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Biomedical subjects

F Richards

Publications and source records attributed to F Richards.

At least 19 recordsLinked to original sources
PubMed1992

Smoking and pulmonary function in five Solomon Island populations.

The relationship between smoking and lung function was examined in a large sample of healthy Solomon Island Melanesians and Polynesians as part of a multidisciplinary study carried out in 1985 and 1986. Comparisons are made between samples of smokers and non-smokers to determine if smoking is associated with a reduction in pulmonary function among males and females between 25 and 75 years of age. The results of this study indicate that cigarette smoking causes significant reductions in the pulmonary function of these populations. In addition, a clear difference in pulmonary function between males and females, as well as a general reduction in female FEV1 values, suggests that cooking smoke inhalation may be operating as a possible risk factor to the pulmonary health of women. Further research is needed to quantify exposure to smoke of both males and females and relate this measure to declines in pulmonary function.

Adult↗
PubMed1992

Menogaril in the treatment of relapsed multiple myeloma. A phase II trial of the Cancer Center of Wake Forest University.

Fifteen patients with relapsed multiple myeloma (MM) were treated with menogaril 160 mg/m2 intravenously (IV) every 28 days. No responses were seen: 8 patients had stable disease, 4 progressed after one course of therapy, and 3 patients were removed from study after 1 course for other reasons. Four of the 8 patients with stable disease had an improved performance status, and 3 had a decrease in analgesic use. The major toxicity was myelosuppression. The median progression-free interval was 3.0 months with a range of 0.7 to 22 months and median survival was 11.3 months with a range of 0.7 to 39+ months. Menogaril displays little activity in patients with previously treated MM.

Antineoplastic Agents↗
PubMed1992

Correlation between the conformational phenotype of p53 and its subcellular location.

In order to obtain insight into the parameters determining the subcellular localization of mutant and wild-type forms of p53, we analysed the subcellular distribution of p53 in four Balb/c mouse-derived cell lines ranging in their cellular phenotypes from normal (3T3), via minimal transformant (T3T3), to maximally transformed (3T3tx, Meth A). Epitope mapping showed the p53 proteins in 3T3 and in T3T3 cells to be in a wild-type conformation, as they reacted with PAb246, whereas p53 in 3T3tx and in Meth A cells were PAb246 negative and thus displayed a mutant conformation. Despite its reactivity with PAb246, p53 in T3T3 cells had an extended half-life and accumulated to abnormally high levels. We show that the conformationally wild-type p53 in 3T3 and T3T3 cells predominantly localized to the cell nucleus, with about half of it being tightly associated with nuclear structures. In contrast, approximately 60% of mutant p53 in 3T3tx and Meth A cells localized to the cytoplasm, the rest residing in the cell nucleus; all the nuclear p53 in these cells appeared to be structurally bound. The cytoplasmic location of mutant p53 in 3T3tx and Meth A cells was not seen by immunofluorescence microscopic analysis, and required cell fractionation for its detection. Both cytoplasmic and nuclear p53 of the mutant phenotype bound to hsc proteins with a similar stoichiometry, suggesting that hsc binding is not directly related to the subcellular distribution of these proteins. We suggest that the conformational phenotype of p53 is a major determinant of its subcellular location.

Animals↗
PubMed1991

Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. The Piedmont Oncology Association.

BACKGROUND: Chemotherapy for metastatic breast cancer is palliative, and the optimal duration of therapy is unknown. We designed a trial to determine whether continuous treatment is superior to stopping treatment after a brief induction period and resuming treatment when the disease progresses. METHODS: We treated 250 women with metastatic breast cancer with six courses of cyclophosphamide, doxorubicin, and fluorouracil given every three weeks. At the completion of this induction period, women whose disease either regressed or remained stable were randomly assigned to receive either continued treatment with cyclophosphamide, methotrexate, and fluorouracil (maintenance therapy) or no further treatment (observation) followed by treatment with cyclophosphamide, methotrexate, and fluorouracil when disease progression became evident (reinduction). RESULTS: The combined rate of complete and partial responses after initial therapy was 30 percent (71 of 233 patients who could be evaluated; 95 percent confidence interval, 25 percent to 37 percent). In another 42 percent (98 patients), the disease remained stable. A total of 145 patients were randomized. Seventy-one were randomly assigned to the maintenance-therapy group, and 74 to the observation group. The median time to progression was 9.4 months for patients in the maintenance-therapy group and 3.2 months for patients in the observation group (P less than 0.001). After reinduction therapy, the median time to progression was 3.5 months. The median length of survival from the time of initial therapy was 14.8 months for all 250 patients; it was 21.1 months for the 71 patients in the maintenance-therapy group and 19.6 months for the 74 patients in the observation group (P = 0.67). Maintenance therapy was the most important determinant of the time before progression (P less than 0.001), but it was not associated with prolonged survival. The changes in performance status were similar in the patients in both groups, but nausea, vomiting, and mucositis were significantly more frequent in the maintenance-therapy group. CONCLUSIONS: In patients with breast cancer who received induction chemotherapy for 18 weeks, subsequent continuous chemotherapy was associated with a significant prolongation of the time before progression as compared with those receiving no further therapy; overall survival, however, was not significantly different in the two groups.

