Comparison of SGLT2 inhibitors vs. DPP4 inhibitors for patients with metabolic dysfunction associated fatty liver disease and diabetes mellitus.

PURPOSE: This study aimed to examine the potential benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and diabetes mellitus (DM) using a real-world database. METHODS: We analyzed individuals with MAFLD and DM newly initiated on SGLT2 or dipeptidyl peptidase 4 (DPP4) inhibitors from a large-scale administrative claims database. The primary outcome was the change in the fatty liver index (FLI) assessed using a linear mixed-effects model from the initiation of SGLT2 or DPP4 inhibitors. A propensity score-matching algorithm was used to compare the change in FLI among SGLT2 and DPP4 inhibitors. RESULTS: After propensity score matching, 6547 well-balanced pairs of SGLT2 and 6547 DPP4 inhibitor users were created. SGLT2 inhibitor use was associated with a greater decline in FLI than DPP4 inhibitor use (difference at 1-year measurement, - 3.8 [95% CI - 4.7 to - 3.0]). The advantage of SGLT2 inhibitor use over DPP4 inhibitor use for improvement in FLI was consistent across subgroups. The relationship between SGLT2 inhibitors and amelioration of FLI was comparable between individual SGLT2 inhibitors. CONCLUSIONS: Our analysis using large-scale real-world data demonstrated the potential advantage of SGLT2 inhibitors over DPP4 inhibitors in patients with MAFLD and DM.

Factors that predict in-hospital mortality in eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic small-vessel vasculitis associated with asthma, eosinophilia, and necrotizing vasculitis. EGPA is potentially life-threatening and often involves peripheral neuropathies, peptic ulcers, cerebral vessel disease, and cardiovascular disease. However, there is limited understanding of the prognostics factors for patients with EGPA. We investigated the clinical features and factors affecting patients' in-hospital mortality, using a national inpatient database in Japan. METHODS: We retrospectively collected data of EGPA patients who required hospitalization between July 2010 and March 2013, using the Diagnosis Procedure Combination database. We evaluated EGPA patients' characteristics and performed multivariate logistic regression analyses to assess the factors associated with in-hospital mortality. RESULTS: A total of 2195 EGPA patients were identified. The mean age was 61.9 years, 42.1% (924/2195) were male, and 41.6% (914/2195) had emergent admission. In-hospital deaths occurred in 97/2195 patients (4.4%). Higher in-hospital mortality was associated with age older than 65 years, disturbance of consciousness on admission, unscheduled admission, respiratory disease, cardio-cerebrovascular disease, renal disease, sepsis, and malignant disease on admission. Lower mortality was associated with female gender and peripheral neuropathies. CONCLUSIONS: Our study revealed the clinical features of EGPA patients who required hospitalization and the factors associated with their mortality. These results may be useful for physicians when assessing disease severity or treatments for hospitalized EGPA patients.

The modulation of large airway smooth muscle phenotype and effects of epidermal growth factor receptor inhibition in the repeatedly allergen-challenged rat.

Allergen challenges induce airway hyperresponsiveness (AHR) and increased airway smooth muscle (ASM) mass in the sensitized rat. Whether the remodeled ASM changes its phenotype is uncertain. We examined, in sensitized Brown Norway rats, the effects of multiple ovalbumin (Ova) challenges on ASM remodeling and phenotype and the role of the epidermal growth factor receptor (EGFR) in these processes. Rats were sensitized with Ova and challenged three times at 5-day intervals with phosphate-buffered saline or Ova and pretreated with the EGFR inhibitor AG-1478 (5 mg/kg) or its vehicle dimethyl sulfoxide. Ova challenges increased ASM mass in all-sized airways and in large airway mRNA expression of smooth muscle myosin heavy chain (sm-MHC), assessed by laser capture. Myosin light chain kinase and the fast myosin isoform SM-B mRNA expressions were not affected. Ova induced AHR to methacholine, and, based on the constant-phase model, this was largely attributable to the small airways and lung derecruitment at 48 h that recovered by 1 wk. The EGFR ligands amphiregulin and heparin-binding epidermal growth factor (HB-EGF) were increased in bronchoalveolar lavage fluid at 48 h after Ova exposure. AG-1478 inhibited AHR and prevented ASM growth. Epithelial gene expression of EGFR, HB-EGF, matrix metalloproteinase (MMP)-9, Gro-α, and transforming growth factor-ß was unaffected by Ova challenges. We conclude that EGFR drives remodeling of ASM, which results from repeated Ova challenge. Furthermore, the latter results in excessive small airway and, to a lesser degree, large airway narrowing to methacholine, and large airway gene expression of contractile protein is conserved.

