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Biomedical subjects

F Merlo

Publications and source records attributed to F Merlo.

At least 55 records · Page 3Linked to original sources
PubMed1993

Para-aminobenzoic acid suppression of cis-diamminedichloroplatinum(II) nephrotoxicity.

Concurrent administration of para-aminobenzoic acid (PABA) reduced the toxicity of cis-diamminedichloroplatinum(II) (DDP) in a dose-related manner in rats. When administered i.p. simultaneously with 7.5 mg/kg DDP, PABA (100 mg/kg) significantly reduced plasma urea nitrogen (PUN) and plasma creatinine levels as well as DDP-induced weight loss. Increasing doses of PABA (25, 50 and 100 mg/kg) correlated with progressively better parameters of renal activity and body wt and with lower levels of platinum in plasma and tissues in rats killed 5 days after drug administration. The formation of cisplatin-DNA adducts, the total platinum levels in kidney and testes and the DDP-induced tumor response were investigated in the presence and absence of PABA exposure in mice bearing P388 leukemic cells. Renal and testicular DNA-adducts in mice treated i.p. with 16 mg/kg DDP in normal saline were higher than those observed in mice receiving the same protocol and added PABA. Analysis of tissue platinum content demonstrated significantly lower platinum levels both in kidneys (P < 0.05) and testes (P < 0.01) of mice receiving DDP and PABA in normal saline compared to those receiving only DDP in normal saline. PABA did not affect the in vivo and in vitro antitumor activity of DDP against P388 leukemia, and there was no significant PABA-induced modification in the concentration of platinum both in the tumor cells and in DNA samples isolated from P388 leukemic cells of DDP-treated mice. We conclude that PABA may be a promising compound for reducing DDP-toxic side effects, including nephrotoxicity, without compromising its antitumor activity.

4-Aminobenzoic Acid↗
PubMed1993

[Separation and identifying features of the cardiac aglycones and glycosides of Nerium oleander L. flowers by thin-layer chromatography].

The present work was aimed at extracting some cardiotonic glycosides from Nerium oleander L. (N.o.L.) flowers, free from phytosterols and their esters and at resolving themselves by thick- and thin-layer chromatography. This work may contribute to the scientific recognition of N.o.L. drugs in the field of forensic medicine. MATERIALS AND METHODS. Apparatus. Kieselgel F254 thin-layer (250 mu) and Kieselgel thick-layer (2 mm) glass plates were used. MATERIALS. Chromatographic solvents were used; detectors were p-toluene sulphonic acid (PTSA) and antimony trichloride (SbCl3). STANDARDS. The following standards were used: gitoxigenin, oleandrin, digitoxin, and stigmasterol. Standard solutions were prepared at a M-3 concentration. The solvent system is described in Table I. EXTRACT. The extract was prepared using a mixture of solvents (hexane-diethylether-acetic acis, 50:50:1 v/v). With this mixture we noted that, in thin-layer chromatography, the used standards remained at the origin, while phytosterols and their esters migrated. White flowers of N.o.L. were air dried in the shade at room temperature, powered, and macerated in hexane-diethylether acetic acid for 24 hours. After removal of the phytosterols the remacerating powder was further percolated using a chloroform-methanol mixture (1:1.7 v/v) in order to extract the aglycone and the cardiac glycosides. As the medium's thin-layer chromatogram showed the absence of corresponding spots to test samples, the chloroform-methanol media were combined and evaporated under vacuum. The residue was redissolved in the chloroform-methanol mixture. The obtained extract concentration consisted of 5 grammes of dried flowers in 1 milliliter of solution, called extract E (Fig. 1). RESULTS. The results are reported in Figures 2 and 4 and in Table II (see text for explanation of symbols). Extract E (Fig. 2) and the F1, F2, and F3 concentrated fractions were examined by thin-layer chromatography (Fig. 1 and 3). Only the F3 fraction revealed compounds with the same chromatographic path and colours (detected by PTSA and SbCL3) as the reference standards gitoxigenin, oleandrin, and digitoxin. This finding was confirmed by using five different solvent-systems (Fig. 4). DISCUSSION AND CONCLUSION. The present study shows that the cardiac steroids and other constituents of Nerium oleander's flowers are separated in three fractions by thick-layer chromatography free from phytosterols and their esters. This result may have useful implications in the fields of analytical toxicology and forensic medicine and potential application in clinical practice given that cytotoxic and antileukemic activities of the extracts from plants containing cardiac glucosides have been reported.

Cardiac Glycosides↗
PubMed1992

Protective effect on cisplatin hematotoxicity by procaine hydrochloride.

