Biomedical subjects

R Jenkins

Publications and source records attributed to R Jenkins.

At least 19 recordsLinked to original sources

PubMed2000

Detection of ventricular enlargement in patients at the earliest clinical stage of MS.

The aim of this study was to determine whether atrophy could be detected at the earliest clinical stages of MS. Patients were selected from a 1-year follow-up MRI study of clinically isolated syndromes. Nine patients who developed MS were compared with eight matched patients who had no further symptoms. Significant ventricular enlargement occurred in the group that developed MS but not in the other group. Our findings show that atrophy, albeit mild, can be detected early in the course of MS.

Adolescent↗

PubMed2000

Progressive cerebral atrophy in MS: a serial study using registered, volumetric MRI.

OBJECTIVE: To assess the potential of registered volumetric MRI in measuring rates of atrophy in MS. BACKGROUND: Pathologic and imaging studies suggest that the development of permanent neurologic impairment in MS is associated with progressive brain and spinal cord atrophy. Atrophy has been suggested as a potential marker of disease progression. Conventional atrophy measurements requiring manual outlining are time-consuming and subject to reproducibility problems. Registration of serial MRI may offer a useful alternative in that cerebral losses may be measured directly from automated subtraction of brain volumes. METHODS: Twenty-six patients with MS and 26 age- and gender-matched controls had two volumetric brain MR studies 1 year apart. Baseline brain and ventricular volumes were measured using semiautomated techniques, and follow-up scans were registered to baseline. Rates of cerebral atrophy were calculated directly from the registered scans. RESULTS: Baseline brain volumes in the MS group were smaller (mean difference 78 mL [95% CI 13 to 143; p = 0.02]) and ventricular volumes greater (mean difference 12 mL [95% CI 6 to 18; p < 0.001]) than controls. The rate of cerebral atrophy in the MS group (0.8% per year) was over twice that of controls (0.3%), and the rate of ventricular enlargement was five times greater than the controls (1.6 versus 0.3 mL/year). CONCLUSION: Progressive cerebral atrophy is an important feature of MS. Registration-based measurements are sensitive and reproducible, allowing progressive atrophy to be detected within 1 year and may have potential as a marker of progression in monitoring therapeutic trials.

Adult↗

PubMed2000

Intracranial volume and Alzheimer disease: evidence against the cerebral reserve hypothesis.

BACKGROUND: Total intracranial volume (TIV) measurement commonly is used to correct for variations in premorbid brain size in imaging studies of cerebral structures in Alzheimer disease (AD). This assumes no intrinsic difference in TIV between patients and control subjects and that TIV measurements are unaffected by cerebral atrophy. However, an autopsy study has suggested that a larger premorbid brain may protect against AD onset. A recent computed tomographic study lent support to this by finding a correlation between intracranial size and age at onset of AD in women. OBJECTIVE: To investigate the relationship between TIV and sporadic and familial AD. DESIGN: Retrospective case study. SETTING: Specialist dementia clinic. PATIENTS: Eighty-five patients with AD and 52 healthy volunteers. MAIN OUTCOME MEASURES: Age at symptom onset and TIV measured using a semiautomatic interactive thresholding technique on magnetic resonance imaging spanning the entire intracranial cavity. RESULTS: Reproducibility measurement was high (intrarater coefficient of variation, 1.2%; interrater coefficient of variation, 0.7%). Unlike brain atrophy in the patients with AD, TIV did not vary over time. Mean TIV did not differ significantly between any of the subject groups. There was no association between TIV and age or age at symptom onset. The only significant predictor of TIV was sex. CONCLUSIONS: Measurements of TIV are independent of atrophy and can be used safely to adjust for differences in head size in studies of cerebral structure in AD. Premorbid brain size does not differ between patients with familial and sporadic AD and controls and does not delay disease onset.

Adult↗

PubMed2000

Loss of expression of the DRR 1 gene at chromosomal segment 3p21.1 in renal cell carcinoma.

