RESUMO
OBJECTIVE: Gynaecological cancer surgery is associated with high rates of venous thromboembolism (VTE) despite recommended prophylaxis. We sought to investigate the impact of extended prophylaxis with fixed dose and weight based LMWH in patients undergoing gynaecological cancer surgery. METHODS: VTE rates were recorded in patients who received LMWH prophylaxis (4500 IU Tinzaparin once daily) for the duration of hospital stay (2006-2012) (n = 610) and were compared with VTE rates in patients who underwent surgery after the introduction of extended prophylaxis (3500/4500 IU Tinzaparin for patients with BMI < 40kg/m2 and 75 IU/kg for BMI > 40 kg/m2) (2012-2017) (n = 651). Peak (4 h) anti-Xa levels in a subset of patients were also evaluated. RESULTS: 73 (5.7%) cases of VTE were recorded during 1 year of follow-up. 20 cases occurred during hospital stay. There was no significant difference in the rate of VTE between the extended prophylaxis cohort and the standard prophylaxis cohort. 23/24 patients who developed VTE in the extended prophylaxis cohort received a fixed (4500 units) dose of Tinzaparin. 63% of patients who received a fixed LMWH dose had peak anti-Xa levels below the target range (0.2-0.4 IU/ml). Peak anti-Xa was lower in patients who subsequently developed VTE compared with those who received either fixed dose (P = 0.041) and weight adjusted Tinzaparin (P = 0.0006). CONCLUSIONS: Extended prophylaxis with Tinzaparin does not significantly reduce VTE rates in gynaecological cancer patients post surgery. Peak anti-Xa levels may be suboptimal in many patients receiving a fixed LMWH dose. Further studies are required to determine whether weight adjusted doses of Tinzaparin may provide more effective prophylaxis following gynaecological cancer surgery.
RESUMO
INTRODUCTION: Gynaecological cancer is associated with some of the highest rates of venous thromboembolism (VTE) with some subtypes of ovarian cancer associated with rates as high as 20%. VTE prophylaxis is an important part of post-operative management in gynaecological cancer patient care. Despite the evidence base and guidelines recommending extended VTE prophylaxis for patients undergoing major cancer surgery, adherence to best practice guidelines has been found to be low. AIM: The aim of this study is to assess gynaecological oncologist's awareness of the guidelines surrounding VTE prophylaxis for post-operative gynaecological cancer patients and to determine the type and duration of VTE prophylaxis implemented by gynaecological oncologists. MATERIALS AND METHODS: The study used the European Society Gynaecology Oncology (ESGO) membership as the population studied. ESGO is a multidisciplinary, non-profit association, founded in 1983. ESGO consisit of more than 1800 professional of different specialities dealing with gynaecological oncology. The e mail address of 650 member were avilable on the ESGO website. We send a Survey Monkey link to the questionnaire by email to a total of 650 ESGO member whose email addresses were obtained from the ESGO directory. 205 e mails returned back as the email used was invalied, only 445 e mail successfully delivered. The survey remained open for 44 days. Results were analysed on Survey Monkey. RESULTS: A 59.3% of respondents said that they decided upon appropriate VTE prophylaxis for a patient according to national/international best practice guidelines. A further 39.4% respondents said that they made their choice based upon clinical judgement. 59.8% of respondents said that they begin VTE prophylaxis pre-operatively for the high risk patients. 6.1% said that they begin prophylaxis in the operating theatre, 18.9% begin prophylaxis 6 hours post-operatively and 9.1% begin prophylaxis 12 hours post-operatively. The remaining respondents said that they begin VTE more than 24 hours post operatively 44.7% said that they prescribe VTE prophylaxis for 4 weeks. A further 15.9% said that they prescribe VTE prophylaxis for 6 weeks and 4.75% for longer than 6 weeks. CONCLUSIONS: In conclusion, the adherence to current guidelines for VTE prophylaxis in the peri-operative period for gynaecological oncology patients is still poor. Awareness needs to be raised in order to decrease the morbidity/mortality of VTE in this high risk group of patients. The adoption of multidiscplinary approach to manage gynaecological cancer patients, which includes the involvment of thrombosis specialist, may reduce post operative VTE rates and improve cancer care.
