First Evidence of Cardiac Stem Cells From the Left Ventricular Apical Tip in Patients With Left Ventricular Assist Device Implantation.

BACKGROUND: Recent studies have challenged the dogma that the adult heart is a postmitotic organ and raise the possibility of the existence of resident cardiac stem cells (CSCs). Our study aimed to explore if these CSCs are present in the "ventricular tip" obtained during left ventricular assist device (LVAD) implantation from patients with end-stage heart failure (HF) and the relationship with LV dysfunctional area extent. METHODS: Four consecutive patients with ischemic cardiomyopathy and end-stage HF submitted to LVAD implantation were studied. The explanted "ventricular tip" was used as a sample of apical myocardial tissue for the pathological examination. Patients underwent clinical and echocardiographic examination, both standard transthoracic echocardiography (TTE) and speckle tracking echocardiography (STE), before LVAD implantation. RESULTS: All patients presented severe apical dysfunction, with apical akinesis/diskinesis and very low levels of apical longitudinal strain (-3.5 ± 2.9%). Despite this, the presence of CSCs was demonstrated in pathological myocardial samples of "ventricular tip" in all 4 of the patients. It was found to be a mean of 6 c-kit cells in 10 fields magnification 40×. CONCLUSIONS: Cardiac stem cells can be identified in the LV apical segment of patients who have undergone LVAD implantation despite LV apical fibrosis.

Resposta humoral de bovinos vacinados contra as toxinas botulínicas tipos c e dem diferentes faixas etárias / Humoral response of vaccinated cattle against toxins of Clostridium botulinum types c and d at different ages

Foi verificada pelo teste de ELISA indireto a resposta humoral contra os toxoides botulínicos C e D em bovinos de diferentes idades. O estudo envolveu 90 animais, que foram divididos em três grupos (n = 30), de acordo com a sua faixa etária; inferior a 2 anos de idade (G1), entre 2 e 5 anos (G2) e superior a 5 anos (G3). Os grupos experimentais foram vacinados com duas doses de vacina antibotulínica bivalente (C e D) comercial, nos dias 0 e 42 após a primo-vacinação (booster). Na avaliação, quando realizada 30 dias após o booster, os animais do G3 apresentaram maior produção de anticorpos (p < 0,05) em relação aos demais grupos. Entre o G1 e G2 não houve diferença significativa na resposta humoral contra a toxina C, no entanto, contra a toxina D, os animais do G1 apresentaram maior produção de anticorpos. Todos os grupos produziram uma resposta significativa de anticorpos contra as toxinas botulínicas após a 2ª dose da vacina bivalente comercial, principalmente contra o tipo D.

Humoral response of vaccinated cattle against toxins of clostridium botulinum types C and D at different ages. Cattle humoral response against type C and D botulinum toxoids (indirect ELISA) was verified in animals of different ages. The animals (n = 90) were divided in three groups (n = 30): group one (G1): less than two years old; group two (G2): from 2 to 5 years old; group three (G3): more than 5 years old. The groups were vaccinated with two doses [0 and 42 days after primary vaccination (booster)] of bivalent (C and D) antibotulinum vaccine. Group three had higher antibody production (p ≤ 0.05) compared to the other groups, 30 days after the booster. There was no difference (G1 and G2; p ≥ 0.05) in the humoral response against C toxin, however, against D toxin, group one had higher antibody production. It was possible to conclude that after two doses of the commercial bivalent vaccine all groups produced a significant antibody response against botulinum toxins, especially against D type.