Prediction of outpatient visits and expenditure under the Universal Coverage Scheme in Bangkok using subscriber's attributes: A random forest analysis.

Objectives: There is limited evidence on methods to allocate budgets to healthcare providers under capitation schemes. The objective of this study was to construct and test models that predict outpatient visits and expenditure for each healthcare facility using subscriber data from the preceding year. Study design: We used the database of the Universal Coverage Scheme in Bangkok, Thailand that stores subscriber information and healthcare service utilization data. One-percent and ten-percent random samples of subscribers were selected as training and testing groups, respectively. Methods: Using data of the training group, we constructed a model using a random forest algorithm to predict outpatient visits and expenditure in 2017 from the 2016 data. The model was applied to the testing group and facility-level predicted number of visits and expenditure were compared with actual data. Results: The identically-structured training and testing groups consisted of 37,259 and 371,650 subscribers, respectively. Approximately 25% of subscribers utilized outpatient services. The R2 for models predicting facility-level utilization rate (visits/subscribers) and expenditure per subscriber in 2017 were 0.85 and 0.75, respectively. Conclusions: The model to predict outpatient visits and expenditure performed well. Such a prediction model may be useful for allocating budgets to healthcare facilities under capitation systems.

A multi-centre, retrospective case series of oocyte cryopreservation in unmarried women diagnosed with haematological malignancies.

STUDY QUESTION: Is oocyte cryopreservation an applicable option for fertility preservation in unmarried patients with haematological malignancies? SUMMARY ANSWER: Oocyte cryopreservation via the vitrification method is accessible and may be considered an option for fertility preservation in unmarried patients with haematological malignancies. WHAT IS KNOWN ALREADY: Haematological malignancies are most commonly observed amongst adolescent and young adult women. Although the survival rate and life expectancy of those with haematological malignancies have improved, chemotherapy and radiotherapy may impair their reproductive potential. Oocyte cryopreservation is thus an ideal option to preserve their fertility. STUDY DESIGN SIZE DURATION: This study retrospectively evaluated 193 unmarried patients (age: 26.2 ± 0.4 years) with haematological malignancies, who consulted for oocyte cryopreservation across 20 different fertility centres in Japan between February 2007 and January 2015. The primary outcome measures were the oocyte retrievals and oocyte cryopreservation outcomes. The secondary outcome measures were the outcomes following oocyte warming for IVF. PARTICIPANTS/MATERIALS SETTING METHODS: The patients had commenced ovarian stimulation cycles via antagonist, agonist, natural and minimal methods for oocyte retrievals, defined according to the treatment strategy of each respective fertility centre. A vitrification method using the Cryotop safety kit was used for oocyte cryopreservation. ICSIs were used for insemination of warmed oocytes. The endometrial preparation method for embryo transfer was hormonal replacement therapy, except in the case of a patient who underwent a spontaneous ovulatory cycle. MAIN RESULTS AND THE ROLE OF CHANCE: Among 193 patients, acute myeloid leukaemia (n = 45, 23.3%) was most common, followed by acute lymphoid leukaemia (n = 38, 19.7%) and Hodgkin's lymphoma (n = 30, 15.5%). In total, 162 patients (83.9%) underwent oocyte retrieval, and oocytes were successfully cryopreserved for 155 patients (80.3%). The mean number of oocyte retrieval cycles and cryopreserved oocytes were 1.7 ± 0.2 and 6.3 ± 0.4, respectively. As of December 2019, 14 patients (9.2%) had requested oocyte warming for IVF. The survival rate of oocytes after vitrification-warming was 85.2% (75/88). The rates of fertilisation and embryo development were 80.0% (60/75) and 46.7% (28/60), respectively. Ten patients (71.4%) had successful embryo transfers, and seven live births (50.0%) were achieved. LIMITATIONS REASONS FOR CAUTION: This study was limited by its retrospective nature. Additionally, there remains an insufficient number of cases regarding the warming of vitrified oocytes to reliably conclude whether oocyte cryopreservation is effective for patients with haematological malignancies. Further long-term follow-up study is required. WIDER IMPLICATIONS OF THE FINDINGS: Oocyte retrieval and oocyte cryopreservation were accessible for patients with haematological malignancies; however, the number of oocyte retrievals may have been limited due to the initiation of cancer treatments. Acceptable embryonic and pregnancy outcomes could be achieved following oocyte warming; therefore, our results suggest that oocyte cryopreservation can be considered an option for fertility preservation in patients with haematological malignancies. STUDY FUNDING/COMPETING INTERESTS: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Safety studies conducted on a proprietary high-purity aloe vera inner leaf fillet preparation, Qmatrix.

