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Biomedical subjects

M Esposito

Publications and source records attributed to M Esposito.

At least 109 records · Page 6Linked to original sources
PubMed1997

Spectral analysis of demodulated ultrasound returns: detection of scatterer periodicity and application to tissue classification.

Ultrasound returns from tissue display variations in amplitude on several spatial scales. Although large-scale variations result from factors such as attenuation, variations on smaller scales are caused by tissue characteristics such as variations in scatterer spacing and reflectance. These small scale variations cause a corresponding variation in the amplitude of the ultrasound return. A simple and direct method for detecting and quantifying periodicity in these variations in the presence of attenuation is described. The radiofrequency ultrasound return is first demodulated by full-wave rectification. The normalized power spectrum of the demodulated return then yields an index that we call the relative Fourier energy. Both computer simulations and in vitro experiments were performed in order to study how relative Fourier energy performed in discriminating between periodic and random scatterer distributions. Computer simulations demonstrated significant differences between the returns from periodic and random scatterer distributions. Ultrasound returns from aortic tissue yielded a relative Fourier energy index that was significantly different between normal vs. atherosclerotic tissue (normal: 0.868 +/- 0.076, mean +/- s.d., fibrofatty plaque: 0.705 +/- 0.109, p < 0.01 vs. normal, calcified plaque: 0.753 +/- 0.078, p < 0.01 vs. normal). In contrast, no difference was found in comparisons of overall reflectance.

Aorta, Thoracic↗
PubMed1997

[Effects of adjuvant hyaluronidase in tumors refractory to chemotherapy. Review of the literature and pharmacokinetics of cisplatin after regional administration in animals and humans].

Several clinical studies have recently suggested that topical or systemic adjuvant hyaluronidase may increase the therapeutic index of anticancer drugs. In cases of disease progression, further objective responses have been observed after the association of hyaluronidase to the previously employed drugs. Some evidences suggest that hyaluronidase improves local diffusion as well as tissue and tumor uptake of the associated drugs. Hence, plasma and tissue concentrations of platinum following administration of cisplatin alone and associated with hyaluronidase have been investigated in 20 rats after intraperitoneal injection and in 10 patients with colorectal liver metastases and local progression of the disease after regional and systemic chemotherapy with intraarterial cisplatin and intravenous 5-fluorouracil. Three out of six refractory patients treated with hepatic intraarterial cisplatin + hyaluronidase showed one minor response and two stable diseases, respectively, without any apparent increase of treatment related toxicity. In turn, adjuvant hyaluronidase increased both the extent distribution and lasting time of cisplatin in the body and reduced plasma levels of total and free platinum originating from cisplatin, without any modification of either unbound fraction of platinum or total body clearance. Hence, adjuvant hyaluronidase seems to increase tissue extraction of cisplatin and, particularly, liver extraction after intraarterial administration in man. These results encourage further studies aimed to determine the clinical role of adjuvant hyaluronidase in patients refractory to regional chemotherapy.

Animals↗
PubMed1997

Treatment of localized gingival recessions using a bioresorbable membrane: a case report.

A patient with a localized gingival recession suffering from esthetic and hypersensitivity problems was selected for treatment with the guided tissue regeneration procedure. The use of a bioresorbable membrane (Guidor) made reentry surgery for membrane removal unnecessary. A complete root coverage was obtained, and 6 mm of clinical attachment gain was recorded after 6 months. The guided tissue regeneration procedure may represent an effective alternative to traditional mucogingival therapy for the treatment of recessions and permit the management of severe bone destruction with minimal soft tissue retraction. Furthermore, the guided tissue regeneration technique is likely to result in a greater amount of new connective attachment formation, although clinical relevance must still be confirmed by long-term trials.

Adult↗
PubMed1996

Differences between normal and autoimmune T cell responses to autologous erythrocytes and haemoglobin: impairment of haptoglobin-mediated inhibition in NZB spleen cells.

