[Deceased Schizophrenic Patients--Focus on QT Prolongation].

We retrospectively evaluated factors affecting the lifespan of schizophrenic patients, who are known to have a shorter life expectancy than healthy people, focusing on the relationship with QT prolongation associated with antipsychotics. In a total of 406 patients who died at Asai Hospital the mean age at death was compared between schizophrenic patients and nonpsychiatric patients. In deceased schizophrenic patients, drug-related factors, hematology results, and electrocardiographic findings for 3 years before death were compared with those for the same period in age-matched surviving schizophrenic patients. In addition, QT values in schizophrenic patients and healthy controls were evaluated by age group. The mean age at death was significantly younger in schizophrenic patients (63.4 +/- 2.63 years) than in nonpsychiatric patients (84.0 +/- 0.57 years) (p<0.001). Bivariate analysis between deceased and surviving schizophrenic patients showed significant differences in QT values at 2 years, 1 year, and 0.5 years before death and in AST and ALT values at 0.5.years before death. The incidence of QT prolongation in deceased schizophrenic patients (52.0%) was about twice as high as that in surviving schizophrenic patients (24.5%). Multiple logistic regression analysis suggested that the proportion of deceased patients was higher when QT intervals were longer and ALT values were relatively higher, even if within the normal range. In both schizophrenic patients and medical checkup examinees, QT values were positively correlated with the age (R2 = 0.9061 and 0.9276, respectively), and QT intervals in schizophrenic patients were significantly longer in the 30- to 70-year age groups. In both schizophrenic patients and medical checkup examinees, QT values were positively correlated with the age, and QT intervals in schizophrenic patients were significantly longer than those in medical checkup examinees in the same age groups. Deceased schizophrenic patients showed significantly longer QT intervals from 2 years before death than age-matched surviving schizophrenic patients. QT prolongation may influence the lifespan of schizophrenic patients, which are shorter than those of nonpsychiatric patients. This highlights the importance of following electrocardiographic findings and hematology results of schizophrenic patients over time.

Assessment of the severity of organophosphate (fenitrothion) poisoning based on its serum concentration and clinical parameters.

BACKGROUND: Fenitrothion (MEP) is the most frequent cause of organophosphate pesticides (OP) poisoning in Japan, but clinical parameters to predict its severity remain uncertain. METHOD: We evaluated 26 cases (12 males and 14 females) of MEP poisoning brought to our critical care center. Regarding acute lung injury (ALI) as a hallmark complication leading to poor recovery, we divided patients into two groups: cases without ALI (Grp1, n = 14), and cases who developed ALI (Grp2, n = 12) at various points after the poisoning. Serial changes in clinical parameters and laboratory test results were compared between them. RESULTS: The median MEP concentrations on arrival (min~max) for Grp1 and Grp2 were 2.3 (0.5-5.1) and 4.6 (1.1-14.0) µg/ml, respectively. Serum pseudo-cholinesterase (PChE) levels on arrival were 21(< 10-59) U/L in Grp1 and < 10 in Grp2. Based on individual patient kinetics, we estimated MEP concentration at 2 and 24 hours after ingestion, and determined cutoff values for differentiating the two groups for each time point as 4.0 µg/ml and 0.5 µg/ml, respectively. By logistic regression analysis, two groups were distinguished with accuracy of 92.3% based on their time of arrival after ingestion and initial MEP concentration. Clinical parameters associated with ALI were days with miosis, days with PChE below 100 U/L, and days requiring administration of atropine. CONCLUSION: The severity of MEP poisoning is closely associated with both time to presentation after ingestion and initial MEP concentration. Serial monitoring of MEP concentrations in the first 24 hours is also useful in predicting the clinical course.

[Practical study for seminar program certified by Japanese Society of Hospital Pharmacists for Clinical Psychiatric Pharmacists organized by Chiba Society of Hospital Pharmacists, and investigation of participants' background and issues for taking board certified psychiatric pharmacy specialists and board certified pharmacists in psychiatric pharmacy certifications using questionnaires].