Neonatal immune response of Brazilian beef cattle to vaccination with clostridium botulinum toxoids types C and D by indirect ELISA

Types C and D strains of Clostridium botulinum are commonly related to avian and mammalian botulism. Although there are numerous vaccine recommendations, little research has been conducted to indicate the real effectiveness of vaccine timing or the ideal immunization protocol for young beef calves. Four commercially available vaccines, two bivalent (Clostridium botulinum types C and D; vaccines 1 and 2) and two polyvalent (all Clostridium spp. including Clostridium botulinum types C and D; vaccines 3 and 4), that are currently used in Brazilian herds, were tested in order to verify the maternal immune response. One hundred cows, divided into four vaccinated groups and one unvaccinated group, were given a two-dose subcutaneous immunization, at day zero, followed by a second dose given at 42 days post-vaccination, which corresponded to 40 days before birth. Serum samples (n = 75) were collected only from healthy neonatal calves at 0, 7, 45 and 90 days post-calving (DPC) and subjected to indirect ELISA using the purified C and D holotoxins as capture antigens. The serological profile showed that all vaccines were able to induce a satisfactory neonatal immune response to both holotoxins at 7 DPC. However, at 45 and 90 DPC, a significant reduction (p < 0.05) was observed in the antibody level against C and D holotoxins in all tested vaccines. Neonatal immunization in calves is compromised by significant levels of maternal antibodies so that the necessity of planning a calf vaccination program involves assessment of disease risks at the production site. Finally, our findings represent the first demonstration of maternal immunity transferred to neonatal beef calves, including immunity levels after vaccination against Clostridium botulinum toxoids C and D.

Kaposi's sarcoma misdiagnosed as a diabetic plantar foot ulcer.

In this report, the authors describe the case of a patient with Kaposi's sarcoma that was initially misdiagnosed as a plantar ulcer. The ulcer typically appeared as a neuropathic foot ulceration located on the plantar aspect of the first metatarsal head. There was hyperkeratosis on the plantar surfaces of the other metatarsal heads. However, the lesion had mushrooming granulation tissue, without undermined perilesional edges. A wound biopsy revealed the presence of Kaposi's sarcoma. The presence of cancerous lesions on the plantar aspect of the foot is an infrequent event in diabetic patients. However, given the malignant nature of some skin cancers careful clinical examination and biopsy of the wound are advisable.

Angioplasty for diabetic patients with failing bypass graft or residual critical ischemia after bypass graft.

OBJECTIVE: To evaluate the efficacy of peripheral angioplasty (PTA) in the treatment of diabetic patients with previous peripheral bypass graft and recurrent critical limb ischemia (CLI). METHODS: Between January and December 2006, 293 diabetic patients presenting with critical limb ischemia (CLI) according to the TASC 2000 criteria were admitted to our footcare centre. Among these patients, 32 of them had previously undergone bypass grafting: femoropopliteal in 26 patients, femoroposterior tibial in 3 patients, femoroperoneal in the remaining 3. All these patients underwent angiography and, whenever possible, a concomitant PTA procedure. RESULTS: Six patients presented with stenosis at the distal anastomosis, 2 with stenosis at the proximal anastomosis and in 5 patients both the distal and proximal anastomosis were stenosed. In 12 patients the graft was completely occluded. In 7 patients the graft appeared patent but all the infrapopliteal arteries were occluded. The average time interval between bypass and subsequent hospital admission because of CLI was 6.3+/-4.2 months for patients with patent grafts and 20.5+/-12.0 months for those with failing grafts (p=0.004). A successful PTA was performed in 25 patients (78.1%). In all patients with patent grafts, PTA recanalized one infrapopliteal artery. Recanalization of the graft was obtained in all 13 patients with non-occluded graft. Recanalization of superficial femoral artery occlusion by means of PTA was obtained in 5 out of the 12 patients in whom the graft was completely occluded. Five patients underwent major amputation within 30 days and 3 further patients during the follow-up period. Patients were followed up until December 31 2007, with a mean follow-up of 1.89+/-0.27 years. Restenosis occurred in 7 (28.0%) of the 25 patients in whom a successful PTA was performed. In 5 of these 7 patients, PTA was repeated successfully. In 2 patients in whom a further PTA was not feasible a major amputation was performed. At the end of the follow-up period the cumulative primary patency rate was 72%, the assisted patency rate was 92%. CONCLUSIONS: PTA is an effective method for revascularizing secondary obstructions in patients with graft failure (and no possibility of a redo graft). PTA also is effective in at least one subgenicular artery in patients with diabetes with inadequate run-off after femoropopliteal bypass grafting.

