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Biomedical subjects

R Vera

Publications and source records attributed to R Vera.

At least 37 records · Page 2Linked to original sources

Frequent dose delays and growth factor requirements with the sequential doxorubicin-CMF schedule.

Doxorubicin for four cycles plus cyclophosphamide, methotrexate and 5-fluorouracil (CMF) for eight cycles is an effective adjuvant regimen for breast cancer patients with more than three involved axillary lymph nodes. We reviewed the incidence of dose delays and growth factor requirements when this regimen is administered to patients receiving concurrent irradiation. Thirty-six patients with more than three involved axillary lymph nodes were treated with the sequential regimen doxorubicin-CMF and irradiation. Patients with two or more dose delays received G-CSF treatment. Seventy-five percent of the patients required dose delays for day-22 neutropenia, and growth factors were needed for half of the patients in order to maintain a received dose intensity of 0.940. The first delayed cycle occurred in 74% of the patients while receiving concomitant chemoradiotherapy. Frequent dose delays were required when the sequential regimen doxorubicin-CMF was administered along with radiotherapy. Growth factors are needed to maintain dose intensity similar to that achieved in the original trial.

Adult↗

M-CAVI, a neoadjuvant carboplatin-based regimen for the treatment of T2-4N0M0 carcinoma of the bladder.

Carboplatin, methotrexate, and vinblastine (M-CAVI) is an active and well-tolerated regimen for bladder cancer patients ineligible for cisplatin-based regimens. We treated 47 T2-4 N0 M0 bladder cancer patients with M-CAVI in a neoadjuvant phase II trial. These 47 patients are evaluable for clinical response and toxicity. Clinical overall response rate was 34%, for a 95% confidence interval (CI95%) of 21-49%. Pathological response was seen in 40% of the patients (CI95%, 26-56%) with a 26.5% rate of pathological complete response (CI95%, 15-42%). Factors associated with the achievement of a response to therapy were the initial TNM stage (pT3a or lower, greater than pT3a, p = 0.001) and a Karnofsky score greater or equal than 90%, which was marginally significant (p = 0.08). With a median follow-up of 14 months, the disease-specific actuarial survival at 2 years is 42%. No patient has relapsed beyond 21 months of follow-up in a disease-free status. Toxic effects have been moderate. In conclusion, M-CAVI is an active and well-tolerated regimen that should be compared in terms of response rate and survival with a cisplatin-based regimen for invasive bladder cancer.

Actuarial Analysis↗

Five-day course of granulocyte colony-stimulating factor in patients with prolonged neutropenia after adjuvant chemotherapy for breast cancer is a safe and cost-effective schedule to maintain dose-intensity.

PURPOSE: To analyze the safety and efficacy of a short course of granulocyte colony-stimulating factor (G-CSF) to maintain dose-intensity of subsequent cycles of chemotherapy after a prior episode of prolonged neutropenia, without febrile complications, in patients receiving adjuvant treatment for breast cancer. PATIENTS AND METHODS: Thirty-two patients undergoing adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin-CMF for stages I to II breast cancer were included after having chemotherapy delays due to neutropenia (absolute neutrophil count [ANC] < 1.5 x 10(9)/L) on day 22. G-CSF was administered subcutaneously on days 15 to 19 of each subsequent cycle. RESULTS: None of the patients included in this study had to be admitted to the hospital for fever and neutropenia. The median percentage of the projected dose-intensity for CMF or doxorubicin-CMF on an intent-to-treat basis was 0.994, which was significantly higher than the delivered dose-intensity before the start of G-CSF treatment (P < .0001). Patients who received concomitant G-CSF and radiotherapy achieved a similar dose-intensity as patients who did not undergo radiotherapy. Seven patients discontinued G-CSF treatment due to musculoskeletal pain. These patients had more subsequent cycle delays because of day 22 neutropenia than the 25 patients who followed the G-CSF schedule (P = .0028). CONCLUSION: A 5-day course of G-CSF in patients with prior chemotherapy delays due to prolonged neutropenia seems to be a safe and cost-effective schedule to maintain CMF or doxorubicin-CMF dose-intensity in the adjuvant treatment of breast cancer.

Adult↗

[C-erbB-2 protein in ovarian epithelial cancer: correlation between expression in tumor tissue and blood levels].

