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PubMed2004

A catalog of dermatology utilities: a measure of the burden of skin diseases.

Utilities are measures of quality of life that reflect the strength of individuals' preferences or values for a particular health outcome. As such, utilities represent a measure of disease burden. The aim of this article is to introduce the concept of utilities to the dermatology community and to present a catalog of dermatology utilities obtained from direct patient interviews. Our data are based on 236 total subjects from Grady Hospital (Atlanta, GA), Stanford Medical Center (Palo Alto, CA), and Parkland Hospital (Dallas, TX). The mean time trade-off utilities ranged from 0.640 for blistering disorders to 1.000 for alopecia, cosmetic, and urticaria. The mean utility across all diagnoses was 0.943. We present utilities for 17 diagnostic categories and discuss the underlying reasons for the significant disease burden that these utilities represent. We also present these dermatology categories relative to noncutaneous diseases to place the cutaneous utilities in perspective and to compare the burden of disease. We have demonstrated that skin diseases have considerable burden of disease and provided a preliminary repository of utility data for future researchers and policy makers.

Cost of Illness↗
PubMed2003

Assessment of oesophageal motor function in patients with dysphagia or chest pain - the Clinical Outcomes Research Initiative experience.

BACKGROUND: Available prospectively acquired data on the distribution of oesophageal motor abnormalities in patients being evaluated for non-cardiac chest pain and/or dysphagia are relatively scarce. AIM: To evaluate the distribution of oesophageal motor abnormalities in patients with dysphagia, non-cardiac chest pain or both using the national Clinical Outcomes Research Initiative (CORI) database. METHODS: The CORI oesophageal motility database originates from 19 community, university and VA medical centres. Data were collected using a computerized motility report-generating program, combined with the CORI module. Data from each site were encrypted and sent to the CORI National Repository for analysis. The database includes the assessment of the lower and upper oesophageal sphincter function and the motor activity of the oesophageal body. RESULTS: Five hundred and eighty-seven consecutive patients who underwent motility studies between 1998 and 2001 were included in the CORI database and analysed for this report. Four hundred and three patients (69%) had dysphagia as their primary indicator for the examination, 140 patients (24%) had non-cardiac chest pain and 44 patients (7%) had both dysphagia and non-cardiac chest pain. In all three groups, a normal motility study was the most frequent finding (dysphagia, 53%; chest pain, 70%; both, 55%). The most common motility abnormality in the group with non-cardiac chest pain was a hypotensive lower oesophageal sphincter (61%). Nutcracker oesophagus and non-specific oesophageal motility disorders were each diagnosed in only 10% of patients with non-cardiac chest pain. In patients with dysphagia, ineffective peristalsis was the most common oesophageal dysmotility (27%), followed by achalasia and non-specific oesophageal motility disorders (18% and 14%, respectively). Achalasia and non-specific oesophageal motility disorders were the most common oesophageal motility abnormalities in patients with both chest pain and dysphagia (35% and 25%, respectively). CONCLUSIONS: The most common oesophageal motility abnormality in patients with non-cardiac chest pain is a hypotensive lower oesophageal sphincter; nutcracker oesophagus and non-specific oesophageal motility disorders are relatively uncommon; the most common oesophageal motility abnormality in patients with dysphagia is ineffective peristalsis and, for those with both dysphagia and non-cardiac chest pain, it is achalasia.

Adolescent↗
PubMed1998

'Best clinical practice': assessment of processes of care and of outcomes in the US Military Health Services System.

