[Laparoscopic apendicectomy vs open approach for the treatment of acute appendicitis]. / Apendicectomía laparoscópica frente al abordaje abierto para el tratamiento de la apendicitis aguda.

BACKGROUND: There is no international consensus on the approach of choice for performing appendectomy. AIMS: To analyze and compare open and laparoscopic approaches in the surgical treatment of acute appendicitis. MATERIAL AND METHODS: A retrospective study was carried out on patients over 14-years-old operated on for suspected acute appendicitis between January 2007 and December 2009. Variables were: age, sex, body mass index, specialized surgeon or resident in training, progression duration, conversion rate, use of drains, abdominal cavity irrigation, macroscopic appearance of the appendix, onset time of anesthesia, ASA classification, postoperative hospital stay, resumption of intake of liquids, and complications. The patients were divided into two groups: laparoscopic approach (LA) and open approach (OA). RESULTS: A total of 533 patients were enrolled (290 LA and 243 OA). Onset time of anesthesia was 75 min (30-190 min) in LA vs 55 min (20-160 min) in OA (p<0,0001). COMPLICATIONS: intraabdominal abscesses in 17 LA cases vs 13 OA cases (p=0,79); surgical wound alterations in 16 LA cases vs 47 OA cases (p=0,0001); incisional hernias in 2 LA cases (1%) vs 10 OA cases (p=0,008). There were no statistically significant differences in postoperative hospital stay (3 days), resumption of intake of liquids (1 day) or readmission rate (8%). CONCLUSIONS: There are fewer surgical wound alterations and incisional hernias with the laparoscopic approach, but there is higher cost, lengthier surgery duration, and a longer learning curve. Our results cannot provide a clear indication for one approach or the other, and therefore each case must be evaluated on an individual basis.

Impact of the total number of harvested lymph nodes after colon cancer resections on survival in patients without involved lymph node.

BACKGROUND: The total number of harvested lymph nodes has been demonstrated to be of prognostic significance for colon cancer. Differences can occur in the total number of harvested lymph nodes between different specialists (surgeons and pathologists). OBJECTIVE: The aim of this study was to analyse if, in our centre, the number of analysed lymph nodes in patients with colon cancer that are classified as pN0 is also related to survival. MATERIAL AND METHODS: A retrospective study was designed, where 148 patients with colon adenocarcinoma (pN0 of TNM classification) who underwent elective surgery between 1 January 1995 and 31 December 2001, with curative intent were included. Three groups were created according to the number of analysed lymph nodes ( < 7, 7-14, > 14 lymph nodes). For survival analysis the Kaplan-Meier and CUSUM curves methods were used. RESULTS: The total number of analysed lymph nodes was 1,493 (mean 10.1 lymph nodes per patient). The rate of 5-years survival was 63.0% in the group with < 7 lymph nodes; 7-14 lymph nodes: 80.6% and those with > 14 lymph nodes: 91.8% (p < 0.01). Prognostic significance was also present for multivariate analysis. CONCLUSION: In our centre, harvesting a larger number of lymph nodes is related to improved rates of 5-years survival for patients with colon cancer staged as pN0. It seems reasonable to recommend obtaining as many lymph nodes as possible, and not to establish a minimum number of lymph nodes to be harvested.

[Influence of surgeon specialization upon the results of colon cancer surgery. Usefulness of propensity scores]. / Influencia de la especialización del cirujano en los resultados tras cirugía por cáncer de colon. Utilidad de los índices de propensión (propensity scores).

INTRODUCTION: surgeon influence on colorectal cancer surgery outcomes has been repeatedly studied in the scientific literature, but conclusions have been contradictory. Here we study whether surgeon specialization is a determinant factor for outcome in these patients. The importance of propensity scores (PS) in surgical research is also studied. PATIENTS AND METHODS: a retrospective study was performed and medical records were reviewed for 236 patients who were intervened for colon cancer in Castellon General Hospital (Spain). Cases were divided into two groups (specialist and non-specialist surgeons), and both 5-year surveillance and disease free survival were compared. Comparisons were first made with no adjustments, and then subsequently using PS analysis. RESULTS: the initial (non-adjusted) analysis was clearly favourable for the specialist surgeon group (5-year surveillance, 64.3 vs. 79.3%, p = 0.028). After adjusting for PS no statistical significance was obtained. CONCLUSIONS: surgeon specialization had no significant impact on patient outcome after colon cancer surgery. Propensity score analysis is an important tool in the analysis of surgical non-randomized studies, particularly when events under scrutiny are rare.

Kimura disease in an African patient.

We operated on a 23-year-old black Nigerian man with a 4-year history of a tumour on the left cheek associated with IgE hypergammaglobulinaemia and peripheral eosinophilia. The lesion recurred.

