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Biomedical subjects

A Bolner

Publications and source records attributed to A Bolner.

At least 19 recordsLinked to original sources
PubMed2004

Entacapone improves the pharmacokinetic and therapeutic response of controlled release levodopa/carbidopa in Parkinson's patients.

The aim of this trial was to evaluate the effects of the COMT inhibitor entacapone on both the pharmacokinetic profile and clinical efficacy of controlled release levodopa in Parkinson's disease (PD) patients. Twelve PD patients experiencing "end-of-dose" type motor fluctuations were evaluated in this single-blind, randomized cross-over study. A single dose of either entacapone (200 mg) or placebo was co-administered with controlled release levodopa. Blood samples were taken every 30 minutes for 3 hours, and in 6 patients, sampling was continued for a further 3 hours. The clinical response to treatment was evaluated using the Unified Parkinson's Disease Rating Scale motor score. Addition of entacapone to levodopa treatment prolonged the "on" phase of the PD patients by 37% (p<0.05). This increased duration of 'on' time was concomitant with a significant increase in levodopa bioavailability (AUC). These data confirm the ability of entacapone to enhance the clinical efficacy of controlled release levodopa formulations, and provide further evidence that entacapone is of value in extending the benefits of levodopa in PD patients experiencing motor fluctuations.

Aged↗
PubMed2002

Proton and carbon NMR spectroscopic analysis of rat liver postnatal development.

BACKGROUND: In the present paper compositional changes of rat liver from birth to adult age were investigated by proton and carbon nuclear magnetic resonance (NMR) spectroscopy. METHODS: The water-soluble and organic (lipid) fraction of pooled liver tissue from rats aged 1,7, 21 days, and 5 months were extracted according to Folch's method and analysed by proton and carbon nuclear magnetic resonance spectroscopy at 500 MHz. Phospholipids separated by chromatography from the organic fraction were also analysed. RESULTS: In proton spectra of the water-soluble fraction several metabolites were identified. Developmental changes in the ratio between betaine and choline and between 3-hydroxybutyrate and several other organic acids were shown. In proton spectra of the total organic fraction, signals from fatty acids chain, phophocholine and glycerol were assigned unambiguously. Phospholipids fatty acid acyl chain length, mean unsaturation and mean polyunsaturation increased from birth to weaning. The relative amounts of unsaturated fatty acids did not show obvious changes during the investigated period. CONCLUSIONS: This study shows that NMR spectroscopy is a useful tool to investigate postnatal developmental changes in the liver chemical constituents with a minimum of preparative procedures.

Journal Article↗
PubMed2001

Optimised determination of clobazam in human plasma with extraction and high-performance liquid chromatography analysis.

The analysis of clobazam by high-performance liquid chromatography and UV detection is described herein. After adding an internal standard, 600 microl of plasma were extracted under basic conditions onto disposable cartridges packed with celite. The organic extract was then evaporated to dryness and the residue reconstituted in 200 microl of mobile phase. A 20 microl aliquot was injected into chromatograph. The HPLC system was equipped with an Ultrasphere C8 analytical column coupled with an UV detector set at 235 nm. The mobile phase was an acetate buffer 20 mM, pH 5.5, containing acetonitrile and triethylamine 70:30:0.01 (v/v); the flow-rate was 1.8 ml/min. Using this method, clobazam can be detected with a sensitivity limit of 6 ng/ml and the RSD% intra- and inter-assay were lower than 5%. For its ruggedness and reliability, the proposed method is particularly suitable for therapeutic drug monitoring in epilepsy.

Anti-Anxiety Agents↗
PubMed2001

NMR spectroscopic analysis of rat brain development: in vitro proton and carbon studies of whole tissue and its phospholipid fraction.

