PubMed Health⌕ Search

Biomedical subjects

S Kemp

Publications and source records attributed to S Kemp.

At least 19 recordsLinked to original sources
PubMed2001

ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations.

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene, which encodes a peroxisomal ABC half-transporter (ALDP) involved in the import of very long-chain fatty acids (VLCFA) into the peroxisome. The disease is characterized by a striking and unpredictable variation in phenotypic expression. Phenotypes include the rapidly progressive childhood cerebral form (CCALD), the milder adult form, adrenomyeloneuropathy (AMN), and variants without neurologic involvement. There is no apparent correlation between genotype and phenotype. In males, unambiguous diagnosis can be achieved by demonstration of elevated levels of VLCFA in plasma. In 15 to 20% of obligate heterozygotes, however, test results are false-negative. Therefore, mutation analysis is the only reliable method for the identification of heterozygotes. Since most X-ALD kindreds have a unique mutation, a great number of mutations have been identified in the ABCD1 gene in the last seven years. In order to catalog and facilitate the analysis of these mutations, we have established a mutation database for X-ALD ( http://www.x-ald.nl). In this review we report a detailed analysis of all 406 X-ALD mutations currently included in the database. Also, we present 47 novel mutations. In addition, we review the various X-ALD phenotypes, the different diagnostic tools, and the need for extended family screening for the identification of new patients.

ATP Binding Cassette Transporter, Subfamily D, Mem↗
PubMed2001

Delayed union stress fractures of the anterior tibia: conservative management.

INTRODUCTION: A conservative method of treating four delayed union stress fractures of the anterior mid-tibia is described, with an illustrative case history. METHODS: Once diagnosed each of the patients was treated in a pneumatic lower leg brace with modified rest. The mean (range) age of the patients was 28 (24-32) years and all were involved in professional or amateur sports. The mean (range) duration of symptoms before diagnosis and definitive treatment of the four fractures was 9 (3-14) months. RESULTS: Use of this technique avoided the need for surgery in this group of patients and allowed return to unrestricted activity an average of 12 months from presentation. CONCLUSION: The treatment is cost effective and avoids the often uncertain results and morbidity associated with surgery for these difficult stress fractures.

Adult↗
PubMed2001

Restoring pleasure: nutritional management of dysphagia.

Dysphagia is associated with many different conditions and although widespread it is frequently not recognized. People with dysphagia are at risk of developing serious complications such at malnutrition, dehydration and aspiration. Texture modification, food fortification and dietary supplements are important elements in effective nutritional management of dysphagia and can also help bring back some of the pleasure to mealtimes. The ideal approach to the management of dysphagia involves a multidisciplinary team.

Deglutition Disorders↗
PubMed2001

What happens if you retest autobiographical memory 10 years on?

Burt (1992a, 1992b) reported data on the autobiographical memory of diarists for events that had occurred on average 3.3 years earlier. This paper reports data on 11 of the diarists, who were recontacted after a further 10 years and who agreed to a retest of their memory. Estimates of event date and event duration from the two recall attempts were compared. As predicted, duration estimation was extremely stable and showed no detrimental effects of the additional 10 years of retention interval. Estimation of event date was predicted to show an increase in forward telescoping due to the increased remoteness of the event sample, but, contrary to this prediction, backward telescoping dominated dating errors. A combination of the establishment of a recent boundary and Kemp's (1999) associative model of dating is proposed as an explanation for these results. It is argued that the nature of dating errors may depend on the time of the event's occurrence in the life span and the age of the individual dating the events.

Adult↗
PubMed2001

Twins dispute memory ownership: a new false memory phenomenon.

In three experiments, we examined a new memory phenomenon: disputed memories, in which people dispute ownership of a memory. For example, in one disputed memory each of two twins recollected being sent home from school for wearing too short a skirt, although only one of them was actually sent home. In Experiment 1, 20 sets of same-sex adult twins were asked to produce a memory for each of 45 words, and most twins spontaneously produced at least one disputed memory. In Experiment 2,20 different sets of same-sex adult twins rated disputed memories as higher in recollective experience, imagery, and emotional reliving than nondisputed memories. In Experiment 3, siblings who were close in age as well as same-sex friends were also found to have disputed memories, but less often than twins.

