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Biomedical subjects

G S Johnson

Publications and source records attributed to G S Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1987

Evaluation of microwave-thawed canine plasma for transfusion.

Units of fresh-frozen canine plasma were thawed rapidly in a microwave oven, using a mean of 15.4 thawing periods of 10 seconds each. The activated partial thromboplastin times, the one-stage prothrombin times, concentrations of fibrinogen, factor-VIII coagulant activity, and von Willebrand factor antigen of microwave-thawed units were not significantly different from those measured in small aliquots of the same units thawed in a warm water bath (n = 5). Five dogs were given a unit of their own microwave-thawed plasma. During the 24 hours after infusion, no significant changes were measured in temperature, heart rate, or respiration rate. In addition, significant changes in PCV, total protein concentrations, estimates of platelet numbers, total RBC counts, total WBC counts, and differential WBC counts were not measured in blood specimens obtained before infusion and 24 hours after the infusion of microwave-thawed plasma.

Animals↗
PubMed1987

Malignant clinical behavior of cardiac myxomas and "myxoid imitators".

The clinical experience with cardiac myxomas and "myxoid imitators" at the Humana Heart Institute International is reviewed and contrasted with a comprehensive review of the world literature. Twenty-two patients with primary cardiac tumors have been treated at our institution. Three (13.6%) of them had myxoid imitators, and 19 had classic myxomas. One of the 19 patients with a classic myxoma had recurrence on two occasions (recurrence rate, 5.3%). The cases of 57 patients from the world literature are reviewed. Recurrence and/or metastases (including formation of mycotic aneurysm) occurred in approximately 50% of these patients. The overall mortality in these patients was 47%. This review provides documentation of the malignant clinical behavior of cardiac myxomas and myxoid imitators. Neither local recurrence nor regrowth of the tumor in a new location, whether intracardiac or extracardiac, can be predicted from the microscopic appearance of the primary tumor. Resection of the myxoma with a wide margin is the recommended surgical procedure but does not ensure a cure. Therefore, long-term follow-up is mandatory.

Fibroma↗
PubMed1987

Comparative in-vitro activity of LY146032 and eight other antibiotics against gram-positive bacteria isolated from children.

LY146032, a cyclic peptide antibiotic active against many Gram-positive bacteria, was compared to methicillin, vancomycin, clindamycin, cefuroxime and gentamicin against methicillin-resistant and methicillin-susceptible strains of Staphylococcus aureus and Staph. epidermidis. LY146032 was uniformly active against clinical isolates of staphylococci, inhibiting 90% of strains of Staph. aureus and Staph. epidermidis at a concentration of 0.5 mg/l. Vancomycin was slightly less active than LY146032 against Staph. aureus and Staph. epidermidis, inhibiting 90% of strains at concentrations of 1.0 and 2.0 mg/l, respectively. All other antibiotics tested were less active than LY146032 or vancomycin against staphylococci. LY146032 was compared to penicillin, ampicillin, vancomycin and chloramphenicol against strains of Streptococcus pneumoniae, group B streptococcus, group D streptococcus (enterococcus) and Listeria monocytogenes and was found to inhibit 90% of the strains at concentrations of 0.25, 1.0, 32.0 and 16.0 mg/l respectively. The combination of LY146032 and chloramphenicol was antagonistic in vitro for one strain each of Staph. aureus and group D streptococcus and showed indifference against other strains of Staph. aureus(2), Staph. epidermidis(2), group D streptococcus(1) and L. monocytogenes(2). LY146032 in combination with gentamicin showed indifference against the same bacteria. On the basis of its in-vitro activity, LY146032 appears to be a promising agent for the treatment of serious community- and hospital-acquired staphylococcal infections.

Anti-Bacterial Agents↗
PubMed1987

Alterations in select immunologic parameters following total artificial heart implantation.

