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Biomedical subjects

C Allegra

Publications and source records attributed to C Allegra.

At least 19 recordsLinked to original sources
PubMed2006

Valves in small veins and venules.

It is commonly believed that valves are absent in veins smaller than two millimetres in diameter. Consequently, current investigations on the pathophysiology of chronic venous disease (CVD) consider and evaluate only the valvular competence of large veins. The authors review literature from their own collections as well as from medical database searches to assess the functional relevance of these valves. Microscopic venous valves (MVVs) were first described in 1934 in the human digits and have subsequently been demonstrated in other parts of the human body as well as in many tissues and organs of animals. Their location and arrangement suggests that MVVs prevent blood reflux in small sized veins and restrict flow from postcapillary venules back into the capillary bed. This haemodynamic role of MVVs is strongly supported by the clinical finding that grafting skin rich in MVVs results in long-lasting healing leg ulcers attributable to CVD. The huge body of knowledge available concerning MVVs urges us to correct textbooks of anatomy. Studies on the pathophysiology of CVI should acknowledge that the valvular "chain" is not limited to large veins, but extends down to the venular level where MVVs play an important role in venous haemodynamics.

Humans↗
PubMed2005

Veno-active drugs in the management of chronic venous disease. An international consensus statement: current medical position, prospective views and final resolution.

BACKGROUND: Veno-active drugs (VAD) have effects on edema and symptoms related to chronic venous disease (CVD), especially so-called venous pain. VAD's effectiveness, although well established, is regularly debated. OBJECTIVE: Our purpose was to select all randomized controlled trials (RCTs) and meta-analyses devoted to VAD and symptoms in CVD, to submit them to a group of international experts in CVD and to vote with secrete ballot to determine the level of efficacy of each drug, according to EBM (Evidence-Based Medicine) rules and critical analysis. METHODS: Publications in any language devoted to VAD and venous symptoms were searched for in different databanks and submitted to the experts prior to the meeting. RESULTS: 83 papers were analyzed, including 72 RCTs or meta-analyses. Experts determined the level of EBM of each drug, according to the literature and personal experience, using 3 levels of recommendation, A, B and C (from large RCTs to non-randomized trials). CONCLUSIONS: VAD are effective and may be applied in CVD when symptomatic, from C0s to C6s. However, etiological treatment of venous reflux and venous hypertension has always priority. In some cases VAD may replace compression and/or complement its effects. If respecting these prerequisites, VAD are safe and effective.

Chronic Disease↗
PubMed2004

Results of a questionnaire regarding improvement of 'C' in the CEAP classification.

BACKGROUND: One of the shortcomings of the CEAP classification is that some of the clinical conditions in the original version were not defined and, therefore, were used in different ways by those who work with CEAP. AIM: To clarify the definitions of the seven clinical classes in the CEAP classification and to improve universal understanding of these in phlebology. METHODS: The authors prepared a short questionnaire regarding the 'C' part of CEAP with five main questions, dealing with definitions of clinical items: telangiectases, corona phlebectatica, reticular veins, varicose veins and the use of CEAP. The questionnaire was translated into 11 different languages and sent around the world by means of International Venous Digest by fax. Two hundred and six answers were received from 67 countries out of 3681 faxes sent (5.6%). RESULTS: There were a wide variety of opinions returned thus demonstrating that the same term is used with various meanings by different physicians. All physicians classify telangiectases of thigh and foot as class C1, but discrepant answers were obtained concerning the differences between reticular veins and reticular varicose veins as well as the diameter of small and large varicose veins. Sixty per cent of physicians answering this survey use the CEAP classification. CONCLUSION: Further clarification and refinement of the CEAP classification are necessary. The authors hope that this will result in broader acceptance of CEAP.

Humans↗
PubMed2004

A randomised controlled study of four-layer compression versus Unna's Boot for venous ulcers.

