Feasibility and efficacy of intraperitoneal docetaxel administration as salvage chemotherapy for malignant gynaecological ascites.

Ovarian and endometrial cancers diagnosed at advanced stages are often associated with malignant ascites. This study aimed to determine the safety, feasibility and efficacy of intraperitoneal (IP) docetaxel (TXT) for the treatment of ascites. A phase I study, including nine patients, was undertaken to determine the maximum tolerable dose. Efficacy was retrospectively assessed in 18 patients treated with 40-70 mg/m(2) IP TXT between 2005 and 2012. In a phase I study, the dose was safely escalated to a maximum of 70 mg/m(2), at which level no patients had grade -3 haematological adverse events. In a retrospective study of 18 patients, seven had an Eastern Cooperative Oncology Group performance status of 3; 16 had prior paclitaxel administration and two, with doses of 40 and 70 mg/m(2), experienced a serological response and a decrease in paracentesis. Thus, palliative treatment of recurrent OC should be further studied with 40 mg/m(2) among more patients, and 70 mg/m(2) could be evaluated for first-line IP chemotherapy.

Frequency and risk factors for sepsis resulting from neuroendovascular treatment.

OBJECTIVE: Endovascular treatments are minimally invasive and rarely cause complicating infections. Although cases complicated by device infections have been reported, we could not find any studies evaluating infections following neuroendovascular treatment in particular. Therefore, we assessed the frequency of sepsis and other associated risk factors. METHODS: From September 2006 to May 2008, we investigated 256 prospective neuroendovascular treatment cases at our facility. We examined the frequency of sepsis and other associated risk factors as well as organisms and the early detection tests such as various cultures and serodiagnoses. RESULTS: The rate of sepsis due to complications was 8.6% in the aggregate and 5.7% in 193 procedures without a central venous catheter and hemodialysis. All sepsis cases were successfully treated with antibiotics. However, in 2 cases, the patients developed methicillin-resistant STAPHYLOCOCCUS AUREUS infections, which were intractable. The highest risk factors for sepsis were a large sheath size [>7 F; OR =5.03; P =0.01; 95% confidence interval (CI) 1.29-19.47] and meningioma embolization (OR =13.25; P =0.04; 95% CI 1.07-163.56). The degree to which experienced staff (OR =0.09; P =0.05; 95% CI 0.09-0.97) affected the incidence of sepsis was less significant. Microorganisms were isolated from half the operating field, and the risk factor, in this case, depended on inexperienced surgical staff (OR =1.98; P =0.03; 95% CI 1.07-3.67). Although we were unable to find a means to predict sepsis, we presumed antibiotic prophylaxis would be useful. CONCLUSIONS: The frequency of sepsis following neuroendovascular treatment is high. We should pay particular attention to the sterilization process and the operating field when undertaking neuroendovascular treatment that requires the use of a large-size sheath in patients with serious conditions.

Dural arteriovenous fistula presenting as an acute subdural hemorrhage that subsequently progressed to a chronic subdural hemorrhage: case report.

OBJECTIVE AND IMPORTANCE: Non-traumatic subdural hemorrhage (SDH) caused by dural arteriovenous fistula (DAVF) is rare and is usually accompanied by intracerebral hemorrhage (ICH) and/or subarachnoid hemorrhage (SAH). This report describes a very rare case of DAVF that caused non-traumatic acute SDH without ICH or SAH, which subsequently progressed into chronic SDH. CASE REPORT: The patient presented with a sudden-onset severe headache, and was diagnosed with acute SDH by computed tomography. Cerebral angiography showed a DAVF on the left convexity adjacent to the superior sagittal sinus (SSS). This DAVF drained to the SSS and to the pterygoid venous plexus via the left middle fossa without retrograde flow (Type I according to the Cognard classification). The SDH was thickest at the lower convexity, which suggested that the draining vein of the DAVF was responsible for the bleeding. INTERVENTION: The SDH slowly progressed for two weeks. The DAVF was successfully treated with transarterial embolization using N-butyl 2-cyanoacrylate. The SDH was resolved via burr-hole drainage surgery. CONCLUSION: This is the first reported case of DAVF that caused non-traumatic progression to SDH. As DAVF can be the cause of acute and chronic SDH, cerebral angiography is recommended for non-traumatic acute SDH as well as for intractable chronic SDH.

Two cases of a dural arteriovenous fistula mimicking a brain tumor.