[Analysis of patient complaints in Primary Care: An opportunity to improve clinical safety]. / Análisis de las reclamaciones de pacientes en Atención Primaria: una oportunidad para mejorar la seguridad clínica.

OBJECTIVE: To determine the prevalence and type of the clinical safety problems contained in the complaints made by patients and users in Primary Care. MATERIAL AND METHODS: An observational, descriptive, cross-sectional study was conducted by analysing both the complaint forms and the responses given to them in the period of one year. RESULTS: At least 4.6% of all claims analysed in this study contained clinical safety problems. The family physician is the professional who received the majority of the complaints (53.6%), and the main reason was the problems related to diagnosis (43%), mainly the delay in diagnosis. Other variables analysed were the severity of adverse events experienced by patients (in 68% of cases the patient suffered some harm), the subsequent impact on patient care, which was affected in 39% of cases (7% of cases even requiring hospital admission), and the level of preventability of adverse events (96% avoidable) described in the claims. Finally the type of response issued to each complaint was analysed, being purely bureaucratic in 64% of all cases. CONCLUSIONS: Complaints are a valuable source of information about the deficiencies identified by patients and healthcare users. There is considerable scope for improvement in the analysis and management of claims in general, and those containing clinical safety issues in particular. To date, in our area, there is a lack of appropriate procedures for processing these claims. Likewise, we believe that other pathways or channels should be opened to enable communication by patients and healthcare users.

A possible interaction of potential clinical interest between digoxin and acarbose.

This case report describes a 69-year-old woman with diabetes mellitus and heart failure who repeatedly had unusual subtherapeutic levels of plasma digoxin. When the drug therapeutic regimen was checked it was found that a new drug, acarbose, had been added to the therapeutic regimen before the unexpected laboratory reported results. Because other drugs included in her therapeutic menu were rejected as being responsible for decreased levels of digoxin, it was recommended to discontinue acarbose to evaluate its role. In the absence of acarbose, the plasma concentration of digoxin increased to the therapeutic range. We concluded that acarbose may be responsible for a pharmacokinetic interaction with digoxin by a still unknown mechanism. Although discontinuation of acarbose was recommended, the attending physician discontinued administration of digoxin because the clinical condition of the patient did not get worse during subtherapeutic levels of digoxin.

Behavioral expression of opiate withdrawal is altered after prefrontocortical dopamine depletion in rats: monoaminergic correlates.

The objective of this study was to establish the effects of prefrontocortical dopamine depletion on opiate withdrawal and prefrontocortical neurochemical changes elicited by morphine dependence and withdrawal. The dopaminergic content was also measured in the nucleus accumbens during withdrawal, in order to detect reactive changes induced by prefrontocortical lesion. Withdrawal was induced by naloxone in morphine-dependent rats. Monoamine levels were analyzed post-mortem by high performance liquid cromatography. The results showed that chronic morphine dependence did not modify basal levels of monoamines in sham rats, revealing neuroadaptation of prefrontocortical dopamine, noradrenaline and serotonin systems to chronic morphine. The neuroadaptive phenomenon remained after prefrontocortical lesion (> 79% dopamine depletion). On the other hand, a strong increase of dopamine, noradrenaline, and serotonin contents in the medial prefrontal cortex of sham rats was detected during opiate withdrawal. However, in lesioned rats, the increase of prefrontocortical dopamine and serotonin content, but not that of noradrenaline, was much lower. In the nucleus accumbens, prefrontocortical lesion reactively enhanced the dopaminergic tone and, although opiate withdrawal reduced dopaminergic activity in both sham and lesioned rats, this reduction was less intense in the latter group. At a behavioral level, some symptoms of physical opiate withdrawal were exacerbated in lesioned rats (writhing, mastication, teeth-chattering, global score) and exploration was reduced. The findings hence indicate that: (i) prefrontocortical monoaminergic changes play a role in the behavioral expression of opiate withdrawal; (ii) the severity of some withdrawal signs are related to the dopaminergic and serotonergic tone of the medial prefrontal cortex rather than to the noradrenergic one, and (iii) an inverse relationship between mesocortical and mesolimbic dopaminergic systems exists.

Possible involvement of epinephrine in the cardiovascular effect of naloxone in humans.

The opioid-receptor antagonist naloxone was administered intravenously in a 0.8-mg bolus to five healthy volunteers, aged 21 to 31, in a double-blind study designed to investigate the effect of endogenous opioids on blood pressure, heart rate, and urinary excretion of catecholamines in healthy adults. Three hours after administration of naloxone there were significant increases in systolic blood pressure (P less than 0.001) and heart rate (P less than 0.05). The amount of epinephrine excreted in urine during the four hours after administration of naloxone or placebo was significantly higher (P less than 0.05) in subjects given naloxone. These effects support the hypothesis that an endogenous opioid system is involved in the regulation of systolic blood pressure and heart rate in healthy adults. The results also indicate that adrenally released epinephrine could mediate the cardiovascular effect of endogenous opioids.

