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1.
Crit Care Res Pract ; 2024: 7765932, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766546

RESUMO

Background: Widespread drug shortages led to higher utilization of ketamine in our intensive care unit, especially among patients with SARS-CoV-2. Objectives: To evaluate the impact of continuous infusion of ketamine on vasopressor requirements in patients with SARS-CoV-2. Method: This was a single-center, retrospective, cohort study comparing mechanically ventilated (MV), adult patients with SARS-CoV-2 receiving either propofol or ketamine for at least 72 hours. Results: 84 patients (mean age of 61-year-old, 68% male) were analyzed. 31 patients received ketamine, and 53 patients received propofol. Mean vasopressor doses were not significantly different between ketamine and propofol groups at prespecified timepoints. However, mean arterial pressures (MAP) were higher in the ketamine group at 24 h, 48 h, and 96 h postsedative initiation. The median opioid infusion requirements were 3 vs. 12.5 mg/hr (p < 0.0001) for ketamine and propofol groups, respectively. Comparing to propofol, C-reactive protein (CRP) values were significantly lower in the ketamine group at 24 h (7.53 vs. 15.9 mg/dL, p=0.03), 48 h (5.23 vs. 14.1 mg/dL, p=0.0083), and 72 h (6.4 vs. 12.1 mg/dL, p=0.0085). Conclusion: In patients with SARS-CoV-2 on MV, there was no difference in the vasopressor requirement in patients receiving ketamine compared to propofol. Nevertheless, the use of ketamine was associated with higher MAP, reductions in CRP in select timepoints, and overall lower opioid requirements.

2.
J Inflamm Res ; 15: 3925-3940, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860230

RESUMO

Background: Sepsis mortality has remained unchanged for greater than a decade, and early recognition continues to be the most important factor in mortality outcome. Plasma resistin concentration is increased in sepsis, but its mechanism and clinical relevance is unclear. As one function, resistin interacts with toll-like receptor 4 in competition with lipopolysaccharide, a main component of the gram-negative bacterial cell wall. It is not known if the type of infection leading to sepsis influences resistin production. The objective of this study was to investigate whether 1) early plasma resistin concentration can predict mortality, 2) elevated plasma resistin concentration is associated with clinical disease severity scores, such as SOFA, mSOFA and APACHE II, and 3) plasma resistin concentrations differ between gram negative versus other etiologies of sepsis. Methods: This was an exploratory study in the framework of a prospective observational design. Peripheral venous blood samples were obtained from subjects admitted to the intensive care unit at clinical recognition of sepsis (0 hour) and at 6 and 24 hours. Vasopressor utilization was not a requirement for inclusion. Plasma was analyzed for resistin concentration by ELISA. Cytokine concentrations including IL-6, IL-8, and IL-10 were determined by cytokine bead array. Cytokine data were evaluated against publicly available sepsis RNA expression datasets to compare protein versus RNA expression levels in predicting clinical disease state. Clinical data were collected from electronic health records for clinical severity index calculations and context for interpretation of resistin and cytokine concentrations. Subjects were followed up to 60 days, or until death, whichever came first. Statistical analysis was completed with R package and SPSS software. Results: Resistin levels were elevated in subjects admitted to the intensive care unit with sepsis. Four-hundred subjects were screened with 45 subjects included in the final analysis. Thirteen of 45 patients were non-survivors. Mortality within 60 days correlated with significantly higher resistin concentrations than in survivors. A resistin concentration of >126 ng/mL at clinical recognition of sepsis and >197 ng/mL within the first 24 hours were associated with mortality within 60 days with an area under the curve of 0.82 and 0.88, respectively. Most subjects with resistin concentration greater than these threshold values were deceased prior to 30 days. Resistin concentrations correlated with SOFA, mSOFA, and APACHE II scores in addition to having association with increases in inflammatory and sepsis biomarkers. These associations were validated with analysis of RNA expression datasets. Conclusion: Plasma resistin concentrations of >126 ng/mL at clinical recognition of sepsis and >197 ng/mL within the first 24 hours of clinical sepsis recognition are associated with all-cause mortality. Resistin concentration within this timeframe also has comparable mortality association to well-validated clinical severity indices of SOFA, mSOFA, and APACHE II scores.

