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Background The rates of newly diagnosed cases of sexually transmitted diseases, including genital chlamydial infection and gonorrhea, are important for prevention and control of these diseases. However, nationwide rates are not reported in Japan. Methods We used the number of cases of sexually transmitted diseases reported by nationwide sentinel surveillance in 2015, together with the number of all disease outpatients in September 2014 at all medical institutions, drawn from the Survey of Medical Institutions of Japan. The number of cases of sexually transmitted diseases in the total population was estimated using the ratio estimation method with the number of all disease outpatients as auxiliary information. This method is currently used for estimating influenza cases from sentinel surveillance data in Japan. Results The estimated number of newly diagnosed cases per 100,000 population in 2015 in Japan was 244 (95% confidence interval 211–277) for genital chlamydial infection, 87 (95% confidence interval 74–100) for genital herpes, 61 (95% confidence interval 29–93) for condyloma acuminatum, and 89 (95% confidence interval 64–113) for gonorrhea. Conclusion We estimated the nationwide number of newly diagnosed cases of sexually transmitted diseases in Japan from sentinel surveillance data. This provides useful information for public health policy-making.

The diagnosis of myelodysplastic syndromes (MDS) is based on morphology and cytogenetics. However, limited information is currently available on the interobserver concordance of the assessment of dysplastic lineages (10% or ≥10% in bone marrow (BM)). The revised International Prognostic Scoring System (IPSS-R) described a new threshold (2%) for BM blasts. However, the interobserver concordance of the categories (0-≤2% and2-5%) has limited data. The purpose of the present study was to investigate the assessment of dysplastic lineages and IPSS-R reproducibility. Our study was divided into two Steps. In each Step, the microscopic examinations were performed separately by two morphologists. Regarding the category of BM blasts ≤2% and2-5%, interobserver agreement was more than 'moderate' in all pairs (kappa test: 0.43-0.90). Regarding dysgranulopoiesis (dysG) and dyserythropoiesis (dysE) in BM, interobserver agreement was more than 'moderate' in all pairs (kappa test, dysG: 0.45-0.96, dysE: 0.45-0.81). Regarding the category of dysmegakaryopoiesis (dysMgk) in BM, interobserver agreement was more than moderate in 4 out of 5 pairs (kappa test: 0.58-1.00), and was fair for one pair (kappa test: 0.37). We consider that high interobserver concordance may be possible for the BM blast cell count (≤2% or2-5%) and dysplasia (10% or ≥10%) of each lineage.

Objectives To assess the performance of the EULAR/ACR idiopathic inflammatory myopathies (IIMs) classification criteria to classify juvenile IIMs (JIIMs) in an Asian paediatric population. Methods Sixty-eight JIIM patients and 49 non-JIIM patients diagnosed at seven major paediatric rheumatology centres in Japan between 2008 and 2015 were enrolled. Retrospective data were collected, and each patient’s data form was submitted. The expert group reviewed the forms and re-examined the diagnoses. The EULAR/ACR criteria were then applied and the probability of having JIIM was determined for each case. The sensitivity and specificity of the EULAR/ACR criteria were compared with those of other existing criteria. Results The sensitivity/specificity of the EULAR/ACR classification criteria were 92.1/100% with muscle biopsy data (n = 38); 86.7/100% without muscle biopsy data (n = 30) and 89.7/100% in our total cohort (n = 68). The sensitivity of Bohan and Peter’s criteria and Tanimoto’s criteria were 80.9 and 64.7% in our total cohort, respectively. Among 68 physician-diagnosed JIIM patients, seven cases (three JDM and four overlap myositis) were not classified as JIIM because the probability did not reach the cut-off point (55%). The three JDM patients all presented with only one of the three skin manifestations that are listed in the criteria: Gottron’s sign. Conclusion Our validation study with Japanese JIIM cases indicates that the EULAR/ACR classification criteria for IIM generally perform better than existing diagnostic criteria for myositis.

The Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes has been conducting prospective registration, central review, and follow-up study for patients with aplastic anemia and myelodysplastic syndrome (MDS) since 2006. Using this database, we retrospectively analyzed the prognosis of patients with MDS. As of May 2016, 351 cases were registered in this database, 186 of which were eligible for the present study. Kaplan–Meier analysis showed that overall survival (OS) curves of the five risk categories stipulated by the revised international prognostic scoring system (IPSS-R) were reasonably separated. 2-year OS rates for the very low-, low-, intermediate-, high-, and very high-risk categories were 95, 89, 79, 35, and 12%, respectively. In the same categories, incidence of leukemic transformation at 2 years was 0, 10, 8, 56, and 40%, respectively. Multivariate analysis revealed that male sex, low platelet counts, increased blast percentage (>2%), and high-risk karyotype abnormalities were independent risk factors for poor OS. Based on these data, we classified Japanese MDS patients who were classified as intermediate-risk in IPSS-R, into the lower risk MDS category, highlighting the need for careful assessment of treatments within low- and high-risk treatment protocols.

Purpose To evaluate the risk factors and prevalence of hyponatremia among epilepsy patients in relation to use of antiepileptic drugs (AEDs). Methods We retrospectively reviewed 14,620 adult patients (aged 18–103 years) and classified them into the following 3 groups: patients without AED treatment (n = 2165, Group I), patients receiving antiepileptic drugs other than carbamazepine (n = 7442, Group II), and patients treated with carbamazepine (n = 5013, Group III). This study did not include the patients receiving oxcarbazepine or eslicarbazepine acetate because these AEDs are not marketed in Japan. Severe hyponatremia was defined as a serum sodium level Results In Groups I, II, and III, the mean sodium level was 140, 139, and 137 mEq/L, respectively. The highest frequency of severe hyponatremia was observed in Group III (7%), and it was much higher than in Group I (0.8%) or Group II (1.2%). In Groups II and III, old age, low body weight, and concomitant use of phenobarbital, benzodiazepines, or antipsychotics were risk factors for hyponatremia. In Group III, the sodium level decreased as the carbamazepine dose increased. At a carbamazepine dose exceeding 600 mg/day, there was 10.9-fold higher prevalence of hyponatremia, and the risk was potentiated by concomitant use of valproate. Conclusion The serum sodium level should be monitored carefully when patients are receiving AED polypharmacy combined with antipsychotics. In particular, concomitant administration of valproate enhances the risk of hyperammonemia in patients receiving carbamazepine. These findings may help clinicians to avoid hyponatremia in patients with epilepsy.

ObjectiveTo externally validate the performance of the new European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria set for idiopathic inflammatory myopathies (IIM) with a Japanese cohort.MethodsThis study included 420 IIM and 402 non-IIM cases. Probability of having IIM in each patient was calculated using the collected data set. The cut-off probability was set at 55%, as recommended by EULAR/ACR. Patients classified as IIM by the criteria were further subclassified with classification trees.ResultsWhen the probability cut-off was set at 55%, the sensitivity/specificity of the new criteria to diagnose IIM were 89.3%/91.0% in the total cohort, 88.1%/95.1% without muscle biopsy data and 90.4%/65.5% with biopsy data. The cohort included 12 overlap syndrome patients with biopsy data, who were included as non-IIM cases in accordance with traditional Japanese methods. When they were included in the IIM cases, the specificity in patients with biopsy increased to 74.4%. The sensitivity/specificity of the new criteria to diagnose polymyositis/dermatomyositis (PM/DM) plus juvenile and amyopathic DM in the Japanese cohort was 87.4%/92.4%, which were greater than those of the Tanimoto’s criteria revised to enable classification of amyopathic DM (ADM) (71.2%/87.8%) and were comparable with those of Bohan & Peter’s criteria to diagnose those diseases except for ADM (88.4%/88.3%).ConclusionsOur study externally validated high specificity of the new criteria for the first time, although with several limitations, including low percentage of child patients. The new criteria have higher sensitivity and/or specificity in classification of PM/DM than the previously reported criteria, demonstrating its usefulness for interethnic patients.