The developmental patterns of the rat brain at several postnatal time points were investigated in Folch (chloroform-methanol) extracts. The chloroform- (lipid-containing) and water-soluble (cytosolic) fractions of whole-tissue extracts and the phospholipid fraction separated from the organic fraction by chromatography were analysed by means of high-resolution (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy. Analysis of the cytosolic fraction showed the changing patterns of several brain metabolites during postnatal maturation, in full agreement with data obtained from perchloric acid extracts. (1)H NMR spectroscopy of the phospholipid fraction allowed for quantitative evaluation of fatty acid acyl chain length, mean unsaturation and mean polyunsaturation. It was found that both mean unsaturation and polyunsaturation are lower in adult brain phospholipids than during the first 3 postnatal weeks. (13)C NMR spectroscopy of the same fraction showed that the molar percentage of C(18) fatty acids (oleic, linoleic, linolenic) in brain phospholipids is similar at all the investigated time points. These results indicate that the combination of Folch extraction with simple chromatographic procedures and NMR analysis yields useful data to define the chemical maturation of the brain.

Animals↗
PubMed1999

[Brachytherapy in the management of the initial stage of the mobile tongue carcinoma].

From 1986 to 1994, 61 patients with oral tongue epidermoid carcinoma were treated using low dose rate iridium brachytherapy. Eleven patients treated with combined external beam and brachytherapy and 8 with nodal metastases at presentation were excluded from the study. The results in 42 fully evaluable and regularly followed patients here retrospectively reviewed. In 22 cases clinical stage was T1 greater than 1 cm and in the remaining 20 T2, N0 M0; all were cases of epidermoid carcinoma. The patients received definitive brachytherapy to the primary site using plastic tube technique at a dose of 5067 Gy (median 60 Gy) at reference isodose. The dose rate ranged from 35 cGy/h to 80 cGy/h (median 53 cGy/h). Elective neck dissection was performed in 24 patients, whereas a surveillance protocol was adopted in the remaining 18 cases. After an average follow-up of 40 months, 5 year absolute and disease specific survival (Kaplan Meier) was 61% and 88% respectively. Two patients failed at the primary site (local control probability 96%). Nodal metastases were found in 6 of 24 electively dissected patients and developed subsequently in 3 of 18 pN0 cases and in 4 of 18 non dissected patients. Four patients died of uncontrolled neck disease (regional control probability 76%). A severe necrosis developed in 9 patients (soft tissue in 4 and bone in 5 patients), but only 3 cases required surgery. This study confirms brachytherapy as an effective treatment modality for the early stage of oral tongue carcinoma.

Adult↗
PubMed1997

Determination of apomorphine in human plasma by alumina extraction and high-performance liquid chromatography with electrochemical detection.

Apomorphine is a powerful agonist of dopaminergic receptors which several years ago was introduced into the therapy of Parkinson's Disease. The pharmacological activity of apomorphine already appears significant at low doses. Unfortunately, the difficulty in determining the drug in plasma at low concentrations hampers the completion of accurate pharmacokinetic studies in humans. Considering the analogy of apomorphine with the molecular structure of catecholamines, the extraction of the drug from plasma was optimized by using adsorption on alumina, a technique widely used for noradrenaline and adrenaline analysis in clinical chemistry laboratories. This method proved particularly efficient and selective in apomorphine extraction from plasma prior to high-performance liquid chromatographic analysis. After pretreatment of 200 microliters of plasma sample with 40 mg of alumina and 10 microliters of tris buffer (pH 8.6), the drug was eluted with 200 microliters of an acidic-organic solution. One volume of the supernatant was mixed with two volumes of phosphate buffer (pH 3.6), and 100 microliters of the obtained mixture were injected into the HPLC system. The chromatograph was equipped with a C18 reversed-phase column and with an electrochemical coulometric detector fitted with a high-sensitivity cell (first electrode 0.00 volts, second electrode +0.35 volts). Sensitivity (20 pg of injected drug), precision (CV within assay and between assays of 3.7% and 5.6%, respectively) and accuracy were comparable to more complex analytical procedures. The miniaturisation of the entire sample pretreatment proved very advantageous for pharmacokinetics studies and, in principle, for therapeutic drug monitoring and toxicological investigations.

Adsorption↗
PubMed1997

Hyperfractionated radiation in combination with local hyperthermia in the treatment of advanced squamous cell carcinoma of the head and neck: a phase I-II study.

