Inhibitory Effects of Pepstatin A and Mefloquine on the Growth of Babesia Parasites

We evaluated the inhibitory effects of pepstatin A and mefloquine on the in vitro and in vivo growths of Babesia parasites. The in vitro growth of Babesia bovis, B. bigemina, B. caballi, and B. equi was significantly inhibited (P < 0.05) by micromolar concentrations of pepstatin A (50% inhibitory concentrations = 38.5, 36.5, 17.6, and 18.1 μM, respectively) and mefloquine (50% inhibitory concentrations = 59.7, 56.7, 20.7, and 4 μM, respectively). Furthermore, both reagents either alone at a concentration of 5 mg/kg or in combinations (2.5/2.5 and 5/5 mg/kg) for 10 days significantly inhibited the in vivo growth of B. microti in mice. Mefloquine treatment was highly effective and the combination treatments were less effective than other treatments. Therefore, mefloquine may antagonize the actions of pepstatin A against babesiosis and aspartic proteases may play an important role in the asexual growth cycle of Babesia parasites.     

Pathological complete response of synchronous multiple liver metastases associated with advanced gastric cancer to gastrectomy and prompt S-1 treatment in combination with fractional cisplatin: report of a case

Systemic chemotherapy is the treatment recommended for prolonged survival in cases of metastatic gastric cancer. There have been a number of clinical reports of surgical resection of liver metastasis in selected patients with gastric cancer. Here, we report on a case of treatment of far advanced gastric cancer with synchronous multiple liver metastases with prompt S-1 in combination with fractional cisplatin sandwiched between twostage surgery. Metastases including peritoneal dissemination and extensive lymph node involvement were absent so it was feasible to completely remove all of the macroscopic liver metastases. Each step of the chemotherapy progressed satisfactorily and histological examination after the hepatectomy yielded a pathologically complete response of liver metastases from the gastric cancer. This strategy provides a promising treatment for far advanced gastric cancer with a limited number of synchronous liver metastases. The referral to surgical oncology is a crucial step for the documentation of pathological complete response.     

Contralateral glissonian pedicle occlusion in a case of portal vein tumor thrombosis

To dissect portal vein branches directly and encircle them separately is a common procedure that is performed to control back flow bleeding during operations for hepatocellular carcinoma with portal vein tumor thrombosis. However, this technique has an increased risk of injuring contralateral portal branches and disseminating thrombosis fragments to the remnant liver. We present an alternative technique using right-sided glissonian pedicle occlusion for hepatocellular carcinoma with left portal vein tumor thrombosis due to complex anatomical vasculatures of the hepatic pedicle. This technique would be very useful for liver resection of hepatocellular carcinoma with the major type of portal vein tumor thrombosis.     

Successful treatment with low-dose etoposide for hemophagocytic syndrome following reduced-intensity conditioning for cord blood transplantation in a patient with acute myelgenous leukemia

A 56-year-old man was diagnosed with acute myeloid leukemia with myelodysplasia-related changes. Chromosomal analysis showed a complex karyotype. Complete remission could not be achieved even after several induction chemotherapy regimens, and the patient suffered from invasive pulmonary aspergillosis. He was transferred to our hospital and underwent reduced-intensity conditioning cord blood transplantation (RIC-CBT) in a non-remission state. The conditioning regimen involved fludarabine 125 mg/m2 combined with melphalan 140 mg/m2 and total body irradiation (4 Gy). GVHD prophylaxis was tacrolimus alone at relatively low concentrations (app. 5 ng/ml). On days 6 and 9 after CBT, he experienced a pre-engraftment immune reaction and hemophagocytic syndrome (HPS). We started steroid pulse therapy, but this failed to resolve the symptoms. We then administered low-dose etoposide (50 mg/m2). The symptoms gradually resolved after three administrations of etoposide and engraftment was achieved on day 35. Satisfactory hematological recovery was noted on day 300 after CBT and the patient has maintained complete remission to date. HPS is one of the most serious complications following CBT and often results in engraftment failure. This case suggests that repeated administration of etoposide may safely and effectively overcome this serious complication in some cases.     

Optimal Combination of Effective ANtihypertensives (OCEAN) study: a prospective, randomized, open-label, blinded endpoint trial--rationale, design and results of a pilot study in Japan

There are limited clinical trials examining the efficacy of antihypertensive drug combinations aimed at preventing cardiovascular events. Therefore, we designed a randomized controlled trial using amlodipine as the base drug of a multi-drug regimen, the Optimal Combination of Effective ANtihypertensives (OCEAN) Study, to determine the drug combination that is most efficacious in the prevention of cardiovascular events, such as stroke. The OCEAN Study is a collaborative study between Japan and China, enrolling 20?000 patients and following them for 3 to 4 years. A pilot study was conducted before the full-scale study to confirm the feasibility of the protocol and that the study groups and infrastructures could function properly. A total of 279 Japanese patients were enrolled from 57 participating medical institutions between June and December 2004. Two hundred and sixty-six patients (mean age: 65.9 years) were treated with amlodipine alone. One hundred and fifty-four of these patients (57.9%) did not reach the treatment targets (<140/90?mm?Hg for the elderly and patients with cerebrovascular disease, <130/80?mm?Hg for those with diabetes mellitus, chronic kidney disease or prior myocardial infarction) and a second agent was added. They were randomly allocated into three different treatment groups using a diuretic, a β-blocker or an angiotensin-converting enzyme inhibitor/angiotensin II receptor antagonist. The pilot study showed that the protocol was appropriate, and the inclusion of patients with slightly higher blood pressures was necessary to increase the randomization rate. It also confirmed that we organized properly functioning study groups and infrastructures.     