The aloe vera plant has a long history of safe use for oral and topical applications. This publication describes safety studies conducted on a proprietary high-purity aloe vera inner leaf fillet preparation, Qmatrix. In a 13-week study in rats, Qmatrix was administered via gavage at 0, 500, 1000 and 2000 mg/kg body weight (bw)/day. There were no significant changes in food or water consumption, body weight, serum biochemistry or hematology at any of the doses tested. Sporadic, significant increases were observed in some of the measured urinalysis parameters; however, these variations were not treatment-related, as most were observed only in one sex, not dose-dependent and within historical control values. Organ weights were unaffected, except for a statistically significant, though not dose-dependent, increase in absolute and relative weights of the right kidney in males at 500 and 2000 mg/kg bw/day, respectively. Histopathological analysis revealed no abnormal signs. Qmatrix was non-mutagenic in an Ames test and a chromosomal aberration test at concentrations up to 10,000 microg/plate, and in an in vivo bone marrow micronucleus test at doses up to 5000 mg/kg bw/day. Based on these results, Qmatrix is not genotoxic in vitro or in vivo and; has an oral NOAEL greater than 2000 mg/kg bw/day following 90 days of oral exposure.

The epidermal growth factor receptor mediates allergic airway remodelling in the rat.

The chronicity of bronchial asthma is attributed to persistent airway inflammation and to a variety of structural changes, or remodelling, that includes smooth muscle and goblet cell hyperplasia. To investigate the mechanisms of airway remodelling, the current authors used an established allergen (ovalbumin; OVA)-driven rodent model (the Brown Norway rat). Brown Norway rats were sensitised to OVA and challenged three times at 5-day intervals to evoke airway remodelling. The effects of an epidermal growth factor (EGF) receptor inhibitor, AG1478, and a cysteinyl leukotriene-1 receptor antagonist, montelukast, on epithelial and airway smooth muscle (ASM) cell proliferation in vivo in response to repeated OVA challenge were tested. Three challenges with leukotriene (LT)D(4) were given, to examine their effects on remodelling with and without AG1478 pretreatment. OVA challenges caused ASM hyperplasia, with an increase in mass, epithelial cell proliferation and goblet cell proliferation. AG1478 prevented the changes, as did montelukast. Multiple OVA challenges increased heparin-binding EGF-like growth factor but not EGF expression by airway epithelium. LTD(4) reproduced the changes in remodelling induced by OVA and this was blocked by AG1478. Allergen-induced airway epithelial and airway smooth muscle remodelling is mediated by cysteinyl leukotrienes via the cysteinyl leukotriene-1 receptor with downstream effects on the epidermal growth factor receptor axis.

