Bortezomib induces thrombocytopenia by the inhibition of proplatelet formation of megakaryocytes

Bortezomib is a potent proteasome inhibitor that has been extensively used to treat multiple myeloma. One of the most common grade 3 adverse events is cyclic thrombocytopenia. In this study, we studied the mechanism by which bortezomib induces thrombocytopenia in a mouse model. After the intravenous administration of bortezomib (2.5 mg/kg) via tail vein, platelet counts significantly decreased on days 2–4 and recovered to the normal range on day 6. Bortezomib (2.5 mg/kg) injected into mice in vivo did not affect colony‐forming unit‐megakaryocytes (CFU‐Mk) or megakaryocytes in the bone marrow. However, proplatelet formation (PPF) significantly decreased on days 2 and 4, after bortezomib administration to mice. Meanwhile, CFU‐Mk formation and the ploidy distribution of cultured megakaryocytes in vitro were not affected by bortezomib used at concentrations of ≤1 ng/mL. The PPF of megakaryocytes in vitro significantly decreased with 0.1, 1, 10, and 100 ng/mL bortezomib. Considering the bortezomib concentration in clinical studies, these data strongly suggest that decreased PPF activity induces thrombocytopenia. To elucidate the mechanism behind decreased PPF, Western blot was performed. Activated Rho expression increased after the incubation of murine platelets with bortezomib. Decreased PPF activity was eliminated by the addition of Y27632, a Rho kinase inhibitor, in vitro. Given that the Rho/Rho kinase pathway is a negative regulator of PPF, bortezomib increases activated Rho, inducing decreased PPF, which results in decreased platelet count.     

Treatment of Status Asthmaticus—Hormone Changes before and after Aminophylline i.v. Drip Therapy

The treatment of status asthmaticus is one of the most important factors in controlling the patient with asthma attacks. We have studied hormone changes in status asthmaticus and considered what is the best treatment in the asthma attack condition in children. Antidiuretic hormone (ADH), renin activity, and aldosterone activity are elevated in severe asthma attack conditions, and these high levels are correlated with high levels in Wood's clinical score. It is theoretical that patients with dehydration and respiratory failure show such elevation in hormones, and it is well known that under such conditions β₂-stimulant enhances renin production. From our study, it is concluded that β₂2 -stimulant subcutaneous injection must be considered in status asthmaticus. In children, amminophylline i.v. drip therapy may be one of the best treatments in status asthmaticus.     

Eosinophilic myelitis associated with atopic diathesis: a combined neuroimaging and histopathological study

Histologically proven eosinophilic myelitis has rarely been reported except in connection with parasitism. To clarify its clinicopathological features, we conducted a nationwide survey of biopsy-proven eosinophilic myelitis of unknown cause throughout Japan. Six such cases were collected and studied immunologically and pathologically. All were young to middle-aged men. All showed a protracted and fluctuating course with mild disability for 3-25 (mean 12.5) months before biopsy. Magnetic resonance imaging revealed localized lesions of T2-high and T1-iso signal intensity with a partial gadolinium enhancement in all cases. Cerebrospinal fluid (CSF) examinations were completely normal except for modest pleocytosis in two cases. Eosinophilia was present in the peripheral blood in two cases but was absent from the CSF of all cases. In spite of the chronic nature of the disease, spinal cord pathology revealed very active lesions with marked cell infiltration consisting mainly of CD8(+) T cells and varying numbers of eosinophils in the perivascular areas and the parenchyma. Both the myelin and axons were severely disrupted in all cases. Moreover, eosinophil cationic protein (ECP), an activated eosinophil product, was heavily deposited in the tissues. All but one case had hyperIgEemia and mite antigen-specific IgE in the sera, and two had accompanying atopic disorders. The present study thus revealed idiopathic eosinophilic myelitis to be a localized and persistent inflammation of the spinal cord, with distinct clinicopathological features, that has a possible link to atopic diathesis.     