The ability of procaine hydrochloride (P.HCl) to modulate the effects of cisplatin (DDP) on pluripotent (CFU-S) and committed (CFU-GM) murine hemopoietic stem cells was investigated. DBA/2NCrlBRF1 mice received DDP alone (10 and 16 mg/kg body wt. single i.p. injection) or in combination with P.HCl (40 mg/kg body wt. single i.p. injection). Hemopoietic progenitor cell (HPC) time survival curves were determined up to 14 days following treatment. The simultaneous administration of the lower DDP dose together with P.HCl greatly reduced the hemotoxicity of the antitumoral drug, while this protection was not significant with the higher DDP dose. These results support a role for P.HCl in protecting against DDP hematological toxicity.

Animals↗
PubMed1992

Prediction of survival by thymidine labelling index in patients with resistant ovarian carcinoma.

The relationship between tumour proliferative activity, evaluated by thymidine labelling index (TLI), clinicopathological variables and clinical outcome, was analysed in a series of 64 chemotherapy-resistant, ovarian cancer patients. The median TLI of 4.6% (range 0.01-45.7) was used as the cut-off to discriminate rapidly from slowly proliferating tumours. Univariate analyses showed a significant advantage in survival for patients with TLI less than or equal to 4.6 (P = 0.0004), ECOG performance status less than or equal to 1 (P = 0.0001) and residual disease after primary surgery less than or equal to 2 cm (P = 0.019). Multivariate analysis demonstrated that performance status was the only independent prognostic variable, although TLI was the last covariate removed from the Cox's regression model.

Carcinoma↗
PubMed1992

Bone scan features in spontaneous knee pain.

In 21 patients with "spontaneous" knee pain, 99mTc-MDP bone scan was found to be more sensitive than clinical and radiographic examination in detecting alterations of the joint components. These alterations were shown by increased radionuclide uptake in the compartments where pain was present, which was most commonly the medial femorotibial compartment, although the femoropatellar compartment was also frequently affected. The authors conclude that bone scan should be the first imaging study performed on the knee in order to establish if further tests are necessary.

Adult↗
PubMed1991

Univariate and multivariate analyses of the relationship between adenocarcinoma and solitary and multiple adenomas in colorectal adenoma patients.

In 584 consecutive patients with no previous history of cancer or polypectomy, 769 adenomas were excised endoscopically and classified retrospectively according to the following parameters: macroscopic growth pattern, size, histological type, grade of dysplasia, anatomical site, presence of adenocarcinoma (ADK), number of adenomas and sex and age of the patient. A multivariate logistic analysis confirmed that size and histological type are the 2 most important predictors of ADK, both in solitary and in multiple adenomas. Adenomas located in the sigmoid portion and in the rectum have an increased probability of ADK, independent of size and histology. Multiple polyps, when compared to solitary polyps, were more frequent in males (p less than 0.01) and were more often larger than 2 cm. Significant similarities in histology, morphology and degree of dysplasia were observed among multiple adenomas from the same patient.

Adenocarcinoma↗
PubMed1991

Liver and tumor uptake and plasma pharmacokinetic of arterial cisplatin administered with and without starch microspheres in patients with liver metastases.

Arterial chemoembolization of liver tumors should improve regional treatment by reducing native blood flow of the whole organ and redistributing residual flow toward hypovascular masses. Plasma cisplatin pharmacokinetics and its tissue uptake and relative tumor and liver vascularity were studied during surgical placement of arterial catheters in four patients and in four patients with colorectal metastases given intraoperative arterial cisplatin (DDP, 25 mg/m2), with an without coadministration of 600 mg degradable starch microspheres (DSM). Mean (+/- standard deviation) filterable plasma platinum levels peaked later (2 minutes) and were significantly lower after DDP with DSM (1.23 +/- 0.69 micrograms/ml) than after DDP alone (2.13 +/- 0.43 micrograms/ml, P less than 0.05), with the area under the curve (AUC0-30 min) values of 15.8 +/- 5.5 and 25.1 +/- 3.8 micrograms x min/ml (P less than 0.05), respectively. No differences in urine excretion, total body clearance, or plasma protein binding of platinum were observed. Tissue biopsies were started 15 minutes after DDP administration and completed in all cases within 5 minutes. Tumor platinum concentrations were significantly higher after DDP with DSM (3.03 +/- 1.60 micrograms/g) than after DDP alone (0.67 +/- 0.49 micrograms/ml, P less than 0.05). Liver concentrations and tumor-liver ratios of platinum also were higher, although not significantly, after DDP with DSM. Preoperative vascularization, studied with arterial perfusion scan, influenced individual tissue drug uptake in cases given DDP alone, with the lowest tumor levels in cold masses. Very high and almost superimposable liver and tumor concentrations were measured in those receiving DDP and DSM. The latter phenomenon was irrespective of native vascularization, indicating that DSM administration induced both an increased whole-liver extraction of the drug and a redistribution of blood flow and flow-dependent tissue uptake of platinum.

