Lupin (Lupinus spp.) seeds exert anthelmintic activity associated with their alkaloid content.

The growing range of drug resistant parasitic nematode populations threatens the sustainability of ruminant farming worldwide. In this context, nutraceuticals, animal feed that provides necessary dietary requirements while ensuring parasite control, could contribute to increase farming sustainability in developed and low resource settings. In this study, we evaluated the anthelmintic potential of lupin seed extracts against the major ruminant trichostrongylids, Haemonchus contortus and Teladorsagia circumcincta. In vitro observations showed that seed extracts from commercially available lupin varieties could significantly but moderately inhibit larval migration. This anthelmintic effect was mediated by the seed alkaloid content and was potent against both fully susceptible and multidrug resistant H. contortus isolates as well as a susceptible T. circumcincta isolate. Analytical chemistry revealed a set of four lupanine and sparteine-derivatives with anthelmintic activity, and electrophysiology assays on recombinant nematode acetylcholine receptors suggested an antagonistic mode of action for lupin alkaloids. An in vivo trial in H. contortus infected lupin-fed ewes and goats failed to demonstrate any direct anthelmintic effect of crude lupin seeds but infected lupin-fed goats suffered significantly less parasite-mediated blood losses. Altogether, our findings suggest that the anthelmintic potential of lupin remains limited. However, the potent alkaloids identified could lead to the development of novel drugs or may be used in combination with current anthelmintics to improve their efficacy.

Exploring the limitations of pathophysiological indicators used for targeted selective treatment in sheep experimentally infected with Haemonchus contortus.

Identifying which sheep to treat as part of a Targeted Selective Treatment approach to gastro-intestinal nematode control relies entirely on the efficacy of the indicators. Indicators such as FAMACHA© (anaemia), DISCO (diarrhea) and reductions in weight gains were designed specifically to reflect those sheep experiencing symptomatic consequences of infection. Using the gastro-intestinal nematode Haemonchus contortus as a model species, this study explored the utility and sensitivity of these indicators under controlled experimental conditions on 63 adult sheep. The potential effect of sheep with different H. contortus resistance phenotypes on indicator efficacy was compared in three different phenotypes, i.e. high (Blackbelly females), medium (Blackbelly rams) and low resistance (Romane rams). The potential effect of the H. contortus isolate on indicator efficacy was also explored by using four different isolates, with varying anthelmintic resistance capacities, to infect the sheep. We limited the study to the first month of infection to evaluate the interest of these indicators as an early predictive means for controlling infection. The pathophysiological indicators FAMACHA© and DISCO do not reflect infection intensity based on Faecal Egg Counts, nor do reductions in weight gains. FAMACHA© was however a good indicator of anaemia with strong correlations to haematocrit. There was little agreement among the three indicators to identify the same animals in need of treatment and even combining them did not increase their predictive value of infection intensity or relative host damage from infection. The indicator sensitivity was influenced by the H. contortus isolate and sheep resistance phenotype in which they were tested. One isolate was poorly infective but induced high levels of anaemia (FAMACHA©) and diarrhea (DISCO) compared to the three others. The FAMACHA© and DISCO had higher values in the sheep group with a medium resistance phenotype (Blackbelly rams) indicating higher levels of damage compared to the high and low resistance phenotypes. We conclude that there is no 'one size fits all' approach to the use of indicators for Targeted Selective Treatment and the indicators should be calibrated to farm-specific conditions to increase their efficacy.

Molecular basis of agonist docking in a human GPR103 homology model by site-directed mutagenesis and structure-activity relationship studies.