RESUMO
INTRODUCTION: The close relationship between coagulation, thrombosis and cancer has long been established. Gynaecological cancers, in particular ovarian cancers, carry a high risk of thrombosis but coagulation activation is also thought to play a role in tumorigenesis and metastasis. In experimental animal models of metastasis, mice with a genetic procoagulant phenotype are prone to develop metastasis and anticoagulant therapy dramatically reduces pulmonary metastasis in these models. The aPC pathway is a key natural anticoagulant pathway, in addition to its role in venous thrombosis, dysregulation of this pathway is also thought to play a role in the pathogenesis of some cancers. No data exists in ovarian and endometrial cancers. AIM: The aim of this study is to determine the expression of key proteins of the activated protein C pathway in endometrial and ovarian malignant tumours compared to benign tumours and to assess their role in patient survival. MATERIALS AND METHODS: RNA was extracted from 78 (54 malignant and 24 benign) fresh frozen ovarian and endometrial tumours samples. Tumour biopsies were mRNA expression of endothelial protein C receptor (EPCR), protein S (PS), protein C (PC), thrombomodulin (TM), Factor V (FV) and VIII (FVIII) and PAR-1 and PAR-2 was measured using TaqMan Low Density Arrays. mRNA fold change relative to benign expression was determined using the 2 -delta delta Ct method with 18s as internal standard. All patients gave full and informed consent and the study had the approval of the hospital ethics committee. Total cell protein was extracted from ovarian tumour tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure protein plasma expression RESULTS: EPCR (P<0.001), protein S (P<0.0001) and Factor VIII (P<0.003) mRNA expression was significantly downregulated in malignant tumours compared with benign. Factor V and PAR-2 were significantly upregulated (P<0.001; P<0.004). Protein C was not consistently expressed. Reduced EPCR and TM protein expression was also observed in malignant tumours with increased plasma levels of Factor V. Reduced protein S and increased FV were associated with decreased survival. Plasma levels of Factor V were related to grade in the endometrial cancer group. PAR-2 mRNA expression was increased in ovarian tumours (P<0.001) however PAR-1 expression remained unchanged. CONCLUSIONS: Our results show reduced expression of key proteins associated with activation of protein C combined with increased expression in FV in gynaecological malignancies. These changes may contribute to local thrombin production and tumour progression and metastasis. Further work is required to determine the precise mechanisms involved.
RESUMO
INTRODUCTION: Increased thrombin production is associated with malignancy and is a marker for venous thromboembolism (VTE). Our group has shown that thrombin generation is increased in gynaecological malignancies. Although tumour derived Tissue Factor (TF) has been implicated, the precise mechanism by which thrombin production is increased is not fully understood. Our group has shown that gynaecological cancers can alter tumour expression of cogulation proteases. These changes may be implicated in the increased thrombin generation observed. Previous studies in normal control patients by other groups have shown that multiple coagulation factors are implicated in thrombin generation and that the effects depend on assay conditions however free Tissue Factor Pathway Inhibitor (TFPI), Factors V, VIIIc and protein S, were significant determinants of thrombin generation. AIM: The aim of this study was to determine the effect of factor V factor, VIIIc, TFPI and free protein S on the thrombin generation in patients with endometrial and ovarian cancer compared with benign controls. MATERIALS AND METHODS: Patients with a gynaecological malignancy (n=43) (ovarian or endometrial) were matched with patients with a benign tumour (n=43) gave full and informed consent. Venous blood samples were obtained prior to surgery and chemotherapy. Thrombin generation was was measured using a fluorogenic assay. Lag time, peak thrombin and area under the thrombin generation curve (ETP) was determined and reported for each sample. Free protein S, free TFPI and factor V were determined using ELISA. Factor VIIIc was determined using a hromogenic assay. RESULTS: Factor V and factor VIIIc were significantly increased in the malignant group compared with the benign group (P<0.03; P<0.006). Increased free TFPI levels were also observed in the malignant group but this did not reach significance (P<0.06). There was no difference in free Protein S levels between the groups. Highest levels of peak thrombin generation were observed in the high grade serous and clear cell ovarian cancer patients. Changes were less marked in the endometrial patients. Free TFPI, factor V and factor VIIIc were important determinants of thrombin generation in the malignant group. CONCLUSIONS: Coagulation factors V and VIIIc and free TFPI are altered in patients with gynaecological malignancies and contribute to the increased thrombin generation found in these cancer patients. We have previously found increased expression of factor V in tumours from patients with ovarian cancer in addition to increased TF expression. These changes may explain the high rate of venous thromboembolism found in these patients.
