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Biomedical subjects

L Williams

Publications and source records attributed to L Williams.

At least 325 records · Page 18Linked to original sources
PubMed1983

Administration of gallium nitrate by continuous infusion: lack of chronic nephrotoxicity confirmed by studies of enzymuria and beta 2-microglobulinuria.

Enzymuria and beta 2-microglobulinuria are sensitive markers of injury to renal tubular cells. We evaluated these markers in 41 patients with advanced malignant lymphoma who received gallium nitrate administered as a continuous infusion during a recent phase I-II study. In contrast to our findings with cisplatin, we observed no significant increase in enzyme excretion or beta 2-microglobulinuria in these patients even after long-term treatment. Our results indicate that gallium nitrate administered by infusion does not produce cumulative renal tubular toxicity.

Acetylglucosaminidase↗
PubMed1983

Phase I and clinical pharmacology studies of intravenous and oral administration of 4-demethoxydaunorubicin in patients with advanced cancer.

4-Demethoxydaunorubicin (4-DMDR), an anthracycline analogue available in i.v. and p.o. form, has shown significant antitumor activity in murine tumor models while producing less cardiac toxicity than doxorubicin at equimyelotoxic doses. Phase I and clinical pharmacology studies of the i.v. and p.o. preparation were performed. With i.v. 4-DMDR, consistent myelosuppression was observed at a dose of 15 mg/sq m at a median Day 15; mild nausea and vomiting were observed in 9% of all treatment courses. In patients given p.o. 4-DMDR, myelosuppression occurred at median Day 14 in 10 of 12 patients given 50 mg/sq m. Nausea and vomiting occurred in 25% of all treatment courses, and dividing the dose over 3 days did not decrease the incidence. Alopecia occurred in 13% of evaluable patients treated with the i.v. preparation and 30% of evaluable patients treated p.o. No stomatitis was observed with either preparation, and no patient developed clinical signs of congestive heart failure. Pharmacokinetic studies were performed with both preparations and revealed prolonged plasma levels of the 13-hydroxy metabolite 4-DMDR-ol. The suggested starting dose for Phase II studies is 12.5 mg/sq m given every 21 days for i.v. 4-DMDR with dose escalation by 2.5 mg/sq m in the absence of myelotoxicity. For p.o. 4-DMDR, the suggested starting dose is 40 mg/sq m given every 21 days with escalation by 10 mg/sq m if no myelotoxicity is observed.

Administration, Oral↗
PubMed1982

Rabbit fibrin: characterization of the separated chains.

In preparation for studies of the time course of production in vivo of the constituent chains of rabbit fibrin, we characterized the structural features of the fibrin molecule. Fibrin was isolated from plasma and reduced and alkylated. The alpha, beta, and gamma chains were separated by CM-cellulose chromatography and their molecular weights and amino acid compositions were determined. The gamma chain was sequenced 36 steps with 32 positive identifications and the beta chain, 12 steps with 12 identifications. No major differences between the sequences of these chains and those of man, chicken, and dog were noted.

Amino Acid Sequence↗
PubMed1982

A scanning and transmission electron microscopical study of the morphogenesis of human colonic villi.

The morphogenetic events that occur in the development of villi in human foetal colon have been observed by light microscopy and scanning and transmission electron microscopy. At nine weeks, the colon is a simple tube composed of pseudostratified columnar epithelium and mesenchyme. By ten weeks, up to eight longitudinal ridges have formed by an elongation of individual epithelial cells. Even as the ridges are forming, the bases of some of the ridges become indented with mesenchyme thus forming longitudinal mucosal folds. By eleven and a half weeks, these have folded in a concertina fashion forming a longitudinal zig-zag pattern. From ten and a half weeks, small lumina develop within the epithelium near to its base. At this stage, they are not in continuity with the main lumen. Extension of these lumina to the main luminal surface and exfoliation of redundant cells result in division of the zig-zag folds into broad primary villi. Division of the primary villi occurs when cyst-like structures which develop within the pseudostratified columnar epithelium of the primary villi enlarge and extend to the lumen. Together with upgrowth of mesenchyme this results in small secondary villi with simple columnar epithelium.

Colon↗
PubMed1982

Evaluation in the community mental health centers program: a bold new reproach?

