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Biomedical subjects

M Jackson

Publications and source records attributed to M Jackson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Infection control dogma: top 10 suspects.

As infection control evolved into an art and science through the years, many infection control practices have become infection control dogmas (principles, beliefs, ideas, or opinions). In this "Reality Check" session of the 4th Decennial International Conference on Nosocomial and Healthcare-Associated Infections, we assessed participants' perceptions of prevalent infection control dogmas. The majority of participants agreed with all dogmas having evidence of efficacy, except for the dogma on the frequency of changing mechanical-ventilator tubing. In contrast, the majority of participants disagreed with dogmas not having evidence of efficacy, except for the dogma on perineal care, umbilical cord care, and reminder signs for isolation precaution. As for controversial dogmas, many of the responses were almost evenly distributed between "agree" and "disagree." Infection control professionals were knowledgeable about evidence-based infection control practices. However, many of the respondents still believe in some of the non-evidence-based dogmas.

Attitude of Health Personnel↗
PubMed2001

Cell wall core galactofuran synthesis is essential for growth of mycobacteria.

The mycobacterial cell wall core consists of an outer lipid (mycolic acid) layer attached to peptidoglycan via a galactofuranosyl-containing polysaccharide, arabinogalactan. This structural arrangement strongly suggests that galactofuranosyl residues are essential for the growth and viability of mycobacteria. Galactofuranosyl residues are formed in nature by a ring contraction of UDP-galactopyranose to UDP-galactofuranose catalyzed by the enzyme UDP-galactopyranose mutase (Glf). In Mycobacterium tuberculosis the glf gene overlaps, by 1 nucleotide, a gene, Rv3808c, that has been shown to encode a galactofuranosyl transferase. We demonstrate here that glf can be knocked out in Mycobacterium smegmatis by allelic replacement only in the presence of two rescue plasmids carrying functional copies of glf and Rv3808c. The glf rescue plasmid was designed with a temperature-sensitive origin of replication and the M. smegmatis glf knockout mutant is unable to grow at the higher temperature at which the glf-containing rescue plasmid is lost. In a separate experiment, the Rv3808c rescue plasmid was designed with a temperature-sensitive origin of replication and the glf-bearing plasmid was designed with a normal original of replication; this strain was also unable to grow at the nonpermissive temperature. Thus, both glf and Rv3808c are essential for growth. These findings and the fact that galactofuranosyl residues are not found in humans supports the development of UDP-galactopyranose mutase and galactofuranosyl transferase as important targets for the development of new antituberculosis drugs.

Bacterial Proteins↗
PubMed2001

An echocardiographic assessment of cardiac morphology and common ECG findings in teenage professional soccer players: reference ranges for use in screening.

OBJECTIVE: To assess physiological cardiac adaptation in adolescent professional soccer players. SUBJECTS AND DESIGN: Over a 32 month period 172 teenage soccer players were screened by echocardiography and ECG at a tertiary referral cardiothoracic centre. They were from six professional soccer teams in the north west of England, competing in the English Football League. One was excluded because of an atrial septal defect. The median age of the 171 players assessed was 16.7 years (5th to 95th centile range: 14-19) and median body surface area 1.68 m(2) (1.39-2.06 m(2)). MAIN OUTCOME MEASURES: Standard echocardiographic measurements were compared with predicted mean, lower, and upper limits in a cohort of normal controls after matching for age and surface area. Univariate regression analysis was used to assess the correlation between echocardiographic variables and the age and surface area of the soccer player cohort. ECG findings were also assessed. RESULTS: All mean echocardiographic variables were greater than predicted for age and surface area matched controls (p < 0.001). All variables except left ventricular septal and posterior wall thickness showed a modest linear correlation with surface area (r = 0.2 to 0.4, p < 0.001); however, left ventricular mass was the only variable that was significantly correlated with age (r = 0.2, p < 0.01). Only six players (3.5%) had structural anomalies, none of which required further evaluation. All had normal left ventricular systolic function. Sinus bradycardia was found in 65 (39%). The Solokow-Lyon voltage criteria for left ventricular hypertrophy were present in 85 (50%) and the Romhilt-Estes points score (five or more) in 29 (17%). Repolarisation changes were present in 19 (11%), mainly in the inferior leads. CONCLUSIONS: Chamber dimensions, left ventricular wall thickness and mass, and aortic root size were all greater than predicted for controls after matching for age and surface area. Sinus bradycardia and the ECG criteria for left ventricular hypertrophy were common but there was poor correlation with echocardiographic left ventricular hypertrophy. The type of hypertrophy found reflected the combined endurance and strength based training undertaken.