RESUMO
BACKGROUND: Gynaecological cancers are associated with high rates of venous thromboembolism (VTE). Studies on ambulatory cancer patients do not support thromboprophylaxis during chemotherapy. Approximately 6-7% of gynaecological cancer patients suffer a postoperative VTE despite Low Molecular Weight Heparin prophylaxis (LMWH). Large cancer studies have shown that Calibrated Automated Thrombogram (CAT) and Microparticles (MP) assays may be useful in predicting VTE but data on gynaecological cancer patients is scarce. OBJECTIVE: Our objective was to identify whether the CAT assay and MP functional assays have potential as biomarkers predictive of VTE in gynaecological cancer patients. PATIENTS AND METHODS: Gynaecological cancer patients were investigated before surgery (n=146) and at 5, 14 and 42days post-surgery (n=78). Fourteen additional patients were investigated before chemotherapy and after 3 and 6 cycles of therapy. Thrombin generation was measured before and after addition of thrombomodulin. RESULTS: Patients with clear cell cancer (CCC) of the ovary and patients with endometrial cancer had higher ETP and peak thrombin compared with patients with benign disease. Patients who developed VTE (n=8) following surgery had enhanced thrombin generation prior to surgery which persisted during the post-operative period despite LMWH prophylaxis. Both neoadjuvant and adjuvant chemotherapy showed increased thrombin generation following addition of thrombomodulin. There were no differences in MP levels during the study. CONCLUSIONS: CAT assay shows potential as a promising biomarker for the prediction of VTE in gynaecological cancer patients. The identification of high risk patients combined with individualised LMWH prophylaxis might reduce VTE in this high risk group.
Assuntos
Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/cirurgia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Tromboembolia Venosa/complicações , Idoso , Anticoagulantes/uso terapêutico , Antineoplásicos/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Micropartículas Derivadas de Células/metabolismo , Quimioterapia Adjuvante , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/tratamento farmacológico , Endométrio/cirurgia , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/tratamento farmacológico , Ovário/cirurgia , Trombina/análise , Trombina/metabolismo , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/prevenção & controleRESUMO
Secondary healing of complicated vulvar and groin wounds is a major challenge due to its moist condition and at risk of contamination by colonic flora. Vacuum assisted closure is the controlled application of sub-atmospheric pressure to the local wound environment using a sealed dressing connected to a vacuum pump. MATERIALS AND METHODS: The NPWT consists of an open-pore polyurethane ether foam sponge, an adhesive cover, fluid collection system, and suction pump that generates negative pressure. Direct application of sponge to blood vessels, bone, nerves or intact skin is avoided. The dressing and tubing are changed every 48-72 hours. RESULTS: Eight patients had NPWT following the vulva and/or groin surgery. Pain during removal of the sponge was the main adverse event requiring narcotic analgesia. All wounds healed completely. One patient is dead of disease progression. Others are alive without disease at four to 48 months. CONCLUSION: Wound breakdown in vulvar and groin surgery is an infrequent occurrence because of the rarity of full radical excision for vulva cancer and infralevator pelvic exenterative surgery. The present experience with NPWT was favourable.
Assuntos
Virilha/cirurgia , Tratamento de Ferimentos com Pressão Negativa/métodos , Exenteração Pélvica , Vulva/cirurgia , Neoplasias Vulvares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Vulvares/fisiopatologia , CicatrizaçãoRESUMO
PURPOSE OF INVESTIGATION: Embolisation of the internal iliac artery has been described as an effective and safe method of treating massive vaginal haemorrhage in small series of advanced uterine cancer and case reports of cervical cancer. Selective embolization of the bleeding vessel is potentially less morbid. The aim of this study was to assess the efficacy of selective arterial embolisation (SAE) in controlling intractable haemorrhage due to gynaecological malignancy. MATERIALS AND METHODS: This retrospective observational study comes from in a tertiary cancer center with 300 new gynecologic cancers per annum. The authors reviewed all gynecology cancer patients who had intractable major vaginal haemorrhage in the first five years following the introduction of selective arterial embolisation at their unit. The outcomes measured were the control of acute haemorrhage and discharge to planned pathway of treatment. RESULTS: SAE was successful in all cases. Identification of the bleeding point facilitated highly selective embolisation in more than half of the patients. The uterine arteries were embolised in the remaining cases. Bleeding stopped immediately. The expedient control of haemorrhage facilitated early discharge to commencement/continuation of radiation treatment or palliative care as appropriate. CONCLUSIONS: Since the introduction of SAE the authors have avoided emergency radiotherapy, surgery, and repeat vaginal packing in patients with intractable vaginal bleeding due to gynaecological cancer. Patients were discharged to their appropriate treatment pathways in a timely manner. The authors recommend the application of SAE.
