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PubMed1968

Some factors influencing carbon dioxide production by Leuconostoc citrovorum.

This study was undertaken to determine whether Leuconostoc citrovorum plays a role in carbon dioxide production in milk. The ability of L. citrovorum strains to produce gas was studied by two methods. A qualitative method, in which an agar plug was forced up the neck of a volumetric flask, measured gas visually. This method demonstrated that 0.25% yeast extract, in a milk medium at 30 C, stimulated the production of at least 10 ml of gas. Studies using a Gilson Differential Respirometer revealed that L. citrovorum produced 500 to 900 muliters of CO(2) in 6.5 hr, whereas 800 to 1,500 muliters of CO(2) was produced in nonfat milk which contained 0.33% yeast extract. Cell extracts of Streptococcus cremoris, S. lactis, Lactobacillus lactis, L. casei, and L. helveticus also enhanced gas production of L. citrovorum from 20 to 70%. Autolysates of these bacteria, present during the ripening or ageing of certain cheeses, may stimulate L. citrovorum, a common organism in starter cultures, to produce gas, causing, for example, the slit-open defect of cheddar cheese. Yeast extract caused an increase in acid and gas production per cell but did not cause an increase in growth. Experiments indicated that one metabolic source of carbon dioxide was the decarboxylation of pyruvate produced during catabolism of citric acid. Yeast extract stimulated this reaction by 16%.

Animals↗
PubMed1976

The effect of methotrexate on spontaneous mammary adenocarcinomata in female C3H mice.

The effect of methotrexate on solid rodent tumours has been investigated using the spontaneous mammary adenocarcinoma of the female C3H/Bts mouse. As these tumours exhibit a wide range of volume doubling times, calculations of tumour response to methotrexate must be related to doubling time. When methotrexate is injected into the tumour a dose-dependent tumour response is obtained. Systemic citrovorum "rescue" prevents methotrexate lethalities but reduces tumour response by a factor of 2. Methotrexate-treated tumours have an increased volume doubling time post treatment.

Adenocarcinoma↗
PubMed1970

Growth stimulants in plant extracts for Leuconostoc citrovorum.

The growth of Leuconostoc citrovorum ML 34, an isolate associated with the malo-lactic fermentation of wine, was stimulated in part by grape, orange, cabbage, and tomato juices. The stimulatory activity of tomato serum was associated with the carbohydrate fraction. Further purification of the fraction showed that fructose was the factor responsible for initiating growth. In addition to fructose, the organism required CO(2) for establishing growth. Saturated CO(2) atmosphere and catalytic amounts of fructose served as substitutes for plant extracts in a complex glucose medium.

Carbon Dioxide↗
PubMed1978

Significance of the 48-hour plasma level in high-dose methotrexate regimens.

Plasma methotrexate (MTX) concentrations at 48 hours were determined for 40 patients with osteosarcoma who received 256 infusions of high-dose methotrexate-citrovorum rescue (HD-MTX-CF) regimen. Five manifestations of toxicity (dermatitis, stomatitis, myelosuppression, liver dysfunction, and kidney dysfunction) were considered in the assessment of the overall toxicity. Logistic regression analysis was applied to study the effect of number of prior infusions, age, and 48-hour MTX plasma level on the risk of moderate or severe overall toxicity. Each factor had a significant effect with P less than 0.08. The predicted incidence of moderate-severe overall toxicity in the high-risk group (48-hour MTX level greater than 1.00 x 10(-6) mol/l., prior infusions greater than 10, age greater than or equal to 15 years) was 33.2% compared to only 2.4% in the "low-risk" group (48-hour MTX level less than or equal to 1.00 x 10(-6) mol/l., prior infusions less than or equal to 10, age less than 15 years). The plasma MTX determination at 48 hours postinfusion was found to be independent of both dose infused and patient's age.

Adolescent↗
PubMed1975

Citrate lyase from Streptococcus diacetilactis. Association with its acetylating enzyme.