Twenty-seven patients with cervical metastases from squamous cell head and neck tumours were treated with hyperfractionated XRT (total dose 69.60-76.80 Gy, 1.2 Gy b.i.d. five times a week) combined with a total of two to six sessions of superficial external HT. Acute local toxicity was mild; as major acute side effects, only one ulceration was recorded. No severe late side effects were observed. Late toxicity was similar to that observed in our previous studies with the combination of heat and radiation. Nodal complete response was observed in 77% of patients, partial response was observed in 15% of patients and no change was observed in 8% of patients. Five-year actuarial nodal control was 64.5 +/- 19% and 5-year actuarial survival was 24 +/- 10%. The treatment of nodal metastases from head and neck tumours with the combination of HT and hyperfractionated XRT is feasible with an acceptable acute and late toxicity profile.

Adult↗
PubMed1997

Combined chemotherapy and radiation with selective organ preservation for muscle-invasive bladder carcinoma. A single-institution phase II study.

OBJECTIVE: To assess in a phase II trial the effectiveness and toxicity of combined chemotherapy and radiation with selective bladder preservation by response in the treatment of muscle-invasive bladder carcinoma. PATIENTS AND METHODS: Fifty-six eligible patients with T2-4 M0 transitional cell bladder cancer suitable for radical surgery and multi-agent chemotherapy received two courses of methotrexate, cisplatin and vinblastine, followed by 40 Gy of pelvic radiotherapy in 1.8 Gy fractions with concomitant cisplatin. Tumour response was evaluated by cystoscopy and biopsy. Those responding completely were given a 24 Gy bladder boost plus cisplatin; patients with residual tumour were assigned to immediate cystectomy. RESULTS: After induction therapy, 28 patients (50%) responded completely; 22 operable patients with residual tumour underwent immediate cystectomy, while 34 patients were consolidated with cisplatin and radiation. Bladder relapses developed in 16 patients; seven had successful endovesical therapy for superficial disease and salvage cystectomy was possible in four of nine cases with invasive recurrence. Distant metastases occurred in 22 cases (39%). After a median follow-up of 46 months, the 5-year actuarial disease-specific survival was 59%, disease-free survival 54% and local control without cystectomy (bladder preservation) 41%. There were no treatment-related deaths; grade 3 late complications occurred in two patients. CONCLUSION: This combined chemotherapy-radiotherapy regimen with selective organ preservation should be considered as an option for muscle-invasive bladder carcinoma. The initial results suggest the possibility of retaining a functioning bladder in many patients, without compromising survival, compared with elective cystectomy approaches. A longer follow-up and quality-of-life assessment remain essential for a better definition of selection criteria and long-term results of this combined modality.

Adult↗
PubMed1997

Biogenic amines in the vomeronasal organ.

The vomeronasal organ of frog and mouse was investigated for the presence and content of serotonin and catecholamines by means of high-performance liquid chromatography. Measurable amounts of serotonin, adrenaline and noradrenaline were found in the vomeronasal organ of adult individuals of both species. The amine content varied with sex of adult frogs and mice and sexual maturity of mice. In preliminary experiments, acute exposure to male urine containing pheromone affected the amine content in the vomeronasal organ of adult female mice. These data suggest that functional sex dimorphism is present in the vomeronasal organ, and biochemical changes therein take place according to stage of sexual maturity. The role of biogenic amines in the vomeronasal organ deserves further study.

Animals↗
PubMed1996

Left ventricular diastolic function during adrenergic stress in essential hypertension: acute and chronic effects of ACE inhibition.

