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PubMed1999

An analysis of risk factors for upper urinary tract deterioration in patients with myelodysplasia.

OBJECTIVE: To identify the risk factors for upper urinary tract deterioration in a retrospective study of patients with myelodysplasia. PATIENTS AND METHODS: The medical history, radiographic studies and urodynamic results from 39 children with myelodysplasia who were treated at our hospital were reviewed retrospectively to obtain more accurate data in the prognosis of such patients. The upper urinary tracts were assessed by cysto-urethrography and excretory urography to determine the incidence of vesico-ureteric reflux (VUR) and hydronephrosis. The relationships between the urodynamic variables, including vesical compliance, detrusor hyper-reflexia, detrusor-sphincter dyssynergia (DSD) and the maximum urethral closing pressure (MUCP) to such upper tract deterioration were evaluated using both univariate and multiple logistic regression analysis. RESULTS: The univariate analysis showed low vesical compliance, a high level of MUCP and the presence of DSD to be significant factors for the incidence of VUR. Low vesical compliance and a high level of MUCP also correlated with the incidence of hydronephrosis. The multivariate analysis showed a significant relationship between urodynamic values and upper urinary tract deterioration. The incidence of VUR was strongly correlated with a high MUCP and the presence of DSD. A high MUCP was also a significant factor in the incidence of hydronephrosis. CONCLUSION: Urodynamic results associated directly with the abnormal function of urethral control are significantly correlated with the cause of upper tract deterioration in patients with myelodysplasia.

Adolescent↗

PubMed1993

Urologic aspects of traumatic central cord syndrome.

Central cord syndrome (CCS) is a subset of spinal cord injury, characterized by more motor involvement of the upper extremities than the lower extremities and sacral sensory sparing. Patients with central cord syndrome have been reported to have a good rehabilitation and urologic outcome. Our purpose was to assess the urologic outcome in a group of patients with central cord syndrome. We reviewed 23 patients with central cord syndrome who were admitted to Hines VA Hospital between 1983 and 1991, 20 of whom were older than 50 years of age. Urodynamic studies showed detrusor hyperreflexia with a synergistic EMG in 15 patients and detrusor hyperreflexia with external urethral sphincter dyssynergia (DSD) in five patients. Three patients with no urologic problems were not tested. Bladder sensation was preserved during filling in all patients. At follow-up (median = 2-4 months), 16 patients (70 percent) were voiding, seven of whom required either occasional external or intermittent catheterization; nine were voiding independently. The seven other patients (30 percent) required either continuous external or intermittent catheterization (including the five with DSD). Urologic morbidity in the period after SCI included: urinary tract infections (12), renal (2) and bladder calculi (2), superficial bladder cancer (1), epididymitis (1) and none (6). Fifteen patients (65 percent) were ambulatory at follow-up while four patients needed wheelchairs. Data were not available for the other four patients. Urodynamic studies in three of the wheelchair-bound patients showed that two of them had DSD. Most patients with central cord syndrome have favorable urologic and rehabilitation outcomes and can be managed conservatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed2003

Preliminary observations of a synergistic bladder-sphincter relationship following spinal cord injury in a quadruped animal.

