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Biomedical subjects

A Capozzi

Publications and source records attributed to A Capozzi.

At least 19 recordsLinked to original sources

Biological properties of some benzopsoralen derivatives.

The biological activity of some benzopsoralen derivatives, prepared with the aim of obtaining new drugs for photochemotherapy, has been studied. The more interesting compounds are 4-hydroxymethyl-4',5'-benzopsoralen and 4-hydroxymethyl-4',5'-tetrahydro-benzopsoralen, which were found to be active in the dark also: DNA and RNA synthesis were both inhibited in Ehrlich cells, even if in a partially reversible fashion, while protein synthesis remained unaffected. In Chinese hamster ovary cells cultured in vitro, the clonal growth was strongly inhibited by incubation in the dark with both drugs, while a number of chromosomal aberrations was observed in the fraction of growing cells. Using alkaline elution, DNA strand breaks were detected. In addition, in the presence of aphidicolin, a specific inhibitor of DNA polymerase, the clonal growing capacity was completely restored; in contrast, the number of DNA strand breaks remained unchanged. All these results suggest that DNA topoisomerases are probably the target of these two benzopsoralens. These compounds are also good sensitizers; by UV-A irradiation they have a good capacity to produce singlet oxygen, but they appeared to be unable to induce erythemas on guinea-pig skin. Under UV-A light, they induced a strong inhibition of DNA synthesis in Ehrlich cells. Thus, benzopsoralens appear to be capable of inducing strong antiproliferative effects by two different mechanisms, by UV-A irradiation and in the dark.

Animals

[Clinical and prognostic significance of echocardiographic parameters in dilated cardiomyopathy: a prospective study on 225 patients. The Italian Multicenter Study of Cardiomyopathies Group].

To assess the prognostic role of echocardiographic indexes and their relation to clinical conditions, 225 patients with dilated cardiomyopathy were studied prospectively. All cases had a normal coronary angiogram and non specific endomyocardial biopsy findings. 163 men (72.4%) and 62 women (27.6%), mean age 41.5 +/- 12.3 (range 8-61), were studied. Clinical, electrocardiographic and echocardiographic parameters, normalized for body surface area, were tested according to NYHA class and presence of segmental or diffuse wall motion abnormalities. One hundred-four patients were in NYHA class I-IIa, 94 were in class IIb-III and 27 were in class IV. Left ventricular end systolic diameter index, right ventricular end diastolic diameter index, left atrial diameter index, left ventricular fractional shortening and ejection fraction, and radius to wall thickness ratio were significantly more impaired in patients with more severe symptoms. Twenty-eight patients (13%) showed segmental wall motion abnormalities and had smaller left ventricular end systolic and left atrial diameter index and higher left ventricular fractional shortening and ejection fraction. During a mean follow up of 23 +/- 15 months (range 1-67 months), 25 patients (11.1%) died from cardiac causes and 16 (7.1%) underwent heart transplant because of refractory heart failure. Prognostic evaluation was performed separately for cardiovascular mortality alone and for cardiac events (cardiovascular mortality and heart transplantation). At Cox multivariate analysis only right ventricular end diastolic diameter index (p < 0.005) predicted cardiovascular mortality, while left atrial diameter index (p < 0.001), right ventricular end diastolic diameter index (p < 0.01) and left ventricular ejection fraction (p < 0.05) were significant independent predictors of cardiac events.

Adolescent

Photochemical and photobiological properties of 4,8-dimethyl-5'-acetylpsoralen.

The photochemical and photobiological properties of 4,8-dimethyl-5'-acetylpsoralen (AcPso), proposed for the photochemotherapy of some skin diseases, were investigated. The photoreaction of AcPso with DNA is weaker in the presence of air than in a nitrogen atmosphere, in terms of total photobinding and DNA cross-linking; when UVA irradiation is performed in air, AcPso behaves as a monofunctional reagent. The quenching effect of oxygen is related to the high capacity of AcPso to produce singlet oxygen. Furthermore, it is demonstrated that AcPso photoadducts are better producers of singlet oxygen than free AcPso in solution. Using DNA sequencing methodology, two modes of DNA photosensitization by AcPso are shown, these lead to the formation of photoadducts mainly at T residues (and at C to a lesser extent) and to photo-oxidized G residues probably via singlet oxygen. Chemical or enzymatic cleavage were used as probes in these experiments. A rapid assay for the detection of the photodynamic effect of a photosensitizer on DNA, involving oxygen, is also described. Finally, the cytotoxicity and genotoxicity of AcPso on E. coli WP2 cells appear to be related to its ability to form photoadducts, in particular cross-links, rather than to its capacity to produce singlet oxygen.

Animals

Long-term complications of polyurethane-covered breast implants.

