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E Testa

Publications and source records attributed to E Testa.

At least 37 records · Page 2Linked to original sources

Impairment of cytochrome P-450-dependent liver activity in cirrhotic patients with Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori gastric infection has been associated with various digestive and extra-digestive diseases. The systemic influence of gastric H. pylori infection seems to be mediated by the release of various cytokines. In liver disease, bacterial infections have been associated with the impairment of liver metabolic function. AIMS: To evaluate the influence of H. pylori infection on liver function as assessed by means of the monoethylglycinexylidide test, which depends upon liver blood flow and cytochrome P-450 activity, and the 13C-galactose breath test, which depends on cytosolic enzymatic activity and is correlated with hepatic functional mass. Moreover, to evaluate whether H. pylori-associated modifications of liver function may be related to tumour necrosis factor-alpha serum levels. PATIENTS AND METHODS: Thirty-five patients with liver cirrhosis of various aetiologies, who underwent monoethylglycinexylidide and 13C-galactose breath tests, were retrospectively evaluated for H. pylori infection by means of anti-H. pylori immunoglobulin G. The main clinical, biochemical and functional characteristics of the patients as well as their tumour necrosis factor-alpha serum levels were then analysed on the basis of the presence of H. pylori infection. RESULTS: Twenty-one patients tested positive for H. pylori infection (60%), and 11 tested negative (31.4%). No clinical or biochemical differences were observed between H. pylori-infected and non-infected patients. H. pylori infection showed no difference in distribution according to Child-Pugh classes (A, 55%; B and C, 67%). The monoethylglycinexylidide test results were significantly lower at each sampling time in H. pylori-positive patients compared to H. pylori-negative patients (MEGX15, P=0.027; MEGX30, P=0.014; MEGX60, P=0.028), while 13C-galactose breath test showed no significant differences considering both cumulative percentage dose and percentage dose/h. The median tumour necrosis factor-alpha serum levels were no different between H. pylori-positive (16.1 pg/mL, 95% confidence interval, 8.7-28.7) and H. pylori-negative (12.3 pg/mL, 95% confidence interval, 8.7-23.4) patients. CONCLUSIONS: In cirrhotic patients, H. pylori infection seems to selectively affect cytochrome P-450 liver activity, while hepatic functional mass does not seem to be impaired. Tumour necrosis factor-alpha does not seem to be the mediator of this impairment. Further studies are needed to evaluate the impact of H. pylori eradication on parameters of liver function.

Aged↗

Long-term follow up of chronic hepatitis C patients after alpha-interferon treatment: a functional study.

AIM: To evaluate the long-term functional outcome of chronic hepatitis C (CHC) patients treated with interferon (IFN) therapy. METHODS: Thirty-six patients with CHC were followed up for a mean of 36 months (+/- 19, SD) after a course of IFN therapy. Biochemical, virological (qualitative hepatitis C virus (HCV)-RNA and HCV genotype), and functional (monoethylglycinexylidide (MEGX) test) evaluations were carried out at the time of liver biopsy. Patients were divided into long-term responders (LTR), relapsers (RR), or non-responders (NR) according to IFN therapy outcome. At the end of follow up, patients were non-invasively re-evaluated by means of biochemistry, qualitative HCV-RNA, MEGX test, and liver ultrasonography. RESULTS: A significant decrease in MEGX values was observed in all patients. However, when patients were examined according to treatment outcome, only NR and RR showed a significant decrease in liver function as compared to pretreatment levels (MEGX30, 80.5 +/- 26.8-62.9 +/- 24.2 ng/mL, P< 0.01; MEGX60, 72.9 +/- 18.1-60.5 +/- 19.7 ng/mL, P< 0.05; MEGXAUC, 3,816 +/- 1,243-3,095 +/- 1,205 ng/mL per h, P< 0.05). On the contrary, LTR patients showed no significant modifications in MEGX values at each sampling time (MEGX,5, 72.9 +/- 31.4-70.3 +/- 29.7 ng/mL; MEGX30, 84.0 +/- 27.6-71.5 +/- 21.8 ng/ mL; MEGX60, 69.5 +/- 26.8-63.2 +/- 14.4 ng/mL; MEGXAUC 4028 +/- 1,378-3,620 +/- 1,041 ng/mL per h). At the end of follow up, LTR patients showed normal liver biochemistry and negativity of serum HCV-RNA, while NR and RR patients showed a significant decrease in platelets. CONCLUSIONS: In CHC patients long-term response to IFN therapy, besides favoring positive clinical and virologic long-term outcome, results in maintaining preserved liver function. Furthermore, IFN therapy seems to determine a decrease in the rate of functional disease progression, even in NR and RR. The MEGX test may be considered as a useful tool for performing serial follow up of CHC patients.

