Updated European Consensus Statement on diagnosis and treatment of adult ADHD.

Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness. Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated. Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated? Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.

Umbilical cord nucleated red blood cell counts: normal values and the effect of labor.

OBJECTIVE: To determine the umbilical cord blood nucleated red blood cell (UC-nRBC) count in uncomplicated pregnancies delivered by elective cesarean section or delivered vaginally. METHODS: A total of 57-term singleton pregnancies were studied: 33 with elective cesarean sections and 24 with vaginal deliveries. UC-nRBC was analyzed for its nucleated red blood cell counts. A logarithmic transformation of the data was used for statistical analysis. RESULTS: The mean+/-standard deviation (s.d.) for nucleated red blood cell per 100 white blood cells (nRBC/100WBC) from the elective cesarean section group was 7.8+/-7.4. The vaginal delivery group had a mean value of 9.3+/-10.5, which was not significantly different. A value of 22 nRBC/100WBC defined the upper 95% confidence limit. The correlation between absolute nRBC and nRBC/100 WBC was 0.97. CONCLUSION: Although chronic hypoxia is associated with elevated nRBC, the stress of uncomplicated labor does not change the level. This adds credence to its use as a marker for hypoxia preceding labor and delivery.

A statistical method for the determination of absorption rate constant estimated using the rat single pass intestinal perfusion model and multiple linear regression.

The guide "Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Dosage Forms Containing Certain Active Moieties/Active Ingredients Based on a Biopharmaceutical Classification System" (Rockville, MD: CDER, 2000) outlined non-in vivo tests of permeability that may satisfy the classification of a compound in the biopharmaceutical classification system. However, absent from that document were specific statistical methods to legitimatize the non-in vivo tests. This report describes the appropriate statistical treatment of absorption data, and recommends its adoption in the estimation of absorption and/or permeability measurements. The calculation of the absorption rate constants (k(a)) of ten compounds by a new multiple linear regression (MLR) method was completed after the separate perfusion of each compound through the rat single pass intestinal perfusion model (n = 3 rats per compound). Studentized residuals were evaluated to determine whether any statistically significant outliers were present in the data. The standard error of k(a) was estimated using variance components from the random effects model. The results were compared with the "traditional method" for k(a) calculations. Although both methods produced similar values of k(a), the MLR method's error estimate included multiple components of variability, which was largely ignored by the traditional method. The MLR method provided objective tests for outliers and achievement of steady-state. A preferred method for the statistical analysis of absorption data was demonstrated. These methods should be applied to all forms of permeability measurements, especially the non-in vivo measurements that classify a compound in the biopharmaceutical classification system.

Effects of storage conditions and hemolysis on vitamin E concentrations in porcine serum and liver.

Vitamin E (alpha-tocopherol) is an antioxidant vitamin important in protecting unsaturated fatty acids in lipid membranes from peroxidation. Variation in collection, storage, and shipping conditions of samples can potentially lead to breakdown of vitamin E prior to analysis. Therefore, the purposes of this project were 1) to determine the stability of vitamin E in refrigerated and frozen porcine liver and serum and 2) to evaluate the effects of red blood cell (RBC) hemolysis on porcine serum vitamin E concentrations. Porcine liver and nonhemolyzed serum were collected and stored refrigerated or frozen. Samples were analyzed for vitamin E immediately or on days 2, 3, 7, or 14. In addition, porcine RBCs were added to normal serum at concentrations from 1 x 10(6) to 1 X 10(9) RBC/ml and hemolyzed by freeze-thaw prior to analysis for vitamin E or products of lipid peroxidation.

Individual differences in multiple dimensions of aggression: a univariate and multivariate genetic analysis.

Previous behaviour genetic studies of aggression have yielded inconsistent results: reported heritabilities for different types of aggressive behaviour ranging from 0 to 0.98. In the present study, 247 adult twin pairs (183 MZ pairs; 64 same-sex DZ pairs) were administered seven self-report questionnaires which yielded 18 measures of aggression. Univariate genetic analyses showed moderate to high heritabilities for 14 of these 18 measures and for a general aggression factor and three correlated aggression factors extracted from the measures. Multivariate genetic analyses showed sizeable genetic correlations between the different dimensions of aggression. Thus, individual differences in many types of aggressive behaviour are attributable to some extent to genetic factors and there is considerable overlap between the genes that operate on different types of aggressive behaviour.

An epidemiologic investigation of unexpected refractive errors following cataract surgery.

