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Biomedical subjects

P Churchill

Publications and source records attributed to P Churchill.

At least 19 recordsLinked to original sources
PubMed1998

DRG reimbursement: geriatric hip fractures in the community hospital trauma center.

BACKGROUND: The purpose of this paper was to determine whether Medicare reimbursement for hip fracture reaches cost in geriatric patients. METHODS: We conducted a retrospective review using the hospital trauma registry. Demographics, operations, length of stay, clinical outcome, discharge disposition, hospital charges, and hospital costs were reviewed and compared with diagnosis-related group (DRG) reimbursement. RESULTS: The study included 153 Medicare patients. Mortality was 3.9%, 71% were discharged to a nursing home or rehabilitation unit, and 25% went directly home. DRG reimbursement constituted 58% of charges. Compared with costs, the DRG amount represented a mean loss of nearly $1,000 per patient. CONCLUSIONS: DRG reimbursement undercompensates the community hospital trauma center for treating a common malady among the geriatric population. A population shift toward the elderly, decreasing Medicare remuneration, and the advance of managed care will make correct identification and control of costs extremely important for the hospital caring for hip fractures in the geriatric population.

Aged↗
PubMed1998

Breast conservation surgery for breast cancer at a regional medical center.

BACKGROUND: This study examined trends in breast conservation surgery (BCS) at our hospital and factors associated with BCS. METHODS: We retrospectively reviewed breast cancer surgeries in patients eligible for BCS (size <4 cm, N0, N1) from 1990 through 1996 (n = 634). We calculated the yearly prevalence of BCS and used multiple logistic regression (MLR) to determine tumor, patient, and surgeon factors associated with BCS. RESULTS: BCS increased from 17% in 1990 to 41% in 1996. Women with T1a and T1b tumors were 3.8 and 2.0 times, respectively, as likely to have BCS compared with those who had T2 tumors. Other factors associated with BCS included nonpalpable tumors, age <50, Medicare, Medicaid, or self-pay patients, and women whose surgeons graduated since 1961, with odds ratios of 1.8, 1.9, 2.4, and 2.3, respectively. CONCLUSION: Women with small, nonpalpable tumors, age <50, without private insurance, operated on by younger surgeons were more likely to receive BCS.

Adult↗
PubMed1997

Succinyl-CoA:3-ketoacid coenzyme A transferase (SCOT): development of an antibody to human SCOT and diagnostic use in hereditary SCOT deficiency.

Succinyl-CoA:3-ketoacid CoA transferase (SCOT) is a key enzyme for ketone body utilization. Hereditary SCOT deficiency in humans (McKusick catalogue number 245050) is characterized by intermittent ketoacidotic attacks and permanent hyperketonemia. Since previously-available antibody to rat SCOT did not crossreact with human SCOT, we developed an antibody against recombinant human SCOT expressed in a bacterial system. The recombinant SCOT was insoluble except under denaturing conditions. Antibody raised to this polypeptide recognized denatured SCOT and proved useful for immunoblot analysis. On immunoblots, SCOT was easily detectable in control fibroblasts and lymphocytes but was detected neither in fibroblast extracts from four SCOT-deficient patients, nor in lymphocytes from two SCOT-deficient patients. These data indicate that immunoblot analysis is useful for diagnosis of SCOT deficiency in combination with enzyme assay.

Animals↗
PubMed1996

Clinicopathologic factors and patient perceptions associated with surgical breast-conserving treatment.

