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Biomedical subjects

L Pike

Publications and source records attributed to L Pike.

13 recordsLinked to original sources

Modulation of nucleotide sensitivity of ATP-sensitive potassium channels by phosphatidylinositol-4-phosphate 5-kinase.

ATP-sensitive potassium channels (K(ATP) channels) regulate cell excitability in response to metabolic changes. K(ATP) channels are formed as a complex of a sulfonylurea receptor (SURx), a member of the ATP-binding cassette protein family, and an inward rectifier K(+) channel subunit (Kir6.x). Membrane phospholipids, in particular phosphatidylinositol (PI) 4,5-bisphosphate (PIP(2)), activate K(ATP) channels and antagonize ATP inhibition of K(ATP) channels when applied to inside-out membrane patches. To examine the physiological relevance of this regulatory mechanism, we manipulated membrane PIP(2) levels by expressing either the wild-type or an inactive form of PI-4-phosphate 5-kinase (PIP5K) in COSm6 cells and examined the ATP sensitivity of coexpressed K(ATP) channels. Channels from cells expressing the wild-type PIP5K have a 6-fold lower ATP sensitivity (K(1/2), the half maximal inhibitory concentration, approximately 60 microM) than the sensitivities from control cells (K(1/2) approximately 10 microM). An inactive form of the PIP5K had little effect on the K(1/2) of wild-type channels but increased the ATP-sensitivity of a mutant K(ATP) channel that has an intrinsically lower ATP sensitivity (from K(1/2) approximately 450 microM to K(1/2) approximately 100 microM), suggesting a decrease in membrane PIP(2) levels as a consequence of a dominant-negative effect of the inactive PIP5K. These results show that PIP5K activity, which regulates PIP(2) and PI-3,4,5-P(3) levels, is a significant determinant of the physiological nucleotide sensitivity of K(ATP) channels.

Adenosine Triphosphate↗

Augmentation of distal radius fracture fixation with coralline hydroxyapatite bone graft substitute.

We implanted coralline hydroxyapatite bone graft as a substitute for autogenous bone graft to support the reduced articular surface of 21 consecutive patients with distal radius fractures treated with external fixation and K-wires. The purpose of this single-cohort retrospective study was to report the outcomes of treatment with this material, complications associated with its use, and its efficacy in supporting the articular surface reduction. Eighteen patients were available for independent evaluation of motion, subjective outcome analysis, and final radiographic analysis at an average of 35 months after surgery. Wrist motion averaged 90% of the uninjured wrist and grip strength measured 75% of the uninjured side. Results in 17 of the 18 cases were rated as good or excellent by the criteria of Gartland and Werley; 12 by the criteria of Green and O'Brien. Seventeen had good or excellent radiographic results by the modified Lidstrom radiographic scoring system. The average DASH functional/symptom score was 90.3 (maximum, 100). Radiographic parameters were restored to an average of 12 mm radial length, 4 degrees volar tilt, 23 degrees radial inclination, and 0.6 mm positive ulnar variance. Articular reduction was maintained in all patients. A complication related to the use of coral was a 0.5 mm prominence of coralline hydroxyapatite beyond the subchondral line at the radiocarpal joint in 1 patient, which was not present on final radiographs. Coralline hydroxyapatite was effective at maintaining articular surface reduction when used in combination with external fixation and K-wires and had a safety profile comparable to other forms of treatment.

Bone Substitutes↗

Design of a clinical notification system.

We describe the requirements and design of an enterprise-wide notification system. From published descriptions of notification schemes, our own experience, and use cases provided by diverse users in our institution, we developed a set of functional requirements. The resulting design supports multiple communication channels, third party mappings (algorithms) from message to recipient and/or channel of delivery, and escalation algorithms. A requirement for multiple message formats is addressed by a document specification. We implemented this system in Java as a CORBA object. This paper describes the design and current implementation of our notification system.

Algorithms↗

Acceptability of opportunistic screening for occult gastrointestinal blood loss.

OBJECTIVE: To test patient compliance for faecal occult blood testing in suburban and inner city general practice. DESIGN: Prospective opportunistic trial using the Haemoccult test kit. Tests were offered during routine surgery attendance. SETTING: Three group general practices in Birmingham. SUBJECTS: All patients aged 40 years or older on the start date who routinely attended surgery during two years. MAIN OUTCOME MEASURES: Numbers of patients approached for testing and the numbers refusing, accepting, and returning the test kits. RESULTS: Only 26.3% (1230/4677) of the potential target population had been screened within the two years, although 988 (39.3%) of the suburban practice target were screened. However, 55.7% (1230/2207) of patients actually offered a test returned completed kits, with only 6% (133) refusing the kit. 683 (61.6%) patients aged 50-69 returned kits, compared with 343 (54.3%) aged 70 or over and 204 (43.8%) aged 40-49. These differences were significant (p less than 0.001). Patients from the inner city practice were significantly less likely to be offered the test than those in suburban practice (242 (11.2%) v 988 (39.9%), p less than 0.001) and return the samples (242 (38.8%) v 988 (62.4%), p less than 0.001). Patients from the inner city practice were also more likely to refuse the test (78 (12.5%) v 55 (3.5%), p less than 0.001). CONCLUSIONS: Opportunistic testing for occult faecal blood in asymptomatic patients was reasonably acceptable to patients, especially those in a suburban practice. If the test is shown to reduce mortality from colorectal cancer then formal screening would probably achieve acceptable target rates, especially among patients aged 50-69, who represent the prime risk group.