Consistent deletion of DNA sequences in chromosomal band 3p21 observed in a variety of human tumors suggests the presence of one or more tumor suppressor genes within this region. Previously, we reported on the construction of two distinct cosmid contigs and our identification of several new genes within 3p21.1. In our search for tumor suppressor genes from this region, we have cloned a gene that we have called DRR 1 (downregulated in renal cell carcinoma). The gene was first mapped to 3p21.1 by fluorescence in situ hybridization analysis. Further analysis of yeast artificial chromosome clones in 3p14.2-p21.1 refined its localization. DRR 1 spans about 10 Kb of genomic DNA with a 3.5-Kb mature transcript. The putative protein encoded by this gene is 144 amino acids and includes a nuclear localization signal and a coiled domain. The gene showed loss of expression in eight of eight renal cell carcinoma cell lines, one of seven ovarian cancer cell lines, one of one cervical cancer cell line, one of one gastric cancer cell line, and one of one non-small-cell lung cancer cell line. Southern blot analysis did not show any altered bands, indicating that gross structural changes or deletions did not cause the loss of expression. This gene was also found to have reduced expression in 23 of 34 paired primary renal cell carcinomas. Mutational analysis detected three polymorphic sites within the gene, but no point mutations were identified in the 34 primary tumors. However, we did detect base substitutions in 4 of 12 cell lines that had undetectable expression of the gene. We also transfected the gene into DRR 1-negative cell lines and observed clear growth retardation. Our results suggest that loss of expression of the DRR 1 gene may play an important role in the development of renal cell carcinoma and possibly other tumors. Genes Chromosomes Cancer 27:1-10, 2000.

Amino Acid Sequence↗

PubMed2000

Psychiatric disorder and dysfunction in the UK National Survey of Psychiatric Morbidity.

BACKGROUND: Psychiatric symptoms are wide-spread in the general population, but have little effect on performance. Deficits in performance and psychiatric symptoms may be the end point of processes common to both, or they may be caused by quite different factors. In this paper we examine the epidemiological distribution of psychiatric symptoms and performance deficits, as indicated by difficulties in activities of daily living (ADL). We hypothesised that ADL difficulties are partly independent of psychiatric symptoms, and that this is reflected in a different demographic distribution. METHOD: The household component of the National Surveys of Psychiatric Morbidity was based on a sample of around ten thousand subjects selected at random from the population of Great Britain. Psychiatric symptoms were elicited by lay interviewers using the revised Clinical Interview Schedule. Performance was assessed by asking about difficulties experienced in performing seven types of everyday activity. In this paper, our chosen variables were overall symptom and ADL deficit scores, and these were related to standard demographic variables. RESULTS: There were significant differences in the epidemiological distribution of psychiatric symptoms and ADL difficulties. In particular, men experienced more ADL difficulties at a given symptom level than women. There were also differences in relation to social class, employment status, marital status, ethnic group and age. CONCLUSIONS: ADL deficits and psychiatric symptoms are related in the general population, and this probably represents common factors in their origin. However, discrepancies in the social distribution of these phenomena suggest there are also aetiological differences. These do not appear to be the result of the impact of physical illness on activities of daily living. Our results emphasise that ADL difficulties should be studied separately, particularly in investigations of treatment seeking.

Activities of Daily Living↗

PubMed2000

Urban-rural mental health differences in great Britain: findings from the national morbidity survey.

BACKGROUND: Studies of urban-rural differences in prevalence of non-psychotic mental disorder have not given consistent findings. Such differences have received relatively little study in Great Britain. METHODS: Data from 9777 subjects in the Household Survey of the National Morbidity Survey of Great Britain were analysed for differences between urban, semi-rural and rural areas. Psychiatric morbidity was assessed by scores on the Revised Clinical Interview Schedule (CIS-R), together with alcohol dependence, drug dependence, receipt of treatment from general practitioners. Associations with other characteristics were examined by logistic regression. RESULTS: Urban subjects had higher rates than rural of CIS-R morbidity, alcohol dependence and drug dependence, with semi-rural subjects intermediate. Urban subjects also tended to be members of more deprived social groups, with more adverse living circumstances and greater life stress, factors themselves associated with disorder. Urban-rural differences in alcohol and drug dependence were no longer significant after adjustment for these factors by logistic regression, and differences on CIS-R morbidity were considerably reduced. There were no differences in treatment. CONCLUSIONS: There are considerable British urban rural differences in mental health, which may largely be attributable to more adverse urban social environments.

