RESUMO
In common variable immunodeficiency (CVID) defects in early stages of B-cell development, bone marrow (BM) plasma cells and T lymphocytes have not been studied systematically. Here we report the first morphologic and flow cytometric study of B- and T-cell populations in CVID BM biopsies and aspirates. Whereas the hematopoietic compartment showed no major lineage abnormalities, analysis of the lymphoid compartment exhibited major pathologic alterations. In 94% of the patients, BM plasma cells were either absent or significantly reduced and correlated with serum immunoglobulin G levels. Biopsies from CVID patients had significantly more diffuse and nodular CD3(+) T lymphocyte infiltrates than biopsies from controls. These infiltrates correlated with autoimmune cytopenia but not with other clinical symptoms or with disease duration and peripheral B-cell counts. Nodular T-cell infiltrates correlated significantly with circulating CD4(+)CD45R0(+) memory T cells, elevated soluble IL2-receptor and neopterin serum levels indicating an activated T-cell compartment in most patients. Nine of 25 patients had a partial block in B-cell development at the pre-B-I to pre-B-II stage. Because the developmental block correlates with lower transitional and mature B-cell counts in the periphery, we propose that these patients might form a new subgroup of CVID patients.
Assuntos
Linfócitos B/patologia , Células da Medula Óssea/patologia , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/patologia , Linfócitos T/patologia , Adolescente , Adulto , Idoso , Biópsia , Estudos de Coortes , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Endothelial nitric oxide synthase (eNOS) is essential for neovascularization. Here we show that the impaired neovascularization in mice lacking eNOS is related to a defect in progenitor cell mobilization. Mice deficient in eNOS (Nos3(-/-)) show reduced vascular endothelial growth factor (VEGF)-induced mobilization of endothelial progenitor cells (EPCs) and increased mortality after myelosuppression. Intravenous infusion of wild-type progenitor cells, but not bone marrow transplantation, rescued the defective neovascularization of Nos3(-/-) mice in a model of hind-limb ischemia, suggesting that progenitor mobilization from the bone marrow is impaired in Nos3(-/-) mice. Mechanistically, matrix metalloproteinase-9 (MMP-9), which is required for stem cell mobilization, was reduced in the bone marrow of Nos3(-/-) mice. These findings indicate that eNOS expressed by bone marrow stromal cells influences recruitment of stem and progenitor cells. This may contribute to impaired regeneration processes in ischemic heart disease patients, who are characterized by a reduced systemic NO bioactivity.
Assuntos
Neovascularização Fisiológica/fisiologia , Óxido Nítrico Sintase/fisiologia , Células-Tronco/fisiologia , Animais , Precursores Enzimáticos/metabolismo , Gelatinases/metabolismo , Isquemia/terapia , Metaloendopeptidases/metabolismo , Camundongos , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo IIIRESUMO
The detection of clonality in lymphomas was recently improved by the BIOMED-2 approach, but analysis of fixed tissues is limited. Here, we adapted the BIOMED-2 protocol for examining immunoglobulin H (IgH) receptor rearrangements in fixed, decalcified bone marrow biopsies (BMBs) for clonality analysis in B-cell non-Hodgkin's lymphomas (B-NHL). The study included 111 decalcified BMBs (12 formalin fixed and 99 glutardialdehyde fixed), with B-NHL (n = 85), T-NHL (n = 8), or reactive infiltrates (n = 18). Initially, IgH FRIII polymerase chain reaction (PCR) analysis of crude DNA extracts from 75 glutardialdehyde-fixed BMBs (B-NHLs) using a standard seminested PCR resulted in clonal peaks in 46 of 75 (61.3%) BMBs compared with 19 of 70 (27.1%) for the original BIOMED-2 protocol. Modifications to both DNA extraction and PCR reaction improved the detection rate to 26 of 36 (72.2%) for BIOMED-2 primers, including 10 of 15 (66.7%) cases not detected by our standard IgH analysis. Moreover, introducing the same modifications for analysis of the FRII region by BIOMED-2 primers revealed clonal peaks in 19 of 36 (52.8%) B-NHLs compared with 5 of 70 (7.1%) for the original BIOMED-2 protocol. Together, analysis of FRII and FRIII regions by the modified BIOMED-2 protocol increased the detection rate to 31 of 36 (86.1%), particularly for BMBs with histological evidence of follicular lymphoma (FRIII, 70%; FRII, 90%). In summary, this study provides an improved protocol for detection of clonality by IgH-specific BIOMED-2 primers in fixed, decalcified bone marrow biopsies.
