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Biomedical subjects

D Clark

Publications and source records attributed to D Clark.

At least 91 records · Page 5Linked to original sources
PubMed1998

The road to recovery in panic disorder: response, remission, and relapse.

A standard set of definitions and criteria for the terms commonly used in panic disorder research is required to aid clinicians in their management of patients with panic disorder. Furthermore, the use of a simple, psychometrically sound assessment procedure such as the Panic Disorder Severity Scale, which considers all of the essential domains of panic disorder, will provide clinicians with an appropriate instrument for diagnosing and monitoring patients. The use of this more comprehensive scale for monitoring patients should alert clinicians to the reemergence of associated symptoms of panic disorder and allow for the rapid modification of treatment. By responding quickly to the recurrence of symptoms, a full relapse may be prevented.

Agoraphobia↗
PubMed1998

Fixed polarizer ellipsometry for simple and sensitive detection of thin films generated by specific molecular interactions: applications in immunoassays and DNA sequence detection.

Biological thin films may form on a surface by specific molecular interactions. The fixed polarizer ellipsometer (FPE) is a sensitive instrument that detects biological thin films either qualitatively or quantitatively. The design is simple and inexpensive. The assays are formatted on an optical surface, and the FPE detection is based on the phase shift of linearly polarized light after reflection through a thin film. We have constructed mathematical models of the FPE response to reflection through single-layer and two-layer films that agree closely with experimental data. Several biological assays have been measured with the FPE to demonstrate the application of this technology to clinical targets, including ultrasensitive immunoassays for hepatitis B surface antigen (0.1 ng/mL) and alpha-fetoprotein (0.01 ng/ mL) and DNA hybridization (0.5 fmol/microL target probe). A clinical study for detection of group A streptococcus from patient throat swabs demonstrated the qualitative application of the FPE to infectious disease targets. The flexibility and sensitivity of the FPE makes this technology suitable for numerous target analytes and applications.

Antigens, Bacterial↗
PubMed1997

The Family Attitude Scale: reliability and validity of a new scale for measuring the emotional climate of families.

Research on outcomes from psychiatric disorders has highlighted the importance of expressed emotion (EE), but its cost-effective measurement remains a challenge. This article describes development of the Family Attitude Scale (FAS), a 30-item instrument that can be completed by any informant. Its psychometric characteristics are reported in parents of undergraduate students and in 70 families with a schizophrenic member. The total FAS had high internal consistency in all samples, and reports of angry behaviour in FAS items showed acceptable inter-rater agreement. The FAS was associated with the reported anger, anger expression and anxiety of respondents. Substantial associations between the parents' FAS and the anger and anger expression of students was also observed. Parents of schizophrenic patients had higher FAS scores than parents of students, and the FAS was higher if disorder duration was longer or patient functioning was poorer. Hostility, high criticism and low warmth on the Camberwell Family Interview (CFI) were associated with a more negative FAS. The highest FAS in the family was a good predictor of a highly critical environment on the CFI. The FAS is a reliable and valid indicator of relationship stress and expressed anger that has wide applicability.

Adolescent↗
PubMed1997

Conjunctival impression cytology in the preterm infant and it's relation to outcome.

UNLABELLED: The preterm infant is deficient in vitamin A (retinol) and this has been implicated in the pathogenesis of chronic lung disease of prematurity. Conjunctival impression cytology (CIC) has been used in adults to assess retinol status. We aimed to assess the feasibility of performing CIC in the preterm infant and to determine the significance of abnormal CIC findings. CIC samples were collected during routine retinopathy screening, and classified as inadequate, normal, borderline normal or abnormal. Ninety preterm infants were studied. Seventy-four (82%) CIC specimens produced a positive yield, whereas 16 (18%) were inadequate. Of the 74 adequate samples, 61 (82%) were normal or borderline normal and 13 (18%) abnormal. Seventy-three CIC specimens were assessed by a second histopathologist with complete agreement on 64 (88%) samples and disagreement on 9 (12%) samples. Ten sets of conjunctival impressions, taken from both eyes, gave identical results in all adequate samples. Birth weight was significantly lower in this abnormal group. Four infants (32%) in the abnormal group required treatment for retinopathy compared to two (3%) in the normal/borderline normal group, (P < 0.01). CONCLUSION: Conjunctival impression cytology is simple and reproducible technique which maybe easily applied to the preterm infant. Abnormal CIC is associated with retinopathy of prematurity requiring treatment.

