Targeted Electromyographic Biofeedback With Endoanal Electrostimulation for Anal Incontinence.

Purpose. Anal incontinence (AI) is a disabling condition with a variable response to conservative physical therapies. We assess the utility of combining electromyographic biofeedback with endoanal electrostimulation targeted to the weakest areas of the pelvic floor using the MAPLe® probe (Multiple Array Probe Leiden Novuqare). Methods. Patients with AI unresponsive to conservative measures were assessed before and after treatment with anorectal manometry (ARM), electromyography (EMG), Wexner Continence Scoring, Visual Analog Scoring (VAS), FIQL and SF-12 quality of life determination. Results. Of 29 patients in the final analysis, there was an improvement in the mean Wexner continence score from 13.59 to 8.03 and a concomitant improvement in the reported VAS from 3.45 to 6.72. Both Wexner continence and VAS scores were maintained during follow-up. Maximum voluntary manometric contraction significantly improved from 91.76 mmHg to 110.33 mmHg with no changes in resting pressure. The EMG values ​​(µV) that significantly improved included the average and peak resistance, the average general voluntary contraction, and the average and peak voluntary contraction for both the external anal sphincter and the puborectalis. In the FIQL, behavior, depression and shame domains improved after treatment and during follow-up with lifestyle improvements detected at 6 and 12 months. Physical and mental components of the SF-12 improved at 6 and 12 months. Conclusions. Targeted electromyographic biofeedback and endoanal electrostimulation using MAPLe® probe in AI patients sustainably improves objective ARM and EMG parameters along with subjective reporting of continence severity, VAS, and quality of life.

Influence of Er:YAG and Ti:sapphire laser irradiation on the microtensile bond strength of several adhesives to dentin.

The aim of the present study was to evaluate the influence of erbium:yttrium-aluminum-garnet (Er:YAG) and Ti:sapphire laser irradiation on the microtensile bond strength (MTBS) of three different adhesive systems to dentin. Flat dentin surfaces from 27 molars were divided into three groups according to laser irradiation: control, Er:YAG (2,940 nm, 100 µs, 2.7 W, 9 Hz) and Ti:sapphire laser (795 nm, 120 fs, 1 W, 1 kHz). Each group was divided into three subgroups according to the adhesive system used: two-step total-etching adhesive (Adper Scotchbond 1 XT, from now on XT), two-step self-etching adhesive (Clearfil SE Bond, from now on CSE), and all-in-one self-etching adhesive (Optibond All-in-One, from now on OAO). After 24 h of water storage, beams of section at 1 mm(2) were longitudinally cut from the samples. Each beam underwent traction test in an Instron machine. Fifteen polished dentin specimens were used for the surface morphology analysis by scanning electron microscopy (SEM). Failure modes of representative debonded microbars were SEM-assessed. Data were analyzed by ANOVA, chi-square test, and multiple linear regression (p < 0.05). In the control group, XT obtained higher MTBS than that of laser groups that performed equally. CSE showed higher MTBS without laser than that with laser groups, where Er:YAG attained higher MTBS than ultrashort laser. When OAO was used, MTBS values were equal in the three treatments. CSE obtained the highest MTBS regardless of the surface treatment applied. The Er:YAG and ultrashort laser irradiation reduce the bonding effectiveness when a two-step total-etching adhesive or a two-step self-etching adhesive are used and do not affect their effectiveness when an all-in-one self-etching adhesive is applied.

Coordinated and sequential activation of neutral and acidic DNases during interdigital cell death in the embryonic limb.