The National Quality Management Program of the Military Health Services System of the United States has undertaken a series of projects whose objective is the active, on-going monitoring and improvement of the effectiveness and efficiency of the care provided to a broad population that encompasses troops on active duty, retirees and dependents. The analytic activities consist of (1) identification by clinical panels of conditions and procedures of interest; (2) collection of data from electronic repositories and from charts to characterize the patients, how they are managed, the clinical outcomes they experience, the resource costs their care entails, and, from questionnaires, their functional status and level of satisfaction, and (3) generation of 'report cards' that inform organizational units down to the level of the hospital of the characteristics of their patients, their practices, and the risk-adjusted outcomes they achieve. The patterns of care employed by the hospitals that obtain the best risk-adjusted outcomes and resource utilization ('best clinical practice') are identified and made known. In addition, (4) a systematic process of developing outcomes-based practice guidelines has been devised. It intent is to serve as a decision-support tool for clinicians. Initial estimates have been obtained of the probable consequences of the application of this tool to operative interventions in childbirth. Use of the tool would result in a higher occurrence of elective Caesarean sections, a reduced rate of emergency Caesarean sections and much lower use of forceps, with an overall improvement in outcomes and lower resource costs. This program is currently in the early phases of implementation. The two principal requirements for the immediate future are (1) education of the clinical and administrative communities in the use of the data and the decision-support tools and (2) evaluation of the consequences of the use of the data by the clinical and administrative communities.

Benchmarking↗
PubMed1997

Using telematic interventions to meet older peoples' needs (ACTION).

The overall conclusion from both the focus group interviews and the survey are that carers want: more information about a range of professional services and other facilities; a central repository for information storage, access and retrieval; and local, flexible, respite facilities.

Aged↗
PubMed1997

An evaluation of introgression of Atlantic coast striped bass mitochondrial DNA in a Gulf of Mexico population using formalin-preserved museum collections.

Striped bass Morone saxatilis populations in drainages along the Gulf of Mexico coast (Gulf) were depleted in the 1950s and 1960s, probably because of anthropogenic influences. It is believed that only the Apalachicola-Chattahoochee-Flint (A-C-F) river system continually supported a naturally reproducing population of Gulf lineage. Striped bass juveniles of Atlantic coast (Atlantic) ancestry were introduced to restore population abundances in the A-C-F from the late 1960s to the mid 1970s and in many other Gulf rivers from the 1960s to the present. We previously identified mtDNA polymorphisms that were unique to approximately 60% of striped bass from the A-C-F and which confirmed the continued successful natural reproduction of striped bass of Gulf maternal ancestry within the system. However, the genetic relatedness of the extant A-C-F population to 'pure' Gulf striped bass was not addressed. In this study, we determined the frequency of a diagnostic mtDNA XbaI polymorphism in samples of 'pure' Gulf striped bass that were collected from the A-C-F prior to the introduction of Atlantic fish, that were obtained from museum collections, and that were originally preserved in formalin. PCR primers were developed that allowed for amplification of a 191-bp mtDNA fragment that contained the diagnostic XbaI restriction site. Using RFLP and direct sequence analyses of the PCR amplicons, we found no significant differences in mtDNA XbaI genotype frequencies between the archived samples and extant A-C-F samples collected over a 15-year period. This indicates that significant maternally mediated introgression of Atlantic mtDNA genomes into the A-C-F gene pool has not occurred. Additionally, we found no evidence of the unique Gulf mtDNA genotype in striped bass from extant populations in Texas, Louisiana and the Mississippi River. These results highlight the importance of the A-C-F as a repository of striped bass to restore extirpated Gulf populations and the potential use of museum collections in retrospective population studies.

Animals↗
PubMedDate not supplied

Development of anti-dsDNA autoantibodies prior to clinical diagnosis of systemic lupus erythematosus.

Anti-double stranded (dsDNA) antibodies are of considerable diagnostic value and are thought to be involved in the pathogenesis of systemic lupus erythematosus (SLE). Fluctuations in anti-dsDNA antibody levels are also used as markers for disease activity and exacerbations. In this study we sought to evaluate the anti-dsDNA antibody level in serum samples collected before the onset of SLE diagnosis. A total of 130 SLE patients were identified with stored serum samples available prior to diagnosis within the US Department of Defense serum repository. All 633 sera available from these patients were screened for anti-dsDNA antibodies using an enzyme linked immunosorbant assay (ELISA). Within this cohort 55% of cases had detectable anti-dsDNA antibodies prior to SLE diagnosis. The onset of anti-dsDNA antibodies ranged from 9.3 years before to within the same month as diagnosis (with a mean onset 2.7 years before diagnosis). In order to assess for fluctuations in anti-dsDNA levels relative to diagnosis, cases were selected with at least two positive samples, one within 6 months and a second greater than 6 months prior to diagnosis (n = 26). Seven of these cases also had samples available shortly after diagnosis (< or = 6 months) for comparison. Fifty-eight percent of the 26 cases developed a significant rise in anti-dsDNA antibody levels within 6 months of diagnosis. A significant decline in anti-dsDNA levels ensued after diagnosis (and following treatment with corticosteroids) in all seven cases with samples available. Patients with a significant rise in anti-dsDNA antibodies at diagnosis were more likely to have renal disease than those who did not (66.7% compared to 27.3%, chi2 =3.94, P<0.05). These data suggest that anti-dsDNA antibodies are present in SLE patient sera much earlier than previously suspected. In addition, the data are consistent with increases in anti-dsDNA levels contributing to the onset of clinical illness in some patients with SLE.

