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Biomedical subjects

M E Hammond

Publications and source records attributed to M E Hammond.

At least 37 records · Page 2Linked to original sources

Cardiac retransplantation: a viable option? The Registry of the International Society for Heart and Lung Transplantation.

To evaluate cardiac retransplantation as an appropriate utilization of scarce donor organs we analyzed data from the registry of the International Society for Heart and Lung Transplantation (ISHLT) (n = 449) and the Utah Cardiac Transplant Program (n = 20). Actuarial survival among retransplants was lower than in patients who received only one transplant in both the ISHLT registry patients (1 year survival, 48% versus 78%; p = 0.001) and the Utah series (1 year survival, 74% versus 88%; p = 0.06). Uncontrolled rejection, short interval (< 6 months) between transplantations, and the need for mechanical circulatory support were identified as risk factors for retransplantation. The incidence of rejection and infection was similar in first and second transplant recipients. Second transplant recipients had a higher level of sensitization, a greater incidence of donor-specific positive crossmatches, and an increased early mortality. Repetition in the second donor of mismatched HLA antigens present in the first donor did not adversely affect survival. If patients who underwent retransplantation within 6 months of their initial transplantation, those receiving transplants for uncontrolled rejection, and those requiring mechanical assistance were eliminated from the study, the short-term and long-term survival after cardiac retransplantation does not differ from that in patients having a single transplant.

Actuarial Analysis↗

Diagnosis of cytomegalovirus pneumonitis on bronchoalveolar lavage fluid: comparison of cytology, immunofluorescence, and in situ hybridization with viral isolation.

Forty-three bronchoalveolar lavage (BAL) specimens from 40 immunocompromised patients were studied for the presence of cytomegalovirus (CMV) by rapid diagnostic methods. DNA in situ hybridization, cytology, and immunofluorescence were compared to conventional cell culture. Eleven (25%) of the 43 BAL samples grew CMV in culture. In situ hybridization detected 6 of these 11 for sensitivity, specificity, and predictive values of positive and negative of 55%, 94%, 75%, and 86%, respectively. Cytology had a sensitivity of 73% and specificity of 100%. Six Papanicolaou-stained cytospins were screened cytologically versus one hybridization cytospin, and the higher sensitivity of cytology may reflect this extensive sampling. The immunofluorescent method had a sensitivity equal to that of cytology (73%): however, the specificity (72%) was significantly less than that of either the probe or cytology. These data suggest that although in situ hybridization can be a rapid, useful method for detecting CMV in BAL specimens, cytology appears to be a more sensitive method.

Bronchoalveolar Lavage Fluid↗

Chronic encephalitis, epilepsy, and cerebrovascular immune complex deposits.

Refractory epilepsy, electroencephalographic abnormalities, progressive hemiplegia, and contralateral hemicerebral atrophy developed in a previously healthy 3-year, 9-month-old girl. Extensive laboratory testing showed elevated serum antinuclear antibody titers, cerebrospinal fluid oligoclonal bands, and elevated immunoglobulin G (IgG): albumin ratio, IgG index, and IgG synthesis rate. Pathological study of a subtotal hemispherectomy specimen revealed widespread cerebral vasculitis with immunofluorescence staining for IgG, IgM, IgA, C3, and Clq, and ultrastructural evidence of vascular injury in addition to severe cortical atrophy with marked neuronal loss. Cerebrospinal fluid abnormalities in other reported patients suggest that immunological abnormalities may not be unique to this girl. These data suggest possible immunopathogenetic mechanisms in these patients.

Antibodies, Antinuclear↗

Correlation between class II antigen (DR) expression and interleukin-2-induced lymphocyte proliferation during acute cardiac allograft rejection.

