Anti-tumor Effect of All-<Emphasis Type="BoldItalic">Trans</Emphasis> Retinoic Acid Loaded Polymeric Micelles in Solid Tumor Bearing Mice

Purpose All-trans retinoic acid (ATRA) polymeric micelles were developed for parenteral administration. The distribution characteristics and antitumor activities of ATRA polymeric micelles were evaluated after intravenous administration to mice bearing CT26 solid tumors. Methods ATRA incorporated in poly(ethylene glycol)-poly(benzyl aspartate) block copolymer was prepared by the evaporation method. The levels of [³H]ATRA in blood and tissue including tumor were determined by measuring the radioactivity after injection into mice. The tumor volume and the survival of the mice were determined to assess the anticancer activity. Results The delivery of ATRA by polymeric micelles prolonged the blood circulation and enhanced the accumulation of ATRA in the tumor tissue compared with the administration of free ATRA. Tumor growth was significantly delayed and the survival time of mice was prolonged following the treatment by ATRA polymeric micelles demonstrating the improved anticancer activity of ATRA. Conclusion Polymeric micelles are a promising and effective carrier of ATRA in order to enhance tumor delivery and they have a promising potential application in the treatment of solid tumors.     

Hypertension and dementia

Hypertension is one of the principal risk factors for cerebrovascular diseases. Several epidemiologic studies have also indicated a positive correlation between cognitive decline or dementia and blood pressure level. Indeed, the results of most longitudinal studies show that cognitive functioning is often inversely proportional to blood pressure values measured 15 or 20 years previously. Cerebral infarcts, lacunae, and white matter changes are implicated in the pathogenesis of vascular dementia, but may also favor the development of Alzheimer’s disease. Microcirculation disorders and endothelial dysfunctions are also advanced to explain the deterioration in cognitive functions in hypertensive subjects. Data from recent therapeutic trials open the way to the prevention of dementia (vascular or Alzheimer’s type) by antihypertensive treatments and must be confirmed by other studies.     

Preoperative evaluation of hepatic arterial and portal venous anatomy using the time resolved echo-shared MR angiographic technique in living liver donors

The purpose of this study was to determine whether MR angiography utilizing the time resolved echo-shared angiographic technique (TREAT) can provide an effective assessment of the hepatic artery (HA) and portal vein (PV) in living donor candidates. MR angiography (MRA)was performed in 27 patients (23 men and 4 women; mean age, 31 years) by using TREAT. Two blinded radiologists evaluated HA anatomy, origin of segment IV feeding artery and PV anatomy in consensus. Qualitative evaluations of MRA images were performed using the following criteria: (a) overall image quality, (b) presence of artifacts, and (c) degree of venous contamination of the arterial phase. Using intraoperative findings as a standard of reference, the accuracy for the HA anatomy, origin of segment IV feeding artery and PV anatomy on TREAT-MRA were 93% (25/27), 85% (23/27), and 96% (26/27), respectively. Overall image qualities were as follows: excellent (n=22, 81%), good (n=4, 15%), and fair (n=1, 4%). Significant artifacts or venous contamination of the arterial phase images was not noted in any patient. TREAT-MRA can provide a complete evaluation of HA and PV anatomy during preoperative evaluation of living liver donors. Furthermore, it provides a more detailed anatomy of the HA without venous contamination.     

Topiramate in the prevention of pediatric migraine: literature review

Pediatric migraine is a disabling condition, which can cause a significant impact on quality of life. Currently, no drugs have been approved by the FDA for its preventive treatment. Our aim was to review the medical literature concerning the efficacy and tolerability of topiramate in the prophylactic treatment of migraine in children and adolescents. A total of five papers were reviewed: two randomized controlled trials (RCTs), a post-hoc subset analysis of adolescents who had been included in three RCTs carried out on adults and two open studies. Topiramate has been proven to reduce headache frequency and the accompanying disability. The frequency of side effects varied considerably among studies, the most frequent being weight loss, anorexia, abdominal pain, difficulties in concentrating, sedation and paresthesia. Since these adverse events, although often transitory, may be distressing for the child, we strongly recommend to assess the disability caused by the migraine episodes before deciding to initiate a prophylactic treatment. Nevertheless, dropout rates due to side effects in the studies were very low.     

Laparoscopic Pancreatic Resection: The Past,Present, and Future

Since the early 1990s, laparoscopic techniques have been applied to a growing number of pancreatic surgeries. Laparoscopic pancreatic resections have been performed in patients with a variety of diseases including chronic pancreatitis, pancreatic trauma, congenital hyperinsulinism, and neoplasms of the pancreas; e.g., insulinoma, mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, etc. Laparoscopic pancreatic resections with an en bloc lymph node dissection have also been performed for invasive carcinomas. The long-term results after laparoscopic resections for invasive pancreatic cancer, however, are still not well defined. Laparoscopic distal pancreatectomies with or without spleen preservation may benefit patients with reduced postoperative pain, shorter hospital stay, a quicker recovery to normal activity, and better cosmetic appearances based on retrospective analyses of collective series and case reports. Prospective randomized controlled trials are needed to validate these benefits. In contrast, laparoscopic proximal pancreatectomies with or without duodenum preservation remain controversial. Although a laparoscopic pancreaticoduodenectomy and laparoscopic duodenum-preserving pancreatic head resection are technically feasible, laparoscopic reconstruction after proximal pancreatectomies is not yet generally practicable but limited to personal experiences by highly skilled endoscopic surgeons. To justify the performance of laparoscopic proximal pancreatectomies, it is mandatory to demonstrate the potential clinical benefits and safety of these complicated procedures.     