When is a technically successful peripheral angioplasty effective in preventing above-the-ankle amputation in diabetic patients with critical limb ischaemia?

AIM: To determine parameters predictive of avoidance of major (above-the-ankle) amputation after a technically successful peripheral angioplasty (PTA) in patients with diabetes with critical limb ischaemia. METHODS: From January 1999 to December 2003, 420 consecutive patients with diabetes admitted to hospital because of critical limb ischaemia underwent peripheral angiography and concomitant technically successful PTA. Transcutaneous oxygen tension (TcPO(2)) was measured before and after PTA. Major amputation at 30 days was recorded. RESULTS: After PTA, the iliac-femoral-popliteal axis was patent in all patients. In 67 patients, all three crural arteries were patent, in 143 patients 2 crural arteries were patent, and in 186 patients one crural artery was patent (104 peroneal, 62 anterior tibial, 20 posterior tibial). In 24 patients, all three crural arteries were occluded. Twenty-two major amputations were performed. Of these, 15 were performed in the 24 patients with occlusion of all the infrapopliteal arteries. Seven of the 186 patients in whom only the peroneal artery was patent required amputation. In patients not requiring amputation, TcPO(2) increased from 15.5 +/- 11.9 to 45.0 +/- 12.0 mmHg (P = 0.000), while in those requiring amputation, TcPO(2) increased from 9.6 +/- 7.7 to 18.6 +/- 8.1 mmHg (P < 0.082). Multivariate analysis indicated an independent role of occlusion of infrapopliteal arteries after PTA (OR 8.20 for every crural obstructed artery, P = 0.022, CI 1.35-49.6) and TcPO(2) after PTA (OR 0.80 for increase of 1 mmHg, P < 0.001, CI 0.74-0.88). CONCLUSIONS: In patients with diabetes, PTA is effective in avoiding major amputation, provided recanalization occurs in at least one tibial artery down to the foot. In a few patients, re-canalization of the peroneal artery alone is not sufficient to avoid major amputation.

Predictive values of transcutaneous oxygen tension for above-the-ankle amputation in diabetic patients with critical limb ischemia.

OBJECTIVE: To assess the values of transcutaneous oxygen tension (TcPO2) capable of predicting above-the-ankle amputation in diabetic patients diagnosed for critical limb ischemia (CLI) according to the criteria of the TransAtlantic Inter-Society Consensus. DESIGN: Retrospective study. METHODS: From January 1999 to December 2003, 564 diabetic patients were consecutively hospitalized for CLI in one limb. Revascularization with angioplasty or bypass graft was performed when possible and, if not possible, prostanoid therapy was used. In patients in whom therapies did not relieve the rest pain or the gangrene was extended above the Chopart joint, an above-the-ankle-amputation was performed. After treatment TcPO2 values were evaluated in all patients at the dorsum of the foot. RESULTS: Fifty-five (9.8%) patients underwent an above-the-ankle amputation: 22 of 420 patients who underwent angioplasty, 17 of 117 patients who underwent bypass (14.5%) and 16 of 27 patients in whom revascularization was not possible. Post-treatment TcPO2, measured by a receiver operating characteristic (ROC) curve, showed a value 34 mmHg as the best threshold for determining the need for revascularization, with an area under the curve of 0.89 (95%CI 0.85-0.94). Using logistic regression analysis the probability of above-the-ankle amputation for this threshold is 9.7% and reduces to 3% for TcPO2 > 40 mmHg. CONCLUSION: TcPO2 levels<34 mmHg indicate the need for revascularization, while for values >or= 34 < 40 mmHg this need appears less pressing, although there remains a considerable probability of amputation. TcPO2 levels greater than 40 mmHg suggest that revascularization is dependent on the severity of tissue loss and possible morbidity caused by the procedure.

Early and five-year amputation and survival rate of diabetic patients with critical limb ischemia: data of a cohort study of 564 patients.

