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Biomedical subjects

C Manca

Publications and source records attributed to C Manca.

At least 37 records · Page 2Linked to original sources

Aortic intramural hematoma: an increasingly recognized aortic disease.

Aortic intramural hematoma (IMH) is a rarely diagnosed pathological condition that is not well characterized to date. We diagnosed IMH in 4 of 31 patients with suspected aortic dissection admitted to our coronary care unit from 1992 to 1995. In all 4 cases, IMH was located in the ascending aorta. At the time of hospitalization, all patients showed tachycardia, hypotension and pericardial effusion. Diagnosis of IMH was made by transesophageal echocardiography and computed tomography. We performed aortography in 2 patients, but it was non-diagnostic in both of them. One patient died before surgery. Autopsy confirmed the diagnosis of IMH and showed severe pericardial effusion. In another patient, the diagnosis was confirmed during successful surgery, while the remaining 2 patients recovered after medical therapy. The 3 surviving patients are still under follow-up control 12, 16 and 20 months after the initial acute event. We briefly discuss the epidemiological, clinical, diagnostic, therapeutic and prognostic aspects of IMH.

Aged↗

Abnormal ventricular repolarization mimicking myocardial infarction after heterocyclic antidepressant overdose.

In 2 young adult women who experienced acute heterocyclic antidepressant intoxication, we found a quite unusual electrocardiographic pattern characterized by abnormal ST-tract elevation in the right precordial leads associated with a marked QRS widening (right bundle branch block and left anterior fascicular block type). Because serum electrolyte imbalance and acute myocardial ischemic events were excluded, the mechanism by which antidepressant overdose may produce such elevation of the ST tract remains unclear.

Adult↗

Mechanism of action of human calcitonin gene-related peptide in rabbit heart and in human mammary arteries.

We investigated the effects of human calcitonin gene-related peptide (CGRP) on isolated rabbit hearts to evaluate the mechanisms responsible for the vasodilatory action of the peptide on the coronary district, monitoring contemporaneously the effects on left ventricular pressure (LVP) and heart rate (HR). We also evaluated the reactivity of the human internal mammary artery (IMA) to excitatory drugs acting with different mechanisms and the inhibitory response to CGRP in comparison with the commonly used vasodilatory agents. The peptide induced a slight inhibitory effect on the basal coronary perfusion pressure (CPP), whereas it was ineffective on the inotropism and chronotropism. A more detectable coronary vasodilation was evident when CPP was increased by spasmogenic agents [vasopressin, methoxamine, Bay K 8644, and prostaglandin F2 alpha (PGF2 alpha)]. This inhibitory effect was dose dependent (10(-11)-10(-8) M) and apparently not specific, occurring to the same extent on different stimuli. Forskolin (10(-8) M), an adenylate-cyclase activator, and indomethacin (1.4 x 10(-5) M), a cyclooxygenase inhibitor, did not modify the spasmolytic activity of CGRP on precontracted coronary smooth muscle. The experiments performed on the segments of IMA, used for myocardial revascularization of patients affected by coronary diseases, have shown an evident spasmolytic action of CGRP on increased vascular tone induced by KCl (90 mM), noradrenaline (10(-5) M), serotonin (10(-6) M), and angiotensin II (10(-6) M). These inhibitory responses of CGRP on the spasmogenic compounds disappeared when the endothelial function of IMA, validated by the acetylcholine test, was abolished by mechanical ablation. A series of IMA segments was incubated (30 min) with N(G)-monomethil-L-arginine (L-NMMA), which inhibits nitric oxide (NO) synthase. In these experiments, the peptide failed to induce the vasodilation, suggesting that its action may be related to synthesis of NO. All these results show that CGRP is able to induce a potent vasodilatory action on different vessels of humans (internal mammary artery) and animals (rabbit coronary arteries). In particular the data obtained from IMA demonstrated that the vasorelaxant effect was related to synthesis of NO, one of the most studied endothelium-derived relaxing factors (EDRFs).

Adult↗

Molecular cloning, purification, and serological characterization of MPT63, a novel antigen secreted by Mycobacterium tuberculosis.

