Expression of eight genes of nuclear factor-kappa B pathway in multiple myeloma using bone marrow aspirates obtained at diagnosis

Purpose: To evaluate the expression of NF-kappa B pathway genes in total bone marrow samples obtained from MM at diagnosis using real-time quantitative PCR and to evaluate its possible correlation with disease clinical features and survival. Material and methods: Expression of eight genes related to NF-kappa B pathway (NFKB1, IKB, RANK, RANKL, OPG, IL6, VCAM1 and ICAM1) were studied in 53 bone marrow samples from newly diagnosed MM patients and in seven normal controls, using the Taqman system. Genes were considered overexpressed when tumor expression level was at least four times higher than that observed in normal samples. Results: The percentages of overexpression of the eight genes were: NFKB1 0%, IKB 22.6%, RANK 15.1%, RANKL 31.3%, OPG 7.5%, IL6 39.6%, VCAM1 10% and ICAM1 26%. We found association between IL6 expression level and International Staging System (ISS) (p = 0.01), meaning that MM patients with high ISS scores have more chance of overexpression of IL6. The mean value of ICAM1 relative expression was also associated with the ISS score (p = 0.02). Regarding OS, cases with IL6 overexpression present worse evolution than cases with IL6 normal expression (p = 0.04). Conclusion: We demonstrated that total bone marrow aspirates can be used as a source of material for gene expression studies in MM. In this context, we confirmed that IL6 overexpression was significantly associated with worse survival and we described that it is associated with high ISS scores. Also, ICAM1 was overexpressed in 26% of cases and its level was associated with ISS scores.

Primary Hyperparathyroidism as the First Clinical Manifestation of Multiple Endocrine Neoplasia Type 2A in a 5-Year-Old Child

Background: Primary hyperparathyroidism occurs in only 10%-30% of patients with multiple endocrine neoplasia type 2A (MEN2A), rarely as the sole clinical manifestation, and is usually diagnosed after the third decade of life. Summary: A5-year-old girl was referred for prophylactic thyroidectomy as she carried the p.C634R RET mutation. She was clinically asymptomatic, with a normally palpable thyroid and with the cervical region free of lymphadenopathy or other nodules. Preoperative tests revealed hypercalcemia associated with elevation of parathyroid hormone (PTH) (calcium = 11.2mg/dL, calcium ion = 1.48mmol/L, phosphorus = 4.0 mg/dL, alkaline phosphatase = 625U/L, parathyroid hormone (PTH) PTH = 998 pg/mL). A thyroid ultrasound was normal and parathyroid scintigraphy with (99m)Tc-Sestamibi revealed an area of radioconcentration in the upper half of the left thyroid lobe suggesting hyperfunctioning parathyroid tissue. She underwent total thyroidectomy and parathyroidectomy and developed hypocalcemia. The anatomopathological examination showed no histopathological changes in the thyroid tissue and an adenoma of the parathyroid gland, confirming the diagnosis of hyperparathyroidism. Conclusions: Primary hyperparathyroidism can be a precocious manifestation of MEN2A. This case report highlights that asymptomatic hypercalcemia should be scrutinized in children related to patients with MEN2A who carry a mutation in the RET proto-oncogene, especially mutations in the codon 634, before the currently recommended age of 8 years.

Kernel machines for epilepsy diagnosis via EEG signal classification: A comparative study

