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Biomedical subjects

K Graham

Publications and source records attributed to K Graham.

At least 73 records · Page 4Linked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Diagnosis of cytomegalovirus (CMV) disease in renal allograft recipients: the role of semiquantitative polymerase chain reaction (PCR).

BACKGROUND: Cytomegalovirus disease remains a significant cause of morbidity and mortality in the renal allograft recipient. There is a need for rapid and sensitive techniques predictive of CMV disease to allow initiation of early antiviral therapy. METHODS: Seventy-seven renal allograft recipients were enrolled in a prospective study where CMV viruria (shell vial culture/DEAFF test), viraemia (shell vial culture), serology and detection of virus DNA in peripheral blood leukocytes by PCR (CMV DNAemia) were correlated with clinical evidence of CMV disease. RESULTS: Serology and shell vial culture had poor sensitivity for the early diagnosis of CMV disease. CMV DNAemia appeared to correlate with active virus replication. CMV DNAemia had a sensitivity and negative predictive value of 100% and a positive predictive value of 27% for CMV disease. Patients with symptomatic CMV disease were shown to have higher levels of CMV DNAemia than those with asymptomatic infection. CONCLUSIONS: A negative CMV DNAemia result excluded CMV disease with confidence, but a positive result (given the low positive predictive value) did not by itself provide a reliable guide for the initiation of pre-emptive antiviral therapy. However, the semiquantitative CMV DNAemia result taken together with the clinical findings provided useful information for patient management.

Adolescent↗
PubMed1995

Skin closure in hip surgery: subcuticular versus transdermal. A prospective randomized study.

A randomized parallel-group clinical trial was conducted between March 1991 and December 1993 to compare the effectiveness of subcuticular suture using absorbable material (Dexon) and continuous transdermal blanket suture using nonabsorbable material (silk) in hip surgery. Eighty patients (48 females and 32 males) aged between 19 and 94 years (average 71.4 years) who underwent 97 hip operations were studied. Patients were followed up between 2 and 20 months. The two groups were evaluated with respect to infection rate, patient satisfaction with the scar, extra time and cost in removal of suture and the cosmetic appearance assessed by a plastic surgeon evaluating photos of patients' wounds using a specific scoring method without knowledge of the suturing method used. Five patients died during the study. There was no significant difference in superficial infection rate between the two groups (5% with positive bacteriological swab and 16% requiring extra antibiotics on clinical grounds). No deep infection was suspected in either group. The average score of patient satisfaction with the scar was 9.6/10 in the subcuticular group and 8.68/10 in the continuous mattress with a significant difference between the two groups (p < 0.05). Cosmetic evaluation by the plastic surgeon using a 6-category scoring system showed a better cosmetic result in the subcuticular group with a significant difference (p < 0.01). An average of 17 minutes of extra nursing time was needed for removal of suture material in the nonabsorbable group in addition to the cost of the suture removal set. We conclude that absorbable subcuticular skin closure is an effective method and offers some advantages over the traditional transdermal suturing method in hip surgery.

Adult↗
PubMed1994

Receiver operating characteristic evaluation of computer display of adult portable chest radiographs.

RATIONALE AND OBJECTIVES: The suitability of using an image console monitor for interpretation of adult portable chest radiographs was evaluated with receiver operating characteristic (ROC) analysis and subjective techniques. METHODS: Radiologists read 80 chest images, once on a display monitor and once on computed radiography film, for the presence or absence of pneumothorax or atelectasis. Judgments of correct or incorrect positions of tubes and lines were reported, and total viewing time was recorded. RESULTS: A statistically significant difference was found in favor of monitor reading for detection of pneumothoraces. Atelectasis detection also was higher with monitor reading, but the difference did not reach statistical significance. Tube/line judgments were equivalent for both modes. Total viewing time was approximately 1 minute longer per image with the monitor. CONCLUSIONS: Viewing computed radiography images on a workstation monitor does not seem to affect diagnostic accuracy compared with film viewing. Preset image defaults tailored to the individual radiologist could decrease total viewing time to acceptable levels.

Adult↗
PubMed1994

Guidelines for using standardized outcome measures following addictions treatment.

