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Biomedical subjects

M Williams

Publications and source records attributed to M Williams.

At least 127 records · Page 7Linked to original sources
PubMed2001

The point-of-referral barrier--a factor in the success of telehealth.

A feasibility study was carried out to test the hypothesis that, for an effective telehealth service, a full-time coordinator is required to act as a single point of contact for consultation requests. By shifting the responsibility for telepaediatrics from the referrer to the provider, the telehealth process becomes equally (or more) attractive as the conventional alternative. Preliminary results showed that, within six months, telepaediatric activity increased to an average of 8 h per month. Not only did certain health services become more accessible to children and their families in remote areas of Queensland, but significant savings were also made. At least 12 patient transfers were avoided to and from the tertiary facility, with an estimated minimum saving of $18,000 to the health-care provider.

Child↗
PubMed2001

Improving dementia care through community linkages: a multi-site demonstration project.

The purpose of the multi-site project was to develop and implement a model for dementia care which improved linkages of caregivers to community services. Key components of the model included a single point of informational contact, provider education, case-finding, caregiver education and support, internal linkages, and linkages with community services. The model was implemented at six medical centers. Outcome measures included caregiver, provider, and community agency satisfaction. Caregivers reported high satisfaction with information provided to them about community resources. Primary care providers reported that dementia services had improved from one year earlier. Community agencies reported high satisfaction with the dementia program initiatives.

Aged↗
PubMed2001

Anti-inflammatory effects of ABT-702, a novel non-nucleoside adenosine kinase inhibitor, in rat adjuvant arthritis.

Adenosine (ADO) is a homeostatic inhibitory autocoid that is released at sites of inflammation and tissue injury, and exerts anti-inflammatory effects via multiple interactions at ADO receptor subtypes. Inhibition of ADO kinase (AK) increases extracellular ADO concentrations and AK inhibitors have demonstrated ADO-mediated anti-inflammatory effects in acute models of inflammation. To evaluate the potential utility of this approach in chronic inflammation, a novel, potent, and selective non-nucleoside AK inhibitor, ABT-702, was tested in the rat adjuvant arthritis model. Animals were immunized with complete Freund's adjuvant on day 0 and were treated with vehicle or ABT-702 (20 mg/kg/b.i.d. p.o.) beginning on day 8. ABT-702 significantly inhibited arthritis as determined by paw volume. In addition, histologic and radiographic evidence of bone and cartilage destruction was significantly decreased in the treated group. Coadministration of the ADO receptor antagonist theophylline attenuated the anti-inflammatory effects of ABT-702, suggesting that this action was mediated through endogenous ADO release. To evaluate the mechanism of chondroprotection, Northern blot and electrophoretic mobility shift assays were performed on joints samples. These studies demonstrated that ABT-702 suppressed collagenase and stromelysin gene expression in treated animals. In addition, the activator protein-1 and nuclear factor-kappaB binding activity was also decreased. Therefore, ABT-702 inhibited clinical, radiographic, and histologic evidence of chronic inflammatory arthritis. The mechanism of joint protection is likely related to suppressed transcription factor activation and matrix metalloproteinase gene expression.

Adenosine↗
PubMed2001

Synonymy between two spider mite species, Tetranychus kanzawai and T. hydrangeae (Acari: Tetranychidae), shown by ribosomal ITS2 sequences and cross-breeding experiments.

Amplification of the second internal transcribed spacer (ITS2) of ribosomal DNA was used to compare seven samples of the Tetranychus kanzawai Kishida-- T. hydrangeae Pritchard & Baker mite complex from five different countries: Australia, the Congo, Indonesia, Japan and the USA. No morphological differences were detected between these mites and their ITS2 sequences displayed strong similarity except for a small nucleotide divergence of 0.2% in specimens from Australia and Indonesia. Reciprocal crosses and backcrosses between mites assumed to be T. kanzawai and T. hydrangeae respectively showed reproductive compatibility. Fertile hybrid females were obtained in all cases, indicating conspecificity of the mites tested. It is concluded that T. hydrangeae is a synonym of T. kanzawai. The evidence suggests that T. kanzawai originated in South-east Asia and probably spread throughout the world on Hydrangea spp. cuttings.

Animals↗
PubMed2001

Metabolic impact of puberty on the course of type 1 diabetes.

Puberty is characterised by important physiological and hormonal changes. In type 1 diabetes, abnormalities in the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis play a important role. Spontaneous hyper-GH secretion arises, with reduced circulating IGF-1 levels, both leading to a reduction in insulin sensitivity. From a clinical point of view, these abnormalities are linked to a deterioration glycaemic control, often more marked in females (in whom the degree of insulin resistance during puberty seems to be higher). These abnormalities in the GH/IGF-1 axis in may constitute a risk for the development of microangiopathic complications. Optimisation of insulin therapy has practical limitations and intensification of insulin therapy poses problems (weight gain, nocturnal hypoglycaemia). Several alternative therapeutic approaches have been explored to restore insulin sensitivity, either through a direct effect on the GH/IGF-1 axis, or through drugs with a direct insulin sensitivity effect, but all these approaches remain to be confirmed and the safety and acceptability of these treatments to be established on a long-term basis.

