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A case of adenocarcinoma of the small bowel arising in pre-existing transmural ileitis (Crohn's disease) is reported and 28 previously reported cases are reviewed. Carcinoma associated with transmural enteritis occurs more often in the distal ileum, in younger patients, and in more males than expected from published data on carcinoma not associated with transmural enteritis. If the patient has had exclusion procedures, the carcinoma has been found to arise in the excluded bowel segment.

Subcutaneous nodules from a newborn boy with "multiple fibromatosis" involving the head, neck, trunk, and all four extremities were studied by light microscopy, transmission electron microscopy, and immunofluorescent techniques. Light microscopy suggested a hamartomatous process with fibroblastic adipose, vasoformative and apparent smooth muscle components. The principal cell population combined ultrastructural characteristics of both fibroblasts and smooth muscle cells. Immunofluorescent studies revealed binding of human anti-smooth muscle antibody to the cytoplasm of the spindle cell population of the subdermal nodules but not to fibroblasts of the overlying un-involved skin. The ultrastructural and immunofluorescent studies revealed the previously underscribed fact that fibrous hamartoma of infancy is principally a proliferation of myofibroblasts. At age 8 months, there was complete spontaneous regression of all subcutaneous nodules not previously altered by excisional biopsy. The authors conclude that myofibroblasts are fibrocontractile cells, which play a role in shrinkage and eventual disappearance of these subdermal hamartomas.

Recurrence and metastases of a cystosarcoma phyllodes are poorly correlated with the histologic type and treatment used. There is some evidence, however, that the prognosis is more favorable for small tumors and minimal cellular atypism. Local excision seems to be associated with a higher incidence of recurrence of the tumor. Metastases can develop later from what appears primarily a benign, as well as a malignant, type. Mastectomy as primary treatment was not always effective in preventing the local recurrence of the tumor. If the tumor recurred after mastectomy, it gave rise to fatal metastases. The recurrence of the tumor after local excision is secondary to microscopic foci retained after enucleation. If a local excision is done, it should include a wide margin of mammary tissue around the tumor. Wide local excision, for small, slow growing and clinically benign tumors can be used as a first operation, with wider re-excision and later mastectomy if the tumor recurs. Large and rapidly growing tumors that suggest malignant disease should be treated primarily by mastectomy.

With the advent of cardiac catheterization, cardioangiography, and selective coronary arteriography, specific types of cardiac disease can be recognized and clearly defined. This is appropriate because myocardial biopsy alone rarely plays a major role in cardiac diagnosis. Excluding Aschoff's nodules in patients with rheumatic valve disease, the light microscopic findings in patients with rheumatic heart disease, congenital heart disease, pericardial disease, hypertensive and arteriosclerotic heart disease are similar and nonspecific. In these, interstitial fibrosis and/or myocardial hypertrophy is the dominant tissue diagnosis. Occasionally a pericardial and myocardial specimen is helpful to distinguish constrictive pericarditis and restrictive cardiomyopathy. Myocardial biopsy has provided the only method for diagnosis in a small number of patients with normal hemodynamics, normal coronary arteriograms and normal ventriculograms. The patients were studied because of chest pain and/or cardiac arrhythmias. Supraventricular and/or ventricular arrhythmias were encountered. In these patients the tissue diagnosis was interstital fibrosis and/or myocardial hypertrophy. These findings are consistent with primary myocardial disease which was not recognized clinically or by angiographic studies. The procedure seems to play a major role in the diagnosis of specific types of primary myocardial disease. It is valuable in the recognition of glycogen storage disease, amyloidosis, hemochromatosis, and myocarditis. On the basis of current experience, the indications for myocardial biopsies depend on the need for a tissue diagnosis in determining the management of the patient and the availability of adequately trained personnel to perform the procedure and manage the complications.

Data for 500 patients with Crohn's disease who underwent operations were analyzed (316 patients, 1966 to 1969; 184 patients, 1972 to 1973) by comparison of various anatomic disease locations (clinical pattern): (1) ileocolic, 225 patients; (2) small intestinal, 130 patients; (3) colonic, 127 patients; (4) anorectal, 18 patients. Indications for surgery were tabulated and compared using statistical analysis for the three large patterns. For patients with ileocolic Crohn's disease, the primary surgical indications were internal fistula and abscess, 44%, intestinal obstruction, 35%, and perianal disease, 12%. For patients with Crohn's disease of the small intestine, the primary surgical indications were intestinal obstruction, 55%, and intestinal fistula and abscess, 32%. Patients with colonic Crohn's disease had a significantly more diverse surgical indication, with poor response to medical therapy, 26%, internal fistula and abscess, 23%, toxic megacolon, 20%, and perianal disease, 19%. These values were highly statistically significant (P less than 0.0001) in all instances but one. This study demonstrates that statistically significant differences occur in the surgical indication depending on the location of Crohn's disease. Patients with ileocolic, small intestinal, and colonic involvement have striking differences in clinical course. It is concluded that Crohn's disease is not a homogeneous entity, but should be recognized as having a varying course depending on clinical pattern.