BACKGROUND: Clinical studies have shown equivalent survival rates between breast-conserving surgery (BCS) and mastectomy in early breast cancer; however, rates for BCS remain low. The purpose of this study was to determine (a) the prevalence of BCS in a regional medical center, (b) clinicopathologic factors associated with BCS, and (c) patient perceptions of the treatment decision-making process. METHODS: We retrospectively reviewed 251 consecutive breast cancer cases during January 1990-December 1991; 77 patients were ineligible for BCS because of unfavorable pathology. We then interviewed 118 of the 160 women available for interview. RESULTS: BCS was performed in 31 of the eligible patients (18%). Multivariate analysis revealed that tumor size < 10 mm (p = 0.03) was the only significant predictive variable for BCS. Patient interviews revealed that 93% said their surgeon was the primary source of information regarding treatment options. Among 69% of the women whose surgeons reportedly recommended a particular option, 89% recommended mastectomy with 93% compliance, and 11% recommended BCS with 89% compliance. The BCS group more often obtained a second opinion (p = 0.04) and 60% said they made the decision themselves compared with only 37% of the mastectomy group (p = 0.05). CONCLUSION: Limiting BCS to women whose tumor size is < 10 mm is too restrictive; this excludes a large number of women who are clinically eligible for BCS. The surgical decision-making process for early-stage breast cancer is very much surgeon-driven, with a high degree of patient compliance.

Aged↗
PubMed1993

BAY K 8644 inhibits renin secretion in isolated perfused rat kidneys.

There are only a few previous reports of the renal effects of the Ca channel agonist BAY K 8644, and the renin secretory effects in particular are unclear. In the present experiments, isolated rat kidneys were perfused at 120 and 100 mm Hg before and after adding BAY K 8644 to the perfusate (0.05 microM final concentration), and perfusate flow rate, glomerular filtration rate (GFR), urine flow, Na excretion, and renin secretory rate were measured. BAY K 8644 increased renal vascular resistance, as evidence by decreases in perfusate flow and GFR at constant perfusion pressure, and decreased urine flow and Na excretion. Renin secretory rates were 51 +/- 4 versus 23 +/- 3 ng A I hr-1 min-1 at 120 mm Hg (p < 0.01), and 184 +/- 54 versus 38 +/- 14 ng A I hr-1 min-1 at 100 mm Hg (p < 0.01), in the absence versus the presence of BAY K 8644, respectively. Therefore, BAY K 8644 inhibits renin secretion at constant perfusion pressure and blunts the stimulatory effect on renin secretion of decreases in renal perfusion pressure. Collectively, these observations add to the growing evidence that the renin secreting juxtaglomerular cells have voltage-operated Ca channels, that depolarization-induced Ca influx inhibits renin secretion, and that Ca is an inhibitory second messenger in the renin secretory process.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Streptozotocin-induced renal hemodynamic changes in isogenic Lewis rats: a kidney transplant study.

Streptozotocin (STZ)-induced diabetes mellitus is associated with decreased renal clearances of inulin and p-aminohippurate (PAH). The present experiments were designed to determine whether STZ-induced renal hemodynamic changes are due to the drug per se, rather than to the diabetic state that it induces. Isogenic Lewis rats with native right and transplanted left kidneys were studied. In one group, kidney donors received 50 mg STZ/kg body wt on day 1 and transplantation was performed on day 4 (untreated recipients). On day 29, the inulin and PAH clearances of these nondiabetic recipients were, respectively, 0.94 +/- 0.04 and 2.58 +/- 0.11 ml.min-1 x g-1 for the transplanted left kidney (previously exposed to STZ) and 0.95 +/- 0.07 and 2.54 +/- 0.14 ml.min-1 x g-1 for the native right kidney (never exposed to STZ). In another group, recipients received STZ on day 1 and transplantation was performed on day 4 (untreated donors). On day 29, the inulin and PAH clearances of these diabetic recipients were, respectively, 0.62 +/- 0.04 and 1.46 +/- 0.11 ml.min-1 x g-1 for the transplanted left kidney (never exposed to STZ) and 0.61 +/- 0.05 and 1.42 +/- 0.08 ml.min-1 x g-1 for the native right kidney (previously exposed to STZ). We conclude that the diabetic state, rather than STZ, is responsible for the decreased renal clearances of inulin and PAH in this experimental model.

Animals↗
PubMed1993

The baroreceptor mechanism for controlling renin secretion: effect of calcium channel blockers.