Assuntos
Embolização Terapêutica , Neoplasias dos Genitais Femininos/complicações , Hemorragia Uterina/terapia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Artéria UterinaRESUMO
Surgery is the mainstay of treatment for vulvar cancer. FIGO staging requires histopathological detail of the primary tumor and inguinofemoral lymph nodes but groin node dissection carries a substantial risk of short and long-term morbidity. The trend in current practice is towards sentinel lymphadenectomy for cancers with a low risk of metastases. Full lymphadenectomy is undertaken if the sentinel lymph node contains metastasis. The predictive value of 18F-FDG-PET in preoperative assessment of the groin in vulvar squamous cancer was assessed in retrospect at a single institution. A period of three years prior to the introduction of sentinel lymph node mapping was chosen in order to have full histopathological assessment of inguinal and femoral lymph nodes available as the gold standard for correlation with positron emission tomography-computerized tomography (PET-CT) to determine the accuracy of the enhanced radiological technique. In patients with histologically proven metastases to groin nodes, comparisons between PET-CT positive (True-positive/TP) and negative (False-negative/FN) groups vis-à-vis histology showed a tendency towards higher FDG avidity in the vulvar lesions, more bilateral nodes, multiple metastases, larger metastases and more extra-capsular extension in the TP group. Calculations per patient for PET-CT yielded a sensitivity of 50% and specificity at 100%. The positive predictive value (PPV) was 100% and the negative predictive value (NPV) was 57.1%. The test accuracy was 70% per patient. The high positive predictive value of PET-CT can be used to advance treatment planning prior to surgical staging of patients identified with Stage III disease. The poor sensitivity makes it unsuitable as a substitute for staging lymphadenectomy.
Assuntos
Fluordesoxiglucose F18 , Excisão de Linfonodo , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X/métodos , Vulva/cirurgia , Neoplasias Vulvares/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgiaRESUMO
OBJECTIVE: Salpingectomy is proposed as a prophylactic measure to reduce the incidence of tubo-ovarian/pelvic serous cancers. We surveyed the attitudes of obstetrician/gynecologists to incorporating salpingectomy opportunistically into surgery for benign conditions, and electively for young BRCA mutation carriers. STUDY DESIGN: A questionnaire, designed to assess current standard clinical practice and willingness to perform salpingectomy for female sterilization at abdominal hysterectomy for benign disease (ABH), vaginal benign hysterectomy (VBH) and electively for women with BRCA mutations who wish to postpone oophorectomy was mailed to obstetrician/gynecologists working in Irish hospitals. RESULTS: In their current practice of interval female sterilization 96% of gynecologists applied clips at laparoscopy and 4% performed salpingectomy, and 73% were willing to consider salpingectomy. Eighty-one percent were willing to consider salpingectomy for sterilization at cesarean section. Gynecologists performing hysterectomy (without oophorectomy) for benign conditions did salpingectomy in 26% at ABH and 5.4% at VBH, and now 90% would consider salpingectomy at ABH and 66% at VBH. Two-thirds of respondents would consider salpingectomy for women at genetic risk of ovarian cancer who want to postpone oophorectomy. CONCLUSION: Changing general gynecological practice to include more opportunistic salpingectomy has the potential to reduce the incidence of serous cancers. The majority of gynecologists are willing to incorporate more salpingectomies into their surgical practices and consider elective salpingectomy as an interim measure for women with defined genetic risk of pelvic serous cancer.
Assuntos
Atitude do Pessoal de Saúde , Cistadenocarcinoma Seroso/prevenção & controle , Neoplasias dos Genitais Femininos/prevenção & controle , Salpingectomia/psicologia , Feminino , HumanosRESUMO
The mylohyoid is a muscular diaphragm in the floor of the oral cavity. Its superficial and deep surfaces have important anatomical relationships. The submandibular gland is uniquely related to both surfaces at the posterior free edge of the muscle. It is here that the submandibular and sublingual tissue spaces become continuous. This case report describes an unusual range of anatomical variations of the mylohyoid muscle and reviews their clinical significance.
