Quantitative analysis of changes in blood concentrations and 'presumed effect-site concentration' of sevoflurane during one-lung ventilation.

During one-lung ventilation, ventilation-perfusion mismatch decreases the arterial concentration of inhaled anaesthetics due to the arterial-to-venous concentration difference. This study tested the hypothesis that in humans, the 'presumed effect-site concentration' (taken as the mid-point between the arterial and superior jugular venous concentrations) of inhaled anaesthetic falls during one-lung (vs two-lung) ventilation. Four patients scheduled for elective prostatectomy (two-lung ventilation) and four patients for elective thoracotomy (one-lung ventilation) were randomly selected and assigned to receive sevoflurane (vaporiser-dial setting, 1.5%). Sevoflurane concentrations were measured periodically from radial artery and superior jugular vein (via a catheter advanced cephalad from the jugular vein). During one-lung ventilation, the end-expiratory sevoflurane concentration was stable at ∼1.3% but the mean (SD) presumed effect-site concentration declined initially from 58 (6.7) to 43 (4.7) µg.ml(-1) (p=0.011) before slowly recovering. A period of insufficient depth of anaesthesia is thus a risk during one-lung ventilation.

Tumour necrosis factor alpha signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice.

BACKGROUND: While tumour necrosis factor alpha (TNF-alpha) appears to be associated with the development of non-alcoholic steatohepatitis (NASH), its precise role in the pathogenesis of NASH is not well understood. METHODS: Male mice deficient in both TNF receptors 1 (TNFR1) and 2 (TNFR2) (TNFRDKO mice) and wild-type mice were fed a methionine and choline deficient (MCD) diet or a control diet for eight weeks, maintaining isoenergetic intake. RESULTS: MCD dietary feeding of TNFRDKO mice for eight weeks resulted in attenuated liver steatosis and fibrosis compared with control wild-type mice. In the liver, the number of activated hepatic Kupffer cells recruited was significantly decreased in TNFRDKO mice after MCD dietary feeding. In addition, hepatic induction of TNF-alpha, vascular cell adhesion molecule 1, and intracellular adhesion molecule 1 was significantly suppressed in TNFRDKO mice. While in control animals MCD dietary feeding dramatically increased mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) in both whole liver and hepatic stellate cells, concomitant with enhanced activation of hepatic stellate cells, both factors were significantly lower in TNFRDKO mice. In primary cultures, TNF-alpha administration enhanced TIMP-1 mRNA expression in activated hepatic stellate cells and suppressed apoptotic induction in activated hepatic stellate cells. Inhibition of TNF induced TIMP-1 upregulation by TIMP-1 specific siRNA reversed the apoptotic suppression seen in hepatic stellate cells. CONCLUSIONS: Enhancement of the TNF-alpha/TNFR mediated signalling pathway via activation of Kupffer cells in an autocrine or paracrine manner may be critically involved in the pathogenesis of liver fibrosis in this NASH animal model.

Interleukin-6 concentrations in the placenta and blood in normal pregnancies and preeclampsia.

AIM: To evaluate whether IL-6 concentrations in the placenta and blood from women with preeclampsia differed from those in normal pregnancies. METHODS: This study involved 41 pregnant women carrying single fetuses. Of these pregnancies, 23 were normal pregnant and 18 were preeclamptic patients. The average gestational age at entry was 37-38 weeks of gestation. Blood was collected before the onset of labor. Serum was separated and stored at -20 degrees C. A tissue segment of the placenta was cut and chilled in liquid nitrogen immediately after delivery and stored at -80 degrees C. The frozen tissue was added to phosphate-buffered saline and fully homogenized. After centrifugation, the separated supernatant was stored at -80 degrees C. IL-6 levels in separated serum and IL-6 and total protein (TP) levels in separated supernatant were measured. The presence of IL-6 in the placenta was evaluated by immunohistochemistry in five preeclamptic and five normal pregnant patients. RESULTS: Neither IL-6/TP levels in the placenta nor IL-6 levels in blood differed significantly between the two groups. IL-6 immunostaining on trophoblastic cells in the placenta was weak in one and absent in four in normal pregnancies, and absent in all patients with preeclampsia. There was no strong immunostaining for IL-6 in preeclampsia by immunohistochemistry. CONCLUSIONS: Our findings suggest that IL-6 in the placenta and blood does not play a significant role in the induction of an immunologic imbalance, which may contribute to the etiological mechanism leading to preeclampsia.