Recently, certification systems for Board-Certified Psychiatric Pharmacy Specialists (BCPPS) and Board-Certified Pharmacists in Psychiatric Pharmacy (BCPPP) were established by the Japanese Society of Hospital Pharmacists (JSHP) in 2008, to meet the increasing needs for specialists in psychiatric pharmacy. However, there was no report on the background and opinion of pharmacists who have intention to take the BCPPS or BCPPP and/or seminar programs for BCPPS or BCPPP. The Chiba Society of Hospital Pharmacists has started to provide a seminar program certified by the JSHP to study psychiatry for pharmacists and also investigated the participants' background, demand for the program, and issues in taking the BCPPS or BCPPP using questionnaires. We found that many participants wanted lectures to obtain information on issues they face in routine work as well as for certification testing. For many participants, satisfying the requirements for applying for the BCPPS or BCPPP was one of the most important issues in receiving the qualifications. We found that over 40% of participants working at community pharmacies intended to take the BCPPS or BCPPP, although working experience at a community pharmacy does not entitle them to apply for the BCPPS or BCPPP. The intention of community pharmacists indicates that discussion of the requirements for BCPPS or BCPPP certification systems is necessary to improve psychiatric community care. We will plan a practical seminar program with feedback from this investigation.

Philadelphia chromosome-positive acute myeloid leukemia (Ph + AML) treated with imatinib mesylate (IM): a report with IM plasma concentration and bcr-abl transcripts.

We studied the efficacy and pharmacokinetics of imatinib mesylate (IM) and bcr-abl expression in a Philadelphia chromosome-positive acute myeloid leukemia (Ph + AML) patient, a rare disease with a poor prognosis. Although sufficient IM trough concentrations were maintained, bcr-abl transcripts revealed only one-log reduction with IM monotherapy, suggesting a resistance against IM, and this patient required additional chemotherapy. Despite the resistance against IM at induction therapy, the patient has been in complete molecular response for more than 6 months with IM maintenance monotherapy. Our experience suggests that IM might have a positive role in consolidation and/or maintenance therapy in remission Ph + AML patients.

[Patient with warfarin poisoning caused by coumarin rodenticide].

We report a patient who attempted suicide by taking warfarin as a coumarin rodenticide twice, and showed oral bleeding and an abnormally prolonged bleeding tendency after 10 days. He was conscious. His body temperature was 36.6 degrees C, the respiratory rate was 23/min, and blood pressure was 142/87 mmHg. A bite wound showing continuous bleeding was observed on the right side of the oral cavity. CT of the head and upper gastrointestinal endoscopy showed no intracranial and gastrointestinal bleeding,respectively. The PT and INR were extremely high, and complete blood count revealed anemia. Blood chemistry showed hypoproteinemia. Occult blood was strongly positive. Routine urine examination and electrocardiography showed neither abnormal nor characteristic findings. In drug/ poison screening tests, GC/MS analysis revealed warfarin artifacts in serum and urine samples. Warfarin was isolated from each sample, converted to a TMS derivative, and quantified by SIM analysis of GC/MS. During the clinical course, KaytwoN (vitamin K) was intravenously administered at a dose of 20 mg since the INR at the first consultation was 20.89. After admission to the ICU, 20 mg Kaywan (vitamin K) was orally administered, and the INR after 5 hours improved to 2.32. Kaywan administration (20 mg/day) was initiated, and he improved and was discharged 5 days after admission. The definite cause could be clarified by drug/poison analysis, and effective treatment could be performed.

[Toxicological analysis of a case of Datura stramonium poisoning].

We encountered a patient in a restless excitable state after eating boiled jimson weed grown in the patient's garden. The patient mistook the weed for Angelica keiskei. Pupillary dilation (7/7mm), weak light reflex, body temperature of 37 degrees C, respiratory frequency of 19/min, blood pressure of 138/88 mmHg, pulse rate of 108/min, and hot feeling were observed. No abnormalities nor special findings were detected by general examination of the peripheral blood, biochemical examination of the blood, general examination of the urine, or electrocardiography. Atropine and scopolamine, which are tropane alkaloids, were detected by the GC/MS. The retention time of atropine-TMS was 17.0 min, and the mass spectra were m/z 124, 82, and 140. The retention time of scopolamine-TMS was 17.7 min, and the mass spectra were m/z 138, 108, 154 and 375. At the time of consultation, the serum concentrations of atropine and scopolamine were 31.3 ng/ml, and 30.6 ng/ml, respectively, and decreased to 6.7 ng/ml and 8.5 ng/ml, respectively, after 2 hours. The patient underwent injection of activated carbon after gastrolavage with 2,000 ml warm water, and neostigmine was administered. The patient awoke the following morning, and was discharged with mild pupillary dilation 2 days after poisoning.