We examined select immunologic parameters in three recipients of a total artificial heart and correlated changes with the clinical course. Two patients remain alive and were studied for 320 and 240 days, respectively; the third died 10 days after implantation. All patients demonstrated transient complement activation immediately postoperatively, as indicated by an increase in plasma levels of C3a des Arg. In the two long-term survivors, C3a des Arg levels again increased, concomitant with intravascular hemolysis associated with high blood shear rates imposed by the drive system of the heart. All three patients had a marked lymphopenia immediately postoperatively, and the two long-term survivors demonstrated marked fluctuations in total lymphocyte count. There was a progressive decline in the number of peripheral blood helper/inducer T cells in the two long-term survivors. A large number of activated (HLA-DR positive) suppressor/cytotoxic T cells were also noted in these two patients. A progressive decrease in B cells was also observed; however, total IgG and IgM levels were not decreased. No changes in neutrophil phagocytic or respiratory burst capacities were identified. The cause of these changes in lymphocyte populations is not clear; however, they may have impact on the use of this device as a bridge to transplantation and may lead to decreased immunocompetence during long-term use.

Blood Transfusion↗
PubMed1987

Thromboembolic and infectious complications of total artificial heart implantation.

Thromboembolic and infectious events were found to be major complications of long-term total artificial heart implantation in two patients. Similar complications have been reported in other patients, as well as in animal studies. The thromboembolic events and the infectious complications appear to be interrelated. On the one hand, thrombi located on the valves and at the vascular anastomoses of the artificial heart were found to be infected at autopsy; such infections are known to exacerbate formation of thromboemboli. On the other hand, the generation of microthrombi may have contributed to the RES blockade seen in our patients. We hypothesize that this RES blockade led to a progressive decrease in lymphoid system function and impaired the patients' capacity to clear microorganisms from the circulation. These phenomena arose, in part, from the design of the artificial heart and were exacerbated by associated therapy, such as blood transfusions. Our data suggest several measures that might be taken in order to reduce the severity of both the thrombogenic and infectious complications. Improved anticoagulation regimens, which increase the ability of the physician to maintain the proper balance between thrombotic and hemorrhagic potential, are needed. This may require not only improved methods of monitoring anticoagulation and predicting changes in the effectiveness of various agents as other events supervene, but also new anticoagulant and antithrombotic drugs, for example, low molecular weight heparins and prostacyclin derivatives. It is also clear that the design of the artificial heart should be modified in order to improve fluid dynamics so that they will approximate as closely as possible those of the natural heart. This includes redesigning the mounting of the valves to eliminate crevices and discontinuities that allow stagnant flow and predispose to thrombus formation as well as imposing a dP/dt that minimizes shear-related hemolysis, thereby minimizing the need for blood transfusions. Prevention of infections presents a more difficult problem. Transcutaneous lines (regardless of their use) are an obvious route for infection, and attention should be given to minimizing the number and length of use of monitoring lines. However, until a totally implantable drive system is available, the drive lines will remain a potential avenue for the introduction of infections. The risk may be minimized by rigorous attention to care of the exit sites and by improved designs that will provide a better mechanical barrier by, for example, enhancing epithelial ingrowth into the materials of the drive line.(ABSTRACT TRUNCATED AT 250 WORDS)

Candidiasis↗
PubMed1987

Infective endocarditis: diagnosis, treatment, and mortality, as related to surgical timing and infectious organism.

To evaluate the timing of surgical treatment in infective endocarditis and to determine the relationship between the risk of mortality and the species of infectious organism, we reviewed a consecutive series of 65 cases involving patients with infective endocarditis who had been treated over a 17-year period. The patients included 41 males and 24 females, who ranged in age from 6 to 85 years (mean, 39.3 years). Forty-five had native valve endocarditis, 14 had prosthetic valve endocarditis, and six had endocarditis associated with congenital heart defects. Fifty-two patients underwent valve replacement, which was associated with an overall operative mortality of 19%. Those who underwent valve replacement during the early active stage (first 3 weeks) of infection had a higher mortality rate than those who had surgery either during the late active stage (second 3 weeks) of infection or after 6 weeks of antibiotic therapy. S. aureus and Pseudomonas organisms were responsible for the most deaths. On the basis of this study, we recommend that, when cardiovascular function permits, patients who are hemodynamically stable and free of emboli should receive 4 to 6 weeks of antibiotic therapy before undergoing surgical treatment. In contrast, patients with high-risk organisms are more likely to survive if subjected to early surgical intervention.

