The Rho family of GTPases are involved in actin cytoskeleton organization and associated with carcinogenesis and progression of human cancers. We investigated the roles of Rho family GTPases, prototypes RhoA, Rac1, and Cdc42, and the major downstream targets of RhoA, ROCK-I, and ROCK-II in testicular cancer. We quantified protein expression in paired tumor and nontumor samples from surgical specimens from 57 consecutive patients with testicular germ cell tumors using Western blotting. Protein expression of RhoA, ROCK-I, ROCK-II, Rac1, and Cdc42 was significantly higher in tumor tissue than in nontumor tissue (P < 0.0001). Expression of protein for RhoA, ROCK-I, ROCK-II, Rac1, and Cdc42 was greater in tumors of higher stages than lower stages (P < 0.0001, P < 0.001, P < 0.001, P < 0.0001, P < 0.0001, respectively). Within stage II nonseminoma (31 patients), protein levels of RhoA, ROCK-I, ROCK-II, Rac1, and Cdc42 in the primary tumor were lower in the group of 24 patients with no evidence of disease after therapy compared with 7 patients with disease that was refractory/recurrent (P < 0.05). Rho family GTPases may be involved in the progression of testicular germ cell tumors.
Objectives-Urinary dysfunction is a prominent autonomic feature in Parkinson's disease (PD) and multiple system atrophy (MSA), which is not only troublesome but also a cause of morbidity in these disorders. Recent advances in investigative uroneurology oVer a better insight into the underlying pathophysiology and appropriate management for urinary dysfunction. Methods-twenty one patients with PD (15 men, six women, mean age 64 (49-76), mean disease duration 4 years (1-8 years), median Hoehn and Yahr grade 3 (1-4), all taking 300 mg/day of levodopa (100-500 mg)) and 15 with MSA (eight men, seven women, mean age 59 (48-72), mean disease duration 3 years (0.5-6 years)) were recruited. Videourodynamic and sphincter motor unit potential analyses in the patients with PD and MSA were carried out, looking for distinguishing hallmarks that might be useful in the diVerential diagnosis of these two diseases. Results-Urinary symptoms were found in 72% of patients with PD and in 100% with MSA. Filling phase abnormalities in the videourodynamic study included detrusor hyperreflexia in 81% of patients with PD and 56% with MSA, and uninhibited external sphincter relaxation in 33% of patients with PD and 33% of those with MSA. However, open bladder neck at the start of filling was not seen in patients with PD but was present in 53% of those with MSA, suggestive of internal sphincter denervation. Sphincter motor unit potential analysis showed neurogenic motor unit potentials in 5% of patients with PD and in 93% of those with MSA, suggestive of external sphincter denervation. On voiding, detrusor-external sphincter dyssynergia was not seen in patients with PD but was present in 47% of those with MSA. Pressure-flow analysis showed that the Abrams-GriYths number, a grading of urethral obstruction (outflow obstruction >40), in PD (40 in women and 43 in men) was larger than that in MSA (12 in women and 28 in men). Weak detrusor in PD (66% of women and 40% of men) was less common than that in MSA (71% of women and 63% of men). Postmicturition residuals >100 ml were absent in patients with PD but were present in 47% of patients with MSA.Conclusion-Patients with PD had less severe urinary dysfunction with little evidence of internal or external sphincter denervation, by contrast with the common findings in MSA. The findings of postmicturition residuals >100 ml, detrusorexternal sphincter dyssynergia, open bladder neck at the start of bladder filling, and neurogenic sphincter motor unit potentials are highly suggestive of MSA. (J Neurol Neurosurg Psychiatry 2001;71:600-606)
