In vitro growth and drug sensitivity of tumor colony-forming units from human tumor xenografts

To investigate the feasibility of using tissue obtained from human tumor xenografts for in vitro screening of antineoplastic agents, we grew human tumor colony-forming units (CFU) in semisold agar from xenografts serially passaged in nude mice. Growth of human tumor CFU was accomplished from nine xenografts representing five different histological tumor types (ovarian carcinoma, adenocarcinoma of the colon, malignant melanoma, epidermoid carcinoma of the lung, and malignant astrocytoma). Cloning efficiency ranged from 0.04 to 0.1% and showed significant variability both between tumor types and between individual animals bearing the same type of xenograft. A high percentage of tumor CFU was in S phase [47 +/- 20% (S.D.)] as determined by the thymidine "suicide" technique. The number of tumor CFU observed increased linearly with increasing numbers of cells plated. In vitro drug sensitivity of the tumor CFU was assessed to Adriamycin, cis-platinum, and melphalan. The patterns of drug sensitivity were found to be reproducible and stable over a period of 9 months. Drug sensitivity curves to Adriamycin for five xenografts representing four tumor types showed complex patterns with plateau portions similar to those described for tumor CFU from primary tumors. The rank order of sensitivity of the tumors was compared to that of normal granulocyte-macrophage progenitors and, with the exception of the melanomas, was found to correlate well with clinical experience (order of sensitivity = colon less than ovary less than bone marrow). Growth of human tumor CFU from xenografts represents a reproducible and stable means for the study of the biology of tumor CFU and has potential applications as a means for screening new anticancer agents.     

The John Charnley Award. Prophylaxis of fat and bone marrow embolism in cemented total hip arthroplasty

The efficiency of a new cementing technique developed to prevent the risk of intraoperative pulmonary embolism was assessed. Seventy patients with coxarthrosis entered into a prospective, randomized clinical trial. In the control group of 35 cases the total hip replacement was cemented conventionally. In the second group a proximal drainage placed along the Linea aspera, and a distal drainage placed in the diaphysis, created a vacuum in the medullary cavity of the femur during the insertion of the stem. The operation was performed with the patient under blood gas analysis and hemodynamic and transesophageal echocardiography monitoring. Severe transatrial embolic events were observed during the insertion of the femoral component in 94% of the cases of the control group and in 14% of the cases of the vacuum group; the difference is statistically significant. A significant decrease of arterial partial pressure of O2 (-40.8 mm Hg) and increase of the pulmonary shunt values (+28.3%) occurred 5 minutes after the observation of embolic events in the cases operated on conventionally, but these parameters showed minimal changes in the vacuum group. The rise of intramedullary pressure in the femur is the most decisive pathogenic factor of pulmonary embolism during total hip arthroplasty. The logical prophylactic measure to prevent intravasation of fat and bone marrow is to create sufficient drainage. The cohorted investigation showed the value of the vacuum cementing technique for a substantial reduction of intraoperative embolism and pulmonary impairment.     

Techniques for tuning excitation system parameters

The basic small signal-characteristics that are typical for most modern excitation systems are examined. A common-sense approach to model tuning is suggested. The procedure is based on emulation of the open-circuit step response test, a standard control-tuning practice for several decades. Where simulations with excitation system and generator model data result in unacceptable responses, guidelines are provided for tuning models until well-behaved, realistic responses are achieved. Frequency-response techniques are used. Two basic types of models are analyzed, and the means of reducing most models to these are shown. An application example is given     

Spironolactone-induced pemphigoid

BACKGROUND: Sporadic observations would suggest that certain drugs play a role in the development of pemphigoid. A recent case-control study on long-term drug use associated with pemphigoid was unable to confirm the suspected role of these drugs, but did demonstrate a significant association between the development of pemphigoid and use of spironolactone. CASE REPORT: An 82-year-old patient had bullous erythematous lesions on the left thigh suggestive of pemphigoid. Histology and direct cutaneous immunofluorescence confirmed the diagnosis. The patient had been taking alimemazine, adrafinil, flunarizine, spironolactone and furosemide as long-term treatment. Spironolactone alone was withdrawn. The cutaneous lesions regressed and have not recurred during the 18-month follow-up. DISCUSSION: The causal effect of spironolactone in this case of pemphigoid is quite plausible. This hypothesis is favored by the agreement with epidemiological data. Other observations are however required before the causal role of spironolactone in development of pemphigoid can be confirmed.