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Biomedical subjects

E Warner

Publications and source records attributed to E Warner.

At least 55 records · Page 3Linked to original sources
PubMed1995

Expression of the multiple drug resistance gene in human renal cell carcinoma depends on tumor histology, grade, and stage.

Levels of mRNA expressed by the multidrug resistance gene MDR1 were examined in 23 renal cell carcinoma samples and adjacent normal kidney cortex using reverse-transcription PCR. Comparison of MDR1 levels between histological types revealed that there was on average significantly more MDR1 in clear cell tumors than in oncocytomas (0. 89 +/- 0.10 versus 0.28 +/- 0.20, ratio of MDR1 in tumor cells to the drug-resistant cell line KB-8, P < 0.05). The mean MDR1 level of all of the non-oncocytoma tumors was not significantly different from the mean MDR1 level of normal adjacent kidney (0.89 +/- 0.10 versus 1.11 +/- 0.12, P = 0.07). However, the mean MDR1 level of the more undifferentiated clear cell tumors was significantly lower than the mean MDR1 level of adjacent normal kidney (0.74 +/- 0.10 versus 1.11 +/- 0.12, P < 0.05). MDR1 levels in early stage, clear cell tumors (n = 14) were lower than in tumors that had spread into perinephric tissue or had metastasized (n = 6) (0.77 +/- 0.08 versus 1.24 +/- 0.30, P < 0.05). In conclusion, MDR1 expression decreases in the more undifferentiated tumors, but still remains at levels high enough to be drug resistant. Higher MDR1 expression in the invasive tumors compared with noninvasive tumors suggests that MDR1 expression and invasiveness may be linked.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

VP-16, ifosfamide and cisplatin (VIP) for extensive small cell lung cancer.

Thirty-seven extensive disease SCLC patients were treated with ifosfamide 1.0 g/m2 (maximum 1.75 g), VP-16 (etoposide) 75 mg/m2 and cisplatin 20 mg/m2 (VIP) daily for 5 days in hospital. Mesna was given as a continuous infusion until 12 h after the last ifosfamide dose. Treatment was reduced to 4 days after the first 8 patients experienced serious myelotoxicity. 30 patients were evaluable for response. 8 (27%) achieved a complete response and 60% had a partial response. The median duration of response was 23 weeks. The median survival of all 37 patients was 41 weeks, and 47 weeks for the 30 evaluable patients. Fifty per cent and 26% of the evaluable treatment courses were associated with grade 4 and 3 granulocytopenia, respectively. There were eight febrile events including four treatment-related deaths from sepsis on the 5-day regimen. Although the response to VIP was generally rapid, the proportion achieving complete response (27% of evaluable patients) and the median survival is similar to standard chemotherapy regimens which are less toxic and less complex to administer.

Adult↗
PubMed1994

Bronchogenic carcinoma in patients seropositive for human immunodeficiency virus.

The purpose of this report is to describe an association between bronchogenic carcinoma and HIV. Three HIV-seropositive patients are described who developed bronchogenic cancer (two large cell, one adenocarcinoma) before developing an AIDS-defining illness. A critical review of the literature revealed 22 other patients in which the association of HIV infection and lung cancer is reported. These patients are characterized by a relatively young age at diagnosis (median, 43 years) and prevalence of the adenocarcinoma subtype (13 of 25 patients). Twenty of 21 patients had a history of smoking. Among 21 patients for whom data were available, 6 patients (28 percent) had AIDS at time of diagnosis of lung cancer while 11 patients (55 percent) did not have AIDS or AIDS-related complex at diagnosis.

Adenocarcinoma↗
PubMed1994

Phase II trial of Virulizin in patients with pancreatic cancer.

Twenty-two patients were enrolled in a clinical trial to determine the toxicity and efficacy of the novel immunomodulator Virulizin in patients with measurable, biopsy-proven pancreatic cancer. The dose was 0.11 ml/kg (minimum 7.5 ml) 3 times weekly for the first week, then twice weekly until disease progression. No toxicity was encountered. In the 17 evaluable patients there was no evidence of tumour regression. Six patients (35%) had disease stabilization for more than 3 months, and 2 are still alive with progressive disease, having had disease stabilization for 15 and 17 months. While the results do not suggest any cytotoxic activity at this dose and schedule, the possibility of an antiproliferative effect warrants further study of this agent.

