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Biomedical subjects

M Sullivan

Publications and source records attributed to M Sullivan.

At least 163 records · Page 9Linked to original sources
PubMed1996

Measurement of quality of life in localized prostatic cancer patients treated with radiotherapy. Development of a prostate cancer-specific module supplementing the EORTC QLQ-C30.

The purpose of this study was to construct a multidimensional self-administered quality of life questionnaire specific to prostate cancer within the EORTC framework and to test its applicability, clinical relevance and psychometry. A proposed prostate cancer-specific module and the standardized EORTC QLQ-C30 version 1.0 were tested in 192 post-irradiated patients. Psychometric analyses comprised item convergent and discriminant validity for scaling success, analysis of the internal consistency of the multi-item scales and the validity of the scales. The clinical relevance was explored by correlation analysis including disease and treatment related parameters. The minimum psychometric criteria were met. The measurements revealed problem areas in sexuality with a mean score of 54 (SD = 33) on a 0-100 scale, and in bowel functioning, scoring 25 on average (SD = 17). Urinary complaints only reached a mean score of 6 (SD = 19). Compared to earlier measurements on untreated or irradiated localized cancer patients using the same core questionnaire, the physical and psychological scales showed higher values and the symptom scales lower symptom burden. The constructed questionnaire seems applicable and clinically relevant. The psychometric analysis revealed a few items to be revised. Patients with localized prostatic carcinoma treated with radiotherapy have a high quality of life compared to patients with localized cancer of other origin.

Aged↗
PubMed1996

Quality of life in gastric cancer prior to gastrectomy.

A growing number of surgical trials include quality of life variables in the overall assessment of outcomes. This is believed to broaden the criteria for choice of treatment and the evaluation of treatment regimens. The present study is a baseline evaluation of the health-related quality of life in patients with gastric cancer facing surgery. The quality of life in these patients was related to that of other patient groups referred for surgical interventions and general population groups. Our study included 103 consecutive patients with carcinoma of the stomach considered amenable to a curative major surgical procedure. The quality of life evaluation was based on a battery of questionnaires, covering general body symptoms, mood level and functional limitations. Patients with gastric cancer reported more neurasthenic complaints such as reduced sexual interest, insomnia and poor appetite as well as a lower mood level than the general population. The gastric cancer group also showed a markedly lower mood level in comparison with a group of cancer survivors 2-3 years after diagnosis and patients with intermittent claudication. The mental well-being of gastric cancer patients matched that of cancer survivors with one or more recurrences. Overall, 25% of the gastric cancer patients reported functional limitations regarded as clinically significant. Patients with intermittent claudication reported more and patients with small cell lung cancer markedly more limitations. We conclude that although patients with gastric cancer showed a low level of limitations on average, problems in the areas of sleep/rest, home management and, especially, eating were frequently reported.

Adult↗
PubMed1996

Sexual adjustment and quality of relationship in spinal paraplegia: a controlled study.

OBJECTIVE: To identify determinants of sexual adjustment by persons with spinal cord injury (SCI) and quality of the relationship compared with persons in the general population. DESIGN: Controlled survey. SETTING: Postdischarge community setting. PARTICIPANTS: A consecutive series of 252 persons admitted to our spinal unit between November 1982 and July 1991 with traumatic SCI were contacted, 85 of whom persons were excluded: 36 were dead, 37 had recovered, 5 could not be located, 4 were younger than 18 years, 2 had language difficulties, and 1 had a psychiatric illness. Of the remaining 167 persons with SCI, 85 had a stable partner relationship, 75 of whom (88%) completed and returned the questionnaires (median age, 33 years; range 19 to 76). An age- and sex-matched control group was randomly selected from the general population. Of the 264 respondents, 155 (59%) had a stable partner relationship. MAIN OUTCOME MEASURES: The 80-item questionnaire addressed experiences concerning sexual functioning, desire, and activity, sexual behavior, satisfaction with sex life, and aspects of the emotional quality of the relationship. RESULTS: Sexual activity and satisfaction was lower among persons with SCI compared with the controls; the emotional quality of the relationship did not differ. The most important correlates for sexual fulfillment in both groups were found to be the use of a varied repertoire of sexual behaviors and the perception that the partner enjoys and is satisfied with the sexual part of the relationship. CONCLUSION: Psychosocial rather than physical factors were important for a satisfying sexual life and relationship. A qualitative study should be undertaken to further explore the complexity of sexual adjustment after SCI.

