Acute paraquat poisoning: report of a survival case following intake of a potential lethal dose

When properly used, paraquat (PQ) is a widely used bipyridil herbicide with a good safety record. Most cases of PQ poisoning result from intentional ingestion, with death resulting from hypoxemia secondary to lung fibrosis in moderate to severe poisonings. With high ingestion volumes (>50 mL of a 20% wt/vol formulation), death results from multiple organ failure and cardiovascular collapse within 1 week after intoxication. The present report describes a successful clinical case regarding the intoxication of a 15-year-old girl by a presumed lethal dose of PQ. The adolescent ingested approximately 50 mL of a commercialized concentrate (20% wt/vol of dichloride salt) formulation of PQ. High serum and urinary levels of PQ confirmed the bad prognosis. However, the therapeutic protocol followed in the present clinical case led to a positive outcome. Besides the measures for decreasing PQ absorption and increasing its elimination, other protective procedures were applied in aiming to reduce the production of reactive oxygen species (ROS), to scavenge ROS, to repair ROS-induced lesions, and to reduce inflammation. The status-of-the-art concerning the biochemical and toxicological aspects of PQ poisoning and the pharmacologic basis of the respective treatment is also presented.     

Congenital stapes ankylosis: study of 28 cases and surgical results

OBJECTIVE: The objective of this study was to analyze functional results after stapes surgery in patients with congenital nonprogressive conductive deafness resulting from an isolated fixation of the stapes according to age and surgical procedure. STUDY DESIGN: The authors conducted a retrospective case series from March 1993 to December 2003 in patients from two tertiary referral centers. METHODS: Twenty-eight patients were operated on by stapedotomy or partial stapedectomy using Teflon stapes prostheses. The median age at surgery was 14.2 years (range, 8.3-29.1 years). Main outcome measures were clinical and audiometric evaluation before and after surgery. Mean air conduction (MAC) and bone conduction (MBC) thresholds were recorded at 0.5, 1, 2, and 4 kHz. The evaluation of functional outcome was based on the MAC gain, the MBC comparison, and the mean postoperative and residual air-bone gaps. RESULTS: The median preoperative MAC was 50 dB (range, 19.0-65.0 dB) with a 35.0 dB median dB air-bone gap. With a mean follow up of 19 months, postoperative hearing improvement was statistically significant: median gain of 32.5 dB (P<.001) and median residual air-bone gap of 3.5 dB. The MBC was also statistically improved with median pre- and postoperative MBC of 11.5 and 6.5 dB, respectively (P<.001). Results were not dependent on the age group or type of surgery (stapedotomy or partial stapedectomy). No perceptive hearing loss was observed despite one gusher case. CONCLUSION: Surgical treatment of isolated congenital stapes ankylosis allows good functional results regardless of age or type of surgery.     

Hydrogen peroxide production in mouse tissues after acute d-amphetamine administration. Influence of monoamine oxidase inhibition

The toxicity of amphetamines is conditioned by a complex array of mechanisms, involving the increase of neurotransmission (e.g. leading to hyperthermia) and enzymatic and non-enzymatic oxidation of amphetamines and biogenic amines. Considering that all these processes may increase the generation of hydrogen peroxide (H2O2) by metabolic or non-metabolic redox pathways, the main objective of this work was to evaluate d-amphetamine-induced H2O2 production in mice liver, kidney and heart. The contribution of monoamine oxidase (MAO) to H2O2 production after d-amphetamine administration was studied using the MAO inhibitor pargyline. H2O2 production was measured indirectly using the catalase-H2O2 complex I irreversible inhibitor 3-amino-1,2,4-triazole (AT). Using this method, the measurement of residual catalase activity following administration of AT permits the monitoring of H2O2 production in vivo. Charles River CD-1 mice (30-35 g body weight) were injected with AT just before the injection of d-amphetamine sulphate (20 mg/kg). d-Amphetamine stimulated the production of H2O2 in all tissues studied, although to different degrees. MAO inhibition by itself led to a remarkable decrease of basal H2O2 production in the kidney and a slight decrease in the liver, although no effect was observed in the heart. d-Amphetamine-induced H2O2 production in the heart and kidney was reduced in MAO-inhibited mice. However, in the liver, H2O2 production was transiently potentiated at 30 min under MAO inhibition. In conclusion, d-amphetamine administration leads to an increase in H2O2 production in mouse liver, kidney and heart, and monoamine oxidase plays an important role in this effect.     

