PubMed Health⌕ Search

Biomedical subjects

G De Palma

Publications and source records attributed to G De Palma.

At least 19 recordsLinked to original sources

Perceptions of veterinarians and clients to expressions of clinical uncertainty.

OBJECTIVES: The aim of this study was to explore the attitudes of veterinarians and clients towards expressions of clinical uncertainty. METHODS: Questionnaires that assessed the respondent's attitudes towards expressions of clinical uncertainty were completed by clients at six small animal practices. In addition, questionnaires that evaluated what veterinarians thought their client's attitudes would be towards expressions of clinical uncertainty were completed by veterinarians. The responses from clients and veterinarians were statistically compared. RESULTS: Veterinarians significantly underestimated the desire of clients to be told about uncertainties in treatment and significantly overestimated how the expression of uncertainty would generally reduce client confidence. Veterinarians significantly overestimated the loss of client confidence resulting from saying "I am not sure about this" and from asking a nurse for advice. Both clients and veterinarians considered that verbal expressions of uncertainty would lead to a greater reduction in client confidence than behavioural expressions of uncertainty. CLINICAL SIGNIFICANCE: This study suggests that most clients want to be told about their veterinarian's clinical uncertainties, and how this uncertainty is expressed can markedly influence client confidence.

Attitude of Health Personnel↗

Mean and long-term results of the surgical treatment of early gastric cancer.

AIM: Interest in the diagnosis and treatment of early gastric cancer (EGC) has been steadily increasing due to the high 5-year survival rate which can reach 85-100% after curative resection. The aim of this retrospective study was to analyze the clinical and histologic characteristics as well as the results of 45 patients undergoing surgical resection for EGC. METHODS: Between 1998 and 2004, 45 patients, 14 females and 31 males with a mean age of 60.2+/-15 years (range: 31-85) were recruited. Subtotal gastrectomy was performed in 28 (62.2%) patients and total gastrectomy in 17 (37.3%). D1 and D2 resections were performed in 36 and 9 patients, respectively. The carcinoma was limited to the mucosa in 26 (57.8%) patients and extended into the submucosa in 19 (42.2%). Lymph node invasion occurred in 4 (8.8%) patients. Mean follow-up was 36 months (range: 3-63). Survival was calculated using the Kaplan-Meier method. Multivariate analysis of clinic and histologic factors was performed to identify predictive factors for survival. RESULTS: The 5-year actuarial survival rate was 85% and there was no postoperative mortality. Statistical analysis did not demonstrate any significant statistical relationship between survival and parietal penetration (P = 0.67) or superficial extension (P = 0.38) of the tumor. Survival was clearly influenced (P < 0.001) by lymph node involvement. CONCLUSIONS: Prognosis of EGC is usually excellent but can be influenced by the presence of lymph node metastases.

Journal Article↗

Glutathione S-transferases M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals.

AIMS: To investigate the possible interaction between occupational risk factors and genotype for glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) in renal cell cancer (RCC). METHODS: One hundred patients with RCC and 200 outpatient controls were enrolled at Parma University Hospital. The polymorphisms of glutathione S-transferase M1-1 (GSTM1) and T1-1 (GSTT1) were investigated by PCR; occupational history was collected by a structured questionnaire. RESULTS: Subjects with GSTM1 present genotype showed higher risks for RCC, compared to GSTM1 null subjects, if exposed to metals (OR 2.73; 95% CI 0.91 to 8.22 v 1.14; 95% CI 0.46 to 2.82) or pesticides (OR 3.46; 95% CI 1.12 to 10.74 v 1.59; 95% CI 0.48 to 5.34). The GSTT1 present genotype also enhanced the risk (about twofold) of RCC among subjects exposed to solvents and pesticides, compared with those GSTT1 null. CONCLUSIONS: Results support the hypothesis that GSTM1 and GSTT1 polymorphisms can interact with several occupational exposures to significantly modify the risk of RCC among exposed subjects.

Aged↗

Polymorphism of xenobiotic-metabolizing enzymes and excretion of styrene-specific mercapturic acids.

