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There is a liver damage in a serious side effect of regorafenib. Case 1 was a 54-year-old woman, and she had an operation of rectal cancer and metastasized to multiple organs afterwards and started regorafenib as third-line. Erythema exudativum multiform developed on the 8th day after a start and regorafenib was canceled once and reduced on the 21st day when a skin symptom was relieved and restarted. However, because a significant rise of AST, ALT, T -Bil was recognized afterwards, regorafenib was canceled on the 27th day and enforced steroid pulse therapy and was relieved afterwards. Case 2 was a 61-year-old woman, and she had an operation of ascending colon cancer, ovarian metastasis and peritoneum dissemination. Regorafenib was started by frequent occurrence lung metastasis, cancerous pleurisy afterwards as fifth-line. Dissemination erythema developed on the 16th day and a liver damage developed on the 22nd day. Because a rise of AST, ALT went and was prolonged, liver biopsy was enforced in a cause close inspection purpose on the 45th day. A medicamentosus liver damage was diagnosed. The liver enzyme decreased afterwards. It may be easy to make the liver damage by regorafenib serious, and attention is necessary.

Clobetasol propionate ointment (CLP O ) formulations have been classified as members of the "strongest" steroidal efficacy group, with eight of these formulations currently marketed in Japan. Evaluations of pharmaceutical properties of each formulation revealed three classification types: droplet dispersion type containing propylene glycol (PG) and surfactant, type with surfactant but not PG, and other types. These rheological properties were diverse, with no correlation found between viscosity and ointment type. However, when CLP O and six types of heparinoid oil-based cream (HP OC ) formulation mixtures were stored at 37℃, a liquid layer was observed starting at 24 h for one CLP O formulation in which polyoxyethylene hydrogenated castor oil 40 was used as a surfactant out of the four droplet-dispersion type ointments and two low-viscosity HP OC formulations. In contrast, one other type of CLP O formulation that contained a surfactant with polysorbate 80, but not PG, exhibited a liquid layer for all of HP OC formulations. This suggests that CLP O formulations that contain a surfactant with a high hydrophilic-lipophilic balance value are likely to generate a liquid layer for mixtures containing HP OC formulation. The present results demonstrate that not only the pharmaceutical properties of the eight CLP O formulations differ from one another, but also that the stabilities of HP OC formulation mixtures are significantly different. Therefore, pharmacists need to focus on inactive as well as active pharmaceutical ingredients to select formulations that patients will want to use, in addition to successfully treating their pathological conditions.

Particular batches of Moderna mRNA Coronavirus Disease 2019 (COVID-19) vaccine were recalled after foreign particles were found in some vaccine vials at the vaccination site in Japan in August 2021. We investigated the foreign particles at the request of the Ministry of Health, Labour and Welfare. Energy dispersive X-ray spectroscopy analysis suggested that the foreign particles found in the vials recalled from the vaccination sites were from stainless steel SUS 316L, which was in line with the findings of the root cause investigation by the manufacturer. The sizes of the observed particles ranged from <50 μm to 548 μm in the major axis. Similar foreign particles were also detected in 2 of the 5 vaccine vials of the same lot stored by the manufacturer, indicating that the foreign particles have already been administered to some people via vaccine. Observation of the vials of the same lot by digital microscope found smaller particles those were not detected by visual inspection, suggesting that more vials were affected. Contrarily, visual inspection and subvisible particulate matter test indicated no foreign particles in the vials of normal lots. Possible root cause and strategies to prevent such a deviation were discussed from technical and regulatory aspects.

A 66-year-old Japanese woman was admitted to our hospital for jaundice. Abdominal computed tomography(CT) showed dilatation of the intra- and extra-hepatic bile duct, and a hypovascular lesion measuring 30mm in diameter in the head of the pancreas. This tumor was in contact with the(superior mesenteric vein: SMV)and(inferior vena cava: IVC), but there were no obvious signs of invasion. Upper gastrointestinal endoscopy showed obstruction of the duodenum. We chose to perform an upfront surgery, considering the patient's general condition being stable and the difficulties associated with endoscopic biliary drainage. During surgery, stiff attachment between the tumor and IVC was identified and wedge resection of the IVC wall was performed. SMV resection and end-to-end reconstruction were also carried out. Pathological studies of the surgical specimen revealed direct invasion by the pancreatic adenocarcinoma into the adventitia of the IVC. The postoperative course was uneventful, and the patient was discharged from the hospital on the 27th postoperative day; she underwent adjuvant chemotherapy(S-1 100mg/day)and is still alive without tumor recurrence, 21 months after surgery. Cases of resected pancreatic adenocarcinoma directly invading the IVC are rare. In this case, pancreaticoduodenectomy along with wedge resection of the IVC wall could safely be performed, and no complications were observed. There is a need for further accumulation of similar cases.