Objective: We carry out a systematic assessment on a suite of kernel-based learning machines while coping with the task of epilepsy diagnosis through automatic electroencephalogram (EEG) signal classification. Methods and materials: The kernel machines investigated include the standard support vector machine (SVM), the least squares SVM, the Lagrangian SVM, the smooth SVM, the proximal SVM, and the relevance vector machine. An extensive series of experiments was conducted on publicly available data, whose clinical EEG recordings were obtained from five normal subjects and five epileptic patients. The performance levels delivered by the different kernel machines are contrasted in terms of the criteria of predictive accuracy, sensitivity to the kernel function/parameter value, and sensitivity to the type of features extracted from the signal. For this purpose, 26 values for the kernel parameter (radius) of two well-known kernel functions (namely. Gaussian and exponential radial basis functions) were considered as well as 21 types of features extracted from the EEG signal, including statistical values derived from the discrete wavelet transform, Lyapunov exponents, and combinations thereof. Results: We first quantitatively assess the impact of the choice of the wavelet basis on the quality of the features extracted. Four wavelet basis functions were considered in this study. Then, we provide the average accuracy (i.e., cross-validation error) values delivered by 252 kernel machine configurations; in particular, 40%/35% of the best-calibrated models of the standard and least squares SVMs reached 100% accuracy rate for the two kernel functions considered. Moreover, we show the sensitivity profiles exhibited by a large sample of the configurations whereby one can visually inspect their levels of sensitiveness to the type of feature and to the kernel function/parameter value. Conclusions: Overall, the results evidence that all kernel machines are competitive in terms of accuracy, with the standard and least squares SVMs prevailing more consistently. Moreover, the choice of the kernel function and parameter value as well as the choice of the feature extractor are critical decisions to be taken, albeit the choice of the wavelet family seems not to be so relevant. Also, the statistical values calculated over the Lyapunov exponents were good sources of signal representation, but not as informative as their wavelet counterparts. Finally, a typical sensitivity profile has emerged among all types of machines, involving some regions of stability separated by zones of sharp variation, with some kernel parameter values clearly associated with better accuracy rates (zones of optimality). (C) 2011 Elsevier B.V. All rights reserved.

Improving Critical Thinking and Clinical Reasoning With a Continuing Education Course

Background: Continuing education courses related to critical thinking and clinical reasoning are needed to improve the accuracy of diagnosis. Method: This study evaluated a 4-day, 16-hour continuing education course conducted in Brazil. Thirty-nine nurses completed a pretest and a posttest consisting of two written case studies designed to measure the accuracy of nurses` diagnoses. Results: There were significant differences in accuracy from pretest to posttest for case 1 (p = .008) and case 2 (p = .042) and overall (p = .001). Conclusion: Continuing education courses should be implemented to improve the accuracy of nurses` diagnoses. J Contin Educ Nurs 2009;40(3):121-127.

Lumbar Epidural Anesthesia in the Treatment of Discal Lombosciatalgia: A Comparative Clinical Study between Methylprednisolone and Methylprednisolone with Levobupivacaine

Sousa FAEF, Colhado OCG - Lumbar Epidural Anesthesia in the Treatment of Discal Lombosciatalgia: A Comparative Clinical Study between Methylprednisolone and Methylprednisolone with Levobupivacaine. Background and objectives: Lumbar epidural technique has been used in the treatment of lombosciatalgia since 1953. In most cases, methylprednisolone is used along with a local anesthetic, and it is not known whether the isolated use of methylprednisolone is equally effective in relieving symptoms. The objective of this study was to compare the efficacy of two different solutions - methylprednisolone with saline and methylprednisolone with levobupivacaine injected in the epidural space to heal lombosciatalgia secondary to lumbar herniated disk. Methods: Sixty individuals ASA I and II, of both genders, ages 18 to 65 years participated in this randomized, double-blind study over a period of one year. They underwent interlaminar lumbar epidural analgesia without radioscopic control to heal a lombosciatalgia and they were divided into two groups: G-M (methylprednisolone + saline) and G-M + L (methylprednisolone + levobupivacaine + saline) both at a volume of 10 mL. Diagnosis was based on history, physical exam, and imaging exam (MRI). The Visual Analogue Scale (VAS) was applied in a total of two blockades, 15 days apart. Results: A reduction in pain severity was observed in the methylprednisolone-levobupivacaine group, but without statistical significance. Conclusions: The analgesic efficacy of the G-M + L solution was superior to that of the G-M solution in the treatment of discal lombosciatalgia regarding the shorter time to onset of analgesia, but this was not significant at the time of discharge, and both solutions were effective in the treatment of discal lombosciatalgia.

