Usefulness of resuscitative endovascular balloon occlusion of the aorta (REBOA) in controlling puerperal bleeding in patients with abnormal placental implantation.

BACKGROUND AND AIMS: Abnormalities of placental implantation, which make up the spectrum of placenta accreta, are associated with high maternal morbidity and mortality due to massive bleeding during delivery. Placing aortic occlusion balloons helps control the bleeding, facilitating surgical intervention. A new device, resuscitative endovascular balloon occlusion of the aorta (REBOA), minimizes the risks and complications associated with the placement of traditional aortic balloons and is also efficacious in controlling bleeding. The aim of this study is to evaluate the usefulness, efficacy, and safety of REBOA in puerperal bleeding due to abnormalities of placental implantation. MATERIAL AND METHODS: Between November 2019 and November 2021, our interventional radiology team placed six REBOA devices in six women scheduled for cesarean section due to placenta accrete. RESULTS: Mean blood loss during cesarean section after REBOA (3507.5 mL) was similar to the amounts reported for other aortic balloons. The mean number of units of packed red blood cells required for transfusion was 3.5. Using REBOA provided the surgical team with adequate conditions to perform the surgery. There were no complications derived from REBOA, and the mean ICU stay was <2 days. CONCLUSION: The technical characteristics of the REBOA device make it a safe and useful alternative for controlling massive bleeding in patients with placenta accreta.

Sacral neuromodulation for fecal incontinence in Latin America: initial results of a multicenter study.

BACKGROUND: Sacral neuromodulation (SNM) is a widely used therapeutic option for fecal incontinence (FI). Larger series are mainly from Western countries, while few reports address the results of SNM in less developed or less wealthy countries. The aim of the present study was to evaluate the efficacy of SNM in patients with FI in Latin America. METHODS: A retrospective study was conducted on patients with FI who had SNM between 2009 and 2016 at 15 specialized colorectal surgery centers in Latin America. Main outcomes measures were functional outcomes, postoperative complications, requirement of revisional surgery, and requirement of device removal. All patients had failed conservative management and had clinical assessment including recording of the validated Cleveland Clinic Florida Fecal Incontinence Score (CCF-FIS) and, when available, anal manometry and endoanal ultrasound. Patients were followed up for a median of 36.7 (1-84) months. RESULTS: One hundred and thirty-one patients [119 females, median age of 62.2 (range 19-87) years] were included. The most common etiology of FI was obstetric injury (n = 60; 45.8%). After successful test lead implantation, the stimulator was permanently placed in 129 patients (98.5%). One patient failed to respond in the test phase and one patient did not proceed to permanent implantation for insurance reasons. Nineteen patients (14.7%) had 19 complications including infection (n = 5, 3.8%), persistent implant site pain (n = 5, 3.8%), generator/lead dislodgment (n = 5, 3.8%), malfunctioning device (n = 3, 2.3%), and hematoma (n = 1, 0.7%). Reimplantation after the first and second stages was necessary in 2 (1.5%) and 3 patients (2.3%), respectively. The device removal rate was 2.2%. At a median follow-up of 36.7 (range 1-84) months, the CCF-FIS significantly improved from a preoperative baseline of 15.9 ± 2.98 to 5.2 ± 3.92 (95%CI: 15.46 vs 4.43; p < 0.0001). Overall, 90% of patients rated their improvement as "significant". CONCLUSIONS: Sacral nerve stimulation for FI is safe and efficient, even in less wealthy or less developed countries.