BACKGROUND AND PURPOSE: The neuropeptide 26RFa and its cognate receptor GPR103 are involved in the control of food intake and bone mineralization. Here, we have tested, experimentally, the predicted ligand-receptor interactions by site-directed mutagenesis of GPR103 and designed point-substituted 26RFa analogues. EXPERIMENTAL APPROACH: Using the X-ray structure of the ß2 -adrenoceptor, a 3-D molecular model of GPR103 has been built. The bioactive C-terminal octapeptide 26RFa(19-26) , KGGFSFRF-NH2 , was docked in this GPR103 model and the ligand-receptor complex was submitted to energy minimization. KEY RESULTS: In the most stable complex, the Phe-Arg-Phe-NH2 part was oriented inside the receptor cavity, whereas the N-terminal Lys residue remained outside. A strong intermolecular interaction was predicted between the Arg(25) residue of 26RFa and the Gln(125) residue located in the third transmembrane helix of GPR103. To confirm this interaction experimentally, we tested the ability of 26RFa and Arg-modified 26RFa analogues to activate the wild-type and the Q125A mutant receptors transiently expressed in CHO cells. 26RFa (10(-6) M) enhanced [Ca(2+) ]i in wild-type GPR103-transfected cells, but failed to increase [Ca(2+) ]i in Q125A mutant receptor-expressing cells. Moreover, asymmetric dimethylation of the side chain of arginine led to a 26RFa analogue, [ADMA(25) ]26RFa(20-26) , that was unable to activate the wild-type GPR103, but antagonized 26RFa-evoked [Ca(2+) ]i increase. CONCLUSION AND IMPLICATIONS: Altogether, these data provide strong evidence for a functional interaction between the Arg(25) residue of 26RFa and the Gln(125) residue of GPR103 upon ligand-receptor activation, which can be exploited for the rational design of potent GPR103 agonists and antagonists.

Effect of feeding extruded flaxseed with different grains on the performance of dairy cows and milk fatty acid profile.

Sixteen Holsteins cows were used in a Latin square design experiment to determine the effects of extruded flaxseed (EF) supplementation and grain source (i.e., corn vs. barley) on performance of dairy cows. Extruded flaxseed diets contained 10% [dry matter (DM) basis] of an EF product that consisted of 75% flaxseed and 25% ground alfalfa meal. Four lactating Holsteins cows fitted with rumen fistulas were used to determine the effects of dietary treatments on ruminal fermentation. Intakes of DM (23.2 vs. 22.2 kg/d), crude protein (4.2 vs. 4.0 kg/d), and neutral detergent fiber (8.3 vs. 7.9 kg/d) were greater for cows fed EF diets than for cows fed diets without EF. Milk yield and composition were not affected by dietary treatments. However, 4% fat-corrected milk (30.5% vs. 29.6 kg/d) and solids-corrected milk (30.7 vs. 29.9 kg/d) were increased by EF supplementation. Ruminal pH and total volatile fatty acid concentration were not influenced by EF supplementation. However, feeding barley relative to corn increased molar proportions of acetate and butyrate and decreased that of propionate. Ruminal NH3-N was lower for cows fed barley than for cows fed corn. Milk fatty acid composition was altered by both grain source and EF supplementation. Cows fed EF produced milk with higher polyunsaturated and lower saturated fatty acid concentrations than cows fed diets without EF. Feeding EF or corn increased the milk concentration of C18:0, whereas that of C16:0 was decreased by EF supplementation only. Extruded flaxseed supplementation increased milk fat α-linolenic acid content by 60% and conjugated linoleic acid content by 29%. Feeding corn relative to barley increased milk conjugated linoleic acid by 29% but had no effect on milk α-linolenic concentration. Differences in animal performance and milk fatty acid composition were mainly due to EF supplementation, whereas differences in ruminal fermentation were mostly due to grain source.

Effect of feeding extruded flaxseed with different forage: concentrate ratios on the performance of dairy cows.

Twenty Holstein cows were used in a Latin square design experiment with a 2×2 factorial arrangement to determine the effects of extruded flaxseed (EF) supplementation with 2 different forage to concentrate ratios on the performance of dairy cows. Extruded flaxseed diets contained 9% (dry matter basis) EF product which consisted of 75% EF and 25% ground alfalfa meal. Four lactating Holsteins cows fitted with rumen fistulae were used to determine the effects of dietary treatments on ruminal fermentation. Intakes of dry matter and crude protein were not influenced by dietary treatments. However, neutral detergent fiber intake was greater for the high-forage (8.4 kg/d) than the low-forage (7.8 kg/d) diet. Milk yield (average 40.2 kg/d) was similar for all dietary treatments. However, cows fed the high-forage diets produced milk with higher fat (3.76 vs. 2.97%) and total solids (12.58 vs. 11.95%) concentrations, but lower protein (3.19 vs. 3.33%) and lactose (4.66 vs. 4.72%) contents. Ruminal pH and total volatile fatty acid concentration were not affected by dietary treatments. However, feeding high forage relative to low forage diets increased molar proportion of acetate but decreased that of propionate. Ruminal NH3-N was reduced by feeding high forage relative to low forage diets. Milk fatty acid composition was altered by both forage level and EF supplementation. Feeding diets containing EF or low forage reduced the concentrations of saturated fatty acids and increased those of mono-unsaturated fatty acids. Concentrations of poly-unsaturated fatty acids were increased by feeding EF or low-forage diets. Extruded flaxseed supplementation increased milk fat α-linolenic acid content by 100% and conjugated linoleic acid by 54%. It was concluded that differences in animal performance and ruminal fermentation observed in this study were mostly due to differences in forage to concentrate ratio. However, EF supplementation caused most of the differences observed in milk fatty acid composition.

