals (compared to medical care providers) and among those receiving mental health treatment in the MS Center (compared to in the community). CONCLUSIONS: The unmet need for mental health treatment for people with MS is high. Options for MS care providers to help meet this need include hiring mental health professionals to provide on-site treatment; providing mental health treatment themselves; and referring patients to mental health professionals in the community and collaborating in integrated care. This study provided preliminary data for two related hypotheses that warrant further testing: MS patients will receive better mental health care if their mental health treatment is co-located with their MS care and if it is provided by mental health professionals.

Patients' perspectives on quality of mental health care for people with MS.

OBJECTIVE: The objective was to obtain multiple sclerosis (MS) patients' report on their experience receiving mental health care. METHODS: We convened focus groups at four MS clinical care centers to identify the aspects of mental health care that were important to people with MS. All patients (n=54) had received mental health care in the past year. Data were analyzed by coding comments under specific themes. RESULTS: Patients wanted prompt intervention after diagnosis and ongoing screening for mental health problems; they prefer providers with knowledge about MS and experience working with people with MS; they appreciated being able to access mental health services that were on-site at their MS center and noted the benefit of inclusion of family members in treatment. CONCLUSIONS: Mental health care should be provided promptly after diagnosis, with regular screening and interventions that include family members as indicated thereafter. Mental health providers should be familiar with MS, collaborate with neurologic care providers and provide services on-site at MS centers.

Efficacy and safety of androgen deprivation therapy after switching from monthly leuprolide to monthly degarelix in patients with prostate cancer.

OBJECTIVES: To evaluate whether switching prostate cancer (PCa) patients from leuprolide to degarelix is associated with any change in the efficacy of testosterone suppression or safety profile during the first 3 months. METHODS: Participants were 134 patients with histologically confirmed PCa who had completed 1 year of treatment with leuprolide 7.5 mg monthly before being switched to degarelix. These patients were re-randomised for the extension trial to receive a starting dose of 240 mg degarelix followed by monthly maintenance doses of either 80 (n = 69) or 160 mg (n = 65). For efficacy assessment, serum testosterone, prostate-specific antigen (PSA), luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels measured at days 3, 7, 14, 28, 56 and 84 assessed whether treatment efficacy is sustained. Safety and tolerability assessments included adverse events (AEs), physical examinations, electrocardiograms and clinically significant changes in laboratory safety parameters. RESULTS: Serum testosterone, LH, and PSA levels were all sustained in both treatment arms during the observation period. Interestingly, FSH levels were further decreased by 30% following the switch to degarelix. With the exception of injection site reactions, the overall prevalence and pattern of AEs during the first 3 months after the switch was comparable to that during the last 3 months leuprolide treatment in the main trial. There were five (4%) patients discontinued to treatment-related AEs including injection site pain (n = 3) and fatigue (n = 2). CONCLUSIONS: This 3-month analysis indicates that patients with prostate cancer can be safely switched from leuprolide to degarelix treatment with sustained efficacy as measured by biochemical markers.

ApoE alleles, depression and positive affect in multiple sclerosis.

BACKGROUND: The role of apolipoprotein E (ApoE) alleles has received recent attention in depressive disorders, the ApoE epsilon4 conferring greater risk for poorer outcomes, and the ApoE epsilon2 allele providing some protective effects. Depression is common in multiple sclerosis (MS) and the role of ApoE alleles is unknown. AIMS: To evaluate ApoE alleles in relation to symptoms of depression in a cohort of patients with MS participating in the Sonya Slifka Longitudinal Multiple Sclerosis Study (Slifka Study). To examine risk and protection, depressed mood and positive affect were each investigated with respect to the ApoE epsilon4 and ApoE epsilon2 alleles, respectively. RESULTS: Of the total 101 participants, 22.8% were ApoE epsilon2 carriers and 21.8% were ApoE epsilon4 carriers. Hierarchical linear regression analyses suggested that after controlling for demographics, disease duration, and disability, ApoE epsilon2 significantly predicted increased positive affect (R2Delta=0.05, F(1,94)=5.44, P=0.02) and was associated with decreased severity of depressive symptoms, although this did not reach statistical significance (R2Delta=0.03, F(1,94)=3.44, P=0.06). ApoE epsilon4 did not significantly predict depression status. CONCLUSION: The presence of the ApoE epsilon2 allele in this study is suggested to be protective against depressive symptoms in our subsample of patients recruited from the Slifka Study. These findings are consistent with reports in psychiatric populations linking ApoE epsilon2 with decreased incidence of depressive disorders. Further investigation would be warranted to understand the role of ApoE genotypes and risk for depressive symptoms.