Assuntos
Medula Óssea/patologia , Primers do DNA/genética , Rearranjo Gênico de Cadeia Pesada de Linfócito B/genética , Genes de Cadeia Pesada de Imunoglobulina/genética , Linfoma de Células B/genética , Linfoma de Células B/patologia , Reação em Cadeia da Polimerase/métodos , Biópsia , Extratos Celulares , Células Clonais/patologia , DNA/genética , DNA/isolamento & purificação , Técnica de Descalcificação , Análise Heteroduplex , Humanos , Sensibilidade e Especificidade , Análise de Sequência de DNA , Fixação de TecidosRESUMO
OBJECTIVE: The bacteria Bartonella henselae has been known as the principal causative agent of cat-scratch disease (CSD) since 1992. It is an important cause of infectious lymphadenopathies in the head and neck. Nevertheless, CSD often remains unrecognized in cases of cervicofacial lymph node enlargement. STUDY DESIGN: Between January 1997 and May 2003, we conducted a prospective clinical study including 721 patients with primarily unclear masses in the head and neck. RESULTS: CSD was diagnosed by serology and molecular investigations in 99 patients (13.7%; median age 33 years). Cervicofacial lymphadenopathy was the most common manifestation. Atypical manifestation of CSD including Parinaud's oculoglandular syndrome, swelling of the parotid gland and erythema nodosum were diagnosed in 8.1%, 8.1%, and 2.0% of cases, respectively. CONCLUSIONS: Our results demonstrate that CSD is a major cause of enlarged cervicofacial lymph nodes and should therefore be included in the differential diagnosis of lymphadenopathy in the head and neck region.
Assuntos
Doença da Arranhadura de Gato/complicações , Otorrinolaringopatias/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Arranhadura de Gato/diagnóstico , Doença da Arranhadura de Gato/tratamento farmacológico , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: To study the clinical course and outcome of deep neck infections (DNI), with special emphasis on microbiology and histopathology. STUDY DESIGN: Two hundred thirty-four patients with DNIs were included in this study. Patients with peritonsillar or dental infections, infections arising from salivary glands, as well as subjects with abscesses caused by neck trauma were excluded. METHODS: Clinical analysis of all patients with DNIs who were treated between January 1, 1997 and May 31, 2005 in a single center. RESULTS: In 13 patients, the DNI was the first manifestation of a malignant tumor. In 17 cases, the DNI was associated with cat-scratch disease (CSD). Six patients suffered from tuberculosis, and in another 7, an infected lateral cleft cyst was found. In 176 patients, the origin of DNI remained unclear. CONCLUSIONS: Our results demonstrate that CSD, tuberculosis, and malignant tumors must be considered as possible causes of DNIs. The current study represents one of the largest series of DNIs in the modern medical literature. EBM RATING: C.
Assuntos
Infecções Bacterianas/epidemiologia , Infecções Bacterianas/terapia , Abscesso Peritonsilar/epidemiologia , Abscesso Peritonsilar/terapia , Abscesso Retrofaríngeo/epidemiologia , Abscesso Retrofaríngeo/terapia , Adulto , Distribuição por Idade , Idoso , Antibacterianos/uso terapêutico , Infecções Bacterianas/microbiologia , Estudos de Coortes , Terapia Combinada , Feminino , Alemanha/epidemiologia , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Abscesso Peritonsilar/diagnóstico , Prognóstico , Abscesso Retrofaríngeo/diagnóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Procedimentos Cirúrgicos Operatórios/métodos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Bartonella henselae is the causative agent of cat-scratch disease (CSD), which usually manifests as acute regional lymphadenopathy. The causes of cervical lymphadenopathy, with special regard to CSD, were investigated in a study of 454 patients who presented with unclear masses in the head and neck from January 1997 through January 2001. Sixty-one patients (13.4%) experienced CSD; 54 (11.9%) had primary lymphadenopathy due to other infectious agents, and 41 (9.0%) had lymphadenopathy that occurred in association with primary infections of other organs. For 171 patients (37.7%), the cause of the cervical lymph node enlargement could not be found. B. henselae DNA was detected in extirpated lymph nodes only during the first 6 weeks of lymphadenopathy, which indicates that the results of polymerase chain reaction strongly depend on the duration of illness. CSD should be included in the differential diagnosis of adenopathy in the otorhinolaryngologic patient population, to avoid unnecessary treatment.
