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Biomedical subjects

J Carlos Manivel

Publications and source records attributed to J Carlos Manivel.

18 recordsLinked to original sources

Thymic hyperplasia in a child treated with growth hormone.

OBJECTIVE: To report a case of thymic hyperplasia diagnosed three months after initiation of recombinant human growth hormone (GH) for the treatment of GH deficiency. DESIGN: Retrospective chart review was conducted to evaluate the temporal relationship between treatment with GH and thymic enlargement in a 7-year-old girl who had a history of embryonal rhabdomyosarcoma of the nasopharynx diagnosed at the age of 3 years. RESULTS: The diagnosis of GH deficiency was made based on clinical and auxological criteria, an insufficient response to clonidine-arginine stimulation testing (peak GH level of 4.8 microg/L) and low insulin-like growth factor 1 (IGF-1) level (30 ng/mL, -2.7 SD). The patient was started on GH at a dose of 0.3mg/kg/week. At the initiation of treatment with GH, the baseline growth velocity was 0.8 cm/year (-6.0 SD) and height was 112.5 cm (-1.7 SD). After three months of treatment with GH, her height increased by 4.2 cm (from -1.7 to -1.2 SD), and the IGF-1 level from -2.7 SD to -1.1 SD. A chest CT performed at that time for recurrence surveillance showed 89% increase in thymic volume relative to previous scan before treatment with growth hormone. A thoracoscopic biopsy of the thymus was performed and revealed hyperplasia with normal thymic architecture without evidence of malignancy. CONCLUSIONS: The timing of the development of thymic hyperplasia, along with data from in vitro and in vivo animal studies showing that GH and IGF-1 can directly stimulate growth of the thymus, suggests that GH contributed to the development of thymic hyperplasia in this patient.

Child↗

Angiomyofibroblastoma-like tumors (cellular angiofibroma).

Angiomyofibroblastoma-like tumor (cellular angiofibroma) is a rare, circumscribed, slow-growing mesenchymal tumor that occurs predominantly in the vulva, perineum, and pelvis of women. We report two cases of this tumor in men arising as paratesticular masses of the scrotum, summarize the history of this tumor, and discuss why efforts should be made to differentiate it from aggressive angiomyxoma. Recommended treatment is complete surgical excision with long-term follow up exams, as local recurrence may occur many years after resection of the lesion.

Adult↗

Prostatic glands and urothelial epithelium in a seminal vesicle cyst: report of a case and review of pathologic features and prostatic ectopy.

We report a case of a seminal vesicle cyst containing prostatic glands and urothelial epithelium in a patient with no other urogenital anomalies. The detection of prostatic tissue, which is of endodermal origin, in a seminal vesicle cyst, a mesonephric duct derivative, is unusual. We review the pathologic features of seminal vesicle cysts and discuss the histogenesis of prostatic and urothelial tissue.

Adult↗

Persistent, asymptomatic, microscopic hematuria in prospective kidney donors.

BACKGROUND: Asymptomatic, microscopic hematuria is seen in 8-21% of the general population, has a good prognosis, and is generally not an indication for kidney biopsy. But whether it should preclude kidney donation is unclear. METHODS: Of 512 consecutive prospective donors, 14 (2.7%) continued to have asymptomatic, microscopic hematuria over 1 month. If the medical history, physical examination, and computerized tomographic angiography were unremarkable, and if they still wished to donate, a kidney biopsy was performed. RESULTS: In two prospective donors, hematuria resolved after treatment for urinary tract infection; two others declined donation and were referred to their primary care provider. Kidney biopsy in the remaining 10 showed: two normal; four thin basement membrane nephropathy (TBMN); one nonhomogeneous basement membrane abnormalities; one IgA nephropathy, 5 of 16 glomeruli globally sclerotic; one in a patient with a family history of Schimke's Syndrome, 7 of 30 glomeruli globally sclerotic; and one TBMN and early hypertensive changes without systemic hypertension. Only 4 of the 10 who underwent kidney biopsy donated (two normal, two TBMN). CONCLUSIONS: Kidney abnormalities are common in young, otherwise healthy, prospective kidney donor candidates with persistent, asymptomatic, microscopic hematuria. A kidney biopsy is often abnormal and aids in the decision-making process.