BACKGROUND: Among 20 to 30% of the patients with ovarian cancer present overexpression of the c-erbB protein in the tumor tissue although its clinical significance has not been clearly established. In patients with a disseminated neoplasm and overexpression of c-erbB an increase in the extracellular portion of this protein may be detected in serum. The aim of this study was to determine the c-erbB protein in serum and in tumoral tissue in patients diagnosed with ovarian epithelial carcinoma. METHODS: The serum concentration of the c-erbB protein was quantified by ELISA techniques in 60 blood donor women (control group) and in 99 patients with ovarian cancer. Likewise, the expression of the c-erbB protein was determined in tumoral tissue by immunohistochemical techniques in the 99 patients with ovarian cancer. The correlation between overexpression and elevated serum values was analyzed. RESULTS: The mean c-erbB values obtained in the serum of the control group was 10.9 U/ml (SD: 2.8) with a range of 1.5-17.0. Serum determination was carried out in absence of the tumor in 49 patients being positive in 2 cases. In 7 patients the determination was performed in the presence of peritoneal implants of a diameter of less than 2 cm with none being positive. Serum determination was carried out in 43 patients in the presence of implants greater than 2 cm and 14 (32.5%) were positive. A further 153 determinations were performed during follow up of the 99 patients, 62 in tumor absence (3.2% positive), 2 in the presence of a tumor of less than 2 cm (none positive) and 89 in the presence of a tumor greater than 2 cm (34.8% positive). A correlation was found between elevated c-erbB serum values in the presence of a disseminated tumors and overexpression of tumoral tissue (p: 0.0011). CONCLUSIONS: A third of the patients with ovarian cancer and peritoneal implants of a diameter greater than 2 cm present elevated serum levels of the c-erbB.2 protein. A correlation was found between serum c-erbB positivity and overexpression of the protein in tumoral tissue.

Carcinoma↗

Glutathione-S transferase activity in cultured human hepatocytes.

Glutathione S-transferase (GST) activity was measured in human hepatocytes just after isolation and during culture in various media. Individual variations in enzyme activity, using 1-chloro-2,4-dinitrobenzene as substrate, were observed for freshly isolated human hepatocytes. When the hepatocytes were cultured, GST activity decreased dramatically during the first two days, to be stabilized around 30% of the initial value. Even factors known to favour maintenance of liver functions in vitro, such as nicotinamide and dimethylsulfoxide (DMSO), did not prevent this decline. In contrast to rat hepatocytes, no increase of GST activity was observed following the early decrease.

Adolescent↗

Hodgkin's disease, intracranial involvement. Report of a case and review of the literature.

Intracranial hodgkin's disease, an extremely uncommon finding, is reported in a 21-year-old man. This diagnosis, confirmed histologically, occurred in the presence of recurrent systemic disease, mixed cellularity type, which is typical for patients who have developed this complication. Review of the reported cases suggests there may be increasing incidence of intracranial involvement of Hodgkin's disease.

Adult↗

A randomized study of low and high doses of leukocyte alpha-interferon in metastatic renal cell carcinoma: the American Cancer Society collaborative trial.

A prospective randomized trial of low versus high doses of human leukocyte alpha-interferon (1 X 10(6) units/day for 28 days versus 10 X 10(6) units/day for 28 days) was carried out in 30 patients with metastatic renal cell carcinoma, to test the tolerance and relative antitumor effects of these interferon doses. Both doses were tolerated well, and responses to the human leukocyte alpha-interferon were observed overall in seven individuals, including complete, partial, and minimal tumor regressions. Six of the seven responses occurred in patients who received the high dosage, and three of these responses were major responses. While not statistically significant, this result suggested a dose-response relationship. One minimal response was observed in a patient treated at low dosage. Nine individuals who were stable after 1 month of therapy at low dosage were randomized to a further month of therapy at low or high dosage, during which one of four at high dosage had a partial response, and none of five at low dosage manifested response. Regression of pulmonary disease in one individual was delayed, occurring 3 months after therapy at the high dose and enduring for a period of 28 months. Major objective responses in other patients were of 4 and 15 months duration. Human leukocyte alpha-interferon is an active agent in renal cell carcinoma at the dosage of 10 million units daily. No relationship of toxicity to response was evident in this trial. Optimum dosage and duration of treatment have yet to be established.

Adenocarcinoma↗

Malignant histiocytosis. Response to VP-16-213 and cytosine arabinoside.

A patient with malignant histiocytosis who relapsed after receiving an Adriamycin (doxorubicin)-containing combination and radiation therapy subsequently had a complete remission on VP-16-213 and cytosine arabinoside. She remains free of disease 32 months after achieving a complete remission. VP-16-213 and cytosine arabinoside (Ara-C) deserve further evaluation in the treatment of this neoplasm.

Aged↗

Varying responses of ovum transport in mice related to dose and time of administration of oestradiol.

The dose-response relationships between exogenous oestradiol and ovum transport in mice and the effect of treatment on different days of pregnancy were reinvestigated in detail. In addition, serum levels of oestradiol were measured, and their correlation with the various responses was examined. Control animals injected with vehicle alone had the majority of ova in oviductal loops 1 and 2; 3 and 4; or 6 and 7 on days 1, 2, or 3 of pregnancy, respectively. On day four, the majority of ova were found in the uterus. Varying the dose or time of administration of oestradiol determined qualitatively different responses. A single sc injection of oestradiol 5 micrograms or less on day 1 produced scattering of the embryos along the oviduct on day 3 and their accumulation in loops 7 and 8 on day 4, suggesting an increased randomness of the direction of propulsive forces, as well as decreased luminal permeability of the tubo-uterine junction. Doses of 25 and 125 micrograms injected on day 1 caused accelerated transport of ova, some of which entered the uterus as early as 8 hr after treatment. The predominant effect following injection of 1 micrograms on day 2 or days 1 and 2 was acceleration, indicating that oestradiol given on day 2 has opposite effect to and can counteract that of oestradiol given on day 1. Following injection of 25 or 125 micrograms, but not 5 micrograms, on day 1, plasma oestradiol remained significantly elevated through day 2, indicating that tube-locking results from high levels of plasma oestradiol restricted to day 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effective use of combined modality therapy for the treatment of patients with Hodgkin's disease who relapsed following radiotherapy.

