Achieving optimal clinical outcomes in autologous fat grafting: A systematic review of processing techniques.

BACKGROUND: Autologous fat grafting (AFG) is a versatile technique in reconstructive and cosmetic surgery. Graft processing is a key source of variability resulting in unreliable clinical outcomes, with no consensus on the optimal methodology. This systematic review identifies the evidence base supporting different processing paradigms. METHODS: A systematic literature search was conducted using the PubMed, Scopus and The Cochrane Foundation databases. Studies comparing AFG processing methods and reporting long-term patient outcomes were identified. RESULTS: Twenty-four studies (2413 patients) were identified. Processing techniques evaluated included centrifugation, decantation, washing, filtration, gauze rolling, as well as commercial devices and adipose-derived stem/stromal cell (ASC) enrichment methods. Objective volumetric and subjective patient-reported outcomes were discussed. There was a variable reporting of complications and volume retention rates. Complications were infrequent; palpable cysts (0-20%), surgical-site infections (0-8%) and fat necrosis (0-58.4%) were the most reported. No significant differences in long-term volume retention between techniques were found in AFG in the breast. In head and neck patients, greater volume retention was documented in ASC enrichment (64.8-95%) and commercial devices (41.2%) compared to centrifugation (31.8-76%). CONCLUSIONS: Graft processing through washing and filtration, including when incorporated into commercial devices, results in superior long-term outcomes compared to centrifugation and decantation methods. ASC enrichment methods and commercial devices seem to have superior long-term volume retention in facial fat grafting.

Assessment of Small Paediatric Burns: A Coin-Based System.

A review of paediatric burns in our burns facility in the United Kingdom demonstrated variable accuracy of size, and a majority documented as <1% total body surface area (TBSA). Accurate assessment is important for medical records, clinical management and non-accidental injuries. We propose to assess burn size with a coin-based system, where small burns are described by single/multiple sterling coins. Participants were asked about their confidence in evaluating small paediatric burns. Participants were given ten scenarios which included photographs of paediatric patients with small burns. They were asked to assess burn size in their normal manner (TBSA, measurement) and with a coin-based system. The 'burns' were drawn on children based on a given coin size and percentage so that the accuracy of the participant's answer was quantifiable. Participants provided qualitative feedback in a questionnaire on the coin-based system. Thirty nurses and medical staff of varying seniority actively involved in referral/management of paediatric burns took part, creating over 300 responses. In preliminary questions, 66% of participants did not feel confident in estimating paediatric burns and 83% needed to refer to a paediatric burns chart. Accuracy of burn size using TBSA and the coin-based system was 45% and 67%, respectively. The majority (97%) stated estimating size was easier, and 93% found it more accurate. A total of 87% found communication between colleagues easier. Results highlight the improved assessment of small burns in our hospital using a coin-based approach in comparison to TBSA, and could facilitate accurate communication between health care professionals.

En revoyant les évaluations de SB des brûlures pédiatrique dans notre centre du Royaume Uni, nous avons constaté une grande variabilité quant à leur exactitude, avec une majorité d'entre elles touchant moins de 1%. Hors, une évaluation exacte est nécessaire pour la stratégie thérapeutique, la bonne tenue du dossier et sur le plan légal (en particulier après brûlure non accidentelle). Nous proposons, pour ces petites brûlures, une évaluation utilisant la taille d'une pièce de monnaie. Les volontaires à cette étude se sont vus remettre 10 scenarii de petites brûlures, photos à l'appui. Il leur était demandé d'évaluer la SB comme à leur habitude et en utilisant le système de taille de pièce (avec multiples si nécessaire), et d'estimer l'intérêt de l'évaluation « à la pièce ¼. Trente personnels (médecins et infirmières) expérimentés ont participé, générant réponses. En préambule, 66% des participants s'estimaient peu fiables quand à l'évaluation des SB de l'enfant et 83% utilisaient des tables spécifiques. L'exactitude de l'évaluation était de 45% avec les techniques habituelles et 67% à la pièce. La grande majorité estimait que la mesure à la pièce facilitait l'évaluation (97%), la rendait plus précise (93%) et facilitait les transmissions (87%). L'évaluation à la pièce des brûlures pédiatriques pourrait la rendre plus précise et faciliter la communication entre professionnels.

O 089 - A soft robotic exosuit assisting the paretic ankle in patients post-stroke: Effect on muscle activation during overground walking.

