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Biomedical subjects

A Bonet

Publications and source records attributed to A Bonet.

At least 19 recordsLinked to original sources

Time course of cytochromes P450 decline during rat hepatocyte isolation and culture: effect of L-NAME.

The present work describes an isozyme-related effect of collagenase perfusion on hepatocyte microsomal cytochrome (CYP)-dependent monooxygenase activities: CYP 1A1/2-, 2B1/2-, 3A1/2- and 2E1-dependent activities in microsomes from rat hepatocytes after isolation were about 60% of that of liver microsomes, and CYP 4A1-dependent activity was equivalent to liver microsomes. In contrast, the microsomal protein content of the various CYP isoforms was not affected by hepatocyte isolation. This is in accordance with the hypothesis of CYP inactivation during the process of hepatocyte isolation by collagenase digestion. L-NAME (1 mM) was found unable to protect from the decline of CYP-dependent monooxygenase activities following hepatocyte isolation. It is possible that the decrease in glutathione peroxidase activity observed in the presence of L-NAME, namely depression of defense against peroxynitrite, could counteract the beneficial effect of L-NAME on nitric oxide synthesis inhibition. The present work also shows that L-NAME could not avoid the progressive, isoform-specific, most probably turnover-related, decline of CYP proteins and related monooxygenase activities in cultured hepatocytes. Dysregulations in the mechanisms of CYP expression in rat hepatocyte cultures, presently unknown but nitric oxide independent, thus appear to occur in cultured rat hepatocytes.

Animals↗

[What lines of action should the Valencia Society of Family and Community Medicine adopt over the next 4 years?].

OBJECTIVE: To identify the areas of activity in which the Valencia Society of Family and Community Medicine (SVMFyC) should become involved over the next four years. DESIGN: Qualitative research.Setting. SVMFyC members. PATIENTS AND OTHER PARTICIPANTS: 27 experts belonging to the SVMFyC took part. INTERVENTIONS: Qualitative consensus-seeking techniques. Reliability and validity of the technique were ensured through triangulation and the selection of experts from among the different professional groups within the SVMFyC. MEASUREMENTS AND MAIN RESULTS: To determine the recommended lines of action, productivity, spontaneous representativity, intensity of recommendation and degree of agreement were analysed. The priority lines recommended were: defending the MIR path, proposing reforms in undergraduate study plans, watching over the transparency of job selection procedures and the annual OPE selection, promoting the professional degree course, creation of posts for teachers in family and community medicine, defining the size of the population registered with a doctor, proposing an incentives list and studying alternatives to uniform salaries in the form of target-linked remuneration. CONCLUSIONS: The lines of action recommended by the experts were established.

Community Medicine↗

Usefulness of patch tests for diagnosing selective allergy to captopril.

Captopril, enalapril, and lisinopril are angiotensin-converting enzyme (ACE) inhibitors widely prescribed for hypertension and heart failure. Cutaneous side effects of captopril include angio-edema, anaphylactoid reactions, maculopapular eruptions, pitiryasis rosea-like rash, toxic erythema, and exfoliative dermatitis. Some of the immunological captopril-induced cutaneous adverse reactions have been diagnosed in recent years by patch tests. A case of a cutaneous immune adverse reaction to captopril with tolerance to enalapril and lisinopril demonstrated both by patch tests and double-blind challenge tests is reported for the first time. A 71-year-old nonatopic woman suffered a generalized pruriginous maculopapular rash. Two months earlier, she had started oral treatment with captopril 50 mg t.i.d and glibenclamide 5 mg daily. After the rash appeared, she stopped both drugs and the reaction cleared. A skin biopsy from one of the lesions showed perivascular lymphocytic infiltrate of the upper dermis. Skin prick tests with captopril and glibenclamide and patch tests with enalapril, lisinopril, and glibenclamide at 1% and 10% pet., and with mercaptobenzothiazole (a sulfhydryl group-containing chemical at 1% pet were negative. Only patch tests with captopril at 1% and 10% concentrations were positive at 48 h. Oral double-blind challenge tests with glibenclamide, enalapril, lisinopril, and placebo showed good tolerance. The patient was advised to avoid only captopril. Because captopril is the only ACE inhibitor containing a sulfhydryl group and has occasionally been implicated in complex immunological diseases, this chemical group has been considered the culprit of allergic reactions to captopril. The lack of cross-reactivity between captopril, enalapril, and benazepril has been demonstrated in a few patients by patch tests. In our patient, patch tests identified captopril as the drug responsible for a probably immune adverse reaction not due to the sulfhydryl group. Patch tests are useful and safe in the diagnostic work-up of allergic drug reactions and in studies of cross-sensitivity among ACE inhibitors.

