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W K Clark

Publications and source records attributed to W K Clark.

At least 19 recordsLinked to original sources
PubMed2004

Tegaserod for the treatment of irritable bowel syndrome.

BACKGROUND: IBS is a complex disorder that encompasses a wide profile of symptoms. Current drug treatments for irritable bowel syndrome (IBS) are of limited value. Many target specific symptoms only. Tegaserod, a 5HT(4) partial agonist, represents a novel mechanism of action in the treatment of IBS. OBJECTIVES: The objective of this review was to evaluate the efficacy and tolerability of tegaserod for the treatment of IBS in adults and adolescents aged 12 years and above. SEARCH STRATEGY: MEDLINE 1966-November 2002 and EMBASE 1980-November 2002 were searched. The text and key words used included "tegaserod", "HTF 919", "irritable bowel", and "colonic diseases, functional". The Cochrane Central Register of Controlled Trials, the Inflammatory Bowel Disease Review Group Specialized Trials Register, and Science Citation Index were also searched. Proceedings from the British Society of Gastroenterology Annual Meeting, and Digestive Disease Week (1998-2002) were hand searched. The manufacturer of tegaserod was contacted. Relevant articles were retrieved, and their reference lists were also reviewed. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing tegaserod with placebo, no treatment or any other intervention (pharmacological or non-pharmacological) in subjects aged 12 years and above with a diagnosis of IBS, focusing on clinical endpoints were considered for review. DATA COLLECTION AND ANALYSIS: Study inclusion and exclusion, data extraction and quality assessment was undertaken by two reviewers independently. Meta-analysis was performed where study populations, designs, outcomes, and statistical reporting allowed combination of data in a valid way, using the summary statistic relative risk with 95% CI. Eight short-term placebo-controlled studies fulfilled our inclusion criteria. These were predominantly conducted in women. Seven studies evaluated the efficacy of tegaserod on global gastrointestinal (GI) symptoms in patients with constipation-predominant IBS (C-IBS). One small study evaluated safety in patients with diarrhoea-predominant IBS. MAIN RESULTS: The relative risk (RR) of being a responder in terms of global relief of GI symptoms was significantly higher with tegaserod 12 mg (RR 1.19, 95% CI 1.09, 1.29) and tegaserod 4 mg (RR 1.15, 95% CI 1.02, 1.31) compared with placebo, with a number needed to treat (NNT) of 14 and 20 respectively. When all tegaserod doses were combined and compared with placebo (n=4040), the RR of being a responder was 1.17 (95% CI 1.08, 1.27), with a NNT of 17. Although the pooled results indicate statistically significant benefit with tegaserod, the a priori minimal clinically important differences set in two of the four pooled studies were not reached. Tegaserod did not significantly improve the patients' individual symptoms of abdominal pain and discomfort although bowel habit showed a statistically significant improvement with tegaserod 4 mg and there was a non-significant trend in favour of tegaserod 12 mg. When GI symptoms were assessed separately, those indicative of GI motility such as number of bowel movements and days without bowel movements were generally improved with tegaserod although the proportion of patients experiencing diarrhoea was significantly higher in the tegaserod 12 mg group compared with placebo (RR 2.75, 95% CI 1.90, 3.97), with a number needed to harm (NNH) of 20. Effects of tegaserod on GI symptoms such as bloating, stool consistency, and straining were not consistent across the studies. REVIEWER'S CONCLUSIONS: Tegaserod appears to improve the overall symptomatology of IBS but there are currently few data on its effect on quality of life. In addition, more information is needed about its efficacy in men. It would also be of interest to know whether treatment with tegaserod leads either directly, or indirectly, to changes in visceral sensitivity or psychopathology, which are also considered important in the pathophysiology of this condition.

Adolescent↗
PubMed1989

Lester A. Mount.

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History, 20th Century↗
PubMed1981

Significance of the so-called absorptive reserve in communicating hydrocephalus: a preliminary report.

Twelve patients with communicating hydrocephalus were studied with a servocontrolled lumbar infusion technique to measure net cerebrospinal fluid (CSF) absorptive capacity and resting pressure. Each patient showed a significant absorptive reserve; the rate of CSF absorption exceeded the rate of formation over a physiological range of pressure. The size of the ventricles did not correlate with either the absorptive capacity or the resting pressure parameter, or both. The data suggest that communicating hydrocephalus does not reflect a simple imbalance between the rates of CSF formation and absorption. Other factors must be of etiological importance and are considered in the discussion.

Absorption↗
PubMed1981

Osmotic blood-brain barrier disruption: pharmacodynamic studies in dogs and a clinical phase I trial in patients with malignant brain tumors.