3.
J Leukoc Biol ; 110(6): 1253-1268, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34558746

RESUMO

Systemic infections, especially in patients with chronic diseases, may result in sepsis: an explosive, uncoordinated immune response that can lead to multisystem organ failure with a high mortality rate. Patients with similar clinical phenotypes or sepsis biomarker expression upon diagnosis may have different outcomes, suggesting that the dynamics of sepsis is critical in disease progression. A within-subject study of patients with Gram-negative bacterial sepsis with surviving and fatal outcomes was designed and single-cell transcriptomic analyses of peripheral blood mononuclear cells (PBMC) collected during the critical period between sepsis diagnosis and 6 h were performed. The single-cell observations in the study are consistent with trends from public datasets but also identify dynamic effects in individual cell subsets that change within hours. It is shown that platelet and erythroid precursor responses are drivers of fatal sepsis, with transcriptional signatures that are shared with severe COVID-19 disease. It is also shown that hypoxic stress is a driving factor in immune and metabolic dysfunction of monocytes and erythroid precursors. Last, the data support CD52 as a prognostic biomarker and therapeutic target for sepsis as its expression dynamically increases in lymphocytes and correlates with improved sepsis outcomes. In conclusion, this study describes the first single-cell study that analyzed short-term temporal changes in the immune cell populations and their characteristics in surviving or fatal sepsis. Tracking temporal expression changes in specific cell types could lead to more accurate predictions of sepsis outcomes and identify molecular biomarkers and pathways that could be therapeutically controlled to improve the sepsis trajectory toward better outcomes.


Assuntos
COVID-19/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Leucócitos , Sepse/imunologia , Transcriptoma/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Análise de Célula Única
5.
Am J Dermatopathol ; 43(5): 377-380, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33464752

RESUMO

ABSTRACT: The synchronous incidence of 2 different subtypes of melanoma is very rare. Desmoplastic melanoma (DM) can be a diagnostic challenge because of its frequent appearance as a dermal banal spindle cell proliferation. We present a case of a 30-year-old man who developed an irregular, purple, tender plaque measuring 2.5 cm on the right pretibial region. Wide excision of the right leg lesion showed superficial spreading melanoma with epithelioid cells and no spindle cell component. Sentinel lymph node (SLN) biopsy showed an atypical melanocytic proliferation involving one inguinal lymph node with subcapsular and intraparenchymal components. There were spindled tumor cells in lymph node capsule with hyperchromatic nuclei, which were nested within desmoplastic stroma, and were S100- and SOX10-positive and MART1- and HMB-45 negative; in addition to epithelioid tumor cells, which were S100-, SOX10-, and MART1-positive. Multiple discontinuous foci, subcapsular atypical melanocytes, and extracapsular extension helped in excluding capsular nevus. These findings were consistent with DM. Herein, we present an unusual case of primary cutaneous superficial spreading melanoma of the right leg with a predominantly epithelioid morphology that developed metastases to the SLN. The metastasis exhibited divergent differentiation, including both epithelioid morphology identical to the primary, but with additional features of DM that were nonoverlapping with the primary lesion.