Clinical indicators of ineffective airway clearance in children with congenital heart disease

To analyse the sensitivity and specificity of clinical indicators of ineffective airway clearance in children with congenital heart disease and to identify the indicators that have high predictive power. The precise establishment of nursing diagnoses has been found to be one of the factors contributing to higher quality of care and cost reduction in healthcare institutions. The use of indicators to diagnose ineffective airway clearance could improve care of children with congenital heart disease. Longitudinal study. Participants consisted of 45 children, <= 1 year of age, with congenital heart disease, who had not had definitive or palliative surgical correction. Six assessments were made at 2-day intervals. Each clinical indicator was defined based on previously established operational criteria. Sensitivity, specificity and positive and negative predictive values of each indicator were calculated based on a model for the longitudinal data. A nursing diagnosis of ineffective airway clearance was made in 31% of patients on the first assessment, rising to 71% on the last assessment, for a 40% increase. Sensitivity was highest for Changes in Respiratory Rates/Rhythms (0.99), followed by Adventitious Breath Sounds (0.97), Sputum Production (0.85) and Restlessness (0.53). Specificity was higher for Sputum Production (0.92), followed by Restlessness (0.73), Adventitious Breath Sounds (0.70) and Changes in Respiratory Rates/Rhythms (0.17). The best positive predictive values occurred for Sputum Production (0.93) and Adventitious Breath Sounds (0.80). Adventitious Breath Sounds followed by Sputum Production were the indicators that had the best overall sensitivity and specificity as well as the highest positive predictive values. The use of simple indicators in nursing diagnoses can improve identification of ineffective airway clearance in children with congenital heart disease, thus leading to early treatment of the problem and better care for these children.

Cannabis use and psychosis: a review of clinical and epidemiological evidence

Objective: This paper evaluates evidence for two hypotheses about the relationship between cannabis use and psychosis: (i) that heavy cannabis use causes a 'cannabis psychosis', i.e, a psychotic disorder that would not have occurred in the absence of cannabis use and which can be recognised by its pattern of symptoms and their relationship to cannabis use; and (ii) that cannabis use may precipitate schizophrenia, or exacerbate its symptoms. Method: Literature relevant to drug use and schizophrenia is reviewed. Results: There is limited clinical evidence for the first hypothesis. If 'cannabis psychoses' exist, they seem to be rare, because they require very high doses of tetrahydrocannabinol, the prolonged use of highly potent forms of cannabis, or a preexisting (but as yet unspecified) vulnerability, or both. There is more support for the second hypothesis in that a large prospective study has shown a linear relationship between the frequency with which cannabis had been used by age 18 and the risk over the subsequent 15 years of receiving a diagnosis of schizophrenia. Conclusions: It is still unclear whether this means that cannabis use precipitates schizophrenia, whether cannabis use is a form of 'self-medication', or whether the association is due to the use of other drugs, such as amphetamines, which heavy cannabis users are more likely to use. There is better clinical and epidemiological evidence that cannabis use can exacerbate the symptoms of schizophrenia.

The clinical utility of the Hopkins Verbal Learning Test as a screening test for mild dementia

Objective. The purpose of this study was to determine whether the Hopkins Verbal Learning Test (HVLT) could be used as a valid and reliable screening test for mild dementia in older people, and to compare its performance to that of the Mini-Mental State Examination (MMSE). Method. Using a cross-sectional design, we studied three groups of older subjects recruited from a district geriatric psychiatry service: (1) 26 patients with DSM-IV dementia and MMSE scores of 18 or better; (2) 15 patients with psychiatric diagnoses other than dementia; and (3) 15 normal controls. The relationship of each potential cutting point on the HVLT and the MMSE was examined against the independently ascertained DSM-IV diagnoses of dementia using a Receiver Operating Characteristic (ROC) analysis. Results. The subjects consisted of 21 (37.5%) males and 35 (62.5%) females with a mean age of 74.7 (SD 6.1) years and a mean of 8.5 (SD 1.8) years of formal education. ROC analysis indicated that the optimal cutting point for detecting mild dementia in this group of subjects using the HVLT was 18/19 (sensitivity = 0.96, specificity = 0.80) and using the MMSE was 25/26 (sensitivity = 0.88, specificity = 0.93). Conclusions. The HVLT can be recommended as a valid and reliable screening test for mild dementia and as an adjunct in the clinical assessment of older people. The HVLT had better sensitivity than the MMSE in detecting patients with mild dementia, whereas the MMSE had better specificity. Copyright (C) 2000 John Wiley & Sons, Ltd.