Undifferentiated endometrial carcinoma of the uterus: marked effect of chemotherapy with tetrahydropyranyl-adriamycin, paclitaxel, and carboplatin.

Undifferentiated endometrial carcinoma of the uterus is rare, and is thought to show a poor prognosis. To date, there is no consensus as to the optimal chemotherapy for this carcinoma. We report a rare case of this carcinoma in a patient who was treated surgically in combination with chemotherapy using a regimen designed by us. This chemotherapy consists of tetrahydropyranyl-adriamycin, paclitaxel, and carboplatin. This regimen is called TTJ [tetrahydropryanyl-adriamycin, taxan (paclitaxel), JM-8 (carboplatin)] chemotherapy and showed a marked effect. The patient was a 52-year-old woman with a giant tumor of the uterus measuring 28 x 18 x 13 cm and weighing 3386 g. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy, but residual carcinoma remained on the surface of the small intestine. Pathologically tumor tissues comprised the whole uterus except for the uterine cervix and there were tumor tissues in the omentum. She was treated with six courses of TTJ chemotherapy without major side-effects. Currently, she remains alive without metastasis 41 months after hysterectomy. This report describes a rare case of undifferentiated endometrial carcinoma of the uterus and introduces TTJ chemotherapy resulting in the remarkable effect on this carcinoma.

Increased levels of serum macrophage colony-stimulating factor before the onset of preeclampsia.

Macrophage colony-stimulating factor (M-CSF) is known to play a central role in maintaining pregnancy. The present study determined whether the increase in serum M-CSF levels preceded the onset of preeclampsia. Blood was collected from 110 normotensive pregnant women at risk for preeclampsia who were carrying single fetuses at about 30 weeks of gestation. After centrifugation, serum was stored at -20 degrees C until assay. Eighteen women developed preeclampsia at a later stage of pregnancy (group 1), while 88 women continued to have normotensive pregnancies until delivery. Thirty-four of the 88 women with normotensive pregnancy who were matched for age and parity were selected to form a control group (group 2). Serum M-CSF levels were determined by the sandwich ELISA method using three antibodies. Serum level of M-CSF was 1,266 U/ml (median) in group 1 and 1,082 U/ml in group 2. Serum M-CSF levels were significantly higher in group 1 than in group 2 (p < 0.0002). Increased levels of serum M-CSF markedly precede the development of clinical manifestations of preeclampsia. High serum M-CSF levels support M-CSF elevation in the placenta. This elevation at 30 weeks of gestation may be associated with placental hypoxia, which is considered the cause of preeclampsia.

Platelet aggregation response and adenosine triphosphate secretion after abdominal total hysterectomy.

This study was designed to clarify the quantitative relationship between platelet aggregation and the secretion of adenosine triphosphate (ATP) after surgery. Peripheral blood was collected from 41 patients who underwent abdominal total hysterectomy. Platelet count, volume, aggregation and the amount of secreted ATP were determined using live platelets before, one day after and two weeks after surgery. Platelet aggregation and ATP secretion were investigated using a lumi-aggregometer. The aggregating reagents used were 5 microM of adenosine diphosphate (ADP) (final concentration) and 5 microg/ml of collagen. Structural alterations of platelets at these time points were also investigated by electron microscopy. Platelet aggregation induced by collagen was significantly lower (p<0.05) one day after surgery. ADP-induced aggregation two weeks after surgery was more intense than before (p<0.05) and one day after (p<0.05) surgery. The amount of secreted ATP induced by each of ADP and collagen was significantly lower (p<0.05-0.01) one day after surgery and correlation coefficients between platelet aggregation and secretion of ATP showed lower values in both ADP- and collagen-induced aggregation. One day after surgery electron microscopy showed that granule concentrations were markedly reduced in platelets. In conclusion, after consumption of circulating platelets at the site of operation, in addition to being lost by bleeding, the remaining platelets in circulation consist of platelet subpopulations different from those present before surgery, exhibiting low values of correlation coefficients between platelet aggregation and secretion of ATP and low concentrations of granules.

