Four cases of sodium nitrite suicidal ingestion: A new trend and a relevant Forensic Pathology and Toxicology challenge.

Sodium nitrite (NaNO2) is an inorganic compound commonly used as a food additive, antifreeze admixture, and fertilizer. Its toxicity mechanism is mainly represented by the oxidation of ferrous iron to ferric iron of one of the four heme structures in haemoglobin with the onset of methaemoglobin. The mechanism of death by sodium nitrite toxicity is severe hypoxia. We present four cases of suicidal sodium nitrite ingestion that closely occurred within a two months-period. Self-poisoning with sodium nitrite actually represents an increasing trend in nitrates' related deaths. In order to reach a precise diagnosis of NaNO2 intoxication, a complete toxicological analysis should be carried out including not only MetHb blood levels but also nitrites and nitrites in standard or alternative matrices as a routine procedure. Autopsy should be carefully performed to detect common indicators of hypoxia or more rarely evident typical by themselves-non specific signs of sodium nitrite toxicity. Suicidal manner of death should be carefully considered when circumstantial data support that ingestion of large amounts of NaNO2 occurred as a consequence of a self-injurious behaviour. Relevant informations include victim's previous Internet or book researches about paths to follow to commit suicide with sodium nitrate, employment and past medical history, with strong regard to psychiatric diseases as well as eventual taking psycotropic drugs. Finally, an accurate integration of autoptic and toxicological results with circumstantial data is necessary to make correct diagnosis of death due to acute respiratory failure secondary to suicidal sodium nitrite ingestion.

Post-operative complications of tibial plateau fractures treated with screws or hybrid external fixation.

PURPOSE: To assess the complications and second surgeries rates at 1 year follow-up in a group of patients underwent minimally invasive fixation with screws or hybrid external fixation (HEF) for tibial plateau fractures (TPF). The hypothesis was that low Schatzker (I-IV) TPF would have shown a lower complication rate with respect to high Schatzker (V-VI) TPF. METHODS: 148 patients who underwent minimally invasive surgery with screws or HEF for TPF were included and pooled in two groups: mono-condylar (Schatzker I-IV) and bi-condylar (Schatzker V-VI). The rate of second surgeries and complications, such as stiffness, infection, wound dehiscence and malunion occurred within 1 year, were reported. RESULTS: Statistically significant difference between mono-condylar and bi-condylar groups was found in terms of stiffness (18% vs. 37%, p = 0.01), malunion (4% vs 21%, p = 0.004) and second surgeries (32% vs. 48%, p = 0.049). Associated procedures performed during TPF fixation increased risk of second surgeries (OR 2.1, p < 0.001). No differences in terms of second surgeries and complications were found in bi-condylar group treated with screws and HEF. CONCLUSION: Bi-condylar TPF treated with minimally invasive surgery developed a significantly higher rates of stiffness, malunion and second surgeries within 1 year compared to mono-condylar fractures. Moreover, when an associated procedure was performed, the risk of a reoperation was nearly doubled. Trial registration number PG 0012506 CE AVEC 620/2018/Oss/IOR.

Entomotoxicology in burnt bodies: a case of maternal filicide-suicide by fire.

One of the most common methods of maternal filicide is by fire. In this case study, a 40-year-old female and her children were found completely burned in a burnt out car. All bodies showed a degree of destruction by fire consisting to a level 3 of the Crow-Glassman Scale (CGS) and early stage of insect activity. Toxicological analyses were performed on soft tissues and body fluids still available. The results were positive for diazepam and its metabolites only for children with blood concentrations consistent with therapeutic doses of benzodiazepines. Home video surveillance cameras confirmed sedation prior to death recording the mother while administering some drops of sedative drugs in a soft drink to the children just a couple of hours before setting fire to the car. Based on autopsy findings, all victims were still alive at the time of fire. The cause of death was determined as carbon monoxide poisoning and fatal thermal injuries by fire. This case study has a special focus on the entomotoxicology and the potential role of insects in death investigations of burnt bodies, supposed to be an inadequate substratum for insect colonization. It demonstrates that in burnt bodies, arthropod colonization can be quite immediate after fire is extinguished. Toxicological analyses performed on larvae actively feeding on the children's bodies were positive for diazepam and its metabolites in small amount compared with blood concentrations, whereas the larvae collected from the mother's body were totally negative. These data, according to the autopsy findings and the toxicological results from the victim's blood and tissues, supported the suspect of a non-lethal sedation prior to death, which is a common behaviour in maternal filicide.