BACKGROUND/OBJECTIVES: High urethral resistance or detrusor-sphincter dyssynergia (DSD) is characterized by obstructed voiding during bladder contractions. DSD is caused by an exaggerated pelvic floor reflex resulting from sensory input from elevated pressure in the bladder that produces reflex constriction of the urethral sphincter. The objective of this study was to determine whether sensory input from the bladder produced synergistic or dyssynergic pelvic floor reflexes following SCI in an animal model. METHODS: A pelvic floor reflex that shares the same motor pathway with DSD is the bulbocavernosus (BC) reflex. The BC reflex was elicited with electrical stimulation in 4 male cats with T1 spinal injury, and recorded as an anal sphincter contraction. Recordings were obtained during control and elevated bladder pressures. Increased bladder pressure was induced with either manual pressure (Crede procedure) or spontaneous contractions resulting from bladder filling. RESULTS: During the control period, the BC reflex indicated by the peak anal pressure response was 23 +/- 6 cmH2O. During elevated bladder pressure of 34 +/- 18 cmH2O, the BC response decreased to 10 +/- 3 cmH2O (not significant), showing a synergistic relationship. Anal sphincter tone between BC reflex tests showed a dyssynergic response. All 4 animals showed increased tone during elevated bladder pressures that averaged 9 +/- 5 cmH2O. Because abdominal pressure was not recorded, the significance is not clear. However, there was further support of a dyssynergic relationship based on increases in the anal and urethral electromyography recordings and some pelvic floor spasms during the elevated bladder pressure. CONCLUSIONS: Because 2 different pelvic floor activities were observed during increased bladder pressures, this animal model may be described best as a mixed model. This model shows both synergistic and dyssynergic relationships between the bladder and the BC contractions. Although observed changes were not significant, the unique observations of synergistic bladder-sphincter activity shown by the inhibited BC reflex is in marked contrast to the strictly dyssynergic bladder-sphincter relationship seen in SCI patients.

Anal Canal↗

PubMed2000

The tissue plasminogen activator (tPA)/plasmin extracellular proteolytic system regulates seizure-induced hippocampal mossy fiber outgrowth through a proteoglycan substrate.

Short seizure episodes are associated with remodeling of neuronal connections. One region where such reorganization occurs is the hippocampus, and in particular, the mossy fiber pathway. Using genetic and pharmacological approaches, we show here a critical role in vivo for tissue plasminogen activator (tPA), an extracellular protease that converts plasminogen to plasmin, to induce mossy fiber sprouting. We identify DSD-1-PG/phosphacan, an extracellular matrix component associated with neurite reorganization, as a physiological target of plasmin. Mice lacking tPA displayed decreased mossy fiber outgrowth and an aberrant band at the border of the supragranular region of the dentate gyrus that coincides with the deposition of unprocessed DSD-1-PG/phosphacan and excessive Timm-positive, mossy fiber termini. Plasminogen-deficient mice also exhibit the laminar band and DSD- 1-PG/phosphacan deposition, but mossy fiber outgrowth through the supragranular region is normal. These results demonstrate that tPA functions acutely, both through and independently of plasmin, to mediate mossy fiber reorganization.

Amygdala↗

PubMed1997

Use of Memokath temporary urethral stent in treatment of detrusor-sphincter dyssynergia.

In spinal-injured patients, detrusor-sphincter dyssynergia (DSD) can lead to high intravesical pressures, upper tract dilation, and recurrent infections. The standard treatment for DSD is sphincterotomy and, more recently, permanent sphincter stenting. Many spinal-injury patients would prefer a reversible treatment because of concern about fertility or because they are awaiting a "miracle cure." There is also concern over the theoretical long-term risk of squamous carcinoma after permanent stenting. In view of this, the Memokath, a thermosensitive temporary stent, has been undergoing trials at our center to determine which patients could benefit. Fourteen Memokath stents have been inserted in spinal-injured patients with DSD at our center, and they have been followed up for as long as 2 years. Stents were placed under cystoscopic guidance as a day case procedure. The stents were inserted either through the sphincter alone (short [4-cm] stents; 3 patients) or through the sphincter and bladder neck (long [5-7-cm] stents; 11 patients). There were no complications during surgery in either placement or removal of these stents. There was a significant (p < 0.001) reduction in the residual urine volume after stenting. Preoperative hydronephrosis and attacks of autonomic dysreflexia noted in some patients also resolved after stenting. Short stents that bridge the external urethral sphincter were ineffective in emptying the neuropathic bladder. Therefore, we advise that only long stents that lie across both the bladder neck and the external sphincter be used. Because of its easily reversible nature, the Memokath should be adopted for use in patients who are unsure about their preferred option of bladder management and those involved in a fertility program.

Adult↗

PubMed2026

Post-translational modification of proteins in the human testis development pathway.