The mock patches were prepared with novel acrylic polymers as adhesive layer where biphenyl-4-ylacetic acid (BAA) or 2-(2-fluorobiphenyl-4-yl) propanoic acid (FPA) was used as model active pharmaceutical ingredients (APIs). In addition, the mock patches were formulated with typical ester ingredients for transdermal dosage forms. The molecular state of the model APIs in the adhesive layer was observed by polarized microscope and microscopic Raman spectroscopy, which contains both conventional and low frequency (LF) region. Crystallization behavior would be depended on the interaction between API and polymers in the adhesive layer. In particular, LF Raman measurement was useful to discriminate API polymorphs. The pharmaceutical properties including dissolution and skin permeation of APIs were also evaluated for mock patches. The drug release and transdermal permeation were enhanced with the ester ingredients such as isopropyl myristate and diethyl sebacate due to their diffusion to the test solution or the skin stratum corneum as well as reducing the interaction between API and polymers. Further, the tack strength was not changed, but the peel strength was weakened by the additives. Thus, the adhesive properties were controllable by formulation with the additives. These findings could enable to evaluate the interaction between API and the polymers for adhesive layer and select the appropriate polymer and additives for used APIs when designing the drug products.

The normal tube voltage in computed tomography colonography (CTC) is 120 kV. Some reports indicate that the use of a low tube voltage (lower than 120 kV) technique plays a significant role in reduction of radiation dose. However, to determine whether a lower tube voltage can reduce radiation dose without compromising diagnostic accuracy, an evaluation of images that are obtained while maintaining the volume CT dose index (CTDI vol ) is required. This study investigated the effect of reduced tube voltage in CTC, without modifying radiation dose (i.e. constant CTDI vol ), on image quality. Evaluation of image quality involved the shape of the noise power spectrum, surface profiling with volume rendering (VR), and receiver operating characteristic (ROC) analysis. The shape of the noise power spectrum obtained with a tube voltage of 80 kV and 100 kV was not similar to the one produced with a tube voltage of 120 kV. Moreover, a higher standard deviation was observed on volume-rendered images that were generated using the reduced tube voltages. In addition, ROC analysis revealed a statistically significant drop in diagnostic accuracy with reduced tube voltage, revealing that the modification of tube voltage affects volume-rendered images. The results of this study suggest that reduction of tube voltage in CTC, so as to reduce radiation dose, affects image quality and diagnostic accuracy.

A 54-year-old man was introduced to our hospital for follow-up examinations after renal transplantation. At the initial visit, a 25 mm renal transplant stone was noted, which had enlarged to 32 mm at an examination 1 year later. We first attempted transurethral lithotripsy (TUL), but failed due to ureteral stricture. However, we could completely remove the stone in 2 sessions of percutaneous nephrolithotripsy (PNL). The incidence of urinary lithiasis after renal transplantation ranges from 0.17-1.8%, for which PNL and TUL are frequently used. Although considered to be accompanied with risks of bleeding, bowel injury, and renal dysfunction, PNL is effective for urinary lithiasis after renal transplantation. TUL is less invasive, but access may be difficult when the ureter has an unusual course or ureteral stricture exists, as in our patient.

A 67-year-old man with castration-resistant prostate cancer associated with multiple bone metastases had been treated with zoledronic acid and docetaxel. Although there was no evidence of damage around the right lower jaw bone, the patient complained of pain in May 2011, which worsened during the next 2 weeks and was followed by difficulty with breathing. Computed tomographic (CT) findings of the cervical area showed swelling of the cervical tissue with air and tightening of the trachea, suggesting cellulitis caused by gas gangrene. He was intubated and treated with antibiotics. On the 12th hospital day, CT scan revealed a pharyngeal abscess and we performed a drainage operation. On the 20th hospital day, bone of the intraoral lower jaw was exposed, revealing that the infection was caused by osteonecrosis. Additional CT findings showed the abscess extending to the mediastinum and multiple liver metastases. Although antibiotic therapy was continued, the patient died of liver failure on the 61st day.

Lenalidomide treatment for refractory or relapsed multiple myeloma in elderly patients may be feasible in an outpatient setting. However, difficulties have been associated with the management of adverse effects. Therefore, a dose reduction in lenalidomide has been recommended in some cases. In this report, we encountered the successful treatment of myeloma in 6 elderly patients (aged above 70 years) with very low-dose lenalidomide (5 mg daily). Four patients exhibited more than a partial response with an 8.6 months median follow-up period, which was comparable with previous findings. The major adverse effect observed was infection, which occurred during the first several cycles. Others were less toxic, especially the absence of grade 3/4 toxicities for hematological adverse effects.Although a dose reduction in lenalidomide therapy for elderly patients is controversial, a very low dose could be safe and effective. Our group is currently conducting a multi-center prospective trial to evaluate the efficacy of low-dose lenalidomide therapy.

