Biomedical subjects
Publications and source records attributed to A Numata.
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OBJECTIVE: To assess the correlation between retinal vascular findings and penile cavernosal arterial blood flow, as it is probable that systemic atherosclerotic vascular disease is important in male erectile dysfunction (ED), and being systemic, it might be possible to evaluate the extent of atherosclerosis from retinal vascular findings. PATIENTS AND METHODS: The study included 75 patients with ED; any with a history of pelvic injury, pelvic surgery, or diabetes mellitus were excluded. All patients gave fully informed consent. Ocular fundus photographs were taken with an automatic-focus fundus camera under amydriatic conditions. Three ophthalmologists, unaware of the patients' detailed data, evaluated the photographs using Hyman's classification to evaluate retinal vascular findings. Blood flow in the penile cavernosal artery was measured with colour Doppler ultrasonography, and the peak systolic velocity used as a haemodynamic variable. Correlations among the peak systolic velocity, retinal vascular findings and vascular risk factors (including hypertension, age, cigarette smoking, and hyperlipidaemia) were investigated using multivariate analysis. RESULTS: Of the 75 patients, 72 (96%) had both right and left retinal vascular images of sufficient quality for evaluation; 37 were classified as normal and 35 as Grade I, while no patient was Grade II. From a logistic regression multivariate analysis, the peak systolic velocity was the only significant factor correlating with retinal vascular findings, with an odds ratio of 3.34. In contrast, hypertension, age, cigarette smoking and hyperlipidaemia did not correlate significantly with the retinal vascular findings. Similarly, the retinal vascular finding was the only significant factor correlating with the peak systolic velocity of cavernosal blood flow (odds ratio 3.28) and again hypertension, age, cigarette smoking and hyperlipidaemia were not significant factors. CONCLUSIONS: These findings support the assumption that penile erectile function is one of the diseases of atherosclerosis, and emerges nearly simultaneously with retinal vascular disease. It is possible to predict penile arterial conditions in patients with ED from their retinal vascular findings. Thus, amydriatic fundoscopy, a simple practical examination, may be helpful for primary physicians in diagnosing and treating ED.
Ascidiacyclamide (ASC), cyclo(-Ile1-Oxz2-d-Val3-Thz4-)2 (Oxz=oxazoline and Thz=thiazole) has a C2-symmetric sequence, and the relationships between its conformation and symmetry have been studied. In a previous study, we performed asymmetric modifications in which an Ile residue was replaced by Gly, Leu or Phe to disturb the symmetry [Doi et al. (1999) Biopolymers49, 459-469]. In this study, the modifications were extended. The Ile1 residue was replaced by Gly, Ala, aminoisobutyric acid (Aib), Val, Leu, Phe or d-Ile, and the d-Val3 residue was replaced by Val. The structures of these analogs were analyzed by X-ray diffraction, 1H NMR and CD techniques. X-Ray diffraction analyses revealed that the [Ala1], [Aib1] and [Phe1]ASC analogs are folded, whereas [Val1]ASC has a square form. These structures are the first examples of folded structures for ASC analogs in the crystal state and are similar to the previously reported structures of [Gly1] and [Phe1]ASC in solution. The resonances of amide NH and Thz CH protons linearly shift with temperature changes; in particular, those of [Aib1], [d-Ile1] and [Val3]ASCs exhibited a large temperature dependence. DMSO titration caused nonlinear shifts of proton resonances for all analogs and largely affected [d-Ile1] and [Val3]ASCs. A similar tendency was observed upon the addition of acetone to peptide solutions. Regarding peptide concentration changes, amide NH and Thz CH protons of [Gly1]ASC showed a relatively large dependence. CD spectra of these analogs indicated approximately two patterns in MeCN solution, which were related to the crystal structures. However, all spectra showed a similar positive Cotton effect in TFE solution, except that of [Val3]ASC. In the cytotoxicity test using P388 cells, [Val1]ASC exhibited the strongest activity, whereas the epimers of ASC ([d-Ile1] and [Val3]ASCs), showed fairly moderate activities.