Characterization of the respiratory pattern in patients with chronic heart failure applying joint symbolic dynamics / Caracterización del patrón respiratorio de pacientes con insuficiencia cardíaca crónica mediante análisis de dinámica simbólica conjunta

Abstract: This work proposes a method to characterize the respiratory pattern of patients with chronic heart failure (CHF) to determine non-periodic breathing (nPB), periodic breathing (PB) and Cheyne-Stokes respiration (CSR) through non-linear, symbolic analysis of biological signals. A total of 43 patients were examined for their cardiorespiratory profiles, their ECG and respiratory pattern signals were processed, analyzed and studied for parameters that could be of potential use in clinical decision making, specifically in patient classification. Patients in the study were characterized through their cardiorespiratory signals, applying joint symbolic dynamics (JSD) analysis to cardiac beat and respiratory interval durations. The most statistically significant parameters across all groups were identified through a Kruskal-Wallis two tailed test (α = 0.05) and a linear discriminant analysis (LDA) classification method based on such parameters was developed. The best result achieved with this classification method uses 10 features to discriminate patients with a 97.67% Accuracy (Acc). The best features to discriminate among groups are related to cardiorespiratory interaction rather than just respiration patterns alone. Results further support the idea that abnormal breathing patterns derive from physiological abnormalities in chronic heart failure.

Resumen: El trabajo propone un método para identificar el patrón respiratorio de pacientes con insuficiencia cardiaca crónica (CHF) con la finalidad de determinar respiración no periódica (NPB), respiración periódica (PB) y respiración de Cheyne-Stokes (CSR) a través de análisis simbólico no lineal de señales biológicas. Se examinaron los perfiles cardiorrespiratorios de 43 pacientes; sus señales de ECG y patrón respiratorio fueron procesados, analizados y estudiados en busca de parámetros que pudieran ser de utilidad, específicamente en la clasificación de pacientes. Estos pacientes se caracterizaron por medio de sus señales cardiorrespiratorias, aplicando un análisis de dinámica simbólica de conjuntos al ritmo cardíaco y a la duración de los intervalos respiratorios. Los parámetros de mayor significancia estadística entre todos los grupos se identificaron a través de una prueba Kruskal-Wallis de dos colas ( α = 0,05) y mediante un método de clasificación por análisis discriminante lineal (LDA). El mejor resultado conseguido con este método utiliza 10 características para discriminar a los pacientes con una precisión de 97,67% (Acc). Las características para discriminar entre grupos estuvieron relacionados con la interacción cardiorrespiratoria más que con solo los patrones de respiración, respaldando así la idea de que los patrones de respiración anormales derivan de anomalías fisiológicas presentes en la insuficiencia cardíaca crónica.

Mechanical unloading of bone in microgravity reduces mesenchymal and hematopoietic stem cell-mediated tissue regeneration.

Mechanical loading of mammalian tissues is a potent promoter of tissue growth and regeneration, whilst unloading in microgravity can cause reduced tissue regeneration, possibly through effects on stem cell tissue progenitors. To test the specific hypothesis that mechanical unloading alters differentiation of bone marrow mesenchymal and hematopoietic stem cell lineages, we studied cellular and molecular aspects of how bone marrow in the mouse proximal femur responds to unloading in microgravity. Trabecular and cortical endosteal bone surfaces in the femoral head underwent significant bone resorption in microgravity, enlarging the marrow cavity. Cells isolated from the femoral head marrow compartment showed significant down-regulation of gene expression markers for early mesenchymal and hematopoietic differentiation, including FUT1(-6.72), CSF2(-3.30), CD90(-3.33), PTPRC(-2.79), and GDF15(-2.45), but not stem cell markers, such as SOX2. At the cellular level, in situ histological analysis revealed decreased megakaryocyte numbers whilst erythrocytes were increased 2.33 fold. Furthermore, erythrocytes displayed elevated fucosylation and clustering adjacent to sinuses forming the marrow-blood barrier, possibly providing a mechanistic basis for explaining spaceflight anemia. Culture of isolated bone marrow cells immediately after microgravity exposure increased the marrow progenitor's potential for mesenchymal differentiation into in-vitro mineralized bone nodules, and hematopoietic differentiation into osteoclasts, suggesting an accumulation of undifferentiated progenitors during exposure to microgravity. These results support the idea that mechanical unloading of mammalian tissues in microgravity is a strong inhibitor of tissue growth and regeneration mechanisms, acting at the level of early mesenchymal and hematopoietic stem cell differentiation.

