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Although population characteristics and antimicrobial prescribing practices suggest that the hospitalized population in Japan is at high risk of Clostridioides difficile infection (CDI), the epidemiology of CDI in Japan is poorly understood.This prospective cohort study aimed to investigate the epidemiology of CDI at 12 hospitals in Japan.Patients with clinically significant diarrhoea (CSD) were enrolled. Stool specimens were tested for C. difficile by toxin A and/or B enzyme immunoassay (EIA) in the hospital laboratories, and a toxigenic culture and nucleic acid amplification tests were performed at a central laboratory. The risk factors of CDI and the impact of CDI on mortality were investigated.In total, 566 patients with CSD were included in the analyses. A total of 152 patients received the diagnosis of CDI by Toxin A/B EIA, toxigenic culture, or nucleic acid amplification test. Factors associated with CDI included low albumin (adjusted odds ratio (aOR): 1.56; 95% confidence interval (CI): 1.03-2.34) and length of hospital stay before stool collection18 days (aOR: 1.73; 95% CI: 1.09-2.75). CDI was associated with an increased mortality on univariate analysis (OR: 1.6, 95% CI: 1.0-2.6) but was not associated with an increased risk of mortality on multivariable analysis.Risk factors for CDI in Japan were similar to those identified in the USA and Europe. However, CDI was not associated with an increased risk of mortality in this population of patients with CSD.

Twelve high schools in Japan (of which six are in Fukushima Prefecture), four in France, eight in Poland and two in Belarus cooperated in the measurement and comparison of individual external doses in 2014. In total 216 high-school students and teachers participated in the study. Each participant wore an electronic personal dosimeter 'D-shuttle' for two weeks, and kept a journal of his/her whereabouts and activities. The distributions of annual external doses estimated for each region overlap with each other, demonstrating that the personal external individual doses in locations where residence is currently allowed in Fukushima Prefecture and in Belarus are well within the range of estimated annual doses due to the terrestrial background radiation level of other regions/countries. © 2016 IOP Publishing Ltd.

We examined whether topical administration of a bisphosphonate clodronate could prevent alveolar bone loss in rats with experimental periodontitis.On day 0, elastic rings were placed around the cervix of the right and left maxillary first molars (M1) to induce inflammatory periodontitis. Fifty microl of clodronate solution at a concentration of either 0 (0.9% NaCl), 20, 40, or 60 mM was injected into the subperiosteal palatal area adjacent to the interdental area between M1 and M2 on either the left or right (experimental) side on days 0, 2, 4, and 6. The contralateral side served as a control and received 0.9% NaCl solution without clodronate. The animals were sacrificed on day 7.Histological examination and determination of bone mineral density in the interdental alveolar bone area between M1 and M2 revealed that placement of an elastic ring caused severe vertical and horizontal bone resorption on the control side, while the topical administration of clodronate significantly prevented such alveolar bone loss. The number of osteoclasts on the experimental side was decreased compared with the control side. Furthermore, many of the osteoclasts on the experimental side were detached from the surface of the alveolar bone and had degenerated appearances, such as rounded shapes and a loss of polarity.These results suggest that topical administration of clodronate may be effective in preventing osteoclastic bone resorption in periodontitis.

The present study was designed to examine whether systemic administration of a bisphosphonate, risedronate, could prevent alveolar bone resorption in rats with experimental periodontitis. On Day 1, an elastic ring was placed around the neck of the right mandibular 1st molar to induce inflammatory periodontitis. The animals were given daily injections of either 0.9% NaCl (control group), or 0.8, 1.6 or 3.2 mumoles/kg (s.c.) of risedronate (experimental groups) from Days 1 to 7, and were killed on Day 8. Histological examinations and determination of bone mineral density in the interdental area between the 1st and 2nd molars with an image analyzer revealed that the presence of the elastic ring induced a loss of attachment and bone resorption in the control group. Vigorous bone resorption, with appearance of a large number of osteoclasts, was observed in the interdental and bifurcation areas. In the experimental groups, however, the resorption of alveolar bone and the loss of bone mineral content in these areas were prevented in a dose-dependent fashion, especially at doses of 1.6 and 3.2 mumoles/kg. Many osteoclasts were detached from the surface of the alveolar bone and had degenerated appearances, such as rounded shapes, loss of polarity and pyknosis. These results suggest that administration of risedronate is effective in preventing bone resorption in periodontitis.

