Comparison of free software platforms for the calculation of the 90% confidence interval of f2 similarity factor by bootstrap analysis.

INTRODUCTION: The calculation of the 90% confidence interval of f2 based on the bootstrap methodology has been proposed and accepted by the main regulatory authorities when the dissolution data shows excessive variability. Different free software platforms allow the calculation of the 90% CI of f2 by means of bootstrapping. Their use in regulatory submissions is growing, but divergent results have been observed between the available software platforms. Therefore, the objective of this work is to analyze the characteristics of these software platforms and evaluate their results. METHODS AND MATERIALS: Highly variable in vitro dissolution data from two products were selected. Three different similarity factors, f2, E(f2) and bc-f2, and their corresponding 90% confidence intervals were calculated with three free software platforms, Pheq_bootstrap, Bootf2bca and DDSolver, and computed by four different approaches, normal approximation, bootstrap-t-CI, percentile CI, and bias corrected and accelerated CI. RESULTS: All three platforms report the same f2 value, 49.66 upon comparison of products 1 and 3 and 54.87 for products 2 and 3 (no truncation rule). Bootf2bca and Pheq_bootstrap provided the same f2 and E(f2) also under other truncation rules (EMA or FDA), which are not implemented in DDSolver. Pheq_bootstrap allowed the calculation of bc-f2. The conclusion of similarity is based on a bootstrap percentile CI of E(f2) and f2 in Pheq_bootstrap and DDSolver, respectively. Bootf2bca provides all four 90% CI. DISCUSSION: Bootf2bca or Pheq_bootstrap should be considered for the estimation of the 90% CI of the f2 similarity factor when dissolution profiles show high variability.

[An abdominal Burkitt's lymphoma in acute phase. Case report]. / Il linfoma di Burkitt a localizzazione addominale con presentazione acuta. Caso clinico.

Burkitt's lymphoma is a highly malignant, aggressive and rapidly growing B-cell neoplasm, which has low long-term survival rates. Abdomen is the most frequent onset site of nonendemic Burkitt's lymphoma. The rapidity of volumetric doubling of this neoplasm frequently justifies an abdominal acute presentation, that may mime other less rare diseases. Symptoms are often misleading and make diagnosis difficult. The aim of this work is to report a case of a 13-year-old boy affected by terminal ileum Burkitt's lymphoma with hepatic metastasis, which initially was mistaken for acute appendicitis complicated by hepatic abscesses and, following a second surgical operation, for terminal-ileum inflammatory bowel disease. The rapidity of growth of this neoplasm justifies the finding, during the second surgical operation, of a mass that was not clinically manifested during first operation, carried out only a week ago. Clinical signs and instrumental investigations were not diagnostic, as well as the literature reports. The role of surgery remains controversial, and is usually limited to collection of specimens for histological diagnosis or to management of acute complications, as in our case report. Mostly treatment protocols are based on chemotherapy, because of the high sensibility of this neoplasm.

[Sliding hiatal hernia in patients with gastroesophageal reflux: physiopathology and surgical treatment]. / Ernia iatale da scivolamento nel paziente con malattia da reflusso gastroesofageo. Fisiopatologia e terapia chirurgica.

BACKGROUND: The aims of the study were to evaluate how the sliding hiatal hernia, in patients with gastroesophageal reflux disease (GERD), acts on the lower esophageal sphincter (LES) and esophageal clearance, and how surgical therapy corrects the physiopathological parameters. METHODS: Records of 25 patients with only GERD and of 15 with GERD associated to hiatal hernia (> 3.5 cm) were reviewed. Ten subjects without symptoms and/or endoscopic and functional signs of GERD were considered as control group. The selection of the patients was done by reviewing radiographic examination, endoscopy and functional tests (esophageal manometry, pH-monitoring). RESULTS: Manometry showed a greater LES incompetence (pressure and length) and a worse peristalsis (distal amplitude) in the group with reflux and hiatal hernia against patients with reflux only. Also, patients with hiatal hernia had more acid exposure (total time pH < 4 in the distal esophagus) and a longer time of esophageal clearance, at pH-monitoring. The functional tests in 8 patients, before and after laparoscopic Toupet fundoplication with posterior closing of the crura, showed a normalised LES, esophageal clearance and acid exposure. Esophageal peristalsis did not show any statistically significance. CONCLUSIONS: The presence of hiatal hernia, in patients with GERD, causes worse LES, peristalsis and clearance with a greater acid exposure of the esophagus. Fundoplication, by reconstructing the sphincter-diaphragm unit, normalises the preoperative physiopathology situation but without an effective peristalsis improvement.

An evaluation of sampling and laboratory procedures for determination of heterotrophic plate counts in dental unit waterlines.

BACKGROUND: The high numbers of heterotrophic microorganisms that have been cultured from dental unit waterlines (DUWs) have raised concern that this water may exceed suggested limits for heterotrophic plate counts (HPCs). The main purpose of this investigation was to examine HPC variability in DUWs and to examine in detail the effect of laboratory processing of water samples on HPC values. METHODS: Water samples were collected from dental offices either at the beginning of or during the clinic day and were transported to the laboratory, where they were analyzed. RESULTS: Measuring HPC levels within an office would involve testing all units, because significant differences were found between units connected to the same municipal water supply. Within a unit, the average microbial count from high-speed lines was approximately twice the average count from air/water lines. The laboratory processing of water samples significantly affected the numbers of heterotrophic microorganisms that were recovered. Incubation temperature, time and media, as well as neutralization of residual chlorine, all had significant effects on the HPC values. However, no significant differences in microbial counts were found between samples plated with the spread plate method on R2A agar and those plated with the pour plate method with Plate Count Agar. CONCLUSIONS: Dental organizations have suggested target limits in terms of numbers of heterotrophic microorganisms recovered in water from dental units, but standards for laboratory handling must be established as well. A protocol for sample collection and laboratory handling is proposed.

