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Biomedical subjects

M Fontana

Publications and source records attributed to M Fontana.

At least 91 records · Page 5Linked to original sources

Breathing pattern during and after maximal exercise testing in young untrained subjects and in obese patients.

More rapid and more shallow breathing (RSB) than usual, manifested by a lower tidal volume and greater breathing frequency at a given level of ventilation, may be caused by inspiratory muscle fatigue and pulmonary congestion. It has been observed during recovery in young trained adults after very high exercise levels and in middle-aged patients with cardiac disease, after their maximal work load. We studied the breathing pattern during and after exercise testing up to the maximal work capacity in a group of normal untrained, young people and in a group of young obese subjects. RSB was present in normal subjects after a work load which required a maximal O2 consumption near the theoretical value (93% in our cases) and was not present in obese patients probably because neither inspiratory muscle fatigue, nor pulmonary congestion occurs in these subjects. Maximal heart rate at peak of exercise was significantly higher in normal subjects and a direct correlation between delta Vt and maximal heart rate was found in all normal subjects. This is compatible with the hypothesis that RSB is mainly due to an initial interstitial pulmonary edema, as supposed by other authors.

Adult↗

Ranitidine treatment in newborn infants: effects on gastric acidity and serum prolactin levels.

Data about the use of ranitidine in the early postnatal period are lacking. In this study, 30 term newborn infants < 2 days old with bleeding erosions in their upper gastrointestinal tracts were treated with ranitidine by continuous i.v. infusion (0.2 mg/kg/h) for 48 h and thereafter by mouth (5 mg/kg b.i.d.) for 1 month. Mean gastric pH (SD) rose from 4.27 (1.62) to 5.70 (0.95) during i.v. infusion; after oral therapy it was still 5.55 (1.25). Serum ranitidine concentrations were 642.4 (376.5) and 321.5 (368.2) ng/ml after i.v. and oral therapy, respectively, with wide interindividual variations; the correlation between serum ranitidine and gastric pH was found to be weak. No untoward effect was observed either on the cardiorespiratory rate or on creatinine and aminotransferase values. Mean serum prolactin concentration after i.v. therapy was found to be lower, although within the reference range, than in control infants; no significant correlation was observed between serum ranitidine and prolactin concentrations. From these data, a < 0.2 mg/kg/h rate seems to be advisable for continuous ranitidine infusion in neonates, whereas the 5 mg/kg b.i.d. regimen could be considered adequate for oral therapy.

Administration, Oral↗

The inhibition of bovine serum amine oxidase by cysteamine.

Bovine serum amine oxidase (BSAO) is inhibited by cysteamine, while cystamine is a good substrate. The activity of BSAO is not restored following removal of excess cysteamine by N-ethylmaleimide, by iodoacetate or by filtration through a G-25 Sephadex column.

Animals↗

Malabsorption of different lactose loads in children with human immunodeficiency virus infection.

Thirty children infected with human immunodeficiency virus (HIV) (18 P1 and 12 P2, according to the classification system of the Centers for Disease Control) and 54 noninfected children were evaluated for lactose malabsorption with use of the hydrogen breath test after different lactose loads. Lactose malabsorption after load of 2 g/kg occurred in 75% of P2, 67% of P1, and in 46% of noninfected children. With a lower lactose load (1 g/kg), the prevalence of malabsorption was significantly higher among P2 children than P1 and noninfected cases. A similar figure was obtained after the lowest load (0.5 g/kg). Infected children with lactose malabsorption were significantly younger than noninfected malabsorbers (mean age +/- SD; 50.3 +/- 22 vs. 63.5 +/- 20.9 months) when the load of 2 g/kg was used. The use of lower lactose loads seems to be helpful in finding the dose that can be tolerated. This finding could have nutritional importance and could lead to better dietary management.

Breath Tests↗

Catecholamine-stimulated potassium transport in erythrocytes from normal and obese subjects.

