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Biomedical subjects

L S Williams

Publications and source records attributed to L S Williams.

At least 19 recordsLinked to original sources
PubMed2003

Prevalence and impact of depression and pain in neurology outpatients.

BACKGROUND: We examined the prevalence and health related quality of life (HRQoL) of depression and/or pain in neurology outpatients. METHODS: Patients at outpatient clinics completed depression, pain, and HRQoL scales. Group comparisons between those with pain alone, depression alone, both conditions, and neither condition were done. RESULTS: Overall, pain was present in 2/3 and depression in 1/3 of patients. Pain with depression was present in 25%; 75% of depressed patients had pain. These conditions had significant negative impact on mental and physical health status scores. The odds ratio (OR) for having pain was significantly increased in women (OR 2.0), those with depression (OR 2.4), and those with neuropathy/neuromuscular (OR 3.8) or pain syndromes (OR 4.8). The odds of having depression were increased in those with pain (OR 2.4) and with cognitive (OR 4.8) or cerebrovascular (OR 3.3) diagnoses. Neurologists were more likely to recognise and treat pain than depression. CONCLUSIONS: Depression and pain are common in newly referred neurology outpatients and have substantial negative effects on patients' physical and mental health. Pain is more likely than depression to be recognised and treated by neurologists.

Adult↗
PubMed2002

Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke.

BACKGROUND: Hyperglycemia at the time of acute ischemic stroke has been linked to worse outcome in both human and animal studies. OBJECTIVE: To describe the prevalence and severity of hyperglycemia on hospital admission among acute ischemic stroke patients, to examine the independent relationship of admission hyperglycemia to all-cause mortality, and to document the inpatient management of hyperglycemia. METHODS: Patients hospitalized with acute ischemic stroke at one hospital from July 1993 to June 1998 (n = 656) were identified. Demographic data, diagnoses, and blood glucose (BG) values were retrieved from the electronic medical record system. Admission stroke severity, fingerstick BG results, and new diabetes diagnoses were obtained by chart review. Hyperglycemia was defined as admitting random serum BG > or = 130 mg/dL. Hazard ratios (HR) for 30-day, 1-year, and 6-year mortality were calculated using multivariable Cox regression models. RESULTS: Hyperglycemia at admission to hospital was present in 40% of patients with acute stroke. Patients with hyperglycemia were more often women and more likely to have prior diagnoses of diabetes and heart failure. Almost all of these patients remained hyperglycemic during their hospital stay (mean BG = 206 mg/dL), and 43% received no inpatient hypoglycemic drugs. Hyperglycemic patients had longer hospital stay (7 vs 6 days, p = 0.015) and higher inpatient hospital charges ($6,611 vs $5,262, p < 0.001). Hyperglycemia independently increased the risk for death at 30 days (HR 1.87, p < or = 0.01), 1 year (HR 1.75, p < or = 0.01), and 6 years after stroke (HR 1.41, p </= 0.01). CONCLUSIONS: Admitting hyperglycemia was common among patients with acute ischemic stroke and was associated with increased short- and long-term mortality and with increased inpatient charges. Inpatient blood glucose management was suboptimal in this hospital. A trial of intensive treatment of hyperglycemia should be considered.