Collagen family proteins are the predominant components of extracellular matrices existing in all multicellular animals. They provide mechanical strength to tissues, and maintain structural integrity of organs. Also, collagens regulate various biological events, including cell attachment, migration, tissue regeneration and animal development. The specific functions of collagens are generally elicited by interactions of collagen-binding molecules (membrane receptors, soluble factors and other matrix components) with certain amino acid sequences displayed on the collagen triple helices. To date, numbers of functional sequences have been identified from the triple helical domains. Collagen is also acknowledged as one of useful biomaterials in regenerative medicine and tissue engineering. In this review, I summarize challenges made for the development of safer and highly-functional collagen surrogates by means of self-assembly of synthetic collagen-like peptides. I also describe other possible applications of collagen-like peptides in drug delivery focusing on the particular biophysical properties of the triple helical structure.

A 61-year-old man came to our hospital with a complaint of lower abdominal pain. Computed tomography (CT) and magnetic resonance imaging (MRI) around his abdominal area showed large multiple cysts in the pelvis suggesting a malignant tumor. He showed high levels of serum carbohydrate antigen 19- 9 (CA19-9) and carcinoembryonic antigen (CEA). The complete diagnostic studies, including upper gastrointestinal endoscopy and colonoscopy examinations, failed to demonstrate the presence of alimentary primary tumors. With the diagnosis of cystic tumor in the pelvis, the operation was performed. The cysts adhered firmly to the surrounding organs including bladder and peritonium, which could not be resected completely. A histopathological diagnosis was papillary adenocarcinoma positive for prostate specific antigen (PSA). Because the level of serum PSA was 9.39 ng/ml, prostate biopsy was performed and ductal adenocarcinoma of prostate was revealed. After the operation, the levels of serum CA19-9 and CEA decreased to a normal level. Androgen deprivation therapy (ADT) was started, and the level of PSA was normalized one month later. Ductal adenocarcinoma forming cysts is rare. We reviewed 15 cases reported in the Japanese literature.

A 65-year-old man was referred to our hospital because of an elevated value of prostate specific antigen (PSA) (10.9 ng/ml). An eight-core prostate biopsy was negative. One year later, serum PSA increased to 55. 8 ng/ml and pelvic magnetic resonance imaging (MRI) showed a left external iliac lymph node enlargement. A ten-core prostate biopsy was negative. Six months later, the serum PSA increased to 88.1 ng/ml, but an seventeen-core prostate biopsy was negative again. A positron emission tomographycomputed tomography scan showed nothing other than increased uptake localized to the left enlarged external iliac lymph node. Pelvic lymphadenectomy was performed and histological examination, including immunohistological staining with PSA, confirmed lymph node metastasis from prostate cancer. Androgen deprivation therapy was started and 2 month later, serum PSA declined to below 1.0 ng/ml.

The patient was a 67-year-old man who was started on peritoneal dialysis for treatment of diabetic nephropathy in March 2010. He received an ABO-compatible living-donor kidney transplant from his wife in October 2010. The immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, steroid and basiliximab. Before the operation, a bump on his forehead/temple region that was increasing in size for years was noted. The bump had a scaly surface and the top of the bump was sloughed on postoperative day 14. Histological examination suggested malignancy. On postoperative day 21, a skin biopsy was performed by dermatologists and squamous cell carcinoma was confirmed. On postoperative day 36, wide excision and transposition flap procedures were performed by the plastic surgeon. At 15 months after transplantation, the kidney graft was functioning well with a serum creatinine level of 0.84 mg/dl and there was no sign of recurrence of the squamous cell carcinoma.

A 43-year-old woman presented to our hospital with the chief complaints of gross hematuria and dysuria. Cystoscopy and magnetic resonance imaging showed a tumor on the dome of the bladder and large blood clots. Computed tomography demonstrated no findings of distant metastasis. Following transurethral resection of the tumor, the tumor was histologically diagnosed as myxofibrosarcoma with muscular invasion, and partial cystectomy was performed in September 2009. There has been no evidence of recurrence or metastasis for 24 months postoperatively. In addition, the Japanese literature on myxofibrosarcoma of the bladder was reviewed and discussed.

