Marco Di Paolo

Postmortem molecular analysis in victims of sudden unexplained death

Among several conditions that can be responsible for sudden cardiac death (SCD), an important role is played by long QT syndrome (LQTS). LQTS is a congenital electric heart disease that can be asymptomatic or have very severe clinical manifestation, leading to cardiac arrest. In fact, the first manifestation of LQTS can be hyperkinetic ventricular arrhythmias. The presence of LQTS should be considered in all cases of SCD where autopsy is negative for anatomic and histopathological findings. In these cases, after an accurate anamnesis, a genetic screening should always be performed. The screening on LQTS genes is performed on DNA extracted from paraffin-embedded tissues. Making a proper diagnosis in such cases can help to find new affected subjects among the family members of SCD victims and treat them. In these cases, if the pathologist does not make a correct diagnosis, can he or she be sued for malpractice?

Intracranial and intraspinal hemorrhage following spinal anesthesia

Spinal anesthesia (SA), accounting for more than 50% of regional anesthesias in the spinal region, is generally perceived as simple and safe. Our purpose is to increase awareness of hemorrhagic complications following SA. A 69-year-old male without either coagulation disorders or anticoagulant/antiplatelet therapy developed acute radiculopathy, and severe mental confusion after SA for prostatectomy. CT showed intracranial subarachnoid and intraventricular acute hemorrhage. Cerebral angiography was negative. MRI showed subarachnoid and subdural hematoma in the dorsolumbar spine. Seven-year follow-up showed permanent cognitive and radicular damage. Multiple attempts for SA most likely caused spinal vessels rupture, either directly or indirectly by inducing differential pressure changes between cerebrospinal fluid and intravascular spaces; however, definite mechanisms have not been completely understood. Patients undergoing spinal puncture must report any neurological abnormality, which may result in irreversible damage. Cases of altered consciousness require an extensive neuroradiological evaluation. Proper competency of physicians responsible for spinal puncture is mandatory.

Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice

Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidneys reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways.

Forensic Entomology and the Estimation of the Minimum Time Since Death in Indoor Cases

Eight cases that occurred indoors in which the insects played an important role in the mPMI estimation are presented. The bodies of socially isolated people and old people living alone were discovered in central Italy between June and November. mPMI ranged from a few days to several weeks. Insects were collected during the body recovery and the postmortem. Climatic data were obtained from the closest meteorological stations and from measurements performed on the site. Sarcophagidae and Calliphoridae species were present in 75% of the cases with Lucilia sericata and Chrysomya albiceps collected in 50% of the cases. Chrysomya albiceps was always found in association with Lucilia species. Scuttle flies (Phoridae) were found in 37.5% of the cases, confirming the ability of these species in indoor body colonization. We show that if sealed environment may delay, the insect arrival dirty houses may create the environment where sarcosaprophagous insects are already present.

Anabolic Steroid - and Exercise - Induced Cardio-Depressant Cytokines and Myocardial β1 Receptor Expression in CD1 Mice

Few animal model studies have been conducted in order to evaluate the impact of androgenic anabolic steroids (AAS) supraphysiological doses on the cardiovascular system and myocardial injury. Twenty-five male CD1 mice (8-10 weeks old; 35g initial body weight) were randomized into three AAS treated groups and two control groups. The AAS mice received intramuscular Nandrolone Decanoate (DECA-DURABOLIN), vehicled in arachidis oil, for 42 days, twice per week, with different dosages, studying plasma lipid analysis, cardiac histopathological features, cardiac β (1) adrenergic receptor expression, and the effects of the myocardial expression of inflammatory mediators (IL-1β, TNF-α) on the induction of cardiomyocytes apoptosis (HSP 70, TUNEL), using proteomic and immunohistochemical analysis. The mice had free movements in their animal rooms (two groups) or exercised by running on a motor-driven treadmill the others three groups. Recurring high dose AAS administration and physical training in mice produce significant increase in body weight and for total cholesterol. A moderate increase of the heart weight, cardiac hypertrophy and wide colliquative myocytolysis, were observed in high dose AAS administration and physical training group. The expression of HSP70 and inflammatory cytokine IL-1β, increased in the three AAS-treated groups. TNF- α showed a more extensive expression in the AAS-high dose group. A significant apoptotic process randomly sparse in the myocardium was described. Our data support the hypothesis that the combined effects of vigorous training, anabolic steroid abuse and stimulation of the sympathetic nervous system, may predispose to myocardial injury.