Infusion of 25% mannitol in saline into the internal carotid artery of dogs disrupts the blood-brain barrier (BBB) in a controlled and reproducible manner (osmotic disruption), whereas mannitol infused through the common carotid artery produces variable disruption of the BBB. Compared to controls, infusion of methotrexate in dogs after osmotic disruption produced significantly higher drug levels in brain. We report very preliminary data on the effects of osmotic disruption with mannitol in five patients harboring malignant brain tumors.

Animals↗
PubMed1980

Servo-controlled lumbar infusions in children. A quantitative approach to the problem of arrested hydrocephalus.

Servo-controlled variable-rate lumbar infusions were performed in 11 children with presumed cerebrospinal fluid (CSF) absorptive defects. The CSF dynamics were determined as a function of intracranial pressure in terms of CSF absorptive capacity and resting pressure. These physiological measurements showed poor correlation with traditional clinical signs. On the basis of the CSF measurements there were four children with arrested hydrocephalus, one with compensated hydrocephalus, three with active hydrocephalus, and three with brain atrophy. Retrospective management decisions based on the clinical presentations, physical findings, and traditional diagnostic tests disagreed with management as indicated by the CSF measurements in eight of 11 cases. It is suggested that this technique may be a useful diagnostic tool for difficult clinical problems.

Atrophy↗
PubMed1980

Physiological features of the pressure-volume function of brain elasticity in man.

The intracranial pressure-volume relationship of brain elasticity was examined in 20 patients with suspected disorders of the cerebrospinal fluid (CSF) system. Elasticity measurements were made as the patients were studied with a servo-controlled lumbar infusion technique to measure CSF absorptive capacity. The data were evaluated to determine the relationship between intracranial pressure (ICP) and volume, and between ICP variability and the level of ICP. The results confirm the exponential nature of the pressure-volume elasticity function in patients who are not critically ill. Eight of the 20 patients were shown to have normal CSF absorptive capacities, and there was no difference between their elasticity measurements and those of patients with absorptive defects. In addition, ICP variability was shown to be linearly related to the actual level of ICP. The physiological features of the pressure-volume elasticity function are reviewed. Based on these considerations, the clinical value and significance of elasticity measurements is questioned.

Adolescent↗
PubMed1980

Brain elasticity changes with ventriculomegaly.

The pressure-volume relationship of brain elasticity was determined in 32 patients during servo-controlled variable-rate lumbar infusions to measure net cerebrospinal fluid (CSF) absorptive capacity. Several indices were used to estimate ventricular size from computerized tomography scans. The results show a linear relationship between ventricular size and the elasticity slope which relates the natural logarithm of pressure to volume. It follows that a hydrocephalic patient should show a greater intracranial pulse amplitude at a given pressure than does a patient with normal-sized ventricles. Although these elasticity changes may simply be the result of the ventriculomegaly, it seems possible that the pressure-volume elasticity relationship may be of etiological importance in disorders of the CSF system.

Adolescent↗
PubMed1979

Microsurgical treatment of transient cerebral ischemia. Preliminary results in 50 patients.

Extracranial-intracranial arterial bypass is a microneurosurgical procedure recently introduced in the treatment of a variety of cerebrovascular ischemic states. Fifty patients with transient ischemic attacks (TIAs) localized to the distribution of the internal carotid artery underwent this procedure during a 48-month period. All have been followed up for at least 14 months after surgery. There were no operative deaths, and notable postoperative morbidity has been experienced in less than 8% of cases. Seventy-six percent of patients have been asymptomatic since surgery, 14% have continued to experience TIAs, and 6% have had completed strokes (2% occurring in the operative hemisphere).

Adult↗
PubMed1979

Computed tomography findings in ruptured arteriovenous malformations of the corpus callosum.

Computed tomography (CT) is of proven value in the evaluation and localization of intracranial hemorrhage. The recognition of various patterns of subarachnoid, intracerebral, and intraventricular hemorrhage is necessary in order to provide accurate localization and to predict probable etiology of the bleed. We present three cases with angiographically proven ruptured arteriovenous malformations involving the midline of the corpus callosum. The clinical presentation and CT findings are discussed. We believe this represents a distinctive pattern of hemorrhage specific for this entity.

Adult↗
PubMed1979

Enhancement of experimental cerebral edema after decompressive craniectomy: implications for the management of severe head injuries.