Acute Disease↗
PubMed2001

Cerebellar dysfunction is associated with overexpression of proinflammatory cytokine genes in lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology accompanied by central nervous system involvement in up to 60% of patients. The current study chronicles the expression of cerebellar dysfunction in SLE using MRL-lpr/lpr mice as the experimental model. These mice spontaneously develop an illness that has immunological and clinical features of human lupus. We found that MRL-lpr/lpr mice manifest severe and progressive behavioral disturbances indicative of cerebellar dysfunction beginning at 11 weeks of age. Although the lpr gene is known to induce autoimmune features, immunologically normal mice rendered congenic for lpr failed to exhibit disturbances in cerebellar function. Because lupus is a cytokine-driven disease and overexpression of certain proinflammatory cytokines has been associated with neurodegeneration, the relationship between cerebellar dysfunction and cytokine gene expression was examined. Relative to immunologically normal CBA/J mice, the cerebellum of young (11-15 weeks of age) MRL-lpr/lpr mice contained high levels of interleukin (IL)-6 and interferon-gamma (IFNgamma) mRNA, which became even more pronounced in old (22-30 weeks of age) autoimmune mice. mRNA levels for the cytokines IL-1beta and IL-10 were elevated in the cerebellum of old, but not young, MRL-lpr/lpr mice relative to CBA/J. In contrast, the levels of cerebellar transcripts for IL-3 and tumor necrosis factor-alpha were comparable in autoimmune and normal mice, indicating that enhanced gene expression of IL-6, IFNgamma, IL-1beta, and IL-10 was selective. These results suggest a potential role for certain proinflammatory cytokines in the pathogenesis of cerebellar disturbances in SLE.

Aging↗
PubMed2001

Perineural spread of cutaneous squamous and basal cell carcinoma: CT and MR detection and its impact on patient management and prognosis.

PURPOSE: To analyze the pretreatment imaging findings and outcome of patients with perineural spread of squamous or basal cell carcinoma of the face and scalp treated with radiotherapy, to determine whether CT (computed tomography) or MR (magnetic resonance) imaging can be effectively used to identify patients who would benefit from aggressive treatment, and to characterize the imaging features associated with cure. METHODS: Thirty-five patients had perineural spread of squamous and basal cell carcinoma along the divisions of the trigeminal and/or facial nerves based on clinical findings and/or histopathological proof. Perineural extension seen on imaging was divided into three zones of involvement. The volume of perineural disease was graded semiquanitatively. All patients received radiotherapy with curative intent. RESULTS: Eighteen of the 35 patients had imaging evidence of perineural spread of tumor, and the remaining 17 were imaging negative for perineural spread. The absolute 5-year survival of the imaging positive group was 50% compared with 86% in the imaging-negative group (p = 0.048). CONCLUSIONS: Imaging can be used to identify patients with advanced perineural spread who warrant aggressive radiotherapy. Imaging evidence of perineural invasion worsens prognosis; however, low-volume and peripheral perineural disease is radiocurable. Greater perineural tumor volume with more central disease was associated with an unfavorable outcome.

Adult↗
PubMed2001

GABA(A) receptors containing (alpha)5 subunits in the CA1 and CA3 hippocampal fields regulate ethanol-motivated behaviors: an extended ethanol reward circuitry.

GABA receptors within the mesolimbic circuitry have been proposed to play a role in regulating alcohol-seeking behaviors in the alcohol-preferring (P) rat. However, the precise GABA(A) receptor subunit(s) mediating the reinforcing properties of EtOH remains unknown. We examined the capacity of intrahippocampal infusions of an alpha5 subunit-selective ( approximately 75-fold) benzodiazepine (BDZ) inverse agonist [i.e., RY 023 (RY) (tert-butyl 8-(trimethylsilyl) acetylene-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate)] to alter lever pressing maintained by concurrent presentation of EtOH (10% v/v) and a saccharin solution (0.05% w/v). Bilateral (1.5-20 microgram) and unilateral (0.01-40 microgram) RY dose-dependently reduced EtOH-maintained responding, with saccharin-maintained responding being reduced only with the highest doses (e.g., 20 and 40 microgram). The competitive BDZ antagonist ZK 93426 (ZK) (7 microgram) reversed the RY-induced suppression on EtOH-maintained responding, confirming that the effect was mediated via the BDZ site on the GABA(A) receptor complex. Intrahippocampal modulation of the EtOH-maintained responding was site-specific; no antagonism by RY after intra-accumbens [nucleus accumbens (NACC)] and intraventral tegmental [ventral tegmental area (VTA)] infusions was observed. Because the VTA and NACC contain very high densities of alpha1 and alpha2 subunits, respectively, we determined whether RY exhibited a "negative" or "neutral" pharmacological profile at recombinant alpha1beta3gamma2, alpha2beta3gamma2, and alpha5beta3gamma2 receptors expressed in Xenopus oocytes. RY produced "classic" inverse agonism at all alpha receptor subtypes; thus, a neutral efficacy was not sufficient to explain the failure of RY to alter EtOH responding in the NACC or VTA. The results provide the first demonstration that the alpha5-containing GABA(A) receptors in the hippocampus play an important role in regulating EtOH-seeking behaviors.

