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Biomedical subjects

C Bullock

Publications and source records attributed to C Bullock.

14 recordsLinked to original sources
PubMed2001

Urban-rural differences in the quality of care for medicare patients with acute myocardial infarction.

BACKGROUND: There are urban-rural differences in health care utilization in Kansas. This study was conducted to determine if similar differences exist in the quality of inpatient care provided for patients with acute myocardial infarction (AMI). METHODS: All acute care hospitals in the state were stratified into 12 urban, 31 semirural, and 76 rural hospitals according to their location. Data from medical records of 2521 Medicare patients 65 years and older who had survived AMI and were discharged alive from hospitals during an 8-month period in 1994/1995 were abstracted. The measures of the quality of care (quality indicators [QIs]) were the use of aspirin (during hospital stay and at discharge) and the administration of beta-blockers, intravenous (IV) nitroglycerin, heparin, and reperfusion by thrombolytic therapy or primary angioplasty. RESULTS: A significantly higher proportion of ideal candidates for the use of aspirin during hospital stay and at discharge, heparin, and IV nitroglycerin received these medications in urban hospitals, and a lower proportion of similar patients received these medications in rural hospitals compared with the patients in semirural hospitals (P<.001). Similar trends in each of the 6 QIs were observed for less than ideal patients (P<.05). Patient age was associated with a relatively poor quality of care in terms of the 6 QIs. Except for the administration of IV nitroglycerine to less than ideal patients, age adjustments did not change the observed urban-rural differences in the QI measures. CONCLUSION: Relatively poor quality of care for patients with AMI was provided by rural hospitals where greater opportunity for improvement exists.

Adrenergic beta-Antagonists↗
PubMed2001

Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein.

Many structural determinants for G protein-coupled receptor (GPCR) functions have been defined, but little is known concerning the regulation of their transport from the endoplasmic reticulum (ER) to the cell surface. Here we show that a carboxy-terminal hydrophobic motif, FxxxFxxxF, which is highly conserved among GPCRs, functions independently as an ER-export signal for the dopamine D1 receptor. A newly identified ER-membrane-associated protein, DRiP78, binds to this motif. Overexpression or sequestration of DRiP78 leads to retention of D1 receptors in the ER, reduced ligand binding, and a slowdown in the kinetics of receptor glycosylation. Our results indicate that DRiP78 may regulate the transport of a GPCR by binding to a specific ER-export signal.

Amino Acid Motifs↗
PubMed2001

A case-control study of differences between regular and causal adult attenders in general dental practice.

OBJECTIVES: To assess whether adults attending a dental practice for regular dental care have better oral health than adults attending casually in response to a dental problem, and to explore the barriers to asymptomatic attendance. METHODS: An observational case-control study comparing the characteristics of 100 regular attenders with 100 causal attenders in one general dental practice in North Staffordshire. All study subjects were aged 18 years or over. Sociodemographic characteristics of the two groups were collated, including age, gender, social class, marital status, employment status and smoking status. The primary outcome measure was the observed number of teeth with dentinal caries diagnosed using bitewing radiographs. RESULTS: Regular attenders were observed to have better oral health with respect to dental caries and tooth mobility (p < 0.05). This was not explained by the observation that causal attenders were more likely than regular attenders to be male, aged 18-44 years, in social class III or IV. Secondary outcomes, including number of subjects with mobile teeth and teeth with > 30% bone-loss, were also significantly worse in the casual attenders. However, the median number of teeth present in both groups was 27. In regular attenders, the most common reason for attending was to 'keep the teeth' (96%). In casual attenders, 'fear/dislike of dental treatment' was the most frequent indicator of non-attendance (56%). CONCLUSIONS: In our study, adults who regularly attended general dental practice were shown to have better oral health, including less overall tooth decay, mobility and bone-loss, compared with adults who did not attend on a regular basis. Assuming this result to be externally valid, a challenge for the dental profession in the future will be to develop effective oral health promotion initiatives.

Adolescent↗
PubMed2000

Site-specific gene targeting for gene expression in eukaryotes.

Major advances in the use of site-specific recombinases to facilitate sustained gene expression via chromosomal targeting have been made during the past year. New tools for genomic manipulations using this technology include the discovery of epitopes in recombinases that confer nuclear localization, crystal structures that show the precise topology of recombinase-DNA-substrate synaptic complexes, manipulations of the DNA recognition sequences that select for integration over excision of DNA, and manipulations that make changes in gene expression inducible by drug administration. In addition, endogenous eukaryotic and mammalian DNA sequences have been discovered that can support site-specific recombinase-mediated manipulations.

