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Biomedical subjects

J Warner

Publications and source records attributed to J Warner.

At least 73 records · Page 4Linked to original sources
PubMed1998

Correlation of body mass index with thoracic and abdominal panniculus.

Obesity can play a significant role in chronic diseases, sudden unexpected death, and morbid obesity may be important as a cause of death for forensic pathologists. Our study attempted to determine if there is a correlation between panniculus measurements and body mass index (BMI) since BMI has been used in most studies to categorize obesity. Using data obtained from a review of 524 adult autopsies conducted at the University of Michigan from 1990 to 1992 we were able to show a correlation between both thoracic and abdominal panniculus and BMI (r2 = 0.335 and 0.296 respectively) which is statistically significant (p = 10(-47) and 10(-41) respectively). A prospective study confirmed the correlation (r2 = 0.552 for thoracic and 0.436 for abdominal panniculus) when the measurements were taken at the xyphoid process and 3 cm below the umbilicus. Using these data we calculated a panniculus index (PI) which is equal to the thoracic + abdominal panniculus in centimeters divided by the square of the height (in meters). The PI strongly correlated with BMI and was able to predict obesity. Using a BMI cutoff of 39 for morbid obesity, a PI value of 4.07 for females and 3.25 for males predicted morbid obesity with the probability of a false positive less than or equal to 2.5%. Mild and severe obesity could also be determined using the PI. Based on these data we've concluded that a concise mathematical relationship does exist between BMI and panniculus measurements. Therefore panniculus measurements can be used either as a surrogate measurement of morbid obesity or to support BMI calculations.

Abdomen↗
PubMed1998

Presymptomatic testing for Huntington's disease by linkage and by direct mutation analysis: comparison of uptake of testing and characteristics of test applicants.

In Edinburgh, we have compared presymptomatic testing by linkage and by direct mutation analysis by investigating the demand for testing and characteristics of test applicants. Annual new requests for the direct test (DT) are now double the peak with the linkage test (LT) but only 6% individuals have requested re-testing. DT applicants were older with a smaller proportion having lived with an affected relative that LT applicants. This was because many were relatives of newly diagnosed first known cases in their family. This may also explain why DT applicants were less likely to expect a negative result and more likely to be uncertain about their risk. A greater proportion of DT applicants first heard about the test from relatives or their GP than LT applicants who were more likely to hear from Genetic Centre. The demand for follow-up by the Geneticist/Genetic Nurse was much less for DT than for LT applicants largely due to the support offered by the HD Advisors.

Adult↗
PubMed1997

Anti-vector immunoglobulin induced by retroviral vectors.

Replication-incompetent retroviruses have been employed as gene therapy vectors in experimental settings for more than a decade. More recently, these vectors have been tested in the clinic as immunotherapeutic agents and anticancer agents. One potential problem with the use of such vectors is the possible development of immune responses directed against the vector particles themselves. Here, we examine immunoglobulin (Ig) responses specific for retroviral vectors derived from murine leukemia virus (MLV). Anti-MLV Ig is seen following intramuscular (i.m.) administration of retroviral vectors in mice, and in nonhuman primates; as expected, these responses are dependent upon the vector dose delivered. Furthermore, serum from vector-treated animals is capable of partially neutralizing vector-mediated transduction of target cells in an in vitro assay. Nevertheless, even in the presence of significant levels of anti-vector Ig in vivo, i.m. administration of retroviral vector is still capable of driving both Ig and cytotoxic T lymphocyte (CTL) responses specific for vector-encoded gene products. This work suggests that although retroviral vectors may readily induce immune responses directed against the vector particles themselves, such responses will not significantly affect the efficiency of these vectors in an immunotherapeutic protocol.

Animals↗
PubMed1997

Comparison of human tissues and mechanical prostheses for aortic valve replacement in children.

