Comparative study of the effects of radiation, indomethacin, prednisolone, and ethane-1-hydroxy-1,1-diphosphonate (EHDP) in the prevention of ectopic bone formation

Forty male New Zealand white rabbits were treated with immobilization and forcible manipulation of the right knee known to cause ectopic bone formation in the quadriceps muscle. The animals were also treated with either: A) A total radiation dose of 1840 rad (18.4 Gy); B) A 0.5 mg/kg/day oral dose of prednisolone; C) 10 mg/kg/day of indomethacin, given in two oral doses; D) Ethane-1-hydroxy-1,1-diphosphonate (EHDP) given in a 20-mg/kg/day oral dose; or E) with the vehicle given alone as a control. The experimental period was four weeks, and the amount of ectopic bone was determined by planimetry of serial transverse sections of the femur. The degree of knee stiffness was recorded during the experiment. The amount (mean +/- SEM) of ectopic bone was 1.412 +/- 0.264 cm3 in controls; it was insignificantly higher in the EHDP-treated group, but significantly lower (p less than 0.01) in rabbits treated with radiation (0.390 +/- 0.094 cm3), prednisolone (0.181 +/- 0.076 cm3), and indomethacin (0.314 +/- 0.112 cm3). In control animals and those given EHDP, the treatment invariably led to almost complete stiffness of the right knee. The rabbits treated with prednisolone and indomethacin offered the least resistance to the manipulations, and the group treated with radiation showed intermediate stiffness. Semiquantitative histologic evaluation demonstrated less inflammation in the group treated with prednisolone than in the control group.     

Tissue expression of the tumour associated antigen CA242 in benign and malignant pancreatic lesions. A comparison with CA 50 and CA 19-9

The expression of a novel tumour associated antigen CA 242, defined by the monoclonal antibody C 242, was studied by immunoperoxidase staining in formalin-fixed, paraffin-embedded tissue sections from normal pancreata, pancreata with pancreatitis and benign and malignant pancreatic neoplasms. The antigenic determinant of the C 242 antibody is a sialylated carbohydrate structure, related but chemically different from tumour marker antigens CA 19-9 and CA 50. Thirty-eight of 41 (93%) well to moderately differentiated ductal adenocarcinomas of the pancreas and all cystadenocarcinomas were positive for CA 242. The staining was most intense in the apical border of the cells, and in the intraluminal mucus. Only two out of seven poorly differentiated adenocarcinomas stained, and the number of positive cells was smaller than in well differentiated carcinomas. Only occasional cells were stained in one out of five anaplastic carcinomas. Part of large ducts were positive in 91% (21/23) specimens of chronic pancreatitis. In acute pancreatitis small terminal ducts, centro-acinar cells and some large ducts stained for CA 242. In normal pancreas only a few small terminal ducts were CA 242 positive. Carcinomas always stained more strongly for CA 242 than normal pancreatic tissue adjacent to the carcinoma. The results of CA 242 are compared with those of tumour marker antigens CA 50 and CA 19-9. Serum CA 242 levels were determined in 23 of the patients with pancreatic cancer using a fluoroimmunoassay. Fifteen (65%) patients had an elevated value. There was no clear-cut correlation between the serum levels and the immunohistochemical expression of the CA 242 antigen. The expression of CA 242 in pancreatic tissue resembles that of CA 50 and is similar to CA 19-9. The antigen is expressed in serum of many patients with pancreatic cancer and, therefore, is a potential candidate for a serum tumour marker.     

The economics of general thromboembolic prophylaxis

The clinical and economic effects of each of 3 alternatives—no prophylaxis, general prophylaxis, and selective treatment—have been assessed in conjunction with 3 types of surgery—general surgery, the subset surgery for cholelithiasis, and elective hip surgery. The costs of thromboembolic and hemorrhagic complications have been calculated from the figures for 28 patients hospitalized at the Department of Surgery, Malmö General Hospital, Malmö, Sweden. The anticipated number of thromboembolic complications—and thus even the number of fatal pulmonary embolisms—can be minimized in all 3 types of surgery by means of general prophylaxis. General prophylaxis with low-dose heparin is, however, accompanied by the greatest incidence of hemorrhagic complications. Health care costs are minimized with general prophylaxis in elective hip and general surgery, while no prophylaxis is the best alternative in surgery for cholelithiasis. From the patient's point of view, general prophylaxis minimizes the duration of thromboembolic disease in general surgery as well as in elective hip surgery. In surgery for cholelithiasis, however, no differences in health loss for the individual are shown between the 2 main alternatives, no prophylaxis and general prophylaxis. Selective treatment means treatment after diagnosis of thrombosis with some screening method. The alternative selective treatment was the least satisfactory of those 3 studied.

