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Desmoid tumors are benign neoplasms, arising from musculoaponeurotic tissues, which tend to be locally infiltrative, resulting in a high rate of local recurrence following surgical resection. Nineteen patients with desmoid tumors underwent radiation therapy at the University of California, San Francisco, between 1970 and 1980. Fifteen patients were referred with local recurrence following one or more surgical resections. Three patients were referred for initial radiation therapy with unresectable tumors, and one patient received planned postoperative irradiation following subtotal tumor resection. At the time of treatment, 8 patients had nonresectable disease measuring greater than 10 cm. Five patients had residual tumor masses measuring 4 to 6 cm, and six had only microscopic disease following resection. The majority of patients were treated to a tumor dose of 50-55 Gy at 1.6 to 1.8 Gy per fraction. With a median follow-up of 8 years, 13 patients remained free of recurrent disease following radiation therapy. The 5 year relapse free survival was 72% with 10 patients continuing to be free of disease 5 to 11 years following therapy. Local control was not related to the amount of disease present at the time of treatment. Of the 6 patients who developed recurrent disease, only 1 patient had a true in-field recurrence. Four patients recurred at the margin of the radiation field 1 to 5 years following therapy. Of these four patients, 3 were successfully salvaged while 1 died as a result of tumor extension into a major vessel. One patient with an extensive mesenteric mass did not respond to therapy and died 1 month post irradiation. The patient with the in-field recurrence and 1 patient with a marginal recurrence were successfully treated with combination chemotherapy. Moderate dose radiation therapy to desmoid tumors can result in lasting local control when surgical resection is not possible. Post operative radiation can improve the rate of local control for patients with a high risk of recurrence. As desmoid tumors tend to be locally infiltrative, fields must be very generous to prevent marginal recurrence. Systemic chemotherapy offers an alternative to ablative surgery in the event of local failure following radiation therapy.

To demonstrate the potential impact of computed tomography on orthopaedics, a brief review was done of four generations of scanners and of one new development (assay of bone mineral in the spine) that is presently being researched. To assess the utility of the method in treating orthopaedic problems, the cases of 140 patients, including patients with congenital anomalies, tumors, infections, and traumatic lesions, were analyzed. In the majority of the patients the technique provided useful information, often unobtainable with any other technique.

Factor VIII assays are the most common specific coagulation factor assay performed in the United States. Interlaboratory proficiency studies have documented persistent problems with variation in results between laboratories. The Coagulation Resource Committee of the College of American Pathologists conducted a workshop to analyze variables that may affect performance of the one-stage factor assay. The results indicate that accuracy of the assay can be improved by uniform standardization of reference plasma samples and that reproducibility can be enhanced through appropriate choice of reagents and instruments. Optimizing performance of this assay should lead to more reproducible interlaboratory results.

Malignant tumors around fracture fixation implants have been reported sporadically for many years. Recently, however, reports of sarcomatous degeneration around a standard cemented hip arthroplasty and around cobalt-chromium-bearing hip arthroplasties raise new questions of the malignant potential of metallic ends prostheses. Sarcomatous changes around aluminum oxide ceramics seem not to have been reported in the literature. The present report may be the first documented case of an aggressive soft tissue sarcoma detected 15 months after the patient had an uncemented ceramic total hip arthroplasty. If a causal relationship exists, the incidence of this phenomenon in the United States is 250 times greater than would be expected from statistics on soft tissue sarcoma at the hip. Because of the similarity on plane roentgenograms of this tumor to lesions known to be caused by wear debris, tumors should be included in the differential diagnosis of cases of total hip loosening.

Decreased endothelial cell production of prostacyclin (PGI2) in response to the lupus anticoagulant has been previously demonstrated and postulated to have a causal relationship to the thrombotic events associated with the lupus anticoagulant. Five patients who exhibited the anticoagulant were studied in an effort to determine if a relationship exists between exposure of endothelial cells to the lupus anticoagulant and decreased production of PGI2. Human endothelial cells derived from human umbilical vein grown in culture were exposed to IgG fractions of patient plasmas containing the lupus anticoagulant. PGI2 released per 10(6) cells was determined by radioimmunoassay for 6-keto-PGF-1-alpha. The overall means for the patient and control groups are given by 47 pM/10(6) cells and 12 pM/10(6) cells respectively. This is a statistically significant difference (F = 10.65, p = 0.017) when the effects of different batches of endothelial cells and thrombin stimulation are adjusted for in the analysis of variance model. These results demonstrate that in this homologous human system exposure of endothelial cells to the lupus anticoagulant leads to stimulation rather than inhibition of PGI2 release.

