Analysis of the morphometric characteristics of the thoracic and lumbar pedicles.

A total of 2,905 pedicle measurements were made from T1-L5. Measurements were made from spinal computerized tomography (CT) scan examinations and individual vertebral specimen roentgenograms. Parameters considered were the pedicle isthmus width in the transverse and sagittal planes, pedicle angles in the transverse and sagittal planes, and the depth to the anterior cortex in a line parallel to the midline of the vertebral body and along the pedicle axis. There was no significant difference between data obtained from CT scans and specimen roentgenograms. Pedicles were widest at L5 and narrowest at T5 in the transverse plane. The widest pedicles in the sagittal plane were seen at T11, the narrowest at T1. Due to the oval shape of the pedicle, the sagittal plane width was generally larger than the transverse plane width. The largest pedicle angle in the transverse plane was at L5. The posterolateral to anterolateral pedicle axis orientation in the transverse plane, seen at other levels throughout the thoracolumbar spine, reversed at T12. In the sagittal plane, the pedicles angled caudally at L5 and cephaladly from L3-T1. The depth to the anterior cortex was significantly longer along the pedicle axis than along a line parallel to the midline of the vertebral body at all levels with the exception of T12 and T11.

Free-living fungi as artifacts on hematology preparations.

The appearance of Helicosporium sp., a free-living fungus, is reported as a contaminant resembling nematode microfilaria on a Wright's stained blood smear. Also, an unidentified object with structures resembling the septate hyphae of the Fungi Imperfecti and two other forms with some features similar to the fungal genus Fusarium were found on leukocyte alkaline phosphatase preparations of blood smears. The possible incorrect identification of these pseudoparasites is discussed and a review of the pertinent literature included.

Amphotericin B serum concentrations during therapy.

Therapeutic outcome of patients being treated for systemic mycoses with amphotericin B is possibly related to the serum concentrations of this drug that are produced in these patients. Because current data are conflicting, the magnitude of these concentrations was restudied by using a bioassay which gave precise and accurate results. The highest of 155 serum concentrations was 2.01 mug/ml. Mean concentrations were 1.21, 0.62, and 0.32 mug/ml, at 1, 18, and 42 hr, respectively, after intravenous infusion of amphotericin B. This drug was detected in serum 7 weeks after completion of treatment, but it could not be detected 13 weeks after treatment. Drug levels did not appreciably decrease in serum stored for 8 to 9 months at - 10 C. Unequal serum content in assay tubes and measurement of assay turbidity by visual inspection may explain previously reported amphotericin B levels of 3.0 to 12.5 mug/ml.

Effect of rapid intravenous infusion on serum concentrations of amphotericin B.

The magnitude of the concentrations of amphotericin B produced in serum of patients with systemic mycoses may significantly influence the outcome of therapy with this drug. Since amphotericin B is conventionally administered in intravenous infusions lasting 4 to 6 hr, we asked whether faster infusions of this drug might yield higher serum concentrations without an increase in dose. This question was studied in three patients who received 16 infusions of this drug: eight infusions administered slowly (5 hr) and eight administered rapidly (45 min). Serum concentrations after each rapid infusion were compared with those after a slow infusion administered to the same patient. The mean serum concentration of amphotericin B 1 hr after the rapid infusions (2.02 mug/ml) was significantly higher (P < 0.001) than the mean serum concentration of amphotericin B 1 hr after the slow infusions of this drug (1.18 mug/ml). Mean serum concentrations 18 and 42 hr after rapid infusion remained slightly but not significantly higher than respective mean concentrations after slow infusions. By yielding higher initial serum concentration, rapid intravenous infusion may be therapeutically more effective than slow infusion of amphotericin B. Although rapid infusions caused no more toxicity than did slow infusions, the lack of greater toxicity with rapid infusion of amphotericin B should be further documented prior to extensive clinical application of this procedure.

Polymyxin B and rifampin: new regimen for multiresistant Serratia marcescens infections.

Polymyxin B and rifampin were given to 12 patients with multi-drug-resistant nosocomial Serratia marcescens infections. Eight cures were achieved; drug hepatotoxicity occurred once; one fatal suprainfection was encountered; and two patients died during therapy of causes related to severe underlying illnesses. Polymyxin B and rifampin were uniformly synergistic in vitro against the infecting strains and against 40 additional clinical isolates of S. marcescens.

Disseminated histoplasmosis with embolic endovascular complications: a case report.