Disease-modifying agents in the Sonya Slifka Longitudinal Multiple Sclerosis Study.

BACKGROUND: Although experts recommend that people with multiple sclerosis (MS) should begin treatment with disease-modifying agents (DMAs) as soon as possible after diagnosis and continue indefinitely, many do not use these agents or discontinue them prematurely. Since DMAs reduce relapse rates and slow disease progression, and since even benign relapses and course can lead to axonal damage and permanent neurologic impairment, it is important that all appropriate candidates have access to treatment. We used a population-based sample of people with MS to determine rates, predictors, and reasons for use, non-use, and discontinuation of DMAs. METHODS: We collected data from 2156 people with MS on their use of and experience with DMAs. We used chi-squared tests to compare current, past, and never users of any DMA and ever users of individual DMAs, and logistic regression to identify predictors of use. RESULTS: One-half of the participants were using a DMA at the time of the interview; 12.2% had used previously, but stopped. Reasons for never using and reasons for stopping were at odds with expert recommendations. Characterization of users, and of their experiences by type of DMA, was consistent with current knowledge of these agents. Seeing a neurologist for usual MS care was an important factor in starting and persisting with DMA therapy. CONCLUSIONS: Dissemination of expert opinion about, and management strategies for, use of DMAs to non-neurologic professionals and patients and their families might help more people who are appropriate candidates for DMA therapy to start and continue treatment.

Access to and utilization of neurologists by people with multiple sclerosis.

OBJECTIVE: This study examined access to and use of neurologists among a broad, national sample of people with multiple sclerosis (MS); identified demographic, economic, and clinical factors associated with access and use; and examined differences in treatment and management of MS. METHODS: We used computer-assisted telephone interviews to collect data from 2,156 people with MS on demographics, disease characteristics, and use of neurologists, other specialists, and disease-modifying agents (DMAs). We used chi(2) tests and logistic regressions to compare patients of neurologists and other providers and identify predictor variables and treatment factors associated with seeing neurologists. RESULTS: For their usual MS care, 72.2% of participants saw a neurologist. The probability of seeing a neurologist was significantly lower for people who lacked health insurance, were poor, lived in rural areas, or were African American; had been ill for more than 15 years; had difficulty walking but did not use an assistive device; or required a wheelchair/scooter or were confined to bed. People who reported one to two relapses in the preceding year and women were significantly more likely to see neurologists. Patients of neurologists were significantly more likely to take a DMA, attend an outpatient rehabilitation program, or see an occupational therapist, urologist, or physical therapist. CONCLUSIONS: People with multiple sclerosis who see neurologists are more likely than people who see other providers to receive treatment with disease-modifying agents and see rehabilitation specialists and urologists. While some people may choose other providers, economic, insurance, racial, and geographic factors appear to limit access to neurologists.

Local anesthesia for inguinal hernia repair in adolescents.