Adolescent↗
PubMed2001

Experts discuss findings on drug resistance.

John Mellors, MD, professor of medicine and chief of infectious diseases at the University of Pittsburgh, and Sharon Kemp, director of HIV Research for Virco UK in Cambridge, United Kingdom, answer questions about a study presented at the 5th International Workshop on HIV Resistance and Treatment Strategies, held in June in Scottsdale, AZ. The study found that a change at position 318 in the genetic code of HIV can make the virus highly resistant to treatment with non-nucleoside reverse transcription.

Anti-HIV Agents↗
PubMed2000

Understandings and experiences of cruelty: an exploratory report.

The authors investigated popular understandings of cruelty among 103 undergraduates who identified the cruelest acts that they had experienced vicariously and personally. The authors also examined the reasons that the cited acts were defined as cruel. Results indicated that most of the vicarious cruel acts involved intense aggression or sexual imposition, whereas personally experienced cruelty was milder, frequently consisting of teasing or gossip. Offense, victim, and perpetrator characteristics were all cited as reasons that acts were considered cruel. The authors also investigated gender differences in reported acts and reasons. Future researchers should address the discrepancies between vicarious and personally experienced cruelty. Findings with regard to personal acts also call for links to the literature on callousness and victimization.

Adolescent↗
PubMed2000

Ordering autobiographical experiences.

This study examined individuals' memory for the temporal order of autobiographical events and for the components that constitute autobiographical events. Study 1 measured performance on an across-event ordering task that involved the chronological arrangement of cards that displayed event labels. Results indicated poor ordering ability across events, but a reasonable ability to order clusters of events. Study 2 compared within-event and across-event ordering using computer-presented digital photographs. Participants were better at ordering the photographs in their own across-event trials than in their within-event trials. The results are discussed in terms of the retrieval of temporal information under within- and across-event conditions.

Adolescent↗
PubMed2000

Resistance profile of the human immunodeficiency virus type 1 reverse transcriptase inhibitor abacavir (1592U89) after monotherapy and combination therapy. CNA2001 Investigative Group.

Abacavir (1592U89) is a nucleoside inhibitor of human immunodeficiency virus (HIV) type 1 reverse transcriptase (RT). Resistance to abacavir was studied with abacavir alone and with abacavir in combination with other nucleoside analogues in cell culture, in virus isolates from zidovudine/lamivudine clinical trials, and in the first dose-escalating 12-week clinical trial (CNA2001) to evaluate abacavir clinical potency. Abacavir alone in vitro selected for mutations at HIV RT codons K65R, L74V, Y115F, and M184V. However, abacavir combined with zidovudine selected against virus with the M184V mutation. Abacavir therapy in vivo resulted in large decreases in HIV load (>1 log), even in 1 subject who had the M184V mutation at baseline. A total of 51% of subjects showed new mutations at any of codons K65R, L74V, and M184V after abacavir monotherapy, compared with 11% who received zidovudine/abacavir. Small changes (2- to 4-fold) in abacavir susceptibility were detected. On stopping therapy, reselection of the pretherapy sequence occurred within 4 weeks.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Pharmacological induction of peroxisomes in peroxisome biogenesis disorders.