Interdigital tissue regression during embryonic development is one of the most representative model systems of morphogenetic cell death, but the degenerative cascade accounting for this process awaits clarification. Although the canonical apoptotic caspase pathway appears to be activated in the interdigital mesenchyme committed to die, neither genetic nor chemical blockage of caspases or their downstream effectors, is sufficient to prevent cell death. Hence, alternative and/or complementary dying pathways must also be responsible for this degenerative process. In this work we have chosen to study the endonucleases during the regression of the interdigital tissue of avian embryos to gain insights into the molecular mechanisms accounting for programmed cell death in this system. We show that caspase activated DNase, which is a neutral DNase associated with the caspase apoptotic pathway, appears to be the main endonuclease only at an initial phase of interdigit regression. However at peak stages of the degenerative process, the acidic DNases L-DNase II and lysosomal DNase IIB become predominant in the system and markers for cell autophagy become moderately up-regulated. Consistent with the activation of acidic endonucleases we observed that microenvironmental pH value in the interdigits decreased to levels only appropriate for acidic enzymes. Furthermore, we found that overexpression of lysosomal DNase IIB in embryonic limb mesoderm promoted cell death, which was also accompanied by up-regulation and activation of L-DNase II. Up-regulation of acidic DNases was maintained in interdigits explanted to culture dishes, where the participation of exogenous professional phagocytes of hematopoietic origin is avoided. Finally, and consistent with all our findings, up-regulation of acidic DNases was much reduced in the webbed interdigits of duck embryos, characterized by a rudimentary interdigital degenerative process. We conclude that the regression of the interdigital tissue involves a coordinated and sequential activation of the caspase and lysosomal degenerative molecular cascades.

[Assessment of the efficiency of the clinical management of neuropathic pain in specialist clinics compared to general clinics in neurology health care units in Spain]. / Evaluación de la eficiencia del manejo clínico del dolor neuropático en consultas especializadas frente a consultas generales en unidades asistenciales de neurología en España.

OBJECTIVES: To analyse the cost-consequences of chronic neuropathic pain (NeP) outpatients care comparing management in general clinics (GC) versus specialised pain clinics (SPC) in neurology settings in Spain. METHODS: A 6-month retrospective, cross-sectional, comparative observational study including NeP subjects was designed. Sociodemographics and clinical characteristics of subjects along with pain-related healthcare and non healthcare resources utilization were recorded. Lost-work-days equivalent missed as a consequence of pain were also collected to compute indirect costs. Costs to society were calculated in euros for the year 2008. Severity and interference of pain were used for the main effectiveness evaluation. RESULTS: A total of 234 patients (53% in SPC), 56.8% women, and 59.3+/-14.7 years were included. Patients were allocated according to usual administrative procedures in each participant centre, consecutively and independently of the diagnosis and clinical status of patients. Yearly indirect costs were euro1,299+/-2,804 in SPC compared to euro1,483+/-3,452 in GC (p=0.660), while annual direct costs were, euro2,911+/-3,335 and euro3,563+/-4,797, respectively (p=0.239), with total costs of euro4,210+/-4,654 and euro5,060+/-6,250, respectively (p=0.249). Mean pain severity at the time of evaluation was 3.8+/-2.3 in subjects in SPC vs. 5.2+/-2 in GC (p<0.001), while the average interference of pain on daily activities were 3.3+/-2 and 4.7+/-2.5, respectively (p<0.001). CONCLUSIONS: In neurology settings in Spain, the outpatient clinical management of chronic NeP in SPC was a dominant alternative compared with GC healthcare, since it has shown better patients healthcare outcomes with less severity and interference of pain on daily activities, while maintaining a similar level of costs. These results could help health decision makers when planning the use of health care resources.

Recomendaciones GEIPC-SEIMC y GTEI-SEMICYUC para el tratamiento antibiótico de infecciones por cocos grampositivos en el paciente crítico / GEIPC-SEIMC and GTEI-SEMICYUC recommendations for antibiotic treatment of gram positive coccal infections in the critical patient

En los últimos años se ha constatado un incremento en las infecciones causadas por cocos grampositivos tanto en infecciones comunitarias como nosocomiales. En algunos países, se ha observado un rápido desarrollo de resistencias a los antibióticos habitualmente empleados para su tratamiento, y se supone que esa situación puede llegar en el futuro a nuestro país. Se están desarrollando nuevos antimicrobianos específicamente dirigidos para el tratamiento de estas infecciones, pero es necesario profundizar en el conocimiento de las propiedades farmacocinéticas de los antibióticos tanto antiguos como nuevos, para aprovechar al máximo sus cualidades frente a estos patógenos y evitar en lo posible su toxicidad. En el paciente crítico estos problemas son más acuciantes, ya que la inadecuación del tratamiento, tanto en la elección del antibiótico como en la dosis y en la administración, se acompañan frecuentemente de fracasos terapéuticos y por tanto de mal pronóstico. Expertos de dos grupos de trabajo de dos Sociedades científicas, pertenecientes al Grupo de estudio de Infecciones en el Paciente Crítico de la SEIMC (GEIPC-SEIMC) y al Grupo de trabajo de Enfermedades Infecciosas de la SEMICYUC (GTEI-SEMICYUC) se han reunido con el objetivo de elaborar un documento de consenso, basado en la evidencia científica, que recoge las recomendaciones para el tratamiento antibiótico de las infecciones graves causadas por cocos grampositivos en el paciente crítico y que ayude en la toma de decisiones asistenciales (AU)