Early diagnosis of lymphedema in postsurgery breast cancer patients

Lymphedema is an accumulation of lymph fluid in the limb resulting from an insufficiency of the lymphatic system. It is commonly associated with surgical or radiotherapy treatment for breast cancer. As with many progressively debilitating disorders, the effectiveness of treatment is significantly improved by earlier intervention. Multiple frequency bioelectrical impedance analysis (MFBIA) previously was shown to provide accurate relative measures of lymphedema in the upper limb in patients after treatment for breast cancer, This presentation reports progress to date on a three-year prospective study to evaluate the efficacy of MFBIA to predict the early onset of lymphedema in breast cancer patients following treatment. Bioelectrical impedance measurements of each upper limb were recorded in a group of healthy control subjects (n = 50) to determine the ratio of extracellular limb-fluid volumes. From this population, the expected normal range of asymmetry (99.7% confidence) between the limbs was determined, Patients undergoing surgery to treat breast cancer were recruited into the study, and MFBIA measurements were recorded presurgery, at one month and three months after surgery, and then at two-month intervals for up to 24 months postsurgery, When patients had an MFBIA measure outside the 99.7% range of the control group, they were referred to their physician for clinical assessment. Results to date: Over 100 patients were recruited into the study over the past two years; at present, 19 have developed lymphedema and, of these, 12 are receiving treatment. In each of these 19 cases, MFBIA predicted the onset of the condition up to four months before it could be clinically diagnosed. The false-negative rate currently is zero, The study will continue to monitor patients over the remaining year to accurately ascertain estimates of specificity and sensitivity of the procedure.

Perceived need for mental health care: influences of diagnosis, demography and disability

Background. Recent major epidemiological studies have adopted increasingly multidimensional approaches to assessment. Several of these have included some assessment of perceived need for mental health care. The Australian National Survey of Mental Health and Wellbeing, conducted in 1997, included a particularly detailed examination of this construct, with an instrument with demonstrated reliability and validity. Methods. A clustered probability sample of 10641 Australians responded to the field questionnaire for this survey, including questions on perceived need either where there had been service utilization, or where a disorder was detected by administration of sections of the Composite International Diagnostic Interview. The confidentialized unit record file generated from the survey was analysed for determinants of perceived need. Results. Perceived need is increased in females, in people in the middle years of adulthood, and in those who have affective disorders or co-morbidity. Effects of diagnosis and disability can account for most of the differences in gender specific rates. With correction for these effects through regression, there is less perceived need for social interventions and possibly more for counselling in females; disability is confirmed as strongly positively associated with perceived need, as are the presence of affective disorders or co-morbidity. Conclusions. The findings of this study underscore the imperative for mental health services to be attentive and responsive to consumer perceived need. The substantial majority of people who are significantly disabled by mental health problems are among those who see themselves as having such needs.