Aged↗

Tracheal colonisation within 24 h of intubation in patients with head trauma: risk factor for developing early-onset ventilator-associated pneumonia.

OBJECTIVE: To investigate if tracheal colonisation within 24 h of intubation is a risk factor for developing early-onset ventilator-associated pneumonia (EP) in patients with head trauma. DESIGN: A prospective study in an intensive care unit of a university hospital. POPULATION: One hundred intubated patients were included with head trauma and Glasgow coma score at admission < or =12. METHODS: We took tracheal aspirate samples within 24 h of intubation and performed a protected bronchoalveolar mini-lavage when clinical diagnosis of pneumonia was made. MEASUREMENTS AND RESULTS: On admission time 68 patients (68%) were colonised in trachea, 22 patients were colonised by Staphylococcus aureus, 20 by Haemophilus influenzae, six by Streptococcus pneumoniae and 20 by gram-negative bacilli. The incidence of EP was 26%, and the microorganisms involved were Staph. aureus (44%), H. influenzae (31%), Strep. pneumoniae (12%), and gram-negative bacilli (13%). A multivariate logistic regression analysis showed that the tracheal colonization by Staph. aureus, H. influenzae or Strep. pneumoniae within 24 h of intubation was an independent risk factor for developing EP (odds ratio: 28.9; 95% confidence interval: 1.59-52.5). CONCLUSION: Colonisation of the trachea within 24 h of intubation by Staphylococcus aureus, Haemophilus influenzae or Streptococcus pneumoniae is a risk factor for developing EP in patients with head trauma.

Adult↗

Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group.

The duration of spontaneous breathing trials before extubation has been set at 2 h in research studies, but the optimal duration is not known. We conducted a prospective, multicenter study involving 526 ventilator-supported patients considered ready for weaning, to compare clinical outcomes for trials of spontaneous breathing with target durations of 30 and 120 min. Of the 270 and 256 patients in the 30- and 120-min trial groups, respectively, 237 (87.8%) and 216 (84.8%), respectively, completed the trial without distress and were extubated (p = 0.32); 32 (13.5%) and 29 (13.4%), respectively, of these patients required reintubation within 48 h. The percentage of patients who remained extubated for 48 h after a spontaneous breathing trial did not differ in the 30- and 120-min trial groups (75.9% versus 73.0%, respectively, p = 0.43). The 30- and 120-min trial groups had similar within-unit mortality rates (13 and 9%, respectively) and in-hospital mortality rates (19 and 18%, respectively). Reintubation was required in 61 (13.5%) patients, and these patients had a higher mortality (20 of 61, 32.8%) than did patients who tolerated extubation (18 of 392, 4.6%) (p < 0.001). Neither measurements of respiratory frequency, heart rate, systolic blood pressure, and oxygen saturation during the trial, nor other functional measurements before the trial discriminated between patients who required reintubation from those who tolerated extubation. In conclusion, after a first trial of spontaneous breathing, successful extubation was achieved equally effectively with trials targeted to last 30 and 120 min.

Aged↗

[Mortality and risk factors in patients with acute renal failure and multiple organ dysfunction].