Biliodigestive fistulae and gallstone ileus: diagnostic and therapeutic considerations. Our experience.

The biliodigestive fistula is not a rare affection in the context of acute pathology of the gastrointestinal tract. It often affects patients between 63 and 85 years old , particularly the female sex, and the most common cause is acute or chronic cholecystolithiasis. Open issues are the delayed in the pre-operative diagnosis, and controversies exist regarding the best surgical approach. The choice of treatment options is influenced by the age of the patients and their clinical conditions and also by the presence of comorbidities and of a delayed right diagnosis. In the 1 to 3% of cases, the biliodigestive fistula presents a gallstone ileus as complication, whose diagnosis is particularly difficult for the lack of specific signs and symptoms. The contrast-enhanced CT is considered the gold standard for a specific pre-operative diagnosis, as it directly shows the fistula. Surgical treatments include one-stage procedure or two-stage procedure. Many studies seem to favor a deferred definitive procedure. The Authors describe 4 cases: in 3 cases, women between 70 and 80 years old presenting an history of recurrent cholecystitis, in 2 cases, and in 1 case presenting a bowel obstruction; in 1 case a 50-years-old man, with no significant past medical history, presenting a bowel obstruction. The Authors have performed in the 2 cases of gallstone ileus an enterolithotomy with cholecysto-duodenal fistula repair and cholecystectomy, in one-stage, and this has been possible because of the good clinical conditions of the patients and their low operative risk. In the case of fistula without the complication of gallstone ileus, the treatment approach has been cholecysto-gastric fistula closure with a gastroplastic using separate stitches and cholecystectomy, in one-stage. We are in agreement with data in the literature regarding the delay into the diagnosis of biliodigestive fistula and with the importance to suspect it or gallstone ileus presence, although the clinical presentation is extremely non-specific. In our experience, cholangiopancreatography-CT and CECT have made easier the pre-operative diagnosis and so reducing the delay of the treatment.

Small bowel intussussception due to metastatic melanoma of unknown primary site. Case report.

Malignant melanoma is characterized by metastases also to the gastrointestinal tract, especially in the small bowel. The diagnosis is often delayed because unspecific clinical presentation (frequently as chronic iron deficiency anemia, rectal bleeding or intestinal obstruction). We present a case of melanoma of unknown primary site, with clinical presentation of intestinal obstruction. A segmental resection of the ileum was performed including mesentery with lymph nodes. Histology revealed metastatic melanoma from unknown primary. PET and MRI confirmed disseminated disease without brain metastasis.

Simultaneous determination of morphine, codeine and 6-acetyl morphine in human urine and blood samples using direct aqueous derivatisation: validation and application to real cases.

Opiates play a relevant role in forensic toxicology and their assay in urine or blood is usually performed for example in workplace drug-testing or toxicological investigation of drug impaired driving. The present work describes two new methods for detecting morphine, codeine and 6-monoacethyl morphine in human urine or blood using a single step derivatisation in aqueous phase. Propyl chloroformate is used as the dramatizing agent followed by liquid-liquid extraction and gas-chromatography-mass spectroscopy to detect the derivatives. The methods have been validated both for hydrolysed and unhydrolysed urine. For hydrolysed urine, the LOD and LOQ were 2.5ng/ml and 8.5ng/ml for codeine, and 5.2ng/ml and 15.1ng/ml for morphine, respectively. For unhydrolysed urine, the LOD and LOQ were 3.0ng/ml and 10.1ng/ml for codeine, 2.7ng/ml and 8.1ng/ml for morphine, 0.8ng/ml and 1.5ng/ml for 6-monoacetyl morphine, respectively. In blood, the LOD and LOQ were 0.44ng/ml and 1.46ng/ml for codeine, 0.29ng/ml and 0.98ng/ml for morphine, 0.15ng/ml and 0.51ng/ml for 6-monoacetyl morphine, respectively. The validated methods have been applied to 50 urine samples and 40 blood samples (both positive and negative) and they can be used in routine analyses.

