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S Adam

Publications and source records attributed to S Adam.

At least 19 recordsLinked to original sources
PubMed1995

Are we all of one mind? Clinicians' and patients' opinions regarding the development of a service protocol for predictive testing for Huntington disease. Canadian Collaborative Study for Predictive Testing for Huntington Disease.

There are currently different research programs in place to assess the effects of predictive testing for a few late-onset disorders, including Huntington disease (HD) and familial cancers. Prior to providing predictive testing as a service, we sought the views of both the patients and the clinicians as to the importance and value of different items in a research protocol for HD. We mailed questionnaires to 41 clinicians and 351 at-risk patients who had participated in the research protocol, to solicit their opinions on the relative importance of various components of the HD predictive testing research protocol. Completed questionnaires were received from 256 patients (73%) and 33 clinicians (80%). Most participants (96%) were satisfied with the program, and < 3% of persons receiving a modification of risk felt that predictive testing had impaired their quality of life. While there was consensus on the importance of most components of the protocol, significantly more clinicians than patients (97% vs. 72%; P = 0.02) felt it was essential to keep written material about HD as part of a service protocol. More patients than clinicians (83% vs. 27%) considered it essential to have 24-hr contact numbers following disclosure of test results (P < 0.0001). Patients also felt more strongly about the importance of counseling about technical aspects of predictive testing (84% vs. 77%; P < 0.02), and about having a support person attend counselling sessions with the patient (62% vs. 48%; P = 0.04). Nearly 25% of participants indicated that they would not want their general practitioner routinely involved in the predictive testing program. These findings have influenced the development of our service protocol, and they underscore the importance of involving both providers and consumers of predictive testing in the development of a service protocol for genetic testing.

Adolescent↗
PubMed1995

Clinical trial of cross-linked human type I collagen as a barrier material in surgical periodontal treatment.

This study was undertaken to evaluate freeze-dried cross-linked human type I collagen when used as a barrier membrane for guided tissue regeneration (GTR) in periodontal surgery. 14 patients with radiographic evidence of bone loss and residual pocketing of > 6 mm on bilaterally matched sites were given preliminary scaling, polishing and oral hygiene instruction before undergoing contralateral flap surgery. At the experimental sites, a collagen membrane was adapted to the root surfaces, extending from 2 mm apical to the bone crest to just subgingival, before replacing the flap and closing with sutures. The control sites underwent a similar procedure but without the placement of the collagen barrier. The experimental sites were selected at random. Plaque index (PLI), gingival index (GI), bleeding index (BI), probing pocket depth (PPD) and probing attachment level (PAL) were recorded at baseline, 6, 12 and 26 weeks post-operatively. The bony defects were classified and furcation involvement noted. The clinical parameters were recorded by an examiner, previously assessed for accurate reproducibility of measurement, who was not the surgeon and unaware of the experimental sites. PPD and PAL were measured using a constant pressure probe localised by a soft stent. There was significant improvement in the PLI, GI and BI at both test and control sites at 6, 12 and 26 weeks compared to baseline (P < 0.001 for PLI; P < 0.0001 for GI and BI) but not significant difference between these sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A comparative clinical study: the use of human type I collagen with and without the addition of metronidazole in the GTR method of treatment of periodontal disease.

This investigation was undertaken to evaluate cross-linked human type I collagen, with and without added metronidazole, when used as a barrier membrane in the guided tissue regeneration (GTR) principle of treatment for periodontal disease. 16 patients suffering from moderate to severe periodontitis with 78 bilaterally matched periodontal defects underwent similar contralateral surgical flap procedures after preliminary scaling, polishing and oral hygiene instruction. At the experimental sites, which were selected at random, the flap was closed over metronidazole impregnated collagen as a GTR membrane, the contralateral sites receiving a plain collagen barrier as control. The plaque index (PLI), gingival index (GI), bleeding index (BI), probing pocket depth (PPD) and probing attachment level (PAL) were recorded at baseline, 6, 12 and 26 weeks post-operatively. The bony defects were classified and furcation involvement noted. The clinical parameters were recorded by an examiner, other than the surgeon, who had been previously assessed for accurate reproducibility of measurements and was unaware of the experimental sites. PPD and PAL were measured with a constant pressure probe, localised by a soft stent. Post-operative discomfort was evaluated by means of a questionnaire. PLI, GI and BI were significantly improved compared to baseline for both test and control sites at 6, 12 and 26 weeks post surgery (p < 0.001) but there was no significant difference between these sites (p > 0.05). There was a reduction in PPD at 6 weeks which was significant at 12 and 26 weeks post-operatively (p < 0.001) for both test and control sites, but no difference between these sites was evident (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Interaction between gamma delta T cells and B cells regulating IgG production.