BACKGROUND: Acute renal failure (ARF) associated to multiple organ dysfunction (MOD) deserves currently a poor survival. The aim of this study was to analyze the risk factors for mortality in ARF-MOD patients treated by means of continuous renal replacements strategies. PATIENTS AND METHODS: All the ARF-MOD patients treated by means of continuous renal replacement techniques (CRRT) in a single center in the period 1989-1995 have been evaluated. MOD was defined by the 1992 American Conference criteria. Both demographic and the scored clinical data were analysed by means of descriptive and comparative statistics and by multiple logistic regression for the mortality risk factors. RESULTS: 103 patients have been evaluated. The median age was 62 years (range 20-80), 73.8% were males and the mean APACHE II score was 22.7 (SD 5.5). In the 17.4% the ARF-MOD condition corresponded to multiple trauma, the other medical and surgical pathologies represented the 82.6% of cases. At least two organic systems were involved in all patients. Both urea and creatinine values significantly decreased in all the patients and the fluid removal was of 8.9 (2.6) l/24 h. The mortality rate was 78.6%. The risk for death, as evaluated by logistic regression, was higher in patients older than 60 years (OR: 3.45; Cl 95%: 1.1-10.78; p = 0.03), and lower in those with remaining diuresis (OR: 0.65; Cl 95%: 0.48-0.9; p = 0.008). Survival was better among ARF-MOD traumatic patients. CONCLUSIONS: The mortality rates among ARF-MOD patients remains high. The CRRT were useful for removing uremic toxins and fluids. By logistic regression only advanced age and low urine output were the main risk factors for mortality.

APACHE↗

Protective effect of intravenously administered cefuroxime against nosocomial pneumonia in patients with structural coma.

In comatose patients admitted to an ICU, particularly those with head injury, the incidence of early onset pneumonia is exceedingly high. We performed an open, prospective, randomized, and controlled clinical trial aiming at the reduction of the incidence of ventilator-associated pneumonia in head-injured patients and patients with stroke requiring mechanical ventilation. One hundred patients were included because of head injury or coma caused by medical stroke and with Glasgow coma scores < or = 12 and mechanical ventilation > 72 h. Patients eligible for the study (n = 50) received cefuroxime intravenously (two 1,500-mg doses 12 h apart after intubation) (the cefuroxime group) and 50 patients not receiving cefuroxime formed the control group. In the former group patients did not receive any other antibiotics before the end-point determination, whereas in the latter, 17 patients received prophylactic antibiotics as prescribed by the attending physician. The global incidence of microbiologically confirmed pneumonia was 37% (n = 37); 12 (24%) belonged to the cefuroxime group, and 25 (50%) belonged to the control group (p = 0.007). Early-onset pneumonia accounted for 70% of all the pneumonia episodes (n = 26), eight (67%) belonging to the cefuroxime group, and 18 (72%) belonging to the control group (p = 0.02). In the control group, four of 17 (23%) patients receiving prior antibiotics developed pneumonia, whereas 21 of 33 (64%) patients who did not receive antibiotics developed pneumonia (p = 0.016). The multivariate analysis revealed that the duration of mechanical ventilation (per each day) was an independent risk factor significantly associated to the development of pneumonia. Furthermore, the use of cefuroxime and/or prior antibiotics in the control group, before the pneumonia episode, had a protective effect against its development. No differences were found with regard to mortality and morbidity when comparing the study population with the control group. Nevertheless, when comparing patients with pneumonia (from both study and control groups) with those without it, there was a decrease in total hospital stay (35 +/- 13 versus 25 +/- 14 d, p = 0.048) and ICU stay (20 +/- 11 versus 11 +/- 7 d, p = 0.001). The study demonstrated that the administration of two single high doses 1,500 mg each of cefuroxime after the intubation of patients comatose because of head injury or medical stroke is an effective prophylactic strategy to decrease the incidence of ventilator-associated pneumonia.