Adult↗

Second trimester maternal serum alpha-fetoprotein as an indicator of fetal risk.

Serum alpha-fetoprotein levels were raised to 2.0 or more times the median for gestation in 30 of 507 singleton pregnancies after excluding pregnancies complicated by fetal neural tube defects. The serum alpha-fetoprotein levels were significantly more often elevated in pregnancies complicated by prematurity, fetal heart rate abnormalities, delivery of a small for dates infant, a perinatal death and admission of the baby to the neonatal unit. While the predictive value of an elevated serum alpha-fetoprotein was 76% for abnormal outcomes in general it ranged between only 16% and 46% for specific abnormalities. The usefulness of this assay relates only to its ability to predict an abnormal outcome when performed during the second trimester.

Apgar Score↗

Antibody to the nonapeptide Glu-Glu-Glu-Glu-Tyr-Met-Pro-Met-Glu is specific for polyoma middle T antigen and inhibits in vitro kinase activity.

Middle T antigen of polyoma virus has an associated tyrosine kinase activity which phosphorylates tyrosine residue 315 on middle T in immunoprecipitates. A peptide representing the sequence of middle T from residue 311 to 319 has been synthesized. This peptide acts as a weak inhibitor of the kinase reaction. An antiserum has been raised against this peptide after conjugation to bovine serum albumin. The antibody is middle T-specific. Middle T antigen precipitated by this serum is largely inactive in the kinase reaction. Dissociation of the immune complex with peptide releases middle T in a kinase-active form.

Animals↗

Glycerol-utilizing mutants of Rhodopseudomonas capsulata.

The isolation and study of glycerol-utilizing mutants of Rhodopseudomonas capsulata indicated that the wild-type organism has genes capable of coding for the catabolism of glycerol but is unable to express them. Furthermore, the genetic lesion in the original glycerol-utilizing mutant, L1, occurred very close to these genes.

Glycerol↗

Histoplasmosis in Belize, Central America.

After two small outbreaks of histoplasmosis in Belize, an epidemiologic survey was carried out. Forty percent of 141 persons in two groups tested demonstrated a positive histoplasmin reaction. In one study group there was a significant association between visiting caves and histoplasmin positivity. Histoplasma capsulatum was not isolated in 20 soil specimens collected from outbreak-associated caves, but was isolated from 1 of 26 bats collected from the same caves. The presence of histoplasmosis in Belize, C.A. is documented, and this disease should be considered in differential diagnosis in patients, both residents and visitors in Belize, with compatible clinical presentations.

Adolescent↗

Glycerol utilization by a mutant of Rhodopseudomonas capsulata.

The glycerol-catabolizing enzymes of a mutant of Rhodopseudomonas capsulata were found to be constitutive and modulated coordinately, although apparently not functional in the presence of malate. No difference in glycerol permeation was found between the mutant and wild type.

Flavin Mononucleotide↗

Glycerol dissimilation in Rhodopseudomonas sphaeroides.

Rhodopseudomonas sphaeroides followed a diauxic growth curve when grown on a malate-glycerol medium, the first phase of growth being supported by malate and the second by glycerol. A soluble glycerokinase and a particulate, pyridine nucleotide-independent glycerophosphate dehydrogenase, were induced by the presence of glycerol in the medium, but neither was fully expressed nor functional until all malate had been consumed.

Adenosine Triphosphate↗

Hip function and gait in patients treated for bladder exstrophy.

Patients with bladder exstrophy demonstrate pubic diastasis with external rotation of the ilia and posterolateral orientation of the acetabula. Iliac osteotomy is performed to approximate the pubis and thus facilitate the genitourinary repair. The role of iliac osteotomy in the correction of gait abnormalities is controversial. Our goals in this study were to define the presence of hip pathology and gait abnormalities in patients treated for bladder exstrophy and to evaluate the effect of iliac osteotomy. We reviewed pelvic radiographs and gait studies in 15 children. The treatment included bilateral iliac osteotomy in nine of 15 of these patients. We found minor hip dysplasia in two patients, but we saw no evidence of subluxation or dislocation. Pubic diastasis increased with age and was not related to osteotomy. Patients had slightly less passive hip internal rotation than age-matched controls. There was no correlation between the restriction of hip internal rotation and the amount of pubic diastasis. Two thirds (10 of 15) of the patients exhibited increased lower extremity external rotation during gait. None of the subjects demonstrated a waddling gait (gluteus medius lurch) described in the literature. Based on our results, iliac osteotomy does not affect gait patterns in children with bladder exstrophy. However, we believe that it is indicated to improve the results of genitourinary repair.

Adolescent↗