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1.
J Pain Res ; 12: 117-125, 2019.
Article in English | MEDLINE | ID: mdl-30613160

ABSTRACT

BACKGROUND: Previous studies have shown the efficacy of tapentadol (TP) for chronic cancer pain. We evaluated multiple effectiveness aspects of TP prolonged release on moderate-severe cancer-related pain, neuropathic pain (NeP), patient satisfaction, and quality of life. METHODS: An observational prospective study was conducted on 80 cancer patients. Opioid-naïve patients received a starting dose of prolonged-release TP 50 mg twice daily, and opioid-experienced patients were switched to TP, not to exceed 500 mg/day. Treatment response was evaluated at 3, 6, 30-40, and 60-70 days through response rate, numeric rating-scale scoring, survival analysis (time to event for response), pain-intensity difference, TP escalation-index percentage, and effects on NeP. The drug-sparing effect on concomitant therapies was evaluated. RESULTS: Seventy of 80 patients (88%) were responders to treatment (95% CI 78%-94%). Compared to T0, pain-intensity reductions were statistically significant for all intervals (P<0.01), with better results at T3/T4. NeP was significantly reduced at T4 (P<0.01). The probability of response was low at the initial stages and increased during the study. Pain-intensity differences decreased during the study, though without significance. Two patients (2.5%) left the study for TP-induced side effects. A significant improvement in quality of life was observed after 30-40 days (P<0.01). The majority of patients were "satisfied", "very satisfied", or "extremely satisfied" (T3-T4). CONCLUSION: TP was effective in terms of drug-sparing effect, response rate, TP escalation-index percentage, and NeP management. By comparing data from the survival analysis with the response rate and time to response (numeric rating scale from T0 to T4), we found that although TP induced a quick response, a longer period of therapy and higher doses were needed to improve the positive result.

2.
Aliment Pharmacol Ther ; 47(11): 1464-1471, 2018 06.
Article in English | MEDLINE | ID: mdl-29655196

ABSTRACT

BACKGROUND: Nonsteroidal anti-inflammatory drugs, low-dose aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors and corticosteroids increase the risk of gastroduodenal bleeding. AIM: To determine in a retrospective cohort study the contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients taking these drugs. METHODS: Among patients with peptic ulcer disease diagnosed by endoscopy from 01/2004 to 12/2014 (N = 1719, 60% males, age 65.8 ± 14.5), 56.9% had peptic ulcer bleeding (cases) and 43.1% uncomplicated peptic ulcer disease (controls). Demographics, intake of nonsteroidal anti-inflammatory drugs, aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors, proton pump inhibitors and corticosteroids were documented. H. pylori status was determined by histology, rapid urease test or serology. Adjusted odds ratios (OR) were estimated by logistic regression analysis. RESULTS: Helicobacter pylori infection increased the risk of peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users (OR = 2.91, 95% CI = 1.71-4.98 and OR = 2.23, 95% CI = 1.52-3.28, respectively), but not in patients on anticoagulants, selective serotonin reuptake inhibitor or corticosteroid therapy. H. pylori-positive status substantially increased the risk of peptic ulcer bleeding in patients on non-aspirin antiplatelet agents (OR = 4.37, 95% CI = 1.28-14.99), concomitant aspirin/nonsteroidal anti-inflammatory drug intake (OR = 5.85, 95% CI = 1.68-20.36) and combined antiplatelet therapy (OR = 8.43, 95% CI = 1.09-65.17). After further adjustment for proton pump inhibitor intake, H. pylori infection was still a risk factor for peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users. CONCLUSIONS: Helicobacter pylori infection increases the risk of peptic ulcer bleeding in peptic ulcer disease patients on nonsteroidal anti-inflammatory drugs, aspirin and non-aspirin antiplatelet agents. H. pylori-positive patients on combined antiplatelet therapy carry the highest risk for peptic ulcer bleeding.


