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Objective: To investigate the rationality of nerve-plane sparing radical hysterectomy (NPSRH) for cervical cancer by observing the anatomical and histological characteristics of pelvic autonomic plane based on fresh cadaver. Methods: From October 2015 to September 2020, 14 fresh female cadavers were anatomically and histologically studied in the Laboratory of Anatomy and Embryology Department, Peking Union Medical College, Chinese Academy of Medical Sciences. The median age of the specimens was 79 years (range: 67 to 92 years). Twenty-eight hemi-pelvic specimens were obtained from 14 fresh female cadavers. NPSRH procedures were simulated in 8 hemi-pelvic cavities to prove its feasibility. Detailed dissection was conducted to recognize nerve plane and to observe the distribution of pelvic nerves in 10 hemipelvis. In the other 10 hemipelvis, whole parametrium tissue was taken from the crossing of ureter and the uterine artery to the ureterovesical entrance and be embedded, then continuous section was performed, and was stained by hematoxylin-eosin staining (HE) to observe the relationship of nerves and vessels. Immunohistochemical staining of S100, tyrosine dehydrogenase (TH), and vasoactive intestinal peptide (VIP) were performed to count and distinguish sympathetic and parasympathetic nerves, respectively. Results: (1) The pelvic autonomic nerve-plane was completely preserved in 7 of 8 hemipelvis by simulating NPSRH. (2) After detailed dissection in 10 hemipelvis, it was found that hypogastric nerve, pelvic splanchnic nerve, and their confluence of inferior hypogastric plexus were distributed in a planar statelocating in the ureteral mesentery and its caudal extension. This nerve plane showed a cross relationship with deep uterine vein and its branches. The bladder branches and vesical venous plexus were closely related to the inferior hypogastric plexus. The middle vesical vein and inferior vesical vein were intact in 7 of 10 hemipelvis, and either vesical vein was missing in 3 of them. It was observed that the vesical venous plexus communicated with the deep uterine vein trunk on the medial side of the nerve plane in 6 hemipelvis, while flowed into the deep uterine vein on the lateral side of the nerve plane in 2 hemipelvis, and in the other 2 hemipelvis it directly flowed into the internal iliac vein. (3) It was revealed that autonomic nerves were continuously distributed beneath the ureteral with sagittal plane by HE staining. The average nerve content below the ureteral width was 70.9% of the total in nerve plane by S100 staining. TH and VIP staining showed that the average number of sympathetic fibers was 13.5 and parasympathetic fibers was 8.2, reminding sympathetic predominated. Conclusion: Pelvic autonomic nerves are mainly distributed within the mesangial plane below the ureter, which provides an anatomic justification for NPSRH.
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Plexo Hipogástrico , Pelve , Idoso , Idoso de 80 Anos ou mais , Vias Autônomas/anatomia & histologia , Cadáver , Feminino , Humanos , Plexo Hipogástrico/anatomia & histologia , Histerectomia/métodosRESUMO
Objective: To evaluate the security and clinical outcomes of open nerve-plane sparing radical hysterectomy (NPSRH) for operable locally advanced cervical cancer, compared with conventional radical hysterectomy (CRH). Methods: All 389 cases with International Federation of Gynecology and Obstetrics (FIGO, 2009) stage â b2 and â ¡a2 cervical cancer were retrospectively analyzed in Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences between January 2008 and December 2014. Of all the patients, 69 cases underwent laparotomic NPSRH, and other 320 cases underwent CRH. Patients' general characteristics and intraoperative parameters were evaluated between the two groups. Basic clinical and pathological informations between the two groups were matched. After median 82 months' follow-up,disease-free survival (DFS), overall survival (OS), and postoperative recovery of bladder function were compared between the two groups. Results: (1) Compared to CRH group, NPSRH group had less intraoperative bleeding [(366±302) vs (457±301) ml; t=2.305, P=0.022], and a little bit longer operation time [(262±51) vs (245±52) minutes; t=2.621, P=0.009]. (2) Compared to CRH group, NPSRH group had shorter duration of urethral catheterization [(11±9) vs (16±7) days; t=3.906, P<0.01], and better postoperative bladder sensation and function in one year (6.1% vs 16.0%; χ2=4.418, P=0.036). (3) The 5-year DFS rate and 5-year OS rate of all patients were 89.6% and 89.9%, respectively. Either preserving pelvic autonomic nerves or not had little effect on the 5-year DFS rate (NPSRH vs CRH: 90.9% vs 89.4%; P=0.714) or on 5-year OS rate (NPSRH vs CRH: 90.0% vs 89.9%; P=0.910) for locally advanced cervical cancer. Univariate analysis showed that lymphatic vascular space infiltration (LVSI) and pelvic lymphatic metastasis were significantly correlated with prognosis (P<0.05). Multivariate analysis showed that pelvic lymphatic metastasis was the independent prognostic factor of 5-year DFS rate (HR=1.31, 95%CI: 1.01-1.68, P=0.040) as well as 5-year OS rate (HR=1.30, 95%CI: 1.01-1.67, P=0.046) for locally advanced cervical cancer. Conclusion: Open NPSRH is feasible for patients with locally advanced cervical cancer, which could improve both short-term and long-term bladder function, and is not a risk factor for the prognosis of patients.