We studied the changes in left ventricular (LV) diastolic function induced by angiotensin-converting enzyme (ACE) inhibition at rest and during adrenergic stimulation and their relation to blood pressure (BP) variations to determine whether reductions in the renin-angiotensin system may improve diastolic function irrespective of BP reduction. Echocardiographic indices of systolic and diastolic function, plasma catecholamines as estimated by high-pressure liquid chromatography, and BP variations (Dynamap) were determined at rest and during the cold pressor test (CPT) before and 6 hours and 20 days after ACE inhibition (lisinopril), 20 mg/day by mouth in 10 subjects with uncomplicated essential hypertension. Blood Pressure was significantly reduced after both 6 hours and 20 days of therapy. The cold pressor test induced similar increases in BP in both basal conditions and after acute and chronic treatment. Catecholamine levels were unchanged by the therapy. Systolic function, evaluated by fractional shortening, ejection fraction, and systolic dV/dt, was normal and unchanged during CPT and after treatment. Diastolic function, assessed by volume curve analysis, showed a reduced percentage contribution of rapid filling to total diastolic filling, an increase in the contribution of the atrial systole, and an increase in the isovolumetric relaxation time. During CPT these parameters deteriorated further in response to increased afterload. Lisinopril therapy induced significant increases in end-diastolic volume (p < 0.005) with a progressive increase in the rapid filling dV/dt (p < 0.005 at rest; p < 0.001 during CPT) and a reduction in isovolumetric relaxation (p < 0.0001 at rest and p < 0.01 during CPT). The correlation between systolic BP (afterload) and the rapid filling dV/dt, both at rest and during CPT, was modified by treatment with the ACE inhibitor, with significantly higher rapid filling dV/dt values, and with the pressure loads equal (reduction of the slope and rightward shift of the correlation line). The improvement in diastolic function achieved by ACE inhibition at rest and during CPT appears unrelated to plasma catecholamines and only partly ascribable to the reduced pressure load. The tissue angiotensin II reduction might by itself improve the myocardial response to the pressure load and adrenergic stimulation.

Adult↗
PubMed1996

[Hyperthermia and palliative radiotherapy for sarcoma].

The current treatment of bone and soft tissue sarcomas consists of a multimodality approach based on the combination of surgery, radiotherapy and, more rarely, chemotherapy. Since local recurrence is an important cause of failure and morbidity, new treatment modalities such as hyperthermia, have been proposed to try to overcome this problem. July, 1982, to June, 1993, twelve patients (15 lesions) with recurrent or locally advanced sarcoma, were treated at the Department of Radiation Oncology, S. Chiara Hospital-Trento (Italy) with irradiation and hyperthermia. Radiation therapy was delivered with different techniques using palliative or radical doses (24-70 Gy) and different fractionation schedules. Local microwave hyperthermia was given in 2-9 sessions (mean 4.7). Eight (53.3%) complete responses and 4 (26.6%) partial responses were observed. Three lesions recurred at 11, 13, and 30 months; 5-year actuarial local control was 25.4 +/- 13.4%. Actuarial 5-year overall survival was 49.5 +/- 16.4%. Toxicity was mild: two superficial necroses, spontaneously healed after few months, were observed; local pain during hyperthermic treatment was recorded in 15% of sessions. Lesion volume and total radiation dose appeared to be correlated with the response. In our experience, the combination of radiotherapy and hyperthermia seems to be a valuable therapeutic approach in the treatment of locally advanced or recurrent sarcomas.

Actuarial Analysis↗
PubMed1995

Biogenic amines in the taste organ.

The presence and content of biogenic amines in taste disk-bearing fungiform papillae of the frog, Rana esculenta, the only available model of an isolated taste organ, were verified by means of HPLC. Fungiform papillae were found to contain measurable amounts of serotonin, epinephrine and norepinephrine. The amounts of serotonin and epinephrine were significantly higher in fungiform papillae than in the general mucosa of the tongue. Moreover, the epinephrine content of fungiform papillae was found to differ across the tongue, in accordance with previous physiological studies showing an inhomogeneous response of different tongue regions to taste stimuli. Ultrastructural and histochemical investigations confirmed the presence of catecholamine and serotonin. The latter was found to be contained mainly in the basal cells of the frog taste disk. These results extend previous qualitative data on the presence of biogenic amines in taste chemoreceptors.

Animals↗
PubMed1995

[Radiotherapy of T1N0 neoplasms of the glottis. Analysis of the parameters that influence local control].