Helper T cells are required for development of the autoantibody responses to native mouse erythrocytes (MRBC) that spontaneously develop in NZB mice. However, the stimulus for these Th is not known. Therefore, we compared the abilities of splenic T cells from actively autoimmune old NZB mice and preautoimmune, young NZB mice with those of T cells from nonautoimmune strains of mice to respond to autologous erythrocytes. We found that autologous RBC ghosts, washed free of haemoglobin, induced low, but statistically significant, proliferative responses in T cells from old NZB mice but not in T cells from young NZB or from normal young and old BALB/c mice. In addition, autologous RBC lysates induced proliferative responses detectable by 3H-thymidine uptake in T cells from nonautoimmune as well as autoimmune mice. CD4+ T cells accounted for most of the observed RBC lysate-induced proliferation, with virtually no response made by CD8+ T cells or B cells. T cells from actively autoimmune NZB mice were not more active in their responses to RBC lysates than T cells from normal strains of mice in terms of their level of proliferation, kinetics, or dose response. Haemoglobin was the major stimulus in the autologous RBC lysates and a similar stimulation was seen with lysates and haemoglobins from horse, human, and mouse sources. Haptoglobin, a haemoglobin-binding serum protein, inhibited T cell responses to haemoglobin and haemoglobin-containing RBC lysates but did not have the same effect on these responses in T cells from either young or old NZB mice. Therefore, either or both of the RBC stimuli from autologous RBC might account for the helper T cell activity in autoimmune NZB mice. T cells in normal mice do not respond either to RBC lysates in the presence of haptoglobin or to RBC ghosts.

Animals↗
PubMed1996

Effect of the antiarrhythmic drug procainamide on the toxicity and antitumor activity of cis-diamminedichloroplatinum(II).

The class I antiarrhythmic drug procainamide (Pd) was tested on BDF1 mice for its chemoprotective activity against cis-diamminedichloroplatinum(II) (DDP) toxicity. Pd at the dose of 50 mg/kg protected mice against otherwise lethal doses of DDP (survivors at Day 14 after 25 mg/kg DDP or 25 mg/kg DDP-Pd treatment: 0% vs 100%) and greatly reduced the weight loss induced by DDP. Moreover, the increased plasma urea nitrogen levels caused by a single ip administration of DDP in water (8 or 16 mg/kg) as well as the tubular degenerative changes detected by light microscopy were prevented by Pd. Pd had no effect on the sensitivity of P388 leukemic cells to DDP in vitro, but the administration of DDP (16 mg/kg) and Pd (50 mg/kg) to BDF1 mice bearing P388 leukemic cells produced a significant increase in survivals compared to mice receiving ip DDP alone diluted in 0.9% NaCl solution. The increased efficacy of this combination therapy in P388 leukemic mice compared to a single DDP treatment at the same dose was observed both when the drugs were administered ip simultaneously (p = 0.042) and when DDP and Pd were given ip and iv, respectively (p = 0.018). Since procaine, which differs from Pd merely in the replacement of the amide by the ester linkage, has also been reported to significantly enhance DDP efficacy (M. Esposito et al., 1990, J. Natl. Cancer Inst. 82, 677-684.), a comparison of their effects in tumored mice exposed to DDP has been made. Although both drug combinations were superior to that of DDP alone, in terms of both survival time and numbers of cures, Pd treatment seems to offer better protection against DDP-induced lethality than did procaine.

Animals↗
PubMed1996

Isolated lung perfusion with platinum in the treatment of pulmonary metastases from soft tissue sarcomas.

A multimodality approach including operation and isolated lung perfusion with platinum was used in six patients with lung metastases from soft tissue sarcomas. Staged thoracotomies were used in two patients with bilateral lesions. The inclusion criteria generally applied for surgical excision were adopted in this study. The pulmonary artery and a portion of the left atrium were isolated from systemic circulation and cannulated. The cannulas were then connected to a perfusion circuit and normothermic isolated lung perfusion was done for 60 minutes. The lung was then flushed and metastasectomy was done. Serial blood (systemic and pulmonary), tissue (normal lung and tumor), and urine samples were obtained for platinum content measurement by flameless atomic absorption spectroscopy. Lung damage was assessed by light and electron microscopy examination and by serial respiratory tests. Isolated lung perfusion was accomplished in all patients without any death, operative complication, or systemic toxicity. After operation, interstitial and alveolar edema developed in two patients (48 hours after treatment), necessitating respiratory support in one case. Total platinum concentrations in pulmonary plasma were about 43 times greater than those in systemic plasma. No differences in platinum concentrations between normal lung and metastatic tissue were found. Thus the proposed isolated lung perfusion technique is feasible and safe enough to be offered as a valid model to study combined chemosurgical approaches in the treatment of lung metastases.

