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Biomedical subjects

M Albertini

Publications and source records attributed to M Albertini.

At least 55 records · Page 3Linked to original sources

The effects of glibenclamide, a blocker of K+ ATP-sensitive potassium channels, on diaphragmatic fatigue during endotoxaemia in pigs.

An in vivo porcine model of endotoxaemia was used to study the effects of glibenclamide, a K+ ATP-sensitive potassium channel blocker. Escherichia coli lipopolysaccharides (LPS, 70 micrograms/kg, i.v., as a bolus) were infused into anaesthetized, mechanically ventilated, indomethacin-treated pigs. After 120 min of endotoxaemia, glibenclamide was administered (10 mg/kg, i.v., over 5 min) to half the pigs. The strength at different frequencies of stimulation (10, 20, 30, 50 Hz, 20 V,) 1 s) and the endurance capacity (10 Hz, 20 V, 30 s) of the diaphragm were evaluated after 120 min of endotoxaemia and 5, 10, 20 and 30 min after drug infusion. Glibenclamide transiently increased the blood pressure without changing the decreased cardiac output and at the same time further impaired the diaphragmatic activity. The reduced ability of the diaphragm to generate force in response to different electrical stimulations was shown by a significant reduction in strength. The endurance index decreased 5 min after glibenclamide infusion, returning to the pre-glibenclamide values by 150 min. These results indicate that glibenclamide modifies the activity of vascular smooth muscle and of the diaphragm.

Adenosine Triphosphate↗

Differential release of prostacyclin and nitric oxide evoked from pulmonary and systemic vascular beds of the pig by endothelin-1.

The vascular effects of endothelin-1 (ET-1) and the release of prostacyclin and nitric oxide (NO) evoked by this peptide were analyzed in anesthetized, mechanically ventilated pigs. ET-1 induced biphasic responses in both the pulmonary and systemic vascular beds characterized by a transient hypotension followed by a long-lasting hypertension. To evaluate the involvement of prostacyclin and NO in the ET-1-dependent vascular response, we used indomethacin to block cyclooxygenase and NG-nitro-L-arginine methyl ester (L-NAME) to block NO synthase. The results show that the systemic hypotensive response to ET-1 is mediated by the release of prostanoids and NO, but these are not responsible for the pulmonary hypotension. Indomethacin reduced the hypertensive effect of ET-1, showing that this peptide can also activate release of vasoconstrictor cyclooxygenase metabolites. When L-NAME was administered after indomethacin, the pulmonary vasoconstrictor activity of ET-1 was counterbalanced by NO. By contrast, in pigs pretreated with indomethacin plus L-NAME ET-1 caused transient systemic vasoconstriction, followed by progressive reduction of vascular tone, probably because of release of vasodilator agents other than prostanoids or NO.

Animals↗

PGI2 and nitric oxide involvement in the regulation of systemic and pulmonary basal vascular tone in the pig.

In anesthetized, ventilated pigs we analyzed the involvement of nitric oxide (NO) and prostaglandins (PGs) in the regulation of systemic and pulmonary basal vascular tone. Endogenous release of NO was blocked by NG-nitro-L-arginine methyl ester (L-NAME) and prostanoid biosynthesis by indomethacin. Blocking NO raised pulmonary and systemic arterial pressure and vascular resistances. These effects show that in the pig there is continuous release of minute amounts of NO. Blocking prostanoid biosynthesis did not affect the vasoconstrictor effect of L-NAME on the pulmonary vascular bed, but significantly strengthened the hypertensive effect of L-NAME on the systemic vascular bed. These data show that different mechanisms regulate pulmonary and systemic vascular tone. Administration of a stable analogue of PGI2 to pigs pretreated with indomethacin reversed the systemic vasoconstrictor effect of L-NAME. In conclusion, our data show that NO especially modulates pulmonary vascular tone, while PGI2 preferentially modulates systemic vascular tone.

Animals↗

[Non-specific tuberculin reactivity due to sensitization to non-tuberculous mycobacteria (NTM) in children not vaccinated with BCG. Diagnostic value of a comparison of intradermal tests with tuberculin and NTM antigens].