Adolescent↗

PubMed2000

Unequal access and unmet need: neurotic disorders and the use of primary care services.

BACKGROUND: In this paper we use data from the National Survey of Psychiatric Morbidity to examine how many people with neurotic disorders receive professional evaluation, and how this is affected by clinical and sociodemographic differences. We hypothesized that psychiatric symptoms and attendant dysfunctions would both have an effect on contacting, and that key demographic variables would not. METHOD: The household component of the British National Surveys of Psychiatric Morbidity was based on a random sample of > 10,000 subjects. Psychiatric symptoms and ICD-10 diagnosis were established by lay interviewers using the CIS-R. Social dysfunction was tapped by asking about difficulties in performing seven types of everyday activity. We examined symptom score, ADL deficit score and demographic variables in relation to contact with primary care physicians for psychiatric symptoms. RESULTS: The major determinant of contacting a primary care physician was severity, mainly due to the level of psychiatric symptoms, but with an independent contribution from social dysfunction. There were also significant contributions from sex, marital status, age, employment status and whether the subject had a physical condition as well. CONCLUSIONS: The major influence on whether people seek the help of their family doctors for mental health problems is the severity of disorder. Although there are some social inequalities in access to family doctors, these are less important. The most salient finding from our study is that even people suffering from high levels of psychiatric symptoms very often do not have contact with professionals who might help them.

Activities of Daily Living↗

PubMed2000

Neurotic disorders and the receipt of psychiatric treatment.

BACKGROUND: Access to psychiatric treatment by people with neurotic disorders in the general population is likely to be affected both by the severity of disorder and by sociodemographic differences. METHOD: In the household component of the National Surveys of Psychiatric Morbidity > 10,000 subjects in Great Britain with psychiatric symptoms were interviewed using the CIS-R. They were also asked about difficulties experienced in performing seven types of everyday activity. All subjects classed as having an ICD-10 disorder were questioned about their experience of treatment with antidepressants, hypnotics, and counselling or psychotherapy. RESULTS: Less than 14% of people with current neurotic disorders were receiving treatment for them. Within the previous year, only a third had made contact with their primary care physician for their mental problem: of these < 30% were receiving treatment. Overall, 9% of people with disorders were given medication and 8% counselling or psychotherapy. A diagnosis of depressive episode was that most associated with antidepressant medication. Treatment access was affected by employment status, marital status, and age, but the major determinant was symptom severity. Neither sex nor social class influenced which people received treatment. CONCLUSIONS: People with psychiatric disorders seldom receive treatment, even when they have consulted their primary care physician about them. In many cases, this must represent unmet needs with a strong claim on health resources. There are also inequalities in the receipt of treatment, although the major influence is the severity of disorder.

Adolescent↗

PubMed2000

The prevalence of personality disorder among UK primary care attenders.

OBJECTIVE: To determine the prevalence rate of personality disorder among a consecutive sample of UK primary care attenders. Associations between a diagnosis of personality disorder, sociodemographic background and common mental disorder were examined. METHOD: Three hundred and three consecutive primary care attenders were examined for the presence of ICD-10 and DSM-4 personality disorders using an informant-based interview. RESULTS: Personality disorder was diagnosed in 24% (95% CI: 19-29) of the sample. Personality-disordered subjects were more likely to have psychiatric morbidity as indicated by GHQ-12, to report previous psychological morbidity, to be single and to attend the surgery on an emergency basis. 'Cluster B' personality disorders were particularly associated with psychiatric morbidity. CONCLUSION: There is a high prevalence rate of personality disorders among primary care attenders. These disorders are associated with the presence of common mental disorder and unplanned surgery attendance. Personality disorders may represent a significant source of burden in primary care.

