Genetic Analysis Workshop II: pedigree analysis of a binary trait without assuming an underlying liability

A model for concordance in a binary measure that does not rely on the assumption of an underlying latent liability dichotomized about a threshold has been demonstrated for twin pairs [Hannah et al, 1983]. It is extended here to pedigrees of arbitrary structure by making an assumption that is, for small incidence rates, almost equivalent to postulating that relative risks are multiplicative. The model is applied to the workshop data to determine the extent to which the known structure of the simulated models can be recovered.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

Proton magnetic resonance spectroscopy improves outcome prediction in perinatal CNS insults.

OBJECTIVE: Prediction of neurologic outcome is difficult in neonates with acute nervous system injury. Previous studies using proton magnetic resonance spectroscopy ((1)H-MRS) have been used to predict short-term neurologic outcome in neonates with a variety of neurologic insults. We were interested in determining the effectiveness of combining clinical evaluation and spectroscopy obtained at the time of injury in predicting neurologic outcome at 24 months. STUDY DESIGN: We studied 33 neonates with acute central nervous system injury, 5.8+/-3.7 days of injury, owing to hypoxic-ischemic encephalopathy. Neonates were assessed using clinical variables (initial arterial pH, initial blood glucose, Sarnat score, electroencephalography) and spectroscopy (NAA/Cho, NAA/Cre, Cho/Cre, and lactate). Neonates were divided into two outcome groups: good/moderate and poor. Differences between the groups were assessed using chi(2) and t-test analyses. We analyzed the best predictors of outcome using discriminant analysis and calculated sensitivity, specificity, positive, and negative predictive values for each variable independently and in combination. RESULTS: There were significant differences between the good/moderate and poor outcome for the Sarnat score, EEG, lactate, and NAA/Cho. Spectroscopy combined with clinical variables improved sensitivity, but not specificity for predicting outcome. The presence of lactate had the best individual predictive value. Combination of the clinical with the MRS variables had the highest predictive value. CONCLUSION: Proton magnetic resonance spectroscopy done early after injury improves the ability to predict neurologic outcome at 24 months of age.     

Comparison of in vivo wear between polyethylene liners articulating with ceramic and cobalt-chrome femoral heads

At yearly intervals we compared the radiological wear characteristics of 81 alumina ceramic femoral heads with a well-matched group of 43 cobalt-chrome femoral heads. Using a computer-assisted measurement system we assessed two-dimensional penetration of the head into the polyethylene liner. We used linear regression analysis of temporal data of the penetration of the head to calculate the true rates of polyethylene wear for both groups. At a mean of seven years the true rate of wear of the ceramic group was slightly greater (0.09 mm/year, SD 0.07) than that of the cobalt-chrome group (0.07 mm/year, SD 0.04). Despite the numerous theoretical advantages of ceramic over cobalt-chrome femoral heads, the wear performance in vivo of these components was similar.     

Breast cancer in Australian women under the age of 40

Objectives: A case-control-family study of breast cancer in women under the age of 40 was carried out in Melbourne and Sydney, Australia, from 1992 to 1995 to determine the risk factors for these women. Subjects included 467 incident cases identified by state cancer registries and 408 population-based controls. Methods: All participants completed a structured risk-factor questionnaire and family pedigree during an in-person interview. Where possible, cancers in first- and second-degree relatives were verified. Results: Multiple logistic regression analysis showed that the strongest risk factor for breast cancer was a family history of the disease - having at least one affected first-degree relative trebled the risk (relative risk [RR] = 3.3, 95 percent confidence interval [CI] = 1.9-5.8). Risk increased with height by three percent (standard error [SE] of one percent) per cm, and after adjusting for height, there was evidence for a decreased risk in women weighing 73 kg or more. There was an increased risk of breast cancer after the first full-term birth (RR = 1.8, CI = 1.0-3.5) but this risk fell by 30 percent (SE = 11 percent) with each subsequent livebirth. Conclusions: The effects of other reproductive factors and oral contraceptive use, although not nominally significant, were in accord with published findings from similar studies in young women. This study of Australian women has indicated that some risk factors for breast cancer in women under age 40 differ from those reported for older women either in direction (e.g., weight) or relative importance (e.g., family history).     

Acetabular revision with use of a bilobed component inserted without cement in patients who have acetabular bone-stock deficiency

BACKGROUND: Massive deficiency of acetabular bone stock is a challenging problem in the increasing number of patients who need a revision of a failed hip arthroplasty. The bilobed cup has been presented as one alternative reconstruction technique for hips with extensive acetabular bone loss. The purpose of this study was to assess the results with use of a bilobed acetabular component inserted without cement for revision reconstruction in hips with acetabular bone deficiency in order to clarify the indications for its use and to identify the factors that influence the clinical and radiographic outcome. METHODS: Forty-one hips in thirty-eight patients had an acetabular revision with a bilobed acetabular component inserted without cement between December 1991 and December 1995. These hips were a subset of the 414 hips treated with an acetabular revision during the same period of time. One patient was lost to follow-up, and one died during the study period. Two patients who could not return for radiographic evaluation completed questionnaires. The remaining thirty-four patients (thirty-seven hips) were evaluated radiographically and clinically and were followed for an average of forty-one months (range, twenty-four to sixty-six months). RESULTS: Radiographic analysis demonstrated an improvement in the average vertical displacement of the hip center. At the time of the latest follow-up examination, 76 percent (twenty-eight) of the thirty-seven cups were stable, 8 percent (three) were probably unstable with a change in the screw position but no definite migration of the cup, and 16 percent (six) were unstable. Eight of the nine loose or probably loose components were in patients who had more than two centimeters of superior migration of the component and disruption of Kohler's line on preoperative radiographs. Additionally, implants were more likely to become unstable (demonstrating more than 4 degrees of change in the abduction angle or more than four millimeters of radiographic migration) when the inferior aspect of the component did not extend to or distal to the interteardrop line, which indicated that the component was undersized. CONCLUSIONS: On the basis of our early rate of probable or definite loosening of 24 percent (nine of thirty-seven cups) and the technical difficulties involved, we do not recommend the routine use of this component. We believe that this device is indicated when a patient has an oblong-shaped acetabular defect and the surgeon wants to correct an elevated hip center. However, the medial wall of the acetabulum (Kohler's line) should be intact if the failed component has migrated more than two centimeters. An alternative reconstruction technique, such as use of a structural allograft with or without an acetabular cage, is also an option in this situation.     

Peroneal latency in normal and injured ankles at varying angles of perturbation

The aim of this study was to determine whether there was a difference in latency of the peroneus longus muscle at varying amplitudes of ankle inversion perturbation and between individuals with and without a history of ankle injury. Thirty-four male athletes from different football codes (soccer, rugby) received four random tilts to their left ankles at 5 degrees, 10 degrees, and 15 degrees in the frontal plane on a dual platform trap door. Peroneal latency was defined as the time difference between onset of the trap door movement, as detected by an accelerometer, and the onset of muscle activation above a resting baseline, as recorded using surface electromyography. Latency was determined using an algorithm. A series of repeated measures analyses of variance indicated that the latency was reliable between trials. There was no statistical evidence that history of injury or subjective ankle instability influenced the latency; however, there was a systematic difference between dominant and nondominant legs (dominant, 6.3 ms faster), and there was a small systematic effect (3 ms) for the angle of inversion perturbation. Muscle latency responses in male football players are thought to be influenced more by dominance than by history of injury or amplitude of perturbation.