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Biomedical subjects

C J Williams

Publications and source records attributed to C J Williams.

At least 145 records · Page 8Linked to original sources

Surgery after initial chemotherapy for localized small-cell carcinoma of the lung.

Despite the high response rates induced by chemotherapy, many patients with limited small-cell lung cancer (SCLC) relapse at the site of primary disease. Failure of radiotherapy to overcome this has led to the use of surgery as part of a combined modality approach. Between December 1981 and December 1985, 189 patients with SCLC were assessed for suitability for surgery after an initial three cycles of chemotherapy (doxorubicin, cyclophosphamide, and etoposide). Fifty-seven were found to have limited disease, and of these, 19 were ineligible or unfit for surgery. Of the 38 eligible patients, 84% had an objective response to three cycles of chemotherapy and 25 were deemed suitable for surgery after restaging. At thoracotomy, four were inoperable, nine had a lobectomy, and 12 had a pneumonectomy. There was no evidence of viable SCLC in four resection specimens (one stage 1, two stage 2, one stage 3 at presentation), no viable SCLC but an entirely separate focus of viable poorly differentiated squamous carcinoma (SqLC) in one, and the remaining specimens contained viable SCLC. Survival of patients selected to undergo tumor resection was excellent (median survival, 33 months; plateau phase, 48% alive at 3 to 5 years), but survival of the entire group with limited SCLC was not dissimilar from that reported in previous series of limited-stage tumor treated with chemotherapy alone. Long-term survival appeared to be largely restricted to those with no evidence of viable SCLC at surgery (no viable SCLC, zero of five relapsed; viable SCLC, 13 of 16 relapsed and/or died). This prospective study confirms the feasibility of the combined modality approach, but suggests that any improvement in overall survival is likely to be small. Until the results from multicenter randomized trials are available, surgery, as part of a combined modality program, should be regarded as experimental.

Actuarial Analysis↗

Prepartum supplementation of selenium and vitamin E to dairy cows: assessment of selenium status and reproductive performance.

Incidence of retained placenta in dairy cows was evaluated in 627 parturitions. The herd was divided prepartum into three groups: 1) control, no treatment (n = 217 cows); 2) cows injected intramuscularly (n = 190) 21 to 10 d prior parturition with 45 mg Se and 2040 IU of vitamin E; and 3) cows intraruminally administered (n = 220) with two 30-g pellets containing 10% elemental selenium 2 mo prior to expected calving. Incidence of retained placenta (22.1%) was not reduced by Se in combination with vitamin E injection or intraruminal Se pellet nor were other measures of reproduction improved for cows fed a prepartum diet adequate in Se. At parturition the blood plasma Se concentrations were higher in treated postpartum with Se than in untreated cows. No difference in blood plasma Se was observed at parturition between cows with or without placenta retention. Cows dosed intraruminally with Se had a significant increase in milk Se, but this was too small to be a danger to human health. The present results on placenta retention suggest that this disorder is not a Se responsive disease in the dairy cow.

Animals↗

Multicenter study of trilostane: a new hormonal agent in advanced postmenopausal breast cancer.

Trilostane, an inhibitor of the production of adrenal estrogens, was administered, together with dexamethasone, to 97 eligible postmenopausal women with advanced breast cancer. Seventy-four patients who had either received trilostane for a minimum of 10 weeks or whose disease had progressed while on trilostane before this period were assessed for tumour response. Eighteen patients (25%) had objective responses (two complete, 16 partial); a further 21 patients had stable disease. The response rate among all 97 patients, including those not treated for a minimum 10-week period, was 19%. Thirty-two of 97 patients reported adverse reactions which were attributed to trilostane and/or dexamethasone. Therapy was stopped for 15 patients, and the dose of trilostane was reduced for ten. Diarrhea was the commonest side effect, being reported in 16 patients, of whom nine stopped treatment. Trilostane, given with a corticosteroid, is an effective alternative hormonal agent acting by adrenal blockade for postmenopausal women with advanced breast cancer.

