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Biomedical subjects

L S Williams

Publications and source records attributed to L S Williams.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

Development of a stroke-specific quality of life scale.

BACKGROUND AND PURPOSE: Clinical stroke trials are increasingly measuring patient-centered outcomes such as functional status and health-related quality of life (HRQOL). No stroke-specific HRQOL measure is currently available. This study presents the initial development of a valid, reliable, and responsive stroke-specific quality of life (SS-QOL) measure, for use in stroke trials. METHODS: Domains and items for the SS-QOL were developed from patient interviews. The SS-QOL, Short Form 36, Beck Depression Inventory, National Institutes of Health Stroke Scale, and Barthel Index were administered to patients 1 and 3 months after ischemic stroke. Items were eliminated with the use of standard psychometric criteria. Construct validity was assessed by comparing domain scores with similar domains of established measures. Domain responsiveness was assessed with standardized effect sizes. RESULTS: All 12 domains of the SS-QOL were unidimensional. In the final 49-item scale, all domains demonstrated excellent internal reliability (Cronbach's alpha values for each domain >/=0.73). Most domains were moderately correlated with similar domains of established outcome measures (r2 range, 0.3 to 0.5). Most domains were responsive to change (standardized effect sizes >0.4). One- and 3-month SS-QOL scores were associated with patients' self-report of HRQOL compared with before their stroke (P<0.001). CONCLUSIONS: The SS-QOL measures HRQOL, its primary underlying construct, in stroke patients. Preliminary results regarding the reliability, validity, and responsiveness of the SS-QOL are encouraging. Further studies in diverse stroke populations are needed.

Adult↗
PubMed1998

Physical activity and cardiovascular health in the elderly.

People over the age of 65 constitute a growing proportion of the world population both in western and in developing countries. A unique feature of this group is the high prevalence of cardiovascular diseases, which negatively affect its quality of life as well as its life expectancy. Among the interventions able to reduce the health burden of cardiovascular diseases is physical activity. The benefits of physical activity have been demonstrated both in healthy and chronically ill elderly subjects, while the risks have been found to be modest. Physicians should recommend moderate-intensity physical activity to sedentary older subjects, who are still the majority within the elderly population.

Aging↗
PubMed1998

The opioid receptor antagonist nalmefene reduces responding maintained by ethanol presentation: preclinical studies in ethanol-preferring and outbred Wistar rats.

Nalmefene, the 6-methylene derivative of naltrexone, was examined after subcutaneous (s.c.) (0.0001 to 8.0 mg/kg) and oral (10 to 80.0 mg/kg) administration in ethanol (EtOH)-preferring rats whose responding (i.e., lever pressing) was maintained by the presentation of EtOH. Naltrexone (0.01 to 40 mg/kg) was used as a reference opioid antagonist. EtOH (10% v/v) and saccharin (0.025 to 0.1% w/v) solutions were concurrently available for 1 hr each day under a two-lever, fixed-ratio schedule in which four responses on one lever produced the EtOH solution and four responses on the other lever produced the saccharin solution. When basal response rates for saccharin were 10% that of EtOH, all routes of nalmefene administration reduced control levels of responding maintained by EtOH by 38 to 84%. When basal response rates for saccharin-maintained responding were 60% or 82% that of EtOH, only lower s.c. naltrexone (e.g., 0.01 to 0.025 mg/kg) and nalmefene (e.g., 0.01 to 0.10 mg/kg) doses produced a selective dose-dependent suppression of EtOH-maintained responding. Higher nalmefene (0.25 to 8.0 mg/kg) and naltrexone (1.0 to 20.0 mg/kg) doses failed to produce a dose-dependent suppression on EtOH or saccharin maintained responding. Both antagonists suppressed responding maintained by EtOH primarily during the initial 10-min period, with little additional suppression occurring across the remainder of the 60-min period. Subcutaneous nalmefene was 3200- to 6400-fold more potent than oral nalmefene, suggesting bioavailability was optimized using the s.c. route. Nalmefene (0.5 mg/kg, s.c.) treatment for 10 consecutive days produced mild tolerance development, whose effects dissipated by day 8. Naltrexone (10 to 40 mg/kg) and nalmefene (1.5 to 3.0 mg/kg), given 8 to 24 hr before the test session, reduced control levels of responding maintained by EtOH by 82%. Thus, immediate opioid receptor occupancy was not required to observe antagonism. These data demonstrate that, under a variety of experimental conditions, nalmefene is an effective antagonist of responding maintained by EtOH and lend support to clinical reports that nalmefene may function as an alternative pharmacotherapy to naltrexone to reduce EtOH-motivated behavior and prevent relapse.