Adaptation, Physiological↗
PubMed2001

Canine model and genomic structural organization of glycogen storage disease type Ia (GSD Ia).

A canine model of glycogen storage disease Ia (GSD Ia), similar clinically, biochemically, and pathologically to the human disease, was established by crossbreeding Maltese and Beagle dogs carrying a mutated, defective glucose-6-phosphatase (G-6-Pase) gene. Ten puppies were born in three litters from these crossbreedings. Six were homozygous for the previously described M121I GSD Ia mutation. Of these six affecteds, two were stillborn, and one died at 2, 32, and 60 days of life, respectively (puppies A, B, C, D, E), while one is alive at age 15 months (puppy F). Affected puppies exhibited tremors, weakness, and neurologic signs when hypoglycemic. They had postnatal growth retardation and progressive hepatomegaly. Biochemical abnormalities included fasting hypoglycemia, hyperlactacidemia, hypercholesterolemia, hypertriglyceridemia, and hyperuricemia. Microscopic examination of tissues from affected puppies showed diffuse, marked hepatocellular vacuolation, with distended clear hepatocytes and central to marginally located rounded nuclei. In the kidneys of puppies D and E, there was segmental glomerular sclerosis and vacuolation of proximal convoluted tubular epithelium. Biochemical analysis revealed increased liver glycogen content and isolated markedly reduced G-6-Pase enzyme activity in liver and kidney. The canine G-6-Pase gene was characterized by screening a canine genomic library. It spans approximately 11.8 kb and consists of five exons with >90% amino acid sequence homology to the derived human sequence. The first 1.5 kb of the 5' region was sequenced and contains several putative response element motifs homologous to the human 5' region. Establishment of this canine colony of GSD Ia that closely resembles human disease and isolation of the canine genomic gene provides an excellent model for studying pathophysiology and long-term complications and an opportunity to develop novel therapeutic approaches such as drug and gene therapy.

Animals↗
PubMed2001

Effect of increased dietary protein and decreased dietary carbohydrate on performance and body composition in racing Greyhounds.

OBJECTIVE: To determine effects of increased dietary protein and decreased dietary carbohydrate on hematologic variables, body composition, and racing performance in Greyhounds. ANIMALS: 8 adult Greyhounds. PROCEDURE: Dogs were fed a high-protein (HP; 37% metabolizable-energy [ME] protein, 33% ME fat, 30% ME carbohydrate) or moderate-protein (MP; 24% ME protein, 33% ME fat, 43% ME carbohydrate) extruded diet for 11 weeks. Dogs subsequently were fed the other diet for 11 weeks (crossover design). Dogs raced a distance of 500 m twice weekly. Rectal temperature, hematologic variables before and after racing, plasma volume, total body water, body weight, average weekly food intake, and race times were measured at the end of each diet period. RESULTS: When dogs were fed the MP diet, compared with the HP diet, values (mean +/- SD) differed significantly for race time (32.43 +/- 0.48 vs 32.61 +/- 0.50 seconds), body weight (32.8 +/- 2.5 vs 32.2 +/- 2.9 kg), Hct before (56 +/- 4 vs 54 +/- 6%) and after (67 +/- 3 vs 64 +/- 8%) racing, and glucose (131 +/- 16 vs 151 +/- 27 mg/dl) and triglyceride (128 +/- 17 vs 104 +/- 28 mg/dl) concentrations after racing. CONCLUSIONS AND CLINICAL RELEVANCE: Greyhounds were 0.18 seconds slower (equivalent to 0.08 m/s or 2.6 m) over a distance of 500 m when fed a diet with increased protein and decreased carbohydrate. Improved performance attributed to feeding meat to racing Greyhounds apparently is not attributable to increased dietary protein and decreased dietary carbohydrate.

