Implementation and assessment of a fast-track programme to improve communication between primary and specialized care in patients with suspected cancer: how to shorten time between initial symptoms of cancer, diagnosis and initiation of treatment.

PURPOSE: This study aims to asses a cancer fast-track programme (CFP) to shorten the time since a patient with suspicion of cancer is referred by the primary care (PC) physician to the specialized medical team. METHODS: Guidelines for main suspected tumours were designed to help PC physicians to detect and rapidly refer cases to the CFP oncology coordinator, who sent them to the appropriate department to accelerate diagnosis, staging and therapy. All patients analysed in this report were referred from June 2009 to July 2012. RESULTS: A total of 897 suspected cancer cases were submitted and finally 705 were studied. In 205 (29 %) a cancer diagnosis was confirmed within 23 days (median). Therapy was initiated within 46 days after referral (median). Early diagnoses with a potential curative approach were made in 166 (82 %). CONCLUSIONS: This CFP decreased the waiting time for cancer diagnosis, by improving communication between PC physician and specialized care teams. Most patients included in this program could get therapy with curative intent.

Retrospective analysis of the use of G-CSF and its impact on dose response for anthracycline plus taxane-based schedules in early breast cancer.

PURPOSE: To evaluate the impact on survival of the relative dose intensity (RDI) achieved in patients with early breast cancer receiving anthracycline plus taxane-based chemotherapy in the adjuvant setting. PATIENTS AND METHODS: Patients with early breast cancer diagnosed from January 1999 through December 2006 were included. Dose intensity was evaluated according to the number of delayed cycles and days and the percentage of RDI. RESULTS: A total of 231 breast cancer patients were included. Granulocyte colony-stimulating factor (G-CSF) was given to 39 % of patients. Few patients delayed chemotherapy administration ≥2 cycles (6 %) and ≥15 days (2 %), and the majority of them received ≥85 % of the RDI (98 %). Overall survival was statistically lower at 5 years in patients who received <85 % of RDI in comparison with those who received ≥85 % of RDI (80 vs. 97 %; p = 0.026). CONCLUSIONS: With a wide use of G-CSF in patients treated with adjuvant anthracyclines plus taxane-based schedules, 98 % of patients received a RDI ≥85 %. A significant although inconsistent impairment of survival was found in those patients with lower RDI.

Oxidative damage increases intracellular free calcium [Ca2+]i concentration in human erythrocytes incubated with lead.

One important effect of lead toxicity in erythrocytes consists of increasing [Ca(2+)](i) which in turn may cause alterations in cell shape and volume and it is associated with cellular rigidity, hemolysis, senescence and apoptosis. In this work, we proposed the use of erythrocytes incubated with Pb(2+) to assess association of the mechanisms of lead erythrocyte oxidative damage and calcium homeostasis. Lead incubation produced an increase in [Ca(2+)](i) dose- and time-dependent, which mainly involved Ca(2+) entry mechanism. Additionally, in this in vitro model alterations similar to erythrocytes of lead-exposed workers were produced: Increase in Ca(2+) influx, decrease in (Ca(2+)-Mg(2+))-ATPase activity and GSH/GSGG ratio; increase in lipoperoxidation, protein carbonylation and osmotic fragility accompanied of dramatic morphological changes. Co-incubation with trolox, a soluble vitamin-E analog is able to prevent these alterations indicating that lead damage mechanism is strongly associated with oxidative damage with an intermediate toxic effect via [Ca(2+)](i) increase. Furthermore, erythrocytes oxidation induced with a free radical generator (APPH) showed effects in [Ca(2+)](i) and oxidative damage similar to those found in erythrocytes incubated with lead. Co-incubation with trolox prevents the oxidative effects induced by AAPH in erythrocytes. These results suggest that increase of [Ca(2+)](i) depends on the oxidative status of the erythrocytes incubated with lead. We consider that this model contributes in the understanding of the relation between oxidative damage induced by lead exposure and Ca(2+) homeostasis, the consequences related to these phenomena and the molecular basis of lead toxicity in no excitable cells.

Relationships between stable fly infestation with some physical facility characteristics and sanitation practices in several dairy farms in the State of Aguascalientes, Mexico.