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Resumen Los efectos clínicos y económicos de cada una de 3 alternatives en la profilaxis tromboembólica (no profilaxis, profilaxis general con heparina de baja dosis, y tratamiento selectivo) fueron valorados en 3 tipos de cirugía: cirugía general (abdominal), el subgrupo de cirugía general para colelitiasis, y cirugía electiva de cadera. Los costos de las complicaciones tromboembólicas y hemorrágicas fueron calculados a partir de las cifras observadas en 28 pacientes hospitalizados en el Departmento de Cirugía. El número de predicción de complicaciones tromboembólicas, y el número de embolismos pulmonares fatales pueden ser minimizados en los 3 tipos de cirugía mediante la profilaxis general. Sin embargo, la profilaxis general con heparina de baja dosis se acompaña de la más alta incidencia de complicaciones hemorrágicas.Los costos de la atención pueden ser minimizados mediante la profilaxis general en cirugía electiva de cadera y en cirugía general abdominal, en tanto que la no profilaxis es la mejor alternativa para la cirugía de colelitiasis.Desde el punto de vista del paciente, la profilaxis general minimiza la duración de la enfermedad tromboembólica en la cirugía general abdominal así como en la cirugía electiva de cadera. En la cirugía para colelitiasis, sin embargo, no se demuestran diferencias entre las dos alternatives principales, no profilaxis y profilaxis general.El tratamiento selectivo significa tratamiento una vez establecido el diagnóstico de trombosis mediante algún método de tamizaje. La alternativa de tratamiento selectivo fue la menos satisfactoria de las 3 alternatives estudiadas.

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Résumé Les effets cliniques et financiers de 3 comportements variables: absence de prophylaxie, prophylaxie, traitement sélectif ont été évalué en fonction de trois types de chirurgie: chirurgie générale, chirurgie spéciale de la lithiase biliaire, chirurgie élective de la hanche. Les coûts des complications thrombo-emboliques et hémorragiques ont été calculés à partir des données numériques concernant 28 malades hospitalisés dans le service de chirurgie. Le nombre envisagé des complications thromboemboliques et par conséquent le nombre d'embolie pulmonaire fatale a été réduit dans les 3 types de chirurgie choisis grâce au traitement prophylactique. Cependant il convient de noter que le traitement prophylactique à l'aide de faible dose d'héparine s'accompagne de complications hémorragiques plus nombreuses.Les coûts des soins de la chirurgie élective de la hanche et de la chirurgie générale sont réduits grâce au traitement prophylactique alors que l'absence de traitement prophylactique représente la meilleure modalité à observer dans le traitement de la chirurgie biliaire.En ce qui concerne le point de vue du malade le traitement prophylactique réduit la durée de la maladie thromboembolique compliquant la chirurgie générale ou la chirurgie de la hanche. En revanche dans la chirurgie de la lithiase biliaire aucun inconvénient pour la santé du malade ne s'observe que le traitement prophylactique soit ou ne soit pas appliqué.Le traitement sélectif qui répond au traitement institué après que le diagnostic ait été posé par des méthodes de dépistage est la moins satisfaisante des trois attitudes envisagées.

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Supported by grant no. 00759 from the Swedish Medical Research Council.     

The role of radiation therapy in Hodgkin disease: experience and controversy. The 54th annual Janeway Lecture: 1989.

BACKGROUND. Beginning in 1970, a series of patients with Hodgkin disease were treated at the University of Minnesota, after staging laparotomy, with radiation therapy (RT) for Stage I, II, and IIIA Hodgkin disease. This report is an analysis of the results of the treatment and of treatment modifications. METHODS. From 1970 to 1974, all patients were treated with standard RT. In 1975, an analysis of these patients indicated that patients with large mediastinal mass (LMM) and patients with Stage IIIA spleen-positive (IIIAS+) disease had a higher recurrence rates than patients without these factors. Subsequently, a schema of radical radiation therapy (RRT) was devised, which included low-dose lung RT for patients with LMM and low-dose liver RT for patients with IIIAS+ disease. RESULTS. Analysis of the results of the two treatments indicates that the use of low-dose lung RT in patients with LMM and low-dose liver RT in patients with IIIAS+ Hodgkin disease produced survival and recurrence-free survival results equivalent to those achieved by use of combined modality treatment (CMT) or chemotherapy (CT) alone. CONCLUSIONS. The use of RT with whole lung and liver irradiation for patients with LMM and IIIAS+ Hodgkin disease, respectively, produces results that are equivalent to those of CMT or CT alone with the advantage of a decreased incidence of second malignant neoplasms. In addition, patients who do not respond to initial RT have a greater chance of being saved with chemotherapy than do patients initially treated with CMT of being saved with RT. The authors suggest that radical RT is the treatment of choice for patients with LMM and/or IIIAS+ Hodgkin disease.     