Animal Feed↗
PubMed2000

Autosomal recessive cerebellar ataxia with oculomotor apraxia (ataxia-telangiectasia-like syndrome) is linked to chromosome 9q34.

Ataxia with oculomotor apraxia (ataxia-telangiectasia-like syndrome [AOA]; MIM 208920) is an autosomal recessive disorder characterized by ataxia, oculomotor apraxia, and choreoathetosis. These neurological features resemble those of ataxia-telangiectasia (AT), but in AOA there are none of the extraneurological features of AT, such as immunodeficiency, neoplasia, chromosomal instability, or sensitivity to ionizing radiation. It is unclear whether these patients have a true disorder of chromosomal instability or a primary neurodegenerative syndrome, and it has not been possible to identify the defective gene in AOA, since the families have been too small for linkage analysis. We have identified a new family with AOA, and we show that the patients have no evidence of chromosomal instability or sensitivity to ionizing radiation, suggesting that AOA in this family is a true primary cerebellar ataxia. We have localized the disease gene, by linkage analysis and homozygosity mapping, to a 15.9-cM interval on chromosome 9q34. This work will ultimately allow the disease gene to be identified and its relevance to other types of autosomal recessive cerebellar ataxias to be determined.

Acid Anhydride Hydrolases↗
PubMed2000

Phosphatidylinositol is an essential phospholipid of mycobacteria.

Phosphatidylinositol (PI) and metabolically derived products such as the phosphatidylinositol mannosides and linear and mature branched lipomannan and lipoarabinomannan are prominent phospholipids/lipoglycans of Mycobacterium sp. believed to play important roles in the structure and physiology of the bacterium as well as during host infection. To determine if PI is an essential phospholipid of mycobacteria, we identified the pgsA gene of Mycobacterium tuberculosis encoding the phosphatidylinositol synthase enzyme and constructed a pgsA conditional mutant of Mycobacterium smegmatis. The ability of this mutant to synthesize phosphatidylinositol synthase and subsequently PI was dependent on the presence of a functional copy of the pgsA gene carried on a thermosensitive plasmid. The mutant grew like the control strain under permissive conditions (30 degrees C), but ceased growing when placed at 42 degrees C, a temperature at which the rescue plasmid is lost. Loss of cell viability at 42 degrees C was observed when PI and phosphatidylinositol dimannoside contents dropped to approximately 30 and 50% of the wild-type levels, respectively. This work provides the first evidence of the essentiality of PI to the survival of mycobacteria. PI synthase is thus an essential enzyme of Mycobacterium that shows promise as a drug target for anti-tuberculosis therapy.

Amino Acid Sequence↗
PubMed2000

Noninvasive localization of tumors by immunofluorescence imaging using a single chain Fv fragment of a human monoclonal antibody with broad cancer specificity.

BACKGROUND: A single chain antibody fragment, NovoMAb-G2-scFv, derived from a human anti-tumor monoclonal antibody recognizes tumor antigen molecules expressed on a wide variety of human cancers including melanoma, breast carcinoma, colon adenocarcinoma, squamous cell carcinoma, lung carcinoma, and prostate carcinoma. This study was designed to evaluate the use of a NovoMab-G2-scFv/cyanine fluorochrome (Cy5.5.18) conjugate as diagnostic tool for in vivo imaging of tumors. METHODS: The NovoMab-G2-scFv-Cy5 complex was administered to athymic mice injected subcutaneously with human melanoma tumor cells, and the distribution of fluorescence was imaged noninvasively using a charge-coupled device camera. Images were acquired 2, 6, 12, 24, 48, and 72 hours after injection. RESULTS: Fluorescence was detected at the tumor site after injection of NovoMab-G2-scFv-Cy5 but not after injection of a labeled irrelevant control antibody fragment. Fluorescence from the tumor site peaked 2 hours after injection and gradually declined, reaching a minimum 72 hours after injection. Fluorescence was also apparent in the kidneys, indicating clearance of the complex through the kidneys. Results suggest that 16% and 73% of the antibody is located in the tumor and kidneys, respectively. Imaging of isolated organs confirmed the presence of the NovoMab-G2-scFv-Cy5 complex in tumors, kidneys, and liver. No fluorescence was observed in other organs. CONCLUSIONS: Specific binding of the antibody-dye complex to the tumor was observed, and the kinetics of binding to tumors and kidneys were determined. These results suggest that the NovoMab-G2-scFv-Cy5.5 complex may be used for noninvasive tumor localization.