In recent years, an increment of infections caused by gram-positive cocci has been documented in nosocomial and hospital-acquired-infections. In diverse countries, a rapid development of resistance to common antibiotics against gram-positive cocci has been observed. This situation is exceptional in Spain but our country might be affected in the near future. New antimicrobials active against these multi-drug resistant pathogens are nowadays available. It is essential to improve our current knowledge about pharmacokinetic properties of traditional and new antimicrobials to maximize its effectiveness and to minimize toxicity. These issues are even more important in critically ill patients because inadequate empirical therapy is associated with therapeutic failure and a poor outcome. Experts representing two scientific societies (Grupo de estudio de Infecciones en el Paciente Crítico de la SEIMC and Grupo de trabajo de Enfermedades Infecciosas de la SEMICYUC) have elaborated a consensus document based on the current scientific evidence to summarize recommendations for the treatment of serious infections caused by gram-positive cocci in critically ill patients (AU)

Incontinencia fecal en el anciano / Faecal incontinence in the elderly

Es importante que los médicos consideremos la incontinencia fecal como un serio problema y no como una parte normal del envejecimiento. Con frecuencia, el paciente anciano no refiere su existencia y se deberá preguntar específicamente por su presencia. Muchos médicos desconocen que pueden existir tratamientos para la incontinencia fecal. Hay numerosas causas de incontinencia fecal, y las secundarias a traumatismos obstétricos, junto a la impactación fecal, son las más frecuentes. Una correcta historia clínica y una minuciosa exploración física permitirán descubrir la causa. El tratamiento conservador consistirá en antidiarreicos, dieta rica en fibra, "bio-retroalimentación" o enemas. Si falla el tratamiento médico, el paciente deberá ser evaluado por un equipo multidisciplinario que incluya a un cirujano. La meta final es mejorar la calidad de vida del paciente (AU)

Tratamiento integral de la obesidad y su prevención / Comprehensive treatment of obesity and its prevention

La obesidad abre la puerta a entidades metabólicas crónicas que ensombrecen la calidad y el pronóstico de vida. Si algo tiene en su favor es que su tratamiento precoz y sostenido, si eficaz, entrecierra esa puerta, que una vez traspuesta no puede ser vuelta a cruzar. La normalización de la composición corporal, de las reservas energéticas y su distribución, así como la minimización de los trastornos metabólicos peso dependientes y el establecimiento de prioridades terapéuticas, de acuerdo a las repercusiones de la obesidad, son factores importantes para el tratamiento de esta enfermedad. La prevención es importante y su base es la enseñanza y puesta en práctica de un estilo de vida más saludable con modificación de la oferta alimentaria e incorporación de trabajo físico a las actividades cotidianas. La dietoterapia, la actividad física, la farmacoterapia, la cirugía y la psicología son las formas propuestas de tratamiento y prevención de la obesidad. (AU)

[L-carnitine levels in critical septic patients receiving parenteral nutrition]. / Niveles de L-carnitina en pacientes críticos sépticos con nutrición parenteral.

