A case of fungemia due to Candida krusei.

A forty-eight-year old male diagnosed with acute lymphocytic leukemia was further complicated by Candida krusei fungemia despite introduction of fluconazole prophylaxis during antileukemic therapy. The fungemia subsided after intravenous amphotericin B therapy followed by itraconazole therapy. Multiple ulcerative lesions and a carcinoid lesion were observed in the transverse colon, and it was thought that the C. krusei had invaded from the ulcerative lesions. Azole antifungal agents, especially fluconazole, have frequently been used for therapy and the prophylaxis of fungal infections. Though infections due to fluconazole-resistant Candida species such as C. krusei are a growing problem, in the hematology division of our hospital there is no evidence of an increasing incidence of C. krusei fungemia or an increasing rate of C. krusei in surveillance culture from admitted patients. However, future increases in infections due to fluconazole-resistant Candida species like C. krusei and C. glabrata are entirely possible, making it necessary to identify isolated fungi, perform susceptibility tests on antifungal agents against isolates, measure the serum concentrations of antifungal agents, and then to treat patients with the appropriate therapies.

A newly identified horseshoe crab lectin with specificity for blood group A antigen recognizes specific O-antigens of bacterial lipopolysaccharides.

A 14-kDa lectin, named tachylectin-3, was newly identified from hemocytes of the Japanese horseshoe crab, Tachypleus tridentatus. This lectin exhibited hemagglutinating activity against human A-type erythrocytes, but not against the B- and O-types of erythrocytes and animal erythrocytes, including those of sheep, rabbit, horse, and bovine. The hemagglutinating activity of tachylectin-3 was equivalent to that of a previously identified lectin, named tachylectin-2, with affinity for N-acetyl-D-glucosamine or N-acetyl-D-galactosamine. However, the activity of tachylectin-3 was not inhibited by these two N-acetylhexosamines at 100 mM but was inhibited by a blood group A-pentasaccharide at a minimum inhibitory concentration of 0.16 mM. Furthermore, the hemagglutinating activity was strongly inhibited by bacterial S-type lipopolysaccharides (LPSs) from Gram-negative bacteria but not by R-type LPSs lacking O-antigens. One of the most effective S-type LPSs was from Escherichia coli O111:B4, with a minimum inhibitory concentration of 6 ng/ml. These data suggest that tachylectin-3 specifically recognizes Gram-negative bacteria through the unique structural units of O-antigens. Ultracentrifugation analysis revealed that tachylectin-3 is present in dimer in solution. A cDNA coding for tachylectin-3 was isolated from a hemocyte cDNA library. Tachylectin-3 consisted of two repeating sequences, each with a partial sequence similarity to rinderpest virus neuraminidase. Tachylectin-3 and three previously isolated types of tachylectins were all predominantly expressed in hemocytes and released from hemocytes in response to external stimuli. These lectins present at injured sites suggest that they probably serve synergistically to accomplish an effective host defense against invading microbes.

[Relief of neuropathic pain with intravenous magnesium].

We investigated the effect of intravenous magnesium, a N-methyl-D-asparate (NMDA) receptor antagonist, in 8 patients suffering from neuropathic pain (post herpetic neuralgia or causalgia etc.). After the nerve block, magnesium sulphate (0.5 mol.l-1) 5 ml was administered intravenously by bolus infusion taking 5 min, followed by continuous infusion of the same dose for one hour. All patients were treated with this therapy once a week. In 4 patients, VAS score decreased 3 points or more when this therapy had been administered 3 to 11 times. In 2 patients, VAS score did not change, and the analgesic effect of magnesium was not certain in other 2 patients. Some patients felt heat sensation immediately after the bolus infusion of Mg, and had a good sleep after this therapy. However, there were not any severe side effects and significant change in HR or BP. We conclude that this therapy with magnesium once a week is safe and effective for relieving neuropathic pain.

[Sixty percent lidocaine tape alleviates pain on injection of propofol after diminishing venipuncture pain].