Animals↗
PubMed2000

Rapid quantitative bioassay of osteoinduction.

We developed a reproducible, relatively rapid bioassay that quantitatively correlates with the osteoinductive capacity of demineralized bone matrix obtained from human long bones. We have found that Saos human osteosarcoma cells proliferate in response to incubation with demineralized bone matrix and that an index of this proliferative activity correlates with demineralized bone matrix-induced osteogenesis in vivo. The bioassay (Saos cell proliferation) had an interassay coefficient of variation of 23 +/- 2% and an intra-assay coefficient of 11 +/- 1%. Cell proliferation was normalized to a standard sample of demineralized bone matrix with a clinically high osteoinductive capacity, which was assigned a value of one. The Saos cell proliferation for each sample was related to the standard and assigned a value placing it into the low (0.00-0.39), intermediate (0.40-0.69), or high (0.70-1.49) osteoinductive index group. Osteoinduction of human demineralized bone matrix was quantitated by expressing new bone formation as a function of the total bone volume (new bone plus the demineralized bone powder). The demineralized bone matrix was placed in pouches formed in the rectus abdominis muscles of athymic rats, and endochondral bone formation was assessed at 35 days following implantation, when marrow spaces in the ossicles were formed by new bone bridging the spaces between demineralized bone matrix particles. The proliferative index correlated with the area of new bone formation in histological sections of the newly formed ossicles. When the proliferative index (the osteoinductive index) was divided into low, intermediate, and high groups, the correlation between it and new bone formation (osteoinduction) was 0.850 (p < 0.0005) in 25 samples of demineralized bone matrix. There was no overlap in the osteoinduction stimulated between the samples with low and high osteoinductive indices. We conclude that the proliferation assay is useful for the routine screening of bone allograft donors for osteoinductive potential. Furthermore, the two-dimensional area of new bone formation, as it relates to total new bone area, is a quantitative measure of osteoinduction.

Adolescent↗
PubMed2000

Reengineering and infection control programs: commentary and a case study.

Transformation of the health care system has been an ongoing process for generations, but many changes in the past 2 decades have focused on reducing costs in concert with rapidly changing technologies and demands for high quality care. Many cost-containment efforts in the 1990s are characterized by attempts to apply the business model for "reengineering the corporation" to health care systems. This commentary reviews principles of reengineering and how strategies to reduce costs through market forces, competition, and downsizing can result in substantial problems for bureaucratic organizations unaccustomed to rapid change and innovation. A case study drawn from experiences of a large metropolitan academic health care system is presented, with specific focus on lessons that will be helpful to infection control professionals (ICPs) confronted with similar situations.

Academic Medical Centers↗
PubMed2000

The effects of central aromatic amino acid DOPA decarboxylase inhibition on the motor actions of L-DOPA and dopamine agonists in MPTP-treated primates.