SUMMARY: Dural arteriovenous fistula (d-AVF) is relatively rare. Some cases of atypical locations are often difficult to distinguish from other vascular disorders or tumors because those d-AVFs show various onsets, such as subcortical bleeding and venous infarctions. We encountered two cases of d-AVF with severe brain edema that took adequate time to distinguish from brain tumors. A 68-year-old man visited his local physician complaining of dizziness. He was diagnosed with a cerebral infarction due to the presence of an abnormal cerebellar signal on magnetic resonance imaging (MRI) and was treated by drip infusion. However, he did not recover and was admitted to our hospital with suspicion of a brain tumor. A 75-year-old woman with an onset of progressive dementia and gait disturbance showed severe edema of the right-front temporal lobe on MRI. Both these cases were examined by single photon emission computed tomography or positron emission tomography and were scheduled for craniotomy and biopsy based on the diagnosis of brain tumor. We performed preoperative angiography and found d-AVFs. We embolized the d-AVFs with liquid material and both patients recovered well. Brain edema from d-AVF or a tumor can be distinguished by carefully reading the MRI with findings such as the distribution of the edemas, differences on diffusion-weighted images, and contrast-enhanced images. Therefore, it is important to provide initial accurate diagnoses to prevent patient mistrust and irreversible disease conditions.

A successful treatment with carotid arterial stenting for symptomatic internal carotid artery severe stenosis with ipsilateral persistent primitive hypoglossal artery: case report and review of the literature.

A 68-year-old male presented with a syncopal attack subsequent to acute myocardial infarction. His ultrasonographic and radiological examination revealed severe left internal carotid artery (ICA) stenosis and the presence of a persistent primitive hypoglossal artery (PPHA) immediately distal to the stenosis. The bilateral anterior and left middle cerebral arteries, and the vertebrobasilar system were opacified via the stenotic ICA. Carotid arterial stenting was selected as the treatment method because the lesion was high and a shunt placement during carotid endarterectomy was considered to be technically difficult. A self-expanding stent was successfully deployed with flow control, and the patient was discharged six days after surgery without any neurological deficit. There are sixteen reported cases including ours of PPHA associated with ICA stenosis presenting with ischemic attacks of the vertebrobasilar system. To the best of our knowledge, the current case is the first report of a cervical ICA stenosis with ipsilateral carotid-basilar anastomosis treated with carotid arterial stenting.

Screening for deletions in interval D16-22 of the Y chromosome in azoospermic and oligozoospermic Japanese men.

The genetic basis of infertility remains unclear in a majority of infertile men. In this study, the Y chromosome long arm involving the DAZ (deleted in azoospermia) gene was screened in order to evaluate the occurrence of microdeletion in Japanese infertile men. One hundred and fifty-seven infertile Japanese men with azoospermia and oligozoospermia were analyzed for microdeletions in interval D16-22 of the Y chromosome, using polymerase chain reaction with sequence-tagged site markers. Sixteen sets of oligonucleotide primers were synthesized for the polymerase chain reaction, and Southern blot analysis was also performed. The men were divided into five categories on the basis of sperm concentration: functional azoospermia (A; n = 24), azoospermia caused by obstruction (AO; n = 20), oligozoospermia I (OI, sperm concentration less than I x 10(5)/ml; n = 33), oligozoospermia II (OII, sperm concentration less than 1 x 10(6)/ml; n = 30), and oligozoospermia III (OIII, sperm concentration less than 1 x 10(7)/ml; n = 50). Thirty fertile men with a sperm concentration of more than 2 x 10(7)/ml were also analyzed as controls. Microdeletions were identified, in 12 (7.6%) of the 157 infertile men, as follows: 1 man in category A, 1 in category AO, 5 in category OI, 4 in category OII, and 1 in category OIII. No deletion was identified in the fertile men. One common region around sY240 was identified in 11 of the infertile men with microdeletions. This locus may contain specific genes for spermatogenesis. The sperm concentration in the ten oligozoospermic men with microdeletions was below 1 x 10(6)/ml. There were no correlations between the severity of spermatogenic defects and the extent of the microdeletions. These results suggested that genes in the interval D16-22 of the Y chromosome might have important roles in spermatogenesis.

Chondroblastoma of the temporal bone.