Assuntos
Metástase Linfática/patologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adulto , Humanos , Masculino , Melanoma Maligno Cutâneo
6.
Am J Case Rep ; 19: 1216-1221, 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30310049

RESUMO

BACKGROUND Anti-N-methyl D-Aspartate (anti-NMDA) receptor encephalitis is a rare autoimmune panencephalitis that typically presents with acute psychiatric disturbances and neurological deficits. Anti-NMDA receptor encephalitis is associated with certain tumors, most commonly ovarian teratomas. First-line therapy typically involves immunotherapy and tumor resection, if present, with up to 53% of patients experiencing improvement within 4 weeks. Cardiac arrhythmias and increased intracranial pressure have been reported in anti-NMDA receptor encephalitis, but these complications have usually been self-limited. CASE REPORT We report the case of a previously healthy, obese 21-year-old female who presented with acute encephalopathy. Her psychiatric and neurological function rapidly deteriorated, warranting intubation and mechanical ventilation. Lumbar puncture was performed. Cerebrospinal fluid (CSF) opening pressure was elevated and a lumbar drain was placed. Infectious disease work-up was negative and anti-NMDA receptor antibodies were present in the CSF and serum. Initial treatment included intravenous immunoglobulin (IVIG) therapy, plasmapheresis, methylprednisolone, and bilateral salpingoophorectomy, without clinical improvement. Second-line immunotherapy with cyclophosphamide and rituximab was then administered. The patient also developed intermittent episodes of severe bradycardia and asystole that remained refractory to treatment and required placement of a permanent cardiac pacemaker. CONCLUSIONS Anti-NMDA receptor encephalitis presents with rapidly progressive psychiatric and neurologic dysfunction and can develop a severe and prolonged course with limited response to treatment. Patients can develop severe autonomic dysfunction with bradycardia and asystole that may require placement of permanent cardiac pacemakers. Elevated intracranial pressure may also be associated with anti-NMDA receptor encephalitis, and might contribute to the autonomic instability.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/metabolismo , Arritmias Cardíacas/etiologia , Autoimunidade , Sistema Nervoso Autônomo/fisiopatologia , Imunoterapia/métodos , Hipertensão Intracraniana/etiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Arritmias Cardíacas/fisiopatologia , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Hipertensão Intracraniana/diagnóstico , Adulto Jovem
8.
Am J Dermatopathol ; 36(2): 186-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24394304

RESUMO

The term "induction" has been used to describe epidermal changes overlying a dermatofibroma (DF). Follicular induction is most often associated with DF, but can be observed in other lesions, including focal mucinosis, nevus sebaceous, seborrheic keratosis, wart, neurofibroma, and scars. Dermatofibrosarcoma protuberans (DFSP) is a malignant fibrohistiocytic tumor that may be difficult to distinguish from DF. In contrast to DF, the epidermis overlying DFSP is usually attenuated or ulcerated. Here, we report a case of DFSP exhibiting follicular induction of the overlying epidermis. This epidermal change has been rarely reported in DFSP and may present a diagnostic pitfall in superficially sampled lesions.


Assuntos
Dermatofibrossarcoma/patologia , Folículo Piloso/patologia , Neoplasias Cutâneas/patologia , Adolescente , Dermatofibrossarcoma/cirurgia , Feminino , Humanos , Cirurgia de Mohs , Neoplasias Cutâneas/cirurgia
9.
Mod Pathol ; 20(1): 102-7, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17143262

RESUMO

The potential role of stem cells in neoplasia is a subject of recent interest. Three markers of melanocytic stem cells have been described recently. CD166 is expressed on the surface of mesenchymal stem cells and has been found on human melanoma cell lines. CD133 is expressed on the surface of dermal-derived stem cells that are capable of differentiating into neural cells. Nestin is an intermediate filament expressed in the cytoplasm of neuroepithelial stem cells. In this study, we evaluate the expression of these markers and possible differences among banal nevi, primary melanoma, and metastastic melanoma. Tissue microarrays containing normal tissue and 226 melanocytic lesions (71 banal nevi, 71 in situ and invasive melanomas, and 84 metastatic melanomas) were studied by immunohistochemistry using monoclonal antibodies CD166, CD133, and nestin. A significantly greater percentage of melanomas (combined primary and metastatic) contained cells that expressed CD166 (P=0.005), CD133 (P=0.003), and nestin (P=0.03) than banal nevi. Only nestin showed a statistical difference when comparing primary and metastatic melanoma (P=0.05). A stepwise increase in the proportion of lesions expressing all three markers was observed from banal nevi (2/19) to primary melanomas (8/17) to metastatic melanoma (19/28), P=0.0005. All cases of metastatic melanoma expressed at least one stem cell marker. The increased expression of CD166, CD133, and nestin in melanoma suggests that progression to malignant melanoma likely involves genetic pathways instrumental to stem cell biology and normal tissue development. Further studies and characterization of these pathways may also reveal new prognostic markers for a disease whose prognosis in advanced stages is dismal.