Familial partial epilepsy with variable foci: Clinical features and linkage to chromosome 22q12

Background: Familial partial epilepsy with variable foci (FPEVF) is an autosomal dominant syndrome characterized by partial seizures originating from different brain regions in different family members in the absence of detectable structural abnormalities. A gene for FPEVF was mapped to chromosome 22q12 in two distantly related French-Canadian families. Methods: We describe the clinical features and performed a linkage analysis in a Spanish kindred and in a third French-Canadian family distantly related to the original pedigrees. Results: Onset of seizures was typically in middle childhood, and attacks were usually easy to control. Seizure semiology varied among family members but was constant for each individual. In some, a pattern of nocturnal frontal lobe seizures led to consideration of the diagnosis of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The Spanish family was mapped to chromosome 22q (multipoint lod score, 3.4), and the new French-Canadian family had a multipoint lod score of 2.97 and shared the haplotype of the original French-Canadian families. Conclusions: Identification of the various forms of familial partial epilepsy is challenging, particularly in small families, in which insufficient individuals exist to identify a specific pattern. We provide clinical guidelines for this task, which will eventually be supplanted by specific molecular diagnosis. We confirmed linkage of FPEVF to chromosome 22q 12 and redefined the region to a 5.2-Mb segment of DNA.

Breast cancer in Western Australia: clinical practice and clinical guidelines

Objectives: To review changes in patterns of care for women with early invasive breast cancer in Western Australia from 1989 to 1999, and compare management with recommendations in the 1995 National Health and Medical Research Council guidelines. Design and setting: Population-based surveys of all cases listed in the Western Australian Cancer Registry and Western Australian Hospital Morbidity Data System. Main outcome measures: Congruence of care with guidelines. Results: Data were available for 1649 women with early invasive breast cancer (categories pT1 or pT2; pN0 or pN1; and M0). In 1999, 96% had a preoperative diagnosis by fine-needle aspiration or core biopsy (compared with 66% in 1989), with a synoptic pathology report on 95%. Breast-conserving surgery was used for 66% of women with mammographically detected tumours (v 35% in 1989) and 46% of those with clinically detected tumours (v 28% in 1989), with radiotherapy to the conserved breast in 90% of these cases (83% in 1989). Adjuvant chemotherapy was given to 92% of premenopausal women with node-positive disease and 63% with poor-prognosis node-negative tumours (v 78% and 14%, respectively, in 1989). Among postmenopausal women with receptor-positive tumours, tamoxifen was prescribed for 91% of those with positive nodes (85% in 1989) and 79% of those with negative nodes (30% in 1989). Among postmenopausal women with receptor-negative tumours, chemotherapy was prescribed for 70% with positive nodes (v 33%) and 58% with negative nodes (v none). Conclusions: Patterns of management of women with early invasive breast cancer in Western Australia during the 1990s changed significantly in all respects toward those recommended in the 1995 guidelines.

Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of schizophrenia and related disorders