Emodepside and SL0-1 potassium channels: a review.

Nematode parasites infect humans and domestic animals; treatment and prophylaxis require anthelmintic drugs because vaccination and sanitation is limited. Emodepside is a more recently introduced cyclooctadepsipeptide drug that has actions against GI nematodes, lungworm, and microfilaria. It has a novel mode of action which breaks resistance to the classical anthelmintics (benzimidazoles, macrocyclic lactones and cholinergic agonists). Here we review studies on its mode of action which suggest that it acts to inhibit neuronal and muscle activity of nematodes by increasing the opening of calcium-activated potassium (SLO-1) channels.

Functional reconstitution of Haemonchus contortus acetylcholine receptors in Xenopus oocytes provides mechanistic insights into levamisole resistance.

BACKGROUND AND PURPOSE: The cholinergic agonist levamisole is widely used to treat parasitic nematode infestations. This anthelmintic drug paralyses worms by activating a class of levamisole-sensitive acetylcholine receptors (L-AChRs) expressed in nematode muscle cells. However, levamisole efficacy has been compromised by the emergence of drug-resistant parasites, especially in gastrointestinal nematodes such as Haemonchus contortus. We report here the first functional reconstitution and pharmacological characterization of H. contortus L-AChRs in a heterologous expression system. EXPERIMENTAL APPROACH: In the free-living nematode Caenorhabditis elegans, five AChR subunit and three ancillary protein genes are necessary in vivo and in vitro to synthesize L-AChRs. We have cloned the H. contortus orthologues of these genes and expressed them in Xenopus oocytes. We reconstituted two types of H. contortus L-AChRs with distinct pharmacologies by combining different receptor subunits. KEY RESULTS: The Hco-ACR-8 subunit plays a pivotal role in selective sensitivity to levamisole. As observed with C. elegans L-AChRs, expression of H. contortus receptors requires the ancillary proteins Hco-RIC-3, Hco-UNC-50 and Hco-UNC-74. Using this experimental system, we demonstrated that a truncated Hco-UNC-63 L-AChR subunit, which was specifically detected in a levamisole-resistant H. contortus isolate, but not in levamisole-sensitive strains, hampers the normal function of L-AChRs, when co-expressed with its full-length counterpart. CONCLUSIONS AND IMPLICATIONS: We provide the first functional evidence for a putative molecular mechanism involved in levamisole resistance in any parasitic nematode. This expression system will provide a means to analyse molecular polymorphisms associated with drug resistance at the electrophysiological level.

On the mode of action of emodepside: slow effects on membrane potential and voltage-activated currents in Ascaris suum.

BACKGROUND AND PURPOSE: Anthelmintics are required for treatment and prophylaxis of nematode parasites of humans and domestic animals. Emodepside, a cyclooctadepsipeptide, is a modern anthelmintic that has a novel mode of action involving a Ca-activated K channel (SLO-1) in Caenorhabditis elegans, sometimes mediated by a latrophilin (LAT) receptor. We examined mechanisms of action of emodepside in a parasitic nematode, Ascaris suum. EXPERIMENTAL APPROACH: RT-PCR was used to investigate expression of slo-1 and lat-1 in A. suum muscle flaps, and two-micropipette current-clamp and voltage-clamp techniques were used to record electrophysiological effects of emodepside. KEY RESULTS: Expression of slo-1 and lat-1 were detected. Emodepside produced a slow time-dependent (20 min), 4-aminopyridine sensitive, concentration-dependent hyperpolarization and increase in voltage-activated K currents. Sodium nitroprusside increased the hyperpolarizations and K currents. N-nitro-L-arginine inhibited the hyperpolarizations and K currents. Phorbol-12-myristate-13 acetate increased the K currents, while staurosporine inhibited the hyperpolarizations and K currents. Iberiotoxin reduced these emodepside K currents. The effect of emodepside was reduced in Ca-free solutions. Emodepside had no effect on voltage-activated Ca currents. CONCLUSIONS AND IMPLICATIONS: Asu-slo-1 and Asu-lat-1 are expressed in adult A. suum muscle flaps and emodepside produces slow activation of voltage-activated Ca-dependent SLO-1-like K channels. The effect of emodepside was enhanced by stimulation of protein kinase C and NO pathways. The data are consistent with a model in which NO, PKC and emodepside signalling pathways are separate and converge on the K channels, or in which emodepside activates NO and PKC signalling pathways to increase opening of the K channels.

