Estudio preliminar del ganglio centinela en el cáncer oral: a propósito de 12 casos / Preliminary study of the sentinel node in oral cancer: in conjunction with 12 cases

El manejo de los cuellos N0 en pacientes con carcinoma epidermoide de cabeza y cuello es controvertido. Objetivo. Demostrar la eficacia diagnóstica de la biopsia del ganglio centinela (GC) en los pacientes con carcinoma epidermoide oral con cuello clínicamente negativo. Metodología. Se realiza un estudio prospectivo de 12 pacientes consecutivos, hasta el momento, con carcinoma epidermoide oral de cualquier tamaño y cuello clínicamente negativo que no habían recibido tratamiento antitumoral, asistidos en el S. de Cirugía Maxilofacial del área del H.U.V.M de Sevilla. A estos pacientes se les realiza una linfografía cervical con nanocoloides -Tc 99 para localizar el GC, y una dosis de recuerdo antes de iniciar el ttº quirúrgico. Durante la cirugía se localiza el GC con la sonda y se extirpa, se completa la disección cervical funcional y la extirpación de la lesión con posteriores estudios histológicos independientes. Resultados. índice de linfolocalización: 91 por ciento, índice de radiolocalización 100 por ciento, falsos negativos 0 por ciento, la sensibilidad y VPN del 100 por ciento, cocientes de probabilidades positivo > 10 y negativo < 0,1. Conclusiones. La técnica es eficaz para detectar GC-metástasico y es una guía prometedora para indicar la disección cervical (Subvención FIS 2002) (AU)

Llanto del recién nacido y del lactante / Newborn and infant crying

El llanto inmediato de los recién nacidos disminuye de forma muy significativa si éstos permanecen en contacto íntimo con sus madres (piel con piel). Además son varios los estudios que demuestran que este precoz contacto madre-hijo aumenta la prevalencia de la lactancia materna tanto poco después del parto como al cabo de 2 y 3 meses. Así pues el lugar más adecuado tras el parto para los recién nacidos sanos es el del íntimo contacto con sus madres. Los lactantes sin llanto excesivo parecen llorar menos si son llevados en brazos durante un tiempo suplementario. Ante el cólico del lactante la actitud que se ha mostrado más conveniente para aliviarlo ha sido la de tratar de responder al llanto. En casos seleccionados los cambios dietéticos pueden resultar útiles (exclusión de la leche de vaca en la dieta de la madre en los niños amamantados o cambio a fórmula de hidrolizado de proteínas en caso de niños alimentados artificialmente). La diciclomina, aunque eficaz en el alivio del cólico, puede dar lugar a efectos secundarios graves por lo que está contraindicada. En todos los casos es importante la realización de la anamnesis y exploración física cuidadosas y el apoyo y seguimiento frecuentes (AU)

[Treatment of Helicobacter pylori infection in patients with duodenal ulcer: a cost-benefit study]. / Tratamiento de la infección por Helicobacter pylori en pacientes con úlcera duodenal: estudio de costo-beneficio.

BACKGROUND: Epidemiological differences suggest that treatments for H. pylori eradication should be locally validated. AIM: To perform a cost benefit study of different treatment options for H. pylori infection. PATIENTS AND METHODS: One hundred and sixty-seven patients with active duodenal ulcer and H. pylori infection who completed a 2-week treatment with one of the following regimens were included: famotidine plus amoxycillin plus metronidazole (FAM), omeprazole plus amoxycillin plus tinidazole (OAT) or lansoprazole plus clarithromycin plus amoxycillin in 3 (LAC1) or 2 (LAC2) daily doses. We compared efficacy, adverse effects and cost. RESULTS: Eradication rate was 74.6, 72.9, 96.4 y 91.7% for FAM, OAT, LAC1 and LAC2 respectively (p < 0.05). Direct cost ranged from US$ 50 for FAM to US$ 220 for LAC1. A decision analysis was carried out in a model including direct and indirect costs and considering retreatment with antibiotics after the first treatment failure and one-year treatment with H2-blockers in case of a second failure. FAM was selected as the most cost-effective option, with an estimated cost of about US$ 300 +/- 148 per patient. However, cost associated to LAC2 was very similar (US$ 320 +/- 58) and the lower standard deviation suggests less variation. Sensitivity analyses, considering reasonable fluctuation in parameters such as eradication rate, cost and follow-up period suggest that a regimen containing a proton pump inhibitor, clarithromycin and amoxycillin may be the most cost-effective treatment. CONCLUSIONS: These results should be confirmed in other settings, specially in ordinary clinical practice, far from clinical research.

