Biomedical subjects

John Hodges

Publications and source records attributed to John Hodges.

5 recordsLinked to original sources

PubMed2006

Patterns of frontal lobe atrophy in frontotemporal dementia: a volumetric MRI study.

OBJECTIVES: Frontotemporal dementia (FTD), the second commonest degenerative cause of dementia under the age of 65, often presents with striking changes in behaviour and personality in association with frontal lobe atrophy. Based on the behavioural changes observed in FTD, it is commonly assumed that the orbitofrontal cortex is the earliest and most severely affected frontal sub-region. However, evidence to support this assumption has to date been largely lacking. METHODS: Using a novel volumetric MRI method, we performed a detailed volumetric analysis of six frontal regions in 12 subjects with the frontal or behavioural variant of FTD (fvFTD) and 12 age-, education- and sex-matched normal controls. The regions studied were: the orbitofrontal and insula regions (representing the orbitobasal cortex); the inferior and middle frontal regions (representing the dorsolateral prefrontal areas); and the superior frontal and anterior cingulate regions (representing the medial prefrontal areas). RESULTS: As a group, the fvFTD patients showed atrophy involving all six regions. We then segregated the 12 patients into three sub-groups according to their overall degree of atrophy. In the mildest group (n = 3) all regions fell within 2 standard deviations of normal. In the intermediate group (n = 6) only the orbitofrontal region (bilaterally) fell clearly outside the control range (>2 z scores below the control mean); the next most atrophic region in this group was the right insular region. The severe group (n = 3) had generalized atrophy throughout the frontal regions measured. CONCLUSIONS: In conclusion, patients with the earliest stages of fvFTD show no significant loss of volume in any frontal lobe area as measured by a novel MRI volumetric technique. When volume loss does occur, changes are initially seen in the orbitofrontal cortex before atrophy becomes more widespread. These results provide some partial support for the often-quoted assumption that the orbitofrontal cortex is the locus of earliest pathology in fvFTD, although these findings must be regarded as preliminary in view of the small numbers of patients involved.

Atrophy↗

PubMed2005

Pathologically proven frontotemporal dementia presenting with severe amnesia.

Early and severe memory impairment is generally held to be an exclusion criterion for the clinical diagnosis of frontotemporal dementia (FTD). However, clinical experience suggests that some patients with otherwise typical FTD can be amnesic from presentation, or even present solely with amnesia. A review of severe amnesia at presentation in patients with pathologically proven FTD is therefore warranted. The present study examined the records of all patients in the joint Cambridge-Sydney neuropathological series of patients with dementia and a pathological diagnosis of FTD to identify those for whom memory complaints were dominant at presentation. Eight of 71 patients met these criteria. For two patients, memory loss was the only complaint; for one patient, memory loss was accompanied by personality change; for two patients, memory loss was accompanied by prominent dysexecutive symptoms; and for three patients, memory loss was accompanied by apathy but no other behavioural changes. In seven patients local specialist teams initially diagnosed Alzheimer's disease; four patients entered anticholinesterase drug trials. All eight later developed behavioural features: in four, the diagnosis was revised to FTD, while in four the diagnosis of FTD was made only on neuropathological examination after death. In conclusion, severe amnesia at presentation in FTD is commoner than previously thought and the clinical consensus criteria for the diagnosis of FTD may need to be revised. The underlying basis of the memory impairments in patients with FTD may be heterogeneous, with different explanations in different subgroups.

Adult↗

PubMed2004

Developing a directly administered antiretroviral therapy intervention for HIV-infected drug users: implications for program replication.

Directly administered antiretroviral therapy (DAART) is one approach to improving adherence to among human immunodeficiency virus (HIV)-infected drug users. We evaluated the essential features of a community-based DAART intervention in a randomized, controlled trial of DAART versus self-administered therapy. Of the initial 72 subjects, 78% were racial minorities, and 32% were women. Social and medical comorbidities among subjects included homelessness (35% of subjects), lack of interpersonal support (86%), major depression (57%), and alcoholism (36%). At baseline, the median CD4+ cell count was 403 cells/mL and the median HIV-1 RNA load was 146,333 copies/mL (log10 5.31 copies/mL). During the prior 6 months, 33% of subjects had missed a medical appointment, and 47% had visited an emergency department. Although most subjects (67%) preferred to take their own medications, 76% would accept DAART if it were made compulsory. A methadone clinic was the DAART venue acceptable to the fewest subjects (36%), and a mobile syringe-exchange program was acceptable to the most subjects (83%). Adherence was higher for supervised than for unsupervised medication administration (P<.0001), a finding that supports use of daily supervision of once-daily regimens. Moreover, DAART should incorporate enhanced elements such as convenience, flexibility, confidentiality, cues and reminders, responsive pharmacy and medical services, and specialized training for staff.

Adult↗

PubMed2004

Effectiveness of antiretroviral therapy among HIV-infected prisoners: reincarceration and the lack of sustained benefit after release to the community.

Responses to highly active antiretroviral therapy (HAART) in correctional settings and their sustained benefit in prisoners after release are currently not known. To examine the human immunodeficiency virus type 1 (HIV-1) RNA level (VL) and CD4 lymphocyte response to HAART during incarceration and upon reentry to the correctional system, we conducted a retrospective cohort study of longitudinally linked demographic, pharmacy, and laboratory data from the Connecticut prison system. During incarceration, the mean CD4 lymphocyte count increased by 74 lymphocytes/ mu L, and the mean VL decreased by 0.93 log10 copies/mL (P<.0001). Fifty-nine percent of the subjects achieved a VL of <400 copies/mL at the end of each incarceration period. For the 27% of subjects who were reincarcerated, the mean CD4 lymphocyte count decreased by 80 lymphocytes/ mu L, and the mean VL increased by 1.14 log10 (P<.0001). Although HAART use resulted in impressive VL and CD4 lymphocyte outcomes during the period of incarceration, recidivism to prison was high and was associated with a poor outcome. More effective community-release programs are needed for incarcerated patients with HIV disease.

Antiretroviral Therapy, Highly Active↗

PubMed2004

Relationship between hippocampal volume and CA1 neuron loss in brains of humans with and without Alzheimer's disease.

Hippocampal volumetry has been proposed to aid in the early diagnosis of Alzheimer's disease (AD) and to monitor progression of the disease. While this is believed to be as a result of hippocampal neuron loss, this association has not been firmly established and loss of other tissue elements may be responsible for the observed atrophy. We investigated the relationship between neuron loss and hippocampal volume in 11 patients with autopsy-confirmed AD and 11 non-demented age-matched controls. Strong correlations were found between neuron number and both hippocampal volume and brain volume demonstrating that volume and neuron content are related in normal subjects and that the relationship is maintained in AD. In AD, neuron number and volume measures significantly decline with increasing disease duration. These findings support the suggestion that hippocampal atrophy in AD is as a result of neuron loss and confirm the usefulness of volumetry as an indirect measure of neurodegeneration in this disease.

Aged↗