OBJECTIVE: To evaluate the early and late major amputation and survival rates and related risk factors in diabetic patients with critical limb ischemia (CLI). DESIGN: Retrospective study. METHODS: Revascularization feasibility, major amputation, survival rate and related risk factors were recorded in 564 diabetic patients consecutively hospitalized for CLI from 1999 to 2003 and followed until June 2005. RESULTS: Peripheral angioplasty (PTA) was carried out in 420 (74.5%), bypass graft (BPG) in 117 (20.7%) patients. In 27 (4.8%) patients both PTA and BPG were not possible. Twenty-three above-the-ankle amputations (4.1%) were performed at 30 days: 6 in PTA patients, 3 in BPG patients, 14 in non revascularized patients. In the follow-up of 558 patients (98.9%), 62 repeated PTAs and 9 new BPGs, 32 new major amputations (16 in PTA patients, 14 in BPG patients and 2 in non-revascularized patients) were performed. Major amputation was associated with absence of revascularization (OR 35.9, p < 0.001, CI 12.9-99.7), occlusion of each of the three crural arteries (OR 8.20, p = 0.022, CI 1.35-49.6), wound infection (OR 2.1, p = 0.004 CI 1.3-3.6), dialysis (OR 4.7, p = 0.001 CI 1.9-11.7) increase in TcPO2 after revascularization (OR 0.80, p < 0.001 CI 0.74-0.87). One hundred seventy three patients died during follow-up and this was associated with age (HR 1.05, p < 0.001 CI 1.03-1.07), history of cardiac disease (HR 2.16, p < 0.001 CI 1.53-3.06), dialysis (HR 3.52, p < 0.001 CI 2.08-5.97), absence of revascularization (HR 1.68, p < 0.001, CI 1.29-2.19) and impaired ejection fraction (HR 1.08, p < 0.001, CI 1.05-1.09). CONCLUSIONS: In diabetic patients with CLI the revascularization is feasible in most cases and allows a low rate of early major amputation. This rate is higher in the follow-up period. Major amputation is very high in patients where revascularization is not feasible while the high mortality rate is due to the serious comorbidities observed in these patients.

Peripheral angioplasty as the first-choice revascularization procedure in diabetic patients with critical limb ischemia: prospective study of 993 consecutive patients hospitalized and followed between 1999 and 2003.

OBJECTIVE: To evaluate the effectiveness of peripheral angioplasty (PTA) as the first-choice revascularisation procedure in diabetic patients with critical limb ischemia (CLI). DESIGN: Prospective study. METHODS: PTA was employed as first choice revascularisation in a consecutive series of diabetic patients hospitalized for CLI between January 1999 and December 2003. RESULTS: PTA was successful performed in 993 patients. Seventeen (1.7%) major amputations were carried out. One death and 33 non-fatal complications were observed. Mean follow-up was 26+/-15 months. Clinical restenosis was observed in 87 patients. The 5 years primary patency was 88%, 95% CI 86-91%. During follow-up 119 (12.0%) patients died at a rate of 6.7% per year. CONCLUSIONS: PTA as the first choice revascularisation procedure is feasible, safe and effective for limb salvage in a high percentage of diabetic patients. Clinical restenosis was an infrequent event and PTA could successfully be repeated in most cases.

Patología tumoral de ovario en edad pediátrica: experiencia del Hospital de Niños "Superiora Sor María Ludovica" / Pediatric ovarian tumors