Background: The Royal Australian and New Zealand College of Psychiatrists is co-ordinating the development of clinical practice guidelines (CPGs) in psychiatry, funded under the National Mental Health Strategy (Australia) and the New Zealand Health Funding Authority. This paper presents CPGs for schizophrenia and related disorders. Over the past decade schizophrenia has become more treatable than ever before. A new generation of drug therapies, a renaissance of psychological and psychosocial interventions and a first generation of reform within the specialist mental health system have combined to create an evidence-based climate of realistic optimism. Progressive neuroscientific advances hold out the strong possibility of more definitive biological treatments in the near future. However, this improved potential for better outcomes and quality of life for people with schizophrenia has not been translated into reality in Australia. The efficacy-effectiveness gap is wider for schizophrenia than any other serious medical disorder. Therapeutic nihilism, under-resourcing of services and a stalling of the service reform process, poor morale within specialist mental health services, a lack of broad-based recovery and life support programs, and a climate of tenacious stigma and consequent lack of concern for people with schizophrenia are the contributory causes for this failure to effectively treat. These guidelines therefore tackle only one element in the endeavour to reduce the impact of schizophrenia. They distil the current evidence-base and make recommendations based on the best available knowledge. Method: A comprehensive literature review (1990-2003) was conducted, including all Cochrane schizophrenia reviews and all relevant meta-analyses, and a number of recent international clinical practice guidelines were consulted. A series of drafts were refined by the expert committee and enhanced through a bi-national consultation process. Treatment recommendations: This guideline provides evidence-based recommendations for the management of schizophrenia by treatment type and by phase of illness. The essential features of the guidelines are: (i) Early detection and comprehensive treatment of first episode cases is a priority since the psychosocial and possibly the biological impact of illness can be minimized and outcome improved. An optimistic attitude on the part of health professionals is an essential ingredient from the outset and across all phases of illness. (ii) Comprehensive and sustained intervention should be assured during the initial 3-5 years following diagnosis since course of illness is strongly influenced by what occurs in this 'critical period'. Patients should not have to 'prove chronicity' before they gain consistent access and tenure to specialist mental health services. (iii) Antipsychotic medication is the cornerstone of treatment. These medicines have improved in quality and tolerability, yet should be used cautiously and in a more targeted manner than in the past. The treatment of choice for most patients is now the novel antipsychotic medications because of their superior tolerability and, in particular, the reduced risk of tardive dyskinesia. This is particularly so for the first episode patient where, due to superior tolerability, novel agents are the first, second and third line choice. These novel agents are nevertheless associated with potentially serious medium to long-term side-effects of their own for which patients must be carefully monitored. Conventional antipsychotic medications in low dosage may still have a role in a small proportion of patients, where there has been full remission and good tolerability; however, the indications are shrinking progressively. These principles are now accepted in most developed countries. (vi) Clozapine should be used early in the course, as soon as treatment resistance to at least two antipsychotics has been demonstrated. This usually means incomplete remission of positive symptomatology, but clozapine may also be considered where there are pervasive negative symptoms or significant or persistent suicidal risk is present. (v) Comprehensive psychosocial interventions should be routinely available to all patients and their families, and provided by appropriately trained mental health professionals with time to devote to the task. This includes family interventions, cognitive-behaviour therapy, vocational rehabilitation and other forms of therapy, especially for comorbid conditions, such as substance abuse, depression and anxiety. (vi) The social and cultural environment of people with schizophrenia is an essential arena for intervention. Adequate shelter, financial security, access to meaningful social roles and availability of social support are essential components of recovery and quality of life. (vii) Interventions should be carefully tailored to phase and stage of illness, and to gender and cultural background. (viii) Genuine involvement of consumers and relatives in service development and provision should be standard. (ix) Maintenance of good physical health and prevention and early treatment of serious medical illness has been seriously neglected in the management of schizophrenia, and results in premature death and widespread morbidity. Quality of medical care for people with schizophrenia should be equivalent to the general community standard. (x) General practitioners (GPs)s should always be closely involved in the care of people with schizophrenia. However, this should be truly shared care, and sole care by a GP with minimal or no special Optimal treatment of schizophrenia requires a multidisciplinary team approach with a consultant psychiatrist centrally involved.

Depression in women living with HIV: clinical and psychosocial correlates

The number of Brazilian women living with HIV has increased significantly in past years, rendering studies of their particular care demands including psychiatric issues. This study measures the prevalence of major depression, using the Structured Clinical Interview for DSM-IV Axis I Disorders, in a sample of 120 women living with HIV in treatment at a reference centre in So Paulo. Socio-demographic variables, HIV-related clinical and laboratory data, including CD4+ cell counts and HIV plasma viral loads, as well as psychosocial features (intimate relationships, disclosure of HIV serostatus, partner`s serostatus and patient`s emotional and financial support) were investigated as factors potentially associated with depression. The prevalence of major depression at the time of evaluation was 25.8% (95% CI 18.2-33.4%). Clinical status (p = 0.002), lack of emotional support (p = 0.02), use of antidepressants (p = 0.028) and length of time since HIV diagnosis (p = 0.05) were associated with major depression in univariate analysis. In multivariate multiple-regression model, HIV clinical status, lack of emotional support and higher plasma viral loads were associated with depression. Sixty per cent of the women have a major depression diagnosis during lifetime. We conclude that major depression is highly prevalent among women living with HIV, but it is still underdiagnosed and undertreated.