Subject(s)
Adrenal Cortex Hormones/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anticoagulants/adverse effects , Helicobacter Infections/epidemiology , Peptic Ulcer Hemorrhage/epidemiology , Platelet Aggregation Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/adverse effects , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anticoagulants/therapeutic use , Cohort Studies , Female , Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Helicobacter pylori , Humans , Male , Middle Aged , Peptic Ulcer Hemorrhage/chemically induced , Platelet Aggregation Inhibitors/therapeutic use , Retrospective Studies , Risk Factors , Selective Serotonin Reuptake Inhibitors/therapeutic use
3.
Clin Ter ; 168(2): e136-e139, 2017.
Article in English | MEDLINE | ID: mdl-28383626

ABSTRACT

Primary testicular lymphoma (PLT) represents 5% of testis tumors, the incidence increases in patients older than 60 years of age. Bilateral hydrocele is an unusual clinical presentation. Relapse in the central nervous system and in the contralateral testis is often observed. The US shows hypoechoic nodular lesions with a complete structural involvement of didymus and hypervascularization at Color Doppler. Orchiectomy should be performed in all cases as it is indispensable for the histopathological diagnosis and to characterize the immunophenotypic features. The most common histotype is diffuse large-B cell lymphoma. Combined biological approach and chemotherapy with rituximab and doxorubicin has radically changed the prognosis of disease. The authors report two patients of 81 and 82 years-old who referred for evaluation of massive bilateral hydrocele causing severe limitation of deambulation. Negative cytological findings for neoplastic cells in the scrotal effusion made difficult the differential diagnosis between inflammatory and malignant disease. Histopathologic findings made a diagnosis of high grade diffuse large B-cell NHL, respectively stage IV-E and stage III-E. The 82 years old patient was treated with 6 chemotherapy cycles of rituximab, cyclophosphamide, vincristine, prednisone. The exitus was dued to the umbilical hernia complications. In the 81 years old patient, cognitive deficit and severe impairment of general conditions constituted an absolute contraindication to polychemotherapy treatment. Rapid tumor progression led the patient to exitus 2 months after diagnosis. In both patients the delayed diagnosis of PLT was probably due to the reduction of welfare protection in the elderly with adverse social conditions.


Subject(s)
Lymphoma, Large B-Cell, Diffuse/diagnosis , Testicular Hydrocele/diagnosis , Testicular Neoplasms/diagnosis , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Neoplasm Recurrence, Local , Prednisone/administration & dosage , Prognosis , Rituximab/administration & dosage , Vincristine/administration & dosage
4.
Rhinol Suppl ; 54(26): 1-30, 2017 03.
Article in English | MEDLINE | ID: mdl-29528615

ABSTRACT

Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: • Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. • Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. • Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. • Comprehensive chemosensory assessment should include gustatory screening. • Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.


Subject(s)
Olfaction Disorders/diagnosis , Olfaction Disorders/therapy , Humans , Neuropsychological Tests , Olfactometry , Olfactory Perception , Quality of Life
5.
Rhinology ; 56(1): 1-30, 2016 01 31.
Article in English | MEDLINE | ID: mdl-28623665

ABSTRACT

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

6.
Pathol Res Pract ; 209(6): 393-6, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23642451

ABSTRACT

Extraskeletal osteosarcoma (ESOS) is a malignant mesenchymal tumor in which neoplastic cells produce bone osteoid in variable amounts. An 81-year-old woman presented with severe abdominal pain, tenesmus, constipation and rectal bleeding. The digital rectal exploration showed a large lesion of hard consistency, occupying the lumen, with the presence of splinters that "pierced" the endoscopist's glove. Endoscopic examination and CTscan revealed an ulcerative exophytic neoplasia of the lower rectum in which multiple calcified areas were found. The lesion showed no bone involvement. An abdominal perineal resection sec Miles was performed. The histological examination revealed a highly cellular mesenchymal lesion, with spindle and epithelioid cells with moderate nuclear pleomorphism. The calcified component consisted of widespread osteoid deposition. The immunohistochemical investigations of neoplastic cells showed strong positivity for vimentin and osteonectin. The definitive histological diagnosis of primary extraskeletal osteosarcoma arising from the colon-rectum was made. To our knowledge, only one previous case of colonic osteosarcoma was published in the literature in 2001, reported by Shimazu and other authors. The extreme rarity of the tumor at this location, also confirmed by morphological and immunohistochemical data, prompted us to present this case report and to review the literature.


