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Biomedical subjects

B R MacPherson

Publications and source records attributed to B R MacPherson.

18 recordsLinked to original sources

Gross and histologic effects of topical misoprostol on canine gastric mucosa.

This study reports the histological effects of topical misoprostol, a synthetic PGE1 analog, administered in varying dosages on the resting canine gastric mucosa. Misoprostol did not macroscopically or microscopically damage the mucosa but its presumed permeability effects on the gastric vasculature induced marked edema of the mucosa and submucosa. Consistent features included increased thickness of both layers, dilated interglandular regions of the lamina propria, marked subepithelial edema, reduced depth and width of gastric foveolae, vasodilation of the vascular channels, reduced height of surface epithelial cells, swelling of their basolateral intercellular spaces, and increased amounts of surface adherent mucus. It is speculated that the mucosal edema, in addition to an increased mucus layer, may be important in the mechanism of gastric cytoprotection by increasing the distance of penetration or absorption for a mucosal-damaging agent, diluting its concentration, and disseminating any focal accumulations of red blood cells.

Administration, Topical

Selection of platelets for refractory patients by HLA matching and prospective crossmatching.

A multi-site clinical study compared platelets chosen for refractory patients by prospective platelet crossmatching using stored donor platelets and HLA-based selection. Seventy-three patients who were refractory to random-donor platelets received two plateletpheresis components, one chosen by HLA-based criteria and the other by crossmatching. Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results. Each of the five study sites used a crossmatch procedure with which it had experience. Results from this study indicate the following: 1) The overall rate of successful transfusion was similar when an HLA-based method of donor selection that includes all grades of matching and mismatching was compared to a crossmatch-based method of donor selection. 2) HLA-based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone. Donor selection based on HLA matching (grades A or BU) was also superior to selection based on any degree of HLA mismatching (grades BX, C, or D). 3) Selection of donors based on HLA-cross-reactive groups (defined by in vitro serologic crossreactivity) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone. 4) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients, even though patients demonstrating nonimmune factors were eliminated from the study. It can be concluded that HLA-compatible (grades A and BU) platelets provide optimal support for refractory patients, but that crossmatch-selected platelets are acceptable as an alternative component.

Adult

Lymphoproliferative disorder of granular lymphocytes. A heterogeneous disease.

Lymphoproliferative disorders of granular lymphocytes (LDGLs) represent a family of diseases that are morphologically similar but diverse with regard to immunophenotype, function, and clonality. In this article, we report three informative cases and propose a modification of the current classification of LDGLs. Our first case is an example of natural killer cell LDGLs (CD2+, CD3-, CD16+, CD57+/-). Based on a review of the literature, we suggest that natural killer cell LDGLs can be divided into two subgroups (types 1 and 2) according to the expression of CD57. Reduced expression of CD57 may distinguish between patients with a poorer prognosis. The remaining two cases illustrate examples of T-cell LDGLs (CD2+, CD3+, CD8+, CD57+) that differ mainly in their expression of CD16. The CD16+ T-cell LDGLs (type 1) usually show a clonal rearrangement of the T-cell receptor-beta chain gene, whereas CD16- T-cell LDGLs (type 2) may show a germline configuration, suggesting a reactive rather than a neoplastic process. Pathologists should differentiate LDGLs from other chronic lymphoproliferative diseases, since most cases evolve slowly and aggressive cytoreductive therapy is usually unwarranted.

Adult

The detection of platelet alloantibodies by flow cytometry.

A flow cytometric procedure was investigated for its ability to detect antibodies directed against blood group A, HLA, and PlA1 (HPA-1a) antigens. When type O sera were tested against platelets from blood group A donors, only 9 of 14 positive reactions were observed. Furthermore, the expression of blood group A varied more than 100-fold on platelets derived from individual donors. When anti-HLA-A2 and -B7 were evaluated, 11 of 11 individuals with HLA-A2 and -B7 antigens reacted. In contrast, when platelets from donors whose HLA antigens included HLA-B8 or -B12 were tested with anti-HLA-B8 or -HLA-B12, respectively, positive reactions were observed in only 3 of 7 instances, despite the fact that the lymphocytes reacted strongly. Platelets from 10 HLA-A2-positive donors, which had been stored for up to 20 months at -70 degrees C, were studied. In all cases, frozen-stored platelets reacted well with an anti-HLA-A2. Limited testing with an anti-PlA1 (anti-HPA-1a) showed equal reactivity with fresh and frozen platelets. Finally, the method was compared to a visual immunofluorescence assay using sera from patients who were refractory to platelet transfusions. The results agreed in 30 of 37 comparisons, and most discrepancies were resolved in favor of flow cytometry. It is concluded that flow cytometry is useful for detecting platelet alloantibodies and possibly for prospective platelet crossmatching, as HLA- and platelet-specific antibodies can be identified by using platelets stored frozen for several months.

ABO Blood-Group System

Cobalt as a gastric juice volume marker: comparison of two methods of estimation.

