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Biomedical subjects

D H Moore

Publications and source records attributed to D H Moore.

At least 127 records · Page 7Linked to original sources

In vivo measurement of breast cancer growth rate.

S-phase cells of 66 primary breast cancers were labeled in vivo by preoperative infusion of the thymidine analogue bromodeoxyuridine. A monoclonal antibody specific for DNA-incorporated bromodeoxyuridine was used to identify positive cells and compute a labeling index on histologic sections. The labeling index (the percentage of cells in S-phase) ranged from 0.1% to 23.9%; it correlated positively with poorly differentiated cancer, higher mitotic counts on routine histologic examination, and tumor size; and it correlated inversely with estrogen and progesterone receptors. The labeling index did not correlate with nodal involvement or ploidy. Of the 15 patients with a labeling index greater than 12%, three died and one had systemic disease after a median follow-up of 19 months. No other patients had recurrences. There were no clinical complications of bromodeoxyuridine infusion.

Breast Neoplasms↗

HI-6 and 2-PAM in sheep: pharmacokinetics and effects on muscle tissue following intramuscular injection.

The pharmacokinetics of 2-PAM, a component of the current nerve agent antidote therapy for U.S. military forces was compared to the pharmacokinetics of another acetylcholinesterase reactivator HI-6. Additionally, the effects of these compounds on muscle tissue following intramuscular injection was examined. Plasma concentrations of the oximes were determined by HPLC. Plasma concentration-time profiles for both oximes fit a one-compartment open model with first-order absorption and elimination. The results demonstrate that the half-time of absorption of HI-6 was significantly higher than that for 2-PAM. Musculoirritancy was assessed on the basis of quantitative histological examinations of the injection sites and by the measurement of serum creatinine phosphokinase. Comparison of the scores from the histological sections demonstrate no difference between the two oximes. Serum creatinine phosphokinase values were elevated following injections of HI-6, but were not consistently elevated following the 2-PAM injections.

Animals↗

The pharmacokinetics of atropine and diazepam in sheep: intramuscular co-administration.

The purpose of this study was to determine whether the co-administration of atropine and diazepam affect the rate and extent of absorption of either drug. A triple crossover pharmacokinetic study using adult sheep was conducted. Each of nine animals received single injections of atropine (2 mg), diazepam (10 mg), and a combination of the two compounds weekly over a 3-week period. The combination of the drugs was injected into a single intramuscular site through a specially designed tandem syringe. Blood samples were obtained from time 0 to 300 min post-injection. Serum samples were analyzed for atropine by radioimmunoassay and for diazepam by gas chromatography/mass spectrometry. Pharmacokinetic parameters were evaluated by non-compartmental analysis. The co-administration of atropine and diazepam intramuscularly in sheep caused a delay in the time to reach maximal concentration of atropine. However, at the time when a single injection of atropine reached its maximum serum concentration, 92 per cent of that concentration was reached by atropine in the presence of diazepam. Additionally, no difference was detected in the rate or extent of diazepam absorption when administered intramuscularly in combination with atropine at the same site.

Animals↗

Malignant endometrioid cystadenofibroma of the ovary.

Malignant endometrioid cystadenofibroma is recognized as a distinct category of epithelial ovarian cancer and yet is rarely reported. Three patients from the University of North Carolina experience are described to emphasize similarities between this unusual tumor and common epithelial ovarian cancer with respect to clinical behavior, surgical staging, and treatment.

Adenofibroma↗

Hexamethylmelamine chemotherapy for persistent or recurrent epithelial ovarian cancer.

The purpose of this study was to determine the activity and toxicity of hexamethylmelamine chemotherapy in patients with persistent or recurrent epithelial ovarian cancer. Forty-nine women received hexamethylmelamine 100 to 150 mg/day for 14 days, repeated at 4-week intervals. All patients had previously received at least one chemotherapy regimen, and 46 (94%) had received cisplatin. Among 25 patients with clinically measurable disease there were three complete and two partial responses, for an objective response rate of 20%. The mean progression-free interval for responders was 38.6 months versus 9.6 months for nonresponders or patients with nonmeasurable disease (p less than 0.001). Thirteen patients are alive, eight with no clinical evidence for disease. Only four patients discontinued therapy because of toxic reactions. Hexamethylmelamine appears to be a well-tolerated drug with activity against ovarian cancer previously treated with cisplatin.