Animals↗
PubMed2001

Middle ear prosthesis displacement in high-strength magnetic fields.

HYPOTHESIS: Middle ear prostheses made from nonmagnetic, magnetic resonance (MR)-compatible metals reportedly displace ex vivo in the presence of high magnetic fields used in MR imaging (MRI). The authors postulate that the prosthesis displacement seen with "nonmagnetic" MR-compatible prostheses ex vivo may not be clinically significant in vivo. METHODS: Middle ear prostheses made from ferromagnetic (420F stainless steel) and nonmagnetic MR-compatible metals (316L stainless steel and platinum) were examined for magnetic field interactions at 4.7 Tesla (T). Ex vivo testing consisted of measurements of the translational and rotational motion of the prosthesis induced by the static magnetic field. In vivo testing was assessed by implanting prostheses in cadaveric temporal bones and performing clinical MRI sequences. Prosthesis displacement was measured semiquantitatively. RESULTS: Angular deflection was observed in all samples made from nonmagnetic stainless steel. The negative control (platinum) demonstrated no deflection, and the positive controls (ferromagnetic stainless steel) deflected >90 degrees. Torque analysis showed movement in five of five nonmagnetic stainless steel prostheses. Prostheses made from nonmagnetic stainless steel remained in place without appreciable loosening in vivo after MRI. Prostheses made with known ferromagnetic properties were displaced at 4.7 T but not at 1.5 T. CONCLUSION: Middle ear prostheses made from low-magnetic stainless steel do move in the presence of high magnetic fields ex vivo; however, this does not appear to be clinically or statistically significant in vivo at 4.7 T. Magnetic resonance imaging should be undertaken with caution in individuals with prostheses made from stainless steel with strong ferromagnetic properties.

Electromagnetic Fields↗
PubMed2001

Protocol violations in community-based rTPA stroke treatment are associated with symptomatic intracerebral hemorrhage.

BACKGROUND: Recombinant tissue plasminogen activator (rTPA) is an established treatment for acute ischemic stroke. The rate and type of protocol violations in rTPA use and their effect on patient outcomes in this setting are not well understood. OBJECTIVE: The objective of this study was to examine associations between protocol violations and outcomes in community-based rTPA use. METHODS: We reviewed medical records of stroke patients treated with rTPA in 10 acute-care hospitals in Indianapolis from July 1996 to February 1998 and assessed complications and outcome. Retrospective National Institute of Health Stroke Scale (on admission and discharge), Canadian Neurological Scale, and length of hospital stay were calculated. Appropriate use of rTPA was determined by the National Institute of Neurological Disorders and Stroke (NINDS) protocol. RESULTS: Fifty patients (mean age, 66 years; 76% white; 56% men) were treated by general neurologists (70%), stroke neurologists (24%), or emergency physicians (6%). Mean times to hospital arrival, brain CT, and start of rTPA infusion were 44, 86, and 141 minutes, respectively. In-hospital mortality rate was 10% (4 intracerebral hemorrhage [ICH], 1 cardiogenic shock). Complications were more frequent among patients with protocol violations (n=8) compared with those without all hemorrhages (75% versus 10%, P:<0.001), symptomatic ICH (38% versus 5%, P:<0.02), and ICH attributable to rTPA, occurring within 36 hours (38% versus 2.4%, P:<0.01), respectively. CONCLUSIONS: NINDS protocol violations are relatively common and are associated with symptomatic cerebral and systemic hemorrhages. When the NINDS protocol is strictly followed, hemorrhage rates in community-based rTPA use are similar to those in the NINDS trial.