OBJECTIVE: This study set out to compare healing rates, handling properties and patient comfort of a four-layer bandage system (Profore) and Unna's Boot in the treatment of venous leg ulcers. METHOD: This was a prospective randomised parallel-group trial. Patients with venous leg ulcers from four centres in Italy were randomised to receive treatment with either Unna's Boot or Profore. Time to healing was recorded for a maximum of 24 weeks. Pain was assessed using a visual analogue scale. Staff assessed ease of application, while patients rated comfort. RESULTS: Data were available for 68 patients with 68 wounds. At 24 weeks complete healing was seen in 74% of the Profore group compared with 66% of the Unna's Boot group. The median time spent in the study was 50 days (range: 7-175 days), corresponding to 51 days (range: 7-175 days) for Profore patients and 49 days (range: 7-168 days) for Unna's Boot patients. There was no difference (p = 0.13) between the groups in time to closure. Overall, more Profore than Unna's Boot applications were rated as excellent. There was a significant difference, in favour of Profore, in ease of application at the final application (p = 0.013). At the initial application, there was a significant difference in bandage appearance (p = 0.04), again favouring Profore, but this was not sustained at the final application (p = 0.18). CONCLUSION: Profore is as effective as Unna's Boot in the treatment of venous leg ulcers.

Adult↗
PubMed2003

Chronic venous insufficiency: the effects of health-care reforms on the cost of treatment and hospitalisation--an Italian perspective.

OBJECTIVES: This study evaluated the evolution of chronic venous insufficiency (CVI)-related costs in Italy over 8 years by focusing on the impact of the Italian health-care reforms (drug de-reimbursement) of 1993-94. RESEARCH AND DESIGN METHODS: The global cost of CVI to the Italian health system (Sistema Sanitario Nazionale, SSN) was divided into three sub-costs: hospitalisation, GP consultation and prescription costs. Indirect costs, such as loss of working days, were not included. CVI-related hospitalisation costs included inpatient treatment for varicose veins, venous leg ulcers and other venous disorders. They were calculated using the US-derived system, Diagnosis Related Group (DRG), used in Italian hospitals. Calculations for the whole country were based on figures determined for the Lombardy region and extrapolated. It was considered reasonable to assume that this region was representative of the whole of Italy. CVI-related GP consultation and prescription costs were derived from Intercontinental Medical Statistics (IMS) data. These costs, pre- and post-reforms, were determined and compared to evaluate the impact of the reforms on CVI-related expenditure. RESULTS: Pre-reforms CVI-related costs analysis (1991): hospitalisations, 210 million Euro; GP consultations, 35.4 million Euro; prescriptions,115 million Euro . The total CVI-related direct costs (i.e. CVI diagnosis and management) were 360.4 million Euro. Post-reforms CVI-related costs analysis (1999): hospitalisations, 288 million Euro; GP consultations, 13 million Euro; prescriptions, 83 million Euro . The total CVI-related direct costs were 384 million Euro. Hospitalisation costs increased predominantly due to an increase in hospitalised patients. GP consultation and prescription costs decreased predominantly due to drug de-listing. The 23.6 million Euro increase in CVI management expense, post-reforms, was due to cost-redistribution from prescriptions and GP consultations to hospitalisations. CONCLUSION: Short-term goals were achieved by the reforms, but long-term expectations were not. Drug de-reimbursement reduced both drug costs for the SSN and the number of GP consultations. Fewer patients were treated overall (mostly with advanced disease), with consequent disease worsening and increase in complications. An increase in CVI-related hospitalisation resulted. In contrast, preventative measures, including patient education and prophylactic treatment, exhibit both clinical and cost effectiveness. Larger studies are required to confirm these preliminary results.

Chronic Disease↗
PubMed2002

Morphologic and functional changes of the microlymphatic network in patients with advancing stages of primary lymphedema.

Using fluorescent microlymphography, we examined the morphology andfunctional characteristics of the microlymph-vascular network in 36 subjects including 9 patients with "compressible" lymphedema (Group I), 14 with minimally compressible lymphedema (Group II), 9 with noncompressible lymphedema (Group III), and 4 healthy individuals. As lymphedema progressedfrom early to advanced stages (Group I-III), an increasingly greater lymphatic capillary density and diameter were depicted and eventually fibrosis/sclerosis with lymphangiectasia, fragmentation and a gradual decrease in the number of microlymphatics. Concomitantly, there was a prolongation in transport and disappearance of fluorescent dye and a progressive increase in endolymphatic and interstitial hydrostatic pressures.

Adult↗
PubMed2001

Tumor marker expression is predictive of survival in patients with esophageal cancer.