Adult↗

Squamous cell carcinoma of the vulva in pregnancy.

Two women presenting with invasive squamous cell cancer of the vulva during pregnancy are reported. The first patient was successfully treated by radical vulvectomy 2 weeks after cesarean section delivery; the second patient died of disseminated cancer despite radical vulvectomy and postoperative radiation therapy. In the second case the diagnosis was not established until 3 months after delivery. Only 12 cases of invasive squamous cell vulvar cancer during pregnancy have been previously reported. Liberal use of punch biopsy for any suspicious vulvar lesions is mandatory to enhance the potential for early diagnosis and successful treatment.

Adult↗

The effects of exercise following exposure to bis(trifluoromethyl) disulfide.

Bis(trifluoromethyl) disulfide (TFD) was originally designed for use as an agricultural fumigant. Inhalation of toxic doses of TFD results in varying degrees of pulmonary edema. The purpose of this study was to determine if exhaustive exercise would potentiate the toxic effects of TFD. One group of treadmill-acclimated rats was exercised to exhaustion following a 10-minute whole-body exposure to TFD. A second group was similarly exposed but not exercised. Two other groups of rats were sham exposed; one was exercised while one remained sedentary following the sham exposure. Twenty-four hours after exposure, the animals were sacrificed; the lungs were removed and weighed, and a portion was collected for histopathologic examination. The remaining lung tissue was allowed to dry to constant weight. There was no difference in endurance times between exposed and sham-exposed rats. There was a significant increase in the amount of pulmonary edema and associated pulmonary pathology in rats exercised following exposure to TFD. Eleven of twelve animals exercised following exposure to TFD and three of twelve animals which remained sedentary following exposure died by 24 hours. The degree of pulmonary pathology in all rats exposed to TFD was profound.

Administration, Inhalation↗

Class I histocompatibility antigen expression: a prognostic factor for aneuploid ovarian cancers.

Epithelial ovarian cancers with aneuploid DNA content are associated with a poorer clinical course than diploid tumors. Flow cytometric analysis may further categorize aneuploid tumors based on the relative expression of cell surface histocompatibility (HLA) antigens. Surgical specimens from 20 patients with aneuploid tumors were stained using an indirect immunofluorescence method with primary murine monoclonal antibodies W36/22 (class I HLA surface antigens) and L5.1 (irrelevant antibody), counterstained with propidium iodide (DNA stain), and analyzed with the flow cytometer using a computer program to correct staining intensity for cell size. Patients with high or low class I expression were similar with respect to age, stage, histology, grade, and residual disease following surgical debulking; all patients were treated with cisplatin-based chemotherapy. Women with low class I HLA antigen expression had higher progression rates and death rates than patients with high class I HLA expression. Low class I HLA antigen expression is a poor prognostic factor among patients with aneuploid ovarian cancers.

Aneuploidy↗

5-Fluorouracil neurotoxicity.

Two cases of 5-fluorouracil-induced neurotoxicity from the University of North Carolina are presented. 5-Fluorouracil metabolism is briefly discussed with reference to possible mechanisms for the neurotoxicity. A possible role for thiamine supplementation in the prevention of this unusual complication is supported by our experience.

Adult↗

Early diagnosis of cutaneous malignant melanoma at Lawrence Livermore National Laboratory.

The Lawrence Livermore (Calif) National Laboratory (LLNL) has observed a threefold increase in incidence of cutaneous malignant melanoma (CMM) since 1972. A consultant pathologist reviewed 49 of 50 cases of CMM diagnosed from 1969 to 1984 and reclassified 4 cases; this did not significantly affect the elevated rate. A comparison of the thicknesses of CMM at LLNL from 1976 to 1984 with those from a nearby community histopathology laboratory showed that 74% of the LLNL cases were Clark level I or II, compared with 40% of the comparison laboratory cases. A matched-pair comparison controlling for age, sex, and year of diagnosis showed the LLNL cases were thinner in 58% of the pairs. The median thickness of CMMs at LLNL decreased faster than those from the comparison laboratory.

Adult↗

Cisplatin, vinblastine, and bleomycin in advanced and recurrent ovarian germ-cell tumors. A trial of the Gynecologic Oncology Group.