The extracellular polysaccharides (EPS) produced by lactic acid bacteria (LAB) are associated with the rheology, texture, and mouthfeel of fermented milk products, including yogurt. This study investigated the immunomodulatory effects of EPS purified from the culture supernatant of Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) OLL1073R-1. The crude EPS were prepared from the culture supernatant of L. bulgaricus OLL1073R-1 by standard chromatographic methods, and were fractionated into neutral EPS and acidic EPS (APS). Acidic EPS were further fractionated into high molecular weight APS (H-APS) and low molecular weight APS (L-APS). High molecular weight APS were shown to be phosphopolysaccharides containing D-glucose, D-galactose, and phosphorus. Stimulation of mouse splenocytes by H-APS significantly increased interferon-gamma production, and, moreover, orally administered H-APS augmented natural killer cell activity. Oral administration of yogurt fermented with L. bulgaricus OLL1073R-1 and Streptococcus thermophilus OLS3059 to mice showed a similar level of immunomodulation as H-APS. However, these effects were not detected following administration of yogurt fermented with the starter combination of L. bulgaricus OLL1256 and S. thermophilus OLS3295. We conclude from these findings that yogurt fermented with L. bulgaricus OLL1073R-1, containing immunostimulative EPS, would have an immunomodulatory effect on the human body.

In adult human beings, remodeling creates nearly all of new bone tissue. However, Frost hypothesized that modeling can go on in trabeculae throughout life. As this hypothesis has not been verified, we looked for histologic evidence of trabecular modeling (minimodeling) during bone histomorphometry of transiliac bone biopsy specimens obtained from 34 patients (age range, 38-81 years; mean age, 58.4 years; female, 31/34) at the time of total hip arthroplasty. Before the bone biopsy study, we performed quantitative bone scintigraphy of bilateral hip joints and bilateral iliac crests in 10 other patients with unilateral hip disease and confirmed that the bone biopsy site was not affected by ipsilateral hip joint disease. Patients who had metabolic bone diseases or who had taken medications known to affect bone metabolism were excluded from the study. During modeling where bone formation and bone resorption are not coupled, bone formation can occur on quiescent bone surfaces without preceding bone resorption and create smooth cement lines. Therefore, the combination of fluorochrome labeling and a smooth cement line without interruption of surrounding collagen fibers was regarded as evidence of minimodeling. Histologic evidence of minimodeling was detected in 21 of the entire 34 specimens (62%) and 17 of 27 specimens obtained from postmenopausal patients (63%). Bone volume of minimodeling sites was less than 1% of the trabecular bone volume, and these sites accounted for less than 2% of the entire bone surface on average. However, osteoid volume of minimodeling sites comprised approximately one-tenth of the entire osteoid volume, and their labeled surface constituted one-fourth to half of the entire labeled surface on average. Therefore, when performing bone histomorphometry of adult cancellous bone, minimodeling should be taken into account when dealing with parameters related to osteoid volume and mineralization. A comparison of specimens with and without minimodeling demonstrated that the presence of minimodeling was correlated with smaller physique of patients, accelerated mineralization (as indicated by the higher mean MS/BS and MAR values and the shorter mean Omt), and higher metabolic turn-over of bone (as indicated by the higher mean BFR/BV value). Although the findings still need to be verified in a larger number of normal subjects without hip joint disease, they support Frost's hypothesis that minimodeling can continue throughout human life.