Renin secretion is inversely related to afferent arteriolar transmural pressure, or to some function of it such as stretch (the baroreceptor mechanism). It has been suggested that increased pressure depolarizes the renin-secreting juxtaglomerular cells, and that increased Ca influx through voltage-operated Ca channels mediates the inhibitory effect on renin secretion. If true, then Ca channel blockers should antagonize the inhibitory effect of increased pressure on renin secretion. To test this prediction, isolated rat kidneys were perfused with an oxygenated physiological salt solution in a single-pass system. Perfusate flow rate and renin concentration in the venous effluent were measured and their product, the renin secretory rate (RSR), was calculated. During the control period, increasing renal perfusion pressure (RPP) from 100 to 120 mm Hg decreased RSR to 42 +/- 5% of the control value. This inhibitory effect of increased RPP was blunted by 1 microM nifedipine, nearly blocked by 5 microM verapamil and completely blocked by 50 microM diltiazem. Inasmuch as nifedipine, verapamil and diltiazem are Ca channel blockers and because all three have been shown previously to block the inhibitory effect of depolarization on RSR, these results are consistent with the hypothesis that a depolarization-induced influx of Ca mediates the inhibitory effect of increased RPP on RSR.

Animals↗
PubMed1992

Primary structure of rat liver D-beta-hydroxybutyrate dehydrogenase from cDNA and protein analyses: a short-chain alcohol dehydrogenase.

The amino acid sequence of D-beta-hydroxybutyrate dehydrogenase (BDH), a phosphatidyl-choline-dependent enzyme, has been determined for the enzyme from rat liver by a combination of nucleotide sequencing of cDNA clones and amino acid sequencing of the purified protein. This represents the first report of the primary structure of this enzyme. The largest clone contained 1435 base pairs and encoded the entire amino acid sequence of mature BDH and the leader peptide of precursor BDH. Hybridization of poly(A+) rat liver mRNA revealed two bands with estimated sizes of 3.2 and 1.7 kb. A computer-based comparison of the amino acid sequence of BDH with other reported sequences reveals a homology with the superfamily of short-chain alcohol dehydrogenases, which are distinct from the classical zinc-dependent alcohol dehydrogenases. This protein family, initially discerned from Drosophila alcohol dehydrogenase and bacterial ribitol dehydrogenase, is now known to include at least 20 enzymes catalyzing oxidations of distinct substrates.

Alcohol Dehydrogenase↗
PubMed1991

High osmolality-low pH flush solutions improve renal transplant function in rats.

Although transplanting rat kidneys is an established microsurgical technique, inulin clearance is abnormally low, due to rejection and/or warm ischemia-induced damage. In the present studies, rejection was avoided by using inbred Brown Norway rats as donors and recipients. Donor kidneys were flushed with ice-cold solutions of various composition (saline, saline + 200 or 400 mM mannitol) and pHs (5.7, 6.4, and 7.4), and the kidneys were kept cold during transplantation into unilaterally nephrectomized recipients. Renal function was assessed by clearance techniques 1 week later. In control rats, with both native kidneys intact, the ratio of inulin clearance, left kidney to right kidney, was 0.99 +/- 0.02. In rats with a native right kidney and a transplanted left kidney that had been flushed with saline, the ratio was considerably lower (0.46 +/- 0.09). Adding 200 mM mannitol to the saline flush solution increased the ratio (0.89 +/- 0.09). In comparison, adding 200 mM mannitol and 5 mM phosphate buffer at pH 7.4 resulted in a somewhat lower ratio (0.80 +/- 0.09), whereas adding 200 mM mannitol and 5 mM phosphate buffer at pH 5.7 resulted in a higher ratio, one that was indistinguishable from control (0.97 +/- 0.09). Thus, in this latter group, the inulin clearances of the transplanted kidneys were identical to those of the contralateral native kidneys.

Animals↗
PubMed1991

Patient awareness of health precautions after splenectomy.