Anticoagulants↗
PubMed2001

Validating the Questionnaire for Verifying Stroke-Free Status (QVSFS) by neurological history and examination.

BACKGROUND AND PURPOSE: The Questionnaire for Verifying Stroke-Free Status (QVSFS) is an 8-item structured interview designed to identify stroke-free individuals. Previously, the QVSFS was validated with medical record review in a cohort with a low prevalence (7.1%) of stroke or transient ischemic attack (TIA). The objective of this study was to evaluate the validity of the QVSFS by comparing it with stroke status as determined by neurological history and examination in a population with a higher prevalence of stroke. METHODS: A research assistant administered the QVSFS to outpatients from Veterans Administration stroke and general medicine clinics. Subjects were defined as QVSFS negative if responses to all 8 questions were negative. Questions requiring rephrasing or clarification were noted. Neurologists, blinded to QVSFS scores, interviewed and examined all subjects to determine stroke-free status, defined as no history or examination findings of previous stroke and/or TIA. RESULTS: One hundred fifty-five subjects were examined; mean age was 70 years; 98.1% were male. Seventy-eight subjects were determined to be stroke free by the neurologist. The negative predictive value of the QVSFS was 0.96, with positive predictive value of 0.71. No question required rephrasing or clarification >5 times. Twenty-two subjects (14.2%) required rephrasing or clarification of at least 1 question. CONCLUSIONS: The QVSFS can effectively identify stroke-free individuals with a high degree of accuracy, even in a population with a large proportion of patients with prior stroke or TIA. Accuracy for identifying subjects with stroke and/or TIA is lower, but the QVSFS may still be useful as a screening tool in that regard.

Adult↗
PubMed2001

Recurrence in pituitary adenomas in childhood and adolescence.

Pediatric pituitary adenomas are thought to behave more aggressively than their adult counterparts, and the ability to predict the degree of such behavior remains elusive. Proliferation marker Ki-67 and tumor suppressor gene p53 mutations have been used in adults to assist in the evaluation of invasiveness and recurrence; however, their use in childhood and adolescence remains anecdotal. Our study evaluates the proliferative potential in pituitary adenomas of five patients and its relationship with recurrence or persistence of endocrinologic or clinical abnormalities. For such assessment, tissues were stained with monoclonal antibodies BP53-12 forp53 tumor suppressor gene mutation and MIB-1, which binds to cell cycle-specific nuclear antigen Ki-67. In our series, one patient with recurrent adenoma demonstrated the highest (50%) p53 immunoreactivity. Ki-67-stained nuclei ranged from 0 to 2%, failing to identify the recurrent tumor. Therefore, p53 immunoreactivity, rather than Ki-67 nuclear stain, may be useful for identification of recurrent pituitary adenomas in childhood and adolescence.

Adenoma↗
PubMed2000

Effects of fosinopril or sustained-release verapamil on blood pressure and serum catecholamine concentrations in elderly hypertensive men.

A randomized, double-blind, placebo-controlled clinical trial showed 14 of 18 (78%) of the elderly hypertensive men in this study had an uncomplicated and beneficial response to either fosinopril or verapamil. There was a well-tolerated reduction in systolic blood pressure (SBP) and diastolic blood pressure (DRP). There were no significant adverse drug events. Only the sitting SBP and the sitting DBP were significantly lowered by fosinopril and verapamil SR. Because reduction in both SBP and DBP in elderly hypertensives has been shown to be beneficial, these findings take on further importance when considering the choice of medication for antihypertensive therapy in the elderly. The increase in norepinephrine in the fosinopril-treated patients may explain why patients treated with long-term angiotensin-converting enzyme inhibitors alone or in combination with diuretics rarely complain of orthostatic symptoms.

Aged↗
PubMed2000

Retrospective assessment of initial stroke severity with the NIH Stroke Scale.