The long-term reinfection rate and the course of duodenal ulcer disease after eradication of Helicobacter pylori in a developing country.

OBJECTIVE: The aim of this study was to evaluate the effect of Helicobacter pylori (H. pylori) eradication on the natural history of duodenal ulcer disease and the reinfection rate after treatment in a developing country. METHODS: A total of 111 H. pylori-infected patients with duodenal ulcer were treated with either omeprazole or famotidine plus two antibiotics for 2 wk. Those failed to respond to treatment were retreated with bismuth-based triple therapy. RESULTS: The radication rate was 76% (95% CI: 67-83%). Eventually, H. pylori was eradicated in 96 of the 111 patients (86%), who were followed-up clinically and endoscopically for a mean of 37.2 months. The cumulative reinfection rate after eradication (Kaplan-Meier) was 8%+/-3% in yr 1, 11%+/-4% in yr 2, and 13%+/-4% in yr 3. Nine of the 12 reinfections occurred during yr 1. Recurrence of duodenal ulcer was detected in five patients (5.2%), all of them during yr 1 of follow-up. Histologically, gastritis scores (according to the Sydney system) improved significantly after eradication. CONCLUSIONS: In a high prevalence setting, H. pylori eradication and early reinfection rates after treatment are similar to rates observed in a low prevalence environment, whereas the late reinfection rate seems to be higher. However, up to 3 yr after treatment, most treated patients are free of H. pylori infection and/or ulcer activity. Even longer follow-up studies are necessary to determine whether specific retreatment policies are necessary to maintain long term eradication in developing countries.

Serological response to Helicobacter pylori recombinant antigens in Chilean infected patients with duodenal ulcer, non-ulcer dyspepsia and gastric cancer.

We have previously cloned 10 Helicobacter pylori antigen genes from a Chilean strain including: cytotoxin VacA, a truncated region of CagA (called A17), a species-specific protein (Ag26), urease subunits (UreA, UreB), a flagellin, (FlaB), heat shock proteins (HspA and HspB), an adhesin (HpaA) and a lipoprotein (Lpp20). Immunogenicity of these antigens was tested by immunoblot with sera of Chilean infected patients, revealing that HpaA, A17, HspB and VacA were more frequently recognized (86%, 82%, 68% and 68%, respectively). According to the clinical condition, it was determined that Lpp20 was preferentially recognized by sera from non-ulcer dyspepsia patients (80%), A17 and VacA by patients with duodenal ulcer (92% and 83% respectively), and HspB by patients with duodenal ulcer (83%) and gastric cancer (90%). An ELISA was developed with a purified mixture of A17 and VacA antigens to test the different groups of patients. It was found that sera from duodenal ulcer patients showed higher values than those from non-ulcer dyspepsia patients, but this difference was not significant (p<0.2). Moreover, sera from gastric cancer patients showed values lower than those from non-ulcer dyspepsia patients (p<0.019). These results indicate that, in the Chilean population, antibodies raised against VacA and A 7 are not markers either for duodenal ulcer or for gastric cancer.

[99mTc red blood cell scintigraphy for the assessment of active gastrointestinal bleeding]. / Rol de la cintigrafía con glóbulos rojos-Tc-99m en la evaluación de hemorragia digestiva alta.

