Histologic upgrading of prostate cancer occurs frequently over a short period of time: single hospital experiences of radical prostatectomy.

A total of 163 patients with localized prostate cancer underwent retropubic radical prostatectomy and pelvic lymphadenectomy at a single hospital from 1989 to 1998. We reviewed the patients in terms of their prognostic factors and survival. The patients without advanced diseases were diagnosed as having prostate carcinoma, using either biopsies or transurethral resection of the prostate. The carcinomas were categorized into localized prostate carcinomas (stage A, B or C) as a result of digital rectal examinations, computed tomography scans and bone scans. The patients were informed of the risk of surgery and, if they agreed to sign the consent form, underwent radical prostatectomy under general and epidural anesthesia usually 2 months after a positive biopsy. The surgical specimens were sent for pathology and were graded according to classifications of well-, moderately and poorly differentiated adenocarcinoma. The patients were usually discharged from the hospital 2-3 weeks postoperatively and had regular follow-up treatment. The mean age (+/- SD) was 68.75 (+/- 5.59) years and the mean follow-up period was 47.2 months. There was a significant difference (34.4%) in pathologic grades between biopsy and surgical specimen. In a quarter of the patients (approximately 26.4%) upgrading of the surgical report occurred despite neoadjuvant therapy. Three-year, 5-year and 7-year actuarial survival rates were 91.8%, 79.9% and 71.9%, respectively. Patients with organ-confined prostate cancer underwent radical prostatectomy and survived a fairly good period of time. Histologic upgrading was frequently observed within a short period of time (2 months).

[A case of metachronous adenocarcinoma of the urinary bladder and the right upper urinary tract].

Bilateral hydronephrosis identified by a local physician brought a 65-year-old man to our hospital. Emergency percutaneous nephrostomy was bilaterally established for obstructive renal failure. After recovering renal function, the patient underwent radical cystectomy under the diagnosis of invasive bladder cancer and the construction of an ileal conduit. The pathology reported well differentiated adenocarcinoma (pT2, pL1, pV1). Five years after the surgery, gross hematuria developed. A computed tomographic scan revealed right hydronephrosis with a solid mass in the upper calyx. The urinary cytology was negative. The patient underwent right nephrectomy in May, 1999. The pathology then revealed well differentiated adenocarcinoma in the renal pelvis and ureter (pT3, pL0, pV0 and pT1, pL0, pV0, respectively). He is alive with mild chronic renal insufficiency with evidence of tumor at ten months after surgery. To our knowledge, this is the first case of metachronous adenocarcinoma of the urinary bladder and the upper urinary tract reported in the Japanese literature.

Increased brain serotonin synthesis in migraine.

OBJECTIVE: To measure brain serotonin synthesis with PET using the tracer alpha-[11C]methyl-L-tryptophan in migraine patients. BACKGROUND: Although the cause of migraine remains poorly understood, there is considerable evidence to support a role of the neurotransmitter serotonin in the pathophysiology of migraine. METHODS: We studied 11 women (aged 33+/-7.7 years) with a diagnosis of migraine according to International Headache Society criteria and 8 healthy women (aged 29+/-9.2 years). Five patients were studied before and after chronic treatment with propranolol or nadolol. RESULTS: Serotonin synthesis capacity (K-complex) values in migraine patients were higher than those measured in controls throughout the brain (p = 0.016); mean K-complex for whole brain was 0.0077 + 0.0020 mL/g/min in patients with migraine and 0.0054+/-0.0003 mL/g/min in controls. The regional pattern did not differ between the two groups. However, the K-complex for whole brain in the subgroup of migraine patients with aura (n = 3) did not differ from that of the control group (p = 0.32). In the five patients studied twice (before and after treatment), we found a trend of increased whole-brain K-complex after drug treatment (p = 0.06). CONCLUSIONS: Our findings indicating increased brain serotonin synthesis capacity in migraine patients are consistent with previous reports of systemic alteration of serotonin metabolism in patients without aura. Our results also suggest that the mechanism of action of beta-adrenergic antagonists for migraine prophylaxis may involve regulation of serotonin synthesis.

[Transurethral resection of the prostate for patients with dementia].