Citrate lyase (EC 4.1.3.6) was purified 38-fold from cell-free extracts of Streptococcus diacetilactis. The enzyme was homogeneous in analytical ultracentrifugation and polyacrylamide gel electrophoresis. The final enzyme preparation contained acetate: HS-citrate lyase ligase--an acetylating enzyme which converts inactive HS-citrate lyase into enzymatically active acetyl-S-citrate lyase. This enzyme activity was purified 25-fold over the crude extract and seemed to be associated with citrate lyase. Partially purified citrate lyase from Leuconostoc citrovorum contained also its acetylating enzyme. Purified citrate lyases from Klebsiella aerogenes and Rhodopseudomonas gelatinosa were devoid of acetylating enzyme activity. The HS-form of citrate lyase from S. diacetilactis was completely acetylated and hence activated by incubation with ATP and acetate for 25 min at 25 degrees C. The enzyme did not acetylate the HS-lyases from R. gelatinosa and K. aerogenes. In contrast to the citrate lyases from R. gelatinosa and K. aerogenes the enzymes from S. diacetilactis and L. citrovorum showed only a very weak reaction inactivation. It is assumed that this is due to the association of the acetylating enzymes with these lyases.

Acetates↗
PubMed1976

Immunochemotherapy of lung cancer.

After surgical resection of their primary lung cancer, 33 patients were randomized into one of three groups. The first received high-dose methotrexate once per month with citrovorum rescue, for 3 months. The second group were immunized monthly with a homogenate of Freund's complete adjuvant and carefully characterized soluble antigen derived from allogeneic lung cancer cells of appropriate histology, for 3 months. The third group received a combination of methotrexate and immunization monthly, for 3 months. Each patient was monitored immunologically before, during, and after the treatment period, by use of delayed hypersensitivity reactions to recall and cancer antigens, in vitro lymphocyte response to mitogens, and mixed lymphocyte blocking factor activity. The group that received methotrexate showed little change in skin reactivity, a reduction of blocking factor activity, and significant rebound overshoot in in vitro lymphocyte performance. The immunized group showed a tendency to production of blocking factor activity, striking conversion and enhancement of skin reactivity, and little change in in vitro lymphocyte performance. The immunochemotherapy group showed dramatic increases in specific skin reactivity to cancer antigens, up to 2 years after treatment, in vitro lymphocyte rebound overshoot, and reduction of blocking factor activity production. Classic life table analysis of the probability of freedom from metastases in patients with stage-I cancer indicate that the disease-free interval in patients who received methotrexate is longer than in historic and concomitant controls but not as long as in those who received immunization. The best group appear to be those who received combination immunochemotherapy. We emphasize that the small numbers in this pilot study do not yet allow firm conclusions to be made.

Adult↗
PubMed1980

Methotrexate in the treatment of penile carcinoma.

Eight patients with epidermoid carcinoma of the penis received methotrexate, five with high-dose methotrexate, 250--1500 mg/m2 with citrovorum rescue Q 2--4 weeks, and three with low-dose methotrexate, 0.5--3.0 mg/kg weekly. Three (38%) patients achieved a complete or partial remission which persisted for 11, 3 and 2 months, respectively. Methotrexate appears to be an active agent in the treatment of advanced penile cancer.

Adult↗
PubMed1987

High-dose chemotherapy. Concepts and strategies.

In experimental tumors, a steep dose-response curve has been demonstrated for chemosensitive malignancies. In clinical practice, increasing dose over the conventional dose results in higher responses. These observations have prompted efforts to use chemotherapy in higher doses. Initial empiricism lends itself to more rational use of high-dose chemotherapy. Strategies are based on alteration in drug schedules [e.g., high-dose cytosine arabinoside (Ara-C)], drug-to-drug interaction [e.g., high-dose methotrexate (MTX) with citrovorum rescue], and drug pharmacokinetics (e.g., regional chemotherapy). In general, increasing the dose of cytotoxic agents leads to increasing toxicity. Methods to circumvent unacceptable toxicity have been explored. Autologous bone marrow transplant is one such method that provides new avenues of therapy and has resulted in the emergence of a new spectrum of dose-limiting toxicity. Despite the improved response rate, high-dose chemotherapy has resulted in short response durations and no significant impact on the survival of cancer patients as yet. The greater benefit of such a modality may be in the consolidation of drug-sensitive tumors (e.g., lymphoma and small cell carcinoma) with minimal residual disease after minimal conventional therapy. We review various factors and concepts as they relate to the current use of high-dose chemotherapy. We conclude that drug resistance is multifactorial, and one variable that can be manipulated by clinicians is drug dose. The drug concentration appears crucial in enhancing cytotoxicity. All frontiers examining this approach in clinical practice deserve continued enthusiasm and cautious exploration while other factors are being fully understood and exploited.