Despite profound knowledge about the molecular structure of the gamma delta T-cell receptor (TCR), the physiological function of gamma delta T cells remains enigmatic. Participation of these cells in complex immune reactions, however, is suggested by the appearance of gamma delta T cells in sites of infectious and autoimmune-induced inflammations. Only a few in vitro models of gamma delta T-cell stimulation have been established: besides a reactivity in the presence of microbial ligands, human gamma delta T cells proliferate upon in vitro challenge with cells from an allogeneic B-lymphoblastic cell line (B-LCL). We present data here demonstrating that this reactivity is not confined to allogenic B-LCL. Autologous B-LCL are also very strong stimulators for gamma delta T cells; more important, autologous B cells can stimulate gamma delta T cells after a period of mitogen-activation but not in a resting state. This activation seems to address a subgroup of gamma delta T cells, as the percentage of V delta 1+ cells is increased after stimulation. Activated gamma delta T cells, on the other hand, are able to exert an influence on B cells by inhibiting the secretion of IgG in coculture experiments. These data define a simple regulatory circle of B cells and gamma delta T cells in vitro and propose a model for gamma delta T-cell function which could explain many in vivo observations of gamma delta T-cell activation.

B-Lymphocytes↗
PubMed1994

Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm.

Huntington disease is associated with an unstable and expanded (CAG) trinucleotide repeat. We have analysed the CAG expansion in different tissues from 12 affected individuals. All tissues examined were found to display some repeat mosaicism, with the greatest levels detected in brain and sperm. Regions within the brain showing most obvious neuropathology, such as the basal ganglia and the cerebral cortex, displayed the greatest mosaicism, whereas the cerebellar cortex, which is seldom involved, displayed the lowest degree of CAG instability. In two cases of childhood onset disease we detected differences of 8 and 13 trinucleotides between the cerebellum and other regions of the brain. Our results provide evidence for tissue specific instability of the CAG repeat, with the largest CAG repeat lengths in affected regions of the brain.

Adult↗
PubMed1994

Proceed with care: direct predictive testing for Huntington disease.

The cloning of the Huntington disease (HD) gene allows highly accurate predictive testing using direct analysis of the CAG repeat. This new test provides results with almost complete certainty but poses unique counseling issues related to direct testing for an adult-onset disease. These include testing individuals who are at 25% risk, without the need for blood from a 50% at risk relative; the assessment of symptomatic individuals; the need for ongoing counseling despite simplification of laboratory procedures; and counseling of persons from families who represent a new mutation for HD. This paper describes protocols for direct predictive testing for adult and prenatal assessment, on the basis of the experience of the Canadian Collaborative Study on Predictive Testing (CCSPT). Over the past 8 years, we have provided > 400 results by using linked markers and, more recently, 416 results by using direct assessment of CAG expansion in the HD gene. The vast majority (86%) of requests for direct predictive testing have been from persons who have not previously received results by using linked markers. Despite the ability to now directly assess for the mutation associated with HD, we still recommend assessment of DNA from an affected relative, as this may significantly enhance the accuracy of information to be provided to the at-risk individual. Distance from a genetics center has previously limited the availability of testing, and therefore we have developed approaches to providing predictive testing in the patient's own community.

Adult↗
PubMed1994

Huntington disease without CAG expansion: phenocopies or errors in assignment?

