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Biomedical subjects

K Graham

Publications and source records attributed to K Graham.

At least 55 records · Page 3Linked to original sources

Should alcohol consumption measures be adjusted for gender differences?

Because of biological differences between men and women, the same quantity of alcohol consumed over the same time period produces higher blood alcohol levels (BALs) in women than in men. Some alcohol researchers have proposed that quantity and volume measures of alcohol consumption (e.g. usual number of drinks per drinking day and overall amount of alcohol consumed) should be adjusted to reflect these biological differences. To date, no standard adjustment for biological gender differences has been adopted. In this paper, we review the literature on biological and behavioral differences related to alcohol consumption and effects and discuss the implications of these differences in terms of adjusting alcohol consumption measures. Our review suggests that adjusting measures of alcohol consumption to compensate for biological sex differences is most appropriate for research or policy applications involving the short and long-term physiological effects of alcohol in contexts where gender differences in how alcohol is consumed can be assumed to be minimal. In other circumstances, non-biological gender differences relating to alcohol use, such as pace of drinking, may moderate the relationship between alcohol consumption and biological gender differences, making an adjustment less defensible. We also identify areas where more knowledge is needed not only to address the issue of adjusting alcohol measures for gender differences but also to understand better the relationship between alcohol consumption and effects.

Alcohol Drinking↗

The effects of drinking on health of older adults.

As part of a larger health-promotion project focused on safer use of alcohol and medications by older people, 826 persons living in a small community in Eastern Ontario participated in a survey conducted by nurses in the participant's home. The survey interview varied in length from 30 to 210 minutes and covered alcohol use, medication use, health status, and other aspects of life. This report examines the relationship between drinking practices and self-reported health (overall rating of health, hospital admissions, etc.) as identified by the survey. Among survey participants who abstained from alcohol during the 12 months prior to the survey, former drinkers reported significantly poorer health than did lifetime abstainers and previous drinkers who happened to abstain in the previous year but considered themselves to be infrequent drinkers rather than former drinkers. Among current drinkers, poorer health was associated with drinking more on each occasion of drinking and with a greater total overall volume of alcoholic beverages consumed (as estimated from the drinker's usual weekly consumption), but not with more frequent drinking. Even when controlling for sex, age, education, and depressant medication use, quantity of alcoholic beverage consumption per occasion and overall volume consumed were found to contribute significantly to predicting perceived health. The implications of the findings are discussed in terms of the best ways to assess the risk level of alcohol use among older people, and with recommendations for safer alcohol use.

Aged↗

Cholecystadenocarcinoma in a cat.

A malignant neoplastic process originating from gall bladder epithelium was diagnosed in a 14-year-old, spayed female, domestic shorthair cat. The tumor produced widespread pulmonary and lymphatic metastases. The clinical and pathological manifestations are described. Neoplasia arising from the gall bladder epithelium is rarely reported in animals.

Adenocarcinoma↗

Fingertip reconstruction with a dorsal island homodigital flap.

A distal dorsal island homodigital flap has been used for reconstruction of fingertips in nine patients who sustained traumatic amputations either obliquely or transversely through the middle of the distal phalanx. Seven of the nine patients attended for follow-up. All the flaps survived with the exception of a small area of partial necrosis in one patient. Fingertip reconstruction with this flap is a one-stage procedure, safe, easy to perform and provides durable tissue support for the nail to regrow undeformed.

Adolescent↗

The purified myxoma virus gamma interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines.

