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Biomedical subjects

A Burgess

Publications and source records attributed to A Burgess.

At least 19 recordsLinked to original sources

Neurophysiological changes associated with psychiatric symptoms in HIV-infected individuals without AIDS.

HIV-1 infection may be complicated by a number of psychopathological conditions. While organic mental disorders, such as HIV-related psychosis and dementia, are late manifestations, mood disorders may occur during both asymptomatic and symptomatic stages of infection. The possible impact of brain involvement due to neurotropism of HIV-1 has not been investigated systematically in these latter conditions. The psychiatric caseness of HIV-seropositive individuals without AIDS and seronegative controls was assessed using a standardized clinical interview (Present State Examination). A comparison was made between individuals with and without psychiatric caseness using clinical, neuropsychological, and neurophysiological assessments. An increased prevalence of current psychiatric illness was found in subjects with early symptomatic HIV infection compared to those with asymptomatic infection and controls. This could not be attributed to psychiatric history, as well as to clinical and immunological markers of HIV infection, however, psychiatric caseness in early symptomatic infection was associated with marked neurophysiological changes, detectable by quantitative electroencephalography. Altogether, this study provided preliminary evidence that psychiatric symptoms in symptomatic but not asymptomatic HIV infection may be associated with subtle brain involvement preceding the immunological and neurocognitive impairment characteristic for AIDS.

Adult

Prospective evaluation of local excision for small rectal cancers.

OBJECTIVE: Most data on local excisions for rectal cancer are based on retrospective studies. We review the results of a prospective registry of patients eligible for local excision of rectal cancer using a transanal, transsphincteric, or transcoccygeal technique combined with multimodality therapy for lesions penetrating the muscularis propria (T2) or perirectal fat (T3). METHODS: Patients with lesions less than 4 cm in diameter and less than 10 cm from the dentate line, with no evidence of distant metastases or invasion into the perirectal fat, were eligible for local excision. Patients with invasion into the muscularis propria (T2) or greater (T3) received adjuvant chemoradiation therapy. RESULTS: Forty-eight patients have been followed prospectively. Average age is 63 years. Thirty-three patients underwent a transanal excision. Fifteen patients underwent either a transsphincteric or technique excision. There was no perioperative mortality. Pathology revealed 1 Tis, 21 T1, 21 T2, and 5 T3 cancers. Mean follow-up is 40.5 months. Cancer-related overall mortality was 4 percent. Overall local or distant recurrence rate was 8 percent (4/48). Recurrence appeared to be related to presence of a positive margin or aggressive histology (lymphatic invasion). Local recurrences were treated with salvage therapy. CONCLUSION: Local excision can be used selectively for small rectal cancers, with minimum morbidity. Recurrence rates are low (8 percent). Patients with either a positive margin or lymphatic invasion need to be considered for further therapy, including abdominoperineal resection, even with T1 lesions. Adjuvant chemoradiation appears to be a benefit for all T2 or T3 cancers.

Adenocarcinoma

Cloning, expression and sequence analysis of the Bartonella henselae gene encoding the HtrA stress-response protein.

A cloned fragment of Bartonella (Rochalimaea) henselae (Bh) DNA was found to direct synthesis of an immunoreactive protein in Escherichia coli (Ec). Sequence analysis revealed an open reading frame of 1509 nucleotides encoding a protein of 503 amino acids that exhibited extensive identity (over the entire protein) with the HtrA stress-response proteins of Brucella abortus (59%), Ec (37%) and Salmonella typhimurium (36%). When the putative htrA gene was amplified by polymerase chain reaction and used as template for in vitro transcription and translation, a protein with an apparent molecular mass of 62 kDa was synthesized from the plasmid template. These results suggest that the immunoreactive Bh protein is homologous to the HtrA class of stress-response proteins.

Bartonella henselae

Hypothesis: "Rogue cell"-type chromosomal damage in lymphocytes is associated with infection with the JC human polyoma virus and has implications for oncopenesis.

The hemagglutination inhibition antibody titers against the JC and BK polyoma viruses (JCV and BKV, respectively) are significantly elevated in individuals exhibiting "rogue" cells among their cultured lymphocytes. However, the elevation is so much greater with respect to JCV that the BKV elevation could readily be explained by cross reactivity to the capsid protein of these two closely related viruses. The JCV exhibits high sequence homology with the simian papovavirus, simian virus 40 (SV40), and inoculation of human fetal brain cells with JCV produces polyploidy and chromosomal damage very similar to that produced by SV40. We suggest, by analogy with the effects of SV40, that these changes are due to the action of the viral large tumor antigen, a pluripotent DNA binding protein that acts in both transcription and replication. The implications of these findings for oncogenesis are briefly discussed.

