Ipsilateral somatic nerves mediate histamine-induced vasosensory reflex responses involving perivascular afferents in rat models.

Reflex cardiorespiratory alterations elicited after instillation of nociceptive agents intra-arterially (i.a) are termed as 'vasosensory reflex responses'. The present study was designed to evaluate such responses produced after i.a. instillation of histamine (1 mM; 10 mM; 100 mM) and to delineate the pathways i.e. the afferents and efferents mediating these responses. Blood pressure, electrocardiogram and respiratory excursions were recorded before and after injecting saline/histamine, in a local segment of femoral artery in urethane anesthetized rats. Paw edema and latencies of responses were also estimated. Separate groups of experiments were conducted to demonstrate the involvement of somatic nerves in mediating histamine-induced responses after ipsilateral femoral and sciatic nerve sectioning (+NX) and lignocaine pre-treatment (+Ligno). In addition, another set of experiments was performed after bilateral vagotomy (+VagX) and the responses after histamine instillation were studied. Histamine produced concentration-dependent hypotensive, bradycardiac, tachypnoeic and hyperventilatory responses of shorter latencies (2-7 s) favouring the neural mechanisms in eliciting the responses. Instillation of saline (time matched control) in a similar fashion produced no response, excluding the possibilities of ischemic/stretch effects. Paw edema was absent in both hind limbs indicating that the histamine did not reach the paws and did not spill out into the systemic circulation. +NX, +VagX, +Ligno attenuated histamine-induced cardiorespiratory responses significantly. These observations conclude that instillation of 10 mM of histamine produces optimal vasosensory reflex responses originating from the local vascular bed; afferents and efferents of which are mostly located in ipsilateral somatic and vagus nerves respectively.

Inhaler intoxications developed during autopsy of the corpse due to cyanide intake: Case series.

The primary cause of cyanide intake is suicidal attempts, most of which result in death. People who interfere with suspicion of cyanide intoxication may also be exposed to cyanide poisoning. During the autopsy of the corpse in the morning of that day, five people in the autopsy room within the hospital were admitted to the ED with suspicion of cyanide intoxication. Meanwhile, a 36-year-old patient who had come into contact with the patient at night also presented to the ED. Some of the precautionary measures to be taken against inhalation of cyanide may be wearing appropriate masks as well as suitable clothes and keeping the surroundings below 28 °C when exposed to cyanide.

[Symptoms of lithium toxicity at therapeutic levels]. / Klachten van lithiumintoxicatie bij een therapeutische spiegel.

A 60-year-old woman was admitted to the medical psychiatric unit with neurological and psychiatric symptoms. She was being treated with a maintenance dose of lithium for bipolar I disorder. Lithium toxicity and manic state were both considered. However, serum lithium levels appeared to be non-toxic. During hospital admission, her symptoms worsened and many diagnostic tests were performed. Lithium toxicity was considered again and lithium was discontinued, despite therapeutic blood levels. The neuro-psychiatric symptoms subsequently disappeared and the patient improved without residual symptoms. When neuro-psychiatric symptoms occur without elevated lithium levels, the possibility of chronic lithium toxicity should still be considered. More caution is required when risk factors are present, such as: old age, interacting medication, reduced renal function, dehydration and fever. Finally, electroencephalography can contribute to the diagnosis of chronic lithium toxicity.

Phenobarbital-induced anticonvulsant hypersensitivity syndrome in a cat.

In this study, we document a case of phenobarbital-induced anticonvulsant hypersensitivity syndrome (AHS), which has been rarely reported in veterinary medicine. A 2-year-old, 5.4 kg, neutered male Russian Blue cat was diagnosed with idiopathic epilepsy and started on phenobarbital treatment. Eight days after initiation of phenobarbital treatment, the cat showed tachypnea and hyperthermia. CBC and serum biochemistry were unremarkable. However, the patient showed high serum amyloid A (SAA). On abdominal ultrasonography, generalized enlargement of abdominal lymph nodes and splenic multiple hypo-echoic nodules, which were consistent with reactive lymphadenopathy were found. The cat was diagnosed with AHS, and phenobarbital was discontinued. After 10 days of cessation, the patient had normal SAA, and clinical signs were resolved.