Single-incision laparoscopic appendectomy is comparable to conventional laparoscopic and laparotomic appendectomy: our single center single surgeon experience.

Several studies have demonstrated the clinical and technical benefits of the laparoscopic surgery for complicated and uncomplicated appendicitis. Our retrospective study included 12 patient who underwent SILS appendectomy (SILS-A), 14 who received conventional laparoscopic surgery (VL-A), and 12 who received laparotomic appendectomy (OA); performed in all cases by the same surgeon (C.F.). The aim of this study was the comparison between this three different surgical techniques on same features: post operative leukocytosis, post operative pain, need abdominal drainage, esthetic viewpoint, incidence of complication, hospital stay. The results showed no significant differences between SILS-A and VLS-A, while an evident improvement shows versus O-A, even though not statistically significative. SILS was more effective in decreasing the risk of postoperative wound infection.

Frailty in patients affected by atrial fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia among elderly people. However its relationship with the frailty syndrome is not well understood. It has been suggested that AF may be a marker of frailty in elderly, leading to the loss of independence in performing of routine daily activities. The aim of this study is to investigate the association between AF, frailty and cognitive decline in elderly patients. A total of 140 hospitalized patients, mean age 79.2 ± 7.4 years were enrolled in our study. Of these, 70 were affected by parossistic, persistent or permanent AF and 70, matched for age and gender, were concurrently studied as control. Cognitive impairment and frailty state has been evaluated in each patient using the Mini Mental State Examination (MMSE) and a standard score of accumulated deficits for constructing a frailty index. We have observed a higher number of frail patients in the AF group as compared with controls (88.6% vs 67.1%, p=0.004). The group of patients with frailty syndrome had MMSE score significantly lower than those of the nonfrail group (16.8 ± 9.8 vs 22.2 ± 6.4, p=0.005). Furthermore, a negative correlation between MMSE score and frailty index (rho = -0.517, p < 0.001) has been shown. Our study points out a statistical association between frailty and AF. Atrial fibrillation could worsen the frailty state, but perspective studies are necessary to confirm an increased mortality in patients affected by AF and frailty.

Synergistic interaction between PPAR ligands and salbutamol on human bronchial smooth muscle cell proliferation.

BACKGROUND AND PURPOSE: An important objective in asthma therapy is to prevent the accelerated growth of airway smooth muscle cells which leads to hyperplasia and bronchial hyperreactivity. We investigated the effect of combination of salbutamol and PPARγ agonists on growth factor-stimulated human bronchial smooth muscle cell (BSMC) proliferation. EXPERIMENTAL APPROACH: Synergism was quantified by the combination index-isobologram method. Assays used here included analyses of growth inhibition, cell viability, DNA fragmentation, gene transcription, cell cycle and protein expression. KEY RESULTS: The PPARγ gene was highly expressed in BSMC and the protein was identified in cell nuclei. Single-agent salbutamol or PPARγ agonists prevented growth factor-induced human BSMC proliferation within a micromolar range of concentrations through their specific receptor subtypes. Sub-micromolar levels of combined salbutamol-PPARγ agonist inhibited growth by 50% at concentrations from ∼2 to 12-fold lower than those required for each drug alone, without induction of apoptosis or necrosis. Combination treatments also promoted cell cycle arrest at the G1/S transition phase and inhibition of ERK phosphorylation. CONCLUSIONS AND IMPLICATIONS: The synergistic interaction between PPARγ agonists and ß(2) -adrenoceptor agonists on airway smooth muscle cell proliferation highlights the anti-remodelling potential of this combination in chronic lung diseases.

