piperidines and Multiple-Organ-Failure

Thrombocytepenia, anasarca, fever, renal insufficiency, and organomegaly (TAFRO) syndrome is a novel disease entity characterized by a constellation of symptoms (thrombocytopenia, anasarca, fever, renal insufficiency, and organomegaly). Here, we describe the development of TAFRO syndrome-like features during the treatment of rheumatoid arthritis with a Janus kinase (JAK) inhibitor.. In this report, a 74-year-old woman treated with a JAK inhibitor (tofacitinib) for rheumatoid arthritis was admitted because of fever and thrombocytopenia.. On laboratory examination, marked thrombocytopenia and elevated creatinine and C-reactive protein levels were present. A computed tomography scan revealed lymphadenopathy, hepato-splenomegaly, and anasarca. A left axillary lymph node biopsy revealed Castleman's disease-like features. These clinical features satisfied the proposed diagnostic criteria for TAFRO syndrome. Since autoimmune disorders should be excluded when diagnosing TAFRO syndrome, it is not strictly correct to diagnose her as TAFRO syndrome. Therefore, we diagnosed her as rheumatoid arthritis complicated by TAFRO syndrome-like features.. The patient was treated with high-dose glucocorticoid, tacrolimus, eltrombopag, intravenous immunoglobulin, and rituximab.. Her condition was refractory to the above-mentioned treatment, and she eventually died because of multi-organ failure 6 months after the first admission.. TAFRO syndrome-like features can develop during treatment with a JAK inhibitor for rheumatoid arthritis. Patients with autoimmune diseases complicated by TAFRO syndrome-like features can follow a fatal clinical course, and thus, an intensive combined treatment is warranted for such patients, especially in cases refractory to glucocorticoid.

Topics: Aged; Arthritis, Rheumatoid; Castleman Disease; Fatal Outcome; Female; Humans; Janus Kinase Inhibitors; Multiple Organ Failure; Piperidines; Pyrimidines; Pyrroles; Thrombocytopenia

We previously reported the Bruton's tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib improve outcomes in a mouse model of polymicrobial sepsis. Now we show that genetic deficiency of the BTK gene

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Animals; Benzamides; Disease Models, Animal; Inflammasomes; Macrophages; Male; Mice; Mice, Inbred CBA; Multiple Organ Failure; Phagocytosis; Piperidines; Protein Kinase Inhibitors; Pyrazines; Sepsis; X-Linked Combined Immunodeficiency Diseases

Topics: Abdomen; Adenine; Aged; Fatal Outcome; Humans; Invasive Fungal Infections; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Mucorales; Mucormycosis; Multiple Organ Failure; Neoplasm Recurrence, Local; Opportunistic Infections; Piperidines; Pyrazoles; Pyrimidines; Thorax; Tomography, X-Ray Computed

Over the past decade, there has been a sharp increase in the number of newly identified synthetic drugs. These new drugs are often derivatives of previously abused substances but have unpredictable toxicity. One of these drugs is gacyclidine, a derivative of phencyclidine (PCP). Gacyclidine has been studied as a neuroprotective agent in trauma and as a therapy of soman toxicity. There are no previous reports of its use as a drug of abuse.. During a two-month period in the summer of 2013, a series of patients with severe agitation and end-organ injury were identified in an urban academic Emergency Department (ED). A urine drug of abuse screen was performed on all patients, and serum samples were sent for comprehensive toxicology analysis. A total of five patients were identified as having agitation, rhabdomyolysis, and elevated troponin (Table 1). Three of the five patients reported use of methamphetamine, and all five patients had urine drug screens positive for amphetamine. Comprehensive serum analysis identified methamphetamine in three cases, cocaine metabolites in one case, and a potential untargeted match for gacyclidine in all five cases. No other drugs of abuse were identified.. This is the first series of cases describing possible gacyclidine intoxication. The possible source of the gacyclidine is unknown but it may have been an adulterant in methamphetamine as all patients who were questioned reported methamphetamine use. These cases highlight the importance of screening for new drugs of abuse when patients present with atypical or severe symptoms. Gacyclidine has the potential to become a drug of abuse both by itself and in conjunction with other agents and toxicity from gacyclidine can be severe. It is the role of the medical toxicology field to identify new agents such as gacyclidine early and to attempt to educate the community on the dangers of these new drugs of abuse.

