Fatal poisoning of four workers in a farm: Distribution of hydrogen sulfide and thiosulfate in 10 different biological matrices

We evaluate the distribution of sulfide and thiosulfate (TS) in biological samples of four dairy farmers died inside a pit connected to a manure lagoon. Autopsies were performed 4 days later. Toxicological analyses of sulfide and TS were made using an extractive alkylation technique combined with gas chromatography/mass spectrometry (GC/MS). Autopsies revealed: multiorgan congestion; pulmonary edema; manure inside distal airways of three of the four victims. Sulfide concentrations were cardiac blood: 0.5–3.0 μg/mL, femoral blood: 0.5–1.2 μg/mL, bile: <0.1–2.2 μg/mL; liver 2.8–8.3 μg/g, lung: 5.0–9.4 μg/g, brain: 2.7–13.9 μg/g, spleen: 3.3–6.3 μg/g, fat: <0.1–1.5 μg/g, muscle: 2.6–3.5 μg/g. TS concentrations were cardiac blood: 2.1–4.9 μg/mL, femoral blood: 2.1–2.3 μg/mL, bile: 2.5–4.4 μg/mL, urine: <0.5–1.8 μg/mL; liver <0.5–2.6, lung: 2.8–5.4 μg/g, brain: <0.5–1.9 μg/g, spleen: 1.2–2.9 μg/g, muscle: <0.5–5.6 μg/g. The cause of death was assessed to be acute poisoning by hydrogen sulfide (H2S) for all the victims. Manure inhalation contributed to the death of three subjects. The measurement of sulfide and TS concentrations in biological samples contributed to better understand the sequence of the events. Subjects 3 provided the highest concentration of sulfide in brain, thus, supporting the hypothesis of a rapid loss of consciousness and respiratory depression. One by one, the other farmers entered the pit in attempts to rescue the coworkers but collapsed. Despite the rapid death, subject 3 was the only one with TS detectable in urine. This could be due to differences in metabolism of H2S

Broca&#8217;s Area as a Pre-articulatory Phonetic Encoder : Gating the Motor Program

The exact nature of the role of Broca's area in control of speech and whether it is exerted at the cognitive or at the motor level is still debated. Intraoperative evidence of a lack of motor responses to direct electrical stimulation (DES) of Broca's area and the observation that its stimulation induces a "speech arrest" without an apparent effect on the ongoing activity of phono-articulatory muscles, raises the argument. Essentially, attribution of direct involvement of Broca's area in motor control of speech, requires evidence of a functional connection of this area with the phono-articulatory muscles' motoneurons. With a quantitative approach we investigated, in 20 patients undergoing surgery for brain tumors, whether DES delivered on Broca's area affects the recruitment of the phono-articulatory muscles' motor units. The electromyography (EMG) of the muscles active during two speech tasks (object picture naming and counting) was recorded during and in absence of DES on Broca's area. Offline, the EMG of each muscle was analyzed in frequency (power spectrum, PS) and time domain (root mean square, RMS) and the two conditions compared. Results show that DES on Broca's area induces an intensity-dependent "speech arrest." The intensity of DES needed to induce "speech arrest" when applied on Broca's area was higher when compared to the intensity effective on the neighboring pre-motor/motor cortices. Notably, PS and RMS measured on the EMG recorded during "speech arrest" were superimposable to those recorded at baseline. Partial interruptions of speech were not observed. Speech arrest was an "all-or-none" effect: muscle activation started only by removing DES, as if DES prevented speech onset. The same effect was observed when stimulating directly the subcortical fibers running below Broca's area. Intraoperative data point to Broca's area as a functional gate authorizing the phonetic translation to be executed by the motor areas. Given the absence of a direct effect on motor units recruitment, a direct control of Broca's area on the phono-articulatory apparatus seems unlikely. Moreover, the strict correlation between DES-intensity and speech prevention, might attribute this effect to the inactivation of the subcortical fibers rather than to Broca's cortical neurons

Distribution of quetiapine and metabolites in biological fluids and tissues

Quetiapine is an atypical antipsychotic drug, frequently found in post-mortem samples. The quantitative determination of active metabolites may help in the interpretation of the potential toxic effects of the parent drug and its role in death. A fully validated LC–MS/MS method was developed for the identification and quantification of quetiapine and two main metabolites (N-desalkylquetiapine and 7-hydroxyquetiapine) in blood, biological fluids and tissues. Then, the distribution of analytes in different matrices was evaluated. LODs of 0.9, 0.3 and 0.3 ng/mL were calculated for quetiapine, N-desalkylquetiapine and 7-hydroxyquetiapine respectively; while a LOQ at the concentration of 10.0 ng/mL was defined for the three analytes. 13 post-mortem positive real cases have been included in the experiment. The results revealed that quetiapine and N-desalkylquetiapine might undergo a significant post-mortem redistribution, while 7-hydroxyquetiapine is less affected by this factor. N-desalkylquetiapine could be found in blood in relatively high concentrations in comparison to those of quetiapine; therefore, it should be always advisable to measure both the analytes. The analysis of tissues could provide additional data on potential intoxication with quetiapine

Supratotal resection in low grade gliomas (LGGs) : feasibility and clinical impact

Surgical strategy for LGGs aims at maximal tumor removal and at the maintainance of patient full integrity, performing resection according to functional boundaries. Maximal resection is accomplished to reach tumor borders as visibile in volumetric FLAIR (total resection) and when possible even further (supratotal resection). Maximal tumor resection (GTR) is associated with prolonged progression free survival (PFS) and malignant progression free survival (MPFS). While these goals are reached when a GTR is obtained, the feasibility, the clinical and oncological impact of supratotal resection is still a matter of debate. In this work we explore the feasibility of supratotal resection, its short and long term on patient performance, and its oncological impact. A series of 375 LGGS were submitted to surgery according to functional boundaries with intraoperative neurophysiology and neuropsychology. The extent of resection was evaluated on volumetric FLAIR images. The number of cases in which a total or supratotal resection was reached, tumor volume and location, the duration of surgery, the technical adjunts needed, and the rate of surgical complication were assessed. The percentage of immediate and permanent post operative deficits were evaluated by neurologic and neuropsychological evaluation. A separate group of 75 patients submitted to total and supratotal resection were followed up for at least 7 yrs (mean 8 yrs, 7\u20139 yrs) to evaluate the impact on PFS and MPFS. A total and supratotal resection were obtained in 95 and 94 patients, with tumors located in both dominant and non dominant hemisphere. Supratotal resection was obtained mainly in frontal lobe tumor (52%), but reached also in temporal (20%), insular (20%) and parietal (5%) tumors. Median tumor volume was 18,8 cm3. 33,3% tumors were oligodendroglioma. No difference in term of duration of surgery, technical adjunt needed to perform the procedure, and no complications were registered. The rate of immediate post operative deficits was comparable and related to functional tumor location. No neurological permanent deficits were documented. The neuropsychological evaluation showed a difference at 1 month, with an moderate increase of deficits in the supratotal group, but no differences at 6 months evaluation (10% and 8%, mostly memory and attention deficits). In the group of patients with longer followup no recurrence were observed in the subgroup of patients submitted to supratotal resection while 78% of patients in the subgruop of total resection recurred within 7 years and in 25% showed with malignant transformation. Supratotal resection when performed according to functional boundaries is a feasible and safe procedure to be considered in each case of LGGs. The oncological followup suggests a stronger impact of the supratotal resection on the natural history of the disease wich should be confirmed with a further longer follow up