Temporal trends in the relative prevalence of dysphagia etiologies from 1999-2009

AIM: To examine the relative prevalence and temporal variation of dysphagia etiologies in patients undergoing upper endoscopy (EGD) over the past decade.METHODS: EGDs with the indication of dysphagia at an urban, university medical center in 1999, 2004 and 2009 were retrospectively identified from the electronic medical record. The entire patient chart, including EGD, pathology, manometry, radiographic and clinician reports, was reviewed for demographic and clinical data and to determine the etiology of dysphagia. The number of EGDs in which an esophageal biopsy was performed was also noted. Gastroesophageal reflux disease (GERD) as a cause of dysphagia independent of peptic stricture was defined by symptoms with erosive esophagitis or symptom response to proton pump inhibition (PPI). Cases of eosinophilic esophagitis (EoE) were defined by an appropriate clinical history and histological criteria of ≥ 15 eosinophils per high powered field. PPI-responsive esophageal eosinophilia was not routinely reported prior to 2008. Statistical analysis was performed using one-way analysis of variance to analyze for trends between 1999, 2004 and 2009 and a post-hoc Tukey analysis was performed following a significant main effect.RESULTS: A total of 1371 cases (mean age 54 years, 43% male) met pre-specified inclusion criteria with 191, 504 and 675 cases in 1999, 2004 and 2009, respectively. Patients were older in 2004 compared to 2009 (mean ± SD, 54.0 ± 15.7 years vs 52.3 ± 16.8 years, P = 0.02) and there were more males in 1999 compared to 2004 (57.5% vs 40.8%, P = 0.005). Overall, GERD (27.6%) and EoE (7.7%) were the most common identifiable causes of dysphagia. An unspecified diagnosis accounted for 21% of overall cases. There were no significant differences in the relative prevalence of achalasia or other motility disorders, peptic stricture, Schatzki’s ring, esophageal cancer or unspecified diagnoses over the 10-year time period. There was, however, a decrease in the relative prevalence of GERD (39.3% vs 24.1%, P < 0.001) and increases in the relative prevalence of EoE (1.6% vs 11.2%, P < 0.001) and oropharyngeal disorders (1.6% vs 4.2%, P = 0.02) from 1999 to 2009. Post-hoc analyses determined that the increase in relative prevalence of EoE was significant between 1999 and 2009 as well as 2004 and 2009 (5.4% vs 11.6%, P < 0.001), but not between 1999 and 2004 (1.6% P 5.4%, P = 0.21). On the other hand, the decrease in relative prevalence of GERD was significant between 1999 and 2009 and 1999 and 2004 (39.3% vs 27.7%, P = 0.006), but not between 2004 and 2009 (27.7% vs 24.1%, P = 0.36). There were also significantly more EGDs in which a biopsy was obtained in 1999 compared to 2009 (36.7% vs 68.7%, P < 0.001) as well as between 2004 and 2009 (37.5% vs 68.7%, P < 0.001). While total EGD volume did increase over the 10-year time period, the percentage of EGDs for the indication of dysphagia remained stable making increasing upper endoscopy an unlikely reason for the observed increased prevalence of EoE.CONCLUSION: EoE has emerged as a dominant cause of dysphagia in adults. Whether this was due to a rise in disease incidence or increased recognition is unclear.     

Primary amyloidoma in epidural and paravertebral space of the lumbar spine

Background context

Localized amyloid deposits result in a mass, that is, so-called amyloidoma; it has been reported in every anatomic site, although systemic amyloid deposition is much more common. However, primary lumbar epidural amyloidoma without bony involvement is extremely rare. To the best of our knowledge, only one case has been reported previously.

Purpose

To report and review the clinical presentations, imaging studies, and treatment of epidural and paravertebral amyloidoma.

Study design

A case report and review of the literature.

Methods

Lumbar epidural and paravertebral amyloidoma in a 75-year-old man with neurologic compromise is presented. Laminectomy with mass resection was performed.

Results

After surgery, almost complete neurologic improvement was observed. Histologically, definite diagnosis was obtained only after the specific staining of tissue. No sign of local recurrence was evident 1 year after surgery.

Conclusions

Primary amyloidoma, although rare, should be included in the differential diagnosis of epidural mass of the spine. Diagnosis before surgery is difficult as there were no characteristic findings in clinical and imaging studies. Special histologic technique and stains are useful to make a definite diagnosis.     

Effect of functional shift of the mandible on lubrication of the temporomandibular joint

Lubrication of synovial joints reduces the coefficient of friction of the articular cartilage surface. To investigate the effect of malocclusion on the lubrication of the temporomandibular joint (TMJ), we evaluated lubricin expression in the rat TMJ immunohistochemically, under conditions of functional lateral shift of the mandible, during period of growth. Thirty 5-week-old male Wistar rats were divided into experimental, recovery, and control groups. Each rt in the experimental and recovery groups was fitted with an acrylic-plate guiding appliance. The rats in the experimental and control groups were killed at 14 and 28 days after the appliance was attached. Each rat in the recovery group was detached from the appliance at 14 days, and was killed 14 days after the appliance was removed. In the experimental group, the expression of lubricin staining in TMJ cartilage was significantly decreased during the experimental period. In the recovery group, the expression of lubricin staining in TMJ cartilage was significantly greater than in the experimental group, and there was no significant difference at 28 days between the control and recovery groups. Analysis of these data suggests that a functional lateral shift of the mandible during the growth period influences lubrication of the TMJ.