Interleukin-1 (IL-1)-induced IL-6- and IL-6-receptor-mediated release of human chorionic gonadotropin by choriocarcinoma cell lines (Jar and HCCM-5) activates adenosine 3',5'-monophosphate-independent signal transduction pathway.

The status of preservation of the ability to secrete cytokines, such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF alpha), and IL-6, and the cytokine-mediated regulatory cascade was investigated in four choriocarcinoma cell lines. Each cell line constitutively produced IL-6, but not IL-1 alpha, IL-1 beta, or TNF alpha. Jar and HCCM-5 cells responded to IL-6, releasing hCG by direct activation of IL-6 receptors (IL-6-R) with IL-6. Both cell lines also responded to IL-1, but failed to responded to TNF alpha. When stimulated with recombinant IL-1 alpha, both cell lines released IL-6 and activated the IL-6-R system to release hCG, whereas stimulation with TNF alpha failed to release hCG. The experiments showed that both the Jar and HCCM-5 cell lines possessed a partially intact cytokine-mediated cascade, suggesting that IL-1-induced IL-6 release and IL-6-R activation operate in an autocrine manner. In contrast, NUC-1 and SCH cells failed to respond to IL-6, IL-1, or TNF alpha. Although 8-bromo-cAMP, which is a cAMP analog, stimulates hCG release by Jar cells, it failed to stimulate IL-6 release. Moreover, cAMP-mediated hCG release was not blocked by PM1, an anti-IL-6-R antibody. This suggests that elevation of the cytoplasmic cAMP level might activate a pathway different from the IL-6- and IL-6-R-dependent pathway. Moreover, IL-1- and IL-6-mediated hCG release was not blocked by H8, a cAMP-dependent kinase inhibitor, which further suggests that the IL-1- and IL-6-mediated pathway functions independently of the cAMP-dependent pathway in releasing hCG in Jar cells.

Trophoblast-derived transforming growth factor-beta 1 suppresses cytokine-induced, but not gonadotropin-releasing hormone-induced, release of human chorionic gonadotropin by normal human trophoblasts.

Using a transforming growth factor-beta (TGF beta)-sensitive cell line, Mv1Lu (or CCL 64), we demonstrated that trophoblasts predominantly produced a latent form of TGF beta. After converting latent TGF beta to active TGF beta in vitro by acid (pH 2.5), alkali (pH 10.0), or heat (90 C; 10 min) treatment, addition of rabbit anti-TGF beta 1 antiserum resulted in the elimination of TGF beta activity, thus suggesting that trophoblasts produced at least a certain amount of latent TGF beta 1. To investigate the role of TGF beta 1 in placental hormonogenesis, we first studied the effect of recombinant (r) TGF beta 1 on the production of interleukin-6 (IL-6) and hCG by trophoblasts. rTGF beta 1 exerted no inhibitory activity on IL-6 and hCG production. The effect of rTGF beta 1 on cytokine-induced IL-6 and hCG release was then examined. While rTGF beta 1 failed to inhibit basal hCG secretion, it did inhibit recombinant tumor necrosis factor-alpha (rTNF alpha)-induced IL-6 release as well as rTNF alpha- and rIL-6-induced hCG release in a dose-dependent manner. However, rIL-1 alpha-induced IL-6 and hCG release was remarkably sensitive to rTGF beta 1-mediated suppression. In contrast, GnRH-induced hCG release, the response of which is independent of the IL-6 and IL-6 receptor system in trophoblasts, was completely resistant to rTGF beta 1. Thus, trophoblast-derived TGF beta 1 is an important regulatory molecule of cytokine-dependent, but not cytokine-independent, hCG release, possibly by converting latent TGF beta to active TGF beta at the local site of trophoblasts.