BACKGROUND AND PURPOSE: It is important to adjust stroke outcomes for differences in initial stroke severity. The NIH Stroke Scale (NIHSS) is a commonly used stroke severity measure but has been validated for retrospective scoring only in a subset of stroke clinical trial participants. The purpose of this research was to assess the validity and reliability of an algorithm for retrospective NIHSS scoring in a setting with usual chart documentation. METHODS: An algorithm for retrospective NIHSS scoring was developed with written history and physical admission notes. Missing physical examination data were scored as normal. One investigator prospectively scored the admission NIHSS in 32 consecutive stroke patients. Two raters retrospectively scored the NIHSS by applying the algorithm to photocopied admission notes. Linear regression was used to assess interrater reliability and agreement between prospective and retrospective NIHSS scores. The Wilcoxon signed rank test was used to assess systematic scoring bias. Weighted kappa statistics were calculated to assess the level of agreement of individual NIHSS items. RESULTS: Only 1 admission note was complete for all NIHSS elements. Interrater reliability was near perfect (r(2)=0.98, P<0. 001). Agreement between prospective and retrospective NIHSS score was also excellent (r(2)=0.94, P<0.001) and there was no systematic bias in retrospective scores. Agreement for individual items was moderate to high for all items except level of consciousness. CONCLUSIONS: Retrospective NIHSS scoring with the algorithm is reliable and unbiased even when physical examination elements are missing from the written record. Stroke research using retrospective review of charts or of administrative databases should adjust for differences in stroke severity using such an algorithm.

Aged↗
PubMed1999

Measuring quality of life in a way that is meaningful to stroke patients.

OBJECTIVE: To identify predictors of poststroke quality of life. BACKGROUND: Health-related quality of life (HRQOL) measures assess the impact of disease on the physical, emotional, and social aspects of patients' lives. Although HRQOL measures are used increasingly, factors associated with HRQOL poststroke and the ability of stroke-specific versus generic HRQOL measures to predict patient-reported HRQOL are not well known. METHODS: A total of 71 patients were evaluated 1 month postischemic stroke with a new stroke-specific HRQOL measure-the SS-QOL-and the SF-36, a generic HRQOL measure. Stroke severity, impairments, and functional limitations were also measured. Demographic variables and outcome measure scores were compared between patients rating their overall HRQOL the same as pre-stroke versus those with overall HRQOL worse than prestroke. Independent predictors of overall HRQOL were identified using multivariable modeling. RESULTS: Variables associated with better overall HRQOL were higher (better) SS-QOL and Barthel Index scores, and lower (better) NIH Stroke Scale and Beck Depression Inventory scores. Independent predictors of good overall HRQOL were the SS-QOL score (odds ratio [OR], 2.97; 95% CI, 1.3, 7.1; p = 0.01) and NIH Stroke Scale score (OR, 0.69; 95% CI, 0.47, 0.99; p = 0.05). Demographic factors and SF-36 scores were not associated with overall HRQOL ratings. CONCLUSIONS: Stroke-specific quality of life score and patient impairments predict patient-reported overall health-related quality of life (HRQOL) poststroke. SF-36 scores were not associated with overall HRQOL ratings. Disease-specific HRQOL measures are more sensitive to meaningful changes in poststroke HRQOL and may thus aid in identifying specific aspects of poststroke function that clinicians and "trialists" can target to improve patients' HRQOL after stroke.

Aged↗
PubMed1999

Acute blood glucose level and outcome from ischemic stroke. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators.