Adolescent↗

Improving surgical wound healing with basic fibroblast growth factor after radiation.

OBJECTIVES/HYPOTHESIS: Delayed wound healing in surgical patients who have received previous irradiation continues to be a significant problem. We investigated whether radiation decreases basic fibroblast growth factor (bFGF) production in skin and whether supplemental bFGF can improve irradiated postsurgical soft tissue healing. STUDY DESIGN: Experimental study in the porcine skin flap model. METHODS: Pigs were subjected to orthovoltage radiation (1,300 cGy). To test whether radiation alters bFGF production in skin, semiquantitation of bFGF message was compared in irradiated and nonirradiated skin by reverse transcription-polymerase chain reaction (RT-PCR). To determine whether supplemental bFGF can improve postsurgical soft tissue healing after radiation, bFGF was given intravenously or intracuticularly preoperatively. To investigate whether additional oxygen tissue levels would modify the effects of supplemental bFGF, one test group received hyperbaric oxygen. Six weeks later, 108 skin flaps (random and arterial) were created in 27 pigs and monitored over 2 weeks. Tissues were analyzed for flap viability, vascularity, endothelial cell apoptosis by caspase-3 activation, and histologic analysis. RESULTS: Radiation statistically increased endothelial cell apoptosis in porcine skin by 650%. Radiation also significantly reduced bFGF message by 75% in porcine skin by RT-PCR analysis. Supplemental intravenous bFGF in irradiated tissue significantly increased skin flap viability by 25% compared with controls (P < .001). Intravenous bFGF also significantly reduced gastrointestinal side effects from irradiation by 50% compared with controls. BFGF treatment induced a trend to decrease endothelial cell apoptosis in irradiated skin, but this was not statistically significant. Histologically, the intravenous bFGF-treated flaps had similar cellularity, fibroblasts, and extracellular acid mucopolysaccharides as controls. When bFGF was administered by intracuticular injection with and without hyperbaric oxygen, skin flap survival and flap vascularity were similar to controls. CONCLUSIONS: Decreased local levels of bFGF in skin may play an important role in the delayed healing of irradiated wounds. Radiation appears to decrease bFGF production by significantly reducing bFGF message in irradiated tissue. Supplemental intravenous bFGF reduced irradiated soft tissue injury and improved random skin flap viability in this porcine model. More studies are needed to investigate the effects of bFGF in the surgical healing of irradiated wounds.

Animals↗

Ki-67 immunoreactivity in the differential diagnosis of pulmonary neuroendocrine neoplasms in specimens with extensive crush artifact.

The aim of the present study was to evaluate the usefulness of immunohistochemical markers in the differential diagnosis of pulmonary neuroendocrine tumors with particular emphasis on the preservation of immunoreactivity in areas showing crush artifacts. Specimens from 9 carcinoid tumors (CTs) and 13 small cell carcinomas (SCCs) with crush artifact were stained with antibodies to Ki-67, chromogranin A, synaptophysin, and cytokeratin. The immunoreactivity was well preserved in the crushed areas. Ki-67 was expressed in the crushed areas of all SCCs. Reactivity was diffuse or at least present in 25% of the crushed areas. In contrast, the immunoreactive areas in CTs never exceeded 10%. Immunoreactivity for Ki-67, synaptophysin, chromogranin A, and cytokeratin is well preserved in tissue with crush artifacts and can be interpreted reliably. The diagnosis of SCC should be questioned if fewer than 25% of cells show reactivity for Ki-67.

Artifacts↗

Radiation treatment decreases bone cancer pain through direct effect on tumor cells.