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Histerectomia/métodos , Neoplasias do Colo do Útero/cirurgia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologiaRESUMO
Objective: To compare the clinical effects and the subjective perception of surgeons with three-dimensional (3D) and two-dimensional (2D) laparoscopic C1 radical hysterectomy surgeries for cervical cancer. Methods: The retrospective cohort study was conducted. The clinicopathological data of 101 patients with cervical cancer who received C1 laparoscopic radical hysterectomy (C1-LRH) surgery from June 2015 to August 2017 were collected. Of all patients, 42 cases undergoing 3D laparoscopic surgery and 59 cases undergoing 2D laparoscopic surgery were respectively allocated into the C1-3DLRH group or C1-2DLRH group. The clinical effect and the subjective perception of surgeons were compared between the two groups. Results: (1) There was no significant difference between the C1-3DLRH group and C1-2DLRH group in terms of age, body mass index (BMI), International Federation of Gynecology and Obstetrics (FIGO) stage, pathologic type, etc. (all P>0.05). Compared with C1-2DLRH group, the operation time was significantly shortened [(192±54) vs (221±54) minutes, P<0.01], blood loss was significantly less [(102±88) vs (167±117) ml, P<0.01], and the success rate of inferior hypogastric plexus (IHP) bladder branch preservation was significantly increased [86% (36/42) vs 66% (39/59), P<0.05] in C1-3DLRH group. There were no significant difference in the number of lymph nodes, the incidence of operative complications, the infection rate, the time of catheterization and the length of hospitalization between the two groups (all P>0.05). The long-term bladder function was evaluated at the twelfth month after operation, 39 patients in the C1-3DLRH group and 53 patients in the C1-2DLRH group were completed the survey. The results showed that 13% (5/39) of the patients in the C1-3DLRH group had long-term bladder dysfunction, which was lower than that 21% (11/53) of the C1-2DLRH group, but there was no significant difference between the two groups (χ(2)=0.980, P=0.322). (2) A total of 251 laparoscopic surgeons questionnaires were eligible. The incidence of side effects in the first and second generation of 3D and 2D laparoscopic surgeons was 20.4% (10/49), 6.9% (6/87) and 3.5% (4/115), respectively. The incidence of side effects in the first generation of 3D laparoscopic surgeons was higher than that in the second generation of 3D (χ(2)=5.463, P=0.019) and 2D laparoscopic surgeons (χ(2)=12.475, P<0.01). There was no difference between the second generation of 3D and 2D laparoscopic surgeons (χ(2)=1.208, P=0.272). Conclusions: 3D laparoscopy is advantageous to the preservation of autonomic nerve in C1-LRH operation and may improve the quality of operation compared with 2D laparoscopy. The second generation of 3D laparoscopic device might overcome the side effects of the surgeons.