Journal Article↗
PubMed1987

Experimental endotoxemia increases plasma von Willebrand factor antigen concentrations in dogs with and without free-radical scavenger therapy.

Pentobarbital-anesthetized beagles were infused with physiologic saline (control dogs) or E. coli endotoxin (1.5 mg/kg i.v.) for 1 min. The plasma von Willebrand factor antigen (vWf:Ag) concentration, a potential index of endothelial damage, was monitored before and for 4 h after endotoxin challenge. The plasma vWf:Ag concentration increased only slightly in the control dogs (n = 6); whereas, in dogs infused with endotoxin (n = 20), the vWf:Ag concentration increased progressively to 2.1 times prechallenge values in 4 h. In addition to endotoxin, some of these dogs were treated with free-radical scavengers; allopurinol (n = 3), allopurinol plus superoxide dismutase and catalase (n = 6), or deferoxamine (n = 5). The free-radical scavengers did not prevent endotoxin-induced increases in vWf:Ag concentration.

Animals↗
PubMed1987

Buccal mucosa bleeding times of healthy dogs and of dogs in various pathologic states, including thrombocytopenia, uremia, and von Willebrand's disease.

The buccal mucosa bleeding time (BMBT; duration of hemorrhage from standardized cuts made with a spring-loaded disposable device in the mucosal surface of the upper lip) was used to evaluate the hemostatic competence of dogs. The mean (+/- SD) BMBT for 34 healthy dogs was 2.62 +/- 0.49 minutes. The BMBT of healthy dogs anesthetized with halothane or tranquilized with xylazine were not significantly different from the BMBT of healthy dogs evaluated without chemical restraint. The BMBT was significantly (P less than 0.01) prolonged 21 hours after aspirin (10 mg/kg of body weight) was administered orally to 10 healthy dogs; however, the mean aspirin-induced increase in BMBT was only 0.40 minutes. The BMBT of 28 of 30 dogs with various diseases not traditionally associated with hemostatic deficiencies were near or within the range of BMBT for healthy dogs; however, 2 dogs had BMBT of greater than 8 minutes. In contrast, BMBT were prolonged in most dogs with diseases known to induce deficient primary hemostasis; the 3 dogs with thrombocytopenia (less than or equal to 20,000 platelets/microliter), the 7 Doberman Pinschers with von Willebrand's disease (von Willebrand factor antigen; less than or equal to 18 U/dl), and 5 of the 6 dogs with severe azotemia (serum urea nitrogen; greater than or equal to 124 mg/dl) had prolonged BMBT. The BMBT of 16 dogs were determined immediately before they were subjected to various surgical procedures, and the severity of the hemorrhage encountered during these procedures was subjectively evaluated; the amount of hemorrhage from 12 of the 16 dogs was considered to be appropriate for the corresponding surgical procedures, but the remaining 4 dogs bled excessively during surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Multimeric analysis of von Willebrand factor before and after desmopressin acetate (DDAVP) administration intravenously and subcutaneously in male beagle dogs.

Eight adult male Beagles were given 1 microgram of 1-deamino-8-D-arginine vasopressin (DDAVP)/kg of body weight, SC or by slow IV infusion on separate occasions. Both routes of administration induced highly significant increases (P less than 0.0001) in plasma concentrations of von Willebrand factor (vWf) antigen (Ag) and botrocetin cofactor (BCf) activity, an indication of platelet-associated vWf activity. In most instances, increases in plasma vWf:Ag and BCf values induced by SC injection were as large as or larger than those induced by slow IV infusion. With both routes of administration, BCf activity increased more than the vWf:Ag concentration, so that high BCf-to-vWf:Ag ratios were found in plasma after DDAVP administration. In plasma samples obtained before DDAVP administration, sodium dodecyl sulfate-electrophoresis resolved the vWf into a series of multimeric proteins with molecular weights similar to those of human vWf. Sodium dodecyl sulfate-electrophoresis of plasma samples obtained after DDAVP administration revealed mainly the larger molecules of vWf that were increased by DDAVP administration.