[Present condition of the poisoning reason substance analysis in an advanced critical care center].

We investigated the significance of analyzing substances causing intoxication in emergency centers. The poison analysis room was established 6 years before this study. We analyzed a total of 504 patients with intoxication (203 males and 301 females). Concerning the prognosis, 23 patients died; 16 patients (10 males, 6 females) died of paraquat/diquat intoxication, 3 patients (3 males) died of intoxication with organic phosphate agents, 1 patient (male) died of intoxication with a phenoxy agent, and 3 patients (1 male, 2 females) died of intoxication with antipsychotic agents. The other 481 patients were discharged after improvement or referred to another department. Furthermore, we examined the presence or absence of information on intoxication at consultation in the patients with intoxication. In 69 (71.9%) of 96 episodes of intoxication with pesticides, the results of analysis were consistent with the information. In 27episodes (28.1%), there was no information at consultation, or the results of analysis were not consistent with the information. In 299 (79.9%) of 374 episodes of drug poisoning, the results of analysis were consistent with the information. In 75 episodes (20.1%), there was no information at consultation, or the results of analysis were not consistent with the information. These results suggest that the analysis of substances causing intoxication is essential in 20% of patients. We investigated the serum cholinesterase (ChE) level on the initial consultation in the patients with intoxication with pesticides. Ingestion of organic phosphate agents markedly reduced the serum ChE level. However, our results suggest that the serum ChE level depends on the type/amount of pesticides and the interval after ingestion. In addition, many patients took several types of pesticides or drugs, suggesting the importance of analyzing substances causing intoxication.

[Toxicological analyses over the past five years at a single institution].

We investigated 352 patients with acute poisoning, 145 males and 207 females, who were sent to the Department of Emergency and Critical Care Center between June 1999 and March 2004. The insurance application rate averaged 72.5%. The causative agents included 98 prescribed drugs, 23 pesticides and herbicides, cyanide, arsenic and boric acid. Hypnotic and psychotropic drugs accounted for 192 cases (47.5%); antipyretics and analgesics, 93 (23.0%); pesticides and herbicides, 65 (16.1%); amphetamine-like drugs, 6 (1.5%); boric acid, 4 (1.0%); cyanide, 3 (0.7%); arsenic, 1 (0.2%); and other agents, 40 (9.9%). In young people, the most prevalent cause of poisoning was hypnotic,or psychotropic drugs prescribed in psychiatry clinics. In people older than 30, poisoning due to pesticides and herbicides was increased, reaching a peak among those in their 40s. Of 23 patients who died, 20 took Paraquat and Diquat, 2 took organophosphates and 1 took an overdose of antidepressants. The other 329 were transferred to different medical departments or were discharged from our hospital after recovery.

[Development of GC/MS library for analyzing pesticides and drugs].

To analyze the root components of compounds causing drug addiction, we have developed our own GC/MS libraries(PESTICID.LIB consisting of 20 pesticides and Herbicides, and DRUG.LIB with 57 drugs). We have usually utilized standardized agents, but gastric contents, gastric specimens, serum and urine samples from patients were also used for the analyses. We were able to add libraries of various difficult to purchase psychotropic drugs and legally restricted agents by extracting them from the patient samples. Comments about the retention time, the base peak of the mass spectrum and 5 typical ion chromatograms in the libraries have been useful for laboratory analysis, and consequently have improved the accuracy of detection and identification. They were also found to be a useful guideline for discrimination of the unchanged materials and the metabolites. We are attempting to improve the accuracy of the library to avoid the effects of GC column conditions such as the column size, column temperature and different inserts by using a retention time index.