Simultaneous bilateral pneumothorax in an HIV-infected patient.
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Biomedical subjects
Publications and source records attributed to A Miller.
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Non-amyloid-beta component precursor (NACP) is a presynaptic protein which may play a role in amyloidogenesis in Alzheimer's disease (AD). Since an abnormal function of platelets has been demonstrated in AD, platelets could be used as a model to investigate the role of NACP in this disease. We characterized the patterns of NACP and beta-synuclein expression in a megakaryocyte-platelet system (K562). In this hematopoietic cell line, NACP expression was up-regulated during phorbol ester-induced megakaryocytic differentiation, while beta-synuclein was down-regulated. Consistent with this, NACP but not beta-synuclein was abundantly expressed in platelets. Immunogold electron microscopy of platelets showed that NACP is loosely associated with the plasma membrane, the endomembrane system and, occasionally, with the membrane of secretory alpha-granules. These findings suggest that coordinate expression of the synuclein family members may play a critical role during hematopoietic cell differentiation. Additionally, expression of the synuclein family members may be developmentally regulated during neural differentiation.
Recent evidence indicates that chronic autoimmune disease can result from breakdown of regulation and subsequent activation of self-reactive T cells. In many murine autoimmune disease systems and in the Lewis rat, antigen-specific T cells utilizing the T cell receptor (TCR) Vbeta8.2 gene segment play a major role. In the myelin basic protein-induced experimental autoimmune encephalomyelitis (EAE) model in H-2(u) mice, we had shown that T cells recognizing a peptide determinant within the framework 3 region of the Vbeta8.2 chain have a critical role in influencing the course of the disease. Here, we report experiments in another disease system, collagen II (CII)-induced arthritis (CIA) in DBA/1LacJ (H-2(q)) mice, indicating a remarkably parallel control circuit to that found for EAE. A critical role is played by CII-specific Vbeta8.2-bearing T cells in the CIA system, which we have confirmed. Animals treated with the superantigen SEB before CII administration are significantly protected from CIA. Next, we tested the ability of peptides encompassing the entire Vbeta8.2 chain to induce proliferative responses. Only TCR peptide B5 (amino acids 76-101), a regulatory peptide in EAE, induced proliferation. B5 was then used to vaccinate DBA/1LacJ mice and was shown to reduce greatly the severity and incidence of CIA as measured by joint inflammation or histology. Furthermore, similar protection was found when B5 was administered after CII immunization. It was shown that there is physiological induction of a proliferative response to B5 during CIA and that the determinant within B5 is produced from a single chain TCR construct containing the entire Vbeta8.2 chain. Finally, the regulation of CIA is discussed in the context of other experimental autoimmune diseases, especially EAE, with emphasis on what appear to be strikingly common mechanisms.
Communication Deviance (CD) characterizes the speech of schizophrenic patients and their relatives. The relationship between specific types of CD as measured from verbatim transcripts of Thematic Apperception Test protocols and attentional performance was investigated in 27 patients with schizophrenia. Assessments were conducted just prior to hospital discharge. Results revealed that a continuous performance attentional test with visually presented stimuli was most highly related to the CD factor indicating that the respondent had misperceived elements of the card. A continuous performance attentional test with auditory stimuli was found to be associated with the factor reflecting odd language use in the speaker. A measure of selective attention/executive control, from the Stroop Color-Word test, was found to be most highly related to the CD factors which involve higher level functions such as abstraction and integration of various elements of the card into a coherent story. Results suggest that CD may be a behavioral consequence of deficits in attention and executive control, and add to the growing literature suggesting that specific types of neuropsychological deficits can be linked to specific overt behaviors.
The bacteriophage N4 single-stranded DNA binding protein (N4SSB) activates transcription by the Escherichia coli final sigma70-RNA polymerase at N4 late promoters. Here it is shown that the single-stranded DNA binding activity of N4SSB is not required for transcriptional activation. N4SSB interacts with the carboxyl terminus of the RNA polymerase beta' subunit in a region that is highly conserved in the largest subunits of prokaryotic and eukaryotic RNA polymerases.