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Histerectomia/métodos , Laparoscopia/métodos , Neoplasias do Colo do Útero/cirurgia , Feminino , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico por imagemRESUMO
PURPOSE: Somatostatin analogs (SSAs) are considered one of the most effective medical treatments for patients with growth hormone-secreting pituitary adenomas (GH-PAs). The postoperative electron microscopy (EM) pathological subtype and SSTR2 expression in the tumor are the most established predictors of patient response to SSA therapy. The aim of this study was to evaluate how will magnetic resonance spectroscopy (MRS) measurements before surgery predict the EM pathological subtypes and SSTR2 expression of tumors, and thereby serve as an indicator for the therapeutic sensitivity to SSAs of patients with GH-PAs. METHODS: Eighteen patients with GH pituitary macroadenomas who underwent transsphenoidal surgery were included in this retrospective study. The preoperative MRS data and T2 signal intensity were obtained from patients by 1.5 T MR spectroscopy of the sellar mass. The EM pathological subtypes of tumors were determined after surgery through examination of cell granulations. The expressions of somatostatin receptor 2 (SSTR2), SSTR5, P21, P27, and Ki-67 were evaluated by immunohistochemistry. RESULTS: The MRS parameters that were found to significantly predict the EM pathological subtypes of tumors, as calculated by the receiver operating characteristic curve, were the choline (Ch) value at 3140.5 MR units (sensitivity 69.2%, specificity 100%) and the choline/creatine (Ch/Cr) ratio at 1.27 (sensitivity 92.3%, specificity 100%). Further, the Ch/Cr ratio, but not other MRS data, was shown to negatively correlate with the expression of SSTR2 (P = 0.02). The Ch/Cr ratio was also found to positively correlate with the Ki-67 value (P < 0.05) and T2 signal (P < 0.05), but not with other factors that were examined in this study. Moreover, the Ch/Cr ratio could predict the EM pathological subtypes of tumors with an accuracy of 83.3% (5/6) for patients with an isointense T2 signal. CONCLUSION: The Ch/Cr ratio by MRS could effectively predict the tumor subtype and was significantly correlated with the expression of SSTR2, which was consistent with other predictors. It was also able to distinguish the patients with isointense T2 signals. Our results provide a potentially new and non-invasive method to predict the response to SSAs in patients with GH pituitary macroadenomas.
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Adenoma/patologia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Antagonistas de Hormônios/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Cuidados Pré-Operatórios , Receptores de Somatostatina/metabolismo , Somatostatina/análogos & derivados , Adenoma/tratamento farmacológico , Adenoma/metabolismo , Adenoma/cirurgia , Adulto , Idoso , Biomarcadores/análise , Feminino , Seguimentos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/tratamento farmacológico , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: The hematologic response is critical in patients with light chain amyloidosis because a good response is known to improve organ response and overall survival. We present a retrospective analysis to compare the hematologic and organ response in patients who received bortezomib-based therapy before autologous stem cell transplantation (ASCT) versus those who received non-bortezomib-based therapy before ASCT and those who underwent ASCT at diagnosis. PATIENTS AND METHODS: Of a total of 63 patients who underwent ASCT for light chain amyloidosis, 34 received bortezomib-based therapy before ASCT (Bor-ASCT) and 29 did not receive bortezomib therapy (non-Bor-ASCT). A greater number of patients had involvement of ≥ 3 organs and cardiac involvement in the Bor-ASCT group, suggesting a greater risk at baseline in the Bor-ASCT group. RESULTS: At 3, 6, and 12 months after ASCT, the hematologic response was better in the Bor-ASCT group, with a statistically significance difference at 6 months (partial response or better in 82% vs. 20%; P = .002) and 12 months (partial response or better in 76% vs. 33%; P = .02). Organ responses (66% vs. 21%; P < .001) and median overall survival (not reached vs. 53 months; P = .001) were also greater in the Bor-ASCT group. CONCLUSION: Our study has shown that bortezomib-based therapy before ASCT improves the hematologic response, organ response and overall survival, potentially by decreasing the light chain load before ASCT.