Cholecystectomy by single incision laparoscopic surgery (SILS): early experience and technique standardization.

Single Incision Laparoscopic Surgery (SILS) is a recent surgical technique, first described in the 1990s. Its aim is to optimize the esthetic result offered by laparoscopy by minimizing the number of abdominal incisions. Various preliminary studies have been carried out on the application of SILS, especially in cholecystectomy and appendectomy. This study evaluates the preliminary results of cholecystectomy by SILS (SILS™ Port) conducted between October 2009 and February 2011 on 21 patients (4 men and 17 women) with a mean age of 49.9 years and a mean Body Mass Index (BMI) of 22.8. All patients were treated by the same team, which had previously undergone six months' simulator training. There were two main selection criteria, both evaluated intraoperatively: absence of adhesions and of significant inflammatory sequelae from previous cholecystitis; and suitable distance between gallbladder and SILS access port. Conversion to traditional laparoscopy was necessary in just two cases, while an accessory trocar was introduced in another two cases. Conversion to open surgery was not necessary in any case. One case of SILS cholecystectomy was complicated by postoperative bile leakage, which was treated conservatively, as the fistula had a low output. The mean duration of hospitalization was 3.6 days. This preliminary experience led us to conclude that SILS is safe and highly satisfactory in the postoperative phase, thanks to the reduced need for painkillers and the improved esthetic result.

Liver resection for hemoperitoneum caused by spontaneous rupture of unrecognized hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an increasingly common form of cancer. Although its spontaneous rupture is rare in Western countries, it constitutes a surgical emergency and is associated with high mortality. There is a lack of consensus as to the best approach and what parameters to use in choosing it. The three main approaches are conservative, endovascular and resection - the treatment of choice for acute abdominal bleeding. We report a case of hemoperitoneum following the spontaneous rupture of an unrecognized HCV-related HCC in a patient with no history of liver disease. The patient was successfully treated by emergency surgery, with resection of two segments of the left liver.

[Unusual cause of acute abdomen in adult patient: gallstone ileus]. / Insolita causa di addome acuto in paziente adulto: l'ileo biliare.

INTRODUCTION: Gallstone ileus is a rare complication of cholecystolithiasis. It causes 1-3% of the mechanical obstructions of the small bowel. It often affects patients between 63 and 85 years old. Pre-operative diagnosis is usually delayed 1-10 days because there is not a specific symptomatology. CASE REPORT: The authors report the case of a 50 year-old man with diagnosis of mechanical obstruction of the small bowel caused by a voluminous gallstone. Ileal occlusion was showed by CT. The patient underwent to one-stage emergency surgery with enterolithotomy, cholecystectomy and duodenal fistula repair. Patient's recovery was regular and he was discharged fourteen days after surgery. DISCUSSION: In our case gallstone ileus was diagnosed with a delay of 5 days. Ultrasonography was not able to show the gallbladder. Diagnosis was made by CT, which is the diagnostic gold standard. CONCLUSION: Patient's performance status influences surgical strategy. In our experience, the patient underwent one-stage surgery because he was considered at low risk. Instead staged procedure with enterolithotomy and delayed cholecystectomy and fistula repair, is performed only in patients at high risk.

Modification of respiratory function parameters in patients with severe Parkinson's disease.

Respiratory dysfunction remains one of the most common causes of death in patients with complicated Parkinson's disease (PD). The aim of this study was to investigate pulmonary function in fluctuating PD patients during "on" and "off" states of the disease. We studied 12 fluctuating, non-smoking PD patients (H&Y stages 3-5) without a history of lung or cardiovascular disease; all patients underwent Hoehn and Yahr scale (H&Y) and Unified Parkinson Disease Rating Scale (UPDRS items 18-31) to evaluate extrapyramidal impairment, as well as pulmonary function tests (PFT) and arterial blood gas analyses to assess respiratory function. All evaluations were performed during a stable on state of disease and in an off state produced by 12 hours of therapy withdrawal. A restrictive pattern of flow-volume loop was observed both in on and off states of disease. In the off state, we found a significant worsening in both FEV1 and FVC; the FEV1/FVC ratio was unmodified. These results suggest a restrictive pattern of flow-volume loop in these patients.