The possible relationships between stable fly infestation with dairy farm facilities and sanitation practices were studied using path analysis. Twelve dairies located in four counties of Aguascalientes dairy region were selected. The dairies were monitored from May to November 2003. In each occasion, fly infestation, individual physical facility characteristics, and sanitation practices were recorded. In all, 11 independent variables were involved in the study and related variables were grouped together and analyzed in two blocks by path analysis for each one of five population events (begin of fly season, first peak, fluctuation, second peak and decrease). There were significant regression coefficients only in the second peak for two variables, the distance to the silos and the distance to the dung heap (r(2)=0.96 for the full model). Among the 11 variables examined in the study, none had a statistical significant indirect contribution to fly infestation; direct contribution was observed for distance to the silos and for distance to the dung heap variables. However, only the distance to the silos variable was significantly related to stable fly Infestation.

Presence of Hypoderma lineatum stage I larvae in the esophagus of cattle slaughtered in Chihuahua, Chih., Mexico.

In order to detect the presence of Hypoderma lineatum stage I larvae within the esophagus of cattle slaughtered in Chihuahua, Chihuahua, Mexico, a total of five samplings were carried out between July and November 2000. In each instance, a random sample was taken from 10% of the animals slaughtered in a single work shift in each of the two slaughterhouses included in this study. The esophagus were cut longitudinally in order to carry out visual inspection and detect the presence of H. lineatum stage I larvae in the submucosa. The larvae were separated and counted. We identified the presence of H. lineatum stage I larvae in the esophagus for all sampling dates, nevertheless, within the last sampling only one esophagus had them. For all sampling dates the prevalence ranged between 11 and 33%; the latter corresponded to the sampling in October. A total of 287 esophagus was inspected of which 54 were positive with one or more larvae (19%); 233 larvae were obtained from these cases. The number of larvae recovered per sampling ranged from 46 to 74 between July and October, the highest number was found in September's sampling. The largest amount of stage I larvae per esophagus was 22 in the months of July and August. Larvae were always located in the submucosa of the esophagus and all were oriented longitudinally.

Intracellular free calcium concentration and calcium transport in human erythrocytes of lead-exposed workers.

Erythrocytes are the route of lead distribution to organs and tissues. The effect of lead on calcium homeostasis in human erythrocytes and other excitable cells is not known. In the present work we studied the effect of lead intoxication on the uptake and efflux (measured as (Ca(2+)-Mg(2+))-ATPase activity) of calcium were studied in erythrocytes obtained from lead-exposed workers. Blood samples were taken from 15 workers exposed to lead (blood lead concentration 74.4+/-21.9 microg/dl) and 15 non-exposed workers (9.9+/-2 microg/dl). In erythrocytes of lead-exposed workers, the intracellular free calcium was 79+/-13 nM, a significantly higher concentration (ANOVA, P<0.01) than the one detected in control (30+/-9 nM). The enhanced intracellular free calcium was associated with a higher osmotic fragility and with important modifications in erythrocytes shape. The high intracellular free calcium in lead-exposed workers was also related to a 100% increase in calcium incorporation and to 50% reduction of (Ca(2+)-Mg(2+))-ATPase activity. Lipid peroxidation was 1.7-fold higher in erythrocytes of lead-exposed workers as compared with control. The alteration on calcium equilibrium in erythrocytes is discussed in light of the toxicological effects in lead-exposed workers.

Seasonal transmission of Fasciola hepatica in cattle and Lymnaea (Fossaria) humilis snails in central Mexico.

A 19-month study on the prevalence of fasciolosis in 30 naturally infected cows, the presence of infected and non-infected Lymnaea (Fossaria) humilis snails, and variation in soil temperature and humidity is reported. The prevalence of fasciolosis in cattle declined from around 50% in March to 30% in July, then, it increased from August, reaching a plateau of 100% in November-January, before gradually declining thereafter. A rise in soil humidity and temperature in June and July, respectively, which peaked between August and November was observed. In July, L. (F.) humilis snails appeared, but the infection could only be found in these in August and November. The number of infected snails did not reflect the infestation rate in cows, even though the infestation kinetics in both hosts behaved as predicted from the life cycle of the parasite.

A sustained increase in intracellular Ca(2+) is required for the acrosome reaction in sea urchin sperm.