Assuntos
Biomarcadores Tumorais/análise , Melanócitos/patologia , Melanoma/patologia , Células-Tronco Neoplásicas/patologia , Nevo/patologia , Neoplasias Cutâneas/patologia , Antígeno AC133 , Antígenos CD/análise , Moléculas de Adesão Celular Neuronais/análise , Transformação Celular Neoplásica/patologia , Proteínas Fetais/análise , Glicoproteínas/análise , Humanos , Imuno-Histoquímica , Proteínas de Filamentos Intermediários/análise , Melanócitos/química , Melanoma/química , Invasividade Neoplásica , Células-Tronco Neoplásicas/química , Proteínas do Tecido Nervoso/análise , Nestina , Nevo/classificação , Peptídeos/análise , Prognóstico , Neoplasias Cutâneas/química , Análise Serial de Tecidos , Regulação para Cima
10.
Psychother Psychosom Med Psychol ; 56(9-10): 370-5, 2006.
Artigo em Alemão | MEDLINE | ID: mdl-17031768

RESUMO

The influence of psychiatric comorbidity (ICD-10 categories F1, F3, F4 and F5) on the length of hospital stay of 4936 medical inpatients of two medical departments of a hospital of tertiary care level was studied. In 994/4936 patients (20.2%) at least one F (1,3,4,5)-diagnosis had been coded. 160/994 patients (16.1%) had undergone psychosomatic consultation (CL) service treatment. The median of the time of from admission until first contact with CL-service was 3 days. Patients with psychiatric comorbidity had a significant longer hospital stay (median stay without CL-service 5 days, with CL-service 8 days) than patients with no F-diagnoses coded (4 days) (p<0.01). There were no differences as to patient complication and complexity level PCCL between the three groups. Even within a diagnosis related groups system psychiatric comorbidity has a negative effect on the length of hospital stay.


Assuntos
Transtornos Mentais/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Grupos Diagnósticos Relacionados , Feminino , Alemanha/epidemiologia , Humanos , Tempo de Internação , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Medicina Psicossomática , Encaminhamento e Consulta
11.
Acad Emerg Med ; 13(1): 109-13, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16365336

RESUMO

OBJECTIVES: To describe our experience with early goal-directed therapy (EGDT), corticosteroid administration, and recombinant human activated protein C (rhAPC) administration in patients with severe sepsis or septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) II score > or =25 in the emergency department (ED). METHODS: This was a retrospective case series of a prospectively maintained ED sepsis registry. Data are presented as median (25th, 75th percentile). The setting was an academic tertiary ED with approximately 60,000 annual patient visits. Patients with severe sepsis or septic shock and an APACHE II score > or =25 entered in an ED sepsis registry over a four-month period were included. Patients who received rhAPC in the intensive care unit were excluded. Central venous catheterization for central venous pressure and central venous oxygen saturation monitoring, antibiotics, fluid resuscitation, mechanical ventilation, vasopressors, inotropes, corticosteroids, and rhAPC were initiated by the emergency physicians and continued in the intensive care unit by intensivists. RESULTS: Twenty-four patients were enrolled. Patient characteristics were as follows: age, 79.5 (68.0, 83.5) years; APACHE II score, 31.5 (29.8, 36.0); ED length of stay, 6.5 (4.0, 10.5) hours; predicted mortality, 76.7% (71.9, 86.4); and in-hospital mortality, 45.8%. All patients received broad-spectrum antibiotics, 54.2% completed EGDT, 33.3% received corticosteroids, and 33.3% received rhAPC. Time of antibiotic administration was 1.5 (1.0, 2.0) hours, time of central venous pressure/central venous oxygen saturation monitoring was 1.0 (0.5, 2.5) hour, and time of rhAPC administration was 9.5 (6.8, 10.5) hours after patients met criteria for severe sepsis or septic shock. In-hospital mortality of patients who received rhAPC in addition to other therapies was 25.0%. CONCLUSIONS: EGDT, corticosteroid administration, and rhAPC administration are feasible in the ED setting. While these evidence-based therapies individually have been shown to improve outcomes for patients with severe sepsis or septic shock, further studies are needed to examine their combined effectiveness during the early stages of this disease.