Blood Glucose↗
PubMed2001

Burr holes.

Neurosurgical procedures may sometimes take place in general operating theatres, usually when a patient has sustained a life-threatening head injury. Burr holes may be made in accident and emergency departments before patients are transferred for further treatment. For these reasons it is useful for perioperative nurses in general hospitals to have some knowledge of neurosurgical operating techniques and instrumentation.

Craniocerebral Trauma↗
PubMed2001

Cardiac rhabdomyoma in infancy. A case report.

We describe a case of rhabdomyoma of the heart in a newborn infant and present an overview of current knowledge about the natural history of these lesions, with implications for management. This is the only case of its kind seen at this hospital.

Diagnosis, Differential↗
PubMed2000

Multifidus spasms elicited by prolonged lumbar flexion.

STUDY DESIGN: The electromyogram of the L1-L7 multifidus muscles of the in vivo cat were recorded while applying a prolonged steady displacement to the lumbar spine through the L4-L5 supraspinous ligament, simulating a moderate anterior flexion. OBJECTIVE: To demonstrate that tension-relaxation and laxity of the viscoelastic structures (ligaments, discs, and capsules) induced by prolonged static flexion of the spine results in loss of reflexive muscular stabilizing activity and in muscular disorders that may lead to or are associated with low back pain. SUMMARY OF BACKGROUND: Epidemiologic data show that prolonged loading of the spine, such as in some occupational activities, can cause low back pain and muscle spasms. Direct experimental evidence linking prolonged loading to a decrease in spinal stability, low back pain, and muscle spasms was not found. It was hypothesized, however, that mechanoreceptors in the viscoelastic structures, when strained, reflexively activate the multifidus muscles to maintain intervertebral stability; that the reflexive muscular activity decreases with stress-relaxation and laxity in the viscoelastic structures; and that when severe strain and possible damage of the viscoelastic structures occurs with time, nociceptive receptors elicit spasms in the musculature and possible pain. METHODS: The lumbar spine of seven in vivo cat preparations was displaced through the L4-L5 supraspinous ligament into moderate flexion that was steadily maintained for 50 minutes while intramuscular electromyograms were recorded from each of the multifidus muscles of L1-L2 through L6-L7. Load and electromyogram were continuously monitored and recorded. Five additional preparations were used as controls, in which dissection and recordings were identical, but the lumbar flexion was excluded. RESULTS: Prolonged flexion of the lumbar spine resulted in initial reflexive electromyogram from the multifidus muscles that decreased to approximately 5% of its initial value as tension-relaxation began in the viscoelastic structures within the first 3 minutes, after which, random and unpredictable electromyogram discharges (i.e., spasms) of high amplitude were recorded from different levels. In some preparations the spasms were present in L1-L4, and in others in all the levels. In other preparations the spasms were recorded only at L5 and L6. The onset of the spasms was also unpredictable, because they were initiated in some cases within 2-3 minutes after the spine was loaded. In other cases, the spasms were observed anytime during the test period and up to 20 minutes after the load was removed. Spasms were also observed in the spinalis and longissimus muscles. CONCLUSIONS: Prolonged flexion of the lumbar spine results in tension-relaxation and laxity of its viscoelastic structures, loss of reflexive muscular activity within 3 minutes and electromyogram spasms in the multifidus and other posterior muscles.

Animals↗
PubMed2000

Replacement of tyr62 by trp in the designer protein milk bundle-1 results in significant improvement of conformational stability.

Protein design is currently used for the creation of new proteins with desirable traits. In our lab, we focus on the synthesis of proteins with high essential amino acid content, having potential application in animal nutrition. One of the limitations we face in this endeavor is the achievement of stable proteins in spite of a highly biased amino acid content. We report here the synthesis and characterization of MB-1Trp, a protein with a tailored content in selected essential amino acids. The protein is a Tyr62-Trp mutant of the parent molecule MB-1 described earlier. The new protein is largely helical as per design, is well folded, and has a melting temperature of 55 degrees C. Its resistance to proteolytic degradation compares to that of cytochrome c, a protein of similar size. Design strategy used for MB-1Trp is discussed with regards to its applicability toward the creation of efficient nutritional proteins.

Amino Acid Substitution↗
PubMed2000

Anticonvulsant activity of two metabotropic glutamate group I antagonists selective for the mGlu5 receptor: 2-methyl-6-(phenylethynyl)-pyridine (MPEP), and (E)-6-methyl-2-styryl-pyridine (SIB 1893).