Carcinoide gastrointestinal: experiencia de siete años en el Instituto Nacional del Cáncer (2000-2006) / Carcinoid tumors: retrospective review of 25 patients

Background: The incidence of carcinoid tumors (CT) has increased in the last five decades. These supposedly benign tumors may not always behave as such. The largest series of CT show that the most common primary tumor site (appendiceal) changed over the years. Aim: To evaluate the management of gastrointestinal CT at the National Cancer Institute from 2000 to 2006, describe their anatomic location and estimate disease specific survival. Material and Methods: Review of the database of the Cancer Committee, during a period of 7 years, looking for patients with a pathological diagnosis of CT, whose clinical records were analyzed. Results: The records of 25 patients with gastrointestinal CT, aged 18 to 79 years (19 females) were analyzed. Five years disease specific survival was 91.1 percent. The most common location was appendiceal in 56 percent of cases, with a 5 years disease specific survival of 100 percent. Right hemicolectomy was performed in seven patients with appendiceal carcinoid. Other seven patients only underwent appendectomy. Five years disease specific survival was 100 percent in both groups. Conclusions: The appendix is still the most common location of CT in this series and long term survival is acceptable.

Los tumores carcinoides (TC) gastrointestinales han aumentando su incidencia en las últimas 5 décadas. Inicialmente estos tumores eran considerados de comportamiento benigno, sin embargo, con el tiempo han mostrado ser capaces de diseminarse y tener una evolución más agresiva. En general se considera al apéndice cecal como la ubicación más frecuente de TC pero esto ha cambiado en el último tiempo según publicaciones internacionales. El objetivo de este trabajo es presentar nuestra experiencia en el manejo de los TC gastrointestinales en el período 2000-2006 en el Instituto Nacional del Cáncer (INC) reportando una serie de casos, describir su ubicación anatómica y estimar la sobrevida específica de enfermedad. Método: Estudio descriptivo. Se revisó la base de datos del Comité Oncológico del INC, durante un período de 7 años, incluyendo pacientes con diagnóstico anatomopatológico de TC. Se revisaron las fichas clínicas y se recolectaron registros de defunción. Resultados: 25 pacientes con diagnóstico de TC confirmado por patología, presentando una sobrevida específica de enfermedad a 5 años de 91,1 por ciento. La ubicación más frecuente de TC fue apéndice cecal (56 por ciento) y este grupo de pacientes presenta sobrevida específica de enfermedad de 100 por ciento a 5 años. De los TC apendiculares, en 7 pacientes se realizó una hemicolectomía derecha en un segundo tiempo, y en 7 pacientes sólo se realizó apendicectomía, con sobrevida específica de enfermedad de 100 por ciento en ambos grupos a 5 años (p = 0,475). Conclusiones: El apéndice cecal continúa siendo el lugar más frecuente de presentación del TC y la sobrevida alejada es adecuada en esta serie de pacientes.

[Gastrointestinal stromal tumors. An update]. / Tumores del estroma gastrointestinal (GIST), un particular tipo de neoplasia.

Gastrointestinal stromal tumors (GIS) are a heterogeneous group of tumors that express CD 117 molecule in their sur face. They may behave as benign tumors or be highly aggressive. A better survival of patients with these tumors has been achieved using the new molecular therapies such as imatinib mesylate, sunitinib and others. This review analyzes the prognostic factors of these tumors, their clinical features and the criteria for malignant behavior. The value of therapeutic alternatives such as radiotherapy chemotherapy and the new molecular therapies are also discussed.