Adult↗

PubMed2000

Mental health economic studies from developing countries reviewed in the context of those from developed countries.

OBJECTIVE: Mental health economic studies from developing countries were reviewed in the context of such studies from developed countries. METHOD: Mental health economic studies were ascertained through a systematic Medline search, chasing references at the end of papers acquired from the initial medline search and details of studies furnished by members of the WHO collaborating centre. RESULTS: Only a small number of mental health economic studies from developing countries were identified. They were mainly cost-of-illness and cost-effectiveness studies. CONCLUSION: Psychiatric disorders impose a significant burden in developing countries. It is not always possible to extrapolate findings from developed countries to developing countries. Potential avenues for future research and development are discussed.

Clinical Trials as Topic↗

PubMed2000

Steatosis in donor and transplant liver biopsies.

The purpose of this study was to identify the significance and clinical correlation of steatosis in donor and posttransplantation liver biopsies. One hundred twenty-six liver biopsies with fatty change from 86 liver transplant patients were reviewed. Micro- and macro-steatosis were graded semiquantitatively and correlated with clinical and other pathologic parameters. Fifty-one donor biopsy specimens, from 50 patients, had combinations of micro- (predominantly) and macro-steatosis. One of 2 patients with high-grade micro- and macro-steatosis required a retransplantation on the third day. Three early deaths were not related to graft dysfunction. In 36 patients, steatosis developed after transplantation. In 13 of 36, steatosis was seen in the early postoperative period with a background of severe ischemic injury, 6 of whom died within 45 days posttransplantation. Other causes of steatosis developing after liver transplantation included hepatitis C (n = 12), alcoholic steatohepatitis (n = 3), diabetes mellitus or obesity (n = 7) and poor nutrition (n = 2). The presence of steatosis in 1 patient's donor and all posttransplantation biopsy specimens remained unexplained. In conclusion, (1) microsteatosis in donor liver biopsy specimens has no effect on graft function; (2) ischemic injury with development of steatosis in the early posttransplantation period may be associated with poor clinical outcome; and (3) steatosis in the posttransplantation period is uncommon and usually related to recurrent or acquired hepatitis C.

Biopsy↗

PubMed2000

Recency and suffix effects with immediate recall of olfactory stimuli.

In contrast to our understanding of the immediate recall of auditory and visual material, little is known about the corresponding characteristics of short-term olfactory memory. The current study investigated the pattern of immediate serial recall and the associated suffix effect using olfactory stimuli. Subjects were trained initially to identify and name correctly nine different odours. Experiment 1 established an immediate correct recall span of approximately six items. In Experiment 2 participants recalled serially span equivalent lists which were followed by a visual, auditory, or olfactory suffix. Primacy was evident in the recall curves for all three suffix conditions. Recency, in contrast, was evident in the auditory and visual suffix conditions only; there was a strong suffix effect in the olfactory suffix condition. Experiment 3 replicated this pattern of effects using seven-item lists, and demonstrated that the magnitude of the recency and suffix effects obtained in the olfactory modality can equate to that obtained in the auditory modality. It is concluded that the pattern of recency and suffix effects in the olfactory modality is reliable, and poses difficulties for those theories that rely on the presence of a primary linguistic code, sound, or changing state as determinants of these effects in serial recall.

Acoustic Stimulation↗

PubMed2000

Psychosocial and psychiatric risk factors for suicide. Case-control psychological autopsy study.

BACKGROUND: Few studies of suicide have simultaneously examined the individual and combined effects of psychosocial and psychiatric risk factors. AIMS: To do so in a representative sample of suicides. METHOD: A case-control psychological autopsy was conducted among 113 consecutive suicides and 226 living controls matched for age, gender, ethnicity and area of residence in Taiwan. RESULTS: Five major risk factors (loss event, suicidal behaviour in first-degree relatives, ICD-10 major depressive episode, emotionally unstable personality disorder and substance dependence) were found to have independent effects on suicide from multivariate conditional logistic regression analysis. CONCLUSIONS: Effective intervention and management for loss event and major depressive episode among emotionally unstable subjects with a family tendency of suicidal behaviour, frequently also comorbid with alcohol or other substance dependence, may prove to be most effective for suicide prevention in different populations.