Sensitisation to non tuberculous mycobacteria (NTM) may provoke a non specific tuberculin reaction and can cause problems in the interpretation of tuberculin tests in subjects who have not been vaccinated with BCG. The practice of testing for antigens to NTM (sensitins) should be useful for pointing to the right diagnosis. Our study was carried out on 24 asymptomatic children aged between 11 months and 8 years 9 months; these children were considered to be sensitive to NTM based on comparative cutaneous tests (reactions to sensitins > or = 5 mm and > or = 3 mm vs tuberculin) and were selected from a group of 53 children who had either initially achieved a positive tuberculin reaction or who had undergone conversion on subsequent prevaccination testing. The tests were carried out with tuberculin RT 23, tuberculin Merieux and sensitins from M. avium and M. intracellulare. They had been repeated two to four months later in cases of a response to one of the different reactants. At the first examination the tuberculin reactions were most often weak, the Merieux tuberculin induced a stronger response than the RT23 tuberculin. A dominant response for one or both sensitins was present in 18 cases. The tuberculin reactions became weaker whilst the sensitins remained relatively stable. The difference became significant in the six remaining cases. Although tests for tuberculin and sensitins have some diagnostic value which is necessarily imprecise, comparative analysis of the cutaneous reactions to the different antigens may contribute to avoid an erroneous interpretation for tuberculin allergy in asymptomatic young children without any risk factors for tuberculous infection. It is important to identify those subjects having non specific tuberculin reactivity induced by sensitisation to NTM in order to avoid non justified chemoprophylaxis and also to be able to vaccinate these children with BCG.

Antigens↗

Idiopathic disseminated bacillus Calmette-Guérin infection: a French national retrospective study.

OBJECTIVE: Disseminated bacillus Calmette-Guérin (BCG) infection after inoculation of live vaccine is considered to result from impaired immunity of the child. However, in half of the cases, regarded as idiopathic, no well-defined immunodeficiency condition can account for the infection. The objective of the present study is to report the prevalence, clinical features, associated infections, and outcomes of children with idiopathic disseminated BCG infection. DESIGN: National retrospective survey during the period from 1974 through 1994 in France. SETTING: All neonatology and pediatrics units in primary care and referral centers throughout France. PATIENTS: Data were collected from 595 (82%) of 721 units, 377 (93%) of 407 centers, and 320 (93%) of 345 cities. Selection criteria included BCG infection, dissemination to at least two areas beyond the inoculation site, and no well-defined immunodeficiency condition. Sixteen children (8 girls and 8 boys), born to families unrelated to each other but often consanguinous (5 of 16) or abroad (5 of 16). RESULTS: The minimal prevalence rate was estimated at 0.59 cases per 1 million vaccinated children born in France. Clinical features included fever and cachexia, disseminated BCG infection to lymph nodes (15 of 16), skin (13 of 16), soft tissues (11 of 16), lungs (11 of 16), spleen (11 of 16), liver (11 of 16), and bones (9 of 16). Eight children had associated or subsequent severe opportunistic infection (50%), with either nontyphi Salmonella enterica serotypes (7 of 16) or Mycobacterium abscessus (1 of 16). The outcome was poor: 8 children (50%) died; the cause of death was BCG infection for most children (7 of 8); 8 survived until the last follow-up (50%). CONCLUSIONS: Idiopathic disseminated BCG infection is a rare but severe complication of BCG vaccination. The infection probably results from an as yet unknown genetically determined immunodeficiency condition that affects the killing of intracellular bacteria such as BCG and Salmonella.

BCG Vaccine↗

Inhaled nitric oxide reverses PAF-dependent bronchoconstriction in the pig.

In six anesthetized, paralyzed, mechanically ventilated pigs we evaluated the respiratory effects of inhaled nitric oxide (NO) (80 ppm in O2) under control conditions and after platelet-activating factor (PAF) administration (50 ng/kg, i.v.). PAF was also administered to the same pigs after pretreatment with indomethacin (3 mg/kg, i.v.). The mechanical properties of the respiratory system were evaluated by the rapid airway occlusion technique. With this technique the overall respiratory resistances, the airway resistances, and the additional resistances of respiratory system and lung can be evaluated. The results show that NO inhaled by the pig at 80 ppm for 6 min under control conditions reduced static and dynamic elastances of the respiratory system and lung and pulmonary arterial pressure, without modifying bronchomotor tone. Therefore, NO reduced the PAF-dependent changes in resistances and in static and dynamic elastances of the respiratory system and lung. The modest change in elastances caused by PAF in pigs pretreated with indomethacin was reduced by NO inhalation, which also has a mild bronchodilatory effect. The changes in elastances appear to be correlated with the pulmonary vasodilator activity of inhaled NO.

