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Biomedical subjects

P Ferraro

Publications and source records attributed to P Ferraro.

At least 55 records · Page 3Linked to original sources

Antithymocyte globulin and methotrexate therapy of severe or persistent cardiac allograft rejection.

BACKGROUND: The treatment of severe or persistent acute rejection remains difficult despite newer immunosuppressive agents available. METHODS: To evaluate the effectiveness of rabbit antithymocyte globulin and methotrexate as therapy for severe or persistent acute cardiac allograft rejection, we conducted a retrospective analysis of clinical and laboratory data from 150 consecutive heart transplant recipients between 1983 and 1994. RESULTS: Thirteen episodes of severe or refractory acute rejection were treated with rabbit antithymocyte globulin in 10 patients. Rabbit antithymocyte globulin (125 mg/day for 3 consecutive days) was effective in 90% of patients. Therapy was well tolerated, and contributed to one infectious complication, no malignancy, and long-term survival in 8 of 10 patients. Recurrent rejection developed in 60% of patients. Methotrexate (7.5 to 15 mg/wk for 16 weeks) was administered to 8 patients with persistent rejection documented on three consecutive endomyocardial biopsies. Therapy was effective in 6 of the 8 patients, with one infectious complication and no malignancy on follow-up. White blood cell count decreased significantly during therapy (p = 0.008). Seven of the 8 patients in the methotrexate group are long-term survivors. CONCLUSIONS: Rabbit antithymocyte globulin is a valuable alternative in patients with severe or refractory acute rejection. Methotrexate is an important adjunct in patients with persistent rejection unresponsive to conventional immunosuppressive regimens.

Adult↗

Beauty treatments and risk of parenterally transmitted hepatitis: results from the hepatitis surveillance system in Italy.

The role of ear-piercing, tattooing, attendance at chiropodist or manicurist and barber shop shaving in transmitting hepatitis B and hepatitis non-A, non-B was evaluated. Data reported here were collected from 1985 to 1993 by the National Viral Hepatitis Surveillance System. The association between parenterally transmitted hepatitis and the considered risk factors was estimated, comparing 6,395 hepatitis B and 2,558 hepatitis non-A, non-B cases with 4,789 hepatitis A cases, using the case-control method. Of the non-A, non-B cases tested from 1991 to 1993, 56.6% were anti-HCV positive. The incidence of parenterally transmitted hepatitis cases reporting specific beauty treatments was also evaluated. Tattooing, ear-piercing and barber shop shaving were associated with both parenterally transmitted hepatitides, while attendance at a chiropodist or manicurist was associated only with hepatitis B. During the study period the incidence of acute hepatitis B and non-A, non-B cases reporting beauty treatments declined by 49%. In spite of this decline, considering that a large part of the general population is exposed to the considered risk factors, the role of beauty treatments in transmitting hepatitis B and hepatitis non-A, non-B should not be underestimated.

Adolescent↗

[Reduced endothelium-dependent peripheral vasodilation in the aged].

Endothelial dysfunction may be present years before the clinical manifestations of atherosclerosis, which is particularly frequent in the late decades of life. Therefore, we have evaluated the presence of endothelial dysfunction in the elderly by measuring, by echo-Doppler technique, the vasodilatation of brachial artery in response to the hyperemia following forearm occlusion and decompression, a response that is dependent on endothelial function. We studied 10 subjects > 65 years (mean 72 +/- 8) and 10 subjects < 65 years (mean 40 +/- 6) all without clinical signs and without risk factors for atherosclerosis. The increase in brachial arterial flow during reactive hyperemia was similar in the young and elderly subjects (152 +/- 74% vs 129 +/- 63%, NS). While in the young at peak hyperemia we found a significant increase in brachial artery diameter from 3.4 +/- 0.9 to 4.1 +/- 1.0 mm (p < 0.005), there was no significant change in the elderly (from 3.0 +/- 0.7 to 3.1 +/- 0.7 mm, NS). In both groups sublingual glyceryl trinitrate produced a significant increase in brachial artery diameter (from 3.0 +/- 0.7 to 3.5 +/- 0.8 mm in the elderly, p < 0.01, and from 3.4 +/- 0.9 to 3.9 +/- 0.9 mm in the young subjects, p < 0.01, NS among groups), showing the absence in the elderly of structural vascular changes potentially responsible for absence of dilatation. In conclusion, elderly subjects without clinical signs or risk factors for atherosclerosis have a vascular endothelial dysfunction that may play an important role in pathologic processes of the cardiovascular system in the late decades of life.

Adult↗

[Endoscopic YAG laser and palliative therapy of cancer of the esophagus].