Tumores del estroma gastrointestinal (GIST), un particular tipo de neoplasia / Gastrointestinal stromal tumors: an update

Gastrointestinal stromal tumors (GIS) are a heterogeneous group of tumors that express CD 117 molecule in their sur face. They may behave as benign tumors or be highly aggressive. A better survival of patients with these tumors has been achieved using the new molecular therapies such as imatinib mesylate, sunitinib and others. This review analyzes the prognostic factors of these tumors, their clinical features and the criteria for malignant behavior. The value of therapeutic alternatives such as radiotherapy chemotherapy and the new molecular therapies are also discussed.

Experiencia de 10 años en el manejo del cáncer de pene, Instituto Nacional del Cáncer (1997-2006) / Penile cancer: a ten years experience

Introducción: El cáncer epidermoide de pene es una enfermedad infrecuente en occidente, sin embargo tiene alta incidencia en algunos países de Latinoamérica, África y Asia. Se le considera una patología asociada a ciertas costumbres higiénicas y pobres condiciones socioeconómicas. En Chile no hay cifras reales de incidencia del cáncer de pene, pero pareciera ser baja; esto además dificulta la generación de guías y ensayos clínicos para determinar cual es el mejor manejo de los casos que se presentan. El objetivo de este trabajo es presentar la experiencia en el tratamiento del cáncer de pene en el Instituto Nacional del Cáncer entre los años 1997 y 2006. En la actualidad sigue siendo la cirugía el tratamiento de elección para el manejo del tumor primario y los ganglios regionales, asociada a quimioterapia y/o radioterapia. La mayoría de los pacientes consultan en promedio 20 meses después de iniciados los síntomas, lo que determina un estadio muy avanzado (74 por ciento estadios III y IV) al momento del diagnóstico, lo que se traduce en una altísima letalidad y un mal resultado oncológico. La pesquisa de lesiones en estadios precoces, la consulta oportuna, el manejo agresivo de la patología y la concentración del manejo de este cuadro en centros especializados podrían mejorar estos resultados.

Background: Penile epidermoid cancer is uncommon and is associated to certain hygienic behaviors and poor economical conditions. There is no information about the incidence of this cancer in Chile, but it is probably low. Aim: To report the experience in the management of penile cancer between 1997 and 2006. Material and methods: Retrospective review of 23 patients aged 26 to 80 years, with a penile cancer. Results: The mean delay between symptom appearance and consultation was 20 months. The cause for consultation was a penile mass in 19, that was ulcerated in 11. Nineteen patients had lymph node involvement and no patient had distant metastases. Therefore, 74 percent of patients were in stage II or IV at the moment of consultation. Mean survival was 19, 36, 16 and 8 months for stages I, II, III and IV respectively. Conclusions: In patients with penile cancer, there is a great delay between the onset of symptoms and time of consultation. This results in a high mortality and bad treatment results.

[Management of hazardous waste in a hospital]. / Residuos hospitalarios peligrosos en un centro de alta complejidad.

BACKGROUND: An inadequate management of hospital waste, that have toxic, infectious and chemical wastes, is a risk factor for humans and environment. AIM: To identify, quantify and assess the risk associated to the management of hospital residues. MATERIAL AND METHODS: A cross sectional assessment of the generation of hazardous waste from a hospital, between June and August 2005, was performed. The environmental risk associated to the management of non-radioactive hospital waste was assessed and the main problems related to solid waste were identified. RESULTS: The rate of generation of hazardous non-radioactive waste was 1.35 tons per months or 0.7 kg/bed/day. Twenty five percent of hazardous liquid waste were drained directly to the sewage system. The drug preparation unit of the pharmacy had the higher environmental risk associated to the generation of hazardous waste. The internal transport of hazardous waste had a high risk due to the lack of trip planning. The lack of training of personnel dealing with these waste was another risk factor. CONCLUSIONS: Considering that an adequate management of hospital waste should minimize risks for patients, the hospital that was evaluated lacks an integral management system for its waste.