Objectives: This study aimed to investigate the clinical characteristics of polymyositis/dermatomyositis (PM/DM) in Japan by analyzing data from the nationwide registration system.Methods: The data of the registration system in 2009 were analyzed to investigate patient numbers, sex, clinical symptoms, therapies, complications, and prognosis of PM/DM.Results: The total number of PM/DM cases was approximately 17,000, and the female/male sex ratio was 2.7:1. Almost all patients improved as a result of therapy, but many suffered from sequelae such as muscle weakness.Conclusions: The results characterize significant aspects of Japanese PM/DM patients. However, a further prospective survey is required to clarify the true epidemiology and natural history of PM/DM.

Infectious disease surveillance systems provide information crucial for protecting populations from influenza epidemics. However, few have reported the nationwide number of patients with influenza-like illness (ILI), detailing virological type. Using data from the infectious disease surveillance system in Japan, we estimated the weekly number of ILI cases by virological type, including pandemic influenza (A(H1)pdm09) and seasonal-type influenza (A(H3) and B) over a four-year period (week 36 of 2010 to week 18 of 2014). We used the reported number of influenza cases from nationwide sentinel surveillance and the proportions of virological types from infectious agents surveillance and estimated the number of cases and their 95% confidence intervals. For the 2010/11 season, influenza type A(H1)pdm09 was dominant: 6.48 million (6.33-6.63), followed by types A(H3): 4.05 million (3.90-4.21) and B: 2.84 million (2.71-2.97). In the 2011/12 season, seasonal influenza type A(H3) was dominant: 10.89 million (10.64-11.14), followed by type B: 5.54 million (5.32-5.75). In conclusion, close monitoring of the estimated number of ILI cases by virological type not only highlights the huge impact of previous influenza epidemics in Japan, it may also aid the prediction of future outbreaks, allowing for implementation of control and prevention measures.

The aim of this study was to describe age, gender distribution, and age at onset of systemic lupus erythematosus (SLE), polymyositis/dermatomyositis (PM/DM), and systemic sclerosis (SSc) in Japan. We used epidemiological information on 21,405, 6,327, and 10,058 patients with SLE, PM/DM, and SSc, respectively, in a Japanese nationwide registration database of patients with intractable diseases. All three diseases occur predominantly in women, with the female-to-male ratio being 8.2:1, 2.6:1, and 7.7:1 for SLE, PM/DM, and SSc, respectively. The most susceptible age for SLE is 15–44 and 20–39 years for males and females, respectively. For PM/DM it is 45–64 and 40–64 years and for SSc, 50–69 and 40–59 for men and women, respectively. The basic descriptive epidemiological characteristics of SLE, PM/DM, and SSc in Japan, such as gender distribution, present age, and age at onset, were surveyed nationwide for fiscal 2007. It was found that these characteristics were similar to those in Western populations. Our finding provides new information on the natural history of disease development.

BACKGROUND: Drug-resistant bacteria have been increasing together with advancement of antimicrobial chemotherapy in recent years. In Japan, the target diseases in the National Epidemiological Surveillance of Infectious Diseases (NESID) include some drug-resistant bacterial infections.METHODS: We used the data in the NESID in Japan, 2001-2005. Target diseases were methicillinresistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP) and multi-drug-resistant Pseudomonas aeruginosa (MDRPA) infections. The numbers of patients reported by sentinel hospitals (about 500) on a monthly basis were observed.RESULTS: The numbers of patients per month per sentinel hospital of 2001-2005 were 3.37-3.98 in MRSA, 0.96-1.19 in PRSP, and 0.11-0.13 in MDRPA infections. The sex ratios (male / female) of patients were 1.69-1.82, 1.34-1.43, and 1.71-2.52, respectively. More than 50% of all patients were adults aged 70 years or older in MRSA and MDRPA infections, but more than 60% were children under 10 years in PRSP infections. The number of patients per sentinel hospital in MRSA infections showed little variation between months, but evidenced a large variation in PRSP and MDRPA infections. The annual trend in the number of patients per sentinel hospital was increasing significantly for the 5-year period in MRSA and PRSP infections, but not in MDRPA infections.CONCLUSIONS: We revealed sex-age distributions of the patients reported to NESID in Japan, 2001- 2005. An increasing incidence of MRSA and PRSP infections and monthly variation in PRSP and MDRPA infections were observed for the 5-year period. Extended observation would be necessary to confirm these trends and variations.J Epidemiol 2007; 17: S42-S47.