BACKGROUND: Aortic valve replacement in children is problematic because of complications of mechanical valves and uncertain outcomes associated with human valves. The results of pediatric aortic valve replacements over 5 years were reviewed. METHODS AND RESULTS: Mechanical valves were used exclusively during the first part of this series (n = 26). Thereafter, 25 consecutive aortic valve replacements were performed with autografts (n = 19) or allografts (n = 6). Allografts were used for Marfan's syndrome patients or those with unusable pulmonary valves. Among autograft/allograft recipients, 16 patients underwent 27 prior operations. In the mechanical group, 18 patients underwent 19 previous operations. Three patients in each group underwent a previous mechanical aortic valve replacement. Operative complications included two mild strokes and one pacemaker in the autograft/allograft group and three deaths and two pacemakers in the mechanical group. One autograft recipient required reoperation for pulmonary allograft stenosis. In the mechanical group, late complications included six cases of nonstructural degeneration and two cases of endocarditis, with three reoperations. Reoperation-free survival was 96% at 2 years in the autograft/allograft group and 80% at 2 years and 75% at 3 years in the mechanical group. Event-free survival was 96% at 2 years in the autograft/allograft group compared with 67% at 2 years and 49% at 3 years in the mechanical group (P < .05). CONCLUSIONS: The frequency of reoperations for mechanical aortic valve replacement has been surprisingly high. Aortic valve replacement in children with only autografts or allografts achieves good early results.

Adolescent↗
PubMed1997

The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: efficacy, safety, and pharmacokinetics.

CGP 51901 is a non-anaphylactogenic mouse/human chimeric anti-human IgE antibody that binds to free IgE and surface IgE of IgE-expressing B cells but not to IgE bound to high affinity IgE receptors (Fc epsilonR1) on mast cells and basophils or low affinity IgE receptors (Fc epsilonR2) on other cells. A phase 1 double-blind, placebo-controlled, single dose study with doses of 3, 10, 30, and 100 mg of CGP 51901 was conducted in 33 pollen-sensitive subjects who had raised levels of serum IgE and received either intravenous CGP 51901 or placebo. The administration of CGP 51901 was well tolerated and resulted in a decrease of serum free IgE levels in a dose-dependent manner, with suppression after 100 mg of CGP 51901 reaching > 96%. Time of recovery to 50% of baseline IgE correlated with the dose of administered antibody and ranged from a mean of 1.3 d for the 3 mg to 39 d for the 100 mg dose. Total IgE, comprised of free and complexed IgE, increased as stored and newly synthesized IgE bound to CGP 51901. Complexed IgE was eliminated at a rate comparable with the terminal half-life of free CGP 51901 (11-13 d at all doses). Only one subject showed a weak antibody response against CGP 51901. We conclude that the use of anti-human IgE antibody is safe and effective in reducing serum IgE levels in atopic individuals and provides a potential therapeutic approach to the treatment of atopic diseases.

Adolescent↗
PubMed1997

Bedtime rituals of nursing home residents: a study.

This article explores the bedtime rituals espoused by a sample of elderly residents' in a nursing home and the extent to which care assistants meet individual needs. Residents perceptions of choice, status and dependency are identified as important factors. The author suggests that care assistants could be given more information and responsibility for residents' bedtime care. The accompanying commentary highlights the importance of choice and individual care.

Aged↗
PubMed1997

Structural features and biochemical properties of TNF-alpha converting enzyme (TACE).

Tumor necrosis factor-alpha is a potent cytokine, secreted primarily by activated monocytes and macrophages, that possesses a broad range of immunomodulating properties. Involvement of this cytokine has been validated in disease states such as arthritis and Crohn's disease and implicated in diverse neuroimmunological pathologies such as multiple sclerosis, Alzheimers and stroke. TNF-alpha is initially synthesized as a 26 kDa precursor molecule that is subsequently processed to the mature form by cleavage of the Ala76 Val77 bond. The 17 kDa carboxy-terminal protein is then secreted to function in a paracrine manner. The enzyme that processes precursor TNF-alpha has previously been identified as a microsomal metalloprotease called TNF-alpha converting enzyme (TACE). We have now purified and partially cloned the enzyme. TACE represents a novel target for therapeutic intervention in a variety of inflammatory and neuroimmunological diseases.

ADAM Proteins↗
PubMed1997

Shifting categories of the social harms associated with alcohol: examples from late medieval and early modern England.

This paper offers a historical perspective on our own attempts to define the social harms associated with the abuse of alcohol. Challenging the notion that categories are necessarily objective and constant, it instead emphasizes the extent to which even harms that are visible and thus susceptible to measurement are in fact socially constructed. English sources from the preindustrial era revealed six broad categories of social harms associated with the abuse of alcohol. Four of the categories consisted of visible harms in the form of income lost, domestic violence, brawling, and accidents, all of which are still recognized as social harms associated with the abuse of alcohol. The other two categories, reversal of the established moral order and susceptibility to trickery, were of an essentially intrinsic or subjective nature and have since dropped from the lexicon of social harms.

