Comparing an apple to a fruit salad.
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Biomedical subjects
Publications and source records attributed to M Nucci.
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The role of bone marrow biopsy in the staging of Hodgkin's disease is undergoing reevaluation. We have studied the relationship of clinical factors to the presence of bone marrow involvement in 130 previously untreated patients with Hodgkin's disease. The presence of fever, spleen enlargement, anemia, leukopenia, poor performance status and poor histologic subgroups were positively correlated with the presence of bone marrow involvement in the univariate analysis. In the multivariate analysis, only fever, spleen involvement, leukopenia and poor histologic subgroups were significant. The predictive value of the absence of fever in regard to the absence of bone marrow involvement was 98%. The likelihood of bone marrow involvement in the absence of all four significant factors was only 0.05%. Patients without these clinical factors should probably not be submitted to a bone marrow biopsy as part of the staging procedures performed in Hodgkin's disease.
Extramedullary hematopoiesis is a common accompaniment of a variety of hematologic diseases such as hereditary spherocytosis, thalassemia and myelofibrosis. The association of extramedullary hematopoiesis with polycythemia vera in the proliferative phase is much less usual. We report a patient who presented with paraplegia due to spinal cord compression; clinical investigation revealed a paravertebral hematopoietic tumor, and the diagnosis of polycythemia vera was then established.
The performance of polyethylene glycol-modified bovine hemoglobin (PEG-Hb) was evaluated in dogs following the replacement of 30% or 50% of their blood volume with PEG-Hb or lactated Ringer's solution (LRS). Dogs fully instrumented with catheters and blood pressure probes were transfused by simultaneous bleeding from the jugular vein and infusion of PEG-Hb or LRS via the cephalic vein. Animals were monitored for abnormal behavior and clinical signs for fourteen days. No mortalities, overt toxicity, changes in body weight, food consumption or ophthalmology, or discernable trends in hematology, blood chemistry coagulation, urinalysis or hemodynamic parameters that could be attributed to PEG-Hb were noted. Blood gas analyses were steady and within physiological ranges. Dose-related histopathological findings of vacuolated histiocytes in the femoral bone marrow, splenic parenchyma, the medulla of the mesenteric and mandibular lymph nodes, and vacuolated sinusoidal cells in the liver and the renal tubular epithelial cells were believed to be related to the phagocytosis and degradation of PEG-Hb by the reticulo-endothelial system. The maintenance of high oxygen levels in the circulation for the two-week treatment period, as well as the insignificant physiological and histopathological findings indicate that PEG-Hb could be a successful blood substitute.
Fusarium infection is increasingly reported in immunocompromised patients. The role of central venous catheters as potential portals of entry for Fusarium is possibly underestimated. Four cases of catheter-related fusarial infection in children with acute leukemia or a solid tumor are described. These patients had an excellent response to removal of the central venous catheter and treatment with amphotericin B.
We retrospectively studied 343 consecutive patients treated between 1979 and 1992. Ninety patients whose stool was not examined were excluded. Fifty-three patients with strongyloidiasis were compared with 200 controls with regard to outcomes and the following characteristics: age, sex, underlying disease, use of corticosteroids, abdominal pain, diarrhea, fever, pulmonary symptoms, and eosinophilia. Patients with strongyloidiasis more commonly had eosinophilia (P = .01) and fever (P = .03). There was a single but fatal case of the disseminated disease syndrome (1.9% of patients with strongyloidiasis). In multiple logistic regression analysis, the factors predictive for strongyloidiasis were schistosomiasis (odds ratio [OR], 6.58), ascariasis (OR, 2.78), and the use of steroids (OR, 2.29). Strongyloidiasis was highly prevalent among patients with hematologic malignancies in Brazil. Occurrence of the disseminated disease syndrome seems to be unusual.
Aminoglycoside-containing combination therapy has been the standard empirical approach for febrile neutropenic cancer patients. With the advent of the broad-spectrum oral fluoroquinolones, it is now possible to evaluate an initial empirical alternative therapy. A prospective randomized study was conducted comparing oral ciprofloxacin plus penicillin V (group A) with amikacin plus carbenicillin or ceftazidime (group B). Main criteria for eligibility were febrile patients with solid tumor or nonlymphoblastic lymphoma, a Zubrod PS equal to 1 or 2, no diarrhea, mucositis, or long-term central venous catheter. A total of 108 consecutive neutropenic febrile episodes were randomized (5 exclusions); 55 episodes were assigned to group A and 48 to group B. Most febrile episodes were of unknown origin. There were 10 microbiologically documented episodes with two cases of bacteremia. Both regimens were well tolerated. Oral regimen was substantially cheaper than parenteral regimen. Treatment success without regimen modification was 94.5% for group A and 93.8% for group B (p = .86; CI -0.08-0.10). Oral therapy with ciprofloxacin and penicillin V is a safe alternative to standard parenteral therapy in this low-risk group of neutropenic patients, with unquestionable cost containment.