Adult↗

Prevalence of mental disorders among children in Valencia, Spain.

A 2-stage survey was carried out to establish the point-prevalence of mental disorders and help-seeking behaviour in children aged 8, 11 and 15 living in the city of Valencia. Global prevalence rates, rates by age and rates by sex, as well as rates of specific diagnosis according to DSM-III-R criteria are described. Help-seeking behaviour was found to be related to an interaction between internalizing and externalizing symptoms and sex.

Adolescent↗

[Value of the transcranial Doppler examination in the diagnosis of brain death].

BACKGROUND: Transcranial Doppler examination (TCD) is a non invasive method capable of detecting the interruption of cerebral flow in patients with criteria of brain death. Its recognition as an alternative to isoelectric EEG for the diagnosis of brain death requires previous validation. METHODS: Twenty-six patients in profound coma were examined by TCD. Of 23 patients with technically adequate study 13 manifested clinical criteria and EEG of brain death. Of these patients 9 had received barbiturate treatment and 4 had not. RESULTS: Changes in the flow waves of the TCD were observed in the form of diastolic reflux or systolic points of slight amplitude without diastolic flow in at least 2 arteries in 12 of 13 patients with criteria of brain death (sensitivity = 92%) and in none of the 10 patients without criteria of brain death (specificity = 100%). The use of barbiturates did not modify the normal anterograde flow detected by TCD in the absence of criteria of brain death. CONCLUSIONS: Transcranial Doppler is a good method for confirming the clinical diagnosis of brain death, fundamentally in patients undergoing treatment with drugs depressing the central nervous system.

Adolescent↗

Treatment charts in radiation therapy. An analysis of European treatment records.

The radiotherapy treatment chart (dose prescription, set-up parameters, dose computation and daily dose recording form) represents an important working tool in radiotherapy, not only as a compilation of data, but also as a method of communication among physicians, physicists and technicians. In addition to administrative and medical data, physical and simulation data that are indispensable for the daily accurate reproduction of the therapy procedures should be recorded, as well as accurate daily entries of the fractional and cumulative absorbed doses. Moreover, any radiation therapy quality assurance programme must rely on the accessibility of the radiation treatment history and a correct record of the therapy protocol in order to be verifiable. We have analysed the treatment charts of 92 European Departments of Radiation Oncology, with the aim of identifying their salient characteristics and data recorded. The study shows strong differences among the charts analysed, not only in the amount of information recorded, but also in the kind of data and concepts used.

Demography↗

Functional sequences of the myosin head.

Muscle contraction originates from the sliding of myosin filaments on actin filaments, the energy for which is supplied by the hydrolysis of adenosine-5-triphosphate (ATP) by myosin. The nucleotide first binds to the acto-myosin complex in the myosin head (or subfragment-1), producing a conformational change which induces actin dissociation. The release of phosphate (Pi) then allows a return to the strong actin-myosin association, corresponding to the rigor state. We discuss here certain controversial points arising from current concepts of the actin and nucleotide binding regions at the amino acid sequence level within the subfragment-1 heavy chain. We consider the actin and nucleotide binding regions to be two distinct sites (for each of these regions) one of which is shared competitively between actin and the nucleotide. In our model the cyclical actin-S1 association-dissociation steps correspond to different ATP, actin and ADP affinities for the same amino acid sequence of the S1 heavy chain, contributing alternatively to a single hydrolytic nucleotide site or a strong actin site. We propose the existence of a flexible segment that forms or dismantles the nucleotide or actin sites. The large region (amino acids 540-707) overlapping the actin-myosin interface appears to be the main flexible region of the S1 molecule and we propose that this particular sequence plays a key role in the dissociation pathway of the actin-myosin complex and in the conversion of chemical energy into the mechanical energy of contraction.

Actins↗

The actin-myosin subfragment-1 complex stabilized by phenyldiglyoxal.