Mature adrenomedullin concentrations in plasma during pregnancy.

OBJECTIVE: Adrenomedullin is a novel peptide that exerts a potent, dose-dependent and long-lasting hypotensive effect. In human plasma, adrenomedullin consists of two molecular forms: mature and immature. Immature adrenomedullin is much less bioactive than mature adrenomedullin. Although a gradual increase in plasma adrenomedullin has been reportedly observed as pregnancy progressed, mature adrenomedullin has not been examined. The aim of this study was to elucidate the plasma level of mature adrenomedullin in pregnant women. METHODS: We measured the concentrations of mature adrenomedullin in ten pregnant women in the first trimester, ten pregnant women in the third trimester, and ten non-pregnant controls with the immunoradiometric assay. RESULTS: The mean concentration of mature adrenomedullin was significantly increased in pregnant women in the first trimester compared to age-matched non-pregnant subjects (p < 0.05). The mean concentration of mature adrenomedullin was significantly increased in pregnant women in the third trimester compared with pregnant women in the first trimester (p < 0.005). CONCLUSION: Our study demonstrated that concentrations of mature adrenomedullin were elevated in pregnant women compared with non-pregnant women and its concentration in the third trimester was significantly higher than that in the first trimester.

Successful pregnancy following gonadotropin therapy in a patient with hypogonadotropic hypogonadism resulting from craniopharyngioma.

The authors report a rare case of a patient with panhypopituitarism who became pregnant by gonadotropin therapy and gave birth to a healthy baby. A brain tumour and/or the surgical resection of a brain tumour occasionally results in pituitary dysfunction. An 18-year-old Japanese patient developed hypogonadotropic secondary amenorrhoea because of a craniopharyngioma, which was surgically removed. The patient came to us, and peripheral blood was collected every 15 minutes for four hours. The levels of luteinising hormone (LH) and follicle-stimulating hormone (FSH) were measured. Results showed that LH and FSH levels were very low and did not fluctuate. Several years later, the patient complained of infertility, and treatment with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) was started. The therapy was repeated for several cycles, but she did not conceive, so hMG-hCG therapy combined with conjugated oestrogen administration was started. The patient became pregnant at the seventh cycle of this combined therapy. She was not treated with supplementary growth hormone.

CD26 and CD30 expression on the surface of lymphocyte during normal pregnancy.

It is increasingly apparent that the Th1/Th2 cell ratio is decreased during pregnancy. In a previous study, we revealed that combined analysis of soluble CD26 and CD30 might be a potent surrogate tool for evaluating the Th1/Th2 balance during pregnancy. Therefore, in the present study, we elucidated whether the CD26 and CD30 expression on the surface of lymphocyte is useful marker for Th1 and Th2 lymphocytes, respectively, during pregnancy with flow cytometric technique. The peripheral blood samples were obtained from 6 non-pregnant healthy women, 8 healthy pregnant women in the first trimester and 12 pregnant women in the third trimester. The mean percentages of CD26 expression did not differ significantly among these groups (p = 0.45). Also, the mean percentages of CD30 expression did not differ significantly among these groups (p = 0.32). From the present study, the expression of CD26 and CD30 did not appear to be a useful marker for Th1 and Th2 lymphocytes during pregnancy.

[Endoscopic transthoracic sympathectomy (ETS) with a fine 2-mm thoracoscope in palmar hyperhidrosis].