The myxoma virus T7 protein M-T7 is a functional soluble gamma interferon receptor homolog that has previously been shown to bind gamma interferon and inhibit its antiviral activities in a species-specific manner, but gene knockout analysis has suggested a further role for M-T7 in blocking leukocyte influx into infected lesions. We purified M-T7 to apparent homogeneity and showed that M-T7 is an N-linked glycoprotein that appears to be a stable homotrimer with a molecular mass of approximately 113 kDa in solution. M-T7, in addition to forming inhibitory complexes with rabbit gamma interferon, was also shown to bind to human interleukin-8, a prototypic member of the chemokine superfamily. Moreover, M-T7 was able to interact promiscuously with all members of the CXC, CC, and C chemokine subfamilies tested. Binding of human RANTES to M-T7 can be competed by rabbit gamma interferon and also by cold RANTES competitor with a 50% inhibitory concentration of 900 nM. Although M-T7 retains binding to a number of interleukin-8 N-terminal (ELR) deletion mutants, binding to mutants containing deletions in the C-terminal heparin-binding domain of interleukin-8 is abrogated. Furthermore, heparin effectively competes the interaction of M-T7 with the chemokine RANTES but not with rabbit gamma interferon. We propose that this novel M-T7 interaction with members of the chemokine superfamily may be facilitated through the conserved heparin-binding domains found in a wide spectrum of chemokines and that M-T7 may function by modulating chemokine-glycosaminoglycan interactions in virus-infected tissues.

Animals↗

Resolution of cavopulmonary shunt-associated pulmonary arteriovenous malformation after heart transplantation.

A child with heterotaxia, azygous continuation of an interrupted inferior vena cava, single ventricle, and pulmonary atresia underwent the Kawashima modification of the Fontan procedure, which excluded hepatic venous return from the pulmonary blood flow. After the operation, the patient had development of pulmonary arteriovenous malformations, increasing cyanosis, and ventricular dysfunction. He underwent orthotopic heart transplantation at 7 years of age with prompt resolution of the pulmonary arteriovenous malformations.

Arteriovenous Malformations↗

Virus-encoded serine proteinase inhibitor SERP-1 inhibits atherosclerotic plaque development after balloon angioplasty.

BACKGROUND: Recurrent atherosclerotic plaque growth, restenosis, is a significant clinical problem after interventional procedures. Initiation of restenosis involves activation of inflammatory and thrombotic cascades, which are regulated by serine proteinase enzymes and inhibitors. We have investigated the use of a viral serine proteinase inhibitor, SERP-1, to reduce plaque development after primary balloon angioplasty. This is the first experimental report of the use of a viral anti-inflammatory protein for the prevention of atherosclerosis. METHODS AND RESULTS: Seventy-four cholesterol-fed rabbits were treated with either local or systemic infusions of SERP-1 protein (or control solutions) after balloon-mediated injury. Sites of SERP-1 infusion in rabbits had dramatically reduced plaque compared with control infusions at the 4-week follow-up. At low-dose infusions (30 to 300 pg), only the primary infusion site had a demonstrable decrease in plaque, whereas at higher-dose infusions (> 3000 pg), a generalized reduction in plaque development was detected. An associated decrease in mononuclear cell infiltration of the arterial wall was detected after SERP-1 infusion within the first 24 hours. Infusion of an active-site mutant of SERP-1 (P1-P1', ala-ala) lacking serine proteinase inhibitory activity failed to prevent plaque growth. CONCLUSIONS: Purified SERP-1, a virus-encoded secreted glycoprotein, reduces plaque growth after primary balloon-mediated injury. Plaque development is decreased by inhibition of serine proteinase activity and is associated with a focal reduction in macrophage infiltration immediately after injury. Investigation of serine proteinase inhibitors may provide new insight into the regulation of arterial responses to injury.

Angioplasty, Balloon↗

Mapping of Reis-Bücklers' corneal dystrophy to chromosome 5q.

PURPOSE: Recently several autosomal dominant corneal stromal dystrophies have been mapped to chromosome 5q. Therefore, we tested whether Reis-Bücklers' corneal dystrophy, an autosomal dominant trait, was also linked to the same region. METHODS: Five generations of a single family with Reis-Bücklers' corneal dystrophy were ascertained. Twenty-two family members were examined, and 11 were found to be affected. Blood was obtained for genetic linkage analysis. RESULTS: Several genetic markers on chromosome 5q were strongly suggestive of linkage or confirmed linkage (LOD score > 3.0). Multipoint analysis generated a maximum LOD score of 4.25 between D5S414 and IL-9. CONCLUSIONS: Reis-Bücklers', lattice type 1, Avillino, and granular corneal dystrophies all map to the same genetic locus. This suggests that one of the following might be true: (1) that a corneal gene family exists in this region; (2) that these corneal dystrophies represent allelic heterogeneity (that is, different mutations within the same gene manifest as different phenotypes); or (3) that these are all the same disease.