This study compared overground walking with and without exosuit assistance in post-stroke patients. Exosuit-assisted walking was found to improve paretic propulsion and ground clearance during swing, two common gait deviations in stroke patients. No changes in leg muscle activity was found, motivating further study of the exosuit as a tool for gait training during stroke rehabilitation.

Response of duck breeders to dietary L-Carnitine supplementation during summer season.

A total number of 300 (225 ducks and 75 drakes) Sudani ducks, 28-wk-old were divided into five groups to investigate the effects of dietary L-carnitine (LC) supplementation on productive, hatching and physiological performance as well as nutrients digestibility coefficients. The results indicated that the productive performance and Semen quality parameters (ejaculate volume, sperms concentration and advanced motility) were significantly improved by LC supplementation (150-450 mg /kg diet) as compared to the control. Hatchability of fertile eggs (%) was significantly improved, while total embryonic mortality was significantly decreased by supplementing 300 and 450 mg LC/kg diet. Supplementing different dietary LC levels resulted in significantly high values of hemoglobin, red and white blood cells count and lymphocyte (L) cells percentage, while it decreased heterophils (H) cells and H/L ratio. Serum albumin, total cholesterol and AST enzyme values were significantly low in ducks fed diets supplemented with LC. Serum triglycerides were significantly the lowest by feeding 300 and 450 mg LC/kg diet. Nutrients digestibility coefficients were significantly improved in drakes fed diet supplemented with 450 mg LC/kg diet. Conclusively, dietary LC supplementation at 300 or 450 mg/kg for duck breeders in summer could improve productive, hatching and physiological performance and nutrients digestibility coefficients.

Changes in Post-Stroke Gait Biomechanics Induced by One Session of Gait Training.

The objective of this study was to determine whether one session of targeted locomotor training can induce measurable improvements in the post-stroke gait impairments. Thirteen individuals with chronic post-stroke hemiparesis participated in one locomotor training session combining fast treadmill training and functional electrical stimulation (FES) of ankle dorsi- and plantar-flexor muscles. Three dimensional gait analysis was performed to assess within-session changes (after versus before training) in gait biomechanics at the subject's self-selected speed without FES. Our results showed that one session of locomotor training resulted in significant improvements in peak anterior ground reaction force (AGRF) and AGRF integral for the paretic leg. Additionally, individual subject data showed that a majority of study participants demonstrated improvements in the primary outcome variables following the training session. This study demonstrates, for the first time, that a single session of intense, targeted post-stroke locomotor retraining can induce significant improvements in post-stroke gait biomechanics. We posit that the within-session changes induced by a single exposure to gait training can be used to predict whether an individual is responsive to a particular gait intervention, and aid with the development of individualized gait retraining strategies. Future studies are needed to determine whether these single-session improvements in biomechanics are accompanied by short-term changes in corticospinal excitability, and whether single-session responses can serve as predictors for the longer-term effects of the intervention with other targeted gait interventions.

Novel regioselective hydroxyl-alkylation of 4,5-diphenylimidazole-2-thione and a competitive intramolecular ring closure of the S-hydroxyalkyl-imidazoles to imidazo[2,1-b]thiazines and thiazoles. Role of catalyst, microwave irradiation, and solid support.

Under both conventional method (CM) and microwave (MW) irradiation (MWI) conditions, alkylation of 4,5-diphenylimidazole-2-thione (1) with halogeno-alkanols 2 or 5, chloroglycerol 11 and 2,3-O-isopropylidene-1-O-(p-tolylsulfonyl)-glycerol (8) in presence of sodium ethoxide or sodium acetate in alcohol afforded regioselectively the corresponding S-alkylated analogues 3, 6, 9, and 12; they also were obtained using MW in absence and presence of bentonite as solid support with no change in regioselectivity. In the presence of potassium carbonate in DMF, the bisalkylated analogues 4, 7, 10, and 13 were obtained except in case of compound 13 where it was accompanied with the imidazothiazine 14. A convenient approach for imidazo-[2,1-b]thiazines and thiazoles 14-16 could be achieved by intramolecular dehydrative ring closure of the S-hydroxyalkylated imidazoles 3, 6, and 12 using potassium carbonate in DMF under both conventional and microwave methods. Isopropylidenation of 12 and 13 and deprotection of 9 and 10 also were investigated.

