Biomedical subjects
Publications and source records attributed to A Carotti.
A series of amidinosulfonic acids IIIa-f, analogs of taurine and homotaurine, was synthesized by reacting 2-aminoethane or 3-aminopropane sulfonic acid with lactim ethers Ia-c and then cyclized to sultams IVa-c and Vd-f. The effects of some selected amidinosulfonic acids III on membrane ionic conductances of rat skeletal muscle are described.
Molecular lipophilicity can be expressed by log P or more conveniently by log kw, determined by the so-called "shake-flask" (SF) technique or by reversed-phase high-performance liquid chromatography (RP-HPLC), respectively. In the present study, the lipophilicity of a large set of solutes was measured by RP-HPLC on a silanol-deactivated octylsilane (OS) reversed phase, namely Inertsil OS (IN). IN lipophilicity parameters were found to be fairly well correlated with log P. A Linear Solvation Energy Relationship (LSER) study revealed that cavity term (modeled by intrinsic molar volume, V1) and hydrogen-bond acceptor capacity (modeled by the solvatochromic parameter beta) of solutes are the most important factors affecting retention on Inertsil OS. The comparison of LSER model for retention on Inertsil with those obtained for two other silanol-deactivated OS stationary phases, namely Deltabond OS and RP Select B, shows that alpha (H-bond donor activity of solutes) can be used as a parameter able to discriminate the behaviour of different stationary phases. QSAR studies indicated that lipophilicity parameters determined on silanol-deactivated OS phases have potential in medicinal chemistry applications.
Title compounds 1-36 were synthesized by reacting hydrazine with aldol adducts obtained from ninhydrin and methyl or alpha methylene ketones and aldehydes. Some of them showed a low, but significant benzodiazepine receptor affinity whose variation was interpreted through a structure-activity relationships study based on qualitative correlations and Comparative Molecular Field Analysis (CoMFA). Some indeno-pyridazine derivatives were found to possess an interesting anticonvulsant activity which however does not seem simply related to the benzodiazepine receptor modulation.
A series of thiazolo[3,4-a]benzimidazole derivatives were evaluated in vitro as antitumor agents against 60 human tumor cell-lines. The influence on the antitumor activity of the nature and type of substitution on the phenyl ring at C-1 is examined and a preliminary quantitative structure-activity relationships is presented.
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Chondrocalcinosis is an important, common, age-related joint disease. Its characteristic is the deposit of calcium pyrophosphate dihydrate crystals in hyaline and fibrous cartilages. Occasionally, it is a familial disorder; more often, it is a sporadic disease of adults sometimes in association with hormonal and metabolic disorders. The relationship between CC and diabetes mellitus (DM) is disputed. In this study the prevalence of radiographic CC (knee and/or wrist) in 184 DM patients was evaluated. For comparison two matched groups without DM were studied: i) 184 consecutive unselected out-patients seem in Rheumatology Department of Ancona University with X-rays of knee and/or wrist; ii) 184 consecutive unselected outpatients observed in a Radiology Department with X-rays of knee and/or wrist. No statistical difference was found between the prevalence of CC in DM patients vs controls. Moreover 113 CC patients were studied. No statistical difference was observed between the prevalence of DM and impaired glucose tolerance in CC patients vs controls. These results may suggest that there is no relationship between CC and diabetes mellitus, as other studies have recently shown.
A 2.5-year-old boy with a diagnosis of situs solitus, tricuspid atresia, anatomically corrected malposition of the great arteries (S,D,L), left juxtaposition of atrial appendages, and pulmonary stenosis underwent successful total cava-to-pulmonary connection by means of a superior vena cava-to-pulmonary artery end-to-side anastomosis associated with an inferior vena cava-to-pulmonary artery direct anastomosis. Anatomic features and surgical technique are described.
A series of 2-aryl-2,5-dihydropyridazino[4,3-b]indol-3(3H)-ones 5 were prepared and evaluated for their ability to inhibit radioligand binding to BZR, and to prevent sound and pentylenetetrazole (PTZ) induced seizures in mice. The biological and pharmacological results are discussed in the light of some recently proposed pharmacophore models and compared through molecular orbital and molecular modeling studies to those obtained from the close pyrazoloquinoline analogs 6.