Case-Control Studies↗

PubMed2000

Depression diagnoses and antidepressant use in primary care practices: a study from the Practice Partner Research Network (PPRNet).

BACKGROUND: We examined the pharmacologic management and follow-up of adults with newly diagnosed depression, and the use of antidepressants among patients not diagnosed with depression in primary care practice. A total of 389 physicians in 39 practices in the Practice Partner Research Network (PPRNet), a national network of primary care physicians provided data for the study. METHODS: We performed a retrospective cohort study for the year 1996 using demographic, contact, diagnosis, and prescription data available in the December 1997 PPRNet database. We identified patients with new diagnoses of depression from the problem lists in the electronic medical record. Psychopharmacologic agents prescribed within 5 days of the diagnosis, follow-up contacts within 6 months of the diagnosis, and diagnoses of patients prescribed antidepressants without a new diagnosis of depression were also identified. We performed descriptive analyses for all practices and for individual practices. RESULTS: During 1996, there were 149,327 active adult patients in the 39 participating practices. Of the 131,141 patients without a history of depression or antidepressant prescription, 2103 (1.6%) had a new diagnosis of depression in 1996. Incidence among the 39 practices ranged from 0.4% to 4.0%. Forty-nine percent of the newly diagnosed patients received an antidepressant prescription within 5 days of diagnosis; 81% of the prescriptions were for selective serotonin reuptake inhibitors. Ninety percent of the patients prescribed antidepressants had at least one contact in the 6 months after diagnosis (mean = 5.3 contacts). One third of the patients who had not begun antidepressants within 5 days of their diagnoses started taking one by the end of 1996. Among the 149,327 active patients, 6.3% received a prescription for an antidepressant in 1996. More than 40% of these patients had never been diagnosed with depression. CONCLUSIONS: Our study highlights the high prevalence and wide interpractice variations of diagnosing depression and prescribing antidepressants in primary care. Follow-up of patients newly diagnosed with depression was common and consistent with published guidelines. Opportunities for increased detection and treatment of depression exist in approximately half of the study practices.

Adolescent↗

PubMed2000

The evaluation of a mental health facilitator in general practice: effects on recognition, management, and outcome of mental illness.

BACKGROUND: Facilitation uses personal contact between the facilitator and the professional to encourage good practice and better service organisation. The model has been applied to physical illness but not to psychiatric disorders. AIM: To determine if a non-specialist facilitator can improve the recognition, management, and outcome of psychiatric illness presenting to general practitioners (GPs). METHOD: Six practices were visited over an 18-month period by a facilitator whose activities included providing guidelines and organising training initiatives. Six other practices acted as controls. Recognition (identification index of family doctors), management (psychotropic prescribing, psychological consultations with the GP, specialist mental health treatment, and the use of medical interventions and investigations), and patient outcome at four months were assessed before and after intervention. RESULTS: The mean identification index of facilitator GPs rose from 0.51 to 0.64 following intervention, while that of the control GPs fell from 0.67 to 0.59 (P = 0.046). The facilitator had no detectable effect on management or patient outcome. CONCLUSIONS: The facilitator improved recognition of psychiatric illness by GPs. Generic facilitators can be trained to take on a mental health role; however, the failure to achieve more fundamental changes in treatment and outcome implies that facilitator intervention requires development.

Allied Health Personnel↗

PubMed1999

A novel region of deletion on chromosome 6q23.3 spanning less than 500 Kb in high grade invasive epithelial ovarian cancer.