The acrosome reaction (AR), necessary for fertilization in many species, requires an increase in intracellular Ca(2+) ([Ca(2+)](i)). In sea urchin sperm, the AR is triggered by an egg-jelly factor: the associated [Ca(2+)](i) elevation lasts minutes and involves two Ca(2+) permeable channels. Both the opening of the second channel and the onset of the AR occur approximately 5 s after treatment with egg factor, suggesting that these events are linked. In agreement, removal of Ca(2+) from sea water or addition of Ca(2+) channel blockers at the time when opening of the second channel is first detected inhibits AR and causes a "rapid" (t(1/2) = 3--15 s) decrease in [Ca(2+)](i) and partial inhibition of the intracellular pH change associated with the AR. Simultaneous addition of NH(4)Cl and either EGTA, Co(2+), or Ni(2+) 5 s after egg factor prevents the partial inhibition of the evoked pH(i) change observed but does not reverse AR inhibition. Therefore, the sustained increase in [Ca(2+)](i) caused by the second Ca(2+) channel is needed for the sperm AR. Experiments with agents that induce capacitative Ca(2+) uptake (thapsigargin and cyclopiazonic acid) suggest that the second channel opened during the AR could be a store-operated Ca(2+) channel.

Glucose induces a Na(+),K(+)-ATPase-dependent transient hyperpolarization in human sperm. I. Induction of changes in plasma membrane potential by the proton ionophore CCCP.

When human sperm was incubated in medium deprived of glucose, glucose restoration caused a transient hyperpolarization of the plasma membrane. This hyperpolarization was also induced by fructose but not by 2-deoxyglucose, a substrate that cannot be metabolized. The hyperpolarization was inhibited by NaF, a glycolysis inhibitor, but not by mitochondrial inhibitors (cyanide, rotenone and antimycin), suggesting that it depended on glycolysis. Furthermore, the hyperpolarization was still induced in medium containing a high concentration of KCl and was insensitive to the K(+) channel blocker TEA and the Cl(-) channel blocker niflumic acid, but it was blocked by ouabain. This suggested that upon glucose addition, there was an increase in the concentration of ATP, that in turns increased the Na(+),K(+)-ATPase activity. Since this pump is electrogenic (2K(+)/3Na(+)) the plasma membrane hyperpolarized. On the other hand, CCCP, a proton ionophore, inhibited the hyperpolarization induced by glucose. When CCCP was added to glucose-treated hyperpolarized sperm, it caused a depolarization that triggered a Ca(2+) influx sensitive to nickel, an inhibitor of voltage-dependent calcium channels. Moreover, CCCP caused hyperpolarization in sperm incubated in medium without calcium, a known condition that depolarizes sperm. This indicated that CCCP induced proton permeability in the plasma membrane that was able to change the membrane potential to a value corresponding to the E(H) and that was also able to clamp it, so that it prevented the hyperpolarization induced by glucose.

Effect of nitric oxide releasers on some metabolic processes of rabbit spermatozoa.

The authors investigated the possible effect of nitric oxide (NO) releasers (the free radical form of nitrogen monoxide, which control some functions of many cells) on rabbit spermatozoa. A significant (P < .01) increment was found in the percentage of the acrosome reaction in rabbit spermatozoa incubated for 30-60 min in presence of the NO releasers sodium nitroprusside (SNP) and N-acetyl-S-nitroso cysteine (NACysSNO), but not with S-nitroso cysteine (CysSNO). This effect was reverted or lowered when the NO scavenger HbO2 was included in the medium. The effects of SNP and NACysSNO on acrosome reaction do not appear to be related to glucose utilization, viability, or lipid peroxidation.

Construction of a gene encoding the insect bactericidal protein attacin. Studies on its expression in Escherichia coli.

Attacin, a bactericidal small protein is produced by the giant silk moth Hyalophora cecropia. This paper deals with our efforts to clone the attacin cDNA in a bacterial vector to express it in Escherichia coli and produce the protein in sufficient amount, for further studies. We chose two inducible expression vector/bacterial cell systems: pPL-lambda/N99cI+ cells which is able to be induced by nalidixic acid, and pET3d/BL21(DE3) cells carrying a T7 RNA polymerase gene which is IPTG-inducible. After cloning in the pPL-lambda system and under no addition of the inducer, isolated transformants carried this plasmid with at least 2 concurrent deletions that drastically affected attacin expression, even though attacin gene seems to be intact as deduced by its PCR amplification. It was concluded that basal attacin expression occurred in this system and bacterial growth was limited. Plasmid deletions may have emerged by selection pressure as a way to avoid bactericidal expression and allow bacteria survival. The second cloning attempt was done in pET3d vector/BL21 cells, that should not express the cloned sequence (they lack T7 RNA polymerase gene). Transformed BL21 cells gave 3 recombinant plasmids, 2 of them presented a C deletion that generated an early stop signal in the attacin coding region. The third clone, pET-ATT18, carrying an intact gene, was transferred to BL21(DE3)-IPTG inducible cells in order to be expressed. Attacin was undetectable in stained gels or by Western blot analysis. However, expression was visualized in grown cells after 30 min of IPTG induction and 5 min of [35S]-methionine labeling, as a 22.5 kDa protein band by using gel electrophoresis and fluorography. This low level of expression drastically affected bacterial growth. Considering that attacin has no lytic activity, these results suggest that this molecule should block bacterial growth directly at the cytoplasm by an unknown mechanism, since no signal peptide coding sequence was incorporated in this gene construction, precluding periplasmic or external destination of this protein.