Basement Membrane↗

A controlled field trial of group versus individual cognitive-behavioural training for relapse prevention.

Results are presented of a randomized field trial comparing two aftercare regimes, namely individual versus group delivery of a structured relapse prevention approach. Two addictions treatment programs (one a 12-Step 26-day residential program, the other an evening group counselling program) implemented structured relapse prevention in either group or individual format as part of the first three months of aftercare. Process measures (e.g. attendance, client satisfaction) indicated that both group and individual formats were delivered very successfully at both sites. Follow-up rate at 12 months across both programs was 74%, and drinking and drug use at the 12-month follow-up was substantially less than use at entry into treatment. However, there were no significant differences in outcomes between individual and group delivery on any of the alcohol or drug use measures. Only one psychosocial outcome measure (social support from friends at 12-month follow-up) showed a significant difference for format and it favored the group format. These findings suggest some important directions for future research.

Adult↗

Kinetics of the humoral immune response to multiple treatments with exogenous gonadotropins and relation to ovarian responsiveness in domestic cats.

OBJECTIVE: To investigate ovarian responses and kinetics of gonadotropin-binding immunoglobulin production in domestic cats repeatedly treated with equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) at short or long treatment intervals. DESIGN: Queens were treated 3 or 4 times with a standard eCG/hCG regimen at short (49 to 57 days) or long (130 to 135 days) intervals and subjected to laparoscopy after each treatment to evaluate ovarian follicular development. Serial serum samples were assessed by ELISA for the presence of eCG-binding immunoglobulins. ANIMALS: 11 clinically normal sexually mature female cats. RESULTS: Queens repeatedly stimulated with eCG/hCG at long intervals typically had no decrease (P > 0.05) in ovarian follicle production or in maturity of recovered oocytes, whereas queens treated at short intervals had reduced (P < 0.05) follicular development and compromised oocyte maturity by the third stimulation. For both interval groups, ELISA data indicated individual variability in seroconversion after eCG/hCG challenge exposure. In general, queens treated at short intervals had higher peak anti-eCG immunoglobulin titer than did queens treated at long intervals; high titer at the time of eCG/hCG injection, or rapid increases in titer immediately after injection were predictive (P < 0.05) of poor ovarian responses. CONCLUSIONS: Results suggest that individual variability in immune responses and intervals between repeated gonadotropin treatments determine whether queens develop immunologically mediated ovarian refractoriness to exogenous gonadotropins. Intervals of at least 4 months between successive eCG/hCG treatments are recommended for assisted reproductive procedures in domestic and nondomestic cats.

Analysis of Variance↗

Genetic mapping in human and mouse of the locus encoding TRBP, a protein that binds the TAR region of the human immunodeficiency virus (HIV-1).

Productive infection with HIV-1, the virus responsible for AIDS, requires the involvement of host cell factors for completion of the replicative cycle, but the identification of these factors and elucidation of their specific functions has been difficult. A human cDNA, TRBP, was recently cloned and characterized as a positive regulator of gene expression that binds to the TAR region of the HIV-1 genome. Here we demonstrate that this factor is encoded by a gene, TARBP2, that maps to human chromosome 12 and mouse chromosome 15, and we also identify and map one human pseudogene (TARBP2P) and two mouse TRBP-related sequences (Tarbp2-rs1, Tarbp2-rs2). The map location of the expressed gene identifies it as a candidate for the previously identified factor encoded on human chromosome 12 that has been shown to be important for expression of HIV-1 genes. Western blotting indicates that despite high sequence conservation in human and mouse, the TARBP2 protein differs in apparent size in primate and rodent cells.

Animals↗

Interruption of cytokine networks by poxviruses: lessons from myxoma virus.

