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Biomedical subjects

G Bonardi

Publications and source records attributed to G Bonardi.

At least 19 recordsLinked to original sources
PubMed1998

Association of multiple endocrine neoplasia type 2 and Hirschsprung disease.

In a few patients with Hirschsprung disease (HSCR) and no clinical symptoms of multiple endocrine neoplasia type 2 (MEN-2A) or medullary thyroid carcinoma (MTC), missense mutations in the cysteine residues 609 and 620 of the Ret gene have been identified. In several pedigrees with either MEN-2A or familial MTC (FMTC) a documented germline mutation in cysteine 618 or 620 follows the segregation of the disease phenotype. The appearance of the HSCR phenotype in such patients and pedigrees cannot be easily reconciled with the gain of function which is associated with the dominant oncogenic effect of MEN-2A mutations. Gastrointestinal manifestations are known to occur also in association with MEN-2B but, to the best of our knowledge, in only very few cases the intestinal phenotype of MEN-2B has been investigated by enzymo-histochemical techniques, as in the present work. We report an extensive molecular study of patients, two with HSCR and FMTC carrying a Cys620Arg or Ser mutation and two with MEN-2B and gastrointestinal symptoms carrying a Met918Thr mutation. One of the latter two patients showed aganglionosis of the last 5 cm of rectum which caused a congenital megacolon leading to the diagnosis and operation for HSCR. The mutation screening of all the exons of Ret in 3 of these patients did not reveal any additional mutation. Therefore these results do not support the hypothesis of additional constitutional Ret mutations in patients showing association of MEN-2 and HSCR, whilst the histochemical and clinical data in one of these patients indicate that MEN-2B can be associated with a true form of short segment HSCR.

Drosophila Proteins↗
PubMed1996

Development of nerve fibres in the temporomandibular joint of the human fetus.

The development of nerve fibres in the temporomandibular joint (TMJ) in relation to the development of bone, muscle and fibre components was investigated in human fetuses ranging from 9 weeks of gestation to birth. Immunohistochemistry for the glia-associated protein S-100 and for the neuro-specific marker protein gene product 9.5 (PGP 9.5) were used; specimens were compared to specimens of adult TMJ capsule and disc. At 9-10 weeks, a small number of neural elements are already present in the connective tissue around the joint and in the mesenchyme between the two articular blastemas from which the disc will differentiate. By 19 weeks many nerve fibres are clearly visible. Immunohistochemical results suggest diffuse disc innervation extending along the entire disc but not in the thin central area. More complex structures, i.e. encapsulated corpuscles, were also seen. The fetal disc appears highly innervated compared to adult tissue; already at this developmental stage morphology and distribution of nerves and corpuscles in the joint capsule are comparable to those in the adult joint. It may be concluded that the innervation of the TMJ is detectable from the end of the second month and that it develops fully between the third and the fifth month of gestation. Nerve endings in the disc are most numerous at 20 weeks, after which a progressive reduction, possibly secondary to the growth of articular tissues, is observed throughout the last trimester of fetal life and into adult life. The innervation of the lateral pterygoid muscle, on the contrary, is much less than that seen in adult muscles, even at full-term.

Adult↗
PubMed1990

4'-EPI-doxorubicin in advanced lung cancer. A phase II trial.

Fifty evaluable patients with advanced lung cancer (28 small cell and 22 non-small cell carcinomas), mainly pretreated by chemotherapy, received 4'-epi-doxorubicin 90 mg/m2 every 3 weeks. Two partial responses were obtained in small cell lung cancer patients, which lasted 153 and 168 days. Leukopenia, emesis and alopecia were the most frequent side effects. Two patients who previously received anthracyclines died suddenly of cardiac failure, another patient had severe congestive heart failure, and four others had minor cardiac dysfunctions. 4'-epi-doxorubicin has a modest activity in advanced lung cancer, mainly pretreated by chemotherapy and is not devoid of significant cardiotoxicity in this patient population.

Adult↗
PubMed1990

Doxorubicin and etoposide in the treatment of advanced measurable breast cancer.