Predictive value of exhaled nitric oxide and aerobic capacity for sepsis complications after liver transplantation

Our objective was to investigate the predictive value of fractional nitric oxide (NO) concentration in exhaled breath (FeNO) and aerobic capacity (peak VO₂) for postoperative sepsis in liver transplantation candidates. Patients were identified and charts of all consecutive patients were prospectively reviewed. Bacterial sepsis represented the commonest postoperative complications (30%), which was attributed to peritonitis, pneumonia, and catheter‐related infections. Preoperative FeNO and peak VO₂ values were lower in patients with postoperative sepsis. Patients with sepsis required higher needs for mechanical ventilation and ICU length of stay. Inverse correlation was found between logarithmically FeNO‐transformed data and systolic pulmonary artery pressure (r = ?0.348; P = 0.018). Multivariate analyses using bootstrap sampling method indicated that odds of sepsis were associated with lower values of peak exercise VO₂ [OR = 0.790 (0.592; 0.925)] and reduced log(FeNo) [OR = 0.027 (0.001; 0.451)], but not with higher MELD scores [OR = 1.141 (0.970; 1.486)]. By evaluating the cutoff for the ROC curves in each bootstrap resampling, median and 95% confidence interval were calculated for peak VO₂: 17 [16.2; 22] ml/kg/min and FeNO: 17.2 [13.0; 33.9] ppb. We conclude that low peak exercise VO₂ and reduced FeNO may help identify patients who are at risk to develop perioperative sepsis.     

The Canadian Trial of Carbohydrates in Diabetes (CCD), a 1-y controlled trial of low-glycemic-index dietary carbohydrate in type 2 diabetes: no effect on glycated hemoglobin but reduction in C-reactive protein

BACKGROUND: The optimal source and amount of dietary carbohydrate for managing type 2 diabetes (T2DM) are unknown. OBJECTIVE: We aimed to compare the effects of altering the glycemic index or the amount of carbohydrate on glycated hemoglobin (HbA1c), plasma glucose, lipids, and C-reactive protein (CRP) in T2DM patients. DESIGN: Subjects with T2DM managed by diet alone (n=162) were randomly assigned to receive high-carbohydrate, high-glycemic-index (high-GI), high-carbohydrate, low-glycemic-index (low-GI), or low-carbohydrate, high-monounsaturated-fat (low-CHO) diets for 1 y. RESULTS: The high-GI, low-GI, and low-CHO diets contained, respectively, 47%, 52%, and 39% of energy as carbohydrate and 31%, 27%, and 40% of energy as fat; they had GIs of 63, 55, and 59, respectively. Body weight and HbA1c did not differ significantly between diets. Fasting glucose was higher (P=0.041), but 2-h postload glucose was lower (P=0.010) after 12 mo of the low-GI diet. With the low-GI diet, overall mean triacylglycerol was 12% higher and HDL cholesterol 4% lower than with the low-CHO diet (P<0.05), but the difference in the ratio of total to HDL cholesterol disappeared by 6 mo (time x diet interaction, P=0.044). Overall mean CRP with the low-GI diet, 1.95 mg/L, was 30% less than that with the high-GI diet, 2.75 mg/L (P=0.0078); the concentration with the low-CHO diet, 2.35 mg/L, was intermediate. CONCLUSIONS: In subjects with T2DM managed by diet alone with optimal glycemic control, long-term HbA1c was not affected by altering the GI or the amount of dietary carbohydrate. Differences in total:HDL cholesterol among diets had disappeared by 6 mo. However, because of sustained reductions in postprandial glucose and CRP, a low-GI diet may be preferred for the dietary management of T2DM.     

A mean three-dimensional atlas of the human thalamus: Generation from multiple histological data

Functional neurosurgery relies on robust localization of the subcortical target structures, which cannot be visualized directly with current clinically available in-vivo imaging techniques. Therefore, one has still to rely on an indirect approach, by transferring detailed histological maps onto the patient's individual brain images. In contrast to macroscopic MRI atlases, which often represent the average of a population, each stack of sections, which a stereotactic atlas provides, is based on a single specimen. In addition to this bias, the anatomy is displayed with a highly anisotropic resolution, leading to topological ambiguities and limiting the accuracy of geometric reconstruction. In this work we construct an unbiased, high-resolution three-dimensional atlas of the thalamic structures, representing the average of several stereotactically oriented histological maps. We resolve the topological ambiguity by combining the information provided by histological data from different stereotactic directions. Since the stacks differ not only in geometrical detail provided, but also due to inter-individual variability, we adopt an iterative approach for reconstructing the mean model. Starting with a reconstruction from a single stack of sections, we iteratively register the current reference model onto the available data and reconstruct a refined mean three-dimensional model. The results show that integration of multiple stereotactic anatomical data to produce an unbiased, mean model of the thalamic nuclei and their subdivisions is feasible and that the integration reduces problems of atlas reconstruction inherent to histological stacks to a large extent.     