Cytomegalovirus (CMV) antigenemia and quantitative real-time polymerase chain reaction (PCR) were compared for monitoring of CMV reactivation after allogeneic stem cell transplantation. The number of CMV antigen-positive cells by the antigenemia assay and the level of CMV DNA by real-time PCR correlated well. The sensitivity and specificity of the antigenemia assay was 55.4% and 95.5%, respectively, using real-time PCR as the reference standard. The probability of positive antigenemia at day 100 was 76.5%, with a median of first detection at day 37 in 51 patients, compared with a positive PCR of 84.3% and day 33, respectively. When HLA-identical sibling donor transplant recipients and other donor transplant recipients were analyzed separately, there was no difference between the two tests. However, temporal patterns of first detection of CMV antigen-positive cells and CMV DNA differed between HLA-identical and alternative recipients; patients without CMV (29%) or with sporadic positive PCR results (14%) were more common in HLA-identical sibling transplants, whereas patients with simultaneous antigenemia and positive PCR occurred more in alternative transplants (48%). Two of 51 patients (4%) developed CMV colitis despite antigenemia-guided prophylaxis, but both were successfully treated with ganciclovir. Although PCR is more sensitive than antigenemia, both tests are useful in the early detection of CMV after allogeneic stem cell transplantation.
Erection is a hemodynamic event and accordingly, erectile dysfunction (ED) is closely related with ischemic heart disease. We should confirm that the cardiac condition of the ED patient is safe enough to perform sexual intercourse prior to beginning treatment for ED. Asymptomatic ischemic heart disease cannot be diagnosed only in an interview, but it's difficult to perform cardiac exercise tests on all patients complaining of ED. Therefore, screening methods to evaluate patients who should undergo exercise tests are needed. Sixty patients with erectile dysfunction participated in this study. Physical examinations, interviews, and color Doppler examinations were conducted. Chest X-rays and electrocardiograms of all patients in the resting position were obtained, as were electrocardiograms following exercise. Echocardiograms, treadmill test results, thallium exercise scintigrams, and coronary angiograms were obtained as required for diagnosis. Two patients were excluded because they had obvious arteriogenic ED due to perineal injury. Fifty-eight patients underwent Doppler evaluations of their cavernous arteries and heart exercise tests. Fourteen patients (24.1%) were diagnosed with ischemic heart disease. Although six of them had already been diagnosed with ischemic heart disease, eight were newly diagnosed by the exercise tests. Cardiovascular risk factors such as advanced age, hyperlipidemia, diabetes mellitus, hypertension, smoking, and obesity were not sufficient predictive factors. The mean peak systolic velocity of the patients without ischemic heart disease was 34.6 cm/s vs 22.0 cm/s in those with ischemic heart disease. Only 3.7% of patients whose peak systolic velocity in the cavernous artery was equal to or exceeded 35 cm/s had ischemic heart disease. On the other hand, 41.9% of patients with peak systolic velocity of less than 35 cm/s had ischemic heart disease. The sensitivity of peak systolic velocity against ischemic heart disease was 92.9%, and specificity was 59.1%. In ED patients, incidences of complications involving symptomatic or asymptomatic ischemic heart disease were found to be high. The peak systolic velocity in the cavernous artery is thought to be a useful predictive factor of ischemic heart disease in ED patients. When a patient reveals a peak systolic velocity of less than 35 cm/s, he should undergo heart exercise tests prior to treatment of ED.
We studied the voluntary contractile activity of the ischiocavernosus muscle (ICM) in 21 sexually potent and 97 erectile dysfunction (ED) subjects using a spring balance. A strap was placed around the coronal grove of the glans penis and tensioned with the spring balance. Subjects were asked and encouraged to contract the ICM against the spring balance. We evaluated the length of stroke, duration of contraction, and maximum contractile force. The length of stroke, duration of contraction, and maximum contractile force showed statistically significant differences between potent and ED subjects. Diagnosed psychogenic ED and arteriogenic ED showed higher contractile activity than cavernous ED and neurogenic ED. Our results corresponded to those of previous studies that have urged consideration of the role of the ICM during the process of erection in animal experiments and in human electrophysiological studies. The spring balance evaluation is a useful, inexpensive method for evaluating the ICM.