Interstitial pneumonia is one of the major causes of morbidity and mortality after bone-marrow transplantation. We here report a series of 58 patients suffering from hematological malignancies who received HLA-matched T-lymphocyte depleted bone-marrow transplants between July 1985 and January 1990. Interstitial pneumonia occurred in 7/58 patients (12%) and was fatal in six. Three different pre-bone-marrow transplantation conditioning regimens were employed. Total body irradiation was delivered according to a hyperfractionated scheme of 12 fractions given three per day 5 hr apart for 4 days. Twenty-three patients received 36 mg/Kg procarbazine, 1275 UL/Kg antithymocite globulin, 14.4 Gy hyperfractionated total body irradiation and 120 mg/Kg cyclophosphamide. Only one patient developed interstitial pneumonia, but two rejected the graft and 10 relapsed. As a consequence, the total hyperfractionated scheme was increased to 15,6 Gy, cyclophosphamide to 200 mg/Kg, antithymocite globulin to 3400 UL/Kg and procarbazine eliminated. There were three cases of interstitial pneumonia, no rejection and four relapses in the 17 patients who received this regimen. In the last 18 patients hyperfractionated total body irradiation was reduced to 15 Gy, cyclophosphamide to 100 mg/Kg, and 10 mg/Kg of the myeloablative agent thiothepa added to enhance the cytoreductive effect without significantly increasing extramedullary toxicity. Three cases of interstitial pneumonia, one relapse but no rejection were recorded. Our results demonstrate that the absence of graft-versus-host disease due to T-cell depletion, and radio-chemotherapy doses and schedules used for the conditioning regimen each contributed to reducing the risk of interstitial pneumonitis. Hyperfractionated total body irradiation therefore, seems to play an important role in lowering the incidence of this complication.
The pulmonary circulation is dependent on the ductus arteriosus in all patients with pulmonary atresia and intact ventricular septum and in some with pulmonary atresia and ventricular septal defect (tetralogy of Fallot type). To assess the time of ductal closure in these two patient categories, we compared the ages at first operation in 58 patients with pulmonary atresia and intact ventricular septum and 32 with pulmonary atresia and septal defect. The age distribution differed significantly between the groups. Whereas 90% of the children with intact ventricular septum required surgery in the first week of life, 50% of those with ventricular septal defect underwent surgery after the first month and 25% after the third month. The previously described and now confirmed anatomic differences of ductus arteriosus or different levels of endogenous prostaglandins may explain persistent patency of the ductus in pulmonary atresia with ventricular septal defect. The phenomenon may have important clinical implications regarding the timing and choice of surgical procedure.
Between December 1986 and December 1990, a bidirectional cavopulmonary anastomosis was performed in 27 patients younger than 2 years of age, including 12 with heterotaxia syndrome. Age and weight of patients averaged 14.2 +/- 6.6 months and 8.1 +/- 2.2 kg, respectively. Eleven had pulmonary atresia and 16 had pulmonary stenosis. The main pulmonary artery was ligated in seven patients in the latter group (subsequently reopened in one) and left open in nine (subsequently ligated in two). There were four hospital deaths (15%). All patients were discharged with anticoagulant/antithrombotic therapy to be continued for 6 months. There were two late deaths before further operations (8.7%). Two patients, one with acquired massive pulmonary arteriovenous fistulas and one with progressive common atrioventricular valve regurgitation, subsequently underwent definitive repair (biventricular in one), and both died. Heterotaxia syndrome (p = 0.087) and preoperative mean pulmonary artery pressure higher than 15 mm Hg (p = 0.09) were the only risk factors for overall mortality.
We report on two patients with congenitally corrected transposition of the great arteries in situs inversus who underwent successful anatomic repair of associated cardiac anomalies--ventricular septal defect and pulmonary outflow tract obstruction. Surgical intervention was influenced by the recently introduced technique of Ilbawi and colleagues in cases of congenitally corrected transposition in situs solitus. Principles of the correction are as follows: (1) patch redirection of venous flows at the atrial level through an incision in the left-sided right atrium; (2) patch closure of the ventricular septal defect through a right ventriculotomy, baffling the left ventricle to the aorta; and (3) valved conduit interposition between the right ventricle and the pulmonary artery. If the ventricular septal defect is restrictive, it can be safely enlarged by extensive resection of the anterosuperior border, because of the posteroinferior location of the bundle of His in this anomaly. With this technique, the left ventricle and the native mitral and aortic valves are recruited for systemic work, with intrinsic long-term advantages. It is, however, a complex procedure involving substantial use of prosthetic material. More experience is necessary to establish whether this approach is superior to currently available physiologic repairs.
A large homologous series of quaternary ammonium derivatives of perhydropyrrolo[3,4-c]pyridine 5 was synthesized and tested for in vitro antibacterial activity against different Gram-positive and Gram-negative bacteria. Compounds 5 proved to be always more potent than benzalkonium chloride, taken as reference. Antibacterial activity, expressed as log 1/MIC, was found linearly related to lipophilicity up to C13-C14 homologs, where a break in the linear relationship was observed.