Adaptation, Psychological↗
PubMed1996

Fever in patients with HIV infection.

Fever is a common sign during the course of HIV infection, usually represents a superimposed opportunistic infection, and is almost always a treatable condition. Proper management generally requires detection of the underlying cause, and the diagnostic evaluation is largely driven by the clinical symptoms, associated conditions such as injection drug use, and stage of disease based largely on the absolute CD4 cell count. This article provides guidelines for the management of fever in the patient with HIV infection.

Bacterial Infections↗
PubMed1996

The analytic initiation: the effect of the archetype of initiation on the personal unconscious.

The author proposes the term "analytic initiation' to describe a rite of passage from childhood to adult life effected by psychotherapy. He suggests this passage is based upon a personal regression within the embrace of an archetypal symbolic process. Archetypal symbols orientate the analysand towards the transformative potential of a regressive experience. They also contain him as he separates from parental complexes and tolerates their dissolution. The analysand's growth depends on his submitting to an intrapsychic and interpersonal experience of the initiatory process with its attending regression. Correspondingly, it relies on the analyst being available for both the personal and impersonal transference/countertransference interaction. Over time, the analysand's participation in this process brings his ego in greater relationship to the Self. The most important outcome of a successfully constellated analytic initiation is not the dissolution of a group of complexes. Rather, it is the establishment of a symbolic process that allows the individual to continue to evolve. The author supports his findings with a critical review of Jung's writings on initiation and additional case material.

Adolescent↗
PubMed1996

Functional status and well being in chronic obstructive pulmonary disease with regard to clinical parameters and smoking: a descriptive and comparative study.

BACKGROUND: Self-assessment questionnaires which measure the functional and affective consequences of chronic obstructive pulmonary disease (COPD) give valuable information about the effects of the disease and may serve as important tools with which to evaluate treatment. METHODS: A cross sectional comparative study was performed between patients with COPD (n = 68), stratified according to pulmonary function, and a healthy control group (n = 89). A battery of well established clinical and quality of life measures (the Sickness Impact Profile (SIP), Mood Adjective Check List (MACL), and Hospital Anxiety and Depression scale (HAD)) was used to examine in which functional and affective aspects the patient group differed from the control group and how these measures related to pulmonary function and smoking habits. RESULTS: Compared with the controls, COPD affected functional status in most areas, not just those requiring physical activity. Forty six patients with forced expiratory volume in one second (FEV1) below 50% predicted showed particularly high levels of dysfunction in ambulation, eating, home management, and recreation/ pastimes (SIP). Despite this, their level of psychosocial functioning and mood status was little different from that of the healthy controls. Among the patients, a subgroup reported substantial psychological distress, but mood status was only weakly, or not at all, related to pulmonary function. Smoking habits did not affect functional status or well being. CONCLUSIONS: Quality of life is not significantly affected in patients with mild to moderate loss of pulmonary function, possibly due to coping and/or pulmonary reserve capacity. This suggests that generic self-assessment questionnaires are of limited value for detecting the early consequences of COPD. However, in later stages of the disease they are sensitive enough to discriminate between patients with different levels of pulmonary dysfunction. The low correlations between the indices of pulmonary function and the indices of affective status suggest that well being depends, to a large extent, on factors outside the clinical domain.

Affect↗
PubMed1996

National Asthma Education and Prevention Program working group report on the financing of asthma care.

The financing of asthma care is the third topic of the National Asthma Education and Prevention Program Task Force Report on the Cost Effectiveness, Quality of Care, and Financing of Asthma Care. This working group explored the effects of financing on access to services, treatment of asthma, and potential health outcomes. Over the course of a year, the working group collected and analyzed information pertaining to the various types of public and private health care financing mechanisms, including both insurance-based and non-insurance-based issues. The group examined the published literature and gathered information from four public hearings conducted across the nation. The result of this synthesis of information on health care financing and asthma care is a set of 12 recommendations that seek to improve the financing of asthma care.