1. Endogenous L-DOPA may act as a neuromodulator contributing to the production of motor activity. We now investigate the effects of the centrally acting aromatic amino acid dopa decarboxylase (AADC) inhibitor NSD-1015 (3-hydroxybenzyl hydrazine) on the motor actions of L-DOPA and dopamine agonist drugs in MPTP treated common marmosets. 2. Pretreatment with NSD-1015 (10 - 50 mg kg(-1); i.p.) worsened baseline motor deficits in MPTP-treated common marmosets. Similarly, it abolished L-DOPA (5 - 18 mg kg(-1) s.c.) induced locomotor activity and reversal of disability. NSD-1015 pretreatment inhibited dopamine formation and elevated L-DOPA levels in plasma. 3. The increase in locomotor activity and improvement in disability produced by the administration of the D-1 agonist A-86929 (0.03 - 0. 04 mg kg(-1) s.c.) or the D-2 agonist quinpirole (0.05 - 0.3 mg kg(-1) i.p.) was abolished by NSD-1015 (25 mg kg(-1) i.p.) pretreatment. While the effects of a low dose combination of A-86929 (0.04 mg kg(-1) s.c.) and quinpirole (0.05 mg kg(-1) i.p.) were inhibited by NSD-1015 (25 mg kg(-1) i.p.), there was little effect on the action of a high dose combination of these drugs (0.08 mg kg(-1) A-86929 and 0.1 mg kg(-1) quinpirole). 4. Following central AADC inhibition with NSD-1015 (25 mg kg(-1) i.p.), locomotor behaviour induced by administration of high dose combinations of A-86929 (0.08 mg kg(-1) s.c.) and quinpirole (0.1 mg kg(-1) i.p.) was unaffected by L-DOPA (5 mg kg(-1) s.c.) pretreatment. 5. These results do not support a role for endogenous L-DOPA in spontaneous or drug induced locomotor activity. Rather, they strengthen the argument for the importance of endogenous dopaminergic tone in the motor actions of dopamine agonists.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Underreporting of energy intake in four populations of African origin.

OBJECTIVE: To investigate the frequency of dietary underreporting in four African populations in different geographic and cultural settings. SUBJECTS: Seven-hundred and forty three men and women from rural Cameroon, 1042 men and women from urban Cameroon, 857 men and women from Jamaica and 243 male and female African Caribbeans from the UK. Subjects who reported dieting or weight control were excluded. MEASUREMENTS: Habitual dietary intake was estimated with a quantitative food frequency questionnaire, developed specifically for each country. Underreporting was defined using three cut-off levels for energy intake/estimated basic metabolic rate (EI/BMRest), based on age, sex and weight, in each site. RESULTS: The EI/BMRest was highest in rural Cameroonian men at 3.07 (95% confidence interval: 2.97, 3.17) and women at 2.84 (2.74, 2.94), intermediate in urban Cameroon and Jamaica and lowest in the UK men and women at 1.44 (1.26, 1.62) and 1.41 (1.21, 1.61). This trend existed even after adjustment for age, BMI and education (P for trend<0.0001). The trend in the frequency of underreporting using the lowest cut-off level for EI/BMRest of 1.15 was 6% and 6% in rural Cameroon for women and men, respectively, 4% and 5% in urban Cameroon, 24% and 19% in Jamaica and 28% and 39% in the UK. With higher cut off levels this trend was similar. CONCLUSION: The results suggest that the frequency of dietary underreporting differs between societies and that Westernization may be one of the factors underlying this phenomenon.

Adult↗
PubMed2000

Age is not an impediment to effective use of patient-controlled analgesia by surgical patients.

BACKGROUND: Obstacles to the use of patient-controlled analgesia (PCA) by elderly surgical patients have not been well-documented. Age differences in preoperative psychological factors, postoperative pain and analgesic consumption, treatment satisfaction, and concerns regarding PCA were measured to identify factors important to effective PCA use. METHODS: Preoperatively, young (mean age +/- SD, 39 +/- 9 yr; n = 45) and older (mean age +/- SD, 67 +/- 8 yr; n = 44) general surgery patients completed measures of attitudes toward and expectations of postoperative pain and PCA, psychological distress, health opinions, self-efficacy, and optimism. On the first 2 postoperative days, pain at rest and with movement and satisfaction with pain control were assessed using visual analog scales. Daily opioid intake was recorded. When PCA was discontinued, satisfaction and concerns about it were assessed. RESULTS: The older patients expected less intense pain (P </= 0.003) and preferred less information about (P </= 0.02) and involvement in (P </= 0.002) health care than young patients. There were no age differences with regard to pain at rest (P </= 0.22) or with movement (P </= 0.68). The older group self-administered less opioid than the young group (P </= 0.0001) and received PCA for more days than the young group (P </= 0.004). The groups did not differ in concerns about pain relief, adverse drug effects, including opioid addiction, and equipment use or malfunction. Satisfaction with PCA was high and did not differ between the groups. CONCLUSIONS: Patient-controlled analgesia use was not hindered by age differences in beliefs about postoperative pain and opioids. Younger and older patients attained comparable levels of analgesia and were equally satisfied with their pain control.

