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Biomedical subjects

R S Abernathy

Publications and source records attributed to R S Abernathy.

At least 19 recordsLinked to original sources

Vertebral blastomycosis with paravertebral abscess: report of eight cases and review of the literature.

Bone is the third most frequent site of disease in patients with blastomycosis, and the vertebrae are among the bones affected most often. We describe the clinical features and treatment of eight patients with vertebral blastomycosis and review the literature regarding this disease. All eight patients had destructive vertebral lesions evident on radiographs, and all had clinical or radiographic evidence of a contiguous abscess. The lower thoracic or lumbar regions were affected most often. Fever and skin lesions typical of blastomycosis were variably present. All but one patient had an abnormal chest radiograph. Treatment included long-term antifungal therapy and drainage of large fluid collections. Five of the eight patients were cured of their disease. Of the other 3 patients, 1 is still receiving therapy and is probably cured, 1 died of blastomycosis, and the status of 1 is unknown. In areas of endemicity, blastomycosis should be a diagnostic consideration for any patient with a destructive vertebral lesion.

Abscess

Stem cell responses in myelosuppressed mice following sequential treatment with recombinant human interleukin 1 (rHuIL-1), recombinant murine interleukin 3 (rMuIL-3) and recombinant human macrophage colony-stimulating factor (rHuM-CSF).

In vivo, recombinant human interleukin 1 alpha (rHuIL-1 alpha) + recombinant human macrophage colony-stimulating factor (rHuM-CSF) (IL-1 + M-CSF) effectively serves as a rescue agent for myelosuppression by enhancing the recovery of hematopoietic stem cell (HSC) subpopulations following treatment with 5-fluorouracil (5-FU). Because in vitro studies have suggested that hematopoietic recovery in 5-FU-treated bone marrow (FUBM) may proceed from a 5-FU resistant, (IL-1 + IL-3 + M-CSF-responsive) high proliferative potential HSC subpopulation of colony forming cells (HPP-CFC), studies were carried out to determine whether the addition of recombinant murine interleukin 3 (rMuIL-3) (IL-3) to either IL-1 or IL-1 + M-CSF would further enhance the recovery of HSC subpopulations in myelosuppressed C57Bl/6 mice. With the exception of the HPP-CFC, IL-3 dampened, rather than enhanced, the accelerated recovery of 8 d and 12 d colony forming units-spleen (8 d and 12 d CFU-S) and the committed macrophage progenitor (CFU-M) associated with in vivo treatment with IL-1 alone. Similarly, IL-3 interfered with the enhanced recovery of those HSC subpopulations in FUBM influenced by the synergistic interaction of IL-1 + M-CSF. This interference, however, was observed only when the rMuIL-3 was administered on day 2 or 3 of a four-day treatment with IL-1 + M-CSF. There was, however, no evidence that IL-3 exerted a negative influence on the restoration of granulocytes in the myelosuppressed animals. Moreover, sequencing studies provided data suggesting that the dampening effects of IL-3 on the synergistic interaction of IL-1 + M-CSF resulted from both an enhanced differentiation of the more primitive HSC subpopulations and a significant, but preferential, mobilization of the more mature 8 d CFU-S and CFU-M to extramedullary organs and that the mobilization of these more mature HSC subpopulations was temporally linked to their generation from the recovering HPP-CFC and 12 d CFU-S subpopulations.

Animals

Accelerated marrow recovery following total-body irradiation after treatment with vincristine, lithium or combined vincristine-lithium.

Accelerated post-irradiation recovery of hematopoietic marrow has been reported following treatment with lithium (Li) or vincristine (VcR). Because these two agents appear to exert their effects on different, albeit overlapping, hematopoietic populations, it was felt that combining them might lead to a wider spectrum of enhanced post-irradiation marrow regeneration. Results demonstrated that an accelerated recovery, which appeared to be additive in nature, was observed in the marrow following combined VcR-Li/4.5 Gy total-body irradiation. The combined schedule significantly enhanced post-irradiation recovery of white blood cells, 12-day spleen colony-forming units, erythroid burst-forming units, and fibroblastic colony-forming units over radiation alone; and recovery of marrow cellularity, multipotential colony-forming units (CFU-gemm) and granulocytic/monocytic colony-forming units (CFU-gm) over both radiation alone and either drug given singly with the 4.5 Gy. In addition, while data on the ability of regenerating stroma to support CFU-gm and CFU-gemm did not suggest that VcR was acting to enhance post-irradiation marrow recovery by increasing stromal production of hematopoietic growth factors, Li did appear to increase production of one or more of these factors, and this may be part of its mechanism of action.