Increasingly, program managers are incorporating existing standardized tests as part of outcome evaluation. This article identifies guidelines for selecting and using standardized measures following addictions treatment. The principles identified in this context, however, are not only applicable to addictions treatment evaluation but also to the use of standardized measures in outcome evaluation of health programs generally. These guidelines cover eight basic criteria for selecting outcome measures: validity, sensitivity to measuring change, suitability for type of clients in the program, acceptability, clinical usefulness, ease of administration, scoring, and low cost. The article also discusses uses of outcome data, comparison of monitoring client outcomes to other forms of evaluation, and some practical issues related to using standardized outcome measures, including selecting what to measure and interpreting results.

Data Collection↗
PubMed1993

Evaluation and counseling of teratogenic risk: the motherisk approach.

The authors present a new approach for evaluation and counseling of teratogenic risk, The Motherisk program in Toronto presently deals with 60 inquiries per day from the public and health professionals. Most calls are answered through the telephone, and 16-20 women per week are scheduled for our clinic following exposure to known or suspected teratogens, to new drugs with sparse information, to chronic drug therapy, or drugs of abuse. Also seen in clinic are women who want to be counseled or whose physicians want them to meet us due to high levels of anxiety. Since its inception in 1985 the Program has been very effective in preventing unnecessary terminations of otherwise wanted pregnancies. In addition to the clinical service we followup the outcome of these prospectively collected exposures, thus creating a large data base necessary to verify safety/risk of various agents. During the last 2 years Motherisk has completed singly, or in collaboration, large prospective studies on gestational exposure to lithium, antiepileptics, cocaine, and fluexitime. To study the reproductive risks of cocaine we compared first-trimester exposure to cocaine with two control groups. Infants exposed to cocaine did not have higher rates of any adverse perinatal outcome. Their cognitive function at 18 months of age was identical to the control infants. Meta analysis of all studies assessing gestational risks of cocaine reveals that the results of these studies were dependent on the type of comparison conducted. When babies exposed to cocaine were compared with middle class nonusers, the cocaine groups seemed to be more often different from their controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Cocaine↗
PubMed1993

Transforming growth factor alpha, Shope fibroma growth factor, and vaccinia growth factor can replace myxoma growth factor in the induction of myxomatosis in rabbits.

The epidermal growth factor (EGF) homologues encoded by vaccinia virus, myxoma virus, and malignant rabbit fibroma virus have been shown to contribute to the pathogenicity of virus infection upon inoculation of susceptible hosts. However, since the primary structures of these growth factors and the disease profiles induced by different poxvirus genera vary substantially, the degree to which the various EGF homologues perform similar roles in viral pathogenesis remains unclear. In order to determine whether different EGF-like growth factors can perform qualitatively similar functions in the induction of myxomatosis in rabbits, we created recombinant myxoma virus variants in which the native growth factor, myxoma growth factor (MGF), was disrupted and replaced with either vaccinia virus growth factor, Shope fibroma growth factor, or rat transforming growth factor alpha. Unlike the control virus containing an inactivated MGF gene, which caused marked attenuation of the disease syndrome and substantially less proliferation of the epithelial cell layers in the conjunctiva and respiratory tract, the recombinant myxoma virus strains expressing heterologous growth factors produced infections which were both clinically and histopathologically indistinguishable from wild-type myxomatosis. We conclude that these poxviral and cellular EGF-like growth factors, which are diverse with respect to primary structure and origin, have similar biological functions in the context of myxoma virus pathogenesis and are mitogenic for the same target cells.

Animals↗
PubMed1992

Hair analysis of cocaine: differentiation between systemic exposure and external contamination.

Cocaine has been shown to accumulate in hair of admitted users. Before using this test to verify cocaine use, however, it is crucial to differentiate between systemic exposure and external contamination from being in contact with crack smoke. In the present studies, the authors document that pyrolysis of crack results in hair accumulation of cocaine, but not its benzoylecgonine metabolite, whereas after admitted cocaine use both species are detectable in hair. External contamination with crack smoke is washable, whereas systemic exposure is not. The authors suggest these two criteria to distinguish systemic exposure from external contamination.

Animals↗
PubMed1992

Accumulation of cocaine in maternal and fetal hair; the dose response curve.

Cocaine and its major metabolites are incorporated into hair during the growth of the shaft and stay there for the whole life of the hair. Cocaine crosses the placenta and its metabolites for example Benzoylecgonine (BZ), have been found in neonatal urine, meconium and hair. In order to utilize hair measurements of cocaine as a biological marker of systemic exposure, we conducted both animal and human investigations on the dose response characteristics of this phenomenon. Our data suggest that both maternal and fetal accumulation of cocaine and its metabolite follow a linear pattern within the clinically used doses. Similarly, a good correlation was observed in animals between maternal dose and fetal hair accumulation.