Asthma↗
PubMed1996

Laboratory studies of the effect of Pall extracorporeal leucocyte filters LG6 and AV6 on patients undergoing coronary bypass grafts.

A total of 14 patients with ischaemic heart disease undergoing coronary artery bypass grafts were studied for the effect of AV6 control filter and LG6 neutrophil filter, used in the extracorporeal circulation, on different laboratory parameters. There was no statistical difference between the effects of AV6 and LG6 filters on total white cells, neutrophils, monocytes, lymphocytes, platelets or haemoglobin. The expression of neutrophil activation antigens identified with a panel of monoclonal antibodies demonstrated that for the LG6 filter the leucocyte tyrosine phosphate CD45Ro fell during the procedure, whilst there were no significant changes in any of the other neutrophil antigens. The AV6 filter did not significantly diminish the expression of any of the neutrophil antigens. An indirect measure of superoxide production using Dihydrorhodamine 123 identified that the more activated cells appeared to be depleted across the LG6 filter which was not evident with the AV6 filter. These studies indicate that the LG6 is not capable of significantly depleting the neutrophil load generated during extracorporeal circulation but may be capable of selectively removing the more activated forms.

Aged↗
PubMed1996

Quality of life evaluation by the EORTC questionnaire technique in patients with generalized malignant melanoma on chemotherapy.

A longitudinal quality of life (QOL) study was performed on patients with advanced melanoma during chemotherapy. The purpose was to describe QOL in this palliative context and to compare the clinical outcome variables and patients' self-assessed QOL. QOL was assessed by the EORTC core questionnaire technique (QLQ-C36), a study-specific melanoma (MM module and the Hospital Anxiety and Depression (HAD) scale. The questionnaires displayed good psychometric qualities and the technique proved to be applicable in this longitudinal study of severely ill patients. Only six patients, out of 95 in total, complied with the full one-year study. Drop-outs occurred early in the course of treatment, most of them due to progressive disease or death. Pretreatment, patients reported a low level of dysfunction and symptom burden but 9 weeks later they exhibited significant deterioration in all QOL measurements, with the exception of pain and emotional functioning. The mean duration of response was short and there was considerable observed treatment-related toxicity. However, no correlation was found between physician-rated clinical outcome variables and QOL measurements, except for neuropathy. Our results are in accordance with earlier data on the supplementary value of QOL measurements to define endpoints in clinical trials.

Adult↗
PubMed1996

Influenza vaccination of children during acute asthma exacerbation and concurrent prednisone therapy.

OBJECTIVES: The influenza vaccination rate is very low among children with moderate to severe asthma. This may be partly because of poor patient motivation and failure to visit clinics for vaccination. Another important factor may be health care providers' deferral of vaccination because of concern about the efficacy and safety of influenza vaccination during asthma exacerbations and concurrent prednisone therapy. We therefore examined the safety and immunogenicity of influenza vaccination during acute asthma exacerbation with concomitant prednisone therapy. SETTING: A pediatric allergy and pulmonology clinic and a pediatric emergency department. DESIGN: Children (n = 109) with a known diagnosis of asthma 6 months to 18 years of age were recruited. All participating patients, 59 without asthma symptoms (no prednisone, control group) and 50 with acute asthma exacerbation requiring prednisone burst therapy (prednisone group) received trivalent subvirion influenza vaccine. Fifteen children in the control group and 12 in the prednisone group received a booster dose according to American Academy of Pediatrics guidelines. Serum antibody titers to influenza A/Beijing/32/92 (H3N2), influenza A/Texas/36/91 (H1N1), and influenza B/Panama/45/90 were measured before and 2 weeks after vaccination. Adverse effects noted within 48 hours after vaccine dose were ascertained during the follow-up visit. RESULTS: The antibody response was analyzed by comparing mean postvaccine titers, the percentage of patients achieving protective antibody levels (> or = 5log2), and the percentage of patients achieving rises in titers of 2log2 or greater. Antibody responses to influenza A/Beijing/32/92 (H3N2) and influenza A/Texas/36/91 (H1N1) in the prednisone-treated and control groups were not different. A significantly better response to the influenza B/Panama/45/90 antigen was seen in the prednisone group for all three parameters. Children who received a booster dose and the subgroup of children with low prevaccination titers (< or = 3log2) showed similar patterns. Adverse effects, including asthma exacerbation, local swelling at the injection site, fever, rash, and headache, were not different in the two groups. CONCLUSIONS: Influenza vaccination can be given safely and effectively to asthmatic children regardless of asthma symptoms or concurrent prednisone therapy when necessary. Vaccination of all moderate to severe asthmatic patients visiting clinics or emergency departments would improve the overall vaccination rate significantly.