OBJECTIVE: To determine the extent and magnitude of unexpected refractive errors following cataract surgery with intraocular lens (IOL) implantation and to determine what characteristics were associated with the errors. DESIGN: In this nonconcurrent prospective study, preoperative, intraoperative and postoperative information was collected from the charts of the 523 consecutive patients who underwent cataract extraction and polymethylmethacrylate IOL implantation performed by one of nine participating surgeons between Jan. 1 and Apr. 30, 1995, or the same dates in 1996. SETTING: University-affiliated eye care centre in Vancouver. OUTCOME MEASURE: Postoperative excess correction, calculated for each patient by subtracting the actual postoperative spherical equivalent from the expected spherical equivalent. Eyes with an excess correction of more than 1.00 dioptre were considered "overcorrected." RESULTS: Univariate analysis showed that the formula used to calculate the lens power, axial length, year of surgery, A-constant/surgeon factor used and lens manufacturer were associated with overcorrection. In a logistic regression model, lens manufacturer was the only variable independently associated with overcorrection. CONCLUSIONS: Routine reporting and follow-up is necessary to identify this kind of "outbreak" and the associated factors. The current guidelines of the Health Protection Branch, Health Canada, for evaluation of IOLs that have changed manufacturers are not adequate to identify the kind of error that we detected.

Nature vs nurture: are leaders born or made? A behavior genetic investigation of leadership style.

With the recent resurgence in popularity of trait theories of leadership, it is timely to consider the genetic determination of the multiple factors comprising the leadership construct. Individual differences in personality traits have been found to be moderately to highly heritable, and so it follows that if there are reliable personality trait differences between leaders and non-leaders, then there may be a heritable component to these individual differences. Despite this connection between leadership and personality traits, however, there are no studies of the genetic basis of leadership using modern behavior genetic methodology. The present study proposes to address the lack of research in this area by examining the heritability of leadership style, as measured by self-report psychometric inventories. The Multifactor Leadership Questionnaire (MLQ), the Leadership Ability Evaluation, and the Adjective Checklist were completed by 247 adult twin pairs (183 monozygotic and 64 same-sex dizygotic). Results indicated that most of the leadership dimensions examined in this study are heritable, as are two higher level factors (resembling transactional and transformational leadership) derived from an obliquely rotated principal components factors analysis of the MLQ. Univariate analyses suggested that 48% of the variance in transactional leadership may be explained by additive heritability, and 59% of the variance in transformational leadership may be explained by non-additive (dominance) heritability. Multivariate analyses indicated that most of the variables studied shared substantial genetic covariance, suggesting a large overlap in the underlying genes responsible for the leadership dimensions.

Gene knockout of the intracellular amylase gene by homologous recombination in Streptococcus bovis.

Streptococcus bovis expresses two different amylases, one intracellular and the other secreted. A suicide vector containing part of the intracellular alpha-amylase gene from Streptococcus bovis WI-1 was recombined into the S. bovis WI-1 chromosome to disrupt the endogenous gene. Recombination was demonstrated by Southern blot, and zymogram analysis confirmed the loss of the intracellular amylase. Amylase activity in cell-free extracts of the recombinant grown in the presence of 1% starch was only 7% of wild type. The rate of logarithmic growth of the recombinant was 15-20% of the wild type in medium containing either 1% glucose, starch, or cellobiose. Revertants and non-amylase control recombinants had logarithmic growth rates that were the same as wild type. Plasmid transformants containing multiple copies of the cloned gene expressed up to threefold higher levels of intracellular amylase activity than wild type but did not demonstrate elevated growth rates. These results suggest that a critical level of expression of the intracellular amylase gene may be important for rapid growth of the bacterium.

Paediatrics at the cutting edge: do we need clinical ethics committees?

OBJECTIVES: To investigate the need for hospital clinical ethics committees by studying the frequency with which ethical dilemmas arose, the perceived adequacy of the process of their resolution, and the teaching and training of staff in medical ethics. DESIGN: Interviews with individuals and three multidisciplinary teams; questionnaire to randomly selected individuals. SETTING: Two major London children's hospitals. RESULTS: Ethical dilemmas arose frequently but were resolved in a relatively unstructured fashion. Ethical concerns included: the validity of consent for investigations and treatment; lack of children's involvement in consent; initiation of heroic or futile treatments; resource allocation. Staff expressed the need for a forum which would provide consultation on ethical issues, develop guidelines for good ethical practice, undertake teaching and training, and provide ethical reflection outside the acute clinical setting. CONCLUSION: Multidisciplinary, accountable and audited clinical ethics committees with predominantly advisory, practice development and educational roles could provide a valuable contribution to UK clinical practice and perhaps in other countries that have not developed hospital clinical ethics committees.

Environmental predictors of personality differences: a twin and sibling study.

Nonshared environmental influences have consistently been shown to account for at least as much of the variance in personality as genetic factors, but the nature of these nonshared influences has largely remained unidentified. To identify environmental predictors of differential personality development, the Personality Research Form and 4 measures of people's perceptions of their background environments were administered to 143 adult twin pairs (93 monozygotic [MZ] and 50 dizygotic [DZ] and 66 pairs of same-sex nontwin (NT) siblings. Differences between MZ twins, DZ twins, and NT siblings in a number of dimensions of personality were significantly related to differences on the environmental measures, and phenotypic correlations between the personality and environment measures were themselves entirely attributable to correlated nonshared environmental effects.