Activated Protein C Reduces Graft Neutrophil Activation in Clinical Renal Transplantation

We studied the role of endogenous activated protein C (APC), the major physiological anti-coagulant with concomitant anti-inflammatory properties, on ischemia/reperfusion (I/R) in 45 patients participating in a larger trial comparing three immunosuppressive protocols in cadaveric renal transplantation: perioperative anti-thymocyte globulin (ATG, Fresenius AG, Bad Homburg, Germany), perioperative basiliximab and conventional triple therapy. Blood samples for assessing plasma APC, protein C, and lactoferrin concentrations, neutrophil CD11b and L-selectin expressions and blood leukocyte differential counts were obtained preoperatively and before reperfusion from central venous cannula, complemented with simultaneous samples from iliac artery and graft vein for calculation of transrenal differences (Delta) of study parameters at 1 and 5 min after reperfusion. Unlike basiliximab or conventional therapy groups, ATG infusion induced a substantial increase in plasma APC concentration (119 [88-144]% before infusion vs. 232 [85-1246]% after infusion, p<0.001), resulting in renal graft sequestration of APC at 1 min after reperfusion (Delta=-72 [-567 to 12]%, p<0.001). Graft APC consumption was associated with transrenal reduction of neutrophil activation markers (L-selectin r=0.7, p=0.01; lactoferrin r=-0.6, p=0.02; CD11b r=-0.8, p=0.001), and with both warm (r=0.6, p=0.01) and cold ischemia time (r=0.6, p=0.02) and donor age (r=0.6, p=0.01). These findings suggest that APC has an anti-inflammatory role in I/R injury in clinical renal transplantation.     

Pharyngeal swallowing in patients with paresis of the recurrent nerve

Pharyngolaryngeal function during swallowing was investigated cineradiographically in 22 patients with paresis of the recurrent nerve. Nineteen of these patients (86%) had defective closure of the laryngeal vestibule: 10 patients had defective apposition of the corniculate cartilages, (paresis of the oblique cricoarytenoid muscle), 9 patients had defective apposition of the arytenoid cartilages, (paresis of the interarytenoid muscle), 13 patients had defective movement of the epiglottis (paresis of, i.a. the thyrohyoid muscle), 1 patient had defective closure of the subepiglottic portion of the vestibule (paresis of the thyroepiglottic muscle), 2 patients had defective closure of the supraglottic portion of the vestibule (paresis of the superior ventricular segment of the thyroarytenoid muscle). Five patients with immobility of the epiglottis also had paresis of the pharyngeal constrictor musculature indicating paresis of the superior laryngeal nerve. Our investigation has shown that patients with paresis of the recurrent nerve who present with dysphagia with or without aspiration should be examined cineradiographically for pharyngolaryngeal function during swallowing.     

Functional significance of heterotopic bone formation after total hip arthroplasty

The effects of heterotopic bone formation on hip function after arthroplasty was studied in 145 cases of total hip arthroplasty. Hip muscle strength was determined 1.8-2.9 years after the operation, using a Cybex II dynamometer. Heterotopic bone formation was seen after 75% of the operations, and in 21% significant amounts developed (Brooker's classes III and IV). The gain in range of motion after surgery was significantly less in the groups with class III or IV heterotopic bone than in those without heterotopic bone formation. Heterotopic bone did not cause pain or Trendelenburg's limp after surgery; in fact, patients with trochanteric pain had less heterotopic bone than those without this pain. Hip flexion strength was greater in men with heterotopic bone than in those without heterotopic bone. Also, men with heterotopic bone formation had a higher mean maximum strength in extension but lower mean strength in abduction than did men without heterotopic bone (NS). When only patients with unilateral hip disease were considered, the same differences were found around the healthy hip; men with heterotopic bone formation had greater strength in flexion and extension than men without heterotopic bone formation and the same tendencies were seen in women. Accordingly, heterotopic bone had no serious impact on hip muscle strength in this study.     

Importance of the superficial tissue layer for the indentation stiffness of articular cartilage

Indentation testing is a widely used technique for nondestructive mechanical analysis of articular cartilage. Although cartilage shows an inhomogeneous, layered structure with anisotropic mechanical properties, most theoretical indentation models assume material homogeneity and isotropy. In the present study, quantitative polarized light microscopy (PLM) measurements from canine cartilage were utilized to characterize thickness and structure of the superficial, collageneous tissue layer as well as to reveal its relation to experimental indentation measurements. In addition to experimental analyses, a layered, transversely isotropic finite element (FE) model was developed and the effect of superficial (tangential) tissue layer with high elastic modulus in the direction parallel to articular surface on the indentation response was studied. The experimental indentation stiffness was positively correlated with the relative thickness of the superficial cartilage layer. Also the optical retardation, which reflects the degree of parallel organization of collagen fibrils as well as collagen content, was related to indentation stiffness. FE results indicated effective stiffening of articular cartilage under indentation due to high transverse modulus of the superficial layer. The present results suggest that indentation testing is an efficient technique for the characterization of the superficial degeneration of articular cartilage.