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Biomedical subjects

P Bello

Publications and source records attributed to P Bello.

At least 19 recordsLinked to original sources

Radioimmunometric assay of natriuretic peptide type-B (BNP) in heart failure.

The aim of this study was to assess the value of the radioimmunometric determination of natriuretic peptide type-B (brain natriuretic peptide, BNP) in the diagnosis and prognosis of heart failure, and to study the association between BNP and the clinical, analytical and echocardiographic variables associated with the evolution of heart failure. The study group included 169 patients (74 women and 95 men; mean, 66 years) with heart failure of different causes, admitted consecutively to our hospital. BNP levels were measured with a radioimmunometric assay (Shionora BNP Cis ) after day 3 of admission. Patients were also studied by echocardiography. A significant association between the cause of heart failure and the BNP concentration was found (patients with ischaemic disease had the highest BNP values). Systolic function was worse in patients with ischaemic disease or dilated cardiomyopathy. High BNP values were also associated with advanced functional class and male sex. Plasma creatinine correlated positively with plasma BNP. However, we found no significant association with the other clinical variables evaluated. Of the echocardiographic variables analysed, BNP correlated positively with the ventricular diameter and pulmonary artery systolic pressure, and inversely with the shortening fraction; patients with severely impaired systolic function had the highest BNP values. It can be concluded that BNP levels (by radioimmunometric assay) are increased in patients with heart failure, and increase in relation to left ventricular dysfunction and the severity of heart failure. The strong independent association of plasma BNP with the left ventricular ejection fraction, its stability and the low cost of measurement suggest that plasma BNP assay could become a routine test. BNP assay could be included as an important factor in clinical and therapeutic decision making, as it complements the information provided by other variables used in the diagnosis of heart failure.

Atrial Natriuretic Factor↗

[Intestinal duplications. A survey of 18 cases].

OBJECTIVE: The present study analyses the experience of two centers in the management of intestinal duplications in children. MATERIAL AND METHODS: We retrospectively reviewed the medical records of a series of 18 children with intestinal duplication (January 1993 to December 1999). The median age was 11 months (range: 9 days to 12 years). The variables analysed were: clinical presentation, diagnosis, localization, anatomic type, treatment, and complications. The relationship between age and clinical presentation was also analysed. RESULTS: Most cases were located in the ileum (n 14; 78 %) and presented with rectal bleeding (36 %) or intussusception (36 %). Most symptomatic cases in the first year of life presented with intussusception (n 5/6). All duplications, except one located in the ascending colon, were cystic. 99mTc-pertechnate abdominal scan was positive in three out of five patients. One case was diagnosed by prenatal ultrasonography. Diagnosis was confirmed by laparoscopy in three patients and by laparotomy in the remaining patients. In one patient, cystic esophageal duplication presented in the neonatal period as respiratory distress. Diagnosis as well as excision was performed by thoracoscopy. Of the two gastric duplications, one was diagnosed by prenatal ultrasonography and the other by laparotomy. Treatment consisted of segmental enterectomy (n 14) or excision of the lesion without enterectomy (n 4). No complications were found during a mean follow-up of 3 years. CONCLUSIONS: The onset of intestinal duplication may be late. The lesions were most commonly located in the ileum and were cystic. Clinical presentation was related to age. Minimally invasive surgery plays an important role in the management of these lesions.

Child↗

A protein-protein interaction map of the Caenorhabditis elegans 26S proteasome.

The ubiquitin-proteasome proteolytic pathway is pivotal in most biological processes. Despite a great level of information available for the eukaryotic 26S proteasome-the protease responsible for the degradation of ubiquitylated proteins-several structural and functional questions remain unanswered. To gain more insight into the assembly and function of the metazoan 26S proteasome, a two-hybrid-based protein interaction map was generated using 30 Caenorhabditis elegans proteasome subunits. The results recapitulate interactions reported for other organisms and reveal new potential interactions both within the 19S regulatory complex and between the 19S and 20S subcomplexes. Moreover, novel potential proteasome interactors were identified, including an E3 ubiquitin ligase, transcription factors, chaperone proteins and other proteins not yet functionally annotated. By providing a wealth of novel biological hypotheses, this interaction map constitutes a framework for further analysis of the ubiquitin-proteasome pathway in a multicellular organism amenable to both classical genetics and functional genomics.

Animals↗

Microvascularized fibular graft for mandibular reconstruction: detection of viability by bone scintigraphy and SPECT.