Detailed deletion mapping of chromosome 6q sequences in invasive ovarian tumors have implicated several broad regions involving 6q14-16, 6q21-23, 6q25-26, and the telomeric portion in band 6q27 as regions of frequent loss in this malignancy. In order to define regions of loss involved in the development of ovarian cancer, we used 23 polymorphic markers on 6q to examine allelic loss in 25 high-grade, late stage ovarian tumors. Four non-overlapping deletion regions were observed: (1) at 6q21-22.3 (D6S301-D6S292); (2) within a 1 cM region at 23.2-23.3 between markers D6S978-D6S1637 (at D6S311); (3) at 6q26 (between markers D6S411-D6S1277) and (4) at 6q27 with the markers D6S297 and D6S193. The highest region of loss was observed with marker D6S311 (lost in 17 of 19 informative cases, 89%) in 6q23.3, followed by D6S977 and D6S1637 (71 and 55%, respectively). The average fractional allele loss in the high-grade tumors was around 35%. Previous reports have shown 6q27 as the region of most frequent loss in invasive ovarian cancer. However, our results indicate a novel region in 6q23.3 (spanning less than 500 Kb distance between the markers) with the highest loss, implicating this region of chromosome 6q to harbor a putative tumor suppressor gene involved in the development of invasive epithelial ovarian cancer.

Chromosome Fragility↗

PubMed1999

Prognostic relevance of monosomy at the 13q14 locus detected by fluorescence in situ hybridization in B-cell chronic lymphocytic leukemia.

Deletion of the chromosome band 13q14, which contains the putative deleted in B-cell malignancy (DBM) gene, and trisomy 12 have been demonstrated by fluorescence in situ hybridization (FISH) techniques in malignant B-cells from patients with B cell chronic lymphocytic leukemia (B-CLL). However, the prognostic relevance of 13q14 abnormalities as detected by FISH is unknown. We prospectively studied malignant blood cells from 54 consecutive, untreated B-CLL patients using FISH probes to the RB1 locus and DBM (markers D13S25 and D13S319) for band 13q14, as well as probes to chromosome 12. The cells from all cases were CD5+ CD20+, expressed clonally restricted surface immunoglobulin light chain, and had typical features for B-CLL on careful blood smear morphologic evaluation. Patients were followed for a mean of 3.9 years and treatment-free survival (TFS) was used in the prognostic factor analysis. Twenty-four (44%) patients were observed to have monosomy of the RB1 locus and 26 (48%) monosomy of D13S25 and D13S319. The 26 patients who had a deletion at at least one of these loci had a 48.4 month (mo) median TFS vs 31.1 mo for those without evidence of deletion at any 13q14 locus (p = 0.07). The seven patients found to have trisomy 12 had a median TFS of 6.9 mo vs 39.3 mo for those diploid for chromosome 12 (p < 0.01). When these seven patients with trisomy 12 were excluded from the analysis, patients who had a deletion at 13q14 tended to have a longer median TFS (50.1 vs 36.2 mos), but this was not statistically significant (p = 0.2). This study confirms the prevalence of 13q14 deletions in B-CLL and suggests that patients with this abnormality have a better TFS than those with trisomy 12.

Adult↗

PubMed1999

Novel mutations of the MET proto-oncogene in papillary renal carcinomas.

Hereditary papillary renal carcinoma (HPRC) is characterized by multiple, bilateral papillary renal carcinomas. Previously, we demonstrated missense mutations in the tyrosine kinase domain of the MET proto-oncogene in HPRC and a subset of sporadic papillary renal carcinomas. In this study, we screened a large panel of sporadic papillary renal carcinomas and various solid tumors for mutations in the MET proto-oncogene. Summarizing these and previous results, mutations of the MET proto-oncogene were detected in 17/129 sporadic papillary renal carcinomas but not in other solid tumors. We detected five novel missense mutations; three of five mutations were located in the ATP-binding region of the tyrosine kinase domain of MET. One novel mutation in MET, V1110I, was located at a codon homologous to an activating mutation in the c-erbB proto-oncogene. These mutations caused constitutive phosphorylation of MET when transfected into NIH3T3 cells. Molecular modeling studies suggest that these activating mutations interfere with the intrasteric mechanism of tyrosine kinase autoinhibition and facilitate transition to the active form of the MET kinase. The low frequency of MET mutations in noninherited papillary renal carcinomas (PRC) suggests that noninherited PRC may develop by a different mechanism than hereditary papillary renal carcinoma.

3T3 Cells↗