Estudo da vascularização dos nervos periféricos e da sua influência na regeneração nervosa : estudo experimental e no cadáver humano

RESUMO: Na clínica, a recuperação funcional que se segue a uma lesão nervosa raramente é atingida na sua totalidade. A reinervação, quer motora, quer sensitiva, ocorre geralmente com maior ou menor deficit. Interessa, então, identificar os factores que podem interferir na regeneração nervosa. O neurónio é a unidade anatómica fundamental do sistema nervoso periférico e é muito vulnerável à isquemia pela grande distância que existe entre o corpo neuronal e a extensão do axónio, que pode ser de apenas alguns milímetros ou até atingir um metro. É, por isso, fundamental o estudo da vascularização do nervo periférico e da sua influência na regeneração nervosa. O resultado deste estudo pode levar ao desenvolvimento de técnicas cirúrgicas que criem as condições que garantam, por sua vez, a revascularização precoce do nervo periférico em caso de lesão, ou mesmo em caso de doenças, nas quais a vascularização do nervo está alterada como, por exemplo, na neuropatia diabética. O estudo da vascularização do nervo periférico realizou-se através da investigação da vascularização do nervo mediano do cadáver humano, pela investigação da vascularização do nervo isquiático do rato Wistar e do Plexo Braquial (PB) do mesmo. A vascularização do PB do rato não é muito diferente daquela que é reportada na espécie humana, existindo uma homologia entre o rato e o Homem no que diz respeito à morfologia e à vascularização do PB. Através da comparação angiomorfológica entre o nervo isquiático do rato e o nervo mediano humano, concluíu-se que a microvascularização do nervo isquiático do rato e do mediano humano são muito semelhantes, o que suporta a utilização do rato como modelo experimental de lesões do nervo mediano humano. Para a avaliação da influência da vascularização na regeneração nervosa foi feita a análise da eficácia de enxerto de tubo de membrana amniótica humana imunologicamente inerte, de enxerto de veia jugular externa autóloga e de auto-enxerto de nervo, na reparação de um defeito de 10 milímetros no nervo isquiático do rato, na presença de um fornecimento vascular axial, comparando-se com os mesmos procedimentos em estudos realizados anteriormente, sem suprimento vascular. Os ratos foram avaliados funcionalmente através do estudo das pegadas, da electroneurografia e da força de flexão ao nível do tornozelo, e estruturalmente, através das avaliações histológicas e morfométricas, da taxa de recuperação do peso dos músculos gastrocnémio e solhear e da marcação axonal retrógrada com True Blue às 4, 8 e 12 semanas. Os nervos reconstruídos apresentaram uma arquitectura normal, incluindo a arquitectura vascular. A membrana amniótica foi bem tolerada, persistindo imunologicamente em torno do nervo até à 12.ª semana. Concluiu-se também que, na presença de um suprimento vascular axial local, a membrana amniótica humana e as veias autólogas são, pelo menos, tão eficazes como os auto-enxertos nervosos na reconstrução de defeitos nervosos de 10 milímetros.--------------------------------------ABSTRACT: At the clinic, the functional recovery that follows a nerve lesion is rarely achieved in full. The neuron is very vulnerable to ischemia that’s why it is essential to study the vascularization of the peripheral nerve and its influence on the nerve’s regeneration. The outcome of this study may lead to the development of surgical techniques that create the conditions which are necessary to ensure an early revascularization in case of a peripheral nerve injury. This study investigated the vascularization of the median nerve of the human cadaver and the vascularization of the sciatic nerve of the Wistar rat and his Brachial Plexus (BP) through animal experimentation. The mouse's BP vascularization is not so different from the one that is reported in the human species. An angiomorphological comparison between the mouse sciatic nerve and the human median nerve concluded that the microvascularizations are very similar, which supports the use of the mouse as an experimental model for the study of median nerve’s lesions. To evaluate the influence of vascularization in the nerve’s regeneration, it was made an assessment of the effectiveness of the human amniotic immuno-inert membrane grafts, of the autologous external jugular vein grafts and of the nerve auto-graft in the repair of a defect of 10 mm on the sciatic nerve of the rat, in the presence of an axial vascular supply, comparing these with the same procedures that were adopted in the previous studies, without vascular supply. The rats were functionally assessed and structurally evaluated (through histological and morphometric evaluations) at the 4.th, 8.th and 12.th weeks. The nerves reconstructed presented a normal architecture, including vascular architecture. The amniotic membrane was well-tolerated immunologically, persisting around the nerve until the 12.th week. As a result, it was also concluded that in the presence of a local axial vascular supply, the human amniotic membrane and the autologous veins are, at least, as effective as the nerve auto-grafts in the reconstruction of the nerve’s defects of 10 mm.