Subject(s)
Colorectal Neoplasms/pathology , Ossification, Heterotopic/pathology , Osteosarcoma/pathology , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Chemotherapy, Adjuvant , Colectomy , Colorectal Neoplasms/chemistry , Colorectal Neoplasms/therapy , Digital Rectal Examination , Fatal Outcome , Female , Humans , Immunohistochemistry , Osteosarcoma/chemistry , Osteosarcoma/therapy , Tomography, X-Ray Computed , Treatment Outcome
7.
Curr Med Chem ; 19(7): 961-71, 2012.
Article in English | MEDLINE | ID: mdl-22214464

ABSTRACT

Bevacizumab is a monoclonal antibody directed against Vascular Endothelial Growth Factor (VEGF). Evidence about its efficacy in addition to first-line chemotherapy in non-small-cell-lung-cancer (NSCLC) has been produced by two large randomized phase III clinical trials (ECOG 4599 and AVAiL), conducted in a clinically selected population with non-squamous histology and without major risk factors for bleeding. In the ECOG 4599 trial, the addition of bevacizumab (15 mg/kg) to carboplatin plus paclitaxel produced a statistically significant and clinically relevant improvement in overall survival (OS), that was the primary endpoint of the trial (12.3 months vs 10.3 months, HR 0.79; p=0.003). Furthermore, patients receiving bevacizumab showed a significant improvement in progression-free survival (PFS) and in objective response rates. Treatment with bevacizumab was well tolerated by the majority of patients, but was still associated with increased risk of clinically significant bleeding (4.4% vs 0.7%, p0.001). In the AVAiL trial the addition of bevacizumab (at the dose of 7.5 and 15 mg/kg) to cisplatin plus gemcitabine produced a small improvement in PFS, but no differences in OS. Information from retrospective analysis and two large observational studies (SAIL and ARIES) have confirmed the safety profile of first-line bevacizumab with a wide range of chemotherapy partners, but whether its efficacy is comparable when combined with the different regimens is still unknown. The identification of predictive factors of efficacy would be relevant for the optimal use of the drug, but to date we have no conclusive data in this direction.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Bevacizumab , Clinical Trials as Topic , Disease-Free Survival , Hemorrhage , Humans
8.
Diabetes Obes Metab ; 13(5): 408-17, 2011 May.
Article in English | MEDLINE | ID: mdl-21226821

ABSTRACT

AIMS: Peptide YY (PYY) is an endogenous anorectic gut-secreted peptide that has been shown to suppress appetite in animals and humans, when given by injection. This study tested if needle-free pulmonary delivery of PYY enables food intake suppression and reduced body weight gain in rats. The PYY pharmacokinetics and effects on brain neuropeptide levels were also examined. METHODS: Rats received single or once-daily 7-day pulmonary administration of saline or PYYs. Food intake and body weight gain were monitored to study the effects of different doses (0.08-0.90 mg/kg) of PYY3-36, PYY1-36 and PYY13-36. Plasma PYY pharmacokinetics were determined via enzyme-linked immunosorbent assay. Changes in orexigenic neuropeptide Y (NPY) and c-Fos protein levels in the hypothalamus arcuate nucleus (ARC) were measured by immunofluorescence microscopy. RESULTS: PYY3-36 caused dose-dependent and 4- to 6-h food intake suppression following pulmonary delivery. At 0.80 mg/kg, the effect was significant with 35.1 ± 5.7 and 19.7 ± 4.2% suppression at 4 and 6 h, respectively. Repeated administration for 7 days reduced cumulative body weight gain by 39.4 ± 11.0%. PYY1-36, but not PYY13-36, was equipotent to PYY3-36 in food intake suppression. The plasma PYY concentration reached its peak at 10 min following pulmonary delivery with 12-14% of bioavailability. Increased c-Fos and reduced NPY expressions were observed in the hypothalamus ARC, consistent with the magnitude of food intake suppression by each of the PYYs. CONCLUSIONS: Pulmonary delivery of PYY enabled significant 4- to 6-h food intake suppression via 12-14% of lung absorption and hypothalamic ARC interaction, leading to reduced body weight gain in rats.


