Evan's syndrome complicating multicentric Castleman's disease -- dramatic response to rituximab.
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Biomedical subjects
Publications and source records attributed to M Horgan.
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BACKGROUND: The increasing clinical application of viral load assays for monitoring viral infections has been an incentive for the development of standardized tests for the hepatitis C virus. OBJECTIVE: To develop a simple model for the prediction of baseline viral load in individuals infected with the hepatitis C virus. METHODOLOGY: Viral load quantification of each patient's first sample was assessed by RT-PCR-ELISA using the Roche MONITOR assay in triplicate. Genotype of the infecting virus was identified by reverse line probe hybridization, using amplicons resulting from the qualitative HCV Roche AMPLICOR assay. RESULTS: Retrospective evaluation of first quantitative values suggested that 82.4% (n=168/204) of individuals had a viral load between 4.3 and 6.7 log(10) viral copies per ml. A few patients (3.4%; n=7/204) have a serum viremia less than the lower limit of the linear range of the RT-PCR assay. Subsequent, prospective evaluation of hepatitis C viral load of all new patients using a model based on the dynamic range of viral load in the retrospective group correctly predicted the dynamic range in 75.9% (n=33/54). CONCLUSION: The dynamic range of hepatitis C viremia extends beyond the linear range of the Roche MONITOR assay. Accurate determination of serum viremia is substantially improved by dilution of specimens prior to quantification.
Mastery motivation refers to the intrinsic motivation children have to interact with their environments in order to learn about them. It appears early in life, and has been regarded by many researchers as a key motivator for development. It has also been suggested that young school age children with Down syndrome show lowered motivation to perform tasks. It is important to know if this low motivation is present from the start, or develops as a result of environmental experiences; studies of mastery motivation have been one way of investigating this issue. However definitions of mastery motivation, and hence empirical studies, have varied. Thus this paper starts by revisiting the issues surrounding definition and measurement. There is general agreement on some issues: that mastery motivation is intrinsic, that it is manifest in different behaviours as the child develops, that there are individual differences in mastery behaviour, and that these are affected by environmental factors. There is also current agreement that it is essential to remove the confound of differing levels of developmental competence by using individualized measurement. However there is disagreement about which behaviours best index mastery motivation. Some empirical work with infants with Down syndrome is reviewed, and results from a recent longitudinal study on the development of mastery motivation are presented. The results concurred with most others in the recent literature, suggesting that low mastery motivation is not inevitable in infancy in Down syndrome. Infants with Down syndrome showed similar patterns of development as typically developing children, with slight delays. It is argued that longitudinal studies are needed to demonstrate such patterns of development. As the children developed from 6 to 24 months mental age there was no evidence for decreasing levels of mastery motivation. Thus there was no support for the view that more failure experiences impact on levels of mastery motivation. In contrast caregivers did see their young children with Down syndrome as less object mastery oriented than did caregivers of typically developing children. The caregivers of children with Down syndrome were also significantly more directive in their interactions with their children, and there was some suggestion that individual differences in mastery behaviours were related to levels of mastery behaviours in their children. The final section speculates on reasons for these results, and makes suggestions for future work.
The number of HIV positive women becoming pregnant in Ireland is increasing, with many pregnancies occurring in women from countries of high HIV prevalence. The management of such patients offers the challenge of reducing the risk of maternal-fetal transmission of HIV infection, avoiding fetal-infant toxicities, and maintaining future maternal antiretroviral options. Guidelines for the optimal management of HIV disease in pregnancy have been produced by a subgroup of the Irish Infection Society consisting of GenitoUrinary Medicine and Infectious Diseases Consultants. They are based on currently available international data and guidelines. The national guidelines offer a broad management outline for HIV positive pregnant patients. Ultimately, each patient is assessed individually by a multidisciplinary team, and a careful plan for antenatal, intrapartum, and postpartum care is determined.