Implication of beta 1- and beta 2-adrenergic receptors in the antinociceptive effect of tricyclic antidepressants.

Tricyclic antidepressants have been shown to be useful for the treatment of pain of varying etiology. Monoaminergic systems seem to be implicated in this phenomenon. In this study, the influence of the selective beta 1- (CGP 20712A) and beta 2- (ICI 118551) adrenergic blockers on the antinociceptive effect of desipramine and nortriptyline was studied in mice using physical and chemical nociceptive tests that implicate different levels of sensory-motor integration in the central nervous system (CNS). An activity test was performed to detect "false positive" or "false negative" results. Results obtained show that both CGP 20712A and ICI 118551 are able to antagonize the antinociceptive effect of these antidepressants in physical tests (hot-plate and tail-flick). However, in chemical tests (acetic acid and formalin), the analgesic effect of the antidepressants used was only antagonized by CGP 20712A. These results suggest that the analgesic effect of desipramine and nortriptyline is mediated by beta-adrenoceptors. The beta-adrenoceptor involved depends on the type of nociceptive stimulus: beta 1 and beta 2 are both implicated when the stimulus is physical, but only beta 1 is involved when the stimulus is chemical.

Effect of peptidyl-dipeptidase inhibitors in experimental convulsions in mice.

The anticonvulsant effect of compounds that inhibit peptidyl-dipeptidase (PDP) on bicuculline (BIC)- and strychnine (STRYC)-induced seizures was assessed after intracerebroventricular (ICV) or intraperitoneal (IP) administration in Swiss albino mice. STRYC-induced seizures were delayed by ICV injections and high IP doses of captopril, but not by ICV or IP injections of enalapril or by lower doses of captopril (0.1 mg/kg and 1 mg/kg IP). BIC-induced seizures were not suppressed by ICV or IP injections of either compound; on the contrary, captopril and enalapril exhibited proconvulsant effects when given IP or ICV by shortening the time of onset of tonic seizures and death. Results indicate that the anticonvulsant effect of captopril against STRYC-induced seizures is not mediated by central gamma-aminobutyric acid (GABA) receptors or by the inhibition of PDP.

Role of K+ -channels in homotaurine-induced analgesia.

In previous articles, antinociceptive activity for homotaurine has been demonstrated to be mediated by opioid, GABAergic and cholinergic mechanisms. GABAB-agonists affect K+-channels and it is known that K+-channels modulate specific activation of opioid receptors. In this study, we examined the involvement of K+-channels in the antinociceptive activity of homotaurine (22-445 mg/kg). Antinociceptive response was obtained after icv pretreatment with the channel specific blockers 4-aminopyridine (voltage-dependent channels), tetraethylammonium (Ca++ and voltage-dependent) and gliquidone (ATP-dependent). The nociceptive tests performed were acetic acid induced abdominal constriction (mice) and tail flick (rats) tests. Acetic acid responses to homotaurine were inhibited by tetraethylammonium (5 microg) and gliquidone (16 microg). Tail flick response to homotaurine was inhibited by tetraethylammonium (50 microg), gliquidone (40 and 80 microg) and 4-aminopyridine (25 and 250 ng). These results suggest an involvement of the three types of K+-channels in antinociception by homotaurine, depending on specific homotaurine and blocker doses. At a spinal level, they appear to be involved together with GABAB and opioid mechanisms. Peripherally, only tetraethylammonium channels would be substantially activated during homotaurine antinociceptive effect.

Age-related changes in the antinociception induced by taurine in mice.

Taurine is a nonessential amino acid that is of medical interest for the nutrition of infants. Taurine has been found in the central nervous system of rodents and humans, and among its potential therapeutic uses, it is interesting to remark its analgesic actions. It is also well known that concentration levels during the fetal and prenatal periods are higher than in adulthood. The data obtained so far indicate that taurine is involved in the development process of the brain and possibly other organs. The taurine levels in old age are still unknown, but it is presumed that they will be different from those of younger animals. Data about age-related alterations and functional modifications of this and other amino acids are still scarce. The aim of the present work was to study the antinociceptive effect of taurine and its relationship with aging in mice. No differences were found between prepubertal and young adult animals; on the contrary, old animals showed significantly reduced sensitivity to the antinociception induced by taurine; in fact, at the tested doses, taurine did not induce antinociception in this group of mice. The mechanism underlying this effect has not been clarified because there are several mechanisms and neurotransmitter systems involved in the antinociception induced by taurine.

