Granulomatous balanoposthitis after intravesical Bacillus-Calmette-Guerin instillation therapy

We report a rare case of granulomatous balanoposthitis after intravesical Bacillus-Calmette-Guerin (BCG) instillation therapy in a 58-year-old man, which followed transurethral resection (TUR) for recurrent bladder cancer, when his anterior urethra was slightly narrow and his foreskin was with phimosis. Intravesical BCG instillation therapy was started for prophylaxis of recurrent bladder cancer after TUR. Multiple painless firm papules on glans penis, edema in the foreskin and low-grade fever appeared after the seventh instillation, for which the single antituberculous agent isoniazid (300 mg/day) was administered. Biopsy of the papules on glans penis and foreskin revealed granulomatous balanoposthitis. Low-grade fever normalized and the papules disappeared within 1 week. The patient continued chemotherapy with isoniazid for the next 12 months. There was no recurrence of bladder cancer or balanoposthitis for 15 months and to date.     

Phase II Study of Mitoxantrone in Patients With Non-Small Cell Lung Cancer

A phase II study of mitoxantrone was performed in 24 patientswith non-small cell lung cancer (NSCLC). Mitoxantrone was administeredby intravenous drip infusion of 12 mg/m² every three weeks.There were no responders among the 21 evaluable patients includingfive patients without prior therapy. The major hematologicaltoxic effect was leukocytopenia. Thrombocytopenia and decreasein hemoglobin were slight. A change in the electrocardiogramwas observed in one patient and one patient experienced cardiogenicshock. Mitoxantrone is not acceptable for the treatment of NSCLC becauseof its low antitumor activity, and careful observation is neededfor administration of this agent to patients with pre-existingrisk factors, such as prior anthracycline exposure, mediastinalradiation or underlying cardiovascular disease.     

Mass Screening for Neuroblastoma and Estimation of Costs

ABSTRACT. On the basis of epidemiological data and medical costs for patients with neuroblastoma, we have calculated the cost of mass screening for neuroblastoma with high performance liquid chromatography (HPLC) compared to the cost when it is not performed. If the sensitivity of the mass screening is 80 % and 22 000 infants are screened annually the cost will be 27809000 yen ($191800). If mass screening is not performed, the cost will be 28 446 000 yen ($196 200). The difference in cost (637 000 yen or $4 400) is fairly small. If the sensitivity is 75 % and 16 500 infants are screened, the difference is also small (174000 yen or $1 200). Therefore, mass screening with the HPLC method will not be an undue financial burden. But re-screening at an older age will be done with less financially favorable results, considering that the sensitivity may not be as high as that of the first screening and that mothers are somewhat reluctant about re-screening. The balance of the cost of mass screening by qualitative methods may also be less favorable, since the detection rate is low.     

Time-dependent Effects of Klebsiella pneumoniae Endotoxin on Hepatic Drug-metabolizing Enzyme Activity in Rats

The time-dependent effects of Klebsiella pneumoniae endotoxin on hepatic cytochrome P450-dependent drug-metabolizing capacity (cytochrome P450 and b₅ content, activity of aminopyrine N-demethylase, p-nitroanisole O-demethylase, aniline hydroxylase and benzphetamine N-demethylase) and on the pharmacokinetics of antipyrine have been determined in rats. Measurement of enzyme activity and antipyrine (after intravenous injection of 20 mgkg^?1) were performed 2, 24 and 96 h after a single intraperitoneal injection of endotoxin (1 mgkg^?1) and after repeated doses (once daily for 4 days). The contribution of tumour necrosis factor α (TNFα) to the endotoxin-induced changes was also examined in rats pretreated with granulocyte colony-stimulating factor (G-CSF). The systemic clearance of antipyrine and the activity of hepatic cytochrome P450-dependent drug-metabolizing enzymes were dramatically reduced 24 h after a single injection of endotoxin, but had returned to control levels by 96 h. The magnitudes of these decreases in these measurements after repeated doses of endotoxin were similar to those seen 24 h after the single dose. The systemic clearance of antipyrine correlated significantly with cytochrome P450 content and aminopyrine N-demethylase activity. In histopathological experiments, moderate hypertrophy of Kupffer cells was observed, with no evidence of severe liver-tissue damage. G-CSF pretreatment suppressed the increased plasma concentrations of TNFα produced 2 h after single endotoxin injection, but did not eliminate the endotoxin-induced decrease in the systemic clearance of antipyrine, suggesting that TNFα is not the sole component responsible for the reduction of cytochrome P450-mediated drug-metabolizing enzyme activity. These results provide evidence that a single intraperitoneal injection of 1·0 mgkg^?1 K. pneumoniae endotoxin in rats reduces hepatic P450 and b₅ levels, and reduces the activity of various cytochrome P450-mediated drug-metabolizing enzymes without causing severe liver-tissue damage. This suggests that the effect of endotoxin on hepatic cytochrome P450-mediated drug-metabolizing isozymes is non-selective.     