Inherited aberrant peroxisome assembly results in a group of neurological diseases termed peroxisome biogenesis disorders (PBDs). PBDs include three major clinical phenotypes that represent a continuum of clinical features from the most severe form, Zellweger syndrome (ZS), through neonatal adrenoleukodystrophy (NALD) to the least severe form, infantile Refsum's disease (IRD). Somatic cell complementation studies have identified 13 PBD complementation groups, each representing a defect in a peroxisomal protein (peroxin) involved in peroxisome biogenesis. Most complementation groups include a range of clinical phenotypes. In this study, peroxisome numbers were determined in fibroblasts from 29 PBD (ZS, NALD, and IRD) patients, with various phenotypes from nine complementation groups, using antibodies against either a peroxisomal membrane protein (anti-Pex14p) or peroxisomal matrix proteins (anti-SKL). A correlation between the number of peroxisomes, determined with either antibody, and PBD phenotype was found, suggesting that induction of peroxisome number might have a favorable effect on PBD. After treatment of PBD fibroblasts with sodium 4-phenylbutyrate, a human peroxisome proliferator, there was an approximate twofold increase in peroxisome number. After 4-phenylbutyrate treatment, an increase in transcription of the adrenoleukodystrophy-related gene and the peroxin gene, PEX11alpha, was found in PBD fibroblasts. In NALD and IRD, but not ZS, fibroblasts there was an increase in very-long-chain fatty acid beta-oxidation and plasmalogen concentrations, and a decrease in very-long-chain fatty acid concentrations. These data suggest that pharmacological agents that induce peroxisome proliferation, such as 4-phenylbutyrate, may have therapeutic potential in the treatment of PBD patients with milder phenotypes (NALD and IRD).

Cells, Cultured↗
PubMed1999

Baseline HIV drug resistance profile predicts response to ritonavir-saquinavir protease inhibitor therapy in a community setting.

OBJECTIVE: To determine whether baseline drug resistance assays could help to predict treatment failure with the protease inhibitor combination ritonavir-saquinavir. METHODS: Baseline HIV-1 drug resistance was determined for 76 consecutive patients who started treatment with the dual protease inhibitor combination ritonavir-saquinavir between September 1996 and June 1997 either alone or in combination with other antiviral agents. Resistance to 10 different antiviral agents was assessed by both phenotype (Virco Antivirogram) and genotype (Vircogen). RESULTS: Resistance inferred from viral genotype was similar to measured phenotypic resistance for both ritonavir and saquinavir (P<0.01). Baseline drug resistance phenotype was predictive of poor virological response to this dual protease inhibitor combination, despite the confounding effects of other antivirals. Patients were at least four times less likely to achieve a 0.5 log10 decrease in plasma HIV RNA viral load if their viral isolates were resistant to ritonavir or saquinavir. Patients classified as resistant to either drug using either method had median decreases in plasma viral load of 0.05 log10 HIV RNA copies/ml or less, compared to >0.8 log10 for those with sensitive virus. Patients resistant to both drugs never achieved plasma viral loads <100000 copies/ml. As little as fourfold increases in baseline resistance appeared to be sufficient to compromise even dual protease inhibitor therapy. CONCLUSION: Baseline resistance to ritonavir or saquinavir or both was associated with a poor antiviral response. Our data suggest that the measurement of drug resistance may assist in optimizing antiretroviral therapy in the clinic.

Anti-HIV Agents↗
PubMed1999

Role of very-long-chain acyl-coenzyme A synthetase in X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is characterized biochemically by decreased ability of cells to activate (via very-long-chain acyl-coenzyme A synthetase [VLCS]) and subsequently degrade very-long-chain fatty acids in peroxisomes. It is noteworthy that the gene defective in X-ALD encodes ALDP, a peroxisomal membrane protein unrelated to VLCS. We cloned human VLCS (hVLCS) and found that peroxisomes from X-ALD fibroblasts contained immunoreactive hVLCS, refuting the earlier hypothesis that ALDP is required to anchor VLCS to the peroxisomal membrane. Furthermore, hVLCS was topographically oriented facing the peroxisomal matrix in both control and X-ALD fibroblasts, contradicting the alternative hypothesis that ALDP is required to translocate VLCS into peroxisomes. However, overexpression of both hVLCS and ALDP in X-ALD fibroblasts synergistically increased very-long-chain fatty acid beta-oxidation, indicating that these proteins interact functionally.

Adrenoleukodystrophy↗
PubMed1999

X-linked adrenoleukodystrophy: genes, mutations, and phenotypes.