The role of polymorphic xenobiotic-metabolizing enzymes in the interindividual variability of phenylhydroxyethyl mercapturic acids (PHEMAs) was investigated in 56 styrene-exposed workers. Ambient monitoring was carried out using passive personal samplers (geometric mean, 157 mg/m3 8-h time-weighted average; geometric standard deviation, 2.90). Biomonitoring was based on mandelic acid and phenylglyoxylic acid in urine spot samples collected at the end of the work shift ("end-of-shift") and prior to the subsequent shift ("next morning"). Four PHEMA diastereoisomers, namely (R,R)-M1, (S,R)-M1, (S,R)-M2, and (R,R)-M2, were determined by HPLC/tandem mass spectrometry. The genotypes of glutathione S-transferases M1-1 (GSTM1), T1-1 (GSTT1) and P1-1 (GSTP1), and microsomal epoxide hydrolase (EPHX) were characterized by PCR-based methods. Workers bearing the GSTM1pos genotype showed PHEMA concentrations five and six times higher (in end-of-shift and next-morning samples, respectively) as compared to GSTM1null people. In GSTM1pos subjects, (R,R)-M1 was the main mercapturate affected by the GSTM1 status, accounting for 54 and 68% of total PHEMAs in end-of-shift and next-morning samples, respectively. Compared to GSTM1null, GSTM1pos subjects excreted more -M1 than -M2 and more (R,R)-M1 and (S,R)-M2 than (S,R)-M1 and (R,R)-M2 diastereoisomers. Thus, GSTM1-1 is the main isoenzyme catalyzing GSH-conjugation of styrene-7,8-oxide in humans and it seems to act in a regio- and stereoselective way. PHEMAs cannot be recommended as biomarkers of exposure to styrene, unless the GSTM1 genotype is considered in data interpretation. Their role as biomarkers of susceptibility deserves further studies.

Acetylcysteine↗

Polymorphism of quinone-metabolizing enzymes and susceptibility to ozone-induced acute effects.

The role of the genetic polymorphism of NAD(P)H:quinone oxidoreductase (NQO1) and glutathione-S-transferase micro-1 (GSTM1) in the responsiveness to O(3)-induced acute effects was investigated in 24 healthy nonsmokers performing 2-h bike rides at ambient O(3) varying from 32 to 103 ppb. Before and after rides, each subject performed spirometric tests and provided a blood sample for the measurement of the Clara cell protein CC16. NQO1 and GSTM1 polymorphisms were characterized by polymerase chain reaction- based methods. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct was also measured in DNA of peripheral leukocytes. Rides at O(3) > 80 ppb resulted in significant decrements of pulmonary function tests and increased levels of serum CC16, consistent with mild impairment in respiratory function and increased lung epithelial permeability, respectively. Whereas NQO1wt and GSTM1null subjects showed both functional changes and increased serum CC16 after acute O(3) exposure, people with other haplotypes showed a rise in serum CC16 but no changes in lung function tests. In NQO1wt and GSTM1null subjects, partial correlation analysis showed that functional decrements and increased serum CC16 are closely associated with each other and with O(3) levels, whereas no such relationships were found among subjects bearing other haplotypes. An increased reaction rate between O(3) and hydroquinones would be consistent with the greater increase in 8-OHdG after O(3) exposure in this "susceptible" group.

8-Hydroxy-2'-Deoxyguanosine↗

A new method for the analysis of styrene mercapturic acids by liquid chromatography/electrospray tandem mass spectrometry.

A new method based on liquid chromatography/tandem mass spectrometry has been developed for the direct determination of specific urinary mercapturic acids arising from the conjugation of (R)-and (S)-enantiomers of styrene 7,8-oxide with glutathione (GSH), i.e. (R,R)- and (S,R)-N-acetyl-S-(1-phenyl-2-hydroxyethyl)cysteine (R,R-M1 and S,R-M1) and (R,R)- and (S,R)-N-acetyl-S-(2-phenyl-2-hydroxyethyl)-cysteine (R,R-M2 and S,R-M2). The four diastereoisomers were separated on a C18-DB (7.5 cm, 3 microm) column using variable proportions of 20 mM aqueous ammonium formate buffer and methanol at a flow-rate of 0.5 mL/min. The analytes were ionized by electrospray, in negative-ion mode. Operating in selected-reaction monitoring mode, linearity of the MS response versus analyte concentration was established over 4 orders of magnitude, the detection limits being 0.7-1.0 microg/L for all the mercapturates. Precision of the method determined at 50 microg/L (n = 12), expressed as relative standard deviation, was respectively 3.1, 4.8 and 6.9% within the run, intra-day and inter-day. The corresponding figures at 1.0 mg/L (n = 12) were respectively 2.0, 3.6 and 5.5%. The method was applied to the quantitative analysis of conjugated metabolites in urine samples from workers occupationally exposed to styrene. The diastereoisomers R,R-M1 and S,R-M2 accounted respectively for 50 and 40% of total mercapturates, whereas the proportion of R,R-M2 was 7% and only minor amounts of S,R-M1 were detectable. Styrene mercapturates represented a minor fraction of total styrene metabolites, less than 1% on average. The ratio mercapturates/main metabolites (mandelic + phenylglyoxylic acid) showed a bimodal distribution, the medians of the two subgroups being 0.2 and 1%, respectively. Such subgroups are probably characterized by the genetic polymorphisms of the drug-metabolizing enzymes to be identified.