Chemoembolization, Therapeutic↗
PubMed1991

Prognostic significance of nuclear DNA content in human neuroepithelial tumors.

The relationship between survival and flow cytometric DNA-ploidy and other prognostic factors such as histological subtype, anatomical tumor site, patient sex and age was investigated in 153 patients with intracranial neuroepithelial tumors who underwent surgical treatment. We found a trend toward poorer survival from anaplastic astrocytomas and glioblastomas with respect to low-grade (I and II) astrocytomas (which did not differ significantly); accordingly, patients were grouped into these 3 histologic subgroups. Thirty-seven of the 153 tumors (24.2%) were aneuploid with a median DNA-index (DI) of 1.3 (range: 1.2-2.0). DNA-ploidy correlated with histology, since anaplastic astrocytomas and glioblastomas were significantly (p = 0.041) more frequently aneuploid (around 30%) than low-grade astrocytomas (around 10%). Patients with DNA-aneuploid tumors (i.e., with DI not equal to 1.00) survived for a shorter time (31.4 weeks) than patients with DNA diploid tumors (75.1 weeks) (p less than 0.001). This difference was confirmed by Cox's multivariate analysis. Aneuploid tumors were associated with a poorer survival (p = .0002) when compared with diploid tumors, resulting in a relative risk point estimate (RR) of 2.41, 95% confidence interval (Cl) = 1.55-3.74. Histological subtype was also significantly associated with survival (p less than 0.0001), with RRs of 2.09, 95% Cl = 1.13-3.86 and 3.59, 95% Cl = 1.96-6.59 for anaplastic astrocytomas and glioblastomas, respectively, compared to low-grade astrocytomas. We therefore suggest that the flow cytometric measurement of DNA-ploidy has relevant significance in predicting survival in patients treated for intracranial neuroepithelial tumors.

Age Factors↗
PubMed1991

Flow cytometric DNA index in the prognosis of colorectal cancer.

The authors investigated the relationship between flow cytometric DNA index (DI, defined as the ratio of the DNA content of malignant cells to that of normal cells) and other prognostic factors (grade and stage, anatomical site, age and sex) with the survival of 115 patients with colorectal cancer. Multiple biopsy specimens from 62 patients were taken during colonoscopy before surgery. Additional samples from 53 patients were obtained from paraffin-embedded material. All patients were treated with surgery only. Fresh-frozen material gave higher incidence of DNA aneuploidy than paraffin-embedded material (79% versus 41%). The patients with DNA diploid tumors (DI = 1) had a better overall survival than those with DNA aneuploid tumors (DI = 1). Among DNA aneuploid tumors, those with DI greater than 1.2 (excluding DI = 2) were worse than those with DI = 1.2 (excluding DI = 1) and DI = 2. Cox's regression analysis showed that pathologic stage was more important for prognosis than DNA index, whereas age, sex, histologic grade, and anatomic site were removed from the analysis as not relevant for prognosis. Relative risk of death (RR), in reference to patients with DI = 1 and Stages A + B (RR = 1), were RR = 1.8 for patients with carcinomas with Stage C. RR = 2.7 for patients with carcinomas with DNA near-diploid and DNA tetraploid tumors. RR = 3.5 for those with DI greater than 1.2 (excluding DI = 2), and RR = 8.0 for those with Stage D. These data indicate that flow cytometrically evaluated DI values have a relevant independent power for predicting the clinical outcome of colorectal cancer patients.

Aged↗
PubMed1991

Regional pharmacokinetic selectivity of intrapleural cisplatin.

The pharmacokinetics and toxicity of cisplatin were investigated in 3 patients affected by malignant mesothelioma who received 90 mg/m2 of the drug intrapleurally. The mean area under the pleural Pt concentration versus time curve (AUC) [12.83 (S.D. 4.06) mg.min/ml] was about 50 times greater than that detected in plasma [0.27 (0.03) mg.min/ml], indicating a clear pharmacological advantage for this route of administration. The mean plasma total Pt concentration was 1.1 micrograms/ml and the apparent total body clearance was 268 (101) ml/min. Platinum plasma pharmacokinetic data measured following intrapleural cisplatin administration (4 patients) were compared with those observed in 7 patients treated intravenously with the same dose of cisplatin (90 mg/m2) under the same modalities of hydration. Intrapleural administration of cisplatin resulted in significantly lower plasma total partial AUC (P less than 0.05) and prolonged plasma levels of filterable Pt compared with intravenous administration. No difference between the two routes of cisplatin administration in the renal clearance (S.D.) of filterable Pt [132 (64) ml/min and 122 (39) ml/min for intravenous and intrapleural cisplatin, respectively] were observed. None of the mesothelioma patients developed clinical symptoms or signs of pleural inflammation. The intrapleural treatment did not produce haemotoxicity and the emetic toxicity was lower compared with that observed in patients receiving cisplatin intravenously.