BACKGROUND: The method for estimating incidence of infectious diseases from sentinel surveillance data has been proposed. In Japan, although the annual incidence rates of influenza and pediatric diseases estimated using the method were reported, their weekly incidence rates have not.METHODS: The weekly sex- and age-specific numbers of cases in the sentinel medical institutions in the National Epidemiological Surveillance of Infectious Diseases in Japan in 2002-2005 were used. Annual and weekly incidence rates of influenza and 12 pediatric diseases were estimated by the above-mentioned method, under the assumption that sentinels are randomly selected from all medical institutions.RESULTS: The annual incidence rate of influenza in 2002-2005 was 57.7-142.6 per 1,000 population. The highest weekly incidence rate was 7.4 at week 8 in 2002, 14.9 at week 4 in 2003, 14.1 at week 5 in 2004, and 21.2 at week 9 in 2005. The annual incidence rate per 1,000 population of 0-14 years old in 2002-2005 was less than 5.0 for pertussis, rubella and measles, 293.2-320.8 for infectious gastroenteritis, and 5.3-89.6 for 8 other diseases. The highest weekly incidence rate was less than 1.0 for exanthem subitum, and was more than 5.0 for infectious gastroenteritis, hand-foot-mouth disease and herpangina.CONCLUSION: We estimated annual and weekly incidence rates of influenza and pediatric diseases in Japan in 2002-2005, and described their temporal variation.J Epidemiol 2007; 17: S32-S41.

To characterize the epidemiology of Sjögren's syndrome (SS), including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatment used in Japan.The Research Team for Autoimmune Diseases, the Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare conducted primary and secondary surveys on epidemiology of SS in 2011. The primary survey covered 4,729 out of 14,095 Japan-wide Hospital Departments to investigate the prevalence of SS. The secondary survey encompassed 214 Hospital Departments that agreed to the survey, to characterize disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatments.The number of patients with SS in Japan estimated by the primary survey was 68,483. The secondary survey involving data collected from 2,195 SS patients from 98 Hospital Departments showed that the mean age of patients was 60.8 ± 15.2 years, male/female ratio was 1/17.4, primary/secondary SS was about 60%/40% and glandular/extra-glandular form in primary SS was about 70%/25%. The satisfaction rate was 53.8% for the 1999 revised Japanese Ministry of Health criteria for the diagnosis of SS, 47.7% for the 2002 American-European Consensus Group classification criteria for SS and 49.6% for 2012 American College of Rheumatology classification criteria for SS. Corticosteroids were used by 752 of 2,195 patients (34%), immunosuppressants by 358 patients (16%), biologics by 68 patients (3%) and secretagogues by 695 patients (32%).The surveys provided valuable information on the epidemiology of SS including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets and treatments used today in Japan.