[Medullary carcinoma of the breast. A review of the literature and a report of the authors' own cases]. / Carcinoma midollare della mammella. Revisione della letteratura e presentazione della casistica personale.

Experience with 5 cases of medullary carcinoma of the breast is reported. Reviewing the literature, medullary carcinoma appears to have a better prognosis than infiltrating ductal carcinoma so the proper surgical approach is represented by conservative procedures for lesions < 3 cm with no more than 3 nodes involved. Chemotherapy and radiotherapy don't seem to improve the survival rate.

[An aneurysm of the extracranial carotid. A report of an interesting clinical case]. / Aneurisma della carotide extracranica. Descrizione di un caso clinico interessante.

One case of extracranial carotid artery aneurysm observed is reported. This uncommon and interesting vascular disorder is still under discussion even if the present tendency is to treat it actively by reconstructive surgical procedures that make it possible to avoid the natural aneurysm complications with a low risk of postoperative neurological lesions.

[Chemotherapeutic prophylaxis in the preparation of the large intestine for surgical interventions: rifaximin P.O. vs. cephalosporin I.V]. / Profilassi chemioterapica nella preparazione del grosso intestino agli interventi chirurgici: rifaximina P.O. vs. cefalosporina E.V.

30 patients were examined: 17 males and 13 females aged between 53 and 83 years (average age 66 years), candidates for large intestine surgery. For 5 days before the operation, they were treated at random, in a balanced way, with cefotaxime (3 g/day intravenously), either alone or associated with rifaximin (1200 mg/day P.O.). Rifaximin, an antibiotic drug endowed with a topical intestinal action, substantially increased the antibacterial activity of the well known and traditional third-generation cephalosporins therapy in the prevention of bacterial infections after major colic surgery. Intestinal bacterial load and pathogenic micro-organisms reduction was substantially increased. Furthermore, a more limited onset of post- surgical complications was observed, together with a better post-surgical clinical course, and a more rapid recovery of normal intestinal functions. The possibility of carrying out an effective chemoprophylaxis by means of an oral drug, such as rifaximin, must be encouraged as, among other things, it substantially reduces the intolerance risk at systemic level, which is nevertheless possible with parenteral antibiotic treatments.

[Hemocholecyst: a rare cause of hemoperitoneum]. / Emocolecisti: rara causa di emoperitoneo.

A rare case of haemoperitoneum due to gallbladder rupture with intraluminal bleeding is reported. The importance of a coagulopathy in the etiology of the disease is pointed out: in the present case it was related to cirrhosis and anticoagulant treatment during dialysis sessions.

[A new technic for esophago-enteral anastomosis with a mechanical stapler without purse-string sutures]. / Una nuova tecnica per eseguire esofago-entero-anastomosi meccaniche senza borsa di tabacco.

Staplers have improved the results of esophageal surgery, in our experience and in others experience, as esophago-enteric anastomoses have become safer and faster than when manual suturing is used. Probably one of the last problems in the stapler technique, especially in the thoracic area, is the performance of on adequate esophageal purse-string suture: an improper performance of this suture can cause a dangerous leak of the anastomosis. So, many surgeons, to reduce the risk of esophageal dehiscence connected with the esophageal purse-string, use either purse-string devices or alternative methods such as a second handsewn purse-string, U stitches of the esophagus, etc. We think that the risk of improper anastomoses after esophageal resection can be reduced if the need for the esophageal purse-string can be eliminated. This work shows our personal technique for performing esophagoenterostomy, especially in the thoracic area, using the new CEEA stapler (Autosuture) without esophageal purse-string sutures. According to the modified procedure the stapler anvil and the mini rod are introduced in the esophagectomy and a 2-0 thread is knotted around the CEEA mini rod. Then the esophageal mutilated part is closed by a linear stapler keeping a syringe needle, which contains the thread, through the linear suture. Then, using the thread as a pulling system, the surgeon makes the needle and the tip of the mini rod slide out of the esophageal suture. Now the surgeon can reassemble the CEEA and perform the anastomosis. There are many clinical reports that cite no leaks following circular stapled anastomoses across linear stapled closures.

[Colonic and rectal cancer screening using fecal occult blood analysis (our experience)]. / Screening per il cancro colo-rettale mediante la ricerca del sangue occulto fecale (nostra esperienza).

The authors describe their experience with colorectal cancer screening by means of the Hemoccult test for the detection of occult fecal blood according to Gregor's method. In particular, the decentralized aspect of the screening is examined, and the results discussed are in agreement with those observed in larger study populations. The authors go on to stress the effective possibility of conducting this type of screening also on the basis of collaboration with general practitioners.

Synthesis of 1-hydroxy and 1-acyloxypyrrolidin-2-ones.

A series of 1-hydroxypyrrolidin-2-ones (v) has been prepared by reduction of gamma-nitrocarboxylic acid esters with Zn dust in the presence of ammonium chloride. Acylation of compounds (v) gave the corresponding 1-acyloxypyrrolidin-2-ones (VI). None of the synthesized compounds showed any significant antiflammatory activity.