The role of percutaneous endoscopic gastrostomy(PEG)in palliative care has not been well discussed. With the evolution of endoscopic techniques and PEG devices, we can perform PEG more safely, even in difficult cases. Actually, PEG is very useful in home care of cancer patients. We should discuss the indications of PEG in the field of palliative medicine. We suggest the following indications for PEG: 1.Difficulty in ingestion of sufficient quantities of food and water because of pain on swallowing, or an obstruction caused by cancer. 2.Normal gastrointestinal function. 3.Expected survival time of more than four weeks in addition to absence of cachexia. 4.Patient's consent for PEG.

A 70-year-old man with diabetes mellitus seen for fever, right chest pain, and right-lung field consolidation on chest X-ray was found in thoracoabdominal computed tomography (CT) to have variable-sized nodules in both lung fields and multiple low-density hepatic areas. On physical examination, his pulse was 145 beats per minute and blood pressure 92/68mmHg, indicating a preshock state. Laboratory tests showed elevated WBC of 15,200/microL, serum-C-reactive protein (CRP) of 34.4 mg/dL, and a decreased platelet count of 16,000/microL. Suspecting liver abscesses complicated by a septic pulmonary embolism, we immediately conducted percutaneous transhepatic abscess drainage (PTAD). Liver abscess blood culture and drainage fluid grew the Klebsiella pneumoniae hypermucoviscosity phenotype, carrying the rmpA gene. Although the man had been in critical condition on admission, broad-spectrum antibiotics and PTAD treatment improved his clinical condition to where he could be discharged without problem.

A 79-year-old man with chronic myeloid leukemia was referred to our department because of dry cough and low-grade fever, 272 days after commencing imatinib mesylate (Gleevec). High resolution computed tomography (HRCT) showed tiny scattered centrilobular nodules and ground-glass opacities throughout both lung fields, suggesting drug-induced pneumonitis. A thoracic video-assisted thoracoscopic surgery (VATS) biopsy specimen from the centrilobular nodules in the right upper lobe demonstrated patchy distribution of epithelioid cell granulomas and intra-alveolar organization. Most of those lesions were predominantly located in the alveolar spaces, which implicated non-transbronchial distribution. Following drug cessation alone, the patient's general condition and radiological abnormalities improved.

Topiramate is an antiepileptic medicine that has been used adjunctively in the treatment of refractory seizures in Japan since 2007. Topiramate has been shown to inhibit specific carbonic anhydrase activity in the kidney and may induce a distal type of renal tubular acidosis. Case 1 : A 22-year-old male was referred to our hospital after complaining of left flank pain. He developed a seizure disorder and had been using topiramate for 4 months. Drip infusion pyelography showed a left ureteral stone. Case 2 : A 7-year-old boy presented with gross hematuria. He developed West syndrome and had been using topiramate for 6 months. A computed tomographic scan showed a right kidney stone.

A postoperative rectum cancer patient with lung metastasis undergoing hemodialysis was treated with mFOLFOX6 therapy. The primary dose of oxaliplatin (L-OHP) ranged from 60 mg/m(2) to 85 mg/m(2), and adverse reactions and serum platinum concentration were monitored. The free platinum concentration (f-Pt), was eliminated efficiently using dialysis. The patient was tolerant of L-OHP doses of 60 mg/m(2) and 70 mg/m(2), but grade 2 neutropenia and grade 3 hemoglobin decrease developed with an L-OHP dose of 85 mg/m(2). The f-Pt after hemodialysis was higher than that before hemodialysis with a dose of 85 mg/m(2). But even with an 85 mg/m(2) dose, mFOLFOX6 therapy could be continued by extending the dosing interval. The monitoring of serum platinum concentrations, as well as therapeutic monitoring based on pharmacokinetics, contributes to safety management of cancer chemotherapy.

A 49-year-old woman with tuberous sclerosis visited our hospital complaining of left abdominal pain. She had been diagnosed with bilateral renal angiomyolipoma (AML) when she was 32 years old and had been on maintenance hemodialysis since the age of 44. Magnetic resonance imaging showed bilateral giant renal AML and hemorrhage in the AML of the left kidney. Transthoracolumbar left nephrectomy was performed in March 2008. The resected specimen weighed 3.2 kg. The histological diagnosis was consistent with AML. In addition, the Japanese literature on giant renal AML was reviewed and discussed.