Conjunctiva↗
PubMed1997

Burst firing in midbrain dopaminergic neurons.

Midbrain dopaminergic (DA) neurons fire bursts of activity in response to sensory stimuli, including those associated with primary reward. They are therefore conditional bursters - the bursts conveying, amongst other things, motivationally relevant information to the forebrain. In the forebrain, bursts give rise to a supra-additive release of dopamine, and possibly favour the release of co-localised neuropeptides. Evidence is presented that in rat DA neurons, bursts are engendered by the activity of cortically-regulated afferents. Certain factors are identified which, in combination, lead to burst production: (1) A burst of activity in EAAergic afferents to DA neurons arising from non-cortical sources, but controlled by the medial prefrontal cortex; (2) N-methyl-D-aspartate receptor activation, producing a slow depolarising wave in the recipient neuron; (3) activation of a high threshold, dendritically located calcium conductance which produces a 'plateau potential'; (4) activation of a calcium-activated potassium conductance, which terminates the burst. These factors are argued to operate in the context of an 'optimal' level of intracellular calcium buffering for bursting. Other factors which appear to be involved in bursting in other systems, in particular a low threshold calcium conductance, are rejected as being necessary for bursting in DA neurons. The factors which do play a crucial role in burst production in DA neurons are integrated into a theory from which arises a series of hypotheses amenable to empirical investigation. Additional factors are discussed which may modulate bursting. These may either act indirectly through changes in membrane potential (or intracellular calcium concentration), or they may act directly through an interaction with certain conductances, which appear to promote or inhibit burst firing in DA neurons.

Animals↗
PubMed1997

Needs assessment and palliative care: the views of providers.

BACKGROUND: A key element within the programme of reform introduced into the UK National Health Service in the 1990s has been the concept of health needs assessment, which must be undertaken by health care purchasers as a guide to the planning process. As part of a wide-ranging study of the impact of the NHS reforms on hospices and specialist palliative care services, providers' perceptions of needs assessment for palliative care were examined, including the extent to which needs assessments had been carried out in local districts, together with the implications. METHODS: The study comprised two key elements. In spring 1995 a postal survey was conducted among all UK hospices and specialist palliative care in-patient units (n = 203) eliciting factual information concerning needs assessment and contracting, together with perceptions and evaluations of the local impact of the NHS reforms. A total of 128 (63 per cent) questionnaires was completed and returned. In addition to the survey, 12 case studies were conducted with a stratified random sample of NHS, independent and large or small hospices and specialist palliative care units. Each of the 12 case study sites was visited by a member of the research team, who conducted interviews with senior staff and analysed financial, planning and management data. Thus the survey allowed a wide analysis of the impact of the NHS reforms, which was enhanced by the more in-depth qualitative data gathered from the case studies. RESULTS: In the survey 49 per cent of those responding reported that their main purchaser had conducted a needs assessment for palliative care in the last five years. Palliative care needs assessment was seen as valuable by providers: 73 per cent considered it very important and 28 per cent of hospices had gone so far as to request a needs assessment from their health authority. In an open-ended question seeking views on the impact of health needs assessment, 66 per cent of those responding (71/107) stated that the impact had been or would be positive. The case studies, however, revealed a more mixed picture. The 12 hospices or specialist palliative care units had contracts with a total of 24 health authorities, 12 of which had conducted some type of needs assessment for palliative care. On close examination the comprehensiveness of these was questionable. Few providers had participated in the design and there were low levels of knowledge about the findings. High expectations of the value of needs assessment were often not fulfilled. There was also a tendency for providers to view needs assessment in a purely instrumental light, as a vehicle to further promote their own interests. CONCLUSIONS: Palliative care needs assessment has considerable potential to influence future purchasing and service provision, yet not all health commissions are undertaking it. There is a high level of provider enthusiasm for palliative care needs assessment, albeit coupled to low levels of technical knowledge and a lack of involvement in the process at local level. Purchaser-provider dialogue on needs assessment should focus on both raising awareness of appropriate techniques and debating 'ethical neutrality' about the outcome.