Joint Attention and Social Competence in Deaf Children with Cochlear Implants

The authors examined the influence of cochlear implants on joint attention and social competence in severe to profoundly congenitally deaf toddlers. Twenty-seven hearing mothers and hearing toddlers (HH dyads), and 26 hearing mothers and deaf toddlers, 9 with cochlear implantation (HD-cochlear dyads), and 17 with no cochlear implantation (HD-no cochlear dyads) were observed engaging in joint attention. Mothers provided ratings of children’s social competence. HH and HD-cochlear dyads displayed more joint attention than HD-no cochlear dyads. Children who were in dyads who engaged in more joint attention were rated by their mothers as higher on expressive and compliance behaviors and lower on disruptive behaviors compared to children who were in dyads who engaged in lower levels of joint attention. Findings suggest that cochlear implants may aid in the early socio-emotional development of some deaf children.     

Usefulness of magnetic resonance imaging for diagnosing deep anorectal abscesses

PURPOSE: We evaluated the usefulness of magnetic resonance imaging for the preoperative diagnosis of deep anorectal abscesses. METHODS: Subjects were 21 patients with deep anorectal abscesses. Deep anorectal abscesses were classified into two types, ischiorectal and pelvirectal, according to their location. Patients were also classified into a single abscess group, which showed either an ischiorectal or pelvirectal abscess, and a double abscess group, which showed both ischiorectal and pelvirectal abscesses. The final diagnosis was made from surgical findings, and the types of deep anorectal abscesses determined by digital examination and magnetic resonance imaging were compared. RESULTS: Sensitivity of ischiorectal abscesses (20 lesions) with digital examination and magnetic resonance imaging was 75 and 95 percent, respectively, and that of pelvirectal abscesses (10 lesions) with digital examination and magnetic resonance imaging was 60 and 70 percent, respectively. Sensitivity of the magnetic resonance imaging was significantly higher than that of digital examination in ischiorectal abscesses. Diagnostic accuracy of digital examination and magnetic resonance imaging were both 83 percent in the single abscess group (12 patients), whereas in the double abscess group (9 patients) it was 22 and 78 percent, respectively. The rate of accurate diagnosis of magnetic resonance imaging compared with digital examination in the double abscess group was significantly higher than that in the single abscess group. CONCLUSION: Magnetic resonance imaging was useful for diagnosing and differentiating ischiorectal and pelvirectal abscesses.     

Suitability of the short-form Mini nutritional assessment in free-living elderly people in the northwest of Spain

Objective  

To evaluate the Mini Nutritional Assessment (MNA) test and the short-form MNA (MNA-SF) as screening tools for malnutrition risk and malnutrition in the free-living elderly of northwestern Spain.     

Pharmacokinetics and dosage adjustment in patients with renal dysfunction

Introduction  Chronic kidney disease is a common, progressive illness that is becoming a global public health problem. In patients with kidney dysfunction, the renal excretion of parent drug and/or its metabolites will be impaired, leading to their excessive accumulation in the body. In addition, the plasma protein binding of drugs may be significantly reduced, which in turn could influence the pharmacokinetic processes of distribution and elimination. The activity of several drug-metabolizing enzymes and drug transporters has been shown to be impaired in chronic renal failure. In patients with end-stage renal disease, dialysis techniques such as hemodialysis and continuous ambulatory peritoneal dialysis may remove drugs from the body, necessitating dosage adjustment. Methods  Inappropriate dosing in patients with renal dysfunction can cause toxicity or ineffective therapy. Therefore, the normal dosage regimen of a drug may have to be adjusted in a patient with renal dysfunction. Dosage adjustment is based on the remaining kidney function, most often estimated on the basis of the patient's glomerular filtration rate (GFR) estimated by the Cockroft–Gault formula. Net renal excretion of drug is a combination of three processes: glomerular filtration, tubular secretion and tubular reabsorption. Therefore, dosage adjustment based on GFR may not always be appropriate and a re-evaluation of markers of renal function may be required. Discussion  According to EMEA and FDA guidelines, a pharmacokinetic study should be carried out during the development phase of a new drug that is likely to be used in patients with renal dysfunction and whose pharmacokinetics are likely to be significantly altered in these patients. This study should be carried out in carefully selected subjects with varying degrees of renal dysfunction. In addition to this two-stage pharmacokinetic approach, a population PK/PD study in patients participating in phase II/phase III clinical trials can also be used to assess the impact of renal dysfunction on the drug's pharmacokinetics and pharmacodynamics. Conclusion  In conclusion, renal dysfunction affects more that just the renal handling of drugs and/or active drug metabolites. Even when the dosage adjustment recommended for patients with renal dysfunction are carefully followed, adverse drug reactions remain common.     

Molecular Basis of Autosomal Recessive Chronic Granulomatous Disease in Iran

Introduction  

Chronic granulomatous disease (CGD) is a rare inherited condition resulting from mutations in the genes that encode the proteins of the NADPH oxidase enzyme in phagocytes, rendering these cells incapable of killing invading pathogens.