Labor induction using modified metreurynters plus oxytocin at an institution in Japan: a retrospective study.

OBJECTIVE: The authors evaluated the effectiveness and safety of "neo-metoro" or 'mini-metoro" metreurynters plus oxytocin for labor induction and assessed differences in parturition outcomes, according to the metreurynter used at induction initiation. MATERIALS AND METHODS: The authors retrospectively reviewed 146 consecutive women with live singleton pregnancies, and who underwent induction. Parturition outcomes were vaginal delivery achieved within the planned schedule (VDPS), vaginal delivery finally achieved (VDF), and induction-to-delivery interval (IDI). Women were divided into neo-metoro, mini-metoro, and without metreurynter groups based on metreurynter use at induction initiation. The authors examined the relationships of metreurynter groups with factors, parturition outcomes, and adverse events. In 113 women who underwent two-day induction, the authors calculated IDI and adjusted odds ratio (AOR) for achieving delivery per unit time. RESULTS: VDPS rates were 65% in nulliparous and 81% in multiparous women. VDF rates were 78% in nulliparous and 96% in multiparous women. AORs for VDPS were 0.30 in nulliparous women and 0.18 in Bishop score (BS) 1-3 class. AORs for VDF were 0.04 in BS1-3 class and 0.14 in BS4-5 class. In 113 women undergoing two-day induction, AORs for achieving delivery per unit time were 0.45 in nulliparous women, 0.46 in obese women, and 0.48 in BS1-3 class. Neo-metoro use at induction initiation tended to reduce IDI. CONCLUSIONS: Labor induction using these metreurynters plus oxytocin is safe and effective. The advantages of neo-metoro over mini-metoro use at induction initiation remain unclear; neo-metoro use at induction initiation may reduce IDI.

Assessment of skin test with varicella-zoster virus antigen for predicting the risk of herpes zoster.

The Shozu Herpes Zoster (SHEZ) Study was designed to clarify the incidence of and predictive and immunological factors for herpes zoster in a defined community-based Japanese population. As part of this series, a total of 5683 residents aged ≥50 years received a varicella-zoster virus (VZV) skin test with VZV antigen, and 48 h later, the erythema and oedema were assessed by measuring the longest diameter. The diameters of both the erythema and oedema decreased with the increasing age of the subject. Sixty-three subjects contracted herpes zoster within a year after receiving the VZV skin test. Analysis of the herpes zoster incidence rate vs. the skin test reaction revealed that the shorter the diameter of erythema or oedema, the greater the likelihood of herpes zoster. These results demonstrated that the VZV skin test is an excellent surrogate marker for predicting the risk of herpes zoster.

Comparison of DNA sequence and transactivation activity of open reading frame 62 of Oka varicella vaccine and its parental viruses.

When nucleotide sequences of Oka vaccine and its parental viruses of varicella-zoster virus (VZV) were compared in 5 open reading frames (ORFs) including glycoprotein C (gC) and 4 immediate-early genes, mutations were detected only in gene 62 which is one of the immediate-early genes. Compared with its parental virus, the vaccine virus contained 15 nucleotide substitutions. With the differentiation method using the simplified restriction-enzyme fragment length polymorphism analysis by Nae I and Bss HII, which was established based on the sequence analysis data in this study, the Oka vaccine virus could be distinguished from its parental virus. Studies of the regulatory activities of the ORF62 gene product (IE62) in a transient assay indicate the IE62 of the parental virus had a stronger transactivational activity than that of the vaccine virus against immediate-early, early and late gene promoters. These data suggest that gene 62 might have an important role for attenuation of VZV. This is the first report in which many substitutions of nucleotides in gene 62 of Oka vaccine virus was found, compared with that of Oka parental virus.

Role of nitric oxide in the peristalsis in the isolated guinea-pig ileum.