Polymerase chain reaction (PCR) assays have been developed for follicular lymphoma-associated BCL-2/J(H) translocations. Few data are available on the quantitation by PCR of these translocations in peripheral blood mononuclear cells (PBM) of follicular lymphoma (FL) patients. We report that only one of five studied FL patients had a high level of these translocations in the circulation, namely, about 35,000 translocations per 5 x 10(6) PBM. This patient was stable with an excellent performance status at the time of this assay; however, he died of leukemia 1 month later.
This article provides recommendations from the National Multiple Sclerosis Society's Clinical Outcomes Assessment Task Force. The Task Force was appointed in 1994 and charged with recommendending improved approaches for clinical outcomes assessment in future controlled clinical trials. The recommendations herein follow extensive deliberation and data analysis during 2.5 years. General principles and desirable measurement attributes were used to assess alternative measurement techniques and clinical scales. On the basis of the analysis of existing multiple sclerosis (MS) data sets, a new measurement approach is proposed. The approach is based on quantitative functional composites that consist of simple quantitative measures from the major clinical dimensions of MS combined into a single score. Quantitative functional composites are likely to provide improved precision and sensitivity in future MS clinical trials. Studies necessary to further refine quantitative functional composites as useful MS clinical trial outcomes are delineated.
Wild mice and voles were tested for Cryptosporidium during a 2-year survey at an agricultural site in Warwickshire, United Kingdom. C. parvum and C. muris, the two cryptosporidial species known to infect mammals, were detected. Prevalence figures of 22%, 21% and 13% noted for C. parvum for Mus domesticus, Apodemus sylvaticus and Clethrionomys glareolus, respectively, were higher than those recorded for C. muris at 10%, 6% and 2%. C. parvum causes the sometimes severe diarrhoeal disease cryptosporidiosis in many hosts, but the wild rodents were asymptomatic. The discovery of C. muris in A. sylvaticus and C. glareolus confirms a wider distribution in wild rodents than has previously been reported. Rodents may represent a significant reservoir of Cryptosporidium with a high potential for infection of man and livestock due to cohabitation.
The purpose of this retrospective study was to review our experience with a consecutive group of end-stage renal disease (ESRD) patients using simple strategies to increase the use of autogenous vascular access, and determine whether the current trend of using synthetic bridge-graft fistula (BGF) rather than autogenous arteriovenous fistula (AVF), could be reversed, despite an aging population and broadening criteria for hemodialysis. All patients for vascular access surgery had careful preoperative clinical examination of the arm veins with outflow occlusion to determine the venous anatomy and continuity. Where no veins were apparent or their continuity in doubt, selective preoperative venography was performed. Where veins were unsatisfactory for forearm AVF, new or modified surgical procedures to use both the basilic and cephalic veins in the upper arm were performed. Intraoperative angioscopy was used to monitor vein quality and surgical technique. Ninety-eight primary vascular access procedures were performed in 76 patients, 75 (76.5%) AVF (forearm, n = 41; upper arm, n = 34) and 23 (23.5%) BGF. Forty-one of 76 (54%) had already had at least one previous access procedure prior to this study. More than one access procedure was needed in 16 patients. Preoperative venography was performed in 22 (22.4%) and intraoperative angioscopy in 45 (45.9%) of the 98 procedures. The number of revisions required to maintain patency was significantly higher for BGF (37 revisions in 14/23) than AVF (16 revisions in 13/75) (p < 0.0001, Poisson test) with an annualized secondary revision rate of 1.168 for BGF and 0.173 for AVF (p < 0.0001, Poisson test). AVF had both longer primary (p = 0.0001, log rank test) and secondary patency (p = 0.038, log rank test) than BGF. AVF as the primary vascular access can be significantly increased and the current trend of using BGF reversed with the use of simple clinical strategies to evaluate the suitability of the arm veins for vascular access.
