Overview on the mechanisms of drug-induced liver cell death

Drug-induced hepatotoxicity is a significant and still unresolved clinical problem. The limitation in current knowledge regarding mechanisms of hepatic toxicity renders most of the preclinical review process failing and most of drug-induced hepatic injury remains unpredictable. Current knowledge on the mechanisms of drug-induced liver cell death is reviewed here. The intervention of both intra- and extracellular factors in determining the appearance of drug-induced cell apoptosis or necrosis is also discussed. Finally, the role of both mitochondria and non parenchymal cells are reviewed with respect to approaches useful to manage drug-induced liver injury.     

Endoscopy-assisted rhinoplasty

In nasal surgery some surgical steps are done without the aid of direct vision. In these situations, surgeons must use their experience and judgment. I have adapted techniques used in endoscopic sinus surgery to perform some of the surgical steps of functional and aesthetic rhinoplasty. Between September 1999 and February 2000, 11 patients underwent endoscopic-assisted septorhinoplasty, and 18 patients underwent traditional closed rhinoplasty. The following parameters were compared: surgical bleeding, postoperative edema and ecchymosis, dorsum irregularity, and operative time for each technique. The following steps were clearly visualized with the endoscope: raising the periosteum from the nasal bone, resecting the nasal hump, and rasping the nasal bones. The use of endoscopic instruments does not change the surgical steps required. Rather, it allows direct vision of steps previously not viewable.     

Temperature related mortality and ambulance service interventions during the heat waves of 2003 in Ticino (Switzerland)

Objectives  

This study investigates a potential increase in mortality and in the demand for ambulance emergency services among the elderly in particular, in Ticino in the summer of 2003.     

Multi-disciplinary clinical protocol for the diagnosis of bulbar amyotrophic lateral sclerosis

Introduction and objectives

The objective of this study was to examine the role of different specialists in the diagnosis of amyotrophic lateral sclerosis (ALS), to understand changes in verbal expression and phonation, respiratory dynamics and swallowing that occurred rapidly over a short period of time.

Leiomyoma of tunica albuginea of testis

Leiomyoma is an uncommon lesion which may originate anywhere within the genitourinary system where smooth muscle is present. The third case of leiomyoma of the testicular tunica albuginea is reported, and other reports of genitourinary leiomyomas are reviewed.     

Cauda equina compression syndrome in a patient affected by thalassemia intermedia: complete regression with blood transfusion therapy

Surgical excision followed by radiotherapy has been reported to be successful in the treatment of spinal cord compressions due to extramedullary hematopoiesis in patients affected by thalassemia. The authors report a case of cauda equina compression in such a patient successfully treated with repeated blood transfusions.     

The role of ultrasound of sentinel nodes in the pre- and post-operative evaluation of stage I melanoma patients

We have investigated the role of high-resolution ultrasound (US) in the analysis of sentinel node(s) in melanoma patients in pre-operative staging and follow-up. One hundred and six lymph node basins in 88 melanoma patients undergoing sentinel node biopsy (SNB) were examined: 25 (23.6%) were US positive for metastases and 81 (76.4%) were negative. Subsequent histological analysis of the 81 negative lymph nodes confirmed the absence of metastases in 80 cases (98.8%), whereas, in the 25 US-positive lymph nodes, metastases were found in 16 cases (64%). The follow-up of all patients submitted to SNB in our unit included a US investigation of operated and contralateral nodal basins every 4 months for the first 3 years and then every 6 months. Of a total of 300 patients, four (1.6%) were found to have locoregional nodal disease during follow-up. In three of these four patients, US was crucial in indicating the presence of nodal metastases, which would have gone undetected on physical examination. The result of this study (negative predictive value of 98.7%) introduces the possibility of selecting patients who may avoid an SNB procedure based on the results of pre-operative US examination.     

The reduced tolerance of rat fatty liver to ischemia reperfusion is associated with mitochondrial oxidative injury

BACKGROUND: Oxidative stress contributes to the pathogenesis of hepatic ischemia-reperfusion injury. This study aimed to determine whether fatty degeneration affects the oxidative damage during warm ischemia reperfusion and whether mitochondria, the major intracellular site of energy synthesis, represent a preferential target of this injury. MATERIALS AND METHODS: Fed rats with control or fatty liver induced by choline deficiency underwent 60' lobar ischemia and reperfusion. Oxidative damage was assessed by measuring in whole liver tissue and in isolated mitochondria the thiobarbituric acid-reactive substances (TBARs), protein carbonyls (PC), and total and oxidized glutathione (GSH and GSSG) concentrations. The mitochondrial F0-F1-ATPase content and the oxidative phosphorylation activity were also determined. Rat survival and ALT release were assessed as parameters of liver injury. RESULTS: In the whole liver tissue, with the exception of TBARs, no differences were observed for GSH, GSSG, and PC between the two groups throughout all of the experiment. In contrast, in isolated mitochondria, fatty infiltration was associated with a mild oxidative imbalance already under basal conditions. The preischemic differences in the mitochondrial TBARs, PC, and GSSG levels were significantly amplified by reperfusion in the presence of steatosis. The enhanced oxidative damage was associated to a reduced F0-F1-ATPase content and oxidative phosphorylation activity in fatty liver mitochondria. Finally, serum ALT levels were significantly greater and survival significantly lower in rats with steatotic liver. CONCLUSIONS: Fatty infiltration exacerbates mitochondrial oxidative injury during warm ischemia reperfusion. The increased oxidative stress can alter mitochondrial functions, including key processes for ATP synthesis, thus, contributing to the reduced tolerance to reperfusion injury.     

Complex anal fistula with a recess above the levator ani muscles: report of a case complicated by haemorrhagic colitis

Anal fistula surgery offers very little in the way of new developments. As early as the 14th century John of Arden defined the rules for surgical therapy. The numerous classifications adopted are often contradictory and unclear, and no clearly defined pathogenesis of the condition has been established. Complex anal fistula with a recess above the elevator ani muscles requires very careful and meticulous therapeutic treatment because of the risk of damaging the sphincter. In the case reported here the patient presented a very complex fistula which was followed by onset of severe haemorrhagic colitis without any clinical, endoscopic, radiological, or histological evidence of inflammatory bowel disease prior to surgical treatment.     

Bacillus clausii exerts immuno-modulatory activity in allergic subjects: a pilot study

Bacillus clausii has been demonstrated to exert some immunomodulatory activities and to be safe. Allergic subjetcs show Th2 polarization and defect of T regulatory cells. Aim of the study was to investigate whether Bacillus clausii administration in allergic subjects might modulate cytokine pattern. Ten subjects (mean age 22.3 years) suffering from allergic rhinitis were enrolled. Bacillus clausii spores (Enterogermina: 2 billions spores/vial) were administered at the dosage schedule of 3 vials a day for 4 weeks. Nasal lavage was performed in all subjects before and after the treatment. A panel of cytokines, including IL4, IL10, IFNgamma, and TGFbeta, was measured by immunoassay in the fluid recovered from nasal lavage, before and after the treatment. RESULTS: Bacillus clausii treatment showed a significant decrease of IL4 levels (p=0.004) and a significant increase of IFNgamma (p=0.038), TGFbeta (p=0.039), and IL10 (p=0.009) levels. In conclusion, this study shows that the Bacillus clausii may exert immuno-modulating activity by affecting cytokine pattern in allergic subjects and confirms previous study conducted in allergic children.