Subject(s)
Appetite Regulation/drug effects , Arcuate Nucleus of Hypothalamus/drug effects , Feeding Behavior/drug effects , Neuropeptide Y/metabolism , Peptide YY/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Weight Gain/drug effects , Animals , Arcuate Nucleus of Hypothalamus/metabolism , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Microscopy, Fluorescence , Neuropeptide Y/drug effects , Peptide Fragments/pharmacology , Peptide YY/administration & dosage , Peptide YY/pharmacokinetics , Proto-Oncogene Proteins c-fos/drug effects , Rats
9.
Drugs Today (Barc) ; 46(9): 683-98, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20967300

ABSTRACT

Vandetanib is an oral inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), epidermal growth factor receptor (EGFR) and Ret tyrosine kinases involved in tumor growth, progression and angiogenesis. Phase I studies indicated that the recommended dose of vandetanib as a single agent is 300 mg/day. Rash, diarrhea, hypertension and asymptomatic Q-Tc prolongation were the most common adverse events. Four randomized phase III clinical trials evaluated the efficacy of vandetanib in non-small cell lung cancer (NSCLC) in combination with docetaxel (ZODIAC), pemetrexed (ZEAL) or as a single agent (ZEST and ZEPHYR). Only the ZODIAC trial met its primary endpoint (progression-free survival [PFS]), while no study showed an advantage in overall survival with vandetanib. No significant antitumor activity has been observed in small cell lung cancer, advanced ovarian, colorectal, breast, prostate cancer and multiple myeloma. In advanced metastatic medullary thyroid cancer, one randomized phase III clinical trial has demonstrated that vandetanib can significantly improve response rate, PFS and time to worsening of pain. Several key questions remain to be addressed regarding the identification of clinical or molecular biomarkers predictive of response, the choice of the optimal dose or schedule of vandetanib and the safety of long-term administration. The results of ongoing trials in untreated patients with advanced NSCLC and other tumors should better define the optimal clinical application of vandetanib.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Neoplasms/drug therapy , Piperidines/therapeutic use , Quinazolines/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/mortality , Clinical Trials as Topic , Humans , Lung Neoplasms/mortality , Piperidines/administration & dosage , Quinazolines/administration & dosage
10.
Fitoterapia ; 78(2): 159-61, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17161920

ABSTRACT

The antifungal activity of methanolic extract and alkaloidal fraction of Berberis aetnensis against Candida species was investigated. The crude extract was active against Candida species, this activity being higher than that of the alkaloidal fraction and berberine.


Subject(s)
Antifungal Agents/pharmacology , Berberis , Candida/drug effects , Phytotherapy , Plant Extracts/pharmacology , Antifungal Agents/administration & dosage , Antifungal Agents/therapeutic use , Candida/classification , Humans , Microbial Sensitivity Tests , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Plant Roots
11.
J Chemother ; 18(2): 164-71, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16736885

ABSTRACT

Propolis is produced by bees and is reported to have several pharmaceutical properties. Its antibacterial activity against strains causing upper respiratory tract infections is particularly important: propolis might be used as a therapeutic agent to prevent the bacterial infections that sometimes overlap viral infections. In this study the in vitro activity of both an alcoholic solution and a hydroglyceric extract of propolis, as well as its active principles, was tested against bacteria responsible for respiratory infections (Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis and Streptococcus pyogenes). We also evaluated the in vitro activity of a combination of propolis and its active principles and some beta-lactams, macrolides and fluoroquinolones. Our results, though not demonstrating a clearly synergistic activity between antibiotics and propolis and its constituents, show the possibility of using natural preparations, due to their antimicrobial and anti-inflammatory properties, to enhance antibacterial therapy.