The beta adrenergic-modulated Na+/K+ ATPase pump rate of red blood cells was measured in vitro in 18 non diabetic obese patients. After challenge of erythrocytes with beta adrenergic selective agonist Salbutamol, the decrement of the K+ concentration in the suspending medium was assumed to be related to the Na+/K+ ATPase pump rate or to the number of beta 2 receptors. The mean K+ uptake was markedly increased in the erythrocytes of obese patients (1.58 mEq/l SD 0.18) if compared with 38 normal subjects (1.30 mEq/l SD 0.11) and with a population of 30 atopic patients that we have previously reported to have a reduced red cells beta 2 receptor activity (1.09 mEq/L SD 0.11). These results are not consistent with the hypothesis that a reduction in the Na+/K+ ATPase pump rate (at least in red blood cells) may be responsible for decreased metabolic rates leading to obesity. Since the autonomic nervous system is involved in the regulation of the cardiovascular system, it is conceivable that an increased Na+ ATPase pump rate (or supersensitivity) may be responsible of the increased incidence of hypertension, congestive heart failure and unexplained sudden death associated with obesity in some patients.

Adult↗

DNA binding properties of FCE24517, an electrophilic distamycin analogue.

The distamycin derivative FCE24517 binds both reversibly and irreversibly to DNA. At 37 degrees C, the drug originates reversible complexes that are strong enough to survive to the electrophoretic separation of the substrate. These complexes slowly evolve to covalent adducts (10(-4) adducts/bp/h) that eventually degenerate to single-strand breaks (1.5 x 10(-5) nicks/bp/h). The site of attack by the drug can be any base in the vicinity of AT-rich regions of the double helix. Rapidly reassociating duplex DNA molecules, indicative of the presence of cross-links, are observed only upon boiling of DNA with FCE24517. While the low rates of formation of covalent adducts and DNA breaks could be relevant for the long-term biological effects of FCE24517, the specific formation of strong but still reversible complexes with DNA could be matched to the drastic and sudden reduction of thymidine incorporation induced by this electrophilic distamycin.

Antineoplastic Agents↗

[Inherent problems of the use of magnetic resonance in patients with metallic implants currently used in orthopedic practice].

Forty-eight patients with oncologic prosthetic devices (modular rotatory shoulder, Kotz, custom made) and metallic means of fixation (Sherman's plates, Ender's rods, etc.) underwent MRI in order to: 1) assess possible physical changes in the magnetic field or the alloys under examination; 2) detect the presence and type of artifacts, and 3) verify the onset of eventual noxious effects of the alloy on the patient. The diagnostic investigation was preceded by an experimental phase which was characterized by: A) a study of the temperature fluctuations of the alloys when submitted to the magnetic field and to radiofrequency; B) the identification and characterization of the artifacts, as well as C) their physical interpretation. During examination, there was no evidence of any mobilization of the means of fixation, sensation of endogenous heat, or other subjective complaints on the part of the patient. The authors observed that, even in the presence of artifacts, MRI provided good evaluation of the soft tissues around the devices by identifying tumor recurrences in the presence of an oncological prosthesis. MRI was also capable of showing trophic changes in the tissues surrounding the means of fixation. Thus, the method exhibits no contraindications in the study of these patients but, on the other hand, does not allow the evaluation of the integrity or mobilization of the prosthetic devices.

Adolescent↗

Sulfur-containing cyclic ketimines and imino acids. A novel family of endogenous products in the search for a role.