Assuntos
Bartonella henselae , Doença da Arranhadura de Gato/complicações , Doenças Linfáticas/etiologia , Antibacterianos/uso terapêutico , Bartonella henselae/genética , Doença da Arranhadura de Gato/tratamento farmacológico , Doença da Arranhadura de Gato/imunologia , Doença da Arranhadura de Gato/microbiologia , DNA Bacteriano/análise , Cabeça , Humanos , Doenças Linfáticas/tratamento farmacológico , Doenças Linfáticas/imunologia , Doenças Linfáticas/microbiologia , PescoçoRESUMO
BACKGROUND: 18F-FDG positron emission tomography (PET) may alter therapeutic management of patients with cervical cancer because 18F-FDG-positive pelvic and para-aortic lymph nodes are associated with lower progression-free survival and vice versa. However, the accuracy of 18F-FDG PET might be impaired by a preceding lymphangiography (LAG). MATERIALS AND METHODS: LAG, magnetic resonance (MR)-imaging and 18F-FDG PET were performed in 6 patients with cervical cancer stage FIGO IB and II. All patients were scheduled for radical hysterectomy and pelvic and para-aortic lymphadenectomy. The results of LAG, MR-imaging and 18F-FDG PET were compared with histological findings. RESULTS: 18F-FDG PET showed false-positive foci in both patients who had LAG before PET-study but not in 4 patients who had LAG thereafter. Histology confirmed false-positive 18F-FDG accumulation in lymphnodes to be consistent with granulomateous changes as induced by foregoing LAG. CONCLUSION: Whenever 18F-FDG PET and LAG are performed in the same patient to assess the extent of lymph-node metastases, LAG should always be done after the 18F-FDG PET study to obviate false-positive results.
Assuntos
Fluordesoxiglucose F18 , Linfografia/efeitos adversos , Compostos Radiofarmacêuticos , Neoplasias do Colo do Útero/diagnóstico por imagem , Adulto , Idoso , Reações Falso-Positivas , Feminino , Radioisótopos de Flúor , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada de EmissãoRESUMO
Localized amyloidosis of the larynx is uncommon, accounting for fewer than 1% of all benign laryngeal tumors. We report 2 cases of laryngeal amyloidosis in which dense plasma cell infiltrates were found in the vicinity of the amyloid deposits; in view of this finding, we suspected a hematologic disease--plasmacytoma in particular: However, molecular genetic analysis did not demonstrate any light-chain restriction, indicating that the plasma cells were of polyclonal origin and therefore consistent with chronic inflammation. We also discuss the available literature with respect to diagnostic and therapeutic procedures in patients with amyloidosis of the upper airway.
Assuntos
Amiloide/biossíntese , Amiloidose/diagnóstico , Neoplasias Laríngeas/diagnóstico , Plasmócitos , Idoso , Amiloide/química , Amiloide/classificação , Amiloidose/patologia , Amiloidose/cirurgia , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Inflamação , Neoplasias Laríngeas/cirurgia , Laringoscopia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Unclear cervicofacial masses are common presentations that often require tissue sampling to guide therapy. While open biopsy is invasive, fine-needle aspiration cytology includes a high rate of nondiagnostic samples. METHODS: A retrospective analysis on 181 core-needle biopsies in 88 patients was performed to determine the diagnostic efficacy of ultrasound-guided core-needle biopsies in the head and neck. RESULTS: We experienced 100% success in obtaining high-quality histopathologic specimens. The target tissue was correctly sampled in 80 of 88 patients. In these patients the sensitivity, specificity, and accuracy rate of core-needle biopsies in differentiating benign from malignant cervicofacial lesions was 98.1%, 100%, and 98.8%, respectively. CONCLUSIONS: Ultrasound-guided core-needle biopsies can be recommended as a safe and reliable technique in the diagnosis of cervicofacial masses with a high diagnostic yield. It obtains tissue samples of high quality and represents a sufficient alternative to open biopsy even in the diagnosis of lymphoma.