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Biomedical subjects

V Rodriguez

Publications and source records attributed to V Rodriguez.

At least 91 records · Page 5Linked to original sources

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↗

Pirbenicillin, a new semisynthetic penicillin with broad-spectrum activity.

Pirbenicillin is a new semisynthetic penicillin which inhibited 67% of isolates of Proteus aeruginosa tested in our laboratory, 93% of P. mirabilis, 31% of Enterobacter spp., 41% of Serratia spp., and 58% of Escherichia coli at a concentration of 6.25 mug/ml. Its activity appeared to be inoculum dependent and it was virtually inactive against 10(7) inocula of P. aeruginosa. It was more active than carbenicillin or ticarcillin, but less active than BL-P1654 against P. aeruginosa. Carbenicillin and ticarcillin appeared to be more active than pirbenicillin against Proteus spp., but pirbenicillin was active against some isolates of Klebsiella spp.

Bacteria↗

Reduction of ifosfamide toxicity using dose fractionation.

Ifosfamide was given in i.v. doses of 600 to 1200 mg/sq m/day for 5 days to 32 cancer patients, refractory to prior therapy, in an attempt to investigate the possibility of reducing toxicity by dose fractionation. Microscopic hematuria occurred in 14% and gross hematuria in only 10% of the patient trials. Azotemia did not occur in any patient on this study. Reversible myelosuppression was comparable to that found by other investigators. Other side effects such as nausea and mental confusion occurred infrequently. Ifosfamide produced antitumor effect in 7 of 27 evaluable patients. This study indicates that the renal and bladder toxicity of ifosfamide can be substantially reduced if the drug is administered in i.v. infusions of 1 to 2 hr daily for 5 days.

Adolescent↗

Role of DTIC (NSC-45388) in the chemotherapy of sarcomas.

DTIC was one of the first of several new agents evaluated by the Southwest Oncology Group (SWOG) and the M.D. Anderson Hospital and Tumor Institute (MDAH) in the therapy of adult patients with metastatic sarcomas. It yielded an overall response rate of 17%. This is similar to that seen in a review of 138 patients who represent the total number reported in either published or unpublished data. The subsequent addition of DTIC to adriamycin in several studies carried out at the MDAH and in the SWOG has increased the complete and partial remission rate over that seen with adriamycin alone, and more importantly has increased remission duration and survival. DTIC is currently used in combination with adriamycin in the first-line therapy of patients with metastatic sarcomas and should be considered for patients who have relapsed on primary therapy not including DTIC.

Clinical Trials as Topic↗

Successful control of systemic Aspergillus niger infections in two patients with acute leukemia.

The diagnosis and successful control of systemic Aspergillus niger infection in 2 adult patients with acute leukemia is reported. During induction therapy, the first patient developed pulmonary infiltrates, skin lesions and abnormal liver function tests. Aspergillus niger was found on skin and liver biopsy. This patient was successfully treated with Amphotericin B and granulocyte transfusions and he remains in remission. The second patient developed a pneumonitis and adynamic ileus with positive sputum and stool cultures for Aspergillus niger. The infection only responded to Amphotericin B and granulocyte transfusions and the leukemia to cytoreductive chemotherapy. The patient later relapsed and died after a febrile illness. Fungi morpholocially consistent with Aspergillus were found in the liver at autopsy. Infection with A. niger is rare even in this patient population; however fungal infections have become an increasing problem. The need for a high index of suspicion, especially when an infection is unresponsive to antibacterial antibiotics, the various diagnostic tools, and the need for aggressive therapy are stressed. Amphotericin B is the chemotherapy of choice but may be insufficient in a severely neutropenic host where the simultaneous use of granulocyte transfusions might be lifesaving.

Acute Disease↗