Biomedical subjects
Publications and source records attributed to D Lewis.
Responding to concerns for weight loss and nutritional status of its patients, a Transitional Care Unit (TCU) began an intensive Medication Pass Supplement Program. It involves nurses administering a dietitian-reviewed and approved nutritional supplement for specified residents with every medication pass. As a result, 94% of discharged patients lost less than 5% of their admission weight.
OBJECTIVE: To test the feasibility and importance of measuring preferences among treatment choices using Healthy Years Equivalents (HYE). DESIGN: Development of scenarios for alternative approaches to caries treatment. Completion of category rating and standard gamble questions elicited in personal interviews. SETTING: The provision of dental care to children in a public-funded dental health clinic. PARTICIPANTS: Random sample of the adult population of Hamilton, Ontario. MAIN OUTCOME MEASURES: The percentage of the sample unable to complete the interviews, time taken to perform interviews, ease of understanding of interviews, correlation between rank ordering and HYE scores. RESULTS: Ninety-six per cent of the sample were able to complete the HYE exercise. Inconsistencies between HYE scores and rank orders implying preference reversal occurred in 6% of those completing HYE scores for the two scenarios. The additional time taken by the HYE was of the order of 17 minutes but increased with the age of the subject. Where problems occurred, they were related to the method of measurement or the sensitivity of the chosen scale as opposed to additional requirements of the HYE. There was some evidence that HYEs and QALYs produced different scores even in the context of chronic constant health states. CONCLUSIONS: HYEs are a feasible and important practical method of measuring preferences among interventions. Alternative utility-based approaches, such as willingness to pay, may be required to detect differences in modest improvements in temporary health states.
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The peptide segment interposed between cation binding and phosphorylation domains retains a high degree of homology in all cation transport ATPases. Mutational analysis and chimeric replacements of Ca2+ ATPase components with corresponding Na+,K(+)-ATPase components indicate that this segment is utilized by various cation ATPases as a common structural device for a long-range functional linkage of enzyme phosphorylation and cation transport. Vectorial displacement of bound cation is rendered possible by a transmembrane channel formed by four clustered helices (M4, M5, M6, and M8). Originating from the four helices, the oxygen functions of Glu309, Glu771, Thr799, Asp800, and Glu908 form a duplex Ca2+ binding site in the middle of the channel, while Lys297 seals the luminal end of the channel with its positively charged side chain. The perturbation triggered by enzyme phosphorylation is apparently transmitted through the linkage segment to produce rotational displacement of the M4 helix with minimal change of secondary structure. The cation binding site is thereby disrupted and the Lys297 side chain removed, permitting Ca2+ to dissociate in exchange for H+ and to flow through the luminal end of the channel.
BACKGROUND: Familial amyloidosis (FAP) is characterized by the progression of neurologic and cardiac impairment ultimately leading to death within 7 to 15 years after the onset of the disease. Liver transplantation represents the only definitive therapy for this disease and has been performed since 1990. METHODS: To determine the effect of liver transplantation on disease progression, electrocardiography and Doppler echocardiography were performed and blindly analyzed on 11 patients with FAP who were followed 0.8 to 8.6 years before liver transplantation and 0.8 to 4.1 years after liver transplantation. RESULTS; After liver transplantation, five patients showed progression of left ventricular wall thickening with increased left ventricular mass, and three of these five showed a reduction in electrocardiographic voltage despite abolition of the mutant protein from the serum. Of the five patients showing progressive wall thickening, four had the transthyretin variant Glu 42 Gly and one patient had the Ala 36 Pro variant; none of the remaining six patients, all of whom possessed the Val 30 Met variant, showed echocardiographic changes. Although 9 of the 11 patients have shown symptomatic improvement in neurologic symptoms, 1 patient has developed heart failure and a second patient has suffered a sudden cardiac death. CONCLUSIONS: After liver transplantation, patients with FAP should have regular clinical evaluations including electrocardiographic and echocardiographic examinations to look for continued deterioration in heart structure or function.
On November 29-30, 1995, the National Academy of Sciences and the Institute of Medicine brought together experts in schizophrenia and specialists in other areas of the biological sciences in a workshop aimed at promoting the application of the latest biological information to this clinical problem. The workshop paid particular attention to evidence of pathology in the brains of people with schizophrenia, and to the possibility that this reflects an abnormality in brain development that eventually leads to the appearance of symptoms. The participants were impressed with the complexity of the problem, and felt that multiple approaches would be required to understand this disease. They recommended that a major focus should be on the search for predisposing genes, but that there should be parallel research in many other areas.