Aged↗
PubMed1991

Phase II study of the pure non-steroidal antiandrogen nilutamide in prostatic cancer. Italian Prostatic Cancer Project (PONCAP).

The activity of the pure non-steroidal antiandrogen nilutamide as a single agent was evaluated in 44 patients with metastatic carcinoma of the prostate. Objective (partial) response rates (95% confidence limits) were 38.5 (18.7)% in 26 previously untreated patients and 5.5 (11%) in 18 patients progressing on primary androgen suppressive procedures. The most frequent side-effects were decreased adaptation to darkness (29.5%), slight nausea (31.8%) and alcohol intolerance (18.2%). In addition, treatment was discontinued in 3 patients because of gastrointestinal symptoms. A non-significant increase in testosterone levels was shown in the untreated group during the first month of treatment, after which the levels remained stable. About half of the sexually active men claimed the maintenance of libido and sexual potency during treatment. Although our study confirms a significant incidence of visual disturbances, the activity data coupled with the ability of maintaining sexual interest suggest that single therapy with non-steroidal antiandrogens may deserve comparison to conventional endocrine treatment in controlled trials.

Aged↗
PubMed1991

Lung cancer risk among refractory brick workers exposed to crystalline silica: a retrospective cohort study.

We conducted a retrospective cohort study among 1,022 refractory brick workers exposed to crystalline silica. Mortality from lung cancer (SMR = 1.77) and respiratory diseases (SMR = 3.15) was elevated in workers first employed less than or equal to 1957 who are likely to have shared the highest exposure to crystalline silica. Workers with at least 19 years of cumulative employment in the plant experienced particularly increased risks for lung cancer (SMR = 2.01) and respiratory diseases (SMR = 3.89). Relative mortality from these specific causes increased with years since first employment (that is, first exposure) and decreased with age at first employment. Indirect adjustment for smoking habits and the lack of excess mortality from cardiovascular diseases and emphysema indicated little effect of smoking on the increased risks for lung cancer and respiratory diseases.

Adult↗
PubMed1991

Fractures of the penis: therapeutic approach and long-term results.

Injury to the external male genitalia is considered, with attention focused on accidental fracture of the corpora cavernosa (by coitus or masturbation). Such injuries are often complicated by urethral lesions. We present 13 patients with either simple or complicated fracture of the penis, all of whom were operated on between 2 h and 8 days following injury, with excellent functional results. The need for immediate surgery is emphasised, in order to avoid erectile failure and curvature, which are typical complications of conservative treatment. Surgery consists of complete evacuation of haematoma, curettage and repair of the albuginea. If the fracture is associated with urethral disruption, the latter is also repaired.

Adult↗
PubMed1991

[General balanced anesthesia and propofol in ablation of the arterioventricular junction].

The Authors compare the results of general balanced anaesthesia and propofol in the anaesthetic management of closed-chest ablation of A-V junction. The best results were obtained with propofol because of the lower incidence of cardiovascular complications. Therefore propofol is a suitable agent in the anaesthetic management of closed-chest ablation of the A-V junction.

Aged↗
PubMed1991

[Propofol in single bolus for treatment of elevated intracranial hypertension].

Eleven patients with intracranial pressure (ICP) above 20 mmHg despite hyperventilation and neurosedation were treated with a bolus of propofol (1.5 mg/kg) i.v. At baseline and 1-2-5-10-15-30-45 minutes after propofol administration we recorded the values of PIC, systolic arterial pressure (SAP) and mean arterial pressure (MAP), heart rate (HR) and cerebral perfusion pressure (CPP), calculated as MAP less PIC. In the first ten minutes after propofol we observed a statistically significant (p less than 0.05) decrease of ICP and SAP. MAP decreased in the first five minutes only. Consequently HR increased at the same time. CPP decreased in the first two minutes after administration of the drug, but without statistical evidence. We conclude that propofol, in our opinion, can be used to treat intracranial hypertension but the hemodynamic effects in hypovolemic patients must be taken into consideration.

Adolescent↗