Decompressive craniectomy has been advocated as a treatment for the cerebral edema associated with massive head injury. Although craniectomy has been successful in lowering intracranial pressure after head injury, a comparison of computerized tomographic scans of comparable patients with traumatic brain edema treated by medical means or decompressive craniectomy showed that bony decompression resulted in apparent exacerbation of edema. To investigate the possibility of enhancement of brain edema by craniectomy, we produced standardized cold lesions in the brains of 10 dogs. Five animals served as controls. In the other 5 animals we performed large decompressive craniectomies after lesioning. Physiological parameters were comparable in both groups. The dogs were killed 8 hours after lesioning. After fixation, their brains were cut into 1-mm-thick slices. We used an image analysis facility built around a PDP 11/105 computer to measure the volume of edema as outlined by Evans blue staining. The mean volume of the brain edema in the control animals was 0.27 +/- 0.19 ml. Mean edema volume was over 7 times greater in craniectomized animals (1.96 +/- 1.89 ml). This difference is statistically significant (p less than 0.05). The driving force for the formation of edema fluid is the difference between intravascular and interstitial presssure. Decompression of the brain by bone removal probably results in a reduction of interstitial fluid pressure and edema enhancement. The clinical literature contains no evidence that craniectomy decreases the morbidity or mortality of human head injury. In view of our experimental findings, this is not surprising. Indeed, pathological evidence indicates that severe edema (such as that accentuated by craniectomy) may produce permanent changes in the neuropil.

Animals↗
PubMed1979

Visual evoked potentials: a noninvasive technique to monitor patients with shunted hydrocephalus.

Visual evoked potentials (VEPs) to repetitive flash stimuli were abnormal in 10 patients with documented hydrocephalus. Abnormalities included latency delays, fatigability, and asymmetries. Both latency and wave form disturbances improved in the postshunt period. Clinical progression of the hydrocephalus occurred in several patients, and this correlated well with worsening of the VEPs. We suggest that this noninvasive technique may be valuable in following patients with cerebrospinal fluid shunts, patients with presumed "arrested" hydrocephalus, and patients who are being weaned from their shunts.

Adult↗
PubMed1979

Cerebrospinal fluid dynamics in patients with pseudotumor cerebri.

CSF dynamics were determined as a function of intracranial pressure in patients with pseudotumor cerebri. Servocontrolled variable rate lumbar infusions were used to determine net CSF-absorptive capacities and resting pressures in 10 patients; serial studies were done in 5 of the patients. Nearly all of the patients had abnormally low CSF-absorptive capacities. On the other hand, marked elevations in resting pressure were not a constant feature of the disease. Concurrent changes in the cerebrovascular bed could introduce errors into this manometric determination of CSF dynamics; the significance of this potential artifact is examined. The results of this study suggest that the CSF compartment may be of etiological importance in the pathophysiology of pseudotumor cerebri.

Adolescent↗
PubMed1979

Risk of intracranial aneurysm surgery in the good grade patient: early versus late operation.

To evaluate the risk of definitive intracranial microsurgical aneurysm obliteration as a function of the timing of the operative intervention, we retrospectively reviewed 106 consecutive patients in good clinical condition who underwent such surgery. The patients who were operated upon within the first 8 days of their most recent subarachnoid hemorrhage formed the "early" group; the patients operated upon between the 9th and 31st day were considered to have undergone "late" surgery. On the basis of their clinical outcome the patients were allocated to one of four outcome categories ("good," "fair," "death") both at the time of their hospital discharge and at their most recent clinical re-evaluation, a minimum of 6 months after discharge from the hospital. There was no significant difference in the operative mortality in each group (early surgery, 5%; late surgery, 4%); additionally, no significant difference was noted in the incidence of either intraoperative complications or postoperative morbidity. A suggestive but statistically insignificant increase in the incidence of postoperative cerebral ischemic events was seen in the "early" surgery group (8% vs. 4% for the "late" surgery group). The potential significance of these findings for the timing of intracranial aneurysm surgery is discussed.

Brain Ischemia↗
PubMed1979

Serial computerized tomographic scanning and the prognosis of severe head injury.

Serial (two or three) computerized tomographic (CT) scans were performed on a series of 58 patients with severe head injury. The protocol called for scans to be done upon admission and on Days 3 and 7 after injury. New lesions (i.e., lesions not visualized on the initial CT scans but appearing on subsequent scans) were a frequent finding, occurring in over half of all patients. For the purposes of this study a new lesion was classified as edema involving two or more lobes, extra-axial hematoma, parenchymal hemorrhage, or infarction. Significant correlation was found between good outcome and the absence of new lesions and between bad outcome and the development of new lesions (p less than 0.001). Several patients did well in spite of the development of new lesions, but these patients were unique in that most had small, unilateral parenchymal hematomas located at or near the frontal or temporal poles. In most cases, patients who did poorly in spite of not developing new lesions had severe injuried visualized on their initial scans (massive intracerebral hematoma, hemorrhage of the corpus callosum) or succumbed to medical complications. The pertinent literature is reviewed, and other CT findings associated with a poor prognosis are noted. The authors suggest that serial CT scanning may be used to make prognostic assessments in severely head-injured patients and may be of value in increasing the confidence in and accuracy of assessments made on clinical grounds alone. (Neurosurgery, 5: 566--569, 1979).

Brain Edema↗