X-linked adrenoleukodystrophy (X-ALD) is a complex and perplexing neurodegenerative disorder. The metabolic abnormality, elevated levels of very long-chain fatty acids in tissues and plasma, and the biochemical defect, reduced peroxisomal very long-chain acyl-CoA synthetase (VLCS) activity, are ubiquitous features of the disease. However, clinical manifestations are highly variable with regard to time of onset, site of initial pathology and rate of progression. In addition, the abnormal gene in X-ALD is not the gene for VLCS. Rather, it encodes a peroxisomal membrane protein with homology to the ATP-binding cassette (ABC) transmembrane transporter superfamily of proteins. The X-ALD protein (ALDP) is closely related to three other peroxisomal membrane ABC proteins. In this report we summarize all known X-ALD mutations and establish the lack of an X-ALD genotype/phenotype correlation. We compare the evolutionary relationships among peroxisomal ABC proteins, demonstrate that ALDP forms homodimers with itself and heterodimers with other peroxisomal ABC proteins and present cDNA complementation studies suggesting that the peroxisomal ABC proteins have overlapping functions. We also establish that there are at least two peroxisomal VLCS activities, one that is ALDP dependent and one that is ALDP independent. Finally, we discuss variable expression of the peroxisomal ABC proteins and ALDP independent VLCS in relation to the variable clinical presentations of X-ALD.

Adrenoleukodystrophy↗
PubMed1999

Visual perception of motion, luminance and colour in a human hemianope.

Human patients rendered cortically blind by lesions to V1 can nevertheless discriminate between visual stimuli presented to their blind fields. Experimental evidence suggests that two response modes are involved. Patients are either unaware or aware of the visual stimuli, which they are able to discriminate. However, under both conditions patients insist that they do not see. We investigate the fundamental difference between percepts derived for the normal and affected hemifield in a human hemianope with visual stimuli of which he was aware. The psychophysical experiments we employed required the patient, GY, to make comparisons between stimuli presented in his affected and normal hemifields. The subject discriminated between, and was allowed to match, the stimuli. Our study reveals that the stimulus parameters of colour and motion can be discriminated and matched between the normal and blind hemifields, whereas brightness cannot. We provide evidence for associations between the percepts of colour and motion, but a dissociation between the percepts of brightness, derived from the normal and hemianopic fields. Our results are consistent with the proposal that the perception of different stimulus attributes is expressed in activity of functionally segregated visual areas of the brain. We also believe our results explain the patient's insistence that he does not see stimuli, but can discriminate between them with awareness.

Adult↗
PubMed1999

Coping with epilepsy: do illness representations play a role?

OBJECTIVES: To determine the relative contributions of neuroepilepsy, coping and illness representation variables to psychological adjustment in epilepsy. DESIGN: The study was a cross-sectional design, contrasting the adjustment of recently diagnosed and chronic patients. Neuroepilepsy, illness representation, coping and adjustment variable were all measured. METHOD: A total of 94 patients were studied comprising three groups: recently diagnosed patients, chronic patients cared for in hospital clinics, and chronic patients cared for by their GP. A measure was developed to assess each patient's illness representations of epilepsy. RESULTS: Overall, the epilepsy patients showed significant adjustment problems relative to a normative group. There were, however, significant differences between epilepsy subgroups: recently diagnosed and chronic (clinic) patients exhibited problems, but chronic (GP) patients were relatively well adjusted. After controlling for the effects of group membership and neuroepilepsy variables, coping and illness representations, each explained significant additional variance on measures of psychological adjustment. Patients presenting with adjustment difficulties were characterized by high seizure frequency, avoidance father than problem-focused coping, doubt about their diagnostic label and belief in poor containment. CONCLUSIONS: We conclude that the illness representations paradigm has value in understanding psychosocial adjustment to epilepsy. This approach offers the potential to identify the critical factors in patients' adaptation to illness. Such insights into the coping process may contribute to the development of effective clinical interventions.

Acute Disease↗