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Biomedical subjects

L Sheppard

Publications and source records attributed to L Sheppard.

At least 55 records · Page 3Linked to original sources
PubMed1995

Oral iron chelation therapy with deferiprone. Monitoring of biochemical, drug and iron excretion changes.

The oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1, deferiprone, CAS 30652-11-0) has been given daily for 3-11 months to 6 transfusion dependent iron loaded patients (myelodysplasia (MDS) 2, Diamond-Blackfan anaemia 1, thalassaemia intermedia 1, thalassaemia major 2). Daily doses of 3 g, 2 x 2 g and 3 x 2 g were administered for the first 2-7 months. Daily doses of 2 x 3 g were also used for periods up to 4 months. Urine iron excretion following 3 g of L1 was found to be related to the number of previous transfusions but not to serum ferritin or the amount of L1 excreted. In each case 24 h urinary iron excretion in response to 3 g L1 ranged from 5-21 mg in MDS, 13-25 mg in a thalassaemia intermedia and a Diamond-Blackfan patient and 16-110 mg in thalassaemia major patients. Further increases of urinary iron were observed in all the patients when the daily dose was increased. Serum ferritin levels have fluctuated but overall have remained unchanged. Biochemical assessment did not show any major abnormalities ascribed to L1 except from subnormal serum zinc levels in two patients and white blood cell absorbate in another. In a separate study we have compared urinary L1 and iron excretions in 7 transfusional iron loaded patients. In all the cases the concentration of L1 was in excess of iron and higher than the level required for 100% iron binding. There was no other apparent correlation between the concentrations of L1 and iron in the urines studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Changing the public perception of physiotherapeutic treatment.

Market research was undertaken to establish the public perception of physiotherapy. Using this market research strategic recommendations for the future marketing of physiotherapy are made within the professional context. Marketing will be used to contribute to changing the public perception of physiotherapy. The market research involved a qualitative study of five focus groups of the general public and one focus group of physiotherapists. The responses from the focus groups were used to construct an appropriate questionnaire for the qualitative study. A random sample of 510 members of the general public were then surveyed. The market research results yielded the following key features: The best known conditions treated by physiotherapists are musculoskeletal. The least known are women and children. Client-centered care is sought. The importance of location gives potential for physiotherapists to capitalise on tailoring to clients in their area. Doctors are important for referral and communication about physiotherapy. Marketing should be used to inform doctors of what physiotherapy has to offer. A marketing orientation has begun within physiotherapy; however, it must 'fit' the culture initially to be successful. A marketing strategy should be developed on national, state and individual levels based on a strategic intent. At the state level, strategies must be responsive to area or regional needs. Marketing needs to target identified market segments such as workers compensation organisations. Individual physiotherapists must promote themselves within their region, particularly to doctors and clients with the use of relationship marketing. Informal presentations to community groups and school students about physiotherapy will increase their profile.

Adolescent↗
PubMed1994

Molecular cytogenetic analysis of inv dup(15) chromosomes, using probes specific for the Prader-Willi/Angelman syndrome region: clinical implications.

Twenty-seven cases of inverted duplications of chromosome 15 (inv dup [15]) were investigated by FISH with two DNA probes specific for the Prader-Willi syndrome/Angelman syndrome (PWS/AS) region on proximal 15q. Sixteen of the marker chromosomes displayed two copies of each probe, while in the remaining 11 markers no hybridization was observed. A significant association was found between the presence of this region and an abnormal phenotype (P < .01). This is the largest study to date of inv dup(15) chromosomes, that uses molecular cytogenetic methods and is the first to report a significant association between the presence of a specific chromosomal region in such markers and an abnormal phenotype.

Adolescent↗
PubMed1993

Selection of a new generation of orally active alpha-ketohydroxypyridine iron chelators intended for use in the treatment of iron overload.

