Twenty strains of Streptococcus thermophilus were classified into five different types characterized by ribotyping after DNA digestion with HindIII and hybridization with cDNA from 16S-23S rDNA of Escherichia coli. Ribotyping after digestion with HaeIII and XhoI enabled the same strains to be gathered into three groups as a consequence of the reduced influence of the flanking sequences within the analysis of rRNA operons. Amplified rDNA restriction analysis clearly confirmed the discrimination of these three different ribotypes, producing evidence to suggest that subtaxa are to be recognized within this species.

Bacterial Typing Techniques↗

PubMedDate not supplied

Genotyping of Lactobacillus delbrueckii subsp. bulgaricus and determination of the number and forms of rrn operons in L. delbrueckii and its subspecies.

Three different approaches (whole-cell protein profiles, DNA fingerprinting combined with pulsed-field gel electrophoresis and analysis of rDNA genes) were used to characterize thirty-one strains of Lactobacillus delbrueckii subsp. bulgaricus from different dairy products, and three type strains belonging to L. delbrueckii subsp. delbrueckii, L. delbrueckii subsp. lactis and L. delbrueckii subsp. bulgaricus. Moreover, the number and different forms of rrn operons in L. delbrueckii and its subspecies were defined. At the strain typing level, Notl macrorestriction analysis permitted grouping of the 32 strains of L. delbrueckii subsp. bulgaricus into 23 restriction patterns, providing a high degree of discriminatory power. Among whole-cell protein profiles, PCR analysis of rDNA genes and ribotyping, the latter method seemed to be the most reliable approach to characterizing the subspecies belonging to L. delbrueckii. Ribotyping combined with enzymes such as HindIII and EcoRI showed that at least six rrn operons were present in L. delbrueckii and its subspecies; two forms of rrn operons were present in the subspecies lactis and bulgaricus and four forms were present in the subspecies delbrueckii.

Blotting, Southern↗

PubMedDate not supplied

Activity and toxicity of 4'-iodo-4'-deoxydoxorubicin in patients with advanced breast cancer.

Based on our previous Phase I study indicating good tolerability of the drug, we have evaluated therapeutic activity and acute and subacute toxicities associated with repeated courses of the new anthracycline 4'-iodo-4'-deoxydoxorubicin (I-Dox) at the maximum tolerated dose (80 mg/m2) every three weeks. Thirty-three patients (31 evaluated for activity and 32 for toxicity) with relapsed (11 cases) or advanced breast cancer at presentation (22 cases) were treated with 108 cycles (median 3, range 1-7) for a median cumulative dose of 240 mg/m2. We observed no complete and 11 (35%) partial responses. Minor response was documented in 5 additional patients. The most frequent and severe toxicity was hematological. In 47% of the cycles and 34% of the patients I-Dox administration was associated with WHO grade 4 neutropenia. Severe neutropenia was more frequent after repeated cycles. Similar cumulative toxicity was observed for thrombocytopenia and anemia. In three patients (7 cycles) fever and possible infection occurred during neutropenia and required oral antibiotics. Extra-hematological side-effects were limited to mild/moderate nausea lasting for a few hours and mild fatigue lasting 1-7 days. Alopecia or oral mucositis were minimal or absent in the majority of patients. One case of potential reversible cardiac toxicity was observed after 240 mg/m2 I-Dox in a patient with preexistent cardiac risk factors. In view of the reported activity, good general tolerability, and selective hematological toxicity, I-Dox should be evaluated at higher than the conventionally defined maximum tolerated dose in combination with recombinant human hemopoietic growth factors.

Adult↗

PubMedDate not supplied

Cardiac and pulmonary effects of alpha tumor necrosis factor administered by isolation perfusion.