Synthesis of 2-bromomethyl-3-hydroxy-2-hydroxymethyl-propyl pyrimidine and theophylline nucleosides under microwave irradiation. Evaluation of their activity against hepatitis B virus.

Alkylation of 2-methylthiopyrimidin-4(1H)-one (1a) and its 5(6)-alkyl derivatives 1b-d as well as theophylline (7) with 2,2-bis(bromomethyl)-1,3-diacetoxypropane (2) under microwave irradiation gave the corresponding acyclonucleosides 1-[(3-acetoxy-2-acetoxymethyl-2-bromomethyl)prop-1-yl]-2-methyl-thio pyrmidin-4(1H)-ones 3a-d and 7-[(3-acetoxy-2-acetoxymethyl-2-bromomethyl)prop-1-yl]theophylline (8), which upon further irradiation gave the double-headed acyclonucleosides 1,1 '-[(2,2-diacetoxymethyl)-1,3-propylidene]-bis[(2-(methylthio)-pyrimidin-4(1H)-ones] 4a-c, and 7,7 '-[(2,2-diacetoxymethyl)-1,3-propylidene]-bis(theophylline) (9). The deacetylated derivatives were obtained by the action of sodium methoxide. The activity of deacetylated nucleosides against Hepatitis B virus was evaluated. Compound 5b showed moderate inhibition activity against HBV with mild cytotoxicity.

Microwave-assisted organic synthesis of 3-(D-Gluco-pentitol-1-yl)-1H-1,2,4-triazole.

The condensation of D-glucono- and D-galactono-1,5-lactone and thiocarbohydrazide to give 3-(D-alditol-1-yl)-4-amino-5-mercapto-1,2,4-triazoles 4 and 5 is accelerated by the use of microwave-assisted organic reaction (MAOS). The deamination and dethiolation of compound 4 to give 6 was also accelerated by the use of MAOS. Condensation of 4 and 5 with p-nitrobenzaldehyde afforded Schiff bases 8 and 9, respectively, within 4 min under microwave irradiation (MWI), whereas with ethyl chloroacetate the thioalkylated products 14 and 15 were obtained in 8 min. The structures of the synthesized compounds were confirmed by 1H NMR, 2D NMR, and mass spectra.

Microwave irradiation for accelerating the synthesis of acyclonucleosides of 1,2,4-triazole.

The 3-(D-alditol-1-yl)-4-amino-5-mercapto-1,2,4-triazoles 4 and 5 can be successfully prepared using microwave irradiation. Condensation of 4 and 5 with p-nitrobenzaldehyde afforded Schiff bases 6 and 7, respectively. Reaction 4 and 5 with ethylchloroacetate gave the corresponding alkylated products 10 and 11. Better yields and much less time were the characteristic features of using the microwave heating over the conventional one. The structure of the prepared compounds was confirmed by 1H-NMR, 2D-NMR and mass spectra.

Predictive factors of survival in patients with advanced colorectal cancer: an individual data analysis of 602 patients included in irinotecan phase III trials.

BACKGROUND: The infusional LV5FU2 and Arbeitsgemeinschaft Internische Onkologie (AIO) regimens are used widely in the treatment of advanced colorectal cancer. Irinotecan combined with these regimens increases survival in front-line treatment. Irinotecan also improves survival in second-line treatment. PATIENTS AND METHODS: Univariate and multivariate analyses based on the individual data of 602 patients included in two phase III trials were performed to determine predictive factors of survival in advanced colorectal cancer. RESULTS: Three factors were independently associated with a better progression-free survival: weight loss <5% [hazard ratio (HR) 1.25; 95% confidence interval (CI) 1.00-1.58], World Health Organization performance status (WHO PS) 0-1 (HR 1.29; 95% CI 1.08-1.54) and irinotecan (CPT-11)-containing regimens (HR 1.48; 95% CI 1.03-2.13). Five factors were independently associated with a better overall survival: weight loss <5% (HR 1.67; 95% CI 1.29-2.14), WHO PS 0-1 (HR 1.88; 95% CI 1.27-2.75), one or two metastatic sites (HR 1.24; 95% CI 1.01-1.53), alkaline phosphatase values not over twice the normal range (HR 1.71; 95% CI 1.30-2.24) and CPT-11-containing regimens (HR 1.31; 95% CI 1.07-1.61). CONCLUSIONS: The present analysis confirms that CPT-11-based chemotherapy regimens are independently associated with a better survival in patients with advanced colorectal cancer. Age was not identified as a prognostic factor in this analysis.