Animals↗
PubMed1992

Adaptation themes for prenatal care delivered by public health nurses.

An adaptation process involving three cognitive themes provides the framework for community nursing model for prenatal care on the island of Hawaii. The themes are based on the cognitive adaptation model developed by Taylor (1983) and include search for meaning, sense of mastery, and self-esteem. Each theme is used to guide public health nurses and is identified during designated encounters between the nurse and woman throughout the duration of prenatal care. A focus on adaptation themes for each trimester of pregnancy expands on the medical model of prenatal care to highlight developmental processes of childbearing and broaden the scope of practice for public health nurses responsible for assessment and intervention in the community.

Adaptation, Psychological↗
PubMed1992

In vitro resolution of poxvirus replicative intermediates into linear minichromosomes with hairpin termini by a virally induced Holliday junction endonuclease.

Available evidence suggests that one or more late viral gene products are involved in processing poxvirus replicative intermediates into mature progeny hairpin-terminated genomes. Cloned versions of the Shope fibroma virus (SFV) replicated telomere in the inverted repeat configuration were used as substrates to assay lysates from poxvirus-infected cells for protein fractions that participate in the resolution of the circular substrate plasmid into a linear minichromosome with viral hairpin termini. An activity in a crude protein fraction obtained from vaccinia virus-infected cells at late times during the replicative cycle was capable of accurately resolving all poxviral inverted repeat replicative intermediates tested. The resolved linear products are identical to the products of in vivo resolution and possessed symmetrical nicks which mapped at the borders of the inverted repeat sequence. Strand-specific nicks were also identified, which mapped within the telomere resolution target sequence known to be required for telomere resolution in vivo. The resolving activity that we have identified is specific to virus-infected cells at late times during replication and cleaves cloned poxviral telomeric substrates in a fashion expected of a classic Holliday junction-resolving enzyme in addition to possessing a telomere resolution target-specific nicking activity. Although a Holliday junction-resolving activity would also be expected to play a role in the recombination induced by poxvirus infection, the appearance of the activity described here only after the commencement of viral late protein synthesis suggests that it functions strictly at late times. Other non-viral Holliday junction analogs can also be cleaved by this extract, suggesting that this component of the resolution activity may also play a role in other viral processes that require cleavage of a branched DNA structure. Thus, we have identified a poxviral activity that may be a part of a protein complex which resolves concatemeric replicative intermediates of viral DNA as well as participate in general recombination late during infection.

Animals↗
PubMed1992

Deletion analysis of two tandemly arranged virulence genes in myxoma virus, M11L and myxoma growth factor.

Myxoma virus (MYX) is a leporipoxvirus of rabbits that induces a lethal syndrome characterized by disseminated tumorlike lesions, generalized immunosuppression, and secondary gram-negative bacterial infection. A MYX deletion mutant (vMYX-GF- delta M11L) was constructed to remove the entire myxoma growth factor (MGF) coding sequence and that for the C-terminal five amino acids of the partially overlapping upstream gene, M11L. Unexpectedly, this deletion completely abrogates the capacity of MYX to cause the characteristic disease symptoms of myxomatosis. Upon inoculation of rabbits with vMYX-GF- delta M11L, recipient animals developed only a benign, localized nodule reminiscent of a Shope fibroma virus-induced tumor in which a single primary lesion appeared at the site of injection and then completely regressed within 14 days, leaving the animals resistant to challenge with wild-type MYX. No evidence of the purulent conjunctivitis and rhinitis that always accompany wild-type MYX infection was observed. To ascertain whether the attenuation observed in vMYX-GF- delta M11L was due to a combined effect of the MGF deletion and alteration of the upstream M11L gene, two additional MYX recombinants were constructed: an MGF- virus (vMYX-GF-) containing an intact M11L gene and an M11L- virus (vMYX-M11L-) containing an intact MGF gene. Infection with vMYX-GF- resulted in moderated symptoms of myxomatosis, but all clinical stages of the disease were still detectable. In contrast, disruption of M11L alone dramatically reduced the virus virulence, resulting in a nonlethal syndrome whose clinical course was nevertheless distinct from that of vMYX-GF- delta M11L. Upon inoculation with vMYX-M11L-, rabbits developed primary and secondary tumors which were larger and more circumscribed than those of wild-type MYX recipients. Whereas wild-type MYX infection always includes severe, purulent conjunctivitis and rhinitis, vMYX-M11L- recipients remained healthy and displayed only minimal signs of respiratory distress. By about 30 days after infection, the tumors induced by vMYX-M11L- had completely regressed and these animals were immune to challenge with wild-type MYX. Histological analysis indicated that tumors induced by vMYX-M11L- are much more heavily infiltrated with macrophages and heterophils and that the sites of viral replication are more edematous and necrotic than those of wild-type infection, suggesting that the host was able to mount a more vigorous inflammatory response to vMYX-M11L- infection.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Biological markers of intrauterine exposure to cocaine and cigarette smoking.