We have previously reported a correlation between biopsy-proven rejection and the presence of IL-2-responsive lymphocytes for biopsy specimens from human cardiac allografts. We thus hypothesized a relationship between tissue expression of HLA class II antigen (DR) and the outgrowth of IL-2-responsive lymphocytes. Employing immunofluorescence DR staining with a propidium iodide counterstain in consecutive specimens from 41 patients, we found two patterns of DR expression: DR expressed on the vascular endothelial surface (donor antigens) and/or on myocardial infiltrating cells (presumably recipient antigens). Specimens were categorized by histologic diagnosis as "baseline nonrejecting controls" that were obtained 7.5 +/- 0.4 (mean +/- SE) days posttransplantation, "nonrejecting" (obtained 59.9 +/- 5.8 days posttransplantation), "prerejecting" (obtained 47.7 +/- 6.3 days posttransplantation), and "rejecting" (obtained 101.3 +/- 10.1 days posttransplantation). Prerejecting specimens were histologically negative specimens obtained from patients a mean of 6.0 +/- 0.4 days before a biopsy-proven rejection episode. The percentage of specimens positive for interstitial DR staining were: less than 1% for controls, 30% for nonrejecting specimens, 68% for prerejecting, and 46% for rejecting. For vascular DR staining, 25% of control specimens were positive, 56% of nonrejecting, 74% of prerejecting, and 73% of rejecting specimens. Culture positivity was seen for 38% of controls, 35% of nonrejecting specimens, 79% of prerejecting, and 70% of rejecting. Vascular DR staining was higher than interstitial staining for all specimen categories. For the vascular pattern, the mean score was significantly higher for culture-positive specimens compared to culture negative (0.87 +/- 0.1 vs. 0.59 +/- 0.1; P less than 0.01). A similar relationship was not found for the interstitial pattern. Lymphocyte growth occurred in conjunction with vascular DR upregulation significantly more frequently than in conjunction with interstitial DR expression (65% vs. 35% of culture-positive specimens, P less than 0.0001). These findings suggest a relationship between DR expression, lymphocyte growth, and acute rejection. Vascular DR and interstitial DR patterns show several differences with respect to kinetics of expression and correlation with histology and culture, and thus may represent different processes.

Blood Vessels↗

Correlation of prostate-specific acid phosphatase and prostate-specific antigen immunocytochemistry with survival in prostate carcinoma.

Prostate-specific acid phosphatase, a secretory product of prostatic cells, may be a secondary product of the interaction of hormones with their receptor proteins. In this study we have examined two independent patient populations to see whether the intensity or extent of prostate-specific acid phosphatase and/or prostate-specific antigen staining correlated with survival and hormonal manipulation. One population of 24 patients was selected from patients undergoing surgical resection for adenocarcinoma Stage B or C at the Mayo Clinic. The second population of 123 patients was obtained from Radiation Therapy Oncology Group Protocols 75-06 and 77-06. Tissue from both populations was analyzed. In both populations, the intensity of prostate-specific acid phosphatase staining correlated with survival in a statistically significant manner. Staining with prostate-specific antigen was present in greater than 90% of specimens; data was therefore not analyzed. In those patients who subsequently relapsed and were subjected to hormonal manipulation, there appeared to be a higher likelihood of response to hormones with intense prostate-specific acid phosphatase staining.

Acid Phosphatase↗

A prospective comparison of murine monoclonal CD-3 (OKT3) antibody-based and equine antithymocyte globulin-based rejection prophylaxis in cardiac transplantation. Decreased rejection and less corticosteroid use with OKT3.

To test the efficacy of murine monoclonal CD-3 antibody (OKT3) in early prophylaxis for cardiac allograft rejection, we conducted a 6-month trial, prospectively assigning 51 patients to receive either equine antithymocyte globulin-based (n = 25) or OKT3-based (n = 26) early prophylaxis. ATG patients received 8 days of ATG (10 mg/kg), with the first dose given preoperatively. OKT3 patients received 14 days of OKT3 (5 mg) beginning on the second postoperative day. Corticosteroid and azathioprine administration were similar during early prophylaxis. Cyclosporine was begun preoperatively in ATG patients and on the fourth postoperative day in OKT3 patients. In addition, patients in both groups were randomized to receive or not receive eight weekly administrations of vincristine (0.025 mg/kg). While infection rate (0.8 +/- 0.2 infections/patient in both groups [mean +/- SEM]) and mortality (1 patient in each group) did not differ, OKT3-based early prophylaxis delayed the first rejection episode (76 +/- 11 days vs. 36 +/- 8 days, P = 0.005) and decreased the risk of rejection during the 6-month follow-up (P less than 0.001, product-limit analysis). Overall, the OKT3 group manifested 1.5 +/- 0.2 episodes of rejection/patient compared with 2.2 +/- 0.2 episodes/patient in the ATG group (P = 0.036). Despite similar 6-month cumulative cyclosporine and azathioprine dosages, six month average corticosteroid administration was less in the OKT3 group (12.2 +/- 1.5 mg prednisone equivalent/m2/day versus 19.3 +/- 2.1 mg prednisone equivalent/m2/day, P = 0.008), fewer OKT3 patients subsequently required additional cytolytic therapy for rejection (2 [8%] versus 12 [48%], P = 0.001), and more patients in the OKT3 group were successfully weaned off maintenance corticosteroids (22 [88%] versus 11 [46%], P = 0.002). We conclude that, relative to an equine ATG-based protocol, OKT3-based early prophylaxis results in less rejection, permitting less chronic corticosteroid administration.

Antibodies, Monoclonal↗

A new experimental model for secondary hyperparathyroidism.