Adult↗
PubMed1996

Cisplatin combined with the new cisplatin-procaine complex DPR: in vitro and in vivo studies.

The administration of combinations of platinum compounds is considered as a useful alternative therapeutic strategy to avoid the complications of toxic events during cancer chemotherapy in order to obtain a therapeutic advantage. On the basis of previous in vitro and in vivo findings, suggesting an antitumour activity of the new cisplatin-derived compound cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR), we investigated the effectiveness of the combination of cisplatin (DDP) and DPR in vitro on murine leukaemic cells, which were either sensitive (P388) or resistant (L1210/DDP) to DDP, and on the murine M5076 reticulum cell sarcoma, and in vivo in BDF1 female mice transplanted with P388 leukaemic cells or cisplatin-resistant L1210/DDP leukaemic cells. The contemporaneous exposure in vitro to both platinum compounds gave a significantly higher cell growth inhibition than that expected on the basis of dose-response curves for single agents in all tumour models tested. In vivo, the combinations of DDP plus DPR elicited significant enhancement over the activity of the drugs alone both in the ascitic and solid P388 models. The combined treatment of 10 mg/kg DDP and 14 mg/kg DPR yielded 62.5% tumour-free mice compared with 6.2% with 10 mg/kg DDP alone, the best single agent. It is noteworthy that the combined application of DDP and DPR was also very effective in the solid cisplatin-resistant L1210/DDP model, inducing a significant reduction in the volume of tumour. A therapeutic advantage was achieved with combination treatments that had no effect on platinum-mediated body weight loss and were generally well tolerated by the mice. At equitoxic concentrations of DPR and carboplatin, the treatment with DDP plus DPR proved to have a higher efficacy against this tumour model compared to that observed after the combined treatment with DDP and carboplatin. In summary, the combination of DDP and DPR showed a therapeutic advantage over single drug treatment and has demonstrated promise at the preclinical level in its ability to circumvent acquired resistance to DDP both in vitro and in vivo.

Animals↗
PubMed1996

Comparison of the toxicities of cisplatin and a new cisplatin-procaine complex to rat renal cortical slices.

1. Procaine has previously been shown to diminish the nephrotoxicity of cisplatin and the nephrotoxic effects of cisplatin and a new cisplatin complex (cis-diamminechloro-[2-(diethylamino) ethyl-4-aminobenzoate, N4]-chlorideplatinum (II) monohydrochloride monohydrate; DPR), that contains procaine hydrochloride were compared with rat renal cortical slices. 2. Cisplatin at 1 mM caused toxicity to the slices, as shown by an increase in the leakage of aspartate aminotransferase and lactate dehydrogenase from the slices into the incubation medium and a decrease in the reduction of a tetrazolium dye (MTT assay). Addition of procaine (1 mM) protected against cisplatin-induced toxicity. DPR either at 1 mM or at 4 mM had no effect either on the enzyme leakage or MTT reduction by the renal slices, but DPR at 10 mM produced a similar magnitude of enzyme leakage to cisplatin (1 mM). 3. DPR lowered the concentration of ATP and glutathione (GSH) in the slices but was less potent than cisplatin. Thiobarbituric acid reactive substances, indicators of lipid peroxidation, released into the medium were increased by the highest concentration of DPR (10 mM), which suggests that DPR has the potential to cause oxidative stress. 4. The results suggest that DPR was far less toxic than either cisplatin alone or a mixture of cisplatin and procaine.

Adenosine Triphosphate↗
PubMed1996

Multicentric metachronous pulmonary and intravagal paraganglioma: a case report with immunohistochemical findings.

