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Biomedical subjects

C Kirk

Publications and source records attributed to C Kirk.

At least 19 recordsLinked to original sources
PubMed2006

Analysis of a care planning intervention for reducing depression in older people in residential care.

Approximately 40% of older people in residential care have significant symptoms of depression. A training and care-planning approach to reducing depression was implemented for 114 depressed residents living in 14 residential care homes in North Yorkshire, UK. Care staff were offered brief mental health training by community mental health teams for older people. They were then assigned to work individually with residents in implementing the care-planning intervention, which was aimed at alleviating depression and any health, social or emotional factors that might contribute to the resident's depression. Clinically significant improvements in depression scores were associated with implementation of the care-planning intervention as evidenced by changes in scores on the Geriatric Mental State Schedule-Depression Scale. There was evidence of an interaction between the power of the intervention and degree of dementia. These improvements were not accounted for by any changes in psychotropic medication. The training was highly valued by care staff and heads of homes, and they considered that the care-planning intervention represented an improvement in quality of care for all residents, irrespective of levels of dementia. Staff also reported improvements in morale and increased confidence in the caring role as a result of their participation. The limitations of this study are discussed. On the basis of a growing body of evidence, it is argued that there is an urgent need for a suitably powered randomised controlled trial and economic evaluation, to test the cost-effectiveness of personalised care planning interventions aimed at reducing depression in older people in residential care.

Adult↗
PubMed2000

Deliberate self-harm and antidepressant drugs. Investigation of a possible link.

BACKGROUND: It is not clear if the frequency of deliberate self-harm (DSH) is the same in patients taking different pharmacological classes of antidepressant drugs. AIMS: To compare the frequency of DSH in patients who had been prescribed a tricyclic antidepressant (TCA) or a selective serotonin reuptake inhibitor (SSRI) prior to the DSH event. METHOD: This was a prospective study in 2776 consecutive DSH cases attending an accident and emergency department. The incidence of DSH in TCA-treated cases and SSRI-treated cases is expressed as number of DSH events per 10 000 prescriptions of each antidepressant. RESULTS: Significantly more DSH events occurred following the prescription of an SSRI than that of a TCA (P<0.001). The occurrence of DSH was highest with fluoxetine and lowest with amitriptyline. CONCLUSIONS: Merely prescribing safer-in-overdose antidepressants is unlikely to reduce the overall morbidity from DSH.

Adolescent↗
PubMed1999

Methods for evaluating treatment of uroliths.

Formation of uroliths is not a disease but rather a complication of several disorders. Some disorders can be identified and corrected (e.g., infection-induced struvite urolith formation), and some can be identified but not corrected (e.g., hyperuricosuria occurring in Dalmatians that form ammonium urate uroliths), although for others, the underlying etiopathogenesis is not known (e.g., calcium oxalate urolith formation in Miniature Schnauzers). A common denominator of these disorders is that from time to time, they can create oversaturation of urine with one or more crystal precursors, resulting in formation of crystals. To develop rational and effective approaches to treatment, abnormalities that promote urolith formation must be identified with the goal of eliminating or modifying them. It is therefore important to understand several basic concepts associated with urolithiasis.

Animals↗
PubMed1998

Identification of a neuregulin and protein-tyrosine phosphatase response element in the nicotinic acetylcholine receptor epsilon subunit gene: regulatory role of an Rts transcription factor.

At the neuromuscular synapse, innervation induces endplate-specific expression of adult-type nicotinic acetylcholine receptors by selective expression of their subunit-encoding genes (alpha2betaepsilondelta) in endplate-associated myonuclei. These genes are specifically regulated by protein-tyrosine phosphatase (PTPase) activity. In addition, neuregulin/acetylcholine-receptor-inducing activity, a nerve-derived factor that stimulates nicotinic acetylcholine receptor synthesis, induces adult-type specific epsilon subunit gene expression via activation of a Ras/mitogen-activated protein kinase pathway. However, the DNA regulatory elements and the binding proteins that mediate PTPase and neuregulin-dependent gene expression remain unknown. Herein we report that PTPase, neuregulin, and Ras-dependent regulation of the epsilon subunit gene map to a 15-bp promoter sequence. Interestingly, this same 15-bp sequence appears to be necessary for low epsilon subunit gene expression in extrajunctional regions of the muscle fiber. Site-directed mutagenesis of a putative Ets binding site located within this 15-bp sequence, reduced PTPase, neuregulin, and Ras-dependent regulation. Overexpression of the rat muscle Ets-2 transcription factor resulted in a sequence-specific induction of epsilon subunit promoter activity. Further, a dominant negative mutant of Ets-2 abolished neuregulin-dependent induction of epsilon subunit gene expression. Thus, these results indicate a crucial role for the 15-bp element in determining synapse-specific and neuregulin-mediated motor neuron control of epsilon subunit gene expression and suggest the participation of Ets transcription factor(s) in this control.