Bifenthrin Fatality in a Canine: A Case Report with Postmortem Concentrations.

A case of canine intoxication and fatality with the pyrethroid insecticide bifenthrin is described. A 5-year-old female spayed Pit Bull Terrier was off leash and unsupervised at home for 15-20 min prior to discovery by her owner. The patient was in lateral recumbency, having what the owner described as a seizure. The patient was transported to an emergency veterinary hospital where she presented with tachycardia, tachypnea and intractable tremors/seizures. Despite aggressive medical intervention, the patient went into respiratory and cardiac arrest and died at 28 h after presentation. A postmortem liver sample screened positive for bifenthrin by gas chromatography-mass spectrometry (GC-MS). During the screening procedure, four additional bifenthrin-metabolic products were also observed. Concentrations for bifenthrin were determined for fat, kidney, liver and urine by GC-MS-MS. This is the first reported case of a canine fatality resulting from bifenthrin.

Energy drink and alcohol combination leads to kidney and liver alterations in rats.

The aim of this study was to evaluate the acute toxicity of the association of energy drink and alcohol in male Wistar rats. Animals were treated by oral gavage with 10 ml/kg distilled water (control); 10 ml/kg energy drink (ED10); 3.2 mg/kg caffeine + 40 mg/kg taurine; 2 g/kg alcohol 20%; 2 g/kg alcohol 20% + ED10; and 2 g/kg alcohol 20% + 3.2 mg/kg caffeine + 40 mg/kg taurine. Behavioral alterations were observed for 6 h after treatment. Animals presented significant differences in the frequency of rearing, ambulation, grooming, wakefulness and tachypnea along time. Caffeine + taurine increased the levels of TBARS and total thiols in kidneys. ED10 increased lipoperoxidation in liver. The association of ED10 + alcohol induced nephrotoxicity observed by the increase of urinary N-acetyl-ß-d-glucosaminidase (NAG) activity. Histopathological analysis showed the presence of congestion and hydropic and hyaline degenerations in the livers of ED10 + alcohol treated rats, and hemorrhage in the liver of alcohol + caffeine + taurine group. In kidneys, hyaline degeneration was observed in ED10; ED10 + alcohol; caffeine + taurine; and alcohol + caffeine + taurine. Hemorrhage was present in the kidneys of all groups. The combination of energy drinks and alcohol is not safe for the consumers. Therefore, precautionary measures should be disseminated among risk populations, especially the teenagers.

Amlodipine (150 mg) Poisoning: A Case Study.

BACKGROUND: Treatments of patients with amlodipine (a calcium channel blocker, CCB) overdose/poisoning remain challenging and death is certain if not intervened timely. Furthermore, for the society, the availability and common use of this drug can drive more vulnerable groups, especially children, towards an accidental/suicidal poisoning. CASE REPORT: Herein, we describe the case of an 18 year-old-adolescent girl who took 150 mg of amlodipine with the suicidal intentions and was admitted in our hospital approximately 4-hours after the ingestion. She developed circulatory failure and tachypnea. Decontamination, calcium, glucagon, and dual vasopressors were started, however, persistent hypotension led to the initiation of hyperinsulinemiceuglycemia therapy. She recovered fully and discharged without any complications in few days. This case educates not only about the successful use of variant drugs in the management of CCB overdose/poisoning, but also calls for the attention of the society for a safe storage of often used drugs, especially away from the children/adolescents.

Gadoxetate disodium-induced tachypnoea and the effect of dilution method: a proof-of-concept study in mice.