Adult↗
PubMed1991

Chemotherapy with 5-fluorouracil (5-FU) and cisplatin or 5-FU, cisplatin, and vinblastine for advanced non-small cell lung cancer. A randomized phase II study of the cancer and leukemia group B.

Two hundred forty-seven patients with previously untreated nonresectable non-small cell lung cancer (NSCLC) were entered in a prospective, randomized Phase II trial. Response assessment was possible in 232 patients, and 237 patients were evaluable for survival. Thirteen partial responses (11%) and 5 regressions (4%) of evaluable disease were obtained for the 116 patients treated with 5-fluorouracil (5-FU) and cisplatin (C) (95% confidence interval [CI], 8.5% to 21.5%). The median time to progression was 2.2 months and the median survival time was 4.6 months for 5-FU plus C. Twenty-three partial responses (20%) and 4 regressions (3%) of evaluable disease were obtained for the 116 patients treated with 5-FU, C, and vinblastine (V) (95% CI, 15.3% to 30.7%). The median time to progression was 2.8 months and the median survival time was 5.6 months for 5-FU, C, and V. The 5-FU and C doses were equivalent in the two treatment regimens. Sixteen of 85 patients (19%) with a performance status of 0 and 18 of 103 patients (17%) with a performance status of 1 responded, whereas only 2 of 44 patients (5%) with a performance status of 2 or greater responded (P = 0.009). Patients who had received locoregional radiation therapy had a lower overall response rate then those in the no prior radiation therapy group (P = 0.028). The median survival time for patients with a performance status of 0 or 1 was 6.3 months compared with 1.9 months for patients with a performance status of 2 or greater (P less than 0.001). Performance status also appeared to be a significant factor for time to progression. More frequent and severe leukopenia, fever, genitourinary (GU) toxicity, and pulmonary toxicity was reported with 5-FU, C, and V. There were three treatment-related deaths with 5-FU, C, and V and one treatment-related death with 5-FU plus C. Grade III/VI myelotoxicity was not influenced by prior radiation therapy or performance status. Neither regimen is active enough to be considered as standard therapy for advanced NSCLC.

Adenocarcinoma↗
PubMed1991

A randomized trial of chemotherapy (L-PAM vs CMF) and irradiation for node positive breast cancer. Eleven year follow-up of a Piedmont Oncology Association trial.

158 evaluable patients with stage II, lymph node positive, carcinoma of the breast were randomized to adjuvant therapy with either melphalan (L-PAM) or cyclophosphamide, methotrexate, and fluorouracil (CMF) after mastectomy. In addition, patients were randomized to be treated with or without post-operative irradiation therapy (RT) in addition to their chemotherapy. At a median follow-up time of 11 years, there is no difference in time to relapse (P = 0.69) or survival (P = 0.55) among the four treatment groups. Multivariate analysis including treatment arm, age, race, tumor size, histologic type, performance status, time to onset of treatment, menopausal status, and number of positive nodes, revealed that only the number of positive nodes (less than 4 vs greater than or equal to 4) was related to disease-free and overall survival. Ten year relapse-free survival for patients with less than 4 positive nodes compared to those with greater than or equal to 4 positive nodes was 63% versus 30%, and overall survival 63% versus 41%, respectively. Patients who received post-operative radiation therapy had significantly less local recurrence than those treated with chemotherapy alone (P = 0.03) but without improvement in relapse-free or overall survival. In this trial, post-operative radiation therapy when added to chemotherapy decreased the risk of local recurrence without adverse effects on survival. Treatment outcome was not influenced by chemotherapy regimen, but differences may have been obscured by the small sample size.