BACKGROUND: This study was designed to determine the prognostic value of immunohistochemical tumor marker expression in a population of patients with node-negative esophageal cancer treated with complete resection alone. METHODS: Resection specimens were collected from 61 patients with node-negative T1 (n = 31), T2 (n = 14), and T3 (n = 16) esophageal cancer. A panel of 10 tumor markers was chosen for immunohistochemical analysis, based on associations with differing oncologic mechanisms: apoptosis (p53), growth regulation (transforming growth factor-alpha, epidermal growth factor receptor, and Her2-neu), angiogenesis (factor VIII), metastatic potential (CD44), platinum resistance (p-glycoprotein and metallothionein), 5-fluorouracil resistance (thymidylate synthetase), and carcinogenic detoxification (glutathione S-transferase-pi). RESULTS: Complete resection was performed in all patients (44 adenocarcinoma, 17 squamous cell carcinoma), with no operative deaths. Multivariable analysis demonstrated a significant relationship between cancer-specific death and the following variables: low-level P-gp expression (p = 0.004), high-level expression of p53 (p = 0.04), and low-level expression of transforming growth factor-alpha (p = 0.03). In addition, the number of involved tumor markers present was strongly predictive of negative outcome (p = 0.0001). CONCLUSIONS: This study supports the prognostic value of immunohistochemical tumor markers, specifically the expression pattern of P-gp, p53, and transforming growth factor-alpha, in patients with esophageal carcinoma treated with complete resection alone.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

The prognostic value of molecular marker analysis in patients treated with trimodality therapy for esophageal cancer.

The purpose of this study was to define the prognostic value of a group of molecular tumor markers in a well-staged population of patients treated with trimodality therapy for esophageal cancer. The original pretreatment paraffin-embedded endoscopic esophageal tumor biopsy material was obtained from 118 patients treated with concurrent cisplatin + 5-fluorouracil (5-FU) + 45 Gy radiation followed by resection from 1986 until 1997 at the Duke University Comprehensive Cancer Center. Three markers of possible platinum chemotherapy association [metallothionein (MT), glutathione S-transferase-pi (GST-pi), P-glycoprotein (P-gp or multidrug resistance)] and one marker of possible 5-FU association [thymidylate synthase (TS)] were measured using immunohistochemistry. The median cancer-free survival was 25.0 months, with a significantly improved survival for the 38 patients who had a complete response (P < 0.001). High-level expression of GST-pi, P-gp, and TS were associated with a decreased survival. MT was not significant in this population. Multivariate analysis identified high-level expression in two of the platinum markers (GST-pi and P-gp) and the 5-FU marker TS as independent predictors of early recurrence and death. In conclusion, this investigation measured three possible markers associated with platinum and one possible marker associated with 5-FU in a cohort of esophageal cancer patients. Independent prognostic significance was observed, which suggests that it may be possible to predict which patients may benefit most from trimodality therapy. These data need to be reproduced in a prospective investigation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Therapeutic effects of Vascupump treatment patients with Fontaine Stage II B arteriopathy.

Intermittent claudication is the primary symptom of chronic obstructive arteriopathies of the lower extremities. Increased walking distance is the aim of all physical or pharmacological treatment of such patients. The study reported aims to assess the increase in distal arterial blood flow in arteriopathic patients achieved by physical treatment using a cuff, generally positioned on the upper third of the thigh to produce pulsed compressions. By tightening for a few milliseconds slightly behind the natural cardiac systole, the cuff reinforces the systolic thrust to increase distal perfusion without making any additional demand, on the cardiac pump. The cuff used is produced by Vascupump Copyright vp-El. The trial was conducted on 36 patients with intermittent claudication divided into 3 groups. Group A included 12 patients given Vascupump Copyright treatment only (20 yen 45 minute sessions); Group B included 12 patients given combined treatment with the Vascupump Copyright and endovenous Pentoxillin (3 fl/per diem for 20 days); Group C included 12 patients given Pentoxyfillin alone (3 n per diem for 20 days). Each patient was examined at the start (D0) and end (D20) of treatment as follows: Treadmill tests at 0 and 12% gradients at a speed of 3 km/h. Doppler arterial tensiometry with calculation of the Winsor Index; photoplethysmography. Group A revealed an increase in relative and absolute walking distance of 230% and 224% respectively on the flat and 357% and 343% respectively uphill. Doppler tensiometry revealed a 40.7% improvement in Group A compared to 29% in Group B and 13.6% in Group C. By contrast the improvement in the plethysmographic reading was higher in Group B (+ 119%) than in Group A (+67.3%). These results suggest that the Vascupump Copyright gives better than expected results on Fontaine Stage B arteriopathies.

Arterial Occlusive Diseases↗
PubMed2000

Endostatin inhibits microvessel formation in the ex vivo rat aortic ring angiogenesis assay.