Sepsis after splenectomy is a lifelong risk, and patients who have had splenectomy should be educated about this risk. This study examines patient knowledge after splenectomy. We reviewed hospital records of 118 patients who had splenectomies performed between 1982 and 1988 at New Hanover Memorial Hospital. Twenty-four patients have died since their surgery; one death was suspected to be due to postsplenectomy sepsis. Of the 89 patients alive and eligible for follow-up, we were able to query 63. Only 16% were aware of any health precautions. After prompting, patient awareness improved to 40%. We also surveyed 11 of the 14 surgeons who performed the splenectomies. They indicated that they always discuss with their patients the immunologic consequences of spleen removal and the increased risks of infection, although they do not always recommend pneumococcal vaccine. We conclude that splenectomy patients have a low level of knowledge about postsplenectomy infection risks and precautions. We developed an educational pamphlet to aid the surgeon in patient education.

Awareness↗
PubMed1991

Cloning and expression of a functional rat liver D-beta-hydroxybutyrate dehydrogenase-beta-galactosidase fusion protein in Escherichia coli.

A rat liver bacteriophage lambda expression library was probed using polyclonal antibodies raised to purified rat liver D-beta-hydroxybutyrate dehydrogenase (BDH). A clone was selected that contained a 1.2-kb insert. The insert placed in an expression plasmid was utilized to transform Escherichia coli. These cells were shown to possess phosphatidylcholine-dependent BDH activity. Cells transformed with only the plasmid had no detectable BDH activity in the presence of phosphatidylcholine. The expressed activity in E. coli could be inhibited in a dose-dependent manner by BDH antiserum.

Animals↗
PubMed1990

Regulation of succinyl coenzyme A:acetoacetyl coenzyme A transferase in rat hepatoma cell lines.

The regulation of succinyl-CoA:acetoacetyl-CoA transferase (CoA transferase) has been studied in 8 rat hepatoma cell lines. Compared with normal rat hepatocytes, which have almost nondetectable activity of the enzyme, the hepatoma cell lines have a wide range of expression of CoA transferase activity, from as low as 45 nmol/min/mg to as high as 960 nmol/min/mg. Western blotting showed that the different levels of CoA transferase activity were due to differing amounts of the enzyme in the cells. This was further attributed to the varying amounts of the enzyme synthesized in the cells as monitored by L-[35S]methionine labeling followed by immunoprecipitation. To study further the differential expression of CoA transferase in the hepatoma cell lines, the relative quantity of functional CoA-transferase mRNA in the cells was measured by in vitro translation. The results showed that the levels of functional CoA transferase mRNA detected were consistent with the differences in the enzyme activity in the cells. Since CoA transferase is the key enzyme responsible for the utilization of ketone bodies as an alternative energy source, the expression of CoA transferase in hepatoma cells may play a role in energy production.

Animals↗
PubMed1990

The use of amphipathic maleimides to study membrane-associated proteins.

A series of amphiphilic polymethlyenecarboxymaleimides has been synthesized for use as sulfhydryl reagents applicable to membrane proteins. Physical properties of the compounds which are relevant to their proposed mode of action have been determined. By comparing rates of reaction in aqueous and aprotic solvents, the compounds have been shown to react exclusively with the thiolate ion. The effects of the reagents on three membrane-associated proteins are reported, and in two cases a comparative study has been made of the effects on the proteins in the absence of membranes. A mechanism is proposed whereby the reagents are anchored at the lipid/water interface by the negatively charged carboxyl group, thus sitting the reactive maleimide in a plane whose depth is defined by the length of the reagent. Supporting evidence for this model is provided by the inability of the reagents to traverse membranes, and variation of their inhibitory potency with chain length when the proteins are embedded in the membrane, but not when extracted into solution. As examples of general use of the reagents to probe sulfhydryl groups in membrane proteins, the reagents have been used to (a) determine the depths in the membrane at which two populations of sulfhydryl groups occur in the mitochondrial phosphate transporter; (b) locate a single sulfhydryl associated with the active site of D-beta-hydroxybutyrate dehydrogenase in the inner mitochondrial membrane; (c) examine sulfhydryl groups in the D-3-glyceraldehyde phosphate dehydrogenase associated with the human red blood cell membrane.