Fatal Hepatitis After Long-Term Pulse Itraconazole Treatment for Onychomycosis

Objective: To report the occurrence of acute cytolytic hepatitis In a patient exposed to pulse itraconazole therapy for 24 weeks and provide a concise review of the literature on cases of itraconazole-induced hepatitis. Case Summary: A 61 -year-old woman with no apparent risk factors for liver injury developed acute hepatitis one week after the final dose of a long-term course of pulse itraconazole therapy (200 mg orally twice daily, 1 wk on, 3 wk off, for 24 wk) for onychomycosis. Monitoring of liver enzymes was not performed during the treatment period. Serologic evaluations on presentation ruled out Infectious diseases or other etiological factors. Liver function tests showed alanine aminotransferase 3330 U/L, aspartate aminotransferase 3250 U/L, and bilirubin 21 mg/dL Liver function continued to deteriorate, and the patient underwent liver transplantation 17 days after admission. Her liver displayed reduced volume and them was a mild accumulation of ascitic fluid in the retroperitoneal cavity. Histologic evaluation showed massive panlobular necrosis. Complications occurred after transplantation and a rejection crisis worsened the clinical picture until the patient died about 4 months later. Use of the Naranjo probability scale showed the relationship of itraconazole therapy and the occurrence of acute hepatitis as probable. Discussion: Itraconazole pulse therapy for onychomycosis appears to be at least as effective as and safer than a continuous treatment regimen, particularly from the perspective of potential liver damage. Only one case of severe symptomatic hepatitis occurring after pulse therapy with itraconazole for onychomycosis and requiring transplantation has been reported previously. In that case, as well as the one reported here, hepatitis symptoms occurred after completion of long-term treatment in patients who were asymptomatic both before and during therapy. Conclusions: Prolonged exposure to itraconazole, administered either continuously or intermittently, may precipitate severe and irreversible hepatotoxic events. Accordingly, careful monitoring of liver function parameters should be performed both during and after treatment when onychomycosis requires prolonged itraconazole administration, even in asymptomatic patients lacking apparent risk factors of hepatic injury.

Severe thrombocytopenia and haemolytic anaemia associated with ciprofloxacin: a case report with fatal outcome.

Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.

Cardiac fibrosis, arrhythmia and sudden death in myotonic dystrophy type 1: Could TGF-ß1 improve the predictive accuracy of patients at risk, opening new therapeutic challenges?

[1] International conferences on harmonization, E14. The clinical evaluation of QT/ QTc interval prolongation and proarrythmic potential for non-antiarrhythmic drugs. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E14/ E14_Guideline.pdf [accessed 2013 May 24]. [2] Tornoe CW, Garnett CE, Wang Y, Florian J, Li M, Gobburu JV. Creation of a knowledge Management system for QT analysis. J Clin Pharmacol 2013;51:1035–42. [3] Drug@FDA. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm.[accessed 2013 May 24]. [4] Stockbridge N, Zhang J, Garnett C, Malik M. Practice and challenges of thorough QT studies. J Electrocardiol 2012;45:582–7.

Transient acute liver failure complicating transurethral resection syndrome

Abstract Transurethral resection (TUR) syndrome, resulting from dilutional hyponatraemia for excessive absorption of irrigating fluid, represents the most relevant complication of transurethral resection of prostate (TURP). Ethanol is used as a tracer in the irrigant solution to monitor fluid absorption with a breathalyser. An unusual case of transient acute liver failure complicating TUR syndrome is reported. A 54-year-old male patient, without risk factors for the development of toxic hepatitis, was subjected to TURP for treatment of benign prostatic hyperplasia. Fluid absorption (2275 ml), estimated by breathalyser, exceeded maximum allowed absorption (2000 ml) only at the end of the surgical intervention. No signs of possible toxicity were evident in the few hours following the intervention. About 10 h after the end of TURP, the patient developed sweating, vomiting and diarrhoea. Laboratory analysis revealed severe hyponatraemia (116 meq/l) with signs of severe liver impairment (total bilirubin 5.8 mg/dl, alanine aminotransferase 56 500 U/l, aspartate aminotransferase 32 700 U/l), kidney failure (serum creatinine 1.93 mg/dl) and serum ethanol levels of 219 mg/dl (0.2%). The patient was treated with acetylcysteine 150 mg/kg i.v. and furosemide 50 mg i.v. Liver and renal functions improved in few days and recovered completely within 30 days. The TUR syndrome observed in this case was probably extravascular in nature, and could have been identified and prevented by measuring ethanol levels 10 min after ending the surgical procedure. The performance of such a test should be strongly recommended to all surgeons. The clinicians attributed the development of liver impairment in this case to ethanol toxicity. However, further studies are warranted to confirm whether hepatic injury can represent a possible complication of TUR syndrome when ethanol solution is used as irrigant fluid.

Case report of a homicide by a shotgun loaded with unusual ammunition

Reported is the case of a man killed by a neighbor with a shotgun loaded with a unusual ammunition. The cartridge contained several shots chained together by metallic wires. Such ammunition has been used for hunting purposes but is now banned, so it can be handmade only. The joined pellets produce a wound with features that are different from those of a wound made by a regular load of pellets. Several interpretive problems are caused by the unknown number of pellets contained in the shell and the effects of the wire holding the shot together.