Assuntos
Soalho Bucal/anatomia & histologia , Músculo Esquelético/anatomia & histologia , Idoso , Cadáver , Dissecação , Humanos , Masculino , Soalho Bucal/anormalidades , Músculo Esquelético/anormalidadesRESUMO
We determined the effect of cystoscopy (flexible and rigid), transrectal ultrasonography (with and without needle biopsy of the prostate) and transurethral resection of the prostate or bladder tumour on the serum prostate-specific antigen (PSA) concentration. Samples were taken from 60 men before and up to 14 days following these procedures. Flexible cystoscopy did not result in a significant increase in serum PSA concentration, with a median increase of 0.1 microgram/L (P > 0.05). Small but statistically significant increases in serum PSA levels 1 day post-procedure were observed following rigid cystoscopy and transrectal ultrasound without biopsy. The median increase in serum PSA concentration following rigid cystoscopy was 0.15 microgram/L (P = 0.04) and following transrectal ultrasound was 0.3 microgram/L (P = 0.01). In both cases the serum PSA level had normalized by 2 days post-procedure. Transurethral resection of bladder tumours resulted in a variable rise in serum PSA, with a median increase of 2.6 micrograms/L after 1 day, which returned to normal over 7-14 days. Ultrasound-guided needle biopsy of the prostate and transurethral resection of the prostate produced significant increases in serum PSA levels, which took up to fourteen days to return to normal. The median increase in serum PSA following needle biopsy was 6.0 micrograms/L and following transurethral resection of the prostate (TURP) was 13 micrograms/L. Samples for PSA measurement may safely be taken within 24-48 h of flexible cystoscopy and transrectal ultrasonography (TRUS) providing prostatic biopsy is not carried out. For other procedures it is necessary to wait for at least 14 days to ensure that false positive PSA results are not obtained.
Assuntos
Antígeno Prostático Específico/sangue , Idoso , Cistoscopia , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodos , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
This work uses a new heart-perfusion technique to measure 125I-insulin binding on capillary endothelium and myofiber cell membranes in Wistar-Kyoto and spontaneously hypertensive rats. Ringer-Lock buffer was infused at a rate of 1 ml min-1 in the presence of 20 meq l-1 K+ and 125I-insulin through an aortic cannula. The effluent was collected through a catheter introduced into the right atrium. The capillary endothelial lining was removed by detergent treatment to expose the cardiac myocyte surfaces. A physical model describing a 1:1 binding stoichiometry of 125I-insulin with its receptors is proposed and the derived mathematical equations allow for the calculation of binding constants (kn), unbinding constants (k-n), dissociation constants (kd), and residency time constants (tau). The results showed that in the spontaneously hypertensive rats' hearts significant alterations were not noticed in the kinetics of insulin binding with its receptor at the capillary endothelial site compared to hearts of the normotensive control Wistar-Kyoto rats. However, at the myocyte site and in the spontaneously hypertensive rats, steric, configurational, and/or structural modifications for insulin binding with the receptor were observed as indicated by changes in insulin affinity for its receptor. Hence, alterations in insulin binding rather than reduction in insulin receptor number due to hyperinsulinemia, can be considered among the peculiarities of insulin resistance in the spontaneously hypertensive rats. Hyperinsulinemia, therefore, may be considered an upregulatory process as a consequence of insulin-resistance. The results support the hypothesis that insulin-resistance on the myocytes could be a pathophysiologic defect in insulin-receptor structure, function and affinity, and therefore myocardial function.
Assuntos
Hipertensão/metabolismo , Insulina/metabolismo , Miocárdio/ultraestrutura , Receptor de Insulina/metabolismo , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/ultraestrutura , Ácidos Cólicos/farmacologia , Detergentes/farmacologia , Endotélio Vascular/metabolismo , Endotélio Vascular/ultraestrutura , Feminino , Hiperinsulinismo/metabolismo , Insulina/farmacocinética , Resistência à Insulina/fisiologia , Radioisótopos do Iodo , Computação Matemática , Modelos Biológicos , Miocárdio/metabolismo , Perfusão , Ligação Proteica , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
The tensor fasciae latae (TFL) muscle has been successfully harvested as a myocutaneous flap in reconstructive surgery. Reports on the vascular supply of this muscle, however, are incomplete or inconclusive. Therefore the arterial pattern was examined by dissection in 100 injected human cadaveric specimens. It was observed that whereas 67 muscles were supplied exclusively by a single vessel derived from the ascending branch of the lateral circumflex femoral (LCF) artery, 13 were supplied by a secondary vessel derived from the same branch, while 20 muscles were supplied by two vessels, the larger one arising as before and the smaller from the descending branch of the LCF. Our observations reveal that although the majority of TFL muscles are clinically Type I (one vascular pedicle) according to the classification of Mathes and Nahai (1981), 20% are actually Type II (major and minor vascular pedicles).