Nineteen evaluable patients with advanced breast cancer were treated with a combination of doxorubicin and etoposide. Patients had measurable disease, received only mild pretreatment and most had good general conditions at start of therapy. Strict criteria for dose adjustments according to nadir counts were applied. A 42% response rate was obtained. Toxicity was mild and treatment well-tolerated. Doxorubicin-etoposide is an active regimen for patients with breast cancer and warrants further testing in a larger patient population with less stringent criteria for evaluation and treatment monitoring.

Adult↗
PubMed1989

The role of induction chemotherapy in inoperable ovarian cancer.

Thirty patients with bulky advanced ovarian cancer surgically not resectable, received combination chemotherapy (median of 4.1 cycles; range, 3-7) including cisplatin or carboplatin, followed by a second surgical effort. Clinical CR + PR was observed in 24/30 (80%) patients after chemotherapy. Our study deals only with these 24 patients, and the 6 patients who did not respond to chemotherapy are not part of this report. At debulking, 7/24 (29.1%) patients had a complete macroscopic resection; 9/24 (37.5%) patients had a partial resection (residual tumor less than 2 cm). These data suggest that debulking is feasible and successful after chemotherapy containing cisplatin or its derivative. Overall median survival from diagnosis was 18.9 months; the 3-year survival rate was 28%. Median progression-free survival from diagnosis was 13.5 months. The results observed in our study indicate that the use of induction chemotherapy can play an important role in increasing the chances of optimal debulking in patients presenting with unresectable ovarian cancer.

Adult↗
PubMed1989

Isolated central nervous system metastasis from ovarian carcinoma: a case report.

Ovarian adenocarcinoma usually disseminates and recurs the abdominal cavity. The detection of central nervous system metastases is rare. In this report we describe a case of intracranial recurrence that developed during a complete local surgical and pathological response and was treated radically with surgery followed by radiation.

Adenocarcinoma↗
PubMed1989

Lonidamine versus polychemotherapy in advanced non-small-cell lung cancer. A preliminary analysis.

No clear evidence of survival benefit has been definitely shown by chemotherapy in advanced non-small-cell lung cancer. We evaluated in a randomized trial the activity of the new drug lonidamine (up to 1050 mg/day) versus MVP (mitomycin C, 10 mg/m2, vinblastine, 5 mg/m2, cisplatin, 100 mg/m2). The preliminary findings on 25 patients showed that lonidamine can be easily administered at these dose ranges, and main toxicity was represented by myalgia and testicular pain. Tolerance to combination chemotherapy (MVP) was superimposable to our prior experience. Responses were recorded in both arms, and no survival difference was apparent. The study is in progress.

Adult↗
PubMed1988

Teniposide in the treatment of small-cell lung cancer: the influence of prior chemotherapy.

Fifty patients with small-cell lung cancer (SCLC) were treated with teniposide (VM26) at 120 to 140 mg/m2 on days 1, 3, and 5, every 3 weeks. Twelve elderly patients were administered VM26 as first-line chemotherapy. Toxicity was manageable, myelosuppression being the major side effect. The response rate for 44 evaluable patients was 34% (36% for untreated patients); the median durations of response and survival were 230 and 208 days, respectively. Effectiveness of prior chemotherapy and time from last administration was found to influence patient response to VM26: 42% of responders to prior chemotherapy responded to VM26, while 0% of the nonresponders to prior chemotherapy responded to the new agent. Moreover, among patients pretreated with chemotherapy, 12% of those recently treated (earlier chemotherapy ending less than or equal to 2.6 months before administration of VM26) responded to VM26, while 53% of patients treated greater than 2.6 months earlier responded to VM26. Survival was influenced by common prognostic factors (performance status, weight loss, prior chemotherapy exposure). Selection of pretreated patients by type of exposure to prior chemotherapy may help in the testing of new drugs in this disease.

Aged↗
PubMed1988

Influence of food on the absorption of flurithromycin in man.