Endoscopic transthoracic sympathectomy (ETS) is an efficient, safe, minimally invasive procedure, and requires only a short period of hospitalization. We performed bilateral ETS using a thoracoscope 2 mm in diameter. We performed 120 ETS for the treatment of palmar hyperhidrosis from August 1997 to April 2000. The patient was placed in the semi-sitting position under general anesthesia, one-lung ventilation being used; the operation was performed with 2-mm two-puncture method. The sympathetic chain could be observed through parietal pleura riding on the costovertebral junctions. A 2-mm Kirschner wire was employed as an electrode, and the second and third thoracic sympathetic chains were electro cauterized. A thoracic drain was not used. The needling sites were only 2 mm in size and could be fixed without suture. For the patient, a small scar of this size means virtually no scar. The operative times were from 11 min to 81 min in bilateral ETS. Immediately and dramatic decrease in the sweat excretion in the palms was noted in all patients. The 95% patients were highly satisfied with the results. The commonest side effects were compensatory sweating. This procedure is recommended as the method of choice for the surgical treatments of palmar hyperhidrosis.

Increased excretion of N-acetyl-beta-D-glucosaminidase and beta2-microglobulin in gestational week 30.

BACKGROUND: Little is known about when the urinary excretion of a combination of N-acetyl-beta-D-glucosaminidase (NAG) and beta2-microglobulin (beta2MG) concentration [relative to creatinine (Cr)] reaches maximal values during uncomplicated normotensive pregnancy. This study was thus designed to analyze when urinary excretion of biochemical parameters was increased during normotensive pregnancy. METHODS: NAG, beta2MG, total protein, albumin, and Cr were simultaneously measured in random (untimed) midstream urine samples from 22 healthy nonpregnant women and from 82 normotensive pregnant women (22 in gestational week 20, 25 in week 30, and 35 in week 37). RESULTS: NAG/Cr and beta2MG/Cr ratios were significantly higher (P < 0.01-0.05) in the normotensive pregnant women in gestational week 30 than in the nonpregnant control subjects and normotensive pregnant women in gestational week 20. The NAG/Cr and beta2MG/Cr ratios showed maximal values in gestational week 30. The total protein/Cr ratio was significantly higher in gestational weeks 20, 30, and 37 than in the control subjects. The albumin/Cr ratio was significantly higher in women in gestational week 30 and 37 than in women in gestational week 20 and in the control subjects. CONCLUSIONS: The excretion of both NAG and beta2MG relative to Cr was increased and showed the maximal values in gestational week 30 during normotensive pregnancy. The increase in a tubular enzyme (NAG) might be caused by renal tubular damage, and that in a low molecular weight protein (beta2MG) might result from decreased renal tubular reabsorption. These findings suggest that renal tubular damage and reabsorption dysfunction were increased in gestational week 30.

Plasma levels of soluble Fas during normal pregnancy.

The Fas/Fas ligand system could reportedly help to identify a mechanism for maternal immunotolerance of the fetus in human pregnancy. However, there are few reports on soluble Fas (sFas) which is an inhibitor of apoptosis during normal pregnancy. Therefore, ascertaining plasma sFas levels during pregnancy would be of interest. The subjects studied were 10 nonpregnant healthy women and 20 healthy pregnant women in the first and third trimester with singleton gestations. The plasma sFas was measured by sandwich enzyme-linked immunosorbent assay. The mean concentration of sFas was significantly decreased in normal pregnant women in the first trimester compared to age-matched control subjects, and it did not differ significantly between normal pregnant women in the third trimester and age-matched control subjects. From these results, we presume that the decreased plasma sFas plays an important role in maternal immunotolerance in the first trimester of pregnancy.

Relationship between exploratory eye movements and clinical course in schizophrenic patients.