Assuntos
Fascia Lata/irrigação sanguínea , Artéria Femoral/anatomia & histologia , Músculo Esquelético/irrigação sanguínea , Idoso , Cadáver , Feminino , Humanos , MasculinoRESUMO
C-Fos-like immunoreactivity (FLI) in the central nervous system, has been associated with the processing of nociceptive information in acute and chronic pain animal models. The aim of this study was to investigate whether intraplantar (i.pl.) injections of endotoxin (ET, 1.25 microg) can induce FLI in the lumbar spinal cord of rats and to assess the effects of morphine injection on c-fos expression. FLI was studied in various groups of rats at 2, 3, 4, 6, 9 and 24 h following ET injections. Labeled neurons were mainly detected in the lumbar segments ipsilateral to the ET-injected leg, with a major peak (71.01 +/- 4.79 positive neurons) at 4 h and a second peak (29.87 +/- 5.97 positive neurons) at 9 h followed by a recovery to the baseline at 24 h after ET injections. Within the laminae, the majority of positive neurons was observed at 2-3 h in laminae I and II and in deep laminae (V and VI mainly) starting at 4 h after ET injections. Rostrocaudally, labeled neurons were observed initially in L4-L5 segments (2-3 h post-ET) after which they extended to L2-L6 segments at 4 h after ET. Morphine injections either i.p. (1 or 2 mg/kg) or i.pl. (50 microg) significantly reduced ET-induced hyperalgesia and simultaneously the FLI. The maximum effect was observed on labeled neurons in the deep laminae (V and VI mainly). We conclude that local injections of ET can induce FLI in the lumbar spinal cord with a temporal and spatial patterns comparable to the described hyperalgesia, and that both FLI and hyperalgesia are reduced by morphine in a dose-dependent manner with a maximal effect shown by the local i.pl. morphine injections.
Assuntos
Analgésicos Opioides/farmacologia , Endotoxinas/administração & dosagem , Morfina/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Relação Dose-Resposta a Droga , Endotoxinas/farmacologia , Pé , Hiperalgesia/induzido quimicamente , Hiperalgesia/fisiopatologia , Imuno-Histoquímica , Injeções , Região Lombossacral , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Fatores de Tempo , Distribuição TecidualRESUMO
A heart-perfusion technique was employed to measure 125I-insulin binding on capillary endothelial and myocyte cell membranes in Sprague-Dawley rats. Animals were anesthetized, and the anterior chest wall excised to expose the mediastinal contents. The right and left superior and inferior venae cavae were dissected and tied, and another tie was passed around the aorta. A polyethylene catheter was introduced into the aortic lumen from cephalad to caudad to sit with its tip above the aortic valve. Another catheter was introduced into the cavity of the right atrium and both were anchored by sutures. Oxygenated Ringer-Lock buffer containing 20 mM/L K+ and 125I-insulin was perfused at a rate of 1 mL/min via the aortic catheter. Concomitantly, the distal ascending aorta and venae cavae were ligated. The effluent was collected from the right atrial catheter at the same infusion rate. Animals were divided into two groups, the normal group and streptozotocin-induced diabetic group. Heart perfusion was done on both groups either without or after treatment with detergent (CHAPS) to remove the capillary endothelial lining. A physical model for 125I-insulin sequestration as a ligand to its receptors on endothelial and/or myocyte plasma membranes was proposed. The model described a reversible binding of ligand on cellular surface receptor concentration to fit a conservation equation and a first order Bessel function. The binding constants (kn), reversal constants (k-n), dissociation constants kd = k-n/kn, and residency time constants tau = 1/k-n of 125I-insulin in normal untreated, normal CHAPS-treated, diabetic untreated, and diabetic CHAPS-treated hearts were estimated using a theoretically generated curve-fit to the data. Since insulin receptor binding on the capillary endothelial cell surfaces may serve to transport insulin from the intravascular to the subendothelial space, and since streptozotocin-induced diabetes was shown to diminish receptor autophosphorylation and kinase activity and hence internalization of insulin, then one can conclude the following from the data. In the normal heart, removal of the capillary endothelial lining with CHAPS did not alter kn, k-n, kd, and tau of insulin binding as compared to the normal untreated, whereas in the diabetic untreated heart these constants were altered, compared to the diabetic treated. Furthermore, the kn and k-n values in the diabetic CHAPS-treated hearts were the same as for the normals untreated and CHAPS-treated, respectively. In conclusion, the dissociation constants and residency time constants of all groups indicated the possible existence of two types of insulin receptors: the capillary endothelial cell surface insulin receptors with lower residency time (low affinity receptor or combination of insulin and IGF-1 receptors) and the myocyte plasma membrane insulin receptors with higher residency times (high affinity).