OBJECTIVE: To assess the effect of radical retropubic prostatectomy on erectile function, by evaluating objectively patients' erectile function before and after surgery. PATIENTS AND METHODS: The study comprised 126 patients with clinically localized prostate cancer who were scheduled to undergo radical retropubic prostatectomy. After giving informed consent for the study, 123 patients underwent intracavernosal injection tests, colour Doppler ultrasonography and nocturnal penile tumescence monitoring before and after surgery. RESULTS: From the intracavernosal injection tests and nocturnal penile tumescence monitoring, 21 patients (17%) were evaluated as having normal erectile function before surgery. After radical retropubic prostatectomy, nine (43%) of these 21 potent men had preserved erectile function. In eight patients whose neurovascular bundles were preserved, five were potent after surgery. The cause of erectile function after surgery was a neurogenic disorder in seven and a related vascular disorder in five. CONCLUSION: From objective tests of erectile function on patients scheduled to undergo radical prostatectomy, 17% had normal erectile function. However, even after nerve-sparing radical retropubic prostatectomy, the proportion retaining potency was unsatisfactory. Although a neurological disorder was the main cause of erectile dysfunction after surgery, vascular disorders were also important.
OBJECTIVE: To compare computed tomography (CT) angiography (CTA) obtained by multi-slice CT (a new minimally invasive method) with the current standard of arterial imaging, digital subtraction angiography (DSA), in diagnosing arteriogenic erectile dysfunction (ED). PATIENTS AND METHODS: Twenty-one patients with suspected arteriogenic ED underwent DSA and CTA after providing informed consent. Prostaglandin E1 was injected into the penile cavernosal body and then non-ionic contrast medium was rapidly infused into the antecubital vein. The DSA and CTA images were diagnosed as showing a normal or abnormal status by three reviewers independently. CTA was undertaken on an outpatient basis but DSA required hospitalization. RESULTS: In the 42 internal pudendal arteries, DSA showed 28 normal and 14 impaired arteries; CTA showed 21 normal arteries and 21 occlusions. The CTA image correlated closely with the diagnosis of stenosis or occlusion in internal pudendal arteries, with a sensitivity of 93%, a specificity of 71% and an accuracy of 79%. In the cavernosal arteries, DSA depicted 14 normal and 28 impaired arteries; CTA showed seven normal arteries and 35 occlusions. The CTA image agreed closely with the diagnosis of stenosis or occlusion in cavernosal arteries, with a sensitivity of 96%, a specificity of 43% and an accuracy of 79%. Of the 42 inferior epigastric arteries, DSA could not depict 11 arteries but CTA showed all 42 inferior epigastric arteries. CONCLUSIONS: CTA images correlated with DSA images; at present DSA is better than CTA in visualizing stenosis in fine arteries. However, CTA is less invasive and relatively inexpensive, and in future will probably provide even greater improvements in graphic quality. CTA would be an adequate replacement for DSA in evaluating internal pudendal arterial stenosis.
OBJECTIVE: We evaluated the efficacy of betamethasone ointment in the treatment of childhood phimosis and determined the most effective concentration of betamethasone. MATERIAL AND METHODS: Between August 1996 and May 2000, 69 patients (median age 3.0, range 0-12) presented to our department with severe phimosis (grade 4, Tsugaya's classification), and were enrolled in this study and treated with betamethasone ointment for 4 weeks. The ointment was applied on the narrowed preputial skin twice a day by parents. During the first week, parents were asked not to retract the foreskin. After this period, parents were encouraged to retract the foreskin gently and without intense tension. The concentration of betamethasone were 0.12%, 0.05% and 0.025%. If the patients become to be able to retract foreskin satisfactory, we consider the state as complete response. If he become to be able to retract to allow partial exposure of the glans, we consider the state as partial response. We compared the efficacy among each of the concentrations, and at 3 months after the end of the treatment, we also assessed the adverse effects and recurrence. RESULTS: The overall success rate was 85.5%. Success rates with 0.12%, 0.05% and 0.025% ointment were 96.8%, 82.8% and 55.6%, respectively (p = 0.0001). The 0.12% ointment was most effective. Recurrence was observed in 3 patients (4.3%). No adverse effects were observed in any of the patients. CONCLUSIONS: Treatment with betamethasone ointment is very effective, easy and safe. We recommend betamethasone ointment as the first treatment of choice for childhood phimosis.