A new series of heteroaromatic GBR 12935 [1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine] (I) and GBR 12909 [1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine] (2) analogs was synthesized and evaluated as dopamine transporter (DAT) ligands. Analogs 5-16, in which the benzene ring in the phenylpropyl side chain of the GBR molecule had been replaced with a thiophene, furan, or pyridine ring, exhibited high affinity and selectivity for the DAT vs serotonin transporter (SERT) and stimulated locomotor activity in rats in a manner similar to the parent compound 2. In cocaine and food self-administration studies in rhesus monkeys, both thiophene-containing (6 and 8) and pyridine-containing (14 and 16) derivatives displayed potency comparable to 2 in decreasing the cocaine-maintained responding at the doses tested (0.8, 1.7, and 3 mg/kg). However, these compounds did not produce the degree of separation between food- and cocaine-maintained responding that was seen with 2. Among the bicyclic fused-ring congeners 17-38, the indole-containing analog of 2, 22, showed the greatest affinity for binding to the DAT, with IC50 = 0.7 nM, whereas the corresponding indole-containing derivative of 1, 21, displayed the highest selectivity (over 600-fold) at this site vs the SERT site.
The use of hair as a specimen for the determination of drug use remains controversial. Scientists disagree upon whether environmental drug contamination (e.g. smoke) can be differentiated from actual drug use. Children whose parents use drugs (particularly crack) at home are considered to be at risk. Using the hair of the children to determine exposure gives extra credibility to the child protective services and allows them to remove children from dangerous households. Children are tested when there are credible reasons for suspecting drug exposure. In Blackhawk Country, Iowa, this program was implemented in late 1994, and since then many children have tested positively for drugs, the majority of the hair containing cocaine or methamphetamine. In some cases, cocaethylene and benzoylecgonine were also found in the hair of the children. While the presence of benzoylecgonine can be explained by exposure to crack smoke, the presence of cocaethylene suggests ingestion of cocaine and alcohol. Blackhawk Country Juvenile Court have found the program to be so useful in helping children, that they have extended hair testing from Child Protective allegation investigations to ongoing court cases and even delinquency hearings.
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Programme Budgeting (PB) has been widely promoted as a model for the better conduct of the work of Health Authorities in the National Health Service in the United Kingdom. This paper reports on a project which looked at the development of PB in Newcastle and North Tyneside Health Authority (NNTHA), concentrating on the construction of a computerised tool for the compilation and analysis of programme budgets. The main activities carried out were a survey of user requirements for PB, a survey of data availability, the collection of data to construct programme budgets, and development of a relational database for storing and manipulating PB information. The main source of data was the Contract Minimum Data Set, which was supplemented by data from a number of other sources to give comprehensive information on spending in NNTHA. Costed activity data were produced, which could be aggregated in a large number of ways, such as by care setting (inpatient, outpatient, community, general practice, etc.), disease group (ICD9 chapter headings), case mix (Healthcare Resource Groups) and socio-demographic variables (age/sex, locality of GPs practice).
Eight samples of 'processed food flavours' (PFFs), chosen from five different categories, were analysed for their mutagenic activity using the Ames Salmonella assay, and also for the presence of eight heterocyclic aromatic amines (HAAs), namely 2-amino-3-(trideuteromethyl)imidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx), 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (4,7,8-TriMeIQx), 2-amino-I-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) using liquid chromatography and mass spectrometry (LC/MS). The isolation of HAAs was based on sequential liquid-liquid extraction procedures of samples at both acidic and basic pH values. The recoveries and the clean-up were monitored by introduction of quality control samples and by spiking with three tri-deuterated standards of HAAs. Although the results for the mutagenicity assay were comparable by testing less-purified and highly-purified extracts, the analysis for identification and quantification of HAAs by LC/MS required highly purified concentrates. Four samples had little or no mutagenic activity and these results were in agreement with their LC/MS results: they had no detectable levels (detection limits 1-3 ppb) of any of the HAAs monitored. The mutagenic activity of one sample was in complete agreement with the quantification of HAAs by LC/MS. Two samples produced strong mutagenic responses (3115 and 2664 revertants/g). In one sample, LC/MS analysis revealed the presence of 9.6 ppb IQ, whereas LC/MS of the other could not confirm the presence of any of the eight HAAs monitored. Two samples produced mild mutagenic activity (204 and 160 revertants/g), but relatively elevated concentrations of IQ (6.7 and 6.8 ng/g) by LC/MS. The extracts from all samples were tested for their modifying effects on mutagenicity of four HAAs. The discrepancy between the Ames test and the LC/MS analysis of some samples indicates several possibilities, such as the presence of some other HAAs, of their isomers or of other mutagens. In addition, the presence of mutagen modifiers (inhibitors or synergists) was observed in most samples. The results indicate that although chemical tests (e.g. LC/MS) can provide quantitative data for the HAAs monitored, the Ames mutagenicity test should also be conducted to determine the mutagenic activities of PFFs, in order to assess their health risk potential.