Evaluation of tear production with modified Schirmer tear test-1 during the neonatal period in cats / Avaliação da produção lacrimal pelo teste da lágrima de Schirmer-1 modificado durante o período neonatal em gatos

The study aimed to evaluate tear production by means of modified Schirmer tear tes-1 (mSTT-1) in neonate cats. Likewise, correlation between mSTT-1 and STT-1 was assessed in vitro. Standard SST strips were cut in half and after eye lid opening, tear production of neonates (n=15) was daily measured in both eyes (mSTT-1), until the 7th day, and at day 14, 21, and 28. Animals were daily weighted until 28 days of age. Results were compared statistically (P<0.05). During the first 7 days, the overall mSTT-1 mean was 0.76 wetting/minute. Significant differences between right and left eyes were not observed at any time point (P=1.00). Tear secretion increased significantly, from the 14th to 28th day, in comparison with 7 first days (P<0.05). Positive correlation between maturity parameters and tear secretion was observed (P<0.0001). Distance between slopes of each strip changed significantly (P<0.0001). It was concluded that tear secretion in the neonatal period of cats is very below the reference values described for young and adults of the same species. It is not possible to extrapolate results obtained with mSTT-1 to standard STT-1.

Objetivou-se avaliar a produção lacrimal, por meio do teste da lágrima de Schirmer-1 modificado (TLS-1m) em gatos neonatos. Outrossim, estabelecer in vitro a existência de correlação entre o TLS e o TLS-1m. Tiras pa-dronizadas para realização do TLS foram partidas ao meio e após a abertura das pálpebras, a produção lacrimal dos neonatos (n=15) foi aferida em ambos os olhos (TLS-1m), diariamente, até o sétimo e aos 14, 21 e 28 dias. Os animais foram pesados diariamente até os 28 dias de idade. Os resultados foram comparados estatisticamente (p<0,05). Durante os primeiros sete dias de avaliação, a média geral obtida pelo TLS-1m foi de 0,76±0,08 mm/minuto. Não se constatou diferença significativa entre os olhos direito e esquerdo, em nenhum dos períodos avaliados (p=1,00). A produção lacrimal elevou-se significativamente, do 14º até o 28º dia, comparativamente aos primeiros sete dias (p<0,05). Observou-se correlação positiva entre parâmetros de maturidade e a produção lacrimal (p<0,0001). A distância entre as linhas de cada tira foi significativa (p<0,0001). Conclui-se que a produção lacrimal no período neonatal em gatos é bem inferior aos valores de referência descritos para adultos e jovens da mesma espécie. Não é possível extrapolar valores obtidos com o TLS-1 modificado para o TLS-1 padrão.

Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity.

BACKGROUND: In obesity, insulin resistance appears frequently after activation of proinflammatory molecules. Caspase-generated cytokeratin-18 (CK-18) fragments are produced during the apoptosis of hepatic cells. The main objective in the present study is to investigate the relationship between insulin resistance and caspase-generated CK-18 fragments in patients with severe obesity. METHODS: Sixty-two patients selected for bariatric surgery were clinically studied (sex, age, weight, waist diameter, body mass index, arterial pressure and type 2 diabetes mellitus) and analytic parameters were measured in blood (glucose concentration, cholesterol, triglycerides, insulin, glycosylated hemoglobin, aspartate aminotransferase, alanine aminotransferase, high-sensitivity C-reactive protein, adiponectin, interleukin 6, interleukin 18 and CK-18 fragments). Patient group division was based on 70th percentile of insulin resistance as measured by homeostasis model assessment (HOMA) and also according to liver histology. RESULTS: Patients with greater insulin resistance (percentile > 70th) showed higher values of CK-18 fragments, interleukin 6 and transaminases. A positive correlation between the HOMA score, value of CK-18 fragments and triglyceride level was found. A correlation between CK-18 fragments with interleukin 6, triglycerides and transaminases was also observed. HOMA score and value of CK-18 fragments correlated with the degree of liver fibrosis. CONCLUSIONS: Greater degree of insulin resistance induces apoptosis of hepatic cells as measured by the serum levels of CK-18 fragments.