Myxoma virus is an infectious poxvirus pathogen that induces a virulent systemic disease called myxomatosis in European rabbits. The disease is rapidly and uniformly fatal to susceptible rabbits and is characterized by generalized dysfunction of cellular immunity and multiple interruptions of the host cytokine network. A number of virus genes are classified as virulence factors because virus constructs bearing targeted gene disruptions induce attenuated disease symptoms. Many of these genes encode proteins that interact directly with effector elements of the host immune system. Included among these immunosubversive viral proteins are secreted mimics of host ligands or regulators (virokines) and homologues of cellular cytokine receptors (viroceptors). Five examples of these immune modulator proteins encoded by myxoma virus are reviewed: (1) myxoma growth factor, a member of the epidermal growth factor ligand superfamily; (2) SERP-1, a secreted serine proteinase inhibitor; (3) M11L, a receptor-like surface protein; (4) T2, a tumor necrosis factor receptor homologue; and (5) T7, an interferon-gamma receptor homologue. The origin of viral strategies designed to subvert immune regulation by host cytokines is considered in the context of the biology of myxoma virus within immunocompetent hosts.

Animals↗

An analysis of specialty journals on alcohol, drugs and addictive behaviors for sex bias in research methods and reporting.

OBJECTIVE: Several studies have considered the extent to which gender bias has characterized addictions treatment research over the past 20 years. Sex bias in this literature has been shown to be most apparent in a reliance on male subjects and representation of male experience as normative. The current study was undertaken to assess the current status of some basic aspects of gender bias in addictions research generally. METHODS: Articles appearing in 1990 in 17 specialty journals on alcohol, drugs and addictive behaviors were coded with respect to type of article and the gender of the primary investigator. Studies on human subjects also were evaluated with regard to subject selection and reporting practices. RESULTS: Although the proportion of females represented in addictions research was found to have increased over earlier historical periods, studies using only male subjects were still common in 1990. Moreover, in studies using subjects of mostly one sex, investigators were likely to provide legitimate reasons for studying females, but provide no rationale for using male samples. Other subtle forms of bias were identified. For example, many single-sex studies (especially those using all male subjects) did not indicate the gender of the sample in the title or abstract of the study, and did not indicate that results of the study could be generalized to only one gender. CONCLUSIONS: Male biased sampling and misleading reporting of findings continue to be evident in addictions research. The need for gender-sensitive research in the field of addictions is discussed, and suggestions for change are offered.

Alcoholism↗

Continuity of care in addictions treatment: the role of advocacy and coordination in case management.

Although advocacy and coordination are recognized as important aspects of the addictions treatment process, little research has been done in these areas. The present study examined advocacy and coordination at two programs where the mandate was assessment, referral, and case management. Both programs spent a similar proportion of client-related effort on advocacy and/or coordination (about 25% of contact time, accounting for about half of contacts made regarding clients). The majority of advocacy and coordination contacts were with other agencies about clients (the remainder with family and friends of clients). A framework for advocacy and coordination was developed that allowed contacts to be categorized into mutually exclusive advocacy or coordination activities. Advocacy was defined as any activity undertaken to obtain something for clients; coordination involved the giving or receiving of information regarding specific clients. Sources of variability in the provision of advocacy and coordination were found between the programs that could be attributed to differences between the systems within which the programs operated, as well as differences in program clientele. In terms of client characteristics, it was found that females were more likely than males to receive advocacy; those over 65 years were most likely to receive both advocacy and coordination; those who were referred by school or employer or by corrections were most likely to receive coordination; those with no prior treatment were most likely to receive advocacy; and self-referrals and those who had had prior treatment were most likely to receive neither advocacy nor coordination. Receiving advocacy or coordination was not found to reduce the need by clients for other case management services, such as supportive counseling. The findings are discussed in terms of the need for knowledge regarding highly variable aspects of treatment such as advocacy and coordination. New research approaches (as taken in the present study) are needed to begin to examine the contribution of these types of flexible and ancillary interventions to the recovery process.

Adult↗