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Biomedical subjects

G Simonetti

Publications and source records attributed to G Simonetti.

At least 145 records · Page 8Linked to original sources

Dose-finding studies with carboplatin, ifosfamide, etoposide, and mesna in non-small cell lung cancer.

Carboplatin, a clinically active analogue of cisplatin, was added to a regimen containing ifosfamide and etoposide, two agents with proven activity in non-small cell lung cancer (NSCLC). From August 1986 until November 1988, 43 consecutive patients (29 men and 14 women), mean age 57 years, performance status of 2 or less, with symptomatic, inoperable NSCLC were accrued and received carboplatin 100 mg/m2 on days 1, 3, and 5, or 300 or 350 mg/m2 on day 1; ifosfamide 1,500 mg/m2 and etoposide 60 or 100 mg/m2 every 4 weeks. Thirty-four patients were previously untreated, nine had been irradiated before, and two had also received previous chemotherapy. So far, 154 courses have been administered; 19 patients have received four or more courses. With the combination of 350 mg/m2 carboplatin and 100 mg/m2 etoposide, myelosuppression was dose-limiting; nephrotoxicity and neurotoxicity did not occur. Evaluation of response after two or four courses in 40 patients showed an objective response in 40%, whereas 30% progressed during therapy. Carboplatin added to etoposide and ifosfamide is a feasible combination that warrants further study in a randomized fashion.

Adult↗

Research on antibacterial and antifungal agents. XIII. Synthesis and antimicrobial activity of 1-arylmethyl-4-aryl-1H-pyrrole-3-carboxylic acids.

Several 1-arylmethyl-4-aryl-1H-pyrrole-3-carboxylic acid derivatives have been synthetized and tested as antifungal and antibacterial agents. Reaction between tosylmethylisocyanide (TosMIC) and beta-arylacrylic esters under basic conditions furnished 4-aryl-1H-pyrrole-3-carboxylic esters, which were then benzylated at 1 position. Alkaline hydrolysis of ethyl 1-arylmethyl-4-aryl-1H-pyrrole-3-carboxylates afforded the title compounds. All tested derivatives were found to be inactive as antifungal agents. Some of them showed appreciable antibacterial activities against Staphylococcus spp.

Anti-Bacterial Agents↗

Glycogen medium, antitrichomonal drug activity in vaginal liquids.

The amount of glycogen in vaginal liquids decreases with Trichomonas vaginalis and this is connected with T. vaginalis activity in specimens. A glycogen-hydrolysed casein medium ("glycogen medium") added to vaginal liquid is a valid maintenance medium for T. vaginalis and therefore enables a direct test for antitrichomonas drugs to be performed.

Animals↗

"Mycelial vaginal test" and Candida susceptibility.

We have investigated the possibility of vaginal liquids affecting the transition from a yeast form (Y) to a mycelial one (M) in C. albicans and the possible relation to microbial flora, pH and glycogen. The C. albicans Y----M conversion, "mycelial vaginal test", in 250 specimens of vaginal liquid shows a 70% positivity rate against a test Candida strain. Results of the vaginal test are not related to bacteria, flora and pH, but to Candida infection and to glycogen concentration. Using a Y----M good-responder Candida strain in the vaginal test it is possible to have a global index of the factors affecting the Candida filamentation in the host. It can be advisable to utilize the vaginal test as a virulence test for Candida strains and as an indicative test of phenotypic drug resistance.

Candida albicans↗

Pharmacokinetics of free and total platinum species after rapid and prolonged infusions of aqua (1,1-bis(aminomethyl)cyclohexane) sulfatoplatinum (II) (spiroplatin) during a phase I trial.

The pharmacokinetics of the second generation platinum complex aqua(1,1-bis-(aminomethyl)cyclohexane)sulphatoplatinum(II) (spiroplatin, TNO-6) were studied during a phase I evaluation. Thirty patients received 49 cycles of spiroplatin by short term (less than or equal to 10-min), 1-, 3- or 6-h infusion. Dosages given ranged from 5 to 40 mg/m2. Platinum determinations were performed by atomic absorption spectrometry. Up to 5 days after administration platinum concentrations in plasma decayed triexponentially. Pharmacokinetic parameters of total platinum in plasma after short-term and prolonged infusion were similar in terms of terminal half-life (3.7 +/- 1.1 and 3.6 +/- 0.5 days), AUC/dose (548 +/- 106 and 616 +/- 278 min.m2/l), volume of distribution (20 +/- 6 and 27 +/- 81) and total body clearance (2.9 +/- 1.0 and 3.4 +/- 1.8 ml/min), whereas peak plasma concentrations were two times lower after prolonged infusion. The cumulative urinary platinum excretion after short-term infusion was 20 +/- 6%, 30 +/- 6% and 47 +/- 7% of the administered dose after 6, 24 and 120 h, respectively. These values are comparable to those after administration of cisplatin. The half-life of ultrafilterable platinum was 4.4 +/- 0.7 min. The curves of free and total platinum diverged rapidly, reflecting the high reactivity of spiroplatin towards plasma proteins. This high reactivity, most likely caused by the abundant presence of aquated compounds in the injection fluid, may also account for severe and unpredictable nephrotoxicity induced by spiroplatin.

Adult↗

Computed tomography and magnetic resonance imaging in spinal hydatidosis.

Computed tomography and magnetic resonance imaging in patients with spinal hydatidosis provide comprehensive evaluation of the actual extent of the disease. Paravertebral uncalcified cysts, hardly recognizable by conventional radiologic examinations, are clearly shown by both methods. Initial involvement of the spongy bone is evident in computed tomography scans, in contrast to what usually appears to be normal in plain films or tomograms. Occurrence of cysts within the spinal canal is revealed by both types of computed scans, with magnetic resonance imaging being able to provide further information on the involvement of the spinal cord.