In an ongoing survey, the presence of heterocyclic aromatic amines (HAAs) was determined in processed, ready-to-eat meat products sold as 'meat cuts'. HAAs are a group of recently recognized mutagenic/carcinogenic contaminants in foods that are produced during the heat processing of meat. 16 samples of meat cuts (e.g. turkey breast, salami, chicken loaf, cooked ham, all beef meat, pepperoni, etc.), randomly purchased from supermarkets and specialty food stores in the Ottawa area, were analysed for the presence of eight HAAs. The isolation of HAAs was based on sequential liquid-liquid extraction procedures of the samples at both acidic and basic pH values. The mutagenic activity of these samples was determined using the Ames/Salmonella microsome assay with the strain TA98 plus rat liver S-9 metabolic activation. The mutagenicity of these samples ranged from undetectable to slightly active. The highest mutagenic activity, 141 induced revertants/g, was found in a smoked turkey breast sample. 11 samples were not mutagenic, including two that indicated a tendency for inhibition of the spontaneous revertants. The remaining four samples exhibited very low mutagenic activity. For chemical analysis, the extracts were purified with two solid phase extraction cartridges. Quantitative analysis was performed by using liquid chromatography for separation and mass spectrometry for detection. With the exception of trace amounts (0.4 ng/g) of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in the sample with highest mutagenic activity, the chemical analysis did not detect the presence of any of the eight most frequently found HAAs in fried or broiled meat products. These data suggest that consumption of meat cuts does not present a serious health risk from HAA-type contaminants.
The epidemiology of the association between migraine and epilepsy is reviewed. Migraine-related epilepsy is categorized using defined diagnostic criteria. Migraine-induced epilepsy is only one of several migraine-related epileptic syndromes.
The purpose of this study was to evaluate the use of ultrasound in identifying fetal position and cervical spine flexion in breech presentations. Radiographic and ultrasonographic determinations of the type of presentation (frank, complete or incomplete) and degree of cervical spine flexion in 52 breech presentations were compared. The angle of flexion was defined as the angle between the fetal mandible and main axis of the cervical spine and categorized as full flexion, military, partial extension and full extension. Ultrasound was concordant with radiographic assessment of the type of presentation in 77% and the angle of flexion in 64% of the subjects and was even more accurate in those in labor. All cases predicted as having full flexion (< 90 degrees C) of the cervical spine by ultrasound had an angle of flexion < or = 90 degrees C on radiographic assessment. Of subjects in labor, ultrasound accurately identified the type of breech presentation in all cases. In addition, sonographic identification of full flexion of the cervical spine excludes cases of fetal neck extension and precludes the need for radiographic assessment prior to a trial of labor.
Abundance of anophelines in 10 villages in the Wosera area of Papua New Guinea was monitored during 1990-1993. Of 85,197 anophelines collected in 1,276 paired indoor and outdoor landing catches, 40.4% were Anopheles koliensis Owen, 36.7% An. punctulatus Donitz, 14.3% An. karwari (James), 4.9% An. farauti s.l. Laveran, 3.1%, An, longirostris Brug, and 0.7% An. bancroftii Giles. Maps of average indoor biting rates were produced using a Bayesian conditional autoregressive model which allowed for heterogeneities in sampling effort over time and space. Differences in spatial distributions among species were observed among and within villages and were related to the distribution of larval habitats and vegetation. Abundance of An. punctulatus and An. koliensis decreased with distance from the main waterway and probably from a sago swamp forest at 6 villages in North Wosera. Abundance of An. punctulatus was associated negatively with those of An. farauti s.l., An. longirostris, and An. bancroftii. The latter 3 species also had relatively low ratios of indoor-to-outdoor biting rates, and earlier biting times than An. punctulatus. Human blood indices of at least 0.79 were observed for all species except An. bancroftii. Abundance of all 6 species was correlated temporally with recent rainfall, but An. koliensis, An. karwari, and An. longirostris showed greater temporal variability than the other species. An punctulatus and An. koliensis tended to occur together in time and space (index of association, I = 0.85). Weaker associations were seen between An. farauti s.l. and An. longirostris (I = 0.44) and An. koliensis and An. karwari (I = 0.34). The most frequently collected species occurred together and were concentrated near the Amugu river; the remaining species tended to occur together but in different parts of the Wosera area. The importance of understanding ecological requirements of the different Anopheles vectors and their association with key household and landscape features are discussed in relation to malaria transmission and control.
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