Adult↗

A phase II study of weekly docetaxel as salvage chemotherapy for advanced gastric cancer.

BACKGROUND: Docetaxel has shown some activity in advanced gastric cancer. Recent phase I studies found low hematologic toxicity and a favourable toxicity profile when docetaxel was administered on a weekly schedule. In this study, we explored the activity of weekly docetaxel in patients with advanced gastric cancer who failed first-line chemotherapy. MATERIALS AND METHODS: Patients with stable or progressing disease after first-line chemotherapy received 36 mg/m2 weekly docetaxel. One cycle consisted of six administrations followed by a two-weeks rest, patients were re-evaluated at week eight. The optimal two-stage design was adopted for early stopping of the trial if responses were one or less in 21 patients (< 20% response rate with alpha and beta error probabilities 0.05 and 0.010 respectively). RESULTS: Twenty-one patients have been enrolled and they are fully evaluable for response and toxicity. One patient achieved partial response, 8 patients had stable disease and 12 patients progressed. Median overall survival from the onset of salvage chemotherapy was 3.5 months. Hematologic toxicity was observed in two patients who experienced grade III leukopenia. Beginning from the third week of treatment, most of the patients (90%) showed grade II asthenia which resulted the commonest side-effect. CONCLUSIONS: This schedule of weekly docetaxel did not show significant activity in pretreated patients with advanced gastric cancer.

Aged↗

Low-dose monitored mitotane treatment achieves the therapeutic range with manageable side effects in patients with adrenocortical cancer.

Eight patients with adrenocortical cancer were treated with low doses of mitotane (2-3 g daily) while monitoring drug plasma levels. When the mitotane concentrations reached the therapeutic range (defined as mitotane plasma levels between 14-20 microg/mL), a dose reduction was performed to avoid toxicity. Thereafter, the mitotane dose was tailored according to plasma levels. A progressive increase in plasma mitotane concentrations was observed during treatment, and a highly significant linear correlation was found between plasma drug levels and the total mitotane dose. The therapeutic threshold was reached in all patients after 3-5 months and a total mitotane dose of 283-387 g/days (median, 363). The duration of treatment was 8-40 months (median, 9). Toxicity was manageable in all but one patient, who discontinued treatment. It is therefore possible to design a standard low dose schedule, e.g. 3 g/daily for about 3-4 months with following dose adjustments guided by the monitoring of plasma mitotane levels. This approach is able to provide therapeutic mitotane concentrations and limit the unwanted effects. The present data provide a rationale to change the approach to mitotane treatment in patients with adrenocortical carcinoma from high dose to low dose regimens.

Adrenal Cortex Neoplasms↗

Treatment with the antibiotic roxithromycin in patients with acute non-Q-wave coronary syndromes. The final report of the ROXIS Study.

