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Biomedical subjects

V Rodriguez

Publications and source records attributed to V Rodriguez.

At least 37 records · Page 2Linked to original sources

Escherichia coli bacteremia in patients with malignant diseases.

Of 142 episodes of Escherichia coli bacteremia that were reviewed, appropriate antibiotics were administered during 98 episodes diagnosed premortem and 74 episodes (71%) responded. The highest cure rates were observed when the portals of entry were the urinary tract and soft tissues. Administration of adrenal corticosteroids did not affect the outcome of these patients. The patients' neutrophil counts at the onset and during infection were important factors in predicting survival. Septic shock occurred in 13% of all episodes, and only 11% of these patients responded. Of those patients who died, 63% died within the first 24 hours. Aminoglycosides, cephalosporins, and semisynthetic penicillins used alone or in combination offered optimal coverage.

Adolescent

Factors predicting for response and survival in adults with advanced non-Hodgkin's lymphoma.

Knowledge of the prognostic factors that characterize a disease can assist in planning and analyzing clinical trials. The present study was conducted to determine the characteristics related to response and survival in patients with stage III and IV non-Hodgkin's lymphoma who were treated with combinations of cyclophosphamide, vincristine sulfate, and prednisone. Considering each characteristic individually and using stepwise regression analysis, tumor bulkiness, prior therapy, sex, and pretreatment lymphocyte count were selected as the four most important prognostic variables. Tumor architecture (diffuse or nodular pattern) and cell type, hemoglobin level, and symptoms although not important in predicting response were found to be important in predicting survival. The hemoglobin level had only marginal importance in predicting response. Factors found not be important were age, stage, symptoms, cell type, nodularity, marrow involvement, prior extensive radiotherapy, and bone involvement. A logistic regression equation has been derived that can be used to predict response rate.

Cyclophosphamide

Gram-negative bacillary infections in cancer patients.

The majority of infectious complications in cancer patients are caused by Gram-negative bacilli. The most common organisms are Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa. Sites of infection are related to the patients' underlying malignancies, but pneumonia and septicaemia occur most often. Important newer antibiotics for the therapy of these infections are aminoglycosides and semisynthetic penicillins. It is advisable to utilize combinations of antibiotics for serious infections in cancer patients, and therapy should be instituted promptly at the onset of infection.

Anti-Bacterial Agents

Sulfamethoxazole-trimethoprim for infections in cancer patients.

A combination of sulfamethoxazole and trimethoprim (Bactrim) was given orally to 35 cancer pattients with infections. Thirty-two patients did not respond to an initial antibiotic regimen that consisted primarily of carbenicillin disodium and an aminoglycoside. There were 18 single-organism, Gram-negative infections. The overall cure rate was 54%. The most common infection was pneumonia (47% responded to treatment). Eighty precent of the cases of septicemia were cured. The most common infecting organism was Klebsiella pneumoniae (45% with this infection responded). Eight cases of infection of unknown origin occurred (63% responded to treatment). Overall, 47% of the patients whose neutrophil count remained unchanged or decreased responded, while 61% of those whose neutrophil count remained unchanged or increased responded. There was no close correlation between the minimum inhibitory concentrations and the clinical responses. Sulfamethoxazole-trimethoprim orally is a well tolerated and effective form of antimicrobial therapy.

Administration, Oral

Comparison of lymphangiograms and gallium scans in the non-Hodgkin's lymphomas.

A total of 92 lymphangiograms (L.G.) and gallium scans (G.S.) done in 51 patients with non-Hodgkin's lymphoma were evaluated to assess their usefulness in detecting infradiaphragmatic disease. It was found that the correlation between both procedures was fairly good before treatment (85%) but decreased considerably after therapy. A significant number of patients persistently had positive L.G. after treatment, with a negative G.S. No histologic examination of tissues was performed, however, to confirm the radiographic findings. A higher number of equivocal G.S. were found both before and after treatment. No significant difference in correlation was found between the histiocytic and lymphocytic lymphomas but the former were found to have a striking frequency of negative L.G. and G.S. in the infradiaphragmatic area.

