Bladder Problems Ebook
Interestingly, the impetus for studying duloxetine was for discovering a treatment of urinary urge incontinence and overactive bladder. Insertion of EMG electrodes into the rhabdosphincter was a compulsion instilled in me during my dissertation studies to obtain as much data as practical from every experiment conducted. Even after seeing pronounced effects on the rhabdosphincter, I was still more impressed with the effects on the bladder and anticipated clinical benefits for urge incontinence and overactive bladder to supersede clinical benefit for SUI. Fortunately we did have the preclinical data regarding enhancement of sphincter activity or we might not have included SUI patients in the initial trials and we might not have been as aggressive in post hoc analyses of the initial low-dose clinical trial results that supported additional trials at higher doses. Interestingly, there are some indications for benefit by duloxetine in urge incontinence and overactive bladder. The first is...
Because meningiomas grow slowly and may become large before raising the ICP, partial or generalized seizures are often the presenting or only clinical manifestations for months or years. Focal neurologic symptoms and signs develop later and indicate the anatomic site. Bilateral parasagittal and falx meningiomas, by pressing on the leg area of the motor cortex, present with spastic paraparesis and urinary incontinence, mimicking a spinal cord lesion. On CT scan and MRI, meningiomas appear as extra-axial mass lesions compressing the brain substance. The surrounding edema and mass effect usually are not marked. CT scan readily identifies a calcified meningioma. On nonenhanced CT scan, a meningioma is iso- or hyperdense it densely enhances with contrast media. It shows a dense homogenous enhancement on T1-weighted MR images, and is iso- or hyperintense on T2-weighted images.
Tissue engineering with viscoelastic hyaluronan focused first on its use as a tissue filler or tissue augmentator (viscoaugmentation). Unlike collagen and non-biological tissue fillers, hyaluronan is an extremely elastic molecule and as such provides elasticity to the intercellular spaces into which it is injected. Hylan B gel was first used for viscoaugmentation of the vitreus after retinal detachment surgery, and later for correcting facial wrinkles and depressed scars for vocal cord augmentation in glottal insufficiency and augmentation of the connective tissue in sphincter muscles to treat urinary incontinence.
Advocates of hyperbaric oxygen therapy for MS cite the positive clinical study from 1983. However, seven studies performed after the 1983 study did not demonstrate any consistent therapeutic effect for hyperbaric oxygen. In a few studies, a mild improvement in bladder problems was noted. A 1995 review of hyperbaric oxygen treatment trials in MS concluded that hyperbaric oxygen did not produce significant
It is important to undergo a medical evaluation for urinary incontinence. Because CAM therapies have not been extensively studied, it is important to consider conventional therapy first in this area. Multiple CAM therapies have produced promising results for urinary incontinence
The first animal studies to demonstrate the usefulness of hylan B gel in viscoaugmentation as a tissue bulking agent for urinary sphincter muscle were completed in 1993 (Biomatrix, Inc., Ridgefield, NJ). Later clinical trials demonstrated the beneficial effect of this viscoelastic gel slurry injected intramuscularly to augment the connective tissue between the sphincter muscles of the urethra in patients with certain types of urinary incontinence. Hyaluronan was also used in pilot clinical studies combined with dextran particles for endoscopic treatment of vesicoureteral reflux in children (77) and in women with a history of stress incontinence (78). In this case the dextran particles were suspended in 1 elastoviscous hyaluronan solution to decrease the foreign body reaction caused by the dextran.
In the early 1990s, therapy for stress urinary incontinence relied on pelvic floor exercises and surgery. Bringing the first drug forward to treat any indication provided a number of challenges, such as extent of medical need and clinical trial design. Unique to duloxetine's trials in incontinence were (1) the fact that urologic thought leaders' prevailing opinion at that time was that stress incontinence was 'an anatomical defect' that would be only amenable to surgery and not pharmacological therapy, and (2) doubts about whether a CNS approach to a urological problem was tenable.
Berghmans LCM, Hendriks HJM, Hay-Smith EJ, et al. Conservative treatment of stress urinary incontinence in women a systematic review of randomized clinical trials. Br J Urol 1998 82 181-191. de Kruif YP, van Wegen Erwin EH. Pelvic floor muscle exercise therapy with myofeedback for women with stress urinary incontinence a meta-analysis. Physiotherapy 1996 82 107-113.