In our institution, the YAG laser has been used to treat 110 patients with inoperable esophageal carcinoma. Therapy was palliative as patients presented metastases (41.8%), advanced systemic disease (22.7%), extensive local disease (18.2%) or recurrent carcinoma (10%). The study group included 92 men (mean age 68.4 years) and 18 women (mean age 67.0 years); 47.3% of the patients had received no previous treatment while 52.7% had been treated previously with either radiotherapy, chemotherapy, surgery, stents or dilatation. The majority of lesions were adenocarcinomas (57.3%) with squamous cell carcinomas in 37.3%; 66.3% of cancers were located in the distal third of the esophagus. The patients received a mean of 2.4 laser treatments with 4883 joules per treatment on average. The rate of major complications was 2.7% and the rate of mortality 1.8%. The median survival for the group was 4.5 months. No significant difference was found in the length of survival according to the histology of the tumour (p = 0.35), the presence of metastases (p = 0.24) and the association of other treatment modalities with the laser (p = 0.06). Functional results were considered good to excellent in 82.1% of cases. In conclusion, the YAG laser does not influence overall survival of inoperable patients, but this therapy is effective and safe and is presently the treatment of choice for these patients.

Adenocarcinoma↗

Inhibition of ribonucleotide reductase by 2'-substituted deoxycytidine analogs: possible application in AIDS treatment.

After phosphorylation to the corresponding diphosphates, 2'-azido-2'-deoxycytidine and 2'-difluorocytidine act as powerful inhibitors of ribonucleotide reductase. Phosphorylation requires deoxycytidine kinase, an enzyme with particularly high activity in lymphoid cells. Therefore, the deoxycytidine analogs can be expected to inhibit the reductase with some specificity for the lymphoid system. Pretreatment of human CEM lymphoblasts with the analogs considerably increased the phosphorylation of 3'-deoxy-3'-azidothymidine (AzT). The increased phosphorylation of AzT is caused by a prolongation of the S phase of the cell cycle. Our results suggest the possibility of a combination of 2'-substituted deoxycytidine analogs with AzT in the treatment of AIDS. Gao et al. [Gao, W.-Y., Cara, A., Gallo, R. C. & Lori, F. (1993) Proc. Natl. Acad. Sci. USA 90, 8925-8928] have suggested the use of the ribonucleotide reductase inhibitor hydroxyurea for this purpose, since the resulting decrease in the size of deoxyribonucleotide pools decreases the processivity of the HIV reverse transcriptase. From our results it would appear that the 2'-substituted deoxycytidine analogs might be preferable to hydroxyurea.

Acquired Immunodeficiency Syndrome↗

Effects of mutational loss of nucleoside kinases on deoxyadenosine 5'-phosphate/deoxyadenosine substrate cycle in cultured CEM and V79 cells.

The functions of a deoxynucleoside kinase and a deoxynucleotidase can give rise to substrate cycles in which the two enzymes catalyze in opposite directions the irreversible interconversion of a deoxynucleoside 5'-monophosphate (dNMP) and its deoxynucleoside. Earlier evidence showed that pyrimidine dNMP cycles occur in cultured cells and participate in the regulation of the size of dNMP pools there by affecting the transport of deoxyribonucleosides across the cell membrane. Here, we apply an isotope flow method using labeled adenine as precursor of dAMP and DNA to quantify deoxyadenosine excretion as a measure of the catabolic activity of a putative dAMP/deoxyadenosine cycle. A comparison of human CEM lymphoblasts and hamster V79 fibroblasts, including mutant cells lacking kinases for the phosphorylation of deoxyadenosine, shows a much lower deoxyadenosine excretion in CEM cells (0.05% of dATP synthesized by reduction of ADP) as compared with V79 cells (4% of dATP). Mutational loss of deoxycytidine kinase increases these values to 0.3% in CEM cells and to 10% in V79 cells. This strongly suggests the presence of a dAMP/deoxyadenosine cycle in both CEM and V79 cells. Additional loss of adenosine kinase only marginally affects deoxyadenosine excretion in CEM cells. The small excretion of deoxyadenosine (also in the absence of both kinases) demonstrates that in CEM cells the in situ activity of the deoxynucleotidase affecting the dAMP/deoxyadenosine substrate cycle is very low and that the cycle has mainly an anabolic function there.

Adamantane↗

Esophageal diverticula.

Diverticula disease of the esophagus is associated with specific motor dysfunctions. Motility disorders at the pharyngoesophageal junction result from a restrictive pathology of the upper esophageal sphincter. Hyperdynamic motor abnormalities are seen with distal esophageal diverticula. Treatment of the motor disorder is essential in the management of these conditions.