AIMS: We studied cardiac and pulmonary function in 22 patients affected by in transit metastases from cutaneous melanoma and metastases from soft tissue sarcoma of the limbs and treated with isolation perfusion in extracorporeal circulation with rTNF alpha at doses ranging from 0.5 to 4 mg/m2 in mild hyperthermia. PATIENTS AND METHODS: All patients experienced a septic-like shock syndrome of variable severity: this feature lasted from 24 to 72 h and was controlled by the infusion of dopamine. Seventeen patients suffered from respiratory insufficiency, which required assisted ventilation (7 cases mechanical ventilation for 1 day, 8 cases for 2 days, and 2 cases synchronized intermittent mandatory ventilation). RESULTS: Spirometric parameters recorded 7-15 days after treatment did not change from baseline values. In contrast, lung transfer factor for carbon monoxide significantly declined in a dose dependent fashion. CONCLUSIONS: Our data confirm that rTNF alpha administered by isolation perfusion technique induces systemic cardiovascular and pulmonary side effects. Further studies are required to better define time course and reversibility of impaired pulmonary function.

Adult↗

PubMedDate not supplied

Genetic heterogeneity of variable number tandem repeats in thymidylate synthase gene in colorectal cancer patients.

PURPOSE: To analyze the genetic variability in a variable number of tandem repeats (VNTR) in the thymidylate synthase (TS) enhancer promoter region and assess the influence of functional alterations in mismatch repair genes by analyzing constitutional and tumoral DNA from patients with colorectal adenocarcinoma with a high microsatellite instability (MSI-H) or microsatellite stability (MSS) status. PATIENTS AND METHODS: Patients who underwent surgery for colorectal adenocarcinoma were selected from the colorectal database of our institute and, on the basis of MSI status, assigned to a study group and a control group: group A, MSI-H; group B, MSS. Microsatellite status was investigated using the Bethesda recommended panel (BAT-26, BAT-25, D2S123, D5S346, D17S250). In MSI-H patients an additional analysis was made of the microsatellite loci D18S61 and D18S58, both mapping in the region containing the TS gene (18p11.2-11.32). Based on the number of altered microsatellites (> or = 2, 1, or 0), tumors were considered as having high (MSI-H) or low (MSI-L) instability or microsatellite stability (MSS), respectively. Genotyping for thymidylate synthase promoter polymorphism was carried out on constitutional and tumor DNA of each patient by PCR amplification of the polymorphic region. RESULTS: MSI-H was found in 55 patients (group A) and MSS in 50 patients (group B). In none of the MSI-H patients was microsatellite instability found in the additional D18S61 and D18S58 loci. In five group A and ten group B cases the analysis was not performed because constitutional DNA and/or tumoral DNA were not amplifiable. Homozygotes for the triple repeat variant (3R/3R) displayed only the large PCR product, homozygotes for the double repeat variant (2R/2R) displayed only the smaller PCR product, while heterozygotes (2R/3R) displayed both the larger and smaller PCR products. In 3/50 (6%) group A patients and 5/40 (12%) group B patients repeat variations were found in tumoral DNA. CONCLUSION: Our findings demonstrate that there is genetic homogeneity between constitutional and tumoral DNA but do not support the hypothesis that mismatch repair genes are involved in VNTR recombinant events in TS gene variability.

Adenocarcinoma↗

PubMedDate not supplied

Long-term results of an intensive regimen: VEBEP plus involved-field radiotherapy in advanced Hodgkin's disease.

PURPOSE: This pilot study was conducted to evaluate the efficacy and toxicity of a new intensive drug regimen, combined with involved-nodal-field radiotherapy, in advanced Hodgkin's disease not treated by chemotherapy. PATIENTS AND METHODS: From September 1990 to March 1993, 73 evaluable patients with newly diagnosed stage IIB, III (A and B), and IV (A and B) Hodgkin's disease or who were relapsing after primary subtotal or total nodal irradiation were treated with eight cycles of etoposide, epirubicin, bleomycin, cyclophosphamide, and prednisolone (VEBEP) followed by radiotherapy (30-36 Gy) to the nodal site or sites of pretreatment disease. The median duration of follow-up was 68 months. RESULTS: The complete remission rate was 94% (95% CI: 86-98). At 6 years, freedom from progression and overall survival rates were 78% (95% CI: 68-88) and 82% (95% CI: 73-91), respectively. There was one episode of fatal sepsis after bone marrow aplasia that occurred after VEBEP and extended-field irradiation. Hematologic toxicity during chemotherapy was acceptable; without the support of growth factors, grade IV leukopenia and grade IV neutropenia, as determined within cycles, occurred in 38% and 85% of patients, respectively, but was reversible in the vast majority of patients by the day of treatment recycle. No episodes of epidoxorubicin-related cardiomyopathy or symptomatic pulmonary toxicity were documented. Overt and/or subclinical hypothyroidism occurred in 38% of cases. Gonadal damage was evident in the large majority of male patients but reversible in half of them, whereas permanent sterility was observed in females at least 35 years of age. No secondary leukemia has been so far detected. DISCUSSION: VEBEP followed by involved-nodal-field radiotherapy is an effective treatment for chemotherapy-naive Hodgkin's disease and is associated to acceptable rates of acute and intermediate-term toxicity. This intensive regimen, which does not routinely require the support of hematopoietic growth factors and can be delivered in an outpatient setting, warrants a prospective comparison in a randomized trial versus one of the more effective standard-combination regimens.