Allopurinol is widely used and generally well-tolerated. However, when used in patients with renal insufficiency it may have life-threatening toxic effects known as allopurinol hypersensitivity syndrome (AHS). We previously found that allopurinol increased ear swelling and mortality in a DNFB-induced contact hypersensitivity mouse model. In the present study, we investigated the toxic effect of allopurinol on DNFB-sensitized mice in order to clarify the mechanism responsible for the lethal effect of allopurinol. Allopurinol increased plasma GPT and GOT in DNFB-sensitized mice and markedly increased plasma creatinine and BUN. The increase in plasma GPT and GOT was moderate and declined time-dependently. In contrast, the increase in plasma creatinine and BUN was striking and continued until 18 hr after administration of allopurinol at 100 mg/kg/day. Although allopurinol increased GOT and GPT in DNFB-sensitized mice, no effect was observed in non-sensitized mice even at 100 mg/kg/day, indicating that allopurinol essentially has no toxic effect on the liver. A high dose of allopurinol induced renal impairment even in non-sensitized mice. These observations indicate that there is some biological interaction between allopurinol and DNFB, and suggest that allopurinol may modulate or enhance the inflammatory reactions induced by DNFB, and/or that DNFB may cause metabolic changes via inflammation, leading to the enhanced toxicity of allopurinol. In contrast, TEI-6720, a newly synthesized XOD/XDH inhibitor, had almost no effect on DNFB-sensitized mice. TEI-6720 at 1 mg/kg, in terms of hypouricemic effect, appeared to be more potent than allopurinol at 3 mg/kg. Therefore, the nephrotoxic effect of allopurinol observed in the present study may not be related to XOD/XDH inhibitory activity.

In this study, the hypouricemic efficacy of a novel xanthine oxidase/xanthine dehydrogenase inhibitor, TEI-6720, was compared with that of allopurinol in a hyperuricemic rat model established by feeding the animals oxonate, a uricase inhibitor. In addition, using normal rats, the changes in xanthine concentration in plasma and the concentrations and absolute quantities of uric acid, allantoin and xanthine in urine were analyzed during a 28-day period of repeated administration of TEI-6720 to determine the changes occurring during this period and the conditions required for the formation of xanthine crystals and calculi in comparison with allopurinol. TEI-6720 and allopurinol caused a significant dose-dependent decrease in plasma uric acid levels in the hyperuricemic rat model and the ED50 of TEI-6720 was lower than that of allopurinol, indicating that in terms of hypouricemic efficacy TEI-6720 is more potent than allopurinol. TEI-6720 also showed more potent activity than allopurinol in decreasing urinary uric acid and allantoin levels in normal rats. In addition, TEI-6720 and allopurinol showed similar dose-response curves for the decrease in uric acid or allantoin concentration, and the associated increase in xanthine concentration, indicating that TEI-6720 and allopurinol have similar pharmacological characteristics although the dosage required differs. The efficacy of TEI-6720 in increasing plasma and urinary xanthine levels in normal rats was approximately 10- to 30-fold greater than that of allopurinol. However, with respect to renal xanthine calculus formation, there was only about a 3-fold difference in dosage comparing TEI-6720 and allopurinol. This difference suggests that there may be another factor independent of xanthine, and dependent on the drug itself, involved in renal calculus formation caused by allopurinol. The daily excretion of purine metabolites per body weight was about 20-fold higher in rats than in humans. From these results, it is concluded that TEI-6720 has potent hypouricemic activity and that, compared to allopurinol, administration of TEI-6720 is not likely to result in a higher incidence of calculus formation.

The prognosis for patients with osteosarcoma has improved over the past 20 years, mainly due to developments in chemotherapy. Some proteins have been reported to show drug resistance. Theoretically, overexpression of some of these proteins makes treatment difficult, leading to poorer outcome.Specimens taken from conventional osteosarcomas of the extremity bones from 60 patients younger than 30 years were used. In all cases, preoperative oncostatic chemotherapy was undertaken after biopsy. If available, biopsy specimens were also used for sequential comparison. Among resistance-related proteins, expression of metallothioneins (MTs), glutathione-S-transferase pi (GST pi), heat shock protein 27 (Hsp27), and lung resistance-related protein (LRP) was evaluated immunohistochemically in paraffin sections. The log rank test was used for univariate analysis and the Cox regression model for multivariate analysis.At biopsy, only overexpression of Hsp27 was associated with poor prognosis. At surgery, a relationship was observed between poor prognosis and overexpression of GST pi, Hsp27, and LRP. Groups overexpressing one protein tended to overexpress another. Overexpression of these proteins in surgical specimens also correlated with histologic response to preoperative chemotherapy and clinical stage. In multivariate analysis, Hsp27 overexpression at biopsy was an independent prognostic factor.Inherent overexpression of Hsp27 is independently related to poor outcome in osteosarcoma patients. Overexpression of GST pi, Hsp27, and LRP at surgery might be associated with failure of preoperative chemotherapy. Control of the expression of these proteins may improve the outcome for patients with osteosarcoma.