Adolescent

The psychological impact on staff of caring for people with serious diseases: the case of HIV infection and oncology.

Psychological stress and work-related burnout in staff working with AIDS and with cancer patients were compared using a self-report method of assessment. Measures included the General Health Questionnaire (GHQ), Maslach Burnout Inventory (MBI), and the Social Adjustment Scale (SAS-M). More than 80% of those staff who were approached responded to the questionnaire, including 70 doctors and nurses working with people with AIDS and 41 doctors and nurses working in oncology. More than a third of staff had substantial levels of psychological morbidity, and about a fifth had significant levels of work-related stress. Factors associated with the presence of high levels of psychological morbidity and with abnormal levels of emotional exhaustion, depersonalization, and concerns about personal accomplishment were identified. Staff described the work situations with which they had difficulty dealing and some of the coping strategies they used. The findings confirm that staff working with people with cancer or AIDS experience psychological difficulties of the kind likely to respond to interventions aimed at improving their ability to cope with work-related stresses. The mental health services could play an important role in carrying out research in this field and in providing practical help to deal with staff's difficulties.

Acquired Immunodeficiency Syndrome

Prospective associations between lateralised brain function and immune status in HIV infection: analysis of EEG, cognition and mood over 30 months.

Prospective relations between individual differences in both lateralised neuro-psychophysiological functions and mood ratings with immune status (CD4 and CD8 counts) were examined in asymptomatic HIV-positive men (n = 27) over thirty months. They participated in a controlled study of zidovudine versus placebo (results published elsewhere). Measures included EEG spectra, neuropsychological tests and mood ratings. A model of reciprocal lateralised influences on the immune system was tested whereby patients with left superior to right hemispheric functions were predicted to show a less deleterious outcome than those with the opposite asymmetry pattern. Prospective relations with immune status were found in the EEG with lateralised theta, alpha and beta activity; among cognitive measures with word fluency, semantic processing, and lateralised motor and recognition memory (word/face) processes; with mood ratings including depression, confusion and the total mood score. The nature of the effects supported the laterality predictions. These unique data, showing that neuro-psychophysiological factors in HIV+ but otherwise healthy subjects predict immune competence and compromise present 2-3 years later, warrant replication in a larger cohort.

Adult

Long-term outcomes after lower extremity trauma.

Previous studies have shown that over one-quarter of patients who were working before a severe lower extremity fracture had not returned to work by 12 months after injury. Disabilities also persisted in household management, recreation, and social interaction. The objective of this study was to determine whether recovery extended beyond 12 months. Three hundred nineteen patients who were previously working and were treated at three level I trauma centers for a severe lower extremity fracture were prospectively followed at 3, 6, and 12 months after injury. Patients were queried at each follow-up about their work status and completed the Sickness Impact Profile (SIP) at 6 and 12 months. The SIP is a widely used and well validated measure of general health status; it was used in this study to measure functional recovery across several domains of daily living. Patients who had not recovered by 12 months (i.e., 204 who were not working, working with limitations, or had limitations in performing other daily activities as measured by elevated scores on the SIP) were contacted again at 30 months and asked to complete an interview and the SIP. At 30 months, an estimated 82% of the study patients had returned to work (compared to 72% at 12 months). SIP scores improved only slightly from 6.4 at 12 months to 5.7 at 30 months. At 30 months, 64% of the patients had no disability (SIP scores less than 4), 17% had mild disability (SIP scores of 4 to 9), 12% had moderate disability (SIP scores of 10 to 19), and 7% had severe disability (SIP scores of 20 or higher). Although the majority of patients with persistent disabilities at 30 months had residual physical impairments at 12 months, the extent of impairment did not fully explain why some people had and had not recovered at 30 months after injury. The results confirm those of other studies that conclude that overall, outcomes after serious trauma are good when appropriate trauma and rehabilitation care are rendered. However, a minority of patients still report limitations at 30 months after injury, with one-fifth not returning to work.

Adolescent

The cost of overseas visitors to an inner city accident and emergency department.

