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PubMed1983

Attempts to validate a classification of unipolar depression based on family data. Symptomatological aspects.

162 depressed patients, consecutively admitted to the Department of Psychiatry, Umeå University, were rated by means of the comprehensive psychopathological rating scale (CPRS) within a few days after their admission, and before any antidepressive treatment had been implemented. The same patients were later subdivided into groups according to the presence or absence of psychiatric illness among their first-degree relatives. Four groups were thus formed: depression pure disease (DPD), i.e., comprised of patients with only secondary cases of depression; depression spectrum disease (DSD), comprised of patients with secondary cases of both depression and alcoholism and antisocial personality among their first-degree relatives; positive family history-others (FH+.O), included those patients with first-degree relatives affected by other psychiatric disorders than those required for inclusion among the DSD; and finally, sporadic depression (SD), comprised of those patients who had no family loading at all. The results showed that the severity of illness was similar in all four groups. Only a few symptomatological differences emerged, and these related consistently to a higher frequency of symptoms of retardation (inability to feel, lassitude, and concentration difficulties) in the DSD group as compared to the SD group. No significant symptomatological differences occurred between patients in the DPD and DSD groups. It is concluded that a classification of unipolar patients based on family data does not predict the occurrence of various symptomatological patterns.

Adult↗

PubMed1985

Dexamethasone suppression test and familial subtypes of unipolar depression.

We have studied the suppression of plasma cortisol after dexamethasone (1 mg) and the peak post-dexamethasone cortisol values in 84 hospitalized patients with a diagnosis of primary unipolar depression. The non-suppressor responses in the three familial subgroups (Winokur) were: 11/22 in familial pure depressive disorder (FPDD), 21/49 in sporadic depressive disease (SDD) and 1/13 in depression spectrum disease (DSD) (FPDD vs. SDD, p less than 0.05; SDD vs. DSD, p less than 0.05). When considering the peak post-dexamethasone cortisol value, or the 8.30-9.00-hour values, the results in the DSD group were lower than in the other two groups (p less than 0.05). These results suggest a different behaviour of DSD as compared with FPDD and SDD.

Adrenocorticotropic Hormone↗

PubMed2003

A second functional RNA domain in the 5' UTR of the Tomato bushy stunt virus genome: intra- and interdomain interactions mediate viral RNA replication.

The 5' untranslated regions (UTRs) of (+)-strand RNA viruses play a variety of roles in the reproductive cycles of these infectious agents. Tomato bushy stunt virus (TBSV) belongs to this class of RNA virus and is the prototype member of the genus Tombusvirus. Previous studies have demonstrated that a T-shaped domain (TSD) forms in the 5' half of the TBSV 5' UTR and that it plays a central role in viral RNA replication. Here we have extended our structure-function analysis to the 3' half of the 5' UTR. Investigation of this region in the context of a model viral replicon (i.e., a TBSV-derived defective interfering [DI] RNA) revealed that this segment contains numerous functionally relevant structural features. In vitro solution structure probing along with comparative and computer-aided RNA secondary structure analyses predicted the presence of a simple stem loop (SL5) followed by a more complex downstream domain (DSD). Both structures were found to be essential for efficient DI RNA accumulation when tested in a plant protoplast system. For SL5, maintenance of the base of its stem was the principal feature required for robust in vivo accumulation. In the DSD, both helical and unpaired regions containing conserved sequences were necessary for efficient DI RNA accumulation. Additionally, optimal DI RNA accumulation required a TSD-DSD interaction mediated by a pseudoknot. Modifications that reduced accumulation did not appreciably affect DI RNA stability in vivo, indicating that the DSD and SL5 act to facilitate viral RNA replication.

5' Untranslated Regions↗

PubMed2001

Fighting by sleep-deprived rats as a possible manifestation of panic: effects of sodium lactate.