Five case histories of patients with fibrous inflammatory polyps of the ileocecum are reported. Clinical impression in all five cases was that these tumefactions represented gastrointestinal malignancies. Gross pathologic examination revealed polypoid intramural growths ranging from 2.5 to 7.0 cm in greatest dimension. Transmural desmoplasia through the bowel wall into subserosal fat was initially thought to be indicative of neoplastic invasion. Microscopic evaluation revealed a fibroblastic and vascular proliferative process. Pseudosarcomatous changes were identified in cellular fibroblastic areas with plemorphism and mitotic activity. The manner of dissection among bundles of muscularis mucosae and muscularis propria suggests an inflammatory process as opposed to the pushing aside of whole large muscle bundles as seen in mesenchymal neoplasms arising in bowel wall. All five patients experienced survival of 6 to 17 years following surgery. These lesions are thought by us to represent localized exuberant polypoid granulation tissue proliferations which simulate mesenchymal neoplasm.

Members of the Klebsiella-Enterobacter-Serratia group now appear to be the most common cuase of gram-negative bacillemia, followed in order of frequency by E. coli, Bacteroides, polymicrobic infection, Pseudomonas aeruginosa, and miscellaneous pathogens. However, E coli continues to be the organism most frequently responsilbe for bacteremia arising from the urinary tract. Although the urinary tract remains the most common portal of entry for gram-negative bacillemia, a wide variety of extraurinary lesions have assumed increased importance in the pathogenesis of this condition. There is marked variability in the clinical course and outcome of gram-negative bacillemia. Grade of underlying disease and grade of illness cuased by infection are major determinants of fatal outcome. When the patient with gram-negative bacillemia has severe illness due to infection, prompt and decisive action is necessary to prevent death. Antimicrobiol drugs are administered on the basis of a presumptive etiologic diagnosis after appropriate smears and cultures are obtained, but before the causal organism is definitively identified or its in vitro susceptibility is determined. The presumptive etiologic diagnosis is based upon knowledge of the anatomic location of the infection, the circujstances involved in its development, and certain clinical clues. Knowledge of the antimicrobial drugs most likely to be effective against the suspected pathogen(s) will provide a rational basis for selection of antimicrobial agents until the results of definitive microbiologic studies are available. Using this approach, the mortality of gram-negative bacillemia arising from the urinary tract has been reduced markedly from the mortality reported in earlier years.

An open study of azaribine was carried out on 38 psoriatic patients for two years. Thirty-five patients had previously taken methotrexate. Thirty-four patients had liver biopsies performed before azaribine therapy and 14 had liver biopsies performed after azaribine therapy. Of these 14, five had grade 1 liver biopsies before and after therapy; one had grade III before and after therapy; and three had grade IV before and after therapy. Liver biopsy findings were slightly worse in two patients, and three patients showed improvement in liver biopsy findings.

All malignant neoplastic cells of papillary carcinoma of the thyroid gland and the majority of follicular carcinoma cells do not demonstrate the presence of normal cytoplasmic microsomal antigen. Follicular adenomas contain cells that demonstrate microsomal antigen, as well as cells that do not. This contrasts with normal and goitrous thyroid glands, which show positive fluorescence of all follicle cells. A concomitant immunofluorescence and ultrastructural study was performed using five normal thyroid specimens, six nodular goiters, five follicular adenomas, four follicular carcinomas, and four papillary carcinomas. The tissues were stained by a sandwich technic with initial incubation with human serum containing high-titer antimicrosomal antibody followed by incubation with fluorescein-conjugated goat antihuman polyspecific serum. The fluorescence findings suggest loss or functional alteration of the normal microsomal antigen in malignant neoplastic cells and some benign neoplastic cells. Ultrastructural study of tissue blocks from the same specimens revealed no conclusive difference in the cytoplasmic organelles of benign and malignant cells. The conclusion is that the immunologic identity of neoplastic follicle cells, as compared with that of normal cells, is altered prior to observable ultrastructural alteration of cytoplasmic constituents.