AIMS: Mounting evidence suggests infection, specifically Chlamydia pneumoniae, plays a role in atherosclerosis. We tested whether antibiotic treatment with the macrolide roxithromycin improves clinical outcome in patients with acute non-Q-wave coronary syndromes. Preliminary reports revealed a reduction in events in the roxithromycin group at 30 days. We now report the long-term follow-up results. METHODS AND RESULTS: Sixty-four per cent of the initial 202 patients with unstable angina who were randomly assigned to receive either roxithromycin or placebo for 30 days completed the active treatment period. At day 30, the primary triple and double end-point rates were 9% and 4% in the placebo group compared to 2% and 0% in the roxithromycin group (unadjusted P = 0.032 and 0.058, respectively). The secondary triple and double end-point rates were again higher in the placebo group at day 90 (12.5% and 6.25% vs 4.37% and 0%, unadjusted P = 0.065 and 0.029, respectively), and at day 180 (14.6% and 7.29% vs 8.69% and 2.17%, unadjusted P = 0.259 and 0.17, respectively). Anti-C, pneumoniae IgG titres were unchanged in both groups while C-reactive protein levels decreased in both strategies, with a more significant decrease in the roxithromycin arm (P = 0.03). Elevated C-reactive protein levels predicted the need for revascularization. CONCLUSIONS: In this pilot trial, roxithromycin appears to extend the clinical benefit of preventing death and re-infarction for at least 6 months after initial treatment.

Aged↗

Mitoxantrone, fluorouracil, and L-folinic acid in anthracycline-pretreated metastatic breast cancer patients.

In this phase II trial we have evaluated the activity and toxicity of a combination regimen containing mitoxantrone, L-leucovorin, and fluorouracil in patients with advanced breast cancer pretreated with anthracyclines. Forty-six patients were included into the study; they received a total of 227 cycles of chemotherapy. Median age was 63 years (range 34-78), median performance status was 80 (range 60-100). Visceral metastases were present in 37 patients, 6 patients had bone involvement only, while 3 patients had soft tissue/lymph node disease. Median number of previous chemotherapy regimens for advanced disease was 2 (range 1-3). Ten patients had anthracycline primary resistance (progressive disease during treatment). Twenty-three patients received mitoxantrone 12 mg/sqm day 1; fluorouracil 370 mg/sqm and L-folinic acid 100 mg/sqm days 1-3 administered every three weeks. Another group of 23 patients were treated with the same regimen using a prolonged 5FU/L-FA schedule (5 days). Two complete responses and 6 partial responses were recorded with the 3-day schedule; 7 partial responses in the 5-day schedule (overall response rate 32.6%, 95% C.I. 19-46%). Two partial responses were observed in patients with anthracycline primary resistance. Median response duration was 9 months (range 3-16). Hematologic toxicity was mild: grade 3-4 leukopenia was recorded in 5 patients, grade 3-4 thrombocytopenia in 3 patients. Grade III-IV stomatitis and diarrhea was recorded in 4 and 5 patients respectively (all receiving the 5-day 5-FU/L-FA schedule). Cardiac toxicity was observed in two cases. This regimen proved active in advanced breast cancer following anthracycline-containing chemotherapy, and the 3-day schedule could be offered to such patients with acceptable toxicity.

Adult↗

Intensive weekly chemotherapy for advanced gastric cancer using fluorouracil, cisplatin, epi-doxorubicin, 6S-leucovorin, glutathione, and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer.