Increased fighting is an effect of desynchronized sleep deprivation (DSD) in rats, and recently this behavior has been suggested to be spontaneous panic and equivalent to panic disorder. In the present study we tested this hypothesis by evaluating the effect of sodium lactate on this aggressiveness, because this substance is recognized to induce spontaneous panic attacks in patients. A total of 186 male albino Wistar rats, 250-350 g, 90-120 days of age, were submitted to DSD (multiple platform method) for 0, 4, or 5 days. At the end of the deprivation period the rats were divided into subgroups respectively injected intraperitoneally with 1.86, 2.98 and 3.72 g/kg of 1 M sodium lactate, or 1.86 and 3.72 g/kg of 2 M sodium lactate. The control animals were submitted to the same procedures but received equivalent injections of sodium chloride. Regardless of DSD time, sleep-deprived animals that received sodium lactate presented a significantly higher mean number of fights (0.13 +/- 0.02 fights/min) and a longer mean time spent in confrontation (2.43 +/- 0.66 s/min) than the controls (0.01 +/- 0.006 fights/min and 0.12 +/- 0.07 s/min, respectively; P<0.01, Student t-test). For the sodium lactate group, concentration of the solution and time of deprivation increased the number of fights, with the mean number of fights and mean duration of fighting episodes being greater with the 2.98 g/kg dose using 1 M lactate concentration. These results support the hypothesis that fighting induced by DSD is probably a spontaneous panic manifestation. However, additional investigations are necessary in order to accept this as a promising animal model for studies on panic disorder.

Aggression↗

PubMed1990

[Effects of alpha-1-blocking agent in the treatment of detrusor sphincter dyssynergia].

Effects of adrenergic alpha-1-blocking agent, prazosin, in the treatment of detrusor external-sphincter dyssynergia (DSD) were evaluated in both experimental and clinical aspects. Experimentally, in the urethral pressure profile in dogs, the maximum urethral closing pressure was depressed after intravenous injection of 1 mg prazosin. When experimental DSD was obtained in dogs by stimulating electrically the unilateral 2nd sacral root, intra-venous injection of 1 mg prazosin inhibited contraction of the external urethral sphincter. Clinically, 74 patients with DSD based on neurogenic bladder from cerebral vascular attack (CVA) (13 cases) and spinal cord injury (61 cases) were retrospectively surveyed in terms of therapeutical effects of prazosin for DSD. Spinal cord injury was subdivided to 4 groups for clinical evaluation; cervical cord injury (C) with complete paralysis, thoracic cord injury (Th) with complete paralysis, lumbar cord injury (L) with complete paralysis and spinal cord injury with incomplete paralysis. Patients with CVA and spinal cord injury with incomplete paralysis showed good response rates in subjective improvement, 69% and 60% respectively. However, those with spinal cord injury with complete paralysis showed a poor response (28% for C, 23% for Th and 14% for L). The amount of residual urine significantly decreased after treatment, in all the groups except that of lumbar cord injury with complete paralysis. In all the groups, however, even after the drug treatment the amount of residual urine ranged from 80 to 170 ml and the rates of needing clean intermittent catheterization unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMedDate not supplied

[Tamsulosin in the treatment of detrusor-sphincter dyssynergia of the urinary bladder in patients with multiple sclerosis].

Urination disorders occur in 80% patients with multiple sclerosis (MS). Most common of them is detrusor-sphincter dyssynergia (DSD). Alpha1-adrenoblockers can relax the neck of the urinary bladder (UB) and urethral sphincters, thus eliminating dynamic obstruction, reducing resistance to urine flow and facilitating voiding. Our study assessed feasibility of using a selective alpha1A/D-adrenoblocker tamsulosin in MS-associated DSD. The choice of this alpha-adrenoblocker was based on its high safety profile in relation to cardiovascular system. The trial enrolled 28 patients (20 females and 8 males) with verified diagnosis of DSD. They were given tamsulosin (omnik) in a dose 0.4 mg/day (1 capsule) for 2 months. To the end of the trial quality of life raised in 96% patients. Occurrence of pollakiuria, number of imperative micturate urges diminished, the IPSS score decreased by 54%, QL index improved by 58%. There was also a decrease in the volume of the residual urine, amplitude of involuntary detrusor contractions, an increase in maximal volumic speed of urine flow, cystometric volume of the UB, mean urine volume in urination. Side effects were not registered. Thus, tamsulosin has a positive effect in voiding disorders in the presence of DSD associated with MS. This considerably improves quality of life of MS patients.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1996

[Prophylaxis of peritoneal carcinomatosis with intraperitoneal administration of cell-adhesion inhibitor, in mice].