Pharmacokinetics of a new Autogel formulation of the somatostatin analogue lanreotide after a single subcutaneous dose in healthy volunteers.

The pharmacokinetics/tolerability of lanreotide Autogel have been evaluated. Healthy volunteers (n = 24) first received immediate-release lanreotide as a single subcutaneous (s.c.) injection. After two days, 40 or 60 mg lanreotide Autogel was injected subcutaneously. Blood was sampled at various intervals for 56 days. Systemic/local adverse events and changes in biological profile/vital signs were recorded. Lanreotide Autogel produced a prolonged-release pharmacokinetic profile: mean area under the serum concentration-time curve from time 0 to infinity (AUC) was 53.73 +/- 8.99 and 79.48 +/- 13.06 ng mL(-1) day for 40 and 60 mg, respectively, mean peak serum concentration (C(max)) was 4.38 +/- 2.91 and 5.71 +/- 3.52 ng mL(-1), respectively, median time to reach C (minimum-maximum) was 0.50 (0.083-18.0) and 0.38 (0.083-9.01) days, respectively, mean apparent elimination half-life was 21.63 +/- 9.42 and 22.01 +/- 9.87 days, respectively, and relative bioavailability was 0.93 +/- 0.12 and 0.82 +/- 0.15, respectively. Thus, lanreotide Autogel exhibited linear pharmacokinetics for the doses studied. Pharmacokinetic profiles were similar in both genders, apart from statistically significant differences in C(max) and C(max)/AUC. The Autogel formulation of lanreotide was well tolerated, with systemic adverse events being mild/moderate. Erythema and a painless subcutaneous induration were the most common local adverse events. Lanreotide Autogel provided a prolonged dosing interval and good tolerability for treating acromegaly and carcinoid syndrome.

Self-association process of a peptide in solution: from beta-sheet filaments to large embedded nanotubes.

Lanreotide is a synthetic octapeptide used in the therapy against acromegaly. When mixed with pure water at 10% (w/w), Lanreotide (acetate salt) forms liquid crystalline and monodisperse nanotubes with a radius of 120 A. The molecular and supramolecular organization of these structures has been determined in a previous work as relying on the lateral association of 26 beta-sheet filaments made of peptide noncovalent dimers, the basic building blocks. The work presented here has been devoted to the corresponding self-association mechanisms, through the characterization of the Lanreotide structures formed in water, as a function of peptide (acetate salt) concentration (from 2% to 70% (w/w)) and temperature (from 15 degrees C to 70 degrees C). The corresponding states of water were also identified and quantified from the thermal behavior of water in the Lanreotide mixtures. At room temperature and below 3% (w/w) Lanreotide acetate in water, soluble aggregates were detected. From 3% to 20% (w/w) long individual and monodisperse nanotubes crystallized in a hexagonal lattice were evidenced. Their molecular and supramolecular organizations are identical to the ones characterized for the 10% (w/w) sample. Heating induces the dissolution of the nanotubes into soluble aggregates of the same structural characteristics as the room temperature ones. The solubilization temperature increases from 20 degrees C to 70 degrees C with the peptide concentration and reaches a plateau between 15% and 25% (w/w) in peptide. These aggregates are proposed to be the beta-sheet filaments that self-associate to build the walls of the nanotubes. Above 20% (w/w) of Lanreotide acetate in water, polydisperse embedded nanotubes are formed and the hexagonal lattice is lost. These embedded nanotubes exhibit the same molecular and supramolecular organizations as the individual monodisperse nanotubes formed at lower peptide concentration. The embedded nanotubes do not melt in the range of temperature studied indicating a higher thermodynamic stability than individual nanotubes. In parallel, the thermal behaviors of water in mixtures containing 2-80% (w/w) in peptide have been studied by differential scanning calorimetry, and three different types of water were characterized: 1), bulk water melting at 0 degrees C, 2), nonfreezing water, and 3), interfacial water melting below 0 degrees C. The domains of existence and coexistence of these different water states are related to the different Lanreotide supramolecular structures. All these results were compiled into a binary Lanreotide-water phase diagram and allowed to propose a self-association mechanism of Lanreotide filaments into monodisperse individual nanotubes and embedded nanotubes.