Inability to store urine is termed urinary incontinence. There are three primary forms of urinary incontinence. 1. Stress urinary incontinence (SUI) is urine leakage resulting from abdominal pressure exceeding urethral resistance during physical 'stress' (i.e., coughing, laughing, or sneezing) and is primarily seen in women. 2. Urge urinary incontinence (UUI) is urine leakage resulting from involuntary activation of the micturition reflex, which in certain circumstances is due to emergence of a pathological spinal reflex (i.e., a 'short circuit' reflex not routed through the brain stem and considerably less influenced by higher levels of the CNS) that is initiated by bladder 'nociceptive' (C fiber) primary afferent (i.e., sensory) fibers. 3. Often, involuntary bladder contractions can occur without leakage of urine but produce symptoms of urinary frequency, urgency, and nocturia. This condition is often referred to as overactive bladder (OAB).
Because memory loss is usually most obvious for newly acquired material, the individual with DAT tries to avoid unfamiliar activities. Typically, the individual is seen by the clinician when confusion, aggression, wandering, or some other socially undesirable behavior ensues. At that time, disorders of perception and language may appear. The individual often turns to a spouse to answer questions posed during the history taking. By this time, the affected individual has lost insight into his or her dementia and abandons attempts to compensate for memory loss. Finally, in the late stage of Alzheimer's disease, physical and cognitive effects are marked. Disorders of gait, extremity paresis and paralysis, seizures, peripheral neuropathy, extrapyramidal signs, and urinary incontinence are seen, and the individual is often no longer ambulatory. The aimless wandering of the middle stage has been replaced by a mute, bedridden state and decorticate posture. Myoclonus occasionally occurs....
In the first series of experiments testing duloxetine's effects on lower urinary tract function,27 I chose to use the cat as the experimental species because most of the preceding experiments with 5HT and norepinephrine had been conducted in cat and thus provided benchmarks upon which to interpret the effects of duloxetine. I also chose to use a model of bladder irritation, i.e., infusion of dilute acetic acid into the bladder, to induce 'overactive bladder' because the importance of nociceptive (i.e., C fiber primary afferent neurons) stimuli in the etiology of overactive bladder was just beginning to emerge. As luck would have it, both of these choices were critical because subsequent studies showed that duloxetine has very little effects on normal (i.e., saline infused - unirritated) bladder activity, presumably because 5HT and or norepinephrine have greater effects on 'irritative,' C fiber-mediated bladder activity than normal bladder primary afferent fibers. Subsequent studies...
Normal-pressure hydrocephalus is generally considered the fifth leading cause of dementia after Alzheimer's, vascular, alcohol-related, and AIDS dementias. Long considered reversible but often merely arrestable, normal-pressure hydrocephalus is a syndrome consisting of dementia, urinary incontinence, and gait apraxia. It results from subarachnoid hemorrhage, meningitis, or trauma that impedes CSF absorption.
Another classic form of incontinence known as urinary urge incontinence (UUI), which is a complaint of involuntary leakage of urine accompanied by or immediately preceded by urgency, is more common in males than females, accounting for 40-80 of male cases.73 UUI is usually caused by detrusor overactivity in men. It is thought that obstruction caused by BPH can affect the local or ventral detrusor control, which results in overactivity, and this explains the higher prevalence in males. The presence of detrusor overactivity can also affect bladder contraction strength, and greater bladder contractions can lead to higher urge severity. It is possible that both UUI and overactive bladder can have similar underlying mechanisms to those observed in BPH patients with detrusor overactivity, which leads some authors to question whether BPH is part of a larger syndrome involving prostatitis (inflammatory), intersititial cystitis, UUI, and overactive bladder.
Psychosocial therapies developed for persons with Alzheimer's disease and other dementias have attempted to minimize disruptive behaviors or increase positive behaviors, support mood and a sense of well-being, or improve or support memory. In early studies with a single dementia patient or a small number of patients, behavior modification approaches using techniques such as time-outs, activity diversion, and selective reinforcement were shown to be effective in reducing urinary incontinence or reinstating important self-care
Several other dietary factors should be kept in mind. Alcohol may, over the short-term, produce or worsen fatigue, bladder problems, walking difficulty, or clumsiness in the arms and legs. Grapefruit juice may increase the effects of many medications, including some that are commonly used for MS diazepam (Valium), clonazepam (Klonopin), carbamazepine (Tegretol), sildenafil (Viagra), and sertraline (Zoloft).