Breast Neoplasms↗

Increased collagen biosynthesis and increased expression of type I and type III procollagen genes in tight skin (TSK) mouse fibroblasts.

The Tight Skin (TSK) mouse is a mutant strain that displays connective tissue abnormalities characterized by excessive accumulation of collagen in skin, subcutaneous tissues, and some internal organs such as the heart. Increased collagen biosynthesis by skin organ cultures from affected mice has been previously demonstrated, but the mechanisms responsible have not been identified. In order to examine the molecular alterations responsible for the increased production of this protein, normal and TSK mouse dermal fibroblast cell lines were established, and studies of collagen biosynthesis and expression of Types I and III procollagen genes were performed. Secondary cultures of 5 normal and 5 TSK mice dermal fibroblasts were incubated in media containing 10% fetal calf serum and 50 micrograms/ml ascorbic acid and after labeling with [14C]proline for 72 h the amount of [14C]hydroxyproline synthesized was determined. The results showed that TSK mice dermal fibroblasts produced significantly greater amounts of [14C]hydroxyproline than their normal counterparts (118 +/- 28.3 X 10(-2) versus 53.7 +/- 21.9 X 10(-2) dpm/micrograms of DNA; p less than 0.004). Subsequently, the expression of three procollagen genes in normal and TSK mice fibroblasts was analyzed by Northern blot hybridization of polyadenylated RNA to the human cDNA clones alpha 12, Hf 32, and RJ 5 which are specific probes for transcripts of alpha 1(I), alpha 2(I), and alpha 1(III) procollagen chains, respectively. It was found that TSK mice fibroblasts consistently displayed increased levels (up to 5-fold) of all three collagen transcripts while beta-actin mRNA levels were unchanged. The results demonstrate that TSK mice dermal fibroblasts produce excessive amounts of collagen in culture concomitant with a dramatic increase in the expression of Types I and III procollagen genes.

Animals↗

A phase II study of tamoxifen in ovarian cancer.

A phase II study of tamoxifen was conducted in 22 patients with stage III and IV ovarian cancer who had failed chemotherapy and who had evaluable disease. Tamoxifen was administered at a dose of 20 mg twice daily continuously until evidence of progression. Twenty-one patients had progression of disease within 3 months and one patient had stable disease for 6 months. There were no objective responses to this treatment.

Adult↗

Attitude accessibility as a moderator of the attitude-perception and attitude-behavior relations: an investigation of the 1984 presidential election.

It was hypothesized that the extent to which individuals' attitudes guide their subsequent perceptions of and behavior toward the attitude object is a function of the accessibility of those attitudes from memory. A field investigation concerning the 1984 presidential election was conducted as a test of these hypotheses. Attitudes toward each of the two candidates, Reagan and Mondale, and the accessibility of those attitudes, as indicated by the latency of response to the attitudinal inquiry, were measured for a large sample of townspeople months before the election. Judgments of the performance of the candidates during the televised debates served as the measure of subsequent perceptions, and voting served as the measure of subsequent behavior. As predicted, both the attitude-perception and the attitude-behavior relations were moderated by attitude accessibility. The implications of these findings for theoretical models of the processes by which attitudes guide behavior, along with their practical implications for survey research, are discussed.

Association↗

A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer.

We randomized 122 premenopausal women to receive tamoxifen or to undergo a surgical oophorectomy. Of 54 evaluable women treated with tamoxifen, 24% had an objective response, as compared with 21% of 53 women having an oophorectomy. The median duration of response for tamoxifen (20 months) was longer than that for surgical oophorectomy (7 months), but this did not achieve statistical significance (P = .056). Overall median survival was 15 months for 58 patients receiving tamoxifen and 25 months for 53 patients undergoing oophorectomy (P = .18). Toxicity was greater in those undergoing oophorectomy, though both treatments were well tolerated. In those premenopausal women for whom hormonal therapy is indicated, tamoxifen is a suitable alternative to surgical oophorectomy.