Enteroscopia por cápsula e doença de Crohn: Caminhos para a otimização

Tese de Doutoramento em Medicina

Critical analyses of the introduction of liquid-based cytology in a public health service of the state of São Paulo, Brazil

OBJECTIVE The aim of this study was to compare the performance of the current conventional Pap smear with liquid-based cytology (LBC) preparations. STUDY DESIGN Women routinely undergoing their cytopathological and histopathological examinations at Fundação Oncocentro de São Paulo (FOSP) were recruited for LBC. Conventional smears were analyzed from women from other areas of the State of São Paulo with similar sociodemographic characteristics. RESULTS A total of 218,594 cases were analyzed, consisting of 206,999 conventional smears and 11,595 LBC. Among the conventional smears, 3.0% were of unsatisfactory preparation; conversely, unsatisfactory LBC preparations accounted for 0.3%. The ASC-H (atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion) frequency did not demonstrate any differences between the two methods. In contrast, the incidence of ASC-US (atypical squamous cells of undetermined significance) was almost twice as frequent between LBC and conventional smears, at 2.9 versus 1.6%, respectively. An equal percentage of high-grade squamous intraepithelial lesions were observed for the two methods, but not for low-grade squamous intraepithelial lesions, which were more significantly observed in LBC preparations than in conventional smears (2.2 vs. 0.7%). The index of positivity was importantly enhanced from 3.0% (conventional smears) to 5.7% (LBC). CONCLUSIONS LBC performed better than conventional smears, and we are truly confident that LBC can improve public health strategies aimed at reducing cervical lesions through prevention programs.

High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16

Invasive cervical cancer (ICC) is the third most frequent cancer among women worldwide and is associated with persistent infection by carcinogenic human papillomaviruses (HPVs). The combination of large populations of viral progeny and decades of sustained infection may allow for the generation of intra-patient diversity, in spite of the assumedly low mutation rates of PVs. While the natural history of chronic HPVs infections has been comprehensively described, within-host viral diversity remains largely unexplored. In this study we have applied next generation sequencing to the analysis of intra-host genetic diversity in ten ICC and one condyloma cases associated to single HPV16 infection. We retrieved from all cases near full-length genomic sequences. All samples analyzed contained polymorphic sites, ranging from 3 to 125 polymorphic positions per genome, and the median probability of a viral genome picked at random to be identical to the consensus sequence in the lesion was only 40%. We have also identified two independent putative duplication events in two samples, spanning the L2 and the L1 gene, respectively. Finally, we have identified with good support a chimera of human and viral DNA. We propose that viral diversity generated during HPVs chronic infection may be fueled by innate and adaptive immune pressures. Further research will be needed to understand the dynamics of viral DNA variability, differentially in benign and malignant lesions, as well as in tissues with differential intensity of immune surveillance. Finally, the impact of intralesion viral diversity on the long-term oncogenic potential may deserve closer attention.