DSD was studied for its prophylactic effect against peritoneal carcinomatosis using B-16 melanoma cell line. In in vitro examinations, incubation in medium containing 0.2% DSD significantly inhibited B-16 melanoma cells from adhering both to the plastic wall and the injured peritoneum, as compared to incubation in normal medium. Upon in vivo examination, intraperitoneal administration of 0.2% of DSD (1 ml/mouse) diminished the cancer cell number implanted into the injured peritoneum more than intraperitoneal administration of DSD-free medium.

Animals↗

PubMed2002

Dejerine-Sottas disease and hereditary demyelinating polyneuropathy of infancy.

Dejerine-Sottas disease (DSD) was originally described as a hypertrophic polyneuropathy characterized by onset in infancy or early childhood in patients born to unaffected parents. The clinical features included distal sensory changes with ataxia; pes cavus, at times with kyphoscoliosis; motor deficit and atrophy predominating in the distal lower limbs and progressing toward the proximal limbs following a length-dependent pattern; palpable nerve hypertrophy; and Argyll-Robertson pupils. The morphological hallmark was the extensive nerve and root hypertrophy associated with demyelination-remyelination of surviving, originally myelinated axons and profuse Schwann-cell proliferation forming onion bulbs. Wide variations in clinical manifestations of chronic demyelinating polyneuropathies of early onset in children born to unaffected parents have now been reported, with only some of the characteristics required in the original study, and at least seven genes encoding the myelin proteins P0, PMP22, the transcriptional factor EGR2, and others have been implicated. Thus, DSD is now a component of the hereditary demyelinating polyneuropathies of infancy that also include subsets of the recently individualized CMT4 neuropathies. The presumed recessive transmission of patients with DSD should be confirmed by molecular genetic analysis, which is still negative in a significant proportion of patients. The nerve biopsy can be useful in patients in whom genealogical or DNA abnormalities in favor of a genetic disorder are missing, because in a few patients with a progressive or relapsing course the diagnosis of early-onset chronic inflammatory demyelinating polyneuropathy must be considered.

Axons↗

PubMed2006

Urodynamic study in the neurogenic bladder dysfunction caused by intervertebral disk hernia.

AIMS: To discuss the clinical significance of urodynamic studies in neurogenic bladder dysfunction caused by intervertebral disk hernia. METHODS: Thirty patients with neurogenic bladder dysfunction caused by intervertebral disk hernia were divided into three groups according to the category of detrusor muscle activity: neurogenic detrusor overactivity without detrusor sphincter dyssynergia (DSD), neurogenic detrusor overactivity with DSD, or detrusor underactivity. The patients were divided into three groups according to the condition of urinary retention and incontinence: urinary retention, urinary incontinence, or neither urinary retention nor urinary incontinence. Also they were divided into three groups according to the location of the intervertebral disk hernia: cervical hernia, thoracic hernia, or lumbar hernia. All patients underwent computer tomography (CT), magnetic resonance imaging (MRI), and urodynamic study. The results were analyzed statistically. RESULTS: There was significant correlation between the category of detrusor muscle activity, bladder compliance (BC, P < 0.05), and the pressure at maximum flow (P(det,Qmax), P < 0.01). There were significant differences in post void residual (PVR), cystometric capacity (CC), and maximum flow rate (Qmax) between the three groups of urinary retention, urinary incontinence, and the group of neither retention nor incontinence (P < 0.05). There was statistical correlation between the location of the intervertebral disk hernia and the urodynamic results. There was significant correlation between the BC (the threshold was 15 ml/cmH(2)O), detrusor pressure (Pdet, the threshold was 40 cmH(2)O), DSD, the location of intervertebral disk hernia, and the upper urinary tract lesion (P < 0.01). CONCLUSIONS: Urodynamic studies are indispensable in the classification, diagnosis, treatment, and prognosis of the neurogenic bladder dysfunction caused by intervertebral disk hernia.

