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Biomedical subjects

B Gray

Publications and source records attributed to B Gray.

At least 55 records · Page 3Linked to original sources
PubMed1997

Development of a reverse transcription-polymerase chain reaction assay for diagnosis of lymphocytic choriomeningitis virus infection and its use in a prospective surveillance study.

Lymphocytic choriomeningitis virus (LCMV), which is one of several arenaviruses that are pathogenic for humans, causes encephalitis and meningitis in man. In this study, single-stage and nested reverse transcription-polymerase chain reaction (RT-PCR) assays were developed that targeted the GPC and N genes of LCMV. Both assays detected < 1 TCID50 unit of LCMV. These assays were used to measure the incidence of LCMV infection by testing cerebrospinal fluid (CSF) samples with > or = 10 leukocytes/microl collected over 1 year from patients undergoing lumbar puncture for diagnostic reasons at two Birmingham hospitals. Samples were tested for the presence of LCMV RNA by using the RT- PCR assay and for LCMV-specific IgM antibody by using an ELISA assay. None of the specimens collected from 813 patients was positive by either assay. Although no cases of acute infection were detected, 4% (11/272) of serum collected from a subset of patients was positive for LCMV-specific IgG. A significantly greater rate of seropositivity was found among subjects over 60 years of age (9.4%; P < 0.025) than was found in younger subjects (2.4% at 30-59 years of age; 0% at < 30 years of age). These data suggest that serious central nervous system disease due to LCMV infection is not common in this population. The high rate of seropositivity in those over 60 years of age suggest that infection was once more common.

Adult↗
PubMed1996

Reciprocal regulation of mucosal surface IgA+ B cells by Ig receptor cross-linking and CD40 ligand.

In the present study, we analyze the role of Ig receptor cross-linking in T cell-dependent stimulation of both preswitch (surface IgM+ (sIgM+/sIgD+) B cells and postswitch (sIgA+) B cells. We demonstrate that purified sIgA+ B cells pretreated with anti-IgA-dextran at low concentrations (10 and 100 ng/ml) exhibited an increased response to activated T cells, whereas pretreatment with higher doses (1 and 10 micrograms/ml) led to a profound suppression of IgA secretion (> or = 90%). The suppressive effect of anti-IgA-dextran was accentuated in the presence of IL-2 and attenuated in the presence of IL-4. Anti-IgA-dextran pretreatment had no effect on sIgA+ B cell survival. sIgM+/sIgD+ B cells pretreated with anti-IgD-dextran or anti-IgM-dextran did not show significant inhibition. The increased susceptibility of sIgA+ B cells, but not of sIgM+/sIgD+ B cells, to Ig cross-linking-mediated suppression was confirmed in cross-linking studies with the same Ab (anti-kappa-dextran). Importantly, anti-IgA-dextran-mediated suppression could be reversed by stimulation of sIgA+ B cells with fibroblasts expressing CD40L; such a reversal required persistent exposure to cells expressing high levels of CD40L. These studies imply that Ig receptor cross-linking renders postswitch sIgA+ B cells unresponsive to subsequent stimulation via activated T cells, but this unresponsiveness is overcome by a persistent high level CD40L signal.

Animals↗
PubMed1996

Differential activation requirements of isotype-switched B cells.

In the present studies, we compared the activation requirements of sIgM+/sIgD+ B cells with those of isotype-switched sIgM-/sIgA+ B cells. We found that whereas sIgM+ B cells respond to T cell-independent (TI) and T cell-dependent (TD) Ag with no significant bias toward one stimulus, sIgA+ B cells were deficient in their ability to respond to antigen receptor cross-linking but responded remarkably well to TD stimuli. Thus, dextran-conjugated anti-IgA antibody (anti-IgA-dextran), anti-kappa-dextran, or various immobilized anti-IgA antibodies (Ab) induced only low-level IgA B cell proliferation and no IgA secretion in the presence of various lymphokines; in marked contrast, sIgA+ B cells responded to cognate and noncognate T cell stimulation as well as to stimulation by CD40 ligand-bearing fibroblasts by secreting large amounts of IgA (up to 240 000 ng/ml per 10(5) cells). This pattern of sIgA+ B cell responsiveness was noted with both germinal center peanut agglutininhi (PNAhi) and non-germinal center PNAlo B cells. In confirmation of these results, whole Peyer's patch or lamina propria cell populations containing less than 15% sIgA+ B cells stimulated with a noncognate T cell stimulus or T cell membranes secreted mainly IgA (68%-94% of the total Ig secreted) and relatively little IgM. The strict T cell dependence of IgA B cell activation and differentiation provides important insights into immune responses of mucosal tissues and must be considered in the development of vaccines, particularly those designed to stimulate mucosal tissues containing large numbers of isotype-switched B cells.