The role of nitric oxide in peristalsis was studied by using NG-nitro-L-arginine, an inhibitor of the biosynthesis of nitric oxide, in the isolated guinea-pig ileum. Constant peristalsis was cyclically induced by distending the ileal wall with intraluminal solution infused at a constant rate. NG-Nitro-L-arginine (10(-6) to 10(-4) M) dose dependently increased the frequency of peristalsis. This effect of NG-nitro-L-arginine was almost hindered by pretreating the ileum with 10(-3) M L-arginine, but not D-arginine. Nitroprusside (5 X 10(-7) M) reversed the frequency increase. In the presence of NG-nitro-L-arginine, peristaltic propulsion occurred at a smaller distension of the ileal wall and the ileum constricted to a smaller diameter at the completion of propulsion. The rate of shortening of longitudinal muscle during distension was raised by NG-nitro-L-arginine, although the peak magnitudes were not changed. Consistent with these effects of NG-nitro-L-arginine on peristalsis, NG-nitro-L-arginine at 10(-5) M increased the contractions of circular muscle in response to electrical field stimulation, but not those of longitudinal muscle. These results suggest that endogenous nitric oxide modulates peristalsis by limiting the contractile activity of the circular muscle of the guinea-pig ileum.

The specific effect of Mn2+ on the tonic components of receptor-mediated contractions in isolated vas deferens of the guinea pig.

Intracellular accumulation of Mn2+ augmented the contractions induced by norepinephrine and acetylcholine in the guinea pig isolated vas deferens. Contractions repeatedly induced by norepinephrine, acetylcholine, or a high concentration of K+ decreased depending on the incubation time in Ca(2+)-free medium. The rate of decrease of all contractions was delayed by intracellularly accumulated manganese. In the Mn(2+)-loaded preparations, the tonic components of the contractions induced by norepinephrine and acetylcholine, but not K+, were highly resistant to extracellular Ca2+ elimination. Ryanodine abolished the initial phasic component but did not affect the tonic component of norepinephrine- and acetylcholine-contractions in Mn(2+)-loaded preparations in Ca(2+)-free medium. In Ca(2+)-depleted preparations, the tonic contraction induced by norepinephrine was restored after the Mn(2+)-loading procedure, and the magnitude of this tonic contraction was comparable to the tonic component of the norepinephrine contraction in the normal medium before Mn2+ loading. The tonic contraction was reproducible in medium without either Mn2+ or Ca2+. These results suggested that intracellular Mn2+ can support norepinephrine-induced tonic contractions. In the Ca(2+)-depleted Mn(2+)-loaded preparations, K+ also induced a tonic contraction in the presence of extracellular Mn2+. However, this contraction was much smaller than that induced by norepinephrine. These results suggested that intracellular Mn2+ augmented contractions not only via an increase in intracellular Ca2+ availability but also via the direct action of Mn2+ on contractile mechanisms, and that this action is highly specific for developing and/or maintaining tonic contractions mediated by receptor activation in the guinea pig isolated vas deferens.

Myosin light chain phosphorylation and Mn2+ -dependent norepinephrine-induced contractions in guinea-pig vas deferens.

We have reported that norepinephrine but not K+ induced a sustained and dose-dependent contraction without extracellular Ca2+ and Mn2+ in Ca2+-depleted Mn2+-loaded vas deferens from the guinea-pig. In the present study, we determined the phosphorylation of the 20-kDa myosin light chain and examined the effects of inhibitors of calmodulin and myosin light chain kinase on the Mn2+-dependent norepinephrine-induced contraction in order to evaluate the contribution of phosphorylation to this contraction. W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], ML-9 [1-(5-chloronaphthalene-1-sulfonyl)-homopiperazine] and wortmannin inhibited this contraction. However, the Mn2+-dependent norepinephrine-induced contraction developed without a significant increase in the phosphorylation of the 20-kDa myosin light chain. In beta-escin-permeabilized preparations, Mn2+ induced contractions that were inhibited by ML-9. These results suggest that the activation of myosin light chain kinase is essential for the development of Mn2+-dependent norepinephrine-induced contractions and that the phosphorylation of myosin light chain may act as a trigger for these contractions.

Inhibitory effect of inaperisone hydrochloride (inaperisone), a new centrally acting muscle relaxant, on the micturition reflex.