OBJECTIVE: To report the occurrence of acute appendicitis as a possible manifestation of the immune restoration inflammatory syndrome (IRIS) following the commencement of highly active antiretroviral therapy (HAART) in HIV patients. DESIGN: Case-note review of HIV patients on HAART with acute appendicitis. METHODS: Review of HIV markers, antiretroviral therapy and abdominal ultrasound results of four HIV patients with acute appendicitis and the histopathology reports on the appendix in two of the patients. RESULTS: From a population of approximately 350 HIV patients on HAART, we found four patients who developed acute appendicitis within 6 months of commencing or changing HAART. CONCLUSION: Acute appendicitis occurring in HIV patients on HAART may represent a variant of IRIS. Further immunohistopathological and epidemiological evaluation will be needed to define this relationship fully.
Visualization of an aneurysm and its associated vessels is necessary for the proper application of aneurysm clips. Microscopes provide binocular magnification and excellent illumination but often visualization is obscured by overriding vessels and the limitation of the operative approach. If this occurs the aneurysm may be incompletely clipped or small perforators may be included in the clip. In an attempt to improve visualization during aneurysm clipping we have incorporated a small endoscope into the aneurysm clip applicator so that the tips of the clip can be observed at all times. Here we report our initial experimental results with this instrument.
Sexually transmitted diseases have the greatest impact on the health of women. They are frequently asymptomatic, so screening for infection is important in preventing the long-term sequelae which include infertility, ectopic pregnancy, and chronic pelvic pain. HIV continues to increase in the female population and the gynecologic complications associated with it are unique to this population. Use of zidovudine in pregnant HIV-infected women has substantially decreased the rate of vertical transmission of HIV infection. The epidemiologic synergy between HIV and STDs is well recognized and prevention of one is dependent on prevention of the other.
We describe a case in which a patient infected with the human immunodeficiency virus (HIV) with high plasma viral titers underwent an arthroscopic partial meniscectomy allowing us the opportunity to measure the HIV titer of serial aliquots of the arthroscopic effluent using the polymerase chain reaction. Two out of six aliquots were found to be HIV positive with 598 and 486 viral copies per milliliter noted. The plasma viral load at the time of surgery was 149,000 copies per milliliter, whereas the prearthroscopy synovial fluid failed to show any detectable virus. This is the first report to our knowledge of HIV detected in an arthroscopic effluent. The clinical implications for the arthroscopist are also discussed.
Fas is a cell surface receptor that mediates apoptosis, and Fas mRNA has been demonstrated in hepatocytes. MRL/MP-lpr/lpr mice carry the mutated lymphoproliferation-associated gene, lpr, that codes for truncated Fas protein, resulting in reduced apoptotic potential in some circumstances. Phenobarbital treatment of experimental animals induces cytochrome P450 enzymes, and thus acts as a growth stimulus to the liver with both hyperplasia and hypertrophy; cessation results in reversion of liver to normal size with apoptosis playing a role. This study has determined the respective contributions of atrophy and apoptosis to this involution in Fas-defective and normal-FAs bearing animals. Between the first day and the fifth day after phenobarbital cessation, the weights of both Fas-defective (lpr/lpr) livers and control (lpr/+) livers reduced. Hepatocyte hypertrophy gradually reverted in both categories of mouse and this was the greater contribution to reduction in liver size. In lpr/lpr animals, there was a consistent level of apoptosis which remained relatively constant, while numbers of apoptotic cells in control livers increased over the period. This investigation has shown that in liver, a mechanism to execute apoptosis is operative even in Fas-defective mice, but it is not sensitive to signals activated by the removal of the growth stimulus. This is in contrast to mice which can mount a Fas-mediated response; thus a separate apoptotic pathway is indicated.