Adult↗
PubMed1991

Knowledge, attitudes and perceptions (KAP) of onchocerciasis: a survey among residents in an endemic area in Guatemala targeted for mass chemotherapy with ivermectin.

If ivermectin distribution programs are to have maximum impact on the morbidity and transmission of human onchocerciasis there must be broad and sustained acceptance within the endemic communities. Educational activities, developed with careful consideration of community attitudes, should promote positive treatment seeking behavior while simultaneously addressing local reservations about the control effort. To better understand the ambient knowledge, attitudes, and practices concerning onchocerciasis in the context of ivermectin use in Guatemala, we conducted a survey among 145 heads of households in five endemic communities. Given the country's long-standing nodulectomy program, it was not surprising that 100% of persons interviewed had heard of the disease 'la filaria', which they defined as a skin nodule that could cause blindness. Ninety-five percent of respondents identified surgery as the only cure for the condition. Relatively few (39%) knew that la filaria was caused by a worm, although slightly more (50%) knew that the condition was acquired by the bite of an insect. The term microfilaria was not broadly recognized. We also determined that onchocerciasis was not perceived as a serious health problem: few persons (12%) mentioned la filaria when requested to provide a complete list of illnesses that occurred in the community, and the gravity of infection (based on rank ordering of common illnesses) was similar to that of a bad cold. Recommendations were made which might assist long-term acceptance of a national chemotherapy initiative against onchocerciasis in Guatemala.

Adolescent↗
PubMed1991

The influence of drug interval on the effect of methotrexate and fluorouracil in the treatment of advanced colorectal cancer.

The importance of the interval between methotrexate (MTX) and fluorouracil (5-FU) was studied in 168 patients with previously untreated, measurable, advanced colorectal cancer. They were randomized to receive MTX 200 mg/m2, followed by 5-FU 600 mg/m2 either 24 hours (arm A) or 1 hour (arm B) after MTX. All patients received leucovorin (LV) 24 hours after MTX, 10 mg/m2 orally every 6 hours for six doses. The regimen was repeated every 2 weeks, with 5-FU escalation as tolerated. Arm A was significantly better than arm B with respect to overall response rate (29% v 14.5%, P = .026), time to progression (TTP; median, 9.9 months v 5.9 months, P = .009), and survival (median, 15.3 months v 11.4 months, P = .003). Significant differences between arms were not found in response rate, median TTP, or median survival for the subgroup of patients with rectal primaries who comprised 20% of the patients in each arm. Significant factors prognostic for survival were performance status and number of metastases, as well as treatment. Age did not influence survival. Toxicity was similar in both arms and was primarily gastrointestinal. More mucositis was seen in arm A. There were four toxic deaths secondary to neutropenia and infection (one from arm A and three from arm B) and three other deaths (two from arm A and one from arm B) that were possibly drug-related. The combination of MTX with LV rescue and 5-FU is an active regimen in advanced colorectal cancer; its efficacy is increased in colon, but not rectal cancer, when the interval between MTX and 5-FU is long (24 hours) rather than short (1 hour).

Aged↗
PubMed1991

Laboratory diagnosis of cysticercosis.

Human cysticercosis is caused by cystic tissue larvae of Taenia solium acquired by ingesting the eggs of the T. solium tapeworm. The diagnosis of human cysticercosis can be made by radiologic imaging, tissue biopsy, or serology. Radiologic imaging, including MRI and CT, currently is the most effective means for diagnosis.

Animals↗
PubMed1991

An urban primary school health program.

This paper summarizes the results of the first three years of an integrated on-site school health demonstration project based on the family practice model of delivering primary health care. An inner city public elementary school was chosen as the study location. Of the 712 study participants, 98% were black or Hispanic. Prior to implementation of the demonstration project, the Health Guarded Index for the study population was computed to be 58%. Among study participants, this index rose to 79% during the first year of the project and eventually reached 95% during the third year of the project. The absentee rates among study participants relative to nonparticipants decreased to 8.7% during the first year of the project and by 36.2% during the third year of the project. The substantial increase in the Health Guarded Index indicates that, among study participants, preventable defects, such as lack of immunizations, dental care, screening for common problems, and follow-up had been largely corrected. The substantial decline in absenteeism among study participants clearly shows the effectiveness of the demonstration project in promoting good health by decreasing morbidity and/or decreasing recovery time. Overall, the results of the three-year demonstration project reported here show that a carefully designed, well-coordinated school health program based on a family practice model can have a substantially favorable impact on the health of participating children.

