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Biomedical subjects

K Graham

Publications and source records attributed to K Graham.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1991

Characteristics of pregnant women exposed to cocaine in Toronto between 1985 and 1990.

OBJECTIVE: To determine the characteristics of pregnant women exposed to cocaine. DESIGN: Case-control study. SETTING: Women attending the Motherisk Program, Hospital for Sick Children, Toronto, from September 1985 to March 1990. PATIENTS: All women who had admitted using cocaine before or during pregnancy. Of the two control groups the first comprised women who had admitted using cannabinoids but not cocaine before or during pregnancy and the second those who attended the clinic just before the cocaine case but who had not used illicit drugs. OUTCOME MEASURES: Age, marital status, ethnic background, number of pregnancies, children and elective or spontaneous abortions, socioeconomic status of woman and male partner, alcohol use, cigarette use, frequency of cocaine use and total amount taken. MAIN RESULTS: Of the 1625 women 91 (5.6%) admitted to using cocaine: 86 during the current pregnancy, 3 before the current pregnancy, 1 before planning a pregnancy and 1 during a previous pregnancy. None of the cocaine users were considered to be addicts; only 20% had used the drug more than 10 times. A total of 74 women used cannabinoids only. The mean age of the cocaine users was 27.1 (standard deviation [SD] 5.3) years; this was significantly lower than that of the control subjects (30.5 [SD 5.2] years) (p less than 0.001). More of the cocaine users than of the women in either of the two control groups were single (60% v. 38% and 14%, p less than 0.001). The cannabinoid users had significantly higher parity and the nonusers a significantly lower incidence of elective abortions than the cocaine users. The cocaine users had a significantly lower socioeconomic status than the control subjects (p less than 0.001); similarly, the male partners of the cocaine users had a significantly lower socioeconomic status than the partners of the control subjects (p = 0.001). CONCLUSIONS: Pregnant cocaine users who seek drug counselling represent a unique risk group, with clustering of factors such as alcohol and cigarette use and low socioeconomic status that compound the risk to the fetus. New strategies should be explored to identify such women, especially addicts, in their communities and to urge them to seek counselling and treatment.

Adult↗
PubMed1991

Relationship between gestational cocaine use and pregnancy outcome: a meta-analysis.

Despite a growing number of studies that have investigated the reproductive effects of maternal cocaine use, a homogeneous pattern of fetal effects has not been established and there is little consensus on the adverse effects of the drug. We used meta-analysis to evaluate the reproductive risks of cocaine. We reviewed the 45 scientific papers published in the English language dealing with effects of cocaine used during pregnancy on pregnancy outcome in humans, and identified 20 papers eligible for meta-analysis (cocaine use in pregnancy, pregnancy/fetal outcome studies, human studies, original work, cohort or case control studies, control group present, English language). Our analysis revealed that very few adverse reproductive effects could be shown to be significantly associated with cocaine use by polydrug users when compared to control groups of polydrug users not using cocaine [genitourinary malformations; odds ratio of 6.08 (95% CI 1.18-31.3); gestation age: Cohen's d 0.37 (CI 0.2-0.55)]. When the control groups consisted of no drug users, the polydrug users abusing cocaine had a higher risk for spontaneous abortions [odds ration 10.50 (CI 11.74-64.1)]. Similarly, comparison of users of cocaine alone or no drug users revealed a higher risk for in utero death, in addition to genitourinary tract malformations. Analysis of continuous variables (head circumference, gestational age, birth weight and length) revealed that the effect size was dependent upon the nature of the comparison. Comparison of cocaine users to no drug users consistently yielded a medium effect size (Cohen's d) between 0.50 and 0.58, while comparison of polydrug/cocaine users to polydrug/no cocaine users provided effect sizes small to non existent (0.06-0.37). These discrepancies suggest that a variety of adverse reproductive effects commonly quoted to be associated with maternal use of cocaine may be caused by confounding factors clustering in cocaine users.

Abortion, Spontaneous↗
PubMed1991

The target DNA sequence for resolution of poxvirus replicative intermediates is an active late promoter.