The most used treatment for bone cancer pain is radiation; however, the mechanism responsible for analgesia after irradiation is unknown. The mechanistic influence of a single, localized 10-, 20- or 30-Gy dose of radiation on painful behaviors, osteolysis, histopathology and osteoclast number was evaluated in mice with painful femoral sarcomas. Dramatic reductions in pain behaviors (P < 0.05) and osteolysis (P < 0.0001) were seen in mice irradiated with 20 and 30 Gy. Irradiation reduced the tumor area by more than 75% (P < 0.05) but did not affect osteoclast frequency per mm2 tumor. Treatment with 20 Gy prior to tumor injection had no effect on tumor growth or pain behaviors, suggesting that radiation reduces osteolysis and pain through direct tumor effects. To demonstrate that tumor elimination was responsible for reduction in osteolysis and pain, sarcoma cells containing the suicide gene cytosine deaminase (CD) were inoculated into femora. After onset of bone cancer pain, mice were treated with the prodrug 5-fluorocytosine (5-FC). 5-FC treatment significantly reduced both osteolysis (P < 0.0005) and bone cancer pain (P < 0.05). The findings in this study demonstrate that one mechanism through which radiation decreases bone cancer pain is by direct effects on tumor cells.

Animals↗

Perivascular epithelioid cell tumor of the oral mucosa.

Perivascular epithelioid cell tumors (PEComas) are a family of tumors defined by the coexpression of melanocytic and muscle markers. Examples have been reported in many organs, soft tissues, and bone. Further expanding the list of locations, we report a case arising in the hard palate. Histologically, the tumor was composed of large elongated or epithelioid cells with granular cytoplasm. Immunohistochemically, tumor cells were positive for HMB-45, Melan A/MART-1, CD10, smooth muscle actin, desmin, and calponin. Ultrastructural examination revealed stage I melanosomes, thin filaments, and dense plaques. Recurrence has not been reported after 20 months. To our knowledge, this is the first detailed description of an intraoral PEComa.

Biomarkers, Tumor↗

Pulmonary complications after bone marrow transplantation: an autopsy study from a large transplantation center.

CONTEXT: Bone marrow transplantation (BMT) is used to treat various malignant and nonmalignant disorders. Pulmonary complications are some of the most common causes of mortality in BMT recipients. Poor general health and bleeding tendency frequently preclude the use of definitive diagnostic tests, such as open lung biopsy, in these patients. OBJECTIVE: To identify pulmonary complications after BMT and their role as the cause of death (COD). DESIGN: The autopsy and bronchoalveolar lavage (BAL) slides and microbiology studies of BMT recipients from a 7-year period were reviewed. RESULTS: Pulmonary complications were identified in 40 (80%) of the 50 cases. The most common complications were diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH). Pulmonary complications were the sole or 1 of multiple CODs in 37 cases (74%). All complications were more common in allogeneic BMT recipients. In 19 (51%) of the 37 cases in which pulmonary complications contributed to the death, cultures were negative. Both DAD and DAH, complications commonly reported in the early post-BMT period, were seen more than 100 days after BMT in 33% and 12% of cases, respectively. Five (83%) of 6 cases of invasive pulmonary aspergillosis diagnosed at autopsy were negative for fungi ante mortem (by BAL and cultures). CONCLUSIONS: Pulmonary complications are a significant COD in BMT recipients, many of which, especially the fungal infections, are difficult to diagnose ante mortem. The etiology of DAD and DAH is likely to be multifactorial, and these complications are not limited to the early posttransplantation period. Autopsy examination is important in determining the COD in BMT recipients.

Adolescent↗

Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells.