Attitude of Health Personnel↗
PubMed1997

Increasing access to health care: a study of pediatric nurse practitioner outcomes in a school-based clinic.

Pediatric nurse practitioners in school-based clinics have the potential to overcome access to care barriers for school-age children and their families by providing primary health care and linking these services with existing health and social services in the community. The article reports a study that examined health care delivered by a pediatric nurse practitioner in an elementary school setting and selected indices of access to health care (Medicaid certification; early periodic screening, diagnosis, and treatment; and linkage with existing resources). Findings suggest that greater availability of care may encourage parents to seek early preventive care for their children.

Ambulatory Care↗
PubMed1997

The initial Australian experience of technetium-99M sestamibi scintimammography: a complementary test in the management of breast cancer.

BACKGROUND: The adjunctive role of Tc-99m sestamibi scintimammography in the diagnosis and management of patients with a high probability of breast cancer was assessed. METHODS: A descriptive study of 16 patients with palpable masses who had a high probability of breast cancer as determined by investigations such as cytology and conventional imaging techniques were carried out. All patients were followed-up to surgery. RESULTS: Scintimammography true positive results were found in 14 of 18 lesions detected in 16 patients. There were two false-positives which included one lobar carcinoma in situ lesion and one complex sclerosing lesion, and one false-negative patient. Scintimammography detected abnormal radiotracer uptake in four of six patients with axillary metastases. Three patients had clinically and mammographically undetected multicentric disease detected on scintimammography which allowed appropriate modification of surgical excision. Breast cancer was detected in a patient with breast prostheses. CONCLUSIONS: Scintimammography would appear to have a useful adjunctive role to mammography in the diagnosis of breast cancer. The diagnosis of breast cancer may be enhanced in difficult cases and the detection of multicentricity on scintimammography may have an impact on subsequent surgical management.

Adult↗
PubMed1997

Cryotherapy and laser treatment for acute retinopathy of prematurity: refractive outcomes, a longitudinal study.

BACKGROUND: Infants who require treatment for threshold retinopathy of prematurity are at increased risk of developing refractive errors. Following the introduction of laser treatment for threshold disease, the clinical impression was that the degree of myopia was reduced compared with cryotherapy. METHODS: A longitudinal study was carried out of refractive error at 3 and 12 months in 19 patients undergoing cryotherapy and 15 patients undergoing laser treatment. RESULTS: At 3 months the median spherical equivalent refractive error in the right eye was -3.25 dioptres after cryotherapy and +0.25 dioptres after laser therapy (similar results left eye). The median spherical equivalent refractive error in the right eye at 12 months was -5.25 dioptres following cryotherapy and -0.50 dioptres after laser (similar results left eye). There was a statistically significant difference in median spherical refractive error between the therapies at 3 months and 12 months (p < 0.05 Wilcoxon rank sum) in both eyes. CONCLUSION: Laser therapy is associated with lower degrees of myopia during the first year of life, which is clinically significant in terms of visual performance and development.

Acute Disease↗
PubMed1997

Standardizing data collection and decision making with an expert system.

The software for the pilot system has been completed. The appropriateness of the risk factor weights needs to be evaluated by clinical testing. However, this does not prevent the system from being used to teach the philosophy of risk group identification and selection of different management strategies according to disease activity. The current system does demonstrate a dynamic relationship between caries risk assessment/activity and different management strategies. A formal scientific evaluation of the effectiveness of the system as a teaching tool is being developed.

Data Collection↗
PubMed1996

Symptomatic coronary artery disease after mantle irradiation for Hodgkin's disease.