Treatment and tumor-related parameters were reviewed in 176 patients with T1N0 carcinoma of the glottic larynx submitted to primary radiation therapy from 1980 to 1992. Our aim was to analyze local control and treatment-related toxicity. Over-all local control rates at 10 years were 88.3% with irradiation alone and 94.5% after salvage surgery (larynx preservation: 91%). Verrucous histology was a negative factor affecting local control and anterior commissure involvement exhibited only a negative trend but had no statistical significance. Among treatment-related factors, local control was 76.5% after split-course and 91.1% after continuous-course irradiation (p < 0.05). With continuous-course irradiation, the total dose influenced local control only for single of 2 Gy (local control rates were 69% with 60 Gy and 93% at > or = 64 Gy; p < 0.05), but not for single doses of 2.25 Gy and total doses ranging 56.25-65.25 Gy (local control failed in 55 patients). Early and late complications did not increase with single doses > or = 2.25 Gy. Our current policy in T1N0 nonverrucous glottic carcinoma is to use a single fraction of 2.25 Gy and a total dose ranging 56.25-63 Gy according to tumor size, with a continuous course.

Actuarial Analysis↗
PubMed1994

Stage I seminoma of the testis: long term results and toxicity with adjuvant radiotherapy.

AIMS AND BACKGROUND: Pure testicular seminoma has historically been treated with post-orchidectomy radiation therapy with excellent results. Recently, several aspects of the treatment of stage I seminoma have been questioned. We assessed long-term results and toxicity of patients with pure testicular seminoma treated at the Department of Radiation Oncology of S. Chiara Hospital, Trento, METHODS: From 1953 to 1987, 102 patients with stage I pure testicular seminoma were given megavoltage irradiation with curative intent. All patients had a minimum follow-up of 3 years (maximum 37 years, median 13 years). They received a mean para-aortic/pelvic dose of 33.07 Gy (range 23.70-45.20 Gy) with different doses and fields reflecting the change in techniques over a long period of time. RESULTS: The cause-specific actuarial survival at 30 years was 99% and crude survival 67%. One patient had an out-field relapse (inguinal) after a few months and was cured with radiotherapy and chemotherapy. Another patient relapsed with widespread metastases and died after 1 year of progressive disease. Early toxycity was mild and the treatment was well tolerated. Late side effects were reported in 8/102 patients. CONCLUSIONS: In our series adjuvant radiation therapy resulted in cure rates corresponding to those reported in the literature. The 30-year actuarial survival of 99% was extremely good and the toxicity of the treatment was mild. Post-orchidectomy radiation to the para-aortic and ipsilateral pelvic nodes is a safe and effective method of preventing recurrences and is currently to be considered the treatment of choice in stage I testicular seminoma.

Adult↗
PubMed1994

Glucose counterregulatory response to acute hypoglycemia in hyperthyroid human subjects.

To evaluate the impact of hyperthyroidism on the counterregulatory response to hypoglycemia, eight hyperthyroid and eight sex-, age-, and body mass index-matched healthy women were given an iv insulin bolus (0.1 U/kg BW), and blood was drawn from 0-120 min for glucose, epinephrine, norepinephrine, glucagon, GH, ACTH, and cortisol measurements. In the basal state plasma glucose, GH, and cortisol levels were similar in the two groups, whereas plasma glucagon and ACTH were increased (135 +/- 17 vs. 80 +/- 10 ng/L and 6.4 +/- 1.5 vs. 2.6 +/- 0.4 pmol/L, respectively; both P < 0.025), and plasma catecholamines were reduced [epinephrine, 142 +/- 25 vs. 371 +/- 71 pmol/L (P < 0.025); norepinephrine, 0.41 +/- 0.07 vs. 1.41 +/- 0.12 nmol/L (P < 0.001)] in hyperthyroid patients. After insulin injection, plasma glucose similarly declined in the two groups (nadir, 1.5 +/- 0.2 vs. 1.6 +/- 0.2 mmol/L). Conversely, recovery from hypoglycemia was significantly faster in the hyperthyroid patients. In this respect, it is noteworthy that the plasma glucagon response had remarkably increased in the latter (peak, 444 +/- 56 vs. 198 +/- 17 ng/L; P < 0.005). On the other hand, the epinephrine responses were similar in the two groups, whereas norepinephrine levels remained consistently lower (peak, 0.97 +/- 0.20 vs. 2.61 +/- 0.24 nmol/L; P < 0.001), and the GH increase was severely impaired (peak, 10.6 +/- 1.9 vs. 29.6 +/- 6.2 micrograms/L; P < 0.01) in hyperthyroid patients. Plasma ACTH remained slightly higher in hyperthyroid subjects, but there were no substantial differences in the cortisol response between the two groups. In conclusion, hyperthyroidism affects plasma levels of several counterregulatory hormones, either in the fasting state or after insulin-induced hypoglycemia, with increased efficiency of plasma glucose recovery from hypoglycemia.