Animals↗
PubMed1986

Formation of the N'-methylnicotinamide adenine dinucleotide derivative of NAD in intact rat pituitary tumor GH3 and human promyelocytic leukemia HL-60 cells.

The NAD analog N'-methylnicotinamide adenine dinucleotide (N'AD) is formed in intact human promyelocytic leukemia HL-60 and in rat pituitary tumor GH3 cells during treatment of the cultured cells with the nicotinamide derivative N'-methylnicotinamide (N'CH3NAm). N'AD formation is associated with the induced maturation of HL-60 cells and increased hormone production by GH3 cells during treatment with the nicotinamide derivative. N'AD is detected by HPLC analysis of cytoplasmic extracts as a peak which elutes near NAD. Four facts indicate that this compound is N'AD. First, a compound which elutes with identical time retention is produced by transglycosylation during reaction of NAD with pig brain NAD glycohydrolase in the presence of excess N'CH3NAm. Second, the putative N'AD is degraded by prolonged digestion with the NAD glycohydrolase to ADP-ribose. Third, N'AD formation is prevented by addition of nicotinamide along with N'CH3NAm to compete with binding of N'CH3NAm to the NAD glycohydrolase. Fourth, radioactive precursor labeling demonstrates that it contains adenosine, but it is not labeled by radioactive nicotinamide. The biological relevance of N'AD formation was evaluated. The appearance of N'AD precedes development of HL-60 maturation, and NAD levels increase, not decrease, as observed in other cell types, during treatment with N'CH3NAm. Therefore, we propose that N'AD, not the pyridine base itself, is the active species in inducing maturation. The results provide support of a role for NAD metabolism, probably ADP-ribosylation, in the regulation of HL-60 maturation and in hormone production by pituitary cells.

Adenosine Triphosphate↗
PubMed1986

Destabilization of cytoplasmic mouse mammary tumor RNA by heat shock: prevention by cycloheximide pretreatment.

Thermal stress of cultured mouse mammary carcinoma cells results in a rapid loss of basal and glucocorticoid-stimulated mouse mammary tumor virus (MMTV) RNA. MMTV RNA is almost nondetectable within 1-2 hr after a shift in the culture temperature to 42 degrees. Actin mRNA is stable over this time period. Pretreatment of the cells with cycloheximide prevents the decay of MMTV RNA. Nuclear associated glucocorticoid receptor is not decreased but rather increased about 95% by the heat shock. The results show that heat shock has pronounced effects on expression of a glucocorticoid-regulated gene, and suggest that a nuclease, which is subject to rapid turnover, is stimulated by thermal stress.

Animals↗
PubMed1986

Glucocorticoid agonists as well as antagonists are effective inducers of mouse mammary tumor virus RNA in mouse mammary tumor cells treated with inhibitors of ADP-ribosylation.

Glucocorticoids increase expression of specific genes by a mechanism involving binding to and "activation" of a specific receptor protein. Other steroids, such as RU 486, bind to the glucocorticoid receptor but the resultant steroid-receptor complex is unable to activate glucocorticoid sensitive genes. In the present study we have observed that steroid regulation of the glucocorticoid-regulated mouse mammary tumor virus (MMTV) genome in cultured mouse mammary tumor cells is altered by treatment of the cells with inhibitors of (ADP-ribose)n synthetase. The ability of glucocorticoid agonists to increase MMTV is about 2-fold increased by the inhibitor treatment. Interestingly, RU 486 and other steroids that are normally inactive in control cells are very good inducers of MMTV in the treated cells. This alteration in MMTV expression is associated with a 37% increase in nuclear binding of the glucocorticoid, triamcinolone acetonide, and also RU 486 in the inhibitor-treated cells. Steroids that do not bind to the glucocorticoid receptor are not inducers in control or in treated cells. The results point to a role for ADP-ribosylation of proteins as a negative regulator of MMTV expression and suggest a mechanism for activation of steroid-sensitive genomes.

Adenosine Diphosphate↗
PubMed1986

Pathogenesis of labyrinthitis associated with Haemophilus influenzae type b meningitis in infant rats.