Acetylcysteine↗

8-OH DPAT can restore the locomotor stimulant effects of cocaine blocked by haloperidol.

In the first experiment, separate groups of rats (n = 7) were treated with either saline, cocaine (10 mg/kg), haloperidol (0.1 mg/kg), or cocaine (10 mg/kg) plus haloperidol (0.1 mg/kg). Locomotor behavior was measured in an open-field environment, and cocaine induced a reliable locomotor stimulant effect compared to saline-treated animals. Haloperidol produced a progressive decline in locomotion over the 5 test days. Haloperidol also blocked cocaine stimulant effects compared to cocaine-treated animals. In the second experiment, five groups (n = 7) of animals were treated either with saline, cocaine (10 mg/kg), 8-OH DPAT (0.2 mg/kg), 8-OH DPAT (0.2 mg/kg) plus haloperidol (0.1 mg/kg), or 8-OH DPAT (0.2 mg/kg) plus haloperidol 0.1 mg/kg plus cocaine (10 mg/kg). Over the course of 5 days of treatment, cocaine induced a locomotor stimulant effect. Saline and 8-OH DPAT animals did not differ in terms of locomotion. The 0.1 mg/kg haloperidol plus 0.2 mg/kg 8-OH DPAT treatment decreased locomotion compared to the saline group, but the group given 0.2 mg/kg 8-OH DPAT plus 0.1 mg/kg haloperidol plus cocaine (10 mg/kg) exhibited a locomotor stimulant effect equivalent to the cocaine group. In a third experiment, it was found that the 0.2 mg/kg 8-OH DPAT treatment did not enhance the locomotor stimulant effect of cocaine. Thus, the 8-OH DPAT treatment was able to restore a cocaine locomotor stimulant effect in animals treated with haloperidol without directly enhancing the locomotor stimulant effects of cocaine. In Experiments 2 and 3, entries into the central zone of the open field were measured. Cocaine reliably increased central zone entries. The 8-OH DPAT treatment, however, selectively blocked this behavioral effect of cocaine suggesting a qualitative influence of 5-HT(1A) receptors upon cocaine, independent of locomotion activation by cocaine. Ex vivo measurements of dopamine and 5-hydroxytryptamine metabolism in limbic tissue were consistent with the established effects of cocaine, haloperidol, and 8-OH DPAT upon dopamine and 5-hydroxytryptamine neurotransmission. In addition, measurement of cocaine brain concentration indicated that neither haloperidol or 8-OH DPAT affected cocaine concentration in brain.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Biomarkers of dose and susceptibility in cyclists exposed to monoaromatic hydrocarbons.