Adult↗

PubMed2005

Normal values of the sagittal diameter of the lumbar spine (vertebral body and dural sac) in children measured by MRI.

BACKGROUND: The definition of normal values is a prerequisite for the reliable evaluation of abnormality in the lumbar spine, such as spinal canal stenosis or dural ectasia in patients with Marfan syndrome. Values for vertebral body diameter (VBD) and dural sac diameter (DSD) for the lumbar spine have been published in adults. In children, normal values have been established using conventional radiography or myelography, but not by MRI. OBJECTIVE: To define normal values for the sagittal diameter of the vertebral body and dural sac, and to calculate a dural sac ratio (DSR) in the lumbosacral spine (L1-S1) in healthy children using MRI. MATERIALS AND METHODS: A total of 75 healthy children between 6 years and 17 years of age were examined using a sagittal T2-weighted sequence. Sagittal VBD and DSD were measured and a DSR was calculated. This was a retrospective and cross-sectional study. RESULTS: With increasing age there is a significant increase of VBD, a slight increase of DSD, and a slight decrease of DSR. There is no significant sex difference. DSR in healthy children is higher than in healthy adults. CONCLUSIONS: MRI is a reliable method demonstrating the natural shape of the lumbosacral spine and its absolute values. These normal values compare well with those established by conventional radiological techniques. Our data may serve as a reference for defining dural ectasia in children with Marfan syndrome.

Adolescent↗

PubMed1998

The role of carbohydrates in the induction of flowering in Arabidopsis thaliana: comparison between the wild type and a starchless mutant.

In order to test whether an increased export of carbohydrates by leaves and starch mobilization are critical for floral transition in Arabidopsis thaliana, the Columbia ecotype as well as its starchless mutant pgm and starch-in-excess mutant sex1 were investigated. Induction of flowering was achieved by exposure of plants to either one long day (LD) or one displaced short day (DSD). The following conclusions were drawn: (i) Both the pgm and sex1 mutants have a late-flowering phenotype in days shorter than 16 h. (ii) When inductive treatments cause a large, percentage of induced plants, there is always a large, early and transient increase in carbohydrate export from leaves. By contrast, when an inductive treatment results in only a low percentage of induced plants (pgm plants exposed to one DSD), the export of carbohydrates from leaves is not increased, supporting the idea that phloem carbohydrates have a critical function in floral transition. (iii) Starch mobilization is not required to obtain an increased carbohydrate export when induction is by one LD (extended period of photosynthesis), but is absolutely essential when induction is by one DSD (period of photosynthesis unaffected). (iv) Floral induction apparently increases the capability of the leaf phloem-loading system.

Arabidopsis↗

PubMed1991

Development of a sleep diary for chronic pain patients.

The present study examined the psychometric properties of the Daily Sleep Diary (DSD), an instrument developed for monitoring sleep among chronic pain patients. As part of a comprehensive evaluation, 46 chronic pain patients completed the DSD each morning. Items assessed the number of hours slept, length of sleep onset, frequency of awakenings during the night that resulted in trouble falling back to sleep, early morning awakening, quality of sleep, lack of restfulness, and the previous night's sleep compared to usual sleep. Reliability coefficients were significant. The sleep diary items significantly correlated with other retrospective measures of sleep. Duration of pain complaint was related to delayed sleep onset and lower quality of sleep. Pain severity was related to fewer hours slept and delayed sleep onset. The DSD items correlated with measures of both depression and anxiety. The results emphasize the importance of including sleep in both assessment and treatment of chronic pain patients.

Chronic Disease↗

PubMed2003

The use of the Memokath stent in the treatment of detrusor sphincter dyssynergia in spinal cord injury patients: a single-centre seven-year experience.