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BACKGROUND: Over the last 15 years, a number of combination chemotherapy regimens have been reported to induce more than 80% complete remissions (CR) in patients with advanced Hodgkin disease (HD). Almost all such studies have been conducted in large institutions from North America and Europe. It remains to be proven, however, that those regimens are equally effective for the larger population of patients with HD who live in very different social conditions in third-world countries. METHODS: Fifty-nine patients with advanced-stage or early bulky HD were treated in two public hospitals with the C-MOPP/ABV hybrid program, in which cyclophosphamide was substituted for mechlorethamine. RESULTS: The median number of cycles administered was six, and the median follow-up was 32 months. Fifty patients (85%) reached a CR. The actuarial failure-free survival (FFS) rate was 69%, and the actuarial overall survival rate was 78% at 68 months. The only significant prognostic factor that predicted for improved FFS rate was the absence of B symptoms (P = 0.02). Overall survival was better for patients who reached a CR (P = 0.0003) and those with no systemic symptoms (P = 0.007). Toxic effects were moderate, with one treatment-related death and six episodes of serious infection. CONCLUSIONS: The target population consisted of lower-class Brazilians, many living in poor social conditions. Nevertheless, these results compare equitably with other results reported in the literature. C-MOPP/ABV is an adequate treatment for HD in third-world populations.
A prospective randomized trial was performed to compare the efficacy of a regimen containing a glycopeptide versus one containing a beta-lactamase inhibitor in the treatment of febrile episodes in neutropenic patients. Fifty-eight patients received piperacillin/amikacin/teicoplanin (group 1) and 56 received piperacillin/amikacin/tazobactam (group 2). In the case of persistence of fever without microbiological documentation of the cause, teicoplanin was also given empirically in group 2 on day 4, and amphotericin B in both groups on day 6. In 114 evaluable febrile episodes, the rate of success without modification of therapy was 60% in patients on piperacillin/amikacin/teicoplanin and 41% in patients on piperacillin/amikacin/tazobactam (p < 0.03). Eleven of 34 patients in the latter group who failed to improve eventually responded upon addition of teicoplanin. Ten and nine patients in group 1 and group 2 respectively required the addition of amphotericin B for definite improvement. There were 14 episodes of gram-positive septicemia in each group: the response rate was 100% in group 1 and 43% in group 2. Three episodes of gram-negative breakthrough septicemia occurred in group 1 versus no cases in group 2 (p = 0.1). Three deaths occurred in each group. Piperacillin/amikacin/tazobactam may be as efficacious as piperacillin/amikacin/teicoplanin in the treatment of febrile neutropenic patients provided the regimen is modified (usually by addition of teicoplanin) in unresponsive cases.
Progression of a low-grade non-Hodgkin's lymphoma into a more aggressive histologic pattern is a well-described phenomenon. The converse phenomenon, often called downgrading, is much less frequent. We report 2 patients in whom relapse with an indolent lymphoma was noted after chemotherapy for higher-grade disease. Other previously reported cases are reviewed. The implications for appropriate management and pathogenesis are discussed.
Three cases are reported of disseminated infection due to Fusarium species in severely neutropenic patients. The clinical findings in all patients included fever, painful disseminated nodular skin lesions and severe myalgia. The outcome was fatal despite early administration of amphotericin B. The portal of entry of the organism was probably the nasal sinus in two cases.
In a series of fourteen patients with adult T-cell lymphoma-leukaemia (ATLL) in Brazil the main features were lymphadenopathy, hepatosplenomegaly, hypercalcaemia, and high leucocyte counts, with abnormal lymphoid cells which had irregular nuclei. The series included the youngest patient with ATLL so far (18 months). Analysis with monoclonal antibodies showed a mature T-cell phenotype (CD4+, CD8-). Antibodies to HTLV-I and/or integration of HTLV-I proviral DNA were found in eleven patients. In the other three HTLV-I DNA could not be demonstrated even by means of the polymerase chain reaction; they therefore had HTLV-I-negative ATLL. This report of ATLL in Brazil corroborates serological reports that HTLV-I may be endemic in some parts of that country. Follow-up studies are required to identify precisely the main route of transmission of HTLV-I in South America and the risk factors for the development of ATLL in carriers.