Extensive subcutaneous emphysema as a presentation of ischemic colitis

Introduction . Subcutaneous emphysema is usually benign and self-limited; however, it may be associated with a life-threating situation. Case Report . An elderly woman with progressive malaise with extensive subcutaneous emphysema (cervical to abdominal wall) was observed at the emergency department. Colonic perforation was diagnosed and the patient underwent surgery. Intraoperatively, necrosis and perforation of the sigmoid colon into the retroperitoneum were found and a Hartmann procedure was performed. Conclusion . Cervical and thoracic subcutaneous emphysema may be the first sign of intra-abdominal lesion.

Aortic stenosis. Gender influence on left ventricular geometry and function in patients under 70 years of age

OBJECTIVE: To verify if adaptive left ventricle (LV) characteristics are also present in individuals under 70 years of age with severe aortic stenosis (AS). METHODS: The study comprised 40 consecutive patients under 70 years of age with AS and no associated coronary artery disease, referred for valve surgery. Out of the 40 patients, 22 were men and 18 women, and the mean age was 49.8±14.3 years. Cardiac symptoms, presence of systemic hypertension (SH), functional class according to the New York Heart Association (NYHA), and valve lesion etiology were considered. LV cavity dimensions, ejection fraction (EF), fractional shortening (FS), mass (MS), and relative diastolic thickness (RDT) were examined by Doppler echocardiography. RESULTS: Fourteen (63.6%) men and 11 (61.6%) women were classified as NYHA class III/IV (p=0.70). There was no difference in the frequency of angina, syncope or dyspnea between genders. The incidence of SH was greater in women than in men (10 versus 2, p=0.0044). Women had a smaller LV end-diastolic diameter index (32.1±6.5 x 36.5±5.3mm/m², p=0.027), LV end-systolic diameter index (19.9±5.9 x 26.5±6.4mm/m², p=0.0022) and LV mass index (MS) (211.4±71.1 x 270.9±74.9g/m², p=0.017) when compared with men. EF (66.2±13.4 x 52.0±14.6%, p=0.0032), FS (37.6±10.7 x 27.9±9.6%, p=0.0046) and RDT (0.58±0.22 x 0.44±0.09, p=0.0095) were significantly greater in women than in men. CONCLUSION: It is the patient gender rather than age that influences left ventricular adaptive response to AS.

Safety and efficacy of coronary stent implantation. Acute and six month outcomes of 1,126 consecutive patients treated in 1996 and 1997

PURPOSE: The authors analyzed the 30-day and 6-month outcomes of 1,126 consecutive patients who underwent coronary stent implantation in 1996 and 1997. METHODS: The 30-day results and 6-month angiographic follow-up were analyzed in patients treated with coronary stents in 1996 and 1997. All patients underwent coronary stenting with high-pressure implantation (>12 atm) and antiplatelet drug regimen (aspirin plus ticlopidine). RESULTS: During the study period, 1,390 coronary stents were implanted in 1,200 vessels of 1,126 patients; 477 patients were treated in the year 1996 and 649 in 1997. The number of percutaneous procedures performed using stents increased significantly in 1997 compared to 1996 (64 % vs 48%, p=0.0001). The 30-day results were similar in both years; the success and stent thrombosis rates were equal (97% and 0.8%, respectively). The occurrence of new Q wave MI (1.3% vs 1.1%, 1996 vs 1997, p=NS), emergency coronary bypass surgery (1% vs 0.6%, 1996 vs 1997, p=NS) and 30-day death rates (0.2% vs 0.5%, 1996 vs 1997, p=NS) were similar. The 6-month restenosis rate was 25% in 1996 and 27% in 1997 (p= NS); the target vessel revascularization rate was 15% in 1996 and 16% in 1997 (p = NS). CONCLUSIONS: Intracoronary stenting showed a high success rate and a low incidence of 30-day occurrence of new major coronary events in both periods, despite the greater angiographic complexity of the patients treated with in 1997. These adverse variables did not have a negative influence at the 6-month clinical and angiographic follow-up, with similar rates of restenosis and ischemia-driven target lesion revascularization rates.