Administration, Inhalation↗

Clinical and immunological effects of treatment with murine anti-CD3 monoclonal antibody along with interleukin 2 in patients with cancer.

Anti-CD3 mAb and interleukin 2 (IL-2) were used in a Phase I study to treat 29 patients with cancer. The anti-CD3 was given as an i.v. bolus infusion over 10 min followed by two i.v. 96-h continuous infusions of IL-2 at 3 x 10(6) units/m2/day with a 3-day rest between the IL-2 infusions. Four patients were treated with 6, 18, 60, and 300 microgram/m2 anti-CD3. One patient received 3000 microgram/m2 anti-CD3. This patient developed profound hypotension and the IL-2 infusions were delayed for 2 weeks. Two patients were treated at an intermediate dose of 600 microgram/m2. These patients developed dose-limiting toxicities including hypotension, dyspnea and increased blood urea nitrogen, creatinine, and bilirubin. They were unable to complete their first course of therapy. In an effort to achieve a dose of anti-CD3 which would activate T cells in vivo, pentoxifylline was given to blunt the toxicities seen with anti-CD3 thought to be due predominantly to the cytokine syndrome and tumor necrosis factor release. Four patients received p.o. pentoxifylline to cover an anti-CD3 dose of 600 microgram/m2. The IL-2 infusion was initiated 1 week after the mAb. While there was an anti-CD3 dose-dependent increase in serum tumor necrosis factor level 1 h after mAb infusion, pentoxifylline did not reduce the serum tumor necrosis factor level. There was also an anti-CD3 dose-dependent increase in the serum soluble IL-2 receptor levels. Other immune parameters monitored, including in vitro cytotoxic and proliferative responses and lymphocyte count, were similar to treatment courses with IL-2 alone. Fourteen of 26 patients examined developed human anti-murine antibodies following a single dose of anti-CD3. There were no objective antitumor responses. We conclude that in vivo treatment with anti-CD3 did not enhance T cell activity or expansion with subsequent IL-2 infusion and that the combination of anti-CD3 followed by IL-2 did not improve upon the antitumor activity previously seen with IL-2 alone.

Antibody-Dependent Cell Cytotoxicity↗

In pigs, inhaled nitric oxide (NO) counterbalances PAF-induced pulmonary hypertension.

In 6 anesthetized mechanically ventilated pigs we have studied the effects of inhalation of 80 ppm of nitric oxide (NO) before and after platelet-activating factor (PAF) administration (50 ng/kg iv). Our results show that NO inhalation causes a decrease in pulmonary arterial pressure and in heart rate without affecting other circulatory parameters. PAF administration causes a pulmonary hypertension and a prompt and brief decrease in systemic pressure. Inhalation of NO reduces the pulmonary hypertension, without completely reversing PAF-dependent vasoconstriction. PAF administration to pigs pretreated with indomethacin produces a lesser increase in pulmonary vascular pressure. In this case, NO inhalation can restore to baseline values. Pretreatment of 3 of the 6 pigs with NG-nitro-L-arginine-methyl-ester did not prevent the prompt and brief PAF-induced systemic hypotension. In conclusion, our results show that NO reduces basal pulmonary vascular tone, acts as a pulmonary vasodilator on PAF-preconstricted vessels and is not involved in the brief systemic hypotension consequent to PAF administration.

Administration, Inhalation↗

[Childhood visceral leishmaniasis in the Alpes-Maritimes from 1985 to 1992].

Here, we present an analysis of clinical and biological data from 15 infantile visceral leishmaniasis recorded between 1985 and 1992 in the French department of Alpes-Maritimes. The association of fever, splenomegalia, tricytopenia remains the most constant and predictive of diagnosis (90% of cases). Bone marrow smear affirms diagnosis in 93% of cases. Leishmania infantum MON-1 is the causative agent. Except for one case of advanced stade with severe hepatic lesions and one case of clinical resistance to Glucantime, prognosis is favourable under treatment with antimony derivatives. The long term results for children considered cured after initial treatment is satisfactory. In the department, the number of cases of combined ages has increased regularly since 1985. The number of infantile forms has increased but now represents nevertheless no more than 28% of total cases. On the other hand, cases are increasing in adults and 40% of those adult cases are in HIV positive patients.

Adolescent↗

[Cystic fibrosis revealed by dehydration with hypochloronatremic alkalosis in 3 infants and a neonate].