Accidents↗
PubMed1997

The sanctuary of sobriety: the emergence of temperance as a feminine virtue in Tudor and Stuart England.

This study examines the reasons why temperance was viewed as an appropriate virtue for women in sixteenth- and seventeenth-century England. It makes use of contemporary literature to document shifts in attitudes toward women who drank in a public and conspicuous fashion, and examines the economic and cultural changes that contributed to those shifts. The literature consulted in this study would suggest that up until the first decades of the sixteenth century men and women both enjoyed considerable freedom as to where and when they might consume alcohol, and would further suggest that it was only during the economic and social crises of the early modern period that two distinct drinking cultures started to emerge, one centred in the home and exclusive of men, the other centred outside the home and exclusive of women. The emergence of temperance as a virtue specific to women happened to occur at a time when real wages were in sharp decline, and effectively sanctioned the redistribution of household income in favour of men, whose right to drink was never seriously challenged. Criticism of women who drank in a public and conspicuous fashion also happened to coincide with the rediscovery of classical texts commending the supposed temperance of the women of early Rome.

England↗
PubMed1995

Molecular analysis of the TK locus in L5178Y large and small colony mouse lymphoma cell mutants induced by hycanthone methanesulfonate.

Mouse lymphoma cells of the L5178Y TK + /-3.7.2C line were exposed to varying concentrations of the anti-schistosomal drug hycanthone methanesulfonate. The trifluorothymidine (TFT)-resistant cells fell into two classes based on colony size. Southern blot analyses were performed using NcoI-digested DNA from a number of large and small mutant colonies from each treatment group. Two different restriction fragment banding patterns were identified in these analyses, those colonies that contained the 6.4 kb NcoI restriction fragment and those that did not. A total of 471 mutant colonies were analyzed and 84.5% (398) of these colonies did not exhibit the 6.4 kb fragment. There did not appear to be a hycanthone methanesulfonate dose response effect in the number of colonies that did not contain the 6.4 kb fragment among the treated groups. In addition, 82% (154 out of 188) of spontaneous mutants did not contain the 6.4 kb fragment. The results imply that greater than 80% of all spontaneous mutations found in the mouse lymphoma assay regardless of colony size do not contain the 6.4 kb fragment and each may be considered to be a large scale mutation. In addition, greater than 80% of the hycanthone induced mutations in the mouse lymphoma assay do not contain the 6.4 kb fragment and thus may be considered to be a large scale mutation.

Animals↗
PubMed1995

Simultaneous initiation of degranulation and inhibition of leukotriene release by soman in human basophils.

Previous studies noted that the serine esterase inhibitor, soman, could induce histamine release from human basophils. To investigate the mechanisms by which soman causes histamine release (a preformed mediator), we also examined its ability to induce leukotriene release (a newly synthesized mediator) from basophils. We found that no leukotriene release followed activation with soman, while histamine release was usually greater than 70%. In addition, soman and diisopropyl-fluorophosphate were found actively to suppress low level spontaneous leukotriene release as well as ongoing leukotriene release induced by anti-IgE antibody. Soman (0.3 mM) was able to stop leukotriene release as rapidly as the calcium chelator, EDTA. In a series of control experiments, it was noted that soman did not influence the metabolism of LTC4 to LTD4 or LTE4 (for which little metabolism occurred), eliminating the possibility that reduced LTC4 release could have resulted from its enhanced metabolism. Therefore, using one compound (soman), basophils could be simultaneously activated to degranulate while having the pathway leading to leukotriene release actively suppressed. These results provide further evidence that histamine and leukotriene release are independent pathways resulting from the activation of basophils.

Basophil Degranulation Test↗
PubMed1995

Inhibitory motor seizures: correlation with centroparietal structural and functional abnormalities.

Six adults and 2 children with focal inhibitory motor seizures (ictal paralysis) were evaluated during a 4-year period. Paresthesias at seizure onset occurred during some seizures in all patients, and focal clonic activity followed paralysis in 4. EEG-CCTV recordings of the seizures in 2 patients showed that ictal paralysis coincided with an ictal discharge starting in one centroparietal area. MRI showed centroparietal structural lesions in six patients. One patient with a normal MRI scan had right centroparietal hypometabolism on PET. Inhibitory motor seizures must be differentiated from transient ischemic attacks and migraine. In our patients a centroparietal epileptogenic focus was suggested by neuroimaging studies, and in 2 instances by ictal EEG.

Adolescent↗