Pharmacokinetic studies on aztreonam in late pregnancy in sheep and humans

The transplacental passage of single intravenous doses of aztreonam (AZT), 1 g or 2 g, was examined in 7 sheep and 14 women in late pregnancy, respectively and the obtained data were analyzed by a two-compartment model. The obtained results were summarized as follows. After single 2 g intravenous doses were given to pregnant sheep, the mean peak level of AZT in maternal blood was 83.79 micrograms/ml and the half-life of the beta-phase was 1.525 hours. After single 1 g intravenous doses were administered to pregnant women, the mean peak level of AZT in blood was 102.62 micrograms/ml and the half-life of beta-phase was 2.128 hours. The peak levels in umbilical venous blood and amniotic fluid were 14.43 micrograms/ml and 11.86 micrograms/ml, respectively.     

Heparin-induced thrombocytopenia with multiple organized thrombi accompanied by unusual cholesterin deposition: Autopsy case after long-term follow up

Heparin-induced thrombocytopenia (HIT) is characterized by a reduction in the platelet count and systemic thromboembolism during heparin therapy. Herein is reported a case of HIT with characteristic thrombus formation. A 68-year-old man who had been treated for hypertension for 27 years suffered a brain infarction and was treated with heparin. After this treatment, other new infarctions occurred in multiple organs. Because serum antibodies against heparin/PF4 complex were detected, he was diagnosed as having HIT, and warfarin and argatroban were administered instead of heparin. He died, however, 119 days after the first onset. At autopsy infarction due to organized thrombi with cholesterin deposition in multiple organs were found, similar to usual atherosclerotic emboli, but different to them with regard to clinical course and distribution of thrombi. This case in which organization and frequent cholesterin deposition were found in thromboembolized lesions of multiple organs after relatively long-term follow up, is unusual. The findings suggest that HIT accompanied by marked hypercholesterolemia of long duration contributes to a characteristic form of thromboembolism that needs careful management.     

Evaluation of the usefulness of upper gastrointestinal endoscopy and the ValsamouthⓇ by an otolaryngologist in patients with Hypopharyngeal cancer

ObjectiveThe aim of this retrospective study is to evaluate the usefulness of upper gastrointestinal endoscopy and the Valsamouth^? by an otolaryngologist in patients with hypopharyngeal cancer to assess the risk.MethodsThe study group comprised 41 patients with untreated hypopharyngeal cancer that was precisely diagnosed by an otolaryngologist using upper gastrointestinal endoscopy and the Valsamouth^? at our hospital from January 2016 to December 2017. With upper gastrointestinal endoscopy and the Valsamouth^?, the oral cavity, oropharynx, larynx, hypopharynx, and esophagus were observed in this order. Narrow-band imaging, and subsequently, white-light observation were performed. At the hypopharynx, vocalization, and subsequently, the Valsalva maneuver were performed. After observing the esophagus, Lugol chromoendoscopy of the esophagus was performed.ResultsThe mean age of the 38 men and 3 women included in the study was 69.7 ± 10.0 years (range, 51–94 years). As for the T category of hypopharyngeal cancer, T1 cancer was observed in 9 patients, T2 cancer in 14, T3 cancer in 11, and T4 cancer in 7. With vocalization, the grade of visualization in the hypopharynx was 1 in 30 patients (73.2%), 2 in 11 patients (26.8%), and 3 or more in 0 patients (0.0%). With the Valsalva maneuver, the grade of visualization in the hypopharynx was 1 in 1 patient (2.4%), 2 in 15 patients (36.6%), 3 in 8 patients (19.5%), 4 in 11 patients (26.8%), and 5 in 6 patients (14.6%). The grade of visualization in the hypopharynx on average was 1.27 after vocalization and 3.15 after the Valsalva maneuver (p < 0.001). With vocalization, the percentage of patients in whom the entire image of hypopharyngeal cancer could be observed was 0.0% for grade 1 and 18.2% for grade 2. With the Valsalva maneuver, the percentage of patients in whom the entire image of hypopharyngeal cancer could be observed was 0.0% for grade 1, 40.0% for grade 2, 50.0% for grade 3, 86.1% for grade 4, and 100% for grade 5. Synchronous esophageal cancers were detected in 17.1% (7/41) of the patients. The grade of Lugol-voiding lesions was A in 5.6%, B in 52.8%, and C in 41.7%.ConclusionThe examination with upper gastrointestinal endoscopy and the Valsamouth^? by an otolaryngologist is feasible in patients with hypopharyngeal cancer. This procedure can detect synchronous esophageal cancer, allowing the risk of metachronous cancer in the head and neck or the esophagus to be recognized after the treatment.     

Studies on non-surgical therapy of tubal pregnancy

8 cases of tubal pregnancy in the pre-abortional stage were detected by B-scope examination. The administration of MTX (total doses: 60-300mg) resulted in complete remission in 7 cases; the other received tubectomy because of the progression of abortion. The dose of MTX used to obtain remission is responsible for the HCG titer of urine before the treatment; 60-150mg of MTX was sufficient in cases which showed a titer below 1,000iu/l, although 75-300mg was necessary in cases over 4,000iu/l. The patency of tubes after the regimen was confirmed in 4 out of 5 cases with hystero-salpingography. Serious side effects were not observed in the present study in spite of the great efficacy; transient suppression of liver has been observed in 2 cases. Two patients had normal intra-uterine pregnancy subsequent to the treatment; one had a matured full-term female neonate and the other received D & C in 9 gestational weeks. These results suggest that the MTX regimen is practical for the treatment of patients with tubal pregnancy. This is characterized by unimpaired fertility following the treatment, although the detection of patients in the pre-abortional stage is absolutely necessary.     

