Search

We examined whether a tool for determining Johnsen scores automatically using artificial intelligence (AI) could be used in place of traditional Johnsen scoring to support pathologists’ evaluations. Average precision, precision, and recall were assessed by the Google Cloud AutoML Vision platform. We obtained testicular tissues for 275 patients and were able to use haematoxylin and eosin (H&E)-stained glass microscope slides from 264 patients. In addition, we cut out of parts of the histopathology images (5.0 × 5.0 cm) for expansion of Johnsen’s characteristic areas with seminiferous tubules. We defined four labels: Johnsen score 1–3, 4–5, 6–7, and 8–10 to distinguish Johnsen scores in clinical practice. All images were uploaded to the Google Cloud AutoML Vision platform. We obtained a dataset of 7155 images at magnification 400× and a dataset of 9822 expansion images for the 5.0 × 5.0 cm cutouts. For the 400× magnification image dataset, the average precision (positive predictive value) of the algorithm was 82.6%, precision was 80.31%, and recall was 60.96%. For the expansion image dataset (5.0 × 5.0 cm), the average precision was 99.5%, precision was 96.29%, and recall was 96.23%. This is the first report of an AI-based algorithm for predicting Johnsen scores.

Objective To compare the efficacy and safety of amoxapine and vitamin B12 for treating retrograde ejaculation (RE). Materials and Methods Between May 2009 and November 2012, this open-label, randomized, crossover study enrolled 26 men suffering with RE at Department of Reproductive Medicine, Omori Hospital. Patients were randomly allocated into two groups (n=13 each). The amoxapine-B12 group received amoxapine (50 mg daily for 4 weeks, orally) followed (after a 1-week washout period) by vitamin B12 (500 μg three-times daily for 4 weeks). The B12-amoxapine group received the opposite regimen. All patients masturbated to ejaculation at least twice during each treatment period. The primary outcome was antegrade ejaculation of semen, as reported by the patient, on more than one occasion during either treatment period (defined as treatment success). Any adverse events were noted. Success rates were compared between treatments using Fisher’s exact test. Results One patient (B12-amoxapine group) withdrew for personal reasons (breakdown of marital relations); all other patients completed the study. Overall success rate was 88% (22/25). Success rate was higher for amoxapine than for vitamin B12 (80%, 20/25 vs 16%, 4/25; P

Introduction Worldwide, certain subsets of men bypass healthcare provider (HCP) interactions and obtain phosphodiesterase type 5 inhibitors (PDE5i) from uncontrolled sources. Aim To stratify men who are PDE5i users based on their obtaining patterns and investigate the characteristics that differentiate these groups. Methods A Web-based observational study conducted between March and June 2009 in Japan. Main Outcome Measures We stratified the reported obtaining patterns into three categories: men who had a prescription for PDE5is from HCP, those who obtained PDE5is from friends, and those who purchased PDE5is via the Internet. Logistic regressions were conducted to determine independent predictors for each obtaining patterns. Erection function was evaluated by erection hardness score (EHS). Results Of 7,710 total recruited subjects, 1,144 men (14.8%) reported PDE5i use within the past year. Among 1,144 men, 625 men (54.6%) were prescribed PDE5i from HCP, whereas 267 men (23.4%) obtained PDE5i from friends and 252 men (22.0%) purchased PDE5i via the Internet. In a multivariable regression analyses, men being prescribed PDE5i from HCP were more likely to live in a northern area of Japan (OR 0.98), have a lower rate of smoking (OR 0.77), and have an awareness of ED (OR 3.04). In contrast, men who obtained PDE5i from friends were more likely to live in a southern area (OR 1.02), to have higher rate of alcohol intake and smoking (OR 1.20, OR 1.45), and lower awareness of ED (OR 0.39). Men purchasing PDE5i via the Internet were more likely to consider themselves to be in worse health (OR 0.85) and to have lower awareness of ED (OR 0.62). Conclusions Our results could help to identify men who may bypass HCP interactions. These findings could aid in the targeting of public service announcements designed to encourage men to avoid obtaining uncontrolled PDE5i and consult with HCPs to protect their health. Kimura M, Shimura S, Kobayashi H, Tai T, Chikano Y, Baba S, Kano M, and Nagao K. Profiling characteristics of men who use phosphodiesterase type 5 inhibitors based on obtaining patterns: Data from the nationwide Japanese population. J Sex Med 2012;9:1649–1658.

Teratomas rarely present as a pediatric congenital primary penile mass. We describe a 14-month-old boy with a blister-like mass on his distal left penis. The subcutaneous mass measured 1.5 cm (length) × 1.0 cm (width) × 1.2 cm (height) on ultrasonography. There were clear margins between these structures and the lesion. At the age of 5 years, he received an extirpation surgery. Histologic analysis revealed that it was a mature teratoma. In our view, surgical resection should be the treatment of choice for a pediatric penile mass with the alertness of teratomas because of the possibility of malignant alteration and invasion of adjacent structures till unresectable.