BACKGROUND--Acute dehydration with hypochloronatremic metabolic alkalosis is a classical complication of cystic fibrosis of the pancreas. Its progressive development as a revealing manifestation of the disease is rare as is its appearance in newborns. Case n. 1.--A 13 month-old girl was admitted because of status epilepticus. She was severely dehydrated (20% weight loss) but had normal diuresis. Investigations showed metabolic alkalosis, hypochloronatremia and hypokalemia. All the manifestations disappeared within 5 days with treatment but three sweat tests were abnormal. Case n. 2.--A 7 month-old girl was admitted because she suffered from progressive loss of weight (10%); she was dehydrated and had metabolic alkalosis plus hypochloronatremia, but her diuresis was normal. Two sweat tests were abnormal. Case n. 3.--A 4.5 month-old boy was admitted because he suffered from severe (12%) weight loss. His diuresis was normal despite dehydration; metabolic alkalosis and hypochloronatremia were found. Two subsequent sweat tests were abnormal. Case n. 4.--A 3 day-old girl was admitted suffering from meconium ileus. Two initial mechanism analysis for protein were abnormal. She had a cardiorespiratory arrest on the 13th day of life, when she had lost 14% of her birth weight; investigations showed metabolic alkalosis, hyponatremia (83 mEq/l), hypochloremia (45 mEq/l); kalemia was 5.9 mEq/l. Peritoneal dialysis was needed to correct hydroelectrolytic changes. A sweat test performed on the 26th day of life was also abnormal. Investigations performed during the periods of dehydration, and repeated later, showed transient functional kidney failure. None of the four patients had any respiratory or gastrointestinal clinical manifestations of cystic fibrosis. CONCLUSION--Metabolic alkalosis with hypochloronatremia plus progressive, severe dehydration in infants whose diuresis is paradoxically normal must be followed by examination for cystic fibrosis.

Alkalosis↗

Plasma catecholamine levels in children.

While blood norepinephrine and epinephrine levels are well established in adults, literature data concerning concentrations in young children are conflicting. This situation prompted us to assay plasma catecholamines in 86 healthy subjects aged two days to fifteen years using a sensitive high-performance liquid chromatography technique with electrochemical detection. Norepinephrine and epinephrine concentrations remained elevated up until 24 months of age, then dropped progressively to adult levels between 24 and 36 months, with fluctuations. These fluctuations, which reflect the sensitivity of children to environmental factors, prevented demonstration of any catecholaminergic secretory abnormality by blood assays in subjects under two years of age. Urinary assays, for which established values exist, are the only applicable procedure in such patients.

Adolescent↗

A direct comparison of immunological and clinical effects of interleukin 2 with and without interferon-alpha in humans.

Interleukin 2 (IL-2) and interferon-alpha (IFN-alpha) are cytokines with synergistic antitumor effects in mouse models. The biological effects of this combination, however, have not been directly compared to each agent alone in humans. We conducted a Phase 1B trial of IL-2 plus or minus IFN-alpha in 38 cancer patients. The objectives of this trial were to determine which doses of IFN-alpha and IL-2 maximally enhanced biological responses, and to determine whether the combined administration of IFN-alpha and IL-2 would result in a potentiation of biological responses over IL-2 alone. Patients received 4 days of IL-2 (1.5 x 10(6) units/m2/day or 3.0 x 10(6) units/m2/day) as a continuous infusion followed by a 3-day rest period, weekly for 3 weeks, with a 3-week rest period between 2 treatment courses. IFN-alpha (0.5 x 10(6) or 5 x 10(6) units/m2/day) was administered s.c. on days 1-4 weekly for 3 weeks with one of the 3-week courses. Patients were randomized to receive either IL-2 alone for course 1, followed by IL-2/IFN-alpha for course 2, or IL-2/IFN-alpha in course 1, followed by IL-2 alone. Immunological parameters were evaluated before treatment, and 24 h after completion of the third week of IL-2. A statistically significant increase in the percentage of circulating natural killer cells (CD56), natural killer cells bearing the Fc receptor (CD16), and activated T cells (CD25) was observed following IL-2 alone, and following IL-2 plus IFN-alpha. Significant increases in lymphocyte-activated killer cell cytotoxicity, antibody cellular cytotoxicity, and serum IL-2 receptor were also observed following both IL-2 and IL-2 plus IFN-alpha. However, no significant differences were observed in the magnitude of the increase in the IL-2-alone group when compared to the IL-2 plus IFN-alpha group. The mean fluorescent intensity of monocytes positive for HLA-DR and Fc receptor expression also increased significantly in both groups, as did serum beta 2-microglobulin expression and indoleamine 2,3-dioxygenase activity. However, increases were not significantly different between patients receiving IL-2 alone and IL-2 plus IFN-alpha. No dose response effect for IFN-alpha was observed for any of the parameters assessed. Toxicities consisted primarily of constitutional toxicities, including fever, rigors, malaise, headache, anorexia, and a decrease in performance status. No clinically significant differences in toxicities were observed between courses consisting of IL-2 and those consisting of IFN-alpha and IL-2.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Severe visceral leishmaniasis with hepatic involvement. Diagnostic value of the immunoblotting serologic technic].

