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Biomedical subjects

D McLaughlin

Publications and source records attributed to D McLaughlin.

At least 37 records · Page 2Linked to original sources

The Minnesota Clinical Comparison and Assessment Project.

Efforts to quantify and improve the effectiveness and efficiency of health care services are critical to the health care system in the United States. Essential components of these efforts are clinician involvement and support and reliable clinical information systems. Organized medicine and the hospital industry in Minnesota have initiated and funded the Minnesota Clinical Comparison and Assessment Project (MCCAP) to begin to document, compare, and improve health care services. Through MCCAP, a forum, comprising leaders in the Minnesota health care community, oversees efforts to collaboratively identify and address quality of care. In addition, MCCAP will adapt guidelines for specific conditions/procedures, collect hospital-level data on clinical practices in the state relative to those conditions/procedures, and provide feedback so that physicians can evaluate their practice and modify it, if necessary, to improve quality of care.

Clinical Competence↗

MHC (RT1) restriction of the antibody repertoire to infection with the nematode Nippostrongylus brasiliensis in the rat.

It might be expected that infections with transmissible agents will elicit an immune response to all of their exoantigens and that immune response (Ir) gene control of responses to individual epitopes on a given parasite component would be obscured by reaction to the molecule as a whole. Humans infected with parasitic nematodes, however, mount antibody responses which are selective for certain parasite components. This was modelled in inbred rats infected with the parasitic nematode Nippostrongylus brasiliensis and their responses to secreted antigens analysed by immunoprecipitation and SDS-PAGE. No strain responded to all the potential antigens and only those of identical major histocompatibility complex (MHC) had similar recognition profiles. This MHC-restricted response applied to whole molecules synthesized by the parasite, rather than merely to epitopes thereon and is, therefore, contrary to expectation. Moreover, the response patterns of F1 hybrid animals were not merely summations of parental responses. This suggests defective antigen presentation of particular parasite components by certain MHC class II molecules and/or cross-tolerance with background gene products.

Animals↗

MHC restriction of the antibody repertoire to secretory antigens, and a major allergen, of the nematode parasite Ascaris.

Humans vary considerably in the antigen specificity of their immune responses to parasitic nematodes, and in the infection loads of individuals living in the same environment. The possibility that the former has a genetic basis operating through repertoire control of the immune system was investigated using infection of mice with the nematode Ascaris. The specificity of the antibody response was examined using excretory/secretory (ES) materials of the parasite as target Ag. No strain of mouse was found to recognize all of the potentially antigenic components of ES, and the Ag recognition patterns varied considerably from strain to strain. Using H-2 congenic mice on both the BALB and B10 backgrounds, it was established that the antigen recognition patterns were MHC-determined. Focusing on one particular component of ES, of Mr 14,000, only H-2s strains responded in IgG. This MHC restriction of the repertoire was confined to infection, and broke down under adjuvant-assisted immunization with the purified protein. The Mr 14,000 molecule was also found to be a potent allergen in a passive cutaneous anaphylaxis assay, and the IgE response to it was also restricted to H-2s. This haplotype was, however, a low IgE responder on the SJL background. There is, therefore, MHC control of the specificity of the immune response to this molecule, but non-MHC control of the amplitude of the IgE antibody response to it. Hybrids between responder and nonresponder strains (BALB/c x SJL)F1, responded to the Mr 14,000, but their responses to other ES components could not be predicted from the response patterns of parental strains. For example, the BALB/c parent responded to a 118-kDa component, but the SJL parent and the F1 progeny did not. Moreover, the response to a 41-kDa Ag was substantially down-regulated in the F1, whereas both parental strains responded vigorously. This new model system, therefore, has implications for MHC control of responses to the allergens of pathogens, and for the complex immunoregulation in heterozygotes in the context of infection.

Allergens↗

The secreted and somatic antigens of the third stage larva of Anisakis simplex, and antigenic relationship with Ascaris suum, Ascaris lumbricoides, and Toxocara canis.