Antibodies, Antinuclear↗
PubMed1999

Mitochondrial small ribosomal RNA is present on polar granules in early cleavage embryos of Drosophila melanogaster.

In Drosophila, formation of the germline progenitors, the pole cells, is induced by polar plasm localized in the posterior pole region of early embryos. The polar plasm contains polar granules, which act as a repository for the factors required for pole cell formation. It has been postulated that the factors are stored as mRNA and are later translated on polysomes attached to the surface of polar granules. Here, the identification of mitochondrial small ribosomal RNA (mtsrRNA) as a new component of polar granules is described. The mtsrRNA was enriched in the polar plasm of the embryos immediately after oviposition and remained in the polar plasm throughout the cleavage stage until pole cell formation. In situ hybridization at an ultrastructural level revealed that mtsrRNA was enriched on the surface of polar granules in cleavage embryos. Furthermore, the localization of mtsrRNA in the polar plasm depended on the normal function of oskar, vasa and tudor genes, which are all required for pole cell formation. The temporal and spatial distribution of mtsrRNA is essentially identical to that of mitochondrial large ribosomal RNA (mtlrRNA), which has been shown to be required for pole cell formation. Taken together, it is speculated that mtsrRNA and mtlrRNA are part of the translation machinery localized to polar granules, which is essential for pole cell formation.

Animals↗
PubMed2000

European snapshot homeless survey: results of questions asked of passers-by in 11 European cities.

Passers-by were interviewed outside McDonalds restaurants in 11 European cities during November and December 1998. Eight questions were asked, mainly exploring the stigma levels of a particularly socially and economically excluded group (homeless people) and also the preferred remedies for homelessness. Answers varied, especially between the countries in Western Europe and those in the former Warsaw Pact countries. Stigma levels were very high in Bucharest, Kiev and Zagreb, presumably making resettlement work difficult. People in these cities saw homeless people as 'dangerous': repositories of infectious disease and likely to make unprovoked attacks. Most passers-by also believed homeless people were under threat, especially from the police, sometimes from other passers-by, from exposure to the winters and, in Cambridge, Vienna and Zagreb, from malnutrition. Suggested remedies were increased employment, improved training and increased affordable housing, rather than the imprisonment of beggars.

Attitude to Health↗
PubMed1999

Paediatrica philatelica.

The world's nations issue postage stamps with themes that their governments regard as being of significant national and international importance. The philatelic record, thus, parallels each nation's history, its themes of contemporary pride and its aspirations for the future. As children's health is one of the most important of all issues of public and political life, it is not surprising that paediatricians are permanently commemorated in many of the world's postage stamps. Hippocrates is portrayed on many of the world's stamps, as are children's illnesses and children's doctors. Paediatricians are portrayed on stamps from New Zealand, Papua New Guinea, Australia, the United States of America, the nations of Africa, Europe and the United Nations. Themes permanently recorded in the philatelic record encompass every discipline within paediatrics, including portraits of Dr Virginia Apgar (of the Apgar score), Dr Truby King (New Zealand) who was responsible for the introduction of universal postnatal nursing visits for every child, and Dr Janusz Korczak (1879-1942), the Polish paediatrician who gave his life at Treblinka in World War II in order that his child patients might not die alone. The paediatric philatelic record is thus an international repository of the chronology of child care.

Child↗
PubMed2003

Transplantation of glial cell line-derived neurotrophic factor-expressing cells into the striatum and nucleus accumbens attenuates acquisition of cocaine self-administration in rats.

Neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), may play a role in drug-induced biochemical and behavioural adaptations that characterize addiction. We found that GDNF mRNA levels are lower in the striatum of rats that chronically self-administered cocaine. Therefore, we examined the effect of transplanted cells used as a biodelivery system for GDNF on cocaine self-administration in rats. A human astrocyte-like cell line, which produces and excretes GDNF, was transplanted into the striatum and nucleus accumbens of rats. These rats showed a significantly lower number of active lever presses in the cocaine self-administration paradigm compared with control rats. Moreover, rats that received a chronic infusion of GDNF via a micro-osmotic pump also exhibited weak cocaine self-administration. Therefore, we conclude that exogenous augmentation of GDNF repositories may be useful in suppressing cocaine self-administration.

Animals↗
PubMed2000

Assessment of the non-HLA-DR-DQ contribution to IDDM1 in British Caucasian families: analysis of LMP7 polymorphisms.

AIMS: Whilst HLA-DRB1 and HLA-DQ alleles contribute to IDDM1, the major determinant of genetic susceptibility to Type 1 diabetes mellitus, other major histocompatibility complex (MHC)-encoded genes may also be involved. The LMP7 (large multifunctional proteasome 7) gene is a potential candidate. The aim of this study was to assess whether LMP7 confers susceptibility to Type 1 diabetes independently of linkage disequilibrium with HLA-DRB1 and HLA-DQ. METHODS: The diallelic LMP7 polymorphism (LMP7*A or *B) was determined in 142 multiplex families from the British Diabetic Association Warren Repository. At least one parent was heterozygous for LMP7 in 112 families and these were informative for calculation of the statistic Tsp. This gives a valid chi2 test of the null hypothesis of no association or no linkage. RESULTS: An excess of transmissions of LMP7*A was observed from parents to affected offspring and the Tsp statistic was significant for association in the presence of linkage. LMP7*A was in positive, and LMP7*B in negative, linkage disequilibrium with the HLA-DRB1*03-DQ2, DRB1*04-DQ8 (group of all DRB1*04 subtypes), DRB1*0401-DQ8 and DRB1*0404-DQ8 haplotypes, although the linkage disequilibrium coefficient (delta) value was not statistically significant for DRB1*0404-DQ8. Analysis of HLA-DR-DQ-LMP7 haplotypes and Tsp analysis of HLA-matched-homozygous parents showed no association between LMP7 alleles and Type I diabetes independent of linkage disequilibrium with HLA-DR-DQ haplotypes associated with increased risk of disease. A contribution of LMP7 alleles to susceptibility to Type 1 diabetes in subjects with low-risk HLA-DR-DQ haplotypes could not be excluded. CONCLUSIONS: LMP7 alleles do not contribute to genetic susceptibility to Type 1 diabetes in subjects with high-risk-associated HLA-DR-DQ haplotypes.

Cysteine Endopeptidases↗
PubMed2001

Size of neocortical neurons in control subjects and in Alzheimer's disease.

The aim of the present study was to estimate mean neuronal volume and absolute size distributions of the neocortical neurons in brains from controls and AD patients using stereological methods based on unbiased principles to determine whether changes in absolute cell size are part of the neuropathological pattern of Alzheimer's disease. The neocortex of 8 patients with Alzheimer's disease (AD), mean age 81.1 (68-94) y was compared with 9 nondemented controls, mean age 80.9 (65-101) y. The brains came from Johns Hopkins University Hospital (JHUH) in Baltimore, USA, the Netherlands Brain Bank (NBB), and from a large brain repository in Denmark. The rotator method was used to obtain an estimate of cell volumes providing absolute size distributions of the volume of both cell perikaryon and cell nuclei. The geometric mean volume of cell nuclei in neocortical neurons was 328 microm3 (interindividual CV = 0.15) in the Alzheimer group compared with 277 microm3 (interindividual CV = 0.17) in controls which was a statistically significant increase (P = 0.049). The perikaryal volume was 1117 microm3 in the Alzheimer group compared with 999 microm3 in controls which was a nonsignificant difference (P = 0.20). There was a highly significant correlation between the nuclear and perikaryal volumes in all individuals. The average slope of the regression lines was significantly higher in the Alzheimer patients than in the controls, illustrating that nuclear hypertrophy was more pronounced in the largest neurons.