Topics: Academic Medical Centers; Adult; Combined Modality Therapy; Cyclohexenes; Designer Drugs; Drug Users; Emergency Service, Hospital; Fatal Outcome; Female; Humans; Illicit Drugs; Male; Middle Aged; Multiple Organ Failure; Neurotoxicity Syndromes; Piperidines; Psychomotor Agitation; Psychotropic Drugs; Rhabdomyolysis; Toxicokinetics; Treatment Outcome; Treatment Refusal

We reported the case of a 61-year-old woman, who has been hospitalized in ICU because of an extensive mesenteric ischaemia, involving the small bowel, secondary to a naratriptan overuse. This mesenteric ischaemia was complicated by multiple organ failure and was responsible for extensive small bowel resection and left colectomy. A concomitant abundant absorption of grapefruit juice, a well-known P450 inhibitor, may have enhanced this naratriptan toxicity. This case underscore that an abdominal pain occurring in the context of headache treatment may be related to a mesenteric ischaemia.

Topics: Abdominal Pain; Citrus paradisi; Colectomy; Electrocardiography; Female; Food-Drug Interactions; Humans; Intestines; Ischemia; Middle Aged; Multiple Organ Failure; Piperidines; Serotonin Agents; Shock; Splanchnic Circulation; Tryptamines

Prolonged sedation with propofol at high doses may lead to fatal multi-organ dysfunction, know as propofol infusion syndrome. We tested the hypothesis that propofol plus remifentanil co-administration attenuates propofol tolerance to its sedative effect and assessed if such an effect has an impact on propofol toxicity in rabbits under prolonged mechanical ventilation.. Eighteen healthy male rabbits were mechanically ventilated and received propofol (group P, n = 6), propofol plus remifentanil (group PR, n = 6), or remifentanil plus sevoflurane (group RS, n = 6) in order to be kept under sedation (group P) or sedation/analgesia (groups PR and RS) for up to 48 h. Initial propofol and remifentanil infusion rates (IRs) were adjusted, if needed, to maintain the desired level of sedation and analgesia, respectively (groups P and PR). In group RS, remifentanil was infused at IRs equivalent to those of group PR. Propofol IRs were recorded, propofol concentrations were measured in the arterial plasma, and blood biochemical parameters and organ histopathology were assessed.. Animals survived for 29-36 h in group P and 22-38 h in group PR (100% mortality rate). Tolerance was developed to propofol's sedative effect. The onset of tolerance was delayed and its magnitude was decreased in group PR compared with group P. Propofol was accumulated in the systemic circulation. Propofol clearance rate was gradually decreased. Arterial lactate, and serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin, cholesterol, triglycerides, and creatine kinase (CK) levels were increased. The heart, lungs, liver, gallbladder, kidneys, urinary bladder, and skeletal muscles were seriously injured in groups P and PR. In group RS, mortality was 0%, while there was only mild injury of the lungs, liver, gallbladder, kidneys, and urinary bladder.. Although propofol tolerance is attenuated in propofol plus remifentanil receiving rabbits under prolonged mechanical ventilation, fatal multi-organ injury occurs resembling human propofol infusion syndrome.

Topics: Anesthetics, Inhalation; Anesthetics, Intravenous; Animals; Drug Interactions; Drug Tolerance; Gallbladder; Kidney; Liver; Lung; Male; Methyl Ethers; Multiple Organ Failure; Muscle, Skeletal; Myocardium; Piperidines; Propofol; Rabbits; Remifentanil; Sevoflurane; Urinary Bladder

A possible role of platelet-activating factor (PAF) in the occurrence of the two septic complications, i.e., disseminated intravascular coagulation (DIC) and multiple organ failure (MOF) was investigated, employing a rabbit model and a novel PAF antagonist E5880. By an instillation of fecal suspension into the common bile duct of the rabbit, manifestations of DIC and MOF were observed with high reproducibility by 9 hours after the septic insult. E5880 was intravenously administered to 12 rabbits for 1 hour after the septic insult at dose of 1 mg/kg (n = 6) or 3mg/kg (n = 6). All the rabbits were subjected to observation of vital signs and serial determination of laboratory tests for 9 hours and then lung, liver and kidney were removed for histological examination. Blood endotoxin level increased significantly by 9 hours after the septic insult. Although administration of E5880 did not affect the endotoxemia, the antagonist attenuated in a dose related manner laboratory manifestation of DIC such as thrombocytopenia and prolonged prothrombin time as well as that of MOF such as increase in serum bilirubin and creatinine level. The beneficial effect of E5880 on MOF was also confirmed by the histological evaluation. These observations indicated that PAF is deeply involved in the occurrence of DIC and MOF due to sepsis and E5880 may be one of the modalities to treat or prevent these two major septic complications.

Topics: Alanine Transaminase; Animals; Bacterial Infections; Blood Cell Count; Blood Urea Nitrogen; Cholangitis; Common Bile Duct; Disseminated Intravascular Coagulation; Endotoxins; Fibrinogen; Hematocrit; Liver; Male; Multiple Organ Failure; Partial Thromboplastin Time; Piperidines; Platelet Activating Factor; Pyridinium Compounds; Rabbits