Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a multifactorial fatal motoneuron disease without a cure. Ten percent of ALS cases can be pointed to a clear genetic cause, while the remaining 90% is classified as sporadic. Our study was aimed to uncover new connections within the ALS network through a bioinformatic approach, by which we identified C13orf18, recently named Pacer, as a new component of the autophagic machinery and potentially involved in ALS pathogenesis. METHODS: Initially, we identified Pacer using a network-based bioinformatic analysis. Expression of Pacer was then investigated in vivo using spinal cord tissue from two ALS mouse models (SOD1G93A and TDP43A315T) and sporadic ALS patients. Mechanistic studies were performed in cell culture using the mouse motoneuron cell line NSC34. Loss of function of Pacer was achieved by knockdown using short-hairpin constructs. The effect of Pacer repression was investigated in the context of autophagy, SOD1 aggregation, and neuronal death. RESULTS: Using an unbiased network-based approach, we integrated all available ALS data to identify new functional interactions involved in ALS pathogenesis. We found that Pacer associates to an ALS-specific subnetwork composed of components of the autophagy pathway, one of the main cellular processes affected in the disease. Interestingly, we found that Pacer levels are significantly reduced in spinal cord tissue from sporadic ALS patients and in tissues from two ALS mouse models. In vitro, Pacer deficiency lead to impaired autophagy and accumulation of ALS-associated protein aggregates, which correlated with the induction of cell death. CONCLUSIONS: This study, therefore, identifies Pacer as a new regulator of proteostasis associated with ALS pathology.

Effect of Hibiscus sabdariffa L. dried calyx ethanol extract on fat absorption-excretion, and body weight implication in rats.

The effect of Hibiscus sabdariffa L. (Hs) calyx extract on fat absorption-excretion and body weight in rats, was investigated. Rats were fed with either a basal diet (SDC = Control diet) or the same diet supplemented with Hs extracts at 5%, 10% and 15% (SD(5), SD(10) and SD(15)). Only SD(5) did not show significant increases in weight, food consumption and efficiency compared to SD(C). The opposite occurred in SD(15) group which showed a significant decrease for these three parameters. The SD(10) responses were similar to SD(15), with the exception of food consumption. In both SD(C) and SD(5) groups, no body weight loss was observed; however, only in the latter group was there a significantly greater amount of fatty acids found in feces. A collateral effect emerging from the study is that components of Hs extract at the intermediate and greater concentrations used in this experiment could be considered possible antiobesity agents.

Our experience with Wallstent self-expanding metal prostheses in 65 patients with malignant dysphagia.

OBJECTIVE: to document the usefulness of self-expanding metal stents in patients with malignant dysphagia. METHOD: from January 1992 to January 1997 we implanted 75 Wallstent prostheses (28 uncovered AV, 20 uncovered Unistep, 15 covered Telestep, and 2 covered double-mesh Permalume stents) in 65 patients with malignant dysphagia. RESULTS: mean survival time was 100 days in patients with uncovered stents, and 215 days in patients with covered stents. Oral feeding was possible throughout the post-implantation course in 58 of 65 patients. Only two severe complications occurred: esophageal perforation with mediastinitis, and migration of the stent from the distal esophagus into the stomach. All implantation procedures were done under radiological guidance. For AV and Unistep prostheses we used a nasal approach without sedation, and for Telestep and Permalume stents we used an oral approach with sedation. CONCLUSIONS: Wallstent self-expanding metal stents are useful in palliating malignant dysphagia. The placement and implantation of these stents are straightforward.

[Prospective evaluation of gastroesophageal reflux in patients with achalasia treated with pneumatic dilatation, thoracic or abdominal myotomy]. / Evaluación prospectiva de reflujo gastroesofágico en pacientes con acalasia tratados con dilatación neumática, miotomía torácica o abdominal.