Proteins that are actively secreted by Mycobacterium tuberculosis generate immune responses in the infected host. This has prompted the characterization of protein components of mycobacterial culture filtrates to develop subunit vaccines and immunodiagnostic reagents. Fractionation of filtrates of M. tuberculosis cultures has yielded an abundant protein called MPT63, which has an apparent molecular mass of 18 kDa. We report the molecular cloning and nucleotide sequence of the mpt63 gene, purification of recombinant MPT63 antigen from Escherichia coli cells, and serological characterization of MPT63. Nucleotide sequence analysis of mpt63 identified an open reading frame encoding a protein of 159 amino acids (aa) consisting of a 29-aa secretion signal peptide and a 130-aa mature MPT63 protein. Recombinant MPT63 protein, purified from E. coli cells, and native MPT63, purified from M. tuberculosis culture filtrates, were indistinguishable in serological assays. Thus, the recombinant protein constitutes a valuable reagent for immunological studies. MPT63 evoked humoral immune responses in guinea pigs infected with virulent M. tuberculosis by the aerosol route. The mpt63 gene is found only in species of the M. tuberculosis complex, as shown by DNA hybridization experiments. Moreover, polyclonal antibody against MPT63 does not cross-react with proteins of a common environmental mycobacterial species, Mycobacterium avium. The absence of cross-reactive epitopes makes MPT63 an attractive candidate as an M. tuberculosis complex-specific diagnostic reagent. In particular, evaluation of MPT63 as an M. tuberculosis complex-specific reagent for diagnostic skin testing is under way.

Amino Acid Sequence↗

Mycobacterial growth and sensitivity to H2O2 killing in human monocytes in vitro.

The intracellular growth and susceptibilities to killing by H2O2 in cultured human monocytes of a number of mycobacterial species including laboratory strains and clinical isolates of Mycobacterium tuberculosis, and Mycobacterium bovis bacillus Calmette-Guerin (BCG) and a clinical isolate of Mycobacterium avium-M. intracellulare were examined. The clinical isolate of M. avium-M. intracellulare did not replicate in freshly explanted monocytes (generation time of >400 h); BCG replicated with a generation time of 95 h, and M. tuberculosis strains CDC551, H37Rv, and H37Ra replicated with generation times of 24, 35, and 37 h, respectively, during the 4-day growth assay. When cultured in monocytes for 4 days, the mycobacteria were variably sensitive to H2O2-induced killing. A positive correlation between the generation time and percent killing of intracellular bacilli was observed. By comparison, mycobacterial strains were similarly sensitive to H2O2 treatment in cell-free culture media and in sonicated cell suspensions. Using a number of inhibitors of reactive oxygen intermediates we determined that other than catalase the inhibitors tested did not affect H2O2-induced killing of intracellular mycobacteria. Our studies suggest that the killing of mycobacteria growing in human monocytes in vitro by the addition of exogenous H2O2 is dependent on the susceptibility to a peroxide-induced killing pathway as well as on the intracellular growth rate of the mycobacteria.

Antioxidants↗

MTC28, a novel 28-kilodalton proline-rich secreted antigen specific for the Mycobacterium tuberculosis complex.

Proteins that are actively secreted by Mycobacterium tuberculosis serve as major targets of immune responses in the infected host. To identify and purify novel proteins in the filtrates of M. tuberculosis cultures, a bacteriophage lambda library of M. tuberculosis H37Rv DNA was immunoscreened by using an anti-culture filtrate rabbit antiserum. Of 20 positive clones isolated, 6 were analyzed and found to express the genes for two known components of the early culture filtrate, the secreted 45/47-kDa antigen complex and the KatG protein, and two novel genes. Here we report the molecular cloning and nucleotide sequence of one of the new genes encoding a culture filtrate protein of 310 amino acid (aa) residues. We called this gene mtc28. The deduced polypeptide sequence contained an NH2-terminal, highly hydrophobic 32-aa region having properties of a secretion signal peptide. The putative 278-aa mature MTC28 protein was characterized at its NH2 and COOH termini by a high content of proline and alanine residues organized in an (AP)n motif. Thus, MTC28 is a new member of a group of proline-rich antigens found in M. tuberculosis and Mycobacterium leprae. As shown by DNA hybridization experiments, the mtc28 gene was present only in species of the M. tuberculosis complex. Purified recombinant MTC28 antigen evoked strong delayed-type hypersensitivity and antibody responses in guinea pigs immunized with Mycobacterium bovis BCG, but not in guinea pigs immunized with Mycobacterium avium. The strong immunological activity of MTC28 and the absence of B- and T-cell epitopes cross-reactive with a common environmental mycobacterial species, such as M. avium, make this novel antigen an attractive reagent for immunodiagnosis of tuberculosis.

