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Biomedical subjects

J White

Publications and source records attributed to J White.

At least 325 records · Page 18Linked to original sources

Appointment access: planning to benchmark a complex issue.

BACKGROUND: Kaiser Permanente-Southern California Region carried out an external benchmarking project to improve appointment access. This article provides practical guidelines for planning a benchmark project around a complex issue such as appointment access. METHOD: Before conducting external site visits, team members determined the goals of the project, defined internal processes, and identified 16 key elements of access (or those factors important to member satisfaction with appointment access). Once a questionnaire was finalized, external benchmark partners were identified and on-site visits conducted. CONCLUSION: On the basis of the on-site visits, team members identified innovative and best practices for each of the 16 key elements of access. Based on these recommendations, some improvements were made across the Southern California region, such as the elimination of provisional booking. Reports of the results have also been sent to Kaiser Permanente medical centers in the region and across the country. Each medical center is encouraged to use these results to internally improve its own appointment access.

Appointments and Schedules↗

Contribution of host-derived growth factors to in vivo growth of a transplantable murine mammary carcinoma.

The contribution of host-derived growth factors to tumour growth in vivo was studied using the transplantable murine mammary carcinoma, MT1, grown in syngeneic mice. Promotion of growth of the mammary carcinoma by a factor(s) from the host was evident in experiments in which the carcinoma cells were inoculated intraperitoneally. In this environment, tumours develop as multiple solid nodules, each probably arising from an individual cell or a small cluster of cells. Tumour growth was found to occur in the peritoneal cavity following inoculation of 10(3) cells, but an inoculum of as few as ten cells grew if a leucocyte-rich exudate had first been induced. To determine which host-derived growth factors might contribute to growth of MT1, extracts of the tumour were first examined for growth factor activity. Fractionation of tumour extracts by either ion-exchange chromatography or gel filtration revealed several peaks of mitogenic activity, but none of this could be attributed to epidermal growth factor (EGF). Accordingly, an anti-EGF antibody was tested as a putative inhibitor of tumour growth as any effect of this antibody could be ascribed to removal of EGF derived from the host. The antibody was found to have potent anti-tumour activity when tested against MT1 tumours that had been inoculated into the peritoneal cavity. In contrast, the antibody had little effect on growth of the discrete tumour mass which formed when MT1 was transplanted subcutaneously. The results suggest that host-derived EGF contributes to establishment of microcolonies of MT1 carcinoma within the peritoneal cavity. This may be directly, by providing growth factors to supplement those produced by the tumour until it reaches a certain critical mass to sustain autocrine growth, or indirectly, by affecting the production of other growth-stimulatory factors or cytokines.

Animals↗

Effects of acidosis and hypoxia on the response of isolated ferret cardiac muscle to inotropic agents.

OBJECTIVE: The aim was to study the effects of acidosis and hypoxia on the response of cardiac muscle to inotropic agents which (a) act predominantly by increasing intracellular [Ca2+] (raising extracellular [Ca2+], noradrenaline, isoprenaline) and (b) act partly (phenylephrine) or predominantly (EMD 57033) by increasing myofilament calcium sensitivity. METHODS: The experiments were performed on isometrically contracting, isolated ferret papillary muscles (n = 45). For each intervention dose-response curves were performed in control solution (pH 7.35), in hypercapnic acidosis (pH 6.85), and in hypoxia (produced by replacing O2 with N2 in the superfusing solution). In some experiments, the photoprotein aequorin was microinjected into superficial cells of the preparation in order to measure intracellular [Ca2+] as well as force. RESULTS: The results were broadly similar for both classes of inotropic agent. Acidosis caused a shift of the pCa-tension curve to the right (desensitisation of the myofilaments to calcium), but had no significant effect on maximum force. A sufficient inotropic stimulus supplied by either class of inotropic agent could completely reverse the negative inotropic effects of acidosis. The main difference between the two inotropic mechanisms was that the enhanced force produced by calcium sensitisers was associated with a reduction in calcium transient amplitude, while the other inotropes increased the amplitude. The main effect of hypoxia was to decrease maximum force. All the inotropes tested were relatively ineffective in reversing the force depression due to hypoxia. CONCLUSIONS: The negative inotropic effects of acidosis can be reversed by a sufficiently large inotropic stimulus. Since calcium transient amplitude is already increased in acidosis, the results suggest that calcium sensitisers are likely to be less arrhythmogenic in this situation. The relative ineffectiveness of the inotropes in hypoxia indicates that the main mechanisms causing reduced force in this situation lie downstream of the mechanisms of action of the inotropic agents tested.