Assuntos
Corticosteroides/uso terapêutico , Anticoagulantes/uso terapêutico , Medicina de Emergência/métodos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Proteína C/uso terapêutico , Sepse/terapia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , California , Terapia Combinada/métodos , Humanos , Tempo de Internação/estatística & dados numéricos , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Retrospectivos , Sepse/diagnóstico , Choque Séptico/diagnóstico , Choque Séptico/terapia , Análise de Sobrevida
12.
Am J Clin Pathol ; 124(4): 512-8, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16146811

RESUMO

Primary liver carcinomas in children and young adults are uncommon and poorly described. We examined primary liver carcinomas in people younger than 30 years and performed immunostains for markers of biliary (cytokeratin [CK] 7, CK19, CD56) and hepatocellular (HepPar) differentiation. We found 23 primary liver carcinomas were found: 13 hepatocellular carcinomas (HCCs), 9 fibrolamellar carcinomas (FLCs), and 1 cholangiocarcinoma. Most HCCs showed compact (n = 7) or trabecular (n = 4) growth patterns. The Edmondson grades were as follows: 1, 3 tumors; 2, 8 tumors; and 3, 2 tumors). All HCCs and FLCs were HepPar(+). All FLCs and 7 of 9 HCCs were CK7(+). In contrast, a control group of 65 adult HCCs showed less CK7 positivity (24 [37%]; P = .03). CK19 was positive in 2 HCCs and CD56 in 1 HCC. No chronic background liver disease was seen, although 3 cases showed foci of altered hepatocytes. HCCs are the most common primary liver carcinoma in children and young adults followed by FLCs. They are morphologically similar to adult HCC, but more likely to be CK7(+).


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias dos Ductos Biliares/química , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/química , Ductos Biliares Intra-Hepáticos/patologia , Biomarcadores Tumorais/análise , Antígeno CD56/análise , Carcinoma Hepatocelular/química , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica/métodos , Queratina-7 , Queratinas/análise , Neoplasias Hepáticas/química , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
J Gastrointest Surg ; 9(2): 254-62, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15694822

RESUMO

Tuberculosis of the pancreas and peripancreatic lymph nodes is an extremely rare disorder that has been reported with increased frequency in the past several years. Despite the fact that abdominal tuberculosis can generally be managed by pharmacotherapy alone, invasive procedures are often used before the establishment of the correct diagnosis, sometimes leading to unnecessary interventions and delayed treatment. To set the stage for our review, we first describe a case of a 31-year-old woman from India who initially presented with nonspecific symptoms and a pancreatic cystic lesion but was later diagnosed with peripancreatic tuberculosis. We then present a review of the current literature on peripancreatic and pancreatic tuberculosis, with a focus on diagnosis and management of the disease, but we also touch on issues such as epidemiology, infection control, and tissue acquisition. Finally, we offer clues that can be used to help identify patients who present with otherwise vague symptoms who may harbor pancreatic or peripancreatic tuberculosis. It is our hope that this case report and review of the literature will raise awareness and improve the management of this uncommon but serious disorder.