OBJECTIVES: A case-control study was undertaken to examine the association of cyclic mastopathy with premenstrual syndrome and prior breast health. STUDY DESIGN: A total of 34 women with severe cyclic mastopathy (cases) and 29 women with no significant breast symptoms (controls) prospectively recorded breast pain and swelling and symptoms of premenstrual syndrome during one menstrual cycle. They also provided information on past breast health. The two study groups were compared by use of standard statistical methods. RESULTS: Women with cyclic mastopathy reported more frequent consultations with physicians for specific breast lumpiness (p = 0.02) or generalized lumpiness (p = 0.004) and for all breast problems (p = 0.0001) and more frequent mammograms (p = 0.04), surgical breast biopsies (p = 0.06), and breast needle aspirations (p = 0.05). Premenstrual symptoms were more severe in women with cyclic mastopathy; this was most pronounced for physical symptoms (water retention and breast symptoms, p < 0.001) but also present for negative affect, behavior change, and impaired concentration (p < 0.05). CONCLUSIONS: Women with cyclic mastopathy have a spectrum of breast concerns and they undergo more frequent breast investigations than do women without the disorder. Most symptoms of premenstrual syndrome are also more severe in women with cyclic mastopathy.
This brief case report describes the successful outcome after surgical excision of multiple adventitial cysts of the popliteal artery in a 75-year-old man with rapidly worsening claudication. It highlights several unsettled points concerning the diagnosis, cause, and management of cystic adventitial disease of the popliteal artery and compares duplex ultrasound, computed tomography, and magnetic resonance angiography in the noninvasive diagnosis and treatment of this condition.
PURPOSE: Surgical outcome data are generally reported as raw morbidity and mortality rates, which do not necessarily reflect quality of surgical care. The Society for Vascular Surgery has led this area with recommendations by the Ad Hoc Committee on Reporting Standards to establish standardized methods of outcome assessment in vascular surgery. The purpose of this study was to evaluate a new method for evaluating the overall quality of surgical care, which includes surgeon, nursing, and hospital system performance. The goal of the method is to identify problem areas in surgical practice that can be targeted for focused improvement to improve outcome. METHODS: A database of more than 9000 general and vascular surgical cases was compiled over a 3-year period. Every postoperative complication was tabulated prospectively by a surgical nurse on a daily basis. Fifty clinically significant complication types specific for vascular surgery patients were identified from a list of 151 postoperative events by a panel of vascular surgeons and were grouped into nine broad categories (vascular, cardiac, pulmonary, etc.). These complications reflect the entire continuum of postoperative care, including surgeon, nursing, and hospital system performance. Each complication type was further stratified into four grades (mild, moderate, severe, death) and assigned a SCOUT severity score from 0 to 100 (0, no complication; 100, death) by the panel of surgeons. For case of data collection and monitoring of outcome, a software program was developed to run on a laptop computer and includes medical history, risk factors, pertinent laboratory data, and the preassigned SCOUT severity scores for measuring outcome. In this study, 170 major vascular procedures performed over the previous 12-month period were prospectively evaluated usig the SCOUT method in an attempt to more easily identify problem areas of practice. In-hospital morbidity and 30-day mortality results were examined. RESULTS: One hundred sixteen postoperative complications were identified in the 170 patients, with an overall morbidity rate of 51% and a 30-day mortality rate of 1.8%. Fifty-three percent of the complications were "mild" and required minimal intervention or observation only. Abdominal aortic aneurysm repair was associated with the highest morbidity rate (mean SCOUT score, 384.35), whereas distal extremity bypass grafting had the lowest morbidity rate (mean SCOUT score, 114.4). However, subgroup analysis demonstrated that cardiac events accounted for 52% of the morbidity associated with distal extremity bypass but only 34.7% of the morbidity associated with abdominal aortic aneurysm repair (p < 0.05). CONCLUSIONS: The SCOUT score is a new technical quality of care measure that can objectively quantify surgeon and other hospital system-related performance. The SCOUT score allows the surgeon to identify problem areas that can then be targeted for improvement to positively affect outcome.