We examined the effects of inaperisone hydrochloride (inaperisone), a new centrally acting muscle relaxant, on bladder function in anesthetized rats and isolated rat tissues. We also investigated its mechanism of action. When a balloon inserted into the bladder was expanded, rhythmic bladder contractions were observed; inaperisone (4 mg/kg i.v.) abolished these contractions, in both normal and decerebrated rats. The bladder tonus or bladder contraction induced by peripheral stimulation of the pelvic nerve was barely inhibited by inaperisone (4 mg/kg i.v.), but this dose of inaperisone abolished the efferent discharge from the pelvic nerve that accompanied the rhythmic bladder contractions. The doses of intracerebroventricularly (i.c.v.) and intrathecally injected inaperisone which abolished the rhythmic bladder contractions were 10 and 100 micrograms, respectively. The inhibitory effects of inaperisone (4 mg/kg i.v.) were not diminished by naloxone (1 mg/kg i.v.) or by bicuculline (0.5 mg/kg i.v.), but were diminished by phaclofen (30 mg/kg i.v. or 300 micrograms i.c.v.). The specific binding of [3H]baclofen to rat brain synaptosomal membranes was barely inhibited by inaperisone (up to 1 mM). From these results, it is speculated that, among other possible mechanisms, inaperisone inhibits the micturition reflex by acting indirectly on GABAB receptors in the brainstem.

Myosin light chain phosphorylation and Mn2+-dependent acetylcholine-induced contractions in guinea pig vas deferens.

We have reported that noradrenaline but not K+ induced a sustained and dose-dependent contraction without extracellular Ca2+ and Mn2+ in Ca2+-depleted Mn2+loaded vas deferens from the guinea pig. The Mn2+dependent noradrenaline-induced contractions developed without an increase in phosphorylation of 20-kDa myosin light chain. To clarify whether such an unusual Mn2+dependent contraction was induced only by noradrenaline or not, we examined effects of acetylcholine on Ca2+-depleted Mn2+-loaded guinea pig vas deferens. Acetylcholine (1 microM(-1) mM) induced a sustained dose-dependent contraction without extracellular Ca2+ or Mn2+. W-7 (10 microM or 100 microM) and wortmannin (1 microM) both reduced the Mn2+dependent acetylcholine-induced contractions similarly to Ca2+-dependent acetylcholine-induced contractions in isolated vas deferens without either Ca2+ depletion or Mn2+ loading. However, the Mn2+-dependent acetylcholine-induced contractions developed without a significant increase in the phosphorylation of the myosin light chain determined by urea-glycerol polyacrylamide gel electrophoresis and immunoblotting. These results indicate that acetylcholine as well as noradrenaline induces Mn2+-dependent contraction and are consistent with our previous assumption that Mn2+ may preferentially support receptor-mediated contractions in the guinea pig isolated vas deferens. The results also suggest that the activation of myosin light chain kinase is essential for the development of Mn2+-dependent acetylcholine-induced contractions, and that Mn2+ may accelerate formation of non-phosphorylated attached cross-bridges during receptor activation.

Effects of the functional elimination of sarcoplasmic reticulum on the manganese-dependent norepinephrine-induced contractions of the guinea pig vas deferens.