Assuntos
Diabetes Mellitus Experimental/metabolismo , Endotélio Vascular/efeitos dos fármacos , Insulina/farmacologia , Radioisótopos do Iodo/metabolismo , Miocárdio/metabolismo , Receptor de Insulina/efeitos dos fármacos , Animais , Capilares/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Técnicas In Vitro , Miocárdio/ultraestrutura , Ratos , Ratos Sprague-Dawley , EstreptozocinaRESUMO
BACKGROUND: To determine if altered tissue perfusion during cardiac surgery results in ischemic tissue damage to the prostate, as suggested by a rise in prostatic-specific antigen (PSA). METHODS: Twenty-nine male patients undergoing elective coronary artery bypass grafting were studied. Ten male patients undergoing elective gastrointestinal surgery served as controls. PSA levels were determined preoperatively and six hourly intervals postoperatively for 48 hr. All patients underwent urethral catheterization at induction of anesthesia. RESULTS: All patients (100%) who had undergone cardiac bypass surgery showed rises in serum PSA during 48 hr of postoperative follow-up. At the 6-hr postoperative interval, the mean PSA was significantly different from the mean baseline value (paired two tailed Student's t test, P < 0.001) in 27 of the 29 (93%) patients. In contrast, the PSA values in the 10 gastroenterological controls did not change at 6 hr (P > 0.2) or during the next 48 hr. One patient in the cardiac group showed a very marked elevation in serum PSA of greater than 50 times normal preoperative levels. CONCLUSIONS: Statistically significant rises in PSA levels are seen following coronary bypass surgery. This rise may be caused by ischemic nontrauma related damage to the prostate and suggests a possible pathophysiological mechanism for the clinically episodic symptoms of prostatism seen in elderly men.
Assuntos
Ponte de Artéria Coronária/efeitos adversos , Isquemia/etiologia , Antígeno Prostático Específico/sangue , Próstata/irrigação sanguínea , Gastroenteropatias/cirurgia , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Fatores de TempoRESUMO
In a combined radiographic-anatomic study, the anterior tibial artery in a stillborn male was a branch of the posterior tibial at about its midpoint. It gave off an unusual lateral calcaneal vessel that coursed initially in the musculoperoneal canal. The variations are discussed in the context of the complex embryologic development of the blood supply to the lower limb.
Assuntos
Artérias da Tíbia/anatomia & histologia , Cadáver , Circulação Colateral , Humanos , Recém-Nascido , Masculino , Radiografia , Artérias da Tíbia/diagnóstico por imagem , Artérias da Tíbia/embriologiaRESUMO
This paper addresses the impact of war-related stressful life events on the health of families living through the war conditions prevailing in Lebanon for the past 12 years. Health outcome is represented by indicators of somatization, depression, psychological symptoms, interpersonal relations and marital relations. Associations are described between elements of war stress and the health outcome variables for mothers, fathers and adolescents in a sample of Beirut families. The role of the mediating factors of social support and social class is also discussed.
Assuntos
Saúde da Família/etnologia , Nível de Saúde , Saúde Mental , Guerra , Adolescente , Adulto , Feminino , Humanos , Líbano/epidemiologia , Masculino , Prevalência , Classe Social , Apoio Social , Estresse Psicológico/etiologiaRESUMO
The arrangement and structure of the fascial layers of the scalp were studied in 48 red neoprene latex-injected cadavers with the aid of an operating microscope. The galea aponeurotica was continuous with a superficial temporal fascia. Deep to the galea, the subaponeurotic connective tissue was bilaminar. There was an outer, vascular, areolar layer, and an inner, avascular, membranous layer. Underlying the temporalis muscle, the pericranium was thinner and more adherent than elsewhere with no subpericranial tissue.