Comparison of fibrin glue, bioresorbable tubing and sutures in peripheral nerve repair

Regeneration of severed rat tibial nerves was functionally and morphologically compared with repair following the use of 3 anastomosis techniques: collagen guide tubes, fibrin glue and conventional microsurgical sutures. In addition, one tibial nerve was crushed in some rats. At ten weekly intervals, functional recovery, assessed by sciatic nerve stimulated evoked contraction of the flexor digitorum muscle, was quicker and more complete following nerve crush than following the anastomosis techniques which were not different from each other. Ten weeks following the surgery, the retrograde transport morphological technique indicated that the anastomosis techniques were not different from each other. The number of labeled tibial motoneurons (tube and suture groups) was significantly less than the crush group, but the glue group was intermediate. Thus, although having less extensive recovery following crush, the quicker and easier techniques of nerve repair, i.e., collagen tubes or fibrin glue, produced comparable anatomical and functional recovery as the more time-consuming, technically demanding microsurgical repair with fine sutures.     

Heterogeneity of toxicant response: sources of human variability.

While risk assessment models attempt to predict human risk to toxicant exposure, in many cases these models cannot account for the wide variety of human responses. This review addresses several primary sources of heterogeneity that may affect individual responses to drug or toxicant exposure. Consideration was given to genetic polymorphisms, age-related factors during development and senescence, gender differences associated with hormonal function, and preexisting diseases influenced by toxicant exposure. These selected examples demonstrate the need for additional steps in risk assessment that are needed to more accurately predict human responses to toxicants and drugs.     

Aminopenicillin allergy

Eight two children with histories of maculopapular or urticarial rashes during aminopenicillin treatment underwent skin tests, patch tests, radioallergosorbent assays and, in some cases, oral challenges. Hypersensitivity was diagnosed in eight (9.8%): immediate in four with urticarial reactions and delayed (that is cell mediated) in four with maculopapular rashes. In 49 children (38 with maculopapular eruptions, 11 with urticarial/angiooedematous reactions), negative allergologic findings were confirmed using oral challenges with the suspected drug. Maculopapular rashes may reflect delayed hypersensitivity to aminopenicillins, which can be diagnosed on the basis of late intradermal reactions and/or patch test positivity. The allergen panel must include the suspected aminopenicillin itself, as many cases are side chain specific. Most patients with urticarial reactions (more typical of immediate hypersensitivity) will also react to penicilloyl polylysine and minor determinant mixture. The time elapsed between the reaction and testing must be considered if negative results emerge, because IgE mediated sensitivity (unlike cell mediated forms) declines in the absence of antigen exposure.     

Sequential endo-laparoscopic treatment in patients with common bile calculi

BACKGROUND: Laparoscopic treatment of common bile duct (CBD) stones is gaining great acceptance worldwide, but actually it requires skills and technologies too expensive for a great part of general surgeons. So endoscopic removal of CBD stones before cholecystectomy is usually performed. Since 1991 in our department we started a policy of selective preoperative cholangiopancreatography (ERCP) in patients suspected for choledocholithiasis and waiting for laparoscopic cholecystectomy. METHODS: A retrospective study has been made on a population of 1100 patients who underwent elective laparoscopic cholecystectomy in the period between January 1991 and December 1997. They were 391 male and 719 female with a mean age of 52 years, 126 of whom (11.5%) were selected to have ERCP preoperatively because they had clinical, biochemical and ultrasound signs of the presence of common bile duct stones (CBDS). RESULTS: Successful cannulation of the CBD was achieved in 124 cases (98.4%), with failures due to ampullary diverticula. In 7 cases (5.5%) a precut was necessary to obtain cannulation. Sphincterotomy was performed in 113 patients (89.7%). In 93 patients (73.8%) stones were found (87 macrolithiasis and 6 microlithiasis); in 91 (97.8%) stones were removed in one (87) or two (4) endoscopic session. There were 2 major complications (one bleeding and one severe pancreatitis) due to ERCP or a sphincterotomy. Two patients developed symptoms from unsuspected common bile duct stones after LC and were removed endoscopically. No complications during LC were due to ERCP or ES. CONCLUSIONS: Selective preoperative ERCP is an effective way of clearing the CBD stones before laparoscopic cholecystectomy, with low rate of complications related to endoscopic and laparoscopic procedures, and short mean hospital stay (5.5 days), according to the concept of minimally invasive treatment.     

Essential Amino Acids-Rich Diet Decreased Adipose Tissue Storage in Adult Mice: A Preliminary Histopathological Study

Background: Excess body adipose tissue accumulation is a common and growing health problem caused by an unbalanced diet and/or junk food. Although the effects of dietary fat and glucose on lipid metabolism regulation are well known, those of essential amino acids (EAAs) have been poorly investigated. Our aim was to study the influence of a special diet containing all EAAs on retroperitoneal white adipose tissue (rpWAT) and interscapular brown adipose tissue (BAT) of mice. Methods: Two groups of male Balb/C mice were used. The first was fed with a standard diet. The second was fed with an EAAs-rich diet (EAARD). After 3 weeks, rpWAT and BAT were removed and prepared for subsequent immunohistochemical analysis. Results: EAARD, although consumed significantly less, moderately reduced body weight and BAT, but caused a massive reduction in rpWAT. Conversely, the triceps muscle increased in mass. In rpWAT, the size of adipocytes was very small, with increases in leptin, adiponectin and IL-6 immunostaining. In BAT, there was a reduction in lipid droplet size and a simultaneous increase in UCP-1 and SIRT-3. Conclusions: A diet containing a balanced mixture of free EAA may modulate body adiposity in mice, promoting increased thermogenesis.     