OBJECTIVES: To directly investigate the rapid respiratory effect of gadoxetate disodium in an experimental study using mice. METHODS: After confirming the steady respiratory state under general anaesthesia, eight mice were injected with all test agents in the following order: phosphate-buffered saline (A, control group), 1.25 mmol/kg of gadoteridol (B) or gadopentetate dimeglumine (C), or 0.31 mmol/kg of gadoxetate disodium (D, E). The experimenter was not blinded to the agents. The injection dose was fixed as 100 µL for Groups A-D and 50 µL for Group E. We continuously monitored and recorded respiratory rate (RR), peripheral oxygen saturation (SpO2), and heart rate. The time-series changes from 0 to 30 s were compared by the linear mixed method RESULTS: Groups D and E showed the largest RR increase (20.6 and 20.3 breaths/min, respectively) and were significantly larger compared to Group A (3.36 breaths/min, both P<0.001). RR change of Groups D and E did not differ. RR change of Groups B and C was smaller (0.72 and 12.4 breaths/min, respectively) and did not differ statistically with Group A. Significant bradycardia was observed only in Group C (P<0.001). SpO2 was constant in all groups. CONCLUSIONS: Gadoxetate disodium causes a rapid tachypnoea without significant change of SpO2 and heart rate regardless of the dilution method. KEY POINTS: • Injection of gadoxetate disodium causes tachypnoea. • Dilution method did not alter the rapid respiratory effect of gadoxetate disodium. • The respiratory effect of gadoxetate disodium was larger than other contrast agents.

A non-fatal intoxication and seven deaths involving the dissociative drug 3-MeO-PCP.

INTRODUCTION: 3-methoxyphencyclidine (3-MeO-PCP) appeared on the illicit drug market in 2011 and is an analogue of phencyclidine, which exhibits anesthetic, analgesic and hallucinogenic properties. In this paper, we report data from a non-fatal intoxication and seven deaths involving 3-MeO-PCP in Sweden during the period March 2014 until June 2016. CASE DESCRIPTIONS: The non-fatal intoxication case, a 19-year-old male with drug problems and a medical history of depression, was found awake but tachycardic, hypertensive, tachypnoeic and catatonic at home. After being hospitalized, his condition worsened as he developed a fever and lactic acidosis concomitant with psychomotor agitation and hallucinations. After 22h of intensive care, the patient had made a complete recovery. During his hospitalization, a total of four blood samples were collected at different time points. The seven autopsy cases, six males and one female, were all in their twenties to thirties with psychiatric problems and/or an ongoing drug abuse. METHODS: 3-MeO-PCP was identified with liquid chromatography (LC)/time-of-flight technology and quantified using LC-tandem mass spectrometry. RESULTS: In the clinical case, the concentration of 3-MeO-PCP was 0.14µg/g at admission, 0.08µg/g 2.5h after admission, 0.06µg/g 5h after admission and 0.04µg/g 17h after admission. The half-life of 3-MeO-PCP was estimated to 11h. In the autopsy cases, femoral blood concentrations ranged from 0.05µg/g to 0.38µg/g. 3-MeO-PCP was the sole finding in the case with the highest concentration and the cause of death was established as intoxication with 3-MeO-PCP. In the remaining six autopsy cases, other medications and drugs of abuse were present as well. CONCLUSION: Despite being scheduled in January 2015, 3-MeO-PCP continues to be abused in Sweden. Exposure to 3-MeO-PCP may cause severe adverse events and even death, especially if the user does not receive life-supporting treatment.

Kerosene-a toddler's sin: A five years study at tertiary care hospital in western India.

Acute kerosene poisoning is a preventable health problem in children perceived mainly in developing countries. It influences socioeconomic and cultural status of country due to its contribution in morbidity and mortality. As kerosene is widely used as household energy source in India at rural areas as well as urban, it accounts for significant number of poisoning cases mainly accidental in manner. As there are only handful studies from India on kerosene poisoning in children, we planned this study to evaluate incidence of kerosene poisoning in Western Indian population and its clinico-epidemiotoxicological profile. In this retrospective cross-sectional study, we collected data of all the cases of kerosene poisoning diagnosed during five years from 2009 to 2013 at Shri Krishna hospital situated at Karamsad, Gujarat state of Western India. We observed among total 42 cases, all victims were under 3 years of age. Evening in summer months, rural areas, storage of kerosene in household containers, inadequate parental supervision and door-to-hospitalization period emerged as most serious associated factors. Fever, cough, vomiting, tachypnoea and leucocytosis were commonest manifestations while pneumonia was the most common complication. Signs of central nervous system involvement, leucocytosis and vomiting were significantly correlated with pneumonia. Deaths occurred due to pneumonia. Early diagnosis and treatment of pneumonia may reduce mortality and recommendations are made to reduce the incidence of kerosene poisoning.

Effect of Gadoxetate Disodium on Arterial Phase Respiratory Waveforms Using a Quantitative Fast Fourier Transformation-Based Analysis.