Adult↗

Interrelationships among liposoluble vitamins in ruminants.

Plasma concentrations of vitamins A and E were examined in sheep, and a transitory decrease was observed after a single massive dose of vitamin D3 (5 X 10(6) IU) was administered orally or parenterally. Administration of a large dose of vitamin E to sheep decreased plasma retinol concentrations within 72 hours, but thereafter, the plasma retinol concentrations returned to near baseline values. Oral administration of a single pharmacologic dose of dl-alpha-tocopherol (5 g) to sheep caused a slow increase of this vitamin in the blood plasma. In cattle, a single IM administration of 3 liposoluble vitamins (A, D3, and E) at acceptable concentrations had no detectable influence on plasma alpha-tocopherol concentrations with the sampling intervals used. Plasma concentrations of alpha-tocopherol in these cattle showed a marked seasonal pattern; the concentrations increased from January to a peak in July, with a subsequent decrease in the fall. Also reported are estimates of inter- and intraindividual variation in plasma liposoluble vitamin concentrations.

Administration, Oral↗

Involvement of the central nervous system by non-Hodgkin's lymphoma in adults. A review of 36 cases.

Thirty-six (10.1 per cent) of a total of 355 adult patients with non-Hodgkin's lymphoma seen over a seven and a half year period developed compression or infiltration of the central nervous system (CNS). In nine patients (2.5 per cent) extradural tumour masses compressed the spinal cord or brain. Five of these patients, all previously untreated, responded well to treatment, with excellent recovery of CNS function and survival in the long term. The prognosis for the four patients with advancing drug-resistant systemic disease at the time of CNS compression was poor. In 27 patients (7.6 per cent) a clinical or cytological diagnosis of meningeal infiltration was made (on cerebrospinal fluid). Meningeal disease was seen most frequently in patients with high-grade lymphoma, either at presentation or during subsequent progression of systemic disease. All of these patients have died of systemic and/or CNS disease less than 20 (median 3) months from diagnosis of meningeal disease. Meningeal infiltration represents a significant clinical problem for which new approaches to prophylaxis and treatment are required.

Adolescent↗

Mineral and amino acid composition of beef cattle hooves.

Twenty-three Hereford X Shorthorn cattle were used to evaluate the effects of seasonal and dietary changes on the mineral composition (Ca, Mg, Cu, Zn, and S) of hooves. A seasonal pattern was found in the Ca, Mg, and Zn composition of hooves in the 12 cattle evaluated in 1982 and in the 11 cattle evaluated in 1983, with the concentrations of 3 minerals decreasing in winter when dietary change did not occur. Copper concentrations significantly decreased during the 1st year (1982) and had a tendency to decrease during the 2nd year. During the 1983 pasturing season, when effects of seasonal vs dietary change could not be distinguishable, hoof concentrations of Ca and Mg decreased, whereas the inverse trend was observed for Cu and Zn. Seasonal patterns for hoof concentrations of S were not found. Results of mineral analysis of hooves indicated strong correlations between calcium and the other minerals (except S), and between Zn and Cu. Amino acid analyses of hooves of the 11 cattle in 1983 indicated differences in their composition related to dietary changes (winter feeding vs pasture) or to management.

Amino Acids↗

Multiexon deletion in an osteogenesis imperfecta variant with increased type III collagen mRNA.