Objectives-To investigate urinary function in the elderly with and without white matter lesion (leukoaraiosis) in relation to cognitive and gait function. Methods-Sixty three subjects were examined, with mean age 73 (range 62 to 86 years). Subjects with brainstem stroke or with large hemispheric lesions were excluded. Spin echo 1.5 T MRI images were graded from 0 to 4 for severity of white matter lesions. Urinary function was assessed by detailed questionnaire and urodynamic studies were performed in 33 of the subjects, including measurement of postmicturition residuals, water cystometry, and sphincter EMG. A mini mental state examination (MMSE) and examination of gait was also performed and compared with urinary function. Results-Urodynamic studies showed subjects with grade 1-4 white matter lesions to have detrusor hyperreflexia more commonly (82%) than those with grade 0 white matter lesions (9%) (p<0.05), indicating that leukoaraiosis was a factor associated with geriatric urinary dysfunction. Postmicturition residuals, low compliance, detrusor-sphincter dyssynergia, and uninhibited sphincter relaxation were also more common in grade 1-4 than in grade 0 white matter lesions, though the diVerence was not significant. In grade 1 white matter lesions urinary dysfunction (urge urinary incontinence) was more common than cognitive (MMSE<19) (p<0.05) and gait disorders (slowness, short step/festination, and loss of postural reflex) (p<0.05), which increased together with the grade of white matter lesions (p<0.05). Conclusions-Urinary dysfunction is common and probably the early sign in elderly people with leukoaraiosis on MRI. (J Neurol Neurosurg Psychiatry 1999;67:658-660) Keywords: geriatric urinary incontinence; leukoaraiosis; autonomic dysfunction; urodynamic study; detrusor hyperreflexia The definite cause of high incidence of nocturnal urinary frequency and urge incontinence in elderly people is not known.1 Sleep disorder, nocturnal polyuria, and benign outlet obstruction of the lower urinary tract are possibly related to this condition. Detrusor hyperreflexia is a recognised finding in urodynamic study, which indicates central aetiology of this condition as well. 2 3 Brain MRI showed frequent white matter signal abnormality (leukoaraiosis) in the brain of elderly people, 4 some of which were considered as normal but others reflected ischaemic pathology.5 6 Leukoaraiosis in elderly people is relevant to cognitive disorder (multiinfarct dementia) 7 8 and gait disorder. 9 However, urinary dysfunction has not been systematically investigated. The present study aimed at evaluating urinary function in elderly people with and without leukoaraiosis in relation to cognitive and gait function. Subjects and methodsWe investigated 63 subjects, 28 men and 35 women, mean age 73 years, range 62-86 years.
The "Japanese Clinical Guideline for Female Lower Urinary Tract Symptoms," published in Japan in November 2013, contains two algorithms (a primary and a specialized treatment algorithm) that are novel worldwide as they cover female lower urinary tract symptoms other than urinary incontinence. For primary treatment, necessary types of evaluation include querying the patient regarding symptoms and medical history, examining physical findings, and performing urinalysis. The types of evaluations that should be performed for select cases include evaluation with symptom/quality of life (QOL) questionnaires, urination records, residual urine measurement, urine cytology, urine culture, serum creatinine measurement, and ultrasonography. If the main symptoms are voiding/post-voiding, specialized treatment should be considered because multiple conditions may be involved. When storage difficulties are the main symptoms, the patient should be assessed using the primary algorithm. When conditions such as overactive bladder or stress incontinence are diagnosed and treatment is administered, but sufficient improvement is not achieved, the specialized algorithm should be considered. In case of specialized treatment, physiological re-evaluation, urinary tract/pelvic imaging evaluation, and urodynamic testing are conducted for conditions such as refractory overactive bladder and stress incontinence. There are two causes of voiding/post-voiding symptoms: lower urinary tract obstruction and detrusor underactivity. Lower urinary tract obstruction caused by pelvic organ prolapse may be improved by surgery.