The prospect of selecting oral alpha-ketohydroxypyridine chelators intended for clinical use in iron overload has been examined using several animal models of efficacy and toxicity. Studies using iron dextran-loaded mice labelled with 59Fe have shown that only the 1-substituted methyl, ethyl, (n)propyl, allyl, cyclopropyl, 2'-methoxyethyl, 3'-ethoxypropyl, or 2-methyl- or 2-ethyl-3-hydroxypyrid-4-one chelators were orally effective in increasing iron (59Fe) excretion by comparison to intraperitoneally administered desferrioxamine at the same dose (250 mg/kg). In contrast, chelators containing -H, mono- or dihydroxyalkyl and diethoxyethyl 1-substituents caused very little or no increase in iron (59Fe) excretion by the oral or intraperitoneal routes. In vitro studies using ferritin and haemosiderin have shown that equivalent iron release took place with both groups of chelators irrespective of their in vivo effects. In most cases there was no correlation between the n-octanol/water partition coefficient (Kpar) and iron removal efficacy but positive correlation between the lipophilicity and acute or subacute toxicity of these chelators in rats. The most toxic chelator in the chronic toxicity studies in rats was the lipophilic 1,2-diethyl-3-hydroxypyrid-4-one (EL1NEt). The most effective chelator in increasing iron excretion in mice and rabbits was 1-allyl-2-methyl-3-hydroxypyrid-4-one (L1NAII), and the chelator with the highest safety margin in mice and rats was 1,2-dimethyl-3-hydroxypyrid-4-one (L1). Overall the oral effectiveness in increasing iron excretion by these chelators in animals does not appear to be related to their lipophilicity or their ability to mobilise polynuclear iron in vitro but rather to other properties possibly related to their rate of biotransformation and excretion.

Absorption↗
PubMed1991

Weight loss in women participating in a randomized trial of low-fat diets.

We examined weight changes over 1 and 2 y in 303 women enrolled in a low-fat dietary-intervention trial. Participants were randomly assigned to an intervention group that received intensive instruction in maintaining a low-fat diet or to a control group. After 1 y intervention-group women had decreased fat intake by 45.3 g (from 39.2% to 21.6% energy from fat) and weight by 3.1 kg (all P less than 0.0001); control-group women decreased fat intake by 8.8 g (from 38.9% to 37.3% energy from fat) and weight by 0.4 kg. In both univariate analyses and multivariate models, weight loss was more strongly associated with change in percent energy from fat than with change in total energy intake. These data, which are consistent with both epidemiologic and clinical studies, suggest that body adiposity is a function both of energy balance and the proportion of energy derived from fat.

Aged↗
PubMed1991

Early results of the Leeds-Keio anterior cruciate ligament replacement.

We report the two- to four-year results following the insertion of the Leeds-Keio prosthetic ligament for chronic anterior cruciate deficiency. Virtually all the 20 patients were less disabled by instability, but objective results were good or excellent in only two-thirds and under anaesthesia the pivot shift sign was still positive in half. Arthroscopic and histological assessment in 16 patients failed to show the development of a functional neoligament, and the common appearance of a synovitic reaction to polyester particles gave concern.

Activities of Daily Living↗
PubMed1990

Dietary fat and cancer: consistency of the epidemiologic data, and disease prevention that may follow from a practical reduction in fat consumption.

International variations and national time trends in disease rates suggest major associations between dietary fat and several important cancers. In contrast, case-control and cohort studies of dietary fat in relation to the same cancers generally report weak associations, or have failed to detect any association with fat intake. This study was undertaken in an attempt to understand the apparent discrepancy between these observations. The results provide an insight into the magnitude of cancer risk reduction that may follow from a practical reduction in dietary fat. Regression analyses of international variations in cancer incidence rates were used to estimate relative risks (RR) as a function of fat intakes for both males and females. These analyses focused on cancers of the breast, colon, rectum, ovary, and endometrium in females, and colon, rectum, and prostate cancers in males. Ages 55-69 and 30-44 were considered in order to compare RR estimates between an older and younger age group, and between post- and pre-menopausal women. Corresponding RR estimates were also calculated, based on the regression of changes in disease rates from the mid-1960s to 1980 on changes in dietary fat, using data from several countries. A strong degree of consistency with the RR estimates from international comparisons was observed. The international regression analyses were also used to project changes in cancer rates among Japanese migrants to the United States. A high level of consistency with the observed disease-rate changes was noted. Similarly, the international data analyses were used to project RRs for the fat intake categories used in specific case-control and cohort studies, while acknowledging measurement error in individual dietary assessment. Although certain exceptions are noted, considerable consistency was found between the aggregate and analytic data results, leaving open the strong possibility that a practical reduction in dietary fat could result in a major reduction in the incidence of several prominent cancers in the United States and in other nations having high fat consumption.