Introduction Vardenafil is reported to improve success rates in the maintenance of an erection sufficient for completion of intercourse (SEP-3) compared with placebo in erectile dysfunction (ED) patients who attempted intercourse from as early as 15 minutes after dosing. However, these data were based on general ED patients, using time from administration to initiation of intercourse. It is unclear whether the results can be applied to difficult-to-treat ED patients, such as those with diabetes mellitus (DM), with the time between dosing and insertion into vagina. Aim To determine whether early onset of activity with vardenafil is also achievable in ED patients with DM. Methods Data from a 12-week Phase III clinical trial (randomized, placebo-controlled, double-blind, parallel-group comparison) in Japanese men with ED and DM was used for analysis. In this study, patients received vardenafil 10 mg, 20 mg, or placebo, and were instructed to start sexual activity 1 hour after dosing. Mean per-patient SEP-3 success rates (intent-to-treat; ITT population), based on patient diary question, were calculated by the time between dosing and insertion. The least-squares means and nominal P values for differences versus placebo were derived by analysis of covariance with terms for baseline. Main Outcome Measures SEP-3 success rates in each time interval. Results The majority of inserts occurred between 60–90 minutes after dosing, but 100 of inserts in 52 patients occurred in the first 30 minutes. SEP-3 success rates in patients who inserted in each interval from 0–15 minutes ( P = 0.0268), 15–30 minutes ( P = 0.0094) through > 120 minutes were all higher in vardenafil-treated patients than those in placebo. Conclusions In this retrospective analysis, a rapid onset of activity was also demonstrated in difficult-to-treat ED patients. Vardenafil improved successful intercourse rates compared with placebo in Japanese DM patients who inserted from as early as 15 minutes to >120 minutes after dosing. Nagao K, Kobayashi H, Fujikawa K, Tachibana T, Iwamoto Y, Ishii N, Turek PJ, Brant WO, and Kamidono S. Vardenafil allows successful intercourse initiated rapidly after dosing in Japanese patients with diabetes mellitus and erectile dysfunction. J Sex Med 2009;6:2851–2857.

Aim: Vardenafil is a selective and highly potent phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), with improved selectivity for PDE5 and demonstrated efficacy for improving sexual function in men with ED. The current study investigated the safety and efficacy of this new PDE5 inhibitor in Japanese men with ED. Methods: This was a prospective, double blind, randomized clinical trial designed to evaluate the efficacy and safety of vardenafil. Following a 4-week treatment-free observation period, 283 eligible patients were randomized to 12 weeks treatment with vardenafil 5 mg, 10 mg, 20 mg, or placebo. Primary efficacy responses were assessed using the scores of Q3 and Q4 of the international index of erectile function (IIEF). Results: All three vardenafil doses showed significantly better improvement than the placebo group in Q3 and Q4 scores of the IIEF questionnaire, either at 12 weeks or at the ‘last observation carried forward’ (LOCF, P

To evaluate current outcomes of seminal tract re-anastomoses in Japan, and to compare them with historical data.A total of 213 patients with obstructive azoospermia who underwent seminal tract re-anastomosis from April 2008 to March 2012 at 25 institutions were enrolled in the present study. The outcomes of the procedure were compared with those reported in a previous multi-institutional study carried out in 2000.The percentage of partners aged over 35 years was 37%. A microsurgical double-layer anastomosis was carried out 83.0% of the time. Sperm were observed in ejaculate postoperatively in 68.9% and 41.5% of patients who underwent a vasovasostomy or a vasoepididymostomy, respectively. Natural conception occurred in 27.5% of patients after a vasectomy and 32.3% of patients with an epididymal obstruction. Except for the ratio of natural conception in patients with vasal obstruction after herniorrhaphies, there were no significant differences in final ratios of sperm appearance and natural conception between the previously reported study and the present study.Compared with historical data, contemporary seminal tract re-anastomosis in Japan seems to provide equivalent or better outcomes, depending on the cause of obstruction. Seminal tract re-anastomosis is a valid treatment option for patients with obstructive azoospermia.

Respiratory insufficiency has been reported frequently in patients with myotonic dystrophy (MyD). Recent data support the hypothesis that this respiratory failure results from a primary dysfunction of the central nervous system. The medullary arcuate nucleus (ARC) has been shown to be involved in the regulation of respiration. We performed a quantitative study of neurons in the ARC in eight MyD patients, ten control subjects with other neurological diseases (control group A) and eight control subjects without neurological diseases (control group B). Alveolar hypoventilation of the central type occurred in three of the MyD patients but not in the remaining MyD patients or controls. The density of neurons in the ARC in MyD patients with hypoventilation was significantly lower than in MyD patients without hypoventilation and control groups A and B. There was no significant difference in the neuronal density of the ARC between MyD patients without hypoventilation and control groups A and B. These data suggest that the neuronal loss of the ARC is associated with the presence of hypoventilation in MyD.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a newly proposed clinicopathologic entity; a few cases of LCNEC have been reported in other sites, such as the uterine cervix and the thymus. In the salivary glands, LCNEC is extremely rare and is not recognized as a specific entity in the World Health Organization classification. We retrospectively reviewed from our files 1675 cases of surgically resected primary parotid gland tumors and found 2 cases of LCNEC that fulfilled the criteria of pulmonary LCNEC. These cases occurred in 72- and 73-year-old men who had short histories of enlarging parotid gland tumors. The tumors were composed of large cells that exhibited organoid, solid, trabecular, and rosette-like growth patterns with a high mitotic rate and a conspicuous tendency for necrosis. The tumor cells were polygonal and characterized by a moderate nuclear:cytoplasmic ratio, coarse chromatin, and conspicuous nucleoli. Immunohistochemical examination revealed that the tumor cells were positive for six general neuroendocrine markers, cytokeratin, p53, bcl-2, epidermal growth factor receptor, and cyclin D1. Markedly reduced expressions of p21Waf1 and p27Kip1 were also noticed. The Ki-67 labeling index was more than 50% in both cases. One case showed loss of heterozygosity at TP53 accompanied by a p53 gene point mutation. Loss of heterozygosity at chromosome 9p21 was detected in both cases; one was accompanied by a p16 gene silent point mutation. Both patients died of the disease, with recurrence 5 months and 4 years after surgery, respectively. These findings indicate that LCNEC is a rare but distinct salivary gland tumor with highly aggressive biologic behavior. Multiple alterations of cell cycle regulators and tumor suppressor genes may play an important role in presenting the biologic characteristics of this rare parotid gland tumor.