Assuntos
Pancreatopatias/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Tuberculose/diagnóstico , Adulto , Feminino , Granuloma/patologia , Humanos , Linfonodos/patologia , Pancreatopatias/microbiologia , Pancreatopatias/patologia , Tuberculose/microbiologia , Tuberculose/patologia
14.
J Cutan Pathol ; 31(6): 448-52, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15186433

RESUMO

BACKGROUND: Castleman's disease (CD) is a rare low-grade B-cell lymphoproliferative disorder that can be associated with a variety of antibody-mediated paraneoplastic syndromes. The disease is classified clinically by two forms and three histologic variants. METHODS: We describe the clinical and pathological features of a 44-year-old woman who presented with an autoimmune hemolytic anemia, thrombocytosis, polyclonal gammopathy, axillary lymphadenopathy, hepatosplenomegaly, and several erythematous and violaceous nodules and plaques without scaling involving the trunk and extremities. RESULTS: Histologic examination of the skin lesions revealed a deep dermal and subcutaneous nodular mononuclear infiltrate composed primarily of polyclonal plasmacytoid cells without atypia and an increased vascular proliferation. Additional studies including a bone marrow and lymph node biopsy, serum and urine protein electrophoresis, and computed tomography scans supported the diagnosis of multicentric plasma cell variant of CD with an associated autoimmune paraneoplastic hemolytic anemia. CONCLUSION: Cutaneous involvement in CD is part of the multicentric nature and should be considered in the differential diagnosis of a polyclonal plasma cell-rich lymphoproliferative disorder associated with paraneoplastic autoimmune disease.


Assuntos
Hiperplasia do Linfonodo Gigante/complicações , Síndromes Paraneoplásicas/etiologia , Plasmócitos/patologia , Dermatopatias/etiologia , Dermatopatias/patologia , Adulto , Anemia Hemolítica/etiologia , Hiperplasia do Linfonodo Gigante/fisiopatologia , Diagnóstico Diferencial , Feminino , Humanos , Síndromes Paraneoplásicas/patologia
15.
Psychosoc Med ; 1: Doc02, 2004 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-19742057

RESUMO

A model calculation was used to assess whether the G-DRG version 1.0 sufficiently represents integrated internal psychosomatic treatment of patients with psychosomatic disorders in relation to diagnosis and resource consumption. The DRGs of the Major Diagnostic Category "Mental Diseases" of the German DRG calculation sample 1.0 (diagnoses, procedures, cost weights) were analyzed. In a division of psychosomatic medicine within a general internal department, proceeds regarding 241 patients treated between 01 Jan and 31 Dec 2002, calculated according to the G-DRG version 1.0, were compared to the costs accrued. The G-DRG version 1.0 includes 7 DRGs of psychosomatic disorders in internal medicine (excluding disorders due to substance abuse). Assuming a base rate of euro 2,900, the total proceeds of the G-DRG Version 1.0 exceeded the costs (+ euro 57,971 /year).