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the relationship between Ras association domain family gene 10 (RASSF10 gene) and the biological behavior of hepatocellular carcinoma (HCC), including proliferation, invasion, and metastasis. MATERIALS AND METHODS: HCC cell lines were generated with stable overexpression or low expression of RASSF10 protein. A cell line transfected with an empty vector was treated as control. At 12, 24, 48, and 72 h, the cell proliferation was determined by MTT assay, the invasion ability was determined by Transwell chambers, and the scratch assay was used to assess the migration ability. Additionally, cell lines were injected subcutaneously in the axillary fossa of nude mice aged 5-6 weeks. Tumors were measured weekly for 6 consecutive weeks to observe tumor volume, tumor growth rate, weight, and tumor metastasis in nude mice of the different groups. RESULTS: In both the control group and low expression group, cell proliferation rates, cell invasion, and migration abilities, increased over time but decreased over time in the overexpression group. At each time point, data in the overexpression group were markedly lower than those in the control group, and highest in the low expression group. The differences were statistically significant (p<0.05). In both control group and low expression group, tumor volume, tumor growth rate, weight, and tumor metastasis number were increased in nude mice over time, while they decreased in the overexpression group (except for tumor metastasis number). At each time point, data in the overexpression group were markedly lower than in the control group, and highest in the low expression group. The differences were statistically significant (p<0.05). CONCLUSIONS: Like a tumor suppressor gene, RASSF10 can inhibit the proliferation, invasion, and migration of HCC cells.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Supressoras de Tumor/genética , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transfecção , Carga TumoralRESUMO
INTRODUCTION: The aim of this study was to determine the role of Prognostic Nutritional Index in predicting gastric cancer. EVIDENCE ACQUISITION: Studies were searched in PubMed, EMBASE and ISI Web of Science. The hazard ratios and 95% confidence interval for survival estimate were extracted from the articles and the pooled HR was computed. EVIDENCE SYNTHESIS: Nine studies with 3203 participants met the inclusion criteria. Low PNI was associated with poor overall survival (pooled HR 1.92, 95% CI: 1.68-2.19). CONCLUSIONS: Prognostic Nutritional Index was an effective indicator for the prognosis of gastric cancer.
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Avaliação Nutricional , Neoplasias Gástricas/mortalidade , Humanos , Prognóstico , Taxa de SobrevidaRESUMO
OBJECTIVE: To investigate the expression of elongation of very long-chain fatty acids family member 6 (ELOVL6) in high-grade serous ovarian carcinoma (HSOC), and explore the correlation between its expression and clinical prognosis in these patients. METHODS: The expression of ELOVL6 at mRNA and protein levels were respectively detected by reverse transcription (RT)-PCR and immune histochemistry method in 12 cases with normal ovarian tissues and 172 cases with HSOC from primary tumor site, forty of which had paired peritoneal metastatic tissues. RESULTS: (1) The results tested by RT-PCR showed that ELOVL6 expression in normal ovarian tissue was 4.8±1.1, while 1.2±0.7 in primary tumors and 1.8±0.9 peritoneal metastatic sites in HSOC. Compared with normal ovarian tissue, the level of ELOVL6 mRNA was significantly lower in HSOC (P<0.05). There was no significant difference between primary and peritoneal metastatic sites in HSOC (P=0.610). It was shown that ELOVL6 protein localized in cytoplasm of ovarian cancer cell by immunostaining assay. (2) ELOVL6 expression was observed in all normal ovarian tissue, 70.2% of G1-G2 and 48.8% of G3 HSOC (P<0.05). ELOVL6 expression in drug-resistant group were significantly lower than that in non-resistant group (39.1% vs 65.0%, P<0.01). The median disease-free survival was 41 months in the ELOVL6-positive group and 39 months in ELOVL6-negative group (P>0.05). The total median survival was 52 months in ELOVL6-positive group and 44 months in ELOVL6-negative group (P>0.05). CONCLUSION: Low expression of ELOVL6 may correlate with the poor differentiation and drug resistance in HSOC.
