A unique case of death by MDPHP with no other co-ingestion: a forensic toxicology case

International Journal of Legal Medicine - Synthetic cathinones are a class of psychoactive drugs that have become, in recent years, of quite common observation in medical and toxicological forensic...     

Co-administration of nitric oxide-aspirin (NCX-4016) and aspirin prevents platelet and monocyte activation and protects against gastric damage induced by aspirin in humans

OBJECTIVES: The goal of this study was to test the hypothesis that NCX-4016 may have broader anti-inflammatory and antithrombotic effects as well as better gastric tolerability than aspirin in humans. BACKGROUND: NCX-4016 is an aspirin derivative containing a nitric oxide-releasing moiety that prevents platelet activation and modulates tissue factor (TF) expression and cytokine release from lipopolysaccharide (LPS)-stimulated monocytes. METHODS: This was a blind-observer, placebo-controlled, parallel-group study in which 48 healthy subjects were randomized to receive NCX-4016 800 mg twice a day, NCX-4016 800 mg twice a day plus aspirin 325 mg, aspirin 325 mg, or placebo for 21 days. RESULTS: Similar to aspirin alone, NCX-4016 effectively inhibited platelet aggregation induced by 0.6 mmol/ arachidonic acid, clot-stimulated thromboxane (TX) B2 generation in whole blood, and urinary excretion of 11-dehydro-TXB2. Unlike aspirin alone, the administration of NCX-4016 significantly inhibited TF expression in monocytes stimulated ex vivo with 10 micromol/l LPS (determined by flow-cytometry analysis of TF on CD14 positive cells). NCX-4016 also inhibited the rapid TF expression induced in monocytes by a proteinase activated receptor agonist (thrombin receptor activator protein, 2 micromol/l) as well as LPS-induced expression of CD11b . Ex vivo, release of MCP-1 and interleukin-6 were significantly inhibited by NCX-4016, but not by aspirin. NCX-4016 was not associated with gastric damage, and significantly reduced gastric injury when co-administered with aspirin, although both drugs reduced gastric PGE2 production to the same extent. CONCLUSIONS: NCX-4016 is equally effective as aspirin in inhibiting cyclooxygenase activity. However, NCX-4016 causes less gastric damage and prevents monocyte activation. Larger multicenter trials are warranted to establish clinical efficacy and safety of NCX-4016.     

Pancreatic metastases: observations of three cases and review of the literature.

BACKGROUND: The aim of the study is to analyze pancreatic metastases and their clinical, radiological, therapeutic and prognostic features. METHODS: Three cases of pancreatic metastases observed and a world literature review of 333 cases were recorded. RESULTS: Pancreatic metastases are due more frequently to renal cell carcinoma; they are usually metachronous and characterized by a long period of time between the resection of the primary tumor and their detection. The differential diagnosis with other pancreatic masses is difficult, but an accurate anamnesis, some peculiar findings of imaging techniques and percutaneous fine needle aspiration could allow preoperative diagnosis. Pancreatic resections are the treatment of choice allowing the better palliation and improving survival. 150/234 pancreatic metastases underwent pancreatic resections (resectability index = 64.1%); 88/132 patients are alive with a mean follow-up of 27.1 months; of the 44 dead patients the mean survival time was 21.3 months. Among pancreatic metastases the primary tumor with better prognosis is renal cell carcinoma. CONCLUSION: Pancreatic metastases are rare; their preoperative diagnosis is difficult but useful and possible. Surgical resection is suggested because the patient still may have a prolonged survival.     

Relationship between idiopathic hypereosinophilic syndrome, eosinophilic leukemia, and systemic mastocytosis

Chronic eosinophilic leukemia is a neoplastic condition with persistent eosinophilia as the major hematological abnormality and with the eosinophils being part of the neoplastic clone. Some cases can be recognized by traditional hematological criteria, but many can be recognized only when a clonal cytogenetic or molecular genetic abnormality is demonstrated. A range of cytogenetic and molecular genetic abnormalities has been recognized, including both those seen in other myeloid malignancies (such as trisomy 8, monosomy 7, and 20q-) and those that are particularly linked to eosinophil differentiation (such as rearrangements of PDGFRB, FGFR1, and PDGFRA, the latter with formation of a FIP1L1-PDGFRA fusion gene). The discovery of the FIP1L1-PDGFRA fusion gene has led to the recognition that many patients who would previously have been regarded as having idiopathic hypereosinophilia actually have chronic eosinophilic leukemia. The same fusion gene has also been found in patients with hypereosinophilia and atypical bone marrow mast cells but whether this syndrome should be regarded as a variant of eosinophilic leukemia or as a variant of systemic mastocytosis remains to be established.     