Absenteeism↗
PubMed1991

Bone marrow and peripheral blood findings in patients with extreme thrombocytosis. A report of 63 cases.

Sixty-three bone marrow (BM) and peripheral blood specimens from patients with platelet counts of 1000 x 10(9)/L or greater were examined in an attempt to determine if any BM or peripheral blood findings could be used reliably to distinguish primary thrombocythemia from other myeloproliferative disorders and extreme examples of reactive thrombocytosis. Our results indicated that the BM findings in primary thrombocythemia were quite similar to those in polycythemia vera and chronic granulocytic leukemia with associated extreme thrombocytosis. However, statistically significant differences between the BM findings in myeloproliferative disorders and extreme reactive thrombocytosis were found in the numbers of megakaryocytes, presence or absence of megakaryocyte clusters, stainable iron, cellularity, and reticulin content. We concluded that BM examination is a useful procedure as an aid in determining the cause of extreme thrombocytosis.

Bone Marrow↗
PubMed1990

A phase II trial of high-dose cytarabine and cisplatin in previously untreated non-small cell carcinoma of the lung. A Piedmont Oncology Association Study.

Thirty-seven chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC) were treated with cytarabine (3 g/m2 intravenously [IV] during 3 hours) after IV bolus cisplatin (100 mg/m2 repeated every 3 weeks). Aside from nausea and vomiting, the principal toxicity was hematologic, with Grade IV myelosuppression in 32% and Grade III in 14%. Four patients died while on study. One complete and four partial responses were observed for an overall response rate of 14%. Responses were limited to lymph node and lung metastases and occurred in two of 17 adenocarcinomas, two of 12 squamous cell carcinomas, and one of eight large cell carcinomas. At this dose, the plasma level of cisplatin is only 3 micrograms/ml and the plasma level of cytarabine is 10 to 50 micrograms/ml, compared with the levels of 10 micrograms/ml and 1000 micrograms/ml, respectively, required for in vitro synergy. The severity of myelotoxicity observed indicates that, even at these levels, cisplatin enhances cytarabine activity. The combination may prove useful in malignancies that are sensitive to cytarabine, but is not of benefit in cytarabine-resistant malignancies such as NSCLC.

Adult↗
PubMed1990

Platinum-based combination chemotherapy in advanced non-small cell lung cancer: a randomized phase II trial of the Cancer and Leukemia Group B.

The Cancer and Leukemia Group B (CALGB) utilized a randomized phase II trial design to evaluate two cisplatin-based combinations, cisplatin-cytarabine (ara-C) and cisplatin-vinblastine, in 151 patients with advanced non-small cell lung cancer. Patients entered on study had not received prior chemotherapy. Platinum doses were equivalent in the two treatment programs. The total response rate (complete response, partial response, regression of evaluable disease) for the cisplatin-vinblastine group was 22% (16/73). Failure-free survival at six months for this group was 41%, survival at six months was 63%. The cisplatin-ara-C group had a total response rate of 9% (7/78) with a failure-free survival at six months of 14% and a six-month survival of 47%. Severe or life-threatening toxicity was seen in 73% of cisplatin-vinblastine cases and 59% of cisplatin-ara-C patients. Neither regimen is active enough to warrant designation as "standard therapy" for patients with M1 disease.

Aged↗
PubMed1990

A phase II trial of PEG-L-asparaginase in the treatment of non-Hodgkins lymphoma.

A polyethylene glycol conjugate of L-asparaginase (PEGLA) was administered to 21 patients with refractory non-Hodgkin's lymphoma. The dose given was 2,000 mu/m2 intramuscularly every 2 weeks. Eligibility required at least one prior trial of chemotherapy and ambulatory performance status. At entry, all patients had measurable lesions and documented disease progression. The median age of the patients was 61 years; 18 (86%) were ambulatory with minimal symptoms, 12 patients (57%) had 3 or more prior regimens, and 13 (62%) had stage IV disease. Histologic subtype was low grade in 11 patients (52%), intermediate in 7 (33%), high grade in 2 (10%) and unclassifiable in one (5%). There were two partial responses (11%) noted (95% confidence interval of response of 1-30%). Eleven patients (52%) were removed from study due to disease progression. Nine patients (43%), required removal for toxicity (7 for protracted nausea and vomiting and 2 for confusion). One patient died of sepsis while on study but this was not considered drug related. Almost one third of patients complained of fatigue or loss of appetite. Nausea and vomiting occurred in approximately half the patients and was moderate to severe in 9. Diarrhea and abdominal pain were also noted in one-third of those treated. Changes in the partial thromboplastin time and fibrinogen were noted in most patients but resulted in no bleeding complications. In this trial, PEGLA displayed modest activity in a heterogenous group of patients with progressive non-Hodgkin's lymphoma.