Adenocarcinoma↗
PubMed1993

Ondansetron compared with dexamethasone and metoclopramide as antiemetics in the chemotherapy of breast cancer with cyclophosphamide, methotrexate, and fluorouracil.

BACKGROUND: Although ondansetron was found to be effective as an antiemetic in numerous clinical trials of highly emetogenic combination-chemotherapy regimens that included cisplatin, its role in milder emetogenic regimens has not been fully defined. To address its use with a widely used but less emetogenic regimen, we performed a double-blind, randomized clinical trial comparing ondansetron with dexamethasone and metoclopramide in patients with breast cancer receiving chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. METHODS: A total of 165 women with breast cancer from 14 Canadian centers who were about to receive this chemotherapy for the first time were randomly assigned to receive either ondansetron (n = 85) or dexamethasone plus metoclopramide (n = 80), a widely used, standard antiemetic regimen. The patients recorded the incidence of nausea, emesis, and other side effects in diaries, and these data were compared in the two groups. RESULTS: The patients who received dexamethasone and metoclopramide had significantly less nausea during the first 24 hours after chemotherapy was begun. Otherwise, there were no statistically significant differences in efficacy between the regimens. The incidence of drowsiness and increased appetite was higher in the group given dexamethasone and metoclopramide. CONCLUSIONS: For women with breast cancer who are being treated with cyclophosphamide, methotrexate, and fluorouracil, the efficacy of dexamethasone and metoclopramide in controlling nausea and vomiting equaled or exceeded that of ondansetron.

Analysis of Variance↗
PubMed1993

Case report: hypothalamic tuberculoma associated with secondary panhypopituitarism.

Tuberculosis of the central nervous system remains quite rare in developed countries, accounting for only 0.53% of cases of tuberculosis in the United States. The most common form of intracranial tuberculosis is tuberculous meningitis; however, involvement may also take the form of a solid granulomatous mass (tuberculoma), which accounts for 15% to 30% of the neurosurgical cases in developing countries. An unusual case of a hypothalamic tuberculoma is presented in a man, who initially presented with signs and symptoms consistent with panhypopituitarism. Brain biopsy on two occasions confirmed caseating granuloma, and treatment with several antituberculous medications led to clinical improvement and radiographic resolution of the disease.

Adult↗
PubMed1992

Type B lactic acidosis and metastatic breast cancer.

A case is presented of a patient with longstanding metastatic breast cancer whose condition suddenly deteriorated due to hypercalcemia and severe lactic acidosis which rapidly proved fatal. Postmortem examination showed no explanation for the lactic acidosis other than extensive metastatic disease. A review of the rare syndrome of malignancy-induced lactic acidosis is presented with particular emphasis on the 5 other cases reported in association with metastatic breast cancer. Theories of pathogenesis and management controversies are discussed.

Acidosis, Lactic↗
PubMed1992

Treatment of AIDS-related non-Hodgkin's lymphoma with a twelve week chemotherapy program.

Current treatment options for acquired-immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) are unsatisfactory because of excessive toxicity rates and frequent recurrence of lymphoma. In this phase II study, we evaluated a novel 12 week chemotherapy program with respect to feasibility, toxicity and therapeutic results. Thirty HIV-seropositive patients with intermediate grade or small non-cleaved cell NHL received a 12 week program of weekly intravenous and oral chemotherapy consisting of etoposide, adriamycin, cyclophosphamide, bleomycin, vincristine, methotrexate and prednisone as well as biweekly intrathecal cytosine arabinoside. Prophylaxis against Pneumocystis carinii pneumonia (PCP) and candida were given routinely. The overall objective response rate was 73% with 33% complete responders. The time to progression for those stable or responding was 9.4 months. Five of 10 complete responders are well and free of disease 13.2 to 24.5 months from diagnosis. Median survival for the 30 patients was 8.1 months. NHL was the most common cause of death (13/22); opportunistic infection caused only one death (cryptococcal meningitis). Only 1 case of PCP occurred. The major toxicity was neutropenia. In conclusion this regimen resulted in response rates similar to other reports with acceptable toxicity and a very low incidence of PCP. Relapse of NHL remains a major challenge, however, and further studies are needed. Routine PCP prophylaxis should be incorporated into new trials of therapy for AIDS-related NHL.

AIDS-Related Opportunistic Infections↗
PubMed1992

Ifosfamide, cisplatin, and etoposide (ICE) in the treatment of advanced non-small cell lung cancer.