We here propose a new index, the difference-change contribution proportion, to quantify contributions of age and cause of death to differences in age-adjusted overall mortality disparities between two groups over time. The present study was conducted with the aim of elucidating age and cause of death contributions to the recent decrease in disparity in life expectancy between males in Okinawa and mainland Japan. The longer-term goal is to apply the findings to developing appropriate preventive measures against diseases for Okinawa people.Changes in disparity between age-adjusted overall mortality of male populations of Okinawa and Japan nationwide during a 15-year period, between 1985 and 2000, were measured and difference-change contribution proportions for age-adjusted overall mortality were computed.Causes of death that showed high difference-change contribution proportions included cerebral infarction (24.26%), cardiac failure (18.45%), other cerebrovascular diseases (15.11%), malignant gastric neoplasms (11.89%), ischemic heart disease (11.06%), hepatic disease (10.93%), suicide (5.71%), and diabetes (5.36%). Of these, cerebral infarction, cardiac failure, other cerebrovascular diseases, malignant gastric neoplasm, ischemic heart disease, and diabetes indicated high difference-change contribution proportions among seniors 65 years old and above, while hepatic disease and suicide ranked highly among the middle-aged.The results of this study revealed the extent of age and cause of death contributions to the decreasing disparity observed between populations of Okinawa and Japan nationwide in male age-adjusted overall mortality. The causes of death and the age revealed by this study are critical to taking preventive measures against diseases. Moreover, this study confirmed that the difference-change contribution proportion is a useful method to quantify contributions of age and cause of death to changes in variation regarding life expectancy.

We examined a clinical database for patients receiving financial aid for treatment to elucidate age at onset of intractable disease.Data were obtained from the clinical database of patients receiving financial aid for treatment in 2003. Age at onset of disease was calculated by subtracting the year of birth from the year of onset as registered in the database. Percentiles for age at onset and peak onset age were evaluated for each intractable disease. Peak onset ages for primary immune-deficiency syndrome, subacute sclerosing panencephalitis, lysosomal diseases, epidermolysis bullosa and neurofibromatosis I and II were under 20 years.Peak onset ages for aortitis syndrome, systemic lupus erythematosus, Behcet's disease, adrenoleukodystrophy, multiple sclerosis, ulcerative colitis and Crohn's disease were between 20 and 50. Distributions of age at onset for aplastic anemia, idiopathic thrombocytopenic purpura, myasthenia gravis, moyamoya disease and sarcoidosis were bimodal. Peak onset age for many other diseases wereor = 40 years.Using a clinical database for patients receiving financial aid for treatment, the distribution of ages at onset and peak onset ages could be systematically clarified for individual intractable diseases. Our study provides new information on the natural history of disease development.

Nationwide surveys of intractable disease patients receiving public financial aid for treatment were performed by Research Committee for Epidemiology of Intractable Disease (Ministry of Health and Welfare, Japan) 4 times in the past, in 1984, 1988, 1992 and 1997. The purpose of the present study was to clarify the features of continuance with intractable disease patients receiving public financial aid for treatment.Individual information collected by each nationwide survey was linked using the disease, the residence, the sex, and the birth date. The proportion of intractable disease patients according to receipt duration, kind of medical insurance, sex and age was calculated with reference to the disease and an estimation of the receipt persistence rate was calculated for every year. Moreover, in consideration of variation in the data, average receipt persistence rates over years were also calculated.According to observation on individual patient's follow up, the proportion for which financial aid was discontinued within four years was 25%, while 70% continued receiving aid for at least four years and some 55% for eight or nine years. The proportion of those who continue receiving support long-term is high about the so-called autoimmune diseases, such as systemic lupus erythematosus, Behçet's disease, and the aortic syndrome. In contrast, with diseases having a poor prognosis, such as fulminant hepatitis, amyloidosis, and amyotrophic lateral sclerosis, periods of continuance are short. The proportion needing long-term continuation is higher in women than in men, especially with diseases which have long been eligible for support. However, with diseases for which receipt was started recently, there is a tendency for persistence to be higher in men than in women.With reform of insurance systems, including the medical system for intractable diseases, it is predicted that receipt continuation will change with alteration of social factors, and it is necessary to monitor receipt continuation carefully from now on.