Seco C-nucleoside analogs of the 1,2,4-triazole.

The seco C-nucleosides 3-(1,2,3,4,5-penta-O-acetyl-D-gluco- and D-galacto-pentitol-1-yl)-1H-1,2,4-triazoles (6 and 7) were obtained in one pot by deamination and dethiolation of 4-amino-3-(D-gluco- and D-galacto-pentitol-1-yl)-5-mercapto-1,2,4-triazoles (1 and 2), respectively, using sodium nitrite in orthophosphoric acid and subsequent acetylation. The structures were confirmed by using 1H, 13C and 2D NMR spectra, DQFCOSY, HMQC and HMBC experiments. The favored conformational structures were deduced from the vicinal coupling constants of the protons.

Novel synthesis of seco type of acyclo C-nucleosides of 1,2,4-triazole and 1,2,4-triazol.

The seco C-nucleosides 3-(1,2,3,4,5-penta-O-acetyl-D-gluco- and D-galacto-pentitol-1-yl)-1H-1,2,4-triazoles (8 and 9) were obtained in a one pot by deamination and dethiolation of 4-amino-3-(D-gluco- and D-galacto-pentitol-1-yl)-5-mercapto-1,2,4-triazoles (1 and 2), respectively, using sodium nitrite in orthophosphoric acid and subsequent acetylation. Condensation of 1, 2, and 4-amino-3-(D-glycero-D-gulo-hexitol-1-yl)-5-mercapto-1,2,4-triazole (12) with phenacylbromide (11) afforded the corresponding 3-(D-gluco-, D-galactopentitol-1-yl) and 3-(D-glycero-D-gulo-hexitol-1-yl)-6-phenyl-7H-1,2,4-triazolo[3,4-b][1,3,4] thiadiazines (15, 16, and 17). Acetylation of 15-17 gave the penta- and hexa-O-acetyl derivatives 18-20, respectively. The structures were confirmed by using 1H, 13C, and 2D NMR spectra, DQFCOSY, HMQC, and HMBC experiments. The favored conformational structures were deduced from the vicinal coupling constants of the protons.

Irinotecan plus fluorouracil/leucovorin for metastatic colorectal cancer: a new survival standard.

BACKGROUND: Irinotecan is a topoisomerase I inhibitor that prolongs survival in patients with colorectal cancer refractory to fluorouracil (5-FU) and leucovorin (LV). This demonstrated activity of irinotecan as effective second-line therapy for colorectal cancer led to evaluation of combination irinotecan/5-FU/LV as first-line therapy for patients with metastatic disease. The results of two prospective phase III randomized, controlled, multicenter, multinational clinical trials in patients with previously untreated metastatic colorectal cancer served as the basis for U.S. and European approval of irinotecan/5-FU/LV for this indication. An overview of the findings of these two pivotal studies provides insights regarding the application of this new combination in clinical practice. METHODS: Patients were randomly assigned to receive 5-FU/LV, either alone, or with concurrent irinotecan. The study conducted primarily in North America (study 1), employed bolus 5-FU/LV schedules, while the study performed primarily in Europe (study 2), employed infusional 5-FU/LV regimens. Major endpoints included tumor response rate, time to tumor progression (TTP), overall survival, quality of life, and safety. RESULTS: In study 1, the respective confirmed response rates for irinotecan/5-FU/LV versus 5-FU/LV were 39% and 21% (p <.001); median TTPs were 7.0 months and 4.3 months, respectively (p =.004). In study 2, response rates for irinotecan/5-FU/LV versus 5-FU/LV alone were 35% and 22% (p =.005); median TTPs were 6.7 months and 4.4 months, respectively (p <.001). Survival time increased significantly with irinotecan/5-FU/LV versus 5-FU/LV alone in both studies (study 1: median 14.8 months versus 12.6 months, p =.042; study 2: median 17.4 months versus 14.1 months, p =.032). The combined analysis of the data from the two studies showed median survivals of 15.9 months versus 13.3 months, favoring the irinotecan-containing combinations (stratified-by-study p =.003). Patients in study 1 had a 36% lower risk of tumor progression and a 20% lower risk of death with the irinotecan combination than with 5-FU/LV alone; comparable risk reduction values in study 2 were 42% and 23%. While grade 3 diarrhea and vomiting were more common with irinotecan/5-FU/LV, grade 4 neutropenia, neutropenic fever, and mucositis were less common with irinotecan/5-FU/LV than with the Mayo Clinic 5-FU/LV regimen. CONCLUSION: The combination of irinotecan/5-FU/LV is superior to 5-FU/LV alone as first-line therapy for patients with metastatic colorectal cancer, offering consistently improved tumor control and prolonged survival. Irinotecan-based combination therapy sets a new survival standard for the treatment of this life-threatening disease.

