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Biomedical subjects

S J Gluckman

Publications and source records attributed to S J Gluckman.

At least 19 recordsLinked to original sources
PubMed1998

First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: safety and host response.

A DNA-based vaccine containing human immunodeficiency virus type 1 (HIV-1) env and rev genes was tested for safety and host immune response in 15 asymptomatic HIV-infected patients who were not using antiviral drugs and who had CD4+ lymphocyte counts of > or = 500 per microliter of blood. Successive groups received three doses of vaccine (30, 100, or 300 microg) at 10-week intervals in a dose-escalation trial. Vaccine administration induced no local or systemic reactions, and no laboratory abnormalities were detected. Specifically, no patient developed anti-DNA antibody or muscle enzyme elevations. No consistent change occurred in CD4 or CD8 lymphocyte counts or in plasma HIV concentration. Antibody against gp120 increased in individual patients in the 100- and 300-/microg groups. Some increases were noted in cytotoxic T lymphocyte activity against gp160-bearing targets and in lymphocyte proliferative activity. The safety and potential immunogenicity of an HIV-directed DNA-based vaccine was demonstrated, a finding that should encourage further studies.

AIDS Vaccines↗
PubMed1997

Histiocytic necrotizing lymphadenitis (Kikuchi's disease): in situ end-labeling, immunohistochemical, and serologic evidence supporting cytotoxic lymphocyte-mediated apoptotic cell death.

Histiocytic necrotizing lymphadenitis (Kikuchi's disease) is a benign, self-limited disorder that is sometimes confused with malignant lymphoma. Kikuchi's disease is characterized by collections of histiocytes and lymphocytes surrounding areas of necrosis containing fragments of karyorrhectic nuclear debris. Polymorphonuclear leukocytes are generally absent. The mechanism of cell death involved has not been extensively studied, and a definitive etiology has not been identified. Recent articles proposed that the mechanism of cell death is more characteristic of coagulative necrosis than apoptosis, but, to our knowledge, this has not been studied with the use of currently available assays of apoptosis. To study the mechanism of cell death in Kikuchi's disease, we employed an in situ end-labeling technique on formalin-fixed, paraffin-embedded sections of lymph nodes with Kikuchi's disease. These studies demonstrated that the lymphocytes and histiocytes within and surrounding the areas of necrosis showed nuclear DNA fragmentation, a feature characteristic of early apoptosis. Immunohistochemical studies revealed an increase in CD8(+)-T lymphocytes and lymphocytes containing TIA-1, a cytotoxic granule-associated protein, within foci of cellular debris, with a relative paucity of CD56+ cells. Moreover, TIA-1-positive granules were present within the cytoplasm of many apoptotic bodies. In one of the patients for whom acute phase serum was available, evaluation by enzyme-linked immunosorbent assay demonstrated that the serum concentrations of the T-cell activating cytokines interleukin-2 and interleukin-6 were increased; no such increase was noted in eight patients with other lymphoproliferative disorders. In contrast, the serum concentrations of the immunosuppressive molecules interleukin-10, soluble interleukin-2 receptor, and soluble tumor necrosis factor receptor were expressed at normal levels in the patient with Kikuchi's disease. These findings suggested that the predominate mechanism of cellular destruction in Kikuchi's disease was apoptosis mediated by cytolytic lymphocytes. These data supported the prevailing hypothesis of a viral or autoimmune pathogenesis in Kikuchi's disease.

Adult↗
PubMed1996

Kikuchi-Fujimoto disease: a benign cause of fever and lymphadenopathy.

PURPOSE: To describe 6 cases of Kikuchi-Fujimoto disease and to review the literature. PATIENTS AND METHODS: Review of 6 patients with biopsy-proven Kikuchi-Fujimoto disease detected at a university hospital over a 5-year period. RESULTS: Six patients presented with localized, mild lymph node enlargement. In 3 cases, dramatic fever, chills, weight loss and systemic complaints were present. These features prompted prolonged antibiotic therapy and extensive evaluations of fever of unknown origin before the diagnosis was made by biopsy of the minimally enlarged lymph nodes. The 3 remaining patients were otherwise asymptomatic and well. All 6 subjects recovered without specific therapy. CONCLUSIONS: Kikuchi-Fujimoto disease is a recently described cause of benign, self-limited lymphadenopathy that is easily confused histologically and clinically with lymphoma and systemic lupus erythematosis. Clinicians and pathologists must be aware of this condition. Although it is an uncommon cause of fever of unknown origin, early recognition of KFD will minimize potentially harmful and unnecessary evaluations and treatments.

Adult↗
PubMed1994

AIDS hot lines and information agencies. The consistency of their information.

OBJECTIVES: To determine the consistency of responses given by acquired immunodeficiency syndrome (AIDS) hot lines and AIDS information agencies to a standard set of questions related to human immunodeficiency virus (HIV) infection and to investigate the training of workers in these telephone information agencies. DESIGN: A two-part questionnaire that addressed issues of HIV transmission and testing (part 1) and sexual behavior, diet, alcohol use, and partner notification (part 2). SETTING: Thirty-three AIDS telephone information agencies. PARTICIPANTS: Information specialists at these agencies were contacted on multiple occasions over a 1-year period. INTERVENTION: Initially, 48 calls were made to these agencies. Responses were recorded in the words of the information specialists, categorized, and assessed for consistency. Two additional surveys using the same questionnaire were also performed, examining the variability of responses within an individual agency and the variability of responses from six agencies, three with and three without formal training of their information specialists. RESULTS: The initial survey revealed inconsistencies and inaccuracies in responses from AIDS telephone information agencies particularly in the areas of HIV testing, risk factor assessment, safe-sex recommendations, and life-style changes for infected persons. The second survey revealed variability in responses from six information specialists within a single agency. The third survey revealed that, overall, agencies with and without formal training of workers were equally inconsistent in their responses. CONCLUSIONS: There are identifiable deficiencies in the quality and consistency of information given by some AIDS telephone information agencies. Training procedures of information specialists at these agencies are variable and may be inadequate.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Evaluation of the painful prosthetic joint. Relative value of bone scan, sedimentation rate, and joint aspiration.