We described a case of advanced gastric cancer accompanied by metastasis to the periaortic lymph node. Two cycles of the neoadjuvant chemotherapy consisting of 5-FU and low-dose CDDP (FP therapy) were given. 5-FU (800mg/body/day) was administered as a continuous intravenous infusion for five days, and CDDP (10mg/body/day) was given as an intravenous infusion for an hour on days 1-5. The FP therapy resulted in a significant effect in the metastatic periaortic lymph node. Then, total gastrectomy with combined resection of spleen was done. Histological examination of the resected specimen revealed the histological effect showing Grade 3 in the primary site and Grade 2 in the periaortic lymph node. The patient is alive with no evidence of recurrence 13 months after operation. Thus, FP therapy is thought to be effective against advanced gastric cancer.

We previously demonstrated that clenbuterol suppressed bronchial hyperresponsiveness in acute bronchitic models. However the effect of clenbuterol on the cough reflex, the main symptom of acute bronchitis, is not clear. The present study was thus undertaken to investigate the influence of clenbuterol on the cough reflex. Oral administration of clenbuterol (3 and 10 micrograms/kg) to guinea pigs markedly inhibited the increase in the respiratory resistance in response to 5-HT in a dose-dependent manner. At doses of 10 micrograms/kg and above, clenbuterol significantly inhibited the cough reflex induced by citric acid in guinea pigs. These doses are comparable with those causing broncho-dilation as described above, suggesting that the suppressive effect of clenbuterol on the cough reflex in guinea pigs may result from mainly its broncho-dilative action via stimulation of beta-2 adrenoceptors in airway smooth muscles however, other mechanisms cannot be ruled out. These results indicate that this agent may be useful for treatment of cough, the main symptom of acute bronchitis.

Histopathologic changes in human lacrimal gland were investigated, and the relation between histopathologic parameters and patient age and sex, as well as the histopathologic differences between palpebral and orbital lobes of the lacrimal gland were analyzed.Samples of the main human lacrimal gland that included the palpebral lobes and orbital lobes were taken in 80 autopsies. A statistical analysis was made based on light microscope observations with the following histopathologic changes as parameters: (1) fibrosis (focal, lobular, and diffuse); (2) acinar atrophy (focal, lobular, and diffuse); (3) periductal fibrosis; (4) interlobular ductal dilatation; (5) interlobular ductal proliferation; (6) lymphocytic foci; (7) periductal lymphocytic infiltration; and (8) fatty infiltration.The incidences of these parameters in the palpebral and orbital lobes ranged from 3.8% to 35.0%. Lobular fibrosis, lobular atrophy, diffuse fibrosis, diffuse atrophy, periductal fibrosis, lymphocytic infiltration, and fatty infiltration were more frequent in the orbital lobes with statistical significance, whereas interlobular ductal dilatation was more frequent in the palpebral lobes. There were statistically significant correlations between age and diffuse fibrosis, diffuse atrophy, and periductal fibrosis in the orbital lobes of women, and periductal fibrosis in the palpebral lobes of men. Diffuse fibrosis and diffuse atrophy in the orbital lobes were observed more frequently in elderly women than in elderly men.Various histopathologic changes were observed in the human lacrimal gland. Diffuse fibrosis, diffuse atrophy, and periductal fibrosis predominantly found in elderly women suggested a relation with keratoconjunctivitis sicca in postmenopausal women. The authors speculate the periductal fibrosis is related to the decrease in tear fluid outflow with age and that interlobular ductal dilatation in the palpebral lobes may be caused by stenosis of the excretory duct in the fornix of conjunctiva. Ductal pathologic changes may be important in lacrimal gland dysfunction.

When guinea pigs were exposed to sulfur dioxide (SO2) gas (800 ppm, 2 h), they showed hyperresponsiveness to intravenously administered serotonin (5-hydroxytryptamine (5-HT)). This hyperresponsiveness continued for over 24 h after the exposure to the gas. The degeneration, desquamation of epithelium, and edema of the lamina propria of the trachea and bronchi were observed in animals after a 2-h exposure of SO2 histopathologically. These changes seemed to be the early phase of acute bronchitis. Then, we examined the effect of clenbuterol, a selective beta-2 adrenoceptor agonist, on the SO2-induced bronchial hyperresponsiveness in these animals. Orally administered clenbuterol (1-10 micrograms/kg) suppressed the hyperresponsiveness to 5-HT in a dose-dependent manner. These results suggest that clenbuterol might inhibit the hyperresponsiveness that accompanies acute bronchitis and that this agent may be useful for remission of broncho-spasm.