Objective: In addition to overactive bladder (OAB) and sleep disorders (disturbance of additional sleep induction), nocturnal polyuria has been reported as an etiology of nocturia in elderly people. To investigate the influence of heart function on nocturnal polyuria in elderly people, we examined the association with nocturnal polyuria using brain natoriuretic peptide (BNP), which are useful for evaluating the prognosis of heart failure., Patients and Methods: The patients were 128 patients (92 males, 36 females) who were treated for nocturia in Kohsei general hospital and other relative hospital between October 2002 and September 2005. We measured BNP levels at physical examination. Simultaneously, the patients were instructed to write a frequency volume chart (FVC) for 4 days. 24-hour urine volume, Daytime urine volume, nocturnal (sleep) urine volume, nocturnal polyuria index (NPi) were calculated from FVC. The association was examined. However, alphal-blockers or anticholinergic agents that had been prescribed to treat urination disorders were continuously administered., Results: Overall, the mean BNP level was high, 46.3+/-39.6 pg/ml. The mean 24-hour urine volume was 1,555+/- 458 ml. The mean daytime urine volume was 935+/-322 ml. The mean nocturnal urine volume was 624+/-251 ml. The mean nocturnal urine volume rate was high, 40.1 - 10.5%. However, there was a close association between BNP and the 24-hour urine volume (p = 0.0215), the daytime urine volume (p = 0.0004), the NPi (p = 0.0003). The daytime urine volume decreased with the BNP level. The NPi increased with the BNP level. Patients were divided into 2 groups, a group with a BNP level less than 50 pg/ml and a group with a BNP level of 50 pg/ml or more. In the group with a BNP level less than 50 pg/ml, the nocturnal urine volume rate was 38.14+/-10.07%. In the group with a BNP level of 50 pg/ml or more, the rate was significantly higher (43.97+/-10.48%, p<0.0029)., Conclusions: These results suggest that many elderly patients latently have mild heart failure, and that relative nocturnal polyuria reduces cardiac load. Therefore, in patients with a high BNP level, administration of antidiuretic hormone to decrease nocturnal urine volume is risky. Administration of diuretics during the afternoon or evening may be safer.

Here, we report a Japanese man with adult Sandhoff disease who presented with a motor neuron disease phenotype with slow progression. At the age of 42, he noticed weakness in his legs. At the age of 46, he was admitted to our hospital. Neurological examination revealed muscle weakness and atrophy of the upper and lower extremities, and hyperreflexia of the upper extremities. Magnetic resonance imaging showed very mild cerebellar atrophy. We diagnosed him as having atypical amyotrophic lateral sclerosis. Because of the atypical course of motor neuron disease, hexosaminidase activity in peripheral leukocytes was indicated. Asseys of hexosaminidase A and hexosaminidase B showed low activities, and we found a membranous cytoplasmic body in the submucosal nerve, leading to the diagnosis of Sandhoff disease. This is the second case of a Japanese adult with Sandhoff disease presenting with a motor neuron disease phenotype, and to our knowledge, this is the latest age of onset in Japan.

Primary hyperparathyroidism is one of the important endocrine disorders in urological field because it very often causes the recurrent urolithiasis. We experienced more than 800 cases of it since the middle of 20th century. We present the general aspect of primary hyperparathyroidism from the view point of urology. The other parathyroid hyperfunction is a secondary hyperparathyroidism, which has increased according to the long time hemodialysis. The management of secondary hyperparathyroidism basically should be performed by the hemodialysist from the first, but not a few patients resist to the medical control of parathyroid function. Total parathyroidectomy with autotransplantation of small cluster of parathyroid in the forarm or subtotal parathyroidectomy is needed in patients whose parathyroid resists to the medical therapy.

A 65-year-old woman was referred to our hospital for further examination of recurrent urinary stone formation. She had undergone 49 sessions of extracorporeal shock-wave lithotripay (ESWL) and 3 sessions of transureteral lithotripsy (TUL) under the diagnosis of idiopathic recurrent urolithiasis at another hospital. An excretory urography showed bilateral hydronephrosis and a retrograde urography revealed bilateral lower ureteral stricture. Ammonium chloride loading test demonstrated incomplete distal renal tubular acidosis. Potassium citrate therapy had begun and bilateral nephrostomies were required in order to prevent recurrent urinary tract infection and new stone formation. Literature was reviewed and discussion was made on the ureteral stricture after ESWL and TUL, and on incomplete distal renal tubular acidosis.

A 54-year-old woman was referred to our hospital for the treatment of secondary hyperparathyroidism due to chronic renal failure. She was on hemodialysis for 7 years and suffered from giant tumor calcinosis of the major joints associated with severe hypercalcemia and hyperphosphatemia. The largest one of the left hip joint caused gait disturbance. Medical therapy was unsuccessful and she underwent subtotal parathyroidectomy. After the operation, although the levels of serum calcium and phosphate were not normalized, the level of parathyroid hormone was lowered to the normal range. The volume of the tumor calcinosis gradually reduced and she became able to walk for a short distance 10 months after the operation.