Oral absorption of flurithromycin, a new fluorinated macrolide, has been evaluated on eight healthy volunteers on fasting and after a standard meal. Serum levels from 0 to 8 hours, peak serum concentrations, times to peak and areas under the curves were compared using a balanced sequence cross-over design. The highest mean concentration was reached after 3 h from administration on fasting (1.36 +/- 0.31 mcg/ml) and after 1 h following a meal (1.36 +/- 0.30 mcg/ml). All the pharmacokinetic parameters considered showed no statistical change. Therefore a meal does not reduce or delay the absorption of flurithromycin, while in the presence of food other macrolides may behave differently. Moreover the tolerability to the drug was good, lacking any report of side-effects, either on fasting or after the food.

Adult↗
PubMed1987

4'-Deoxydoxorubicin, an inactive drug in small cell lung cancer.

4'-Deoxydoxorubicin was administered to 27 evaluable patients with refractory small cell lung cancer. The majority of patients had good initial performance status. One third of patients had never received doxorubicin before, and six had received a single drug alone (VM26). Myelotoxicity was the main side-effect, and leukopenia was more pronounced than thrombocytopenia. No significant non-hematological toxicity occurred apart from skin necrosis due to drug extravasation in one case. Two patients had partial response (7.4%; 95% confidence limits 0-17.2%). The low response rate obtained in this good prognosis patient population does not support further testing of this drug in small cell lung cancer.

Aged↗
PubMed1987

Bone marrow evaluation in small cell carcinoma of the lung.

Bone marrow examination is commonly included in the staging of small cell lung carcinoma (SCLC). We reviewed marrow samples of 103 patients. Marrow examination was mainly performed by unilateral or bilateral biopsy of iliac crests, using a Jamshidi needle. Only 6 of 97 evaluable cases (6.2 per cent) were positive for marrow metastases at staging, and in 3 cases (3 per cent) bone marrow was the only metastatic site. No focal metastases were found in additional sections made from the blocks of negative samples. In our experience bone marrow biopsy was of little value in staging SCLC. Bilateral biopsy plus aspirate, with the addition of more sophisticated staining techniques might, however, provide a higher yield of positive marrow involvement.

Adult↗
PubMed1987

Teniposide in the treatment of non-small cell lung carcinoma.

Forty-two evaluable patients with advanced non-small cell lung cancer were treated with teniposide at doses ranging from 120 to 180 mg/m2 on Days 1, 3, and 5 every 3 weeks. Thirty-four patients had received no prior chemotherapy. Seven partial responses (16.6%) were obtained (21% in chemotherapy-unexposed patients). Marrow toxicity was the main side effect: life-threatening thrombocytopenia occurred in 9% of patients, and 54.5% experienced severe leukopenia. Teniposide, at the doses and schedule employed, has moderate activity in non-small cell lung cancer.

Adult↗
PubMed1987

Synthesis and calcium antagonistic activity of a new class of 1,4-dihydropyridines having an alkoxyimino group in position 3.

The synthesis of new 1,4-dihydropyridines having an alkoxyimino group in position 3 is described. Pharmacological evaluation included calcium antagonistic activity in the guinea pig Taenia coli test, acute toxicity and oral antihypertensive activity in SHR. The compounds had a remarkable calcium antagonistic activity in vitro and low toxicity, but no antihypertensive activity in vivo, probably due to an unfavourable pharmacokinetic profile.

Animals↗
PubMed1986

Stevens-Johnson syndrome and fatal pulmonary toxicity to combination chemotherapy containing bleomycin: a case report.

Bleomycin is a commonly used anticancer agent; in particular, it is an important component of multidrug regimens for germ cell tumors. The limiting toxicity of bleomycin is represented by pulmonary interstitial fibrosis; mucocutaneous side effects are common, but usually harmless. We describe a case of a young girl who developed Stevens-Johnson syndrome following the administration of bleomycin in a three-drug regimen containing vinblastine and cisplatin, for an ovarian immature teratoma. The severe dermatologic toxicity was kept under control, but a rapidly evolving respiratory insufficiency due to lung fibrosis developed soon thereafter and caused the patient's death.

Adolescent↗
PubMed1984

Zidometacin: pharmacokinetic study on oral absorption.