The present article is the abbreviated English translation of the Japanese guidelines for male lower urinary tract symptoms and benign prostatic hyperplasia updated as of the end of 2016. The target patients are men aged >50 years complaining of lower urinary tract symptoms, with or without benign prostatic hyperplasia, and the target readers are non-urological general physicians and urologists. Mandatory assessment for general physicians is medical history, physical examination, urinalysis and measurement of serum prostate-specific antigen. Additional mandatory assessment for urologists is symptoms and quality of life assessment by questionnaires, uroflowmetry, residual urine measurement, and prostate ultrasonography. Nocturia requires special attention, as it can result from nocturnal polyuria and/or sleep disturbance rather than lower urinary tract disorders. Functional lower urinary tract disorders with or without benign prostatic hyperplasia are primarily managed by conservative therapy and medications, such as a 1 -blockers and phosphodiesterase-type 5 inhibitors. Use of other medications or combination pharmacotherapy is to be reserved for urologists. 5a-Reductase inhibitors and anticholinergics or b3 agonists are indicated for men with enlarged prostates and overactive bladder symptoms, respectively. Surgical intervention for bladder outlet obstruction is considered for persistent symptoms or benign prostatic hyperplasia-related comorbidities. Surgical modalities should be optimized by the patient's characteristics, performance of equipment and the surgeon's experience.
Abstract:The Japanese Urological Association has developed Clinical Guidelines for Benign Prostatic Hyperplasia (BPH) for men with suspected BPH, which have been abridged and translated into English. This article is a shortened version of the English translation. The Guidelines were formulated on the basis of evidence retrieved from the PubMed database between 1995 and 2009, as well as other relevant sources. The target patients of these Guidelines are men with suspected BPH, and the target users are urologists. A mandatory assessment should include a medical history, a physical examination, the completion of symptom and quality of life questionnaires, urinalysis, prostate ultrasonography, measurement of serum prostate specific antigen and postvoid residual urine, and an uroflowmetry. Optional tests include a bladder diary, the measurement of serum creatinine, and upper urinary tract ultrasonography. Care should be taken to not overlook coexisting diseases such as an infection or malignancy that may obscure the diagnosis. Treatment should consist of conservative therapy or the use of medications such as a 1-adrenoceptor antagonists, or both. The use of 5a-reductase inhibitors or anticholinergic agents should be considered in patients with an enlarged prostate (>30 mL) or overactive bladder symptoms (overactive bladder symptom score Ն6), respectively. Surgical intervention is indicated when nonsurgical treatments fail to provide sufficient symptomatic relief and bladder outlet obstruction is highly suspected.
Background: Constipation is a prominent lower gastrointestinal tract dysfunction that occurs frequently in Parkinson's disease (PD). Objective: To investigate colonic transport and dynamic rectoanal behaviour during filling and defecation in patients with PD. Methods: Colonic transit time (CTT) and rectoanal videomanometry analyses were performed in 12 patients with PD (10 men and 2 women; mean age, 68 years, mean duration of disease, five years; mean Hoehn and Yahr grade, 3; decreased stool frequency (<3 times a week) in six, difficulty in stool expulsion in eight) and 10 age matched normal control subjects (7 men and 3 women; mean age, 62 years; decreased stool frequency in two, difficulty in stool expulsion in two). Results: In the PD patients, CTT was significantly prolonged in the rectosigmoid segment (p<0.05) and total colon (p<0.01) compared with the control subjects. At the resting state, anal closure and squeeze pressures of PD patients were lower than those in control subjects, though not statistically significant. However, the PD patients showed a smaller increase in abdominal pressure on coughing (p<0.01) and straining (p<0.01). The sphincter motor unit potentials of the patients were normal. During filling, PD patients showed normal rectal volumes at first sensation and maximum desire to defecate, and normal rectal compliance. However, they showed smaller amplitude in phasic rectal contraction (p<0.05), which was accompanied by an increase in anal pressure that normally decreased, together with leaking in two patients. During defecation, most PD patients could not defecate completely with larger post-defecation residuals (p<0.01). PD patients had weak abdominal strain and smaller rectal contraction on defecation than those in control subjects, though these differences were not statistically significant. However, the PD patients had larger anal contraction on defecation (p<0.05), evidence of paradoxical sphincter contraction on defecation (PSD). Conclusions: Slow colonic transit, decreased phasic rectal contraction, weak abdominal strain, and PSD were all features in our PD patients with frequent constipation.
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