Identification of levamisole resistance markers in the parasitic nematode Haemonchus contortus using a cDNA-AFLP approach.

cDNA-AFLP (cDNA-Amplified Fragment Length Polymorphism)-based strategy has been used to identify levamisole (LEV) resistance markers in the nematode Haemonchus contortus. Transcript profiles of adult nematodes from two LEV-resistant and two susceptible isolates were compared. Among the 17 280 transcript-derived fragments (TDFs) amplified, 26 presented a polymorphic pattern between resistant and susceptible nematodes: 11 TDFs were present in both resistant isolates and absent from both susceptible isolates whereas 15 TDFs were present in both susceptible isolates and absent from both resistant isolates. 8 TDFs specifically present in resistant isolates were cloned and sequenced. Some of these TDFs could represent novel genes, as their sequences presented no homologies in databases. Interestingly, specific expression of one candidate (HA17) in resistant nematodes from different isolates was confirmed by RT-PCR experiments. The finding that HA17 expression correlates with LEV resistance in three H. contortus isolates vs five susceptible isolates strongly suggest that we identified a new potential marker of LEV resistance. This differential approach at the transcriptome level could be of great interest for the identification of the molecular mechanism involved in this phenotype.

Residuos hospitalarios peligrosos en un centro de alta complejidad / Management of hazardous waste in a hospital

Background: An inadequate management of hospital waste, that have toxic, infectious and chemical wastes, is a risk factor for humans and environment. Aim To identify, quantify and assess the risk associated to the management of hospital residues. Material and methods: A cross sectional assessment of the generation of hazardous waste from a hospital, between June and August 2005, was performed. The environmental risk associated to the management of non-radioactive hospital waste was assessed and the main problems related to solid waste were identified. Results: The rate of generation of hazardous non-radioactive waste was 1.35 tons per months or 0.7 kg/bed/day. Twenty five percent of hazardous liquid waste were drained directly to the sewage system. The drug preparation unit of the pharmacy had the higher environmental risk associated to the generation of hazardous waste. The internal transport of hazardous waste had a high risk due to the lack of trip planning. The lack of training of personnel dealing with these waste was another risk factor. Conclusions: Considering that an adequate management of hospital waste should minimize risks for patients, the hospital that was evaluated lacks an integral management system for its waste.

Manejo conservador de la fístula quilosa postoperatoria con somatostatina / Treatment of chylous fistula with somatostatin: report of three cases

La fístula quilosa post quirúrgica es una complicación rara pero molesta en la cirugía torácica y abdominal, es en efecto difícil de manejar necesitando en un importante número de casos la reintervención. El abordaje inicial es conservador con dietas bajas en ácidos grasos de cadena media y/o nutrición parenteral total. Ultimamente se ha introducido el uso de la somatostatina, la que aparece como un tratamiento efectivo en el manejo de esta complicación, sugerido por algunos autores como terapia de primera línea .Se presentan tres casos en los que queda de manifiesto la efectividad del fármaco en la resolución de la fístula.

Experiencia quirúrgica en el implante de catéteres con reservorio subcutáneo para quimioterapia con drogas alquilantes / Surgical experience with the placement of catheters with a subcutaneous reservoir with alkylating drugs

Propósito: Realizar un estudio retrospectivo cuyo objetivo principal sea describir la experiencia obtenida por el Instituto Nacional del Cáncer en la implantación de catéteres con reservorio, destinados a la administración de quimioterapia en el tratamiento de tumores malignos. Material y Método: Se describen las características de los pacientes, el tipo de tratamiento, las complicaciones del procedimiento. Se siguieron los implantes hasta su extracción, fin del período de seguimiento o fallecimiento del paciente. Resultados: Entre 1994 y el año 2000, se evaluaron 213 pacientes. Esta serie está constituida principalmente por mujeres. los principales diagnósticos fueron cáncer de mama, sarcomas de partes blandas y osteosarcoma. La tasa global de complicaciones fue de 13,6 por ciento, la infección y el hematoma fueron las más frecuentes en el postoperatorio precoz y la infección de la herida o del bolsillo subcutáneo en el postoperatorio tardío. No se presentó mortalidad ni septicemia asociada al catéter. El tiempo medio de seguimiento del catéter fue de 14,5 meses (0-82). El porcentaje de pacientes a los cuales se le retiró el implante alcanzó el 8,9 por ciento. Discusión: La colocación de catéteres con reservorio es una técnica relativamente segura, que no requiere extracción por alteración de la calidad de vida y permite la conservación del sistema venoso superficial a pacientes sometidos a tratamiento con drogas alquilantes.

Plant sterol-enriched margarine lowers plasma LDL in hyperlipidemic subjects with low cholesterol intake: effect of fibrate treatment.