Mucosal high apoptotic activity and low p21WAF1/CIP1 expression and submucosal low proliferative activity in superficially spreading early gastric cancers: comparison with the penetrating growth type

In order to investigate cell kinetics and cell cycle regulator protein expression with reference to the growth pattern of early gastric carcinomas (EGCs), we evaluated a total of 240 EGCs with submucosal invasion clinicopathologically and 106 submucosal invasive lesions immunohistochemically. The incidence of lymph node metastasis was relatively high (36.4%) in the superficially spreading growth (SUP) type tumors whereas the penetrating growth (PEN) type had a low incidence (5.7%, P < 0.001) and correlated with submucosal tumor size. Ki67 labeling was lower in submucosal areas of the SUP-type tumors (median, 37.3%) than the PEN-type tumors (51.0%, P < 0.001). ssDNA labeling in the lamina propria, indicative of apoptotic activity, was higher in the SUP-type tumors (0.55%) than in PEN-type (0.30%, P < 0.01) lesions. The expression of cell cycle regulator p21WAF1/CIP1 was lower in the SUP-type tumors (lamina propria 15.6%, submucosa 2.6%) than in PEN-type tumors (lamina propria 26.5%, submucosa 4.4%, P < 0.05-0.001). In conclusion, differences in cell kinetics and p21WAF1/CIP1 expression might influence the growth pattern of EGCs. The SUP-type EGC, characterized by high apoptotic in the lamina propria and low proliferative activities in the submucosa, is associated with frequent lymph node metastasis, suggesting a strong correlation between tumor size in the submucosa and metastatic potential.     

Human lymphocyte antigen expression in hydatidiform mole: androgenesis following fertilization by a haploid sperm.

Thirteen hydatidiform moles (complete moles) and lymphocytes from each parent were analyzed for human lymphocyte antigen (HLA-A and HLA-B specificities). It was demonstrated that molar tissues expressed homozygous A and B specificities which were identical to those of the father and not those of the mother. It was concluded that androgenesis was responsible for the pathogenesis of most cases of complete mole. There was homozygous expression of paternal HLA specificities which were heterozygous for A locus and/or B locus in eight of nine cases of complete mole. This suggests that these hydatidiform moles developed from an egg which was fertilized by a haploid sperm which duplicated its own chromosomes after meiosis.     

HMG-HCG therapy in patients with hypergonadotropic ovarian anovulation: one pregnancy case report and ovulation and pregnancy rate

The aim of this study is to advocate the delivery of human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) therapy to patients with hypergonadotropic ovarian anovulation (Hyper-OA). HMG-HCG therapy was carried out in six patients (16 cycles) with Hyper-OA and nine patients (26 cycles) with hypogonadotropic pituitary anovulation (Hypo-PA) as controls. In this study, two patients with Hyper-OA ovulated after HMG-HCG therapy, and one of them conceived in the next cycle of the therapy. This patient is presented in detail as a case report. The ovulation rate in Hyper-OA proved to be 33.3% of patients and 12.5% of cycles as compared with 100% of patients with Hypo-PA and 65.3% of their cycles. These results suggest that although ovulation and pregnancy rate are very low, it is worth trying HMG-HCG therapy in patients with Hyper-OA, at least for one or two cycles.     

MTX resistant mechanisms in human choriocarcinoma cells

Choriocarcinoma cells grown in the presence of MTX have developed resistance in two ways. The HCCM derived sublines (relatively high MTX resistant) produced enhanced levels of DHFR and had relatively unimpaired transport of MTX, though altered transport was the primary determinant of response in the CC1 derived sublines (low MTX resistant). Since the selection procedure used was identical, it was assumed that altered MTX transport was insufficient to account entirely for various degrees of resistance. Increased DHFR activity was necessary for the development of high MTX resistance. The overproduction of DHFR was the consequence of amplification of the DHFR gene sequence. The incidence of DMs in metaphases paralleled the degree of resistance. Since DMs were also present in the cells not showing DHFR gene amplification, mechanisms other than DHFR gene multiplication were responsible for the de novo synthesis of DMs.     

Splenic Infarction after Epstein-Barr Virus Infection in a Patient with Hereditary Spherocytosis

We describe the first patient with hereditary spherocytosis (HS) known to have developed splenic infarction following infectious mononucleosis (IM). An 18-year-old Japanese man was referred to our hospital in November 2004 because of continuous fever and icterus. He had undergone cholecystectomy at the age of 14 years. On patient admission in November 2004, a physical examination showed marked hepatosplenomegaly, icterus, and jaundice. He had a white blood cell count of 14.9 x 10(9)/L with 9.5% atypical lymphocytes, a red blood cell count of 2.93 x 10(12)/L, and a hemoglobin concentration of 7.8 g/dL. Microspherocytes were observed in the patient's peripheral blood smear, and immunoglobulin M antibody to Epstein-Barr virus (EBV) viral capsid antigen was detected. The patient's diagnosis was HS with IM. On day 4 of admission, the patient complained of severe abdominal pain. Abdominal computed tomography scanning revealed findings of splenic infarction. Two months after the occurrence of splenic infarction, a splenectomy was performed. A pathohistologic examination of the resected spleen revealed no evidence of thrombosis or arterial occlusion. We assume that the cause of splenic infarction was insufficient blood flow to oxygenate the entire spleen during the acute enlargement of the spleen.     

Hydralazine-induced liver injury

Summary A 68-year-old man developed hepatic injury with no hypersensitivity reaction after three years of hydralazine therapy. The liver injury histologically showed centrilobular zonal necrosis. Clinical, biochemical, and histological recovery followed discontinuation of the drug. Challenge tests and serial liver biopsies revealed that this liver injury was induced by hydralazine.