Between 1948 and 1977, 84 patients with follicular carcinoma of the thyroid gland were treated at the Cleveland Clinic. The crude survival rate was 73 per cent at five years and 43 per cent at ten years. The most important prognostic factor was the age of the patient--86 per cent of those less then 40 years old appeared to be cured of carcinoma compared with only 26 per cent of those more than 60 years old. The survival of women was a little better than that of men. Patients with large tumors did not do as well as those with small or medium sized ones. Those with highly invasive carcinoma did poorly as did those with oxyphilic tumors. Neither the extent of the operation nor the use of either external radiation or 131I appeared to affect prognosis. Both involvement of lymph nodes and local recurrences had grave prognostic significance. Those who had neither distant metastases nor a history of recurrence after a previous operation when they were first seen by us had good prognoses, 90 per cent of them apparently having been cured.

Patients between the ages of 6 and 45 years with distant metastases from papillary carcinoma of the thyroid can be treated as effectively by subtotal thyroidectomy and suppressive doses of thyroid hormone as by total thyroidectomy followed by treatment with iodine 131 (131I). Moreover, distant metastases can be treated by either 131I or suppression as effectively after they are apparent on x-ray as they can be when treated in a subclinical stage. Therefore, in patients younger than 45 years old it is rarely necessary to perform a total thyroidectomy or to do frequent postoperative scans. In patients older than 44 or younger than 7 who have distant metastases or extensive involvement of both lobes, total or almost total thyroidectomy is justified if it can be done with minimal morbidity. In patients of this age group whose tumors fail to respond to suppressive doses of thyroid, 131I should be used. In view of the importance of diagnostic related groups (DRG) to the economy of hospitals, we note that the cost of total thyroidectomy, ablation by 131I, and intermittent body scans is at least three times that of less radical procedures which, in conjunction with suppression by thyroid feeding, give the same survival with less morbidity.

Giant cell myocarditis (GCM) as a distinct disease entity has been questioned. The superficial morphologic resemblance to cardiac sarcoidosis and incomplete histopathologic assessment of extracardiac organ systems in reported cases has suggested that GCM represents a predominant cardiac manifestation of generalized sarcoidosis. The morphologic and immunocytochemical features at autopsy of this rare disorder were seen in a 15-year-old boy. All other organs were free of granulomatous inflammation. Transition from normal myocardial fibers to giant cells was observed, without a limiting plasma membrane between the two different aspects of the fiber. Immunocytochemistry for cytoplasmic muramidase (CM) showed CM in neutrophils and tissue macrophages. Cytoplasmic muramidase was distinctly absent from the characteristic giant cells. The classification of GCM as a disease separate from generalized sarcoidosis may be justified.

Vesicular myocardial change is a specific and common finding in the diseased hearts of humans and experimental animals. The small to large vesicles are generally bound by a double membrane. They are formed within myocardial cells and then possibly extruded into the extracellular space where they disintegrate or are phagocytosed by mononuclear cells. On the basis of our studies, most vesicles appear to be of mitochonrial origin. In humans, vesicular myocardial change appears to be most extreme in primary cardiomyopathy. It may also be present, but in lesser degree, in the apparently normal hearts of human adults. Vesicular myocardial change probably represents a specific mechanism by which myocardial cells eliminate damage mitochondria or other undesirable elements that build within them as a result of disease, aging, and perhaps normal physiological activity.

The purpose of this study was determination of the prognostic value of clinical and tissue (biopsy) findings of 139 patients with cardiomyopathy. The types of cardiomyopathy were congestive (113 patients) and hypertrophic or constrictive (26 patients). The mean follow-up period of all patients was 4.3 years. Follow-up of the survivors was between 13 months and 11.9 years, mean 5.4 years. Of the 47 cardiac deaths (33.8%), the minimum and maximum follow-up was two weeks and 7.5 years, respectively (mean 2.1 years). Patients with congestive heart failure had the highest five year cardiac mortality rate (51.8%). Coexisting cardiac arrhythmia had no influence on prognosis and an arrhythmia only was benign in most patients. Myocardial hypertrophy or fibrosis or both and myocardium with no pathologic diagnosis had prognostic value. Small-vessel disease was infrequent and not associated with specific clinical manifestations.

The clinical laboratory has achieved an enviable record for safety even though the opportunities for accident and misfortune are ever present. This article provides an overview of what constitutes an adequate safety program for a laboratory, as well as a list of sources from which more detailed information can be obtained.

From November, 1971, to September, 1974, 1,179 patients received aortocoronary saphenous vein bypass grafts at the Cleveland Clinic Hospital. Segments of saphenous vein from each patient were sent for microscopical analysis. These vein segments were classified as normal or abnormal (phlebosclerotic). Four hundred ninety-six normal vein grafts in 295 patients were restudied and had a patency of 87.9%. One hundred forty-four abnormal vein grafts in 86 patients were restudied and showed 89.5% patency. This study suggests that histopathological identification of an abnormal (phlebosclerotic) vein segment does not constitute a determining factor as far as late patency is concerned in a vein segment that is not grossly sclerotic.