Background: We report a patient who was diagnosed as having steroid-induced glaucoma after radial keratotomy (RK) and who suffered from severe visual field defect. Case: A 29-year-old man underwent RK for both eyes. After the operation, he was treated for six months with topical medication including 0.1% and 0.01% betamethasone without an intraocular pressure (IOP) measurement. When he consulted an ophthalmologist, his IOP was 43 mmHg in the right eye and 51 mmHg in the left eye. At our initial examination, his IOP was 8 mmHg in the right eye and 10 mmHg in the left eye. He was taking 750 mg acetazolamide peroral, 0.5% timolol maleate, and latanoprost eyedrops. There were 16 RK incisions on the cornea and we found severe glaucomatous visual field loss. Finally we performed trabeculotomy in both eyes for IOP control with conservative therapy. Conclusion: As keratorefractive surgery becomes popular, we must be alert for problems, such as steroid-induced glaucoma, and the change in refraction following the change in IOP. Nippon Ganka Gakkai Zasshi

To examine rural-urban differences in the relationships of sociodemographic, social network, and lifestyle factors to mortality in middle-aged men, we used the data from a community based prospective cohort study, the Komo-Ise study. The subjects were all men aged 40-69 years living in Komochi Village, the rural group (n=2,295), or the downtown district of Isesaki City, the urban group (n=3,334), as of 1993. They completed a self-administered questionnaire in 1993 and were followed for all-cause deaths until 2000. The Cox proportional hazards model was used to compute relative risks (RRs) with 95% confidence intervals (CIs). Low educated men and men without a spouse in the rural group had an increased risk of mortality (RR=4.4; 95%CI: 1.1-18.2, RR=2.4; 95%CI: 1.2-4.5). Men who did not enjoy good fellowship with their neighbors in the rural group had a decreased risk of mortality (RR=0.58; 95%CI: 0.35-0.97). Mortality risks were significantly higher in urban men not participating in hobbies, club activities or community groups (RR=1.6; 95%CI: 1.1-2.4). These variables remained significant risk factors, even after controlling for all sociodemographic, social network, lifestyle, and health status variables. Educational level, marital status and relation to neighborhoods showed significant rural-urban differences.

Ultrasound biomicroscopy(UBM) was performed on filtering blebs with laser treatment including laser gonioplasty(GP), laser iridotomy(LI), and YAG laser trabeculopuncture(YLT) after non-penetrating trabeculectomy(NPT). The filtering blebs were grouped into four types, L, H, E and F, and the spaces under the scleral flap were classified into three. La, S, and N.In case 1, an F type, an S bleb was not changed despite laser treatment 9 months after NPT. In case 2, YLT was performed twice to release the incarcerated iris. The filtering bleb was changed to the L type, an La bleb. In case 3, an F type, an S bleb was turned into an H type after GP, LI, and YLT. In case 4, GP effectively released peripheral anterior synechia formation and the filtering bleb was kept as an L type, La.Appropriate laser treatment may be effective in turning a flattened and localized bleb into a good filtering bleb.

Background We report a patient with persistent hyperplastic primary vitreous(PHPV) who presented with acute angle-closure glaucoma in his adult life. Case A 30-year-old man had an attack of acute angle-closure glaucoma associated with retrolenticular fibrous tissue, atrophic retina, and elongated cilliary process in his right eye. Result Ultrasound biomicroscopy(UBM) study showed iris bowing, shallow anterior chamber, and elongated cilliary body which were being pulled by the retrolenticular mass. The posterior chamber was normal. Conclusion Although the mechanisms of secondary angle-closure glaucoma in PHPV are complicated, we suspected pupillary block resulting from constriction by the retrolenticular mass in this case.