Alcohol Drinking↗
PubMed1997

The road to Wisconsin.

In this article Lynne Sears Williams of Calgary describes her family's decision to leave for the US, where her husband, Dr. Jim Williams, will pursue his career in family medicine. The decision was not made easily, she writes, but eventually a love for Canada was outweighed by her husband's desire to practise medicine without the financial and other constraints facing physicians in Canada.

Alberta↗
PubMed1997

Stroke patients' knowledge of stroke. Influence on time to presentation.

BACKGROUND AND PURPOSE: New treatments for acute stroke will likely have to be given soon after stroke onset. Little is known about stroke patients' general knowledge about stroke, their interpretation of stroke symptoms, and how these factors influence the timing of their decision to seek medical attention. METHODS: We interviewed consecutive stroke patients within 72 hours of stroke onset to define factors influencing time of arrival to the emergency department. Data recorded included demographic information, method of transportation, type of stroke symptoms, the patient's interpretation of the symptoms, previous stroke, and knowledge of stroke warning signs. Stroke severity was measured with the Barthel Index. Early arrival was defined as within 3 hours of awareness of symptoms. RESULTS: Sixty-seven patients were interviewed; 96% had an ischemic stroke and 4% a cerebral hemorrhage. Although 38% of patients professed to know the warning signs of stroke, only 25% correctly interpreted their symptoms. Patients with prior stroke were more likely to correctly interpret their symptoms (45% versus 16%; P = .03) but were not more likely to present early (19% versus 39%; P = .35). Eighty-six percent of patients presenting more than 3 hours after stroke onset thought that their symptoms were not serious. The 24% (n = 16) of early arrivals were more likely to arrive by ambulance (81% versus 38%; P = .003) and had more severe stroke (Barthel Index score of 49 versus 72; P = .01) than late arrivals. Arrival by ambulance was independently associated with early arrival (odds ratio, 5.55; 95% confidence interval, 1.37 to 22.6). CONCLUSIONS: Approximately one quarter of stroke patients correctly interpret their symptoms as representing a stroke. This knowledge is not associated with early presentation to the emergency department. Ambulance transport is independently associated with early arrival at the emergency department. Even when patients know that they are having a stroke, most present late because they perceive their symptoms as "not serious." Widespread public education of stroke-prone individuals may increase the proportion of patients eligible for new acute stroke treatments.

Aged↗
PubMed1997

Subtypes of ischemic stroke in children and young adults.

Specific strategies for primary and secondary stroke prevention in children and young adults can only be recommended once the causes of stroke in these age groups are well described. ICD-9 codes were used to identify children aged 1 to 18 years with acute ischemic stroke. Young adults aged > 18 to 45 years were identified from the Indiana University and Northwestern University Young Adults Stroke Registries. Validated criteria were used to subtype ischemic stroke as atherothrombotic (AT), cardioembolic (CE), small-vessel (SV), other determined cause, or unknown cause. Ninety-two children and 116 young adults were identified. Stroke subtypes in children/young adults (percentages) were as follows: AT 0/16 (p < 0.001), CE 15/14 (p = 1.0), SV 0/3 (p = 0.26), other 49/44 (p = 0.40), and unknown 36/23 (p = 0.04). Children had more prothrombotic causes (25% versus 14%, p = 0.03), and young adults had more dissections (3% versus 15%, p = 0.005). Children aged 15 to 18 years had causes of ischemic stroke more similar to those in young adults. The cause of ischemic stroke is less often identified in children than it is in young adults. Children have more prothrombotic causes of stroke, and adults have more atherothrombotic causes and dissections. Lacunar strokes are rare in both children and young adults. The age of 15 years should be used to separate childhood from young-adult ischemic stroke.