Animals↗
PubMed2000

The role of the Advanced Casualty Management Team in St John Ambulance Australia (New South Wales District).

St John Ambulance is a household name synonymous with the teaching and provision of first aid. Recently the organisation has developed pre-hospital emergency care services through the introduction of the St John Ambulance Australia Advanced Casualty Management Team in New South Wales. The Advanced Casualty Management Team represents a move away from the practice of first aid by lay personnel and is a natural extension of the traditional work and principles of St John Ambulance. This article provides an overview of the Advanced Casualty Management Team and discusses its contribution to pre-hospital trauma care delivery.

Efficiency, Organizational↗
PubMed1999

A humanized anti-CD3 antibody, HuM291, with low mitogenic activity, mediates complete and reversible T-cell depletion in chimpanzees.

BACKGROUND: An anti-CD3 antibody that reduces cytokine release syndrome (CRS) while maintaining immunosuppression would be a major advance in the treatment of acute allograft rejection. A humanized (Hu) anti-CD3 IgG2 Ab, HuM291 gamma2 M3 (HuM291; Protein Design Labs, Inc., Mountain View, CA), was engineered with mutations in the upper CH2 region of the Fc domain. The mutations were intended to reduce affinity for Fcgamma receptors, thought to be relevant to CRS. METHODS: In vitro studies using chimpanzee peripheral blood mononuclear cells (PBMCs) were conducted to characterize HuM291 and to establish an animal model. A multidose study was conducted in chimpanzees to evaluate the safety, pharmacokinetics, immunomodulatory activity, and immunogenicity of HuM291, when administered at doses ranging from 0.1 to 10 mg. RESULTS: HuM291 bound to and effectively downmodulated CD3 from chimpanzee PBMCs and stimulated substantially less cytokine secretion and proliferation of chimpanzee PBMCs compared with OKT3 (Orthoclone OKT3; Ortho Pharmaceutical Corp., Raritan, NJ). Multiple doses of HuM291 (0.1, 1.0, or 10 mg/dose) were not associated with adverse events, signs of toxicity, or CRS, despite cytokine release. HuM291 exhibited a long elimination t1/2 (81.5 hr) and, after three 10-mg doses, sustained serum concentrations > 1000 ng/ml were maintained for 1 week. Multiple 10-mg doses induced complete depletion of circulating CD2+CD3+ T cells for up to 10 days after the last dose; T cells recovered by Day 28. Anti-HuM291 Abs were observed in only 4 of 12 animals and were transient in 2 of those animals. CONCLUSIONS: In vitro, HuM291 is substantially less mitogenic than OKT3. In chimpanzees, HuM291 effectively depleted peripheral T cells without eliciting clinical signs of CRS, and recovered T cells were functionally normal.

Animals↗
PubMed1999

In vivo studies of gene expression via transient transgenesis using lipid-DNA delivery.

As the sequencing of the human genome proceeds, the need for a new screen for in vivo function is becoming apparent. Many investigators are turning to various transgenic models as a means of studying function. However, these approaches are very time consuming, with a transgene-expressing mouse model often taking months to establish. We have developed an efficient system for delivering genes in vivo, which allows the gene product to be studied as early as 24 h after introduction into the mouse model. The delivery system employs a novel cationic lipid, 1-[2-(9-(Z)-octadecenoyloxy)ethyl]-2-(8-(Z)-heptadecenyl)-3- (hydroxyethyl)imidazolinium chloride (DOTIM), and a neutral lipid, cholesterol, complexed with an expression vector containing the reporter gene chloramphenicol acetyl transferase (CAT). After a single intravenous injection of these complexes, several tissues were seen to express the transgene. High, persistent expression in the vascular endothelial cells in the mouse lung was obtained. Delivery of DNA in vivo has been evaluated by quantitative polymerase chain reaction and protein expression by CAT activity assays. In vivo studies showed reproducible expression in more than 500 mice injected via the tail vein. An early peak of expression was followed by lower, but sustained, expression for > 50 days. Transgene expression of CAT could also be identified by immunohistochemistry staining in mouse lung and appeared to be located within the capillaries. The pattern of in vivo expression could be modulated and targeted to specific organs by altering the lipid-DNA formulation. New expression vectors with altered introns and polyadenylation sites further improved expression. The expression reported here may be sufficient in magnitude, duration, and flexibility to be an attractive alternative, in some cases, to establishing transgenic animals by stable gene transfer.

