Peripartum type B aortic dissection in patients with Marfan syndrome who underwent aortic root replacement: a case series study.

OBJECTIVE: To investigate pregnancy outcomes, especially the risk of pregnancy-related aortic dissection (AD), in patients with Marfan syndrome (MFS) after prophylactic aortic root replacement (ARR). DESIGN: Retrospective case series study. SETTING: Tertiary perinatal care centre at a university hospital. POPULATION: Pregnant women fulfilling the revised Ghent nosology (2010) criteria for MFS who were managed at our institute. METHODS: The pregnancy outcomes of all patients with MFS managed at our institute between 1982 and September 2016 were reviewed retrospectively based on medical records. MAIN OUTCOME MEASURES: Obstetrical management and complication including the incidence of AD throughout the peripartum period. RESULTS: Among 22 patients (28 pregnancies) who had been managed as potential MFS or related disorders, 14 (17 pregnancies) fulfilled the revised Ghent nosology (2010) criteria for MFS and were enrolled in this study. Five patients (five pregnancies) had received ARR before conception: three (60%) developed type B aortic dissection [AD(B)] during the peripartum period, compared with only one of 10 patients (12 pregnancies) without ARR (P < 0.05, Chi-square test). CONCLUSIONS: Our study results suggest that MFS patients after prophylactic ARR are still at high risk of AD(B) during the peripartum period. Careful pre-pregnancy counselling and multidisciplinary care throughout the peripartum period are essential for the management of MFS, even after surgical repair of an ascending aortic aneurysm. TWEETABLE ABSTRACT: MFS patients after prophylactic ARR are still at high risk of type B aortic dissection during the peripartum period.

Evaluation of Virulence Factors In vitro, Resistance to Osmotic Stress and Antifungal Susceptibility of Candida tropicalis Isolated from the Coastal Environment of Northeast Brazil.

Several studies have been developed regarding human health risks associated with the recreational use of beaches contaminated with domestic sewage. These wastes contain various micro-organisms, including Candida tropicalis. In this context, the objective of this study was to characterize C. tropicalis isolates from the sandy beach of Ponta Negra, Natal, Rio Grande do Norte, Brazil, regarding the expression of in vitro virulence factors, adaptation to osmotic stress and susceptibility to antifungal drugs. We analyzed 62 environmental isolates and observed a great variation among them for the various virulence factors evaluated. In general, environmental isolates were more adherent to human buccal epithelial cells (HBEC) than C. tropicalis ATCC13803 reference strain, and they also showed increased biofilm production. Most of the isolates presented wrinkled phenotypes on Spider medium (34 isolates, 54.8%). The majority of the isolates also showed higher proteinase production than control strains, but low phospholipase activity. In addition, 35 isolates (56.4%) had high hemolytic activity (hemolysis index > 0.55). With regard to C. tropicalis resistance to osmotic stress, 85.4% of the isolates were able to grow in a liquid medium containing 15% sodium chloride. The strains were highly resistant to the azoles tested (fluconazole, voriconazole and itraconazole). Fifteen strains were resistant to the three azoles tested (24.2%). Some strains were also resistant to amphotericin B (14 isolates; 22.6%), while all of them were susceptible for the echinocandins tested, except for a single strain of intermediate susceptibility to micafungin. Our results demonstrate that C. tropicalis isolated from the sand can fully express virulence attributes and showed a high persistence capacity on the coastal environment; in addition of showing high minimal inhibitory concentrations to several antifungal drugs used in current clinical practice, demonstrating that environmental isolates may have pathogenic potential.

A case of giant extramammary Paget's disease of the genital area with squamous-cell carcinoma.

Extramammary Paget's disease is a primary carcinoma with apocrine differentiation that begins within the epidermis. Extramammary Paget's disease and squamous-cell carcinoma (SCC) have different neoplastic origins and are different both clinically and histologically. Until now the concurrence of extramammary Paget's disease and SCC in the same area has not been reported to our knowledge. We report on a 76-year-old man with extramammary Paget's disease affecting a large region of the genital area with SCC within the same area. A skin biopsy specimen showed the coexistence of typical Paget's disease and highly differentiated SCC invading the dermis. Immunohistochemical staining of both cell types was completely different.