Antibodies, Viral↗
PubMed1995

Tissue-specific expression and cholesterol regulation of acylcoenzyme A:cholesterol acyltransferase (ACAT) in mice. Molecular cloning of mouse ACAT cDNA, chromosomal localization, and regulation of ACAT in vivo and in vitro.

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) catalyzes the esterification of cholesterol with long chain fatty acids and is believed to play an important part in the development of atherosclerotic lesions. To facilitate the study of ACAT's role in this process, we have used the human ACAT K1 clone previously described (Chang, C. C. Y., Huh, H. Y., Cadigan, K. M. and Chang, T. Y. (1993) J. Biol. Chem. 268, 20747-20755) to isolate mouse ACAT cDNA from a liver cDNA library. The 3.7-kilobase cDNA clone isolated contains a 1620-base pair open reading frame which encodes a protein of 540 amino acids. The predicted mouse ACAT protein is 87% identical to the protein product of human ACAT K1 and shares many of the same secondary structural features, including two transmembrane domains, a leucine heptad motif consistent with dimer or multimer formation, and five regions homologous to the "signature sequences" found in other enzymes that catalyze acyl adenylation followed by acyl thioester formation and acyl transfer. Using the cDNA as a hybridization probe, we mapped the gene encoding mouse ACAT to chromosome 1 in a region syntenic to human chromosome 1 where the ACAT gene is located. Northern blot analysis and RNase protection assays of mouse tissues revealed that ACAT mRNA is expressed most highly in the adrenal gland, ovary, and preputial gland and is least abundant in skeletal muscle, adipose tissue, heart, and brain. To study the dietary regulation of ACAT mRNA expression in mouse tissues, we fed C57BL/6J mice a high-fat, high-cholesterol (HF/HC) atherogenic diet for 3 weeks and measured ACAT mRNA levels in various tissues by RNase protection. The HF/HC diet had little effect on ACAT mRNA levels in the small intestine, aorta, adrenal, or peritoneal macrophages, whereas hepatic ACAT mRNA levels were doubled in mice fed the atherogenic diet. ACAT activity in liver microsomes was similarly increased in cholesterol-fed mice, suggesting that mouse ACAT is regulated at least in part at the level of mRNA abundance. Additionally, a significant positive correlation was observed between ACAT activity and microsomal free cholesterol levels in chow- and cholesterol-fed mice, supporting the concept of cholesterol availability as a regulator of ACAT. To further investigate the regulation of ACAT activity under controlled conditions, ACAT-deficient Chinese hamster ovary cells were stably transfected with the mouse ACAT cDNA clone driven by a cytomegalovirus promoter. Two transfected Chinese hamster ovary cell lines that expressed the mouse ACAT transgene regained the ability to esterify cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Partial structure of the mouse glucokinase gene.

A complementary DNA for glucokinase (GK) was cloned from mouse liver total RNA by a combination of the polymerase chain reaction (PCR) and mouse liver cDNA library screening. Liver- and beta-cell-specific exons 1 were isolated by PCR using mouse and rat genomic DNAs. These clones were then used to screen a mouse genomic library; three genomic clones were isolated and characterized. The mouse GK gene spans over 20 kb, containing 11 exons including a liver- or beta-cell-specific exon 1, which encodes a tissue-specific 15-aa peptide at the N-terminus of the protein. Both types of GK contain 465 amino acid residues. The predicted amino acid sequence of mouse beta-cell-specific GK showed 98 and 96% identity to the rat and human enzymes, respectively; the corresponding values are 98 and 95%, respectively, for the liver-specific GK. Several transcription factor-binding consensus sequences are identified in the 5' flanking region of the mouse GK gene.

