We conclude that the evaluation of antihypertensive drugs concentrations is a useful and precise method for assessment of noncompliance in patients with resistant hypertension. This evaluation is useful before starting the diagnostic work-up of secondary forms of hypertension and before assignment patients into protocols with new therapy modalities such as renal denervation.

During an outbreak of methanol poisonings in the Czech Republic in 2012, we were able to study methanol and formate elimination half-lives during intermittent hemodialysis (IHD) and continuous veno-venous hemodialysis/hemodiafiltration (CVVHD/HDF) and the relative impact of dialysate and blood flow rates on elimination. Data were obtained from 11 IHD and 13 CVVHD/HDF patients. Serum methanol and formate concentrations were measured by gas chromatography and an enzymatic method. The groups were relatively comparable, but the CVVHD/HDF group was significantly more acidotic (mean pH 6.9 vs. 7.1 IHD). The mean elimination half-life of methanol was 3.7 and formate 1.6 h with IHD, versus 8.1 and 3.6 h, respectively, with CVVHD/HDF (both significant). The 54% greater reduction in methanol and 56% reduction in formate elimination half-life during IHD resulted from the higher blood and dialysate flow rates. Increased blood and dialysate flow on the CVVHD/HDF also increased elimination significantly. Thus, IHD is superior to CVVHD/HDF for more rapid methanol and formate elimination, and if CVVHD/HDF is the only treatment available then elimination is greater with greater blood and dialysate flow rates.

Tobacco, containing nicotine as the principal pharmacologically active chemical, has been identified as being a risk factor for the development of osteoporosis. Thirty-two male Wistar rats of two months of age were castrated or sham operated to evaluate the effects of long-term administration (four months) of nicotine in drinking water (9.0 mg/kg/day). The presence of cotinine in urine confirmed successful delivery of nicotine. The bones were tested mechanically by a three point bending test in a Mini Bionix (MTA) testing system. The bones from castrated rats were characterized by a reduction in bone density as well as ash, calcium and phosphate content. Castration significantly altered mechanical properties of bone (9%) and femoral cortical thickness. When intact rats were treated with a high dose of nicotine, nicotine had negative effect on tibial bone density as well as ash, calcium, phosphate content and significantly altered the mechanical properties of bone (12%) and femoral cortical thickness compared to intact animals. Nicotine itself does not exert any anti-androgenic effect and does not produce changes in the weight of seminal vesicles. Nicotine-induced bone loss is associated with high bone turnover in the male rats as expressed by increased TrACP and B-ALP. When castrated rats were treated with the high dose of nicotine the changes in bone density resulting from castration were not further potentiated. These results document the efficacy of nicotine at high doses to cause bone loss and loss of bone mechanical strength in intact rats. The results of the present study may be interpreted as supporting the hypothesis of nicotine as a risk factor for osteoporosis.