To examine the relationship between lifestyle and sociodemographic risk factors and mortality, a population-based prospective cohort study was conducted in two areas of Gunma Prefecture, Japan, and a cohort consisting of 11,565 subjects aged 40-69 at baseline in 1993 was followed. During the five-year follow-up period, 201 men and 103 women died. The relative risks (RRs) of risk factors were estimated by the Cox proportional-hazards model. Significant RRs with multivariate adjustment for all-cause mortality was observed for body mass index (BMI). The curve for the relationship between BMI and all-cause mortality was L-shaped in men and U-shaped in women, with the lowest RRs at a BMI of 22-25 in both men and women. Other significant RRs for all-cause mortality were observed for obesity in the subjects' 30's in both men and women (RR: 2.42 and RR: 2.75), poor perceived health status in men (RR: 4.55), and having had a health examination in the past three years in both men and women (RR: 0.49 and RR: 0.46). These results suggested that increased risk of death was independently associated with a lower BMI, obesity in the subjects' 30's, and not undergoing health examinations, among both men and women, and poor perceived health status among men.

The ability of irreversible acylcarnitine-transferase inhibitors, sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) and 2-tetradecyl-glycidic acid (TDGA), to reduce myocardial ischemic injury was studied in Langendorff-perfused hearts exposed to ischemia (zero mmHg) followed by aerobic reperfusion (60 mmHg). Rat hearts were pretreated with either POCA (15 mg/kg) or TDGA (5 mg/kg) s.c. 120 min before the perfusion. Treated hearts showed a decreased release of creatine kinase and lactate on reperfusion after 30 min ischemia. POCA-treated hearts showed significantly higher ATP concentrations than control hearts on reperfusion. POCA also improved the maximum recovery of the pressure-rate product but with a significant delay. During the ischemic period, though, POCA decreased the ATP concentration at a rate three times that of controls during the first 10 min. No further reductions were observed for up to 30 min of ischemia. TDGA also showed a reduction of ATP. Thus, the observation that POCA stimulated ATP synthesis and reduced creatine kinase release on reperfusion after ischemia suggests that this agent provides some protection to the ischemic myocardium. However, during ischemia, it is likely that the depletion of ATP concentration induced by POCA resulted in delayed recovery of mechanical function on reperfusion.

Using a Langendorff rat heart preparation, we examined effects of nicardipine, a calcium channel blocker, on different stages of ischemic damage, characterized by a development of contracture and leakage of intracellular enzymes. Maximum recoveries of heart rate (HR) and peak left ventricular pressure-HR product after 20 min ischemia were attenuated by about 25% compared with those before ischemia. When nicardipine (0.1 mumol) was added to the perfusate 5 min prior to ischemia, this mechanical failure recovered completely to the pre-ischemic level. Although a significant increase in left ventricular end-diastolic pressure was observed in hearts exposed to 30 min ischemia, the amount of creatine kinase (CK) released during re-flow after 30 min ischemia was not enhanced by contracture but was proportional to the duration of ischemia (compared with that of 20 min ischemia). Nicardipine reduced CK leakage by 25% after 30 min ischemia but did not alter either ATP levels or coronary flow. The beneficial effects of nicardipine on ischemic damage are probably related to inhibition of calcium influx (Terai et al: Biochem Pharmacol 30: 375, 1981), which may accompany reperfusion of ischemic myocardium.

Time-course studies of 3H-choline incorporation into adrenal phospholipids revealed that the specific radioactivity reached to a maximum level at 9 hr after the isotope injection in untreated control animals, while in ACTH-treated animals, a maximum incorporation was already attained by 2 hr postinjection. The effect of ACTH on the incorporation was relatively prompt, the effect became evident as early as 1.5 hr after the treatment of animals. The rate of the incorporation in ACTH-treated animals was about twice that of the control. The incorporated radioactivity was decreased with the half-life of 2.9 days in phospholipids of control adrenals. On the other hand, the incorporated choline was well retained in adrenals of animals which receive daily treatment with ACTH throughout the experimental period of 7 days. The rate of phospholipid exchange between liver microsomes and adrenal mitochondria was not markedly influenced by treatment of animals with ACTH. Physiological implications of these observations were discussed.