Acute Disease↗
PubMed1993

Cisplatin, hyperthermia, and radiation (trimodal therapy) in patients with locally advanced head and neck tumors: a phase I-II study.

PURPOSE: Hyperthermia is now being widely used to treat clinical malignancies especially combined with radiotherapy and more rarely with chemotherapy. The combination of heat, radiation, and chemotherapy (trimodality) can lead to potent interaction. The present Phase I-II study was conducted to evaluate the feasibility and acute toxicity of a combination of cisplatin, hyperthermia, and irradiation in the treatment of superficial cervical nodal metastases from head and neck cancer. METHODS AND MATERIALS: Eighteen patients with measurable neck metastases from previously untreated squamous cell head and neck tumors were entered into the trial. Therapy consisted of a conventional irradiation (total dose 70 Gy, 2 Gy five times a week) combined with a weekly administration of 20 mg/m2 iv of cisplatin and a total of two sessions of local external microwave hyperthermia (desired temperature of 42.5 degrees C for 30 min). RESULTS: Feasibility of the treatment was demonstrated. Acute local toxicity was mild; no thermal blisters or ulcerations were reported and only two patients experienced local pain during hyperthermia. Cutaneous toxicity appeared greater than in our previous studies with irradiation plus hyperthermia and irradiation plus cisplatin. Systemic toxicity was moderate with major toxic effects observed in three patients (World Health Organization (WHO) grade 3 anaemia). Even though it was not an aim of the study to evaluate the nodal response, we observed a complete response rate of 72.2% (95% confidence interval 51-93.4%), 16.6% of partial response and 11.1% of no change. CONCLUSION: The study confirms the feasibility of the combination of cisplatin, heat, and radiation with an acceptable toxicity profile. The trimodal therapy deserves further evaluation as a way to enhance the efficacy of irradiation in the treatment of nodal metastases from head and neck tumors.

Adult↗
PubMed1993

Influence of dietary taurine on vitamin D absorption.

To evaluate the influence of dietary taurine supplementation on vitamin D absorption, we studied three groups of infants: 21 (11 preterm) were fed a taurine-free formula, 21 (10 preterm) were fed a taurine-supplemented formula (50 mg/100 g of powder) and 20 (9 preterm) were fed human, not heat-treated milk. Taurine, total bile acids, glyco-(GBA) and tauro-(TBA) conjugated bile acids, 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 (1,25OH2D3) were determined in all infants at birth in blood cord and at one and three months of life. In preterm infants fed a taurine-free formula, we found lower plasma taurine levels than in infants of other groups at one and three months of life. In these infants, GBA predominated, with a G/T ratio of 1.1 and 1.4 at one and three months of life, whereas in all other infants TBA predominated with a G/T ratio always < 1. Also, 25OHD3 and 1,25OH2D3 levels were significantly lower in preterm infants fed a taurine-free formula than in infants fed a taurine-enriched formula or human milk. Term infants fed a taurine-free formula did not show differences in the parameters studied in comparison to infants of other groups. Low taurine dietary intake appears to compromise vitamin D absorption in preterm infants, and therefore taurine supplementation of preterm infant formulas should be encouraged.

Bile Acids and Salts↗