Adult↗
PubMed1990

Pharmacokinetic studies in humans with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one.

Pharmacokinetic studies have been carried out with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). HPLC analysis of serum of a normal volunteer and seven transfusional iron loaded patients who ingested a 3 gm dose of L1 revealed that L1 was most probably absorbed from the stomach and was transferred to the blood with a half-life of 0.7 to 32 minutes. L1 reached maximum concentration in the serum 12 to 120 minutes after administration with 85% to 90% elimination within the first 5 to 6 hours, with a half-life of 47 to 134 minutes. L1 and its glucuronide metabolite were identified in serum and urine but not in feces. In most cases hydrolysis of 24-hour urine samples with use of beta-glucuronidase resulted in almost complete recovery of the administered dose. Urinary iron excretion was proportional to the iron load but not to the serum or urine concentration of L1. The therapeutic efficiency of L1 can therefore be improved by repeated administration of 2 to 3 gm doses at least every 6 hours.

Adult↗
PubMed1990

Long-term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). I. Iron chelation and metabolic studies.

A long-term clinical trial of 1-15 months has been carried out with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in 13 transfusion-dependent iron-loaded patients. Urinary iron excretion was greatest in patients with thalassaemia major and was related to the number of previous transfusions but not to the serum ferritin level. Substantial increases of urinary iron were observed in all the patients when the frequency of the daily dose was doubled and in response to 2 x 3 g L1 daily 11 of 12 patients tested excreted greater than 25 mg iron daily, the mean daily intake of iron from transfusion. Serum ferritin levels have fluctuated but overall have remained unchanged. Pharmacological studies in five patients have indicated rapid absorption probably from the stomach and variable plasma half life of 77 +/- 35 min (X +/- SD). Glucuronation was identified as a major route of L1 metabolism. Short-term intensive chelation studies using repeated administration of L1 resulted in further increases of urinary iron excretion by comparison to a single dose. In one case 325 mg of iron were excreted in the urine following the administration of 16 g (5 x 2 g + 2 x 3 g) within 24 h. Iron excretion studies were carried out in six transfusional iron-loaded patients who were maintained on a low iron diet before and during chelation. No significant increases of faecal iron excretion were observed with L1 using daily doses of up to 3 x 3 g and 4 x 2 g. The high level of compliance during treatment with L1 and the levels of urine iron excretion that can be achieved increase the prospects for oral chelation in transfusional iron-loaded patients.

Anemia↗
PubMed1989

Validity of international, time trend, and migrant studies of dietary factors and disease risk.

A linear form relative risk model is used to identify circumstances in which various types of aggregate data lead to valid inferences on relative risk parameters. Upon making a random effects assumption, international or time trend data can lead to appropriate relative risk parameter estimation using iteratively reweighted least-squares procedures. Adequate confounding factor control, however, will typically require data on the distribution of confounding factors in each country or time period. For a simple interpretation of relative risk parameters one may also require data on the joint distribution of primary and confounding factors in each country or time period. Hence disease rate data need to be supplemented by dietary and risk factor survey data in order to avoid confounding bias. Measurement error in individual dietary assessment may, however, limit the ability to quantify the dependence of relative risk on dietary factors, unless the relative risk function is approximately linear in the dietary factors of interest. Most studies of migrant populations involve a comparison of migrant mortality rates with those of their countries of emigration and immigration, with little or no data collection on the dietary habits and risk factors of the migrants themselves. The potential of more comprehensive aggregate data and analytic migrant studies in the diet and disease area is briefly indicated. These issues and methods are illustrated using various types of data pertinent to the association between dietary fat and breast cancer.

