Circulating fluorocytes at the first attack of acute intermittent porphyria: A missing link in the pathogenesis

BackgroundAcute intermittent porphyria (AIP) is an autosomal dominant disorder of the haem biosynthesis resulting from a partial deficiency of hydroxymethylbilane synthase (HMBS) with incomplete penetrance. By conventional means, it is able to identify asymptomatic mutation carrier by molecular diagnosis, but one cannot reliably predict an acute porphyric attack. The presence of fluorescent red cells (fluorocytes) in AIP is probably under-recognized since AIP is a hepatic porphyria and not associated with photosensitivity.MethodsWe used an automatic image acquisition platform to detect the circulating fluorocytes at 700 nm emission in a diabetic AIP patient during acute attack. We screened the patient and her family members for the mutation on HMBS, urine porphobilinogen and circulating fluorocytes.ResultsThe patient was heterozygous for a disease-causing mutation on HMBS and several bright circulating fluorocytes were detected. We showed evidence that protoporphyrin contributed to the erythrocyte auto-fluorescence. Interestingly, asymptomatic mutation carriers with increased urine porphobilinogen did not have circulating fluorocytes. All mutation-negative family members revealed no circulating fluorocytes.ConclusionSudden decrease in plasma glucose concentration might invoke acute attack of AIP and appearance of circulatory fluorocytes. Potential of detecting fluorocytes as screening test or for predicting an acute attack of AIP in diabetes is worth investigating.     

Safe Handling of Chemotherapy in the Perioperative Setting

Safe handling of chemotherapeutic agents during administration and disposal is critical. Most antineoplastic agents are toxic compounds that are carcinogenic, mutagenic, or teratogenic. Direct contact may cause irritation of the skin, eyes, and mucous membranes. Perioperative personnel should know how to handle hazardous materials safely to protect the patient, other staff members, and themselves. These safety precautions include appropriately identifying the patient; correctly preparing, verifying, and documenting the chemotherapeutic agents being administered; consistently wearing personal protective equipment; transporting the chemotherapeutic agent in a puncture-resistant container labeled “chemotherapy”; properly disposing of the chemotherapeutic agent and supplies; and handling a spill if one occurs.     

Severe neuropathic attack in a woman with acute intermittent porphyria: a case report

Acute intermittent porphyria (AIP) is a rare autosomal dominant metabolic disease with a broad spectrum of clinical manifestations, and can be easily confused with other diseases. Many patients with porphyria may have symptoms of peripheral nerve damage during an AIP attack, but most such patients are usually only mildly affected. Herein, we describe the case of an undiagnosed woman who developed overall weakness and respiratory failure within 48 hours, leading to her referral to the intensive care unit. Her neuropathy rapidly deteriorated, leading to quadriplegia and bulbar palsy within 14 days. Finally, the reddish color of her urine and further genetic analysis led to a diagnosis of AIP. The patient was treated with intravenous glucose infusion and her condition gradually improved; however, severe neurological sequelae remained. To the best of our knowledge, the AIP reported in this case, involving rapid and severe neuropathy, is extremely rare worldwide. A diagnosis of AIP should therefore be considered when patients present with severe progressive neuropathy. Moreover, early diagnosis may considerably improve patient prognosis.     

Autoimmune pancreatitis with pancreatic calculi and pseudocyst: a case report

Autoimmune pancreatitis (AIP) is a unique form of pancreatitis often associated with infiltration of immunoglobulin G4-positive cells, a swollen pancreas, and diffuse narrowing of the pancreatic ducts. Unlike acute pancreatitis, AIP is rarely complicated with pseudocysts. Pancreatic calculi, a feature of ordinary chronic pancreatitis, are unusual during short-term follow-up in patients with AIP. We herein describe a 46-year-old man who initially presented with a submucosal tumor of the stomach. The patient was finally diagnosed with AIP accompanied by a pancreatic tail pseudocyst located in the gastric wall and pancreatic calculi by endoscopic ultrasonography-guided fine-needle aspiration. He underwent endoscopic retrograde cholangiopancreatography, pancreatic duct stent placement, and steroid treatment and achieved good clinical and laboratory responses. Although AIP is a common autoimmune disease that responds well to steroids, pseudocysts and pancreatic calculi are rare manifestations of AIP and should be given special attention, especially in patients with disease relapse.     