The Federal Community Mental Health Centers Program (CMHC)-from 1963 to 1981-was heralded as a revolution in mental health care. Championed by many, and severely criticized by others, the actual impact of the program on the nation's mental health remains unclear. The authorization to evaluate the CMHC Program came originally from congressional legislation (PL 90-174), and later from the policies and regulations of NIMH under a series of Federal laws, notably PL 94-63. From 1976-1980, two dominant evaluation strategies were prevalent: funds expended by NIMH each year for studies of CMHC services or program-wide evaluations, and a much larger expenditure by CMHCs to conduct their own, independent evaluations following federal guidelines. As the Center's Program was turned over to the states in the form of block grants (PL 97-35), a group of professionals involved with setting and carrying out federal CMHC evaluation policy of both varieties met in public forum to debate the impact of these two evaluation approaches. While some participants cited gains in evaluation technology and impact upon local management of CMHCs, others found the lack of a coordinated and systematic approach to evaluating the CMHC Program to have been an opportunity missed. The impact of CMHC evaluation efforts are also discussed in terms of their major contribution to the field of evaluation research as a whole.

Community Mental Health Centers↗
PubMed1982

Microfiches as an aid to teaching histology.

A set of six colour microfiches and an atlas of black-and-white prints of the photomicrographs used in the microfiches have been prepared by the author and have been used for teaching an Histology course to medical students for 4 years. Students reaction to them and their use has been gauged by voluntary questionnaires. Of students who responded, 78% found the microfiches made the course easier for them; 76% like the microfiches because they can use them for home study; 77% find them useful for class discussion; 62% like them because of their colour reproduction. A small group of fifteen students, who failed the Histology course the year prior to the introduction of microfiches and subsequently repeated the course, felt they could revise better with the help of the microfiches. Also they felt the course was clearer. Comparison of the examination results of the students for the 4 years preceding the introduction of microfiches with those of the 4 years since, shows an improvement in mean percentage achieved together with a decrease in the standard deviation (s.d.).

Australia↗
PubMed1982

Ultrastructural localisation of alkaline phosphatase in adult human large intestine.

The localisation of alkaline phosphatase in human large intestine was investigated at the ultrastructural level. Alkaline phosphatase was found in the mature absorptive cells of the surface, upper, and middle crypt epithelium; the reaction product was localised in the glycocalyx coat of the microvilli, the Golgi apparatus, and the rough endoplasmic reticulum. Slight activity was found in the immature absorptive cells of the middle and lower regions of the crypts. The undifferentiated cells and the enterochromaffin cells were negative. In the lamina propria, alkaline phosphatase was localised in the plasma membrane of the endothelial cells of the venules, in the rough endoplasmic reticulum of the plasma cells, and the cell membrane of macrophages. These results are consistent with the role of alkaline phosphatase in membrane transport.

Alkaline Phosphatase↗
PubMed1982

Phase I clinical trial and pharmacokinetics of 4'-carboxyphthalato(1,2-diaminocyclohexane)platinum(II).

4'-Carboxyphthalato(1,2-diaminocyclohexane)platinum(II) is a new, second generation platinum analog which had demonstrated in vitro activity in L1210 cell lines resistant to cisplatin and had less nephrotoxicity than did cisplatin in preclinical animal testing. A Phase I trial with this agent has been performed in 45 patients with advanced refractory cancers. Nine dosage levels, ranging from 40 to 800 mg/sq m, were studied. Major toxicities seen were myelosuppression, nephrotoxicity (which was generally mild), nausea and vomiting (which was quantitatively less than that seen with cis-platin), allergic reactions, and a peripheral neuropathy. The dose-limiting toxicity was thrombocytopenia. Pharmacokinetics performed at three dosage levels indicates that 4'-carboxyphthalato-(1,2-diaminocyclohexane)platinum(II) has a long t1/2 of 20 to 30 hr (total platinum) and is only partially excreted in the urine and that a high proportion of the drug is nonfilterable within 30 to 60 min of administration. Therapeutic responses were seen in nasopharyngeal carcinoma, adenocarcinoma of the cervix, and lung and gastric cancer. As a starting dose for Phase II studies, which are planned for patients with ovarian, testicular, lung, gastric, and esophageal cancers, 640 mg/sq m given every 3 to 4 weeks is recommended.

Creatinine↗
PubMed1981

Oral VP-16-213 in advanced bronchogenic carcinoma and toxic effects when combined with methotrexate.

Forty-six patients with histologically confirmed lung cancer received treatment with the cytotoxic drug VP-16-213 in a dose of 100 mg twice daily, given orally for five days. The overall objective response rate was 11 out of 46 (24%) or 11 of the 33 (33%) who survived to receive two cycles. The drug was effective in all histological types. Only one patient developed leucopenia. This demonstration of the safety of VP-16-213 and its effectiveness suggested that this drug might be used in combination chemotherapy. A series of pilot studies showed unexplained marrow toxicity when VP-16-123 combined with vincristine was given with either methotrexate of adriamycin.

Bone Marrow Diseases↗