A distinctive pediatric renal neoplasm characterized by epithelioid morphology, basement membrane production, focal HMB45 immunoreactivity, and t(6;11)(p21.1;q12) chromosome translocation.

We report two cases of a hitherto undescribed pediatric renal neoplasm that is distinctive at the morphological, immunohistochemical, ultrastructural, and cytogenetic levels. On light microscopy, the tumors are composed of nests of polygonal, clear to eosinophilic cells associated with a subpopulation of smaller cells that surround hyaline material. Despite their epithelioid morphology, these tumors do not label immunohistochemically for epithelial markers but instead label focally for melanocytic markers HMB45 and Melan A. The hyaline material is positive with periodic acid-Schiff and methenamine-silver histochemical stains, and labels immunohistochemically for type 4 collagen. Ultrastructural examination confirms that it represents basement membrane material. Cytogenetic analysis reveals the identical t(6;11)(p21.1;q12) chromosome translocation as the sole abnormality in these two tumors, confirming their identity and distinctive nature.

Benign metastasizing leiomyoma: clinical, imaging, and pathologic correlation.

OBJECTIVE: We describe the clinical presentation and the radiographic and CT findings of benign metastasizing leiomyoma. CONCLUSION: Benign metastasizing leiomyoma is an asymptomatic disease characterized by well-defined, numerous, pulmonary lesions without a preponderant distribution.

Obstetric conditions and erythropoietin levels.

OBJECTIVE: Our purpose was to evaluate and compare erythropoietin levels as related to obstetric conditions, including acute and chronic bleeding, preeclampsia, and multiple gestations. STUDY DESIGN: During April 1999 all women in the labor and delivery unit with delivery expected to occur within 24 to 72 hours of admission had erythropoietin and hematocrit values obtained. First-trimester hematocrit values, obstetric problems, medications, and history of vaginal bleeding were obtained from patient interview, examination, and the prenatal record. Statistics were analyzed by the Student t test and chi(2). RESULTS: During a 1-month period, 302 consecutive women were divided into 5 groups on the basis of obstetric events. Group 1 consisted of women with normal, uncomplicated term singleton gestations (n = 230); group 2, women with acute vaginal bleeding (n = 10); group 3, women with chronic vaginal bleeding (n = 29); group 4, women with multiple gestations (n = 13); and group 5, women with preeclampsia (n = 16). The mean erythropoietin level in group 1 (20. 2 +/- 10.3 mU/mL) was significantly different from values in the other 4 groups (group 2, 74.2 +/- 29.2 mU/mL; group 3, 65.0 +/- 33.0 mU/mL; group 4, 34.8 +/- 16.8 mU/mL; group 5, 43.4 +/- 11.4 mU/mL; P <.001). The admission hematocrit for group 1 (0.369 +/- 0.029) was significantly greater than for groups 2 and 3 (group 2, 0.323 +/- 0. 024; group 3, 0.321 +/- 0.023; P <.001) and significantly lower than for group 5 (0.384 +/- 0.022; P <.05). CONCLUSION: The maternal serum erythropoietin level varies depending on the events occurring during gestation. Acute and chronic bleeding, multiple gestations, and preeclampsia are all associated with various serum erythropoietin levels.

The mitochondrial DNA C3303T mutation can cause cardiomyopathy and/or skeletal myopathy.

OBJECTIVE: Several mutations in mitochondrial DNA have been associated with infantile cardiomyopathy, including a C3303T mutation in the mitochondrial transfer RNA(Leu(UUR)) gene. Although this mutation satisfied generally accepted criteria for pathogenicity, its causative role remained to be confirmed in more families. Our objective was to establish the frequency of the C3303T mutation and to define its clinical presentation. STUDY DESIGN: Families with cardiomyopathy and maternal inheritance were studied by polymerase chain reaction/restriction fragment length polymorphism analysis looking for the C3303T mutation. RESULTS: We found the C3303T mutation in 8 patients from 4 unrelated families. In one, the clinical presentation was infantile cardiomyopathy; in the second family, proximal limb and neck weakness dominated the clinical picture for the first 10 years of life, when cardiac dysfunction became apparent; in the third family, 2 individuals presented with isolated skeletal myopathy and 2 others with skeletal myopathy and cardiomyopathy; in the fourth family, one patient had fatal infantile cardiomyopathy and the other had a combination of skeletal myopathy and cardiomyopathy. CONCLUSIONS: Our findings confirm the pathogenicity of the C3303T mutation and suggest that this mutation may not be rare. The C3303T mutation should be considered in the differential diagnosis of skeletal myopathies and cardiomyopathy, especially when onset is in infancy.