Procedimiento excisional electroquirúrgico con asa diatérmica para el tratamiento de la neoplasia intraepitelial cervical / Electrosurgical excisional procedure with diatermic asa for the treatment of intraepithelial cervical neoplasia

Objetivo: evaluar la excisión de la zona dr transformación con ASA (EZTA), en nuestras manos. Población y método: un total de 407 pacientes con citología anormal, a las que se les practicó EZTA después de colposcopía con o sin biopsia dirigida, sugestivas de lesión intraepitelial escamosa (LIE) o glandular, del 26 de abril de 1993 al 20 de febrero de 1995. Resultados: el porcentaje de curación fue de 95.09 por ciento el 84.03 por ciento de las pacientes en las que el procedimiento de consideró suficiente como tratamiento, acudieron a control citológico posterior; un 15.74 por ciento con complicaciones graves. CONCLUSION: la excisión de la ZT con ASA, por ser efectiva, barata y relativamente fácil de practicar, parece ser un procedimiento terapéutico con el que se puede disminuir la mortalidad por Cáncer del Cuello Uterino en nuestro país, implementandolo a la par de detección masiva.

Genetic predisposition and environmental factors leading to the development of insulin-dependent diabetes mellitus in Chilean children.

This study was designed to examine the hypothesis that some environmental factors increase the risk for insulin-dependent diabetes mellitus. Data on dietary history was collected from 80 diabetic children from the Santiago de Chile Registry and from 85 nondiabetic control subjects who were comparable in terms of age, sex, and ethnic characteristics. Early exposure was defined as the ingestion of food sources other than maternal milk before 3 months of age. To define genetic susceptibility to insulin-dependent diabetes mellitus each subject was typed in terms of HLA DQA1 and DQB1, and the possible conformation of susceptible heterodimers was considered as a risk marker. Fewer children were exclusively breast fed in the diabetic group than in the control group (21.55 +/- 15.05 vs 33.95 +/- 20.40 weeks, P<0.01). In addition, exposure to cow's milk and solid foods occurred earlier in the diabetic group than in the control group (15.90 +/- 10.95 vs 21.15 13.65 and 16.85 +/- 10.25 vs 21.20 +/- 12.35 weeks, P<0.05). Our data show that a short duration of breast-feeding and early exposure to cow's milk and solid foods may be important factors in the development of insulin-dependent diabetes mellitus. The high relative risk observed in individuals genetically predisposed indicates an interaction effect between genetic and environmental components.

[HLA and insulin-dependent diabetes mellitus]. / HLA y diabetes mellitus insulinodependiente.

The propensity of an individual to develop type I (insulin dependent) diabetes mellitus is directly related to specific HLA class II proteins, specially those from DR and DQ regions. Genetic susceptibility to insulin dependent diabetes arises from a preestablished conformation of alpha and beta chains of DQ and beta chain of DR. Since the classic demonstration by McDevitt and colleagues that DQ beta chain aspartate at position 57 was protective against the development of the disease, many populations have been surveyed to study the association between the incidence Type I diabetes and determined frequencies of DR and DQ haplotypes. The association between these markers and susceptibility to Type I diabetes is well established in caucasians at the present time. However, little information is available for Latin American populations, that share a mixture of european, african and native genes. Our group is studying genetic markers of three Latin American populations (Argentina, Perú and Chile) and their possible association to the different incidence of Type I diabetes mellitus in each country.

[Lipoprotein (a) and other risk factors in Chilean children with type I diabetes mellitus]. / Lipoproteina (a) y otros factores de riesgo en niños chilenos con Diabetes Mellitus Tipo I.