Forty-seven previously untreated patients with histologically or cytologically proven non-small cell lung cancer were treated with ICE (ifosfamide/cisplatin/etoposide). Patients received ifosfamide 4 g/m2 with mesna uroprotection on day 1, and cisplatin 25 mg/m2/d and etoposide 100 mg/m2/d on days 1, 2, and 3; courses were repeated every 28 days. Premedication with prochlorperazine, dexamethasone, and high-dose metoclopramide was given to prevent nausea; lorazepam was added on days 2 and 3 only. Thirty-four men and 13 women (median age, 60 years) received a total of 146 treatment cycles. One patient had stage IIIA disease, seven had IIIB disease, and 39 had hematogenous metastases. Forty-six patients were evaluable for response and toxicity. One patient suffered a myocardial infarction on day 7 that was judged unrelated to treatment. Two patients suffered early death from toxicity and have been classified as nonresponders. Three patients achieved complete response (median, 42+ weeks) and 14 patients achieved partial response (median, 29+ weeks; range, 10 to 82+), for an overall response rate of 37% (95% confidence limits, 23% to 51%). The median survival of the entire group is 26 weeks (1 to 82+). The median nadir granulocyte count was 0.275 x 10(9)/L (range, 0 to 2.3 x 10(9)/L), and there were 14 episodes (in 11 patients) or neutropenia-associated fever, one of which resulted in death. Seven of these patients had not had the required protocol dose reduction for nadir neutrophil count in the preceding cycle. The median nadir platelet count was 120 x 10(9)/L (range, 13 to 385 x 10(9)/L), and three patients required platelet transfusions. Eleven patients had RBC transfusions. Only ten patients had grade 2 gastrointestinal toxicity. Five patients had microscopic hematuria, and one patient had central nervous system toxicity.

Adult↗
PubMed1992

A phase II study of ifosfamide in combination with etoposide and cisplatin in the treatment of extensive small cell lung cancer.

The combination of etoposide and cisplatin has become one of the standard treatments for small cell lung cancer. Ifosfamide, an analogue of cyclophosphamide, has demonstrated single-agent antitumor activity comparable with that of the most active agents used to treat small cell lung cancer. Because ifosfamide is relatively nonmyelosuppressive and its principal dose-limiting toxicity, urotoxicity, has largely been eliminated with the introduction of the uroprotective agent mesna, we undertook a phase II study of the combination of all three agents (etoposide/ifosfamide/cisplatin) in good-performance-status, extensive-disease patients 70 years of age or younger. Twenty-five patients (17 men and eight women; median age, 58 years) were treated with 75 mg/m2 etoposide, 20 mg/m2 cisplatin, and 1.0 g/m2/d ifosfamide administered intravenously for 5 days. Mesna (200 mg/m2) was given as a bolus prior to the first day of chemotherapy and then daily by continuous infusion (900 mg/m2 over 24 hours) between administrations of chemotherapy. Mesna was continued for 12 hours after the last dose of ifosfamide. Treatment cycles were planned every 4 weeks for four cycles. Due to severe toxicities in the first eight patients, subsequent patients received only 4 days of treatment (20% dose reduction). Of the 25 extensive-disease patients studied, 23 are evaluable for response. Seven (30%) achieved a complete response and 10 (43%) had a partial response (overall response rate, 73%). Five patients (22%) had stable disease (< 50% decrease and no evidence of disease progression for at least 4 weeks), and disease progressed in 1 patient (4%). The median survival time was 42 weeks (range, 2 to 160+ weeks). Granulocytopenia was dose-limiting: median granulocyte count was 0.486 x 10(9)/L, 21% of cycles had a granulocyte nadir below 0.2 x 10(9)/L, and four patients died of sepsis. Three patients required platelet transfusion and nine needed blood transfusion. Microscopic hematuria occurred in eight patients (11% of treatment cycles) but was reversible in all cases. A number of central nervous system symptoms were reported but could not be definitely attributed to ifosfamide/mesna. Gastrointestinal toxicity was generally mild, which is attributed to the use of an aggressive antiemetic program. The etoposide/ifosfamide/cisplatin regimen is active and produced a complete response rate of 30% in extensive small cell lung cancer; the duration of response and survival appears similar to that of other standard regimens. The 5-day schedule produced excessive toxicity in this patient population, necessitating a 20% dose reduction (by using a 4-day schedule). The method of administration required a minimum of 5 hospital days per cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

The risk of breast cancer associated with mammographic parenchymal patterns: a meta-analysis of the published literature to examine the effect of method of classification.