The carrier status of two sisters of the mother of a hemophilic boy was clarified by the use of DNA probes in a family with a single case of hemophilia A and no family history of the disease. The extragenic polymorphic site demonstrated by probe DX13 (locus DXS15) and the intragenic polymorphic site demonstrated by BgI I digestion and a factor VIII partial cDNA probe indicated that the mother of the index case carried a mutation in the X-chromosome received from her nonhemophilic father rather than the X-chromosome received from her mother. In spite of equivocal coagulation data, the mother's two sisters were shown not to be carriers of hemophilia A.

The authors report a comprehensive evaluation of the hemostatic system in eight related patients with hereditary hemorrhagic telangiectasia (HHT). Unlike in previous reports, they could find no evidence for abnormalities in platelet aggregation or for qualitative abnormalities of the Factor VIII complex. The authors did identify a subgroup of the more severely affected patients in whom Factor VIIIc levels were increased, with shortened activated partial thromboplastin times (APTTs) associated with mild elevations of antithrombin III.

The utility of computed tomography (CT) in evaluation of musculoskeletal disorders was assessed in 55 selected patients. CT provided unique information leading to a correct diagnosis in 45% of cases. In 78% the extent of a lesion was more clearly defined than on conventional imaging procedures, and in the same percentage the CT findings were used to plan optimal therapy. CT was most useful in demonstrating absence of a suspected mass lesion and in defining the full extent of a lesion involving the soft tissues.

Twenty-four humeral-shaft fractures with associated radial-nerve injuries in twenty-three patients with adequate follow-up were seen over a fifteen-year period. Initial treatment was closed in all but one patient, in whom débridement of an open fracture revealed a lacerated radial nerve. All patients had complete return of radial-nerve function. Two of the twenty-four nerve lesions were treated by delayed operation: one at fourteen weeks for entrapment in fracture callus, and the other at six weeks for repair of the aforementioned lacerated radial nerve. Thus, only 8 per cent of the patients required exploration of the nerve, all of whom did well after delayed repair. We recommend careful observation for return of nerve function and exploration at three and a half to four months after injury if there is still no clinical or electromyographic evidence of recovery at that time.

A monoclonal-antibody-based competitive radioimmunoassay for measuring human protein C is reported. With use of a purified protein C standard, the solid-phase assay was sensitive to less than 80 micrograms of protein C per liter. Intraassay CVs ranged from 5% to 8%; the inter-assay CV was 5.4%. Analytical recovery averaged 104% for purified protein C added to 10 samples of normal plasmas. The assay antibody could deplete plasma of all protein C, as determined by immunoaffinity chromatography followed by polyclonal Western blot analysis. Liquid-chromatographic gel permeation of plasma indicated a single immunoreactive species that had an appropriate molecular mass for monomeric protein C. Studies of monoclonal-antibody specificity showed no significant interferences by other vitamin K-dependent proteins. The mean protein C antigen concentration in plasma of 54 healthy subjects was 3.21 (SD 0.56) mg/L and was 1.51 (SD 0.52) mg/L for 22 patients on long-term warfarin therapy. Results of the monoclonal RIA correlated well with those by a polyclonal RIA also developed in our laboratory (r = 0.93) and an amidolytic functional assay (r = 0.88) for both normal plasma and plasma from patients on long-term warfarin therapy.

The value of computed tomography in the diagnosis and management of lesions of the musculoskeletal system is being determined. Illustrative cases including a lipoma of the thigh, osteochondroma of the hip, simple cyst of the ilium, recurrent liposarcoma of the lumbar spine, desmoid tumor in the gluteal region, and postoperative interspace infection of the lumbar spine are presented to indicate the potential value of this procedure in the diagnosis and planning of treatment of musculoskeletal lesions.

Factor VIII von Willebrand factor was studied by the immunoperoxidase method in 38 cases of first-trimester therapeutic abortion and two cases of early second-trimester therapeutic abortion. Positive immunostaining was observed in endothelial cells at all gestational ages studied. The findings demonstrate the presence of factor VIII von Willebrand factor in endothelial cells as early as four weeks' gestational age.