Acidosis↗

A prospective study comparing SPET with MRI and CT as prognostic indicators following severe closed head injury.

Ten patients were studied prospectively afer severe closed head injury to determine the relationship between long-term clinical outcome and abnormalities detected by single photon emission tomography (99Tcm-HMPAO SPET), CT and MRI obtained within 60 days of injury. The ability of SPET to detect abnormalities not visualized by CT or MRI after cerebral trauma by the results of this study. Changes detected by SPET [global cerebral blood flow (gCBF) and number of regional cerebral blood flow (rCBF) deficits] soon after trauma were shown to be more closely correlated with long-term outcome than changes detected by MRI or CT. Templates were used to classify lesions by site and a multivariate analysis was undertaken to establish the importance of defect position in predicting clinical outcome. The results suggest that lesions in the temporal lobes, frontal lobes and basal ganglia are related to poor prognosis, and that SPET yields more useful prognostic data than the other methods.

Adult↗

Transcriptional regulation of the four promoters of the agarase gene (dagA) of Streptomyces coelicolor A3(2).

The agarase gene (dagA) of Streptomyces coelicolor A3(2) is transcribed from four promoters that are recognized by at least three, and probably four, different RNA polymerase holoenzymes, each containing a different sigma factor. S1 nuclease protection studies revealed that transcription from all four promoters is induced by the products of agar hydrolysis and strongly repressed by glucose. Mutants deficient in glucose kinase activity were defective in glucose repression of all four promoters. Mutants were isolated or identified in which transcription from all four promoters had become inducer-independent (i.e. constitutive), establishing the existence of a repressor gene for dagA that does not appear to be located within 9 kb of the structural gene. The cloned dagA gene was also constitutively expressed in the closely related strain Streptomyces lividans, which does not normally make agarase and which presumably lacks the repressor gene. Glucose was still able to repress dagA transcription even under conditions of constitutive expression, suggesting that glucose kinase does not mediate its effect via inducer exclusion. Relative differences in the use of the four promoters were not detected during different stages of growth of surface-grown cultures, although dagA transcription appeared to peak during the production of aerial mycelium.

Base Sequence↗

The mRNA for the 23S rRNA methylase encoded by the ermE gene of Saccharopolyspora erythraea is translated in the absence of a conventional ribosome-binding site.

Transcriptional analysis of the ermE gene of Saccharopolyspora erythraea, which confers resistance to erythromycin by N6-dimethylation of 23S rRNA and which is expressed from two promoters, ermEp1 and ermEp2, revealed a complex regulatory region in which transcription is initiated in a divergent and overlapping manner. Two promoters (eryC1p1 and eryC1p2) were identified for the divergently transcribed erythromycin biosynthetic gene eryC1, which plays a role in the formation of desosamine or its attachment to the macrolide ring. Transcription from eryC1p2 starts at the same position as that of ermEp1, but on the opposite strand of the DNA helix, suggesting co-ordinate regulation of genes for erythromycin production and resistance. ermEp1 initiates transcription at, and one nucleotide before, the ermE translational start codon. Site-directed and deletion mutagenesis, combined with immunochemical analysis, demonstrated that the ermEp1 transcript is translated in the absence of a conventional ribosome-binding site to give rise to the full-length 23S rRNA methylase. Deletion of the -35 region of ermEp1 reduced, but did not abolish, promoter activity, reminiscent of the 'extended -10' class of bacterial promoters which, like ermEp1, possess TGN motifs immediately upstream of their -10 regions and which initiate transcription seven nucleotides downstream of the -10 region.