Bone allografts are often used in reconstructive mandibular surgery, generally after extensive oncologic resection, post-traumatic pseudoarthrosis, or osteomyelitis. Vascularized fibular bone grafts have advantages compared with other bone grafts in the restoration of the contour and function of defective mandibles. Bone scintigraphy is often used to assess bone revascularization, because positive uptake of Tc-99m hydroxy methylene diphosphonate (HDP) reflects patent anastomoses and viability of the grafted bone. Mandibular reconstruction with a free fibular flap was performed in 11 patients. Bone scintigraphy and SPECT were applied in the follow-up of eight patients. The grafts were assessed semi-quantitatively using a six-grade scoring system based on a comparison of tracer uptake in the graft and in the calvarium. Complications were observed in one graft. Planar scintigrams showed a tracer uptake greater than grade 5 in grafts with an uncomplicated course. SPECT was performed in addition to planar imaging in two patients who had greater graft uptake. A lack of tracer uptake was observed in the failed graft. Bone scintigraphy performed within the first week after the mandibular reconstruction is a useful tool to monitor the viability and early complications of microvascularized fibular grafts and plays an important role in the decision-making process during repeated surgical exploration. SPECT is more sensitive than planar imaging for assessing graft viability.

Adult↗

Is the depth correction using the geometric mean really necessary in a 99Tcm-DMSA scan in the paediatric population?

Determination of the left to right dimercaptosuccinic acid (DMSA) uptake ratio is theoretically one of the easiest quantitative procedures in nuclear medicine. The quantification can be performed on the posterior view, with or without the lateral view for correction of kidney depth. The geometric mean can also be determined using both the anterior and the posterior views. The aim of this study was to evaluate the occurrence of remarkable differences in the results from quantification of the relative renal function using the geometric mean and those obtained using the posterior counts only. Moreover, we evaluated to what extent the patient age influenced these differences. We reviewed 328 99Tcm-DMSA scans. The difference between the relative renal function obtained using the posterior view and that obtained using the geometric mean was calculated and analysed statistically. For the purpose of evaluating the value of performing the geometric mean calculation in patients of different ages, patients were divided into four age groups (group I, < or =2 years; group II, 3-9 years; group III, 10-18 years; group IV, >18 years). Using the Student's t test, no statistical differences were found in the relative renal function obtained by the two methods (posterior projection and geometric mean) in groups I (t = 0.01, P = 0.992) and II (t = 1.43, P = 0.155), which consisted of patients younger than 10 years (77% of the patients). In groups III and IV statistical differences were found (t = 2.27, P = 0.028 and t = 2.170, P = 0.038), respectively. We conclude that for children under 10 years it is unnecessary to perform depth correction using the geometric mean except in rare cases of major malformations and position anomalies.

Adolescent↗

Slap negatively regulates Src mitogenic function but does not revert Src-induced cell morphology changes.

Src-like adapter protein (Slap) is a recently identified protein that negatively regulates mitogenesis in murine fibroblasts (S. Roche, G. Alonso, A. Kazlausakas, V. M. Dixit, S. A. Courtneidge, and A. Pandey, Curr. Biol. 8:975-978, 1998) and comprises an SH3 and SH2 domain with striking identity to the corresponding Src domains. In light of this, we sought to investigate whether Slap could be an antagonist of all Src functions. Like Src, Slap was found to be myristylated in vivo and largely colocalized with Src when coexpressed in Cos7 cells. Microinjection of a Slap-expressing construct into quiescent NIH 3T3 cells inhibited platelet-derived growth factor (PDGF)-induced DNA synthesis, and the inhibition was rescued by the transcription factor c-Myc but not by c-Jun/c-Fos expression. Fyn (or Src) overexpression overrides the G(1)/S block induced by both SrcK- and a Slap mutant with a deletion of its C terminus (SlapDeltaC), but not the block induced by Slap or SlapDeltaSH3, implying that the C terminus is a noncompetitive inhibitor of Src mitogenic function. Furthermore, a chimeric adapter comprising SrcDeltaK fused to the Slap C terminus (Src/SlapC) also inhibited Src function during the PDGF response in a noncompetitive manner, as Src coexpression could not rescue PDGF signaling. Slap, however, did not reverse deregulated Src-induced cell transformation, as it was unable to inhibit depolymerization of actin stress fibers while still being able to inhibit SrcY527F-induced DNA synthesis. This was attributed to a distinct Slap SH3 binding specificity, since the chimeric Slap/SrcSH3 molecule, in which the Slap SH3 was replaced by the Src SH3 sequence, substantially restored stress fiber formation. Indeed, three amino acids important for ligand binding in Src SH3 were replaced in the Slap SH3 sequence; Slap SH3 did not bind to the Src SH3 partners p85alpha, Shc, and Sam68 in vitro, and the chimeric tyrosine kinase Slap/SrcK, composed of SlapDeltaC fused to the SH2 linker kinase sequence of Src, was not regulated in vivo. Furthermore, the Src SH3 domain is required for signaling during mitogenesis and since Slap/SrcK behaved as a dominant negative in the PDGF mitogenic response when microinjected into quiescent fibroblasts. We conclude that Slap is a negative regulator of Src during mitogenesis involving both the SH2 and the C terminus domains in a noncompetitive manner, but it does not regulate all Src function due to specific SH3 binding substrates.