Adult↗
PubMed1990

Metalloproteases of infective Ancylostoma hookworm larvae and their possible functions in tissue invasion and ecdysis.

To infect their hosts, hookworm larvae must exsheath and migrate through connective tissue. A modified in vitro skin chamber was used to show that the human hookworm Ancylostoma duodenale and the zoonotic canine hookworm Ancylostoma caninum penetrate epidermis, basement membrane, and dermis in similar ways. These similarities in tissue invasion properties reflect the observed biochemical similarities in parasite protease composition. The larvae of both species contain protease activity that is inhibited by o-phenanthroline; this identifies the proteases as metalloproteases. The enzyme activities exhibit an alkaline pH optimum between pH 9 and 10. During modified sodium dodecyl sulfate-polyacrylamide gel electrophoresis in which a protein substrate (either casein or gelatin) was used, the protease activities resolved into a major band at an Mr of 68,000 and a minor band at an Mr of 38,000. Proteases were released by living A. caninum larvae in vitro and degraded purified and radiolabeled casein to smaller peptides. Motile hookworm larvae were also incubated with purified and radiolabeled connective tissue macromolecules in vitro. Both Ancylostoma species degraded human fibronectin to a 60,000-Mr polypeptide intermediate, but could not degrade solubilized bovine elastin or human laminin. In contrast, the obligate skin-penetrating nematode Strongyloides stercoralis degraded all three substrates. This biochemical difference may explain some observed differences in invasiveness.

Ancylostoma↗
PubMed1990

High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association.

One hundred seventy-two patients with advanced breast cancer were randomized to receive oral standard-dose megestrol acetate (MA), 160 mg/d or high-dose MA, 800 mg/d. All but two patients had one prior trial of tamoxifen therapy for either metastatic disease (74%) or as adjuvant treatment (26%). Pretreatment characteristics were similar for both arms. High-dose MA resulted in a superior complete plus partial response rate (27% v 10%, P = .005), time to treatment failure (median, 8.0 v 3.2 months, P = .019), and survival (median, 22.4 v 16.5 months, P = .04) when compared with standard-dose therapy. These differences remained significant after adjustment for other covariates. Thirty-four patients were given high-dose MA after failure of standard-dose MA treatment, and none responded. Weight gain was the most distressing side effect, with 13% of standard-dose and 43% of high-dose patients gaining more than 20 lbs. Four major cardiovascular events occurred in patients receiving high-dose treatment and one in patients given standard doses. Other toxicity was modest. High-dose MA may represent a significant improvement in secondary endocrine therapy for advanced breast cancer patients refractory to initial endocrine treatment, but its use on a regular basis should be reserved until these results are confirmed by other clinical trials.

Adult↗
PubMed1990

Vincristine infusion with CHOP-CCNU in diffuse large-cell lymphoma.

Phase I and II trials of vincristine infusion have demonstrated the safety and efficacy of this approach in the treatment of patients with refractory non-Hodgkin's lymphoma. Subsequently, a trial was designed to evaluate this technique in untreated patients. Repeated 5-day infusions of vincristine 0.25 mg/m2 per day were incorporated into a CHOP-CCNU regimen and administered to 24 patients with advanced diffuse large-cell lymphoma. Objective responses occurred rapidly and were observed in 18 (75%) patients in whom 13 (54%) were complete. Toxicity was generally mild to moderate and neurotoxicity appeared to be no worse than typically observed with bolus vincristine. Complete responses have been durable in most patients and 10 (77%) of the complete responders have not relapsed. At this time, 9 (38%) of the total patients remain alive and without evidence of disease from 3.8 to 7.3 years from the start of treatment. One patient died of disseminated gastric cancer at 3.3 years from the start of therapy and there was no evidence of lymphoma at exploratory laparotomy. Infusion of vincristine may be safely incorporated into multiagent chemotherapy programs of the CHOP type for non-Hodgkin's lymphoma. Its potential for protracted nonmyelosuppressive cell kill would appear attractive in designing future trials for this disease.

Adult↗