Se evalúan 44 pacientes ingresadas en el período comprendido entre 1984-2001 con patología ovárica. El 79,5 por ciento (n=35) correspondieron a tumores y el 20,5 por ciento (n=9) a lesiones quísticas. Dentro del primer grupo 31/35 correspondieron a tumores germinales y 16/31 fueron teratomas maduros. Luego de evaluación clínica, imaginológica y de marcadores tumorales en aquellos con marcadores positivos y contenido mixto o sólido se realizó Punción Aspiración con Aguja Fina (PAAF) para corroborar diagnóstico. La conducta inicial fue la cirugía en 32/34 tumores y en 9/9 lesiones quísticas no tumorales. El 67 por ciento de las últimas ingresó con cuadro abdominal agudo por lo que recibió cirugía de urgencia. De obtenerse el diagnóstico sin cuadro de abdomen agudo y con marcadores tumorales negativos se utilizó la vía laparoscópica en 3 pacientes (2 quistes simples y 1 teratoma maduro). De las 15 pacientes con tumores germinales malignos 11 recibieron quimioterapia de acuerdo a protocolos SIOP (consecutivos por el tiempo de estudio) y 2 recibieron radioterapia luego de haberse diagnosticado disgerminoma. Sólo 2 pacientes, por considerarse los tumores irresecables al ingreso, recibieron quimioterapia preoperatoria. La sobrevida global fue del 94.5 por ciento (33/35) y la sobrevida libre de reactivaciones del 90 por ciento (31/35). Las dos pacientes fallecidas correspondieron al período inicial del estudio (1984-5) ingresando con diagnóstico tardío. Cinco pacientes (34 por ciento) de las portadoras de tumores malignos y que recibieron quimioterapia se han casado y tres de ellas tienen actualmente 5 hijos sanos que se controlan en nuestro Hospital

Patología tumoral de ovario en edad pediátrica: experiencia del Hospital de Niños "Superiora Sor María Ludovica" / Pediatric ovarian tumors

Se evalúan 44 pacientes ingresadas en el período comprendido entre 1984-2001 con patología ovárica. El 79,5 por ciento (n=35) correspondieron a tumores y el 20,5 por ciento (n=9) a lesiones quísticas. Dentro del primer grupo 31/35 correspondieron a tumores germinales y 16/31 fueron teratomas maduros. Luego de evaluación clínica, imaginológica y de marcadores tumorales en aquellos con marcadores positivos y contenido mixto o sólido se realizó Punción Aspiración con Aguja Fina (PAAF) para corroborar diagnóstico. La conducta inicial fue la cirugía en 32/34 tumores y en 9/9 lesiones quísticas no tumorales. El 67 por ciento de las últimas ingresó con cuadro abdominal agudo por lo que recibió cirugía de urgencia. De obtenerse el diagnóstico sin cuadro de abdomen agudo y con marcadores tumorales negativos se utilizó la vía laparoscópica en 3 pacientes (2 quistes simples y 1 teratoma maduro). De las 15 pacientes con tumores germinales malignos 11 recibieron quimioterapia de acuerdo a protocolos SIOP (consecutivos por el tiempo de estudio) y 2 recibieron radioterapia luego de haberse diagnosticado disgerminoma. Sólo 2 pacientes, por considerarse los tumores irresecables al ingreso, recibieron quimioterapia preoperatoria. La sobrevida global fue del 94.5 por ciento (33/35) y la sobrevida libre de reactivaciones del 90 por ciento (31/35). Las dos pacientes fallecidas correspondieron al período inicial del estudio (1984-5) ingresando con diagnóstico tardío. Cinco pacientes (34 por ciento) de las portadoras de tumores malignos y que recibieron quimioterapia se han casado y tres de ellas tienen actualmente 5 hijos sanos que se controlan en nuestro Hospital (AU)

Association of obesity and type II diabetes mellitus as a risk factor for gallstones.

Age, female sex, and obesity are well-known risk factors for gallstones; in contrast the possible role of type 2 diabetes mellitus (type-2 DM) is controversial. One reason for this discrepancy might be that type 2 DM is often accompanied by obesity. Therefore, the aim of this study was to evaluate the importance of obesity and of type 2 DM, separately and together, as risk factors for gallstones. In all, 203 obese patients with normal glucose tolerance (obese NGT), 446 obese patients with type 2 DM (obese type 2 DM), 269 lean patients with type 2 DM (lean type 2 DM) and 250 lean subjects with a normal glucose tolerance (lean NGT) were evaluated by ultrasonography for the presence of gallstones. At univariate analysis patients with gallstones (177) were older and were more frequently affected by both obesity and type 2 DM, and had higher triglycerides and fasting blood glucose levels. At multiple logistic regression analysis, only age and obesity, both in the presence or in absence of type 2 DM, were strongly associated with gallstones (P < 0.001); diabetes alone had a lower level of statistical significance (P = 0.07). These data suggest that obesity is a stronger risk factor for gallstones than type 2 DM.