Evidence of a restrictive spirometric pattern in older thalassemic patients.

BACKGROUND: Lung impairment represents one of the complications of thalassemia major whose clinical picture can remain in subclinical form all life long. Few works have been published and the results are contradictory. OBJECTIVES: The aim of this study was to determine the spirometric pattern, the age of onset in thalassemic boys and girls, and to investigate the association with the onset of endocrinological complications. METHODS: We studied 48 patients, divided into three groups according to pubertal stages, in order to better distinguish the periods of life in which different endocrinological complications usually appear. Group A: (n = 14; 8 F, 6 M; age 10.8 +/- 1.7 years): prepubertal patients; group B (n = 21; 10 F, 11 M; age 15.7 +/- 1.1 years): pubertal patients; and group C (n = 13; 9 F, 4 M; age 19.0 +/- 1.4 years): postpubertal patients. Pulmonary function tests (PFTs) and diffusing capacity for carbon monoxide (DCO), corrected for both Hb values (DCO*) and alveolar volume (KCO), were performed 2 days after blood transfusion and were considered pathologic when they fell below 80% of the predicted value. RESULTS: All patients in group A showed normal PFTs, DCO* and KCO values, as well as normal endocrinological assessment. By contrast, all those in group C showed a restrictive spirometric pattern with reduced DCO* (63 +/- 8%), elevated KCO values (120 +/- 14%), a variable degree of hypoxia (PO2 82 +/- 9%), and high serum ferritin levels. Only 2 patients showed a radiological picture of interstitial fibrosis. Furthermore, 9 patients had hypogonadism and 3 hypothyroidism. In group B, only 3 patients showed a restrictive pattern and 1 of them reduced DCO* values, and 2 out of 3 patients had hypogonadism. Considering all patients on the whole, DCO* was negatively correlated with both serum ferritin (r = -0.58; p < 0.05) and age (r = -0.57; p < 0.05). CONCLUSIONS: The presence of a restrictive pattern in 16 older patients associated with both high serum ferritin levels and endocrinological complications in a lot of them was the main feature in this study. Iron overload might be the main factor determining lung impairment, even though a more accurate evaluation is necessary. Possible pathological mechanisms and the role of the genotype are discussed.

Effectiveness and acceptability of a domiciliary multidrug inhalation treatment in elderly patients with chronic airflow obstruction: metered dose inhaler versus jet nebulizer.

The aim of this study was to compare the immediate and long-term bronchodilator effect as well as the patient acceptability of a 2-week, multidrug, inhalation treatment delivered by a metered dose inhaler (MDI) versus a jet nebulizer in a group of elderly patients with chronic obstructive pulmonary disease (COPD) or asthma and an at least partially reversible airflow obstruction. Twenty elderly outpatients (17 men; mean +/- SD age, 67 +/- 2 years; mean +/- SD baseline forced expiratory volume in 1 second [FEV1], 46.5 +/- 14% of predicted value) with COPD or asthma participated in the study, which was of an open, randomized, crossover design. After a 1-day baseline evaluation, including patient history, clinical examination, and spirometry, participants were randomly assigned to receive a multidrug inhalation treatment (a combination of salbutamol, ipratropium, and flunisolide) with either an MDI or a jet nebulizer. Two weeks later, they were shifted to treatment with the alternative system for a further 2 weeks. FEV1 was measured on the first and fourteenth days of each treatment period, on each occasion both before and 30 minutes after the morning inhalation. At the end of the study, patients were asked to express a personal preference for one of the two inhalation treatments with regard to effectiveness and acceptability by filling out a simple questionnaire. Both the MDI and jet nebulizer had a significant immediate bronchodilator effect on the first and fourteenth days of treatment, with no differences between treatments. No long-term bronchodilator effect was seen with either aerosol delivery system. Patient preferences were clearly in favor of the jet nebulizer with regard to effectiveness and in favor of the MDI with regard to acceptability. In conclusion, in elderly patients with COPD or asthma and partially reversible airflow obstruction, a maintenance multidrug bronchodilator/anti-inflammatory inhalation treatment produced a statistically significant and clinically relevant bronchodilator effect without substantial differences between the two delivery systems. Most patients considered the MDI to be more acceptable and the jet nebulizer to be more effective. These preferences should be taken into consideration when prescribing a maintenance aerosol inhalation treatment.