Subject(s)
Anti-Infective Agents/pharmacology , Bacteria/drug effects , Fluoroquinolones/pharmacology , Macrolides/pharmacology , Propolis/pharmacology , Respiratory Tract Infections/microbiology , beta-Lactams/pharmacology , Bacteria/isolation & purification , Drug Therapy, Combination , Haemophilus influenzae/drug effects , Humans , Microbial Sensitivity Tests , Moraxella catarrhalis/drug effects , Respiratory Tract Infections/drug therapy , Streptococcus pneumoniae/drug effects
12.
Br J Cancer ; 92(3): 467-74, 2005 Feb 14.
Article in English | MEDLINE | ID: mdl-15668708

ABSTRACT

The sequential doxorubicin --> CMF (CMF=cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF x 6 cycles (CMF); (b) doxorubicin x 4 cycles followed by CMF x 6 cycles (A --> CMF); (c) CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (CMF --> GT); and (d) doxorubicin x 4 cycles followed by CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (A --> CMF --> GT). The study used a 2 x 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A --> CMF or arms a+c vs b+d) and (2) the effect of adding GT after chemotherapy (arms a+b vs c+d). At a median follow-up of 72 months, A --> CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR)=0.740 (95% confidence interval (CI): 0.556-0.986; P=0.040) and produced a nonsignificant improvement of overall survival (OS) (HR=0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR=0.74; 95% CI: 0.555-0.987; P=0.040), with a nonsignificant improvement of OS (HR=0.84; 95% CI: 0.54-1.32). A --> CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Cyclophosphamide/therapeutic use , Doxorubicin/administration & dosage , Fluorouracil/therapeutic use , Goserelin/administration & dosage , Methotrexate/therapeutic use , Tamoxifen/administration & dosage , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Combined Modality Therapy , Cyclophosphamide/adverse effects , Disease-Free Survival , Drug Administration Schedule , Female , Fluorouracil/adverse effects , Follow-Up Studies , Humans , Lymphatic Metastasis , Methotrexate/adverse effects , Middle Aged
13.
Int J Antimicrob Agents ; 22(1): 48-53, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12842327

ABSTRACT

Previous research showed that berberine-containing Berberis species synthesise the substances 5'-methoxyhydnocarpin-D (5'-MHC-D) and pheophorbide a, which have no antimicrobial activity but inhibit the expression of multidrug resistant efflux pumps (MDRs) in Staphylococcus aureus and potentiate the action of berberine. The MDR pumps extrude synthetic and natural antimicrobials from bacterial cells. We searched for these compounds in Berberis aetnensis C. Presl. (Berberidaceae), an endemic plant of the volcano Mount Etna. This work confirms the presence of pheophorbide a and permits us to hypothesise the presence of 5'-MHC-D in leaf extracts. In fact, the activity of ciprofloxacin was improved when two chromatographic fractions isolated from leaf extracts were added. These results are indicative of the presence of MDR pump inhibitors. Moreover, crude extracts were tested on several micro-organisms and showed antimicrobial activity mainly against Gram-positive bacteria and yeasts.


Subject(s)
Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Berberis , Chlorophyll/analogs & derivatives , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Bacterial Proteins/antagonists & inhibitors , Berberine/administration & dosage , Berberine/chemistry , Berberine/isolation & purification , Berberine/pharmacology , Candida/drug effects , Chlorophyll/administration & dosage , Chlorophyll/chemistry , Chlorophyll/isolation & purification , Chlorophyll/pharmacology , Ciprofloxacin/administration & dosage , Drug Interactions , Flavonoids/administration & dosage , Flavonoids/chemistry , Flavonoids/isolation & purification , Flavonoids/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Molecular Structure , Multidrug Resistance-Associated Proteins , Plant Extracts/pharmacology , Staphylococcus aureus/drug effects
14.
Oncology ; 63(3): 219-25, 2002.
Article in English | MEDLINE | ID: mdl-12381900