A case of tuberculous peritonitis, which has been scarcely encountered in clinical practice in recent years, is reported. A 32-year-old man was admitted to our hospital complaining of abdominal fullness, anorexia, and a 15 kg weight loss. His abdomen was distended. There was neither any previous history nor recent contact with tuberculosis. The laboratory data indicated increased C-reactive protein and erythrocyte sedimentation rate, but the white blood cell count was normal. A chest X-ray examination revealed no abnormalities. Abdominal X-ray showed scattered, small-intestinal gas shadows. Abdominal computed tomography scanning revealed a diffuse thickening of the dilated bowel wall, mainly adjacent to the mesentery. After a detailed examination a diagnosis of peritonitis carcinomatosa of unknown origin was suspected, and an exploratory laparotomy was done. Severe adhesions between the parietal peritoneum and the bowel were found. An excisional biopsy specimen was taken from the peritoneum, and a diagnosis of tuberculosis was thus made. Triple therapy with isoniazid, rifampicin, and kanamycin was started, and both the intestinal obstruction and anorexia were thus resolved.

Abnormalities of collagen and glycosaminoglycans of skin have been reported in patients with amyotrophic lateral sclerosis (ALS). However, little is known concerning laminin in ALS. The aim of this study is to evaluate laminin 1 immunohistochemistry of skin in ALS patients. We studied laminin 1 immunoreactivity of skin from 17 patients with ALS, 17 patients with other neurological or muscular diseases (control group A) and 10 patients without neurological or muscular disorders (control group B). The dermis, the epithelial basement membrane of the epidermal layer and the basement membrane of skin appendages and blood vessels of skin in ALS patients were significantly higher than in control groups A and B, and showed a significant positive correlation with the duration of illness in the optical density for laminin 1 immunoreactivity. In addition, there was an appreciable positive relationship in the laminin 1 immunoreactivity between the dermis and the basement membrane in ALS patients. These data suggest that alterations of laminin 1 in the skin of ALS patients could be related to the pathogenesis of ALS and may contribute to changes in the mechanical properties of the skin, resulting in the absence of bedsores in ALS patients.

Objective: To clarify the possible relation between the extent of involvement of catecholaminergic neurons and the presence of alveolar hypoventilation in patients with myotonic dystrophy (MyD).Background: Respiratory insufficiency has been reported frequently in MyD patients. Recent data support the hypothesis that this respiratory failure results from a primary dysfunction of the CNS.Methods: The authors performed a quantitative immunoreactive study of tyrosine hydroxylase immunoreactive (TH+) neurons linked to hypoventilation in the dorsal central medullary nucleus (DCMN), the ventral central medullary nucleus (VCMN), and the subtrigeminal medullary nucleus (SMN)-where the automatic respiratory center is thought to be located-in eight MyD patients and in 10 age-matched control subjects. Alveolar hypoventilation of the central type was present in three of the MyD patients but not in the remaining MyD patients or the control subjects.Results: The densities of TH+ neurons of the DCMN, the VCMN, and the SMN in MyD patients with hypoventilation were significantly lower than in those without hypoventilation (p < 0.02, p < 0.01, and p < 0.01, respectively) and control subjects (p < 0.01, p < 0.01, and p < 0.01, respectively).Conclusions: These data suggest that the loss of TH+ neurons of the DCMN, the VCMN, and the SMN is associated with the presence of hypoventilation in MyD and may be an important feature of MyD.