A quasi-experimental field study was carried out in 24 volunteers with the aim of: (i) assessing personal exposure to aromatic hydrocarbons polluting urban areas; and (ii) exploring the role of polymorphic enzymes relevant to the biotransformation of benzene in the inter-individual variability of biomarkers. Each subject covered by bicycle: (i) inner city routes with often jammed traffic; and (ii) open rural routes. Time-weighted average airborne concentrations of benzene, toluene, ethylbenzene and xylenes (BTEX) were determined during 2-h runs. BTEX were determined by solid-phase micro-extraction (SPME) followed by gas chromatography coupled with mass spectrometry (GC-MS) in blood and spot urine samples collected just before and immediately after the runs. Urinary t,t-muconic acid was measured by high performance liquid chromatography (HPLC)-UV. Genotypes of epoxide hydrolase (EH) and glutathione-S-transferase class mu-1 (GSTM1) were also characterised. As compared to pre-run values, benzene and toluene in blood, and toluene and xylenes in urine significantly increased after urban runs. Urinary t,t-muconic acid was significantly higher in post-run samples after both urban (P < 0.001) and rural runs (P < 0.05). Despite a narrow range of exposure levels, a significant relationship was observed between airborne benzene and post-run t,t-muconic acid (r2 = 0.349, P < 0.00). When subgroups were distinguished according to EH and GSTM, subjects bearing both the EH wild type and GSTM 'null' genotype showed significant exposure-related changes in t,t-muconic acid excretion. Even at very low exposure levels, a 2-h bike run in a polluted urban environment may give rise to measurable changes in biomarkers of internal dose of selected aromatic hydrocarbons. Genetically-based metabolic differences may account for part of the inter-individual variability of biomarkers of exposure.

Adult↗

[Palliative surgical treatment of thoracic esophageal cancer].

BACKGROUND: Esophageal carcinoma is frequently diagnosed at an advanced stage, therefore most patients may only benefit from surgical or endoscopic palliation. METHODS: From 1982 to 1998, out of 247 patients who underwent palliation for thoracic esophageal carcinoma, 29 (11.7%) underwent surgical palliation. Eight received a palliative resection, 10 a bypass, 5 a jejunostomy and 6 a gastrostomy. A retrosternal transposition of the stomach (17 patients) and colon (1 patient) was performed. In 15 out of 29 patients palliation was decided during surgical exploration. All resected patients underwent postoperative radiotherapy (400 Gy) while 3 received also preoperative chemotherapy (PDD and % FU). RESULTS: Seven temporary neck fistulas and 9 cardiorespiratory complications were recorded. Two patients (11%) died of severe cardiac and respiratory insufficiency. Mean survival for resected patients was 12.5 months (range 3-21), higher than for bypass (11.5 months; range 3-18) and for jejunostomy or gastrostomy (5 months; range 2-12). CONCLUSIONS: Palliative resection, when technically feasible, is the treatment of choice in advanced thoracic esophageal carcinoma in selected patients. The type of procedure to be performed depends on site, extent of the disease and surgeon's experience together with the quality of life expected by the patient.

Aged↗

Endoscopic and surgical palliation of esophageal cancer.

BACKGROUND: Esophageal carcinoma is frequently diagnosed at an advanced stage. Therefore for most patients either surgical or endoscopic palliation with or without radiochemotherapy may be taken into consideration. This retrospective study analyzes immediate and long term results of perendoscopic treatment in patients with unresectable esophageal cancer. Moreover a comparative analysis has been made with a group of patients who underwent palliation surgery. METHODS: From 1982 to 1998 458 patients with esophageal cancer underwent palliation perendoscopic disobstructive treatment (427 patients), palliation surgery (29 patients) and dis-obstruction followed by perendoscopic gastrostomy (2 patients). Among patients treated by perendoscopic procedures, 18 underwent dilation, 53 dilation and radiotherapy, 236 stent implantation, respectively of the plastic (102) and self-expandable metallic (134) type. 120 patients underwent NdYAG laser treatment. RESULTS: The results for patients who underwent perendoscopic procedures are referred to as regards the first 30 days after treatment and on the long run in terms of grade of dysphagia according to Visick's scale. For the group of patients undergoing simple dilation we had an improvement (from Visick III-IV to I-II) in 33% of cases and in 54.7% when radiotherapy was added. Far better results were achieved in all groups undergoing stent implantation, with or without brachytherapy, and NdYAG laser treatment with or without previous chemical necrolysis (range 90.3-100%). Most frequent complications were obstruction and stent displacement. Mean survival was better for patients undergoing laser recanalisation (7.2 months) while among stents the metallic type has given better results than plastic ones both for survival (6.2 vs 5.9 months) and mortality (2.4 vs 4.9%). Comparison with the group undergoing palliation surgery has shown that mean survival is the same for patients undergoing jejunostomy or gastrostomy while it is significantly better for patients undergoing palliation resection or by-pass surgery compared with those treated by stent implantation or laser recanalisation. CONCLUSIONS: The palliation treatment of patients with esophageal and cardial carcinoma is still a complex problem as far as therapeutic strategy is concerned. The best palliation is surgery even though characterized by a greater morbidity and mortality compared with perendoscopic techniques that may represent, in selected cases, a suitable alternative.