We evaluated the efficacy of the 60% lidocaine tape in alleviating pain associated with intravenous propofol administration in 71 gynecological patients. Thirty-eight women had the tape applied for 2.5 h before venipuncture, with the remaining patients acting as the control. A 20 gauge cannula was inserted into the cephalic vein. Propofol at room temperature was injected at a rate of 1200 ml.hr-1. The statistical significance of differences was established with the Mann-Whitney's U test and the chi 2 test. The median level of pain intensity resulting from venipuncture among the patients treated with the tape was smaller than that in the control group (16.5, vs 34, P = 0.006). Thereafter, cannulation was successfully achieved with reduced or no pain (VAS at cannulation < or = 25, n = 39), and only 16% of the treatment group complained of pain on injection as compared with 53.8% of the control group (P = 0.02). Moreover, the pain intensity was decreased with lidocaine tape (P = 0.006). The cost of the lidocaine tape is covered by medical insurance for reducing pain on venipuncture. Thus, as the tape also alleviates the pain on injection of propofol through its anesthetic action, it can be a safe, easy and cost-effective method as "it kills two pains with one tape".

Hemophagocytosis as a para-neoplastic syndrome in NK cell leukemia.

Hemophagocytic syndrome is a proliferative disorder of an activated monocyte-macrophage system and is characterized by fever, hepato-splenomegaly and pancytopenia. The serum level of interferon-gamma in the syndrome is increased but its origin is unknown. Here we describe a case of NK cell leukemia with hemophagocytic syndrome with elevated serum level of interferon-gamma. The levels of various cytokines were monitored during the course and statistic analysis was performed. To identify the clonal component, the NK cell fraction was sorted from the mononuclear layer and was subjected to Southern blot hybridization with a probe for EB virus tandem repeats. The fraction was also stimulated with interleukin-2 and the level of interferon-gamma in the conditioned medium was measured. Levels of M-CSF and interferon-gamma were significantly correlated with the degree of clinical manifestations and laboratory data. Southern blot hybridization revealed monoclonality of an NK cell fraction. The fraction also released interferon-gamma. Since macrophage can be activated through cytokines, the hemophagocytosis might have been triggered by factor(s) released from the abnormal NK cell clone at least in this case.

[The relief of postoperative pain by suppositories of buprenorphine or NSAID].

We evaluated the effects of suppositories of buprenorphine (BN) or NSAID (supp.) preoperatively administered for postoperative pain relief in patients who underwent elective gynecological surgeries. Fifty six patients were randomized into four groups: group B; 0.4 mg BN supp., group B+I; 0.4 mg BN supp. and 50 mg indomethacine (IND) supp., group B+D; 0.4 mg BN supp. and 50 mg diclofenac supp., group C; no supp. given as control. They were administered rectally after induction of general anesthesia. In all the supp. groups the patients had good pain relief during the first 24 hrs after the administration of supp. Group B+I seemed to have better pain relief, but, there was no statistical significance among the 3 groups. Nausea and vomiting were observed more frequently in group B and in control group C than in NSAIDs combined groups. The difference in the incidence rates was not significant. In conclusion, the simultaneous administration of BN and IND supp. was considered to be useful for postoperative pain relief without producing major side effects.

Endothelin-1-like immunoreactivity and endothelin receptors in the human placenta from normotensive and hypertensive pregnancies.