Aged↗
PubMed1998

Pulsed-field gel electrophoresis typing of Hafnia alvei isolated from chub-packed and retail ground beef.

Thirty-eight isolates of Hafnia alvei were characterized by biochemical profiles, ribotyping and pulsed-field gel electrophoresis (PFGE) patterns. The isolates were recovered from chub-packed (19 isolates) or retail (nine isolates) ground beef, or were obtained from culture repositories (10 isolates). Biochemical profiling differentiated the 38 isolates into five groups and a commercial ribotyping method recognized 11 groups, whereas PFGE differentiated the same 38 isolates into 19 groups. These data substantiate that PFGE is a highly discriminatory tool for establishing the relatedness among Hafnia alvei strains.

Animals↗
PubMedDate not supplied

Variation of the prognostic significance of HER-2 expression in breast cancer according to tumor size.

The prognostic importance of HER-2 status in breast cancer has been investigated extensively, but findings have not been uniform across immunohistochemical studies using fixed, paraffin-embedded specimens. We speculate that studies with an overrepresentation of large tumors might not produce evidence for an independent effect of a single marker because breast tumors of larger size tend to exhibit multiple adverse attributes as the malignancy advances through the metastatic cascade. Further, it has been posited that results from certain studies of biologic markers might be generalizable only to larger tumors because tumor repositories tend to house a disproportionate number of larger tumors. To test our hypothesis that the prognostic effect of HER-2 status might be modified by the size of the tumor, we conducted a survival analysis of a nested case-case sample of 156 women diagnosed with primary breast cancer from 1983 to 1995. Relative risks (RRs) and confidence intervals (CIs) for recurrence in relation to HER-2 status were estimated using a multivariate Cox proportional hazards model. Immunohistochemistry of archival tissue was used to detect HER-2 expression. Positive HER-2 status was associated with recurrence (RR = 4.24, 95% CI 1.30-13.78) among patients with axillary lymph node-positive involvement. This analysis identified an interaction (p < 0.01) between tumor size and overexpression. Stratification by tumor size revealed an increased risk of recurrence associated with HER-2-positive tumors that were <or=2 cm in size (RR = 13.68, 95% CI 1.06-175.76), whereas no such association was observed among patients with HER-2-positive tumors larger than 2 cm. Eligible patients without available tumor tissue tended to have smaller tumors compared to study participants. Our results might partly explain the variation in evidence across HER-2 prognostic studies using fixed tissue and might apply to other putative markers of prognosis in breast cancer.

Adult↗
PubMed1994

Epidemiologic background and long-term course of disease in human immunodeficiency virus type 1-infected blood donors identified before routine laboratory screening. Transfusion Safety Study Group.

BACKGROUND: The long-term course of human immunodeficiency virus type 1 (HIV-1)-related disease among seropositive blood donors has not been described. The enrollment and epidemiologic background of HIV-1-infected donors in the Transfusion Safety Study and their immunologic and clinical progression are described. STUDY DESIGN AND METHODS: Through the testing of approximately 200,000 sera from donations made in late 1984 and early 1985, 146 anti-HIV-1-positive donors and 151 uninfected matched donors were enrolled. These two cohorts were followed with 6-month interval histories and laboratory testing. RESULTS: Seropositive donors detected before the institution of routine anti-HIV-1 screening disproportionately were first-time donors and men with exclusively male sexual contacts. The actuarial probability of a person's developing AIDS within 7 years after donation was 40 percent; the probability of a person's dying of AIDS was 28 percent. AIDS developed more often when the donor was p24 antigen-positive at donation. Over a 3-year period, significant decreases occurred in CD4+, CD2+CD26+, CD4+CD29+, and CD20+CD21+ counts, but not in CD8+ subsets, CD20+, or CD14+. CONCLUSION: The high proportions of first-time donations and exclusively homosexual men among seropositive donors suggest that test-seeking may have contributed to the high HIV-1 prevalence in the repository. Implementation of alternative test sites when routine donor screening began in 1985 may have averted many high-risk donations. The disease course in HIV-1-infected donors had the same wide spectrum of immunologic and clinical manifestations as were reported for other cohorts.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Transfusion transmission of retroviruses: human T-lymphotropic virus types I and II compared with human immunodeficiency virus type 1.