Pathological studies were performed on 23 cases of focal nodular hyperplasia (FNH) under the hypothesis that FNH is a hyperplastic lesion caused by abnormal vasculatures of portal tracts within the nodule. For a comparison of the histological features of portal tracts, nodular regenerative hyperplasia (NRH), idiopathic portal hypertension (IPH), chronic hepatitis and so-called normal liver were used as control tissues. Extranodular areas of FNH nodules were also examined. Clinical data were briefly summarized. Most of the portal tracts within FNH nodules showed various abnormal findings, such as dilatation and/or stenosis of portal vein, muscular thickening of arterial wall with dilated or stenotic lumina, lymphocyte infiltration, and bile ductule proliferation. However, portal vein thrombi were not found. These findings were not thought to represent compensatory reaction to portal vein thrombosis. Similar abnormal features were also observed in extranodular areas of FNH although to a milder degree. These abnormal features resembled those of NRH and IPH. Moreover, the characteristic scar-like tissues within FNH nodules were proved to be abnormally large portal tracts including large feeding arteries, portal veins and bile ducts. It has been believed that septa and scar-like tissue within FNH nodules are not portal tracts and that arterial malformation independent of portal tracts are related to the development of FNH. In addition, venous structures within FNH modules have until now not been considered to be portal veins. However, this study revealed that severe anomaly of portal tracts including portal veins and hepatic arterial branches existed in FNH nodules. Moreover, portal tracts in extranodular areas were also abnormal. Clinically, only one patient had a history of oral contraceptives. Based on these findings, congenital anomaly of the portal tracts histologically resembling the abnormal portal tracts of NRH and IPH may be related to the pathogenesis of FNH.

A case of intraosseous well-differentiated osteosarcoma in one phalanx of the hand is reported. A 78-year-old man noticed swelling in the little finger of his right hand approximately 7 years before referral. Imaging disclosed a tumour with a "ground glass" appearance and irregular mottled calcification occupying almost all of the phalanx marrow and suggested slight invasion into the soft tissue. Open biopsy suggested a diagnosis of well-differentiated fibroblastic osteosarcoma. The finger and its metacarpal bone were amputated and a tumour measuring 3.5 x 2.2 x 2.0 cm and with an indistinct soft tissue margin was found in the bone marrow. Histologically, the tumour was composed of fibroblastic cells with few mitoses, and neoplastic bone formation was apparent. Although the tumour appeared to be a fibrous dysplasia, the presence of nuclear atypia, hypercellularity, and the absence of a typical woven bone pattern in addition to the soft tissue invasion indicated otherwise. Ultrastructural examination showed focal myofibroblastic differentiation, and immunohistochemistry revealed smooth muscle actin, vimentin, osteocalcin, osteonectin and MIBI in the tumour cells. This ultrastructural and immunohistochemical study is believed to be the first detailed report of an intraosseous well-differentiated osteosarcoma of phalangeal bone.

Malignant transformation of basal cell adenoma (BCA) of the parotid gland is rarely reported, and when occurred, may principally become manifest as a malignant basaloid tumor, i.e. basal cell adenocarcinoma or adenoid cystic carcinoma. We describe herein three cases of non-basaloid carcinoma arising in BCA. The incidence of this malignant tumor was 0.2% of all parotid gland tumors and 4.3% of BCAs in our series. One case was salivary duct carcinoma showing histologic evidence of transition between malignant and benign elements. The remaining two cases were well-encapsulated parotid gland tumors, which were composed of BCA and scattered foci of malignant transformation. Malignant components were adenocarcinoma, not otherwise specified (NOS), and sometimes intermixed with neoplastic myoepithelial cells included BCA cells. These two cases were regarded to be intracapsular carcinoma in BCA. BCA components showed solid, tubular and trabecular arrangements. The patients' prognosis was quite variable among these three cases; the first case died of disease after 27 months, whereas the latter two cases are alive and well for 4 and 10 years after surgery. Ki-67 labeling index indicated that cell proliferative activity was at least five times higher in carcinomas than BCAs. Non-basaloid carcinomas such as salivary duct carcinoma or adenocarcinoma, NOS, do develop in BCAs as in the case of a pleomorphic adenoma with malignant transformation, though the incidence may be extremely rare.

Testosterone enhances DA release in the MPOA at rest and with sexual challenge, possibly by upregulating NOS, which increases NO and thereby increases DA release. Androgens have beneficial effects on endothelial cells and smooth-muscle cells. Testosterone and dihydrotestosterone may also relax penile artery and cavernous smooth muscle through their nongenomic effects. In rats, castration has been reported to decrease arterial flow, induce venous leakage, and reduce the erectile response to stimulation of the cavernous nerve. Hypogonadal patients in whom PDE5 inhibitor failed could be rescued by the administration of testosterone.

We performed morphological studies of skin and measured glycosaminoglycans in the urine from patients with sporadic amyotrophic lateral sclerosis (ALS) and control subjects. The wide spaces separating collagen bundles reacted strongly with alcian blue stain in ALS patients and stained more markedly as ALS progressed. Staining with alcian blue was virtually eliminated by Streptomyces hyaluronidase. The urinary excretion of hyaluronic acid (HA) (mg/day) was significantly increased (P < 0.01) in ALS patients compared with that of control subjects, and there was a significant positive correlation between the excreted amount of HA and the duration of illness in advanced ALS patients with a duration of more than 2 years from clinical onset (r = 0.72, P < 0.02). We suggest that sporadic ALS includes a metabolic disorder of HA in which an accumulation of HA in the skin is linked to an increased urinary excretion of HA.