Adoptive T-cell therapy for EBV-associated post-transplant lymphoproliferative disease

Increased understanding of the mechanisms by which T lymphocytes recognize virus and tumor-specific antigens has fueled the use of adoptive immunotherapy for viral and malignant diseases. An ideal candidate for such treatment is Epstein-Barr virus (EBV). EBV-associated post-transplant lymphoproliferative disorder (PTLD) is a serious complication post-solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). The disease is essentially the result of suppression of cytotoxic T-cell function and despite various treatment strategies the course may still be fulminant and lethal. Therefore, an adoptive immunotherapeutic approach using ex vivo derived EBV-specific CTL offers a promising solution not only for the treatment but also as prophylaxis for PTLD. The infusion of EBV-CTL has been demonstrated to be safe and effective in allogeneic HSCT recipients and their use post-SOT is being evaluated.     

Effects of hypocaloric diet and exercise training on inflammation and adipocyte lipolysis in obese postmenopausal women

The purpose of this study was to determine whether a hypocaloric diet with and without exercise training is effective in reducing plasma C-reactive protein, IL-6, TNFalpha, and their soluble receptors (sIL-6R, sTNFR1, and sTNFR2), and whether changes in these inflammatory markers are related to changes in regional lipolysis in obese (body mass index, 32.78 +/- 4.73) postmenopausal women (diet alone, n = 17; diet plus exercise, n = 17). All inflammatory markers were measured by an ELISA method. In vitro lipolysis was evaluated by measuring glycerol release using a one-step enzymatic fluorometric technique. Six months of diet and diet plus exercise decreased total and abdominal fat to a similar degree. Diet plus exercise, but not diet alone, decreased plasma levels of C-reactive protein, IL-6, sIL-6R, and sTNFR1 and increased basal and postreceptor stimulated lipolysis in both abdominal and gluteal regions. Changes in abdominal stimulated lipolysis correlated significantly with changes in plasma IL-6 (r = -0.39) and TNFR1 (r = -047). Thus, diet plus exercise training, but not diet alone, is effective in reducing chronic inflammation in obese postmenopausal women. In addition, modification of chronic inflammation is associated with changes in local adipose tissue metabolism in response to diet and exercise.     

Consecutive regression of concurrent laryngeal and gastric MALT lymphoma after anti-Helicobacter pylori therapy

The most common primary lymphoma of the gastrointestinal tract is B-cell lymphoma arising from mucosa-associated lymphoid tissue known as MALT lymphoma. Although the majority of these lesions affect the stomach and are associated with Helicobacter pylori organisms, sites other than the gastrointestinal tract may be affected. This case report describes a patient with concomitant laryngeal MALT lymphoma and Helicobacter pylori-related gastric MALT lymphoma derived from the same clone as confirmed by PCR. Treatment of Helicobacter pylori infection in this patient using antibiotics led to regression of both lesions. This patient remains in remission at 46-month follow-up. This is the first case report on the regression of a laryngeal MALT lymphoma after Helicobacter pylori eradication. We suggest that all patients presenting with extragastric MALT lymphoma should undergo upper gastrointestinal endoscopy with gastric biopsies for the determination of Helicobacter pylori status and presence of concomitant gastric MALT lymphoma, followed by a course of anti-Helicobacter pylori antibiotic therapy. Nonresponders may subsequently be considered for surgery and/or chemo/radiation therapy.     

Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenon

OBJECTIVE: To document disease activity and functional status in patients with scleroderma (systemic sclerosis [SSc]) and Raynaud's phenomenon (RP) and to determine the sensitivity to change, reliability, ease of use, and validity of various outcome measures in these patients. METHODS: Patients with SSc and moderate-to-severe RP participating in a multicenter RP treatment trial completed daily diaries documenting the frequency and duration of RP attacks and recorded a daily Raynaud's Condition Score (RCS). Mean scores for the 2-week periods prior to baseline (week 0), end of trial (week 6), and posttrial followup (week 12) were calculated. At weeks 0, 6, and 12, physicians completed 3 global assessment scales and performed clinical assessments of digital ulcers and infarcts; patients completed the Health Assessment Questionnaire (HAQ), the Arthritis Impact Measurement Scales 2 (AIMS2) mood and tension subscales, 5 specific SSc/RP-related visual analog scales (VAS), and 3 other VAS global assessments. We used these measures to document baseline disease activity and to assess their construct validity, sensitivity to change, and reliability in trial data. RESULTS: Two hundred eighty-one patients (248 women, 33 men; mean age 50.4 years [range 18-82 years]) from 14 centers participated. Forty-eight percent had limited cutaneous SSc; 52% had diffuse cutaneous SSc. Fifty-nine patients (21%) had digital ulcers at baseline. Patients had 3.89 +/- 2.33 (mean +/- SD) daily RP attacks (range 0.8-14.6), with a duration of 82.1 +/- 91.6 minutes/attack. RCS for RP activity (possible range 0-10) was 4.30 +/- 1.92. HAQ scores (0-3 scale) indicated substantial disability at baseline (total disability 0.86, pain 1.19), especially among the subscales pertaining to hand function (grip, eating, dressing). AIMS2 mood and tension scores were fairly high, as were many of the VAS scores. Patients with digital ulcers had worse RCS, pain, HAQ disability (overall, grip, eating, and dressing), physician's global assessment, and tension, but no significant difference in the frequency of RP, duration of RP, patient's global assessment, or mood, compared with patients without digital ulcers. VAS scores for digital ulcers as rated by the patients were not consistent with the physician's ratings. Factor analysis of the 18 measures showed strong associations among variables in 4 distinct domains: disease activity, RP measures, digital ulcer measures, and mood/tension. Reliability of the RCS, HAQ pain and disability scales, and AIMS2 mood and tension subscales was high. The RP measures demonstrated good sensitivity to change (effect sizes 0.33-0.76). CONCLUSION: Our findings demonstrate that the significant activity, disability, pain, and psychological impact of RP and digital ulcers in SSc can be measured by a small set of valid and reliable outcome measures. These outcome measures provide information beyond the quantitative metrics of RP attacks. We propose a core set of measures for use in clinical trials of RP in SSc patients that includes the RCS, patient and physician VAS ratings of RP activity, a digital ulcer/infarct measure, measures of disability and pain (HAQ), and measures of psychological function (AIMS2).     

Effects of insulin resistance and insulin secretion on the efficacy of interventions to retard development of type 2 diabetes mellitus: the DA Qing IGT and Diabetes Study

OBJECTIVE: To investigate the effects of insulin resistance (IR) and insulin secretion (IS) on the development of diabetes mellitus in individuals with impaired glucose tolerance (IGT) who underwent lifestyle interventions. METHODS: 284 out of 577 individuals with IGT identified by population-based screening in Da Qing, China, who were randomized to undergo diet change and/or increased physical activity had baseline fasting and 2 h post-load insulin determinations. They were followed for 6 years for the development of diabetes. IR and IS were assessed using calculated indices based on fasting plasma insulin and glucose. The interactions of IR, IS, obesity and plasma glucose and the effects of the lifestyle interventions were evaluated using Cox Proportional Hazards analysis. RESULTS: Both IR and IS were significantly associated with the development of diabetes. Lifestyle interventions were more effective in those with lower IT and higher IS at baseline. Diet plus exercise interventions resulted in significantly lower incidence of diabetes, even after controlling for IR, IS, BMI and 2hrPG. CONCLUSION: Both IR and beta-cell function were predictors of diabetes in Chinese with IGT. Lifestyle intervention reduced the incidence of DM and these interventions were more effective in those with less IR.