The case of a 13 year old boy with a severe form of visceral leishmaniasis (VL) mimicking portal hypertension and of unfavorable outcome is presented. The authors stress the usefulness of investigating humoral immune response by using Western Blot assay in order to confirm the diagnosis when the parasite cannot be isolated. Since VL may be responsible for death if the treatment is delayed, screening of the disease in children presenting with chronic liver disease is important in endemic area.

Adolescent↗

Methylated catecholamine metabolites for diagnosis of neuroblastoma.

Assays of urinary catecholamines and their metabolites (HVA, VMA, dopamine) permit biochemical diagnosis of neuroblastoma in approximately 80% of patients. The urinary methylated catecholamine metabolites normetanephrine (NMN), metanephrine (MN), and 3-methoxytyramine (3-MT) were analyzed in 18 patients with neuroblastoma and compared with reference values established for 69 healthy pediatric controls. All 18 neuroblastoma patients had raised urinary excretion of at least one of the three commonly assayed metabolites (HVA, VMA, dopamine). Similarly, raised urinary excretion of a methylated metabolite was noted in all but one of the neuroblastoma patients. The 3-MT level was pathologic in 16 of the 18 patients (89%). In this series, 3-MT assay sensitivity was sufficient to warrant trials on a larger population including comparison with patients considered nonsecretors by routine assay procedures.

Adolescent↗

Limitations of the electrocardiographic diagnosis of left ventricular hypertrophy: the influence of left anterior hemiblock and right bundle branch block.

We analysed the performance of the electrocardiogram in diagnosing left ventricular hypertrophy in 70 patients with isolated left anterior hemiblock and in 75 patients with right bundle branch block, either isolated (44 cases) or associated (31 cases) with left anterior hemiblock. Left ventricular hypertrophy defined as an echocardiographically determined left ventricular mass greater than 261 g in men and 172 g in women or left ventricular mass index greater than 125 g/m2 in men and 112 g/m2 in women was present in 48 subjects (57%) with isolated left anterior hemiblock and 33 subjects (44%) with right bundle branch block. In patients with isolated left anterior hemiblock the best results were obtained using the SV1 or SV2 + (RV6 + SV6) greater than 25 mm with 74% in sensitivity and 67% in specificity; the criterion SIII + (R + S) maximal in a precordial lead greater than or equal to 30 mm showed a sensitivity of 74% but a specificity of 47%. In the whole group of patients with right bundle branch block none of the criteria nor combination of criteria achieved an acceptable performance (sensitivities ranged from 17% to 41% and specificities ranged from 54% to 85%). When these patients were divided according to the presence or absence of concomitant left anterior hemiblock the electrocardiographic indexes mostly showed, in comparison to whole group, higher values in sensitivity and lower values in specificity in right bundle branch block plus left anterior hemiblock and an opposite behaviour in isolated right bundle branch block.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PAF and the role of the vagus nerve in the breathing pattern of the pig.

In 14 anesthetized, spontaneously breathing pigs we examined the changes in breathing pattern, in respiratory mechanics and in systemic and pulmonary vascular parameters after i.v. PAF administration. In another 3 pigs, the effects of PAF were also examined after bilateral vagotomy. In intact pigs, PAF induces apnea, bronchoconstriction, pulmonary hypertension and systemic hypotension. Our results also show that administration of PAF alters the phasic vagal activity, modifying the slope of VT vs TI and TE vs TI relationships and the TI0/TI ratio. These effects and apnea are vagus-dependent. The central excitatory timing effect of PAF on inspiratory duration (TI0) was correlated with a decrease in passive compliance but not with active compliance. We postulate that the activation by vagal input strengthens the mechanisms that counteract the bronchoconstrictor effect of PAF.

Animals↗