Coexistence of migraine with tension-type headache, that is, so-called combined headache is a disabling chronic headache disorder and is often seen in daily practice. Combined headache is a common disease, but it is not so easy to do an accurate diagnosis and adequate treatment because clinical spectrum is wide. For clinician, it is especially important to understand characteristics of patient's headache enough to diagnose correctly by using such as a headache diary and, to educate patients to differentiate between migraine and tension-type headache in order to select the right treatment and to prevent medication-overuse headache.

A 50-year-old woman lost about 10 kg of body weight within two months. Thereafter, she developed dysphagia and dysphonia. She visited our hospital and presented with a weak elevation of the soft palate, fasciculation of the tongue, hoarseness of voice, muscle weakness of the neck and extremities, and a decrement in vital capacity. She was admitted with a provisional diagnosis of motor neuron disease. The results of laboratory examinations showed an elevation in serum lysozyme and liquor protein levels, and pleocytosis in the liquor. Needle electromyography showed neurogenic changes, and bilateral hilar lymphadenopathy was revealed by computerized tomography. A biopsy specimen was excised from lymph nodes near the right anterior scalene muscle, which showed noncaseating granulomas consistent with sarcoidosis. All her symptoms improved after steroid administration. Such patients can be treatable with steroids. Moreover, the differential diagnosis from motor neuron disease is important.

Papillary muscle rupture is a rare but severe complication of acute myocardial infarction. Two cases successfully underwent mitral valve replacement and concomitant coronary artery bypass grafting (CABG) for acute myocardial infarction with the anterior papillary muscle rupture in cardiogenic shock. Each of them needed preoperative massive inotropic infusion, respiratory support and intraaortic balloon pumping assist. The first case was a 76-year-old female. Double vessel disease (seg 7 : 90%, seg 11 : 100%) was revealed by coronary angiography and rupture of the papillary muscle was confirmed by transesophageal echocardiography. The second case was a 69-year-old female. Double vessel disease (seg 2 : 90%, seg 11 : 100%) was revealed and severe mitral regurgitation due to prolapse of the anterior leaflet was confirmed by transthoracic echocardiography. To assess the diagnosis of postinfarction papillary muscle rupture, transthoracic and/or transesophageal echocardiography is mandatory. Coronary angiography is also desirable because concomitant myocardial revascularization may improve the prognosis.

We describe the case of a patient with cavernous angioma (CA). A 44-year-old woman complained of numbness on the left side of the body as an initial symptom of the disease. The initial magnetic resonance (MR) imaging revealed a cystic mass with a fluid-fluid level without perifocal edema in the right thalamus on the T 2-weighted image (T 2WI) and T2*-weighted image (T2*WI). Her symptoms were self-controllable; therefore we decided to observe her natural course only with serial MR imaging. The cystic mass was not enhanced by gadolinium on T1-weighted images, although, we suspected the tumor was complicated by vascular malformation. Therefore, we performed cranial angiography to eliminate the possibility of bleeding from the vascular malformation. Angiography did not demonstrate tumor staining nor vascular malformation. Longitudinally, the tumor demonstrated mosaic signal intensities on each sequence with perifocal edema. Moreover, the tumor exhibited hypointensities on T2* WIs without perifocal edema. The natural history of the tumor on MR imaging exhibited a typical case of CA. Some previous reports described cystic CA with perifocal edema and vascular malformation. In our present case, we clinically diagnosed CA on the basis of the final MR imaging together with previous reports. An intra-axial fluid-fluid level is a very rare finding of MR imaging. Here, we report the case of a patient with cystic CA accompanied by a fluid-fluid level. This finding is not a pathognomonic sign of CA; although, we consider that it is very important to follow up carefully the natural history of such cases.

We report a case of squamous cell carcinoma of renal pelvis associated with giant hydronephrosis. A 71-year-old woman presented to our hospital with a complaint of abdominal fullness due to the right giant hydronephrosis. Although the diagnosis of her hydronephrosis was made about 20 years ago at another hospital, it had been left untreated. Computed tomography showed the right hydronephrosis of 20 x 20 x 25 cm in diameter and no evidence of tumor or calculus in the right urinary tract. For relief of her complaint, right nephrectomy was performed. The fluid content was bloody and 4,200 ml in volume. Histological examination revealed a flat type squamous cell carcinoma of the renal pelvis. This is the 30th case of renal pelvic malignant tumor associated with giant hydronephrosis reported in Japan. The literature was reviewed and the management of giant hydronephrosis was discussed.