BACKGROUND: The foetal testes produce the androgens necessary to masculinise the developing embryo and support the maturation of germ cells, that will eventually develop into sperm, thus ensuring future reproductive capacity. The testes develop from the bi-potential gonads in a highly orchestrated process resulting in the differentiation of a complex tissue with multiple cellular lineages. While recent transcriptomic and chromatin-based analyses of human foetal testes have provided an unprecedented level of insight into signalling pathways activated during this process, proteomic studies of the human foetal gonads remain limited. Proteins are active molecules and post-translational modification (PTM) of proteins influences protein activity, stability and localisation. Studies have shown that PTMs regulate critical proteins in testis development, and their disruptions are implicated in congenital disorders including differences of sex development (DSD), in which sex development is atypical. Despite this, the role and regulation of protein PTM during human testis development remains poorly understood due to limited access to human foetal gonadal tissue, a paucity of large-scale proteomics studies, and a lack of robust of human gonad in vitro models. OBJECTIVE AND RATIONALE: This review aims to provide a comprehensive analysis of validated PTMs affecting proteins critical for testicular development. We discuss PTMs with evidence for a role in normal testis development, and highlight those disrupted in DSD. We review emerging techniques, including proteomic technologies and organ modelling systems that may advance our understanding of PTMs in foetal testis development. We discuss challenges that have restricted the application of these technologies and how overcoming these will significantly improve our understanding of testis development and disease, diagnostics and patient outcomes. SEARCH METHODS: We searched PubMed and the University of Melbourne library for peer-reviewed English-language studies using keywords such as phosphorylation, SUMOylation, acetylation, ubiquitination alongside each protein of interest. PTM sites in proteins involved in testis development were identified using the PhosphoSitePlus database focusing those confirmed in in vitro or animal model studies. ClinVar and the Human Gene Mutation Database were used to identify patient variants that may disrupt PTM sites. OUTCOMES: Our review finds that proteins required for human foetal testis development are subject to extensive PTM. Several PTM sites and PTM-mediated pathways [e.g. MAPK (mitogen-activated protein kinase) pathway] are disrupted in patients with DSD or related conditions. While recent advances in proteomics technologies hold considerable promise, their application to human foetal gonads has been constrained by technical, ethical, and logistical challenges. Encouragingly, emerging high-sensitivity and low-input technologies, alongside stem cell-based approaches, offer viable pathways to overcoming these barriers. WIDER IMPLICATIONS: The relationship between gene regulation, protein expression, and cellular outcome is inherently non-linear, shaped by additional regulatory layers-most notably PTMs. The contribution of PTMs to human testis development in both typical and atypical contexts is a major knowledge gap. Addressing this gap has broad clinical and biological relevance: it may help improve genetic diagnosis or shed light on how proteins or pathways critical for testis development respond to environmental signals-an increasingly pressing question as declining global fertility rates bring testicular function under greater scrutiny. REGISTRATION NUMBER: N/A.

Humans↗

PubMed1998

Ethnicity and adolescent depression: the case of Chinese Americans.

This paper is concerned with whether an instrument developed in the U.S. may identify lower rates of major depression among Chinese, because its content may not cover culture-specific symptoms of depression. Data were obtained from approximately 952 Anglo and Chinese American middle school students, aged 10 to 17 years, in the Teen Life Changes Survey conducted in the spring of 1994. We investigated the hypothesis that rates of missing values would be higher, the mean score for total depression items would be lower, and internal consistency reliability and construct validity of the DSM Scale for Depression (DSD) would be lower for Chinese American adolescents compared with Anglo American adolescents. We also examined whether response functions on the DSD item would differ for these two groups. Only the latter was observed. Five of 26 items in the DSD exhibited differential functioning between Anglo and Chinese students. The results suggest that the lower prevalence of depression was not due to the ethnocentric character of the instrument in the Chinese sample. Stronger immunity to depression or other cultural factors may contribute to the lower rate of depression for the Chinese American adolescents in the Teen Life Changes study.

Acculturation↗

PubMed2004

Roles of opiate in lower urinary tract dysfunction associated with spinal cord injury in rats.