BACKGROUND: 99mTc red blood cell scintigraphy is a non invasive diagnostic method for low flow gastrointestinal bleeding. AIM: To assess the diagnostic yield of this method in patients admitted with gastrointestinal bleeding in whom upper gastrointestinal endoscopy was negative. PATIENTS AND METHODS: The clinical records of 59 patients, aged 6 to 90 years old (35 male), with active gastrointestinal bleeding subjected to a 99mTc red blood cell scintigraphy were reviewed. All had non diagnostic upper gastrointestinal endoscopic studies, and in 20 a selective arteriography was performed. RESULTS: In 40 patients the scintigraphy was positive for gastrointestinal bleeding, and in 57% of these the exam was positive during the first hour. Fifteen of the 19 patients with a negative scintigraphy did not have an active clinical bleeding at the moment of the examination. In 24 patients, a final etiological diagnosis was reached. In 93% of these patients scintigraphy correctly identified the bleeding site. In one patient with a negative scintigraphy, angiography disclosed a pseudo aneurysm of the splenic artery that was not bleeding actively. CONCLUSIONS: In these patients with negative upper gastrointestinal endoscopy 99mTc red blood cell scintigraphy had a 91% sensitivity for the diagnosis of active gastrointestinal bleeding.

Real time confocal laser scanning microscopy: potential applications in space medicine and cell biology.

Photodynamic therapy (PDT), in which tissues may be rendered fatally light-sensitive represents a relatively novel treatment for cancer and other disorders such as cardiovascular disease. It offers significant application to disease control in an isolated environment such as space flight. In studying PDT in the laboratory, low energy lasers such as HeNe lasers are used to activate the photosensitized cellular target. A major problem associated with these studies is that events occurring during actual exposure of the target cells to the system cannot be examined in real time. In this study HeLa cells were photosensitized and photodynamic activation was accomplished using the scanning microbeam from a confocal laser scanning microscope. This form of activation allowed for simultaneous photoactivation and observation and facilitated the recording of events at a microscopic level during photoactivation. Effects of photodynamic activation on the target cells were monitored using the fluorophores rhodamine 123 and ethidium homodimer-1. Potential applications of these forms of analyses to space medicine and cell biology are discussed.

Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection after antibiotic treatment.

OBJECTIVES: To compare the diagnostic accuracy of the most widely available tests for diagnosis of Helicobacter pylori infection after antibiotic treatment. METHODS: A total of 59 H. pylori-positive, duodenal ulcer patients (mean age, 40.7 +/- 11.7 yr; 40 male and 19 female) were treated for 2 wk with either amoxicillin-metronidazole (n = 36) or omeprazole-amoxicillin-tinidazole (n = 23), and after 4 wk, were tested for H. pylori infection by [14C]urea breath test (UBT), serum IgG antibody level, and multiple antral biopsies for rapid urease testing, histology, Warthin-Starry stain, and polymerase chain reaction to detect H. pylori DNA. Infection status was established by a concordance of test results. RESULTS: H. pylori was eradicated in 47 patients (80%). UBT and rapid urease testing had the best sensitivity and specificity, although not statistically different to Warthin-Starry stain and polymerase chain reaction. Serology and histology had little diagnostic value in this setting due to high proportion of false-positive results. CONCLUSIONS: Noninvasive UBT is as accurate in predicting H. pylori status after antibiotic treatment as rapid urease testing and Warthin-Starry stain. Especially for duodenal ulcer patients, UBT could be considered the gold standard to confirm eradication of H. pylori.

[Occult gallbladder disease or microlithiasis in patients with acute pancreatitis: a frequent clinical event]. / Enfermedad vesicular inaparente o microlitiasis en pacientes con pancreatitis aguda: una situación clínica frecuente.