Summary Accumulating evidence indicates that varicocele repair improves sperm quality. However, longitudinal changes in sperm parameters and predictors of improved semen characteristics after surgery have not been fully investigated. We retrospectively reviewed data from 100 men who underwent microsurgical subinguinal varicocele repair at a single centre. Follow-up semen examinations were carried out at 3, 6 and 12 months post-operatively. Logistic regression was used to identify predictors of early (3 months) and late (≥6 months) improvement in semen parameters after varicocele repair. At 3 months post-operatively, 76.1% of the patients had improved total motile sperm counts, which continued to improve significantly up to 12 months post-operatively (p = .016). When comparing changes in semen parameters between younger (

We describe a case of malignant "dermal" melanoma that arose within a preexisting intradermal nevus. Clinically, the lesion had recently enlarged. Histologically, two patterns were noted. One was an intradermal nevus in the upper portion of the dermis; the other was a deeper nodule composed of malignant neoplastic cells that extended into the reticular dermis. No melanocytic epidermal junctional activity was noted. Despite careful clinical investigation, no alternative primary source was found. Neoplastic transformation of the intradermal nevus without junctional activity is our proposed interpretation of the lesion's histology. Immunohistochemical stains demonstrated that the deeper dermal neoplastic cells were positive for both HMB-45 and PCNA, whereas the superficial nevoid-appearing cells were negative; these findings support our postulate that this melanoma arose within an intradermal nevus. It is important to distinguish this neoplasm from other diagnostic possibilities, including a metastatic lesion originating from another site.

A morphological study using the Golgi impregnation method was carried out on the anterior horn cells at cervical (C), thoracic (Th), and lumbar (L) levels of the spinal cord in a patient with neuronal type of Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy type II) and an age-matched control. The present study demonstrated an uneven cell body surface, loss of cells (particularly large cells), loss of dendrites, reduced dendritic extent and an irregular surface and shape of dendrites at the C and L levels. In contrast, hematoxylin and eosin and Klüver-Barrera staining showed only simple atrophy or no change. The Th level of the patient showed none of these changes. Our results suggest that the degeneration or loss of dendrites of anterior horn cells by the Golgi staining method, which is most severe at the L level, is closely related to clinical findings such as muscle atrophy and weakness in neuronal type of Charcot-Marie-Tooth disease.

Vardenafil is a highly selective and potent phosphodiesterase type-5 inhibitor for the treatment of erectile dysfunction (ED). The efficacy of vardenafil has been demonstrated in a broad range of ED populations, but has not yet been assessed in Japanese patients with diabetes mellitus (DM), although DM is frequently associated with difficult-to-treat ED. This is the first study to investigate whether high-dose vardenafil (20 mg) can demonstrate superior efficacy to the usual dose (10 mg) in this subpopulation in Japan.The study was a randomized, placebo-controlled, double-blind, multi-centre, parallel group comparison 12-week study. Following 4 weeks observation period, 778 patients aged 26-64 years old with ED and DM (HbA1c12% at screening was excluded) both of more than 3 years duration were randomly allocated to one of the three groups, vardenafil 10 mg, 20 mg, or placebo (randomization ratio 3:3:1). Erectile function (EF) domain score of the International Index of Erectile Function was estimated as the primary efficacy parameter.Vardenafil 10 and 20 mg both significantly improved the EF domain score from 13.6 and 13.9 at baseline to 21.8 and 22.9 at last observation carried forward (LOCF), respectively, compared to placebo (13.7 at baseline to 16.3 at LOCF; p0.0001). In addition, vardenafil 20 mg demonstrated superior efficacy to 10 mg (p0.05), and the difference was more evident in severe ED patients (baseline EF domain score11). The safety profile was comparable between these two doses (drug-related adverse events: 6.6, 22.0 and 24.2% in placebo, vardenafil 10 mg, and 20 mg arms, respectively). The most common adverse events were hot flush, headache and nasal congestion, which were mild in intensity and transient, and are known to be common to PDE5 inhibitors.In Japanese men with DM and ED, vardenafil 10 mg and 20 mg were effective in improving erectile function with comparable safety profiles. Vardenafil 20 mg demonstrated superior efficacy compared with 10 mg, suggesting incremental clinical benefit in using the higher dose in this difficult-to-treat population.