Exploratory eye movements are psychophysiological indicators of schizophrenia as well as smooth pursuit eye movements. To investigate whether these eye movements change in accordance with the clinical course of the condition in schizophrenia, exploratory eye movements (number of eye fixations, mean eye scanning length, responsive search score, evaluation of reproduced Fig. 1 and 2) of 28 schizophrenic patients were evaluated in repeat test design, conducted an average of 8 months apart. Subjects were first-medicated schizophrenics, half were outpatients and the remaining half were inpatients at the Neuropsychiatry ward of Tokyo Medical and Dental University Hospital. Exploratory eye movement patterns did not improve despite an improvement in clinical symptoms of schizophrenia. This result and those of previous studies of the exploratory eye movements of schizophrenic patients' families suggest that exploratory eye movements reflect a schizophrenic vulnerability marker. Furthermore, decreased mean eye scanning length (MESL) values were observed in subjects who showed unimproved symptoms, particularly negative symptoms over an extended period of time. The result suggests that a decrease in the MESL value may be the most sensitive indicator in the development of chronicity in schizophrenia.

Changes in plasma soluble CD26 and CD30 during pregnancy: markers of Th1/Th2 balance?

The theory that the Th1 and Th2 cell ratio shifts towards Th2 dominance during pregnancy may improve fetal survival has gained support from recent studies. Also, the variation in the Th1/Th2 cell ratio is reportedly associated with intrauterine growth retardation and preeclampsia. On the basis of these findings, the analysis of the Th1/Th2 balance may be useful in predicting severe complications during pregnancy. However, simple methods for the analysis of Th1/Th2 balance are presently not available. Recently, it has been reported that regulation of CD26 cell surface expression correlates with the production of Th1-like cytokines. On the other hand, previous studies proposed that the sCD30 molecule is an activation marker useful for evaluation of a Th2 immune response. It is, therefore, possible that the analysis of the Th1/Th2 balance during pregnancy by measuring plasma sCD26 and sCD30 simultaneously is a simple and useful method. We herein demonstrate that combined analysis of sCD26 and sCD30 is a potent surrogate tool to evaluate the Th1/Th2 balance during pregnancy.

A 25-year-old patient with low cardiac risk factors having a combination of variant angina and severe coronary arterial lesions--a case report.

A 25-year-old man with low cardiac risks underwent coronary arteriography because of chest pain at rest. His only risk factors for coronary artery disease was smoking. Both right and left coronary arteries were ectatic and the left anterior descending artery was obstructed. In the acetylcholine provocation test, the left circumflex coronary artery showed severe constriction. Thus, this patient was diagnosed as having a combination of variant angina and occlusive coronary artery disease.

Osteochondroma of the pubic symphysis associated with sexual disturbance.

Osteochondroma of the pubic symphysis is a rare benign skeletal tumor. We report here a case of an osteochondroma of the pubic symphysis associated with a sexual disturbance, where a computed tomography scan clearly showed a tumor lesion of the pubic symphysis. The case is reported not only because of its rarity but also because it is important that gynecologists should bear this disease in mind, since a patient with this tumor may not visit an orthopedist but a gynecologist.

Primary small cell neuroendocrine carcinoma of the vagina. Marked effect of combination chemotherapy: a case report.

Primary small cell neuroendocrine carcinoma of the vagina is extremely rare and very aggressive. Nineteen patients with this cancer have been reported in the English-language literature to date. We report a 51-year-old woman with this cancer. Punch biopsy specimens of the vaginal tumor were studied. Electron microscopy demonstrated neuroendocrine granules in the cytoplasm. Tumor cells were strongly stained for cytokeratin, neuron-specific enolase, chromogranin A and serotonin. These findings were consistent with small cell neuroendocrine carcinoma. The patient was treated with combination chemotherapy. The cancer mass completely disappeared after five cycles of the therapy. The patient is still alive without metastasis 41 months after diagnosis. This is the first report of such a remarkable effect of combination chemotherapy on small cell neuroendocrine carcinoma of the vagina.

Angiosarcoma of the chest wall.

A 50-year-old man sustaining bilateral chest wall angiosarcomas at intervals of several months underwent lesion resection. Angiosarcoma is so rare that we found no case in the literature who had undergone bilateral chest wall surgery for such tumors. His second tumor was thought to be metastatic rather than primary. Despite the 2 surgeries, irradiation, and chemotherapy, however, his prognosis was grave, as in other reports on angiosarcoma.