BACKGROUND: Many centers use local anesthesia for adult inguinal hernia surgery in the setting of day-case surgery. There are no reports on, or guidelines for, use of anesthesia for inguinal hernia surgery in adolescents. We describe our initial experience with the use of local anesthesia and intravenous sedation for inguinal hernia surgery in adolescents in the setting of a day-surgery facility. METHODS: The charts of 14 consecutive adolescent patients (aged 12-17) who had inguinal hernia surgery from July 2004 to March 2005 were reviewed retrospectively. Intravenous sedation was administered 1-3 min before injection of local anesthetic. Sedation consisted of midazolam 0.085 mg kg(-1) and either fentanyl 0.85 mug kg(-1) or ketamine 0.085 mg kg(-1), according to the preference of the anesthesiologist. Additional sedation with half the initial dose was administered if required. Local anesthesia using a combination of lignocaine and bupivacaine was administered by the surgeon with infiltration in the skin and deep tissues. RESULTS: Fourteen adolescents aged 12-17 years (mean 14.8 +/- 1.37), weighing 34-100 kg (mean 61.2 +/- 16.5), had 15 inguinal hernia repairs with sedation and local anesthesia. All the patients were male. All completed the surgery with sedation and local anesthesia. None required conversion to general anesthesia. There were no immediate or subsequent complications. Mean time from the end of surgery to discharge home was under 2 h (mean 106 +/- 36 min). Examination of patient charts did not reveal any complaints regarding the surgery or the postoperative course at the postoperative follow up visit. CONCLUSIONS: The use of local anesthesia with intravenous sedation for inguinal hernia repair in the adolescent age group seems feasible and requires further prospective study.

Access to health care for people with multiple sclerosis.

The Sonya Slifka Longitudinal Multiple Sclerosis (MS) Study follows a population-based cohort of approximately 2000 people with MS to study demographic and clinical characteristics, use and cost of health services, provider and treatment characteristics, neurological, economic, and psychosocial outcomes. We examined key indicators of access to health care and found that the majority of participants had health insurance, a usual source of care, and access to specialty care. Nevertheless, 3.8% did not have health insurance which, with application of sampling weights, corresponds to approximately 7000 people with MS in the US population. Even with insurance, population-based estimates indicated that substantial numbers of people with MS have plans that pay nothing toward prescription medication, limit their access to specialists, and restrict their choice of hospitals and providers. Some 9% of the sample, corresponding to 15,800 people with MS, did not have a usual source of MS care; 11.8% or 17,300 people did not have a usual source of general health care; and 31% or 57,400 people did not see the specialists that they or their physicians wanted them to see. Further, 10.5% or 19,400 people reported difficulty obtaining prescription medication, 4.1% or 7600 people encountered obstacles accessing medical care, and 2.4% or 4500 people could not obtain the mental health services they needed. Finally, out-of-pocket health care expenditures were twice those found for the general population. Two-thirds of study participants (representing almost 70,000 people) chose their MS care providers because they were neurologists or MS specialists, creating a demand that almost certainly exceeds current supply.

Formation of hydrogen-bridged cytosine dimers on Cu(110).

Cytosine was adsorbed onto a Cu(110) surface under UHV conditions. Annealing to 370 K resulted in the formation of a (6 x 6)gg low energy electron diffraction (LEED) pattern, even at submonolayer coverages. Examination of this structure with scanning tunneling microscopy (STM) revealed islands of zigzag chains at low coverages and large ordered domains at monolayer saturation. Further annealing to 480 K initiated a phase transition to a (6 x 2)gg structure observed both by LEED and STM. High resolution electron energy loss spectroscopy spectra for both overlayer structures exhibited mainly in-plane modes suggesting upright/tilted species on the surface. Based on the experimental data and supported by density functional theory calculations, a model is proposed for the (6 x 2)gg structure, which involves the formation of deprotonated hydrogen bridge-bonded cytosine dimers, adsorbed through the oxygen atoms.

The Sonya Slifka Longitudinal Multiple Sclerosis Study: methods and sample characteristics.