BACKGROUND: Patients with acute pancreatitis (AP) and a normal gallbladder by standard echographic evaluation may have "occult" gallbladder disease or microlithiasis with recurrent episodes of AP. AIM: To conduct a prospective evaluation of patients with the diagnosis of non-biliary AP in order to detect "occult" gallbladder disease and to compare its clinical presentation with that of biliary AP. PATIENTS AND METHODS: Patients admitted with the diagnosis of AP to a clinical hospital were included in the study. According to an abdominal ultrasound study, patients were classified as having or not cholelithiasis. A duodenal biliary drainage was performed in 15 patients with AP and without gallbladder stones. RESULTS: Patients without cholelithiasis had recurrent AP more often than patients with biliary AP (53 and 3.3% respectively). Excessive alcohol ingestion did not rule out the possibility of biliary etiology. In 6 patients, the analysis of duodenal bile showed cholesterol crystals, and cholecystectomy confirmed the existence of gallbladder disease in 5. All of them remained asymptomatic during a follow-up period of four years. One patient refused surgery, with subsequent development of gallstones and recurrent episodes of AP. In other 4 patients, gallbladder disease was confirmed by percutaneous gallbladder puncture or during cholecystectomy. No recurrence of AP were observed during the follow-up CONCLUSIONS: Microlithiasis or "occult" gallbladder disease accounts for at least 67% of the original "non-biliary" AP. Duodenal bile analysis is a useful and necessary technique for the evaluation of patients with "non-biliary" acute pancreatitis. Careful clinical and echographic follow-up of this subgroup of patients with AP is mandatory.

[Intrasphincteric injection of botulinum toxin in patients with esophageal achalasia]. / Inyección intraesfinteriana de toxina botulínica en pacientes con acalasia esofágica.

BACKGROUND: Intrasphincteric injection of botulinum toxin (BoTx) has demonstrated to be effective in the short-term treatment of achalasia. AIM: To assess the efficacy, safety and long-term outcome of BoTx injection into the lower esophageal sphincter (LES) of patients with achalasia. PATIENTS AND METHODS: Eight patients received 80 units of BoTx. Assessment of response was based on changes in the symptom scores (0-9) and esophageal manometric studies. RESULTS: Six out of 8 patients (75%) had sustained clinical improvement after therapy. This effect was maintained for a mean time of 17.8 months. The symptom score decreased from a mean of 6.7 to 0.5 (p < 0.01) and after treatment, LES pressure decreased from 63 to 25.5 mm Hg (p = 0.07). There were no serious adverse effects. Five of the six responders have relapsed. Two of these patients received a second BoTx injection with satisfactory results, two went to surgery and one refused other type of therapy and died of pneumonia. CONCLUSIONS: Intrasphincteric BoTx injection is a simple, safe and effective method of treatment in patients with achalasia, with a duration of response averaging 1.5 years. Its use may be suggested in some patients with high surgical risk and those who refuse a more invasive therapy. It is also useful in malnourished patients to attain an adequate nutritional status before surgery.

[Eradication of Helicobacter pylori in developing countries]. / Erradicación de Helicobacter pylori en países en desarrollo.

A NIH Consensus Conference recommended Helicobacter pylori eradication to all ulcer patients, based mainly on information coming from countries with a low prevalence of infection in general population. The epidemiological situation is different in developing countries, where a pandemic of H. pylori goes unchecked, and most people become infected at young age. It is possible that response to eradication therapies and reinfection rate were to be included among the differences between developed and developing countries, raising doubts about the worldwide applicability of NIH recommendations. Limited published evidence and our experience suggest that eradication therapies have a lower efficacy and reinfection rate is significantly higher in developing compared to developed countries. In spite of this, the risk of ulcer recurrence after H. pylori eradication is substantially reduced compared to antisecretory therapy. Model analysis to evaluate the cost-effectiveness of H. pylori eradication, using figures that probably include the clinical and costs situation of developing countries, suggests that also from an economic perspective H. pylori eradication should be the standard treatment for peptic ulcer disease in developing countries. Local studies must determine the best eradication therapy for a particular geographical location, and longer follow-up of eradicated patients is needed to determine the true reinfection rate.

[Tuberculosis infection prevalence in children younger than 7 years of age in Cantabria. What is the recommended periodicity for the tuberculin tes?]. / Prevalencia de infección tuberculosa en niños y niñas menorés de 7 años en Cantabria. Con qué periodicidad realizar la prueba tuberculínica?