Modification by covalent attachment of monomethoxypolyethylene glycol (PEG) can reduce the immunogenicity and prolong the circulating life of injected enzymes, making their use as therapeutic agents feasible. We report the first clinical use of PEG-modified Arthrobacter protoformiae uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma and renal insufficiency who was allergic to allopurinol. Two intramuscular injections totaling 3 U/kg body weight during the first 30 hours of treatment lowered the plasma urate level from 910 to 190 mumol/L (15.3 to 3.2 mg/dL), after which a dose of 2 U/kg every 5 to 6 days maintained the plasma urate level at 540 mumol/L (9 mg/dL) or lower. After the injection of PEG-uricase, uricase activity appeared in plasma rapidly, peaking within 24 hours and persisting for approximately 5 days; an inverse relation between plasma uricase activity and plasma urate concentration was noted. The agent was nontoxic and well tolerated. No antibody to either PEG-uricase or unmodified uricase developed over a 3-week period, during which four doses of PEG-uricase were administered. Because of its long circulating life, PEG-uricase is probably a more effective hypouricemic agent than unmodified uricase, which has previously had limited use. As an adjunct to cytolytic therapy for hematologic malignancies when protection from hyperuricemia is needed rapidly, PEG-uricase deserves further study.
In a cohort of 79 febrile episodes in 50 consecutive neutropenic patients seen at the University Hospital, Federal University of Rio de Janeiro, Brazil, between 1987 and 1991, it was observed that the cumulative incidence of disseminated fungal infections rose from 3% to 19% after the introduction of a new empirical antibiotic regimen. In order to identify risk factors, as well as to assess the impact of the new antibiotic regimen on the emergence of fungal infections, a nested case-control study was undertaken, in which 10 cases of disseminated fungal infections were compared with 30 randomly chosen controls, drawn from the same cohort. In a multiple logistic regression analysis, the predictive factors for disseminated fungal infection were younger age (odds ratio 0.85, 95% confidence interval 0.75-0.97) and use of the new antibiotic regimen (odds ratio 14.18, 95% confidence interval 1.05-191.80) The probable explanation for the emergence of fungal infections is that the new antibiotic regimen, by lowering the incidence of bacteraemia-related deaths, allowed patients to be at risk for the development of disseminated fungal infections.
The role of the new triazoles in the treatment of disseminated fungal infections in neutropenic patients is at present under scrutiny. Six neutropenic patients with disseminated fungal infections were treated with amphotericin B during neutropenia and itraconazole after bone marrow recovery. There were three pulmonary aspergillomas, one Aspergillus fumigatus sinusitis, one Fusarium-mycosis and one disseminated candidosis. Four patients were cured of the infection. This approach seems to be safe and effective in the treatment of disseminated fungal infections in neutropenic patients, with the advantages of low side-effects and the possibility of early discharge from hospital.
In this paper we report a eight-year prospective study designed to further characterize incidence, epidemiology, specific syndromes, treatment and prognosis associated with fungal infections in neutropenic patients. During the study period 30 fungal infections were diagnosed in 30 patients among 313 episodes of fever and neutropenia (10%). There were 15 cases of candidiasis, 5 pulmonary aspergillosis, 3 sinusitis by Aspergillus fumigatus, 5 infections by Fusarium sp., one infection by Trichosporon sp., and one infection due to Rhodotorula rubra. Blood cultures were positive in 18 cases (60%). The predisposing factors for fungal infection in multivariate analysis were the presence of central venous catheter (p < 0.001), longer duration of profound (< 100/mm3) neutropenia (p < 0.001), the use of corticosteroids (p < 0.001), gram-positive bacteremia (p = 0.002) and younger age (p = 0.03). In multivariate analysis only recovery of the neutropenia (p < 0.001) was associated with good prognosis whereas the diagnosis of infection by Fusarium sp. (p = 0.006) was strongly associated with a poor outcome. The death rate was 43%. There was no statistically significant difference in the death rate between patients who did receive (52%) or did not receive (50%) antifungal treatment. Identifying patients at risk, specific syndromes and prognostic factors may help to reduce the high mortality associated with disseminated fungal infections in neutropenic patients.
A prospective randomized trial was performed to compare teicoplanin to vancomycin as part of the empirical antibiotic therapy of febrile neutropenic cancer patients. Fifty-three patients were randomized to receive ceftazidime (100 mg/kg daily every 8 h), amikacin (15 mg/kg daily every 8 h) and teicoplanin (6 mg/kg once a day) and 53 other patients received ceftazidime, amikacin (same dosages) and vancomycin (30 mg/kg/day every 6 h). In 99 evaluable episodes, the success rates were 54% for patients receiving teicoplanin and 52% for patients receiving vancomycin (p=0.76, 95% CI-18-23). The response rates were similar for patients with unexplained fever and for patients with documented infections. There were no differences in renal toxicity or cutaneous side effects between the two groups. The overall death rate was 18.9%, with 10 deaths in each group. The most important factor associated with death was the diagnosis of a fungal infection (p=0.001). Teicoplanin seems to be well tolerated and as effective as vancomycin in the empirical antibiotic therapy of fever in neutropenic cancer patients.