The Sonya Slifka Longitudinal Multiple Sclerosis Study follows a population-based cohort of approximately 2000 people with multiple sclerosis (MS) to study demographic and clinical characteristics, course of illness, utilization and cost of health services, provider characteristics, use of MS specialists and disease modifying agents, and neurologic, economic and psychosocial outcomes. This report describes the study methodology, presents baseline demographic and clinical data, and evaluates the representativeness of the sample. A stratified random sample of persons with established and recently-diagnosed MS selected from the National Multiple Sclerosis Society (NMSS) mailing lists was supplemented with recently-diagnosed patients recruited through systematic nationwide outreach. Baseline data were collected by computer-assisted telephone interviews derived from standardized instruments; data collection continues at six-month intervals. The cohort was comparable to population-based and clinical samples with respect to demographics, course, relapse rate, symptoms, and severity of disability. Almost two-thirds of the cohort needed help with activities of daily living, three-quarters were limited in work or other activities, and half had emotional problems that compromised quality of life. The Slifka Study cohort is broadly representative of the MS population and the database can be used to address questions not answered by natural history studies, clinical databases, or population-based surveys.

Revealing the topography of cellular membrane domains by combined atomic force microscopy/fluorescence imaging.

Simultaneous atomic force microscopy (AFM) and confocal fluorescence imaging were used to observe in aqueous buffer the three-dimensional landscape of the inner surface of membrane sheets stripped from fixed tumor mast cells. The AFM images reveal prominent, irregularly shaped raised domains that label with fluorescent markers for both resting and activated immunoglobin E receptors (FcepsilonRI), as well as with cholera toxin-aggregated GM1 and clathrin. The latter suggests that coated pits bud from these regions. These features are interspersed with flatter regions of membrane and are frequently surrounded and interconnected by cytoskeletal assemblies. The raised domains shrink in height by approximately 50% when cholesterol is extracted with methyl-beta-cyclodextrin. Based on composition, the raised domains seen by AFM correspond to the cholesterol-enriched dark patches observed in transmission electron microscopy (TEM). These patches were previously identified as sites of signaling and endocytosis based on their localization of activated FcepsilonRI, at least 10 associated signaling molecules, and the presence of clathrin-coated pits. Overall the data suggest that signaling and endocytosis occur in mast cells from raised membrane regions that depend on cholesterol for their integrity and may be organized in specific relationship with the cortical cytoskeleton.

Local mobility in lipid domains of supported bilayers characterized by atomic force microscopy and fluorescence correlation spectroscopy.

Fluorescence correlation spectroscopy (FCS) is used to examine mobility of labeled probes at specific sites in supported bilayers consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid domains in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). Those sites are mapped beforehand with simultaneous atomic force microscopy and submicron confocal fluorescence imaging, allowing characterization of probe partitioning between gel DPPC and disordered liquid DOPC domains with corresponding topography of domain structure. We thus examine the relative partitioning and mobility in gel and disordered liquid phases for headgroup- and tailgroup-labeled GM1 ganglioside probes and for headgroup- and tailgroup-labeled phospholipid probes. For the GM1 probes, large differences in mobility between fluid and gel domains are observed; whereas unexpected mobility is observed in submicron gel domains for the phospholipid probes. We attribute the latter to domain heterogeneities that could be induced by the probe. Furthermore, fits to the FCS data for the phospholipid probes in the DOPC fluid phase require two components (fast and slow). Although proximity to the glass substrate may be a factor, local distortion of the probe by the fluorophore could also be important. Overall, we observe nonideal aspects of phospholipid probe mobility and partitioning that may not be restricted to supported bilayers.

Assessing the dog as a model for human total hip replacement. Analysis of 38 canine cemented femoral components retrieved at post-mortem.

