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S Adam

Publications and source records attributed to S Adam.

At least 37 records · Page 2Linked to original sources
PubMed1997

Demonstration of discrete secreted and membrane-bound ocular mucins in the dog.

Our aims were to separate and characterize secreted canine ocular mucins, and to provide definitive evidence of membrane-bound mucins at the canine ocular surface. Mucus was collected by suction from the ocular surface of normal dogs and dispersed in guanidine hydrochloride and a cocktail of protease inhibitors. Caesium chloride density gradient centrifugation separated secreted mucins from membranes, which were collected from the top of the gradients. Membranes were extracted with octyl glucoside and screened using lectins and anti-mucin antibodies. Gradient fractions containing secreted mucins were constituted into pools on the basis of differential lectin and antibody staining. High molecular weight material from each pool was purified by gel filtration. This material, and the membrane extract, were reduced and alkylated. Vacuum blotting of separated materials after agarose gel electrophoresis was used to compare subunit structure. Density gradient profiles indicated three principal secreted glycoprotein peaks: one staining strongly with anti-mucin antibodies. Gel filtration demonstrated that each contained high molecular weight material. Vacuum blots demonstrated the presence of two secreted glycoproteins with differently sized subunits. On the basis of buoyant density, one of these may be lipid complexed. Membrane extracted material stained with anti-mucin antibodies, and vacuum blotting of this material provided evidence for two membrane-bound components. In conclusion, we have shown that normal canine ocular mucus contains two secreted mucins, each exhibiting different subunit structure; one of these mucins may undergo lipid complexation. Normal canine ocular mucus also contains two membrane-bound mucins: one of which is unique among membrane mucins in showing subunit structure.

Animals↗
PubMed1997

A study of problems associated with the delivery of enteral feed in critically ill patients in five ICUs in the UK.

OBJECTIVES: To describe the incidence of problems associated with enteral feeding in different patient groups and intensive care units (ICUs). To compare this incidence with specific feeding protocols and volumes of feed delivered. To identify for future study any interventions likely to improve delivery of enteral feed and to manage or eliminate problems. DESIGN: A prospective, descriptive study of problems associated with enteral feeding in five ICUs over a period of 9 months. SETTING: ICUs in two district general and three university hospitals. PATIENTS: ICU patients (age > 18 years) who received enteral feeding for a period > 24 h. MEASUREMENTS AND RESULTS: 193 patients were studied for a total of 1929 patient-days. On average, only 76% of the quantity of feed prescribed was delivered to the patient. The two main problems preventing delivery of feed were gut dysfunction and elective stoppage for procedures. ICUs with well-defined feeding protocols delivered significantly greater volumes of feed (p < 0.0001) than those without. Feeding was abandoned in 11% of patients, half of these due to gastric dysfunction. Only 2 of 193 patients were fed jejunally. CONCLUSIONS: The major factors associated with the interruption in delivery of feed are problems with gut function and stopping feed prior to a procedure. Use of specific feeding protocols is clearly associated with a greater volume of feed delivered and a greater percentage of the prescription delivered. These should be an integral part of all ICU protocols.

Adult↗
PubMed1997

Pelvic distraction to improve exposure in radical surgery for pelvic tumours in children.

We describe one patient who had pubic osteotomy and three who had symphysiotomy as an aid to radical tumour resections over the last 7 years. In each it was possible to distract the pelvis so improving access to the tumour. All four patients had pelvic rhabdomyosarcomata, three primarily in the prostate and lower bladder and one was a large tumour filling the pelvis, probably of bladder origin. No immediate or long-term complications of the procedure occurred, and in the two patients who died (2.5 years and 1 year post-surgery) or in the two survivors.

Child, Preschool↗
PubMed1997

Risk reversals in predictive testing for Huntington disease.

The first predictive testing for Huntington disease (HD) was based on analysis of linked polymorphic DNA markers to estimate the likelihood of inheriting the mutation for HD. Limits to accuracy included recombination between the DNA markers and the mutation, pedigree structure, and whether DNA samples were available from family members. With direct tests for the HD mutation, we have assessed the accuracy of results obtained by linkage approaches when requested to do so by the test individuals. For six such individuals, there was significant disparity between the tests. Three went from a decreased risk to an increased risk, while in another three the risk was decreased. Knowledge of the potential reasons for these changes in results and impact of these risk reversals on both patients and the counseling team can assist in the development of strategies for the prevention and, where necessary, management of a risk reversal in any predictive testing program.

Adult↗
PubMed1996

Adverse psychological events occurring in the first year after predictive testing for Huntington's disease. The Canadian Collaborative Study Predictive Testing.

A total of 135 participants in the Canadian predictive testing programme for HD were followed for at least one year in one of four study groups: increased risk (n = 37), decreased risk ( n = 58), uninformative (n = 17), or not tested (n = 23). Clinical criteria for an adverse event were a suicide attempt or formulation of a suicide attempt plan, psychiatric hospitalisation, depression lasting longer than two months, a marked increase in substance abuse, and the breakdown of important relationships. Quantitative criteria, as measured by changes on the General Severity Index of the Symptom Checklist 90-R and the Beck Depression Inventory, were also used to identify people who had adverse events. Twenty of the 135 participants (14.8%) had an adverse event. There were no significant differences between those with or without an adverse event with respect to age, sex, marital status, education, psychiatric history, general psychiatric distress, or social supports at baseline. However, evidence for depression was associated with an increased frequency of adverse events (p < 0.04). The adverse events were similar and seen with equivalent frequency in those receiving an increased risk or decreased risk and persons at risk who did not receive a modification of risk. However, a significant difference was found in the timing of adverse events for the increased and decreased risk groups (p < 0.0002). In the increased risk group all of the adverse events occurred within 10 days after results whereas, in the decreased risk group, all of the adverse events occurred six months or later after reviewing test results. These results suggest that people entering into predictive testing with some evidence of clinical depression warrant special vigilance and also suggest that counselling and support should be available for all participants in predictive testing irrespective of the direction of test results.

Adolescent↗
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↗