A rare case of chondroblastoma arising from the temporal bone that occurred in a 60-year-old woman is reported. The tumor appeared well demarcated and osteolytic on the radiographs. CT scan clearly depicted marginal and central calcification in the tumor. MR imaging demonstrated two components in the tumor: a solid component with predominantly low signal intensities on both T1- and T2-weighted sequences, and a multilocular cystic component with T1- and T2-elongation and fluid-fluid levels on the T2-weighted images. Postcontrast MR imaging revealed marked enhancement in the solid component and the septa of the cystic component.

[A case of urinary retention secondary to aseptic meningitis].

A 46-year-old male was admitted to our hospital with headache, high fever and subsequent consciousness disturbance. Spinal fluid examination intimated aseptic meningitis. Not only these symptoms but bladder dysfunction was presented. The patient was treated with conservative therapy and bladder dysfunction was resolved a month and a half later. We report a case of urinary retention secondary to aseptic meningitis and review the clinical presentation and treatment.

Ependymal cyst producing alpha-fetoprotein. Case report.

This 17-year-old man was admitted to the hospital due to progressive headache and diplopia. Neuroradiological studies revealed a cystic mass in the pineal region without a parenchymal lesion. In addition, serum alpha-fetoprotein (AFP) levels were elevated. A cyst-to-third-ventricle and cistern fenestration was performed, but the cyst enlarged 3 months after the first operation. In the second operation, subtotal resection of the cyst was performed. The AFP level in the cyst fluid was very high preoperatively but was decreased postoperatively. The patient was discharged with no neurological deficit. Pathological examination of resected tissue showed a single layer of cuboidal cells that resembled an ependymal structure. The cells were immunoreactive for AFP immunostain, which indicated AFP production from these cells.

IL-18 in pregnancy; the elevation of IL-18 in maternal peripheral blood during labour and complicated pregnancies.

Serum interleukin-18 (IL-18) levels were measured in women in different trimesters of pregnancy, in labour, puerperium and in various complicated pregnancies. There was a significant elevation of IL-18 levels in pregnant sera from the first trimester until the onset of labour. Once labour began, IL-18 levels increased further and remained until at least the third day of puerperium. The high levels of IL-18 in sera were also observed in various complicated pregnancies, such as premature rupture of membranes (PROM), acute fatty liver of pregnancy and fetal growth restriction. IL-18 is likely to play a role in pregnancy.

A pilot study of CPT-11 and cisplatin for ovarian clear cell adenocarcinoma.

BACKGROUND: Ovarian clear cell adenocarcinoma is known to have poorer prognosis than ovarian serous cystadenocarcinoma. Cyclophosphamide plus cisplatin has been the standard therapy for ovarian cancer, but ovarian clear cell adenocarcinoma dose not respond to this therapy. The treatment for ovarian clear cell adenocarcinoma has not been established. We planned a pilot study of CPT-11 and cisplatin for the treatment of ovarian clear cell adenocarcinoma. METHODS: First, three patients were administered 70 mg/m2 of cisplatin intravenously on day 1 and 60 mg/m2 of CPT-11 intravenously on days 1, 8 and 15. Treatment was repeated every 4 weeks. Other patients were administered 75 mg/m2 of cisplatin intraperitoneally on day 1 and 60 mg/m2 of CPT-11 intravenously on days 1, 8 and 15. Treatment was repeated every 4 weeks. RESULTS: A total of 10 patients were entered in this study and a total of 43 courses were administered. 1 CR, 1 PR and 1 PD were observed in patients with measurable lesion. Grade 3 leukopenia was experienced in seven patients, grade 3 thrombocytopenia in two and grade 3 anemia in five. Grade 3 liver toxicity was observed in one patient and grade 3 diarrhea in one patient. No grade 4 toxicity was experienced. CONCLUSION: CPT-11 plus cisplatin is feasible and has efficacy for ovarian clear cell adenocarcinoma. This regimen should be explored in a phase II study.

CAG repeat length in the androgen receptor gene of infertile Japanese males with oligozoospermia.