We investigated the effects of inhibitors of the sarcoplasmic reticulum (SR) functions on the tonic contractions induced by norepinephrine (NE) in the Ca(2+)-depleted Mn(2+)-loaded vas deferens of the guinea pig in the absence of both Ca2+ and Mn2+ (Mn(2+)-dependent NE-contraction). In control preparations without Ca(2+)-depletion and Mn(2+)-loading, either cyclopiazonic acid (CPA, 10 microM) or ryanodine (RYA, 3 microM) inhibited the initial phasic and tonic components but not the large phasic component of NE-induced contraction in normal medium containing 2.2 mM Ca2+. In contrast, CPA did not affect the Mn(2+)-dependent NE-contractions. The inhibitory effect of RYA slowly developed with each repetition of the Mn(2+)-dependent NE-contraction and the magnitude of the inhibition was slight. A23187 (10 microM) inhibited the NE-induced contractions of the control preparations in the same manner as CPA and RYA. Although A23187 did not induce contractions in the Mn(2+)-loaded preparations, A23187 augmented the Mn(2+)-dependent NE-contractions. The augmented tonic contractions returned to the resting level by washing NE and A23187. The augmentation remained for 3 successive contractions in the absence of A23187. However, the 2nd application of A23187 did not augment the contraction. These results suggest that neither Mn(2+)-release from SR nor Mn(2+)-influx from the extracellular space contributes to the Mn(2+)-dependent NE-contractions. We concluded that NE induces Mn(2+)-dependent contractions by increasing Mn2+ sensitivity of contractile processes but not by increasing intracellular Mn2+ concentration.

Inhibitory effects of amlexanox on carbachol-induced contractions of rabbit ciliary muscle and guinea-pig taenia caecum.

Instillation of amlexanox, an anti-allergic drug, over a long period improves myopia in some allergy patients and in monkeys. The relaxing effect of amlexanox on persistent contraction of ciliary muscle may be involved in the improvement of myopia. In this study, the mechanism of the noncompetitive inhibition of carbachol-induced contractions by amlexanox (1-100 microM) was investigated in isolated smooth muscle preparations of the rabbit ciliary body and guinea-pig taenia caecum. In ciliary muscles, amlexanox (100 microM) inhibited both the phasic and tonic components of carbachol-induced contractions even in the presence of cyclopiazonic acid (10 microM) where the function of the sarcoplasmic reticulum was impaired, while diltiazem (3.2, 32 microM) did not. In taenia caecum, diltiazem (3.2 microM) slightly inhibited the phasic component and abolished the tonic component of carbachol-induced contractions. Amlexanox also abolished the tonic component, but it did not decrease the 45Ca2+ uptake into taenia caecum smooth muscle cells induced by carbachol. Amlexanox did not increase the cyclic adenosine monophosphate (cyclicAMP) content of ciliary muscles in the presence of 3-isobutyl-1-methylxanthine (10 microM), while forskolin (1 microM) did. Gel-shift assay showed that the inhibition of carbachol-induced contractions by amlexanox was accompanied by a decrease in phosphorylation of the 20-kDa myosin light chain in taenia caecum tissue preparations. Amlexanox had no effect on calmodulin activity, whereas it inhibited phosphorylation of the myosin light chain by purified myosin light-chain kinase from chicken gizzard. These results suggested that amlexanox may not affect either Ca2+ mobilization or calmodulin activity, although it inhibits myosin light-chain kinase, which may inhibit carbachol-induced contraction.

Cushing's syndrome due to bilateral adrenocortical adenomas with different pathological features.

A 48-year-old woman with Cushing's syndrome due to bilateral adrenocortical adenomas is reported. The patient presented with a typical Cushingoid appearance. The serum cortisol level was elevated with loss of the diurnal rhythm and the plasma adrenocorticotropic hormone (ACTH) level was undetectable. Dynamic testing showed no suppression of urinary 17-OHCS by high-dose dexamethasone and no stimulation by metyrapone. An abdominal computed tomography (CT) scan showed bilateral adrenal tumors. Bilateral adrenalectomy was performed. The right adrenal gland contained a tumor that was encapsulated and consisted mainly of compact cells. The surrounding cortex was atrophic. The left adrenal gland contained an encapsulated tumor composed predominantly of clear cells. There were numerous small adrenocortical nodules in the surrounding cortex. Immunohistochemical analysis of steroidogenic enzymes (P450scc, 3beta-HSD, P450c21, P450c17 and P450c11) was performed. Immunoreactivity of all the enzymes was intense in the compact cells of the right adrenocortical adenoma, while the adjacent non-neoplastic cortex was negative for the enzymes. In the left adrenal tumor, the immunoreactivity of 3beta-HSD was intense, while that of P450c17 was weak. In the adrenocortical nodules, 3beta-HSD activity was sporadically observed. G protein genes encoding Gs alpha and Gi2 were examined for activating mutations at codons 201 and 227 (Gs alpha) and codons 179 and 205 (Gi2 alpha) in the bilateral adrenal tumors, but no mutations were found. The bilateral adenomas of this patient showed marked differences in microscopic and immunohistochemical studies, suggesting that the capacity of steroidogenesis differs between the right and left tumors.