AIMS: A retrospective analysis of our seven-year experience with the Memokath urethral stent for the treatment of detrusor sphincter dyssynergia (DSD) in spinal cord injured (SCI) patients. PATIENTS AND METHODS: Twenty five patients with SCI underwent rhabdosphincter Memokath stent insertion. The mean age was 45.5 years (range 32-65 years). The level of injury was cervical in 14 and thoracic in 11 patients. All patients were shown to have neurogenic detrusor overactivity with DSD associated with high detrusor pressures and incomplete emptying on pre-operative video-cystometrograms (VCMG). The Memokath stent was inserted using a standardized protocol. Follow-up assessment included blood chemistry, ultrasound scan (upper tracts and residual urine) at one and three months after insertion, and a follow-up VCMG at six months. The pre-operative and six-month post-operative VCMG results were analysed by the paired t-test and p value <0.05 was taken as significant. RESULTS: There was a significant reduction in maximum detrusor pressure, duration of contraction and residual urine volume (p<0.05) on the VCMG six months after insertion of the stent. At present six patients have a Memokath stent in situ at a mean of 34.7 months (range 6-86 months). Nineteen stents were removed for several reasons at a mean of 20.3 months (range 0.25-41 months). These include, exacerbation of autonomic dysreflexic symptoms (n=3); stent migration (n=7); encrustation and stone formation (n=5); incomplete bladder emptying without obstruction (n=3); entrance into fertility program (n=1). CONCLUSION: The Memokath stent is safe, easy and quick to insert with minimal trauma to the urethra. It is effective in the management of DSD and decreasing the detrusor pressure and residual urine volume in SCI patients. Moreover the ease of its removal in a non-traumatic fashion makes this stent an attractive option when patients are still contemplating the method of bladder management, in those wishing to be involved in fertility program and in recently SCI patients who may recover some manual dexterity to perform clean intermittent self-catheterisation. It must be remembered that this is a temporary stent, as our study clearly shows that the majority are removed within two years of insertion.

Adult↗

PubMed2000

Attenuation of KATP channel-opener induced shortening of repolarization time by alpha 1-adrenoceptor antagonist during ischemia in canine heart.

The purpose of the study was to determine whether a new KATP channel opener, Y 26763 (Y), can influence the electrophysiological properties in the ischemic myocardium as well as to determine whether the blunting effect of the alpha 1-adrenoceptor antagonist bunazosin (BN) on an ischemia-induced shortening of repolarization time can be related to the KATP channel activity. The anterior descending branch of the left coronary artery was ligated four times for 5 minutes, separated by 15 minutes of reperfusion (stages 1-4) to test the dose-dependent effect of drugs on repolarization. Dogs received either vehicle (n = 9), Y (0.4, 2.0, and 4.0 micrograms/kg at stages 2, 3, and 4, respectively, with 0.4 microgram/kg/min drip infusion at each of stages 2-4, n = 7), BN (0.1 mg at each of stages 2-4, n = 8), or a combination of these two drugs (BN + Y, the same dose of BN and Y in groups BN and Y, respectively, n = 9). Drugs were administered into the left atrium. The monophasic action potential (MAP) and regional electrograms were recorded. The MAP90 and the duration of the slow deflections (DSD) of the regional electrogram were used as markers of repolarization. The Vmax of the MAP and the rapid deflections (DRD) of the regional electrogram were used as markers of conduction. Y augmented an ischemia-induced shortening of MAP90 and DSD in proportion to an increase in the dose given and the plasma concentration (P < .05-.01), especially at the epicardial site. BN and BN + Y blunted the ischemia-related shortening of MAP90 and DSD, causing a reduction in repolarization time dispersion between the ischemic and normal zones. There were no significant changes in the Vmax or DRD in the ischemic zone between periods before and after an increase in each drug dose in the four groups. None of the seven dogs developed ventricular tachycardia (VT)/ventricular fibrillation (VF) in the Y group, whereas two of the eight dogs in the BN group, three of the nine dogs in the BN + Y group, and three of the nine dogs in the control group developed VT/VF. These results suggest that the alpha 1-adrenergic blocker bunazosin blunts the shortening effect of KATP channel activator on repolarization time, and that the KATP channel opener Y may be antiarrhythmic, although the repolarization time dispersion during myocardial ischemia is increased.

ATP-Binding Cassette Transporters↗

PubMed2006

Mechanisms of disease: Transcription factors in sex determination--relevance to human disorders of sex development.