Huntington disease (HD) has been shown to be associated with an expanded CAG repeat within a novel gene on 4p16.3 (IT15). A total of 30 of 1,022 affected persons (2.9% of our cohort) did not have an expanded CAG in the disease range. The reasons for not observing expansion in affected individuals are important for determining the sensitivity of using repeat length both for diagnosis of affected patients and for predictive testing programs and may have biological relevance for the understanding of the molecular mechanism underlying HD. Here we show that the majority (18) of the individuals with normal sized alleles represent misdiagnosis, sample mix-up, or clerical error. The remaining 12 patients represent possible phenocopies for HD. In at least four cases, family studies of these phenocopies excluded 4p16.3 as the region responsible for the phenotype. Mutations in the HD gene that are other than CAG expansion have not been excluded for the remaining eight cases; however, in as many as seven of these persons, retrospective review of these patients' clinical features identified characteristics not typical for HD. This study shows that on rare occasions mutations in other, as-yet-undefined genes can present with a clinical phenotype very similar to that of HD.

Adult↗
PubMed1993

Attitudes toward direct predictive testing for the Huntington disease gene. Relevance for other adult-onset disorders. The Canadian Collaborative Group on Predictive Testing for Huntington Disease.

OBJECTIVE: To assess attitudes toward, and projected utilization of, direct mutation testing by individuals at risk for Huntington disease (HD). DESIGN: Prior to the cloning of the gene for HD, a questionnaire concerning the use of a definitive test was constructed and mailed to 354 participants in the Canadian Collaborative Study for HD. Completed questionnaires were received from 250 participants (response rate, 71%). Persons were asked to indicate whether they would participate in a new predictive test that was either 100% accurate (the definitive test, requiring blood only from the proband) or only 99% accurate. RESULTS: Most (72%) of the persons who had previously received a result in a predictive testing program said they would request testing in either situation. Significantly more persons would request the definitive test than the 99% accurate test (72% vs 58%; P < .02). Respondents for whom testing was uninformative in the linkage test program or who had previously received an increased-risk result were more likely to indicate they would use the test than those who received a decreased-risk result or chose not to have the original test (P = .0003). Less than half (46%) of the participants who initially chose not to have the linkage test said they would return for the new direct test. The major factor that has limited acceptance of predictive testing for this group is the concern about receiving an increased-risk result in the absence of any therapy to alter progression of the disease. CONCLUSIONS: A direct mutation test for HD will most readily be accepted by persons who wanted but could not previously receive a result in the linkage test program and those who previously received an increased-risk result. In the absence of therapy, the majority of persons who previously chose not to have predictive testing are unlikely to participate in a new test despite improved accuracy. This has implications for the expected demands for testing services for other adult-onset genetic disorders.

Attitude to Health↗
PubMed1993

Diagnosis of Huntington disease: a model for the stages of psychological response based on experience of a predictive testing program.

Persons diagnosed as affected with Huntington's disease (HD) may have similar stages of psychological response to the clinical presentation of the illness. Here we describe a model of these stages of response based on our experience during a predictive testing program for HD. During the Warning Stage, asymptomatic persons are aware of their risk status for HD and develop defenses which favor adaptation to their genetic risk. In response to the initial signs and symptoms of HD (the Incipient Stage) unconscious working through of this realization occurs while it is still kept out of conscious awareness. When symptoms become obvious such that recognition of disease onset is inevitable (Breakthrough Stage) the possibility of the diagnosis of HD is assimilated. After the delivery of the diagnosis during the Adjustment Stage, short- and long-term adaptive responses to living with HD occur. Recognition of the stage of psychological response of a patient who presents with HD is important prior to delivering a clinical diagnosis. In a significant minority of cases, the psychological readiness lags behind the clinical symptomatology and premature presentation of a diagnosis may result in significant untoward adverse events. Understanding of the stages of response may provide a framework for evaluating the psychological state of the person with HD and determining their readiness to receiving the diagnosis. This model may have relevance to the psychological responses of patients to the diagnosis of other late onset autosomal dominant disorders.