Aminoethylcysteine, lanthionine, cystathionine and cystine are mono-deaminated either by L-amino-acid oxidase or by a transaminase exhibiting the properties described for glutamine transaminase. The deaminated products cyclize producing the respective ketimines. Authentic samples of each ketimine were prepared by reacting the appropriate aminothiol compound with bromopyruvate, except cystine ketimine which required the interaction of thiopyruvate with cystine sulfoxide. Reduction of the first three mentioned ketimines with NaBH4 yields the respective derivatives with the saturated rings of thiomorpholine and hexahydrothiazepine. The same reduction is carried out enzymically by a reductase extracted from mammalian tissues. Properties of the members of this family of compounds are described. Gas chromatography followed by mass spectrometry permits the identification of most of these products. HPLC is very useful for the determination of the ketimines by taking advantage of specific absorbance at 380 nm obtained by prior derivatization with phenylisothiocyanate. Adaptation of these and other analytical procedures to biological samples disclosed the presence of most of these compounds in bovine brain and in human urine. By using [35S]lanthionine ketimine as a representative member of the ketimine group, the specific, high-affinity, saturable and reversible binding to bovine brain membranes has been demonstrated. The binding is removed by aminoethylcysteine ketimine and by cystathionine ketimine indicating the occurrence in bovine brain of a common binding site for ketimines. The reduced ketimines are totally ineffective in competing with [35S]lanthionine ketimine. Alltogether these findings are highly indicative for the existence in mammals of a novel class of endogenous sulfur-containing cyclic products provided with a possible neurochemical function to be investigated further.

Amino Acids, Sulfur↗

Correlation between anthracycline structure and human DNA ligase inhibition.

A total of 19 anthracycline derivatives were tested for their ability to interfere in vitro with the action of the human replicative DNA ligase. Only those with the sugar devoid of unmodified amino groups or with large configurational modifications were found to be inactive. Maximal inhibition of DNA-joining activity was found to require a 4'-deoxy-3'-amino sugar. Self-adenylation of DNA ligase was largely insensitive to these drugs. An important general finding is that slight modifications of the anthracycline structure have pronounced effects on DNA-ligase-inhibitory activity and might be related to the specificity of anthracycline anti-tumour activity.

Adenosine Monophosphate↗

Specific inhibition of human DNA ligase adenylation by a distamycin derivative possessing antitumor activity.

The antiviral distamycin A and its phenyl mustard derivative FCE24517 possessing antitumor activity were tested for their ability to inhibit macromolecular synthesis in three human and one murine cell line. While distamycin A was poorly active in these systems, FCE24517 inhibited DNA synthesis efficiently, RNA synthesis to a lower extent and had little effect on protein synthesis. These findings suggest that the in vivo activity of FCE24517 derives from the specific inhibition of DNA synthesis. When the two drugs were tested on several enzymes involved in human DNA metabolism a strikingly similar pattern of inhibition appeared, with distamycin A being the more potent. Both drugs showed: A), no inhibitory activity against thymidine kinase and DNA primase; B), low activity against DNA topoisomerases I and II and the 3'-5' exonuclease associated with the DNA polymerase epsilon; C), high activity against DNA polymerases alpha and epsilon, uracil-DNA glycosylase and the joining activity of the replicative DNA ligase; D), the highest inhibitory activity against the AMP-dependent DNA relaxing activity of DNA ligase. The strong in vitro inhibition of several DNA enzymatic activities, including DNA ligase, do not match with the in vivo activities of the two drugs. However a unique difference was observed: only FCE24517 inhibited the DNA-independent reaction of adenylation of human DNA ligase while the adenylation reaction of T4 and E. coli DNA ligase was unaffected by either drug. It is still unclear whether these properties are relevant for modulating the killing activity of FCE24517 against proliferating cells both in culture and in vivo. Nevertheless FCE24517 is the first known molecule capable of interacting directly and specifically with human DNA ligase.

Adenosine Monophosphate↗

Osteoarthritis of the knee after ACL reconstruction.