The authors's personal experience using an earlier manufactured polyurethane-covered gel prosthesis is presented. Very long-term follow-up did not validate the author's initial enthusiasm. It is to be hoped that the newer polyurethane-covered implants will give more satisfactory long-term results.

Breast

Synthesis and photobiological properties of acetylpsoralen derivatives.

In an investigation to find monofunctional reactants for DNA which can act as new agents in the photochemotherapy of psoriasis, we have synthesized and studied some methylpsoralen derivatives which contain an acetyl group at one of the two reactive sites of the furocoumarin skeleton (at the 3 or 5' positions). The compounds do not react easily with DNA; their photobiological properties (e.g. the lack of an ability to inhibit DNA synthesis in Ehrlich ascites tumour cells, to induce T2 phage sensitization and to induce erythema in guinea-pig skin) are exactly in line with this behaviour. Some interesting features are shown by 4,8-dimethyl-5'-acetylpsoralen: it is capable of producing a very large amount of singlet oxygen--an order of magnitude higher than the other compounds and 8-methoxypsoralen (used as reference). In spite of this property, 4,8-dimethyl-5'-acetylpsoralen is non-phototoxic to the skin, and its other photobiological properties appear to be in line with its lack of interaction with DNA rather than its enhanced singlet oxygen production.

Acetylation

Photobiological activity of 3,4'-dimethyl-8-methoxypsoralen, a linear furocoumarin with unusual DNA-binding properties.

The furocoumarin derivative 3,4'-dimethyl-8-methoxypsoralen (DMe-8-MOP) exhibits remarkable antiproliferative activity, but is devoid of skin phototoxicity. To gain insight into this peculiar behaviour we investigated non-covalent and covalent binding of DMe-8-MOP to calf thymus DNA, along with DNA-synthesis inhibition and mutagenic activity. The non-covalent interaction of DMe-8-MOP with the nucleic acid is quite poor as shown by equilibrium dialysis, spectroscopic, chiroptical and hydrodynamic techniques. However, it exhibits relevant photobinding ability to DNA using both isolated nucleic acid samples and cellular systems. Unlike the large majority of congeners, DMe-8-MOP undergoes predominantly photochemical monoaddition to the double helical polynucleotide. Upon examination of the products obtained by enzymatic hydrolysis of DMe-8-MOP photomodified DNA, the formation of an unusual furan side adduct is proposed, which could account for the peculiar photochemical and photobiological properties of the 3,4'-dimethyl furocoumarin derivative.

Animals

Subcutaneous mastectomy data: a final statistical analysis of 1500 patients.

A statistical analysis of 1500 patients who underwent subcutaneous mastectomy is presented. Their data suggest that most patients who were treated by subcutaneous mastectomy had proliferative fibrocystic disease or macrocystic disease, among other high risk factors. The data also suggest that a thoroughly performed subcutaneous mastectomy is an effective means of providing prophylaxis in women who are at high risk for breast cancer. Conclusions were confirmed by many unsolicited comments of patients who underwent the procedure and were grateful to their doctors who performed it.

Adult

Relationship between DNA replicon size and SCE induction in BALB/c and BALB/Mo mouse lymphocytes.

We studied the DNA replicon size in BALB/c and BALB/Mo mouse lymphocytes by the method of bromodeoxyuridine photolysis. After treatment of the BALB/Mo lymphocytes in vitro with mitomycin C, the average DNA replicon size appeared to be significantly smaller than that observed in BALB/c lymphocytes treated similarly. In these conditions an increased susceptibility to SCE induction in BALB/Mo lymphocytes had been observed. In the presence of both mitomycin C and cordycepin (an antiviral drug), both the DNA replicon size and the SCE frequency returned to normal values.

Animals

Treatment of Echinococcus granulosus hydatid disease with mebendazole.

The Authors report their personal experience in the treatment of 70 patients with hydatid cysts of different localization with mebendazole, following protocols approved by WHO. During treatment patients were submitted to careful clinical, biochemical, radiological and immunological controls. On the whole, 150 hydatid cysts and 13 cases of widespread hydatidosis were observed. Follow-up ranged from 6 months to 5 years. Morphological and/or volumetric modifications were observed in 64.3% of the total number of cysts treated, regardless of their localization. 9 relapses were observed, and all but one case showed the same previous sensitivity to a further cycle of mebendazole. The observed side effects were not severe.

Adolescent

The scalp as a donor site in burns.

The scalp can be used as a donor site in the extensively burned patient. A series of 21 patients in whom this procedure has been performed, including up to 12 occasions in the same patient, is reviewed. No associated complications were encountered. The technique of harvesting the split-thickness skin grafts in this area requires the use of Pitkin's syringe and Brown air dermatome. The advantages include the availability of a large donor site that is well concealed and heals rapidly. The anatomic basis of the advantageous characteristics of the scalp and the need for subgaleal injections of fluid to stabilize the scalp are reviewed. The occasionally more pressing need to use this area in the extensively burned child because of relative body surface area distributions is also noted. Excessive blood loss, hypertrophic scarring, and the need for hair transplantation have not been noted. Complete hair regrowth has been experienced in nearly all cases.