We describe two patients with generalized tetanus, a 60-year-old man and a 76-year-old woman, presenting with dysphagia as an initial symptom of the disease. Eighty percent of patients with generalized tetanus manifest dysphagia on admission to a hospital. However, dysphagia is rare as an initial symptom. Both our patients had dysphagia as their initial symptom, followed by neck stiffness and trismus. We made a diagnosis of generalized tetanus based on these neurological findings in the absence of an apparent episode of trauma. After the administration of tetanus immunoglobulin on admission, they recovered without exhibiting generalized convulsion, autonomic storm, or any other serious complications. The vaccination of tetanus toxoid cannot maintain sufficient antibody titers more than ten years. Therefore, elderly people are considered susceptible to tetanus. We suggest that tetanus should be considered in the differential diagnosis of dysphagia particularly in elderly patients. We also suggest that treatment of tetanus should be initiated immediately, because tetanus still has a high mortality rate at present.

We used a urethral stent for management of high-age and high-risk patients with benign prostatic hyperplasia (BPH) who needed surgical therapy. Nine patients were treated by this method. Chief complaints were urinary retention in 6 patients, dysuria with much residual urine in 2 and dysuria in 1. Blood loss and complications of the method were minimal. Postoperatively, 8 of the patients were able to void and on the average, residual urine of the patients was approximately 10 ml. Implantation of the urethral stent is a safe and non-invasive therapy for the patients who are unsuitable for invasive therapy.

A clinical evaluation of 10 patients with Machado-Joseph disease (MJD) was performed by using an acoustic analysis soft (SoundScope, GW Instruments Inc) before and on 4 weeks of treatment of taltirelin hydrate (TH). A rapid repetitive monosyllable/ka/was recorded as the samples were analyzed in a computer. The repetition period (ms) and the maximum intensity (volt) was measured from the sound spectrogram and the amplitude envelope for each speech wave. Three acoustic parameters, which were mean of period (ms) (m-P), coefficient of variation of period (%) (CV-P), and coefficient of variation of amplitude (%) (CV-A), were calculated according to Ishida's acoustic analysis method. The average age in this study group was 52.4 +/- 11.4 years (32-73 years), the mean scores of International Cooperative Ataxia Rating Scale (ICARS) was 35.0 +/- 18.6. Significant correlation was shown between CV-A and ICARS scores before therapy (p < 0.05). CV-P was decreased significantly (p < 0.05) from 10.9 +/- 0.12% to 9.2 +/- 0.26% after TH, and its degree of decrement correlated with ICARS scores (p < 0.05), which means a greater effect of TH is expected in patients with milder symptoms. ICARS scores did not change with a statistical significance. TH was shown to be effective on the ataxic speech of patients with MJD by quantitative methods. The acoustic analysis used in this study is a sensitive and objective evaluation method for following up the clinical severity of MJD and judging effectiveness of a drug.

Thirty two patients with cystinuria were enrolled in this long-term study and 16 patients were treated with tiopronin for 24 weeks. Tiopronin reduced daily urinary cystine excretion from 901.48 mg (before treatment) to 488.60 mg (on the average of 12th week and 24th week after tiopronin administration) successfully. Tiopronin therapy was tolerated well, but side effects were observed in 13 events in 6 patients. Thus tiopronin was expected to be effective in preventing cystine stone formation and tolerated well.

The raw material of cholecalciferol was examined for the preparation of the "Cholecalsiferol Reference Standard (Control 031)", The analytical data obtained were: melting point, 86.3 degrees C; UV spectrum, lambda max of 264.6 nm and specific absorbance in ethanol at 265 nm = 483.6; IR spectrum, same as that of the cholecalciferol Reference Standard (Control 003); optical rotation [alpha]20(D) = 105.1 degrees; thin-layer chromatography, one impurity was detected at 50 micrograms; high-performance liquid chromatography, total amount of impurities estimated to be less than 0.04%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Cholecalciferol Reference Standard (Control 031) of the National Institute of Health Sciences.

The "Lysozyme Reference Standard (Control 951031)" of the National Institute of Health Sciences was prepared. The lysozyme potency of the standard material was assayed against the Lysozyme Reference Standard (Control 951) by turbidimetric method two turbidimetric methods using the dried y-cells of Micrococcus luteus as a substrate. The potency of the standard material was in satisfactory agreement with that of Lysozyme Reference Standard (Control 951) and was defined as 1 mg [potency] per mg.

The raw material of paeoniflorin was examined for the preparation of the "Paeoniflorin Reference Standard". The analytical data obtained were: UV spectrum, lambda max, 231.9 nm; and specific absorbance (E(1 cm)1%) in methanol at 230 nm = 263.4 IR spectrum, specific absorptions of the raw material were consistent with those of the Paeoniflorin Reference Standard Standard (Control 012); High-performance liquid chromatography(HPLC), several impurities were detected. The total amount of impurities was 0.86%. Based on the above results, the candidate material was authorized as the Paeoniflorin Reference Standard (Control 021) of the National Institute of Health Sciences.