Inhibitory effects of estrogen, progesterone, androgen and glucocorticoid on death of neonatal mouse uterine epithelial cells induced to proliferate by estrogen.

Female newborn mice were given daily injections of estradiol-17 beta (E2; 25 micrograms/mouse/day) for 4 days from the day of birth, and uterine cell death after this E2 priming was investigated by examining the apoptotic index (percentage of apoptotic cells), and the retention of 3H-radioactivity incorporated into epithelial or stromal DNAs after injection of [3H]thymidine into the mice on the day after birth. With injections of vehicle only after E2 priming, the apoptotic index of the uterine epithelium increased markedly, being maximal on day 4 of injections, and the 3H-radioactivity retained in the epithelium decreased rapidly. Agarose gel electrophoresis of uterine epithelial DNAs on day 4 of injections showed a ladder pattern, characteristic of apoptotic cell death. However, daily injections of E2 (7.2 micrograms/g body wt) completely inhibited the increase in the apoptotic index and the loss of 3H-radioactivity in the epithelium. Daily injections of progesterone (80 micrograms/g body wt), 5 alpha-dihydrotestosterone (DHT; 8 micrograms/g body wt), and dexamethasone (2 micrograms/g body wt) also inhibited both parameters, although not completely. The inhibitory effects of DHT and progesterone were abolished by the antiandrogen, flutamide and antiprogesterone, RU 486, respectively. In contrast, no apoptotic cells and no loss of 3H-radioactivity were found in the stroma for any treatment after E2 priming. The present results suggest that discontinuation of estrogen stimulation results in apoptotic cell death in the uterine epithelium of neonatal mice, but not in the stroma, and that estrogen, progesterone, DHT and dexamethasone inhibit cell death of uterine epithelium.

Cytotoxic actions of cytokines on cultured mouse luteal cells are independent of nitric oxide.

We investigated the cytotoxic effects of various cytokines secreted by macrophages or T lymphocytes on luteal cells, and the role of nitric oxide (NO) produced by luteal cells in cytotoxic actions of cytokines. Mouse luteal cells were cultured in serum-free medium with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta) alone, or with various combinations of these cytokines for 6 days. Cytotoxic actions of cytokines and NO production by luteal cells were evaluated by number of viable cells and the amount of nitrite and nitrate (stable metabolites of NO) in medium, respectively. IFN-gamma (1000 U/ml), TNF-alpha (3000 U/ml), or IL-1 beta (30 U/ml) alone, and the combination of TFN-alpha and IL-1 beta (10 U/ml) did not decrease number of viable cells and was without effects on NO production. The combination of IFN-gamma and IL-1 beta (10 U/ml) also did not decrease the number of viable cells, while it increased NO production a little but significantly. Combinations of INF-gamma and TNF-alpha, and IFN-gamma, TNF-alpha and IL-1 beta (10 U/ml) markedly decreased number of viable cells. The combination of IFN-gamma and TNF-alpha increased NO production a little but significantly, and the combination of three cytokines (IFN-gamma, TNF-alpha, and IL-1 beta) caused a greater increase in NO production. An NO synthase inhibitor, L-NG-monomethy-L-arginine (0.5 mM) or aminoguanidine (0.5 mM) abolished increases in NO production induced by combinations of IFN-gamma and TNF-alpha, and IFN-gamma, TNF-alpha and IL-1 beta completely without effects on number of viable cells. The present results indicate that combinations of cytokines including IFN-gamma and TNF-alpha induce death of cultured mouse luteal cells, and that the cytotoxic actions of these cytokines are independent of NO production by luteal cells.

Plasma M-CSF as an indicator of response to chemotherapy in adult T cell leukemia patients.