OBJECTIVE: To estimate, in a metropolitan accident and emergency (A&E) department, the annual cost of treating overseas visitors whose countries of origin do not have reciprocal arrangements with Britain. METHODS: The study was retrospective. A 24 h period (00.01 h to 24.00 h inclusive) on consecutive days in consecutive weeks (that is, Monday in week 1, Tuesday in week 2, etc) was costed over 52 weeks (1.8.92-31.7.93 inclusive) and extrapolated to 365 days. All visitors between those dates were divided into eligible (from countries with a reciprocal agreement) or non-eligible (from countries without a reciprocal agreement). Costs were calculated for medical and nursing care, investigation and treatment, and fixed costs. RESULTS: The annual St Mary's Hospital A&E budget for the study period (01/08/92 to 31/07/93) was 2,612,200 pounds; the average medical and nursing cost per major or minor case was 66.88 pounds and 20.08 pounds respectively. Investigation, treatment, and fixed costs were 16.31 pounds per patient. In total 2704 non-eligible patients (498 major and 2206 minor cases) were treated at a cost of 121,705 pounds (95% confidence interval 114,234 pounds to 129,176 pounds), which was 4.7% of the total annual budget. CONCLUSIONS: The cost of non-eligible patients to the NHS is substantial. One possible solution would be for visitors from countries which do not offer subsidised emergency treatment to British nationals to purchase health insurance compulsorily on or before entry to Britain. The revenue could be used to improve standards of care for all A&E patients.

Confidence Intervals

In vivo biologic effects of PIXY321, a synthetic hybrid protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 in cancer patients with normal hematopoiesis: a phase I study.

PIXY321 is a novel fusion protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 that exhibits biologic effects of both its parent cytokines in vitro and in preclinical studies. To evaluate the clinical safety and hematopoietic effects of this hybrid cytokine, PIXY321 was administered by subcutaneous injection twice daily at doses of 25 to 1,000 micrograms/m2/day over 14 days to 24 patients with sarcoma before chemotherapy as part of a phase I trial. The treatment was associated with significant increases in white blood cell, neutrophil, platelet, and reticulocyte counts (all P < .001). The increase in neutrophil count was dose-related and was seen during treatment with the cytokine, whereas the increase in platelet count was gradual and peaked after the cessation of the cytokine treatment and was not clearly dose related. PIXY321 treatment also increased bone marrow (BM) cellularity and the percentage of BM cells in S phase (P < .001). In addition, there was a significant increase in the number of CD34+ cells and committed and multipotential progenitors in the peripheral blood. The ex vivo expansion capacity of peripheral blood and BM progenitor cells was preserved after the in vivo treatment with PIXY321. The treatment was well tolerated, with the most common side-effect being injection site reactions. The results of this study show the biologic and clinical activity of a genetically engineered fusion molecule of two hematopoietic cytokines in humans with normal hematopoietic function.

Agranulocytosis

Linkage of preaxial polydactyly type 2 to 7q36.

We have characterized a 6-generation North American Caucasian kindred segregating one form of preaxial polydactyly type 2 (PPD-2). We demonstrate linkage to the 7q36 region and describe a submicroscopic telomeric chromosomal deletion in phase with the PPD-2 phenotype. Recently, several kindreds segregating triphalangeal thumb (TPT) with and without associated hand anomalies (syndactyly and/or postaxial polydactyly) have also been linked to the subtelomeric region of chromosome 7q [Heutink et al., 1994: Nat Genet 6:287-291; Tsukurov et al., 1994: Nat Genet 6:282-286]. We demonstrate by haplotype analysis that our North American pedigree represents a PPD allele that is independent of the founder PPD allele present in the previously described kindreds.

Base Sequence

Patterns of cognitive asymmetry and syndromes of schizotypal personality.

The Schizotypal Personality Questionnaire, modeled on the nine components of DSM-III-R schizotypy, was administered to 122 medical students along with the Thayer Activation-Deactivation Adjective Checklist and the Warrington Recognition Memory Test for words and faces. Close affinities were found between a three-factor schizotypal personality structure and a three-syndrome model of schizophrenia. Different patterns of cognitive asymmetry (word-face discrepancy scores) were related to Active and Withdrawn syndromes as in schizophrenia, and were related to high activation and general deactivation differences as predicted. A prospective single case study showed that a face-word discrepancy before a first episode of schizophrenia accurately predicted a Withdrawn presenting syndrome. The consistency between syndromes of schizophrenia and schizotypal personality in a normal population suggests possible etiological links between the two, and it supports a dimensional view of psychosis and subclinical predispositions.