During the period from July 1995 to June 1996 we performed transurethral resection of the prostate (TURP) on 824 patients with benign prostatic hyperplasia (BPH). Among them, 13 were dementia patients between 74 and 96 years old; they presented with urinary hesitancy in 6, retention in 4, frequency in 2 and incontinence in 1 patient. Past history included stroke in 7, hypertension in 6, pulmonary tuberculosis in 4, diabetes in 3, asthma in 2, angina pectoris in 1, Parkinson's disease in 1, pneumonia in 1, and hepatitis in 1. Careful preoperative examination revealed that they were proper candidates for TURP. They underwent TURP under spinal anesthesia. The mean operative time was 34 min, ranging from 20 to 60 min. The adenoma resected weighed 24 g on the average, ranging from 7.5 to 48 g. During surgery, although hypotension was noted in 2 patients, there was no serious morbidity. Their mental condition was well controlled with ketamine and diazepam during and after surgery. Postoperative complications included acute myocardial infarction in 1, multiple gastric ulcer in 1, and decubitus in 1. None died within 3 months after TURP, 3 died there after, and 10 patients were alive at the mean follow-up period of 26 months. Six patients reported good urination, 3 reported some improvement in urination after surgery, although requiring intermittent catheterization and 1 developed mild incontinence. In conclusion, TURP appears to provide some benefit in selected patients with dementia and should not be considered to be a contraindication for such patients.

Cerebellar reorganization following cortical injury in humans: effects of lesion size and age.

OBJECTIVE: The authors investigated chronic cerebellar reorganization following unilateral cortical lesions in children and adults using PET to measure benzodiazepine receptor (BZR) binding with [11C]flumazenil (FMZ) and glucose metabolism with 2-deoxy-2[18F]fluoro-D-glucose (FDG). BACKGROUND: Crossed cerebellar diaschisis (CCD) is defined as decreased metabolism or blood flow in the cerebellum contralateral to a cortical insult measured by functional neuroimaging, and is typically seen in adults with large frontal or parietal lesions. The authors previously reported that CCD of glucose metabolism was not as prominent in children as in adults, and that some children showed a paradoxical pattern of increased glucose utilization in cerebellar cortex contralateral to the cortical lesion. The current study investigated whether CCD is associated with alterations in the gamma-aminobutyric acid (GABA(A))/BZR complex. METHODS: Patients with frontal lesions alone or with parietal lesions were compared with patients with temporal lesions, which are typically not associated with CCD. RESULTS: Children with lesion onset before 1 year of age showed significantly higher glucose utilization in contralateral posterior quadrangular and superior semilunar lobules of cerebellar cortex than did adults. Two patterns of change in cerebellar BZR binding were seen in children: 1) Five of 10 children showed increased BZR binding in the dentate nucleus contralateral to the lesion, and 2) the remaining five children showed no increase in dentate nucleus BZR binding but showed increased binding in the lateral lobules of the cerebellar cortex contralateral to the lesion. Adults showed increased binding only in contralateral dentate nucleus and not in cerebellar cortex. The size and severity of the supratentorial lesion, as well as age at the time of injury, were important factors in these findings. CONCLUSIONS: Reorganization of GABA-mediated mechanisms and glucose metabolism in cerebellum following cortical injury differs with size of lesion and age at the time of injury.

[11C]flumazenil PET: activity images versus parametric images for the detection of neocortical epileptic foci.