PURPOSE: a) To assess the age-related incidence of morbid cardiac events including cardiac death (CD), nonfatal myocardial infarction (MI), and angina pectoris (AP) in all patients treated for Hodgkin's disease at a single institution; b) to examine the prevalence of cardiac risk factors and presence of coronary artery disease (CAD) in affected patients. METHODS AND MATERIALS: 475 patients were treated for Hodgkin's disease in our institution between 1954 and 1989. The status of 97% of the cohort was established either by patient visit and examination in 1992-1993, personal telephone contact, or documentation of death. The 326 of these patients who had mantle irradiation (RT) and survived 3 years formed the study population. Patients who experienced AP, MI, or CD secondary to CAD were assessed for the presence of specific cardiac risk factors. Cardiac catheterization and necropsy data were reviewed to determine the presence and degree of coronary artery stenosis. RESULTS: Eighteen of 326 patients (5.5%) have had a morbid cardiac event directly related to CAD. Seven patients had CD. Seven patients experienced nonfatal MI, and four patients had AP. The mean interval from RT to morbid cardiac event was 13.1 years (range: 4.4-27.0), and the mean age at the time of the event was 39.4 years (range: 24-65). Four of these patients had morbid cardiac events between ages 24-29 years. Based on US statistics of CD secondary to MI, the relative risk of CD for the treated group was 2.8 (3.1 for males and 1.8 for females). Remarkably, no difference was found in the risk of experiencing a morbid cardiac endpoint in patients stratified by either decile of age at which RT was given, or by duration of follow-up. Only one patient experiencing an event (AP) had received an anthracycline. The mean RT dose to the central cardiac volume for the affected patients was 44.3 Gy (range: 35-60.4). Autopsy or catheterization data were available on 15 patients and revealed 90-100% stenosis of at least one major vessel in 11 patients (73%), and no single artery was more commonly stenosed. Specifically, the left anterior descending and right coronary arteries were each greater than or equal to 60% stenosed in 10 out of 15 patients (67%), and either the left main or circumflex arteries were greater than or equal to 50% stenosed in 5 out of 15 patients (33%); triple vessel disease was present in seven patients. Risk factor data were available on all patients experiencing morbid cardiac events: 72% smoked, 72% were male, 78% had hypercholesterolemia, 61% were obese, 28% had a positive family history, 33% had hypertension, and 6% (one) had diabetes. The average number of risk factors per patient was 2.9; seven patients had at least four risk factors, and all patients had at least one risk factor. This frequency of risk factors is elevated when compared to the US population. CONCLUSIONS: In our institution, 5.5% of patients treated for Hodgkin's disease experienced a morbid cardiac event following RT to the central cardiac volume. The doses given were greater than commonly used today. Some patients experienced events at a young age, and the likelihood of experiencing CD was increased compared to the general population. This observation is consistent with RT as an additional risk factor in the induction of morbid cardiac events. Appropriate cardiac shielding and radiation doses, careful follow-up, which includes monitoring of cardiac function, and a preventative program of sensible dietary habits, exercise, and nonsmoking may be beneficial in reducing cardiac morbidity in long-term survivors of Hodgkin's disease.

Adolescent↗
PubMed1996

Preferential occupation of mineralocorticoid receptors by corticosterone enhances glutamate-induced burst firing in rat midbrain dopaminergic neurons.

Sensitisation to the behavioural effects of amphetamine, a phenomenon which appears to involve the potentiation of excitatory amino acid (EAA)-mediated transmission at the level of dopaminergic (DA) neurons in the ventral tegmental area (the A10 cell group), is known to be affected by corticosteroid manipulations. Since there is evidence that corticosteroid manipulations can also influence unpotentiated EAA-mediated transmission elsewhere in the brain, the possibility was examined that the same may be true for midbrain DA neurons. The effect of iontophoretically administered glutamate on the activity of A10 DA neurons was investigated in adrenalectomised animals given a low dose of corticosterone intravenously (equivalent to 13.4 micrograms/100 ml plasma - likely to preferentially occupy the mineralocorticoid subtype of corticosteroid receptor) at least 45 min (median 132.5) prior to recording. Cells from these animals were compared to those from adrenalectomised and sham operated animals administered saline. Adrenalectomy significantly reduced the firing rate of A10 cells, and this effect was reversed by corticosterone replacement. Adrenalectomy did not affect basal burst firing. However, in those cells which could be classified as "bursting' under basal conditions, cells from animals administered corticosterone showed enhanced glutamate-induced bursting relative to the other two groups. The degree of enhancement was strictly determined by the basal bursting level of the cell. Since the distinction between "bursting' and "non-bursting' DA neurons is probably not related to differences at the level of the EAA receptor/effector mediating bursting, it is argued that corticosterone's facilitation of glutamate-induced bursting is not produced at this level, but rather at the level of an intrinsic membrane property which modulates bursting.

Adrenalectomy↗
PubMed1996

Chromatin structure and gene expression.