False Negative Reactions

Chemoimmunotherapy of metastatic large bowel cancer: nonspecific stimulation with BCG and levamisole.

The administration of two chemoimmunotherapy programs to 103 consecutive patients with metastatic colorectal cancer resulted in improved survival for patients who achieved either objective tumor regressions or disease stabilization for more than 8 weeks. Objective tumor regression was observed in 47% of patients treated with the Ftorafur-methyl-CCNU-methotrexate-Bacillus Calmette-Guerin (FTOR-MeM-BCG) program and in 34% of patients treated with the 5-fluorouracil-methotrexate-Baker's antifol (FU-M-BAF) +/- Levamisole program. The combinated median duration of survival for patients who achieved objective tumor regression and disease stabilization with FTOR-MeM-BCG was 13 months compared with 6 months for patients who had progression of disease (p = 0.001). The corresponding values for patients treated with FU-M-BAF +/- levamisole were 11 months and seven months, respectively (p = 0.001). While the role of BCG immunotherapy in these results remains speculative, the administration of levamisole immunotherapy did not appear to have influenced results significantly. Patients who presented at diagnosis with Dukes A, B and C lesions, and therefore had longer disease-free intervals, responded more frequently to chemoimmunotherapy and survived longer than patients who presented at diagnosis with Dukes D lesions. Similarly, greater antitumor effect was observed in patients with lower pretreatment plasma CEA levels evaluation of these pretreatment characteristics may have insignificant implications for the design of future clinical trials.

BCG Vaccine

Comparison of amikacin and tobramycin in the treatment of infection in patients with cancer.

Two new aminoglycoside antibiotics, tobramycin and amikacin, were compared in a randomized study of the treatment of infections in patients with cancer. For the identified infections, the response rate for tobramycin was 60% and for amikacin was 64%. Pneumonia, urinary tract infection, and septicemia were the most frequent infections. Most (78%) of the identified pathogens were gram-negative bacilli; Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa were the most frequently isolated organisms. When only infections due to gram-negative bacilli were considered, 67% responded to tobramycin and 69% responded to amikacin. All infections except pneumonias had at least a 50% response rate to either antibiotic. The major form of toxicity of both antibiotics was azotemia and occurred in 22% of cases treated with tobramycin and in 20% treated with amikacin. Tobramycin and amikacin are equally effective in the treatment of gram-negative infections and have similar toxicity.

Adolescent

Phase 2 study with Baker's Antifol in solid tumors.

One hundred thirty-eight adults with advanced cancers were treated with Baker's Antifol. The complete response + partial response rate was only 10%. Best responses were obtained in 31 patients with lung adenocarcinoma (complete response + partial response, 13%), in 25 patients with colorectal carcinoma (partial response, 16%), and in 6 patients with renal cell carcinoma (partial response, 50%). Two partial responses occurred in 15 patients with squamous cancer. No significant responses were seen in 27 patients with other adenocarcinomas, 13 with sarcomas, 14 with melanomas, and 8 with miscellaneous tumors. The most frequent toxicities were dermatitis, stomatitis, gastrointestinal symptoms, and mild myelosuppression. The incidence of dermatitis was significantly decreased by shortening the schedule of Baker's Antifol administration from 5 to 3 days. Baker's Antifol has some degree of antitumor activity, and studies of combination of this agent with other effective chemotherapeutic agents are indicated.

Adenocarcinoma

Combination chemotherapy ("CHOP-Bleo") in advanced (non-Hodgkin) malignant lymphoma.

Forty-seven adults with advanced malignant lymphoma (the majority in stage IV) were treated with a combination of cyclophosphamide, hydroxyldaunorubicin (Adriamycin), vincristine (Oncovin), prednisone, and bleomycin (CHOP-Bleo). The complete remission (CR) rate was 66%. The overall response (complete + partial remission) was 92%. The CR rate in patients with diffuse histiocytic lymphoma (DHL) was 69%. Only 3 of the 18 patients with DHL in CR have relapsed; the projected median duration of response was calculated to be greater than 2 yr. In patients with nodular poorly differentiated lymphocytic lymphoma (NPDL), the CR rate was 62%. One of the eight patients with NPDL in CR has relapsed; the projected median duration of complete response will be greater than 4 yr. The median survival for all patients entered in this study has not been reached; however, it was estimated that it will be greater than 3 yr. The survival curves became flat at 70 wk for the patients with DHL and at 1 yr for the patients with NPDL. Major complications during chemotherapy with CHOP-Bleo were myelosuppression and alopecia. Only six severe infections occurred during myelosuppression. No hemorrhagic problems were observed. This study indicates that combination chemotherapy with these agents is effective in increasing the CR rate and survival in patients with diffuse histiocytic lymphoma. In patients with NPDL, further observation will be needed to assess the effect of this combination on survival.