Sex determination is the series of molecular events that direct the undifferentiated bipotential gonad to become either a testis or an ovary. In humans, disruption of this process results in intersexuality, also referred to as disorders of sex development (DSD). Despite the discovery of the sex-determining gene SRY (sex-determining region Y) 15 years ago, the molecular mechanisms of sex determination remain poorly understood. Analysis of clinically relevant mutations of sex-determining genes in individuals with DSD has provided considerable insight into the function of these genes. The majority of disorders of sex determination with known causes are explained by mutations in one of three transcription factors at the core of the sex-determining pathway: SRY, SOX9 (SRY-box 9) and NR5A1 (nuclear receptor subfamily 5, group A, member 1). These mutations either affect the level of protein available at its nuclear site of action (via changes in regulatory sequences, deletions, non-sense mutations or mutations in nuclear localization sequences), or alter the structure of the protein (via modifications of binding or bending activity, or of interactions with other proteins). Deciphering the functional diversity of the mutations affecting the sex-determining pathway has immediate clinical impact on the diagnosis, outcome studies and classification of patients with DSD.

Animals↗

PubMed2006

Management of detrusor-external sphincter dyssynergia.

Detrusor-external sphincter dyssynergia (DSD) is a debilitating problem in patients with spinal cord injury. DSD carries a high risk of complications, and even life expectancy can be affected. The mainstay of treatment is the use of antimuscarinic medication and catheterization, but in those for whom this is not possible external sphincterotomy has been the traditional management route. External sphincterotomy, however, is associated with significant risks, including hemorrhage, erectile dysfunction and the need for repeat procedures, and over the last decade alternatives have been investigated, such as urethral stents and botulinum toxin injection. We present a review of DSD, including the current management strategies and prospects for future treatment.

Adrenergic alpha-Antagonists↗

PubMed2026

GFPT1 as a cross-ancestry validated target for degenerative spinal disease: genetic association in a Chinese cohort and functional characterization in zebrafish.

Degenerative spinal disease (DSD), including spinal stenosis and spondylosis, lacks effective pharmacological treatment. To identify druggable targets and assess cross-ancestry applicability, we integrate multi-omics analyses using Summary-data-based Mendelian Randomization (SMR), colocalization, and two-sample Mendelian randomization with European whole-blood, peripheral-blood, and CSF eQTL/pQTL datasets, followed by whole-genome sequencing (WGS) validation in a Chinese cohort. We identify 7 genes/proteins associated with spinal stenosis and 5 with spondylosis, with GFPT1, GPX1, and SERPINA1 shared by both. Two-sample MR further supports the causal associations of these targets with DSD. Phenome-wide MR prioritization selects GFPT1 and GPX1 as favorable candidates with no predicted adverse effects and potential beneficial effects on hypertension. In the Chinese cohort (67 lumbar spinal stenosis patients and 100 controls), WGS identifies 4 GFPT1 cis-eQTL loci (rs13016371, rs35392088, rs12997521, and rs13019789) associated with lumbar spinal stenosis risk; all risk alleles are linked to increased GFPT1 expression, and all 24 variant carriers show L4/L5 stenosis on imaging. Druggability analysis identifies IOX1 as the sole preclinical-stage compound targeting GFPT1, and molecular docking supports robust binding to GFPT1 (- 6.39 kcal/mol). Functional assays show that IOX1 directly inhibits GFPT1 enzymatic activity and induces fructose-6-phosphate accumulation. In zebrafish, IOX1 significantly rescues GFPT1-induced degenerative phenotypes. These findings establish GFPT1 as a cross-ancestry validated therapeutic target for DSD and nominate IOX1 as a promising disease-modifying candidate.

Animals↗

PubMed1994

Urolume urethral wallstent in the treatment of detrusor sphincter dyssynergia.

Neuropathic voiding dysfunction with detrusor sphincter dyssynergia (DSD) is a common complication of spinal cord injury (SCI) and multiple sclerosis. Sphincterotomy has been recommended for treatment of DSD if the patient lacks the ability to do intermittent self catheterization. We report our preliminary results of the Urolume urethral wallstent for the treatment of DSD in 10 patients. The insertion technique proved simple, with a short hospital stay and low morbidity; however, its long term safety has not yet been established.

Adult↗