Common human malignancies acquire derangements of the translation initiation complex, eIF4F, but their functional significance is unknown. Hypophosphorylated 4E-BP proteins negatively regulate eIF4F assembly by sequestering its mRNA cap binding component eIF4E, whereas hyperphosphorylation abrogates this function. We found that breast carcinoma cells harbor increases in the eIF4F constituent eIF4GI and hyperphosphorylation of 4E-BP1 which are two alterations that activate eIF4F assembly. Ectopic expression of eIF4E in human mammary epithelial cells enabled clonal expansion and anchorage-independent growth. Transfer of 4E-BP1 phosphorylation site mutants into breast carcinoma cells suppressed their tumorigenicity, whereas loss of these 4E-BP1 phosphorylation site mutants accompanied spontaneous reversion to a malignant phenotype. Thus, eIF4F activation is an essential component of the malignant phenotype in breast carcinoma.

Adaptor Proteins, Signal Transducing↗

Pulmonary nodular lesions in bone marrow transplant recipients: impact of histologic diagnosis on patient management and prognosis.

Bone marrow transplantation is associated with numerous pulmonary complications, which may manifest as nodules. We studied 33 bone marrow transplant (BMT) recipients in whom pulmonary nodular lesions (PNLs) developed during a 5-year period and who underwent open lung biopsy (OLB) for diagnosis. Of 33 patients with PNL, 15 (45%) had pulmonary cytolytic thrombi (PCT), a recently described condition characterized histologically by occlusive vascular lesions and hemorrhagic infarcts and clinically by a favorable outcome. Clinical symptoms and radiologic abnormalities disappeared during a period of a few weeks. None of the patients died of PCT; 10 were alive at last contact. The second most common cause of PNL (8/33 [24%]) was Aspergillus infection, which was the cause of death in 6. OLB is an effective way of obtaining diagnostic tissue in BMT recipients with PNLs. Histologic examination is accurate in determining the cause of PNLs and identifying lesions that have a favorable outcome and those that require a change in treatment.

Adolescent↗

The pattern of CD10 expression in selected pathologic entities of the prostate gland.

There is increasing evidence that neuropeptides, including bombesin, may influence growth, angiogenesis, invasiveness, and metastasis in prostate cancer. One of the molecules tightly involved in the regulation of neuropeptide activity is the integral membrane glycoprotein CD10, or neutral endopeptidase 24.11. The pattern of CD10 expression in hyperplastic and neoplastic conditions of the prostate gland has not been previously described. Immunohistochemical staining for CD10 and high-molecular-weight cytokeratin was performed on 92 cases of paraffin-embedded tissue from needle-core biopsy specimens and prostatectomy specimens. Normal and hyperplastic acini showed strong and distinct membrane (apical and intercellular) and cytoplasmic CD10 expression in basal and secretory cells. In contrast, no intercellular membrane or cytoplasmic staining of secretory cells was seen in any cases of adenocarcinoma with Gleason patterns 2 or 3. A subset of high-Gleason grade adenocarcinoma (patterns 4 and 5) displayed CD10 expression in the secretory cells; those cases shared a distinct morphological pattern. Prostatic intraepithelial neoplasia (PIN) showed consistent absence of intercellular membrane and cytoplasmic CD10 expression in the secretory cells, with preserved expression in basal cells. Interestingly, the basal cells in basal cell hyperplasia lacked CD10 expression, and no expression was noted in the secretory cells in all cases examined. Atrophic acini and those associated with acute and chronic inflammation retained CD10 expression. In conclusion, a consistent differential pattern of CD10 expression was seen in basal cell hyperplasia, PIN, and adenocarcinoma, suggesting a role for CD10 in the pathobiology of the prostate gland.

Adenocarcinoma↗

Germ cell tumor-like neoplasms occurring outside the anatomic midline.

Most germ cell tumors occur in the gonads or in extragonadal sites in the anatomic midline; this article reviews tumors with similar or identical histologic features that arise in other topographic locations. Such lesions often represent the presence of "germ cell-like" or "germinal" components in what is otherwise recognized as a somatic neoplasm; however, they may also occur in pure form. The morphologic and immunohistochemical features of these proliferations are reviewed, according to the types of germ cell tumors that they recapitulate.