Adolescent↗
PubMed1997

A brief overview of the initial location decisions of immigrants.

"The current longitudinal survey of recent migrants has provided information on the factors shaping their locational choices within Australia. The main finding is that family and friends are the dominant influence. Job opportunities are much less influential, even amongst Independent migrants."

Australia↗
PubMed1997

[Stroke therapy in children].

OBJECTIVE: To evaluate the treatment modalities used in children (ages 1-18 years) with cerebral infarction. BACKGROUND: [corrected] Cerebrovascular disease in children is more common than once suspected but its treatment has not been rigorously studied. MATERIAL AND METHODS: We reviewed all cases of cerebral infarction at the James Whitcomb Riley Hospital for Children at the Indiana University Medical Center from 01.01.80 to 31.12.95. RESULTS: Ninety-three children who experienced ischemic strokes were followed over the past fifteen years. Fifty-seven males and thirty-six females comprised the sample. Mean age was 6.9 years at the time of stroke. No medication or surgical intervention was the therapeutic recommendation in 44% of patients. For cardioembolic strokes, warfarin was used later in the course for a few patients who went on to have atrial fibrillation or valve replacement. Aspirin was used in all patients with carotid artery dissections. Aspirin was used in most children with Moya-Moya, with calcium channel blockers and surgical intervention used in later cases. Exchange transfusion followed by monthly transfusion and chelation therapy has been the treatment of choice for children with cerebral infarction complicating sickle cell disease. CONCLUSIONS: In most instances, treatment was widely disparate, probably reflecting the lack of firm therapeutic guidelines for this age group, with a better understanding of the etiology and pathophysiology of strokes in children, multicenter, international, randomized therapeutic trials based strictly on an etiological basis should be organized in the future.

Adolescent↗
PubMed1996

Evidence for human thromboxane receptor heterogeneity using a novel series of 9,11-cyclic carbonate derivatives of prostaglandin F2 alpha.

1. The pharmacological activity of a novel series of 9,11-cyclic carbonate derivatives of prostaglandin F2 alpha (PGF2 alpha) was investigated in various isolated smooth muscle preparations possessing different prostanoid receptor subtypes as well as in human platelets. Since subdivision of thromboxane (TP-) receptors into vascular/smooth muscle and platelet subtypes is a controversial subject, our studies included a human smooth muscle preparation (myometrium) in addition to the widely used rat aorta and human platelets as TP-receptor preparations. 2. Two members of that series, AGN191976 and AGN192093 were found to be highly potent and selective thromboxane-mimetics. AGN191976 and AGN192093 contracted isolated tissues of the rat thoracic aorta with EC50 values of 0.32 +/- 0.08 and 1.30 +/- 0.53 nM, respectively. Both agonists were at least 10 times more potent than the benchmark TP-agonist, U-46619, in this preparation, whilst being at least 500 times less potent at other prostanoid receptors (DP, EP1, EP3, FP, IP) in vitro. 3. In human myometrial strips from pregnant and non-pregnant donors, both AGN191976 and AGN192093 were potent contractile agonists. The rank order of potency in myometrium of AGN191976 > AGN192093 > U-46619 correlated well with that in the rat aorta. In human platelet-rich plasma (PRP), however, AGN191976 had potent proaggregatory activity (EC50 = 16.3 +/- 1.4 nM), which is a TP-receptor-mediated event, whereas AGN192093 was a much weaker agonist (EC50 = 37.9 +/- 2.0 microM). AGN192093 did not behave as an antagonist in the platelets, since it did not antagonize platelet aggregation induced by ADP, arachidonic acid, U-46619 or AGN191976. In human washed platelets, the activity profile of AGN191976 (EC50 = 4.15 +/- 0.52 nM) and AGN192093 (no aggregation up to 10 microM) was similar to that obtained in PRP. 4. The involvement of TP-receptors was verified with the potent TP-antagonist, SQ29548. SQ29548 (0.1 microM in myometrium; 1 microM in aorta; 1 microM and 10 microM in platelets) antagonized responses to U-46619, AGN191976 and AGN192093 as expected. 5. In conclusion, AGN191976 and AGN192093, both 9,11-cyclic carbonate derivatives of PGF2 alpha, were found to be highly potent and selective thromboxane-mimetics in rat vascular and human myometrial smooth muscle. However, only AGN 191976 was a potent agonist at TP-receptors in human platelets. The differential activity of AGN192093 on TP-receptor-mediated events in platelets and smooth muscle provides further evidence for a subdivision of TP-receptors. AGN192093 appears to be a useful tool for the pharmacological distinction of TP-receptor subtypes.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Non-isotopic method for quantitation of platelets and erythrocytes in experimental thrombi.