We have developed an animal model to study the pathogenesis of secondary hyperparathyroidism by inducing stable uremia in Sprague-Dawley rats by selective microligation of terminal branches of the left renal artery, followed by right nephrectomy. After 4 weeks the animals were killed, the parathyroid glands were removed and weighed, and blood samples were obtained. Of 30 rats, uremia developed in 22 (73%; uremic group) and eight (27%) died or did not become uremic. A sham-operated group of 15 rats served as control (control group). Creatinine levels were 1.8 +/- 0.5 mg/dl in the uremic group versus 0.5 +/- 0.1 mg/dl in the control group (p less than 0.0001). Parathyroid glands were hyperplastic in all rats with uremia and were heavier than parathyroid glands of control animals (70.3 +/- 26 vs 19.1 +/- 8 micrograms; p less than 0.0001). In the group with uremia, parathyroid hormone levels were increased over those of the control group (112.6 +/- 13 vs 28.9 +/- 6.2 pg/ml; p less than 0.0001), whereas osteocalcin levels were similar (36.6 +/- 11 vs 37.5 +/- 1 ng/ml). Serum calcium, phosphate, and alkaline phosphatase levels were similar in both groups. Our model can be used to test hypotheses concerning the treatment of secondary hyperparathyroidism and the relative pathogenetic relevance of vitamin D deficiency and phosphate retention.

Alkaline Phosphatase↗

Clinical, ultrastructural immunohistochemical and DNA content analysis of lymphomas having features of interdigitating reticulum cells.

Interdigitating reticulum cells (IRC) are dendritic, nonphagocytic histiocytes found in thymus-dependent areas of lymphoid tissues. We report two cases of large cell lymphoma having features of IRC in patients 13 and 17 years old. In each case the diagnosis was suggested by light and electron microscopic features, positive immunoperoxidase staining for S-100 protein, and additional immunoperoxidase findings. Both patients presented with aggressive lymphomas and were treated with intensive combination chemotherapy. Each patient achieved a complete clinical remission, then rapidly relapsed and died with disseminated disease 3 and 9 months after presentation. Novel findings included strong staining of specimens with an antibody to epithelial membrane antigen, staining of one specimen with peanut agglutinin in the pattern previously described in normal IRC, and a DNA content analysis that showed aneuploid stem cell lines in both patients.

Adolescent↗

Reproduction in Brahman cows calving for the first time at two or three years of age.

A comparison of the subsequent reproduction of heifers that calved for the first time at 2 vs. 3 yr of age was conducted on a purebred Brahman herd from 1971 to 1978 in central Florida. Pregnancy rate, birth rate and weaning rate were obtained on 1,612 animals. Sire of the cow had a significant effect on all three reproduction traits, indicating possible genetic differences in these important traits. Age at first calving (either 2 or 3 yr) had no significant effect on overall reproduction rates; however, subsequent pregnancy and weaning rate was 4% higher in females calving first at 2 yr of age. Thirty-eight percent of the females that became pregnant at 15 to 17 mo of age, weighed 650 to 700 lbs. These heifers had been born early in the previous calving season. It is suggested that Brahmans can be selected to calve at 2 yr of age if good nutrition and management are provided.

Journal Article↗

Simultaneous cytomegalovirus and herpes simplex virus pneumonia.

A 35-year-old patient who underwent renal transplant developed persistent fever, hypoxemia, and diffuse interstitial pulmonary infiltrates one month after allograft implantation. An open lung biopsy specimen demonstrated simultaneous infection with cytomegalovirus and herpes simplex virus type 1. This initially was unsuspected on routine histology, but was confirmed by the demonstration of both viruses with immunofluorescence, as well as the timely recovery in culture of both. The clinical and pathologic implications of an accurate diagnosis of such a simultaneous infection are discussed.

Adult↗

Hypocomplementemic urticarial vasculitis syndrome responsive to dapsone.

A 45-year-old woman with cutaneous urticaria-like lesions subsequently developed polyarthritis, glomerulonephritis, and chronic obstructive pulmonary disease. Biopsy of skin showed leukocytoclastic vasculitis of superficial capillaries. Biopsy of the kidney revealed mesangioproliferative glomerulonephritis, and lung biopsy revealed severe emphysema and thick-walled blood vessels with immunoglobulin deposition. Therapy with dapsone produced dramatic improvement of the patient's cutaneous vasculitis and arthritis. This case uniquely demonstrates the efficacy of dapsone for both the urticarial vasculitic and the arthritic components of this syndrome and reemphasizes the potentially severe pulmonary and renal complications.

Arthritis↗

Amniotic epithelial ultrastructure in normal, polyhydramnic, and oligohydramnic pregnancies.