3T3 Cells↗

Hemoperfusion in diabetic coma.

Hemoperfusion on ionic exchange resins in the therapy of diabetic keto-acidosis (DKA) coma is proposed. Resins used are strong anionic resins in mixed form able to release bicarbonates and to trap ketoanions and organic anions in a stoichiometric manner. A series of trials in open circuit are performed in order to search for a suitable mixture of resins and to establish the amounts of HCO3- and ketoanions respectively released or entrapped. Therefore, ten simulated hemoperfusions in closed circuit systems were performed, utilizing cartridges containing 1,700 g of mixed resin (9% HCO3- form and 91% Cl- form). The results indicate that all side effects of bicarbonate i.v. therapy of DKA coma are avoided because of the smooth HCO3- administration to the patient. Furthermore, a good removal of ketoanions and organic acids is obtained without changing the blood osmolality.

Bicarbonates↗

Further studies on the realization of a cold carbon portable artificial kidney.

Optimal conditions have been determined for the realization of a closed-loop, cold carbon, portable artificial kidney to depurate the dialysate of urea and other catabolites. It has been noticed that a dialysate flow rate of about 250 ml/min represents an optimal compromise between urea mass transfer through the dialytic membrane and its mass adsorption on cold carbon. Under this condition, the use of a 2-kg carbon column to remove urea is satisfactory for a routine dialysis treatment. Our experiments have been performed on simulated dialysis. A portable cold carbon artificial kidney requires a cooling unit and a heat exchanger to recover the power necessary to produce the 0 degrees C temperature. A flat heat exchanger, consisting of three superposed plates, with a heat exchange surface of about 0.09 m2 and a total coefficient of thermal exchange Ht, of 380 Kcal/m2-degrees C-hour has been chosen. With heat recovery, the cooling power required is 1/3 hp to allow for parasitic cold losses and the power necessary to reach a steady state. All mechanical parts necessary for heating and cooling weigh about 12 kg.

Adsorption↗

Cold carbon haemofiltration apparatus.

Four uraemic patients underwent haemofiltration (HF) for two months, three times a week, with an infusion of about 20L of electrolyte solution. For another two months, HF was performed with diafiltrate reinfusion after regeneration on cold carbon and ionic exchange resins. Carbon (26.8g) and resins (10g/kg b.w) were needed. The data obtained in HF and in closed-circuit HF periods were similar, but during the closed-circuit HF treatment there was better control of acid-base balance.

Blood↗

Cold carbon apparatus for hemodialysis.

A prototype of artificial kidney with regeneration of the dialysis fluid in active carbon at low temperature is presented. The data obtained through a series of simulated dialysis show that carbon adsorbs, besides creatinine and other compounds, urea in satisfactory quantities. Furthermore, the possibility of completely regenerating carbon with tap water washing makes the routine use of an artificial kidney based on a cold operating carbon depurator extremely practical.

Adsorption↗

[Myocardial damage following neonatal severe asphyxia].

Sixteen newborn infants with severe asphyxia were prospectively studied for evidence of secondary myocardial damage and, in that case, their clinical findings. Myocardial damage was diagnosed in three term newborn infants of adequate weight for gestational age (18.7%) by means of serial electrocardiograms taken in the first 72 hours of life. Two of them showed evidence of diffuse subendocardial ischemia and a third one showed electrocardiographic signs suggesting necrosis of the left ventricular posteroinferior wall. Neither creatine-phosphokinase serum activity nor its muscle brain MB isoenzyme were useful in the identification of myocardial damage. All three affected neonates developed respiratory distress syndrome without signs of cardiac failure and one of them died. The histopathological study of this late one showed localized hemorrhage of the papillary muscles and interventricular septum. These finding underscore the need for serial electrocardiographic recordings in newborns with severe asphyxia, since cardiac dysfunction may inadvertently occur under the appearance of respiratory distress syndrome.

Asphyxia Neonatorum↗

[Bacteriocins as cytotoxic agents in experimental neoplasms: considerations on the role of possible contaminants].

In most recent papers some Authors have demonstrated that several bacteriocins are able to markedly inhibit the division of various neoplastic mammalian cell lines; also in vivo the inhibition of tumor growth or even regression relative to controls are statistically significant. Since such preparations are "crude" and it's possible that contaminating agents may represent a possible source of variability in the results, mostly in vivo; we have examined a preparation of Pyocin employed in this study for the possible endotoxin contamination using the Limulus assay. Such test was positive in triplicate and semiquantitative determination has shown and endotoxin amount of 5 to 10 microgram/ml. This level is, in vitro, not anough to give cytotoxic effect, but in vivo is able to influence experimental results. In addition, since some bacteriocins and enterotoxins are produced under exactly identical conditions, there is this a possibility that the enterotoxin are coproduced in these preparations and are causing some of the cytotoxic effects on experimental tumors. A more complete separation and purification of preparations will be required before definitive comments.

Animals↗