INTRODUCTION: Symptomatic gastroesophageal reflux (GER) occurs in 0-20% of patients treated with pneumatic dilation and in 5-30% with cardiomyotomy. However, the prevalence of GER evaluated with esophageal pH-monitoring is unknown. AIM: To investigate the frequency of GER in achalasia patients treated with pneumatic dilation or myotomy. MATERIAL AND METHODS: Patients with achalasia were evaluated prospectively and classified in 4 groups: group A = treated with pneumatic dilation; group B = treated with open abdominal myotomy; group C = transthoracic myotomy; and group D = submitted to laparoscopic abdominal myotomy with antireflux procedure. Esophageal manometry and 24 h pH-monitoring were performed in all patients. GER was defined as a pH < 4 in more than 4% of the total time. RESULTS: Thirty-one patients, 22 women and 9 men, with a mean age of 44.7 years were evaluated. Nine patients had GER symptoms and 22 were asymptomatic. GER was detected with pH-metry in 42% of the total group: 33% for group A, 75% for group B, 44% for group C and none for group D. CONCLUSIONS: Prevalence of GER in achalasia patients treated with pneumatic dilation and surgical myotomy was high. We suggest the inclusion of 24 hr esophageal pH-metry in the follow-up due to the significant prevalence of asymptomatic GER. Minimal hiatus dissection and antireflux procedure were surgical factors related with a lower frequency of GER after achalasia myotomy.

[Results of the participation of resident physicians in the surgical treatment of gallbladder lithiasis]. / Resultados de la participación de médicos residentes en el tratamiento quirúrgico de la litiasis vesicular.

The aim of this retrospective study was to evaluate the impact of resident participation in the results of surgical treatment in 1149 consecutive patients operated for biliary disease between January, 1980 and December, 1987 at the Instituto Nacional de la Nutrición "Salvador Zubirán". Patients were divided in three groups: GROUP I. 640 cases treated by surgical residents under a senior surgeon supervision. GROUP II. 168 patients operated by the chief surgical resident. GROUP III. 341 patients treated by senior staff surgeons. Age, sex and risk factors were similar between groups. Residents performed more operative cholangiograms (p less than 0.05). In general, senior surgeons performed more transduodenal sphincteroplasties (p less than 0.05) and other additional procedures like appendectomies and gastrostomies during the same surgery. Wound infection was more frequent in group III patients (p less than 0.005) but there was no significant clinical difference in other postoperative complications like intraabdominal abscess, bile fistula, wound dehiscence, intraabdominal bleeding, iatrogenic injury of the biliary tract, and residual common duct stone. The duration of the in-hospital convalescence period was similar in all three groups. The mortality rate for the total series was 2.2%. In group II there were more patients affected for acute cholecystitis, and more patients died postoperatively (p = less than 0.01). We may consider this difference attributable to the more complex patients handled by the chief resident. Mortality rate among patients with chronic biliary tract disease was less than 1%. We were not able to demonstrate any significant difference in mortality and complication rates between those patients operated by residents, chief residents and senior surgeons.(ABSTRACT TRUNCATED AT 250 WORDS)

[Bacterial count as an infection prognostic factor in the delayed primary closure of abdominal surgical wounds]. / La cuenta bacteriana como factor pronóstico de infección en el cierre primario tardío de heridas quirúrgicas abdominales.

STUDY OBJECTIVE: To determine the prognostic value of the soft-tissue biopsy to handle contaminated or infected surgical wounds with delayed primary closure. DESIGN: Comparative, prolective, blind and observational. PLACE: Referral tertiary care center. PATIENTS: We included 70 patients distributed in two groups: Group I: 50 patients who underwent contaminated or infected abdominal surgery; and Group II: 20 patients who underwent clean or clean contaminated abdominal surgery and developed surgical wound abscess. INTERVENTIONS: Daily cleaning and water irrigation and periodic debridement were done in all the cases; after five days (excluding infection), two tissue biopsies for quantitative culture and wound closure were performed. MEASUREMENTS AND MAIN RESULTS: In Group I, nine of 26 patients (35%) with positive culture (greater than 10(5) colony forming units/g) developed infection and none of 24 with negative culture (p less than 0.01, Fisher); the negative predictive value (nPV) was 100% and the positive predictive value (pPV) was 35%. In Group II, seven of 12 patients with positive culture and one of eight with negative culture developed infection (p less than 0.05); the nPV was 87% and the pPV was 58%. CONCLUSIONS: The biopsy of soft-tissue seems to be a helpful tool for the treatment and prognosis of infected or contaminated surgical wounds.