An unprecedented presentation of multicentric paraganglioma in a 48-year-old man is described. One of the paragangliomas, originally diagnosed as a carcinoid tumor, presented as a lung mass and was removed. Four years later, an intravagal paraganglioma was discovered. The lung and intravagal tumors had identical morphologic and immunoreactive characteristics. Both tumors consisted of chief cells (type 1) and sustentacular cells (type 2). The chief cells were immunoreactive with neuroendocrine markers (synaptophysin and chromogranin), but nonreactive with epithelial markers (CAM 5.2, high- and low-molecular-weight keratins, epithelial membrane antigen, and carcinoembryonic antigen). The sustentacular cells were positive for S100 protein. Although pulmonary carcinoids may mimic paragangliomas and occasionally contain sustentacular cells, the diagnosis was rejected because the tumor cells did not demonstrate reactivity with epithelial markers.

Biomarkers, Tumor↗
PubMed1995

Cytotoxicity and cellular accumulation of a new cis-diammineplatinum (II) complex containing procaine in murine L1210 cells sensitive and resistant to cis-diamminedichloroplatinum (II).

The emergence of drug resistance during tumor chemotherapy is one of the main problems associated with cancer treatment, particularly with cisplatin (cis-DDP). In the hope of overcoming this problem, various cis-DDP-derived compounds have been synthesized, and their pharmacological activity was compared with that of cis-DDP. In this paper we report on studies on the cytotoxic activity induced by cis-diamminechloro-[2-(diethylamino)ethyl-4-aminobenzoate, N4]- chlorideplatinum(II) monohydrochloride monohydrate (DPR), a new complex of platinum containing procaine. All experiments were carried out on murine leukemic cells, which were either sensitive (L1210) or resistant (L1210/DDP) to cis-DDP. A tetrazolium dye (MTT) assay conducted 5 days after a 2-h exposure of cells to both drugs was utilized to determine the resistance factor (RF) of L1210/DDP cells as compared with the sensitive wild-type cells. Drug accumulation and efflux, together with the amount of platinum bound to DNA, were also investigated. The activity of DPR on sensitive cells was not significantly different from that of cis-DDP. Conversely, DPR was 4.3 times more effective than cis-DDP on resistant cells. A decreased drug accumulation is one of the mechanisms of resistance to cis-DDP of L1210/DDP cells. However, DPR accumulation was not significantly different in sensitive and resistant L1210 cells. Under culture conditions that yielded similar intracellular platinum concentrations, treatment with DPR produced significantly greater DNA platination than did treatment with cis-DDP in both cell lines. No difference in efflux was observed between L1210 and L1210/DDP cells exposed to either cis-DDP or DPR. Our results show that in parental cells, DPR is as potent as cis-DDP on a molar basis, and it is also minimally cross-resistant with cis-DDP in L1210/DDP cells. A direct implication of our results is that DPR could be useful in those human tumors showing a mechanism of resistance similar to that of L1210/DDP cells.

Animals↗
PubMed1994

High doses of intrapleural cisplatin in a case of malignant pleural mesothelioma. Clinical observations and pharmacokinetic analyses.

BACKGROUND: The authors report a feasibility study of intrapleural cisplatin in a patient with inoperable malignant pleural mesothelioma. METHODS: Total and filterable platinum in pleural effusion and in plasma were monitored for two intrapleural courses of 120 mg/m2 cisplatin, and a weekly schedule was adopted. Platinum concentrations in pleural effusion, plasma, and urine were determined by flameless atomic absorption spectroscopy. RESULTS: A lower peak of filterable platinum in plasma, a decrease in systemic filterable platinum exposure (AUC [area under the concentration-time curve]), and a greater pleural exposure to filterable platinum were observed after Course 2 compared with Course 1. After the second cycle of intrapleural treatment, the systemic AUC for filterable platinum was reduced by 40%. CONCLUSIONS: The authors' findings may have some implications for the clinical use of intrapleural chemotherapy with high doses of cisplatin. Both infusions of cisplatin were generally well tolerated by the patient and were associated with the local pharmacologic advantage of sustained exposure to cisplatin of the pleural cavity. No sign of myelosuppression, neuropathy, or ototoxicity was observed, and acute toxicity consisted of mild nausea, vomiting, and prolonged anorexia. A transient presence of granular casts was the only observed nephrotoxic effect of cisplatin. Excellent local control of the disease with absence of recurrence of the effusion was observed.

Absorption↗
PubMed1994

Pelvic perfusion in the adjuvant therapy of locally advanced rectal cancer. Feasibility trial and initial clinical experience.