PURPOSE: It has been reported that the opiate receptor system in the spinal cord is involved in bladder and urethral function. We determined whether U-50488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide), a kappa opioid receptor agonist, could decrease detrusor-sphincter dyssynergia (DSD) and, thus, improve voiding efficiency in conscious, spinal cord injured (SCI) rats. MATERIALS AND METHODS: Experiments were done in female Sprague-Dawley rats in which the spinal cord was completely transected at the T6-8 level 4 weeks prior to performing cystometry while conscious and held in a restraining cage. Experiments were also performed in normal spinal cord rats. Saline was infused (0.1 ml per minute) via the cystostomy catheter into the bladder. Voiding efficiency was determined by measuring voided and residual volumes. After performing a control cystometrogram increasing doses of U-50488 (0.01, 0.1, 1 and 10 mg/kg) were administered intravenously at 1-hour intervals. The effects of nor-binaltorphimine dihydrochloride, a kappa opioid receptor antagonist, on U-50488 induced changes in voiding parameters were also examined. RESULTS: A high dose of U-50488 (1 to 10 mg/kg) significantly decreased contraction amplitude and bladder capacity (p <0.01 to 0.05) in normal spinal cord and SCI rats. A low dose of U-50488 (0.01 mg/kg) increased voiding efficiency by 32.7% without decreasing bladder capacity in SCI rats. Nor-binaltorphimine hydroparameters counteracted the effect of U-50488 induced changes. CONCLUSIONS: These results suggest that the kappa opioid receptor system is related to DSD caused by spinal cord injury. The kappa opioid receptor agent is believed to have therapeutic potential for treating DSD associated with SCI.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1979

Transfer of a gene for sucrose utilization into Escherichia coli K12, and consequent failure of expression of genes for D-serine utilization.

As the first stage in investigating the genetic basis of natural variation in Escherichia coli, the gene(s) conferring the ability to use sucrose as a carbon and energy source (given the symbol sac+) was transferred from a wild strain to K12, which does not use sucrose. The sac+ region was transferred by two different methods. On both occasions it took a chromosomal location at minute 50.5 on the linkage map, between aroC and supN, in the region of the dsd genes, which confer the ability to use D-serine as a carbon and energy source. When the sac+ region was present in the K12 chromosome the bacteria were unable to use D-serine as a carbon and energy source. In F' sac+/dsd+ diploids, the dsd+ genes were similarly not expressed. Strain K12(sac+) bacteria were sensitive to inhibition by D-serine; they mutated to D-serine resistance with much greater frequency than did a dsd mutant of K12. Such bacteria also mutated frequently to use raffinose. Strain K12(sac+) bacteria did not utilize sucrose when they carried a mutation affecting the phosphotransferase system.

Chromosome Mapping↗

PubMed1981

Segregation and linkage analysis of a large kindred of unipolar depression.

We studied segregation and linkage in a large kindred of unipolar depression. We subtyped the kindred on the basis of best fit to a single gene model and found that the cluster of "definite and probable depression, alcoholism, and drug dependency" gave the best fit. Since this is essentially the definition of depression spectrum disease (DSD), this was considered to be a DSD kindred. Using this definition of "affected" the genetic model provided a better fit to the data than the environmental model, although the difference was not statistically significant. A linkage analysis using 30 genetic markers did not suggest linkage at any of the loci tested. Finally, there was no evidence for an association between DSD and any of the 30 genetic markers.

Adult↗

PubMed1996

Do low levels of MHPG in depressive spectrum patients normalize after successful treatment?

Patients with depressive spectrum disorder (DSD) have low levels of the norepinephrine metabolite, MHPG. This study examines what happens to the low levels of MHPG following improvement of depressive symptoms. Sixteen depressed patients with a family history consistent with DSD showed no change in MHPG after 6 weeks of treatment. This was true for both treatment responders and nonresponders. The lack of change in low levels of MHPG suggests that reduced norepinephrine turnover is a biological trait of DSD patients. Implications of this finding are discussed.

Adult↗

PubMed2006

Germ cell tumors in the intersex gonad: old paths, new directions, moving frontiers.