The in vitro-released 'excretory/secretory' (ES) and somatic antigens of the third stage (infective) larva of Anisakis simplex were characterised by radioiodination, immunoprecipitation, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Oral infection with the parasite elicited a substantial IgG antibody response to ES in infected rabbits and humans, with a minimal response to somatic materials. Serial serum sampling in experimental infection showed that there was a sequential recognition of distinct ES components. In contrast to oral infection, intraperitoneal exposure of rats with living parasites induced a strong response to both ES and somatic antigen preparations. Sequential recognition of ES antigens, and differential responses to somatic components, might, therefore, have application in the estimation of the age and degree of penetration by the nematodes in human infection. Extensive antigenic relationships were found between A. simplex and three other species of ascaridoid nematodes, namely Ascaris lumbricoides, Ascaris suum, and Toxocara canis, but none with a panel of non-ascaridoid nematodes. Evidence is presented that a Mr 14,000 component of A. simplex has a homologue in all of the ascaridoids examined, but does not elicit an antibody response in anisakiasis. Finally, the ES of A. simplex is shown to contain two proteinase activities, of approximately Mr 23,400 and 46,100, as revealed by separation on gelatin substrate gels, although the antigenicity of the enzymes remains to be established.

Animals↗

A 30-day forearm work protocol increases maximal forearm blood flow.

To evaluate the local circulatory changes that accompany chronic localized work, we studied the effects of a 4-wk handgrip work protocol on maximal forearm work-related blood flow (ml X min-1 X 100 ml-1) in the nondominant forearms of six normal subjects. The reactive hyperemic blood flow response (RHBF) was also evaluated pre- and posttraining in both forearms of each subject to determine whether maximal vasodilatory capacity would be enhanced. In addition, maximal O2 consumption (VO2max) was measured. We found that chronic handgrip work led to an increase in work-related blood flow (before, 22.4; after, 32.1; P less than 0.05); a drop in work-related minimal resistance (R) (before, 6.4; after, 4.1; P less than 0.05). RHBF rose in the chronically exercised extremity by 30% (before, 33.5; after, 43.7; P less than 0.05) as minimal R fell (before, 3.2; after, 2.2; P less than 0.05). RHBF and R in the unstimulated dominant forearm remained unchanged (blood flow: before, 33.5; after, 31.0; NS; R before, 3.2; after, 3.2; NS). VO2max (ml X kg-1 X min-1) did not change (before, 35.7; after, 34.0). These findings show that localized skeletal muscle forearm work is associated with a localized increase in vasodilation (RHBF). Thus the vascular system appears to be an independent integral partner in the training process.

Adult↗

Rescue of rats from large dose cyclophosphamide toxicity using protein A.

Cyclophosphamide (Cy) is widely used as an effective cytotoxic drug, but its use is limited because of its toxicity. In this report, we describe for the first time the ability of purified protein A (P) of Staphylococcus aureus to reduce Cy-induced toxicity in rats. Protein A-treated animals recover quickly from the toxic effects of Cy. The antitumor property of Cy is not reduced in the P + Cy group. In fact, the latter showed a persistent decrease in tumor volume compared with the Cy group. Protein A may prove to be an effective agent in increasing the therapeutic index of Cy.

Agranulocytosis↗

Lidocaine and the reduction of post-venographic pain.

Venography remains the standard method for the diagnosis of deep venous thrombosis but it is invasive and frequently causes discomfort. A randomised double-blind study was performed to determine the efficacy of lidocaine in reducing pain and discomfort associated with venography. Sixty patients undergoing ascending venography received 40 mg of lidocaine (2 ml of 2% lidocaine mixed with 50 ml of contrast medium) in one leg and saline in the other. Assessment of pain was by a standard questionnaire administered by an investigator unaware of the sequence of administration of lidocaine or saline placebo. Twenty-four patients reported no difference in pain or discomfort between the two limbs. Of the 36 patients experiencing an overall difference in pain between the two legs, 12 reported more pain in the leg receiving lidocaine and 24 reported more pain in the leg receiving saline (p = 0.023). There were no significant side effects attributable to lidocaine. These results indicate that lidocaine is beneficial in reducing pain and discomfort associated with venography.

Aged↗

Adsorption of plasma from tumor-bearing hosts over protein A--containing nonviable Staphylococcus aureus Cowan I: possible mechanism of antitumor reactions.