Adult

Late intensification therapy for acute leukemia in remission. Chemotherapy and immunotherapy.

Nineteen patients in continous complete remission of acute leukemia for at least one year received late intensification therapy, after which they received no further chemotherapy, but most received BCG immunotherapy. Five patients have relapsed. The 14 patients still in remission have been followed up for at least 60 weeks after late intensification, with a median time of 98 weeks. The length of complete remission subsequent to a comparable time was 44 weeks for a reference control group and 24 weeks for a matched control group. These results support this type of approach for long-term control of acute leukemia in adults.

Acute Disease

Phase I studies with Baker's Antifol (BAF) (NSC 139105).

Phase I studies were conducted in 58 adult cancer patients with Baker's Antifol (BAF), a new active-site directed inhibitor of dihydrofolate reductase. Dose escalation ranged from 10 to 250 mg/m2/day X 5 days and courses of treatment were repeated every 2-3 weeks. Biologic effects were observed mostly at doses greater than 100 mg/m2/day X 5 days. The patients developed myelosuppression during 19% of the trials. Other types of toxicity were dermatitis in 12 to 30% and stomatitis in 7 to 38% of the trials. Toxicity was directly related to the impairment of the patient's liver function. Two partial responses (in a patient with adenocarcinoma of the lung and a patient with transitional cell carcinoma of the bladder) occurred. BAF is an active new chemotherapeutic agent which deserves further clinical trials in patients with various malignancies.

Adolescent

Clinico-pathologic correlation of liver damage in patients treated with 6-mercaptopurine and Adriamycin.

Eleven adults with refractory leukemia treated with a combination of 6-mercaptopurine and Adriamycin developed hepatic dysfunction manifested by elevations of serum total bilirubin, alkaline phosphatase, and glutamic oxaloacetic transaminase. Liver tissue obtained at necropsy showed intrahepatic cholestasis (eight cases), hepatocellular necrosis (ten cases), leukemic infiltration (two cases), and fatty change (nine cases). Neither this frequency nor severity of hepatocellular destruction has hitherto been associated with 6-mercaptopurine at the dose levels used in this study, nor has Adriamycin previously been found to be hepatotoxic. It is postulated that Adriamycin potentiated the hepatotoxicity of 6-mercaptopurine in these patients.

Adult

Fungemia due to Torulopsis glabrata in the compromised host.

Ten episodes of Torulopsis glabrata fungemia occurring in nine patients with terminal illnesses are described. Eight patients had underlying malignancies and one patient had a plastic anemia. Two episodes of fungemia were considered transient since they were clearly related to the administration of intravenous hyperalimentation (IVH). Most patients were adult women and had solid tumors of the genitourinary tract. Contributory factors were: antibiotic therapy (100%), immunosuppressive drugs (75%), abdominal surgery (63%), IVH (50%), neutropenia (38%), and diabetes mellitus (13%). The clinical course was indistinguishable from a severe bacterial infection. However, endotoxic shock was not observed. The infection was rapidly fatal in four patients. In the remaining five patients, the infection was altered favorably by the discontinuation of infected intravenous hyperalimentation catheters. However, tissue invasion by T. glabrata was found in two of these patients who died shortly thereafter from tumor progression. At autopsy, T. glabrata was identified in tissue sections of the lungs, kidneys, and mucosas of the gastrointestinal and genitourinary tracts. In all cases there was tissue necrosis with a minor inflammatory response consisting of mononuclear cells. To our knowledge, this is the single largest series of T. glabrata fungemia ever reported.