Amino Acid Sequence↗

Left-ventricular outflow tract obstruction by mitral valve ring calcification and proximal septal hypertrophy in elderly patients. Presentation of 2 clinical cases.

The pathophysiology, clinical presentation and prognosis of left-ventricular obstruction still represent an important cardiological problem. Various anatomical and/or functional mechanisms can cause this phenomenon. This report concerns 2 patients over 75 years old in whom the simultaneous presence of localized proximal septal hypertrophy and massive calcification in the anterior portion of the mitral valve ring provoked significant systolic intraventricular gradients. Cardiac rhythm disturbances and consequent variability of R-R intervals, found in both subjects, appear fundamental in determining the value of such gradients. Occasionally an anterior mitral ring calcification may bring about left-ventricular outflow tract obstruction in aged hearts where localized hypertrophy of the proximal portion of the intraventricular septum is present.

Aged↗

Clinical, electrocardiographic, and echocardiographic features in patients with asymptomatic aortic abdominal aneurysm.

Cardiac involvement in peripheral vascular diseases can present interesting patho-physiological aspects and can influence the prognosis. The authors evaluated the cardiac condition of patients with asymptomatic aortic abdominal aneurysm (AAAA) by using clinical, electrocardiographic, and echocardiographic techniques. Seventy-eight patients were studied, 74 men and 4 women, with ages ranging from fifty-five to eighty-one years (mean 69.5 +/- 6.4). All patients were submitted to a complete clinical examination, usual blood tests, a 12-lead resting electrocardiogram, and an echo-Doppler evaluation. Forty-eight subjects (61.5%) were affected by hypertension, 53 (67.9%) were smokers, 25 (32.1%) were alcohol abusers, 39 (50%) had a history of angina pectoris, 20 (25.6%) had had previous myocardial infarction, and 30 (38.5%) were receiving active cardiovascular treatment. All patients except 2, who had chronic atrial fibrillation, manifested sinus rhythm. Electrocardiographic signs of left ventricular (LV) hypertrophy were present in 20 cases (25.6%), intraventricular conduction disturbances in 19 (24.4%), pathological Q waves in 20 (25.6%), and primary repolarization abnormalities in 25 (32.1%). Echocardiography showed a slight increase in left atrial diameter and intraventricular septum thickness (41.5 +/- 4.3 and 12.3 +/- 2 mm respectively). A clearer increase was found in LV mass index (159 +/- 44 g/m2). In 31 patients one or more LV asynergic segments were found. In our patients with AAAA the prevalence of major risk factors for atherosclerosis and ischemic heart disease including previous myocardial infarction was high. Echo-derived LV myocardial mass index was higher than normal even though electrocardiographic criteria for LV hypertrophy did not match echocardiographic data in all subjects. Finally a moderate prevalence of intraventricular conduction disturbances was recorded.

Aged↗

Left ventricular false aneurysm: an unusually prolonged natural history.

A case of left ventricular false aneurysm of postinfarctual etiology with an unusually prolonged natural history (12 years survival) is reported. A first diagnosis of this rare cardiac complication was made in 1982 on the basis of hemodynamic and echocardiographic results. At that time the patient rejected surgical therapy. Eleven years later the patient came back to our attention after resuscitation from a sudden cardiac death. Hemodynamic and echocardiographic (transesophageal) tests showed a remarkable impairment of left ventricular function and an abnormal enlargement (10 x 8 cm) of a pseudoaneurysmatic cavity full of thrombi. The patient died suddenly in April 1994. We emphasize the unusual, prolonged survival of our patient suffering from an unresected left ventricular false aneurysm of postinfarctual etiology.

Aged↗

Effect of aging on left ventricular filling in untreated hypertensive patients.