Adolescent↗

PubMedDate not supplied

Lung function and serum concentration of tumor necrosis factor-alpha, interleukin-6 and fibronectin in patients treated with ABVD chemotherapy followed by radiotherapy for mediastinal Hodgkin's disease.

UNLABELLED: Mediastinal radiotherapy and polychemotherapy regimens can produce late toxicity leading to pulmonary fibrosis. There is evidence for the involvement of various cytokines in this process. We evaluated lung function in 20 patients with stage I-IIA Hodgkin's disease and submitted to chemotherapy including bleomycin (ABVD) and radiotherapy. Lung function tests were performed before, at the end of treatment and after a median of 12 months from the end of therapy. Tumor necrosis factor-alpha (TNF-alpha), fibronectin and interleukin-6 (IL-6) were determined on serum samples collected at the same time intervals. A modification of tests indicative of a restrictive lung disease was observed at end of treatment, whereas a persistent decline of transfer lung factor for carbon monoxide (DLCO) was documented. TNF-alpha constantly decreased, fibronectin increased and IL-6 showed a decline after treatment and a rise during the follow-up but the differences were not statistically significant. No significant correlations were observed between changes of lung function tests and serum cytokine concentration. CONCLUSIONS: This lack of correlation could be due to: a) incorrect selection of serum collection time, or b) to the fact that cytokine plasma concentration does not reflect events occurring in the alveolar phase.

Adult↗

PubMedDate not supplied

[Polycardiographic evaluation of the cardiotoxicity of adriamycin].

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Adult↗

PubMedDate not supplied

Evaluation of the cardiovascular toxic effect of recombinant interleukin-2 in rats.

Cardiac and vascular toxicity of recombinant interleukin-2 (rIL-2) was evaluated by in vitro and in vivo experiments in rats. Using isolated spontaneously beating atria, no changes were detected in heart rate or myocardial contractility in response to rIL-2 treatment at concentrations ranging from 0.1-100 U/ml. Daily sc administration of rIL-2 for 7 consecutive days (at doses of 2.3 X 10(4) to 1.15 X 10(6) U/ml) produced a prolongation of the QaT interval and significant modifications in serum electrolyte concentrations. Ex vivo contractility of atria excised at the end of rIL-2 treatment showed no deterioration in myocardial contractility with increasing dosage. rIL-2, at concentrations of 0.1-1000 U/ml, did not induce any modification of perfusion pressure in isolated rat tail artery but produced a significant displacement to the left of the dose-response curves for norepinephrine compared to basal conditions. The relative potencies were not dose-dependent. Our results indicate that rIL-2 does not exert a direct cardiotoxic effect, and suggest an indirect action on vascular smooth muscle, i.e., an aspecific modulation of vascular response to mediators.

Animals↗

PubMedDate not supplied

Detection of cardiac arrhythmias and ischaemic events in combination chemotherapy with cisplatin, etoposide and bleomycin for testicular cancer.

Ten patients treated with combination chemotherapy regimen containing Cisplatin, Bleomycin and Etoposide (PEB) were submitted to Holter monitoring during the first cycle of treatment. No modifications of heart rate, ST-T segment were observed and only a slight increase of incidence of sopraventricular ectopic beats was recorded. One patient developed a transient second degree atrio-ventricular block in the first day during episodes of vomiting. These data suggest that combination chemotherapy with PEB, at least during the first cycle of treatment, has no significant arrhythmogenic effect.

Adult↗