The elderly with a learning disability (mental retardation): an overview.

This article is a review of the literature on the elderly with a learning disability, focusing on demographic data, functional abilities, mental health, physical health, and service use. This particular population is increasing and will have high health and social care needs. They share with their non-learning-disabled peers the problems of aging, namely the age-related infirmities of dementia, sensory impairment, urinary incontinence, and poor mobility. They develop psychiatric disorders that remain unrecognized and untreated. Some are cared for by aging parents who also may be frail with serious health problems. Further research is required on the quality of life, successful indicators of aging, and guidance on the type of service that will meet the needs of this group.

A 5-year survival study of general surgical patients aged 65 years and over.

A prospective 5-year survival study of 900 patients, aged 65 years and over, undergoing a general surgical procedure, demonstrated that following an initial high mortality rate the survival of the group as a whole approached that of an age-matched population. Non-elective admissions, age 75 years and over, ASA grade 4-5 and major surgery were associated with a high early mortality. Mortality associated with malignancy extended over 1 year. The study reinforces the conclusion that age alone should be no bar to surgery and anaesthesia, endorses the findings of the National Confidential Enquiry into Peri-operative deaths and emphasises the need to re-examine the provision of anaesthetic and surgical services in District General Hospitals. The benefits of elective admission in the very old are highlighted, along with the potential for extension of day case surgery.

Evaluation of multiple frequency bio-electrical impedance analysis in paediatric subjects.

The efficacy of multiple frequency bio-electrical impedance analysis (MFBIA) at discrete frequencies in predicting body cell mass, total body water, and fat-free mass compartments was investigated in healthy (n=30) and diseased (n=40) paediatric populations. Correlation coefficients achieved by comparing MFBIA with reference techniques using Deming's regression analysis were in excess of 0.9, but were not superior to those achieved comparing reference techniques with the traditional BIA application at 50 kHz. Applying the 95% limits of agreement procedure to the results showed that the agreement between the techniques was not sufficient for the technique to be of value in individual body composition assessments. The use of MFBIA at discrete frequencies does not improve the accuracy of estimations of body compartment sizes in paediatric subjects compared with those obtained with BIA at 50 kHz.

Activity of antiphospholipid antibody ELISA cofactor in different animal sera.

A plasma protein cofactor, beta 2-glycoprotein I (beta 2GPI), also known as apolipoprotein H, is necessary to detect certain antiphospholipid antibodies (aPA) to negatively charged phospholipids (PL) in the ELISA. Inasmuch as sera are diluted 1:100 before testing, the concentration of native beta 2GPI may be insufficient to provide an optimal aPA ELISA signal. Therefore, many laboratories add adult bovine serum (ABS) to the diluent buffer to provide a consistent level of cofactor for optimal aPA binding. To determine if other animal sera can provide the cofactor, cat, chicken, dog, horse, goat, guinea pig, mouse, pig, rat, and sheep were tested as diluent supplements in the aPA ELISA. To measure cofactor activity in these animal sera, ELISA for aPA to anionic phospholipids were performed. Two aPA positive patient plasmas were selected for study; one with cofactor-dependent and one with cofactor-independent aPA. Only four of the animal sera tested (bovine, pig, sheep, and cat) supported the cofactor-dependent aPA in ELISA. The cofactor-independent aPA was positive in the presence of each animal serum except bovine and rat. In order to determine whether these animal sera contain a beta 2GPI-like molecule, Western blot analyses were performed. By using a polyclonal antiserum produced to human beta 2GPI, specific beta 2GPI-like cross-reactivity was observed with all animal sera except the chicken. In summary, cofactor activity in animal sera varied significantly; however, bovine and pig sera appear to allow optimal binding of cofactor dependent aPA.

Idiopathic sclerosing inflammation of the orbit: immunohistologic analysis and comparison with retroperitoneal fibrosis.

Idiopathic sclerosing inflammation of the orbit is clinically characterized by an insidious, chronic and progressive fibrosing process damaging orbital structures through entrapment and mass effect. Histologically, desmoplasia and a sparse infiltrate of lymphocytes, histiocytes, plasma cells, and occasional neutrophils and eosinophils are seen. An immune pathogenesis is suspected but presently poorly understood. To characterize the inflammatory infiltrate and to compare orbital and other inflammatory fibrosing lesions, immunoperoxidase studies using the streptavidin method were performed on 16 formalin or Bouins' fixed, paraffin-embedded orbital biopsy specimens and six specimens of retroperitoneal fibrosis. Positive staining of orbital tissue occurred as follows: T-cells (UCHL-1) 94% of cases, B-cells (L26) 40%, tissue macrophages (KP-1) 56%, HLA Dr positive antigen presenting cells and activated T-cells (LN3) 44%, and immunoglobulins (kappa, 80%; lambda, 63%, IgG, 73%, IgA, 44% and IgM, 31%). Results were strikingly similar for retroperitoneal fibrosis. These findings imply a cell mediated pathogenesis in idiopathic sclerosing inflammation of the orbit that is similar to retroperitoneal fibrosis and suggest therapeutic potential for agents modifying this facet of the immune system.