Effects of Acute Lead Acetate Exposure on Adult Guinea Pigs: Electrophysiological Study of the Inner Ear

The effects on humans of lead acetate exposure may involve thecranial nerves, since vertigo and sensory neuronal deafnesshave been reported in lead workers; however, there exist onlya few reports concerning the dose effects of lead acetate bothon the cochlea and the eighth cranial nerve. The effects oflead acetate on the cochlea and the eighth nerve were investigatedsystematically using cochlear microphonics (CM), wholenerveaction potential (AP), and endocochlear potential (EP) in guineapigs (male albino Hartley). Guinea pigs were injected with 2ml of a 1% solution of lead acetate (20 mg) once a week for1–5 weeks. The threshold of whole-nerve AP (N₁) was elevatedby injection of lead acetate, even 40 mg, and whole-nerve AP(N₁) output voltage decreased after injection of 100mg of leadacetate. On the other hand, no change was observed in CM afterlead acetate injection (100 mg) or in EP after lead acetateexposure (40 mg). The blood concentrations of lead acetate wereas follows (mean): control, 4.5 µg/dl; Expt 1, 80 µg/dl;Expt 2, 126 µg/dl; Expt 3, 142 µg/dl;. We concludethat dysfunction of the eighth nerve is induced by high-doselead exposure, but that lead exposure does not induce electrophysiologicaldysfunction of the organ of Corti and the stria vascularis.     

Vitamin D-dependent rickets type I and type II

Two distinct hereditary defects, vitamin D-dependent rickets type I (VDDR I) and type II (VDDR II), have been recognized in vitamin D metabolism. VDDR I is suggested to be a deficiency of the renal 25-hydroxyvitamin D (25(OH)D)-1α-hydroxylase. Muscle weakness and rickets are the prominent clinical findings. A normal physiologic dose of 1α-hydroxyvitamin D₃ and 1,25-dihydroxyvitamin D₃ is sufficient to maintain remission of rickets in this disorder. VDDR II consists of a spectrum of intracellular vitamin D receptor (VDR) defects and is characterized by the early onset of severe rickets and associated alopecia. This can be attributed to mutations in the VDR gene. Massive doses of vitamin D analogs and calcium supplementation is usually required for the treatment; however, the response to therapy is sometimes variable.     

A sensitive sandwich ELISA for measuring thrombopoietin in human serum: serum thrombopoietin levels in healthy volunteers and in patients with haemopoietic disorders

A sensitive sandwich enzyme-linked immunosorbent assay (ELISA) has been established to estimate serum thrombopoietin (TPO) concentrations in healthy volunteers and patients with haemopoietic disorders. The ELISA uses a mouse monoclonal antibody (Ab) as the capture Ab and a biotinylated rabbit polyclonal Ab as the detector. The ELISA was reproducible, highly sensitive and specific for human TPO. The coefficients of intra- and inter-assay variation were from 3.0% to 4.9% and from 5.9% to 6.1%, respectively. The quantitative limit of the ELISA was 0.09 fmol/ml in serum. The quantitative limit was lower than the normal level. The dose–response curves of serum samples from healthy volunteers and patients with haemopoietic disorders were parallel to the standard curves. The ELISA did not cross-react with a variety of blood components and cytokines to produce false-positive results.
The serum TPO concentrations from 29 normal males and 21 females were 0.79 ± 0.35 and 0.70 ± 0.26 fmol/ml, respectively. Serum TPO levels in patients with aplastic anaemia (AA), acute lymphocytic leukaemia (ALL) and essential thrombocythaemia (ET) were measured using the ELISA. The serum TPO levels in the patients with ET ( n  = 6, 2.80 ± 1.55 fmol/ml) were higher than the normal level. The patients with AA ( n  = 7, 18.53 ± 12.37 fmol/ml) and ALL ( n  = 5, 10.36 ± 5.57 fmol/ml) had significantly higher serum TPO levels than normal individuals. These results indicate that the ELISA specific to TPO should prove useful in measuring the TPO concentration in serum samples.     