AIMS: To study serum Lp(a) levels and other metabolic cardiovascular risk factors in children with type I diabetes mellitus (DM) in comparison with sex and age matched nondiabetic children. To determine the influence of diabetes control on serum lipoprotein (a) concentrations. DESIGN: Transversal observational study. TARGET POPULATION: diabetic group: 70 type I DM children without microalbuminuria and no macro-microvascular nor neurological complications, aged from 8 to 15 years; 30 boys, 40 girls. Mean duration of type I DM was 8 +/- 4 years. Non diabetic group: composed by 123 healthy children with no family history of DM, aged from 8 to 15 years, 53 boys, 70 girls. METHODS: The lipids profile include: total cholesterol (TC) and triglyceride (TG), cholesterol high-density lipoproteins (C-HDL) cholesterol very-low-density lipoproteins (C-LDL) and cholesterol low-density lipoproteins (C-LDL). ApoAI, APOAII and ApoB, Lp(a) and fructosamine. RESULTS: Fructosamine concentration in diabetic children was 340 +/- 108 uM/1 in 240 +/- 25 uM/l nondiabetic children. Lp(a) serum levels did not significantly differ among both groups 17 +/- 16 mg/dl in diabetics 19 +/- 18 mg/dl in controls. Multivariate analysis showed that in the diabetic children the worsening of metabolic control as reflected by fructosamine, was positively correlated with the increase in total Lp(a) serum concentration. CONCLUSIONS: In children aged 8-15 years with uncomplicated IDDM lasting less than 15 years duration, Lp(a) serum levels are positively correlated with the poorest metabolic control.

[Lipoprotein (a), atherosclerosis, and diabetes mellitus]. / Lipoproteina (a), aterosclerosis y diabetes mellitus.

Diabetes mellitus is associated with a three to fourfold increased risk for coronary artery disease and diabetic patients frequently have an abnormal plasma lipid profile. Lately, lipoprotein (a) has received attention as an important independent risk factor for cardiovascular disease. This lipoprotein is elevated in patients with type II diabetes mellitus and there may be an association between the metabolic control of these subjects and its levels. In this review the main features of lipoprotein (a) and its relationship to the fibrinolytic system and atherosclerosis are reviewed.

A depolarization can trigger Ca2+ uptake and the acrosome reaction when preceded by a hyperpolarization in L. pictus sea urchin sperm.

The acrosome reaction (AR) is an exocytotic event that allows sperm to recognize and fuse with the egg. In the sea urchin sperm this reaction is triggered by the outer investment of the egg, the jelly, which induces ionic movements leading to increases in intracellular Ca2+ ([Ca2+]i) and intracellular pH (pHi), a K(+)-dependent transient hyperpolarization which may involve K+ channels, and a depolarization which depends on external Ca2+. The present paper explores the role of the hyperpolarization in the triggering of the acrosome reaction. The artificial hyperpolarization of Lytechinus pictus sperm with valinomycin in K(+)-free seawater raised the pHi, caused a small increase in 45Ca2+ uptake, and triggered some AR. When the cells were depolarized with KCl (30 mM) 40-60 sec after the induced hyperpolarization, the pHi decreased and there was a significant increase in 45Ca2+ uptake, [Ca2+]i, and the AR. This waiting time was necessary in order to allow the pHi change required for the AR to occur. Thus, the jelly-induced hyperpolarization may lead to the intracellular alkalinization required to trigger the AR, and, on its own or via pHi, may regulate Ca2+ transport systems involved in this process. Because of the key role played by K+ in the triggering of the AR, the presence and characteristics of ion channels in L. pictus isolated sperm plasma membranes are being explored. Planar lipid bilayers into which these membranes were incorporated by fusion displayed 85 pS single channel transitions which were cation selective.

Induction of a latency period in the time-course of phospholipase A2 action on dipalmitoylphosphatidylcholine liposomes in the gel phase.

The hydrolysis of dipalmitoylphosphatidylcholine liposomes by porcine pancreatic phospholipase A2 was studied at 31 degrees C, i.e., with the substrate in the gel phase. Addition of delipidated bovine serum albumin to the assay medium induces the appearance of a latency phase in the time course of the enzymatic action. The lag period can be abolished by addition of free palmitic acid whereas no reversal by lysolecithin is found. The generation of a latency period by albumin appears to be due to its ability to sequester the palmitic acid newly released by the phospholipase A2 catalysis. Thus, the nascent fatty acid seems to be an essential activator of the enzymatic process.