Multiple sclerosis patients present with a broad array of symptoms including reduced or abnormal sensations, weakness, vision changes, clumsiness, and loss of bladder control. The diversity of initial symptoms is a reflection of the focal nature of the disease and makes accurate diagnosis a challenge. A number of signs can be assessed to help in making the diagnosis including abnormal eye movements or pupillary response, altered reflex responses, impaired coordination or sensation, and evidence of spasticity or weakness in the arms or legs. Definitive diagnosis is made by a number of tests including blood tests to rule out other possible diagnoses (e.g., Lyme disease), an examination of cerebrospinal fluid to assess the presence of elevated immunoglobulin G (IgG), and oligoclonal banding, a visual evoked potential test to determine if there is a slowing in signal conduction, and a magnetic resonance imaging (MRI) scan to assess the presence of periventricular lesions. Multiple...
Without any historical pharmaceutical sales data for an indication, the market potential is difficult to predict because most financial models are based on sales of competitors' products. Since there were no well-marketed products for stress urinary incontinence, it was difficult to develop a financial model. In 1992, even sales of urge incontinence products were remarkably small for example, the top UUI medicine was Ditropan, which only had 92 million days of therapy prescribed in the USA, and there were virtually no drug sales in the USA for SUI. This absence of therapy highlighted the need for new therapy with a mechanism of action that was different from previous therapy and was emphasized in 1992 by the Agency for Health Care Policy and Research (AHCPR) which released its first guideline on urinary incontinence and reported 1 in 4 women ages 30-59 have experienced an episode of urinary incontinence
Dr Thor received his PhD in Pharmacology from the University of Pittsburgh School of Medicine where he trained under William (Chet) de Groat, PhD and was supported by a PhARMA predoctoral fellowship. He held a National Research Service Award postdoctoral fellowship from the NIH at Uniformed Services University of the Health Sciences in Bethesda, Maryland, and was a Senior Staff Fellow in the Laboratory of Neurophysiology at the NIH. He joined Eli Lilly in the Neuroscience Division in 1990, where he discovered duloxetine (Yentreve) as a treatment for stress urinary incontinence. In 1998, he formed PPD GenuPro as a subsidiary of PPD Inc., where he discovered the clinical potential of dapoxetine as a therapy for premature ejaculation. These two drugs are the first agents to be submitted to regulatory agencies for their respective indications. In 2002, he founded Dynogen Pharmaceuticals Inc., a neurosci-ence-based drug discovery and development company targeting genitourinary and...
This trial34 was the first to show efficacy in neurogenic bladder (and is the only trial published for any overactive bladder condition to date). This important trial also supported the early positive results for duloxetine in SUI. This study showed a reduction from 1.7 to 0.3 incontinence episodes per day in neurogenic bladder patients at 20 mg (but no effect at 10 mg) and a reduction from 3 to 1 incontinence episodes day at both 10 and 20 mg doses in SUI patients. Although the trial was a single-blinded study and contained no placebo group (which was traditional in Japan at that time to ensure all patients were treated with something), these results added to the early suggestions of duloxetine's efficacy.
Cerebral cysticercosis, granular ependymitis, and acute obstructive hydrocephalus. A 44-year-old woman experienced episodic fever and two episodes of lymphocytic meningitis within 1 year prior to her death. Six days before she died, she developed acutely severe headache, confusion, constantly falling backwards, and urinary incontinence due to an acute hydrocephalus from occlusion of the third ventricle. A. A collapsed, dead cystocercous cyst in the dorsomedial aspect of the thalamus displays a structureless wavy collagenous wall (van Gieson). B. Wall of the third ventricle shows perivascular lymphocytic cuffing (HE). C. Granulation tissue infiltrates the floor of the third ventricle (von Gieson). Cerebral cysticercosis, granular ependymitis, and acute obstructive hydrocephalus. A 44-year-old woman experienced episodic fever and two episodes of lymphocytic meningitis within 1 year prior to her death. Six days before she died, she developed acutely severe headache, confusion, constantly...
Disorders involving bladder dysfunction are captured under the acronym LUTS lower urinary tract symptoms. These disorders include benign prostatic hyperplasia or hypertrophy (hyperplasia being an increase in the number of the prostate cells and hypertrophy an increase in cell size), incontinence or overactive bladder, and bladder outlet obstruction.1'2
NPH occurs in individuals 60 to 70 years of age or older. The clinical criteria include the triad of progressive gait disorder, often the presenting symptom dementia and urinary incontinence. The gait disorder manifests with short shuffling steps and postural instability (frontal gait apraxia). The dementia has components of frontal lobe dysfunction psychomotor slowing, loss of initiative, and apathy. Spasticity in the legs and the