Experimental animal models of thrombosis have been established in several species to examine factors responsible for thrombotic disorders in man. One technical facet of all thrombosis models is the need to quantitate cell deposition on thrombogenic surfaces, and this is routinely accomplished with radioisotopic labeling of specific components. Data reported here demonstrate that formalin-fixed thrombi can be hydrolyzed with chymotrypsin allowing recovery and quantitation of platelets and erythrocytes incorporated within the clot. Recovery of platelets from in vitro generated, model thrombi averaged 99 +/- 10% (mean +/- 1 SD; n = 7; range 88-116%) of calculated content; recovery of erythrocytes was 94.1 +/- 1.1% (n = 6) as measured by recovery of cellular hemoglobin after chymotrypsin hydrolysis of clots. Chymotrypsin was also shown to release platelets and erythrocytes from string-bound thrombi generated in vivo with an arterio-venous shunt model in beagle dogs. Platelet recovery from these string clots after chymotrypsin hydrolysis was independently verified with a quantitative Western blot assay of platelet antigens. These data demonstrate that experimental thrombi can be hydrolyzed with chymotrypsin, thereby not only eliminating the need for radioisotopes, but also permitting flow cytometric analysis of cells comprising the thrombus.

Animals↗
PubMed1995

Texas beckons.

Many Canadian medical families have been approached by US headhunters anxious to recruit family physicians to practise in the US. Lynne Sears Williams and her husband, Calgary family physician Jim Williams, went to Texas to see what opportunities awaited. In this article she describes the high and low points of recruitment efforts south of the border.

Canada↗
PubMed1995

Alberta hospital tries to boost revenue by attracting gastroplasty patients from US.

The fate of a surgical weight-reduction program at the 25-bed hospital in Cardston, Alta., is in limbo as Alberta's Conservative government decides whether it will allow the hospital to keep profits made by performing gastroplasty on American patients last year. Cardston Municipal Hospital, which has had more than 1200 Canadian banded-gastroplasty patients since 1979, began recruiting American patients from Montana and Idaho last year. However, rumours that the Klein government will reduce the regional health authority's operating budget by an amount equal to the hospital's profit have jeopardized the program's future. The hospital first marketed the program in the US to cushion short-falls in government funding.

Alberta↗
PubMed1995

University of Calgary marks 25 years of medical training.

The University of Calgary Faculty of Medicine celebrates 25 years of innovative medical training in October. Its 3-year degree program has produced more than 1450 physicians since the first students entered the medical school in 1970. A reunion for former staff and students is planned for Oct. 12-14.

Alberta↗