Encrusted cystitis with ammonium acid urate calculi: a case report

We present a case of encrusted cystitis with ammonium acid urate calculi. An 88-year-old man was referred to our hospital to determine the cause of hematopyuria. He was a patient at another hospital for treatment of interstitial pneumonia with predonisolone. After admission to our hospital, kidney, ureter, bladder X-ray, computed togography and cystoscopy revealed calcification of about two-thirds of the mucosa of the bladder, and biopsy of the bladder revealed bacterial colonies with inflammation and calcification. Calculographic analysis revealed ammonium acid urate calculi. After treatment with antibiotics and irrigation with solita T1, an acidic solution of pH 3.5-6.5, inflammation and calcification were significantly reduced.     

Associations of length of employment and working conditions with neck,shoulder and arm pain among nursery school teachers

A cross-sectional questionnaire study was carried out on nursery school (NS) teachers in public nursery schools in N city in Japan to determine the magnitude of associations of probable risk factors with neck, shoulder, and arm pain, adjusting for potential confounders in logistic regression models. Of 1438 subjects, responded to the questionnaire, 959 NS teachers in charge of a separate or mixed group of children were subjected to analyses. Prevalence of neck and/or shoulder pain was 33.6%-35.4% in NS teachers in charge of children aged 0, 0-1, 4, and 5 in contrast to 25.0-29.8% in those in charge of children aged 1,2, and 3. The prevalence of neck/shoulder pain tended to increase with the length of employment in all groups classified according to the age of children under care. In a logistic regression model that simultaneously adjusted demographic and personal variables, length of employment and care for children aged 0 in the workplace were found significantly associated with musculoskeletal pain. In further logistic models, pain in the neck/shoulders and arms had associations with some specific variables: care for children aged 0, holding/lifting a child/material, overwork, and poorly supported job situations. The odds ratios for those variables varied from 1.37 to 2.41. This results suggest that pain in the neck/shoulders and arms is induced by a wide variety of risk factors in NS teachers that include high physical workload, long working hours, job demand-support imbalance, and cumulative influence of workloads.     

Symptoms of sick house syndrome and contributory factors; study of general dwellings in Hokkaido

OBJECTIVE: The aim of this study was to clarify the "Sick House Syndrome" which has recently received increasing attention, and to investigate relationships between symptoms and the state of general dwellings in Hokkaido. METHODS: Questionnaires were sent to residents in 1775 dwellings, mainly solitary houses built or remodeled within the past few years by 24 construction companies in Sapporo and its environs, and answers was received from 564. The questionnaires included queries about building structure and characteristics, the residents' habits in the home, and subjective symptoms. We requested one resident who had the most severe symptoms in the dwelling to answer a questionnaire about symptoms. We classified the symptoms into 11 categories, and selected those that developed or were aggravated after the building or remodeling. We defined dwellings in which inhabitants complained of one or more categories of symptoms as the group with sick-house-related disease (developed or aggravated group: DA group), and those in which the inhabitants complained of two or more symptoms as the group with sick house syndrome (more than one organic symptom group: MO group)". Associations between symptoms and dwellings were then studied. RESULTS: There were 201 dwellings for which residents complained of symptoms (37.2%). Of these, 94 were in the DA group (16.7%), and 57 (10.1%) in the MO group. The symptoms that developed or were aggravated after building or remodeling of the dwellings were throat, 7.1%, dermal, 6.9%, psychoneural, 5.3%, eye, 5.1%, and nasal problems, 4.1%. Unpleasant odors form furniture were significant in both groups (DA: crude odds ratio (OR) 2.66, MO: OR 3.24). Use of aromatics was significant in group DA (OR 1.78). Condensation on windows and mold growth in the dwellings were significant in both groups (condensation on windows; DA: OR 2.98, MO: OR 3.32, mold growth; DA: OR 3.11, MO: OR 3.24). In addition, the percentage of dwellings for which residents complained of symptoms increased with signs of dampness (condensation on windows and mold growth). On logistic regression analysis, condensation on windows and mold growth were significant in both groups, and unpleasant odors from furniture in the MO group. CONCLUSION: It is suggested that symptoms of sick house syndrome are associated with high humidity such as condensation on windows and mold growth, odors from furniture and use of aromatics.     