Zidometacin is a new nonsteroidal antiinflammatory agent structurally related to indomethacin. Pharmacological studies show its favourable activity/ulcerogenicity ratio in comparison to indomethacin. Preliminary clinical data indicate a good analgesic effect after a single dose and an improvement of functional conditions of the joint after short-term therapy. Pharmacokinetic parameters and bioavailability of the drug were evaluated in the present study after the administration of a single oral dose. Nine healthy volunteers without impairment of hepatic and renal function were selected. According to a 3 X 3 replicated latin square they received a 100 mg capsule, a 200 mg capsule and a 100 mg solution (sodium salt). After various time intervals, blood samples and urines were collected. Plasma and urine levels were evaluated by means of a specific high-performance liquid chromatography method. No difference between plasma levels of capsules (100 mg) and solution (100 mg) was observed. Capsules showed a dose/level relationship between 100 mg and 200 mg. Mean half-lives (+/- s.d.) of capsules (100 and 200 mg) and solution were respectively 3.5 +/- 2.33, 2.8 +/- 1.22, 4.4 +/- 2.96 h. The 0-48 h recovery of total zidometacin (free + conjugated) was 27.4% (100 mg capsule), 20.7% (200 mg capsule) and 24.6% (solution). Only a small amount of zidometacin was excreted unchanged. The drug is well absorbed and its bioavailability appears satisfactory.

Administration, Oral↗
PubMed1983

[14C]cadralazine: absorption, distribution and excretion in rat and dog.

Absorption, distribution and excretion of [14C]cadralazine in rat after oral and i.v. administration of 3 mg/kg were studied. Plasma levels after oral administration of 10 and 45 mg/kg were also evaluated. A direct relation between dose and plasma levels was demonstrated. The drug was well absorbed, disappeared very rapidly from plasma, and was distributed in all the organs examined, with the highest concentration in liver, kidney, and gastrointestinal tract. For more than 4 days excretion was essentially through the urine (75.6% after i.v. and 80% after oral administration), whereas faecal and biliary excretions were quite low. The total recovery was respectively 77.6% and 83.2% after i.v. and oral administration of 3 mg/kg, with the greatest amount (65-70% of the administered dose) appearing in the first 4 to 7 hours. Placental transfer and excretion of radioactivity with milk were demonstrated. Drug-protein binding was 25.9%. Elimination of 14CO2 was not observed. Plasma levels in dog, after oral and i.v. administration of 1 mg/kg of labelled compound, showed similar behaviour to that observed in the rat. Binding of the radioactivity to erythrocytes was found; the radioactivity values observed up to 24 hours were constant with time and not dependent on the decreasing plasma levels. The total recovery (urine and faeces) in the dog over 4 days was 71.1% and 82.1% after oral and i.v. dose, respectively. Preliminary metabolic approaches in rats showed that cadralazine was essentially excreted as unchanged drug in the presence of minor metabolites.

Animals↗
PubMed1981

Absorption, distribution and excretion of DL-gamma-amino-beta-hydroxybutyric acid-1-14C (GABOB-1-14C) in the rat.

1. Serum levels of DL-gamma-amino-beta-hydroxybutyric acid-1-14C (DL-GABOB-1-14C) in the rat (50 mg/kg) were quite similar after single i.v. and p.o. doses. Also the disappearance from the serum was similar with both administration routes. Within 6 days after p.o. treatment with the same single dose, about 26.5% and 1.6% of the dose were excreted in the urine and the faeces, respectively, and after i.v. administration excretion was 10.15% in urine and 1.75% in faeces. The results show that the compound is well absorbed and retained by the organism. After repeated oral doses (200 mg/kg three times daily for 4 days) the serum levels tended to become constant. 2. Urinary excretion after repeated administration increased progressively every day. Investigations on bile-cannulated rats showed that about 0.4% of the p.o. dose was excreted in 24 h. 3. After single (50 mg/kg) or multiple p.o. doses (200 mg/kg) of GABOB-1-14C, there was no unusual localisation of radioactivity in the organs the highest concentrations being present in the liver and the kidneys. Brain radioactivity was not related to serum levels or to administration route. Radioactivity concentration in other organs, for example the liver, was a function of serum levels. 4. Investigations performed to identify the radioactive products in the brain showed that the radioactivity was mainly ascribable to the unchanged DL-GABOB-1-14C.

Administration, Oral↗