Prognostic factors for tumour response, progression-free survival and toxicity in metastatic colorectal cancer patients given irinotecan (CPT-11) as second-line chemotherapy after 5FU failure. CPT-11 F205, F220, F221 and V222 study groups.

Our purpose was to determine, in patients with metastatic colorectal carcinoma treated with irinotecan single-agent after 5-FU failure, the most significant predictive parameters for tumour response, progression-free survival and toxicity. Between October 1992 and April 1995, 455 patients with 5-FU resistant metastatic colorectal carcinoma entered four consecutive phase II trials. The first two studies assessed tumour response, the other two were randomized studies which assessed the efficacy of racecadotril to prevent irinotecan-induced diarrhoea. Due to homogeneous main eligibility criterias, data from those studies could be pooled for statistical analysis. Potential clinical and biological predictive factors (PF) for toxicity, tumour growth control, e.g. response or stabilization and progression-free survival (PFS), were studied in multivariate analysis. 363 patients were evaluable for response, 432 were evaluable for PFS, 368 for neutropenia and 416 for delayed diarrhoea, respectively. Normal baseline haemoglobin level (Hb), time since diagnosis of colorectal carcinoma, grade 3 or 4 neutropenia or diarrhoea at first cycle and a low number of organs involved were the most PF for tumour growth control (P<0.05). Significant prognostic variables for PFS were WHO Performance Status, liver and lymph-node involvement, time since diagnosis, age and CEA value (P < or =0.02). Six groups of patients based on the number of unfavourable prognostic factors are presented. Baseline bilirubin, haemoglobin level, number of organs involved and time from diagnosis were PF for neutropenia; PS, serum creatinine, leukocyte count, time from 5-FU progression and prior abdominopelvic irradiation were PF for delayed diarrhoea (P< or =0.05). These PF should help clinicians to anticipate for a given patient the probability to observe a response/stabilization or a toxicity. These results should also be prospectively confirmed in ongoing or future trials using irinotecan, both as a single agent and in combination with other drugs.

Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial.

BACKGROUND: Irinotecan is active against colorectal cancer in patients whose disease is refractory to fluorouracil. We investigated the efficacy of these two agents combined for first-line treatment of metastatic colorectal cancer. METHODS: 387 patients previously untreated with chemotherapy (other than adjuvant) for advanced colorectal cancer were randomly assigned open-label irinotecan plus fluorouracil and calcium folinate (irinotecan group, n=199) or fluorouracil and calcium folinate alone (no-irinotecan group, n=188). Infusion schedules were once weekly or every 2 weeks, and were chosen by each centre. We assessed response rates and time to progression, and also response duration, survival, and quality of life. Analyses were done on the intention-to-treat population and on evaluable patients. FINDINGS: The response rate was significantly higher in patients in the irinotecan group than in those in the no-irinotecan group (49 vs 31%, p<0.001 for evaluable patients, 35 vs 22%, p<0.005 by intention to treat). Time to progression was significantly longer in the irinotecan group than in the no-irinotecan group (median 6.7 vs 4.4 months, p<0.001), and overall survival was higher (median 17.4 vs 14.1 months, p=0.031). Some grade 3 and 4 toxic effects were significantly more frequent in the irinotecan group than in the no-irinotecan group, but effects were predictible, reversible, non-cumulative, and manageable. INTERPRETATION: Irinotecan combined with fluorouracil and calcium folinate was well-tolerated and increased response rate, time to progression, and survival, with a later deterioration in quality of life. This combination should be considered as a reference first-line treatment for metastatic colorectal cancer.

Isolation and identification of the intermediates during pyrazole formation of some carbohydrate hydrazone derivatives.