We investigated the use of cobalt-EDTA, a novel, nonabsorbable liquid phase marker, in the estimation of secretory volumes during topical misoprostol (synthetic PGE, analog) administration in the canine chambered gastric segment. We compared atomic absorption spectrophotometry (AAS) and instrumental neutron activation analysis (INAA) in the estimation of [Co]. Mucosal bathing solutions containing cobalt-EDTA were instilled into and recovered from the chamber by gravity every 15-min period as follows: (i) basal--60 min; (ii) misoprostol periods--150 min (plus 0.1-, 1-, 10-, 100-, and 1000-micrograms doses of misoprostol for two periods per dose). The recovered solutions were analyzed for [Co] by AAS and INAA. Total cobalt recovery by AAS after chamber washout was 102.97 +/- 0.98%. Mean +/- SE volumes (12.14 +/- 0.33 and 13.24 +/- 0.60 ml/15 min) obtained respectively from AAS and INAA were significantly higher (P less than 0.001) than the recovered mean volumes (10.51 +/- 0.17 ml/15 min). The percentage error in volume collection increased (range: 9.3-52.7%) with the volume of secretion. Values of [Co] obtained by the two techniques were comparable and not significantly different from each other (P greater than 0.05). INAA-estimated mean +/- SE [Co] showed consistently higher coefficients of variation. Spectra obtained for all samples during INAA measurements showed significant Compton background activity from 24Na and 38Cl. Cobalt-EDTA did not grossly or histologically damage the gastric mucosa. We conclude that cobalt is not adsorbed, absorbed, or metabolized, and is a suitable and reliable volume marker in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation Analysis

Ionic fluxes induced by topical misoprostol in canine gastric mucosa.

We studied the dose response of ionic fluxes in canine chambered gastric segment mucosa to increasing doses of topical misoprostol (0.1, 1, 10, 100, and 1000 micrograms). The fluxes were also correlated with the simultaneous changes in focal gastric mucosal blood flow measured by laser-Doppler flowmetry. After misoprostol administration, there was a dose-dependent increase in focal gastric mucosal blood flow (Emax = 8.23 +/- 3.25 V at 10 micrograms; ED50 = 1.05 micrograms), pH, and the outputs of ions (Na+, K+, Cl-, and HCO3-) and fluid (Emax for pH and fluxes greater than or equal to 1000 micrograms). ED50 values for these outputs ranged from 215.40 to 340 micrograms (mean +/- SE = 279.08 +/- 24.27 micrograms). H+ output showed a dose-dependent decrease to zero at the 10-micrograms dose, the dose at and after which net HCO3- secretion became obvious. The slopes of the dose-response curves for the fluxes of fluid, Na+, K+, Cl-, and HCO3- were significantly different (p less than 0.01) from the slope of the curve for mucosal blood flow changes. There were no correlations between the changes in these fluxes and blood flow changes. Na+ and Cl- were the predominant cation (98.84%) and anion (98.19%), respectively, in the misoprostol-induced secretion. Misoprostol stimulates a composite alkaline gastric nonparietal secretion, predominantly Na+ and Cl-, but also containing K+ and HCO3-. Our results suggest different mechanisms for the effects on nonparietal secretion and focal gastric mucosal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil

The dose-response of canine focal gastric mucosal blood flow to misoprostol.

We studied the dose-response of focal gastric mucosal blood flow measured simultaneously by laser-Doppler flowmetry and hydrogen gas clearance in the canine chambered gastric segment to topical misoprostol (0.1, 1.0, 10, 100, and 1000 micrograms in 10 ml of 150 mM NaCl for two 15-min periods per dose). Simultaneously obtained mucosal blood flow values showed a highly significant linear correlation (r = 0.63, n = 20, p less than 0.01) in the basal but not misoprostol periods between the two techniques. Laser-Doppler flowmetry measured a dose-dependent increase in blood flow (Emax = 6.4 +/- 2.8 V at the 100-micrograms dose; equivalent to 92.8% increase above the basal mean blood flow value; ED50 = 1.0 micrograms). Peak increase in blood flow by laser-Doppler flowmetry after dosing was attained in 6.1 +/- 0.7 min and maintained for 1.9 +/- 0.3 min. In contrast, hydrogen gas clearance showed a gradual decline in blood flow after misoprostol administration throughout all experiments. The duration of each hydrogen gas clearance measurement was 13.1 +/- 0.1 min. In conclusion, misoprostol dose-dependently and transiently increases focal gastric mucosal blood flow. However, only laser-Doppler flowmetry is sensitive enough to detect it. Although it can measure steady-state blood flow, owing to the duration of one measurement, hydrogen gas clearance is incapable of detecting rapid flow changes.

Alprostadil

Antileukocyte antibodies in patients refractory to platelet transfusions.