Difference between consciousness of intervention for improving lifestyle by public health nurses and recipients of a company health check

Improving an unhealthy lifestyle decreases risk of incidence and death of lifestyle-related diseases. Consultation about a healthy lifestyle to recipients of health checkups conducted by public health nurses is one method for such improvement. The objective in the present study was to investigate the difference between consciousness of intervention by (1) the public health nurses who conducted consultations with recipients of health checkups and (2) the recipients who were consulted by the public health nurses. Data on 1,370 male white collar workers who underwent health checks were analyzed. When public health nurses determined that recipients required health consultation regarding lifestyle from the health checkup, they consulted with the recipients regarding improvement of lifestyle. The consultation regarding lifestyle included abstinence from smoking, drinking in moderation, exercise, and eating. The results of the analysis regarding difference in consciousness of the intervention by the public health nurses and the recipients show that (1) most drinkers did not think they were being discouraged to drink despite intervention by the public health nurses and (2) the smokers and the subjects with no habitual physical exercise tend to think that they were being consulted even though the public health nurses did not intervene regarding smoking and exercise.     

A case report of effective chemoradiation with 5'-DFUR and concomitant preoperative radiotherapy of the lower rectum

We treated a lower rectal carcinoma patient with preoperative radiation and chemotherapy, resulting in a downstaging, and the findings are reported herein. The patient is a 55-year-old woman endoscopically diagnosed with advanced rectal carcinoma at a site 3 cm from the dental line. Preoperative radiation and chemotherapy included whole pelvis irradiation (44 Gy in total) and 800 mg/day of 5'-DFUR administered until one day before the operation. On the 20th day after completing irradiation, a low anterior resection of the rectum was conducted. During the operation, we found serositis of the small intestine and retroperitoneal fibrosis thought to be due to the irradiation. Histopathologic findings showed: invasion degree, sm2; stage I with N0; and histologic grading, Grade 2. The patient started drinking water from postoperative day 1, and was discharged on postoperative day 11. At present, in Europe and the USA, large scale studies are being conducted to evaluate preoperative radiation and chemotherapy in patients with lower rectal carcinoma. We think that this therapy is an effective treatment, since a distance (AW) from the lower margin of the tumor and the cut edge of the anal end can be established.     

Neo-adjuvant chemotherapy with carmofur for colorectal cancer--a multi-institutional randomized controlled study

The efficacy and safety of preoperative chemotherapy with carmofur (HCFU) for colorectal cancer were evaluated in a randomized controlled study involving 63 institutes in the Kanto area. Patients aged 75 or younger with Dukes' B or C colorectal cancer were eligible if curative surgery was expected. In the end, 326 were eligible from 405 consecutive colorectal cancer patients. Patients in both the control (n = 162) and the new treatment group (n = 164) were given intravenous mitomycin C (MMC) 6 mg/m2 on day 0 and 7 after surgery and HCFU 300 mg/day orally from day 14 for a year. Patients in the new treatment group were also given oral HCFU for 14 days or more prior to surgery. All 326 patients were followed for 5 years or longer. Five-year overall and disease-free survival rates were not significantly different between the two groups (75.4% and 71.6% for the control, and 71.8% and 71.5% for the study group, respectively). In the subset analysis, neither cancer site nor nodal status affected the differences in overall- and disease-free survival rates between the groups. The present findings show no additional efficacy of preoperative chemotherapy with HCFU in survival from advanced colorectal cancer. Further investigations in terms of patient selection, treatment regimen, combined use of radiotherapy, and other factors would be required to determine the significance of preoperative chemotherapy against advanced colorectal cancer.