To investigate the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in Japanese men with erectile dysfunction (ED).This multicenter, randomized, double-blind, placebo-controlled, 12-week study enrolled 343 Japanese men with ED. The men were stratified into those with mild, moderate, or severe ED and then randomly assigned 1:1:1:1 to placebo and 5 mg, 10 mg, and 20 mg tadalafil. Co-primary outcomes were the International Index of Erectile Function erectile function domain score, the percentage of "yes" responses to the Sexual Encounter Profile Diary Questions 2 and 3, and tolerability. Secondary outcomes included the International Index of Erectile Function intercourse satisfaction and overall satisfaction domain scores and the percentage of "yes" responses to a global assessment question.The least square mean change from baseline was 7.5, 9.1, and 9.4 for 5, 10, and 20 mg tadalafil versus 2.1 for placebo for the International Index of Erectile Function erectile function domain; 28.5, 36.0, and 36.5 for 5, 10, and 20 mg tadalafil versus 8.6 for placebo for Sexual Encounter Profile question 2; and 34.3, 47.3, and 50.8 for 5, 10, and 20 mg tadalafil versus 12.3 for placebo for Sexual Encounter Profile question 3, respectively (P0.001 for all doses and all measures). Patients taking tadalafil had significantly greater changes from baseline for the intercourse satisfaction and overall satisfaction domains compared with patients taking placebo (P0.001). Also, 76.5%, 81.4%, and 83.7% of patients taking 5, 10, and 20 mg tadalafil, respectively, reported improved erections (global assessment question) versus 31.4% of patients taking placebo (P0.001). Most (98%) treatment-emergent adverse events were mild or moderate in severity. One patient (tadalafil 5 mg) discontinued because of an adverse event (ureteral calculus). Of the 343 patients, 302 (88%) completed the study. No deaths were reported.All doses of tadalafil studied were efficacious and well tolerated in Japanese men with ED.

MX-68 is a newly synthesized antifolate, which is a derivative of methotrexate (MTX). In this paper, the effect of MX-68 on allergic airway responses in mice and guinea-pigs was studied. In the first experiment, antigen-induced airway inflammation and airway hyperresponsiveness (AHR) to acetylcholine in mice were examined and compared with the effects of classical antifolate methotrexate and prednisolone. Mice were sensitized with ovalbumin as an antigen and challenged with ovalbumin inhalation three times. After the last inhalation, AHR and airway inflammation were observed. An increase in Th2 cytokines (IL-4 and IL-5) and a decrease in a Th1 cytokine (IFN-γ) in the bronchoalveolar lavage fluid (BALF), as well as an elevation of the immunoglobulin level in serum, were observed in sensitized mice. Oral administration of MX-68 had no effect on changes of body weight, but prednisolone reduced body weight during the experiment. The antigen-induced AHR and increases in the number of eosinophils and lymphocytes in BALF were significantly inhibited by MX-68. MX-68 interfered with the elevation of IL-4 and IL-5 levels in BALF, but had no effect on the decrease in IFN-γ. Moreover, MX-68 significantly inhibited the elevation of serum IgE and IgG levels. In the guinea-pig model for bronchial asthma, biphasic increases in airway resistance (immediate asthmatic response, IAR, and late asthmatic response, LAR), as well as accumulated inflammatory cells in BALF, were observed after repeated antigen challenge. These asthmatic responses and inflammatory signs were significantly decreased by administration of MX-68. These results suggest that MX-68 obviously has an anti-inflammatory effect in an animal model of asthma and would be useful clinically for the treatment of bronchial asthma.

Oncocytic carcinoma is a rare malignant tumor of the salivary gland. Abundant, granular, eosinophilic cytoplasm is recognized as an oncocytic feature that reflects an accumulation of mitochondria. Ultrastructural study or immunohistochemical staining using antimitochondrial antibody can confirm the oncocytic nature of the tumor. However, there have been no data on whether immunocytochemical staining for human mitochondria aids in the confirmation of the oncocytic nature of oncocytic carcinoma.A 61-year-old man presented with a swelling in the left lower cheek. Computed tomography demonstrated a solid, isodense tumor in the parotid gland. An excisional biopsy of the tumor was performed, and an enlarged regional lymph node was removed. Imprint cytology of the lymph node showed cohesive cell clusters with lymphocytes. The clusters were composed of tumor cells that had characteristic abundant, granular cytoplasm and round to oval, centrally or eccentrically located nuclei with increased, fine chromatin and distinct nucleoli. Immunocytochemical staining revealed granular immunoreactivity of the cytoplasm for human mitochondria. Histology demonstrated tumor invasion in the normal gland and adjacent skeletal muscles. All tumor cells showed positive cytoplasm with antimitochondrial antibody by immunohistochemistry. Ultrastructural studies demonstrated packed mitochondria in the cytoplasm of the tumor.Immunocytochemical staining for human mitochondria help confirm the oncocytic nature of oncocytic carcinoma in cytologic specimens.

To evaluate the occurrence and prevalence of microdeletions in the gamma chromosome of patients with azoospermia.DNA from 29 men with idiopathic azoospermia was screened by polymerase chain reaction (PCR) analysis with a set of gamma chromosome specific sequence-tagged sites (STSs) to determine microdeletions in the gamma chromosome.Deletions in the DAZ (deleted in azoospermia) loci sgamma254 and sgamma255 were found in three patients with idiopathic azoospermia, resulting in an estimated frequency of deletions of 10.7% in idiopathic azoospermia men.We conclude that PCR analysis is useful for the diagnosis of microdeletions in the Y chromosome, which is important when deciding the suitability of a patient for assisted reproductive technology such as testicular sperm extracion-intracytoplasmic sperm injection (TESE-ICSI).