UNLABELLED: [11C]flumazenil (FMZ) imaged with PET allows the computation of parametric images of both tracer influx (K1) and volume of distribution (VD). The VD images, which allow visualization of a quantitative measure of benzodiazepine receptor binding, are reported to have high sensitivity and specificity for the delineation of epileptic foci. However, the clinical feasibility of this method is compromised by the necessity of arterial blood sampling. We therefore compared the performance of parametric VD images against simple FMZ activity images for the detection of neocortical epileptic foci. METHODS: FMZ PET data from 7 children with extratemporal lobe epilepsy (mean age [+/- SD] 9.8+/-4.4 y) and 6 healthy adult volunteers (mean age [+/- SD] 40+/-8 y) were analyzed using a semiautomated analysis algorithm. FMZ activity images and parametric VD images were analyzed for asymmetry with cutoff thresholds of 8%, 10% and 12%. RESULTS: The time frame between 10 and 20 min after injection represented overall the best agreement between FMZ activity and VD images independent of the threshold. The normal asymmetry in VD images was determined as 6.4%+/-1.4% and was significantly higher in the FMZ activity images (7.6%+/-1.4%, P = 0.001). Increasing the cutoff threshold resulted in a significant decrease in the area defined as abnormal in both the VD and the FMZ activity images. Abnormalities defined in FMZ activity images identified additional brain regions as abnormal at the 8% threshold, but there was good agreement with VD images at the 10% asymmetry threshold. In those regions where abnormalities in VD and FMZ activity images were not matched, the asymmetry indices obtained from K1 images were significantly higher than those derived from the VD images (P = 0.01). CONCLUSION: Differences between VD and activity images above the 8% threshold are mainly due to K1. Abnormalities defined in FMZ activity images using a threshold of 10% agree well with those obtained from parametric VD images, indicating that activity images obtained from the time frame of 10-20 min are essentially equivalent to VD images with regard to detection of regions of abnormality for seizure focus localization.

Infantile myofibromatosis located in the temporal bone.

Infantile myofibromatosis (IM) is a proliferative disorder of infancy and early childhood characterized by the nodular or diffuse growth of lesions that are comprised of a mixture of mesenchymal elements. Intracranial involvement is reportedly rare, only eight such patients having been reported to our knowledge. We report on a 4-year-old boy with intracranial IM with a mass in his left temporal bone. A previous report on intracranial IM proposed that the underlying dura mater should be resected because of the possibility of early recurrence. At surgery in this case, the tumor was noted to be located in the bone itself and did not arise from the underlying dura. Therefore, the underlying dura mater and venous sinus were preserved. The follow-up MRI showed no sign of recurrences. It may not to be necessary to resect the dura mater in patients with intracranial IM.

Impaired locomotor activity and exploratory behavior in mice lacking histamine H1 receptors.

From pharmacological studies using histamine antagonists and agonists, it has been demonstrated that histamine modulates many physiological functions of the hypothalamus, such as arousal state, locomotor activity, feeding, and drinking. Three kinds of receptors (H1, H2, and H3) mediate these actions. To define the contribution of the histamine H1 receptors (H1R) to behavior, mutant mice lacking the H1R were generated by homologous recombination. In brains of homozygous mutant mice, no specific binding of [3H]pyrilamine was seen. [3H]Doxepin has two saturable binding sites with higher and lower affinities in brains of wild-type mice, but H1R-deficient mice showed only the weak labeling of [3H]doxepin that corresponds to lower-affinity binding sites. Mutant mice develop normally, but absence of H1R significantly increased the ratio of ambulation during the light period to the total ambulation for 24 hr in an accustomed environment. In addition, mutant mice significantly reduced exploratory behavior of ambulation and rearings in a new environment. These results indicate that through H1R, histamine is involved in circadian rhythm of locomotor activity and exploratory behavior as a neurotransmitter.

Perivascular coating with fibrin glue of cerebral arteries in patients with aneurysmal subarachnoid hemorrhage; incidence of chronic hydrocephalus.

The incidence of chronic hydrocephalus was studied in 39 patients with subarachnoid hemorrhage, who underwent perivascular coating with fibrin glue of cerebral arteries after clipping of aneurysm. A use was made of this procedure in order to prevent vasospasm by keeping the main cerebral arteries away from direct contact with subarachnoid clots. Most cases in this series belonged to group 3 of Fisher's CT grade (33/39, 84.6%). As a result, despite the high CT grade, the incidence of chronic hydrocephalus was as low as 17.9% (7/39), almost in agreement with those of the previous literature. In conclusion, (1) coating with fibrin glue did not increase the incidence of chronic hydrocephalus and (2) intrathecal application of fibrin glue is a promising method in the field of clinical neurosurgery.

Aromatase inhibitors: synthesis, biological activity, and structure of 1,2-imidazolylmethylcyclopentanol derivatives.