Incidence and epidemiological factors of hepatocellular carcinoma in Valencia during the year 2000.

AIM: to ascertain the incidence and epidemiological factors of hepatocellular carcinoma in the Province of Valencia, Spain. DESIGN: a prospective study was made of hepatocellular carcinoma during the year 2000 collecting all diagnosed cases from four hospitals during that year. RESULTS: a total of 64 cases of hepatocellular carcinoma with a male predominance (42/22) and a mean age of 73.4 years (range of 42-90) were diagnosed. Incidence rate was 8.2 per 100,000, and cirrhosis was known to pre-exist in most cases, half of which were Child-Pugh A. Anti-VHC positive, alone or alcohol or virus B related was detected in 3 of every 4 cases. In the majority of the cases the tumours were located in the right hepatic lobe and the size at first diagnosis was less than 3 cm in 37.3% of the cases. Alpha-fetoprotein levels only exceeded 200 mg/ml in 37.3% of the patients and bore a good size relation to the tumour (R=0.245, p=0.003. No relation vis-à-vis aetiology with age, sex, tumour location or Child-Pugh stage was found. CONCLUSIONS: the incident rate of hepatocellular carcinoma in Valencia province during 2000 was 8.2 per 100,000 individuals. This lesion appeared more frequently in men between the ages of 60-80. Hepatitis C virus was the main etiologic agent found. Key words: Hepatocellular carcinoma. Incidence. Hepatitis C virus. Epidemiology. Child-Pugh grade. Alpha-fetoprotein.

Balanced reciprocal translocation (X;20) limited to Wilms' tumor in a Wiedemann-Beckwith syndrome.

A girl aged 4 years 3 months with sporadic unilateral Wilms' tumor associated with Wiedemann-Beckwith syndrome, but without aniridia, was found to have a t(X;20) in the tumor cells. Karyotypes of peripheral blood of the patient and her parents were normal. This translocation was confined to the tumor and not been previously reported either in nephroblastoma or any other neoplastic processes. Although there is no microscopic deletion on chromosome 11 and catalase activity was not decreased, we cannot rule out the possibility of a point mutation or a submicroscopic deletion.

The 18p- syndrome. Report of five cases.

Five children, three males and two females were found to have a short arm deletion of chromosome 18. Four of them display some of the typical features of this syndrome: microcephaly, round face, hypertelorism, broad-based nose, "carp-mouth", microrethrognathia, pterygium colli, dysplastic and low set ears, clinodactily, failure to grow, muscular hypotony and mental retardation. Different hypotheses are discussed in order to explain the variable phenotypical expression of the 18 p-syndrome.

Induction of protective immunity against experimental infection with malaria using synthetic peptides.

Synthetic peptides are potential vaccine candidates because they may be able to induce high antibody titres and specific cellular immune responses against native proteins and thus the whole invading organism. In a previous study we showed that immunization with molecules of relative molecular mass (Mr) 155,000 (155K) 83K, 55K and 35K, specific for the late schizont and merozoite stages of Plasmodium falciparum, could elicit either partial or total protection in Aotus trivirgatus monkeys experimentally infected with P. falciparum. Here we have chemically synthesized 18 peptides corresponding to different fragments of these proteins to immunize Aotus trivirgatus monkeys. Some peptides gave partial protection from challenge with P. falciparum parasites, but none provided complete protection individually. A combination of three partially protective peptides gave complete or almost complete protection, however, suggesting that this particular combination of peptides is a good candidate for a malaria vaccine.

Comparison between the meiotic activities in the male with hypogonadotropic hypogonadism and in the human fetal ovocytes.

In the testicles of males with postpuberal hypogonadotropic hypogonadism, we have detected a preleptotene phase similar to that described in the human ovary. The two characteristic stages of this phase, contraction and despiralization, were noted. In this paper the origin and the significance of preleptotene in relation to the hormonal levels are discussed.