The appearance of the breast parenchyma as seen on mammography is known to vary between individuals. The evidence is reviewed that some of the sources of this variation, namely, the densities referred to as "dysplasia", are related to breast cancer risk. We have carried out a meta-analysis of the published literature to determine the magnitude of the risk of breast cancer associated with mammographic densities by calculating summary odds ratios for studies grouped according to their design and the method used to classify mammographic parenchymal patterns. This has shown that subjects with mammographic densities have an increased risk of breast cancer relative to those without densities. Of the studies that used Wolfe's method of classification, cohort studies (n = 8) had a summary odds ratio of 5.19 (95% CI, 3.6 to 7.48); case control studies (n = 13) had a summary odds ratio of 1.8 (95% CI, 1.5 to 2.13); and prevalence surveys had a summary odds ratio of 0.54 (95% CI, 0.4 to 0.7). Other methods of classification, using quantitative estimates of the proportion of the breast occupied by densities, gave substantially higher odds ratios than Wolfe's system. The ability to recognize individuals within the population at different risks for breast cancer could be exploited in studies of potential etiological factors.

Breast↗
PubMed1991

Slippery context effect and critical bands.

This article explored the slippery context effect: When Ss judge the loudness of tones that differ in sound frequency as well as intensity, stimulus context (relative intensity levels at the 2 frequencies) can strongly influence the levels that are judged equally loud. It is shown that the size of the slippery context effect depends on the frequency difference between the tones: Small frequency differences (less than a critical bandwidth) produced essentially no slippery effect; much larger differences produced substantial effects. These results are consistent with a model postulating the existence of a central attentional or preattentive "filter-like" process whose weighting coefficients represent the size of the absolute as opposed to the relative (contextual) component of loudness perception and judgment.

Adult↗
PubMed1991

Dexamethasone/ifosfamide/cisplatin/etoposide (DICE) as therapy for patients with advanced refractory non-Hodgkin's lymphoma: preliminary report of a phase II study.

Twenty-two patients with refractory intermediate- or high-grade non-Hodgkin's lymphoma were treated with dexamethasone 10 mg every six hours and ifosfamide 1 g/m2, cisplatin 25 mg/m2, etoposide 100 mg/m2 (DICE), and mesna uroprotection daily x4 every 3 to 4 weeks. Pretreatment with prochlorperazine and metoclopramide was given to prevent nausea and vomiting. Eighteen men and four women, aged 21 to 74 years (median age, 65) have received a total of 64 cycles. Seventeen patients had stage IV, one had stage III, and four patients had stage II disease. Seven patients had B symptoms and 11 had marrow involvement. Only two patients had had more than one previous chemotherapy regimen. Median time from last chemotherapy to DICE was 7 months (range 1 to 41). Two patients who suffered early treatment-related deaths (from sepsis) were classified as nonresponders. Six of 22 patients (27%) achieved complete remission (2 to 22+ months), and 11 (50%) had partial remissions (1 to 8+ months) for an overall response rate of 77%. Median survival has not been reached yet, and 12 patients are alive 1 to 22 months from the start of treatment. Nine patients had nadir granulocyte counts less than 0.5 x 10(9)/L; six required RBC transfusions and five, platelet transfusions. The platelet nadir was less than 50 x 10(9)/L in 13 patients. Four patients had microscopic hematuria, two had grade 3 gastrointestinal toxicity, and one had a transient episode of delirium and blurred vision.

Adult↗
PubMed1990

Intradural granulocytic sarcoma presenting as a lumbar radiculopathy. Case report.

Granulocytic sarcoma usually occurs in the setting of leukemia and myeloproliferative disorders. Rarely, it can occur in isolation at various anatomical sites without hematological evidence of leukemia. The unique case of an elderly man presenting with right L2-3 radiculopathy is described. Intradural granulocytic sarcoma of the L-2 and L-3 nerve roots with extradural extension was found at surgery and he was treated with incomplete resection and antileukemic chemotherapy. Local recurrence at 3 months was treated with irradiation. Granulocytic sarcoma is frequently misdiagnosed and invariably progresses to acute leukemia. The chloroacetic acid esterase, granulocytic immunohistochemical markers, and electron microscopy appearance can aid in diagnosis. The prognosis is improved with initial aggressive antileukemic chemotherapy and local irradiation.

Aged↗