Two series of 1,2-disubstituted imidazolylmethylcyclopentanol derivatives (5a-d, 10a-d) were prepared by using easily available methyl 2-oxocyclopentanecarboxylate as the starting material. Evaluation of the aromatase inhibitory activities in vitro was performed. Their activities were compared with those of a steroidal aromatase inhibitor, Formestane, and a non-steroidal inhibitor, Fadrozole. Among these compounds, the aromatase inhibitory activities of 5d, 10a, 10b, 10c, 11a, 15a, and 15b were more potent than Formestane. One compound, 1-(4-chlorobenzyl)-cis-2-(1H-imidazol-1-ylmethyl)cyclopentanol+ ++ (10a) was in particular identified as a potent aromatase inhibitor in vitro, exhibiting an IC50 value of 4 x 10(-8)M. The enantiomers of 10a were separated, and their absolute configuration were determined by X-ray crystallography.

Detection of 1-phenyl-N-methyl-1,2,3,4-tetrahydroisoquinoline and 1-phenyl-1,2,3,4-tetrahydroisoquinoline in human brain by gas chromatography-tandem mass spectrometry.

1-Phenyl-N-methyl-1,2,3,4-tetrahydroisoquinoline and 1-phenyl-1,2,3,4-tetrahydroisoquinoline were detected for the first time in parkinsonian human brain using gas chromatography-tandem mass spectrometry (GC-MS-MS). Since these compounds are structural analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that produces parkinsonism in humans, they might be candidates for endogenous MPTP-like neurotoxins.

[An acute epidural hematoma soon after nose blowing: a case report].

We reported a very rare case of an epidural hematoma soon after nose blowing. A 22-year-old male visited our hospital complaining of severe headache and nausea soon after he blew his nose. Thirteen years ago, he had a ventriculo-peritoneal (V-P) shunt operation for a pineal region tumor which had not recurred after irradiation. His left auditory tube had been patent. He hit his head about 3 months ago. On his arrival, his consciousness was almost clear but we observed slight right hemiparesis. Computed tomography of his head obtained on the first day showed the air in the hematoma in the left parietal epidural space which penetrated his petrosal bone from the mastoid air cells. Removal of his epidural hematoma was performed the next day and there was no abnormality of his parietal bone, dura and meningeal arteries. We supposed that nose blowing was what triggered his epidural hematoma. From pressure of nose blowing, the air of his nasopharyngeal space passed through his patent auditory tube into the tympanic cavity, and entered into the epidural space penetrating a microfracture or dissociation in the petrosal bone. In addition to this, V-P shunt system and the looser adhesion of dura to the skull in the young promoted entrance of air. Associated with formation of epidural hematoma in this case were four factors, "patency of auditory tube", "defect or microfracture of petrosal bone", "V-P shunt", "younger age" and triggered by nose blowing.

Elevated serum levels of 3-deoxyglucosone, a potent protein-cross-linking intermediate of the Maillard reaction, in uremic patients.

3-Deoxyglucosone (3-DG) has been identified as an intermediate of the Maillard reaction in vitro. We measured serum 3-DG levels using gas chromatography/mass spectrometry and found a marked elevation in serum 3-DG levels in uremic patients compared with healthy subjects. The uremic patients with diabetes showed significantly higher serum concentrations of 3-DG than those without diabetes. 3-DG was demonstrated to be a potent protein-cross-linking agent in the reaction with lysozyme, leading to browning, fluorescence formation and polymerization of the protein by formation of advanced glycation end products (AGE). The increase in serum 3-DG levels in the uremic patients suggests that 3-DG may be responsible for the development of uremic complications by promoting the formation of AGE.

[Clinical experience with modified Studer's bladder substitute].

We modified Studer's bladder substitute technique and constructed continent urinary reservoir for 7 patients with bladder tumors after transprostatic cystoprostatectomy. Studer's bladder substitute technique is characterized by both a tubular isoperistatic proximal limb of 20 cm of the ileum in continuity with the pouch constructed using the detubularized ileum and the ureters reimplanted into the proximal part of the limb using a simple lateral anastomosis of the ureters to the end of the limb. Our modifications, transprostatic resection, was that distal one third or fourth of the prostate was left after cystoprostatectomy followed by either enucleation of the whole residual prostatic tissue including the urethra (type II) or sharp resection of the tissue leaving the urethra (type III). A small hole in the lowest part of the pouch was anastomosed either to the residual prostatic capsule (type II) or to the residual prostatic urethra (type III). Our modified Studer's technique was simple, easy to perform, and had low risk of massive bleeding especially from the central vein overlying the appex of the prostate. Clinical results were as follows; 1) all patients were satisfied with the passing of their urine per urethra without any cutaneous stoma, 2) no patients had clinical signs of pyelonephritis after discharge, 3) urine was not infected.(ABSTRACT TRUNCATED AT 250 WORDS)

Presence of 3-deoxyglucosone, a potent protein crosslinking intermediate of Maillard reaction, in diabetic serum.

