Acetabular bone reconstruction in revision arthroplasty: a comparison of freeze-dried, irradiated and chemically-treated allograft vitalised with autologous marrow versus frozen non-irradiated allograft.

Deficiencies of acetabular bone stock at revision hip replacement were reconstructed with two different types of allograft using impaction bone grafting and a Burch-Schneider reinforcement ring. We compared a standard frozen non-irradiated bone bank allograft (group A) with a freeze-dried irradiated bone allograft, vitalised with autologous marrow (group B). We studied 78 patients (79 hips), of whom 87% (69 hips) had type III acetabular defects according to the American Academy of Orthopaedic Surgeons classification at a mean of 31.4 months (14 to 51) after surgery. At the latest follow-up, the mean Harris hip score was 69.9 points (13.5 to 97.1) in group A and 71.0 points (11.5 to 96.5) in group B. Each hip showed evidence of trabeculation and incorporation of the allograft with no acetabular loosening. These results suggest that the use of an acetabular reinforcement ring and a living composite of sterile allograft and autologous marrow appears to be a method of reconstructing acetabular deficiencies which gives comparable results to current forms of treatment.

Chronic bioassays: relevance to quantitative risk assessment of carcinogens.

Conventional carcinogenic potency estimates for chemicals have been compared across rodent species. The high correlations previously demonstrated between maximum likelihood estimates (MLE) for chemicals identified as positive carcinogens in both rats and mice (r = 0.83, n = 83) are shown to occur also for chemicals that were negative in both species (r = 0.85, n = 51), for chemicals causing tumors in rats but not mice (r = 0.55, n = 15), and for those causing tumors in mice but not rats (r = 0.68, n = 25). Corresponding upper-bound estimates of carcinogenic potency are also highly correlated across rodent species. The correlations arise from (i) the strong interspecies correlation between maximum doses tested in chronic bioassays, (ii) the small group sizes utilized, and (iii) the narrow range of doses typically tested. These factors constrain conventional ML and upper-bound potency estimates to lie very close to the inverse maximum doses tested, irrespective of the bioassay's qualitative outcomes. The potency estimates are thus artifacts of experimental design and would seem to provide little information on the actual human cancer risks from chemical exposure. Risk assessment models can reveal true potency differences across species, but they must incorporate relevant mechanistic information before quantitative risk extrapolation from rodents to humans is scientifically defensible.

Experimental design constraints on carcinogenic potency estimates.

The multistage model is used by U.S. regulatory agencies to calculate estimates of the carcinogenic potency (beta) of chemicals; the data for these estimates are generally obtained from chronic rodent bioassays. Three quantities characterize each group tested in the chronic bioassay: the dose level, the sample size, and the number responding to the dose. The dose levels tested are fixed by conventional protocols; the typical National Toxicology Program (NTP) experimental design calls for use of the maximum tolerated dose (MTD), one-half and one-fourth MTD, plus a control group. Only rarely are doses even one order of magnitude less than the MTD utilized in chronic bioassays. This experimental design constraint on dose selection limits the possible values of beta that can arise from multistage model analyses of chronic bioassay data. Sample size is also constrained by the experimental design of the chronic bioassay; the typical sample size in NTP studies is 50 animals. Occasionally, fewer animals are used, but only rarely are more. Thus, the multistage model which theoretically has three variable quantities with which to estimate carcinogenic potency, has in practice only one: the incidence of treatment-related response. Even this can vary within only a narrow range determined by sample size, the control incidence, and the level of statistical significance desired. The net result of these design constraints is that carcinogenic potency estimates derived from multistage-model analyses of chronic bioassay data may vary within only a narrow range surrounding the inverse maximum dose tested. We have illustrated this by calculating the largest possible finite potency estimates that could have arisen from the experimental designs used to test 82 mouse carcinogens in chronic bioassays. On average these maximum potency estimates were within one order of magnitude of the inverse maximum dose tested. We thus conclude that the chronic rodent bioassay, in and of itself, is altogether inadequate as a data source for estimating the risk to humans from exposure to carcinogenic chemicals.

[Clinical and patho-anatomic aspects of metastases of breast cancer]. / "Klinische und patho-anatomische Aspekte zur Metastasierung des Mammakarzinoms.

The importance of carcinoma of the breast in female malignancies demands a critical examination of the condition of metastases by means of certain clinical and pathological data. The clinical data and the results of autopsies of 384 patients with breast carcinoma were examined. The frequency and the chronology of occurrence of metastases put out metastases of lymphnodes , skeleton, lung, liver and local recurrences. The importance of the mediastinal lymph node metastases in the distribution of metastases in thoracical organs was established and is discussed. The relation of frequency of the metastases to primary tumour staging (TNM) shows a 63% rate of metastases in patients with No and 86% in patients with N+. A comparison of two decades (I = 1960-1969; II = 1970-1979) shows certain trends 1. In decade II more patients with primary stage T1-T2 NoMo were found in autopsies having less metastases. 2. More local recurrences and metastases of genital organs were diagnosed. 3. In decade II more "late-metastases" (2-10 years after primary diagnosis) were found. These developments are explained by better primary diagnostic methods, more frequent follow-up examinations after primary therapy, and more frequent application of secondary therapies (chemotherapy, radiotherapy).

Cardiac tamponade: an initial study in the development of a predictive tool.

This exploratory study was conducted over a 12-month period to describe the relationship between selected clinical variables and the occurrence of postoperative cardiac tamponade. Data were collected on 19 variables. A total of 739 patients were included in the study. A postoperative diagnosis of cardiac tamponade was made in nine of these patients who then comprised the tamponade group. A matched non-tamponade control group of 18 patients was identified for comparison. The following were found to be significantly different in a statistical comparison between variable values in the tamponade and non-tamponade groups: (1) serum creatinine level (p = 0.005), (2) chest tube drainage (p = 0.009), (3) sustained pressure plateau (p = .018), and (4) mediastinal widening (p = 0.039). Two additional variables, pulsus paradoxus and elevated BUN, appeared to be of value in the assessment of late tamponade. Discriminant analysis showed a high predictive accuracy of the above combined variables. Such results warrant the further investigation of these variables in other clinical settings. Both a replication and testing of a tamponade score system would be a fertile and necessary area of research for critical care nurses who provide care for post-cardiac surgery patients. These data suggest that equal weight be assigned to each of the four variables. Thus scores would range from 0 to 4; higher scores would represent greater risk (Table III). With further investigation of this area of clinical practice, the identification of patients at higher risk for tamponade could be greatly facilitated.