Endostatin has demonstrated potent antiangiogenic and antitumor activity in mouse models. We have investigated the ex vivo rat aortic ring assay and a human vein model to assess the biological activity of murine and human endostatin. Rat aortic rings were exposed to recombinant murine endostatin (Spodoptera frugipera; Calbiochem, San Diego, CA) or recombinant human endostatin (Pichia pastoris; EntreMed, Rockville, MD). After 5 days, murine endostatin (500 microgram/ml) demonstrated inhibition of microvessel outgrowth with dose-dependent effects (down to 16 microgram/ml). No significant inhibition was observed with human endostatin in the rat assay. Human endostatin at 250 and 500 microgram/ml inhibited outgrowths from human saphenous vein rings after a 14-day incubation. Electron microscopy assessed the formation of basal lamina, confirming that the microvessels were progenitors of patent vessels. Immunostaining for Factor VIII or CD34 demonstrated that the microvessel cells were endothelial. BrdU incorporation assays supported the presence of proliferating endothelial cells, correlating with neovascularization from the aortic wall. We conclude that the rat aortic ring assay confirms the antiangiogenic activity of murine but not human endostatin, suggesting that the model may have species specificity. However, the human form shows biological activity against human vascular tissue.

Angiogenesis Inhibitors↗
PubMed2000

Induction of Myc-intron-binding polypeptides MIBP1 and RFX1 during retinoic acid-mediated differentiation of haemopoietic cells.

Retinoic acid-mediated differentiation of HL60 cells is associated with an alteration of chromatin structure that maps to protein-binding sequences within intron I of the c-myc gene and with down-regulation of c-myc expression. By using HeLa cell extracts, we previously identified two polypeptides, designated MIBP1 (for Myc-intron-binding peptide) and RFX1, that interact in vivo and bind to the intron I element; we showed that tandem repeats of an MIBP1/RFX1-binding site can exhibit silencer activity on a heterologous promoter. Here we demonstrate that p160 MIBP1 and p130 RFX1 are absent from undifferentiated HL60 cells. In addition, we show that treatment with retinoic acid induces both MIBP1 and RFX1 protein, as well as their DNA-binding activity, upon granulocytic differentiation of HL60 cells, with a gel mobility pattern identical to that of HeLa cells. In the absence of p160 MIBP1 and p130 RFX1, we observed that the altered gel mobility-shift pattern detected in undifferentiated HL60 cells reflects the binding of two novel polypeptides, p30 and p97, that can be cross-linked to the same recognition intron sequence. We also show that the time course of MIBP1 and RFX1 induction is inversely correlated with the down-regulation of c-myc levels during the treatment of HL60 cells with retinoic acid.

Cell Differentiation↗
PubMed2000

The emergency department as a potential site for smoking cessation intervention: a randomized, controlled trial.

OBJECTIVE: To assess the effect of physician counseling and referral on smoking cessation rates and attendance at a smoking cessation program. METHODS: This was a prospective, randomized clinical trial set in a suburban, community teaching hospital emergency department (ED). During study hours, dedicated research associates enrolled consecutive, stable, oriented patients who were smokers. Eligible, consenting patients were randomized to one of two intervention groups. The control group received a two-page "Stop Smoking" pamphlet from the American Heart Association (AHA). Patients in the intervention group were given the AHA pamphlet along with pharmacologic information and standardized counseling by the attending emergency physician, including written and oral referral to a smoking cessation program. The primary outcome measures were telephone contact/attendance at the smoking cessation program by the intervention group and the rate of smoking cessation in both study groups at three months post-ED visit. Categorical data were analyzed by chi-square and Fisher's exact tests. Rank data were analyzed by Mann-Whitney tests and continuous data by t-tests. All tests were two-tailed with alpha set at 0.05. RESULTS: One hundred fifty-two patients were enrolled; 78 were randomized to the intervention group. Nearly 70% of patients (103) were available for telephone follow-up. The study groups were statistically similar with regard to baseline demographic characteristics and the prevalence of moderate or severe nicotine addiction. None of the patients (0%) in the intervention group contacted or attended the smoking cessation program during the study period (95% CI = 0-4%). The percentages of patients who stopped smoking after three months were similar in the two groups [10.4% (5/48) control vs 10.9% (6/55) intervention; p = 1]. CONCLUSION: The authors found no difference in the smoking cessation rates between ED patients who received written material and those who were counseled by emergency physicians. Referral of patients who smoked to a cessation program was unsuccessful.