In a retrospective review of 119 intracapsular hip fractures treated by the Deyerle method (seventy-nine patients treated at San Francisco General Hospital and forty at Brookside Community Hospital), fifty-nine patients were available for follow-up after two or more years or were rated as failures before that time. In the San Francisco General series the incidence of avascular necrosis was 43 per cent and of non-union, 23 per cent, while in the Brookside series the incidences were 12.5 per cent and 12.5 per cent, respectively. The functional end results in the San Francisco General series were rated excellent or satisfactory in 40 per cent and failures in 60 per cent, and in the Brookside series there were 75 per cent excellent or satisfactory results and 25 per cent failures.

We have reviewed the biochemistry of the normal and warfarinized vitamin K-dependent coagulation proteins, both individually and as members of their respective macromolecular enzyme complexes. Much has been learned in the past 10-15 years about the molecular mechanisms of coagulation. However, we have only scratched the surface and are beset by a number of interesting challenges. Clearly, we must begin to dissect the other vitamin K-dependent macromolecular enzyme complexes as has been done for prothrombinase. Prothrombin differs in fundamental ways from the other vitamin K-dependent proteins and we can anticipate significant differences as well as similarities in the other complexes. The presence of potentially functional domains in the non-catalytic portions of the vitamin K-dependent proteins and their similarities within this family of proteins should prove a fruitful area of future research. Finally, the evaluation of warfarinized vitamin K-dependent proteins, both in fundamental studies with purified systems and using uniquely engineered immunoassays, should shed light on basic molecular mechanisms and modes of monitoring warfarin therapy.

The authors present a study of a human myeloma-produced monoclonal protein (IgG-k) directed against von Willebrand factor that caused an acquired von Willebrand's disease (vWD)-like syndrome. The illness was characterized by upper gastrointestinal bleeding, prolonged bleeding time, decreased platelet adhesiveness, lack of platelet aggregation in response to ristocetin, and a qualitatively abnormal Factor VIII related antigen (vWF) by two-dimensional immunoelectropheresis. Patient plasma or IgG fraction mixed with normal platelet-rich plasma completely inhibited aggregation with ristocetin, but patient platelets resuspended in normal plasma aggregated normally with ristocetin. VWF was markedly elevated and the two-dimensional immunoelectropheresis of vWF revealed a vWD type II-like pattern with an absence of the higher molecular weight forms of the vWF. Marked inhibitory activity was observed in the ristocetin cofactor assay but disappeared at the highest dilutions of patient plasma used in the assay. Infusion of cryoprecipitate following plasmapheresis led to a correction of the bleeding time, improvement in platelet adhesiveness, transient disappearance of inhibitory activity in the Factor VIII ristocetin cofactor assay, and no significant normalization of two-dimensional immunoelectropheresis of vWF. This case demonstrated a myeloma-associated monoclonal antibody that interacted specifically with that part of the Factor VIII molecule necessary for Factor VIII ristocetin cofactor activity, normal platelet adhesiveness, and bleeding time.

Three cases of coronary artery dissection secondary to coronary arteriography are presented. Two of these include autopsy material demonstrating medial degeneration in the coronary arteries, which may have predisposed these arteries to dissect. The literature on catheter-induced coronary artery dissection is reviewed and an analysis is presented.

Kenya is a country of marked environmental and ethnic diversity. A study of osteogenic sarcoma occurring in Kenya from 1968 to 1978 revealed 251 cases, representing between 89% and 100% of the predicted number. Variations in age, sex and anatomical location were within classical limits. However, the incidence of osteogenic sarcoma amongst the Central Bantu was significantly higher than predicted (P less than 0.0001), whilst the incidence among the Western Bantu was significantly lower (P less than 0.002), despite their similar ethnic origins. Two geographically dissimilar areas likewise exhibited significant differences in incidence. The Eastern province showed a higher incidence (P less than 0.02), whereas the Nyanza Province (P less than 0.001) and the adjacent Western Province (P less than 0.005) showed a lower than predicted incidence. These observations suggest that in Kenya a geomedical variable affects the incidence of osteogenic sarcoma and that genetic variation has no effect on incidence.

Magnetic resonance imaging of the musculoskeletal system in general and the hip in particular offers many exciting opportunities for innovative and revolutionary diagnostic avenues, the full potential of which awaits further investigative and clinical experience.