OBJECTIVE: The purpose of this study is to investigate the effect of gadoxetate disodium administration on arterial phase respiratory waveforms. SUBJECTS AND METHODS: From 2013 to 2015, 107 subjects undergoing liver MRI with either gadoxetate disodium (10 mL diluted 1:1 with saline; injection rate, 2 mL/s; n = 40) or gadobenate dimeglumine (0.2 mL/kg; maximum, 20 mL; injection rate, 2 mL/s; n = 67) were enrolled. Respiratory waveforms obtained during unenhanced and dynamic contrast-enhanced phases were filtered by a physicist, who was blinded to contrast agent and imaging phase, to eliminate electronic and cardiac noise using fast Fourier transformation. The average root-mean-square difference of two intrasubject control phases (unenhanced and late dynamic) was termed D1, and the root-mean-square deviation of the arterial phase referent to the control record mean was termed D2. D1, D2, and their difference were compared across agents with the Mann-Whitney U test. Bland-Altman plots were generated for D1 and D2 values. RESULTS: D1 values were similar for both agents (mean [± SD], 232 ± 203 for gadoxetate vs 201 ± 230 for gadobenate; p = 0.48), indicating similar intercohort baseline breath-holding capability. D2 was greater and more variable for the gadoxetate cohort (438 ± 381) than for the gadobenate cohort (167 ± 167; p < 0.001), indicating larger and more unpredictable respiratory waveform deviations isolated to the arterial phase (subject-level rate, 48% [19/40] for gadoxetate vs 1% [1/67] for gadobenate; p < 0.001). Aberrant respiratory waveform peaks in the arterial phase were usually associated with transient tachypnea (mean maximum arterial phase respiratory rate for the gadoxetate cohort, 27 breaths/min; range, 11-40 breaths/min). CONCLUSION: Fixed-dose gadoxetate disodium (10 mL; 1:1 dilution with 10 mL of saline; injection rate, 2 mL/s) transiently reduces breath-holding capacity during the arterial phase and is accompanied by brief transient tachypnea.

Death within 44 days of 2,4-dinitrophenol intake.

We report the case of a 50-year-old obese man (115 kg body mass at 1.77 m height), who started taking 2,4-dinitrophenol (DNP) for weight reduction 44 days before his death. After 43 days of taking DNP, the man showed signs of intoxication with nausea, vomiting, and attacks of sweating. After admission to a hospital where the man concealed his DNP intake, sinus tachycardia, tachypnea, and general unrest were noted. The patient died 9 h after the onset of those symptoms. Upon autopsy, a yellowing of palms and soles was striking. The initially uncertain cause of death could only be clarified by the forensic toxicological examinations and subsequent police investigations. Finally, the man had a total intake of 12.3 g of DNP in 44 days which is relatively high compared to other lethal DNP intoxications.

The painted shoes.

A previously well 4-year-old boy presented to the emergency room with progressive cyanosis, pallor and vomiting over the last 5 h. Oxygen saturation on pulse oximetry was 87-89% despite 9 L/min of supplemental oxygen. He was tachypnoeic and had a systolic heart murmur, with no other findings on clinical examination. In his medical history, there was record of a restrictive atrial septal defect, with a normal echocardiogram from 3 years before. He had no relevant family history. His shoes appeared to have been recently painted, which raised the suspicion of methaemoglobinaemia, presumptively caused by aniline-containing shoe dye. The shoes were removed promptly and his feet washed profusely. After confirming the diagnosis, methylene blue was started. The level of methaemoglobin decreased rapidly and the boy made a full recovery.

Activation of 5-HT1A receptors in the preBötzinger region has little impact on the respiratory pattern.