HPV circulating tumor DNA to monitor the efficacy of anti‐PD‐1 therapy in metastatic squamous cell carcinoma of the anal canal: A case report

Squamous cell carcinoma of the anal canal (SCCA) is a rare HPV‐associated cancer with limited sensitivity to standard chemotherapy. In a phase 2 study, nivolumab, an anti PD‐1 immune checkpoint inhibitor, demonstrated significant efficacy as single‐agent therapy in metastatic SCCA patients. Nevertheless, imaging assessment by standard RECIST criteria of the efficacy of immune therapy can be difficult in some patients due to tumor immune cell infiltration, and biomarkers of treatment efficacy are needed. We have previously developed a quantitative droplet digital PCR (ddPCR) technique to detect HPV circulating tumor DNA (HPV ctDNA), with excellent sensitivity and specificity. Here, we report, for the first time, the kinetics of HPV ctDNA during therapy in a patient with metastatic SCCA, who obtained sustained partial response to single‐agent nivolumab. We observed an early and very significant decrease of HPV ctDNA during therapy from the baseline level of 3713 copies/ml plasma to 564 copies/ml plasma at 4 weeks, and 156 copies/ml at 6 weeks, followed by a plateau. This observation provides proof‐of‐concept that HPV ctDNA can be used as a noninvasive early dynamic biomarker to monitor the efficacy of new immunotherapy agents.     

WAGR syndrome: is the 'R' always justified?

Although mild-to-moderate intellectual disability is usually considered part of WAGR syndrome (Wilms' tumour (WT), Aniridia, Genital abnormalities, and metal Retardation, due to 11p13 deletion) the neuropsychological profile of the syndrome is little reported in the literature. We report about a 12-year-old boy presenting with WAGR syndrome (WT, right complete aniridia, bilateral cryptorchidism, interstitial deletion involving band 11p13) but with no mental retardation. An in-depth clinical evaluation revealed no behavioural or social problems and the child's neuropsychological profile was found to be within the normal range for all abilities and functions investigated (with the exception of an impulsive cognitive style and some difficulties in academic skills). This case underlines the importance of in-depth neuropsychological evaluation that includes not only IQ measurement, but also examination of attention and academic skills, in order to establish the complete phenotypical profile of WAGR patients, rather than labelling them as learning disabled (i.e. mental retardation).     

Hopes and facts about mild ovarian stimulation

Over the last two decades, easier and less expensive stimulation treatments have been largely replaced by more complex and more demanding protocols. Since the mid-nineties, long-term gonadotrophin-releasing hormone agonist stimulation protocols have been widely used. Such lengthy expensive regimens are not free from short- and long-term risks and complications. Mild stimulation protocols reduce the mean number of days of stimulation, the total amount of gonadotrophins used and the mean number of oocytes retrieved. The proportion of high quality and euploid embryos seems to be higher compared with conventional stimulation protocols and the pregnancy rate per embryo transfer is comparable. Moreover, the reduced costs, the better tolerability for patients and the less time needed to complete an IVF cycle make mild approaches clinically and cost-effective over a given period of time. However, further prospective randomized studies are needed to compare cumulative pregnancy rates between the two protocols. Natural cycle IVF, with minimal stimulation, has been recently proposed as an alternative to conventional stimulation protocols in normo- and poor responder patients. Although acceptable results have been reported, further large prospective randomized studies are needed to better evaluate the efficacy of these minimal regimens compared with conventional stimulation approaches.     

Transforming growth factor beta1 gene polymorphism 509C/T in deep infiltrating endometriosis

Deep infiltrating endometriosis is characterized by the presence of nodular lesions largely composed of fibromuscular tissue. Transforming growth factor beta 1 (TGF-beta1) is the cytokine most causatively associated with disorders characterized by fibrosis throughout the body. Therefore, the hypothesis was tested that mechanisms increasing the fraction of biologically active TGF-beta1, such as TGF-beta 1 gene polymorphisms, lead to an increased risk of developing deep infiltrating endometriosis. The frequency of the -509C/T polymorphism of the TGF-beta 1 gene was tested in women with deep infiltrating endometriosis (n = 72), gynecological patients without symptoms of endometriosis (n = 95) and healthy females (n = 93). Detection of the -509C/T polymorphisms was performed using PCR-restriction fragment length polymorphism analysis. We did not observe statistically significant differences in the frequency of the -509C/T polymorphism between the groups. Our study does not support an association between the -509C/T polymorphism of the TGF-beta 1 gene and an increased risk of deep infiltrating endometriosis.