Amino Acid Sequence↗
PubMed1995

Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19 [corrected].

We have isolated from a human T-cell Jurkat cDNA library a novel human cDNA (2EL) that is closely related to the human type-IV PDE splice variant family 'A' (PDE-IVA) cDNA characterized previously by us [Sullivan, Egerton, Shakur, Marquardsen and Houslay (1994) Cell. Signalling 6, 793-812]; (h6.1, PDE-IVA/h6.1; HSPDE4A7). (PDE stands for cyclic nucleotide phosphodiesterase). The novel cDNA 2EL (PDE-IVA/2EL; HSPDE4A8) contains two regions of unique sequence not found in PDE-IVA/h6.1. These are a distinct 5'-end and a 34 bp insert which occurs within a domain thought to encode the type-IV PDE catalytic site and which can be expected to result in premature truncation of any expressed protein. HSPDE4A8 appeared to be catalytically inactive. Isolation and characterization of a human genomic cosmid clone revealed that 2EL and h6.1 represent alternative splice variants of the human PDE-IVA gene. Using a unique sequence found at the 5'-end of the 2EL cDNA, a probe was generated which was used to screen the DNA of human-hamster hybrids. This located the human gene for PDE-IVA to human chromosome 19. Through both the analysis of genomic DNAs from a human-hamster somatic cell hybrid panel and also using fluorescent in situ hybridization, it was shown that the human PDE-IVA gene is located on human chromosome 19, between p13.2 [corrected] and q12. This region on chromosome 19 has been shown to be related to genetic diseases such as the autosomal dominant cerebrovascular disease CADASIL, susceptibility to late-onset Alzheimer's disease and changes seen in benign pituitary and thyroid adenomas.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Molecular cloning and functional expression in yeast of a human cAMP-specific phosphodiesterase subtype (PDE IV-C).

We have recently reported increased survival of dopaminergic substantia nigra neurons by inhibition of phosphodiesterase type IV enzymes. As a first step to unravel the involvement of PDE IV subtypes in this process, we isolated phosphodiesterase type IV cDNAs from human substantia nigra. One isolated partial cDNA clone was most homologous to the partially cloned rat and human PDE IV-C isogene. Distribution analysis revealed that the enzyme is expressed in various tissues but not in cells of the immune system. Isolation of the full-length human PDE IV-C isogene cDNA and expression in a PDE-deficient yeast strain resulted in functional complementation of the yeast heat shock response. Inhibition of the enzymatic activity by rolipram characterized this enzyme as a typical type IV phosphodiesterase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Characterization of the human interleukin-5 gene promoter: involvement of octamer binding sites in the gene promoter activity.

To investigate the human interleukin (IL)-5 gene promoter, we have constructed a plasmid with the firefly luciferase reporter gene linked to human IL-5 5' flanking sequence (nucleotides -507 to +44). We have used this plasmid to transfect the mouse EL4 T cell line, which can, under certain conditions, produce IL-5 transcripts. Phorbol 12-myristate 13-acetate, A23187 and N6, 2'-O-dibutyryl-adenosine 3':5'-cyclic monophosphate co-stimulation of EL4 cells transfected with the human IL-5/luciferase reporter gene construct resulted in maximal induction of the luciferase gene. Deletion analysis of the IL-5 promoter revealed the presence of negative regulatory elements between nucleotides -404 and -312 and two regions, located between nucleotides -312 and -227 and between nucleotides -80 and -35, that are involved in the positive regulation of the IL-5 promoter. Using electrophoretic mobility shift assays, we show that the positive element located between nucleotides -312 and -227 involves the binding of factors antigenically related to Oct1, Oct2A and Oct2B, to a perfect octamer motif located at position -244/-237. Introduction of three point mutations in the octamer motif of the IL-5/luciferase reporter gene plasmid, which results in the loss of competition for the factors binding to the IL-5 promoter sequence, reduced the production of luciferase from stimulated, transfected EL4 cells, by 90%. Octamer factors can also bind within the second positive regulatory region.

Animals↗