Adolescent

Management of skin loss in meningococcal infection.

The case of a 17-month-old girl with fulminant meningococcemia is presented to illustrate the protean and fulminant course of the disease. Special attention is given to the meningococcal skin manifestation, with guidelines for its treatment.

Debridement

Abdominal hydatid disease: US findings during medical treatment.

The sonographic appearance of 141 hepatic and abdominal hydatid cysts was studied in 63 patients undergoing therapy with benzoimidazolic compounds. The cysts were evaluated for size, margins of the cyst wall, and echo pattern of cyst contents to establish the response to the drugs. Changes seen on ultrasound (US) scans were classified as decrease in size, detachment of the cyst membrane, and appearance of echogenic material (matrix) in the cyst cavity. These findings, particularly the diffusely hyperechoic pattern, are explained on the basis of the action of the drugs. Twenty-one patients underwent surgery at the end of treatment. The US patterns of treated hydatid cysts are similar to those seen, though more rarely, in cases of spontaneous parasite involution in long-standing hydatidosis.

Abdomen

Clinical experience with Heyer-Schulte inflatable implants in breast augmentation.

Following breast augmentation, 100 patients with inflatable saline implants were followed for a period of 6 months to 8 1/2 years. Capsular contracture rate, Baker II or greater, was 3.4 percent. This low rate of capsular contracture is attributed to early manipulation of the implant. The deflation rate was also 3.4 percent. The Heyer-Schulte (Mentor) inflatable implant offers an acceptable low rate of leakage to justify its continued use. It also offers an advantage in correction of asymmetries and yields softer breasts. The replacement of an occasional deflated implant does not appear to pose more than a minor nuisance nor to materially compromise the possibility of an excellent long-term result.

Adolescent

Photobiological activity of certain pyranocoumarin derivatives: potential agents for the photochemotherapy of psoriasis.

The photobiological properties of a series of pyranocoumarin derivatives having linear (xanthyletines) and angular structure (seselins) have been studied; while the linear derivative carrying the methyl geminal group, typical of the parent natural compound, appeared to be entirely inactive in all tests performed, very probably because of the steric hindrance in the dark interaction with DNA, 4 substances lacking in this group showed a marked capacity for inhibiting DNA synthesis in Ehrlich cells. In particular, 4,6-dimethyl-8-desmethylseselin proved to be about 7 times more active than 8-MOP. Practically all compounds were capable of inducing cross-links in DNA, but this feature, marked in the linear compounds, is very much reduced in the angular ones; this property appears to be clearly related to the mutagenicity in the light and with the skin phototoxicity, which are both marked in the former and low or absent in the latter. In the dark, while all compounds are non-mutagenic in the absence of metabolic activation, in the presence of microsomial enzymes pyranocoumarins become mutagens; only the xanthyletine derivative carrying a geminal methyl group at the 8 position was not activated, suggesting that the enzymes metabolize the pyranic ring.

Animals

Subcutaneous mastectomy: an interim report on 1,244 patients.

Data are presented on 1,244 patients who had subcutaneous mastectomies during the past fourteen years with an average follow-up of seven years. Obscure lobular carcinoma in situ was found in 4.3% of patients and obscure ductal or intraductal carcinoma was found in 5.1%, for a total of 9.4%. Breast cancer developed in only 6 patients after subcutaneous mastectomy, an incidence of 0.5%, indicating that subcutaneous mastectomy is effective in preventing breast cancer. Where obscure breast cancer was found, the prevalent associated benign fibrocystic diseases were microcystic and macrocystic and lobular hyperplasia. Where obscure ductal or intraductal carcinoma was found, the prevalent associated benign diseases were microcysts, macrocysts, intraductal hyperplasia, and sclerosing adenosis.

Adult

Clinical experience with polyurethane-covered gel-filled mammary prostheses.

We have used 104 low-profile polyurethane-covered gel-filled mammary prostheses in 54 patients. Only one patient has developed capsular contracture. Foreign-body reaction to polyurethane was clinically significant in only one patient. Other complications have been few and of the type that can accompany any type of mammary prosthesis. Of the 54 patients studied, 51 still have their implants in place and have soft, compressible breasts. The superior wrinkling and palpable implant edge that is occasionally present when the implant is placed subcutaneously has been of some concern to patients and can be eliminated by submuscular placement. The use of polyurethane-covered low-profile gel-filled prostheses for breast reconstruction has greatly improved our results, and the satisfaction of both surgeon and patient has been gratifying.

Breast