Adaptation, Psychological↗
PubMed1993

The development of a pressure area scoring system for critically ill patients: a pilot study.

At present no suitably sensitive scoring system is available to differentiate degrees of risk of developing pressure sores in critically ill people. The object of this study is to produce a tool that has been validated to identify and weight risk factors associated with critically ill patients. In a pilot study data were collected on 50 patients and analysed, using multiple regression analysis, to produce a set of weighted coefficients (C) suitable for use as a scoring system. The feasibility of the technique is demonstrated and five highly significant factors are described: adrenaline infusions (C = 14), noradrenaline infusions (C = 15), diabetes (C = 15), restricted movement (traction, post-operative pain, intra-aortic balloon pump and haemofiltration) (C = 8) and patients too unstable to turn (C = 17). All coefficients not equal to 0 with p < 0.05. Risk factors which may become significant in a larger study are identified. In order to develop the full tool a further multi-centre study is proposed.

Aged↗
PubMed1993

The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease.

Huntington's disease (HD) is associated with the expansion of a CAG trinucleotide repeat in a novel gene. We have assessed 360 HD individuals from 259 unrelated families and found a highly significant correlation (r = 0.70, p = 10(-7)) between the age of onset and the repeat length, which accounts for approximately 50% of the variation in the age of onset. Significant associations were also found between repeat length and age of death and onset of other clinical features. Sib pair and parent-child analysis revealed that the CAG repeat demonstrates only mild instability. Affected HD siblings had significant correlations for trinucleotide expansion (r = 0.66, p < 0.001) which was not apparent for affected parent-child pairs.

Adolescent↗
PubMed1993

Molecular analysis of new mutations for Huntington's disease: intermediate alleles and sex of origin effects.

Huntington's disease (HD) is associated with expansion of a CAG repeat in a novel gene. We have assessed 21 sporadic cases of HD to investigate sequential events underlying HD. We show the existence of an intermediate allele (IA) in parental alleles of 30-38 CAG repeats in the HD gene which is greater than usually seen in the general population but below the range seen in patients with HD. These IAs are meiotically unstable and in the sporadic cases, expand to the full mutation associated with the phenotype of HD. This expansion has been shown to occur only during transmission through the male germline and is associated with advanced paternal age. These findings suggest that new mutations for HD are more frequent than prior estimates and indicate a previously unrecognized risk of inheriting HD to siblings of sporadic cases of HD and their children.

Adult↗
PubMed1993

Five year study of prenatal testing for Huntington's disease: demand, attitudes, and psychological assessment.

Adult predictive and prenatal testing programmes for Huntington's disease (HD) in Canada have been available since 1986. However, the demand for prenatal testing and the reasons why some people choose not to have the prenatal test for this late onset disorder have not been well documented. In addition, the knowledge and attitudes of adult predictive testing candidates and their partners about prenatal testing are not well known nor are the psychological effects of prenatal testing well understood. As of September 1991, 425 subjects had entered the Canadian Collaborative Study of Predictive Testing and, of these, 47 subjects or their partners had become pregnant. Of this group, 14 (30%) couples requested prenatal testing, 24 (51%) couples did not want prenatal testing, and nine (19%) at risk subjects had already received a decreased risk through adult predictive testing and, therefore, were not eligible for the prenatal test. Of the 14 couples who initially requested prenatal testing, seven withdrew. Thus, demand for the prenatal test by eligible candidates was 7/38 or 18%, which is much lower than the 32 to 65% expected based on early survey data. The most frequently cited reason for declining prenatal testing was the hope that a cure would be found in time for their children. While the majority of adult predictive testing candidates (71%) in our study had accurate information about definitive prenatal testing, many (63%) did not have a correct understanding of exclusion prenatal testing. Although no serious adverse events such as suicide planning or admission to psychiatric hospital have occurred, a particular need for careful counselling was identified for those at risk candidates and their partners who have one prenatal test and feel compelled to use the test again in future pregnancies. Even though prenatal testing for HD is not requested as often originally expected, it still remains a desired option for some at risk persons and their partners.