The ultrastructure of the amniotic epithelial cells from normal, polyhydramnic, and oligohydramnic pregnancies were studied with the transmission electron microscope. The amniotic epithelial cell layer from normal pregnancies was 8- to 12-mu thick. In polyhydramnic pregnancies the cell layer varied widely from the normal thickness to as much as 18 to 56 mu in diabetic patients. Other ultrastructural changes observed in pregnancies complicated by polyhydramnios were abnormal microvilli, diminished intercellular canals, increased tonofilaments, and decreased rough-surfaced endoplasmic reticulum. In pregnancies complicated by oligohydramnios the thickness of the cell layer was 3 to 6 mu. The amniotic epithelial cells had increased tonofilaments, decreased desmosomes, collapsed and fused intercellular canals, and caused a marked decrease of the Golgi apparatus and the rough-surfaced endoplasmic reticulum. The sparse microvilli were short, plump, and had bizarre shapes.

Amnion↗

Large cell neuroendocrine tumors of the lung. Clinical significance and histopathologic definition.

Twenty-five cases of neuroendocrine tumors of lung, including bronchial carcinoids (eight), malignant (atypical) carcinoids (nine), and large cell undifferentiated carcinomas (LCAC) with neuroendocrine differentiation (eight) were analyzed. All carcinoids (BC) could be diagnosed by light microscopy; all patients with these tumors are alive without disease. Five of nine malignant carcinoids (MC) could be recognized histologically; four of nine were called LCAC and required electron microscopy for diagnosis. Survival correlated best with stage of diagnosis. High-grade neuroendocrine carcinomas (LCAC-NE) required electron microscopy for their diagnosis. Seven were LCAC histologically; one was diagnosed as malignant carcinoid (MC). Such tumors resemble small cell anaplastic carcinomas ultrastructurally and behaviorally. All eight patients with such high-grade tumors died of their disease; three of eight had no nodal metastases at the time of resection. This experience suggests it is clinically important to distinguish neuroendocrine neoplasms since behavior is predictable on the basis of morphology.

Adult↗

Ultrastructural localization of specific gonococcal macromolecules with antibody-gold sphere immunological probes.

In an effort to determine the ultrastructural location of specific macromolecules on the surface of intact microorganisms and in experimentally infected tissues, a new method of rapidly conjugating antibodies to gold spheres via a staphylococcal protein A intermediary has been developed. This new technique provides the excellent density of marking and versatility of sphere size provided by existing gold methods, but decreases preparation time, decreases the chance of bacterial contamination of antibody reagents, and increases specificity of marking. Staphylococcal protein A-coated gold spheres were conjugated with antibodies from rabbits immunized with purified gonococcal pili. The resulting gold-antibody conjugates allowed demonstration of antibody binding to pilus structures of the same gonococcal strain whose pili were used to raise the antibody and demonstration of the lack of antibody recognition of pilus structures on two other gonococcal strains. The failure of gold spheres to attach to isogenic nonpiliated clones of the homologous gonococcus indicated the absence of pilus antigens on the surface of these organisms. The use of a double label--small gold spheres conjugated to anti-pilus antibody and larger gold spheres conjugated to anti-protein I antibody--allowed the simultaneous localization of two gonococcal antigens.

Antibodies, Bacterial↗

Anaphylactic degranulation of guinea pig basophilic leukocytes. II. Evidence for regranulation of mature basophils during recovery from degranulation in vitro.

Mature circulating granulocytes have been considered functionally end stage cells unable to reconstitute their specific cytoplasmic granules. We have reevaluated this assumption by studying guinea pig peripheral blood basophils maintained in vitro for periods up to 72 hours after anaphylactic degranulation. Guinea pig basophils degranulated in vitro by exposure to either specific antigen (sheep serum) or lectin (Concanavalin A) synthesized new cytoplasmic granules. This process was characterized by the appearance of abundant rough endoplasmic reticulum, activation of the Golgi zone, interiorization of plasma membrane, and successive formation of empty vacuoles, multivesicular bodies, immature granules, and, finally, typical mature basophil granules. Although basophil neogranulogenesis in vitro was similar in most respects to that occurring in the bone marrow, it differed significantly in that regranulating basophils retained the nuclear characteristics of mature granulocytes. New basophil granule formation was more prominent and developed earlier when sheep serum was employed as the degranulation stimulus. Cultures degranulated with Concanavalin A, and, less commonly, sheep serum, also contained small numbers of basoblasts, large bizarre basophils with immature nuclear and cytoplasmic features, cytoplasmic lipid droplets, and mature, immature, and fused granules. These cells may arise by a process analogous to lymphocytes blast transformation.

Anaphylaxis↗