Recently, the dermal fibroblasts (ATCC CRL 1262) of a lethal perinatal variant of osteogenesis imperfecta have been used for the first molecular characterization of a collagen gene defect (Chu, M. L., Williams, C. J., Pepe, G., Hirsch, J. L., Prockop, D. J., and Ramirez, F. (1983) Nature (Lond.) 304, 78-80). These studies revealed that the patient was heterozygous for an internal deletion of approximately 500 base pairs in the pro-alpha 1(I) collagen gene, consistent with previous investigations indicating that CRL 1262 fibroblasts equally synthesized a normal and a shortened pro-alpha 1(I) chain (Barsh, G. S., and Byers, P. H. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 5142-5146). Cloning and analysis of the affected allele of CRL 1262 has now indicated that the deletion is contained between two introns of the pro-alpha 1(I) gene and results in the elimination of three exons of the triple helical domain. Furthermore, the termini of the rearrangement are located within two short inverted repeats suggesting that the self-complementary nature of these DNA elements may have favored the formation of a DNA secondary structure intermediate which, in turn, served as substrate for the deletion. Evidence are also presented for an elevated Type III collagen mRNA content in the patient fibroblasts.

Base Sequence↗

Cisplatin, adriamycin and cyclophosphamide (PACe) combination chemotherapy in patients with ovarian carcinoma resistant to chlorambucil.

Twenty patients with stage III or IV ovarian carcinoma refractory to chlorambucil were treated with IV cisplatin, adriamycin and cyclophosphamide. Two patients achieved CR and four PR, giving an overall response rate of 30%. All patients have since died at 0-18 (median 8) months. Use of this region was associated with marked toxicity, including three drug-related deaths. Second-time drug combinations should be regarded as experimental, and they should probably only be used in selected patients outside of clinical trials.

Alopecia↗

Cisplatin combination chemotherapy versus chlorambucil in advanced ovarian carcinoma: mature results of a randomized trial.

A randomized study to compare the efficacy of combination chemotherapy (cisplatin, doxorubicin, cyclophosphamide: PACe) with chlorambucil (CB) in International Federation of Gynecology and Obstetrics (FIGO) stage III and IV ovarian carcinoma was conducted between May 1979 and October 1983. Patients failing initial CB were subsequently eligible for treatment with PACe. Eighty-nine patients were randomized and 85 were eligible for analysis; as of date, 72 of these patients have died. The majority of patients in this study had bulky residual disease after their initial laparotomy (76%). Complete response (CR) was documented by a second laparotomy after five cycles of combination therapy or 6 to 12 months alkylating agent therapy. The overall response rate (CR plus partial response [PR]) for the combination (PACe, 68%) was significantly higher (P = .0004) than that for the chlorambucil (CB, 26%). However, the median survival was not improved (PACe, 13 months; CB, 11 months) and the survival curves were not significantly different (log rank test P = .25). The results of this study are comparable to preliminary data reported from other similar randomized studies. PACe, as administered in this study, is not indicated as routine therapy in patients with bulky residual ovarian carcinoma.

Actuarial Analysis↗

Effects of artificial illumination on turkey sperm viability.

The effects of direct exposure of turkey semen to artificial lighting on the quality of the spermatozoa were investigated. Undiluted (neat) and diluted semen were exposed to light or dark treatments for 4 or 6 hr while held at 5, 15, or 25 C. The percentage of normal, abnormal and dead sperm, and the percent fertility was determined after various light and dark treatments. Neat semen held in light at 5, 15, and 25 C, and dilute semen held at 5 and 25 C, contained significantly greater numbers of normal spermatozoa than semen exposed to the dark. A significant rise in the number of abnormal and dead spermatozoa was seen in treated samples held in the dark. Both neat and extended semen exposed to blue light (peak 450 nm) contained significantly greater numbers of normal spermatozoa and fewer abnormal spermatozoa than semen treated with red light (peak 650 nm) after both 4 and 6 hr of treatment. The fertilizing capacity of spermatozoa exposed to light was greater than that of spermatozoa exposed to dark. Artificial insemination of hens with semen exposed to light or darkness for 6 hr resulted in an initial percentage of fertile eggs of about 40% and 24% from the light and dark treated semen, respectively. It was concluded that light resulted in improved quality of turkey semen during a short-term holding period.

Animals↗