The linear double-stranded genomes of poxviruses such as Shope fibroma virus (SFV) replicate autonomously within the cytoplasm of infected cells, and it is believed that all of the replication functions are virally encoded. During DNA replication the incompletely base-paired terminal hairpin loops of the viral genome transiently exist in the form of inverted repeat replicative intermediates. These inverted repeat structures form the target for telomere resolution events that include sequence-specific cleavage and directed strand exchange to form the hairpin termini of progeny virus genomes. The terminal sequence domain which forms the telomere resolution target (TRT) shares considerable sequence similarity with viral late promoters. In this study we demonstrate that the TRT of SFV is capable of functioning as a strong viral promoter late in infection. A spectrum of TRT mutations affects telomere resolution and late transcription in a strictly concordant fashion, suggesting that the two activities may be inextricably linked. Further support for this concept comes from the demonstration that a late SFV promoter sequence designated cryptic TRT, which differs substantially from the native TRT in terms of sequence, can support telomere resolution when placed in the correct spatial context. The proposed model for telomere resolution invokes directed unwinding of the TRT double helix by a transcription initiation complex and processing of the resulting secondary structure by viral late-gene products.

Animals↗
PubMed1990

Case management in addictions treatment.

The need for case management in addictions treatment systems has been recognized for at least 10 years. As more attention is paid to developing this treatment component and as more data are available concerning the implementation of case management in addictions, it is becoming apparent that there is a lack of consensus concerning who should provide case management and how it should be defined. This paper reviews sources of variability of case management services identified in the mental health field and discusses the implications for the development of case management in addictions programs.

Adult↗
PubMed1990

Analysis of linkage between scrapie incubation period and the prion protein gene in mice.

A single gene is known to have a predominant influence on scrapie incubation period in mice. In crosses between strains that give a short incubation period, such as NZW mice, and those which give a long incubation period, such as I/LnJ mice, long incubation period was dominant using a Chandler scrapie agent isolate. Recently a close linkage was found between the incubation period gene and the prion protein (PrP) structural gene in I/LnJ mice crossed to NZW mice. Because this linkage suggested an important role for PrP in the pathogenesis of scrapie we sought to verify the linkage between these genes and extended the analysis to three additional mouse strains. All four of the mouse strains that we evaluated, I/LnJ, P/J, MA/MyJ, and RIIIS/J, had incubation periods longer than those of the NZW mice to which they were crossed. In addition, all four strains shared an XbaI restriction enzyme polymorphism, which suggested that all four strains might also exhibit linkage between the incubation period and the PrP structural gene. Very strong linkage between PrP and incubation period was found in I/LnJ and P/J mice crossed to NZW mice, whereas less obvious linkage was demonstrated for MA/MyJ mice crossed to NZW mice. In MA/MyJ mice genes other than PrP also had an obvious influence on incubation period. In RIIIS/J mice no linkage was shown. Although linkage between PrP and incubation period was very significant in I/LnJ and P/J mice, a few animals were identified in both crosses that represented potential recombinants in which PrP and incubation period did not segregate together. Therefore, although these phenotypes are certainly linked in I/LnJ and P/J mice, it is possible that PrP and incubation period are controlled by separate genes.

Animals↗
PubMed1989

Bias against the null hypothesis: the reproductive hazards of cocaine.

To examine whether studies showing no adverse effects of cocaine in pregnancy have a different likelihood of being accepted for presentation by a large scientific meeting, all abstracts submitted to the Society of Pediatric Research between 1980 and 1989 were analysed. There were 58 abstracts on fetal outcome after gestational exposure to cocaine. Of the 9 negative abstracts (showing no adverse effect) only 1 (11%) was accepted, whereas 28 of the 49 positive abstracts were accepted (57%). This difference was significant. Negative studies tended to verify cocaine use more often and to have more cocaine and control cases. Of the 8 rejected negative studies and the 21 rejected positive studies, significantly more negative studies verified cocaine use, and predominantly reported cocaine use rather than use of other drugs. This bias against the null hypothesis may lead to distorted estimation of the teratogenic risk of cocaine and thus cause women to terminate their pregnancy unjustifiably.

