Unexpected Variation of the Codeine/Morphine Ratio Following Fatal Heroin Overdose

Postmortem samples from 14 cases of suspected heroin overdose were subjected to a preliminary systematic toxicological analysis in order to highlight the presence of unknown exogenous compounds (e.g., drugs of abuse, alcohol) that may have played a role in the mechanism of death. This analysis unveiled histories of poly-drug use in seven of the cases under investigation. Moreover, the concentrations of morphine and codeine in the brain were also investigated, and the results were compared with the data obtained from the blood specimens. The concentration of morphine in blood ranged from 33 to 688 ng/mL, while the concentration of codeine ranged from 0 to 193 ng/mL. However, in the brain, the concentration of morphine was found to be between 85 and 396 ng/g, while the levels of codeine ranged from 11 to 160 ng/g. The codeine/morphine ratio in the blood ranged from 0.043 to 0.619; however, in the brain, the same ratio was found to be between 0.129 and 0.552. In most cases, a significantly higher codeine/morphine ratio was found in the brain, suggesting the accumulation of codeine in brain tissue due its high lipophilicity as compared with morphine

Unexpected Metastasis of High Grade Serous Ovarian Cancer to Breast: Case Report and Literature Review

Introduction: Metastasis of ovarian serous carcinoma to breast and/or axillary lymph nodes represents an unusual event. Nevertheless, their detection and distinction from mammary carcinoma are of huge clinical importance because the treatment and prognosis diverge significantly. Case presentation: We report a case of a 47 year-old Caucasian female patient with unforeseen metastasis to the breast and to axillary lymph nodes due to ovarian serous carcinoma. Conclusion: In patients with history of OSC who present with axillary or breast mass, an accurate histological diagnosis should be obtained since this has a great impact on treatment outcomes

Nephroprotective action of glycosaminoglycans: why the pharmacological properties of sulodexide might be reconsidered

A relatively large body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve biochemical alterations of glycoproteins in these structures. Evidence in experimental animals rendered diabetic reveals that the administration of heparin and other anionic glycoproteins can effectively prevent the biochemical alterations that promote albuminuria. Moreover, angiotensin II inhibits heparan sulfate synthesis, while heparins modulate angiotensin II signaling in glomerular cells, inhibiting aldosterone synthesis and lowering proteinuria in diabetes patients. Sulodexide, a mixture of heparin and dermatan sulfate, appears to be a promising treatment for diabetic proteinuria partially resistant to renin–angiotensin system blocking agents. Sulodexide prevents heparan sulfate degradation, thus allowing reconstruction of heparan sulfate content and restoration of glomerular basement membrane ionic permselectivity. The antiproteinuric effect appears to be mainly related to the basal proteinuria and consequently to the duration of treatment in a relatively large number of small clinical trials. On the other hand, several sulodexide pharmacodynamic properties could improve the prognosis of chronic kidney disease patients, also independently from its antiproteinuric effect. However, sulodexide development as an antiproteinuric drug needs to be continued, in order to define which kind of patients could better respond to this treatment

Determination of propofol by GC/MS and fast GC/MS-TOF in two cases of poisoning

Two cases of suspected acute and lethal intoxication caused by propofol were delivered by the judicial authority to the Department of Sciences for Health Promotion and Mother-Child Care in Palermo, Sicily. In the first case a female nurse was found in a hotel room, where she lived with her mother; four 10 mg/mL vials and two 20 mg/mL vials of propofol were found near the decedent along with syringes and needles. In the second case a male nurse was found in the operating room of a hospital, along with a used syringe. In both cases a preliminary systematic and toxicological analysis indicated the presence of propofol in the blood and urine. As a result, a method for the quantitative determination of propofol in biological fluids was optimized and validated using a liquid-liquid extraction protocol followed by GC/MS and fast GC/MS-TOF. In the first case, the concentration of propofol in blood was determined to be 8.1 \u3bcg/mL while the concentration of propofol in the second case was calculated at 1.2 \u3bcg/mL. Additionally, the tissue distribution of propofol was determined for both cases. Brain and liver concentrations of propofol were, respectively, 31.1 and 52.2 \u3bcg/g in Case 1 and 4.7 and 49.1 \u3bcg/g in Case 2. Data emerging from the autopsy findings, histopathological exams as well as the toxicological results aided in establishing that the deaths were due to poisoning, however, the manner of death in each were different: homicide in Case 1 and suicide in Case 2

Detection and quantitation analysis of cocaine and metabolites in fixed liver tissue and formalin solutions.

This study reports the results of the detection and quantitation of cocaine and its metabolites in liver tissues fixed in formalin and in the formalin solutions in which the same tissues were fixed. Toxicological analyses were performed on formalin-fixed liver samples from four cases of death of cocaine abusers and on formalin solutions (10% buffered, pH 7) in which the samples were preserved. Analyses carried out at the time of autopsy on body fluids and tissues allowed identification of cocaine and the metabolite benzoylecgonine. Liver tissue samples were preserved in formalin solutions for four weeks before analysis. Results only showed the presence of benzoylecgonine in the studied materials. The mean levels of recovery of benzoylecgonine in fixed tissues were 12.31% in liver and 84.47% in formalin from liver. Results indicated that benzoylecgonine has good stability, even in biological specimens subjected to chemical fixation

Capillary electrophoretic and extraction conditions for the analysis of Catha edulis FORKS active principles