We analysed the CAG repeat length in exon 1 of the androgen receptor gene in 59 idiopathic Japanese infertile males with oligozoospermia; 36 fertile males were also analysed as controls. The number of CAG repeats in infertile males ranged from 14 to 32 (mean 21.2+/-4.2), whereas the number of CAG repeats in fertile males ranged from 16 to 31 (mean 21.4+/-3.5). Among infertile males, six possessed a short form of 14 CAG repeats and three possessed 15 CAG repeats. On the other hand, fertile males did not possess the short form of 14 or 15 CAG repeats. The incidence of infertile males with 14 and 15 CAG repeats was significantly higher (P<0.05) than that of fertile males. Although the sample size is small, the results suggest that the reduction of CAG repeats in exon 1 of the androgen receptor is closely related to impaired spermatogenesis in infertile Japanese males.

[Maternal serum alpha-fetoprotein as a screening test for fetal Down syndrome].

An association between a low maternal serum alpha-fetoprotein (MSAFP) level and an increased incidence of Down syndrome is well documented. This study was undertaken to elucidate the diagnostic efficacy of MSAFP as a screening test for Down syndrome in 711 Japanese women who underwent genetic amniocentesis between 14 and 20 gestational weeks of age in Hyogo Medical College Hospital. The mean value for the multiple of the median (MoM) of the MSAFP level in 11 pregnancies associated with Down syndrome was 0.78 +/- 0.47 and 1.12 +/- 0.67, respectively. A cut-off value of < 0.45, < 0.50, < 0.55 and < 0.60 MoM yielded negative predictive values of 98.6%, 98.5%, 99.0% and 99.2%, positive predictive values of 6.3%, 4.0%, 9.1% and 8.6%, a sensitivity of 9.1%, 9.1%, 36.4% and 54.5%, and false positive rates of 2.1%, 3.4%, 5.7% and 9.1%, respectively. The combining of MSAFP and maternal age improves the expected results of a strategy for Down syndrome.

A report on the perinatal diagnosis of 4 cases of cardiac tumors.

Since 1973, we have identified 4 cardiac tumors by ultrasonography in fetal or early postnatal life. Tuberous sclerosis was diagnosed in three infants whose mother was also affected. The first infant died from acute cardiac failure after birth, and the second required cardiac surgery. The third infant had a cardiac tumor and a focal seizure at the age of 8 months. The cardiac tumor disappeared at the age of 2 years. The fourth cardiac rhabdomyoma may be the only sign of tuberous sclerosis.

Phase I study and clinical pharmacological study of muroctasin.

In a first part a phase I clinical study on the immunomodulator N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin) in male healthy volunteers was performed to assess safety, immunological activities, and preliminary pharmacokinetics of the drug by subcutaneous administration. 1. Safety Slight increase (38 degrees C) in body temperature was observed in a high-dose group by subcutaneous administration. Redness was noted as a change in the injection site, but no dose-dependency was seen in this respect. No other noticeable subjective nor objective symptoms were detected. On the other hand, positive C-reactive protein (CRP) (1 case out of 35) and slight increase in gamma-glutamyl transpeptidase (gamma-GTP, 1 case out of 35) associated with the use of this drug were observed. But the causal relationship of gamma-GTP with this drug was not clear because the finding returned to normal value during the treatment. 2. Immunological activities and leucocyte count Mitogenic responses of lymphocytes were augmented after subcutaneous administration of this drug. Increase in peripheral leukocyte count was also observed. This was due to the increase in neutrophil count. 3. Pharmacokinetics Pharmacokinetic parameters (maximum serum levels, area under serum concentration-time curve, time to reach maximum blood level, biological half-life) were obtained after a single administration of 400 micrograms: Cmax: 6.93 +/- 1.32 ng/ml (mean +/- SE), AUC: 37.22 +/- 6.51 ng/ml/h, tmax: 1.32 +/- 0.26 h and t1/2: 2.7 +/- 0.8 h. The safety of subcutaneous administration of MDP-Lys (L18) injection has been confirmed in 35 male healthy volunteers. It was suggested that adequate doses for phase II studies in patients were 200 micrograms to 400 micrograms. In a second part a clinical pharmacological study (single subcutaneous administrations of 100 micrograms and 200 micrograms and multiple 5 day subcutaneous administration of 200 micrograms of MDP-Lys (L18) was performed on male healthy volunteers to assess pharmacokinetics, effect on leukocyte function and on immune system, and safety: 1. Pharmacokinetics a) serum concentration after single administration Cmax in 100 micrograms and 200 micrograms were 1.48 and 2.78 ng/ml, respectively. The AUC values were 6.71 and 15.62 ng/ml/h, respectively, with dose dependency.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of beta-D-galactosidase from Escherichia coli and horseradish peroxidase as labels of anti-human ferritin Fab' by sandwich enzyme immunoassay technique.