自身免疫性胰腺炎二例误诊原因分析并文献复习

目的提高临床对自身免疫性胰腺炎(autoimmune pancreatitis,AIP)的认识,减少误诊误治。方法回顾性分析我院收治的2例AIP临床资料并复习相关文献。结果本组例1以腹痛、黄疸入院,例2以左上腹疼痛入院,均在外院行影像学检查而误诊为胰腺占位性病变,为进一步诊治入我院,入院后经相关影像学检查、血清免疫学检查及糖皮质激素试验性治疗后临床症状及影像学表现明显改善,临床确诊为AIP。2例均带药出院,至症状、胰腺影像学形态正常后停药,随访无复发。结论对AIP缺乏诊治经验是该病误诊原因之一,临床接诊此类患者对应综合分析其影像学表现、血清免疫学检查结果及糖皮质激素治疗效果,以及时对AIP作出正确诊断并治疗。     

Acute intermittent porphyria in the practice of an intensive care specialist]

Acute intermittent porphyria (AIP) is a hereditary disease caused by disordered haem biosynthesis and characterized by paroxysmal exacerbations. It usually manifests in adult women. Provoking factors are pregnancy, alcohol, and "porphyrogenic" drugs. Grave attacks of AIP require urgent hospitalization in intensive care wards, rapid purposeful diagnosis and adequate therapy, determining the prognosis. The number of drugs should be minimized and drugs with a known porphyrogenic effect absolutely ruled out. A 35-year-old patient with the first episode of AIP is described; the disease eventuated in death after 2 months.     

Acute intermittent porphyria in the practice of anesthesiology and intensive care

Acute intermittent porphyria (AIP) is a hereditary disease caused by disordered haem biosynthesis and characterized by paroxysmal exacerbations. It usually manifests in adult women. Provoking factors are pregnancy, alcohol, and "porphyrogenic" drugs. Grave attacks of AIP require urgent hospitalization in intensive care wards, rapid purposeful diagnosis and adequate therapy, determining the prognosis. The number of drugs should be minimized and drugs with a known porphyrogenic effect absolutely ruled out. A 35-year-old patient with the first episode of AIP is described; the disease eventuated in death after 2 months.     

Use of cytarabine and idarubicin in a newly diagnosed AML patient with a severe wound

Acute myeloid leukemia (AML) is malignant tumor of haemopoietic precursor cells of non-lymphoid lineage. AML can atypically present with non-spesific cutaneous lesions or wounds. There are rare acute leukemia cases which present with genital ulcerations or pyoderma gangrenosum in the literature. The effect of acute leukemia on wound healing is not known, but it is thought that cytopenias and chemotherapy can impair wound healing in patients with leukemia. The effects of chemotherapeutic agents on wound healing are arguable. Here we present wound care strategies and simultaneously applied chemotherapy in an AML patient.     

Molecular and biochemical studies of acute intermittent porphyria in 196 patients and their families

BACKGROUND: Acute intermittent porphyria (AIP) is a metabolic disease with clinical manifestations that mimic other abdominal, neurologic, or mental crises. We studied the diagnostic accuracy of current laboratory tests during an acute attack and in remission. METHODS: Since 1966, we have studied all known Finnish AIP patients (n = 196) and their families (n = 45) and identified the porphobilinogen deaminase (PBGD) mutation in each family. Diagnoses or exclusions of AIP were based on clinical data (including family history), biochemical tests, and in 239 cases, mutation testing. We retrospectively evaluated the diagnostic accuracy of erythrocyte PBGD activity, urinary excretion of porphobilinogen (PBG) and delta-aminolevulinic acid, and urinary and fecal excretion of porphyrins in these patients. RESULTS: Measurement of urinary PBG identified all 35 AIP patients studied during an acute attack. The mean excretion of PBG was 50-fold above the reference interval, although the intraindividual increases were modest (1.6- to 4.0-fold). In the mutation-screened population, urinary PBG analysis identified only 85% of 81 AIP patients studied during remission, but by ROC curve analysis it was nonetheless the best of the biochemical tests. It was increased 相似文献   