STUDY OBJECTIVE: To evaluate the efficacy of cisplatin-based combination chemotherapy in patients with advanced ovarian germ-cell tumors. DESIGN: Nonrandom prospective trial with endpoints of tumor response, results of repeat surgical exploration, progression-free interval, and survival. SETTING: Cooperative university-based cancer study comprising 27 participating institutions. PATIENTS: Ninety-seven patients were treated and all were evaluable. Of these, 8 had dysgerminoma and 89 had other cell types. INTERVENTIONS: Patients received 3 to 4 courses of cisplatin. vinblastine, and bleomycin (PVB). After chemotherapy, suitable patients had re-staging laparotomy. Maintenance vinblastine therapy was originally given but was discontinued for all patients in 1981. Patients with persistent or recurrent disease were treated with vincristine, dactinomycin, and cyclophosphamide (VAC) or etoposide plus cisplatin (EP). RESULTS: Of 35 patients with tumors other than dysgerminoma who had clinically measurable disease, 15 (43%; CI, 26% to 61%) had complete responses. Forty of fifty-six second-look laparotomies (71%; CI, 58% to 83%) revealed no tumor or mature teratoma. Forty-seven patients are still disease-free and 59 are alive. The survival rate is 71% (CI, 62% to 89%) and the disease-free rate is 51% (CI, 41% to 62%) at 2 years. Eight patients had durable remissions with second- or third-line therapy. Seven of eight patients with dysgerminoma are also disease-free. CONCLUSIONS: Cisplatin-based chemotherapy is effective for patients with ovarian germ-cell tumors, is superior to previous regimens, and will cure a substantial number of patients.

Adult↗

Morbidity of lymph node sampling in cancers of the uterine corpus and cervix.

To assess the morbidity of lymph node sampling, medical records were reviewed for all patients with cancers of the uterine corpus and cervix who underwent primary surgical therapy between January 1, 1980 and December 31, 1986. Five hundred fifty-four patients were identified. Of the 292 patients with corpus cancer undergoing total abdominal hysterectomy, lymph node sampling was performed in 65.4%. Operative blood loss, transfusion requirements, and length of hospital stay were not increased significantly (P greater than .05) in women having node sampling. Of the 262 patients with cervical cancer, 72 underwent abdominal hysterectomy, 111 underwent radical hysterectomy, and 79 underwent staging laparotomy, with lymph node sampling performed in 82, 100, and 92% of these groups, respectively. The incidence of perioperative complications in this group was similar to that in the corpus cancer group. Vascular injuries, hematomas, and lymphocysts were more frequent after lymph node sampling. One postoperative death was attributed to complications from node sampling, but there were no other long-term sequelae. The low overall risk associated with lymph node sampling supports its inclusion in the surgical evaluation of gynecologic malignancies.

Biopsy↗

Exact versus asymptotic analysis for a matched case-control study.

We compare exact and asymptotic methods for variable selection in matched case-control studies. Data from a study of melanoma among the employees of the Lawrence Livermore National Laboratory illustrate the comparisons. Relative to large sample methods, the exact method almost always yielded larger p-values. The differences in p-values became more pronounced with inclusion of more variables in the logistic model. Thus, when the sample size is not large, and there are many covariates under study, use of the exact method tends to select more parsimonious models and avoids overfit of the data.

Algorithms↗

Significance of multiparameter flow cytometric analysis of ovarian cancer.

A prospective flow cytometric examination of ovarian epithelial tumors was undertaken to further characterize aneuploid (including triploid and tetraploid) tumor cell populations according to expression of ovarian tumor antigen CA125 and to expression of class I (normally present in ovarian epithelium) and class II (normally absent in ovarian epithelium) major histocompatibility complex antigens. Samples from thirty-two of 42 patients (76%) exhibited at least one aneuploid population of tumor cells. Separate analysis of the aneuploid and diploid components of samples with aneuploid populations revealed between-tumor variation: seven of 23 aneuploid populations (30%) were positive for CA125; eight of 22 aneuploid populations (40%) exhibited substantial decreases in major histocompatibility complex class I expression, compared with corresponding diploid components of the same samples; and eight of 22 aneuploid populations (36%) exhibited substantial expression of major histocompatibility complex class II antigens. The frequencies of aneuploid populations and of the foregoing antigen expression categories were independent of tumor cell type, stage, and grade. The significance of these results for prognosis remains to be determined.

Adenocarcinoma↗