Biomedical subjects
Publications and source records attributed to R Saunders.
Hospitals have traditionally looked to income from operations, depreciation, debt, and philanthropy as their major source of revenue. This viewpoint, however, is changing as hospitals move from being the hub of the healthcare provider network to being spokes in an integrated delivery network (IDN), and the traditional tools of debt financing and revenue optimizing become less effective.
The acute phase response, cell-mediated immunity and delayed type hypersensitivity in pulmonary tuberculosis (TB) may be mediated and regulated by the synthesis and release of interleukins 1 and 6 (IL-1, IL-6) and tumour necrosis factor (TNF) alpha. To examine this, peripheral blood mononuclear cells (PBMC) from TB patients, healthy controls and socially matched controls were cultured in the presence or absence of 5 micrograms/ml lipopolysaccharide-endotoxin (LPS) for 48 hours. IL-6 in the supernatant fluids (SNF) was measured using biological and immunoassays. Spontaneous release of functionally active IL-6 was significantly increased in PBMC SNF of TB patients when compared with both healthy controls and socially matched controls (median values of 4265, 356 and 1245 pg/10(6) cells respectively, p < 0.001). PBMC of social controls produced markedly more IL-6 than those of healthy controls (p < 0.001). LPS stimulated IL-6 production showed similar patterns for TB patients, healthy and social controls (median values of 6806, 1291 and 2667 pg/10(6) cells respectively, p < 0.001). In all three groups, LPS-stimulated cells produced significantly more IL-6 than non-stimulated cultures (p < 0.001). Constitutive production of IL-6 by PBMC from TB patients implies pre-activation of cells and suggests that IL-6 may be important in the regulation of the acute phase response in TB. Discrepant IL-6 release between the two control groups may be secondary to subclinical mycobacterial infection with non-specific immunological activation in the social controls.
Unexpectedly high blood oxygen tension in intensive care patients occurring over a 5-year period were found to have been caused by an apparently normally functioning ventilator which was intermittently acting as a conduit between the oxygen and air pipelines. Responses to a circular letter sent to Quality Control Pharmacists in England and Wales suggest that similar faults may have occurred at least five times in the past 10 years. Recommendations are given for the prevention of this problem, including monitoring of gas pipeline composition.
An investigation of the mechanism of action of the antitumour agent trimelamol has established that it is an efficient interstrand DNA cross-linker in vitro, comparable to nitrogen mustards such as melphalan. Studies have shown that the cross-linking reaction is acid-catalysed but, unlike the nitrogen mustards, only partially reversible after treatment with piperidine. The bisalkylation (cross-linking) reaction appears to be concerted, and no "second arm" reaction has been detected. The results of thermal denaturation studies are consistent with general DNA binding, and suggest a preference for GC-rich sites. The acid-catalysed reaction of trimelamol with a model nucleophile (thiophenol) has also been investigated and an adduct resulting from displacement of the three carbinolamine functions has been isolated and characterized.
The stability of trimelamol (N2,N4,N6-trimethylol-N2,N4,N6-trimethylmelamine) a synthetic carbinolamine-containing antitumor drug, has been studied. Two major degradation pathways have been characterized and a unified mechanism proposed to rationalize the chemistry involved. One degradation pathway involves the consecutive loss of hydroxymethylene units by elimination of formaldehyde until the parent trimethylmelamine (4) results. An HPLC method was used to obtain kinetic data for the loss of trimelamol and to monitor the order of appearance of three degradation products. This pathway was shown to follow first-order kinetics at all pH values studied at both 18 and 37 degrees C. The second pathway involves the coupling of two trimelamol molecules via a methylene bridge to form bis(trimelamol) (6) which had been previously referred to in the literature as a "polymer". This reaction is acid catalyzed and temperature dependent. Bis(trimelamol) is virtually water insoluble and adheres strongly to glass surfaces. Finally, t1/2 values have been determined for trimelamol in aqueous solution at different temperatures, and the kinetics of formation of degradation products has been studied over a period of 30 h under a variety of conditions of pH and temperature. The data reported here are relevant to both the formulation and clinical administration of trimelamol, and may contribute to an understanding of mechanism of action and future analogue development studies.
The Philadelphia Chapter of N.E.H.A. submits the following proposal for publication. We feel very strongly about the need to formalize some staffing standards for hospitals and all related healthcare facilities. The incentive comes from the current trend in administrative philosophies to "do more with less." The less means less for the support departments whose contribution is viewed most times as less worthy because we do not directly generate revenue. Oddly enough, the revenue generators cannot make money without the non-revenue generators.
Explore the source record for details and available documents.