Amino Acid Sequence↗

Tetanus: delay in diagnosis in England and Wales.

A 7 day delay occurred in the diagnosis of cephalic tetanus in a 69 year old woman who developed an ipsilateral facial palsy 5 days after a facial laceration. Cranial nerve palsies often precede trismus in this form of tetanus.

Aged↗

Inhibition of 1,25-dihydroxyvitamin D3 stimulated osteocalcin gene transcription by tumor necrosis factor-alpha: structural determinants within the vitamin D response element.

Control of osteoblast function requires the coordinate activity of systemic and local regulatory factors. We have investigated the mechanism of interaction between the secosteroid 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and the cytokine tumor necrosis factor-alpha (TNF-alpha) by measuring their effects on two 1,25-(OH)2D3 responsive matrix protein genes, osteocalcin (OC) and osteopontin (OP). Our previous studies revealed that an inhibitory effect of TNF-alpha on 1,25-(OH)2D3-stimulated OC gene transcription is conferred by the same 25 base pair region of 5'-flanking DNA that confers a response to vitamin D (VDRE). Gel mobility shift studies of [32P]VDRE binding to ROS 17/2.8 cell nuclear extract revealed that TNF-alpha inhibits 1,25-(OH)2D3 stimulated formation of specific retinoid X receptor/vitamin D receptor (RXR/VDR)-DNA complexes in vitro. To determine if TNF-alpha was inhibiting nuclear protein-VDRE binding by modulation of VDR availability, we measured intranuclear VDR in cells treated with 1,25-(OH)2D3 (10(-8) M), TNF-alpha (100 ng/ml), or both, by western blot. 1,25-(OH)2D3 caused upregulation of the nuclear VDR. Treatment with TNF-alpha inhibited the 1,25-(OH)2D3-stimulated up-regulation of VDR nuclear protein content. However, down-regulation of VDR was unlikely to be the mechanism of TNF-alpha action because TNF-alpha had no effect on 1,25-(OH)2D3 stimulation of steady state OP messenger RNA or transcription of an OP-VDRE-chloramphenicol acetyl transferase reporter construct. These results suggest that decreased VDR alone does not explain the mechanism of TNF-alpha action. VDRE structural requirements for TNF-alpha action were characterized by comparing binding of mutant and hybrid forms of mouse (m)OP-, rat (r)OC-, and human (h)OC-VDRE probes to nuclear protein from cells treated with 1,25-(OH)2D3 and/or TNF-alpha. These homologous vitamin D response elements differ in that an AP-1 sequence is included in the rOC-VDRE and hOC-VDRE but not in the OP-VDRE. Gel mobility shift analysis revealed that TNF-alpha inhibited 1,25-(OH)2D3 stimulation of nuclear protein binding to rOC-VDRE and hOC-VDRE to 59% and 69% of control, respectively, but had no effect on 1,25-(OH)2D3 stimulation of nuclear protein binding to OP-VDRE. The effect of TNF-alpha could not be conferred in a mutant OP-VDRE in which the rOC-VDRE AP-1 sequence was inserted.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗

Metatarsocuneiform coalition.

This was clearly a case of an unusual anomaly. Clinically, this was a case of an osseous coalition of congenital origin. Since the patient eventually became asymptomatic, no further treatment was necessary. Unfortunately, the patient's parents were unavailable to be radiographed to test the hereditary nature of this disorder. The radiographs and fluoroscopy films were sent to a radiologist. The radiology report stated a total and complete coalition (osseous fusion) between the third metatarsal base and the third cuneiform, with no indication of a joint space present in the left foot scan. Since this pathology is more of an incidental finding and caused the patient no discomfort, surgical correction was not necessary. Certainly, more coalitions of this nature may exist without patient knowledge. This case demonstrates another pathology that the podiatric physician may need to address.

Adult↗

Therapeutic footwear for patients with diabetes.

The proper prescription and utilization of therapeutic footwear is crucial to successful prevention of diabetic foot complications. The author reviews shoe alternatives' characteristics and proper fit. The concept of foot risk categories is explained and appropriate shoe selections are discussed.

Diabetic Foot↗