Animals↗
PubMed1990

Community hospital carotid endarterectomy in patients over age 75.

We compared the prevalence of stroke and death in 133 patients aged 75 and older in whom 170 carotid endarterectomies were performed with that in 501 patients less than age 75 in whom 640 carotid endarterectomies were performed. There were three strokes (2%) in patients aged 75 and older and nine strokes (1%) in younger patients (p = 0.7). There were 8 deaths (5%) in patients aged 75 and older and 14 deaths (2%) in younger patients (p = 0.1). After controlling for the possible confounding effects of diabetes, prior stroke, history of angina, prior carotid artery disease, previous vascular surgery, history of myocardial infarction, preoperative hypertension requiring medication, and female gender, a logistic regression model showed that patients aged 75 and older were no more likely to have a stroke or death than patients under age 75. We conclude that age alone is not a contraindication to the safe performance of carotid endarterectomy in the community hospital.

Age Factors↗
PubMed1990

Kidney transplants in cyclosporine-treated Sprague-Dawley rats.

Previous studies by others have shown that transplanted rat kidneys have abnormally low clearances of paraaminohippuric acid, inulin, and creatinine, due to rejection and/or to warm-ischemia-induced injury. In the present studies, randomly bred Sprague-Dawley rats were used as donors and recipients. The left kidneys of recipients were removed, and the right kidneys were left intact. Donor kidneys were flushed with an ice-cold hypertonic solution (150 mM NaCl, 200 mM mannitol, pH 6.4), and the kidneys were kept cold during surgery. Renal function was assessed 1 week later. The left transplanted kidneys in untreated recipients exhibited morphologic evidence of rejection, and the clearances of PAH and inulin were approximately 50% of those of the right native kidneys. CsA-treated rats did not reject the transplants, and the PAH and inulin clearances of the left transplanted kidneys were identical to those of the right native kidneys. Untreated and CsA-treated rats with both native kidneys intact served as controls. The amount of CsA given during the 7-day period produced no measurable change in renal function. This is the first demonstration of virtually normal hemodynamics in transplanted rat kidneys when randomly bred animals are used as donors and recipients. Moreover, the results indicate that if both rejection and warm ischemia are avoided, the presence of a functioning native kidney does not have a detrimental effect on the function of a transplanted kidney.

Animals↗
PubMed1990

Purification of D-beta-hydroxybutyrate dehydrogenase from rat brain.

D-beta-Hydroxybutyrate dehydrogenase (BDH), a lipid-requiring enzyme, has been purified to homogeneity from rat brain using a new improved method. The purified rat brain BDH has a subunit molecular mass of 31 kilodaltons on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The apoenzyme, i.e., the enzyme devoid of phospholipid, has no activity, but can be activated by phospholipid to a specific activity of 125 mumol/(min.mg). This is 625-fold greater than the activity in the mitochondrial fraction. The new purification procedure involves chromatography using a quaternary amine Sepharose resin followed by a sulphonate Sepharose resin, and eliminates the need for glass bead adsorption chromatography.

Animals↗
PubMed1990

Comparison of D-beta-hydroxybutyrate dehydrogenase from rat liver and brain mitochondria.

The properties of D-beta-hydroxybutyrate dehydrogenase (BDH) from rat liver and brain mitochondria were compared to determine if isozymes of this enzyme exist in these tissues. The BDHs from these tissues behaved similarly during the purification process. The enzymes were indistinguishable by sodium dodecyl sulfate-polyacrylamide or acid-urea-polyacrylamide gel electrophoresis and they had identical isoelectric points. The BDHs from rat liver and brain were also quite similar in functional parameters determined by kinetic analysis and phospholipid activation of apo-BDH (i.e., the lipid-free enzyme). Antiserum against rat liver BDH inhibited both enzymes to an equivalent extent in a titration assay. The enzymes had similar patterns of peptide mapping by partial digestion with Staphylococcus aureus V8 protease, followed by immunoblotting using antiserum against the liver enzyme. These results suggest that the BDHs in rat liver and brain are very similar and possibly identical.

Animals↗