16.
Am J Surg Pathol ; 27(6): 786-9, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12766582

RESUMO

The distinction of involvement of adenomyosis by endometrial carcinoma from endometrial carcinoma invading the myometrium can at times be difficult. This distinction, however, is important from the standpoint of staging, treatment, and prognosis because the outcome of carcinoma invading the myometrium as compared with involving adenomyosis is significantly worse. CD10 has been recently reported to be expressed by normal and neoplastic endometrial stromal cells. We therefore hypothesized that CD10 may be helpful in distinguishing carcinoma within adenomyosis from endometrial carcinoma directly invading the myometrium. Twenty-two cases of invasive endometrioid adenocarcinoma were identified from the surgical pathology files of the Johns Hopkins Hospital and consultation files of one of the authors (R.J.K.) and immunostained for CD10, desmin, and caldesmon. The pattern of staining was compared with five cases in which carcinoma was confined to adenomyosis. As a control, 14 cases of adenomyosis unassociated with carcinoma were included in the analysis. All 22 endometrial carcinomas that invaded the myometrium expressed CD10 to some extent in cells immediately surrounding the neoplastic glands. In 18, all of the invasive nests displayed CD10 in surrounding cells, but in four cases the staining was patchier, involving the surrounding cells of approximately 50-75% of the invasive nests. In four cases of myoinvasive carcinoma, the CD10-positive cells surrounding the nests of invasive carcinoma were also positive for desmin and caldesmon. In the remaining 18 cases with myoinvasive carcinoma, the cells surrounding the carcinomas failed to react with desmin and caldesmon. All five endometrial carcinomas involving adenomyosis displayed CD10 positivity in what appeared to be endometrial stromal cells surrounding the neoplastic glands. The stromal cells were negative for desmin and caldesmon. The control cases of adenomyosis were all positive for CD10, although in four cases the staining was patchy compared with 10 cases in which it was diffuse. Desmin and caldesmon were negative in all of these cases. Although CD10 identifies endometrial stromal cells in the endometrium and in adenomyosis and endometriosis, this study demonstrates that CD10 does not aid in distinguishing myometrial invasion of endometrial carcinoma from involvement of adenomyosis by endometrial carcinoma because the cells surrounding the tumor in the myoinvasive group express CD10.


Assuntos
Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Endometriose/patologia , Miométrio/patologia , Neprilisina/metabolismo , Proteínas de Ligação a Calmodulina/metabolismo , Desmina/metabolismo , Diagnóstico Diferencial , Endometriose/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Miométrio/metabolismo , Invasividade Neoplásica
17.
Int J Gynecol Pathol ; 22(2): 181-4, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12649674

RESUMO

c-kit is a proto-oncogene that codes for a transmembrane tyrosine kinase receptor (CD117). The gene product KIT is constitutively overexpressed in mastocytosis and gastrointestinal stromal tumors. Recently the use of the tyrosine kinase inhibitors, such as STI-571, has resulted in the successful treatment of bcr-abl-positive leukemias and gastrointestinal stromal tumors. In gastrointestinal stromal tumors, immunostaining for c-kit is diffusely positive. Because the expression of c-kit in mesenchymal tumors of the uterus and ovary has not been previously studied, we evaluated its expression in 38 of these tumors by immunohistochemistry. The number of positive labeled/total tumors were as follows: 0/8 malignant mullerian mixed tumors, 4/7 ovarian fibrosarcomas, 0/1 clear-cell ovarian sarcoma, 0/4 uterine leiomyosarcomas, 1/10 low-grade endometrial stromal sarcomas, 0/2 high-grade endometrial stromal sarcomas, and 3/6 endometrial stromal nodules. In all positive cases, no more than 5% of the cells were labeled. In conclusion, unlike gastrointestinal stromal tumors, mesenchymal tumors of the uterus and ovary rarely express c-kit. Therefore, it is unlikely that patients with these tumors will benefit from treatment with the currently available tyrosine kinase inhibitors.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas c-kit/biossíntese , Neoplasias Uterinas/metabolismo , Feminino , Fibrossarcoma/metabolismo , Fibrossarcoma/patologia , Humanos , Imuno-Histoquímica , Leiomiossarcoma/metabolismo , Leiomiossarcoma/patologia , Mesoderma/patologia , Tumor Mulleriano Misto/metabolismo , Tumor Mulleriano Misto/patologia , Neoplasias Ovarianas/patologia , Proto-Oncogene Mas , Sarcoma de Células Claras/metabolismo , Sarcoma de Células Claras/patologia , Sarcoma do Estroma Endometrial/metabolismo , Sarcoma do Estroma Endometrial/patologia , Neoplasias Uterinas/patologia
18.
Mod Pathol ; 15(4): 441-7, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11950919