[Splenectomy in idiopathic thrombocytopenic purpura]. / Esplenectomía en púrpura trombocitopénica idiopática.

Between January 1976 and December 1987, 44 patients with idiopathic thrombocytopenic purpura were submitted to splenectomy. This study analyzes the results of treatment and the usefulness of several prognostic markers. There were 38 female patients and six males with a median age of 28.5 years (range 11 to 66 years). Forty two out of 44 patients received preoperative steroids. Seventy five percent achieved a satisfactory response to this treatment but 31 relapsed (in eight recurrence was observed when the steroid dose was tapered). Eleven patients persisted symptomatic notwithstanding medical treatment. In two cases splenectomy was performed as an emergency procedure, and in one patient who was already in remission with previous steroid treatment, splenectomy was performed for other medical reasons. Operative mortality rate was 4 percent, and five patients developed postoperative complications (three had pneumonia, one pulmonary thromboembolism and one would infection). Eighty four percent of the patients were free of disease at one year followup survival at 10 year period was 80 percent. No correlation was found between age, duration of symptoms, previous response to steroids or time-period of medical treatment with the results obtained with splenectomy.

[Immunoreactive urinary thromboxane B2 in experimental mesenteric thrombosis in dogs]. / Tromboxano B2 urinario inmunorreactivo en trombosis mesentérica experimental en perros.

Thromboxane B2 (TxB2) the stable metabolite of thromboxane A2 may be released as a response to ischemia. With the aim of investigating its role as an early diagnostic test in mesenteric thrombosis, immunoreactive TxB2 was measured in urine aliquotes in six sham operated dogs, nine dogs subjected to superior mesenteric artery ligation, and twelve dogs with superior mesenteric vein ligation. One hour urine volumes were collected before surgery and during the eight hours after the experimental procedures, and urinary osmolarities were also determined in each sample. Basal TxB2 levels were comparable in all groups. Although all groups showed a significant and rapid (one hour) increase in TxB2 as a response to surgery, in the controls it returned to normal after six hours, whereas in the rest a continuously increased production persisted throughout the study period. There was no difference in t-test comparisons depending on the sort of thrombosis. In spite of the urinary dilution induced during the study, a persistent increase in TxB2 excretion was found. We conclude that urinary TxB2 levels could prove useful in the early diagnosis of mesenteric ischemia.

[Xanthogranulomatous cholecystitis. Clinical entity or pathologic curiosity]. / Colecistitis xantogranulomatosa. Entidad clínica o curiosidad patológica.

Xanthogranulomatous cholecystitis is an uncommon variety of gallbladder inflammation. Its histologic appearance is quite specific but its clinical characteristics, prognostic and physiopathologic implications are unknown. The present study has the aim of analyzing a group of 40 patients with xanthogranulomatous cholecystitis and another of 80 patients with non-xanthogranulomatous inflammation. The clinical characteristics, risk factors, morphologic expression, complications and mortality of both groups were compared. Diffuse xanthogranulomatous cholecystitis comprised 1.8% of all cholecystectomies done between January 1976 and July 1987. This variety was more frequent in males (p less than .05) without any specific risk factors. There was a higher frequency of acute pyogenic inflammation sometimes associated to extrinsic compression of the biliary duct and fistulization, but without any difference in the overall complication rate or mortality. We conclude that xanthogranulomatous cholecystitis is a specific entity which occurs with a higher frequency in males and that has a different clinical behavior than that of other types of gallbladder inflammation.