ABSTRACT

BACKGROUND AND AIM: In vitro, methotrexate (MTX) is the best modulator for bolus 5-fluorouracil (5FU), whereas folinic acid (FA) is the best for continuous infusion. We evaluated the effect of 5FU modulated by both MTX (bolus administration) and FA (continuous infusion) as second-line treatment of patients with metastatic colorectal cancer. PATIENTS AND METHODS: Entry criteria were: at least one 5FU-based chemotherapy regimen as first-line treatment for metastatic disease, or progression within twelve months after 5FU-containing adjuvant therapy. Treatment schedule: MTX 200 mg/m2 i.v. days 1 and 15; 5FU 600 mg/m2 i.v. bolus, days 2 and 16; 5FU 200 mg/m2 i.v. continuous infusion for 21 days, starting on day 29; FA 20 mg/m2 i.v. bolus weekly during the three weeks of 5FU infusion. Cycles were repeated every 56 days. The primary end-point was tumour control rate, including partial responses and stabilizations. RESULTS: 34/35 patients enrolled were evaluable for response. Five (14.7%) had a partial response, 13 (38.2%) disease stabilization, and 16 (47.1%) progressed; tumour control rate was 52.9%. Median TTP was 5.8 months (95% CI 4.03-7.83); 29 patients had died. Median OAS was 15.9 months (95% CI 8.8-21.9). Toxicity was mild. CONCLUSIONS: The regimen constituted by 5FU modulated by MTX (bolus administration) and FA (continuous infusion) is active as second-line treatment of metastatic colorectal cancer.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Leucovorin/therapeutic use , Adenocarcinoma/secondary , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/pathology , Diarrhea/chemically induced , Disease Progression , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Infusions, Intravenous , Injections, Intravenous , Methotrexate/administration & dosage , Middle Aged , Nausea/chemically induced , Neoplasm Staging , Survival Rate , Treatment Outcome , Vomiting/chemically induced
15.
Arch Otolaryngol Head Neck Surg ; 127(5): 497-503, 2001 May.
Article in English | MEDLINE | ID: mdl-11346423

ABSTRACT

OBJECTIVE: To determine whether olfactory loss affects patients' quality of life or level of disability. DESIGN: Retrospective survey using questionnaire data and clinic database review. SETTING: Two university medical center smell and taste clinics. PATIENTS: A total of 1407 patients were tested for smell and taste disturbances from 1984 through 1998. Surveys were mailed to 1093 patients who had abnormal test scores; 420 (38.4%) returned completed surveys. Patients were grouped by self-rated ability to smell as "impaired" (those reporting persisting deficits) or "improved" (those reporting no smell problem when surveyed). MAIN OUTCOME MEASURES: Response frequencies were compared between the 2 groups for questions regarding ability to perform common activities of daily living and quality-of-life issues. RESULTS: Mean (+/-SD) number of activities of daily living affected by olfactory loss was 4.70 +/- 3.56 for the impaired group and 0.61 +/- 1.58 for the improved group (P < .001). Among specific activities, the most common cited impairments were ability to detect spoiled food (impaired vs improved groups, 75% vs 12%; P < .001), gas leaks (61% vs 8%; P < .001), or smoke (50% vs 1%; P < .001); eating (53% vs 12%; P < .001); and cooking (49% vs 12%; P < .001). Differences in quality-of-life issues were reported primarily in the areas of safety and eating. Overall satisfaction with life was reported by 87% of the improved group but only 50% of the impaired group (P < .001). CONCLUSIONS: Patients reporting persistent olfactory impairment after previously documented olfactory loss indicate a higher level of disability and lower quality of life than those with perceived resolution of olfactory compromise.