Adsorption of autologous plasma over nonviable Staphylococcus aureus Cowan I (SAC) followed by reinfusion of the plasma causes regression of (a) chemically induced rat mammary adenocarcinomas (MA), and (b) canine transmissible venereal tumors (TVT) and spontaneously occurring dog tumors. Animal data are more impressive than that from trials in humans. Nine of 41 patients receiving perfusions of adsorbed plasma showed some partial objective response. Eight of these nine patients received multiple perfusions over a period of time. Twenty-one of 41 patients showed subjective responses. Adsorption of autologous plasma over non-protein A--containing S. aureus Wood 46 caused regression of MA. Adsorption of normal rat plasma with SAC, and infusion of this adsorbed plasma into mammary tumor--bearing rats, caused regression of MA. Intravenous infusion of purified protein A alone caused regression of both rat MA and canine TVT. Superimposed on this observation is the finding that, during plasma adsorption, bacterial moieties leach from SAC. It is possible that the immunostimulation observed in plasma-perfused hosts is due to the removal of plasma blocking agents on one hand, and introduction of the bacterial agents on the other.

Adenocarcinoma↗

Adjusted subcutaneous heparin versus warfarin sodium in the long-term treatment of venous thrombosis.

Previously, we compared fixed low doses of heparin with adjusted doses of warfarin for the long-term treatment of venous thrombosis; in that study low-dose heparin was ineffective in preventing recurrence in patients with proximal-vein thrombosis. We have now completed a randomized trial comparing adjusted doses of heparin and of warfarin for prevention of recurrent venous thromboembolism in patients with proximal-vein thrombosis. One hundred six consecutive patients with acute proximal-vein thrombosis confirmed by venography were treated with intravenous heparin and then randomized to secondary prophylaxis. Two of 53 patients receiving heparin, as compared with one of 53 receiving warfarin, had new episodes of objectively documented venous thromboembolism. Nine patients taking warfarin had bleeding complications (which were major in three patients), as compared with one patient taking heparin (P = 0.008). Our data indicate that adjusted-dose subcutaneous heparin therapy provides an effective alternative to warfarin sodium and is associated with a lower risk of bleeding.

Clinical Trials as Topic↗

Ability of nonviable Staphylococcus aureus Cowan I to bind ionized calcium in vitro and ex vivo in an extracorporeal perfusion system.

During immunoadsorption of plasma immunoglobulin G (IgG) and/or its complexes, using nonviable Staphylococcus aureus Cowan I (SA) as an immunoadsorbent, we observed a consistent drop in plasma calcium during every immunoadsorption procedure. The percentage of decrease in plasma calcium was directly dependent on the amount of SA adsorbent present. Although SA can bind both IgG and calcium, the degree of binding of IgG was greater than that of calcium. Calcium could not be detected in the IgG fraction of the plasma SA, however, could bind an appreciable amount of ionized calcium. Extracorporeal perfusion of plasma over SA greatly decreased plasma calcium in a hypercalcemic patient, indicating the feasibility of this method in such patients. Questions concerning the significance of lowering calcium levels as a concomitant of other effects observed in cancer patients undergoing immunoadsorption therapy using SA evolve from the above and become a new focus for attention.

Adsorption↗

Higher cortical dysfunction associated with long term alcoholism.

A number of studies during the past decade have described deficits associated with chronic alcoholism. Although several of these studies have used neuropsychological tests, no study has comprehensively surveyed all recognized neuropsychological skills in a single population. The present study compared 41 chronic alcoholics to 41 matched controls during a two-day battery of neuropsychological tests, including the Halstead-Reitan, Wechsler Memory Scale, and other major tests. It was hypothesized that tests reflecting right and anterior brain function would differentiate between the groups. A factor analysis of the tests which differentiated between the groups indicated five primary deficits in chronic alcoholism: spatial conceptual skills, associative conceptual skills, flexibility, spatial-motor integration, and serial integration. The last factor demonstrated a small but significant verbal loss in the alcoholics. The implications of these factors for understanding and treating chronic alcoholism were discussed.

Adult↗