The levels of endothelin-1-like immunoreactivity (ET-1-LI) and characteristics of endothelin receptors in the chorionic villous tissue of human placenta were determined. The ET-1-LI level in chorionic villous tissue obtained from normal term placenta was 2,450 +/- 940 pg/g wet weight (mean +/- SD, n = 4). Further analysis using gel permeation chromatography and reverse-phase high performance liquid chromatography showed that the main ET-1-LI constituent of ET-1-LI in this tissue was ET-1. Scatchard analysis of [125I]ET-1 binding to the membrane fraction of chorionic villous tissue obtained from term placenta showed high affinity receptor sites with an apparent dissociation constant (Kd) of 23.6 +/- 11.1 pM and a Bmax value of 388 +/- 238 fmol/mg protein (n = 5). The same binding study with [125I]ET 3 showed a Kd of 13.9 +/- 3.8 pM and a Bmax value of 176 +/- 78 fmol/mg protein (n = 5). These results suggest that both ET-A and ET-B receptors (ET-AR and ET-BR) are expressed in chorionic villous tissue. This finding was further confirmed by Northern blot analysis showing the expression of both ET-AR and ET-BR mRNAs in this tissue. ET-1-LI in the umbilical venous plasma of the newborns from women with pregnancy-induced hypertension (PIH) (38.3 +/- 10.4 pg/mL, n = 5) was significantly (P < 0.05) higher than that in the normal newborns from normotensive pregnant women (26.3 +/- 5.2 pg/mL, n = 12). However, in placental chorionic villous tissue obtained from PIH women, both ET-1-LI level and ET binding profile were not different from those in chorionic villous tissue from normotensive pregnant women. These results suggest that the abundant ET-ET receptor system is present in the placental chorionic villous tissue and that this system is not the major factor of the pathogenesis of placental dysfunction occurring in PIH because these systems are similar in normotensive and hypertensive pregnancies.

[Successful treatment of splenomegaly and anemia by VP therapy in idiopathic myelofibrosis complicated with acromegaly: a case report].

Here we report a 65-year-old male patient with idiopathic myelofibrosis (IMF) accompanied with acromegaly. He was admitted because of anemia and splenomegaly. No favorable effects were observed when hydroyurea was administered. However, his symptoms were successfully treated by administration of vincristine and prednisolone (VP therapy), which is usually applied for choronic myelogenous leukemia in the accelerated phase. Therefore, VP therapy might be one possible for IMF. Since there have been several reports suggesting the possible association of hematological malignancies with acromegaly, we speculate that acromegaly was implicated in the initiation or progression of IMF in this case.

[Use of Finapres during warming for postoperative patients].

We used Finapres during rewarming after extracorporeal circulation in 16 patients who underwent cardiac surgery. In patients with passive rewarming there were no differences in blood pressure measured with a Finapres and that by an invasive monitor. On the other hand, in patients rewarmed with the aid of nitroglycerin, there were statistically significant differences between blood pressures measured with indirect and direct methods.

[Effect of the type of an epidural catheter on the flow rate of a disposable balloon infuser].

We examined the effects of the bacterial filter and the type of epidural catheter on the flow rate of a disposable balloon infuser. The presence or absence of bacterial filters, and the material of the catheter did not influence the flow rate. On the other hand, the flow rate becomes smaller, as the diameter of the epidural catheter is reduced.

Endothelin receptors in the human amnion, chorion laeve, decidua vera and placenta.

The levels of endothelin-1 (ET-1) and the characteristics of endothelin (ET) receptors were investigated in the amnion, chorion laeve, decidua vera and placenta by using a specific radioimmunoassay for ET-1 and a saturation binding assay for ET. ET receptor gene expression in these tissues was also examined by Northern blot analysis. The levels of ET-1-like immunoreactivity (ET-1-LI) in the human amnion, chorion laeve, decidua vera and placenta obtained at elective Caesarean section before labour onset at term (mean +/- s.e.m.) were 1260 +/- 380 (n = 6), 3740 +/- 980 (n = 4), 4550 +/- 780 (n = 4) and 2450 +/- 470 (n = 4) pg g-1 wet weight, respectively. The levels of ET-1-LI in the tissues obtained after spontaneous vaginal deliveries at term did not differ from these. Gel-permeation chromatography and reverse-phase high-performance liquid chromatography revealed that the ET-1-LI in these tissues was mainly composed of ET-1. Scatchard analysis of the saturation binding assay for [125I]-labelled ET-1 and [125I]-labelled ET-3 indicated that high concentrations of both ET-A and ET-B subtypes of receptor were present in membrane fractions from the chorion laeve, decidua vera and placenta. However, in membrane fractions from the amnion, no ET receptors could be detected. These results were confirmed by Northern blot analysis using human ET-A and ET-B receptor cDNA probes. Taken together, these results suggest that the amnion is not the site of action of amniotic ET, and that ET may be involved in the regulation of functions of the chorion laeve or decidua vera.