Diverticulum, Esophageal↗

Spontaneous primary and secondary pneumothorax: a 10-year study of management alternatives.

OBJECTIVE: To study the outcome of conservative and surgical management of spontaneous pneumothorax. DESIGN: Retrospective study between January 1980 and December 1990, with a mean follow-up of 6.5 years. SETTING: A tertiary-care university hospital with a referral thoracic surgical unit. PATIENTS: All patients seen in the study period with spontaneous pneumothorax. Those with traumatic, iatrogenic or ventilator-associated pneumothoraces were excluded. There were 366 consecutive patients who had 508 episodes of spontaneous pneumothorax. Two hundred and thirty-nine patients had primary spontaneous pneumothorax (group 1); 127 had secondary spontaneous pneumothorax (group 2). INTERVENTIONS: Tube thoracostomy, apical resection with either pleurectomy or pleural abrasion. MAIN OUTCOME MEASURES: Recurrence and outcome after surgical management relative to recurrence, complications, operative technique and mean hospital stay were evaluated by clinical review and questionnaire by an independent observer. RESULTS: No significant differences were noted between the two groups with respect to the incidence of recurrent spontaneous pneumothorax after the first or second episode, and no significant differences were noted between the two operative techniques with respect to recurrence, complications, operative technique or death rate. However the mean hospital stay was doubled for group 2 patients (9.9 versus 4.3 days). CONCLUSIONS: Conservative treatment, including tube thoracostomy, was effective for primary and secondary spontaneous pneumothorax. Open surgery was effective in preventing recurrence in 95% of cases in both groups.

Adult↗

DNA repair in human lymphocytes treated in vitro with (+)-anti- and (+/-)-syn-benzo[a]pyrene diolepoxide.

Human PBL were treated in vitro with the ultimate reactive metabolites of BaP anti- and syn-BaPDE and DNA damage and repair were measured. The incorporation of radioactivity into DNA due to UDS was higher after treatment with anti-BaPDE. Radioactive DNA adduct dosimetry applied to PBL treated with tritiated syn- and anti-BaPDE demonstrated that anti-BaPDE gave more DNA adducts, which were more efficiently removed than syn adducts in the 24 h following the treatment. HPLC analysis of deoxynucleosides obtained from the enzymatic digestion of DNA showed that in treated PBL the major DNA adduct involved deoxyguanosine. DNA strand breaks, detected by FADU, were induced at comparable levels by anti- and syn-BaPDE (0.1-0.4 micrograms/ml), and persisted after 20 h of post-treatment incubation. Only in the case of syn-BaPDE did the percentage of double-stranded DNA tend to increase with time after the treatment.

Adult↗

Deoxynucleotide pools and DNA synthesis in resting and PHA-stimulated human lymphocytes treated with mutagens.

In resting and PHA-stimulated PBL treated with uv light or MMS we measured the sizes of the dTTP and dATP pools and the variation of ATP content taken as an indicator of cytotoxicity. The effects on DNA synthesis were examined by measuring DNA repair (unscheduled DNA synthesis) in resting PBL and the inhibition of DNA replication in stimulated PBL. While both treatments affected DNA synthesis, only MMS perturbed dNTP pools and decreased the intracellular concentration of ATP. All the effects were more evident in cycling than in resting lymphocytes.

Adenosine Triphosphate↗

Detection by fluorescence analysis of DNA unwinding and unscheduled DNA synthesis, of DNA damage and repair induced in vitro by direct-acting mutagens on human lymphocytes.

The sensitivity and reliability of UDS and FADU in detecting mutagenic effects were compared by measuring DNA damage and repair in PBL treated in vitro with UV light, MMS and BPDE. The results indicate that FADU is more sensitive than UDS, as it is able to detect DNA damage at doses 3-4-fold lower. We also determined the DNA damage and repair induced by the above agents on lymphocyte samples from different donors by FADU and UDS, confirming that the DNA repair process in humans is characterized by interindividually variable efficiency.

Benzopyrenes↗

EGF in breast cyst fluid: relationships with intracystic androgens, estradiol and progesterone.

The relationship between intracystic levels of epidermal growth factor (EGF) and those of dehydroepiandrosterone sulphate (DHEA-S), delta-4-androstenedione (delta-4-A), 17-beta-estradiol (17-beta-E) and progesterone (PROG) have been studied in 77 breast cyst fluid (BCF) samples. EGF and all tested hormones appeared to be inversely correlated with the intracystic Na+/K+ ratio (p less than 0.001). Consequently, when the BCFs were subdivided according to the Na+/K+ ratio, significantly higher levels of EGF, DHEA-S, delta-4-A, 17-beta-E and PROG were found in Na+/K+ less than 3 BCFs compared with Na+/K+ greater than 3 BCFs (p less than 0.001 in all cases). Strong direct relationships were found among all steroid hormones when they were correlated to one another (p less than 0.001). Intracystic EGF concentration was directly and significantly correlated with each tested hormone (p less than 0.001). However, the relationship between EGF and steroid hormones appeared to be different in the 2 BCF types (Na+/K+ less than 3 or greater than 3).