We present the rare occurrence of an inhibitor of factor VIII procoagulant arising in a patient with mild haemophilia A and rheumatoid arthritis. The inhibitor was transient and behaved like a low titre, type II factor VIII procoagulant inhibitor similar to previously reported cases (Biggs et al, 1972b). In vitro studies confirmed the type II-like interaction of this inhibitor with the factor VIII procoagulant molecule. Factor VIII procoagulant antigen level was equal to the factor VIII procoagulant activity, which excluded dysproteinaemia as the cause. This patient's HLA type has no known association with abnormal immune responsiveness or autoimmune disease, and his clinical course as well as in vitro studies were similar to the eight previously reported cases of factor VIII procoagulant inhibitors arising in mild haemophilia A.

MRI is a complementary technique to CT in the examination of the spine, the hip, and musculoskeletal tumors. In some cases, it provides diagnostic information not available with any other modality, including CT. MRI has the potential to be very useful in the assessment of various marrow-based disorders and may someday obviate the need for contrast-aided studies of ligaments, tendons, and cartilage.

A case of testicular malakoplakia is described in which cells other than histiocytes were involved in the tissue response. The abundant cell junctions, some closely related to mitochondria, and the peripheral displacement of rough endoplasmic reticulum by abundant phagolysosomes, suggest involvement of Sertoli cells, in addition to histiocytes. It is suggested that, perhaps, some forms of granulomatous orchitis and malakoplakia represent a single disease process observed at a different stage in its evolution.

Desmoid tumors are locally invasive benign tumors arising from musculoaponeurotic structures which are classified as fibromatoses and which have generally high post-surgical recurrence rates. Sixteen patients with desmoid tumors were treated with irradiation and evaluated for 2 to 6 years post-treatment. Of the 16, 13 cases have been controlled without recurrence. Virtually complete resolution of the tumor mass has been accomplished without the disfigurement and dysfunction characteristic of the radical surgical approach to treatment.

A family with a high incidence of venous thromboembolism was investigated. We performed medical evaluations on 184 of the 411 surviving members of the pedigree, which allowed assignment of individuals into positive, equivocal, or negative categories with respect to their clinical histories of thrombosis. Subjects with antigenic levels of protein C less than 66% of a normal plasma pool were classified as having protein C deficiency. Positive thrombotic histories were found in 13 of the 46 family members determined to be protein-C deficient and in only five of their 138 biochemically unaffected relatives. Statistical analysis of the association between thromboembolic disease and protein-C deficiency was strongly positive chi 2 = 24.95, P less than .0001 with n = 184), indicating that heterozygous protein-C deficiency is an important independent risk factor for the development of thrombotic manifestations in this pedigree. However, the absence of thromboembolic manifestations in many of the protein-C deficient family members to date indicates that other, as yet undefined, factors must play an important role in the clinical expression of this disorder.

Seventy patients received primary surgical or radiotherapeutic treatment for osteosarcoma at the University of California-San Francisco between 1950 and 1974. Twenty-two received surgery alone and 27 received preoperative irradiation followed at varying intervals by surgery. Twenty-one patients received irradiation alone because of tumor location, refusal of recommended surgery, or development of metastatic disease. The results are analyzed and the role of radiation therapy in the primary management of osteosarcoma is discussed. The authors believe that irradiation without chemotherapy offers little in terms of palliation or enhanced survival in patients who are able to undergo radical surgery.

Vitamin K deficiency or administration of vitamin K antagonists results in the biosynthesis of abnormal des-gamma-carboxy forms of the vitamin K-dependent proteins. Monoclonal antibody H-11 binds several vitamin K-dependent proteins at a determinant that includes the first two residues of gamma-carboxyglutamic acid. Antibody H-11 binds fully carboxylated prothrombin and protein C in the presence of EDTA but binding is inhibited by the divalent metal ions, calcium, magnesium, and manganese. By contrast, des-gamma-carboxy prothrombin and protein C bind antibody H-11 the same in the presence of EDTA or calcium ion. Antibody H-11 thus appears to bind a conserved antigenic site containing gamma-carboxyglutamic acid that in the presence of divalent metal ion undergoes a conformational transition. This ability of antibody H-11 to bind des-gamma-carboxy prothrombin and protein C in the presence of calcium ion allowed the development of an immunoassay for these proteins in plasma. Prothrombin and protein C from stably anticoagulated individuals receiving warfarin were characterized by their ability to bind antibody H-11 in the presence of calcium ion. Binding of prothrombin and protein C to antibody H-11 in the presence of calcium correlated temporally with warfarin administration. The inability of calcium ion to inhibit binding of antibody H-11 to abnormal prothrombin and protein C in plasma suggests that the circulating forms of both proteins following warfarin administration cannot undergo the metal ion-dependent conformational transition that includes sequence residues 1 through 12.