Activation of phospholipase D in cultured human amnion cells.

The regulation of phospholipase D (PLD) activity in the human amniotic membrane was examined using primary cultures of amnion cells. Cultured amnion cells were labelled with [3H]oleic acid, and PLD activity was determined as the amount of [3H]phosphatidylethanol (PEt) produced during incubation in the presence of 0.1% ethanol. PLD activity in cultured amnion cells was activated by addition of arginine vasopressin and oxytocin. PLD activity was also stimulated by treatment was arachidonic acid, the product of phospholipase A2 (PLA2), and phospholipase C (PLC). These results indicate that PLD in amnion cells is activated by substances present in amniotic fluid, and that cross-talk between phospholipases A2, C and D may occur in amnion cells.

Transforming growth factor-beta stimulates, and glucocorticoids and epidermal growth factor inhibit brain natriuretic peptide secretion from cultured human amnion cells.

We previously reported the massive secretion of brain natriuretic peptide (BNP) from human amnion cells and suggested the possible role of BNP in the maintenance of human pregnancy. In this study, to elucidate the regulatory mechanism of BNP secretion from amnion cells, we measured the BNP level in the culture medium of amnion cells by RIA after incubation in the presence of various substances. Among the agents examined, cortisol (1 x 10(-7) to 1 x 10(-6) mol/L), dexamethasone (1 x 10(-8) to 1 x 10(-6) mol/L), and epidermal growth factor (EGF; 2 x 10(-11) to 2 x 10(-8) mol/L) inhibited BNP secretion from the cultured amnion cells in a dose-dependent manner. By contrast, transforming growth factor-beta (TGF beta; 4 x 10(-11) to 4 x 10(-9) mol/L) caused a 3- to 5-fold increase in BNP secretion. TGF beta-augmented BNP secretion was abolished by the addition of cortisol or EGF to the culture medium. Moreover, in this study, we revealed the presence of bioactive TGF beta in human amniotic fluid (approximately 4 x 10(-10) mol/L). The present finding of tight regulation of BNP secretion from amnion cells by cortisol, EGF and TGF beta, all at the concentrations physiologically present in human amniotic fluid, implies a physiological role of BNP secretion from amnion cells in the pregnant uterus.

Marked and reproducible increase in trilineage blood cell counts by administration of granulocyte colony-stimulating factor in a patient with refractory anaemia with excess blasts in transformation.

We report a patient with refractory anaemia with excess blasts in transformation (RAEB-t) who presented with severe pancytopenia and received four intermittent series of granulocyte colony-stimulating factor (G-CSF) treatment over 1.5 years. In addition to the increase in mature neutrophils, platelet count and haemoglobin level were dramatically increased. These haematological improvements were dependent on G-CSF during these treatment series. Bone marrow colony assay revealed that G-CSF increased both CFU-E- and BFU-E-derived colonies in vitro. Clinical usage of G-CSF in myelodysplastic syndrome (MDS) is discussed, with particular emphasis on mechanisms of trilineage response.

Clinical application of pulsatility index of flow volume to detect the hemodynamic changes in IUGR fetus.