3-Deoxyglucosone, a potent protein crosslinking intermediate of the Maillard reaction, was first detected in diabetic serum using gas chromatography/mass spectrometry. Serum concentration of 3-deoxyglucosone was elevated in diabetic patients as compared with healthy subjects. More notably, diabetic patients with nephropathy showed higher serum concentration of 3-deoxyglucosone than those without nephropathy. The increased serum concentration of 3-deoxyglucosone in the diabetic patients suggests that 3-deoxyglucosone may be responsible for the development of diabetic complications such as diabetic nephropathy by promoting the formation of advanced glycation end products.

Antitumor effects of 3-[p-(N,N-bis-(2'-chloroethyl)amino)-phenyl]-L- alanine conjugated with human immunoglobulin (K18).

K18 (3-[p-(N,N-bis(2'-chloroethyl)amino)- phenyl]-L-alanine conjugated with human immunoglobulin) is a newly developed antitumor agent. LD50 values of K18 in animals were quite high, suggesting its low acute toxicity. This drug showed anti-tumorigenicity not only on an experimental animal tumor (Walker 256), but also on a human tumor transplantable into nude mice (RCC-13). A distribution study clarified the unique properties of K18 to accumulate and remain in the tumor site with a high rate.

[An epidemiological study on dental caries of children in the town of Fuji].

An epidemiological investigation of dental caries was undertaken during the period of 1987-1989 with all children of nursery school, kindergarten, elementary and junior high school age in the town of Fuji, Saga prefecture which is a mountain villate, experiencing little movement of the population. From this investigation the following results were obtained. 1. Although the number of the children in each age group who had dental caries in deciduous and permanent teeth appeared to have decreased compared with 1987 and 1989, the dental caries prevalence in the children still remained high. 2. It appeared that it was important to give dental health education during the stage of immature young permanent teeth since there was prior to evidence of high dental caries in this stage. 3. The following was suggested for the improvement of caries experienced in immature young permanent teeth in the school in Fuji: (1) no stock of soft drinks in the refrigerator, (2) guardian's strict supervision of their children concerning snacks and, (3) acquiring of the habit of brushing during infancy and preschool years with parental assistance.

Syntheses of 24R,25-dihydroxy-[6,19,19-3H]vitamin D3 and 24R,25-dihydroxy-[6,19,19-2H]vitamin D3.

24R,25-Dihydroxy-[6,19,19-3H]vitamin D3 with a specific activity of 54 Ci/mmol and 24R,25-dihydroxy-[6,19,19-2H]vitamin D3 with 2.6 deuterium atoms/mol were synthesized in four steps starting from 24R,25-Dihydroxyvitamin D3 via its sulfur dioxide adduct.

Mechanism of action of the antitumour effect of K18.

K18 is an anticancer drug for oral administration comprising about five molecules of melphalan, an alkylating drug, covalently bonded to human immunoglobulin G. This study measured the in vitro antitumour activity of K18, melphalan and immunoglobulin G on human myeloma cells (RPMI-8226) and the in vivo antitumour effects of K18 and melphalan in BALB/c nude mice bearing human lung cancer cells (LC-10). The relative tumour-inhibitory effect, in vitro, was found to be: immunoglobulin G less than K18 less than melphalan. This activity of K18 was about half the theoretical value indicating that melphalan molecules are not released easily from the conjugate. K18 showed strong antitumour activity in vivo which continued after stopping administration. On the other hand, the effects of melphalan did not continue after administration was stopped. The distribution of [125I] K18 and [14C]melphalan was examined in BALB/c nude mice 14 days after implantation of LC-10 cells. Radioactivity levels in the major organs showed a transient rapid increase followed by a gradual decline. In tumours, [14C]melphalan levels increased transiently and then decreased, whereas [125I]K18 levels persisted following intravenous administration.