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Acetiltransferases/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/metabolismo , RNA Mensageiro/genética , Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/genética , Intervalo Livre de Doença , Elongases de Ácidos Graxos , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Ovário/metabolismo , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Recent observations suggest a lower incidence of malignancies in patients infected with HIV during treatment with Highly Active Anti-Retroviral Therapy (HAART) utilizing protease inhibitors. We investigated the effects of ritonavir, a FDA approved HIV protease inhibitor, on proliferation of pancreatic ductal adeno-carcinoma (PDAC) cell lines. Human PDAC cell lines BxPC-3, MIA PaCa-2, and PANC-1 were propagated under standard conditions and treated with serial dilutions of ritonavir. Ritonavir inhibited cell growth in a dose-dependent manner as well as activated the intrinsic apoptotic pathway in human pancreatic ductal adenocarcinoma (PDAC) cell lines. We observed down-modulation of cell-cycle promoting and up-regulation of cell-cycle inhibitory genes; enhanced interaction of retinoblastoma protein (RB) with E2F-1 transcription factor; inhibition of phosphorylation of RB, resulting in sequestration of E2F-1 and subsequent down-regulation of S phase genes; decreased interaction of E2F-1 with its consensus binding sites; inhibition of cell motility and invasiveness; and inhibition of the AKT pathway. Our results demonstrate a potential use of ritonavir as part of combination chemotherapy for PDAC. Since ritonavir is FDA approved for HIV, drug repositioning for PDAC would limit the costs and reduce risks.
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Esophageal cancer is the sixth leading causes of cancer-related death in the world. It is suggested that beta-adrenoceptor is involved in the control of cell proliferation, but its role in the pathogenesis of esophageal cancer remains unknown. We therefore studied the role of beta-adrenergic signaling in the regulation of growth of an esophageal squamous-cell carcinoma cell line HKESC-1. Results showed that both beta(1)- and beta(2)-adrenoceptors were expressed in HKESC-1 cells. Stimulation of beta-adrenoceptors with epinephrine significantly increased HKESC-1 cell proliferation accompanied by elevation of intracellular cyclic AMP levels, which were abolished by beta(1)- or beta(2)-selective antagonists. Epinephrine also increased extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation as well as cyclooxygenase-2 (COX-2) and cytosolic phospholipase A(2) expression, which were blocked by beta(1)- or beta(2)-selective antagonists. Moreover, epinephrine increased cyclin D(1), cyclin E(2), cyclin-dependent kinase (CDK)-4, CDK-6, and E(2)F-1 expression and retinoblastoma protein phosphorylation at Ser807/811, all of which were abrogated by beta(1)-adrenoceptor antagonist. Furthermore, epinephrine increased the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1 and -2 in a beta(2)-adrenoceptor-, mitogen-activated protein kinase/ERK kinase (MEK)-, and COX-2-dependent manner. MEK or COX-2 inhibitor also significantly inhibited HKESC-1 cell proliferation induced by epinephrine. Collectively, we demonstrate that epinephrine stimulates esophageal squamous-cell carcinoma cell proliferation via beta-adrenoceptor-dependent transactivation of ERK/COX-2 pathway. Stimulation of beta(1)- and beta(2)-adrenoceptors also elicits a differential response on the expression of cell cycle regulators. These novel findings may shed new light on the understanding of beta-adrenergic signaling in the control of esophageal cancer cell growth.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Ciclo-Oxigenase 2/metabolismo , Epinefrina/farmacologia , Neoplasias Esofágicas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Receptores Adrenérgicos beta/metabolismo , Antagonistas Adrenérgicos beta/farmacologia , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , AMP Cíclico/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , Fosfolipases A2 do Grupo IV/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Receptores Adrenérgicos beta/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Proteína do Retinoblastoma/metabolismo , Ativação Transcricional/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Unchecked mitogenic signals due to the overexpression of epidermal growth factor (EGF) and its receptor (EGFR) is implicated in the promotion and progression of cancer. In addition, beta-adrenoceptor is involved in the control of cancer cell proliferation. This study sought to elucidate whether a functional connection exists between these two disparate receptor systems. EGF was used to stimulate HKESC-1 cells, an esophageal squamous cancer cell line, in which beta-adrenoceptor activity was monitored by measuring intracellular cAMP levels in the absence or presence of beta-adrenoceptor antagonists. Results showed that EGF significantly increased cAMP levels and cell proliferation, both of which were attenuated by atenolol [(+)-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]benzeneacetamide] or ICI 118,551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol], which are antagonists for the beta-adrenoceptor. Further mechanistic investigation revealed that the cellular release of epinephrine and the expression of its synthesizing enzyme tyrosine hydroxylase were induced by EGF. The expression of beta(1)-adrenoceptor and the downstream signal transducer protein kinase A were also up-regulated. In this connection, AG1478 [4-(3-chloroanilino)-6,7-dimethoxyquinazoline], an EGFR tyrosine kinase inhibitor, abrogated all these EGF-elicited alteration. Collectively, this study demonstrates that beta-adrenergic signaling could be up-regulated at multiple levels upon EGFR activation to mediate the mitogenic signals in esophageal cancer cells. This novel finding not only unveils the sinister liaison between EGFR and beta-adrenoceptors but also sheds new light on the purported therapeutic use of beta-adrenoceptor antagonists in the treatment of esophageal cancer.