We investigated histopathological changes in human meibomian glands and analyzed the incidence of histopathological parameters and the relationship between parameters and age or sex of patients. Human meibomian glands, measuring 3 x 3 mm in size, were excised from both upper eyelids of 72 autopsy cases (mean age 63 +/- 12 years; 44 males, 28 females). The specimens were stained with hematoxylin and eosin and examined in detail with the light microscope. The following histopathological changes were investigated as parameters: (1) cystic dilatation of the duct and/or the acini, (2) atrophy of the acini, and (3) granulomatous inflammation. The incidences of the parameters were (1) 34.7% (25 cases), (2) 19.4% (14 cases), and (3) 18.6% (13 cases). There was statistically significant correlation between age and atrophy of the acini, which was found in the older patients. No sex difference was found in any of the parameters. These results suggest that the decrease in the meibomian gland secretion with aging is related to atrophy of the acini. These results further suggest that cystic dilatation, which has been described as a histopathological finding in meibomian gland dysfunction, may be caused by factors other than aging.

We describe a new membrane filter (PORETEC) technique for processing cytopathologic fluid specimens. This procedure provides excellent cytologic preparations because there is no background staining and only a small amount of fluid specimen is necessary, as there is little cell loss. We compared the number of cells collected by the membrane filter technique with that collected by cytocentrifugation using conjunctival brush cytology specimens from 6 subjects. The number of cells obtained by the new method was significantly higher than that obtained by the cytocentrifugation technique. This method was very useful for ocular fluid specimens such as aqueous humor, vitreous specimens, and scrapings from the cornea and conjunctiva. We showed some examples of these specimens including immunocytochemical staining done by this method. We confirm that this is valuable for diagnostic cytopathologic study of various fluid specimens in ophthalmology.

Immunohistochemical localization of epidermal growth factor (EGF) in human main and accessory lacrimal glands has been investigated using monoclonal and polyclonal antibodies. Positive stain of EGF was localized in the cytoplasm of the acinar cells and the epithelial cells of the intra- and interlobular ducts of the main lacrimal glands, including both the palpebral and orbital lobes, and of the accessory lacrimal glands (gland of Krause, gland of Wolfring) as well. Meibomian glands showed weak immunoreactivity. Positive stain in the conjunctival epithelium including goblet cells was not observed. These results suggest that the mature form of EGF is produced in both the main and accessory human lacrimal glands and secreted into the tear fluid as a constant and crucial component.

In order to evaluate the clinical usefulness of a new membrane filter method, PORETEC, for cytopathological diagnosis in ophthalmology, we performed a comparative study on conjunctival cell specimens using this method and a previously developed cytocentrifugation method. The subjects were 5 normal male volunteers (6 eyes) with an average age of 33 years. The conjunctival cells were obtained by brush cytology, and processed for both the new membrane filter and the cytocentrifugation methods. The total numbers of epithelial cells obtained by both methods were counted under a light microscope. The number of cells obtained by the cytocentrifugation method was 4933 +/- 2338 for each specimen, whereas that by the new membrane filter method was 12436 +/- 5281 (mean +/- SD). The difference was statistically significant (Wilcoxon signed-rank test, P0.05). The new membrane filter diagnostic method was also applied to specimens of aqueous humor from patients with uveitis or vitreous body from patients with proliferative diabetic retinopathy or endophthalmitis. The new method provided excellent cytopathological specimens which were also applicable for special staining and immunocytochemical study. We concluded that the new membrane filter is quite useful for cytopathological diagnosis of ocular fluid specimens.