Intraaortic balloon pump support during coronary angioplasty. Initial experience

OBJECTIVE: To evaluate the use of the intraaortic balloon (IAoB) in association with coronary angioplasty in high-risk patients. METHODS: Fourteen high-risk patients unresponsive to clinical therapy and with formal contraindication to surgical revascularization were treated by coronary angioplasty, most of which was followed by stenting. All procedures were performed with circulatory support with the IAoB. This study reports the early results and the late findings after 12 months of follow-up. Six patients had multivessel coronary disease; of these, four had left main equivalent lesions and two had unprotected left main coronary artery disease, one of whom had severe "end-vessel" stenosis and the other was a patient with Chagas' disease with single-vessel lesion. Eleven patients had a left ventricular ejection fraction <30%. RESULTS: In 100% of the patients, the procedures were initially successful. Two patients had severe bleeding during the withdrawal of the left femoral sheath. At the end of twelve months, 4 patients were asymptomatic and the others were clinically controlled. There were two late deaths in the 7th and 11th months. CONCLUSION: The combined use of the intraaortic balloon pump and percutaneous coronary angioplasty in high-risk patients with acute ischemic syndromes provides the necessary hemodynamic stability to successfully perform the procedures.

Stenting of unprotected left main coronary artery in a patient with cardiogenic shock

A 64-year-old female presented with pulmonary edema and cardiogenic shock after coronary arteriography that showed severe suboclusive lesion in the left main coronary artery (LMCA) in a dominant left coronary system. The patient succesfully underwent urgent angioplasty with stent deployment in the LMCA. After an uneventful period, the patient was discharged at day six.

Percutaneous handling of coronary lesions >20mm through stents. Is there a first choice strategy?

OBJECTIVE - This study compared the early and late results of the use of one single stent with those of the use of multiple stents in patients with lesions longer than 20mm. METHODS - Prospective assessment of patients electively treated with stents, with optimal stent deployment and followed-up for more than 3 months. From February '94 to January '98, 215 patients with lesions >20mm were treated. These patients were divided into 2 groups as follows: Group A - 105 patients (49%) with one stent implanted; Group B - 110 patients (51%) with multiple stents implanted. RESULTS - The mean length of the lesions was 26mm in group A (21-48mm) versus 29mm in group B (21-52mm) (p=0.01). Major complications occurred in one patient (0.9%) in group A (subacute thrombosis, myocardial infarctionand death) and in 2 patients (1.8%) in group B (one emergency surgery and one myocardial infarction) (p=NS). The results of the late follow-up period (>6 months) were similar for both groups (group A = 82% vs group B = 76%; p=NS), and we observed an event-free survical in 89% of the patients in group A and in 91% of the patients in group B (p=NS). Angina (group A = 11% vs group B = 7%) and lesion revascularization (group A = 5% vs group B = 6%; p=NS) also occurred in a similar percentage. No infarction or death was observed in the late follow-up period; restenosis was identified in 33% and 29% of the patients in groups A and B, respectively (p=NS). CONCLUSION - The results obtained using one stent and using multiple stents were similar; the greater cost-effectiveness of one stent implantation, however, seems to make this strategy the first choice.

Coronary bilateral ostial enlargement using the saphenous vein in a patient with syphilitic aortitis

A patient with tertiary syphilis presenting with bilateral coronary ostial lesions and aortic regurgitation underwent surgical reconstruction of the coronary ostia by the anterior approach with autogenous saphenous vein grafting and substitution of the aortic valve with a bovine bioprosthesis. The procedure was easily performed and had good outcomes both early and late. The rarity of the association of a lesion in both coronary ostia with aortic regurgitation in syphilis and the surgical technique employed are discussed.