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Proliferação de Células , Fator de Crescimento Epidérmico/farmacologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Receptores Adrenérgicos beta/genética , Receptores Adrenérgicos beta/metabolismo , Ativação Transcricional , Antagonistas Adrenérgicos beta/farmacologia , Atenolol/farmacologia , Proliferação de Células/efeitos dos fármacos , Fator de Crescimento Epidérmico/fisiologia , Neoplasias Esofágicas/genética , Humanos , Masculino , Pessoa de Meia-Idade , Propanolaminas/farmacologia , Receptores Adrenérgicos beta/biossíntese , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/fisiologia , Células Tumorais CultivadasRESUMO
While therapeutic plasma exchanges (TPEs) performed with 5% albumin are considered safe, concerns regarding venous access and hypocalcemic toxicity remain. We reviewed the frequency of complications during TPEs performed with 5% albumin supplemented with calcium gluconate and potassium chloride for a 5 year period in our institution. Eighty-four adult patients (46 males and 38 females) underwent 581 plasma exchanges during the study period. The most common indications were myasthenia gravis (37%), acute inflammatory demyelinating polyradiculoneuropathy (31%), and chronic inflammatory demyelinating polyneuropathy (13%). All procedures used 2.2% ACD-A delivered at a calculated average rate of 0.26 mg/kg/min, which led to a mean dose of citrate per TPE of 2.18 +/- 0.48 g or 27.8 +/- 5.24 mg/kg of body weight. Venous access difficulties occurred in 85 procedures (14.6%), but most TPEs were completed successfully. Hypotension and citrate toxicity were seen in <5% of the TPEs and were mostly reversible. Only 17 exchanges (3%) had to be aborted because of the loss of venous access (n = 9), hypocalcemic toxicity (n = 3), hypotension (n = 2), panic attacks (n = 2), and one atypical reaction due to the interaction with an angiotensin converting enzyme inhibitor. Comparison between pre- and post-TPE potassium levels showed a statistically significant mean decrease of 7%, from 4.1 mequiv/l to 3.8 mequiv/l (P < 0.0001). We attribute the low rate of hypocalcemia to our practice of adding calcium and potassium to the replacement fluid and suggest that this method could become standard of care.
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Gluconato de Cálcio/administração & dosagem , Hipocalcemia/prevenção & controle , Troca Plasmática/efeitos adversos , Adulto , Albuminas/administração & dosagem , Cloratos/administração & dosagem , Feminino , Síndrome de Guillain-Barré/terapia , Humanos , Hipocalcemia/tratamento farmacológico , Hipocalcemia/etiologia , Infusões Intravenosas , Masculino , Miastenia Gravis/terapia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Resultado do TratamentoRESUMO
Recombinant Sendai virus (SeV)-mediated gene transfer to differentiated airway epithelial cells has shown to be very efficient, because of its ability to overcome the intra- and extracellular barriers known to limit gene delivery. However, this virus is transmission competent and therefore unlikely to be suitable for use in clinical trials. A nontransmissible, replication-competent recombinant SeV has recently been developed by deleting the envelope Fusion (F) protein gene (SeV/DeltaF). Here we show that SeV/DeltaF is able to mediate beta-galactosidase reporter gene transfer to the respiratory tract of mice in vivo, as well as to human nasal epithelial cells in vitro. Further, in an ex vivo model of differentiated airway epithelium, SeV/DeltaF gene transfer was not importantly inhibited by native mucus. When compared to the transmission-competent SeV in vivo, no difference in gene expression was observed at the time of peak expression. The development of an F-defective nontransmissible SeV, which can still efficiently mediate gene transfer to the airway epithelium, represents the first important step towards the use of a cytoplasmic RNA viral vector in clinical trials of gene therapy.