Adult↗
PubMed2000

Copulating with multiple mates enhances female fecundity but not egg-to-adult survival in the bruchid beetle Callosobruchus maculatus.

Postcopulatory sexual selection theory has come a long way since the evolutionary implications of sperm competition were first spelled out by Parker (1970). However, one of the most enduring questions remains: why do females copulate with multiple males? Here we show that females copulating with multiple males lay more eggs than those copulating repeatedly with the same male. We also show egg-to-adult survival to be more variable when females copulate multiply with different males and less variable when they copulate multiply with the same male. This supports the notion that egg-to-adult survival may depend on the genetic compatibility of males and females. However, pre-adult survival was highest when females copulated repeatedly with the same male rather than with different males. Thus, it would appear that polyandry in this species does not function to reduce the risk of embryo failure resulting from fertilization by genetically incompatible sperm.

Animals↗
PubMed2000

Acoustic modeling of American English /r/.

Recent advances in physiological data collection methods have made it possible to test the accuracy of predictions against speaker-specific vocal tracts and acoustic patterns. Vocal tract dimensions for /r/ derived via magnetic-resonance imaging (MRI) for two speakers of American English [Alwan, Narayanan, and Haker, J. Acoust. Soc. Am. 101, 1078-1089 (1997)] were used to construct models of the acoustics of /r/. Because previous models have not sufficiently accounted for the very low F3 characteristic of /r/, the aim was to match formant frequencies predicted by the models to the full range of formant frequency values produced by the speakers in recordings of real words containing /r/. In one set of experiments, area functions derived from MRI data were used to argue that the Perturbation Theory of tube acoustics cannot adequately account for /r/, primarily because predicted locations did not match speakers' actual constriction locations. Different models of the acoustics of /r/ were tested using the Maeda computer simulation program [Maeda, Speech Commun. 1, 199-299 (1982)]; the supralingual vocal-tract dimensions reported in Alwan et al. were found to be adequate at predicting only the highest of attested F3 values. By using (1) a recently developed adaptation of the Maeda model that incorporates the sublingual space as a side branch from the front cavity, and by including (2) the sublingual space as an increment to the dimensions of the front cavity, the mid-to-low values of the speakers' F3 range were matched. Finally, a simple tube model with dimensions derived from MRI data was developed to account for cavity affiliations. This confirmed F3 as a front cavity resonance, and variations in F1, F2, and F4 as arising from mid- and back-cavity geometries. Possible trading relations for F3 lowering based on different acoustic mechanisms for extending the front cavity are also proposed.

Humans↗
PubMed2000

Limitations of the Parsonnet score for measuring risk stratified mortality in the north west of England. The North West Regional Cardiac Surgery Audit Steering Group.

OBJECTIVE: To study the use of the Parsonnet score to predict mortality following adult cardiac surgery. DESIGN: Prospective study. SETTING: All centres performing adult cardiac surgery in the north west of England. SUBJECTS: 8210 patients undergoing surgery between April 1997 and March 1999. MAIN OUTCOME MEASURES: Risk factors and in-hospital mortality were recorded according to agreed definitions. Ten per cent of cases from each centre were selected at random for validation. A Parsonnet score was derived for each patient and its predictive ability was studied. RESULTS: Data collection was complete. The operative mortality was 3.5% (95% confidence interval 3.1% to 3.9%), ranging from 2.7% to 3.8% across the centres. On validation, the incidence of discrepancies ranged from 0% to 13% for the different risk factors. The predictive ability of the Parsonnet score measured by area under the receiver operating characteristic curve was 0.74. The mean Parsonnet score for the region was 7.0, giving an observed to expected mortality ratio of 0.51 (range 0.4 to 0.64 across the centres). A new predictive model was derived from the data by multivariate analysis which includes nine objective risk factors, all with a significant association with mortality, which highlights some of the deficits of the Parsonnet score. CONCLUSIONS: Risk stratified mortality data were collected on 100% of patients undergoing adult cardiac surgery in two years within a defined geographical region and were used to set an audit standard. Problems with the Parsonnet score of subjectivity, inclusion of many items not associated with mortality, and the overprediction of mortality have been highlighted.

Aged↗