Seventy-two joint arthroplasties undergoing total hip or total knee surgery were studied prospectively with plain radiographs, three-phase bone imaging (3PBI), erythrocyte sedimentation rate (ESR), aspiration of the joint for culture, and multiple intraoperative cultures at the time of revision. Intraoperative cultures and the operative appearance were used to form a diagnosis of definite infection (unequivocal microbiology and gross sepsis), possible infection (positive microbiology or gross sepsis), or no infection (neither positive microbiology nor gross sepsis). For the preoperative diagnosis of infection, as opposed to aseptic loosening, 3PBI alone had a sensitivity of 33% and a specificity of 86%. In conjunction with plain radiographs, minimal improvement in accuracy was seen. A preoperative ESR greater than 30 had low sensitivity (60%) and a specificity of (65%). However, the ESR was statistically significantly higher in the joints with definite infection as compared to those joints without infection. The preoperative joint aspiration had a sensitivity of 67% and a specificity of 96% and, therefore, appears to be the most useful single test in the workup of a painful total joint arthroplasty.

Aged↗
PubMed1987

Treatment of the septic hip with total hip arthroplasty.

Forty-three patients, 23 with definite infection and 20 with probable infections before total hip arthroplasty (THA), were compared to 41 matched uninfected patients. The 43 infected patients were treated by 45 operative procedures: eight Girdlestone resections, 12 revisions of total hips, and 25 conversions from infected nontotal hip surgery to total hip arthroplasties. (Two revision THAs were converted to Girdlestones). The average follow-up period was 38.8 months, with a range of six-118 months. The statistically significant negative prognosticators were gross sepsis at surgery, number of previous operations, and elevated erythrocyte sedimentation rate (ESR). The type of infecting organism did not affect the outcome. The prosthesis survival rate for total hip arthroplasties revised for sepsis was 83%. The prosthesis survival rate for other infected hips treated by total hip arthroplasty was 100%. All groups except Girdlestone resections improved postoperatively. While Girdlestone resection offered acceptable pain relief, total hip arthroplasty provided unequivocally superior function (p = 0.0001).

Adult↗
PubMed1978

Granulocyte function and levels of immunoglobulins and complement in patients admitted for withdrawal from alcohol.

Chronic alcoholics who had been drinking heavily until admission for withdrawal from alcohol were studied to determine their level of granulocyte function, immunoglobulin concentration, and complement system activity. Although most had some mild derangement in results of liver function tests, serum albumin concentrations were normal, and there was no clinical evidence of malnutrition or cirrhosis. Granulocyte adherence was slightly depressed in two subjects (52.4% and 54.1%; normal, 76.0% +/- 12%), although mean adherence for the group was normal. Mean chemotaxis was significantly below normal (2,103 vs. 7,943 counts per min), and the impairment was related to a defect or inhibitor in the serum of patients. Phagocytic activity was less than half that of control subjects in two alcoholics, but mean values were not depressed. Bactericidal activity was normal in all. Serum concentrations of immunoglobulins and total hemolytic complement activity were above the normal range for the group. The general inhibition of chemotaxis or the occasional defects in other granulocyte functions may contribute to the difficulty that alcoholics have with infection.

Adult↗
PubMed1978

Effect of acute alcohol intoxication on granulocyte mobilization and kinetics.

Granulocyte mobilization into skin abrasions in human volunteers was significantly inhibited by acute alcohol intoxication (45,-800 cells in 8 hr versus 353,000 in normal controls). Alcohol applied locally did not inhibit granulocyte delivery, and protection of the abrasion against heat loss did not reduce the inhibited delivery in intoxicated volunteers. Intoxication inhibited granulocyte adherence and local mobilization in parallel. Alcohol administration to rabbits shifted granulocytes from marginal to circulating pool in a manner similar to epinephrine. Mobilization of bone marrow granulocytes by glucocorticoid or endotoxin administration was not inhibited by intoxication, nor did it prevent the endotoxin-induced shift of granulocytes from circulating to marginal pool.

Alcoholic Intoxication↗
PubMed1977

A randomized clinical trial of granulocyte transfusions for infection in acute leukemia.

In a prospective, controlled, randomized study to evaluate the efficacy of filtration-leukapheresis granulocytes in granulocytopenic, febrile patients with leukemia, 19 patients received antibiotics alone, and 12 received antibiotics plus daily granulocyte transfusions from ABO-matched donors. In skin-chamber studies the granulocytes appeared at sites of inflammation for at least six hours after transfusion. Infected subjects survived longer if they received granulocytes. Differences between control and transfused patients were greatest in patients with persistent bone-marrow failure, the 21-day survival being 20 per cent in controls, and 75 per cent in transfused patients. Granulocytes appeared to have no effect on the outcome of febrile episodes in which infection was not documented, the 21-day survival being 79 per cent for controls and 88 per cent for transfused patients. The transfusion of granulocytes thus appears to offer a survival advantage to infected, persistently granulocytopenic patients.

Acute Disease↗