Clinicopathological and molecular characterisation of ‘multiple-classifier’ endometrial carcinomas

Endometrial carcinoma (EC) molecular classification based on four molecular subclasses identified in The Cancer Genome Atlas (TCGA) has gained relevance in recent years due to its prognostic utility and potential to predict benefit from adjuvant treatment. While most ECs can be classified based on a single classifier (POLE exonuclease domain mutations – POLEmut, MMR deficiency – MMRd, p53 abnormal – p53abn), a small but clinically relevant group of tumours harbour more than one molecular classifying feature and are referred to as ‘multiple-classifier’ ECs. We aimed to describe the clinicopathological and molecular features of multiple-classifier ECs with abnormal p53 (p53abn). Within a cohort of 3518 molecularly profiled ECs, 107 (3%) tumours displayed p53abn in addition to another classifier(s), including 64 with MMRd (MMRd–p53abn), 31 with POLEmut (POLEmut–p53abn), and 12 with all three aberrations (MMRd–POLEmut–p53abn). MMRd–p53abn ECs and POLEmut–p53abn ECs were mostly grade 3 endometrioid ECs, early stage, and frequently showed morphological features characteristic of MMRd or POLEmut ECs. 18/28 (60%) MMRd–p53abn ECs and 7/15 (46.7%) POLEmut–p53abn ECs showed subclonal p53 overexpression, suggesting that TP53 mutation was a secondary event acquired during tumour progression. Hierarchical clustering of TCGA ECs by single nucleotide variant (SNV) type and somatic copy number alterations (SCNAs) revealed that MMRd–p53abn tumours mostly clustered with single-classifier MMRd tumours (20/23) rather than single-classifier p53abn tumours (3/23), while POLEmut–p53abn tumours mostly clustered with single-classifier POLEmut tumours (12/13) and seldom with single-classifier p53abn tumours (1/13) (both p ≤ 0.001, chi-squared test). Finally, the clinical outcome of patients with MMRd–p53abn and POLEmut–p53abn ECs [stage I 5-year recurrence-free survival (RFS) of 92.2% and 94.1%, respectively] was significantly different from single-classifier p53abn EC (stage I RFS 70.8%, p = 0.024 and p = 0.050, respectively). Our results support the classification of MMRd–p53abn EC as MMRd and POLEmut–p53abn EC as POLEmut. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Impact of surgical stress on the haemodynamic profile of isoflurane–induced hypotension

It has been suggested that stimulation of adrenoreceptors could be responsible for some of the haemodynamic effects of isoflurane. But there are no solid data demonstrating the role of sympatho-adrenal stimulation induced by pain during isoflurane administration. The impact of surgical stress on the haemodynamic profile of isoflurane-induced hypotension has been investigated in 28 patients (47-76 years), scheduled for total hip arthroplasty. After premedication with morphine hydrochloride (0.1 mg/kg), patients were randomly assigned to receive either no fentanyl (control group) or fentanyl (5 micrograms/kg before tracheal intubation, 5 micrograms/kg before skin incision, and 2 micrograms/kg each 15 min during the 1st hour). Isoflurane was given to maintain mean arterial blood pressure in the range 6.7-8 kPa in both groups. Haemodynamic data and blood samples for determination of plasma renin activity (PRA) and epinephrine (E) and norepinephrine (NE) levels were collected before and during hypotension. The fentanyl group and the control group differed significantly during hypotension: heart rate, cardiac index, oxygen consumption and E, NE and PRA were lower (P less than 0.01) in the fentanyl group than in control group. Fentanyl lowered the required concentration of isoflurane to achieve the same degree of hypotension (end-tidal concentration: 0.8 +/- 0.2% in the fentanyl group and 1.4 +/- 0.15% in the control group; P less than 0.001). Our results demonstrate that the cardiovascular effects of higher isoflurane concentrations in the absence of narcotic analgesia are counterbalanced by adrenergic stress stimulation of released epinephrine and norepinephrine. Among the likely reasons for catecholamine release during isoflurane administration, inadequate analgesia may be considered.