[Changes in isolated ciliary muscle caused by repeated instillation of carbachol ointment in rabbits and effect of topically applied amlexanox].

PURPOSE: We investigated changes in ciliary muscle caused by continual contraction in rabbits and evaluated the efficacy of topically applied amlexanox, which relaxes the ciliary muscle, on such changes. SUBJECTS AND METHODS: After topical application of carbachol ointment 5 times daily for 2 weeks, the contractile responses of isolated ciliary muscles to carbachol were measured isometrically, and the ciliary smooth muscle fibers were stained with phosphotungstic acid and hematoxylin and observed histologically. 1% amlexanox solution was instilled 5 minutes before every instillation of carbachol ointment. RESULTS: Repeated topical carbachol ointment caused decreases in both contractile responses of isolated ciliary muscles to carbachol and number of ciliary smooth muscle fibers stained by phosphotungstic acid and hematoxylin. Amlexanox inhibited these changes. CONCLUSION: We found that continual contraction of the ciliary muscle caused functional and histological changes in it. These changes are thought to occur in some diseases which cause excessive contraction of the ciliary muscle. Topical amlexanox might be useful for these diseases.

[The outcome of adjusted accumulation dose of treatment of Graves' disease].

We evaluated the outcome of 131I treatment of Graves' disease in two different protocols (old and new protocol) of adjusted accumulation dose from 1988 to 1995. Adjusted accumulation doses of patients with above 50 g thyroid weights were increased by 5-20 Gy/g tissue in new protocol compared to those in old one. In 166 patients treated with single and plural doses of 131I treatment in 1990 (Group In), the therapeutic doses were calculated according to new protocol and in 130 patients in 1988 (Group Io), according to old one, modification of Quimby's formula. The patients treated with plural doses were classified as hyperthyroidism because the efficacies of the first treatments with 131I were insufficient. At the 5-yr follow up, the incidence of hypothyroid in Group In was 9%, subclinical hypothyroid 17%, euthyroid 30%, subclinical hyperthyroid 7%, hyperthyroid 37%. In Group Io, 11% of the patients were hypothyroid, 6% subclinical hypothyroid, 29% euthyroid, 3% subclinical hyperthyroid, 51% hyperthyroid. The incidence of hyperthyroid in Group In was lower than that in Group Io (p < 0.05). There were no significant differences in hypothyroid and euthyroid. In conclusion, we suggest that an adjusted dose of 131I in relation to the patients' thyroid weight shows some room for improvement.

[The outcome of treatment with adjusted dose of 131I to thyroid weight for Graves' disease by estimation of effective half life using a single radioiodine uptake measurement].

In the determination of therapeutic 131I doses, it takes several days to measure effective half life (EHL) of radioiodine in thyroid glands (Ordinary method). We suggested the new method to estimate EHL by a single radioiodine uptake measurement (INDEX method). We evaluated the outcome of 131I treatment with these two methods in outpatients with Graves' disease. Eighty outpatients were treated with INDEX method (Group I) and 108 outpatients with Ordinary method (Group O). At the 5-yr follow up, the incidence of hypothyroidism in Group I was 22.5%, subclinical hypothyroidism 8.8%, euthyroidism 30.0%, subclinical hyperthyroidism 13.7% and hyperthyroidism 25.0%. In Group O, 17.6% of the patients were hypothyroid, 16.7% subclinical hypothyroid, 30.5% euthyroid, 9.3% subclinical hyperthyroid and 25.9% hyperthyroid. There were no significant differences between these two methods. We conclude that INDEX method surpasses Ordinary method in timesaver and is equal in effectiveness.