酪氨酸激酶抑制剂HerbimycinA联合化疗药物对K562细胞凋亡…

探讨慢性髓细胞白血病细胞抗凋亡机制和诱导细胞凋亡的有效方法。方法：采用Ｋ５６２细胞培养，观察酪氨酸激酶抑制剂ＨｅｒｂｉｍｙｃｉｎＡ联合化疗药物对细胞凋主恨的影响，探讨ＨＭＡ对ＣＭＬ细胞的作用。结论ＨＭＡ通过抑制ＣＭＬ细胞内酪氨酸激酶活性促进细胞凋亡而增加对化疗药物的敏感性，表明酪氨酸激酶抑制剂作为治疗ＣＭＬ药物具有潜在应用价值。     

Accidental iatrogenic pneumothorax in hospitalized patients

OBJECTIVE: Iatrogenic pneumothorax (IP) is an inherent risk to patients who undergo procedures that involve the intentional puncturing of the lung. IP also could occur accidentally to patients who do not undergo such procedures; such accidental IP (AIP) is suggestive of lapses in safe care. This study assessed the risk for AIP in patients hospitalized with specific diagnoses who underwent specific procedures. RESEARCH DESIGN: We analyzed 7.5 million discharge abstracts from 994 short-term acute care hospitals across 28 states in 2000 in the Agency for Healthcare Research and Quality (AHRQ), Healthcare Cost and Utilization Project Nationwide Inpatient Sample. AHRQ Patient Safety Indicators (PSIs) were used to identify AIP. AIP incidences and associated diagnoses and procedures were explored. RESULTS: Patients who were admitted for pleurisy, cancer of the kidney and renal pelvis, or conduction disorders and complications of cardiac devices had the highest rates of developing AIP during hospitalization, with AIP rates at 2.24%, 1.14%, and 0.83% respectively. The procedure-specific rates for AIP varied from 2.68% for patients who underwent thoracentesis to 1.30% for those who underwent nephrectomy, to 0.06% for those who underwent gastrostomy. Thoracentesis appeared to be a high-risk procedure for patients who were admitted for secondary malignancies, pleurisy, or pneumonia, with AIP rates at 3.76%, 3.13%, and 2.28%, respectively. CONCLUSIONS: Although AIP is most common after thoracentesis, it is a substantial threat to patients undergoing a wide range of procedures.     

Matching the standards of clinical trial evidence with application in practice

A high standard of proof of efficacy and safety is required in clinical trials. This standard requires careful translation into practice, combining an evidence-based approach with clinical experience and judgment to maximise patient benefits and minimise harms. The tendency to extend application of new treatments to patient groups other than those for whom reliable data exist should be avoided. Equally, extrapolation of the data to agents of the same class untested for particular indications should not occur. If the considerable potential benefits of modern cardiovascular therapeutics are to be maximised and harms avoided, clinicians should observe these principles carefully as new treatments become accessible and are applied.     

Diagnostic value of imaging examination in autoimmune pancreatitis

Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis mediated by autoimmunity factors. It can be divided into two categories according to pathological characteristics: Lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis. In the clinical setting, the imaging manifestations of some AIP cases are atypical, so it is difficult to distinguish it from general pancreatitis, pancreatic ductal adenocarcinoma, lymphoma, and other malignant disorders. Most importantly, the treatment for and prognosis of these diseases are different. Therefore, a timely correct imaging diagnosis of AIP is key for AIP patients. After that, clinicians can take appropriate treatment measures for those patients, which is helpful for the prognosis of AIP.     

Current treatment approaches to obsessive-compulsive disorder.

The two most useful treatments in obsessive-compulsive disorder are pharmacotherapy with potent serotonin reuptake-blocking agents and behavioral techniques, such as exposure and response prevention. Based on the authors' cumulative clinical experience, it is suggested that patient education, cognitive therapy, and psychodynamic psychotherapy are helpful adjuncts during various treatment stages of obsessive-compulsive disorder. The patient's strengths and knowledge of the illness can be used by the nurse-therapist to determine the implementation and timing of these therapeutic measures. Specific behavioral and cognitive techniques that may be useful in treating specific symptoms of obsessive-compulsive disorder are highlighted. Suggestions for future nursing research are outlined.     