Animals↗
PubMed1998

Recombinant human glial growth factor 2 (rhGGF2) improves functional recovery of crushed peripheral nerve (a double-blind study).

This in vivo double-blind study evaluated the effect of recombinant human glial growth factor 2 (rhGGF2), a Schwann cell mitogen, on the recovery of motor function of rat sciatic nerve following crush injury. Seventy three rats were divided into three groups. Group I (n=5), sham operated; Groups II (n=34) and III (n=34) received a 100 g crush load for 2 h over a 5 mm segment of the sciatic nerve. Group III was treated with 1 mg/kg rhGGF2, via subcutaneous injection one day before nerve crush and daily for the following four days. Group II received an equivalent volume of saline as a control. Motor functional recovery was assessed by calculating the sciatic functional index (SFI) and the recovery rate of tetanic contractile force of the extensor digitorum longus (EDL) muscle. Recovery of nerve function was evident at day 11 after crush in the rhGGF2-treated animals, whereas the nerves in controls were still paralyzed. The rhGGF2-treated animals showed a significant improvement of the SFI between days 11-21 postoperatively when compared to controls. The isometric tetanic contractile force was stronger in the rhGGF2-treated group than in controls, with a significant difference at 40 to 70 Hz stimulus frequencies on day 4. Correlation analysis showed that tetanic contractile force had a linear correlation with the SFI. Histologic assessment indicated that the rhGGF2-treated animals showed less severe degeneration and earlier robust remyelination of axons than controls. The results suggest that treatment with rhGGF2 is effective in promoting nerve regeneration as seen in measurements of functional recovery and qualitative assessment of nerve morphology. The mechanism of GGF's protective effect may be related to its direct action on Schwann cells, stimulating their mitosis as well as inducing neurotrophic factors essential to neuronal maintenance and repair.

Animals↗
PubMed1997

Kinetic analysis of drug cleavage of closed-circular DNA.

Various cleavage agents interact with circular double-stranded DNA molecules to convert the closed-circular form (form-I) to the open-circular (form-II) and linear (form-III) forms, and ultimately to small DNA fragments. The various cutting processes which take place in the DNA pool are here analyzed kinetically, and, by solving the kinetic equations, expressions are derived for the amounts of the closed-circular, open-circular, and linear forms of DNA as a function of reaction time and concentration of cleavage agent. Conversions between subspecies of forms II and III, differing in numbers of internal cuts, are taken into account. The only assumption required to solve the kinetic equations is that the concentration of cleavage agent obeys [D] = D0 f(t) where the function of time f(t) is independent of D0, the initial concentration of cleavage agent. By choosing parameters in the expressions for the calculated amounts of forms I, II and III to give the best fit to the measured amounts, one obtains information about the rates and rate constants for the conversions. The rate constants in turn give important information about the specificity and mechanism of action of the cleavage agents. The analysis is applied to the cleavage of pBR322, SV-40 and PM2 DNAs by DNase I, Fe-EDTA, and the antitumor agents calicheamicin and bleomycin. Cleavage rate constants are derived and discussed for these systems.

Antibiotics, Antineoplastic↗
PubMed1996

Stimulation of myogenic differentiation by a neuregulin, glial growth factor 2. Are neuregulins the long-sought muscle trophic factors secreted by nerves?

It has long been known that nerves stimulate growth and maintenance of skeletal muscles in ways not dependent on physical contacts, but numerous attempts to identify and characterize the myotrophic agent(s) secreted by nerves have been unsuccessful. We here suggest that products of the neuregulin gene may be these agents. The neuregulins are a family of proteins made by alternative splicing of a single transcript to give as many as 15 protein products. One member of this family, glial growth factor 2 (rhGGF2) is a very potent stimulator of myogenesis in L6A1 myoblasts, giving a maximal stimulation of cell fusion and creatine kinase elevation at a concentration of 1 ng/ml (18 pM). The stimulation of myogenesis is not rapid, but it is prolonged, continuing over a period of at least 6 days. The effects of rhGGF2 are additive with those of insulin-like growth factor I (IGF-I) or its analog R3-IGF-I, suggesting that the actions of these two myotrophic agents differ in at least one rate-limiting step. We have observed one possible difference; unlike the IGFs, rhGGF2 does not induce elevation of the steady state level of myogenin mRNA.

Animals↗
PubMed1995

Changes in milk composition during lactation in three species of insectivorous bats.