BACKGROUND: CT angiography reconstructed by a multidetector-row helical CT scanner is a newly developed form of imaging. We compared CT angiography and ultrasonic Doppler examination with digital subtraction angiography (DSA) in the diagnosis of arterial lesion. METHOD: Eighteen patients with arteriogenic erectile dysfunction (ED) underwent color Doppler study, DSA, and CT angiography after providing informed consent. The CT angiography images were obtained by a multidetector-row helical CT scanner, Asteion TSX021A (TOSHIBA). We injected prostaglandin E1 into the penile cavernous body, and then rapidly infused nonionic contrast medium into the antecubital vein. DSA and CT angiography images of the bilateral internal pudendal arteries and cavernous arteries were examined for stenotic lesions or occlusion. We also compared the peak systolic blood flow velocity in the cavernous artery measured by color Doppler ultrasound with CT angiography and DSA. RESULTS: The CT angiography and color Doppler studies were performed on an outpatient basis, but DSA required hospitalization. In the 36 internal pudendal arteries, DSA represented 22 normal arteries and 14 stenosis or occlusions. CT angiography showed 15 normal arteries and 21 occlusions. For the diagnosis of stenosis or occlusion in the internal pudendal artery, the CT angiography image had a good agreement, with a sensitivity of 1.00, specificity of 0.68, and accuracy of 0.81. For diagnosis in the cavernous artery, CT angiography image also showed a good agreement with DSA; however, the quality of the images of fine arteries was better in the DSA images. The inferior view and internal view of the pelvis in CT angiography were helpful for visualizing the internal pudendal artery, especially at the pubic bone. There was insufficient correlation between peak systolic blood flow velocity and DSA findings. There were no serious complications involved in either examination. CONCLUSIONS: CT angiography has not yet reached the same level as DSA in the evaluation of fine arteries. However, CT angiography can produced images sufficient for the diagnosis of arteriogenic ED with some advantages. We believe that with improvement, CT angiography will become an adequate replacement for DSA in the diagnosis of penile arterisl lesion.
Janus kinases (Jaks) play an important role in signal transduction via cytokine receptors. Tyk2 is a Janus kinase, and we developed tyk2-deficient mice to study the requirement for tyk2 in vivo. Tyk2-deficient mice show no overt developmental abnormalities; however, they display a lack of responsiveness to a small amount of IFNalpha, although a high concentration of IFNalpha can fully transduce its signal even in the absence of tyk2. Furthermore, IL-12-induced T cell function is defective in these mice. In contrast, these mice respond normally to IL-6 and IL-10, both of which activate tyk2 in vitro. These observations demonstrate that tyk2 plays only a restricted role in mediating IFNalpha-dependent signaling while being required in mediating IL-12-dependent biological responses.
Bioassay (P-388 lymphocytic leukemia cell line)-guided separation of an extract prepared from the bark and stem of the Sri Lankan tree Schleichera oleosa led to the isolation of seven cancer cell growth inhibitory hydroxylated sterols designated schleicherastatins 1-7 (1-7) and two related sterols, schleicheols 1 and 2 (8, 9). The structure of schleicherastatin 1 (1) was completely elucidated by X-ray crystal structure determination. Based upon that defined structure, the remaining new sterol structures were deduced by highfield (300 and 500 MHz) NMR and MS interpretations. In this new series of sterols, hydroxylation at C-22 appears to be important for promoting cancer cell growth inhibition.
In order to elucidate the reaction mechanism of the cyclization between an ethynyl group and an imino group at the ortho-position on an aromatic ring to afford isoquinolines, reaction of 2-ethynylbenzaldehydes under various conditions was examined. It is concluded that reaction proceeds via an ionic process and the isoquinoline 4-hydrogen atom derives from the solvent. In addition, it was found that 2-ethynylbenzaldehyde O-methyloximes underwent cyclization in the presence of primary and secondary alcohols to give 3-substituted isoquinolines.