Septicemia causes multiple and often not very well understood metabolic alterations. In this sense it is controversial whether or not carnitine is decreased, which may have several implications. Our objective is to measure the plasma carnitine levels in septicemic patients, and to find out whether this is modified if there is a multi-organ dysfunction syndrome (MODS), or if it is dependent on the lipid source. For this we carried out a prospective study in septicemic patients with MODS. These were given exclusively parenteral nutrition (PN) without any carnitine supplementation. The PN of 16 patients contained long chain triglycerides (LCT's), while that of another 12 contained a 1:1 mixture of long and medium chain triglycerides (LCT's and MCT's). We measured the plasma carnitine level at the baseline, after 5 days and after 10 days, using an enzymatic method that measures the total carnitine level (free and esterified). The normal values lie between 35 and 70 mumol/l. We included 28 septicemic patients whose ages were 53.41 +/- 16.51 years, and whose APACHE II on admission was 17 +/- 4. The carnitine levels were: baseline: 60.4 +/- 23.7; 5th day 57.7 +/- 22.9; 10th day 55.7 +/- 21.2 (p = n.s.). Of these patients, 10 had an MODS of septic origins with their baseline levels being: 65.3 +/- 30.9; 5th day 60.3 +/- 23.2; 10th day 61.5 +/- 15.5; while the levels of the 18 septicemic patients without MODS, the baseline levels were 61.9 +/- 13.8; 5th day 58.6 +/- 19.1; 10th day 56.6 +/- 19.3 (p = n.s.). In the patients who were given LCT's the baseline carnitine level was 60.7 +/- 23.1, 5th day 60.1 +/- 23.8; 10th day 58.6 +/- 12.8; while those patients who were given LCT/MCT showed baseline levels of 64.3 +/- 19.5; 5th day 58.6 +/- 19.1; 10th day 57.8 +/- 10.7 (p = n.s.). In our septicemic patients the serum carnitine levels we found were within the normal range, and these remained unchanged during the ten days in those patients with MODS or with the lipid mixture used.

Hydrolysis of used frying palm olein and sunflower oil catalyzed by porcine pancreatic lipase.

The enzymatic hydrolysis of frying used vegetable oils with different degrees of alteration were measured using porcine pancreatic lipase (acylglycerol acylhydrolase EC 3.1.1.3). Successive frying of potatoes significantly increased the level of total polar lipid content in the palm olein from 9.3 +/- 0.1 mg/100 mg oil to 26.4 +/- 0.3 mg/100 mg oil after 90 fryings, and from 4.0 +/- 0.1 mg/100 mg oil to 27.7 +/- 0.3 mg/100 mg oil in sunflower oil after 60 fryings. Triacylglycerol polymers, triacylglycerol dimers, and oxidized triacylglycerols also increased 37-, 7.9-, and 7.5-times in palm olein, respectively, and 56-, 22-, and 4.7-times in sunflower oil, respectively. However, diacylglycerols and free fatty acid levels related to hydrolytic alteration did not increase with the number of fryings in both oils. The substrate concentration in the reactor was determined by calculating the molecular weight of each oil showing a different degree of alteration. We compared the methodology used by us and that used by other authors. The results show that the methods are reproducible and that the values obtained are in concordance with theoretical values. The kinetic parameters apparent Michaelis-Menten constant (KMapp) and apparent maximum velocity of hydrolysis (Vmaxapp) were different in unused palm olein (5.1 +/- 0.7 and 166 +/- 7.6, respectively) than in sunflower oil (2.2 +/- 0.3 and 62 +/- 2.2, respectively). However, changes in KMapp and Vmaxapp were not related to the degree of alteration of the oils.

[Basis for changes in medical education]. / Bases para el cambio de la educación médica.

Medicine and medical education are going through a critical period due to a series of factors. Amongst them the explosion of knowledge and the progress in technology, and on the other hand the inefficiency of traditional medicine to cope with frequent and important health problems. We propose a medical education model based on a wider traditional model that incorporates social and psychological aspects of medicine emphasizing on prevention of disease and promotion of health. This model offers new methodological alternatives centered in the identification of problems, the acquisition of information and decision making, rather than in the storage of information.

Pharmacology of the potent new non-steroidal anti-inflammatory agent aceclofenac.