beta-D-Galactosidase from Escherichia coli and horseradish peroxidase were compared as labels of anti-human ferritin Fab' by sandwich enzyme immunoassay technique using fluorogenic substrates for enzyme assay. The anti-human ferritin Fab'-peroxidase conjugates gave lower nonspecific bindings and higher specific bindings than the corresponding Fab'-beta-D-galactosidase conjugates. As a result, the former provided more sensitive dose response curves for human ferritin than the latter. However, the peroxidase conjugates were required in a larger quantity, since peroxidase assay was much less sensitive than beta-D-galactosidase assay.

Mild and efficient conjugation of rabbit Fab' and horseradish peroxidase using a maleimide compound and its use for enzyme immunoassay.

A mild and efficient procedure for conjugating rabbit Fab' and horseradish peroxidase using a maleimide compound was developed. The enzyme was treated with N-hydroxysuccinimide ester of N-(4-carboxycyclohexylmethyl) maleimide to introduce maleimide groups. Then, the maleimide-enzyme was allowed to react with thiol groups of Fab', and the conjugate formed was separated from unreacted components by gel filtration with Ultrogel AcA 44. In the peak fraction of the separated conjugate, 98% of peroxidase was associated with Fab' and 90% of antibodies was associated with peroxidase. The recoveries in the conjugate of peroxidase and Fab' incubated for conjugation were 65-74%. The conjugate formed appeared to be largely monomeric. Both the enzyme activity and antigen-binding activity of Fab' were fairly well preserved in the conjugate. The cross-link formed was stable at 4 degrees C at least 6 months. Use of the conjugates obtained by this method gave greater sensitivity in sandwich enzyme immunoassay for human ferritin and human thyroid-stimulating hormone than conjugates prepared by the periodate method. The conjugation using N-hydroxysuccinimide ester of m-maleimidobenzoic acid provided a similar monomeric preparation but was less efficient.

Major factors limiting sensitivity of sandwich enzyme immunoassay for ferritin, immunoglobulin E, and thyroid-stimulating hormone.

By using IgG-coated polystyrene balls and beta-D-galactosidase-labelled Fab', sandwich enzyme immunoassays for human ferritin, immunoglobulin E (IgE), and thyroid-stimulating hormone (TSH) were developed, and their sensitivities were shown to be largely limited by the purity, binding efficiency, and amount of beta-D-galactosidase-labelled Fab' used. (1) Their sensitivities were enhanced 10 to 50-fold by using affinity-purified Fab' labelled with beta-D-galactosidase. (2) Their sensitivities depended upon the efficiency of specific binding of the labelled Fab' to antigens adsorbed on antibody IgG-coated polystyrene balls. (3) Their sensitivities were improved by using the minimal amount of labelled Fab' that gave a reliable calibration curve. Under optimal conditions the sensitivities obtained for ferritin, IgE, and TSH were 0.09 pg (0.2 amol), 0.48 pg (2.4 amol, 0.2 mIU), and 3.2 millimicronU (5.7 amol) per tube, respectively.

Development of a highly sensitive sandwich enzyme immunoassay for human ferritin using affinity-purified anti-ferritin labelled with beta-D-galactosidase from Escherichia coli.

A highly sensitive sandwich enzyme immunoassay of human ferritin was developed. Polystyrene balls were coated with rabbit anti-human ferritin IgG by physical adsorption, and rabbit anti-human ferritin Fab' was purified by affinity chromatography and labelled with beta-D-galactosidase from Escherichia coli. Using the anti-ferritin-coated polystyrene balls and labelled anti-ferritin, the sensitivity obtained was 23 fg (0.05 amol) of ferritin per tube. The range of serum ferritin levels that could be determined using 0.1 microliter of serum was 0.23-4500 ng/ml, and even 2.3 pg/ml was measurable by using 10 microliter of serum. The coefficients of within-assay (n = 25) and between-assay (n = 10) variations were 5.9-8.8%. The regression equation and coefficient of correlation to a radioimmunoassay were Y(RIA) = 0.92 X(EIA) + 3.0 and 0.99 (n = 78), respectively. The corresponding sandwich radioimmunoassay was less sensitive, partly because the specific radioactivity of 125I-labelled anti-ferritin IgG used was not sufficiently high.