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) in concentrations from 0.1 to 10 nM suppressed immunoreactive thromboxane B2 (iTXB2) release from Propionibacterium acnes (P. acnes)-elicited liver adherent cells stimulated with lipopolysaccharide (LPS, 1 microgram/ml). These suppressive effects of 1,25-(OH)2D3 were also observed in oyster glycogen-elicited peritoneal macrophages. On the contrary, it did not inhibit iTXB2 release from both resident Kupffer cells and peritoneal macrophages stimulated with the same concentration of LPS. Furthermore, 1,24(R)-dihydroxyvitamin D3 (1,24(R)-(OH)2D3), a vitamin D3 analogue, also inhibited iTXB2 release from liver adherent cells, but, another synthesized vitamin D3 analogue, 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) tended to decrease iTXB2 release only at higher concentrations. These results suggest that active vitamin D3 analogues inhibit iTXB2 release from activated macrophages.

The relation between polyploidy and morphological classification of human megakaryocytes was studied in bone marrow aspirates from five normal individuals. On a Wright-Giemsa stained smear, megakaryocytes were morphologically classified into four groups according to a modification of Feinendegen's classification which is considered to reflect megakaryocyte maturation. The DNA of the morphologically classified cell is measured by microcytofluorometry using DAPI (4',6-diamidino-2-phenylindole) staining after removing the Wright-Giemsa stain. Most of the normal megakaryocytes were classified into type III (mature megakaryocytes) and the maximum peak in population of the megakaryocyte ploidy was observed at 16N. In each individual, the ploidy showed a similar pattern regardless of the classification. These findings suggest that the development of ploidy depends on a factor different from the one that determined the megakaryocyte maturation of cytoplasm and the ploidy is determined at the level of a megakaryocyte precursor or the most juvenile megakaryocyte.

Massive bone marrow necrosis was seen in a 42-year-old male with acute leukemia. In December, 1988, on admission, laboratory data revealed pancytopenia and a high level of serum LDH and ALKP. Bone marrow aspiration resulted in dry-tap and showed bone marrow necrosis in the bone marrow biopsy specimen. A bone marrow scintigraphy with 111In faintly visualized the bone marrow but visualized area was expanded in the extremities compared with normal subjects. The second bone marrow biopsy showed proliferation of blasts. In the middle of March, blasts began to appear in peripheral blood. The blasts were cytochemically negative for POX, Es, PAS, AcP, TdT and had surface markers CD3-, CD19-, CD33-, CD13-, LCA-, HLA-DR-. Even by investigation on rearrangement of the immunoglobulin heavy chain region, an origin of the blasts could not be determined. In April, the number of blasts in peripheral blood increased and hepatosplenomegaly developed rapidly. Therefore, he was put on the chemotherapy with vincristine and prednisolone, but he died of cerebral hemorrhage. The autopsy revealed widespread bone marrow necrosis. It has rarely been reported that massive bone marrow necrosis is found prior to the occurrence of acute unclassified leukemia.

Reported is the second documented case in Japan of acute leukemia with Klinefelter's syndrome. The patient, a 52-year-old male, was admitted to hospital on July 9, 1983, after complaining of a fever and general malaise. The hematological examinations revealed a WBC count of 14,300/cmm with 32% being leukemic cells. Bone marrow aspiration disclosed a nucleated cell count of 687,000/cmm with 41.6% being leukemic cells consisting of myeloblasts. The endocrinic laboratory data showed a high level of urine gonadotropin and chromosomal studies revealed a 47,XXY karyotype. A diagnosis of acute myelogenous leukemia (M1) with Klinefelter's syndrome thus was derived from these findings.

1,12b-Cis-1-p-nitrobenzoyloxyindoloquinolizidine as well as 14 beta-p-nitrobenzoyloxyyohimbine possessed potent calcium channel blocking activities in the isolated rat perfused mesenteric vascular bed. Introduction of the bulky substituents to C-14 of yohimbine or to C-1 of indoloquinolizidine resulted in enhancement of the calcium channel blocking activities. By comparison of chemical structures between yohimbine and indoloquinolizidine, it was found that the E ring of yohimbine had no association with the calcium channel blocking activities. On the other hand, alpha 1- and alpha 2-adrenoceptor antagonistic activities which were tested in the rat mesenteric vascular bed and in the rat vas deferens, respectively, were markedly reduced by such introduction of the bulky substituents to yohimbine and indoloquinolizidine. From these results, it is expected that chemical modifications of indoloquinolizidine at the C-1 position provide new types of agents with calcium channel blocking activities.