[Intracranial inhibitory mechanisms in clinically diagnosed corticobasal degeneration: a study of a silent period followed by transcranial magnetic stimulation].

A 52-year-old man with clinically diagnosed corticobasal degeneration (CBD) who developed the asymmetric akinetic-rigid syndrome was studied by means of transcranial magnetic stimulation (TMS) after an interval of two years. TMS of the motor cortex during tonic muscle contraction causes a silent period immediately after a motor evoked potential in an electromyogram. This silent period is considered to reflect activity of an intracortical inhibitory mechanism. In this patient, the motor symptoms started from the left half of the body and spread to the right. The major neurological findings were dystonia, rigidity, clumsiness, and hyperreflexia. The involuntary contraction of the muscles, which was unrelated to voluntary movement, seemed to be responsible for his signs and symptoms. There was laterality of the threshold intensity and the duration of the silent period after a motor evoked potential; the threshold was higher and the duration was shorter on the affected side. Also, we found that the threshold increased and the duration decreased as his motor dysfunction progressed, which has not been reported before. A comparison of the clinical symptoms and the results of TMS in this case together with previous TMS data on CBD suggests that a disorder of the intracortical inhibitory mechanism is closely related to the movement impairment in CBD.

[Habitual mandibular dislocation in two patients with Parkinson's disease].

There have been few case reports of mandibular dislocation in Parkinson's disease (PD) so far. We experienced habitual mandibular dislocation in two PD patients. They were a 74-year-old woman and a 56-year-old man, who were both graded V by Hoehn and Yahr's staging and had a 13- and 14-year history of PD, respectively. Remarkable retroflexion and rigidity of the neck was observed in both patients. Anterior dislocation of the jaw occurred without any special cause. Once the jaw was dislocated, it required unexpected power to reduce the dislocation against the rigidity. In a case of postencephalitic parkinsonism, continuous parkinsonian tremors of the mandible over a long period was indicated as a cause of the recurrent dislocation seen in the patient. No mandibular tremor, however, was observed in the present cases. The common feature of our two patients was retroflexion of the neck, which was assumed to make the suprahyoid muscles stretched and the mouth opened widely, causing the recurrent mandibular dislocation. Since the recurrence was prevented by chin cap, early chin cap therapy for the mandibular dislocation in parkinsonian patients is recommended.

[Valproic acid relieved marked rigidity in three patients with end-stage parkinsonism].

We applied valproic acid (VPA) on the rigidity of three parkinsonian patients, two with Parkinson disease and one with striatonigral degeneration. They were all at Hoehn and Yahr's stage V and showed marked rigidity. In these patients, effect of L-DOPA had become limited or increasing the dosage of L-DOPA was difficult because of its side effects. Parkinsonian symptoms were assessed by using motor score of Unified Parkinson's Disease Rating Scale. The degree of rigidity in these three patients was markedly decreased with 300-600 mg/day of VPA. The blood level of VPA ranged from 24.8 to 66.5 micrograms/ml, which was relatively low compared with the effective blood level as an anti-epileptic agent. Parkinsonian symptoms other than rigidity, and the increased deep tendon reflexes which were present in the patient with striatonigral degeneration were not affected by VPA. Reduction of L-DOPA intensified rigidity again which had been under control. Trials of VPA on parkinsonism have been reported from two groups (Price PA, et al. 1978; Nutt J, et al. 1979), neither of which has observed any benefit of VPA. The difference of their results and ours seems to depend on the stage of patients; their patients had mild to moderate symptoms, whereas ours were in the end stage with marked rigidity. Since the effect of VPA upon parkinsonism is limited to rigidity, the end-stage patients whose care is difficult due to severe rigidity may obtain the best benefit of VPA. VPA is considered to take effect by activating gamma-aminobutyric acid (GABA) system. Because GABA is a common inhibitory neurotransmitter distributed in the wide areas of the central nervous system, it is difficult to locate the action site of VPA with regard to the amelioration of rigidity. The stretch reflex loop in the spinal cord does not seem to be the action site because no change was noted in deep tendon reflex. GABAergic striatal efferent neurons do not seem to be the sole action site either, because parkinsonian symptoms were not affected except for rigidity. The vestibular nucleus which receives strong GABAergic afferents from cerebellar Purkinje cells is an efficient tonus regulator. Since suppression of the function of the nucleus is known to reduce rigidity, it is at least a candidate for the action site of VPA. But there is no direct evidence for this matter. The exact action site of VPA remains to be elucidated.