Thirteen patients, 12 of whom younger than 2 years, underwent a Damus-Kaye-Stansel procedure for complete transposition of the great arteries, ventricular septal defect, or double-outlet right ventricle and subpulmonary ventricular septal defect. In 6 patients, associated cardiac anomalies caused systemic flow obstruction. There were six hospital deaths (mortality rate, 42%). In a mean follow-up period of 57 months, 5 of 7 survivors required relief of right ventricular hypertension through conduit replacement or enlargement (4 patients) or conduit valve balloon dilation (1 patient). The aortic valve became regurgitant in 2 patients in whom it had been left in potential connection with the right ventricle. One patient has moderate pulmonary valve regurgitation. The main advantage of the Damus-Kaye-Stansel procedure is that it avoids coronary relocation; also, the spatial relationship of the great arteries and the coronary anatomy do not affect its feasibility. One drawback is the need for a conduit in infancy. Our present indication for Damus-Kaye-Stansel procedure is confined to double-outlet right ventricle with subpulmonary ventricular septal defect; 5 of 6 patients survived repair in this series. Possible indications are for patients with associated subaortic obstruction or unusual coronary arrangements. Fresh or cryopreserved homografts as extracardiac conduits and primary closure of the subaortic area may reduce the need for reoperation after Damus-Kaye-Stansel procedure.
The lipophilic character of two large series of substituted benzenesulphonamides (BzSA) and 4-aminodiphenylsulphones (4-ADS) has been assessed by two chromatographic methods, i.e. reversed-phase HPLC using a relatively novel octadecylpolyvinyl packing and centrifugal counter-current chromatography (CPC). The octadecylpolyvinyl stationary phase proved an interesting alternative to the more common octadecylsilane type stationary phase for obtaining retention parameters correlated to partition coefficients (i.e. log P). The CPC method, being far less time-consuming and markedly more precise than the classical shake-flask method, offers a promising alternative for measuring partition coefficients. The parameter delta log Poct-hep, i.e. log Poctanol minus log Pheptane, was also determined for both congeneric series and was indicative of a similar H-bonding capacity for the SO2NH2 and 4-NH2-C6H4-SO2 groups. QSAR analyses of carbonic anhydrase inhibition by BzSA and antimycobacterial activity of 4-ADS show the capacity of the new lipophilicity parameters to express the hydrophobic component of the drug-enzyme interactions and to reveal a possible role of H-bond donor capacity in governing the antimycobacterial activity of 4-ADS.
We report 2D-echocardiographic and angiocardiographic assessment of 28 cases of visceral heterotaxia with left atrial isomerism, with particular emphasis on infundibular ventricular morphology. Ventricular D-loop was present in 15 cases (52.6%), and ventricular L-loop in 13 (46.4%); 25/48 patients had concordant ventricular loop and cardiac position (89.3%). In 18 patients (64.3%) there were 2 balanced ventricles; of the other 10 patients, 9 (32.1%) presented right and 1 (3.6%) left ventricular dominance. Ventricular septal defect was present in 12 cases (42.8%). Ventriculo-arterial connections were concordant, with "normally related" great arteries in 9/15 cases with ventricular D-loop (60%). In these cases, ventricular morphology, connections and relations of the great arteries were typical of situs solitus. In the remaining 6 patients there was double-outlet right ventricle, also with normally related great arteries. In 12/13 cases (92.3%) with ventricular L-loop ventriculo-arterial connections were concordant with "mirror image normally related" great arteries. In these cases, ventricular morphology, connections and relations of the great arteries were typical of situs inversus. In one patient there was double-outlet right ventricle, also with mirror image normally related great arteries. Twelve patients (42.8%) had pulmonary stenosis and 5 had a systemic outflow obstruction (17.8%). From these observations we conclude that ventriculo-infundibular morphology, either of situs solitus-type or of situs inversus-type, is a typical anatomical feature of left atrial isomerism. These results may have important implications in the diagnosis and in the surgical management of patients with left atrial isomerism.
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A double-patch technique has been used to repair total anomalous pulmonary venous connection in 35 patients (mean age, 4.9 months; mean weight, 4.2 kg). In all patients with supracardiac or subdiaphragmatic type of total anomalous pulmonary venous connection, repair has been accomplished by enlarging the "new" left atrium. There were three early deaths (3 of 35 = 8.6%) and no late deaths in a mean follow-up of 30 months (3 to 71 months). We propose this double-patch technique as an alternative surgical option for total anomalous pulmonary venous connection.