Adult↗
PubMed2000

Imaging and phase I study of 111In- and 90Y-labeled anti-LewisY monoclonal antibody B3.

B3 is a murine monoclonal antibody (mAb) that recognizes a LewisY carbohydrate antigen present on the surface of many carcinomas. An imaging and Phase I trial was performed to study the ability of 111In-mAb B3 to image known metastasis and determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), kinetics, and biodistribution of 90Y-mAb B3. Patients (n = 26) with advanced epithelial tumors that express the LewisY antigen were entered. All patients received 5 mCi of 111In-mAb B3 for imaging. 90Y-mAb B3 doses were escalated from 5 to 25 mCi in 5-mCi increments. 111In-mAb B3 and 90Y-mAb B3 were coadministered over a 1-h infusion. Definite tumor imaging was observed in 20 of 26 patients. Sites imaged included lung, liver, bone, and soft tissues. The MTD of 90Y-mAb B3 was determined to be 20 mCi. The DLTs were neutropenia and thrombocytopenia. Tumor doses ranged from 7.7 to 65.1 rad/mCi. 111In- and 90Y-mAb B3 serum pharmacokinetics (n = 23) were found to be similar. The amount of B3 administered (5, 10, and 50 mg) did not alter the pharmacokinetics. Bone marrow biopsies (n = 23) showed 0.0038+/-0.0016% of injected dose/gram for 111In-mAb B3 compared to 0.0046+/-0.0017% of injected dose/gram for 90Y-mAb B3 (P = 0.009). When given to patients with carcinomas that express the LewisY antigen, 111In-mAb B3 demonstrated good tumor localization. The MTD of 90Y-mAb B3 is 20 mCi, with myelosuppression as the DLT. Higher doses of radioactivity need to be delivered to achieve an antitumor effect. Humanized mAb B3 is being developed for evaluation in radioimmunotherapy. A clinical trial to explore the use of higher doses of 90Y-mAb B3 with autologous stem cell support is planned.

Adult↗
PubMed1999

A pilot study of interferon alpha-2a, fluorouracil, and leucovorin given with granulocyte-macrophage colony stimulating factor in advanced gastrointestinal adenocarcinoma.

We reported previously that the addition of recombinant Escherichia coli human granulocyte-macrophage colony stimulating factor (GM-CSF) to a 5-fluorouracil (5-FU) and leucovorin (LV) regimen seemed to ameliorate diarrhea and permit increased 5-FU dose intensity (J. L. Grem et al., J. Clin. Oncol., 12: 560-568, 1994). We then tested the effect of GM-CSF given with a more toxic regimen of 5-FU/LV/IFN-alpha (IFN alpha-2a). Thirty-one patients with a good performance status and no prior chemotherapy for systemic disease received IFN alpha(-2a (5 MU/m2 s.c., days 1-7), 5-FU (370 mg/m2 i.v., days 2-6), LV (500 mg/m2 i.v., days 2-6), and GM-CSF (Saccharomyces cerevisiae 250 microg/m2 s.c., days 7-18) every 3 weeks. Toxicities and 5-FU dose intensity were compared with that observed in our prior Phase II trial with 5-FU/LV/IFN alpha-2a (J. L. Grem et al., J. Clin. Oncol., 11: 1737-1745, 1993). In comparison with the prior Phase II study, the WBC and granulocyte nadirs in the present trial were significantly higher. When trends in toxicity grades for all cycles were compared, stratifying for 5-FU dose, the incidence and severity of mucositis, skin rash, WBC toxicity, and granulocyte toxicity were significantly lower in the present trial, whereas nausea/vomiting and fatigue were significantly worse. The delivered 5-FU dose intensity for all cycles of therapy appeared to be significantly higher in the present trial. Six of 28 evaluable patients had a partial response (21.4%), and 13 (46%) had stable disease for > or =12 weeks. Despite treatment-related toxicity, patient quality of life did not worsen during the study. No correlation was observed between thymidylate synthase content in primary tumor specimens and response, time to treatment failure, or survival. The addition of GM-CSF appeared to decrease the severity of leukopenia, granulocytopenia, mucositis, and skin rash when compared with our prior experience with this regimen of 5-FU/LV/IFN alpha-2a, at the cost of greater nausea/vomiting and fatigue. The potential impact of increased 5-FU dose intensity on clinical response, however, remains to be determined.

Adenocarcinoma↗