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Biomedical subjects

W L Hughes

Publications and source records attributed to W L Hughes.

12 recordsLinked to original sources

High-dose combination alkylating agent therapy with autologous bone marrow rescue for refractory solid tumors.

Twenty-six adults, ages 27 to 60, with refractory metastatic solid tumors were treated with high-dose cyclophosphamide (Cy) + carmustine (BCNU) at one of three escalating dose schedules followed by autologous bone marrow transplantation (ABMT). Toxicity was severe and dose-related, with the maximum tolerated dose for the combination determined to be Cy 160 mg/kg and BCNU 900 mg/m2. Median time to WBC recovery (greater than or equal to 1,000/microL) was 13 days post-ABMT (range, nine to 22 days) and to a platelet count of greater than or equal to 50,000/microL, 22 days (range, 13 to 83 days). Sixteen of 20 evaluable patients (80%) responded to therapy with at least 50% reduction in measurable tumor, and three patients achieved complete remission (CR). Responders included eight of nine evaluable patients with breast carcinoma, two of five with melanoma, two of two with sarcoma, and four of four with colon carcinoma. Response durations were short (median, 4 months), even for complete responders, and relapses generally occurred at sites of previous metastases. In order for this approach to have a more significant impact on overall survival, it may need to be applied earlier in the natural history of the malignancy.

Adult

A simple fast micromethod for measuring enzyme activities which release tritium as tritium water.

The entire procedure is carried out in a counting vial by mixing the reagents as a 20- to 30-microliters drop in the cap of a counting vial, incubating, quenching the reaction, and then distilling the tritium water produced into the chilled vial, in which it is assayed after the addition of scintillation solvent and a clean cap. The application of this technique to the analysis of serum transaminases is described.

Humans

Tissue perfusion rate determined from the decay of oxygen-15 activity after photon activation in situ.

Rates of cerebral perfusion were obtained from measurements of the disappearance (wash-out) of oxygen-15 after in situ tissue activation with 45-million-volt x-rays. In an anesthetized cat, typical values were 90 milliliters per minute per 100 grams of tissue, with 55 percent wash-out. In a specific radiotherapy patient, the value was 65 milliliters per minute per 100 grams of tissue, with 63 percent wash-out of oxygen-15 through incorporation into tissue water.

Animals

Chromosome damage in Chinese hamster cells produced by 125I-UdR at the site of its incorporation.

Metaphase chromosomal aberrations were produced by 125I-labeled iododeoxyuridine (125I-UdR) incorporated into Chinese hamster Don cells at the end of the S-period of the cell cycle. Chromosome damage and the number of autoradiographic silver grains were recorded for whole cells, for chromosome pairs No. 4 and No. 5, and for the X and the Y chromosomes. The X and the Y chromosomes, which label late in S, were at least twice as heavily labeled as chromosome pairs No. 4 and No. 5--two readily recognizable autosomes of similar size. The incidence of chromosome damage was at least six times that which would have been expected from equivalent doses of X-rays and the incidence of damage was directly related to the number of silver grains over each chromosome. We estimate that it takes four to ten disintegrations to produce a visible chromosome aberration. The finding that chromosome damage is localized at the site of the 125I decay is most readily explained by the high flux of low energy Auger electrons occurring at the site of the decay of the incorporated 125I atom.

Animals

Blood thymidine level and iododeoxyuridine incorporation and reutilization in DNA in mice given long-acting thymidine pellets.

A long-acting thymidine pellet consisting of 190 mg of cholesterol and 60 mg of thymidine has been developed for the study of thymidine metabolism and reutilization in vivo. Implantation of such a pellet s.c. in adult mice will maintain the blood plasma concentration of thymidine at levels between 40 and 8 X 10(-6) M, which are from 36 to 7 times those of normal mice, for periods up to 48 hr. During this period, in vivo uptake and reutilization of [125I]iododeoxyuridine, a thymidine analog, into intestinal and tumor DNA were almost completely suppressed. While iododeoxyuridine reutilization is not large in normal proliferative tissue even in the absence of pellet implants, reutilization of over 30% was measured in large, rapidly growing ascites tumors. The inhibition of iododeoxyuridine incorporation by elevated thymidine blood levels is directly proportional to serum concentration. This appears to be due to a thymidine pool in rapid equilibrium with blood thymidine. This pool is at least 10 times larger than the 4-nmole pool of extracellular thymidine.

Animals

Total lower lid reconstruction: technical details.

The main complications of this type of lower lid reconstruction are lash loss or malposition, entropion of the upper lid, upper lid retraction, undue laxity of the lower lid, and lid margin deformities. These can all be avioded by meticulous attention to surgical details and dressing techniques. I believe that this is the best and simplest method of providing a lid of acceptable function and appearance. The advantages of this type of operation are: (1) The new lower lid is constructed of lid tissue including the tarsus and conjunctiva from the upper lid. (2) The function and appearance of the new lower lid are acceptable with practically no tendency to late retraction. (3) The function and appearance of the upper lid need not be interfered with. (4) No external scars are produced except when a lash transplant is done. This transplant leaves a small, hardly noticeable scar in the lower part of the opposite brow. (5) The technique is relatively simple and well within the realm of any well-trained ophthalmic surgeon. The obvious disadvantages are the surgeon's inability to inspect the eye for two to four months and the inconvenience to the patient of having one eye closed for such a long period of time.

Alopecia