Phenobarbital plasma level/dose ratio in monotherapy. Influence of age, sex and dose.

Phenobarbital plasma level/dose ratio (L/D) has been studied in 536 outpatients distributed in groups according to age, sex and drug dosage. Samples were obtained prior to the first morning dose. Plasma levels that correspond to the steady-state phase were determined by homogeneous enzymatic immunoassay (EMITR). From the results it must be pointed out: 1) An increase of L/D as the age increases within each group; 2) A decrease of L/D as the dose of phenobarbital increases in the overall sample; 3) Sex does not affect L/D in any of the subgroups studied; 4) For a given dose higher blood levels are reached in children 7 to 15 years old in our sample than in other comparable studies in Spain.

Further evidence of the antiarrhythmic efficacy of taurine in the rat heart.

The potential antidysrrhythmic effect of taurine has been studied both "in vitro" and "in vivo". "In vitro experiments were performed on a model of automaticity induced in the isolated right ventricle of the rat. The "in vivo" studies have been done on anesthetized rats, assessing the effect of taurine on the electrical activity of the heart by continuous ECG records. Taurine decreases the "in vitro" automatic ventricular frequency. "In vivo" reduces heart rate (P-P interval increases) and conduction through the ventricular myocardium (prolongs QRS interval duration). We conclude that taurine possesses experimentally antidysrrhythmic activity "in vitro" and "in vivo", that would warrant further research.

Effect of homotaurine in experimental analgesia tests.

1. The possible antinociceptive action of GABA A receptor agonist homotaurine, has been studied through a battery of chemical (acetic acid) and thermal (hot plate, tail flick and tail immersion) tests in rats and mice. 2. The aminoacid was used at the following doses 22.25; 55.62 and 111.24 mg/kg i.p. and 50-100 micrograms i.c.v.; and measurements were made at the time of and at 5, 15 and 30 min after drug administration. 3. Homotaurine exhibited a significantly antinociceptive effect in all the above mentioned test except hot plate and when administered i.c.v. in the tail flick test. 4. The antinociceptive effect in the chemical test was dose and time dependent. 5. In the tail immersion test, latency time for withdrawal of the tail was significantly increased with the dose of 55.62 mg/kg at 15 min and 111.24 mg/kg at 30 min. 6. In the tail flick test the antinociceptive effect was dose dependent at 15 and 30 min. 7. From the above results the implication of peripheral and spinal mechanisms in the antinociceptive effect of homotaurine may be concluded.

GABA(B) receptors and opioid mechanisms involved in homotaurine-induced analgesia.

1. The involvement of GABA(B) receptors and opioid mechanisms in homotaurine-induced analgesia has been investigated in current models of nociception by using a GABA(B) receptor antagonist, morphine, and naloxone. CGP 35348 (50-200 mg/kg IP), a highly selective GABA(B) antagonist, was administered prior to carrying out a dose-response curve of homotaurine (22.6-445 mg/kg IP) antinociceptive effect in the abdominal constriction (mice) and tail flick (rats) tests. 2. The tail flick test was performed in animals pretreated with morphine (0.5 mg/kg SC) and naloxone (1 mg/kg), 15 min before amino acid. Animals treated with saline 10 ml/kg (mice) or 1.25 ml/kg (rats) were included as control for the vehicle used. 3. CGP 35348 antagonized the antinociceptive effect of homotaurine in both tests. The range of doses affected by the interaction depended on the test assayed, but it was coincident for the main part of the dose-response curve. 4. A subanalgesic dose of morphine potentiated the antinociceptive effect of lower doses of homotaurine in the tail flick test. Naloxone pretreatment inhibited the antinociceptive effect of homotaurine. 5. These data imply that GABA(B) receptor subpopulations and opiate mechanisms are involved in the antinociceptive effect of homotaurine. Because functional relationships have been found between GABAergic and opiate systems in analgesic effects, an interaction of the two mechanisms may be operating in the effects described for homotaurine.

Role of GABAA and GABAB receptors and peripheral cholinergic mechanisms in the antinociceptive action of taurine.

1. Gabaergic and cholinergic mediation in the antinociceptive effect of taurine has been investigated in mice (acetic acid test) and rats (tail-flick test). 2. Scopolamine sulfate and methylnitrate exhibit intrinsic antinociceptive activity and increase the effect of taurine in mice. 3. Baclofen also increases the antinociceptive effect of taurine in mice. 4. Anticholinergic agents and bicuculline but not CGP 35348 antagonize the effect of taurine in rats. 5. These results suggest that the antinociceptive effect of taurine may be partly mediated by spinal GABAA receptors and peripheral cholinergic mechanisms.