Changes in milk composition are described for three species of free-ranging insectivorous bats (Myotis lucifugus, M. velifer, and Tadarida brasiliensis) from early to mid (peak) lactation. Dry matter and energy concentrations in milk increased from early to mid-lactation. In M. lucifugus and T. brasiliensis, but not M. velifer, these increases were due largely to a rise in fat concentration, since protein and carbohydrate remained relatively constant. Energy content of milk (kJ.g-1) for each species from early through mid-lactation was related to dry matter (DM) as follows: M. lucifugus (y = 0.31 DM-0.32, r2 = 0.68), M. velifer (y = 0.48 DM-5.08, r2 = 0.99), and T. brasiliensis (y = 0.37 DM-1.51, r2 = 0.61). Comparison of the effect of sampling method on milk composition of T. brasiliensis indicated that fat, dry matter, and energy concentrations increased significantly from pre-dawn to pre-noon samples. Relatively high fat and low water levels in T. brasiliensis milk may reflect the limited access that lactating females have to free water, as well as need to minimize mass of stored milk during long foraging trips. Conversely, lower fat concentrations and higher water levels in milk in M. lucifugus and M. velifer may relate to the propensity for colonies of these two species to roost and forage near bodies of water. In addition, differences in milk fat concentrations observed among the three species may correlate to daily suckling schedules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

PCR generation of large amounts of purified DNA.

The preparation and purification of PCR generated DNA fragments suitable for footprinting and classical drug binding studies is described. One of the fragments, a 214-mer derived from pBR322 DNA exhibits a biphasic melting profile. This behavior appears to be due to a non-random distribution of base pairs within the fragment causing a region rich in AT base pairs to melt prior to a segment having a high concentration of GC base pairs. The usefulness of large amounts of PCR generated DNA for footprinting and optical binding studies involving drugs is also presented and discussed.

Base Composition↗
PubMed1993

Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system.

Glial growth factors, proteins that are mitogenic for Schwann cells, and several ligands for the p185erbB2 receptor, are products of the same gene. Alternative splicing of the messenger RNA generates an array of putative membrane-attached, intracellular and secreted signalling proteins, at least some of which are expressed in the developing spinal cord and brain. These factors are probably important in the development and regeneration of the nervous system.

Alternative Splicing↗
PubMed1992

Neuroleptic malignant syndrome: a preventive program.

Neuroleptic Malignant Syndrome is a very serious side effect of antipsychotic medications. The paper describes a preventative program which was instituted in an inpatient unit of a provincial psychiatric hospital. There have been no mortalities from Neuroleptic Malignant Syndrome (NMS) during this program. A suspicion of NMS by clinical evaluation and laboratory tests resulted in prompt management. The recommended management plan is described.

Adult↗
PubMed1990

Effects of prospective payment financing on rehabilitation outcome.

A suspected benefit of paying hospitals per diagnostic related groups (DRGs), i.e. the prospective payment system (PPS), is that lengths of stay (LOS) and costs may be reduced. A potential adverse effect is that providers may discharge patients to reduce costs regardless of clinical consequence. The Veterans Administration (VA) is one of the first agencies to adopt PPS for rehabilitation. This study analyzed the effects of PPS on LOS, readmission rate, nursing home placement (NHP), and referral for Home Health Care (HHC) on a 22 bed rehabilitation unit. One hundred and eighty-seven patients discharged in 1987, prior to the program, were compared (using t-tests) with 215 discharges in 1988, after PPS was established. There were no significant differences in demographics, self-care ability, or in readmissions. Referrals for HHC decreased significantly. LOS decreased from 29.3 days (SD = 16.4) in 1987 to 26.4 days (SD = 14.1) in 1988 (t = 5.3, p less than 0.01). However, 24 more patients were discharged to nursing homes in 1988 (N = 54, 25%) than in 1987 (N = 30, 16%), which represents an increase of 64% (p less than 0.05). Findings suggest that PPS may defer home care in favor of placement. Clinicians need to assess whether reducing inpatient LOS justifies increased use of nursing homes. Further research on the effects of PPS is needed to determine: (a) impact on clinical aspects of rehabilitation; and (b) if other funding mechanisms are more appropriate.

Diagnosis-Related Groups↗
PubMed1990

Prospective payment for rehabilitation: effects on hospital readmission, home care, and placement.

Suspected benefits of a prospective payment system (PPS) in which hospitals are paid by diagnosis-related groups (DRGs) are that hospital lengths of stay and costs may be reduced. The US Department of Veterans Affairs is one of the first agencies to adopt PPS funding for rehabilitation; this early adoption of PPS provides a unique opportunity to test for both beneficial and adverse outcomes. This study compared hospital stay, readmission rate, and incidence of nursing home placement before and after introduction of PPS on a 22-bed rehabilitation service. Hospital stay decreased from 29.3 days to 26.4 days, but 64% more patients were discharged to nursing homes. Findings suggest that PPS may overlook home care in favor of placement, which neutralizes the cost benefits of the proposed reimbursement system. Further research on the effects of PPS is needed to determine (1) impact on clinical aspects of rehabilitation and (2) whether other funding mechanisms are more appropriate.