The risk for the development of germ cell tumors is an important factor to deal with in the management of patients with disorders of sex development (DSD). However, this risk is often hard to predict. Recently, major progress has been made in identifying gene-products related to germ cell tumor development (testis-specific protein-Y encoded and octamer binding transcription factor 3/4) and in recognizing early changes of germ cells (maturation delay, preneoplastic lesions, and in situ neoplasia). The newly recognized "undifferentiated gonadal tissue" has been identified as a gonadal differentiation pattern bearing a high risk for the development of gonadoblastoma. It is expected that the combination of these findings will allow for estimation of the risk for tumor development in the individual patient (high risk/intermediate risk/low risk). This article reviews the recent literature regarding the prevalence of germ cell tumors in patients with DSD. Some major limitations regarding this topic, including a confusing terminology referring to the different forms of intersex disorders and unclear criteria for the diagnosis of malignant germ cells at an early age (maturation delay vs. early steps in malignant transformation) are discussed. Thereafter, an overview of the recent advances that have been made in our knowledge of germ cell tumor development and the correct diagnosis of early neoplastic lesions in this patient population is provided. A new classification system for patients with DSD is proposed as a tool to refine our insight in the prevalence of germ cell tumors in specific diagnostic groups.

Biomarkers↗

PubMed1989

[An electromyographic study of detrusor sphincter dyssynergia in the neurogenic vesical dysfunction. Part 1. Its type and further sub-typing based on the analysis of motor units].

Simultaneous recordings of electromyography of the external urethral sphincter (EUS) and bladder pressure were performed in 73 patients. The majority (69 cases) were afflicted with neurogenic vesical dysfunction, while four with benign prostatic hypertrophy (BPH) were also examined as control. Detrusor sphincter dyssynergia (DSD), whereby EUS failed to relax on voiding attempt, was noted in 64 patients. By examining the patterns of DSD throughout the voiding, it was possible to classify them into three distinct types as done by Blaivas. Type 1 was found in 7 patients, Type 2 in 10 patients, and Type 3 in 47 patients. Synergic urethral sphincter activity (Type 0) was found in other 9 patients including all four with BPH. Voiding dysfunction as evaluable by residual urine rate tended to increase as the type deteriorated from 1 to 3. Analysis of motor units revealed that the units noted during continent phase of the bladder disappeared (A0), decreased (A1), and retained or rather increased their activity (A2) during voiding attempt with (B1) or without (B0) recruitment of new units. A0B1 was found in 3 patients, A1B1 in 7, A2B1 in 32, A2B0 in 4, and A1B0 in 2. Again there was a tendency for voiding function to deteriorate as motor units sub-type changed from A0 to A1 and A2. The analysis of these motor units activities suggested that abnormal continence reflex (i.e. failure of vesicourethral and urethrourethral relaxation reflex and exaggeration of urethrourethral contraction reflex) might be contributing to the genesis of DSD.

Electromyography↗

PubMed1989

[Clinical evaluation for voiding dysfunction in patients with cerebral-palsy].

Urological assessments were done on 132 patients with cerebral palsy, ranging from 5 to 59 years in age (mean 23.2). Concerning urological symptoms, urinary incontinence, decreased urinary stream and urinary tract infection were at 31.8, 14.4 and 16.7%, respectively. Patients with functionally impaired ambulation had a high incidence of urinary incontinence and decreased urinary stream. Decreased urinary stream was more prominent in an elderly patient group, and urinary incontinence was observed almost at the same rate in all age-classified groups. Urodynamic studies were performed in 30 patients with cerebral palsy who were referred to with urological symptoms. The patients were classified into two groups according to the presence or absence of spinal cord lesions. In a group of 15 patients with spinal cord lesions, electromyography of the external sphincter demonstrated detrusor-sphincter dyssynergia (DSD) in 9, of whom 6 complained of decreased urinary stream; while in the group without spinal cord lesions there was no DSD. These findings suggest that the cause of decreased urinary stream in cerebral palsied patients could be explained by DSD secondary to spinal cord lesions.

Adolescent↗

PubMedDate not supplied

[The HLA system antigens in delayed sexual development].