Adult↗
PubMed1989

Determination of gestational cocaine exposure by hair analysis.

Drug self-reports are often unreliable and standard blood and urine tests detect only recent cocaine use. Since cocaine is deposited in hair, we have applied a radioimmunoassay to hair extract to detect past cocaine use. Hair from 16 adult users was positive for benzoylecgonine, in the presence of negative findings from urine screening tests. Benzoylecgonine in admitted heavy users averaged 8775 ng/g of hair (range, 640 to 29,089 ng/g of hair), whereas in occasional users it averaged 624 ng/g of hair (range, 32 to 1210 ng/g of hair). Benzoylecgonine was not detected in hair of 21 adults who reported no use of cocaine ever and whose urine samples were negative for the metabolite. Neonatal hair from seven infants whose mothers were known cocaine users averaged 5430 ng of benzoylecgonine per gram of hair (range, 200 to 27500 ng/g of hair). Hair from two infants 2.5 and 3.5 months of age averaged 6050 ng of benzoylecgonine per gram of hair. However, values were negative for infants 1 year and older, corresponding to loss of fetal hair in the few months after birth. Because studies reporting reproductive risks of cocaine compare exposed and nonexposed groups, validation of drug-free status of control subjects is extremely important. Hair analysis may remedy the disadvantages of currently used methods and may identify intrauterine exposure to cocaine in babies when a maternal drug history is not available or of doubtful truthfulness.

Adult↗
PubMed1989

Preparation of antibodies against xanthine oxidase from human milk.

1. Human xanthine oxidase [XO; EC 1.2.3.2.] was isolated by a non-proteolytic method from fresh human milk. Final purification of the protein was achieved by hydroxyapatite chromatography. Most (less than 95%) of the enzyme was released in the 0.40 M phosphate fraction at pH 6.8. 2. The specific activity of this preparation was found to be 0.047 microM min-1 mg-1 with xanthine as substrate. 3. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) separated two subunits, each with a mol. wt approximately 122 kDa. 4. On non-denaturing acrylamide gels both of these subunits exhibited oxidase-like activity with xanthine as substrate in the presence of nitroblue tetrazolium and molecular oxygen. 5. Immunoconjugates of XO were prepared by the keyhole limpet hemocyanin (KLH)- and glutaraldehyde-crosslinking techniques. 6. Polyclonal antibodies to XO were raised by i.m. injection of these conjugates into female New Zealand rabbits. 7. Western blot analysis using the semi-dry technique was employed to confirm the specificity of the antibody.

Animals↗
PubMed1989

The problem of replicability in program evaluation. The component solution using the example of case management.

Specificity and replicability of a program are crucial in order to rigorously evaluate the program's effectiveness. However, the traditional approaches to evaluation have ignored the problem that most social and mental health programs consist of vaguely specified interventions and cannot meet minimal standards of replicability. Consequently, the results of effectiveness evaluations of poorly defined programs have little general generalizability. Nevertheless, effectiveness information concerning su ch programs is much needed. One solution to this problem is to focus on program components, examining interventions at a level where operational definitions can be employed and replicability is possible. In this paper, this approach is expanded using the example of case management programs. A component-oriented approach ensures a systematic evaluation of program effectiveness for which the first question for evaluators is whether a program consists of interventions that reliably produce specific immediate outcomes. Then, and only then, is it possible to address questions concerning whether a program will reliably produce those outcomes that are the overall objectives of the program.

Humans↗
PubMed1989

Mechanisms of hypoxemia during panendoscopy.