The cost impact of cytomegalovirus disease in renal transplant recipients.

A retrospective case controlled study was performed to determine the cost impact of cytomegalovirus disease in the first year following renal transplantation as a basis for the analysis of cost effectiveness of prophylactic and therapeutic regimens directed at CMV infection. Eleven sequential cases of organ-specific CMV disease were matched with 22 controls for age, diabetic status, and donor/recipient CMV serologic status from 119 consecutive first cadaveric renal transplant recipients performed at a single university-affiliated, solid organ transplant unit between January 1, 1988 and March 31, 1990. The groups were comparable for sex, HLA match and mismatch, incidence of initial graft dysfunction, and immunosuppression. Hospitalization data, resource utilization, and costs for all 33 subjects were obtained for a one-year period after transplantation. The mean initial hospitalization time was comparable for both CMV cases and controls (14.5 vs. 15.0 days, P = NS), but patients developing CMV disease averaged 59 hospital days during the first year posttransplant versus 22 days in the control group (P = 0.001). A mean of 31 days hospitalization was directly related to CMV disease. Mean total institutional costs, calculated in 1988 Canadian dollars, were 2.5 times higher for patients with CMV disease than for controls ($42,611 vs. $17,309, P = 0.001), reflecting predominantly a difference in general ward ($19,988 vs. $7484, P = 0.001), hotel ($2508 vs. $927, P = 0.001), clinical laboratory ($5420 vs. $2558, P = 0.0001), radiology ($1581 vs. $640, P = 0.05), and pharmacy ($4916 vs. $1782, P = 0.01) costs and utilization. Operating room, special ward, ancillary, and mean per diem costs ($719 vs. $790, P = NS) were not significantly different between the two groups. Functional graft survival at 1 year was 72% in patients with CMV disease compared with 86% in controls, reducing the mean calculated cost-effectiveness of transplantation by 2.9-fold. These data show that CMV disease has significant economic impact on renal transplantation as a result of extended hospitalization. In order to develop a cost effective management approach to CMV infection, this impact must be considered when assessing therapeutic and prophylactic regimens and protocols of organ allocation.

Conjunctival and uveal melanoma in the dysplastic nevus syndrome.

The dysplastic nevus syndrome was conceptualized in the late 1970s, and the subsequent proposal of a genetic relationship with ocular melanoma has stimulated debate in the literature which remains unresolved. We present the case of a 60-year-old man with histologically proven sporadic dysplasic nevus syndrome and a prior history of nine cutaneous melanomas, who developed a large, exophytic melanoma of the cornea and limbal conjunctiva. Cytogenetic analysis of this melanoma revealed a clonal 1;14 translocation. We believe this is the first reported case to use cytogenetic techniques in the analysis of conjunctival melanoma, either associated with dysplastic nevus syndrome or in isolation. We review the clinical literature as well as the cytogenetic and molecular genetic data related to the possible association of cutaneous melanoma, conjunctival and uveal melanoma and the dysplastic nevus syndrome.

Cyclosporine A for the treatment of necrotizing scleritis and corneal melting in patients with rheumatoid arthritis.

Two of the ocular complications of rheumatoid arthritis (RA), necrotizing scleritis and keratolysis, have been associated with poor response to standard ocular therapy, and thus poor ocular outcome. We describe 6 patients with active ocular disease and active RA who failed to respond to disease modifying agents or immunosuppressive therapy and whose ocular and arthritic disease subsequently responded to cyclosporine A. Drug related complications were consistent with those reported for patients receiving similar doses for RA.

Diffuse anterior scleritis during OKT3 monoclonal antibody therapy for renal transplant rejection.

OKT3, a murine monoclonal antibody, is a potent, specific immunosuppressive agent used in solid-organ transplantation both as an adjunct during induction therapy and for treatment of steroid-resistant graft rejection. Minor, self-limiting ocular complications are often seen with this drug, of which conjunctivitis is the most common, occurring in approximately three-quarters of patients. We describe the more serious and previously unreported complication of diffuse anterior scleritis, which developed on the fifth day of OKT3 therapy in a 47-year-old man who had undergone cadaveric renal transplantation. Despite continuation of OKT3 treatment the scleritis resolved rapidly with increased dosages of prednisone.