BACKGROUND: We report the results of microscopic penile revascularization in patients with arteriogenic erectile dysfunction. METHODS: One patient with localized obstruction of the common penile artery underwent the Michal II penile revascularization, 13 patients underwent the Furlow-Fisher procedure, and 5 patients underwent the Hauri procedure. The mean age was 33.0 years and the mean follow-up period was 32 months (4-80 months). Eight patients were tobacco smokers, one patient was over 50 years old. Surgery was considered successful when the patients had a permeable anastomosis and were able to achieve satisfactory erection resulting in normal sexual intercourse. RESULTS: All surgery was successful except for one patient who had undergone the Furlow-Fisher procedure. In Spite of antithrombotic therapy, graft occlusion occurred in two patients. Post operative glans hypervascularity occurred in two patients. CONCLUSION: Penile revascularization surgery is a highly effective treatment for selected patients. There is a need for further study of graft occlusion and glans hypervascularity.
BACKGROUND: Erection is an hemodynamic event and accordingly, erectile dysfunction is closely related with ischemic heart diseases. Sufficient study has yet to be made of this relation. METHOD: Fifty-eight patients with erectile dysfunction participated in the present study. Intracavernous injection tests and color Doppler examination were conducted for assessment of erectile function. For patients with history of ischemic heart disease, we referred to their doctor for data from their examinations. For patients otherwise, chest X-rays and electrocardiograms in the resting position were obtained and also electrocardiograms following exercise. Echocardiograms, treadmill test results, thallium exercise scintigrams, and coronary angiograms were obtained as requires for diagnosis. RESULTS: Eighteen patients (31.0%) were diagnosed as ischemic heart disease or at high risk. Although 6 of them had been already diagnosed with ischemic heart disease, 12 were newly diagnosed by the exercise tests. Among these 18 patients 16 had one or more significant risk factors for ischemic heart disease such as age, hyperlipidemia, and diabetes mellitus. 3.7% of patients whose peak systolic velocity in the cavernous artery was equal to or exceeded 35 cm/sec had ischemic heart disease or were at high risk. 54.8% of patients with peak systolic velocity of less than 35 cm/sec had ischemic heart disease or were at high risk. CONCLUSIONS: In erectile dysfunctional patients, incidence of complications with symptomatic or asymptomatic ischemic heart disease was found to be high. Therefore, in patients with risk factors or low peak systolic velocity in the cavernous artery, exercise tests should be implemented prior to treatment of erectile dysfunction.
We report here the first case of localized amyloidosis of the ureter and bladder to be treated effectively by occlusive dressing technique therapy using dimethyl sulfoxide. The patient was a 48-year-old woman whose chief complaint was macrohematuria and right back pain. Ultrasound sonography demonstrated right hydronephrosis and an intravesical mass in the region of the right ureteral orifice. Retrograde pyelography revealed severe stricture of the right lower ureter. Cystoscopy demonstrated a yellow submucosal tumor around the right ureteral orifice. We suspected urinary tract amyloidosis, and transurethral biopsy and resection of the intravesical mass were performed under right ureteral stenting. Histopathological diagnosis was amyloidosis. There was no evidence of systemic amyloidosis. To treat residual amyloidosis of the ureter and bladder, we performed occlusive dressing technique therapy using dimethyl sulfoxide every day. After 6 months of therapy, the right hydronephrosis disappeared, and there was no evidence of a recurrence of amyloidosis. We concluded that this therapy was very effective and safe for urinary tract amyloidosis.
We reported a family with dentato-rubro-pallido-luysian atrophy (DRPLA) and chronic renal failure. The proband was a 66-year-old woman who developed gait disturbance, limb ataxia, pyramidal tract signs, and dementia since age 54. T2-weighted brain MR images revealed symmetric high-signal lesions in the cerebral white matter, in addition to cerebellar, brainstem, and cerebral cortical atrophy. She suffered from renal failure and became dialysis-dependent at the age of 59, four years after the onset of chronic nephritic syndrome. At the age of 66, she was admitted to our hospital because of hyperthermia and disturbance of consciousness, and died of DIC. Her CAG repeats in the DRPLA gene were 58 and 12. An autopsy was performed. The brain weighed 910 g. Histological findings confirmed the diagnosis of DRPLA. Her mother died of chronic renal failure. All three siblings had cerebellar ataxia, and two siblings had chronic nephritic syndrome. Among them, only her younger brother was diagnosed as non-IgA glomerulonephritis based on kidney biopsy findings at the age of 48. Though the nature of the association between DRPLA and renal dysfunction remains obscure, the DRPLA gene abnormality may be correlated with chronic renal failure in this family.