Adult↗
PubMed1992

The psychological consequences of predictive testing for Huntington's disease. Canadian Collaborative Study of Predictive Testing.

BACKGROUND: Advances in molecular genetics have led to the development of tests that can predict the risk of inheriting the genes for several adult-onset diseases. However, the psychological consequences of such testing are not well understood. METHODS: The 135 participants in the Canadian program of genetic testing to predict the risk of Huntington's disease were followed prospectively in three groups according to their test results: the increased-risk group (37 participants), the decreased-risk group (58 participants), and the group with no change in risk (the no-change group) (40 participants). All the participants received counseling before and after testing. Standard measures of psychological distress (the General Severity Index of the Symptom Check List 90-R), depression (the Beck Depression Inventory), and well-being (the General Well-Being Scale) were administered before genetic testing and again at intervals of 7 to 10 days, 6 months, and 12 months after the participants received their test results. RESULTS: At each follow-up assessment, the decreased-risk group had lower scores for distress than before testing (P < 0.001). The increased-risk group showed no significant change from base line on any follow-up measure, but over the year of study there were small linear declines (P < 0.023) for distress and depression. The no-change group had scores lower than at base line on the index of general well-being at each follow-up (P < or = 0.045). At the 12-month follow-up, both the increased-risk group and the decreased-risk group had lower scores for depression and higher scores for well-being than the no-change group (P < or = 0.049). CONCLUSIONS: Predictive testing for Huntington's disease has potential benefits for the psychological health of persons who receive results that indicate either an increase or a decrease in the risk of inheriting the gene for the disease.

Adult↗
PubMed1992

Predictive testing for Huntington disease in Canada: the experience of those receiving an increased risk.

Predictive testing for Huntington disease (HD) has been offered in some parts of Canada for nearly 5 years. Candidates who were expected to have a significant likelihood for psychological problems were those who received an increased risk for developing HD. Sixty-six persons have now received such an increased risk result. In this manuscript we describe in detail the experience of 4 such persons who were chosen to illustrate recurrent and common themes which have emerged during counselling, and to highlight the strategies of coping with this information. Themes include difficulties communicating about HD, defensive postures adopted in preparing for testing, ramifications of testing for the whole family, and the impact of being at high risk on the candidates' perception of the future. One candidate has had testing postponed due to active suicidal risk. Only a few candidates have expressed regret at taking the test and no person receiving an increased risk result has made a suicide attempt or required hospitalization. After receiving results, symptoms of depression and anxiety are most common in the first 2 months, but over 1 year, candidates, in general, have less depression but live with a heightened perception of the present. The potential risk of premature diagnosis of HD in an individual with an increased risk results is highlighted. The significant ramifications of testing for the relative are shown. The importance of communication as a means of establishing a social support network, as well as the hazards of open communication, are discussed. Longitudinal evaluation will provide much needed data on the long-term effects of living at increased risk for HD.

Adult↗
PubMed1992

Predictive testing for Huntington disease in Canada: adverse effects and unexpected results in those receiving a decreased risk.

By January 1, 1991, a total of 388 persons had enrolled in the Canadian collaborative study of predictive testing for Huntington disease (HD). Of these participants, 105 persons have been given a decreased risk result. Contrary to expectations, approximately 10% of persons with a decreased risk result have had psychological difficulties coping with their new status. Here, we describe the individual responses of 6 such persons and experimental themes emerging after following these persons for up to 2 years. Individuals who are more likely to suffer an adverse reaction to a decreased risk result include those persons who have made irreversible decisions based on the belief they would develop HD or those who had unrealistic overoptimistic expectations of the positive effects of a decreased risk result. In contrast to those receiving an increased risk result, the most vulnerable time for persons receiving a decreased risk result is between 2 and 12 months after learning the outcome. The need for assessment and counselling of participants in predictive testing programs, even when there is a decreased risk result, is emphasized.

Adult↗