Background: Among hereditary leukodystrophies, a considerable number remain unclassified. Patient and results: We investigated the clinical course and histopathology of one patient in a family of adult-onset leukodystrophy with possible dominant inheritance. A 44-year-old man presented with cerebellar ataxia as the initial symptom, and later, dementia and hyperreflexia with ankle clonus developed. T2-weighted brain MRI showed brain atrophy and diffuse high signal intensity of the cerebral white matter and the brain stem. The patient’s mother and older brother also had cerebellar ataxia and dementia, and his older brother had been diagnosed as having spinocerebellar degeneration. An older sister of our patient possibly had similar neurological symptoms of adult-onset. Our patient died of pneumonia 5 years after the onset of disease. The histopathological findings consisted mainly of patchily observed vacuolar changes in the cerebral and cerebellar white matter and the brain stem. The subcortical regions and the cortex were unaffected. It is suggested that the pathological changes began in the cerebellum, and later spread to the frontal lobe and the brain stem. In the occipital regions, the vacuolations were associated with accumulation of macrophages and astrocytosis, which implied that the vacuolations were of recent origin. Conclusions: The diagnosis in this patient is adult-onset leukodystrophy with possibly autosomal dominant inheritance. The clinicopathological features are different from those, of previously reported adult-onset leukodystrophies.

Little is known concerning the changes of amino acid composition in different regions of the spinal cord in patients with amyotrophic lateral sclerosis (ALS). We performed quantitative amino acid analyses in the posterior funiculus, the lateral corticospinal tract, and the anterior horn of cervical enlargement of the spinal cord from seven ALS patients, and the results were compared with those of seven patients with other neurologic diseases (control A) and seven patients without neurologic diseases (control B). The levels of collagen-associated amino acids, hydroxyproline, proline, glycine, and hydroxylysine, were markedly lower in the lateral corticospinal tract and the anterior horn of ALS patients than in controls A and B. The contents of the acidic amino acids glutamate and aspartate were also significantly decreased in the lateral corticospinal tract and the anterior horn of ALS patients as compared with those of controls A and B. These data suggest that decreased contents of collagen-associated amino acids and excitatory amino acids are related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS.

To study type IV collagen of skin and serum in patients with ALS.Collagen abnormalities of skin have been reported in ALS patients. However, little is known concerning type IV collagen in ALS.We studied type IV collagen immunoreactivity of skin and measured serum levels of the 7S fragment of the N-terminal domain of type IV collagen (7S collagen) in patients with ALS and control subjects.The basement membrane as well as blood vessels of skin in ALS patients was weakly positive for type IV collagen as compared with those of diseased control subjects. This weak immunostaining became more pronounced as ALS progressed. The optical density for type IV collagen immunoreactivity in ALS patients was significantly lower (p0.001) than in diseased control subjects and was significantly decreased with duration of illness (r = -0.85, p0.01). Serum 7S collagen levels in patients with ALS were significantly decreased (p0.01) as compared with those in diseased and healthy control subjects and were negatively and significantly associated with duration of illness (r = -0.81, p0.001). There was an appreciable positive correlation between concentrations of serum 7S collagen and the density for type IV collagen immunoreactivity in ALS patients (r = 0.81, p0.02).These data suggest that a metabolic alteration of type IV collagen may take place in the skin of ALS patients and that the decreased levels of serum 7S collagen may reflect a decreased type IV collagen immunoreactivity of skin in patients with ALS.

Hypersomnia occurs frequently in patients with myotonic dystrophy (MyD). We performed a quantitative immunohistochemical study of serotonin (5-HT)-containing neurons linked to hypersomnia in the dorsal raphe nucleus (DRN) and the superior central nucleus (SCN) in 8 patients with MyD, 5 of whom showed hypersomnia, and in 12 age-matched controls. The densities of 5-HT neurons in the DRN and the SCN were significantly lower in MyD patients with hypersomnia than in MyD patients without hypersomnia and controls. These data suggest that the loss of 5-HT neurons of the DRN and the SCN is associated with the presence of hypersomnia in MyD.

It is well known that diabetes mellitus is accompanied by complications of sexual dysfunction and it is believed that diabetic neuropathy may cause impotence. In our study, we found that not all the patients who visited our center with the chief complaint of diabetic impotence were suffering from organic impotence, and diabetes mellitus per se served as a means of psychological stress in a substantial number of cases. Probably because no method has been available to provide precise information on the state of the penile-controlling nerves, we found that a larger number of patients than expected were suffering from a vascular disorder.

Intracytoplasmic inclusion bodies of the thalamus in eight patients with myotonic dystrophy (MyD) were studied immunohistochemically. The intracytoplasmic inclusion bodies of the thalamus (thalamic inclusions, TIs) were strongly immunostained with anti-ubiquitin antibody (Ab) and some of them were mildly stained with anti-microtubule associated protein 1 (MAP 1) and anti-MAP 2 antibodies. However, TIs did not react with any of the following: anti-neurofilament protein Ab, anti-tau Ab, anti-paired helical filament Ab, anti-tubulin Abs (alpha and beta), anti-neuron-specific enolase Ab, anti-glial fibrillary acidic protein Ab, anti-synaptophysin Ab, anti-myelin basic protein Ab, anti-actin Ab and anti-phosphorylated epitope of neurofilaments Ab. Thus, our study demonstrates the unique immunohistochemistry of TIs in MyD which differentiates them from other intracytoplasmic inclusions in various neurodegenerative disorders.