Synthesis and selective coronary vasodilatory activity of 3,4-dihydro-2,2-bis(methoxymethyl)-2H-1-benzopyran-3-ol derivatives: novel potassium channel openers.

A variety of compounds having a benzopyran such as levcromakalim generally exhibit potent antihypertensive activity. During extensive investigations aimed toward identifying K+ channel openers having selective coronary vasodilation without potent hypotensive and tachycardiac effects, we synthesized a series of 3,4-dihydro-2H-1-benzopyran-3-ol derivatives modified at positions 2, 4, and 6 in the benzopyran ring. Initially, compounds having two methoxymethyl groups at position 2 were found to show a selective effect on coronary blood flow (CoBF) relative to mean arterial pressure (MAP) in anesthetized dogs. To find more potent vasodilators, various benzopyran derivatives modified at position 4 were synthesized and structure-activity relationships were examined by evaluation of the extent and duration of the increase in CoBF in anesthetized dogs. As a result, compounds having a (1,6-dihydro-6-oxopyridazin-3-yl)amino group at position 4, in addition to the two methoxymethyl groups at position 2, were found to be more potent and to have an improved duration of action. Among these compounds, JTV-506, (-)-(3S,4R)-6-cyano-3,4-dihydro-4-[(1,6-dihydro-1-methyl-6-oxopyridaz in-3-yl)amino]-2,2-bis(methoxymethyl)-2H-1-benzopyran-3-ol, exhibited good selectivity for its effect. Administration of this compound (0.03 mg/kg, p.o.) elicited an increase of CoBF without a change of systemic blood pressure and heart rate (HR) in conscious dogs. Further evaluation was performed with respect to (i) the selectivity of its action on the coronary artery versus the aorta and (ii) its effects on MAP, HR, and electrocardiographic ST elevation. As a result, JTV-506 was selected as a potent and selective coronary vasodilator with various pharmacological features favoring clinical development.

Antineuronal antibodies in acute cerebellar ataxia following Epstein-Barr virus infection.

A 29-year-old man developed acute cerebellar ataxia following Epstein-Barr virus infection. Serum IgG and IgM antibodies reacted with both nuclear and cytoplasmic elements of neurons. Western blot revealed IgG binding to the 34- and 29-kd bands and IgM binding to the 44-, 37-, and 29-kd bands. The IgM reactivity gradually reduced. There was no identifiable neoplasm and the ataxia gradually improved. These findings suggest a role for autoimmune mechanisms in the pathogenesis of acute cerebellar ataxia.

Halo congenital nevus undergoing spontaneous regression. Involvement of T-cell immunity in involution and presence of circulating anti-nevus cell IgM antibodies.

BACKGROUND: Halo congenital nevus is a condition in which halo formation is associated with congenital nevocellular nevi. Although several theories have been proposed, the immunologic mechanisms of halo formation and concomitant nevus regression still remain unclear. We presented immunologic findings in a case of halo congenital nevus with unique histologic location of inflammatory cells. OBSERVATIONS: Histologically, the present case of halo congenital nevus undergoing spontaneous regression showed a marked inflammatory infiltrate with remnants of original nevus cell nests. In the infiltrating T cells, CD8+ cells outnumbered CD4+ cells and the infiltrate of natural killer cells was not substantial. Direct and indirect immunofluorescence studies demonstrated the presence of IgM antibodies against nevus cells as well as melanoma cells and cultured melanocytes in the patient's serum. CONCLUSIONS: Our findings suggest that both T-cell-mediated immunity and IgM antibodies may be involved in the regression of halo congenital nevus. However, it is important to point out that our results may simply be epiphenomena and not directly responsible for the destruction of nevus cells.