Hypoxemia during esophagogastroduodenoscopy (EGD), or panendoscopy has been generally attributed to sedation. We studied 49 patients ranging in age from 17 to 71 years with normal or nearly normal lung function undergoing EGD to determine the effects of sedation and the effects of the endoscope on arterial oxygen saturation (SaO2). All patients received intravenous diazepam and 41 also received meperidine. EGD was delayed 10.7 +/- 7.5 min after intravenous diazepam administration in the 42 group 1 patients. Seven patients underwent EGD within 2 min of receiving intravenous diazepam (group 2). Ventilation decreased after diazepam, recovered, then decreased immediately after endoscope insertion in the group 1 patients. Periods of hypopnea, up to 39 s long, were observed during EGD. The average decrease in SaO2 was 4.0% after diazepam (p less than 0.0001). SaO2 returned to the pre-EGD level, then decreased 2.4% during EGD (p less than 0.0005). Maximum SaO2 decrease occurred 27 +/- 6 s after insertion of the endoscope then rapidly recovered. There was a linear correlation between the duration of hypopnea and maximum SaO2 decrease (r = 0.84, p less than 0.001). All group 2 patients experienced a period of hypopnea (13.3 +/- 9.6 s) and SaO2 declined 9.0%. The SaO2 decline was significantly greater in the group 2 subjects (p less than 0.0001). Our results confirm previous findings that intravenous sedation causes hypoventilation and hypoxemia. Moreover, hypoventilation and further arterial oxygen desaturation are caused by either the mechanical effect of the endoscope or a reflex stimulated by it.

Adolescent↗
PubMed1989

Pregnancy outcome following first trimester exposure to cocaine in social users in Toronto, Canada.

Studies of drug-dependent women reveal high rates of adverse fetal effects of cocaine. However, no data are available on the effect of the chemical in social users who discontinue cocaine upon realizing they are pregnant. We report the results of the first phase of a prospective study examining the outcome of pregnancy in women seeking counseling from the Motherisk Program in Toronto. Of 25 women seen in our clinic for 1st trimester cocaine exposure, 92% reported use of less than 10 g of cocaine and 36% reported marijuana use. Other illicit drug use was rare; cigarette and alcohol use was common. The study group did not experience adverse pregnancy outcome above the rate expected in the general population. There were 23 single births 1 pair of twins, and 1 spontaneous abortion. Birth weight and gestation were within normal limits. Only 1 child had a major malformation, syndactyly. Infant development was within normal limits, as measured by developmental milestones. All children are scheduled for assessment using the Bayley Scales of Infant Development. The results of the BSID will be compared to results from a cannabis-exposed control group and a no-drug control group.

Canada↗
PubMed1988

Reasons for consumption and heavy caffeine use: generalization of a model based on alcohol research.

The extent of alcohol consumption and problems has been found to be related to the types of reasons for consuming. At least two types of motives have been identified ("personal effects" and "social") with "personal effects" motives related to higher consumption and more alcohol problems. The present study tested the applicability of this model to caffeine consumption, in particular, coffee and tea. Eighteen motives for consuming coffee and tea were used to predict coffee/tea consumption, dependence, and problems. Principal component analyses identified four types of motives: two social ("sociability" and "beverage") and two personal effects ("stimulant" and "relief"). Overall, the "relief" and "stimulant" types of motives were the best predictors for all criterion measures (consumption, dependence and problems); "beverage" motives strongly predicted consumption and dependence; and "sociability" motives were least useful in predicting all criterion measures. These results are consistent with research on the relationship between extent of alcohol consumption/problems and reasons for consuming.

Alcohol Drinking↗
PubMed1988

Analyses of frequency of infection, specific infectivity, and prion protein biosynthesis in scrapie-infected neuroblastoma cell clones.

Scrapie, a spongiform encephalopathy of sheep and goats, is caused by a poorly understood transmissible agent in which no nucleic acid has been conclusively identified. Biochemical characterization of agent derived from animal tissues has not been precise because of the tenacious association of the agent with tissue components. As an approach toward obtaining homogeneous preparations of agent generated in vitro, we cloned scrapie-infected neuroblastoma cells. By frequency analysis, nearly every cell in expanded cultures contained scrapie agent. We also analyzed cell-dose infectivity relationships and developed a standard curve which allowed various cultures to be compared. Since a proteinase K (PK)-resistant form of a protein designated prion protein (PrP) has been found in partially purified preparations of scrapie agent from infected animal spleens and brains, we sought to identify this protein in cell cultures. No PK-resistant PrP was found in infected or uninfected cultures, although the PK-sensitive PrP was readily detected. These results suggested that PK-resistant PrP may not be an essential component of the infectious scrapie agent.

Animals↗