Maternally inherited mitochondrial cardiomyopathy associated with a C-to-T transition at nucleotide 3303 of mitochondrial DNA in the tRNA(Leu(UUR)) gene.

Disorders associated with mitochondrial DNA (mtDNA) mutations are usually dominated by involvement of the nervous system and skeletal muscle (hence the term "mitochondrial encephalomyopathies"). However, considering the high dependence of the heart on oxidative metabolism, it is not surprising that myocardial dysfunction is often a prominent feature in these disorders, either as isolated cardiomyopathy or as part of a multisystem mitochondrial syndrome. We report an infant with a maternally inherited C-to-T transition at nucleotide 3303 of mtDNA in the tRNA(Leu(UUR)) gene; this is the second kindred with cardiomyopathy identified to have this mutation of mitochondrial DNA. A brief review of other mitochondrial DNA defects is also included.

Lipid-laden macrophage infiltration of human adenocarcinoma in vivo associated with taxol and GCSF treatment.

This brief report illustrates the presence of lipid-laden macrophages in proximity to metastatic adenocarcinoma cells within the bone marrow of a patient receiving taxol and GCSF therapy. The pathophysiological mechanism is uncertain. Taxol, which is associated with macrophage function in vitro, may have been responsible for the recruitment of macrophages in this patient. GCSF could have contributed as well; however, GCSF usually has little effect on monocytes and macrophages.

Fatal graft-versus-host disease associated with transfusions of HLA-matched, HLA-homozygous platelets from unrelated donors.

BACKGROUND: Transfusion-associated graft-versus-host disease (TA-GVHD) due to blood from HLA-homozygous related and unrelated blood donors has been described. CASE REPORT: Fatal TA-GVHD due to the transfusion of HLA-matched platelets from an unrelated HLA-homozygous donor is reported. A 61-year-old man with a history of diabetes mellitus and myelodysplastic syndrome was diagnosed with acute myelogenous leukemia in November 1991. Induction chemotherapy resulted in aplasia, which was followed by a normocellular marrow with mild dysplasia and continued karyotypic abnormalities. High-dose chemotherapy was given in a second attempt to achieve complete remission. HLA-matched platelets were ordered when platelet refractoriness developed. The patient was HLA-heterozygous for HLA-A and -B antigens (A2, 29; B37, 44). Over the next 7 days, four unirradiated HLA-matched plateletpheresis units were transfused; one was probably homozygous for both HLA-A and -B antigens (A2, -; B44, -) and was transfused first, and three were probably homozygous for an HLA-B antigen (A2, 29; B44, -) and were white cell reduced. No blood relatives served as donors. Seven days after the first HLA-matched platelet transfusion, fever, chills, and diarrhea developed; 2 days later, a rash was present. Liver enzymes increased markedly. Renal and respiratory failure ensured. A skin biopsy was consistent with GVHD. Despite immunosuppressive therapy, the patient died 19 days after the first HLA-matched platelet transfusion. CONCLUSION: TA-GVHD has been recognized in immunocompromised, HLA-heterozygous patients receiving blood from blood relatives who are HLA-homozygous. patients receiving blood from either blood relatives or non-blood relatives who are HLA-homozygous. This HLA-heterozygous patient received transfusions of unirradiated, class I HLA-homozygous platelets, which were specifically ordered as HLA-matched, and his death was attributed to TA-GVHD. Consideration should always be given to providing irradiated blood for immunosuppressed patients, especially when HLA-matched platelets are used, to prevent TA-GVHD.

Acquired tracheoesophageal fistula in a premature infant.