Coherent addition of injection-locked high-power AlGaAs diode lasers.

Coherent addition with the use of injection-locked AlGaAs high-power diode lasers has been performed. The linewidths of the master and slave lasers were narrowed to less than 30 kHz by using the optical feedback from an off-axis confocal Fabry-Perot resonator. The coherently added output power of two diode lasers was increased up to 110 mW, which corresponds to an addition efficiency of 0.85. The residual phase fluctuation of the system was controlled within 0.25 rad. Addition of three high-power diode lasers has been also demonstrated for the first time to our knowledge, and a total output power of 150 mW with an addition efficiency of 0.68 was obtained.

Human skin chymotrypsin-like proteinase chymase. Subcellular localization to mast cell granules and interaction with heparin and other glycosaminoglycans.

The subcellular localization of human skin chymase to mast cell granules was established by immunoelectron microscopy, and binding of chymase to the area of the dermo-epidermal junction, a basement membrane, was demonstrated immunocytochemically in cryosections incubated with purified proteinase prior to immunolabeling. Because heparin and heparan sulfate proteoglycans are major constituents of mast cell granules and basement membranes, respectively, the ability of chymase to bind to glycosaminoglycans (GAG) was investigated. Among a variety of GAGs, only binding of chymase to heparin and heparan sulfate appears physiologically significant. Binding was ionic strength-dependent, involved amino groups on the proteinase, and correlated with increasing GAG sulfate content, indicating a predominantly electrostatic association. Interaction with heparin was observed in solutions containing up to 0.5 M NaCl, and interaction with heparan sulfate was observed in solutions containing up to 0.3 M NaCl. Binding of heparin did not detectably affect catalysis of peptide substrates, but may reduce accessibility of proteinase to protein substrates. Measurements among a series of serine class proteinases indicated that heparin binding was a more common property of mast cell proteinases than proteinases stored in other secretory granules. Binding of chymase to heparin is likely to have a storage as well as a structural role within the mast cell granule, whereas binding of chymase to heparan sulfate may have physiological significance after degranulation.

Identification of a chymotrypsin-like proteinase in human mast cells.

An antiserum was produced against a chymotryptic proteinase purified from human skin. The antiserum did not cross-react with human leukocyte cathepsin G and elastase, rat mast cell proteinase I, and human skin tryptase. Indirect immunofluorescent staining of frozen skin sections to localize the proteinase showed cytoplasmic staining of cells scattered about the papillary dermis and around blood vessels and appendages. Restaining these sections with toluidine blue revealed that the fluorescently stained cells contained metachromatically staining granules, the major distinguishing feature of mast cells. A similar correlation was found in lung tissue. Ultrastructural studies employing the ferritin bridge technique to immunologically identify the proteinase additionally localized the proteinase to mast cell granules. Biochemical and immunochemical characterization of chymotryptic activity solubilized from isolated human lung mast cells identified a chymotryptic proteinase that may be identical to the skin chymotryptic proteinase. These studies establish that human skin mast cells contain a chymotrypsin-like proteinase that is a granule constituent and provide evidence that indicates a comparable proteinase is also present in lung mast cells.

Levels of placental protein 10 (PP 10) in maternal serum in normal and pathologic pregnancies.

Concentrations of placental protein 10 (PP 10) were measured by radioimmunoassay and found to be detectable but very low in nonpregnant women and in men. In an assay of 223 samples from normal pregnancies, the mean PP 10 level was 2.7 +/- 1.0 ng/ml (mean +/- SD) at 6 to 7 weeks of gestation. The level of PP 10 in maternal sera increased gradually as pregnancy progressed to a high of 40.2 +/- 19.0 ng/ml at 38 to 39 weeks, followed by a slight decrease to 28.9 +/- 15.6 ng/ml at 40 to 41 weeks. The coefficients of variation were 8.6 to 16.2% in diurnal variation and 10.3 to 34% in day-to-day variation. Relatively lower PP 10 levels were observed in maternal sera in threatened abortion with poor prognosis, toxemia of pregnancy, intrauterine fetal death and placenta previa.