OBJECTIVE: Because of the disparity between the recommendations regarding age and frequency for the realization of tuberculin testing during childhood, a study of tuberculous infection prevalence according to age was made in order to establish at which ages tuberculin testing would be recommendable and to determine if there is a difference in prevalence between vaccinated and non-vaccinated children. PATIENTS AND METHODS: A study was carried out by performing annual tuberculin tests (4,454) using the Mantoux technique on 1,710 boys and girls between 1 and 6 years of age. Of these, 796 (46.54%) had been vaccinated with BCG at birth. Children on which a diagnostic tuberculin test had been carried out were excluded from the study. Indurations larger or equal to 10mm were considered positive, in vaccinated as well as in non-vaccinated children, until the publication and adoption of the criterion recommended by the National Concensus for Tuberculosis Control in Spain in 1992. Thereafter, indurations larger or equal to 5 mm in non-vaccinated children and larger than 14 mm in vaccinates children were considered positive. RESULTS: The prevalence of tuberculosis infection was 0.49%, 1.87%, and 6,66% at one, 4 and 6 years of age, respectively, in non-vaccinated children and 0.31%, 2.25% and 8,69% at the same ages in vaccinated children was compared and no statistically significant difference was found. CONCLUSIONS: We recommend the realization of tuberculin tests at one and 4 years of age and show that, in our medium, vaccinated children have a tuberculous infection prevalence during early childhood similar to their non-vaccinated counterparts.

Differential response of photosensitized young and old human erythrocytes to photodynamic activation.

It has recently been proposed that photosensitized erythrocytes may play an important role in the delivery and targeting of agents such as photosensitizers and chemotherapeutics for use in cancer treatment. It has been suggested that loading of photosensitized erythrocytes with chemotherapeutic agents would provide an ideal means of combining both treatment modalities. The recent application of real-time confocal laser scanning microscopy to the study of immediate effects of photodynamic activation on photosensitized erythrocytes has enabled us, in this study, to distinguish between the differential susceptibility of age-density resolved sub-populations of human erythrocytes to photodynamic activation. In this study we demonstrate that younger (low age-density) sub-populations of photosensitized erythrocytes are less susceptible than older (high age-density) sub-populations to photodynamic activation. We also demonstrate that this phenomenon is exhibited by cells photosensitized using hematoporphyrin derivative and rose bengal as photosensitizers. In both cases no significant difference in uptake of photosensitizer by both populations could be observed using absorbance spectrophotometry. The study suggests that age-density resolution of erythrocytes prior to loading and photosensitization might provide a means of enhancing the release of loaded components from the photosensitized system and this would, in turn, enhance the potential use of photosensitized erythrocytes as delivery or targeting systems for use in combination cancer therapies.

[Results of podoscope screening in 948 non-selected children, with special reference to cavus foot]. / Resultados del screening con podoscopio en 948 niños no seleccionados con especial referencia al pie cavo.

OBJECTIVE: To ascertain the prevalence of cavus foot in a non-selected pediatric population, the percentage of secondary forms and to establish criteria for remission to the specialist. PATIENTS AND METHODS: A randomized study of 948 healthy children older than four years, in which the sole footprint was studied through podoscope, was performed. RESULTS: Cavus foot of different grades was present in 16.3% of the children studied, with a statistically significant difference in favor of girls. There were family antecedents in 60%. Symptoms and/or exploratory abnormal signs were presented in 19.3%, mainly pain, limp and sole dermatitis. Of the diagnoses made, 7.7% were referred to the specialist, with the diagnosis confirmed in 75% and treatment implemented in 50%. There were no cases of secondary cavus foot. CONCLUSIONS: Cavus foot is very frequent in healthy children, has a familiar character and only exceptionally obeys the rules of a neuromuscular cause. We propose four criteria for the selection of patients for referral to the specialist.

The effects of electric fields on photosensitized erythrocytes: possible enhancement of photodynamic activation.