Epidemiological characteristics of congenital heart diseases in Londrina, Paraná South Brazil

OBJECTIVE: To determine the prevalence and other epidemiological characteristics of congenital heart diseases. METHODS: A retrospective population based study of children who were born in Londrina, from January '89 to December '98 (80,262 live births). Diagnoses were confirmed through autopsy, surgery, catheterization, or echocardiography. RESULTS: A total of 441 patients was as certained what corresponds to a prevalence of 5.494:1,000 live births. Ventricular septal defect was the commonest lesion. A small number of transpositions of the great vessels and of left ventricular hypoplasia was observed. A high propation of ventricular septal defect (28.3%) and atrioventricular septal defects (8.1%) occurred. Fifty-one (11.35%) affected children had syndromic diseases and 52 (12.01%) children had nonsyndromic anomalies. CONCLUSION: The prevalence of congenital heart diseases in Londrina is in accordance with that of other regions of the globe. This prevalence also may reflect the reality in the southern region of Brazil, because population characteristics are very similar in the 3 southernmost Brazilian states.

Use of tandem stents for treatment of helicoidal dissection of the right coronary artery

Coronary dissection occurs frequently and in several degrees during coronary angioplasty, which is one of the mechanisms for increasing the lumen diameter of a vessel. However the length of the dissection may affect the procedure, becoming the most frequent cause of total occlusion after coronary angioplasty. We report here a case of extensive dissection that occurred during the coronary angioplasty of a focused lesion, which we treated with two long stents.

Unsupported valvuloplasty in children with congenital mitral valve anomalies. Late clinical results

OBJECTIVE: To analyze late clinical evolution after surgical treatment of children, with reparative and reconstructive techniques without annular support. METHODS: We evaluated 21 patients operated upon between 1975 and 1998. Age 4.67±3.44 years; 47.6% girls; mitral insufficiency 57.1% (12 cases), stenosis 28.6% (6 cases), and double lesion 14.3% (3 cases). The perfusion 43.10±9.50min, and ischemia time were 29.40±10.50min. The average clinical follow-up in mitral insufficiency was 41.52±53.61 months. In the stenosis group (4 patients) was 46.39±32.02 months, and in the double lesion group (3 patients), 39.41±37.5 months. The echocardiographic follow-up was in mitral insufficiency 37.17±39.51 months, stenosis 42.61±30.59 months, and in the double lesion 39.41±37.51 months. RESULTS: Operative mortality was 9.5% (2 cases). No late deaths occurred. In the group with mitral insufficiency, 10 (83.3%) patients were asymptomatic (p=0.04). The majorit y with mild reflux (p=0.002). In the follow-up of the stenosis group, all were in functional class I (NYHA); and the mean transvalve gradient varied between 8 and 12mmHg, average of 10.7mmHg. In the double lesion group, 1 patient was reoperated at 43 months. No endocarditis or thromboembolism were reported. CONCLUSION: Mitral stenosis repair has worse late results, related to the valve abnormalities and associated lesions. The correction of mitral insufficiency without annular support showed good long-term results.

Characteristics associated with the dropout of hypertensive patients followed up in an outpatient referral clinic

OBJECTIVE: To determine the characteristics associated with the dropout of patients followed up in a Brazilian out patient clinic specializing in hypertension. METHODS: Planned prospective cohort study of patients who were prescribed an antihypertensive treatment after an extensive initial evaluation. The following parameters were analyzed: sex, age, educational level, duration of disease, pressure level used for classifying the patient, previous treatment, physical activity, smoking, alcohol consumption, familial history of hypertension, and lesion in a target organ. RESULTS: We studied 945 hypertensive patients, 533 (56%) of whom dropped out of the follow-up. The mean age was 52.3±12.9 years. The highest probabilities of dropout of the follow-up were associated with current smoking, relative risk of 1.46 (1.04-2.06); educational level equal to or below 5 years of schooling, relative risk of 1.52 (1.11-2.08); and hypertension duration below 5 years, relative risk of 1.78 (1.28-2.48). Age increase was associated with a higher probability of follow-up with a relative risk of 0.98 (0.97-0.99). CONCLUSION: We identified a group at risk for dropping out the follow-up, which comprised patients with a lower educational level, a recent diagnosis of hypertension, and who were smokers. We think that measures assuring adherence to treatment should be directed to this group of patients.