Animals

Marrow antioxidant enzyme activity in tumor-bearing and non-tumor-bearing mice following vincristine treatment.

Pretreatment or "priming" with vincristine (VcR) has been documented to radioprotect animals from whole body irradiation by accelerating recovery of hematopoietic marrow. The mechanisms underlying this phenomenon are unclear, but the marked similarities between priming with VcR and with immune stimulants such as endotoxin and glucan have led to speculation that VcR may be inducing such radioprotective immunoregulators as interleukin 1 (IL-1) and tumor necrosis factor (TNF). The radioprotective ability of these cytokines, in turn, has been linked to an induction of the antioxidant enzyme manganese superoxide dismutase (Mn SOD). To establish whether priming with VcR is associated with induction of antioxidant enzymes, the activities of Mn SOD, copper-zinc (Cu-Zn) SOD, catalase (CAT), and glutathione peroxidase (GPX) were measured in the marrow of both LLca tumor-bearing and non-tumor-bearing mice given a priming dose of VcR. Results in non-tumor-bearing mice indicate that, similar to IL-1 and TNF administration, VcR treatment increases Mn-SOD activity, but not Cu-Zn SOD, CAT, or GPX activity. Furthermore, this increase occurs at the time VcR priming has been demonstrated previously to exhibit maximal radioprotection, suggesting that it may be contributing factor. However, VcR priming has been demonstrated to radioprotect both tumor-bearing and non-tumor-bearing animals, and no increase in Mn SOD activity (or the other enzymes monitored) was found in the tumor-bearing group. Rather, the presence of tumor significantly suppressed antioxidant enzyme activity. Collectively, the present data suggest that it is unlikely that increased antioxidant enzyme activity is directly involved in the VcR priming response.

Animals

Accelerated postirradiation recovery of hematopoietic marrow following priming with low doses of vincristine.

The present investigation is a continuation of efforts to characterize the radioprotective potential of priming with vincristine (VcR). In this study, the postirradiation recovery kinetics of the marrow's hematopoietic stem cell, progenitor cell, and stromal cell compartments were monitored following exposure to a range of sublethal radiation doses to determine (a) the optimal VcR/radiation intertreatment interval for achieving maximal hematopoietic protection, (b) whether this optimal interval is influenced by the dose of radiation administered, and (c) whether the radioprotection observed involves the hematopoietic stroma. The results demonstrate that the degree of radioprotection observed was significantly influenced by the scheduling of the VcR priming dose with respect to the radiation exposure. An intertreatment interval of 24 h provided maximal radioprotective benefit irrespective of the radiation dose administered. Additionally, the radioprotection following VcR priming appeared to be more the result of an accelerated recovery in the hematopoietic stem cell and progenitor cell compartments than a change in their intrinsic radiosensitivity. The data also suggest that this accelerated recovery was not a consequence of greater radioprotection of marrow stroma. Finally, the radioprotection observed following VcR priming did not appear to involve a selective lineage response by either the erythroid or the granulomonocytic progenitor compartments.

Animals

Tuberculosis in children and its management.

Children with tuberculosis (TB) in the United States are generally asymptomatic, 60% are under 5 years, 80% belong to racial/ethnic minorities or are foreign born, and most are diagnosed during the investigation of contacts of known cases of pulmonary TB. A presumptive diagnosis of primary TB is made on the basis of a positive tuberculin reaction and a characteristic chest roentgenogram, usually showing hilar adenopathy. Treatment may be with isoniazid (INH) and rifampin (RIF), largely twice weekly for 9 months, or INH, RIF, and pyrazinamide for 2 months followed for 4 months by INH and RIF. Four drugs are needed in cases of infection with drug-resistant organisms or in tuberculous meningitis. All therapy must be closely monitored for toxicity and compliance. In noncompliant families, all medication should be directly administered. This is now possible with short-course therapy, largely twice weekly. Preventive therapy for the tuberculin positive, but disease-free child, is provided more cost-efficiently with 6 months than with 12 months of treatment with INH; less than 6 months is not adequate. All tuberculin reactive children should receive INH for 6 months. More diligence in providing INH prophylaxis to adult reactors will decrease future infectious TB cases, and thus prevent transmission to other children.

Antitubercular Agents

Management of tuberculosis in pregnancy and the newborn.

Tuberculosis in pregnant women and their offspring is a serious and sometimes life-threatening infection. A high index of suspicion is a prerequisite for proper diagnosis. Early detection is essential since treatment is successful in these patients.