In this study it has been found that exposure of photosensitized erythrocytes to short, intense electric pulses, resulted in cell lysis. When erythrocytes were photosensitized with increasing concentrations of the photosensitizer, hematoporphyrin derivative (HPD), and subjected to electric pulses in the absence of light, cell lysis increased with increasing photosensitizer concentration. In addition, it has been shown that exposure of photosensitized erythrocytes to electric field pulses of increasing field strength resulted in increased cell lysis. Light activation of photosensitized erythrocytes, pre-treated with electric pulses, also resulted in increased cell lysis. The results presented here suggest that HPD may be activated in the absence of light using electric pulses. We suggest that enhancement of activation by electric field stimulation may find application in increasing the overall efficiency of photodynamic therapy.

Use of real-time confocal laser scanning microscopy to study immediate effects of photodynamic activation on photosensitized erythrocytes.

With a view towards the design of systems capable of combining the use of chemotherapy and photodynamic therapy in the treatment of cancer and other disorders, it has been proposed that photosensitized erythrocytes might be employed as carriers/vehicles for agents such as cancer chemotherapeutics. In studying the light dependent release of entrapped agents from such a system, the efficacy of light induced release is usually studied by measuring release of an entrapped component into centrifugation supernatants following photoactivation. It has hitherto been extremely difficult to examine what occurs upon immediate irradiation at the microscopic level in real-time. In this study we demonstrate that, using real-time confocal laser scanning microscopy, it is possible to directly observe immediate short-term events occurring during direct irradiation with the visualizing beam. Following irradiation of photosensitized erythrocytes with the visualizing beam form the confocal scanning system, it was noticed that some from of cell-disruptive event occurred. In this study we demonstrate a dose dependent response between this relatively immediate, light induced disruptive event with respect to both irradiation exposure and photosensitizer concentration. We suggest that this system may provide a novel means of observing, at a microscopic level, events occurring in real-time during photodynamic therapy.

Endoscopic intrasphincteric injection of botulinum toxin for the treatment of achalasia.

Three patients with achalasia were treated with endoscopic injection of botulinum toxin (BoTx). BoTx (80 U) was injected via a sclerotherapy needle into the lower esophageal sphincter (LES). One patient complained of transient heartburn that resolved after omeprazole treatment. Two patients reported sustained symptomatic improvement. They were able to eat normally 48 h after treatment and have remained symptom free for 5 and 6.5 months, respectively. In these patients, esophageal manometry 4 months after treatment showed a marked reduction of resting LES pressure and the appearance of a previously absent LES relaxation after swallowing. The third patient had only a transient clinical improvement, with occasional dysphagia beginning 3 months after treatment. All patients showed unchanged aperistalsis of the esophageal body. Its less invasive nature compared with other therapeutic alternatives may give BoTX injection a role in the treatment of some patients with achalasia.

Apolipoprotein E polymorphism in patients with acute pancreatitis.

We have shown that patients with previous acute pancreatitis (AP) may have an abnormal catabolism of chylomicron remnants (CMR). Because apoprotein E (Apo E) genetic polymorphism has an important influence on CMR clearance, we compared frequency distribution of Apo E phenotypes in 52 patients with AP, 109 patients with gallstones, and 110 control subjects. Apo E phenotypes were detected by isoelectric focusing and immunoblotting. After adjusting for differences in age and gender, fasting triglyceride level was comparable between the study groups. The frequency distribution of Apo E phenotypes was not different between the three study groups and it was in Hardy-Weinberg equilibrium. The gene frequency for Apo E2 was 0.212, 0.273, and 0.243 in AP, gallstone, and control group, respectively. For Apo E3 it was 0.701, 0.627, and 0.674, and for Apo E4 0.090, 0.100, and 0.083 in the same groups, respectively. Differences were not statistically significant (chi 2). In conclusion, the abnormal catabolism of CMR in patients with AP is not attributable to Apo E polymorphism. An alternative explanation may be sought in the activity of the recently identified hepatocytic Apo E receptor [LDL-related receptor protein (LRP)].