Post-mortem retrieval of canine, cemented femoral components was analysed to assess the performance of these implants in the dog as a model for human total hip replacement (THR). Mechanical testing and radiological analysis were performed to determine the stability of the implant and the quality of the cement. Thirty-eight implants from 29 dogs were retrieved after time intervals ranging from 0.67 to 11.67 years. The incidence of aseptic loosening was 63.2%, much higher than in human patients (6% in post-mortem studies). Failure of the femoral implants began with debonding at the cement-metal interface, similar to that in implants in man. The incidence of aseptic loosening was much lower in bilateral than in unilateral implants. Significant differences were observed for three different designs of implant. While the dog remains the animal model of choice for THR, results from this study provide insight into interspecies differences in the performance of implants. For example, the performance of THR in dogs should be compared with that in young rather than in elderly human patients.

Metastatic synovial cell sarcoma in two cats.

Synovial cell sarcoma (SCS) with metastasis to the regional lymph node was diagnosed in two cats. Synovial cell sarcomas are rare in cats and metastatic SCS has not previously been reported. In both cases, treatment consisted of limb amputation and adjuvant doxorubicin. Local tumour recurrence and pulmonary metastases were diagnosed in one cat 316 days postoperatively. This cat died of chronic renal failure 444 days after limb amputation. The second cat died of an acute pulmonary thromboembolism 41 days postoperatively without evidence of local tumour recurrence or metastatic disease.

Proinflammatory cytokines promote glial heme oxygenase-1 expression and mitochondrial iron deposition: implications for multiple sclerosis.

Proinflammatory cytokines, pathological iron deposition, and oxidative stress have been implicated in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). HO-1 mRNA levels and mitochondrial uptake of [(55)Fe]Cl(3)-derived iron were measured in rat astroglial cultures exposed to interleukin-1beta (IL-1beta) or tumor necrosis factor-alpha (TNF-alpha) alone or in combination with the heme oxygenase-1 (HO-1) inhibitors, tin mesoporphyrin (SnMP) or dexamthasone (DEX), or interferon beta1b (INF-beta). HO-1 expression in astrocytes was evaluated by immunohistochemical staining of spinal cord tissue derived from MS and control subjects. IL-1beta or TNF-alpha promoted sequestration of non-transferrin-derived (55)Fe by astroglial mitochondria. HO-1 inhibitors, mitochondrial permeability transition pore (MTP) blockers and antioxidants significantly attenuated cytokine-related mitochondrial iron sequestration in these cells. IFN-beta decreased HO-1 expression and mitochondrial iron sequestration in IL-1beta- and TNF-alpha-challenged astroglia. The percentage of astrocytes coexpressing HO-1 in affected spinal cord from MS patients (57.3% +/- 12.8%) was significantly greater (p < 0.05) than in normal spinal cord derived from controls subjects (15.4% +/- 8.4%). HO-1 is over-expressed in MS spinal cord astroglia and may promote mitochondrial iron deposition in MS plaques. In MS, IFN-beta may attenuate glial HO-1 gene induction and aberrant mitochondrial iron deposition accruing from exposure to proinflammatory cytokines.

Hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is a complex combination of cardiac malformations that probably results from multiple developmental errors in the early stages of cardiogenesis and that, if left untreated, invariably proves fatal. A variety of chest radiographic findings are seen in patients with HLHS, including an enlarged cardiac silhouette (notably a prominent right atrium), pulmonary venous hypertension, an atrial septal defect, and valvular stenosis or atresia. The recent evolution of palliative surgical procedures (modified Norwood procedure, bidirectional cavopulmonary shunt, modified Fontan procedure, aortic valvuloplasty, heart transplantation) has increased the survival rate in children with HLHS. Echocardiography allows accurate assessment of the size and location of the ductus arteriosus, the hemodynamics of the aortic root, the patency and size of the foramen ovale or atrial septal defect, and the presence of a ventricular septal defect to help determine whether surgical intervention is appropriate and, if so, to facilitate planning. Pediatric radiologists now view radiologic images obtained in patients with HLHS before surgical intervention and at important intervals during treatment. Familiarity with the malformations that characterize HLHS and the surgical procedures used to enhance postnatal survival will help pediatric radiologists provide better care for patients with this relatively common pathologic condition.