The selective mGlu5 antagonists, MPEP, 2-methyl-6-phenylethynyl-pyridine, and SIB1893, (E)-6-methyl-2-styryl-pyridine, have been evaluated as antiepileptic drugs in DBA/2 mice and lethargic mice. Clonic seizures induced by the selective mGlu5 agonist, (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG), 3 micromol intracerebroventricularly (i.c.v.), are potently suppressed by both compounds (MPEP, ED(50)=0.42 [0.28-0.62] mg/kg intraperitoneally (i.p.); SIB 1893 ED(50)=0.19 [0.11-0.33] mg/kg i.p. ). Clonic seizures induced by the mGlu1,5 agonist, 3, 5-dihydroxyphenylglycine (DHPG), 1.5 micromol i.c.v., are less potently suppressed by both compounds (MPEP, ED(50)=22 [13-38] mg/kg i.p., 110 [67-180] nmol i.c.v.; SIB1893, ED(50)=31 [18-54] mg/kg i.p. , 95 [82-110] nmol i.c.v.). Sound-induced seizures in DBA/2 mice are suppressed at 15 min by MPEP and SIB 1893 (MPEP ED(50) clonic seizures=18 [10-32] mg/kg i.p., 93 [69-125] nmol i.c.v.; tonic seizures=6.1 [4.5-8.3] mg/kg i.p., 46 [26-80] nmol i.c.v.; SIB 1893 ED(50) clonic seizures=27 [17-44] mg/kg i.p., 825 [615-1108] nmol i. c.v., tonic seizures=5.4 [3.4-8.6] mg/kg i.p., 194 [113-332] nmol i. c.v.). The ED(50) for MPEP for impaired rotarod performance is 128 [83-193] mg/kg i.p., at 15 min, i.e. a therapeutic index for sound-induced seizures of 5-20. In lethargic mice (lh/lh), a genetic absence model, MPEP, 50 mg/kg i.p., caused a marked reduction in the incidence of spontaneous spike-and-wave discharges. These selective antagonists of mGlu5 block seizures due to activation of mGlu5 at very low systemic doses. At rather higher doses they block convulsive and non-convulsive primary generalised seizures.

Animals↗
PubMed2000

Purines: from premise to promise.

Geoff Burnstock's remarkable insight and tenacity has established the area of purinergic research as a bona fide target for drug discovery. While efforts in P1 receptor-based medicinal chemistry and biology efforts over the past 25 years have not reached the level of success that the pharmaceutical industry investment may have anticipated, the P2 area, with knowledge of the selective localization of members of the P2X and P2Y family members and data from transgenic knockouts, has identified several potential therapeutic areas of major promise including cystic fibrosis, chronic bronchitis, male contraception and neurodegeneration. In addition, interest in the potential of purinergic therapeutics has extended outside the major pharmaceutical companies to the 'biotech industry' resulting in an environment where the inherent risks of 'first in field' in a therapeutic area may be more appropriately nurtured.

Animals↗
PubMed2000

Purinergic and pyrimidinergic receptors as potential drug targets.

In the last decade, the field of purinergic pharmacology has continued to grow as the complexity of the receptor families and the various enzymes involved in purine metabolism have been defined in molecular terms. A major theme that has emerged from these studies is the functional complexity of the interactions between P1 and P2 receptors, based upon the dynamic interrelationship between ATP and adenosine as extracellular signaling molecules. It is now clear that ATP and its degradation products (particularly ADP and adenosine) form a complex cascade for the regulation of cell-to-cell communication that can function to attenuate the consequences of tissue trauma (e.g. ischemia) that involve alterations in cellular energy charge and depletion of ATP stores. In addition to the P2 receptor family, alterations in cellular ATP stores can also affect the function of other receptors, e.g. K(ATP) channels, and mitochondrial function. The discovery of pyrimidine-preferring (UTP/UDP) P2Y receptors has also raised the possibility that the corresponding nucleoside, uracil, may function as a signaling molecule.

Animals↗
PubMed2000

The identification of novel structural compound classes exhibiting high affinity for neuronal nicotinic acetylcholine receptors and analgesic efficacy in preclinical models of pain.

Neuronal nicotinic acetylcholine receptors represent a new and potentially useful target for the development of novel non-opioid, non-NSAID (nonsteroidal antiinflammatory drug) analgesic agents. A variety of nicotinic acetylcholine receptor agonists such as nicotine, epibatidine and the azetidinyl ether, (R)-5-(2-azetidinylmethoxy-2-chloropyridine (ABT-594) possesses significant efficacy in preclinical models of pain. A preponderance of evidence suggests that nicotinic acetylcholine receptor agonists produce their analgesic effects predominantly via activation of descending inhibitory pain pathways originating in the key brainstem regions of the nucleus raphe magnus, dorsal raphe, and locus coeruleus, and that alpha4-containing nicotinic acetylcholine receptor subunits mediate these effects. Although these studies may provide a pharmacological target for the development of nicotinic acetylcholine receptor analgesics, the rational design of selective ligands based on the protein structure of the binding site is hampered by insufficient structural information. Using an approach based upon homology to known high-affinity ligands for the alpha4beta2 binding site, a four-point model is proposed which defines distance and directionality parameters common to this set of nicotinic acetylcholine receptor ligands.

Analgesics↗