PURPOSE: A multiinstitutional trial was performed to confirm the clinical activity, in terms of response rate and toxicity (primary objectives) and duration of responses and survival (secondary objectives), of an intensive weekly regimen in advanced gastric cancer. PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma received 1-day per week administration of cisplatin (CDDP) 40 mg/m2, fluorouracil (5FU) 500 mg/m2, epi-doxorubicin (epi-ADR) 35 mg/m2, 6S-stereoisomer of leucovorin 250 mg/m2, and glutathione 1.5 g/m2. On the other days, filgrastim was administered by subcutaneous injection at a dose of 5 mg/kg. One cycle of therapy consisted of eight 1-week treatments. Patients who showed a response or stable disease received a further 6 weeks of therapy. RESULTS: Of 105 enrolled patients, 11 had locally advanced unresectable disease only; 33 had primary nonresected and metastatic disease; 48 had metastatic disease and primary tumor resected; 10 had locoregional recurrence and metastatic disease; and three had locoregional recurrence only. After one cycle, 18 complete responses (CRs) and 47 partial responses (PRs) were achieved, for an overall response rate of 62% (95% confidence interval [CI], 53% to 71%). Twenty patients had stable disease and 20 progressed on therapy. The median survival duration of all 105 patients was 11 months, with 1- and 2-year survival rates of 42% and 5%, respectively. World Health Organization (WHO) grade III to IV toxicity, in terms of anemia, neutropenia, thrombocytopenia, and mucositis, was experienced by 40 patients (38%). There were no treatment-related deaths. CONCLUSION: These data support the results of the pilot study and confirmed the high activity of the regimen, with acceptable toxicity. This schedule deserves evaluation in the adjuvant setting.

Adult↗

Patient-controlled analgesia and postoperative urinary retention after hysterectomy for benign disease.

BACKGROUND: Because postoperative urinary retention can result in considerable morbidity and the rate of retention after hysterectomy has recently increased at our institutions, we conducted a study to determine risk factors for the disorder. STUDY DESIGN: A cohort of 366 consecutive patients who had undergone uncomplicated abdominal or vaginal hysterectomy for benign disease and who met strict inclusion criteria were studied retrospectively by means of a review of their medical records. Student's t test and multivariate logistic regression analysis were used to assess the effects of operative time, amount of fluid given perioperatively, type and amount of analgesic agent administered postoperatively, age of the patient, performance of a vaginal versus an abdominal hysterectomy, and the postoperative use of patient-controlled analgesia on the rate of postoperative urinary retention in these patients. RESULTS: After adjustment for confounding factors, only the use of patient-controlled analgesia (p = 0.0001) and vaginal hysterectomy (p = 0.0003) were significantly related to postoperative urinary retention. Patients who used patient-controlled analgesia were 5.7 times (95 percent confidence interval, 2.6 to 12.4) more likely to have urinary retention than those given an intramuscular agent. CONCLUSIONS: Urinary retention after hysterectomy might be avoided by administering analgesic agents intramuscularly or inserting a suprapubic cystostomy catheter postoperatively, especially in patients who have undergone a vaginal procedure.

Adult↗

High-performance liquid chromatographic microassay for methyl ethyl ketone in urine as the 2,4-dinitrophenyl-hydrazone derivative.

We report a high-performance liquid chromatographic procedure for determining methyl ethyl ketone in urine. The method is based on pre-column derivatization with 2,4-dinitrophenylhydrazine and liquid-liquid extraction of the derivative. The analyte is chromatographically separated from other urine constituents in less than 12 min and is detected by UV absorption at 360 nm. Peak height and concentration are linearly related. The relative standard deviation assessed for within-day imprecision was 3.2% at the 2.21 mg/l level. The mean analytical recovery from urines spiked with 1.0 mg/l ketone was 96.0 +/- 6.1%. The simple sample handling, the small volume of urine required and the short amount of time taken for the whole procedure make it suitable for routine biomonitoring of exposure to methyl ethyl ketone in industrial workers. The concentration in urine from nine non-exposed controls was less than 0.1 mg/l. The concentrations measured in urine samples from 60 exposed workers ranged from 0.1 to 1.1 mg/l and from 0.3 to 3.6 mg/l at the before- and the end-shift collections, respectively.

Butanones↗

Rapid high-performance liquid chromatographic determination of urinary N-(1-methylethyl)-N'-phenyl-1,4-benzenediamine in workers exposed to aromatic amines.