Subject(s)
Ageusia/etiology , Olfaction Disorders/complications , Olfaction Disorders/psychology , Quality of Life , Activities of Daily Living , Ageusia/physiopathology , Female , Humans , Male , Olfaction Disorders/physiopathology , Retrospective Studies , Surveys and Questionnaires
16.
Chem Senses ; 26(4): 359-69, 2001 May.
Article in English | MEDLINE | ID: mdl-11369671

ABSTRACT

Re-innervation of the olfactory bulb was investigated after transection of the olfactory nerve using monoclonal antibody RB-8 to assess whether rhinotopy of the primary olfactory projection is restored. In normal animals RB-8 heavily stains the axons, and their terminals, that project from the ventrolateral olfactory epithelium onto glomeruli of the ventrolateral bulb (termed RB-8(+)). In contrast, axons from dorsomedial epithelium are unlabeled (RB-8(-)) and normally terminate in the dorsomedial bulb. Sprague-Dawley rats underwent unilateral olfactory nerve transection and survived for 6 weeks prior to perfusion, sectioning and immunostaining with RB-8. Nerve lesion does not shift the position of the boundary between RB-8(+) and RB-8(-) regions of the epithelium. However, following transection and bulb re-innervation, the distribution of RB-8(+) and RB-8(-) axons is markedly abnormal. First, in all 10 experimental animals RB-8(-) axons displace RB-8(+) axons from anterior glomeruli. Furthermore, the usual target of the RB-8(-) fibers, i.e. the dorsomedial bulb at more posterior levels of the bulb, remains denervated, judging by the lack of staining with antibodies that label axons derived from all epithelial zones. Finally, RB-8(+) fibers invade foreign territory in the dorsolateral bulb on the lesioned side in some cases. The shifts in terminal territory in the bulb after transection contrast with the restoration of the normal zonal patterning of the projection after recovery from methyl bromide lesion, but is consistent with reports of mistargeting by a receptor-defined subset of neurons after transection.


Subject(s)
Nerve Regeneration/physiology , Neural Cell Adhesion Molecules , Olfactory Bulb/physiopathology , Olfactory Mucosa/innervation , Olfactory Nerve Injuries , Wounds, Stab/physiopathology , Animals , Antibodies, Monoclonal/analysis , Axons/physiology , Cell Adhesion Molecules, Neuronal/metabolism , Cell Surface Extensions/physiology , Male , Olfactory Bulb/pathology , Olfactory Mucosa/metabolism , Olfactory Nerve/metabolism , Olfactory Nerve/pathology , Rats , Rats, Sprague-Dawley
17.
Chem Senses ; 26(2): 161-6, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11238246

ABSTRACT

To investigate in detail the distribution of G protein subtypes G(i)2alpha and G(o)alpha along the surface of the vomeronasal epithelium, we used double labeling immunocytochemical methods and electron microscopy. We examined the immunoreactivity of these surface structures with antibodies against G(i)2alpha and G(o)alpha. G(i)2alpha- and G(o)alpha-positive cells were observed at the epithelial surface and were evenly distributed. Electron microscopy revealed that strong immunoreactivities to both antibodies were observed on the microvilli and knob-like surface structures of receptor cells. No immunoreactivity was found on the microvilli or surface membranes of supporting cells. This expression pattern is similar to that reported for putative pheromone receptors. These data confirm that there are two distinct classes of vomeronasal receptor cells expressed at the surface of the epithelium. These two classes of receptors correspond to the same G(i)2alpha- and G(o)alpha-positive cells distributed in cell body layers of the epithelium and in the axon terminals in the accessory olfactory bulb.


Subject(s)
GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , Heterotrimeric GTP-Binding Proteins/metabolism , Proto-Oncogene Proteins/metabolism , Vomeronasal Organ/metabolism , Animals , Chemoreceptor Cells/metabolism , Epithelium/metabolism , Epithelium/ultrastructure , GTP-Binding Protein alpha Subunit, Gi2 , GTP-Binding Protein alpha Subunits , Immunohistochemistry , Male , Microscopy, Immunoelectron , Microvilli/metabolism , Microvilli/ultrastructure , Rats , Rats, Sprague-Dawley , Vomeronasal Organ/ultrastructure
18.
Laryngoscope ; 111(11 Pt 1): 1964-9, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11801979