Phytosterols, found in fat-soluble fractions of plants, chemically resemble cholesterol and inhibit cholesterol absorption in the small intestine. Phytosterol consumption in human subjects reduces plasma total and low density lipoprotein-cholesterol (LDL-C) levels. The primary aim of this study was to determine the efficacy of a low-fat spread enriched with plant sterols in reducing total and LDL-C concentrations in primary hypercholesterolemia. The secondary objective was to evaluate whether patients receiving a lipid-lowering drug (fibrate) might differ in their response to plant sterols. The study was a randomized, double-blind, placebo-controlled two-period cross-over trial with two treatments and three periods. Both treatment periods lasted 2 months, with a washout period (2 months) between them. Spread enriched with plant sterols was compared to non-enriched control spread. Fortified fat spread provided 1.6 g/day of plant sterols derived from edible vegetable oils and fatty acids from sunflower seed oil. The plant sterol content consisted of sitosterol esters (50%), campesterol esters (25%), stigmasterol esters (20%) and 10% of other esters. Data in 53 hypercholesterolemic patients (31 females and 22 males) who completed the study were as follows: patients were 58+/-12 years of age with mean body mass index 23.5+/-2.8 kg/m2 (mean+/-SD). No adverse side-effects of the diet were reported. Plasma total cholesterol and LDL-C concentrations were significantly reduced by 6.4% and 8.8%, respectively, after using the spread enriched in plant sterols, as compared to controls (0.0% and 1.3%, respectively). No effect on high density lipoprotein-cholesterol (HDL-C) and lipoprotein(a) concentrations was detected. When subjects were divided in two subgroups according to fibrate treatment, supplementation with phytosterols decreased plasma cholesterol and LDL-C by 8.5% and 11.1%, respectively in the subgroup of patients treated with fibrates. In the group of patients who did not receive fibrates, consumption of plant sterol margarine reduced plasma cholesterol and LDL-C by 5.5% and 7.7%, respectively. Spread enriched with plant sterol esters significantly lowers blood total and LDL-C levels without affecting HDL-C concentrations, in a hypercholesterolemic population following a strict low cholesterol diet (NCEP step1). In addition, a combination of fibrate treatment and plant sterol ester-supplemented spread offers a safe and effective measure to significantly decrease abnormally high cholesterol levels. We conclude that phytosterol-enriched spread is a useful adjunctive therapy for hypercholesterolemic patients.

[Inpatient and outpatient follow-up of grade I malignant melanoma]. / Etude comparative du suivi des malades atteints de mélanome de stade Ien pratique libérale et hospitalière.

BACKGROUND: In 1995, the French consensus conference on management of patients with grade I malignant melanoma recommended clinical examination for patient monitoring. To date, only one survey has been conducted to evaluate these recommendations and their consequences, providing no means of assessing follow-up practices. The aim of this study was to assess follow-up practices in patients with grade I malignant melanoma followed in an outpatient private practice setting and in a hospital setting with regular appointments. PATIENTS AND METHODS: This retrospective study was conducted in collaboration with private practice and hospital dermatologists, all members of an association of continuing medical education. Medical records of 584 patients with grade I malignant melanoma who had undergone surgery between January 1, 1991 and December 31, 1995 were reviewed. Three hundred twenty-nine patients were followed in an exclusively outpatient setting by their private dermatologist and 265 were followed in a hospital setting. Follow-up data were: age, sex, date of surgical excision of the melanoma, Breslow thickness, date of each follow-up visit, presence of possible metastases and mode of diagnosis. RESULTS: Patient features were different in the two groups: mainly greater Breslow thickness and more frequent metastatic course in patients followed in a hospital setting. Among all patients, 65 (11 p. 100) developed metastases. Diagnosis of metastasis was made clinically in 95 p. 100 whatever the mode of monitoring considered. The number of patients lost to follow-up was 11p. 100 among those followed in a hospital setting and 42 p. 100 in those followed in a private practice setting. Patients lost to follow-up had a higher risk of developing metastasis as their average Breslow thickness was 1.7 mm. CONCLUSION: This study shows that patients followed in a hospital setting have a more severe prognosis than patients followed in private practice. It confirms that systematic use of complementary tests is of little interest in detecting metastases since over the period considered, the diagnosis of metastasis was made clinically in most cases. It also discloses difficulties encountered in exclusively outpatient follow-up as a high number of patients were lost to follow-up in this setting. A systematic appointment fixed by the private dermatologist during the follow-up period appears to be needed to ensure good quality follow-up. Such an appointment system should help reduce the number of patients lost to follow-up.