酪氨酸激酶抑制剂 Herbimycin A 联合化疗药物对 K562 细胞凋亡的影响

目的：探讨慢性髓细胞白血病（ＣＭＬ）细胞抗凋亡机制和诱导ＣＭＬ细胞凋亡的有效方法。方法：采用Ｋ５６２细胞培养，观察酪氨酸激酶抑制剂ＨｅｒｂｉｍｙｃｉｎＡ（ＨＭＡ）联合化疗药物对ＣＭＬ细胞凋亡的影响，探讨ＨＭＡ对ＣＭＬ细胞的作用。结果：ＨＭＡ或化疗药物单独应用可抑制Ｋ５６２细胞增殖，但不能明显诱导其凋亡。ＨＭＡ能明显增强化疗药诱导Ｋ５６２细胞凋亡。加入外源性巯基化合物阻断ＨＭＡ与酪氨酸激酶的结合可完全取消这种作用。结论：ＨＭＡ通过抑制ＣＭＬ细胞内酪氨酸激酶活性促进细胞凋亡而增加对化疗药物的敏感性，表明酪氨酸激酶抑制剂作为治疗ＣＭＬ药物具有潜在的应用价值。     

The management of neuropathic pain with a focus upon older adults

By the year 2030, it is projected that the US population over the age of 65 years will be 70 million (one-fifth of the US population). Pain of various etiologies initiates about 50% of yearly physician visits and is the most frequent reason for health care consultation in the United States identified commonly by the older patient. The negative impact on the patient coupled with less than optimal treatments often presented to the patient elicit patient and prescriber frustration with inadequate outcomes. This article is focused at pharmacotherapeutic selections to be utilized in a polymodal fashion for the older adult presenting with neuropathic pain. The pharmacotherapies are to be titrated in a patient-specific patient centered-patient focused-personalized pharmacotherapeutic care. The classes of agents discussed include antidepressants, mood stabilizers/antiseizure agents, opioids, anesthetics, and miscellaneous agents.     

Updating your peripheral neuropathy "know-how"

Peripheral neuropathy is a condition that can be caused or exacerbated by the administration of certain chemotherapeutic agents. The effects of chemotherapy-induced peripheral neuropathy (CIPN) are dose limiting and might lead to permanent, debilitating disabilities. Oncology nurses should be aware of the impact of CIPN. Nurses should be cognizant of the pathophysiology, pre-existing conditions contributing to an increased risk of CIPN, causative agents, and interventions used in managing CIPN. Awareness that the peripheral nervous system is divided into small fibers, large fibers, and the autonomic nervous system is important in the assessment, detection, and treatment of CIPN. Presenting symptoms are related to the specific fibers that are damaged. Because of the different mechanisms of action, CIPN symptoms vary depending on the chemotherapeutic agents used. This article provides a general overview of CIPN, including pathophysiology, causes, risk factors, assessment, and current treatment. Oncology nurses must be alert for the manifestations of CIPN. Early intervention and patient education can have a positive effect on the quality of life for patients with this disorder.     

Pioglitazone reduces atherogenic index of plasma in patients with type 2 diabetes

BACKGROUND: Insulin resistance is often associated with increased triglyceride (TG) and decreased HDL-cholesterol (HDL-C) concentrations and increased small LDL particles. The Atherogenic Index of Plasma (AIP), defined as log(TG/HDL-C), has recently been proposed as a marker of plasma atherogenicity because it is increased in people at higher risk for coronary heart disease and is inversely correlated with LDL particle size. We studied the effect of pioglitazone, a thiazolidinedione that reduces insulin resistance, on the AIP of patients with type 2 diabetes. METHODS: The data for the analysis of AIP in this report were obtained from four randomized, double-blind, multicenter, parallel-group, placebo-controlled clinical trials. Pioglitazone was used as monotherapy in one study and in combination therapy in three studies. Fasting glucose, insulin, HDL-C, and TGs plus glycohemoglobin (HbA(1C)) were measured at baseline and various points during each study. RESULTS: Patients in this study population with type 2 diabetes had high AIP values at baseline. Pioglitazone treatment significantly decreased AIP from baseline in each of the study groups. Pioglitazone treatment groups had a significantly lower AIP compared with their respective placebo controls. Finally, AIP was inversely and significantly correlated with measures of insulin sensitivity, such as the homeostasis model assessment and quantitative insulin sensitivity check index. In contrast, AIP was not significantly correlated with HbA(1C). CONCLUSIONS: Pioglitazone reduced AIP when used as monotherapy or in combination therapy with sulfonylurea, metformin, or insulin. AIP was inversely correlated with measures of insulin sensitivity.