A procedure has been developed for determining N-(1-methylethyl)-N'-phenyl-1,4-benzenediamine in urine by using high-performance liquid chromatography. The method uses chloroform extraction for partial clean-up of the urine sample. The separation is carried out on a reversed-phase column using 65 mmol/l aqueous ammonium acetate in acetonitrile (30:70, v/v) as the mobile phase. The column effluent is monitored at 290 nm with an ultraviolet detector. The analyte is separated from other normal urine constituents in less than 4 min. Peak height and concentration are linearly related. Coefficients of variation assessed for within-day reproducibility were 5.9 and 3.7% at concentrations of 22.3 and 92.1 micrograms/l, respectively. The mean analytical recovery from urine samples spiked with known amounts of amine was 89.7 +/- 6.8%. The request of only a small volume of urine and the simple pre-treatment procedure makes it suitable for the routine monitoring of the exposure of rubber vulcanization workers to aromatic amines.

Amines↗

Neuroendocrine data in chronic post-traumatic headache.

Twenty chronic post-traumatic headache subjects (16 men and 4 women) were considered, together with age and sex matched normal controls. Pituitary function was challenged by means of luteinising hormone releasing hormone (100 microg, i.v.), thyrotropin (TSH) releasing hormone (200 microg, i.v.) and regular insulin (.1 U/kg, i.v.). The responses of gonadotropins, TSH, somatotropin (STH) and prolactin (PRL) were studied in the group as a whole and in clinical subgroups. No differences were found in the baseline levels of the hormones. No significant changes were observed in the responses of gonadotropins and STH. A decreased response was found for TSH and, in the female series, an enhanced response of PRL was observed. Patients complaining for a decreased libido showed a larger PRL response. The smaller response of TSH exhibits a straight inverse relationship to the clinical severity. The periodicity of PRL secretion studied in male patients with a harmonic analysis according to the Fourier's theorem showed the preservation of the physiological sleep-entrained night surge. The per cent incidence of the harmonics with a period shorter than 24 hours decreases according to the clinical severity, at variance to the finding in normal controls. The only persisting harmonic is the one with a 24 hour period. In the absence of major post-traumatic endocrine syndromes, post-traumatic headache subjects show changes of the neuroendocrine regulation of pituitary secretion. The findings are consistent with the hypothesis of an hyperactivity of serotoninergic neurotransmission.

Adult↗

[Tricyclic homologs of piperazine. III. Synthesis of 4-substituted hexahydro-1H-2,6-methanopyrrolo[1,2a]pyrazines].

The Authors describe the synthesis of some quaternary salts of the hexahydro-1H-2,6-methanopyrrolo[1,2-a]pyrazines mono or disubstituted at carbon-4. These were obtained directly by cyclization of the corresponding diazabicyclooctanes, by formation of a substituted ethylenic bridge between the two nitrogen atoms. The compounds were pharmacologically screened; the hypothesis of enhancement of curare-like activity in comparison with the unsubstituted derivatives was not confirmed.

Animals↗

[Bicyclic analogs of piperazine. XII. (1) - Synthesis of 3,8-diazabicyclo/3,2,1/octanes as potential antiparkinson agents].

As a part of research on 3,8-diazabicyclo [3,2,1] octanes, the Authors report on the synthesis of some amides of methyl, phenyl and cyclohexyltropic acid, potentially active as antiparkinson agents. Also reported is the synthesis of some compounds similar to two known drugs, Caramiphene and Cycrimine. These compounds differ from the said drugs in having a 3,8-diazabicyclo [3,2,1] octane as a basic moiety.

Antiparkinson Agents↗

Synthesis of 1-hydroxy and 1-acyloxypyrrolidin-2-ones.

A series of 1-hydroxypyrrolidin-2-ones (v) has been prepared by reduction of gamma-nitrocarboxylic acid esters with Zn dust in the presence of ammonium chloride. Acylation of compounds (v) gave the corresponding 1-acyloxypyrrolidin-2-ones (VI). None of the synthesized compounds showed any significant antiflammatory activity.

Acylation↗