PURPOSE: The increased risk of pelvic recurrence in patients with locally advanced rectal cancer seems to justify a more aggressive regional therapeutic approach. In this attempt a feasibility study has been recently activated on hyperthermochemotherapeutic pelvic wash in patients with resectable, locally advanced, cancer of the distal rectum. METHODS: Two alternative methods of hyperthermochemotherapeutic pelvic wash have been used in sequence. In the first method 3000 ml of warm (45 degrees C) saline solution containing 30 mg of mitomycin C were injected into the pelvis both intraoperatively and in the immediate postoperative period. In the second method a 60-minute perfusion of the pelvic space with 2000 ml of heated (45 degrees C) saline solution with 40 mg of mitomycin C was provided intraoperatively using an extracorporeal circuit. RESULTS: Four patients submitted to abdominoperineal amputation with pelvic lymph node dissection have been treated following one of the two methods. No complications related to the treatment occurred. Either the first or the second hyperthermochemotherapeutic pelvic wash method showed a high regional pharmacokinetic advantage with a perfusate/blood "AUCs" ratio of 576 and 374, respectively. CONCLUSIONS: The potential role of hyperthermochemotherapeutic pelvic wash as an additional regional treatment in locally advanced rectal cancer and the differences between the two methods, in our limited experience, are discussed.

Aged↗
PubMed1994

Lipids of human gastric mucosa: effect of Helicobacter pylori infection and nonalcoholic cirrhosis.

BACKGROUND/AIMS: Gastric mucosa phospholipids play an important protective role against exogenous and endogenous toxic agents. Recently, we described a significant alteration of phospholipid profile in patients with chronic atrophic gastritis without Helicobacter pylori infection. The aim of the present study was to assess the phospholipid composition of gastric biopsy specimens in 41 subjects with chronic gastritis in relation to H. pylori infection (no. 26) and nonalcoholic cirrhosis (no. 18). METHODS: Phospholipids were extracted from homogenate mucosal samples using Folch's method, purified, and separated by thin-layer chromatography, while bound fatty acids were analyzed by gas liquid chromatography. RESULTS: The amounts of five gastric phospholipid classes, their rank order, and percent distribution of the principal ones (phosphatidylcholine [PC] 58%, phosphatidylethanolamine [PE] 26%, and phosphatidylinositol 11% vs. values of 49, 19, and 14, respectively, in the earlier study) were confirmed in chronic gastritis without H. pylori infection. H. pylori infection induced a dramatic reduction (about 30%) in the absolute amount of total phospholipids (24.2 micrograms/mg protein versus 35.1 of the H. pylori-negative group; P < 0.01), PC and PE being the most affected (-36% and -26%, respectively), while bound fatty acids remained unchanged. There was no difference in cirrhotic vs. noncirrhotic subjects. CONCLUSIONS: (1) The development of gastritis is characterized by an alteration of the lipid mucosal pattern that can change with the different etiologies, the most dramatic variations being observed in the presence of H. pylori infection; and (2) cirrhosis does not affect further the alteration in the phospholipid profile of the antral mucosa caused by chronic gastritis.

Adult↗
PubMed1994

Prescribing endodontic retreatment: towards a theory of dentist behaviour.

The large variations observed in dentists' management of periapical lesions in endodontically treated teeth suggest that disease concepts used in clinical practice should be investigated. In the present study it was hypothesized that dentists regard various periapical conditions as different stages on a health continuum. Variations could then be regarded as the result of the individuals selection of differing cut-off points for prescribing retreatment. The hypothesized decision-making model was tested using dental students in Amsterdam (Holland), Gothenburg (Sweden) and Pavia (Italy). The students were shown six simulated cases among which the quality of root filling seal and presence of post and crown were systematically varied. For each case, management of five periapical conditions was assessed. Five options were offered: no therapy, wait-and-see, nonsurgical retreatment, surgical retreatment, and extraction. For each examiner and case a 'retreatment preference score (RPS)' was established. The investigation showed large interindividual variations in RPS. A statistically significant higher mean RPS was seen among students in Pavia compared with students in Amsterdam and Gothenburg. Among all observers and cases it was found that if retreatment was proposed for a certain size of lesion, retreatment was subsequently selected for all larger lesions. The experiment gave evidence in support of the proposed hypothesis. The data also suggest that the choice of retreatment criterion is affected by values, costs of retreatment and technical quality of the original treatment.