Animals↗
PubMed1982

Continuous infusion vincristine and bleomycin with high dose methotrexate for resistant non-Hodgkin's lymphoma.

Sixteen patients with resistant non-Hodgkin's lymphoma were treated with continuous infusions of vincristine (1-2 mg/m2 daily X 2 days) and bleomycin (0.25 mg/kg bolus dose, then 0.25 mg/kg/daily X 5 days). Responding patients received high dose methotrexate (1500 mg/m2) with citrovorum rescue on days 15, 22, 29, 36. Treatment cycles were repeated every six weeks in responding patients. The response frequency was 50% (three complete and five partial responses). Median response duration was 29 weeks. Major toxicity included stomatitis (63%) and leukopenia (44%). One episode each of possible hypersensitivity pneumonitis and paralytic ileus occurred. Continuous infusions of vincristine and bleomycin should be studied further in less critically ill patients.

Adult↗
PubMed1973

Effect of selected lactic acid bacteria on growth of Staphylococcus aureus and production of enterotoxin.

Representative strains of 15 species of lactic acid bacteria were examined for their ability to influence growth of Staphylococcus aureus and production of enterotoxin in associative culture. Among the organisms used as effectors the streptococci were most inhibitory, followed by Pediococcus cerevisiae. The lactobacilli and Leuconostoc citrovorum were not inhibitory to growth and only slightly inhibitory to production of enterotoxin. Enterotoxin was detected in all cultures in which the population of S. aureus reached 8 x 10(7) per ml. At lower S. aureus populations no enterotoxin was detected after incubation for 48 h. Mechanisms of inhibition of growth and enterotoxin production by S. aureus strain 243 grown in association with Streptococcus lactis A64 or P. cerevisiae 10791 in APT broth were investigated. Competition for vital nutrients, especially niacin and biotin, and probably production of hydrogen peroxide contribute to inhibition. Production of lactic acid appears to inhibit growth of S. aureus in the early but not the late stages of incubation.

Bacteriological Techniques↗
PubMed1980

A randomized combined modality trial in small cell carcinoma of the lung: comparison of combination chemotherapy-radiation therapy versus cyclophosphamide-radiation therapy effects of maintenance chemotherapy and prophylactiv whole brain irradiation.

A randomized trial of combined modality therapy employing combination chemotherapy (cyclophosphamide (CTX) and methotrexate (MTX), CTX, MTX and Vincristine (VCR) and CTX, VCR and high-dose MTX with citrovorum rescue) and radiation therapy was compared to cyclophosphamide and radiation therapy in 258 patients with pulmonary small cell carcinoma. Patients were also rendomized: 1) to determine the effects of prophylactic whole brain irradiation; and 2) to establish the effects of maintenance chemotherapy. Survival, frequency of response and site of relapse were different in patients with limited disease (LD) (disease confined to lung, mediastinum and supraclavicular lymph nodes) when compared with disease spread beyond these sites (extensive disease) (ED). No survival advantage was seen in LD when combination chemotherapy was employed, although the frequency of complete remission was greater with three drugs than with one or two drugs (40% vs. 32%). In ED frequency of response was greater for three drugs than for one and two drugs (60% vs. 40%), but there was no survival advantage. The median survival time for complete responders was similar for limited or extensive disease (12.1 months), but 23.8% were alive at 24 months with LD compared to none with ED. Maintenance chemotherapy significantly prolonged survival by 16.8 months with 33% alive at 24 months compared to 9% who were unmaintained. Prophylactic while brain irradiation prevented brain metastases with only 4% developing this complication as compared to 18% of control subjects, but did not influence survival.

Antineoplastic Agents↗