Factors Associated with Blunt Cerebrovascular Injury in Patients with Cervical Spine Injury

Blunt cerebrovascular injury (BCVI) is known to be a potentially fatal complication of cervical spine injury (CSI). Methods for screening the appropriate population remain to be elucidated, especially in Japan. This retrospective study was conducted to predict the risk factors relevant to BCVIs. Among 92 patients with CSI transferred to our institution from April 2007 to March 2012, 40 patients (35 men, 5 women) with neurological deficits and/or significant cervical spine fracture including fracture of transversarium, facet, body, lamina, and spinous process, underwent multi-detector computed tomography angiography (MDCTA) and magnetic resonance angiography (MRA), which identified 10 patients with BCVI [2 carotid artery injuries (BCAIs) and 9 vertebral artery injuries (BVAIs); 1 patient suffered both]. Univariate analyses exploring associations between individual risk factors and BCVI and BVAI were performed using Fisher''s exact test and Chi-square test for dichotomous variables and the unpaired t-test for continuous variables. Multiple logistic regression analyses for BCVI and BVAI were carried out using stepwise methods. On univariate and multivariate analysis, hyperextension injury was significantly associated with BVAI (p = 0.01 and p = 0.02), and subluxation (dislocation of vertebral body > 5 mm) was a significant predictor of BCVI (p = 0.04 and p = 0.03) and BVAI (p = 0.01 and p = 0.01). Prompt evaluation for BCVIs is recommended in CSI patients with hyperextension injury and dislocation of the vertebral body.     

MORPHOLOGICAL AND BIOCHEMICAL EVIDENCE FOR APOPTOSIS IN THE TERMINAL HYPERTROPHIC CHONDROCYTES OF THE GROWTH PLATE

The purpose of this study was to investigate the mechanism of cell death in chondrocytes of the growth plate. In the degenerative chondrocyte zone of the growth plate, apoptotic chondrocytes were defeated by the in situ nick end labelling method, by DNA analysis in agarose gel, and by electron microscopy. The results of the in situ nick end labelling method and the occurrence of a ladder pattern of DNA in agarose gel analysis indicated the activation of endogenous endonucleases, resulting in DNA fragmentation. Electron micrographs showed the early morphological changes associated with apoptosis. This report presents both morphological and biochemical evidence for apoptosis in the terminal hypertrophic chondrocytes of the growth plate. These data suggest that apoptosis of degenerative chondrocytes may play an important role in the control of normal and pathological endochondral ossification.     

Neuropsychological test for the detection of dementia in elderly individuals: the Nishimura Dementia Test

Background: Progression of the core and accessory symptoms of dementia can be slowed if drug therapies and psychosocial interventions are administered at an early stage. The aim of this study was to develop and standardize a neuropsychological test for the elderly that can detect dementia at an early stage with high sensitivity and can evaluate a wide range of severities of dementia based on assessments of various cognitive functions. Methods: A preliminary test consisting of 23 items and the Nishimura Mental State Scale for the Elderly (NM Scale), which evaluates the mental functions of elderly individuals by observing their actual behaviors in daily life, were administered to 448 elderly subjects. After applying Hayashi’s quantification theory type I to the results, we revised the preliminary test to construct a neuropsychological test for the elderly, which we named the Nishimura Dementia Test (ND Test), and standardized it. Then, we examined its validity and test–retest reliability. Results: Among the 448 subjects, there was a strong correlation between the ND Test scores and NM Scale scores. The ND Test showed a good general agreement rate for the discrimination of the severity of dementia, and good sensitivity and specificity of discrimination of dementia when compared with the actual NM Scale. Using different groups of elderly subjects, the ND Test showed validity and test–retest reliability, and the ND Test scores showed strong correlations with the Revised Hasegawa Dementia Scale scores and the Mini‐Mental State Examination scores. Conclusions: The ND Test is based on assessment of a variety of cognitive functions and can evaluate a wide range of severities of dementia with good validity and reliability.