Adult

Neurophysiological evaluation of zidovudine in asymptomatic HIV-1 infection: a longitudinal placebo-controlled study.

The effect of early antiretroviral medication with zidovudine on neurophysiological functions was evaluated in subjects with asymptomatic HIV-1 infection. Patients were recruited participants of a larger double-blind randomised placebo-controlled treatment trial with zidovudine (Concorde). The main outcome measures included: quantitative electroencephalography (QEEG), auditory event-related potentials (AEP) and pattern-reversal visual evoked potentials (PRVEP), as well as standard clinical, virological and immunological markers. No significant impairment and no difference between treatment groups was found in visual P100 latency and auditory long-latency P3 responses which is in agreement with the absence of neurological and neuropsychological impairment over the study period. Significant treatment effects were revealed by quantitative electroencephalography (QEEG). While the placebo group showed a significant increase in delta and theta slow frequency QEEG activity over the study period, slow wave amplitude remained unchanged in the zidovudine group after a mean follow-up period of 28 months. In summary, the data provide evidence for a low level neuropathological process in asymptomatic HIV-1 infection which can be effectively suppressed by antiretroviral medication.

Adult

Image quality, the ideal observer, and human performance of radiologic decision tasks.

The quality of medical images must be quantified with reference to specific diagnostic tasks. Image quality is limited by fundamental physics, engineering limitations, radiation safety concerns, and imaging time constraints (among other things). There is now a gold standard for assessing human visual decision performance: the ideal Bayesian observer. Unfortunately, there are no mathematical tools to use this gold standard for realistically complex tasks. As an alternative, one can use the optimum linear discriminator (Fisher-Hotelling) model as a silver standard while en route to clinical realism. The goal of scientists working in the area is to develop mathematical models of human observers that will help equipment designers to optimize design trade-offs for specific diagnostic tasks. The current strategy is to modify the Fisher-Hotelling model to include certain limitations of the human observer visual system. The model must be both robust enough and mathematically tractable enough to be used to predict performance for clinical classification and estimation tasks. Statistical models also must be developed that describe realistic signals (lesions and abnormalities) and the normal patient structure that is the background in which these signals must be detected or identified.

Decision Making

The Sickness Impact Profile as a tool to evaluate functional outcome in trauma patients.

Because the ultimate goal of trauma care is to restore injured patients to their former functional status, reliable evaluation of functional status is needed to assess fully the effectiveness of trauma care. We hypothesized that the Sickness Impact Profile (SIP), a widely used measure of general health status, would be a useful tool to evaluate the long-term functional outcome of trauma patients and that the SIP would identify unexpected problems in the recovery process and groups of patients at high risk for long-term disability. A prospective cohort of 329 patients with lower extremity fractures admitted to three level I trauma centers were interviewed using SIP at 6 and 12 months postinjury. Patients with major neurologic injuries were excluded. Overall SIP scores and each of the component subscores may range from 0 (no disability) to 100. In this series, the mean overall SIP was 9.5 at 6 months and 6.8 at 12 months, compared with a preinjury baseline of 2.5. At 12 months, 52% of patients had no disability (SIP 0 to 3), 23% mild disability (4 to 9), 16% moderate disability (10 to 19), and 9% severe disability ( > or = 20). Disability was widely distributed across the spectrum of activities of daily living, including physical functioning (mean score of 5.5), psychosocial health (mean score of 5.5), sleeping (mean score of 10.0), and work (mean score of 21.0). The SIP scores did not correlate with Injury Severity Score.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living

Generation and molecular cytogenetic characterization of a radiation-reduction hybrid panel for human chromosome 6.

A neoR marked chromosome-6 containing hybrid (D113JA) was used to generate a panel of 15 radiation-reduced hybrid cell lines. The panel was constructed by irradiating microcells isolated from D113JA at 800 or 8000 rads, providing different levels of chromosome 6 retention. These hybrids have been systematically analyzed using interspersed repetitive elements, previously assigned markers for chromosome 6, and fluorescent in situ hybridization (FISH). As expected, G418 selection has favored the retention of fragments near the insertion site of the neoR gene (6q16). The panel as constituted provides an important resource for regional assignment of molecular markers, especially to regions on 6q.

Animals