The pathogenesis of labyrinthitis associated with bacterial meningitis was studied by histopathologic examination of inner ears of 114 rats with Haemophilus influenzae type b meningitis produced by ip inoculation of one of 13 clinical isolates. Findings consisted of inflammation of the perilymphatic spaces of the cochlea and semicircular canals with sparing of the endolymphatic space, cochlear nerve fibers, and middle ear. The degree of inflammation peaked at 48 hr after inoculation, then declined by 96 to 144 hr. No interstrain differences in type or degree of pathology were observed. Immunofluorescent staining of cochleae from 15 animals demonstrated that bacteria were present in areas of inflammation and also in the endolymphatic space and organ of Corti. One isolate displayed a tendency to accumulate in the perilymphatic spaces in larger numbers than those seen with three other isolates. These findings suggest that, in this model, inflammation reaches the inner ear by spreading from the subarachnoid space. Bacterial invasion of the organ of Corti may be one mechanism by which deafness occurs in bacterial meningitis.

Animals↗
PubMed1986

DDAVP-induced increases in coagulation factor VIII and von Willebrand factor in the plasma of conscious dogs.

Infusion of the vasopressin analogue DDAVP into five normal dogs at doses of 0.1-2.0 micrograms DDAVP per kg body weight induced dose-dependent increases in the plasma content of coagulation factor VIII and von Willebrand factor. Plasma concentrations of von Willebrand factor (determined antigenically as factor VIII-related antigen and functionally as coagglutinin cofactor activity) and coagulation factor VIII were measured immediately before and at 10, 30, and 120 min after 10-min intravenous infusions of DDAVP. The greatest increases in coagulation factor VIII were produced with the 2.0 micrograms/kg dose. Ten minutes after infusion the mean increase in coagulation factor VIII was 32 units/dl (concentrations of all indices were reported relative to concentrations in a standard canine plasma pool, arbitrarily assigned a concentration of 100 units/dl) and this increase did not change significantly throughout the duration of the experiment. At 10 min post-infusion, the mean factor VIII-related antigen concentration increased 81 units/dl (dose = 2.0 micrograms/kg) and did not change significantly for the duration of the experiment. The maximum mean increase in coagglutinin cofactor activity, 141 units/dl, occurred 10 min after infusion (dose = 1.0 microgram/kg). Coagglutinin cofactor activity decreased significantly from peak activity by 120 min post-infusion.

Animals↗
PubMed1986

Cytochemical properties of chicken blood cells resembling both thrombocytes and lymphocytes.

Generally accepted criteria were used to identify typical nucleated thrombocytes and typical small lymphocytes in chicken-blood smears subjected to modified-Wright staining. Other cells, here referred to as "intermediate cells," were difficult to classify because in some aspects they resembled thrombocytes while they also had features typical of small lymphocytes. The "intermediate cells" had small, round or oval nuclei with coarsely condensed chromatin, characteristic of both thrombocytes and small lymphocytes. In addition, "intermediate cells" had moderately abundant cytoplasmic volumes, typical of thrombocytes but blue cytoplasm lacking both granules and vacuoles, which is characteristic of small lymphocytes. It made little difference to the thrombocyte count whether these cells were classified as thrombocytes or small lymphocytes; however, this decision made a substantial difference to the lymphocyte count in some chicken-blood smears. Most "intermediate cells" (351 of 410 cells examined) were nonfluorescent after treatment with formaldehyde gas. Furthermore, most "intermediate cells" failed to acquire characteristic pigments when subjected to either Grimelius staining (179 of 204 cells examined) or periodic acid-Schiff staining (173 of 206 cells examined). Typical small lymphocytes reacted in the same way, failing to fluoresce after gaseous formaldehyde treatment (65 of 65 cells examined) and failing to react during Grimelius staining (41 of 44 cells examined) or periodic acid-Schiff staining (21 of 21 cells examined). In contrast, almost all typical thrombocytes became fluorescent in response to gaseous formaldehyde (709 of 718 cells examined) and gave positive reactions when subjected to Grimelius staining (381 of 382 cells examined) or periodic acid-Schiff staining (322 of 326 cells examined). These findings suggested that "intermediate cells" should be classified as lymphocytes in differential cell counts.

Journal Article↗