RESUMO

A growing body of morphological, clinical, and genetic observations suggests a progression model for pancreatic ductal adenocarcinoma. In this model, pancreatic ducts progress through a series of architectural and cytological changes that define degrees of pancreatic intraepithelial neoplasia (PanIN). Expressed in dividing cells, Ki-67 has been extensively used as a proliferation marker. Its expression in different grades of PanIN has not been well studied. A total of 76 PanINs from 41 patients were histologically graded according to recently established criteria. These PanINs were then immunolabeled with a monoclonal antibody against Ki-67 (Mib-1). Normal ducts and invasive ductal adenocarcinomas were also labeled with the antibody. In 15 normal ducts, only 0.41% of the epithelial cells expressed Ki-67. Ki-67-labeling indices in the increasing grades of PanIN were as follows: PanIN-1A, 0.69%; PanIN-1B, 2.33%; PanIN-2, 14.08%; and PanIN-3, 22.01%. Fifteen invasive ductal adenonocarcinomas showed an average labeling index of 36.99%. The difference in Ki-67 labeling among these groups was statistically significant (P <.0005, Kruskal-Wallis test). This pattern of proliferation provides additional evidence supporting the recently proposed pancreatic progression model. It also correlates well with known molecular changes, such as activating point mutations in the K-ras oncogene and the loss of DPC4 and p16 gene expression. Ki-67 staining may be useful as an adjunct in the diagnosis of precancerous lesions in the pancreas and may provide a reliable way to identify lesions at high risk for the subsequent development of infiltrating carcinoma.


Assuntos
Antígeno Ki-67/análise , Neoplasias Pancreáticas/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Progressão da Doença , Humanos , Imuno-Histoquímica , Modelos Biológicos , Ductos Pancreáticos/química , Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/metabolismo
19.
Med Ges Gesch ; 21: 63-90, 2002.
Artigo em Alemão | MEDLINE | ID: mdl-13677351

RESUMO

In the course of the nineteenth century, Saarbruck developed from a small provincial town to the centre of a large region rapidly becoming industrialised. The traditional civil hospital underwent a fundamental change: from a residence for the old, the poor, and the neglected it became a modern hospital intended to restore health and fitness to the growing number of young working people in the region. To help the hospital meet its new aims, Reverend Fliedner of the Protestant Deaconesses' Institution in Kaiserswerth on the Rhine sent two young deaconesses to the hospital in Saarbruck. Expecting to work as a nurse and housekeeper, the two inexperienced and under-trained women were virtually overwhelmed by what they encountered. Their work required very hard physical work, with very little or no assistance. This study is based on the series of letters of appeal the deaconesses sent to Kaiserswerth, which depict in great detail the conditions of the hospital during the transition period. Different groups of inmates can be distinguished: old and poor patients representing hospital's traditional function; journeymen and domestic servants who are far from home and no longer under their employers' care, and miners with rather severe injuries. Miners constitute the prototype of the new industrial working class, as the mining industry was by far the most important sector of the developing economy. All groups benefited from the deaconesses' zeal to establish new standards of cleanliness and nutrition, not to mention the beginning of professional medical care. On the other hand, they have to submit to middle class expectations and behaviour. For instance, heman miners were expected to follow orders from female nurses, and domestic servants afflicted with scabies or venereal disease were expected to adopt new standards of moral and orderly demeanour. Resistance was mainly passive, consisting of paying lip service to the rules, taking small liberties, and reverting to the old style after dismissal. Conflicts arose only in certain situations injured Catholic miners, or when patients clung obstinately to their liquor. On the whole, the hospital functioned quite smoothly, at least after the initial difficulties were overcome and the deaconesses gained experience and self-confidence.


Assuntos
Hospitais Urbanos/história , Manuscritos como Assunto/história , Relações Enfermeiro-Paciente , Enfermeiras e Enfermeiros , Protestantismo/história , Alemanha , História do Século XIX
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