A fatality from an acquired tracheoesophageal fistula (TEF) in a very low birthweight premature infant is presented. Neonatal tracheal and esophageal injuries related to endotracheal (ET) intubation are discussed. The infant had important risk factors for the development of subglottic stenosis: birthweight less than 1000 gm, prolonged positive pressure ventilation, and repeated ET intubation. The pathologic examination was consistent with acquired fistula formation resulting from a combination of preexisting subglottic stenosis and prolonged and repeated ET intubation. The recognition of clinical signs of an acquired TEF, as observed in our patient, followed by expeditious diagnostic testing may be lifesaving.

A comparison of patellar tendon autograft and allograft used for anterior cruciate ligament reconstruction in the goat model.

Similar-sized patellar tendon autografts and fresh-frozen allografts were used to reconstruct the anterior cruciate ligament of one knee in 40 female goats. Evaluations of the reconstructions and contralateral controls at the 6-week and 6-month postoperative periods included anterior-posterior translation, mechanical properties determined during tensile failure tests, measurement of cross-sectional area, histology, collagen fibril size and area distribution, and associated articular cartilage degenerative changes. Six months after anterior cruciate ligament reconstruction, the autografts demonstrated a smaller increase in anterior-posterior displacement, values of maximum force to failure two times greater, a significant increase in cross-sectional area, a more rapid loss of large-diameter collagen fibrils, and an increased density and number of small-diameter collagen fibrils compared to the allografts. Clinical significance. More surgeons are allowing their patients to return to running and sports 6 months after anterior cruciate ligament reconstruction. While the structural and material properties of autografts and allografts at time zero are similar, in the goat model during the first 6 months they differ. The allografts demonstrate a greater decrease in their implantation structural properties, a slower rate of biologic incorporation, and the prolonged presence of an inflammatory response. At 6 months the autograft demonstrates a more robust biologic response, improved stability, and increased strength to failure values.

Spine injuries in gymnasts and swimmers. An epidemiologic investigation.

Three groups of top level female gymnasts of preelite, elite, national and Olympic caliber were studied without regard to back pain or injury. These athletes were compared to a similar group of national caliber female swimmers. Magnetic resonance imaging scans of each participant were used to document disk or bony abnormalities. The relationship between magnetic resonance imaging findings and age, height, weight, previous injuries, back symptoms, and hours of training per week each year was examined. Nine percent of preelite (1/11), 43% of elite (6/14), and 63% of Olympic level (5/8) gymnasts had spine abnormalities; 15.8% of all swimmers had spine abnormalities. Average hours of training per week and age were found to be associated with abnormalities seen on magnetic resonance imaging. Increased intensity and length of training correlated with previous data that suggests the female gymnast is prone to spine injuries.

Immunocytochemical analysis of progesterone receptors in breast cancer.

Breast cancer specimens from 116 patients were assayed for the presence of progesterone receptor (PR), with the use of a highly specific monoclonal antibody and the peroxidase-antiperoxidase technique on cryostat and permanent sections. Results were compared with those obtained by the conventional PR determination by dextran-coated charcoal (DCC) assay; they were in concordance in 90% of cryostat sections and 85% of paraffin-embedded tissue. The sensitivity and specificity of the PR immunocytochemical assay (PR-ICA) were 91% and 89% for frozen sections and 83% and 89% for permanent sections, respectively. The immunostained slides also were evaluated for several semiquantitative features, including staining intensity, heterogeneity of staining, and the proportion of positive tumor cells. A statistically significant correlation was found between the percentage of tumor cells stained with the PR immunocytochemical technique and the PR-cytosol levels (P less than 0.05). These results suggest that the PR-ICA is an effective tool in the evaluation of PR content in breast cancer and can be applied in paraffin as well as frozen sections. This technique provides excellent morphologic detail, as well as tissue localization for PR. It also offers an alternative for assessment of PR when fresh tissue is not available for conventional hormone receptor analysis. The immunocytochemical assay can be performed easily at community hospitals. Because it requires only a small amount of tissue, PR-ICA is an ideal method for analyzing specimens of insufficient size for the DCC assay. This technique also is suited to the evaluation of fine-needle aspiration biopsy specimens.

Primary central nervous system lymphoma in acquired immune deficiency syndrome. A clinical and pathologic study with results of treatment with radiation.