Reaction of the oxidation product of L-ascorbic acid, dehydro-L-ascorbic acid, with o-phenylenediamine, followed by 2,4,6-trichlorophenylhydrazine (3) afforded 3-[1-(2,4,6-trichlorophenylhydrazono)-L-threo-2,3,4-trihydroxybut-1-yl]quinoxalin-2(1H)one (4), whose structure was deduced from studying its periodate oxidation, which gave the glyoxal derivative 3-[1-(2,4,6-trichlorophenylhydrazono)glyoxal-1-yl]quinoxalin-2(1H)one (5) that upon reduction afforded 3-[1-(2,4,6-trichlorophenylhydrazono)-2-hydroxyethy-1-yl]quinoxalin-2(1H)one (6). The reaction of 5 with 3 afforded the bishydrazone 3-[1,2-bis(2,4,6-trichlorophenylhydrazono)glyoxal-1-yl]quinoxalin-2(1H)one. The reaction of 5 with acetic anhydride in pyridine afforded the 2,3-dihydrofuro[2,3-b]quinoxaline derivative 2-acetoxy-3-[2-acetyl-2-(2,4,6-trichlorophenyl)hydrazono)]-2,3-dihydrofuro[2,3-b]quinoxaline. Acetylation of 4 with acetic anhydride in pyridine afforded the acyclic diacetate intermediate 3-[3,4-di-O-acetyl-2-deoxy-1-(2,4,6-trichlorophenylhydra-zono)but-2-en-1-yl]quinoxalin-2(1H)one (12), which was also obtained from the reaction of 4 with boiling acetic anhydride. Compound 12 rearranged under the reaction conditions to give the pyrazole derivatives 3-[5-(ace-toxymethyl)-1-(2,4,6-trichlorophenyl)pyrazol-3-yl]quinoxalin-2(1H)one (14) and 2-acetoxy-3-[5-(acetoxymethyl)-1-(2,4,6-trichlorophenyl)pyrazol-3-yl)]quinoxaline (15), as well as the 2,3-dihydrofuro[2,3-b]quinoxaline derivative 2-(2-acetoxyethen-2-yl)-3-[2-(2,4,6-trichlorophenyl)hydrazono]-2,3-dihydrofuro[2,3-b]quinoxaline. Acetylation of 3-[5-(hydroxymethyl)-l-(2,4,6-trichlorophenyl)pyrazol-3-yl]quinoxalin-2(1H)one (16) with acetic anhydride in pyridine or 12 with boiling acetic anhydride afforded 15 and 16, respectively. Treatment of 4 with diluted sodium hydroxide afforded the pyrazolo[2,3-b]quinoxaline (flavazole) derivative 1-(2,4,6-trichlorophenyl)-3-(L-threo-glycerol-1-yl)pyrazolo[2,3-b]quinoxaline whose acetylation afforded the acetyl derivative 3-(2,3,4-tri-O-acetyl-L-threo-glycerol-1-yl)-1-(2,4,6-trichlorophenyl)pyrazolo[2,3-b]quinoxaline. The assigned structures were based on spectral analysis. The activity of compound 4 against hepatitis B virus has been studied.

Inhibition of some hepatic lysosomal glycosidases by ethanolamines and phenyl 6-deoxy-6-(morpholin-4-yl)-beta-D-glucopyranoside.

The hepatic lysosomal glycosidases alpha-glucosidase and beta-glucuronidase were inhibited in vitro and in vivo by mono- and diethanolamines. The in vivo inhibition is dose dependent and occurs at a value less than LD50. Phenyl 6-deoxy-6-(morpholin-4-yl)-beta-D-glucopyranoside inhibited alpha-glucosidase both in vitro and in vivo. The treatment of the enzymes in vitro by ethanolamine exhibited a reversible inhibition of the mixed and competitive types for alpha-glucosidase and beta-glucuronidase, respectively. Diethanolamine showed a reversible inhibition of the competitive type for both enzymes. It is a potent inhibitor for beta-glucuronidase, in vitro, whose inhibition constant (Ki) is 5 x 10(-5) M. Phenyl 6-deoxy-6-(morpholin-4-yl)-beta-D-glucopyranoside is a potent inhibitor only for hepatic alpha-glucosidase with a Ki value of 1.6 x 10(-5) M. The pattern of the pH dependence of enzymic activity was not affected by ethanolamine inhibition. The magnitude of the inhibition of enzymes is dependent on the structure of the inhibitor.

Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer.

BACKGROUND: In phase II studies, irinotecan is active in metastatic colorectal cancer, but the overall benefit has not been assessed in a randomised clinical trial. METHODS: Patients with proven metastatic colorectal cancer, which had progressed within 6 months of treatment with fluorouracil, were randomly assigned either 300-350 mg/m2 irinotecan every 3 weeks with supportive care or supportive care alone, in a 2:1 ratio. FINDINGS: 189 patients were allocated irinotecan and supportive care and 90 supportive care alone. The mean age of the participants was 58.8 years; 181 (65%) were men and 98 (35%) were women. WHO performance status was 0 in 79 (42%) patients, 1 in 77 (41%) patients, and 2 in 32 (17%) patients. Tumour-related symptoms were present in 134 (71%) patients and weight loss of more than 5% was seen in 15 (8%) patients. With a median follow-up of 13 months, the overall survival was significantly better in the irinotecan group (p=0.0001), with 36.2% 1-year survival in the irinotecan group versus 13.8% in the supportive-care group. The survival benefit, adjusted for prognostic factors in a multivariate analysis, remained significant (p=0.001). Survival without performance-status deterioration (p=0.0001), without weight loss of more than 5% (p=0.018), and pain-free survival (p=0.003) were significantly better in the patients given irinotecan. In a quality-of-life analysis, all significant differences, except on diarrhoea score, were in favour of the irinotecan group. INTERPRETATION: Our study shows that despite the side-effects of treatment, patients who have metastatic colorectal cancer, and for whom fluorouracil has failed, have a longer survival, fewer tumour-related symptoms, and a better quality of life when treated with irinotecan than with supportive care alone.

Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer.

BACKGROUND: In phase II trials, irinotecan is active in patients with advanced colorectal cancer, but the survival and clinical benefit of irinotecan compared with second-line fluorouracil by continuous infusion is not known. METHODS: 267 patients who had failed to respond to first-line fluorouracil, or whose disease had progressed after treatment with first-line fluorouracil were randomly allocated irinotecan 300-350 mg/m2 infused once every 3 weeks or fluorouracil by continuous infusion. Treatment was given until disease progression, unacceptable toxic effects, or the patient refused to continue treatment. The primary endpoint was survival, while progression-free survival, response rate, symptom-free survival, adverse events, and quality of life (QoL) were secondary endpoints. FINDINGS: 133 patients were randomly allocated irinotecan and 134 were allocated fluorouracil by continuous infusion. Patients treated with irinotecan lived for significantly longer than patients on fluorouracil (p=0.035). Survival at 1 year was increased from 32% in the fluorouracil group to 45% in the irinotecan group. Median survival was 10.8 months in the irinotecan group and 8.5 months in the fluorouracil group. Median progression-free survival was longer with irinotecan (4.2 vs 2.9 months for irinotecan vs fluorouracil, respectively; p=0.030). The median pain-free survival was 10.3 months and 8.5 months (p=0.06) for irinotecan and fluorouracil, respectively. Both treatments were equally well tolerated. QoL was similar in both groups. INTERPRETATION: Compared with fluorouracil by continuous infusion second-line irinotecan significantly improved survival in patients with advanced colorectal cancer.

Climb every mountain.

PIP: In Egypt, the Association of Garbage Collectors for Community Development (AGCCD), created and administered with government support by Zabballeen (low-income people who have collected, sorted, and recycled Cairo's mountains of garbage since 1970), serves an urban settlement of 16,000 where entire households supplement their living from scavenging by raising pigs, chickens, and rabbits. The AGCCD employs 44 women in a primary health care and credit program for women that involves home visits, provision of primary health care, disease prevention, immunization, and reproductive health care (RHC). The low status of the women has meant that the birth of a girl is rarely registered, so that Zabballeen girls can not enjoy the benefits of citizenship. The main goal of the AGCCD has been to increase the role of women in RHC decision-making in their families. Many women have been successful in convincing their husbands of the need for permanent contraception and have resisted efforts to have daughters married at an early age. Recently, RHC discussions have been conducted with men. Women have also begun to actively oppose female genital mutilation. Future challenges for AGCCD include gender training, increasing the birth registration of girls, forming new groups of girls and women to promote women's health by improving gender relations, and providing legal advice and assistance to women, especially those whose births were not registered.^ieng