Treatment of keratoacanthoma with intralesional bleomycin.

Six patients with keratoacanthoma were successfully treated with intralesional injection of bleomycin. This new therapy produced a marked shortening of the clinical course without any complications.

Circulating levels of placental protein 5 in normal and abnormal pregnancies.

Serum concentrations of PP5 were measured by radioimmunoassay in 219 women with normal pregnancies and 163 women whose pregnancies were complicated. PP5 in serum disappeared rapidly after delivery, with a half-life of 5-10 min in the first 10 min. Serum PP5 levels were higher in uterine than in antecubital venous blood. In normal pregnancies, PP5 was detectable at 7-8 weeks of gestation; its mean concentration rose gradually to a maximum of 17.8 +/- 10.2 ng/ml at 34-35 weeks of gestation. Elevated serum PP5 concentrations were noted in patients whose pregnancies were complicated by toxemia of pregnancy with appropriate-for-date baby or by twin pregnancy. Low serum PP5 concentrations tended to be found in patients whose pregnancies were complicated by abortion, intrauterine fetal death, and hydatidiform mole. Marked abnormal PP5 levels were not found in patients with maternal diabetes and placenta previa. These findings suggest that the assay of serum PP5 concentrations can be a useful parameter in determining the prognosis of abnormal pregnancies.

Possible relationship between the ratio of Factor VIII complex and placental insufficiency in preeclampsia.

The ratios of Factor VIII-related antigen (FVIIIR:Ag) to Factor VIII clotting activity (FVIIIC) were measured in 50 women during normal pregnancy and in 20 patients with preeclampsia and with intrauterine fetal growth retardation (IUGR). The mean ratios of FVIIIR:Ag to FVIIIC ranged from 0.6 +/- 0.22 to 0.8 +/- 0.58 (mean +/- SD) from the 28th to 40th week of normal pregnancy. On the other hand, the mean ratios of FVIIIR:Ag to FVIIIC in patients with preeclampsia and IUGR were 1.40 +/- 0.69 and 1.59 +/- 0.78 (mean +/- SD), respectively. This finding suggests that FVIII complex ratio may be considered an index of endothelial damage in preeclampsia and IUGR. This ratio test could be a more sensitive and reliable indicator of placental insufficiency if applied with non-stress test during late pregnancy.

Cartilaginous nevus on the glabella.

Cartilaginous nevus usually occurs in front of the auricle as an accessory auricle and much less frequently on the cheek or anterior part of the neck. We report a case of cartilaginous nevus found on an unusual location, The glabella of the face, in an otherwise normal newborn girl. We think that it was a remnant of the branchial cartilage derived from the first pharyngeal arch of embryonic life.

Inhibition of interferon-mediated induction of indoleamine 2,3-dioxygenase in mouse lung by inhibitors of prostaglandin biosynthesis.

Inhibitors of fatty acid cyclooxygenase such as indomethacin (0.1 mM), phenylbutazone (0.3 mM), and aspirin (1 mM) were found to suppress almost completely the interferon-mediated induction of indoleamine 2,3-dioxygenase in mouse lung slices. However, phenacetin, an anti-inflammatory agent devoid of cyclooxygenase inhibitory activity, and sodium salicylate, a weak inhibitor of cyclooxygenase, were much less active under identical conditions. Glucocorticoids including dexamethasone, betamethasone, and cortisone, all of which are inhibitors of phospholipase A2, blocked induction of the dioxygenase by interferon in the nanomolar range, whereas other steroid hormones, such as aldosterone, testosterone, and 17 beta-estradiol, were all but ineffective. These results suggest that the enzymes phospholipase A2 and fatty acid cyclooxygenase, both of which are essential for the biosynthesis of prostaglandins, play an important role in the induction of indoleamine 2,3-dioxygenase by interferon.