Animals↗
PubMed1996

Treatment principles in advanced colorectal cancer.

BACKGROUND: Colorectal cancer is an important disease in the Australian community. Whilst there has been much discussion about the appropriate management of local disease, particularly with respect to the issue of adjuvant therapy, there has been relatively little local discussion of treatment options in metastatic colorectal cancer. METHODS: The critical principles underlying treatment in this setting are briefly outlined in the present article, indicating wherever possible what options could be considered standard, and based on the available literature, which approaches must still be considered experimental at this time. RESULTS: Overall, the results of treatment in this group of patients remain poor. CONCLUSION: Further clinical trials are required to address the issues affecting patients with metastatic colorectal cancer.

Colorectal Neoplasms↗
PubMed1996

Endovascular management of unusual aneurysms of the axillary and subclavian arteries.

PURPOSE: Aneurysms of the upper extremity arteries are uncommon and may be difficult to manage with standard surgical techniques. We report the exclusion of three axillary-subclavian aneurysms with covered stents. METHODS AND RESULTS: Palmaz stents were covered with either polytetrafluoroethylene (2 cases) or brachial vein and deployed to exclude pseudoaneurysms in 1 axillary (ruptured) and 2 left subclavian arteries. Two of the patients had advanced cancer and died within 52 days and 3 months of treatment, but their aneurysms were occluded at the time of their death. The repair in the third patient is patent at 9 months. CONCLUSIONS: Endovascular exclusion of axillary and subclavian aneurysms with covered stents may offer a useful alternative to operative repair, particularly in patients with significant comorbidities.

Aged↗
PubMed1996

Charity and community: the role of nonprofit ownership in a managed health care system.

As American medicine has been transformed by the growth of managed care, so too have questions about the appropriate role of nonprofit ownership in the health care system. The standards for community benefit that are increasingly applied to nonprofit hospitals are, at best, only partially relevant to expectations for nonprofit managed care plans. Can we expect nonprofit ownership to substantially affect the behavior of an increasingly competitive managed care industry dealing with insured populations? Drawing from historical interpretations of tax exemption in health care and from the theoretical literature on the implications of ownership for organizational behavior, we identify five forms of community benefit that might be associated with nonprofit forms of managed care. Using data from a national survey of firms providing third-party utilization review services in 1993, we test for ownership-related differences in these five dimensions. Nonprofit utilization review firms generally provide more public goods, such as information dissemination, and are more "community oriented" than proprietary firms, but they are not distinguishable from their for-profit counterparts in addressing the implications of medical quality or the cost of the review process. However, a subgroup of nonprofit review organizations with medical origins are more likely to address quality issues than are either for-profit firms or other nonprofit agencies. Evidence on responses to information asymmetries is mixed but suggests that some ownership related differences exist. The term "charitable" is thus capable of a definition far broader than merely the relief of the poor. While it is true that in the past Congress and the federal courts have conditioned the hospital's charitable status on the level of free or below cost care that it provided for indigents, there is no authority for the conclusion that the determination of "charitable" status was always so limited. Such an inflexible construction fails to recognize the changing economic, social and technological precepts and values of contemporary society. -Circuit Court of Appeals, District of Columbia, Eastern Kentucky Welfare Rights Organization v. Simon (1974).

Charities↗
PubMed1996

The use of community nurses for home peritoneal dialysis: is it cost-effective?

In the late 1970s, continuous ambulatory peritoneal dialysis was first introduced as a mode of treatment for patients with end-stage renal disease. Since that time many patients, themselves or with the help of family members, have routinely performed the therapy at home. There are now 2935 home peritoneal dialysis patients in Canada (36% of the total dialysis population). Today, however, the average patient on dialysis is likely to be older and have other complicating illnesses; moreover, patients may live alone, or have family members who are working. Over the past three years, through the use of innovative assistive devices and strong educational links with community nursing agencies, we have been able to manage peritoneal dialysis patients with complex needs in the home. We performed a retrospective analysis of 18 patients, with severe comorbid conditions, who were managed in the home with the help of community nurses. We will show that this is an economic, efficient, and effective method of caring for home dialysis patients with severe disabilities. Home care agencies need our support so that they can continue to help us manage the complex peritoneal dialysis patient in the 1990s.

Adult↗
PubMed1996

Designing dialysis prescriptions.