A 57-year-old man had subacute embolic ischemia of his right foot and subsequent acute embolic ischemia of his left foot after angiography. Thrombus removed at the time of the left femoral thromboembolectomy grew Histoplasma capsulatum confirming the diagnosis of disseminated histoplasmosis. Surgical revascularization of the right leg and parenteral amphotericin B was followed by chronic ketoconazole therapy for 16 months. The patient has remained asymptomatic at 30 months after operation. Effective treatment of endovascular infection with ischemic complications of Histoplasmosis requires surgical revascularization and intensive chemotherapeutic intervention. Histoplasmosis is a ubiquitous infection in endemic areas that often has an asymptomatic subclinical course. Involvement of the cardiovascular system is rarely reported. Previous case reports have described infected cardiac valves and aortic aneurysms. This report describes the uncommon presentation of disseminated Histoplasma capsulatum infection as a peripheral embolic event and the successful management with revascularization combined with systemic amphotericin B followed by ketoconazole therapy.

Ketoconazole, amphotericin B, and amphotericin B methyl ester: comparative in vitro and in vivo toxicological effects on neutrophil function.

We investigated a number of parameters for host defense after the in vitro addition of the antifungal agents ketoconazole, amphotericin B (AMB), and amphotericin B methyl ester (AME). Similar assays were repeated before and after patients received the former two drugs. Viability by trypan blue exclusion, adherence by nylon wool columns, chemotaxis by the under-agarose technique, phagocytosis and killing by chemiluminescence, colony counts, and acridine orange direct visualization were assayed. In striking contrast to AMB and AME, ketoconazole demonstrated no significant effect on neutrophils. Adherence in the presence of therapeutic plasma levels of AMB and AME was decreased (P less than or equal to 0.005) at low drug concentrations, whereas at higher concentrations, adherence was increased (P less than 0.001). The chemotactic responses of cells incubated with AMB and AME demonstrated marked suppression. Phagocytic capacity and killing were decreased (P less than or equal to 0.005) with AMB as compared with control assays and assays performed in the presence of ketoconazole and AME. However, no difference were observed between two patients who received AMB and two other treated with ketoconazole.

Interactions between human granulocytes and Blastomyces dermatitidis.

We studied interactions in vitro between human granulocytes and the yeast-like form of Blastomyces dermatitidis, because granulocytes are prominent in the host response to systemic blastomycosis. In Boyden chamber assays, broth culture filtrates of B. dermatitidis contained levels of granulocyte chemotactic activity that were significantly higher than those present in similar culture filtrates of Histoplasma capsulatum and Cryptococcus neoformans, two fungi that characteristically do not elicit granulocytes in infected tissues. Microscopic study, including electron microscopy, demonstrated that granulocytes phagocytosed B. dermatitidis promptly and efficiently. Moreover, granulocytes emitted light (chemiluminescence) at a brisk rate during phagocytosis of B. dermatitidis, indicating activation of intracellular metabolic pathways. However, fungicidal assay showed that granulocytes (1:1 cell-yeast ratio, 10% serum) killed only 29% of the B. dermatitidis inoculum during 3 h of incubation. Taken together, these findings suggest that there is disparity between phagocytosis and intracellular killing of B. dermatitidis by human granulocytes, perhaps because of resistance of this fungus to granulocyte microbicidal mechanisms.

A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis.

We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.

Treatment of systemic mycoses with ketoconazole: emphasis on toxicity and clinical response in 52 patients. National Institute of Allergy and Infectious Diseases collaborative antifungal study.

The pharmacology, in vitro mycologic activity, toxicity, and efficacy of ketoconazole were studied in a Phase-II evaluation by the National Institutes of Health and National Institute of Allergy and Infectious Disease Mycoses Study Group. This report emphasizes the toxicity and clinical response data in 52 patients with the following systemic mycoses: blastomycosis in 16 patients; nonmeningeal coccidioidomycosis in 13; histoplasmosis in 8; nonmeningeal cryptococcosis in 7; sporotrichosis in 7; and both blastomycosis and nonmeningeal coccidioidomycosis in 1. Maximum daily doses of ketoconazole were 100 mg in 1 patient; 200 mg in 23; 400 mg in 12; and 600 mg in 16. In 52% of the patients, duration of therapy ranged from less than 1 to 6 months, whereas in 35%, duration ranged from 7 to 12 months, and in 13%, from 12 to 22 months. In 35 patients (67%), evidence of toxicity was not seen. Nausea, anorexia, or vomiting occurred in 21%. Cure or marked improvement was shown in 27 patients (52%), whereas failure of the primary course was seen in 14 (27%) and relapse after ketoconazole was discontinued in 11 (21%). Although this evaluation did not provide clear-cut clinical response data, our results indicate that ketoconazole, in the dosage regimens used, was more effective in patients with histoplasmosis and nonmeningeal cryptococcosis than in patients with blastomycosis and nonmeningeal coccidioidomycosis, and least effective in patients with sporotrichosis.