The plasma concentration of macrophage colony-stimulating factor (M-CSF) was measured in 10 patients with acute type adult T cell leukemia (ATL) during the clinical course before and after chemotherapy. M-CSF concentration decreased significantly when the patients achieved complete remission (CR) or partial remission (PR) (t-test: p = 0.0001). Five of the patients showed disease progression after several months of PR, and plasma M-CSF increased at that time (t-test: p = 0.0456). Thus, plasma M-CSF concentration appeared to accurately reflect the disease activity in ATL. In support of these results, all three ATL cell lines established from these patients secreted M-CSF in vitro after stimulation with phorbol myristate acetate (PMA) or concanavalin A (Con A). Plasma M-CSF concentration, however, increased transiently when the patients were febrile (t-test: p = 0.0001), even though their ATL condition was unchanged. Taken together, these results indicate that there are two sources of increased plasma M-CSF concentration in ATL; ATL cells themselves and normal parenchymal cells that cause this increase as the result of elevated body temperature due to inflammation.

Oral administration of tritiated water (HTO) in mouse. II. Tumour development.

Previously we reported haematopoietic death as an effect of tritiated water (HTO) in drinking water in the concentration range from 5.92 x 10(11) to 1.85 x 10(10) Bq/dm3. In the present study the effects of HTO in a lower concentration range from 9.25 x 10(9) Bq/dm3 (0.240 Gy/day) to 3.70 x 10(8) Bq/dm3 (0.096 Gy/day) are reported. Female (C57BL/6N and C3H/He)F1 mice were maintained on drinking water containing various levels of HTO. Mice survived for > 150 days with a high incidence of tumour development (70 to 80%). In the dose-rate range from 9.25 x 10(9) Bq/dm3 (0.240 Gy/day) to 1.85 x 10(9) Bq/dm3 (0.048 Gy/day) the main cause of death was thymic lymphoma. However, at a dose-rate of 9.25 x 10(8) Bq/dm3 (0.024 Gy/day) the incidence of thymic lymphoma sharply decreased, while the incidence of other tumours increased. The tumour type became more diverse at lower concentrations of HTO. The latent period of tumour development was shorter and the life-shortening effect was more marked by 3H beta-irradiation in this study than b X- or gamma-irradiation reported in other investigations.

RBE of HTO to 60Co gamma-rays for cell killing of a radioresistant E. coli harboring plasmid.

Radioresistant E. coli TGl harboring pUC 18 plasmid which was Ampicillin-resistant was exposed to 60Co gamma-rays or 3H beta-rays in saline to determine whether the relative biological effectiveness of 3H beta-rays is higher than one. After exposure to 60Co gamma-rays at a dose rate of 0.465 Gy/min, the D0 by colony formation was 145 Gy in the presence of Ampicillin in or absence from the agar medium; whereas, the D0 was calculated as 118 Gy with and without Ampicillin after exposure to 3H beta-rays at a dose rate of 0.431 Gy/min. The relative biological effectiveness established for 3H beta-rays to 60Co gamma-rays was 1.23. The reason for the higher effectiveness of 3H beta-rays as compared to the reference 60Co gamma-rays is discussed in terms of nascent 0 production.

Maternal or umblical venous levels of nitrite/nitrate during pregnancy and at delivery.

OBJECTIVE: This study was intended to measure serum concentrations of nitrite plus nitrate as an index of nitric oxide synthesis, in the maternal vein during pregnancy, just after a spontaneous delivery and at the puerperium, and at an elective cesarean section, and in the umblical vein and artery. METHODS: Maternal venous sera, and umblical venous and arterial sera were collected, and serum concentrations of nitrite/nitrate were measured by an automated procedure based on the Greiss reaction after reduction of nitrate to nitrite. RESULTS: Compared to a serum concentration of nitrite/nitrate at the first trimester (12-13 weeks of pregnancy), a serum concentration of nitrite/nitrate slightly increased at the second trimester (27-28 weeks), and became maximal at the third trimester (35-36 weeks), followed by a significant decrease near the term (38-40 weeks). A serum concentration of nitrite/nitrate slightly increased just after a spontaneous delivery with labor pains, and at the puerperium to levels slightly more than that at the first trimester. Serum concentrations of nitrite/nitrate in the umblical vein and artery did not differ. They were significantly higher than a serum concentration of nitrite/nitrate in the maternal vein just after a spontaneous delivery with labor pains but not at an elective cesarean section without labor pains. CONCLUSION: A decrease in maternal serum levels of nitrite/nitrate near term may support a hypothesis that NO is one of factors responsible for the maintenance of uterine quiescence during pregnancy. Moreover, the present results suggest that NO plays some role in the feto-placental circulation during a spontaneous delivery.

