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.

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.

Contrast-induced seizure associated with thrombotic thrombocytopenic purpura. Case report.

A patient with thrombotic thrombocytopenic purpura had a seizure as the result of a contrast media injection given during computed tomographic examination. To our knowledge, ours is the first such case reported.

Short-term case mix management with linear programming.

One short-term economic incentive created by a prospective payment system based on diagnosis-related groups (DRGs) is for hospital managers to optimally and efficiently use the hospital's current mix of services to maximize net contribution. DRGs provide a managerial definition of the hospital's product by determining the number of patients discharged within each of the 467 groupings. Thus, the DRG case mix can be thought of as the hospital's product mix. As in major industry, linear programming models may prove useful in determining the hospital's financially optimal case mix. This article provides a framework for applying the linear programming concept to case mix planning in the hospital setting. It also presents an illustration and interpretation of a linear programming model that provides information about the short-term optimal case mix.

Effects of single-dose irradiation in tumor blood flow studied by 15O decay after proton activation in situ.

A noninvasive technique employing photon activation of tissue oxygen in situ and detection of subsequent 15O positron decay was used to study the effects of single-dose 60Co irradiation on capillary blood flow in transplanted rat rhabdomyosarcomas. Tumor blood flow was measured before irradiation with 16.5, 38.5, or 60.5 Gy and at several intervals afterward (0-72 hr.). Pre-irradiation values of volume-averaged blood flow in the tumor ranged from 7 to 44 ml/min./100 g. Several hours after irradiation, blood flow fell by up to 50% for 60.5 Gy and up to 35% for 16.5 Gy. However, 24 hours after irradiation, tumor blood flow had recovered completely in the 16.5-Gy group and substantially in the others. For smaller doses such as the fractions typically employed in radiotherapy, no changes in tumor blood flow were observed.

Photon activation-15O decay studies of tumor blood flow.

A direct, noninvasive method for measuring absolute values of specific capillary blood flow in living tissue is described. The method is based on the photon activation, in situ, of tissue elements and the measurement of the subsequent decay of the positron activity induced, employing coincidence detection of the photon pairs produced in positron annihilation. Analysis of the time-dependent coincidence spectrum reveals the contribution to the total signal from the decay of 15O, from which the specific capillary blood flow in the imaged, activated volume is ultimately determined. By virtue of its introduction of the radioisotope of interest (15O) directly and uniformly into the tissue volume under investigation, the method described permits both the nonperfused and well perfused fractions of an activated volume to be estimated and hence, the average specific blood flow within imaged tumor volumes to be computed. The model employed to describe and analyze the data is discussed in detail. Results of application of the technique to measurement of specific blood flow in rhabdomyosarcoma tumors grown in WAG/Rij rats are presented and discussed. The method is shown to be reliable and well suited to studies designed to determined the effects of various agents, such as heat, radiation and drugs, on tumor blood flow.

Physiological effects of hyperthermia: response of capillary blood flow and structure to local tumor heating.

Specific capillary blood flow and small-vessel pathology in animal tumors (rhabdomyosarcoma BA-1112) of WAG/Rij rats were examined following local tumor heating to 40-44.5 degrees C. Blood flow in tumors heated to 40-41 degrees C for 40 minutes was reduced initially by about 50%, but returned to near preheating values within 72 hours, consistent with the histopathological observations indicating small-vessel dilation and temporary congestion. The application of hyperthermia greater than 43 degrees C (for 40 minutes) resulted in the virtual elimination of capillary blood flow, consistent with pathological findings of widespread vessel rupture and hemorrhage in this temperature range.

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.

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.

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.

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.