Yohimbine possesses a relatively selective α2-adrenoceptor antagonistic effect and a weak Ca2+ channel blocking activity, so two derivatives, 14β-benzoyloxyyohimbine and 14β-p-nitrobenzoyloxyyohimbine were compared with yohimbine using those parameters. The two derivatives blocked Ca2+-induced contraction of the rat perfused mesenteric vascular bed at 3 times 10−6 M, and developed dose-dependent shifts of the dose-response curve to the right in concentrations from 3 times 10−6 to 10−5M. Yohimbine showed a weak Ca2+ channel-blocking effect only at a concentration of 10−5M. On the other hand, both derivatives at 3 times 10−6 M did not affect the dose-response curve to noradrenaline-induced vasoconstriction. Furthermore, at 10−8 M they had no effect on the dose-response curve to clonidine-induced inhibition of the twitch response of the rat isolated vas deferens evoked by electric stimulation, whereas yohimbine significantly attenuated clonidine-induced inhibition. These results indicate that introduction of bulky substituents into the 14-position of yohimbine intensely potentiated the Ca2+ channel-blocking effects and reduced α-adrenoceptor antagonistic effects compared with those of yohimbine, and suggest that chemical modifications of yohimbine may lead to structurally new types of Ca2+ channel-blockers.

The reticuloendothelial system is important as one of the self defense mechanisms. We performed two investigations to confirm the reliability of the lipid emulsion test for determining the reticuloendothelial system function. 1) The lipid emulsion serum clearance was contrasted with the counts of lipid emulsions phagocytosed by Kupffer cells in liver. 2) Lipid emulsion clearance was contrasted with the hepatic uptake rate of 99mTc-phytate. The result demonstrated a positive correlation among lipid emulsion clearance, the counts of lipid emulsions phagocytosed by Kupffer cells and the hepatic uptake rate of 99mTc-phytate. These results confirm that the lipid emulsion test is sufficient to reflect Reticuloendothelial system function.

A 75-year-old man, previously diagnosed as having chronic myelomonocytic leukemia, suffered an attack of severe left hypochondralgia in July 1986. A splenic infarction was diagnosed by both ultrasound tomography and computerized tomography. The patient was treated with alpha-Interferon (600 M.U./day i.m.) for cytoreduction in order to prevent a recurrence of the splenic infarction. Twenty-one days later, the peripheral white blood cell count decreased from 44,110 microliters to 9800/microliters and the monocytoid immature cells disappeared. However, severe dementia appeared and so alpha-Interferon therapy was abandoned. In this report the beneficial effects and side effects of alpha-interferon in the treatment of chronic myelomonocytic leukemia are discussed.

Percutaneous transvenous mitral commissurotomy was performed in 106 consecutive patients. Significant symptomatic improvement was achieved in 97 patients (92%). Mean left atrial pressure decreased (from 18 +/- 8 to 11 +/- 8 mm Hg, p less than 0.00001), mean mitral diastolic pressure gradient decreased (from 12 +/- 7 to 7 +/- 6 mm Hg, p less than 0.00001), and mitral valve area increased (from 1.40 +/- 0.40 to 2.00 +/- 0.50 cm2, p less than 0.00001). Based on echocardiographic characteristics of the mitral apparatus, patients were grouped retrospectively in three categories: pliable (group 1, n = 37), semipliable (group 2, n = 59), and rigid (group 3, n = 10). Clinical success was achieved in 36 patients of group 1 (97%) and in 55 patients of group 2 (93%). Only six patients in group 3 (60%) improved symptomatically (p less than 0.001 vs. group 1, p less than 0.001 vs. group 2). The severity of mitral regurgitation increased in five patients of group 1 (14%), in 12 of group 2 (20%), and in three of group 3 (33%). Six patients had recurrent symptoms at 9 months after commissurotomy. Recurrence of symptoms was significantly more frequent in group 3 compared with the other two groups (group 1, 3%; group 2, 4%; and group 3, 50%; p less than 0.0001 vs. groups 1 and 2). Multiple regression analysis identified the previously mentioned echocardiographic characteristics of the mitral apparatus as the significant predictor for clinical outcome. Thus, percutaneous transvenous mitral commissurotomy can be considered a safe and effective treatment for patients with pliable valves. Patients with semipliable or with rigid valves should be selected for operation very carefully.