From 1969 to 1977, 124 patients with advanced staged Hodgkin's disease were entered into a treatment protocol which consisted of three cycles of drugs (nitrogen mustard, vincristine, vinblastine, prednisone, and procarbazine) followed by radiation (1500-2000 rad) to previous sites of known disease. After completion of radiation therapy, two more drug cycles were given. There were 63 newly diagnosed patients with Stage IIIB and IVA or B disease and 61 patients who had relapsed from prior radiotherapy. The median follow-up is now in excess of 5 years. Of the relapsed patients, 86.9% entered a complete remission and 90.6% of these patients have remained in complete remission from 1 to 10 years. In comparison, 81% of the newly diagnosed patients entered a complete remission and 78.4% of these patients continue free of disease from 1 to 11 years. These differences were not statistically significant. The 10-year actuarial disease-free survival--79.8% for the 61 relapsed patients compared to 65.6% for the 63 newly diagnosed patients--was not significantly different either. The 10-year actuarial survival for the 40 patients who had relapsed to IIIB and IVA or B was 71.3% and approximated more closely those of newly diagnosed IIIB and IVA or B patients. This drug-radiotherapy protocol is very effective for the treatment of patients who have relapsed from previous radiotherapy.

Drug Therapy, Combination↗

Changes in nuclear estrogen receptor level in the rat oviduct during ovum transport.

The purpose of this study was to assess variations in the concentration of nuclear estrogen receptor in the oviduct during normal embryo transport and to determine its temporal relationship with the passage of eggs to the uterus. Groups of 6--8 rats were sacrificed at different intervals from 0800 h on Day 1 to 1700 h on Day 4 of pregnancy to determine the concentration of nuclear estrogen receptor in the oviduct, the plasmatic estrogen level and the location of eggs in the genital tract. No significant variations in the amount of nuclear estrogen receptor were observed throughout the first 3 days. However, on Day 4 of pregnancy, concomitant with an elevation of plasma estrogen level there was a significant increase in nuclear estrogen receptor which started 4 to 5 h before the first ova began to reach the uterus. The receptor concentration attained a 3-fold elevation over previous days and returned to basal levels when 30% of the ova had been transferred to the uterus. These results provide evidence that estrogen exerts a direct action on the oviduct during embryo transport and that the passage of embryos to the uterus is preceded by a well-defined increment of estrogenic action on the oviduct. This temporal relationship is in keeping with the concept that estrogen receptor mediated events taking place in the oviduct may be involved in timing the transport of ova through the tubouterine junction.

Animals↗

Role of ovarian and adrenal progesterone in the regulation of ovum transport in pregnant rats.

This study was designed to assess the role of postovulatory ovarian and adrenal progesterone secretion in the regulation of ovum transport in pregnant rats. The number and distribution of embryos in the genital tract and the plasma progesterone levels were determined during the first 5 days of pregnancy in ovariectomized (OVX), adrenalectomized (ADX), ovariectomized and adrenalectomized (OVX + ADX), intact control (IC), or sham-operated control (SOC) rats. Some OVX or OVX + ADX rats received subdermal implants of progesterone pellets following surgery. The day of insemination was designated Day 1 of pregnancy. Transport of embryos from the oviduct to the uterus was essentially complete by the morning of Day 5 in IC and SOC. Neither adrenalectomy performed on Day 1, nor ovariectomy done on Day 4 of pregnancy modified the time of passage of ova from the oviduct to the uterus. Retention of some eggs in the oviduct, accompanied by rapid transport of others into the uterus and expulsion through the vagina, was observed when ovariectomy was performed on Days 1, 2 or 3, or when ovariectomy plus adrenalectomy were performed on Day 1. Following ovariectomy plus adrenalectomy or ovariectomy but not adrenalectomy alone, there was a marked and sustained decline in serum progesterone concentration. Subdermal implants of progesterone supplied on Day 1 restored progesterone levels and improved the pattern of ovum transport in OVX or OVX + ADX. It is concluded that postcoital secretion of progesterone by the ovary plays a major role in the physiologic regulation of oviductal embryo transport in the rat. Progesterone secreted by the adrenal is neither essential nor can it substitute for the ovarian source in the regulation of this process.

Adrenal Glands↗