Animals↗
PubMed1999

Vascular inflammation inhibits gene transfer to the pulmonary circulation in vivo.

We report gene transfer to the normal and injured murine pulmonary circulation via systemic (intravascular) and airway (intratracheal) delivery of novel polycationic liposomes (imidazolium chloride, imidazolinium chloride-cholesterol, and ethyl phosphocholine). With use of the reporter genes chloramphenicol acetyltransferase (CAT) or human placental alkaline phosphatase (hpAP), intravascular injection of lipid-DNA complexes resulted in gene expression primarily in the lung, with lesser expression in the heart (11% of lung, P < 0.05) and spleen (8% of lung, P < 0.05). Histochemical staining for the hpAP reporter gene showed localized transgene expression in the microvascular endothelium. Monocrotaline (80 mg/kg body wt sc) treatment produced endovascular inflammation and reduced lung CAT activity (2 days postintravascular transfection) by 75 +/- 8 and 86 +/- 6% at 7 and 21 days, respectively, after monocrotaline (P < 0. 05). Despite the apparent decrease in functional CAT protein, Southern blot analysis suggested maintained plasmid delivery, whereas quantitative PCR (TaqMan) showed decreased CAT mRNA levels in monocrotaline mice. In contrast, intratracheal delivery of lipid-DNA complexes showed enhanced CAT expression in monocrotaline mice. Transfection in alternate pulmonary vascular disorders was studied by inducing hypoxic pulmonary hypertension (4 wk at barometric pressure of 410 mmHg). Efficiency and duration of gene transfer, assessed by CAT activity, were similar in pulmonary hypertensive and normal lungs. We conclude that imidazolinium-derived polycationic liposomes provide a means of relatively selective and efficient gene transfer to the normal and injured murine microvascular circulation, although translation of transgene mRNA may be reduced by preexisting endothelial injury.

Animals↗
PubMed1999

Urban-rural differences in Medicare in Missouri.

Health Care Financing Administration's (HCFA) administrative data were analyzed to examine urban-rural differences in the characteristics of Medicare beneficiaries, their utilization of medical care, the providers of services, and selected outcomes in Missouri. As compared to the residents of urban areas, the residents of the rural counties were a little poorer, had equal access to health care, and utilized more health care services; but the cost of major services was lower.

Hospitalization↗
PubMed1991

Radioprotectant effects of atropine on small intestinal villous shape.

Previous work has shown that irradiation produces changes in small intestinal villous shape, which can be quantified using a villous scoring system applied to scanning electron micrographs. It has already been shown that reserpine, which, like irradiation, increases gastrointestinal motility, produces a similar type of villous collapse, thereby supporting the theory that this form of injury may not be due entirely to changes in the cryptal epithelial compartment, as has been assumed previously. Atropine, chosen for its ability to decrease gut motility, produces a different form of villous shape change. The aim of the current work was to investigate the ability of atropine to decrease the villous damage caused by irradiation and thereby improve the likely absorptive capacity of the small intestine. The current experiments used crypt counting, qualitative light microscopy and villous scoring techniques. Groups of unirradiated mice examined included baseline controls and those treated with atropine, sham irradiation and a combination of these two schedules. Two irradiated groups were studied, one with and one without atropine treatment. The results show that atropine given with irradiation reduces the extent of the damage to villous shape, implying that the total effect on the neuromuscular tissues is less destructive after the combined treatment. It is also of interest that atropine appears to have an additional radioprotectant effect on the radiation induced crypt depletion, implying that neuromuscular behaviour may influence this compartment, hitherto considered as dependent on epithelial proliferative capacity.

Animals↗
PubMed1979

The polypeptides of isolated brain 10nm filaments and their association with polymerized tubulin.

Brain 10 nm filaments were isolated from bovine, rabbit and rat brains by a modification of an existing procedure. The overall polypeptide composition of these preparations was similar to that previously reported for brain neurofilaments. In addition to the major polypeptide component, which has mol. wt. approx. 50 000, three other polypeptides with chain mol. wts. approx. 210 000, 155 000 and 70 000, which correspond to peripheral-nerve neurofilament polypeptides, were consistently found to be present. The mol. wt.-50 000 species was found to be heterogeneous and may contain a component derived from the mol. wt. 70 000 polypeptide. The three higher-molecular-weight polypeptides did not appear to be obviously homologous or to be homologous with myosin or Myxicola neurofilament polypeptides. These same three higher-molecular-weight components were shown to be identical with the polypeptides probably responsible for the 10 nm filaments formed during the early cycles of the tubulin-purification protocol.

Animals↗