Aceclofenac (2-[(2,6-dichlorophenyl) amine]phenylacetoxyacetic acid; CAS 89796-99-6) is a new orally effective non-steroidal anti-inflammatory agent of the phenylacetic acid group which showed remarkable anti-inflammatory, analgesic, and antipyretic properties. Hence, aceclofenac possesses a potent inhibitory activity in several models of acute and chronic inflammation in rodents, and resembles indometacin and diclofenac in its pharmacodynamic profile, being superior to naproxen and phenylbutazone. In addition, aceclofenac was found to be highly active against sodium urate-induced synovitis in dogs and adjuvant-induced polyarthritis in rats, both prophylactically and therapeutically. The analgesic effect of aceclofenac on the pain elicited by chemical and mechanical stimuli was nearly equal to or slightly better than that of indometacin and diclofenac. Fever induced by brewer's yeast injection in rats was also markedly suppressed by aceclofenac. In contrast, the acute gastric ulcerogenic activity of aceclofenac was about 2, 4 and 7-fold lesser than that of naproxen, diclofenac, or indometacin, respectively. As a consequence of its high anti-inflammatory activity and lower potential for gastric damage aceclofenac exhibited the most favourable therapeutic ratio in comparison with indometacin, diclofenac, naproxen, and phenylbutazone. These data indicate that aceclofenac could be a potent anti-inflammatory and analgesic agent with a wide margin of safety in clinical practice.

Potassium supplementation lowers blood pressure and increases urinary kallikrein in essential hypertensives.

In order to eludicate possible mechanism(s) involved in the blood pressure reduction induced by potassium (K) supplementation, we studied the changes of BP and of some of its regulatory systems, including levels of urinary kallikrein (UKal)--an index of renal kallikrein production. Twenty-four untreated essential hypertensives, with a basal BP of 147/96 +/- 13/7 mmHg and normal renal function, received in crossover, double-blind, randomised fashion, 64 mmol KCl or placebo during two periods of 4 weeks each. At the 4th week of potassium supplementation systolic, diastolic and mean BPs decreased by 6.3 +/- 2 (P less than 0.01), 3.0 +/- 2 and 4.1 +/- 2 (P less than 0.05) mmHg respectively for the supine position, and 5.0 +/- 2, 4.0 +/- 2 (P less than 0.05) and 4.0 +/- 1 (P less than 0.05) mmHg for the standing position. Urinary potassium (K) increased from 55 +/- 4 to 123 +/- 6 mmol/24 hours (P less than 0.001) and UKal from 692 +/- 69 to 1052 +/- 141 mU/24 hours (P less than 0.01). Serum K rose from 3.8 +/- 0.1 mEq/l to 4.1 +/- 0.1 mmol/l (P less than 0.001) and PRA from 0.77 +/- 0.12 to 0.99 +/- 0.14 ng/ml/h (P less than 0.05). Correlations were observed between UKal and urinary K (r = 0.44, P less than 0.0001); between differences in UKal and urinary K and in UKal and urinary Na (r = 0.50, P less than 0.0005 and r = 0.48, P less than 0.001 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Ensayo BAY 1040. / Therapeutic trial with BAY 1040

Se hizo ensayo terapeutico con un antagonista del calcio, nifedipina (BAY 1040), en estudio doble ciego randomizado en 40 pacientes ambulatorios, por medio de ergometria (cicloergometro) previa y luego de la administracion de placebo o medicamento a los 7 y 14 dias respectivamente. La dosis utilizada del medicamento fue de 10 mg cada 8 horas. No se observaron modificaciones significativas en la frecuencia cardiaca, ni en la presion arterial en reposo y al esfuerzo, pero di discreta disminucion del ITTM al esfuerzo. En la mayoria de pacientes (61,3%) disminuyeron las crisis anginosas, y en el 16,1% desaparecieron totalmente. El 50% disminuyo el consumo de nitritos diarios. El descenso del S-T al esfuerzo para una misma frecuencia cardiaca, disminuyo o desaparecio en alto porcentaje. Los resultados globales fueron considerados como buenos y muy buenos en el 77,5% y negativos en el 22,5% de casos

The oncostatic and immunosuppressive action of new nitrosourea derivatives containing sugar radicals.

Four new nitrosourea derivatives represent an appreciable progress in the treatment and cure of L1210 leukemia. Their therapeutic index is higher than that of CCNU and MeCCNU. Of these compounds, RFCNU may prove the most promising, as its therapeutic index is the highest of those for all the four compounds studied; moreover, unlike the other products, it is not immunosuppressive, whether administered before or after the antigen.