Adult

Therapy of infections in neutropenic patients: results with gentamicin in combination with cephalothin or chloramphenicol.

Gentamicin in combination with cephalothin (Gent-Ceph) or with chloramphenicol (Gent-Chloro) was utilized in the treatment of 55 infections occurring in 49 cancer patients. Responses were obtained in 78% of the infections treated with Gent-Ceph and in 64% of those treated with Gent-Chloro. Pneumonia and septicemia were the most common infections in this study. Among the cases of penumonia, 64% responded to Gent-Ceph and 67% to Gent-Chloro. Among the cases of septicemia, 88% responded to Gent-Ceph and 50% to Gent-Chloro. All of the identified organisms producing infection were gram-negative bacilli. Of these, E. coli was the most common. All organisms were resistant to cephalothin in vitro, and only 41% of them were resistant to chloramphenicol. However, resistant organisms responded significantly better to the Gent-Ceph combination (p less than 0.025). Also, response to therapy among patients with severe neutropenia (less than 100 neutrophils/mm3) was better for those patients treated with Gent-Ceph (p = 0.07). The combination of gentamicin with cephalothin or with chloramphenicol did not increase the frequency of side effects expected from gentamicin alone. No significant hematological toxicity was seen among those patients treated with chloramphenicol. Gentamicin in combination with cephalothin or chloramphenicol is an effective and safe antibiotic combination against gram-negative bacilli infections occurring in cancer patients. The efficacy of Gent-Ceph in patients with severe neutropenia is particularly advantageous.

Agranulocytosis

Early consolidation chemotherapy for adults with acute leukemia in remission.

Three courses of intensive consolidation therapy were administered to 13 patients with acute leukemia after they achieved complete remission. The patients were randomly allocated to receive their therapy in or out of a protected environment unit and with or without antibiotic prophylaxis. The results suggest that the protected-environment-prophylactic-antibiotic program may have protected the patients from infection, although the numbers in each group are too small for meaningful comparison. However, early consolidation therapy was not beneficial, since the duration of remission and survival of these patients was less than that of a group of comparable patients who received only conventional maintenance therapy.

Acute Disease

Amikacin for treatment of infections in patients with malignant diseases.

Amikacin was evaluated in patients with malignant diseases during 134 episodes of identified infection, most of which were cases of pneumonia and septicemia. The overall rate of response of the identified infections was 63%. The majority of infections were caused by Escherichia coli, the Klebsiella-Enterobacter-Serratia group, and Pseudomonas aeruginosa. The response rate for infections caused by these organisms was 80%. Five of eight infections caused by organisms resistant to gentamicin responded to therapy with amikacin. Nephrotoxicity was observed in 13% of patients who had normal renal function initially.

Adolescent

Causes of death in adults with acute leukemia.

The causes of death were investigated in 315 adults with acute leukemia during a 7-year period (1966-1972). Infection alone or in combination was the most common cause (75%), followed by hemorrhage (24%) and organ failure (9%). Most of the infections were either systemic or pulmonary. Seventy-five percent of the systemic infections and 72% of the pneumonias were caused by bacteria. Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa were the most frequent organisms isolated. After 1968, there was a sharp decrease in the number of fatal infections caused by Pseudomonas aeruginosa and a marked increase in the incidence of fatal infections caused by Klebsiella spp. and E. coli. Infections caused by Gram-positive cocci occurred in only 3% of the cases. The incidence of systemic fungal infections was 13%; most common fungi causing infection were Candida spp. and Aspergillus spp. Eighty-five percent of 159 patients with a terminal neutrophil count of less than 100/mm3 died of infection, compared to 48% of 62 patients with a terminal neutrophil count of greater than 1000/mm3. Hemorrhage was mostly due to thrombocytopenia (61%) and disseminated intravascular coagulation (12%). This study indicates that infection continues to be the most common cause of death in patients with acute leukemia. Although advances in antibiotic therapy have changed the distribution of causative organisms, ultimate control of infection requires further improvements in supportive care measures which rectify impairments in the patients' host defense mechanisms.

Adolescent