It is now well understood that chromatin structure is perturbed in the neighborhood of expressed genes. This is most obvious in the neighborhood of promoters and enhancers, where hypersensitivity to nucleases marks sites that no longer carry canonical nucleosomes, and to which transcription factors bind. To study the relationship between transcription factor binding and the generation of these hypersensitive regions, we mutated individual cis-acting regulatory elements within the enhancer that lies between the chicken beta- and epsilon-globin genes. Constructions carrying the mutant enhancer were introduced by stable transformation into an avian erythroid cell line. We observed that weakening the enhancer resulted in creation of two classes of site: those still completely accessible to nuclease attack and those that were completely blocked. This all-or-none behavior suggests a mechanism by which chromatin structure can act to sharpen the response of developmental systems to changing concentrations of regulatory factors. Another problem raised by chromatin structure concerns the establishment of boundaries between active and inactive chromatin domains. We have identified a DNA element at the 5' end of the chicken beta-globin locus, near such a boundary, that has the properties of an insulator; in test constructions, it blocks the action of an enhancer on a promoter when it is placed between them. We describe the properties and partial dissection of this sequence. A third problem is posed by the continued presence of nucleosomes on transcribed genes, which might prevent the passage of RNA polymerase. We show, however, that a prokaryotic polymerase can transcribe through a histone octamer on a simple chromatin template. The analysis of this process reveals that an octamer is capable of transferring from a position in front of the polymerase to one behind, without ever losing its attachment to the DNA.

Animals↗
PubMed1996

Complementation of an Escherichia coli adhE mutant by the Entamoeba histolytica EhADH2 gene provides a method for the identification of new antiamebic drugs.

The pathogenic protozoan parasite Entamoeba histolytica, the cause of amebic dysentery and amebic liver abscess, is an obligate anaerobe, and derives energy from the fermentation of glucose to ethanol with pyruvate and acetyl coenzyme A as intermediates. We have isolated EhADH2, a key enzyme in this pathway, that is a NAD+- and Fe2+-dependent bifunctional enzyme with acetaldehyde dehydrogenase and alcohol dehydrogenase activities. EhADH2 is the only known eukaryotic member of a newly defined family of prokaryotic multifunctional enzymes, which includes the Escherichia coli AdhE enzyme, an enzyme required for anaerobic growth of E. coli. Because of the critical role of EhADH2 in the amebic fermentation pathway and the lack of known eukaryotic homologues of the EhADH2 enzyme, EhADH2 represents a potential target for antiamebic chemotherapy. However, screening of compounds for antiamebic activity is hampered by the cost of large scale growth of Ent. histolytica, and difficulties in quantitating drug efficacy in vitro. To approach this problem, we expressed the EhADH2 gene in a mutant strain of E. coli carrying a deletion of the adhE gene. Expression of EhADH2 restored the ability of the mutant E. coli strain to grow under anaerobic conditions. By screening compounds for the ability to inhibit the anaerobic growth of the E. coli/EhADH2 strain, we have developed a rapid assay for identifying compounds with anti-EhADH2 activity. Using bacteria to bypass the need for parasite culture in the initial screening process for anti-parasitic agents could greatly simplify and reduce the cost of identifying new therapeutic agents effective against parasitic diseases.

Alcohol Dehydrogenase↗
PubMed1996

Analysis of abrB mutations, mutant proteins, and why abrB does not utilize a perfect consensus in the -35 region of its sigma A promoter.

The Bacillus subtilis global regulator AbrB is a DNA-binding protein composed of six identical monomers of 96 amino acids that shows specificity to the promoter regions of its target genes including its own. We have sequenced thirteen previously uncharacterized abrB mutations. Four mutant AbrB proteins were purified, and their DNA-binding properties and multimeric structures were examined. AbrB23 (R25S) had no appreciable DNA binding activity but retained a hexameric structure, indicating that Arg25 is important in DNA interactions. Three other mutant proteins, AbrB1 (C56Y), AbrB19 (Gln83-->termination codon), and AbrB100 (L69P), showed decreased DNA binding and altered multimeric interactions. Analysis of the expression and AbrB binding affinities of mutant abrB promoters demonstrated that a consensus -35 region is incompatible with proper autoregulation of the abrB gene.

Amino Acid Sequence↗