Adult↗

Pharmacokinetics of ethylenediaminemalonatoplatinum(II) (JM-40) during phase I trial.

Pharmacokinetics of the cis-platin analog ethylenediaminemalonatoplatinum(II) (JM-410) was studied in 28 cycles of 19 patients during the phase I study of this drug. The drug was administered intravenously by short-term (10-60 min) infusion. Doses ranged from 20 to 1,200mg m-2. JM-40 was determined in plasma ultrafiltrate and urine by HPLC. Platinum (Pt) concentrations were determined in plasma, plasma ultrafiltrate, urine and red blood cells by atomic absorption spectrometry up to 5 days after administration of the drug. Ultrafilterable Pt could be determined up to 45 days after the infusion in one patient sampled over such a long period. Pharmacokinetics of JM-40 showed a linear behaviour. The final half-life of total Pt in plasma was 4.1 +/- 0.9 days. The disposition of JM-40 was similar to that of ultrafilterable Pt in respect to t1/2 alpha (10 and 13 min), t1/2 beta (44 and 57 min), volumes of distribution Vc (11 and 121) and Vss (17 and 201), systemic clearance (256 and 223 ml min-1), renal clearance (69 and 73 ml min-1) and metabolic clearance (183 and 154 ml min-1). During the first 6 h 27 +/- 9% of the administered dose was excreted as JM-40. Cumulative platinum excretion in the urine amounted to 29 +/- 13% and 60 +/- 13% over the first 6 h, 24 h and 5 days, respectively. The uptake of platinum in red blood cells was limited, comprising only 0.24 +/- 0.12% of the administered dose. Although JM-40 and carboplatin are structurally closely related, pharmocokinetics and toxicity of JM-40 were more similar to cis-platin than to carboplatin.

Adult↗

[Transluminal urethroplasty. Preliminary experience in 15 cases].

Thirteen patients with urethral stenoses of different etiopathology underwent TUP with an angioplasty balloon catheter. At follow-up, more than 10 months later, 8 out of 10 patients had normal urinary function. Excluding cases of urethral compression due to prostatic hyperplasia, 90% of the stenoses were successfully dilated. The gradualness of the dilatation, the application of a Foley catheter to maintain the dilatation obtained and the prevention of urinary infections are important factors for the success of this method.

Adult↗

[Diagnostic and therapeutic value of angiography of the mesenteric area].

The widespread diffusion of digital imaging progressively reduces the indications to conventional angiography in all vascular districts. On the contrary, angiography of mesenteric arteries still works as a valid complementary diagnostic tool in granulomatous and neoplastic lesions of ileum. Today, in selected patients, angiography is the first diagnostic approach to vascular ischemic and hemorrhagic pathology of ileum; timely resort to interventional angiography improve a dramatic prognosis.

Adult↗

Phase I study of ethylenediamine platinum(II) malonate (NSC 146 068), a second generation platinum analogue.

Ethylenediamine platinum(II) malonate [JM-40 (NSC 146 068)] has been selected for clinical studies because of its favorable preclinical toxicity profile as a "second generation" platinum analogue. When compared to cisplatin, JM-40 was less emetic in the ferret and less nephrotoxic in the dog, while its antitumor activity approached that of cisplatin. Twenty-nine patients received 86 courses of JM-40 as a single dose every 3-4 wk. After 13 dose escalation steps the maximum tolerable dose was reached at 1200 mg/m2. The dose limiting toxicities were nausea, vomiting, and nephrotoxicity. The renal damage seemed reversible up to a dose level of 1000 mg/m2 and consisted of a glomerular and tubular dysfunction. JM-40 did not cause any other dose related side effect or myelo-suppression. Pharmacokinetic studies at a dose of 1000 mg/m2 revealed mean terminal half-lives of 5.0 and 1.9 days for platinum in plasma and plasma ultrafiltrate, respectively. The mean cumulative excretion of platinum in urine accounted for 57% of the dose up to day 5. Two partial responses were observed in a patient with a large cell carcinoma of the lung and in one with a carcinoma of the lacrimal gland. Limited evaluation of JM-40 in phase II studies is warranted. The recommended dose is 1000 mg/m2 every 4 wk and 800 mg/m2 for patients pretreated with platinum analogues.

Adult↗

Digital angiography in evaluation of orthopedic tumors.

Preoperative evaluation of orthopedic tumors using digital subtraction angiography (DSA) proved useful to ascertain the nature of the lesion, its extension to soft tissues and joints, and the presence of arteriovenous (AV) shunts. We report that overall accuracy varied from 89% to 92%, depending on the feature evaluated. The importance of angiographic examination of this entity is discussed as well as the advantages of DSA over conventional angiography.

Angiography↗

Digital celiac arteriography.

Sixty patients underwent intraarterial DSA with injection into the celiac artery for evaluation of various hepatic, pancreatic, and splenic lesions. Twenty of these patients also underwent conventional arteriography for comparison. Excellent images during the early arterial phase (free of bone superimposition and artifacts) were obtained with DSA. The late arterial and parenchymal phases of the examination were less definitive when compared with conventional angiography. The venous phases of the liver studies were good and compared favorably in contrast and resolution to conventional methods. In the late venous phase, good images of the portal system were obtained using a small amount of contrast medium. Respiratory movements and artifacts were overcome with postprocessing. Most of the studies were performed using the 12-inch mode of the image intensifier, which represents the best choice between the size of the field examined and the spatial resolution of the system. We believe that DSA is a suitable substitute for conventional angiography in most patients in whom celiac trunk angiography would be used.

Angiography↗