We attempted to assess feto-placental circulation in fetuses with intrauterine growth retardation (IUGR) by calculating the pulsatility index of flow volume (PIQ) based on the quantitative measurement of blood flow. Doppler sound was processed by an analog to digital converter and a frequency analyzer. Multiplication of frequency and signal strength of the Doppler sound at a certain time theoretically represents a value proportional to flow volume. Using this value, we calculated PIQ of the descending aorta, umbilical artery, and middle cerebral artery in normal fetuses, IUGR fetuses, and distressed fetuses during 24-41 weeks gestation. The PIQ of the fetal descending aorta in the IUGR fetus was significantly higher than that of the normal fetus. When cutoff value was set to mean +1 SD, abnormal PIQ was observed in 88% of IUGR fetuses. In contrast, the abnormal pulsatility index of maximal flow velocity (PIV) of the descending aorta was observed in only 62% of IUGR fetuses. In the distressed fetuses, both PIQ and PIV of the umbilical artery increased, and these indices of the middle cerebral artery markedly decreased. It is suggested that the increased PIQ of the descending aorta is an early indicator of changes in the fetal circulation in IUGR fetuses.

Identification of homeobox genes expressed in human T-lymphocytes.

Homeobox genes encode transcription factors involved in the process of normal development and differentiation of cells and organs. Recently, some homeobox genes are found implicated in hemato-lymphoid neoplasms. To assess the role of homeobox genes in normal development and neoplastic transformation of T-cells, we have surveyed for homeobox-containing gene expression in a human T-cell leukemia line with a polymerase chain reaction. Ten members of homeobox genes were isolated, including one novel sequence. The novel sequence was most related to mouse Cdx. One of the others, HOXB7, is expressed in most malignant T-cell lines and CD4-positive peripheral blood T-cells. Together with the recent observations, these results suggest that the protein products of these genes may participate in normal functions and/or transformation of T-cells.

Brain natriuretic peptide is present in the human amniotic fluid and is secreted from amnion cells.

The presence and biochemical characteristics of human brain natriuretic peptide (hBNP) in the amniotic fluid at various gestational ages were investigated. The hBNP-like immunoreactivity (hBNP-LI) levels in amniotic fluid, determined by RIA, were 118.7 +/- 57.6 pmol/L (mean +/- SEM; n = 5) and 107.7 +/- 8.7 pmol/L (n = 9) in the first and second trimesters of pregnancy, respectively; it was significantly decreased to 28.4 +/- 5.1 pmol/L (n = 9) in the third trimester. However, human atrial natriuretic peptide-like immunoreactivity (hANP-LI) was not detected (< 0.3 pmol/L) in any of these samples. Northern blot analysis demonstrated hBNP mRNA in human amnion tissue. Moreover, cultured amnion cells secreted a significant amount of hBNP-LI (100-200 fmol/10(6) cells/day), but not hANP-LI, into the culture medium. The synthesis of hBNP in cultured amnion cells was further confirmed using the polymerase chain reaction. High performance gel permeation chromatography of hBNP-LI extracted from human amniotic fluid and the culture medium of amnion cells revealed that the predominant molecular form of hBNP-LI in both samples was the hBNP precursor, with an approximate mol wt of 12 kilodaltons. These findings indicate that hBNP is present in the human amniotic fluid, and that amnion cells synthesize hBNP and secrete it into the amniotic cavity.

Lupus anticoagulant (LAC) and its relation to pregnancy outcome: a report of five cases.

We examined the relation between the spontaneous remission and prednisolone-induced suppression of lupus anticoagulant (LAC) or anticardiolipin antibody (ACA) and pregnancy outcome in 5 LAC-positive women. Two women showed a spontaneous remission of LAC and ACA during the observation period. One of these 2 women became pregnant and delivered healthy twin infants at 36 weeks of pregnancy without any therapy. The other woman became LAC positive again after 1 year of remission, and experienced 2 more fetal losses. Two of the remaining LAC-positive women received prednisolone and aspirin. Only 1 woman, whose ACA was suppressed by medication, delivered a healthy newborn. The pregnancy of the other woman, whose LAC and ACA remained positive in spite of medication, terminated in an IUFD. These results suggest that the administration of prednisolone and aspirin is the first choice of therapy for LAC-positive women, and that encouraging such women to become pregnant while LAC is negative might be an alternative therapy.