BACKGROUND Undifferentiated carcinoma with lymphoid stroma (UCLS) arising in the salivary gland is a rare tumor, except for its geographic concentration among Eskimo and southern Chinese populations. Five cases of salivary gland UCLS in Japanese patients are presented here and compared with benign lymphoepithelial lesions (BLELs) with regard to their association with Epstein-Barr virus (EBV), p53 expression, and cell proliferative activity. METHODS Formalin fixed, paraffin embedded sections of 5 cases of UCLS selected from 1676 patients with primary tumors of the major salivary gland and 7 cases of BLEL were examined using in situ hybridization for EBV-encoded RNAs (EBERs), along with immunostaining for p53 and Ki-67 (MIB-1). RESULTS The incidence of UCLS was 0.3% among patients with major salivary gland tumors. EBER hybridization signals were strongly expressed in most of the neoplastic cells in all five cases of UCLS, whereas there was no signal in BLEL and surrounding nontumorous salivary gland tissues. All cases of UCLS showed strongly positive immunostaining for p53 in the tumor cell nuclei. By contrast, only one case of BLEL was positively stained for p53 in dysplastic epimyoepithelial cells, which showed focal immunostaining. Cell proliferative activity assessed using the Ki-67 labeling index was significantly higher in tumor cells of UCLS than in epimyoepithelial cells of BLEL. CONCLUSIONS UCLS of the salivary gland is an extremely rare tumor in Japanese patients characterized by consistent association with EBV. Distinction between BLEL and UCLS is possible by examining for evidence of EBV infection, expression of p53, and cell proliferative activity. Cancer 1996;78:695-703.

Objective: To study the significance of prostate specific antigen (PSA) and prostate specific antigen density (PSAD) for predicting the risk of occult metastatic disease and extra-prostatic invasion of prostate cancer in patients receiving radical prostatectomy. Patients and methods: The cases of 41 consecutive patients who underwent radical prostatectomy were reviewed. Relations of PSA and PSAD using Market M PA1M assay for grade, preopvrative clinical stage, postoperative pathological stage, capsular penetration, seminal vesicle invasion, resection margins and lymphnode metastasis are discussed. Results: Although serum PSA was correlated with PSAD and PSA was correlated with preoperative prostate volume, PSAO was not influenced by prostate volume. PSA correlated only with the grade, while PSAD was correlated with grade, preoperative clinical Stage, postoperative pathological stage, capsular penetration, seminal vesicle invasion, resection margins and lymphnode metastasis. In addition, sixty-two percent (8/13) of margin positive patients showed a PSAD value of more than 0.4, while 93% (26/28) of margin negative patients showed less than 0.4. Sixty-seven percent (6/9) of lymphnode positive patients showed a PSAD of more than 0.4, while 91% (29/32) of lymphnode negative patients showed less than 0.4. Conclusion: We concluded that PSAD was useful for predicting extraprostatic involvement of prostatic cancer.

Aspiration cytology and core needle biopsy were performed in 79 patients who were suspected of having prostate cancer. Aspiration cytology and TURP were done in 77 cases not suspected of the disease. In the former group, they were both positive in 13 cases, aspiration cytology was negative and core needle biopsy positive in 4, and the reverse in 3 cases in whom cancer was confirmed by repeat core biopsy. All of the latter group were judged by aspiration cytology as being benign. Three cancers were detected by TURP. Aspiration cytology is a recommendable method in subjects with suspected prostate cancer.

A quantitative study of neurons in the dorsal raphe nucleus (DRN) and the superior central nucleus (SCN) was performed in seven patients with myotonic dystrophy (MyD), five of whom showed hypersomnia, and in eight age-matched controls. The densities of neurons in the DRN and the SCN were significantly lower in MyD patients with hypersomnia than in MyD patients without hypersomnia and control subjects. There was an appreciable positive correlation in the density of neurons between the DRN and the SCN in all MyD patients. These data suggest that the neuronal loss of the DRN and the SCN is associated with the presence of hypersomnia in MyD.

Retinoblastomas exhibit a unique form of differentiation to produce cell elements similar to those seen in a photoreceptor cell. An ultrastructural study was performed on 29 cases of retinoblastoma to further clarify the cytologic characteristics of the tumor cells. The age of the retinoblastomas averaged 17.1 months and the tumor cells showing photo-receptor differentiation were demonstrated in 10 cases (35%). The findings were especially notable in retinoblastomas with Flexner-Wintersteiner rosette formation (seven cases, 28%). Similar photoreceptor differentiation was also evident in solid cell clusters without rosette formation (four cases, 14%). The presence of photoreceptor elements was assumed to be significantly frequent both in Flexner-Wintersteiner rosettes and in the solid cell clusters. The cell cytoplasm also showed proliferation of long mitochondria and microtubules, reflecting photoreceptor differentiation. The hereditary-type retinoblastoma showed more advanced cell differentiation than the non-hereditary type. Photoreceptor differentiated retinoblastoma showed rather indolent growth compared with the undifferentiated type, and the former can expect a curative treatment by operation. These observations provide additional findings of the biological nature of retinoblastomas.