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Fibrose Cística/terapia , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Mucosa Nasal/enzimologia , Vírus Sendai/genética , Transdução Genética/métodos , Adulto , Animais , Células Cultivadas , Feminino , Deleção de Genes , Expressão Gênica , Vetores Genéticos/genética , Humanos , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Muco , Ovinos , Traqueia/enzimologia , Proteínas do Envelope Viral/genética , beta-Galactosidase/genéticaRESUMO
Renal and perinephric abscess in children are uncommon. Three basic pathophysiologic mechanisms are involved, namely, hematogenous spread, ascending infection and contamination by proximity to an infected area. Six pediatric patients diagnosed with renal abscess were treated at our institution from 1990-2000. Five patients were females; ages ranged from 3-17 years (mean 11.8 years). Diagnosis, as expected, was not readily apparent at presentation. Computerized tomography and renal sonograms were the most useful imaging modalities. Gram-negative bacteria were commonly isolated; only one patient grew Staphylococcus aureus. All patients received broad-spectrum intravenous antibiotics. Additional treatments consisted of percutaneous drainage (4 patients), exploratory laparotomy (1 patient, for presumed Wilm's tumor) and nephrectomy (2 patients). A new classification of the etiologic mechanisms of this condition is proposed along with a simple and practical treatment algorithm.
Assuntos
Abscesso/fisiopatologia , Abscesso/terapia , Perinefrite/fisiopatologia , Perinefrite/terapia , Abscesso/microbiologia , Adolescente , Algoritmos , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Drenagem , Feminino , Humanos , Laparotomia , Masculino , Nefrectomia , Perinefrite/microbiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Photopheresis has been used in the management of rejection of heart and/or lung transplants. Although its mechanism of action remains unknown, irradiated T-helper cell-induced immunosuppression is the main theory. Since transplant recipients are often lymphopenic and lymphocytes are the target cells in phototherapy, we performed this study to determine which factors affect the cellular yield to undergo irradiation. We reviewed the records of all photophereses performed in our institution between July 1998 and April 2000 using the UVAR (first generation) or XTS (second generation) instruments (Therakos, Exton, PA). Our data included patient's blood volume, absolute lymphocyte count and hematocrit, catheter type, flow rate of collection cycles and centrifuge bowl size, as well as volume, hematocrit, and lymphocyte count of the cell suspension. With a mixed model multivariate analysis we sought to determine which variables predicted the lymphocyte yield. A total of 406 procedures in 25 adult patients was analyzed. There was no significant difference between the lymphocyte yield among the procedures performed with the first- and the second-generation instruments. The patient's absolute lymphocyte count was the only parameter, which positively correlated with the total number of lymphocytes collected for irradiation (P < 0.0001). Indeed, based on the mixed model, the total number of lymphocytes for irradiation can be predicted from the pre-procedure lymphocyte count. Additional studies are necessary to correlate the number of treated cells with patient outcome.
Assuntos
Rejeição de Enxerto/terapia , Transplante de Coração , Transplante de Coração-Pulmão , Terapia de Imunossupressão/métodos , Transplante de Pulmão , Fotoferese , Adulto , Idoso , Reagentes de Ligações Cruzadas/farmacologia , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Humanos , Leucaférese , Contagem de Linfócitos , Transfusão de Linfócitos , Linfócitos/efeitos dos fármacos , Linfócitos/efeitos da radiação , Masculino , Metoxaleno/farmacologia , Pessoa de Meia-Idade , Modelos Imunológicos , Fotoferese/instrumentação , Estudos Retrospectivos , Raios UltravioletaRESUMO
We report a case of acute renal failure due rhabdomyolysis as a result of the exaggerated lithotomy position during radical perineal prostatectomy. The pathogenesis, diagnosis, management, and preventive measures of acute renal failure associated with rhabdomyolysis are also reviewed.