Adult↗
PubMed1994

[Hyperthermia in adjuvant therapy of locally advanced carcinoma of the rectum. Study protocol and initial clinical experience].

Since January 1992 a feasibility study was set up to establish the possible role of pelvic hyperthermochemotherapy for the local control of rectal cancer. Patients with resectable rectal cancer (clinical stage III-IV) are eligible for the study. Only patients submitted to abdominoperineal resection with or without extended pelvic linfoadenectomy (PLND) and/or resection of contiguous organs are included in the initial pilot phase of the study. Until now, two patients with stage III rectal cancer submitted to abdominoperineal resection and PLND have been treated. A single (40 mg) push of MMC was injected in the circuit with median local temperature of 46.0 +/- 0.3 and 45.9 +/- 0.5 degrees C and the pelvis was perfused for 60 min. There were no local or systemic complications. The ratio between the pelvis and plasma AUCs showed a high local pharmacokinetic advantage. The treatment can contribute to complete the standard protocols of adjuvant therapy. Since the simple decrease of local recurrence could represent an important clinical aim, this experience, even initial, supports us to continue the study.

Aged↗
PubMed1993

In situ lung perfusion with cisplatin. An experimental study.

BACKGROUND: This research work was planned to evaluate the soundness of in situ lung perfusion as a regional administration modality of chemotherapeutic agents. METHODS: Sixteen pigs were randomly divided into four groups and received cisplatin (2.5 mg/kg) through the pulmonary artery using one of the following techniques: stop-flow (Group 1); stop-flow/out-flow occlusion (Group 2); lung perfusion (Group 3); or lung perfusion with 5 mg/kg of infused drug (Group 4). Serial blood (carotid, pulmonary artery and vein) and tissue samples (lung and mediastinal node), were taken before, at completion of, and 5, 10, 15, 30, 60, 120, 180 and 240 minutes after cisplatin infusion for blood gas and platinum content measurement. Blood circulation was restored to the treated organ (for 60 minutes). The animals were killed, and specimens from lung, thyroid, esophagus, heart, liver, spleen, adrenal glands, kidney, bone marrow, stomach, ileum, colon, psoas muscle, and skin were obtained. Platinum concentrations in plasma, plasma ultrafiltrate (free platinum) urine, and tissues were determined by flameless atomic absorption spectroscopy. Lung damage was evaluated by light and electron microscopic examination. RESULTS: Greater systemic plasma, lower pulmonary plasma, and tissue platinum levels were detected when cisplatin was given using the stop-flow technique with respect to the other administration modalities. No significant difference in regional and systemic platinum exposure was found between Groups 2 and 3. However, lung perfusion resulted in higher mediastinal node and lower bone marrow platinum values. Morphologic alterations and impairment of gas exchanges in the treated lung were not dependent on the applied infusion technique. CONCLUSION: This study provides the pharmacokinetic rationale for the application of lung perfusion to patients with pulmonary metastases.

Animals↗
PubMed1993

Radiological evaluation of marginal bone loss at tooth surfaces facing single Brånemark implants.

A radiologic evaluation of marginal bone loss around single implants ad modum Brånemark and their adjacent teeth was performed: 58 adults with 71 fixtures were followed up to 3 years after crown installation. The following factors were considered: age, cause of tooth loss, vertical relation between fixture and teeth, distance between adjacent teeth, distance between fixture and natural tooth, jaw region. Specified distance were measured as well as marginal bone levels around fixtures and tooth surfaces in magnified standardized intraoral radiographs. The results show a loss of marginal bone support at tooth surfaces adjacent to inserted implants during the interval between preoperative examination and crown installation that exceeds the loss during subsequent years. The largest bone loss was observed when implants were placed next to lateral upper incisors. A strong correlation was found between bone loss at adjacent teeth and the horizontal distance fixture-tooth. With decreasing distance the bone loss increased, especially in the upper incisor region. At present it seems difficult to predict which individual or individual condition may have a higher risk for bone loss, due to large intra- and interindividual variation.

Adult↗