The raw material of tocopherol acetate was examined for the preparation of the "Tocopherol Acetate Reference Standard (Control 021)", The analytical data obtained were: UV spectrum, lambda max of 278.5 and 284.8 nm and specific absorbance in ethanol at 284 nm = 42.9; IR spectrum, same as that of the Tocopherol Acetate Reference Standard (Control 001); thin-layer chromatography, no impurities were detected until 50 micrograms; high-performance liquid chromatography, total amount of impurities estimated to be less than 0.6%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Tocopherol Acetate Reference Standard (Control 021) of the National Institute of Health Sciences.

The raw material of glycyrrhizinic acid was examined for preparation of the "Glycyrrhizinic Acid Reference Standard". The analytical data obtained were: UV spectrum: lambda max, 251 nm; and specific absorbance (E(1 cm)1%) in ethanol at 251 nm, 146.4; IR spectrum, specific absorptions of raw material were consistent with those of Standard (Control 0221). Also, thin-layer chromatography, no impurity was detected; high-performance liquid chromatography, several impurities were detected. The amount of each impurity was estimated at less than 0.2% and total amount of impurities was less than 0.2%. Based on the above results, the candidate material was authorized as the Glycyrrhizinic Acid Reference Standard (Control 031) of the National Institute of Health Sciences.

The raw material of estrone acetate was examined for the preparation of the "Estrone Reference Standard (Control 021)", The analytical data obtained were: UV spectrum, lambda max of 281 nm and specific absorbance in ethanol at 281 nm = 76.1; Melting point, 261.6 degrees C; IR spectrum, exhibited the specific absorptions at 3345, 2867, 1720, 1499 and 1055 cm-1; thin-layer chromatography, 2 impurities were detected at 100 and 200 micrograms; high-performance liquid chromatography, total amount of impurities estimated to be less than 0.3%. Based on the above results, the raw material was authorized as Estrone Reference Standard (Control 021) of the National Institute of Health Sciences.

The "Thrombin Reference Standard (Control 031", of National Institute of Health Sciences was prepared. The precision of filling into ampoule was about 11.5% as C.V. The content of alpha-thrombin was about 89%. The thrombin potency of the standard material was assayed against the Thrombin Reference Standard (Control 961) according to the method of JP-X IV and the potency was 692 +/- 35 units/ampoule. From the results, the potency of the proposed material for Thrombin Reference Standard was defined as 690 units per ampoule.

The raw material of thiamine hydrochloride was examined for preparation of the "Thiamine Hydrochloride Reference Standard". The analytical data obtained were: assay by HPLC, 100.5%; spectrophotometric assay 101.2%. Based on the above results, the candidate material was authorized as the Thiamine Hydrochloride Reference Standard (Control 021) of the National Institute of Health Sciences.

The raw material of ergocalciferol was examined for the preparation of the "Ergocalsiferol Reference Standard (Control 031)", The analytical data obtained were: melting point, 114.5 degrees C; UV spectrum, lambda max of 264.8 nm and specific absorbance in ethanol at 265 nm = 474.7; IR spectrum, same as that of the Ergocalciferol Reference Standard (Control 003); optical rotation, [alpha]20(D) = +104.6 degrees ; thin-layer chromatography, two impurities were detected at 50 micrograms; high-performance liquid chromatography, total amount of impurities estimated to be less than 0.04%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Ergocalciferol Reference Standard (Control 031) of the National Institute of Health Sciences.

To our knowledge, no standard chemotherapy for patients with hormone-refractory prostate cancer (HRPC) has been established. Since most patients with HRPC are elderly and have bone metastasis, cytotoxic chemotherapy causes them to be at high risk for myelosuppression. Therefore, chemotherapeutic agents with low toxicity and good compliance should be elected. We conducted three regimens for HRPC on an outpatient basis. Eligibility criteria were defined as serial rising PSA values on 3 or more occasions at least 2 weeks apart or radiological new or extensive lesions under hormonal therapy. The first regimen is comprised of cyclophosphamide (CPM), 100 mg/day, UFT, 400 mg/day, and estramustine phosphate (EMP), 560 mg/day in two daily fractions. The second regimen is comprised of an oral administration of dexamethasone (DEX) (0.5-2 mg/day). The third regimen is comprised of DEX, 1 mg/day, cyclophosphamide, 100 mg/day and UFT, 400 mg/day in two daily fractions. Post-therapy prostate-specific antigen (PSA) level in serum, objective response on bone scan or measurable disease, and symptomatic response on bone pain were assessed. All regimens showed clinical efficacy with mild toxicity. Indications and limitations of these regimens are discussed. Further, the combination trials of taxane and EMP in patients with HRPC are reviewed.