A case of beta-thalassemia with a C----T substitution at position 654 of the second intervening sequence of the beta-globin gene.

A 26-year-old Chinese-Malaysian female patient with beta-thalassemia is presented. The main hematological values found in this patient were as follows: 1) normocytic hypochromic anemia (RBC 444 x 10(4)/microliters, Hb 11.8 g/dl) with marked anisopoikilocytosis, 2) erythroid hyperplasia, and 3) increased HbF (HbA 41.4%, HbA2 2.9%, HbF 48.9%). DNA obtained from peripheral leukocytes was analyzed using dot blot hybridization of the polymerase chain reaction (PCR)-amplified DNA with allele-specific oligonucleotide probes. A C----T substitution at position 654 of the second intervening sequence (IVS-2) was detected in her beta-globin clone.

Kawasaki disease complicated by acute myocardial infarction due to thrombotic occlusion of coronary aneurysms 19 years after onset.

A 25-year-old man with a history of Kawasaki disease from the age of 7 had acute inferior myocardial infarction. Emergency right coronary arteriogram showed successive coronary aneurysms at the proximal to middle portion of the right coronary artery, and total occlusion at the proximal segment. Intracoronary thrombolysis was performed and the right coronary artery was recanalized. On left coronary arteriography, coronary aneurysms and mild localized stenoses at the inlet and outlet of the aneurysms were found. It was suggested that the myocardial infarction was caused by thrombotic occlusion of coronary aneurysms complicated with Kawasaki disease.

Apoptosis of acinar cells in the pancreas of rats fed on a copper-depleted diet.

Male Fischer 344 rats weighing 80-90 g were fed on a copper-depleted diet supplemented with 0.6% triethylenetetramine tetrahydrochloride (a copper chelator), and the death of pancreatic acinar cells of these rats was investigated morphologically and biochemically. The weight of the pancreas of these rats decreased from 3 weeks after feeding, and concomitantly the percentage of dead acinar cells increased to the maximum in about the 5th week and decreased subsequently. These dead acinar cells showed light microscopic and electron microscopic characteristics of apoptosis. Furthermore, the electrophoretic pattern of DNAs extracted from the pancreas having many dead acinar cells showed a ladder-like distribution, characteristic of apoptosis. The present results indicate that feeding of rats on a copper-depleted diet supplemented with a copper chelator results in apoptosis of acinar cells of the pancreas.

Chronic appendicitis diagnosed preoperatively as an ovarian dermoid.

Recurrent right lower quadrant pain in young women can be a diagnostic dilemma. Chronic appendicitis is often mistakenly excluded from the differential diagnosis. In the present case, pelvic inflammatory disease was diagnosed in a 19-year-old woman with bilateral lower abdominal pain (greater on the right than the left), fever, and elevated white blood cell count. She was treated with intravenous antibiotics until resolution of symptoms. The pain recurred 1 month later, and the patient presented to our emergency department. At that time, she was afebrile and all laboratory results were normal or negative, aside from an elevated white blood cell count. Computed tomography suggested a right ovarian dermoid. At laparoscopy, however, the right tube and ovary were normal, and chronic appendicitis was confirmed. Although computed tomography is often accurate for delineating the cause of pelvic abnormality, it also may be misleading.