Antitubercular Agents

Altered radiosensitivity of hematopoietic stem cells by vincristine pretreatment: superoxide dismutase activity as a possible mechanism.

The effect of vincristine (VCR) on hematopoietic stem cell and progenitor compartments and its ability to induce transient periods of radioresistance was investigated so that we could ascertain the drug-radiation intertreatment interval affording optimal radioprotection and determine if its ability to induce increased levels of superoxide dismutase (SOD) is a potential mechanism for this radioprotection. Measurement of marrow stem cell and progenitor compartments demonstrated that these subsets displayed differential sensitivity to VCR and that this sensitivity appeared to be proportional to how "primitive" the subset was. Treatment with VCR prior to irradiation was observed to enhance significantly both 8- and 12-day spleen colony-forming unit recovery with maximal radioprotection occurring for a drug-radiation interval of 12-48 hours. Monitoring of copper-zinc SOD levels demonstrated an increase in activity following VCR that was localized in a fraction of the bone marrow enriched for stem cells and progenitors. The temporal pattern of this increase, however, did not correlate with the drug-radiation schedules affording optimal radioprotection, which indicates that other factors appear to be operative in this radioprotection as well.

Animals

Childhood sarcoidosis in Arkansas.

Sarcoidosis, a granulomatous disease of unknown etiology, is most often seen in young adults. Childhood cases have been reported primarily from Virginia, North Carolina, and South Carolina. Thirty children have been seen in Arkansas between 1957 and 1982, which suggests that the endemic area for childhood sarcoidosis should include both the south central and southeastern United States. The median age was 11 years; 29/30 were black; and 90% were symptomatic, 60% with systemic symptoms. Manifestations included abnormal chest roentgenograms (100%), restrictive pulmonary functions (79%), lymphadenopathy (63%), splenomegaly (40%), skin lesions (30%), granulomatous uveitis (27%), hyperglobulinemia (72%), and hypercalcemia (30%). Course and prognosis were similar to those in adults at follow-up of two to 11 years. Four with uveitis had serious residua in the eyes, three had crippling restrictive lung disease, and two died of respiratory failure. Sarcoidosis seems to be an immunologic response to an unknown inhaled antigen, probably present in the southeastern and south central US.

Adolescent

Ketoconazole therapy for endemic blastomycosis.

Amphotericin B is effective in therapy for blastomycosis but causes a number of serious adverse reactions. Because ketoconazole has in-vitro activity against Blastomyces dermatitidis, we administered this agent in a dosage of 400 mg/d to 46 patients with blastomycosis, with 43 patients receiving at least 1 month of therapy. Thirty-five patients had cure without relapse over a mean follow-up of 17 months. Six had a relapse of infection but 4 of these had been noncompliant with therapy. Two patients improved initially but ultimately had progression of disease despite maintenance of adequate serum levels. Adverse effects were common but not severe. Three patients with extensive infection died--2 had received only one dose of ketoconazole and 1 had received therapy for only 2 weeks. The cure rate in these patients suggests that ketoconazole may replace amphotericin B as the initial treatment of blastomycosis that is not overwhelming.

Adult

Short-course chemotherapy for tuberculosis in children.

Short-course, largely twice-weekly chemotherapy for tuberculosis was introduced in the United States for treatment of adults with pulmonary disease by the Arkansas State Department of Health in 1976. Since 1977, 50 children with tuberculosis have been treated with rifampin, 10 to 20 mg/kg, and isoniazid, 10 to 20 mg/kg daily for one month followed by 10 to 20 mg/kg of rifampin and 20 to 40 mg/kg of isoniazid twice a week for another 8 months. Ages ranged from 4 months to 15 years with a median age of 3 years. A presumptive diagnosis of tuberculosis was made on the basis of 10 mm or more of induration to 5 TU of purified protein derivative and a chest film or other findings compatible with tuberculosis. Three children had extrapulmonary disease (two had cervical adenitis, one had tuberculosis arthritis). Of the 47 children with pulmonary disease, 32 were asymptomatic. The results were excellent. Symptoms cleared in 1 to 2 months. Most pulmonary infiltrates had cleared by 10 months, but hilar adenopathy rarely cleared in less than 2 years. Drug toxicity occurred in only one patient (vomiting of rifampin). This treatment appears to be safe, effective, inexpensive, short and simple enough to ensure cooperation or to allow personnel to administer drugs directly to children from socially disorganized families.

Adolescent