Journal Article↗

Effectiveness of very low doses of immunotherapy in advanced renal cell cancer.

Twenty-one nephrectomized patients with metastatic renal cell cancer were treated with recombinant interleukin 2 (rlL-2) and interferon alpha (rIFN alpha). rIL-2 was administered s.c. at a dose of 1 x 10(6) IU m(-2) every 12 h on days 1 and 2, followed by 0.5 x 10(6) IU twice daily on days 3-5; rIFN alpha-2 was given i.m. as 1.8 x 10(6) IU m(-2) on days 3 and 5 of each week for 4 consecutive weeks. The cycle was regularly repeated at 4-month intervals and continued ad libitum in patients showing some response and in patients with progressing disease. Of 20 patients evaluable for treatment response, one (5%) had a complete response and three (15%) showed partial response. Three patients (15%) achieved stable disease and 13 (65%) were evaluated as having progressive disease. The estimated actuarial 44-month survival rate was 44%. Toxicity was limited to WHO grades 1 and 2 only.

Adult↗

Thyroid imaging with Tc-99m MIBI in patients with solitary cold single nodules on pertechnetate imaging.

Thyroid imaging was performed in 30 patients with the standard pertechnetate technique, as well as with Tc-99m MIBI using a double-phase acquisition protocol. All patients had normal thyroid function confirmed by hormone measurements and cold solitary thyroid nodules, which were evaluated by pertechnetate scanning. Tc-99m MIBI scans were reported as showing cold (N = 14), warm (N = 7), or hot (N = 9) nodules. Nodule classification was made according to fine needle aspiration biopsy findings in 20 patients. The remaining 10 proceeded to surgery and had histopathologic confirmation of their lesions. Although all cold nodules with Tc-99m MIBI were cystic, six of the warm nodules were benign lesions. No histologically proven benign nodule was hot with Tc-99m MIBI. Of the hot nodules, seven were suspicious for follicular carcinoma with fine needle aspiration biopsy (N = 3), or had histologically proven papillary carcinoma (N = 4). Delayed images in five of seven of these lesions showed nodular retention of the radiopharmaceutical. In conclusion, double-phase Tc-99m MIBI scanning of the thyroid gland could be helpful in the preoperative assessment of patients with cold solitary thyroid nodules in order to evaluate the malignancy probability of these lesions.

Adenocarcinoma, Follicular↗

Laparoscopic cholecystectomy in obese patients compared with nonobese patients.

Obese patients treated by laparoscopic cholecystectomy currently appear to be the largest risk subgroup amenable to consistent scientific evaluation. Here we report our experience and compare the results in obese patients with those obtained in nonobese patients undergoing the laparoscopic procedure. Laparoscopic cholecystectomy in obese patients was technically more difficult with significantly longer operating time (p < 0.01), but intraoperative and postoperative technical complications were not significant in the groups analyzed. Obese patients present significant anesthesiological complications (p < or = 0.001). The results of this experience and the literature review indicate that the therapeutic advantages proved in nonobese patients can be extended to the obese population.

Adult↗

Cocaine stimulant effects vary with cocaine levels in medial prefrontal cortex.

Rats treated with 10 mg kg-1 cocaine exhibited hyperlocomotion. Individual variation in the magnitude of this response was not correlated with serum cocaine concentration. Brain cocaine concentration, particularly in the medial prefrontal cortex, was highly correlated with the cocaine-induced locomotor stimulant effect. These findings indicate that variation in the uptake of cocaine into the brain is a critical variable in determining individual variation in its stimulant effects.

Animals↗

Tc-99m isonitrile uptake in a brain metastatic lesion. Comparison with Tc-99m DTPA using planar and SPECT imaging.

Tc-99m isonitrile uptake in a metastatic brain tumor is demonstrated using planar and SPECT imaging. Comparison with Tc-99m DTPA shows a different distribution pattern and uptake intensity, suggesting a different mechanism for both tracers. It is possible that Tc-99m CPI could reflect metabolic activity of the tumor cells and might be useful to evaluate the grade of malignancy as well as the recurrence of brain tumors.

Brain Neoplasms↗