Nuclear magnetic resonance studies have revealed the importance of arginine residues in the actin-myosin interface (Moir, A. J. G., and Levine, B. A. (1986) J. Inorg. Chem. 27, 271-278). In the present study, we tested the involvement of these residues in the rigor complex between actin and subfragment-1 (S1) by chemical cross-linking experiments using phenyldiglyoxal. Two kinds of linkages were observed, one within the S1 heavy chain itself (120-kDa product) and the other between actin and the S1 heavy chain (200-kDa product). The phenyldiglyoxal had an effect similar to that of phenylglyoxal on S1 ATPase activities. We also show that phenyldiglyoxal (of 0.6-0.8 nm arm length) cross-links an arginine residue of the 50-kDa domain to one in the 20-kDa domain of the S1 heavy chain in the absence of actin or to an arginine in actin when actin is present. The presence of Mg2+, adenosine 5'-diphosphate or 5'-adenylyl imidodiphosphate suppressed the intermolecular linkage with actin, and favored the intramolecular cross-link, (i.e. between 50-kDa and 20-kDa fragments). We propose that the same arginyl residue in the N-terminal part of the 50-kDa domain can be cross-linked to a nearby arginine in either the 20-kDa domain or the actin molecule. In accordance with the amino acid sequence of each protein this also implies that the actin-myosin interaction involves arginine residues located either after residue 28 of the N-terminal part of actin, since this actin region is devoid of arginine residues, or in the N-terminal portion of the 50-kDa domain, i.e. between residues 239 and 455.

Actins↗

The presence of non-neuronal cells influences somatostatin release from cultured cerebral cortical cells.

We examined the effect of non-neuronal cells on somatostatin release from cultured cerebral cortical cells. Three culture models were used: (1) neuron-enriched cultures obtained from cortex of 17-day-old rat embryos and exposed to 10 microM cytosine arabinoside (Ara C) for 48 h between days 3 and 5 after plating; (2) whole cell cultures obtained by using the same protocol but untreated with Ara C; (3) glial primary cultures obtained from newborn rats. We studied: (i) the cellular composition of the cultures by using two astroglial markers: vimentin and glial fibrillary acidic protein (GFAP); (ii) the spontaneous and forskolin-stimulated somatostatin release. In 8-day-old cultures morphological data revealed that Ara C treatment reduced glial cells to 6%. At 7 and 10 days of culture somatostatin spontaneously released from Ara C-treated cells was higher than that measured from untreated cells. On the 17th day of culture, neuron-enriched cultures contained a lower amount of somatostatin than whole cell cultures. Forskolin elicited a dose-dependent release of somatostatin from whole cell cultures, but had no effect on neuron-enriched cultures. Astroglial released media (ARM) from glial primary cultures exposed to forskolin for 20 min induced somatostatin release from neuron-enriched cultures. HPLC analysis of endogenous amino acids of ARM showed that glutamate, glutamine, glycine and alanine were significantly increased after forskolin stimulation. Our results suggest a functional interaction between glial cells and neurons secreting somatostatin.

Amino Acids↗

The internal crosslinking of the S1 heavy chain from smooth muscle probed by dibromobimane.

The reaction of the crosslinker dibromobimane has recently revealed a functionally important internal loop structure within the skeletal myosin S1 heavy chain where Cys-522 of the 50K domain and Cys-707 (SH1) of the 20K region are spatially juxtaposed. Here we have studied the possible relevance of this topological feature to the architecture and transducing activity of the myosin head in general, by extending the dibromobimane modification to smooth muscle myosin. Treatment of chicken gizzard myosin S1 with dibromobimane resulted in intramolecular crosslinking between the C-terminal 25K and central 50K segments of the S1 heavy chain. The data suggest a conservation at the 50K-25K interface of smooth muscle S1 heavy chain and the importance of the neighboring SH1 region, whose conformation may play an important role in energy transduction by the myosin head.

Adenosine Triphosphatases↗