The preBötzinger (preBötC) complex has been suggested as the primary site where systemically administered selective serotonin agonists have been shown to reduce or prevent opioid-induced depression of breathing. However, this hypothesis has not been tested pharmacologically in vivo. This study sought to determine whether 5-HT1A receptors within the preBötC and ventral respiratory column (VRC) mediate the tachypneic response induced by intravenous (IV) (±)-8-Hydroxy-2-diproplyaminotetralin hydrobromide (8-OH-DPAT) in a decerebrated dog model. IV 8-OH-DPAT (19 ± 2 µg/kg) reduced both inspiratory (I) and expiratory (E) durations by ∼ 40%, but had no effect on peak phrenic activity (PPA). Picoejection of 1, 10, and 100 µM 8-OH-DPAT on I and E preBötC neurons produced dose-dependent decreases up to ∼ 40% in peak discharge. Surprisingly, microinjections of 8-OH-DPAT and 5-HT within the VRC from the obex to 9 mm rostral had no effect on timing and PPA. These results suggest that the tachypneic effects of IV 8-OH-DPAT are due to receptors located outside of the areas we studied.

Excitatory amino acid receptors in the dorsomedial hypothalamic area contribute to the chemoreflex tachypneic response.

This study evaluated the effect of blockade of the excitatory amino acid (EAA) receptors in the dorsomedial hypothalamic (DMH) area on the ventilatory and cardiovascular responses of the chemoreflex activation in conscious rats. Bilateral microinjection of kynurenic acid (2.7 nmol, n = 6) into the DMH area reduced the tachypneic (+ 264 ± 13 versus + 204 ± 14 cpm, P < 0.05) and pressor (+ 52 ± 5 versus + 31 ± 6 mmHg, P < 0.05) components of chemoreflex but had no effect on the bradycardic component (-214 ± 7 versus -244 ± 17 bpm) of the chemoreflex. The magnitudes of the reduction in pressor and tachypneic chemoreflex responses were not significantly correlated (r = 0.308, P = 0.330). These data indicate that neurons located in the DMH area are activated by chemoreflex; that this activation is mediated via EAA receptors; and that it is essential for the full expression of the respiratory component of the chemoreflex.

The midbrain periaqueductal grey has no role in the generation of the respiratory motor pattern, but provides command function for the modulation of respiratory activity.

It has previously been shown that stimulation of cell-columns in the periaqueductal grey (PAG) triggers site-specific cardiorespiratory effects. These are believed to facilitate changes in behaviour through coordinated changes in autonomic outflow. Here, we investigated whether PAG-evoked respiratory commands can be studied in situ using the decerebrate perfused brainstem preparation. Phrenic, vagus and abdominal iliohypogastric nerves were recorded before and after microinjection of L-glutamate (30-50 nl, 10 mM) or isoguvacine (GABA-receptor agonist, 30-50 nl, 10 mM) into the PAG. L-glutamate microinjection triggered a range of site-specific respiratory modulations (n = 17 preparations). Subsequent microinjection of isoguvacine into the same PAG sites had no effect on the baseline respiratory motor pattern or rhythm. We conclude that while the PAG has no function in respiratory pattern generation, PAG-evoked respiratory modulations can be evoked in situ in the absence of higher brain centres and while homeostatic parameters that may affect respiratory drive are held static.

Cardiorespiratory effects induced by 2-nitrate-1,3-dibuthoxypropan are reduced by nitric oxide scavenger in rats.

The search for new nitric oxide donors is warranted by the limitations of organic nitrates currently used in cardiology. The new organic nitrate 2-nitrate-1,3-dibuthoxypropan (NDBP) exhibited promising cardiovascular activities in previous studies. The aim of this study was to investigate the cardiorespiratory responses evoked by NDBP and to compare them to the clinically used organic nitrate nitroglycerine (NTG). Arterial pressure, heart rate and respiration were recorded in conscious adult male Wistar rats. Bolus i.v. injection of NDBP (1 to 15mg/kg; n=8) and NTG (0.1 to 5mg/kg; n=8) produced hypotension. NDBP induced bradycardia at all doses, while NTG induced tachycardia at three lower doses but bradycardia at higher doses. Hydroxocobalamin (20mg/kg; HDX), a NO scavenger, blunted hypotension induced by NDBP (15mg/kg), and its bradycardic effect (n=6). In addition, HDX blunted both hypotension and bradycardia induced by a single dose of NTG (2.5mg/kg; n=6). Both NDBP and NTG altered respiratory rate, inducing a biphasic effect with a bradypnea followed by a tachypnea; HDX attenuated these responses. Our data indicate that NDBP and NTG induce hypotension, bradycardia and bradypnea, which are mediated by nitric oxide release.