We describe hair tests for assessment of fetal exposure to cocaine and cigarette smoking. Cocaine and its major metabolites are incorporated into hair during the growth of the shaft and stay there for the whole life of the hair. Cocaine crosses the placenta and its metabolite benzoylecgonine, has been found in neonatal urine, meconium and hair. In order to utilize hair measurements of cocaine as a biological marker of systemic exposure, we conducted both animal and human investigations on the dose response characteristics of this phenomenon. Our data suggest that both maternal and fetal accumulation of cocaine and its metabolite follow a linear pattern within the regularly used doses. Similarly, a good correlation was observed in animals between maternal dose and fetal hair accumulation. To date, no biological markers have been identified that can predict the extent of fetal exposure to the adverse effects of toxic constituents of cigarette smoke. We measured maternal and fetal hair concentrations of nicotine and cotinine in mother-infant pairs. Smoking mothers had a mean of 21.3 +/- 18 ng/mg hair nicotine and 6 +/- 9.2 ng/mg of cotinine, significantly more than nonsmokers (0.9 +/- 0.8 ng/mg nicotine and 0.3 +/- 0.5 ng/mg cotinine, p < 0.0001). Babies of smokers had a mean nicotine concentration of 6 +/- 9.2 ng/mg (range 0-27.3) and cotinine of 2.1 +/- 3.7 ng/mg (range 0-12.2), significantly more than babies of nonsmokers (nicotine 0.6 +/- 0.7 ng/mg and cotinine 0.2 +/- 0.5 ng/mg; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1992

Pregnancy outcome and infant development following gestational cocaine use by social cocaine users in Toronto, Canada.

To determine the effect of first trimester cocaine use on pregnancy outcome we conducted a prospective cohort study of 30 women admitting to social cocaine use (SCU) during early pregnancy, 20 users of cannabis during the first trimester and 30 matched recreational drug-free control subjects. The groups were of similar age, marital status, and obstetric history and were predominantly white. They were of similar socioeconomic status (SES), however the spouses of the cocaine users were of significantly lower SES than those of both control groups (p less than 0.005). The number of years of education of the cocaine users and the fathers of the SCU-exposed fetuses was significantly lower than that of the recreational drug-free control subjects (p = 0.004), however, female IQ was similar among the three groups (109.1 +/- 12.4 cocaine; 109.1 +/- 25.2 cannabis; 114.1 +/- 11.7 drug-free). Alcohol and cigarette use was greater among the cocaine users than among subjects of the recreational drug-free control group (p less than 0.025). Cocaine and the associated lifestyle were not associated with any adverse obstetric or neonatal endpoint (pregnancy weight gain, incidence of delivery complications, gestational age, birth weight, Apgar scores, and rates of major and minor malformations). There were no differences between groups in attaining developmental milestones. Mental and motor scores on the Bayley Scales of Infant Development and Vineland Adaptive Behavior Scales were identical among the three groups, studied at a mean of 19.7 months of age. We conclude that outcome of pregnancy of social cocaine users and subsequent infant physical and cognitive development are within normal limits at 1.6 years of age.

Adolescent↗
PubMed1992

Cocaine in pregnancy: analysis of fetal risk.

During the last decades there has been a substantial increase in the recreational use of cocaine in young adults and parallelly there has been an increase of its use by pregnant women. We analyzed all published papers on cocaine use in pregnancy and found that for most endpoints studied (eg, prematurity, head circumference) there were many studies showing effects and many showing no effects. Upon meta-analysis, most of these effects could not be shown significant when compared to control groups. In a prospective study in Toronto, babies exposed to cocaine during the first trimester only had Bayley scores at 18-mo of life that were identical to unexposed babies or to those exposed to canabinoids. Motherisk presently counsels women who discontinue cocaine use in the first trimester of pregnancy that there is no increased developmental risk for the baby.

Cocaine↗