A capillary electrophoretic method, which allowed the detection and separation of the active principles of Catha edulis, i.e. cathinone, cathine and phenylpropanolamine, was developed. A suitable internal standard (nicotinamide), which permitted the quantification of the analytes reducing the variability of the migration times due to EOF changes, was identified. The analytical method was validated, assessing linearity, sensitivity and repeatability, showing optimal features for the analysis of the vegetable material. Moreover extraction conditions were investigated to achieve the exhaustion of the plant material in the fastest and most efficient way to meet the requirements of the Court

Determination of daptomycin in human plasma and breast milk by UPLC/MS-MS

During the lactation, the choice of a proper antibiotic is crucial since the drug can cross into breast milk causing toxicity to the infant. Therefore, an extraction protocol and LC/MS-MS method for the determination of daptomycin in human milk and plasma were developed, validated and applied to a case of a breastfeeding mother affected by a purulent acute soft skin infection treated with daptomycin. Because of daptomycin high protein binding and its high molecular weight, the optimisation of the extraction protocol and analytical conditions were deeply investigated, and several parameters were taken into account: in particular the type of extraction, internal standard, the type of organic modifier, pH of the aqueous solution, and gradient. The use of a protein precipitation protocol coupled to a C8-reverse phase LC-MS/MS allows for a reliable quantification of daptomycin in both plasma (in the range of 19\u2013199 \u3bcg/mL) and breast milk (in the range of 0.12\u20130.32 \u3bcg/mL). The determination of milk/plasma (M/P) ratio, which ranged from 0.002 to 0.006, allowed to assess that daptomycin, effective for the mother, was contemporarily safe for the breastfed newborn

Blood cyanide determination in two cases of fatal imtoxication: comparison between headspace gas chromatography and a spectrophotometric method

Blood samples of two cases were analyzed preliminarily by a classical spectrophotometric method (VIS) and by an automated headspace gas chromatographic method with nitrogen-phosphorus detector (HS-GC \u2044 NPD). In the former, hydrogen cyanide (HCN) was quantitatively determined by measuring the absorbance of chromophores forming as a result of interaction with chloramine T. In the automated HS-GC \u2044NPD method, blood was placed in a headspace vial, internal standard (acetonitrile) and acetic acid were then added. This resulted in cyanide being liberated as HCN. The spectrophotometric (VIS) and HS-GC\u2044NPD methods were validated on postmortem blood samples fortified with potassium cyanide in the ranges 0.5\u201310 and 0.05\u20135 lg \u2044 mL, respectively. Detection limits were 0.2 lg \u2044mL for VIS and 0.05 lg \u2044mL for HS-GC\u2044NPD. This work shows that results obtained by means of the two procedures were insignificantly different and that they compared favorably. They are suitable for rapid diagnosis of cyanide in postmortem cases

Breast cancer and communication: Monocentric experience of a self-assessment questionnaire

Background: The communication of the diagnosis of breast cancer induces to the patient a strong psychological trauma. Radiologists are at the forefront of communicating, either for a biopsy or the probable diagnosis of malignancy. This is a complex task, which requires the knowledge and application of correct “communicative models”, among which the SPIKES protocol rep-resents a fundamental reference. Design and methods: 110 patients, with a history of breast cancer, filled out a questionnaire consisting of six questions: five aimed at defining communication compliance with the SPIKES protocol, the sixth, consisting of six feelings, aimed at the knowledge of the next emotional state. Results: Regarding compliance with various “strategic points” of the SPIKES protocol, questionnaires show that 70% of patients reported no omissions, while the remaining 30% reported omissions relatively to perception (56%), emotions (23%), setting (13%), knowledge (6%) and invitation (2%). The results showed the existence of a correlation between the final emotional state and the correct application of the SPIKES protocol; in fact, patients who reacted with a positive final emotional state-reported greater adherence to the strategic points of the SPIKES protocol. Conclusions: In healthcare, knowing the communicative compliance of a team in giving “bad news” is fundamental, especially in breast cancer. The SPIKES protocol is recognized by the Literature as a fundamental reference able to affect “positively” the emotional state of patients. The proposed questionnaire is a valid tool to identify the weak points of communication and related criticalities, to improve clinical practice

Hydrocracking of long chain linear paraffins

The hydrocracking reactivity of two model compounds, namely n-C(16)H(34) (n-C16) and n-C(28)H(58) (n-C28), was investigated on a Pt/SiO(2)-Al(2)O(3) catalyst. Conversion and products distribution have been determined under a wide range of operating conditions (i.e. pressure: 20-80 bar; temperature: 270-330 degrees C; weight hourly space velocity: 0.33-1.0 h(-1): H(2)/n-paraffin feeding ratio 0.05-0.15 wt/wt). The latter were changed according to a central composite design. The present paper summarises the results obtained on both the model paraffins, depending on the reaction conditions. A first, simple kinetic elaboration is also presented, based on an ideal PFR model and a first order kinetics. The reaction confirmed to be first order with respect to the n-paraffin. Experimental data showed that for both n-C16 and n-C28 conversion was affected by H(2)/n-paraffin ratio. The change of conversion was explained in terms of vapour liquid equilibrium (VLE), which in turn is affected by the H(2)/n-paraffin ratio, so leading to a different vaporisation degree of reactant. In agreement with the VLE data, the effect of H(2)/n-paraffin on conversion was lower for n-C28. VLE calculations have been carried out to estimate the H(2) partial pressure and degree of vaporisation of the normal paraffin. The reaction order for hydrogen was -1 and -0.5 for n-C16 an n-C28, respectively. However, in the case of n-C16 the data obtained at the lower bound of the pressure range examined displayed an increase of the reaction order. The apparent activation energy was calculated after correction of the contact time taking into account the liquid-vapour equilibrium: similar values have been estimated for n-C16 and n-C28, ca. 32 and 31 kcal/mol, respectively