Our objective was to determine the adequacy of dialysis in our patients currently on home peritoneal dialysis and develop a program of surveillance aimed at maintaining tKt/V (Kt/V calculated from peritoneal clearance and residual renal function) greater than 2.0 as recommended by the CANUSA study. Eighty-nine patients were entered into our study between September, 1993 and September, 1995. Initial dialysate volumes used during the training period were determined by using a patient-specific protocol. Two weeks after discharge a standard peritoneal equilibration test was performed to determine total Kt/V using a computer program, and dialysis prescriptions were changed to achieve a tKt/V > 2.0 in those patients who had tKt/V < 2.0, and those with tKt/V > 2.0 were followed without further intervention. Of the patients who had initial assessments, 33.7% had tKt/V of 1.65 and 66.3% had tKt/V of 2.46, and the difference was mainly due to residual renal function. Forty-four patients were started on continuous ambulatory peritoneal dialysis (CAPD), of whom 34% had tKt/V < 2.0 and 66% had tKt/V > 2.0, and of the 36 patients on continuous cycling peritoneal dialysis (CCPD), 30.5% had tKt/V < 2.0 and 69.5% had tKt/V > 2.0. The cost of changing dialysis prescriptions is less with CCPD than with CAPD, and a 0.8-1.0 L increase in dialysate volume will increase peritoneal Kt/V (dKt/V) by 0.1 on average. Patients weighing less than 53 kg can achieve a dKt/V > 2.0 even in the absence of residual renal function, but as body weight increases there is greater dependence on residual renal function to achieve adequate dialysis. We have been able to maintain patients on adequate dialysis (tKt/V > 2.0) by checking peritoneal clearance and residual renal function initially and on a regular basis. Whether a tKt/V > 2.0 will be sufficient to maintain health and well-being of our patients will require a longer period of observation.

Adult↗
PubMed1995

Delayed myelopathy after trivial neck injury in a patient with a cervical neurenteric cyst.

BACKGROUND: Neurenteric cysts are rare spinal lesions of congenital origin. They usually present insidiously with a long history of local spinal pain, radiculopathy and myelopathy. We report a 14-year-old male with a high cervical neurenteric cyst who developed a progressive myelopathy after minor neck trauma. Full recovery followed a partial cyst excision and decompressive procedure. SIGNIFICANCE AND CONCLUSION: The possible pathogenic mechanisms for this unusual presentation include hemorrhage into the cyst, sudden mechanical compression from abnormal spinal movement of a chronically distorted and compressed spinal cord, or an increase in the size of the cyst secondary to accumulation of cyst fluid. In this case a small increase in the cyst size may have resulted in increased mechanical distortion and spinal cord dysfunction on a compressive and ischemic basis.

Adolescent↗
PubMed1993

Reactions of active oxygen and nitrogen species studied by EPR and spin trapping.

The reactions of hydrogen peroxide (H2O2) with nitrite (NO2-) and of superoxide (O2-.) with nitric oxide (NO.) were studied using EPR and spin trapping techniques. These reactions reportedly have a common peroxynitrite (OONO-) intermediate. It has been suggested that this intermediate when protonated rapidly decomposes producing hydroxyl radicals (.OH) and the nitrogen dioxide radical (NO2.). The production of .OH in the reaction between H2O2 and NO2- was confirmed in spin trapping experiments using the spin trap 5,5-dimethyl-1-pyrroline-1-oxide (DMPO). H2O2 and NO2- were mixed at neutral pH and then the pH was decreased to pH 3-3.5 in the presence of DMPO or DMPO and ethanol. In these experiments, the EPR spectrum of the DMPO-OH adduct was obtained in addition to a weak EPR spectrum consisting of a triplet of triplets (a N = 1.415 mT and a N beta = 0.35 mT) indicating the addition of a nitrogen centered radical to DMPO. The formation of .OH was confirmed using ethanol as an .OH scavenger. The DMPO-hydroxyethyl adduct was produced from the reaction of .OH with ethanol. However, in experiments using an excess of ethanol, the formation of DMPO-OH was not prevented. This suggests that the DMPO-OH formed in the decomposition of HOONO does not entirely originate from a direct addition of .OH to DMPO. The reaction of O2-. with NO. was carried out in deaerated and air-saturated solutions at pH 12.3 where the dismutation of O2-. is minimal. The pH was then decreased to pH 3-3.5 in the presence of DMPO or DMPO and ethanol. In these experiments, the most prominent EPR spectrum obtained was a triplet of triplets (aN = 1.415 mT and a beta N = 0.35 mT) suggesting the addition of a nitrogen centered radical to DMPO. The formation of DMPO-OH was minimal and there was no formation of DMPO-hydroxyethyl adducts in the presence of ethanol. The results suggest that NO. in solution yields additional reactive species which act as nitrating agents in the presence of DMPO.

Electron Spin Resonance Spectroscopy↗