The aim of this study was to evaluate the influence of age and other clinical and echocardiographic parameters on left ventricular filling in a group of 174 untreated patients with mild to moderate hypertension (aged 20-82 years; mean 51.2 years) and in 189 age-matched normotensive subjects. All subjects underwent an echocardiographic study with pulsed Doppler evaluation of left ventricular filling. Left ventricular dimensions and indexes of systolic function were similar and within normal limits in both groups. Left ventricular filling was altered in hypertensive subjects < 65 years with a decrease of peak early velocity (peak E), an increase of peak atrial velocity (peak A) and a reduced E/A ratio. However in subjects > or = 65 years, we did not observe any differences in transmitral flow velocity pattern between hypertensive and normotensive subjects. The stepwise regression analysis showed that age alone explains up to 8% of peak E variance, 14% of peak A and 26% of E/A ratio in hypertensives, while in normotensives it explains up to 18% of peak E variance, 50% of peak A and 61% of E/A ratio. The other variables entered into the regression slightly improved the predictive power. In conclusion, age is the major independent factor affecting left ventricular filling in both groups, even if its predictive power was smaller in the hypertensive group. The similarity of diastolic filling pattern in elderly hypertensive and normotensive subjects suggests that the 'aging factor' plays an important role in influencing left ventricular filling pattern so as to mask the effect of hypertension in the elderly patients.

Adult↗

Single coronary artery-right ventricular fistula with a partially thrombosed large aneurysm of its proximal tract in a 66-year-old man.

An exceptional combination of three major coronary anomalies: a single coronary artery, a congenital coronary-right ventricular fistula and a large proximal coronary aneurysm were found in a living 66-year-old patient suffering from post-myocardial ischaemic heart disease. Each coronary anomally and their influence on the clinical situation of the patient are briefly discussed.

Aged↗

Quinolizidine derivatives with antitubercular activity.

By reacting lupinylmagnesium chloride with suitable aromatic ketones, several lupinyldiarylcarbinols were obtained, whose dehydration gave the corresponding lupinylidenediarylmethanes. By reduction of three of these unsaturated compounds, the corresponding lupinyldiarylmethanes were also obtained. Direct condensation of lupinine with fluorene gave the 9-epi-lupinylfluorene. The quinolizidine derivatives obtained were tested against Mycobacterium tuberculosis H37RV. Nine compounds resulted endowed with good antitubercular activity with MIC < 8 micrograms/ml, while the remaining were only moderately active. Most interesting was the lupinylidene derivative 13 with MIC > 0.1 < 0.5 micrograms/ml.

Antitubercular Agents↗

[Cardiac and skeletal malformations in a 55-year-old man. Holt-Oram syndrome].

A patient with Holt-Oram syndrome, diagnosed in advanced age, in which skeletal anomalies of upper limbs and clavicles are associated with ostium secundum atrial septal defect, great left-to-right shunt and marked pulmonary hypertension is described. The importance of a prompt interdisciplinary instrumental diagnostic approach is underlined.

Abnormalities, Multiple↗

Non-paroxysmal arterioventricular junctional tachycardia during postprandial hypoglycaemia in an obese non-diabetic patient.

We have observed the simultaneous occurrence of postprandial hypoglycaemia and a rare cardiac arrhythmia: non-paroxysmal arteriovenous junctional tachycardia (NPJT) in a patient with suspected coronary heart disease (CHD) submitted to oral glucose tolerance testing (OGTT). To our knowledge the association between hypoglycaemia and NPJT has not been previously described. The pathogenesis of NPJT might involve a myocellular Ca2+ overloading determined by a hypoglycaemia-induced catecholamine discharge in a transiently ischaemic myocardium.

Aged↗

N-[4-(R',R"-phenylazo)aryl]aminolupinanes with antitubercular activity.

A set of twelve N-[4-(R-phenylazo)aryl]aminolupinanes (10a-c; 11a-i) was prepared by coupling the suitably substituted phenyldiazonium salts with N-(2,3-xylyl)-aminolupinane and with N-(5,6,7,8-tetrahydronaphth-1-yl)- aminolupinane. These compounds, as well as the N-(4-amino-2,3-xylyl)aminolupinane and the N-(4-amino-5,6,7,8-tetrahydronaphth-1-yl)-aminolupinane, that could be obtained from the former through an in vivo reductive cleavage of the azo group, exhibited a high activity against Mycobacterium tuberculosis H37RV with M.I.C. in the range 0.1-1 microgram/ml.

Antitubercular Agents↗