Eosinophilic inflammation in stable chronic obstructive pulmonary disease. Relationship with neutrophils and airway function.

The number and significance of airway eosinophils in stable COPD is controversial. Aims of this study were to evaluate airway inflammation in patients with stable COPD compared with other groups, and to examine the correlations between inflammatory markers and functional indices of airway obstruction. Cellular analysis and evaluation of eosinophil cationic protein (ECP) levels in induced sputum were made in 46 subjects (10 patients with clinically stable COPD, 15 patients with asthma, 11 asymptomatic smokers, and 10 healthy control subjects). As expected, eosinophils were significantly (p < 0.01) higher in patients with asthma (22.2%) than in other groups (COPD, 0.7%; smokers, 0.2%; control subjects, 0.2%), and neutrophils were significantly (p < 0.01) higher in patients with COPD (77.5%) than in the other groups (asthma, 26.7%; smokers, 33.1%; control subjects, 35.9%). However, eosinophils were also increased in patients with COPD, as compared with healthy controls (p < 0.05). Sputum ECP levels were significantly and similarly higher in both asthma and COPD groups than in the other two groups (p < 0.01). In patients with COPD and asymptomatic smokers, considered as a whole, good correlations were found between eosinophils and ECP, on the one hand, and between FEV(1) and the FEV(1)/FVC ratio, on the other. Our data suggest that eosinophils may be involved in the airway inflammation of COPD.

Ultrasonic nebulization of hypertonic solution: a new method for obtaining specimens from nasal mucosa for morphologic and biochemical analysis in allergic rhinitis.

Various techniques are used to collect specimens from the nasal mucosa for morphologic and biochemical analysis. The purpose of this study was to devise a method that overcomes some of the disadvantages (e.g., invasive procedure, samples not suitable for cytologic and biochemical analysis, lack of standardization, and poor reproducibility) of these techniques. The new method requires subjects, with neck extended, to inhale an ultrasonic nebulization of a hypertonic (3% NaCl) solution (UNHS) for 5 min. They then blow their nose into a Petri dish, one nostril at a time with the other one blocked. The secretions are dispersed with 0.1% dithiothreitol in phosphate buffer solution for 20 min. Total cell count (TCC) is evaluated, and the cellular suspension is divided into two aliquots: one is centrifuged and the supernatants are collected for eosinophil cationic protein (ECP) measurements; the other is cytocentrifuged and the slides, stained with Diff-Quik, are used for differential cell count. The results obtained with the UNHS and nasal lavage (NL) methods were compared. Eleven nonatopic healthy subjects and 19 allergic rhinitic patients were studied. Total cell count (x10(5)) was significantly higher with UNHS than with NL (13.0+/-12.3 vs 1.9+/-1.6; P<0.01) The differential cell count was similar with the two procedures. ECP levels (microg/l) were higher with UNHS than with NL (39.1+/-38.2 vs 16.7+/-41.2; P<0.01). For evaluation of reproducibility, four healthy and six rhinitic subjects underwent UNHS on two occasions within 5 days, and the results of two samples (sample 1 vs sample 2) were analyzed. Reproducibility was good as to TCC, differential cell count, and ECP.

[Diffuse pulmonary microlithiasis (a clinical case)]. / Microlitiasi polmonare diffusa (il caso clinico).

The authors present a clinical case pertinent to a patient suffering from persistent dry cough and dyspnea by effort. It is described the diagnostic course that enables to identify a diffuse pulmonary microlithiasis, of rare cheeking, whose pathogenetic hypotheses and differential problems are tackled.