OBJECTIVE: To study the relation between acute blood glucose level and outcome from ischemic stroke. BACKGROUND: Hyperglycemia may augment acute ischemic brain injury and increase the risk of hemorrhagic transformation of the infarct. METHODS: The authors analyzed the relation between admission blood glucose level (within 24 hours from ischemic stroke onset) and clinical outcome in 1,259 patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST)-a placebo-controlled, randomized, double-blind trial to test the efficacy of a low-molecular weight heparinoid in acute ischemic stroke. Very favorable outcome was defined as a Glasgow Outcome Scale score of 1 and a modified Barthel index of 19 or 20. Neurologic improvement at 3 months was defined as a decrease by > or =4 points on the NIH Stroke Scale compared with baseline or a final score of 0. Hemorrhagic transformation of infarct was assessed within 10 days after onset of stroke with repeat cerebral CT. Stroke subtype as lacunar or nonlacunar (atherothromboembolic, cardioembolic, and other or undetermined etiology) was classified by one investigator after completion of stroke evaluation according to study protocol. RESULTS: In all strokes combined (p = 0.03) and in nonlacunar strokes (p = 0.02), higher admission blood glucose levels were associated with worse outcome at 3 months according to multivariate logistic regression analysis adjusted for stroke severity, diabetes mellitus, and other vascular risks. In lacunar strokes, the relationship between acute blood glucose level and outcome was related to treatment. In the placebo group, higher admission blood glucose levels were associated with better outcome at 3 months. However, in the active drug group, as the glucose level increased from 50 to 150 mg/dL, the probability of a very favorable outcome decreased sharply and remained relatively unchanged as the glucose level increased further (p = 0.002, for overall effect of glucose on outcome). Acute blood glucose level was not associated with symptomatic hemorrhagic transformation of infarcts or with neurologic improvement at 3 months. CONCLUSIONS: During acute ischemic stroke hyperglycemia may worsen the clinical outcome in nonlacunar stroke, but not in lacunar stroke, and is not associated with an increased risk of hemorrhagic transformation of the infarct.

Acute Disease↗
PubMed1999

Advanced concepts in the imaging of perineural spread of tumor to the trigeminal nerve.

Perineural spread of head and neck tumor represents extension of the primary tumor along the perineurium. Diagnosis of perineural spread of carcinoma often is delayed unless the clinician maintains a high index of suspicion. It may be insidious, and patients may be asymptomatic for years. Perineural spread of carcinoma has been associated with a poor prognosis; however, it is becoming increasingly realized that cure is possible in some cases, if the full extent of the disease is known and treated. Magnetic resonance imaging (MRI) can detect perineural spread of head and neck carcinoma and define its extent. MRI is the imaging modality of choice to assess perineural disease due to its superior tissue contrast and multiplanar capability. Perineural spread of head and neck carcinomas most commonly involves the trigeminal nerve. Obliteration of the fat within (a) the superior medial orbital (ophthalmic division territory), (b) the periantral fat plane (maxillary division distribution), and (c) the pterygopalatine fossa all are useful indicators of distal perineural disease. A perineural vascular plexus (PNVP) surrounds the trigeminal ganglion and proximal portions of the trigeminal nerve divisions. The trigeminal ganglion and proximal portions of its divisions usually are seen as discrete nonenhancing structures separate from the PNVP. Occasionally, isolated enhancement of the ganglion and the proximal portions of the maxillary and mandibular divisions as they exit the skull base may be seen. This may be an artifact related to head position or may represent avid enhancement of the PNVP. In these situations, evaluating all branches, and the entire course, of the trigeminal nerve for perineural spread can aid in determining whether the apparent enhancement is an isolated normal variant or represents nerve pathology such as perineural spread.

Carcinoma, Squamous Cell↗
PubMed1999

Chemotherapy for pancreatic cancer: a neuroimaging clinicopathologic correlation.

This 52-year-old male without a significant medical history was receiving chemotherapy with diethylnorspermine (DENSPM), a polyamine analogue, for a partially resected pancreatic adenocarcinoma. Ten months after his initial diagnosis, he was admitted to an outside hospital for evaluation of altered mental status. Over the course of the next few days the patient developed progressive neurologic signs and symptoms including lethargy, tonic deviation of his eyes to the left, asymmetic pupils, and right-sided decerebrate posturing elicited by painful stimuli. Neuroimaging studies revealed multiple lesions scattered in the periventricular white matter, thalamus, midbrain pons, and cerebellar peduncles. The clinical and neuroimaging differential diagnoses are discussed, and postmortem neuropathologic correlation is presented.

Adenocarcinoma↗