ABSTRACT

OBJECTIVE: To develop an alternative model for studying the regenerative capacity of olfactory neurons. STUDY DESIGN: An immunohistochemical analysis of mouse olfactory epithelium transplanted to the cerebral cortex. METHODS: Strips of olfactory epithelium removed from donor mice at postnatal day 5 to day 20 were inserted into the parietal cortex of adult mice. Recipient animals were allowed to survive for 25 to 120 days and then perfused with 4% paraformaldehyde 1 hour after bromodeoxyuridine injection. The brains were processed, and frozen sections were obtained. Sections through transplant tissue were analyzed using immunohistochemistry and compared with normal olfactory epithelium. RESULTS: Graft survival approached 85% with mature olfactory neurons detected in 35% of the transplants stained for olfactory marker protein. Transplant epithelium resembled normal olfactory epithelium containing mature olfactory neurons and axon bundles. CONCLUSIONS: Studies of olfactory neuron regeneration have been limited by the inability to produce cultures with long-term viability. Olfactory epithelial grafts to the cerebral cortex provide an alternative approach to the study of olfactory neuron regeneration.


Subject(s)
Nerve Regeneration , Neurons/physiology , Olfactory Mucosa/transplantation , Animals , Axons/physiology , Cerebral Cortex/metabolism , Graft Survival , Immunohistochemistry , Mice , Olfactory Mucosa/metabolism , Olfactory Mucosa/physiology
19.
Rev Argent Microbiol ; 32(3): 157-60, 2000.
Article in Spanish | MEDLINE | ID: mdl-11008709

ABSTRACT

Severe mycotic infections are a source of concern in immunocompromised patients or in those who receive chemotherapy for hematological malignant diseases. One of the causes is referred to the appearance of antimycotic resistant microorganisms. Fluconazole is one of the antimycotic used for invasive mycoses treatment. Therefore it is necessary to evaluate the factors that originate this resistance. In the present report the yeast Saccharomyces cerevisiae S288c was used as a model system. In resistant strains the accumulation of the lipophilic cation Rhodamine 6G, L-leucine uptake and growth inhibition by crystal violet dye were determined. The results presented herein demonstrate the correlation between the membrane potential and the resistance to fluconazole presented by S. cerevisiae strain S288c.


Subject(s)
Antifungal Agents/pharmacology , Drug Resistance, Microbial , Fluconazole/pharmacology , Membrane Potentials/drug effects , Rhodamines/metabolism , Saccharomyces cerevisiae/metabolism , Antifungal Agents/metabolism , Culture Media/pharmacology , Fluconazole/metabolism , Gentian Violet/metabolism , Gentian Violet/pharmacology , Leucine/metabolism , Membrane Lipids/metabolism , Proline/pharmacology , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/growth & development , Sterols/metabolism
20.
Rev. argent. microbiol ; 32(3): 157-160, jul.-sept. 2000.
Article in Spanish | LILACS | ID: lil-332520

ABSTRACT

Severe mycotic infections are a source of concern in immunocompromised patients or in those who receive chemotherapy for hematological malignant diseases. One of the causes is referred to the appearance of antimycotic resistant microorganisms. Fluconazole is one of the antimycotic used for invasive mycoses treatment. Therefore it is necessary to evaluate the factors that originate this resistance. In the present report the yeast Saccharomyces cerevisiae S288c was used as a model system. In resistant strains the accumulation of the lipophilic cation Rhodamine 6G, L-leucine uptake and growth inhibition by crystal violet dye were determined. The results presented herein demonstrate the correlation between the membrane potential and the resistance to fluconazole presented by S. cerevisiae strain S288c.


Subject(s)
Antifungal Agents/pharmacology , Fluconazole , Membrane Potentials , Drug Resistance, Microbial , Rhodamines , Saccharomyces cerevisiae , Antifungal Agents/metabolism , Culture Media , Sterols/metabolism , Fluconazole , Gentian Violet , Leucine , Membrane Lipids/metabolism , Proline , Saccharomyces cerevisiae
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