Assuntos
Injúria Renal Aguda/etiologia , Prostatectomia/efeitos adversos , Rabdomiólise/etiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Postura , Prostatectomia/métodos , Neoplasias da Próstata/cirurgiaRESUMO
Recently it has been demonstrated that the guidance of retinal ganglion cell (rgc) axons through the optic disc is dependent on the DCC/netrin-1 axonal guidance system. To gain further insight into the function of the netrin receptors, DCC and Neogenin, in retinal development we have studied the expression patterns of these receptors in the embryonic mouse retina. Neogenin mRNA was restricted to a single neural cell type, the rgc. However, strong Neogenin mRNA expression was observed in the extending fiber cells of the developing lens suggesting a role for Neogenin in the migration events shaping the early lens. Our studies demonstrated that DCC mRNA was expressed at high levels in chains of closely opposed neurons as they migrated towards the emerging mantle layer in the early retina (E12.5-E13.5) suggesting a role for DCC in the migration of neurons out of the ventricular zone. DCC protein expression was high on rgc axons as they actively navigated through the optic disc into the optic nerve. At birth, when the majority of rgc axons had projected through the optic disc, DCC protein was no longer detectable on the distal axonal segments within the optic nerve despite significant DCC protein expression on the proximal axonal membranes in the nerve fiber layer. These observations suggest that a localized down-regulation of DCC protein occurs on projecting axonal membranes once the DCC guidance function is no longer required. We also demonstrated that DCC mRNA and protein were expressed by amacrine cells and Müller glial cells while DCC mRNA was detected in horizontal cells. Taken together, these expression patterns suggest a role for DCC in axon outgrowth and/or pathfinding for a variety of retinal neurons and in the migration of newly born neurons within the developing retina.
Assuntos
Moléculas de Adesão Celular/genética , Proteínas de Membrana/genética , Retina/embriologia , Proteínas Supressoras de Tumor , Animais , Transporte Axonal , Axônios/química , Axônios/metabolismo , Moléculas de Adesão Celular/análise , Movimento Celular , Receptor DCC , Expressão Gênica , Idade Gestacional , Imuno-Histoquímica , Hibridização In Situ/métodos , Camundongos , Camundongos Endogâmicos ICR , Receptores de Superfície Celular , Células Ganglionares da Retina/química , Células Ganglionares da Retina/metabolismoRESUMO
Axon guidance mechanisms are crucial to the development of an integrated nervous system. One family of molecules that may be important in establishing axonal connectivity in mammals is the Netrins, and their putative receptors DCC (deleted in colorectal cancer), Neogenin, and Unc-5. Knockout and mutational analyses of some of these genes have shown that they are critically involved in the development of several specific pathways in the developing brain. However, previous expression analyses of these genes have largely been confined to the developing spinal cord. In the present study, we analyzed the expression of DCC in the developing mouse forebrain. We found that DCC protein is expressed in specific axonal populations projecting from the developing olfactory bulb, neocortex, hippocampus, and epithalamus/habenular complex. In the developing olfactory bulb and neocortex, DCC expression is particularly evident during the targeting phase of axon outgrowth and is then rapidly downregulated. As predicted from the knockout and mutational analyses of this gene, DCC is expressed in axonal commissures, in particular the corpus callosum, hippocampal commissure, and the anterior commissure. In addition, we found that DCC is expressed in the habenular commissure, the fasciculus retroflexus, and the stria medularis. Therefore, this analysis implicates a function for DCC in additional axonal guidance systems not predicted from the knockout and mutational analyses.
Assuntos
Axônios/metabolismo , Moléculas de Adesão Celular/metabolismo , Fatores de Crescimento Neural/metabolismo , Prosencéfalo/metabolismo , Receptores de Superfície Celular/metabolismo , Proteínas Supressoras de Tumor , Animais , Receptor DCC , Feminino , Masculino , Camundongos , Receptores de Netrina , Netrina-1 , Gravidez , Prosencéfalo/embriologiaRESUMO
Cold-reacting autoantibodies occasionally occur in patients requiring cardiac operations. This report describes the clinical course of 1 patient with cold-reacting autoantibodies and intracoronary agglutination of the blood cardioplegia solution. Observations made in vivo and in vitro are considered in discussing recommendations for the management of extracorporeal circulation and cardioplegic arrest in patients with clinically silent cold-reacting autoantibodies.