Hip fracture in patients under age 50 is rare, and is often not attributable solely to the energy of injury. Our aim was to determine if trabecular bone mineral density (BMD) is abnormal in young patients with hip fractures. We reviewed all hip fractures treated at our institution between 1979 and 1986 and contacted 20 patients under the age of 50 at the time of injury, all of whom wished to be studied. The mean age at the time of injury was 39 (range 24-47). Subjects were questioned for osteoporosis risk factors, classified by level of energy producing their injury, and then underwent quantitative computed tomography (QCT) bone densitometry of trabecular bone in the lumbar spine. Bone mineral density by QCT was below the mean for age in 90% of the patients, and was greater than 1 SD below the mean in 75%. Mean percentage BMD decrease from age-matched controls was 34% (P less than 0.005) in women and 19% (P less than 0.005) in men. There was an inverse correlation in the degree of BMD decrease and the energy level of injury. There was a direct correlation of the severity of BMD decrease and the cumulative number of osteoporosis risk factors. This investigation has found that 1-7 years following hip fracture, otherwise presumedly healthy young patients demonstrate a statistically significant decrease in spinal BMD from age/sex-matched controls. These data do not determine if osteopenia is the cause or the result of injury, nor do we wish to infer that measurement of bone density at one site can predict future fractures at other sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Interleukin-1 (IL-1) release from monocyte-macrophages (Mo) appears dependent on pericellular proteolysis mediated by plasmin. Thus plasminogen activator inhibitors (PAI) which bind the serine proteases responsible for the conversion of plasminogen to plasmin, may inhibit IL-1 release from Mo. We have examined the effect of purified PAI from a hepatoma cell line Hep G2, on IL-1 release from Mo with secondary effects on lymphocyte proliferation in vitro. Fast acting inhibitors of both urokinase (u-PA) and tissue plasminogen activator (two chain t-PA) were noted in harvest fluids of Hep G2 cells. These inhibitors were stable at pH 3 but lost activity at 45 degrees C. They were SDS-stable and migrated with Mr53 and 104 kDa. These properties conformed to characteristics of type-1 plasminogen activator inhibitor (PAI-1). Partially purified PAI-1 added to human Mo cultured on 125I fibrin layer both in the presence and absence of plasminogen inhibited secretion of IL-1 by Mo in response to LPS. This effect, however, did not correlate with the inhibition of plasminogen dependent fibrinolysis. This suggested a degree of sequestration and inaccessibility of membrane bound u-PA of LPS activated Mo to PAI-1. PAI-1, in addition, inhibited mitogen stimulated peripheral blood mononuclear cell (PBMC) proliferation at similar concentration ranges. This effect was abrogated by the addition of specific antisera to PAI-1. PAI-1 may be released as part of an acute phase response. In addition to influencing fibrinolysis, PAI-1 may constitute a negative feedback pathway on Mo IL-1 release and subsequent immune activation in vivo.
Explore the source record for details and available documents.
Unlike the case in rat, rabbit, and other species in which nephron formation continues into the newborn period, nephrogenesis in the guinea pig is completed well before the time of birth. Therefore, the marked increase in proximal tubule reabsorption that occurs during the postnatal period in that species can be attributed entirely to an increase in the absorptive capacity of existing nephron units. The purpose of the present morphometric studies was to correlate that change in proximal tubule function with changes in the apical and basolateral cell membrane surface areas. The apical and basolateral membrane surface densities were found to be approximately equal to each other and to remain constant throughout development. Because of increasing tubule volume, however, both membranes doubled in size between 1 and 3 wk of age and eventually increased by a factor of 3.5 in the adult. At the same time, there was little change in the length of tight function complexes measured in the plane of the luminal surface. Using previously published functional data and tubule length data, a good correlation was found between absolute absorption and total basolateral membrane surface area throughout the entire period of development in proximal tubules. Absorption per unit area of basolateral membrane was approximately 0.55, 0.41, 0.56, and 0.42 X 10(-6) nl.min-1.micron-2 in the 1st, 2nd, and 3rd wk, and in adult animals, respectively, and thus was similar to that reported for proximal tubule segments of adult rabbit and juvenile to adult rat.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Experiments were designed to test the effect of a receptor antagonist of platelet activating factor (PAF), SRI63072, on inflammatory injury induced by in situ formation of immune complexes in two vascular districts of the rat that have different structural and hemodynamic characteristics: unilateral glomerulonephritis induced by perfusion of the left kidney of preimmunized animals with cationic human IgG, and passive reversed Arthus reaction in the skin. Three days after perfusion the left kidneys of rats not treated with SRI63072 (group I) were greatly enlarged, and pale and severe exudative and proliferative lesions were present in glomeruli. Granular deposits of human IgG, rat IgG, and rat C3 were seen by immunofluorescence microscopy, and subepithelial electron-dense deposits were visualized by electron microscopy. The right kidneys were consistently normal. The animals were severely proteinuric and had increased levels of PAF in the circulation. In contrast, rats treated with SRI63072 (group II) and studied at the same interval of time developed only mild, focal glomerulonephritis in the perfused kidneys. By immunofluorescence microscopy the glomerular deposits of human IgG and rat IgG were similar in quantity and distribution to those observed in rats of group I. Despite the fact that SRI63072 did not influence the level or the activity of the rat serum complement system, the deposits of C3 were less abundant and more focal. As in animals of group I, electron-dense deposits were present at the epithelial side of the glomerular basement membrane. Proteinuria was slight, and levels of circulating PAF were not significantly increased. These effects cannot be ascribed to interference of SRI63072 with antigen "implantation," antibody binding, or local hemodynamic conditions, because the amounts of glomerular human and rat IgG were the same in treated and untreated rats; SRI63072 did not decrease the glomerular filtration rate; and SRI63072 prevented the increase in vascular permeability and the exudative lesions in passive Arthus reaction in the skin, a model less affected by hemodynamic changes than glomerulonephritis. The beneficial effect of SRI63072 indicates that PAF is an important mediator of the inflammatory process generated either in glomeruli or in the skin by in situ immune complex formation.
Disseminated histoplasmosis is predominantly a disease of the immunocompromised. However, it has been reported infrequently in patients with the acquired immunodeficiency syndrome (AIDS), and then almost exclusively from patients residing in endemic areas. We report five cases of disseminated histoplasmosis in patients with AIDS in a nonendemic area. The initial diagnosis was made by fiberoptic bronchoscopy in three patients and by bone marrow and liver biopsy specimens in one patient each. All patients had fungemia, septic shock, and multiple organ involvement. Three patients had a fulminant course and died within four weeks. Two patients had more prolonged courses, with one survival period of ten months. We conclude that patients with AIDS are at high risk to contract disseminated histoplasmosis with an extremely high morbidity and mortality. This risk is not limited to residents of endemic areas.