Breast Neoplasms↗
PubMed1988

Aspects of the rationale for the Women's Health Trial.

A 5.5-fold range in breast cancer incidence rates in 21 countries shows strong correlation with national estimates of per capita intake of dietary fat, but not with other caloric sources (proteins and carbohydrates). It is argued that certain breast cancer and hormone factors may contribute little to the explanation of such international variations in incidence of this neoplasm. It is further argued that experimental studies in animals support a specific role for dietary fat in the promotion of mammary tumors, but the effects of calories alone seem to be largely restricted to tumor initiation. Finally, data from international, migrant-population, and analytic epidemiologic investigations are used to motivate the basic relative risk assumption of study designs thus far proposed for the Women's Health Trial, and some continuing motivations for a dietary intervention (low-fat diet) trial are discussed.

Aged↗
PubMed1988

Treatment of neonatal necrotizing tracheobronchitis with extracorporeal membrane oxygenation and bronchoscopy.

Necrotizing tracheobronchitis has recently been described as a complication of mechanical ventilation of newborns with respiratory failure. Despite the use of bronchoscopy, 45% of the reported patients to date have died. In this study, we report the use of extracorporeal membrane oxygenation (ECMO) to stabilize two patients with necrotizing tracheobronchitis. While supported by bypass, both patients underwent prolonged bronchoscopies with removal of extensive amounts of tracheal debris. ECMO provided efficient oxygenation in the face of near total airway occlusion, and permitted far more extensive bronchoscopic debridement and lavage than would have been possible if the lungs were required for oxygenation. In addition, ECMO provided a period of lung "rest" during which ventilator settings were reduced, thus minimizing further barotrauma and allowing for lung and airway healing. Both patients recovered without significant respiratory sequelae. ECMO and bronchoscopy are effective forms of therapy for patients with life-threatening necrotizing tracheobronchitis when conventional modalities of treatment have failed.

Bronchitis↗
PubMed1988

Sensory threshold estimation from a continuously graded response produced by reflex modification audiometry.

This article describes the use of reflex modification to determine sensory detection thresholds. The method is based upon the finding that low-intensity sensory stimuli presented shortly before a reflex eliciting stimulus are able to modify the amplitude of the reflex. The extent of such modification is related to the intensity of the initial low-intensity stimulus. In contrast to earlier reported procedures for threshold estimation, the method described in this article consists of fitting a smooth function to the relationship between startle response amplitude and the intensity of the inhibiting stimulus. The method entails fitting a cubic spline function to the medians of the square-root reflex amplitude at each prestimulus intensity. The resulting audiometric curves closely approximate audiometric data obtained from traditional operant methods both in sensitivity and shape. Parametric data are also presented that allow for optimizing stimulus presentation so as to obtain reliable thresholds using a minimal number of test trials. The procedures developed in this article may prove useful in other situations involving the estimation of a threshold effect from a continuously graded response.

Animals↗
PubMed1988

Expert-system-based fuzzy control of arterial pressure by drug infusion.

This paper proposes a new type of fuzzy controller which is based on the general-purpose Fuzzy LOgic Production System shell FLOPS [1, 2, 7, 12, 13]. Human mean arterial pressure was controlled by the proposed fuzzy controller, in digital computer stimulation, by regulating the infusion rate of the drug, sodium nitroprusside. Under nonstationary arterial background pressure noise, mean arterial pressures of different patients with different sensitivities to sodium nitroprusside were controlled satisfactorily. Furthermore, the effects of changing the adjustable parameters of the proposed fuzzy controller on the control results were studied. Finally, the performance of the proposed fuzzy controller was compared to that of a fine-tuned Proportional-Integral (PI) controller by using a first-order linear model.

Blood Pressure↗