Sera from 12 multitransfused patients who were refractory to random-donor platelets were tested for lymphocytotoxic and leukoagglutinating antibodies using panel cells from various volunteers whose HLA-A and -B antigens were known. All sera contained leukoagglutinins reactive with cells from at least one panel member, whereas only 33% had lymphocytotoxic antibodies. Patients whose sera reacted frequently with panel cells using the microcapillary agglutination technic seldom responded to HLA-matched paltelets, whereas those whose sera reacted infrequently usually responded satisfactorily. It is concluded that non-HLA antibodies may play a significant role in determining the responses to platelet transfusions in multi-transfused patients.

Agglutination Tests

Rapid diagnosis of Legionnaires' disease by direct immunofluorescent staining.

A blind reading of direct immunofluorescent staining of sputum smears was positive in five of 21 patients with Legionnaires' disease and none of 47 control patients. Positive slides showed from eight organisms per smear (one slide) to 20 to 100 organisms per oil-immersion (magnification, 100) field (three slides). Two of the positive specimens were obtained through an endotracheal tube, one at bronchoscopy, and the other positive slides were from expectorated specimens. In addition, two open-lung biopsies and a bronchial lavage sediment from three confirmed cases of Legionnaires' disease were positive by direct immunofluorescent staining for Legionnaires' disease bacterium.

Fluorescent Antibody Technique

Effect of cimetidine on chronic gastric ulcers produced experimentally in rats.

The authors have studied the effects of cimetidine on the healing of chronic gastric ulcers induced in rats. Gastric ulcers were produced by topical application of 60% acetic acid to the serosal surface of the lesser curvature of the stomach. Oral administration of cimetidine, 150 mg/kg daily, in two divided doses for a maximum of 14 days failed to produce any significant acceleration of healing.

Acetates

Experimental production of diffuse colitis in rats.

Diffuse, topical application of dilute acetic acid to the serosal surface of rat colon, or standardized intraluminal (per rectum) instillation induced a reproducible, diffuse colitis in a dose-response manner. These lesions were reproduced with 100% reliability and were evaluated up to 60 days when healing occurred. Histopathological features of this chemically induced colitis were diffuse ulceration of the distal colon, occurrence of pseudopolyp-like structures, alterations in crypt depth and mucus secretion, and a transmural, nonspecific inflammatory response.

Acetates

Detection of anti-lymphocyte antibodies using the immunoperoxidase antiglobulin technic.

Anti-lymphocyte antibodies in sera of multitransfused dialysis patients can be readily identified using the indirect immunoperoxidase method. Concordance between the microlymphocytotoxicity and immunoperoxidase methods was obtained in 61/66 paired specimens. The sensitivity of the immunoperoxidase antiglobulin technic is approximately that of the microlymphocytotoxicity method. This test may be used for lymphocyte crossmatching prior to renal transplantation.

Antibody Specificity

Effect of Corynebacterium parvum on colony-stimulating factor and granulocyte-macrophage colony formation.

Because Corynebacterium parvum has tumor-inhibitory properties and stimulates granulocyte-macrophage production, it may have clinical value in combination with chemotherapy. The leukopoietic effect of killed suspensions of C. parvum was studied in mice using the technique of in vitro clonal culture of hematopoietic cells. After C. parvum injection, there was a prompt, sustained elevation of serum colony-stimulating factor followed by an increase in granulocyte-macrophage precursor cells in the spleen and increases in blood mononuclear and granulocyte cells. Colony-stimulating factor production is suggested as a major mechanism of stimulation of granulocyte-macrophage proliferation by C. parvum. Since rapidly proliferating hematopoietic cells may have increased sensititity to cytotoxic agents, the details of hematopoietic stimulation by C. parvum may be critical in the sequential timing of combined C. parvum and chemotherapy treatment to obtain maximal tumor inhibition and minimal hematopoietic toxicity.

Animals

Immunological studies in patients with Crohn's disease.

An investigation of immunological parameters was conducted in 38 patients with Crohn's disease. The immunological tests employed included skin tests with dinitrochlorobenzene and a battery of common skin test antigens, lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen, serum immunoglobulins, and absolute lymphocyte counts. Crohn's disease patients were divided into two groups, those treated with immunosuppressive drugs and those not receiving immunosuppressive medications. The latter group was subdivided into patients with active and inactive disease. Immunosuppressed patients with Crohn's disease did not develop sensitivity to dinitrochlorobenzene and had mildly depressed skin test reactivity to common skin test procedures. Non-immunosuppressed patients with active Crohn's disease also reacted less frequently to common skin test antigens, but 16 of 17 such patients developed sensitivity to dinitrochlorobenzene. Lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen was normal in all groups of patients with Crohn's disease. However, when suboptimal incubation periods were used with phytohaemagglutinin stimulation, there was a significant difference between Crohn's disease patients and controls. Serum immunoglobulin levels and absolute lymphocyte counts were normal in all Crohn's disease patients. We conclude that immunity in Crohn's disease is qualitatively normal.

Adolescent