One hundred and fourteen knees with deficiency of the anterior cruciate ligament (ACL) which had undergone reconstruction of the ligament using semitendinosus and gracilis were reviewed at a mean of 61 months after operation. Radiological and clinical evaluation was undertaken. A significant correlation was found between the number of meniscectomies performed in acute cases and those undertaken on the chronic knee. There was also significant correlation between meniscectomy and the Fairbank grading of degenerative changes seen on the radiographs. There was no correlation between the clinical results, residual laxity and the development of osteoarthritis. In ACL deficient knees with irreparable meniscal tears, or in which meniscectomy had been undertaken, the development of osteoarthritis seemed independent of the degree of stability, but in such knees with no meniscal tear or meniscal repair, reconstruction appeared to save the menisci and preserve the joint.

Adolescent↗

[Congenital toxoplasmosis. Report of a case treated with spiramycin in the 24th week of pregnancy].

The Authors present one case of congenital toxoplasmosis; it was sustained by a primary maternal infection, contracted at the XXIII week of gestation. Even if we started the treatment with spiramycin at the XXIV week of gestation, both the prenatal ultrasound examination of the fetus, and the postnatal investigation of the newborn, showed that the young patient was affected by a severe form of congenital toxoplasmosis.

Female↗

[35S]Lanthionine ketimine binding to bovine brain membranes.

2H-1,4-Thiazine-5,6-dihydro-3,5-dicarboxylic acid (trivial name: lanthionine ketimine) is a cyclic sulfur-containing imino acid detected in bovine brain extracts. This compound has been synthesized in a heavily labeled form starting from L-[35S]cysteine and purified by high performance liquid chromatography. We demonstrate the existence of a saturable and reversible binding of [35S]lanthionine ketimine to bovine brain membranes. A single population of binding sites with a concentration of 260 +/- 12 fmol/mg protein and a dissociation constant of 58 +/- 14 nM is present. Specific binding is competitively inhibited by other structurally similar imino acids, namely S-aminoethyl-L-cysteine ketimine and cystathionine ketimine. These results suggest a possible functional role for these ketimines in nervous system.

Amino Acids, Sulfur↗

Hyperendorphinemia in obesity is not related to the affective state.

In seventy-two patients affected by hyperphagic obesity and forty age-matched, normal weight volunteers we performed a psychological assessment, through various mental tests, and evaluated the beta-endorphin (B-Ep), ACTH and cortisol circulating levels, in basal condition and following an overnight short dexamethasone suppression test (DST). The hormones were measured by radioimmunoassay either directly in the serum (cortisol) and the plasma (ACTH), or after affinity gel column chromatography (B-Ep). In obese subjects B-Ep levels in basal conditions were four times greater than in normal weight controls and showed significantly less reduction after DST. ACTH and cortisol levels, in contrast, were in the normal range and were suppressed following dexamethasone as was also true in the control group. Psychological evaluation on M.M.P.I. (Minnesota Multiphasic Personality Inventory) revealed a trend toward hypochondria, depression, hysterias, psychoasthenia and schizophrenia. However, no significant correlation has been found between M.M.P.I. clinical scale scores and circulating levels of B-Ep and cortisol either in basal conditions or after DST. In conclusion, these data do not support the hypothesis that abnormalities of the hypothalamus-pituitary-adrenal axis in hyperphagic obesity are related to affective disorders.

Adrenocorticotropic Hormone↗

Results of reconstruction of the anterior cruciate ligament with the tendons of semitendinosus and gracilis in acute capsulo-ligamentous lesions of the knee.

This report presents the mid-term results of 55 cases of anterior cruciate ligament (ACL) lesions surgically treated in "acute phase" using intra-articular transfer of the semitendinosus and gracilis tendons, performed at the First Orthopedic Clinic of "La Sapienza" University in Rome since 1979. The follow-up is based on clinical (point system comprising subjective and objective criteria), instrumental (KT-1000 arthrometer), and radiographic (comparative AP view radiographic exam of the knees under load) data. On the basis of the results obtained, ACL reconstruction with the semitendinosus and gracilis tendons in the treatment of acute lesions can provide the patient with a good possibility of complete functional recovery of the knee.

Anterior Cruciate Ligament↗