Adult↗

Effects of intracoronary gallopamil on coronary hemodynamics and myocardial oxygen consumption in humans.

The response of coronary hemodynamics to the intracoronary (i.c.) bolus administration of gallopamil, 1.5 and 3.0 micrograms/kg, was evaluated in 14 patients with normal coronary arteries. Gallopamil, 3.0 micrograms/kg, induced a small and transient decrease in systolic and mean arterial pressure and a small increase in the preejection period. Coronary sinus blood flow increased significantly at 30 s (p less than 0.01) and returned to baseline 10 min after gallopamil administration. Coronary vascular resistance was still reduced at 10 min and returned to baseline at 15 min. Myocardial O2 consumption and extraction decreased significantly (p less than 0.01) at 30 s. While myocardial O2 consumption returned to baseline 15 min after gallopamil administration, myocardial O2 extraction was still significantly reduced at this time. Milder and more transient changes were observed after i.c. administration of the lower dose (1.5 micrograms/kg), and no significant changes were found after i.c. administration of saline. These data show that i.c. gallopamil, in patients with normal coronary arteries, induces direct, transient, and dose-related peripheral coronary vasodilation. The reduction of myocardial O2 consumption and extraction suggests a direct negative inotropic and metabolic effect of gallopamil.

Adult↗

Sensitivity of cultured lymphocytes from patients with nevoid basal cell carcinoma syndrome to ultraviolet light and phytohemagglutinin stimulation.

DNA repair and replication after in vitro UV irradiation were determined in cultured peripheral blood lymphocytes from 6 patients with nevoid basal cell carcinoma syndrome (NBCCS) and from a group of control donors. DNA repair synthesis (UDS) was measured in unstimulated lymphocytes by incubation with 3H-TdR in the presence of hydroxyurea for 3 and 6 h after UV irradiation (6-48 J/m2). DNA replication was measured in PHA-stimulated lymphocytes, UV-irradiated or mock-irradiated, by incubation with 3H-TdR for 24 h. The effect of the mitogen was followed during 5 days after stimulation by determining the incorporation of 3H-TdR, the increase of cell number, and the mitotic index. NBCCS and control lymphocytes showed equal sensitivity to UV light in terms of UDS and reduced response to PHA. On the contrary, the mitotic index and the number of cells in stimulated cultures were significantly lower in the affected subjects. These data suggest an altered progression along the cell cycle, which could be characteristic of stimulated NBCCS lymphocytes.

Adolescent↗

Effects of in vivo exposure to antineoplastic drugs on DNA repair and replication in human lymphocytes.

In peripheral blood lymphocytes of 12 nurses and 3 patients exposed to antineoplastic drugs we determined the ability to repair DNA after UV irradiation and DNA replicative synthesis after stimulation by PHA. In nurses the levels of unscheduled DNA synthesis and DNA replication were not different than in a control group, whereas in patients significant changes were observed during and after chemotherapy in the level of both types of DNA synthesis.

Adult↗

Endoscopic Nd:YAG laser therapy of malignant esophageal obstruction on an outpatient basis.

Between May 1985 and December 1988, 41 patients were treated palliatively with endoscopic neodymium:yttrium-aluminum-garnet laser therapy for obstruction of the esophagus by malignant disease. All were considered incurable, because they presented with distant metastases, severe systemic disease, extensive local disease or recurrent disease. Thirty-nine percent were managed as outpatients; the remainder required admission to hospital. Sixty-three percent of the outpatients had adenocarcinoma, and 31% had squamous cell carcinoma; over 90% of the tumours were less than 8 cm long, and 63% were in the distal one-third of the esophagus or the cardia. Forty-four percent of the inpatients had adenocarcinoma, and 44% had squamous cell carcinoma; in this group, over 90% of the tumours were less than 8 cm long, and 56% were in the distal one-third of the esophagus or the cardia. The mean number of sessions and laser energy administered were 2.6 and 4949 J for outpatients and 2.7 and 4974 J for inpatients. Palliation of dysphagia was good to excellent in all outpatients but was not as good for the inpatient group, in which one major complication occurred. The mean length of survival for outpatients and inpatients was 6.3 months (range from 1 to 16 months) and 3.9 months (range from 1 to 18 months) respectively.

Adult↗