The aim of this article was to study the role of serum formate (S-formate) in diagnosing methanol poisoning. A prospective study was undertaken of 38 patients from the Czech methanol mass poisoning in 2012 -median age 51 [interquartile range (IQR) 37-62] years with confirmed methanol poisoning. S-formate was measured enzymatically. The receiver operating characteristics (ROC) curve was used to examine the predictive ability of S-formate. Asymptomatic patients had median S-formate of 1.9 (IQR 1.5-2.4) mmol/L. The median S-formate was 15.2 (IQR 13.9-17.6) mmol/L in symptomatic subjects with visual disturbances, 15.4 (12.1-18.0) mmol/L in subjects with dyspnoea and 15.7 (IQR 12.8-18.5) mmol/L in comatose patients. The differences in serum formate concentrations in symptomatic patients depending on clinical features were not significant (all p > 0.05). Patients with long-term visual sequelae of poisoning had median S-formate of 16.1 ) mmol/L; with central nervous system (CNS) sequelae, patients had 15.9 (IQR 14.2-19.5) mmol/L. In lethal cases, the median S-formate was 15.2 (IQR 13.8-15.9) mmol/L. The probability of a poor outcome (death or survival with sequelae) was higher than 90% in patients with S-formate ≥17.5 mmol/L, S-lactate ≥7.0 mmol/L and/or pH <6.87. The ROC analysis showed that the corresponding areas under the curve (AUC) were 0.64 (0.44-0.85 CI 95%) for S-formate, 0.75 (0.56-0.93 CI 95%) for 'S-formate+S-lactate' and only 0.54 (0.38-0.69 CI 95%) for serum methanol, which is lower than for S-formate (p < 0.05). The measurement of S-formate is an important tool in the laboratory diagnostics and clinical management of acute methanol poisoning. S-formate ≥3.7 mmol/L can lead to the first clinical signs of visual toxicity, indicating haemodialysis. S-formate ≥11-12 mmol/L is associated with visual/CNS sequelae and a lethal outcome.Acute methanol poisoning remains a challenge for healthcare providers throughout the world because of its high mortality rate and serious health sequelae [1][2][3]. This poisoning generally occurs either intentionally through abuse or attempted suicide or unintentionally through misuse or accident [4,5]. It is a medical emergency in which the rapid administration of antidotes preventing formic acid formation as a toxic metabolite of methanol by blocking alcohol dehydrogenase (ADH) and the enhanced elimination of formate and methanol are crucial for successful treatment [6][7][8].Nevertheless, in cases of poisoning with toxic spirits containing mixtures of methanol and ethanol in adulterated strong alcoholic beverages, timely diagnosis is difficult due to the long latency period and late presentation to hospitals. Therefore, the onset of treatment is often delayed [7,9]. Serum concentrations of methanol in late-presenting patients can be low and even under the level of detection due to its biotransformation. On the other hand, serum concentrations of formic acid rise high above the upper reference limit of 0.4 mmol/L [9].Formate is one of the normal intermediates in human...

We found a positive association between out-of-hospital ethanol administration and improved clinical outcome. During mass methanol outbreaks, conscious adults with suspected poisoning should be considered for administration of out-of-hospital ethanol to reduce morbidity and mortality.

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Objective. During the 2012 outbreak of mass methanol poisonings in the Czech Republic, ethanol, in the main, was used as an antidote. The complex pharmacokinetics of ethanol made it difficult to maintain the requisite 1000-1500 mg/L serum ethanol levels (S-EtOH). The aim of this study was to measure the fluctuations in S-EtOH during the treatment. Methods. A prospective case series in 21 patients, median age 52 (27-79 years), 13 males and 8 females. Serum ethanol, methanol and formate were measured every 2-6 hours during the treatment. Follow-up clinical examination was carried out in 15/18 survivors. Results. The majority of patients (17/21) were late presenters and on admission, almost half (10/21) had suffered a severe grade of intoxication according to the Poisoning Severity Score (PSS). The mean observation time was 90±20 h. The mean period of consistent maintenance of S-EtOH within the recommended therapeutic range lasted 28±7% of the total observation time. For 29±8% of the time, S-EtOH was >1500 mg/L with "peaks" of up to 3500 mg/L. For 44±10% of the observation time, S-EtOH was <1000 mg/L. The mean duration of sub-therapeutic concentration of S-EtOH and toxic serum levels of methanol >200 mg/L or formate >20 mg/L lasted 20±10% and 18±11% of the time of observation, respectively. Complications occurred in 14 (67%) of cases including significant fluctuations of S-EtOH in 9; aspiration pneumonia in 3 and delirium tremens in 2 cases. Other complications included sepsis, bleeding, acidosis rebound, intolerance and set clotting. The outcomes were: 11 survivors free of health impairment, 7 with sequelae and 3 deaths. There was no significant difference in mean duration of sub-therapeutic and supra-therapeutic concentrations of serum ethanol in patients who survived without sequelae and those with poor outcome (P > 0.05). Conclusion. Administration of ethanol according to the present guidelines of the AACT/EAPCCT is effective and relatively safe in the treatment of methanol poisoning during a mass outbreak 31 . Physicians have to be most aware of fluctuations in serum ethanol at the end of short sessions of IHD and after changes in route from intravenous to oral. Rigorous monitoring of serum ethanol concentrations is pivotal for severely poisoned patients with PSS 3 and where there is suspected conversion of significant amounts of methanol to formic acid.

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