Diagnosis-Related Groups↗
PubMed1987

Electrophysiological responses to dopamine of rat hypophysial cells in lactotroph-enriched primary cultures.

1. Cells from 14-day-old and lactating female rat pituitary glands were dissociated, separated and enriched on a continuous gradient of bovine serum albumin at unit gravity. They were maintained for at least 6 days in culture before perifusion and electrophysiological experiments were performed. 2. Immunofluorescent staining of the resulting gradient fractions (numbered F2 to F9) from both groups of animals indicated that the majority of lactotrophs were located in the light fractions (F3-F4). However, a second population of lactotrophs was observed in the heavy fractions (F7-F9) isolated from lactating females. 3. Basal secretion rates of prolactin were in the order of 2-40 ng 2 min-1 10(6) cells-1 and were inhibited by dopamine in a dose-dependent manner. 4. According to their electrophysiological properties, cells from 14-day-old females (first group) were categorized as follows: (1) inexcitable cells, which displayed a low resting potential of about -35 mV (39% of cells tested, n = 118); and (2) excitable cells, which displayed either triggered or spontaneous action potentials and resting membrane potentials higher than -50 mV (61% of cells tested, n = 185). 5. In the light fraction from lactating females (second group), the majority of the cells were excitable (70%) and showed high resting membrane potentials (-50 to -55 mV) and 15% of these cells displayed spontaneous action potentials. 6. Heavy fractions (third group) contained a high percentage of non-spontaneous but excitable cells (80% of the cells tested, n = 65). These cells were able to elicit action potentials after the cessation of hyperpolarizing current pulses ('off' potentials). 7. Action potentials were insensitive to the sodium channel blocker, tetrodotoxin (TTX; 5 x 10(-6) M) but were reversibly blocked by calcium channel blockers such as cobalt, manganese and cadmium (10 mM). 8. In excitable cells from the three groups, dopamine (10(-7) M) induced a hyperpolarizing response due to an increase of the membrane conductance. During this response, action potentials were inhibited. It was shown that this was not a direct effect of dopamine. The reversal potential of the dopamine-induced response in these cells was found to be at -100 mV. This value was shifted to more positive potentials (-50 mV) when high-potassium medium was used (56 mM). 9. In non-excitable cells (first group), dopamine (10(-7) M) induced a hyperpolarizing response due to a decrease of the membrane conductance.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

WRK1 cells: a model system for studying properties of V1a vasopressin receptors.

WRK1 cells, an established cell line derived from a chemically induced mammary tumor in the rat, are sensitive to vasopressin. Binding studies with intact WRK1 cells indicated the presence of a single population of [3H]vasopressin binding sites (dissociation constant, Kd = 12.7 +/- 0.2 nM, maximal binding capacity = 75 +/- 6 fmole/10(6) cells). Competition experiments using a series of vasopressin analogs with enhanced selectivity for the three subtypes of receptors already characterized--that is, renal V2 receptors, V1 receptors of the vascular or hepatic subtype (V1a), and V1 receptors from rat adenohypophysis (V1b)--indicated that vasopressin receptors from WRK1 cells have a ligand specificity very similar, if not identical, to that of V1a receptors. Vasopressin induced a marked (up to tenfold) increase in the production of labeled inositol phosphate (Ins 1,4,5 P3, Ins 1,4 P2, and Ins P) by WRK1 cells prelabeled with [3H]inositol. Antagonists of the vasopressor effect of vasopressin inhibited vasopressin-induced inositol lipid breakdown in WRK1 cells. For the entire series of vasopressin analogs tested, there was a close correlation between the respective Kd values for binding of these peptides to WRK1 cells and the corresponding Ka or Ki values derived from the determination of dose-dependent stimulation of inositol phosphate production, or inhibition of vasopressin-induced stimulation.

Animals↗
PubMed1985

Torpedo electromotor system development: neuronal cell death and electric organ development in the fourth branchial arch.

The fourth branchial arch of Torpedo marmorata has been examined at the light and electron microscopic level during development. Of interest was the determination of the extent of electric organ tissue reported to be present in this arch and its possible relationship to electromotoneuron cell death in the electric lobes. The main electric organ of the torpedo is derived from the hyoid and first three branchial arches and is innervated by four major electromotor nerves. Extensive electromotoneuron cell death occurs in the electric lobes and most notably in the posterior poles. This feature could be due to a tendency for these neurons to innervate the fourth branchial arch where little or no electric tissue is formed. Our findings support this conclusion but are not entirely consistent with the idea that a population mismatch has occurred. This is because cell death precedes the genesis of the target cells. The presence of innervated differentiated electric tissue in this arch is also reported, leading to the conclusion that Torpedo marmorata possesses an accessory electric organ.

Animals↗