Biomarkers, Tumor↗

Promoting healing with recombinant human platelet-derived growth factor--BB in a previously irradiated problem wound.

OBJECTIVES/HYPOTHESIS: Persistent, poorly healing wounds are a significant clinical problem in patients who have had previous irradiation. Despite current treatments, refractory nonhealing soft tissue wounds persist. The study described one of the earliest reported uses of recombinant human platelet-derived growth factor-BB (rhPDGF) gel to improve the healing of a previously irradiated refractory dermal wound to the neck that had been present for 12 years. STUDY DESIGN: Case report and literature review. METHODS: Review of local healing management of previously irradiated wounds and review of patients chart one year after follow-up treatment. RESULTS: A 47-year-old man had a 12-year history of a persistent, painful, nonhealing full-thickness dermal wound on the left side of his neck after radiation therapy and chemotherapy for a T2N2bM0 nasopharyngeal carcinoma. He had been tumor free for 12 years. Despite multiple modalities of therapy over a 1-year period (including moist hydrogel dressings, topical and oral antibiotics, serial debridement, and hyperbaric oxygen), the wound did not heal. After 6 months of topical rhPDGF gel treatment, sufficient granulation tissue developed within the dermal wound that a split-thickness skin graft was successfully performed. Symptomatically, the patient's continuous pain at the neck resolved after rhPDGF treatment. Serial histological biopsy specimens before and after rhPDGF treatment confirmed the wound transformation from a chronic state to a short-term healing state. CONCLUSION: In previously irradiated tissue, rhPDGF can be useful in helping refractory wounds to heal by inducing further granulation formation. If such treatment is planned, the patient should be informed of the possible theoretical risks of its use when it is in proximity to a previously treated neoplastic site.

Administration, Topical↗

Solid-pseudopapillary tumor of the pancreas: a neoplasm with distinct and highly characteristic cytological features.

The solid-pseudopapillary tumor of the pancreas (SPTP) is an unusual low-grade malignant epithelial tumor affecting predominantly adolescent girls and young women. Although approximately 500 cases of SPTP have been described in the last 40 yr, its pathogenesis remains uncertain. However, the clinical features of this neoplasm are very characteristic and SPTP must be suspected in any young woman with a cystic or partially cystic pancreatic mass. In this report, we describe the cytologic features of seven cases of SPTP investigated by preoperative fine-needle aspirates. The analysis of the cytologic features in these cases and in 43 cases collected from the literature reveals that they are highly characteristic and quite distinct from those of other cystic or solid tumors of the pancreas. On this basis, a cytologic diagnosis of SPTP may be rendered with great confidence, not only in clinically typical examples, but also in unusual presentations, such as in older patients, in males, in ectopic locations, and in metastatic sites.

Adolescent↗

Fine needle aspiration cytology of invasive micropapillary (pseudopapillary) carcinoma of the breast. Report of 11 cases with clinicopathologic findings.

OBJECTIVE: To describe the cytologic features of invasive micropapillary carcinoma of the breast, a distinct, unusual variant of infiltrating duct carcinoma characterized histologically by pseudopapillary structures lacking fibrovascular cores and tubuloalveolar structures floating freely within clear spaces separated by a delicate fibrocollagenous stroma and characterized clinically by prominent lymphotropism and an aggressive clinical course. STUDY DESIGN: We reviewed the clinical, cytologic, histologic, immunohistochemical and flow cytometric features in 11 cases of invasive micropapillary carcinoma of the breast diagnosed preoperatively by fine needle aspiration. RESULTS: All patients were women, ranging in age from 31 to 83 years. A preoperative diagnosis of malignancy was made in all cases. Tumor size ranged from 1.2 to 5.5 cm. Ten patients had lymph node metastases. Cytology was characterized by a "dual" pattern formed by round or angulated, three-dimensional, cohesive clusters of neoplastic cells with pseudopapillary configuration and two-dimensional, dyscohesive aggregates and single cells with high grade nuclei and intact cytoplasm.

Adult↗