Primary central nervous system (CNS) lymphoma occurs frequently in patients with the acquired immune deficiency syndrome (AIDS). Seventeen patients with AIDS and biopsy-proven CNS lymphoma were treated with whole-brain radiation. At presentation, most patients were severely debilitated from previous AIDS-related illnesses. Patients generally had focal neurologic symptoms such as seizures and paralysis. Headaches and mental status changes, often noticed after hospital admission, seldom brought our patients to seek medical attention. Computed tomography (CT) scan showed low-density, contrast-enhancing, mass lesions with variable amounts of peritumor edema. Size, location, and pattern of contrast enhancement of the lesions varied. No specific pattern was seen that could be used to distinguish between CNS lymphoma, toxoplasmosis, or other CNS diseases that occur in patients with AIDS. Biopsy results showed angiocentric, high-grade, large cell tumors with frequent necrosis. Immunohistochemical analysis showed B-cell phenotype with small amounts of T-cells, presumably reactive. All patients received irradiation to the whole brain with parallel opposed fields. A variety of doses and treatment regimens were used. Mean survival was only 72 days. Survival was longer in patients with higher pretreatment Karnofsky scores. The correlation between dose and survival was not significant. At completion of therapy, most patients showed improvement in Karnofsky score and had partial improvement in neurologic symptoms. CNS lymphomas in patients with AIDS are responsive to radiation. Posttreatment CT scans showed regression of tumors. Autopsy examinations showed regression of tumors, but also showed concurrent CNS infections, AIDS encephalopathy, and radiation-induced changes within the normal CNS tissue. Opportunistic infections rather than cerebral herniation or uncontrolled lymphoma was the most common cause of death.

CT appearance of primary CNS lymphoma in patients with acquired immunodeficiency syndrome.

Cranial CT studies of 32 patients with biopsy-proven AIDS-related primary CNS lymphoma were reviewed retrospectively. A wide variety of different CT appearances were identified. Mass lesions varied in location, size, and number. Most lesions were either iso- or hyperdense and all enhanced with contrast medium. Several different patterns of enhancement were observed. Mass effect and edema were seen in almost all patients. After radiotherapy, most tumors decreased in diameter, became hypodense, and no longer enhanced with contrast medium. Edema and mass effect decreased or resolved in all but one patient. Postradiotherapy CT scans also revealed interval enlargement of the ventricles and cortical sulci. This study demonstrates the wide diversity of CT appearances of AIDS-related primary CNS lymphoma. The CT findings cannot be used in lieu of biopsy for diagnosis of this disorder. The appearance of postradiotherapy CT scans was consistent with regressing lymphoma.

Development of a reconstituted collagen tendon prosthesis. A preliminary implantation study.

A reconstituted collagen tendon prosthesis was developed and implanted in rabbit Achilles tendons. The prosthesis was prepared by extruding type-I collagen into fibers and crosslinking it either with glutaraldehyde or with dehydrothermal treatment followed by exposure to carbodiimide. A tendon prosthesis was assembled by coating a longitudinal array of the fibers with uncrosslinked collagen. In one leg of the rabbit, the Achilles tendon was replaced with the synthetic tendon; in the contralateral leg of the animal, the tendon was excised, devascularized, and anastomosed as an autogenous graft. The autogenous tendon grafts were seen to be infiltrated centrally by fibroblasts and capillaries ten weeks postoperatively and to have been partially replaced by repair tissue twenty weeks postoperatively. Three weeks after implantation, all collagen implants were noted to have been infiltrated with fibrous tissue. At ten weeks, reorganization of collagenous tissue was observed in and around the prostheses, and the carbodiimide-crosslinked implants had been resorbed and replaced by normal-appearing neotendon. The implants that had been treated with glutaraldehyde were resorbed more slowly and were surrounded by more inflammatory cells, compared with the prostheses that had been treated with carbodiimide. Neotendon in the glutaraldehyde-treated prostheses matured more slowly. When the implants were examined at intervals after the operation, their mechanical properties approached those of fresh tendon. The initial strength of the carbodiimide-treated implants was lower than that of the fresh autogenous grafts. Twenty weeks after implantation, the strength and modulus of the carbodiimide-treated implants approached those of fresh tendon.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastroenterology, diagnosis-related groups, and age.