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BACKGROUND: A relationship between the anticonvulsant and antidepressant properties of electroconvulsive therapy (ECT) has been hypothesized. The goal of this study was to see whether the anticonvulsant effects of ECT could be measured in a clinical setting and whether there was any relationship between the anticonvulsant effects of ECT and the antidepressant response to it. METHODS: We examined the temporal relationship between change in seizure duration (as an index of anticonvulsant activity) and improvement in Hamilton Rating Scale for Depression scores in a retrospective sample of 114 depressed patients who received 145 courses of ECT. A linear mixed effects model was utilized for analysis so that the repeated measures nature of the data could be taken into account. RESULTS: Both seizure duration and depression scores decreased significantly through the course of ECT. However, no evidence was found for a relationship between decrease in seizure duration and clinical improvement as measured by Hamilton ratings. CONCLUSIONS: The process underlying the reduction in seizure duration through a course of ECT may not be related to antidepressant efficacy.
Seventy-three patients with hematological cancers undergoing allogeneic bone marrow transplantation (BMT) were evaluated for event-free survival (EFS) and toxicity. All received 36 g/m2 cytosine arabinoside (HDA) and 1200 cGy fractionated total body irradiation (TBI). We assessed the association of EFS and toxicities with the following risk factors; age, gender, diagnosis, initial relapse risk and patient-donor histocompatibility. The EFS probability is 33% at 800 days post-BMT. Twenty-six patients (36%) died of toxicity within 100 days and 14 (19%) have relapsed. EFS was inversely associated with age (P < 0.0001) and initial relapse risk (P = 0.007). The risk of pulmonary (P = 0.023) and hepatic toxicity (P = 0.011) increased with age. Diagnosis other than acute lymphoblastic leukemia (ALL) was a risk factor (P = 0.015) for graft-versus-host disease (GVHD); and fewer ALL patients died from toxicity (P = 0.014). The probability of sepsis within 100 days post-BMT correlated (P = 0.007) with initial relapse risk. We conclude: (1) the lower EFS and greater pulmonary and hepatic toxicity associated with increasing age indicate a need for less toxic regimens that maintain high antileukemic efficacy for older patients; (2) the high GVHD and sepsis rates seen in certain categories of patients indicate a need for careful definition of eligibility criteria for this still highly toxic treatment.
The number of mice housed in a cage was found to exert a major impact on immune function in male mice. Lymph node cells from hen lysozyme (HEL)-primed C57BL/6 male mice, housed in groups of 6/cage or individually, were tested for T-cell proliferative response. Group-housed males showed markedly lower responses than age-matched females. However, in males housed singly for 4-15 weeks, responses were considerably higher, approaching those of female controls. To examine the cellular site of action of the housing effect, the efficiency of splenic antigen-presenting cells (APC) was examined. APC from grouped males were considerably less efficient than APC from females, whereas males housed singly had increased APC function, reaching female levels. Our results demonstrate that environmental manipulation can profoundly modulate cellular immunity, and provide a first mechanistic indication that APC function is a major target for this modulation.
Extensive research is under way to develop pharmacotherapeutic agents that will prevent the exacerbations and the progression of neurologic disability associated with multiple sclerosis (MS). The most intensive research strategy has involved agents intended to limit demyelination by reducing inflammation and modifying the immune response. In this category are interferon beta-1b, the first compound approved for use outside of clinical trials; interferon beta-1a; and copolymer 1. Experimental agents include other interferons, methotrexate, linomide, monoclonal antibodies, T-cell receptor peptides, and 2-chlorodeoxyadenosine. Although they have been used effectively to treat exacerbations of MS, corticosteroids and corticotropin are now under evaluation as disease-modifying agents. A second strategy, enhancing remyelination by limiting demyelination and oligodendrocyte injury, is represented by protein growth factors. A third therapeutic approach, improving conduction in demyelinated fibers, is represented by the potassium channel blockers 4-aminopyridine and 3,4-diaminopyridine.
A case of a teres minor myopathy causing chronic lameness in a five-year-old working labrador retriever is described. Ultrasonography was used to assist in detection of the condition and a definitive diagnosis was made by histological examination after muscle excision. Medical treatment was ineffective, but excision of the affected muscle resulted in complete resolution of the lameness with no apparent adverse affects on joint function. The aetiology of this condition is unknown.