Frequency distribution of HLA antigens of A and B loci was examined in 138 adolescent boys aged 14-18 with delayed sexual development (DSD) of stages I-III, residing in the north-eastern region of Ukraine. Increase of A28- and B40-antigens and haplotypes A1-B40, A28-B40, A10-B40 determination frequencies was established. There were revealed positive and negative correlation between some of HLA antigens and DSD. Relative and attributive risks of DSD formation were calculated.

Adolescent↗

PubMed1999

[Experimental studies on hyperthermic distilled water combining with saline and dextran for preventing intraperitoneal cancer recurrence due to neoplasm seeding].

In order to know the efficacy of hyperthermic distilled water combining with saline and dextran (DSD) to prevent intraperitoneal cancer from recurrence due to neoplasm seeding, we carried out the experimental studies, including an observation on inhibiting cancer cells from implantation in vivo by abdominal cavity lavation, cytotoxic test and attachment test in vitro. The results of the tests in vitro showed no viable tumor cell exposed to 45 degrees C distilled water for 20 minutes in the tissue culture wells, meanwhile, dextran-40 partially blocked attachment of B16-F10 cells to gelatinized wells. In vivo test, DSD effectively prevented neoplasm seeding of B16-F10 viable melanoma cells in C57BL/6j mouse abdominal cavity and had no obvious toxicity. The efficiency was 70%; when cisplatin was added, the efficiency was enhanced to 88.9% with slight toxicity. These data indicate that the local application of hyperthermic distilled water combined with saline and DSD may prevent intraperitoneal neoplasm from recurring.

Animals↗

PubMed2001

[Study on the enzyme dependant colon targeting prodrug--dexamethasone succinate dextran and its tablets].

AIM: To develop an orally administered colon targeting drug delivery system dexamethasone succinate dextran (DSD) tablets. METHODS: Dexamethasone succinate dextran was synthesized in an anhydrous environment. Using 4-dimethyl aminopyridine and 1,1'-carbonyldiimidazole as the catalyzer. The chemical structure was identified by UV, IR, NMR and MS. The contents of dexamethasone in various samples were determined by HPLC. RESULTS: Dexamethasone was distributed mainly in plasma and gastric contents after the oral administration of common tablets. In contrast, after oral administration of DSD tablets, the recovery of dexamethasone in plasma and gastric contents decreased significantly, while the percentage of dexamethasone in cecum and colon increased obviously. CONCLUSION: The experimental results showed the good colon targeting property of DSD prodrug compared with free dexamethasone.

Administration, Oral↗

PubMedDate not supplied

[Botulinic toxin in patients with neurogenic dysfunction of the lower urinary tracts].

Botulinic toxin (BT) is a new method of lowering intraurethral pressure in symptoms of obstructive voiding in patients with neurogenic dysfunction of the lower urinary tracts (LUT). Transperineal introduction of 100 units of BT type A (botox, Allergan) was used under electromyographic control into the external urethral sphincter of 9 patients (6 males and 3 females) with LUT neurogenic dysfunction aged 17 to 68 years (mean age 37.2 years). Two patients had subnormal detrusor contractility due to myelodysplasia and diabetic polyneuropathy, two other patients--non-incontinent striated urethral sphincter after hemorrhagic stroke and spinal contusion, five patients suffered from detrusor-sphincteral dyssynergia (DSD) resultant from Schmorl's hernia, multiple sclerosis, Charcot-Marie disease and ischemic stroke of the spinal cord. Three patients had cystostomic drainage. The rest of the patients complained of dysuria, three patients performed self-catheterization, mean volume of the residual urine was 170 ml (180-240 ml). In 10 days residual urine was not found in 2 patients with subnormal detrusor contractility and in 4 patients with DSD. Abdominal pressure fell from 75 to 39 cm, on the average. In DSD patients maximal detrusor pressure fell from 59 to 29 cm, on the average. Mean maximal urinary flow rate rose from 4.3 to 9.6 ml/s. In 20 days, on the average, suprapubic fistula healed in all the patients. In a month, therapeutic effect persisted in all the patients. Complications, side effects were not registered. BT treatment to induce adequate urine evacuation in neurological patients is a promising approach in neurourology. Further studies should find answers to questions about regimen of BT introduction, loss of sensitivity, new indications in urology.

Adolescent↗