As an increasing number of women become infected with the human immunodeficiency virus (HIV), it is important to understand their expectations regarding the health care services they receive. In 1995 a new centre was opened at an academic centre in St Louis, Missouri, to provide comprehensive care to women with HIV. To assist in the Centre's development, we interviewed 50 of 119 enrolled clients (42%) using a survey instrument focusing on what they consider important in their care. In response to open-ended questions, clients most often mentioned wanting a sense of personalized caring and respect by medical staff (n = 28, [56%]), having someone to talk to about problems (n = 28, [56%]), honest answers about their condition (n = 23, [46%]), medical follow-up (n = 21, [42%]), reduced barriers to care (n = 20, [40%]), and education about their condition (n = 15, [30%]). The highest-ranked aspects of care were seeing the doctor, learning about their condition, and being seen in a pleasant environment (92% [n = 46%]). Significant differences were found in some responses when analysed according to race, educational level, and severity of disease. It is important that programmes delivering health care services to women with HIV provide services that take into account their individualized needs. Ideally, this requires incorporation of a multidisciplinary team to provide psychological and social support, patient education, and medical management.
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BACKGROUND: CADU/CIS (Clinical and Administrative Decision-support Utility and Clinical Information System) is a clinical decision-support workstation that allows large volumes of clinical information systems data to be analyzed in a timely and user-friendly fashion. CARE PROCESS MEASUREMENT: For any given disease, subgroups of patients are identified, and automated, customized "clinical pathways" are generated. For each subgroup, the best practice norms for use of test and therapies are identified. Practice style variations are then compared to outcomes to focus inquiry on decisions that significantly affect outcomes. CASE STUDY: INTESTINAL OBSTRUCTION: Graduate Health Systems, a multisite integrated provider in the Philadelphia area, has used CADU/CIS to improve quality problems, reduce treatment-intensity variations, and improve clinical participation in care process evaluation and decision making. A task force selected intestinal obstruction without hernia as its first study because of the related high-volume and high-morbidity complications. Use of a ten-step method for clinical performance improvement showed that the intravenous administration of unnecessary fluids to 104 patients with intestinal obstruction induced congestive heart failure (CHF) in 5 patients. Task force members and other practicing physicians are now developing guidelines and other interventions aimed at fluid use. Indeed, the task force used CADU/CIS to identify an additional 250 patients in one year whose conditions were complicated by CHF. CONCLUSION: A clinical decision support tool can be instrumental in detecting problems with important clinical and economic implications, identifying their important underlying causes, tracking the associated tests and therapies, and monitoring interventions.
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We isolated two recombinant baculoviruses each of which expresses a varicella-zoster virus (VZV) homolog of one of the seven herpes simplex virus type 1 (HSV-1) genes required for DNA replication. We performed transient origin-dependent DNA replication assays in insect cells in which we substituted a baculovirus which expresses a VZV protein for a baculovirus which expresses its HSV homolog. VZV gene 51 protein was found to be able to support origin-dependent DNA synthesis when it was substituted for UL9, the HSV-1 origin-binding protein (OBP). This occurred whether an HSV-1 or a VZV origin-containing plasmid was used in the assay. These results suggest that VZV gene 51 protein is able to interact with the HSV replication machinery, and in light of the extensive structural divergence of these proteins, it suggests that initiation of VZV and HSV-1 DNA synthesis may involve a limited number of interactions between the OBP and other replication factors. Substitution of infected-cell protein 8 (ICP8), the major single-stranded DNA-binding protein of HSV-1, with VZV gene 29 protein, however, did not result in amplification of plasmids containing either an HSV-1 or a VZV origin. In the absence of ICP8, addition of both VZV gene 51 protein and gene 29 protein was also negative for origin-dependent replication whether or not UL9 was present. Although demonstration that our baculovirus-expressed VZV gene 29 protein is functional for DNA replication will await development of a VZV replication system, our results suggest that VZV gene 29 protein is unable to interact functionally with one or more of the HSV replication proteins. This approach should contribute to efforts to define the interactions among the alphaherpesvirus DNA replication proteins.
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Three cases of cryptococcal meningitis in patients with HIV infection are described. A high index of suspicion is required for diagnosis. India ink preparation and culture of the CSF for cryptococcus is mandatory in HIV seropositive patients irrespective of the CSF white cell count and biochemistry.
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