BACKGROUND: The incidence of transfusion transmission of human T-lymphotropic virus type I (HTLV-I) and HTLV type II (HTLV-II) has not been compared directly or to that of human immunodeficiency virus type 1 (HIV-1). The effects of refrigerator storage of the blood component on infectivity of the viruses needs definition. STUDY DESIGN AND METHODS: The circumstances influencing the transmission of HTLV-I, HTLV-II, and HIV-1 via blood of donors whose sera were stored in a repository and who were retrospectively documented as having been infected at blood donation were examined. Confirmation and typing of anti-HTLV positivity in donors and recipients used polymerase chain reaction, supplemented by specific peptide testing. RESULTS: Overall, 27 percent (26/95) of the recipients of blood components from anti-HTLV-I- and -II-positive donors became infected (9 with HTLV-I and 17 with HTLV-II). No recipients of acellular blood components became infected with HTLV-I or -II. There was no probable transmission by components stored > 10 days. The rates of transmission for both viruses were similar: 0 to 5 days' storage, 17 (74%) of 23; 6 to 10 days, 8 (44%) of 18; and 11 to 14, 0 (0%) of 10 (trend, p = 0.0002). In comparison, 89 percent (112/126) of the recipients of anti-HIV-1-positive blood were infected regardless of component type, and no effect on transmission occurred with storage for < 26 days. CONCLUSION: Transfusion-transmitted HTLV-I and -II are similar. The data suggest that a donor's lymphocytes become noninfectious when they lose the ability to be activated or to proliferate.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Frequency of HBV DNA detection in US blood donors testing positive for the presence of anti-HBc: implications for transfusion transmission and donor screening.

BACKGROUND: An estimate of the rate of HBV DNA-positive, anti-HBc-positive units is important for evaluating the need for anti-HBc donor screening, especially in the context of HBV NAT. STUDY DESIGN AND METHODS: HBsAg EIA-nonreactive, anti-HBc-reactive (Corzyme, Abbott Laboratories) specimens were retrieved from a repository and were retested for anti-HBc (with PRISM HBcore, Abbott Laboratories, currently under FDA review) and anti-HBs (with PRISM Ausab, Abbott Laboratories, research assay). HBV DNA testing using a PCR assay with a greater than 95 percent detection rate of less than 50 copies per mL was performed on a subset of specimens that were PRISM HBcore-reactive and were anti-HBs- negative or reactive at less than 100 IU per L. RESULTS: A total of 395 of 1231 specimens eligible by our serologic criteria were tested by PCR. Four anti-HBs-negative specimens were PCR-positive with estimated HBV DNA copy numbers of 10 per 30 copies per mL in two specimens and 50 to 100 copies per mL in two others. The HBV DNA detection rate in anti-HBs-negative specimens was 3.7 percent, and the projected rate among all Corzyme-reactive specimens was 0.24 percent, leading to an estimated yield of 1 HBV DNA-positive, anti-HBc-positive unit in 49,000 units that were otherwise eligible for transfusion (95% CI, 1 in 16,600-1 in 152,600). CONCLUSIONS: Anti-HBc screening detects HBsAg EIA-negative, HBV-infected donors at a rate comparable to the estimated residual risk for HBV window-period infections. The low viral load in the HBV DNA-positive samples suggests that minipool NAT will not detect most potentially infectious units from anti-HBc-positive donors.

Blood Donors↗
PubMed2004

Transporting cells with mobile microrobots.

Current research activities on the development of a system for transport and manipulation of biological cells with microrobots are described. If single cells in liquid are to be placed on a grid or sorted by cell type, having a system that can automatically lift, transport and release cells can significantly speed up such a tedious task. Therefore, a system is being developed that can automatically sort different cells by transporting them to different repositories. A method to recognise different types of cells is also being developed. The system consists of several components; a motorised inverted microscope, several different microrobots and a software architecture to control the whole cell manipulation workstation and to provide a user interface.

Journal Article↗