Hospitals are now being reimbursed by a prospective Diagnosis-Related Group (DRG) classification system. There have been no major changes in the Federal Medicare DRG classification system since its inception 5 years ago. In this project, we analyzed all gastrointestinal (GI) medicine admissions by age and resource utilization at a large academic medical center. Total hospital costs for the 3,598 GI patients (January 1, 1985, through December 31, 1987) were $18,460,604. Although DRG reimbursement for all patients for the 3-year period would have generated an aggregate profit of $957,760, four out of five age categories of patients 65 years of age and above would have generated losses; the highest loss was for patients 85 years and over, at $2,235 per patient. Older GI patients (i.e., 65 years and over) had higher hospital costs, longer lengths of stay, more diagnoses and procedures per patient, and a higher mortality rate than younger patients. Both intensive care unit (ICU) and blood utilization rose with age. Thus, older GI patients consumed a disproportionately larger share of hospital resources. Our study suggests that the current DRG reimbursement scheme may be inequitable relative to the older GI medicine patient; financial disincentives from DRGs may affect elderly patients' access to and quality of care in the future.

Mechanical properties of collagen fibres: a comparison of reconstituted and rat tail tendon fibres.

This study involves comparison of the mechanical properties of reconstituted collagen fibres with those of collagen fibres obtained from rat tail tendons. Reconstituted collagen fibres were cross-linked in the presence of glutaraldehyde vapour for 2 and 4 d or using a combination of severe dehydration and carbodiimide treatment. Ultimate tensile strengths for reconstituted fibres cross-linked with glutaraldehyde ranged from 50 to 66 MPa while those cross-linked by severe dehydration and carbodiimide treatment had ultimate tensile strengths between 24 and 31 MPa. Rat tail tendon fibres had tensile strengths that ranged from 33 to 39 MPa. These results indicate that high-strength collagen fibres can be reconstituted in vitro and that these fibres may be useful in repair of dermal, dental, cardiovascular and orthopaedic defects.

Splenic rupture as a cause of sudden death in undiagnosed chronic myelogenous leukemia.

A 35-year-old man died suddenly in a clinic waiting area after repeated visits for flu-like symptoms. At autopsy, hemoperitoneum, splenic capsular rupture, and splenomegaly were found. Microscopic examination, special stains, and immunoperoxidase studies revealed findings consistent with chronic myelogenous leukemia. Spontaneous splenic rupture is an unusual presenting feature of chronic myelogenous leukemia. The symptoms of leukemia may mimic those of other "benign" disorders and misdiagnosis may lead to catastrophic consequences in some instances.

Costs of pulmonary medicine and DRGS. Access and quality of care for the future.

Many changes are under way for the payment of physician and hospital care of patients in medicine and the medical subspecialties, i.e., the hospitalized pulmonary medicine patient. The purpose of this study was to characterize hospital resource consumption and outcome by age for pulmonary patients. All pulmonary medicine admissions treated at a large academic medical center from January 1, 1985 through December 31, 1986 were analyzed using the Diagnostic Related Group (DRG) format. Total costs (exclusive of physician fees) for the 2,647 pulmonary patients studied were $19,751,192. Mean hospital cost per patient, hospital length of stay, percentage of outliers, and mortality increased with age. Under the DRG reimbursement mechanism (i.e., All Payor System), a loss was incurred for all patients 45 yr of age and older, which led to an overall fiscal deficit for pulmonary medicine admissions. Medicare patients (n = 930) demonstrated a stronger expression of these trends. DRG case-mix index and the mean number of diagnoses per patient increased steadily with age. Emergency admissions were highest for the young (i.e., 18 to 35 yr of age), for some middle-aged (i.e., 45 to 65 yr of age), and for the very old (80 yr of age). Utilization of the intensive care unit and blood transfusions was higher for older patients; utilization of plasma products showed a more variable pattern, although older patients had greater consumption than their younger cohorts. This study demonstrated several trends with regard to resource utilization and age for pulmonary patients.(ABSTRACT TRUNCATED AT 250 WORDS)