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Biomedical subjects

R L Mitchell

Publications and source records attributed to R L Mitchell.

At least 19 recordsLinked to original sources

Potential effects of managed care on specialty practice at a university medical center.

BACKGROUND: The growth of managed care presents a challenge to academic medical centers, because the demand for the services of specialists is likely to continue decreasing. We estimated the number of enrollees the University of Michigan Medical Center would need in its health maintenance organization (HMO) system in order to provide revenue equivalent to the total revenue it received for professional specialty care in 1992. METHODS: Rates of utilization and payment were based on the medical center's experience with managed care in 1992 in its independent practice association HMO, in which 25,000 members had capitated coverage and received primary and all specialty care from university physicians, and 15,000 members received primary care and most specialty care from physicians outside the university. We assumed that persons not enrolled in Medicare were all enrolled in managed-care plans. Primary care activity was excluded from the calculations of expense, revenue, and numbers of faculty members. RESULTS: If all specialty services were provided by the university to HMO members, all the 21 specialties examined except obstetrics and gynecology and emergency services would require an enrollment of more than 250,000 to support the 1992 level of professional revenue and maintain the number of faculty members. If university services were provided only for referrals from a loosely affiliated network of community physicians in the HMO system, all the 19 specialties examined except plastic surgery would require an HMO enrollment of more than 1 million. In a combined model in which all specialty services were provided to 100,000 HMO members and network referrals were provided to 500,000 members, substantial changes in faculty composition would be needed in all the departments studied. CONCLUSIONS: Because of the large number of HMO members required, unless other changes occur, it is unrealistic to expect that the University of Michigan Medical Center could create an HMO or network large enough to support the specialty practice of the current number of faculty members at the 1992 level of financing.

Academic Medical Centers

Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors.

The recently cloned CB2 cannabinoid receptor subtype was stably transfected into AtT-20 and Chinese hamster ovary cells to compare the binding and signal transduction properties of this receptor with those of the CB1 receptor subtype. The binding of [3H]CP 55,940 to both CB1 and CB2 was of similar high affinity (2.6 and 3.7 nM, respectively) and saturable. In competitive binding experiments, (-)-delta 9-tetrahydrocannabinol and CP 55,940 were equipotent at the CB1 and CB2 receptors, but WIN 55212-2 and cannabinol bound with higher affinity to the CB2 than the CB1 receptor. HU 210 had a higher affinity for the CB1 receptor. Anandamide, a recently identified endogenous cannabinoid agonist, was essentially equipotent at both receptor subtypes. The structurally related fatty acid ethanolamides dihomo-gamma-linolenylethanolamide and mead ethanolamide also bound with relatively equal affinity to both receptors, but adrenylethanolamide had a higher affinity for the CB1 receptor. The rank order of potency and efficacy for binding of the selected agonists to the CB1 and CB2 receptors was mimicked in functional inhibition of cAMP accumulation experiments for all compounds tested. Both CB1 and CB2 receptors couple to the inhibition of cAMP accumulation that was pertussis toxin sensitive. SR141716A, a CB1 receptor antagonist, was a poor antagonist at the CB2 receptor in both binding and functional inhibition of cAMP accumulation experiments. When expressed in AtT-20 cells, the CB1 receptor mediated an inhibition of Q-type calcium channels and an activation of inward rectifying potassium channels. In contrast, the CB2 receptor did not modulate the activity of either channel under identical assay conditions. Similar to results obtained for CB1 receptor, the CB2 receptor did not couple to the activation of phospholipases A2, C, or D or to the mobilization of intracellular Ca2+. Except for its inability to couple to the modulation of Q-type calcium channels or inwardly rectifying potassium channels, the CB1 and CB2 receptors display similar pharmacological and biochemical properties.

Adenylyl Cyclase Inhibitors

Comparative anticalculus effect of dentifrices containing 1.30% soluble pyrophosphate with and without a copolymer.

A six-month, double blind, clinical study was conducted to determine the effect on supragingival calculus formation of a dentifrice containing 1.30% soluble pyrophosphate (from 2.0% tetrasodium pyrophosphate) and 1.50% of a copolymer of methoxyethylene and maleic acid, as compared to a dentifrice containing the same amount of soluble pyrophosphate but without the copolymer. This pyrophosphate/copolymer dentifrice contained the optimal ratio of pyrophosphate anion to copolymer required for obtaining a comparable anticalculus effect to a clinically proven anticalculus dentifrice containing 3.3% soluble pyrophosphate and 1.0% of a copolymer. The optimal pyrophosphate/copolymer ratio was determined by a series of in vitro laboratory and in vivo animal studies. Male and female adult subjects were stratified into three balanced groups according to baseline calculus scores. They received an oral prophylaxis and were assigned to the use of either the dentifrice containing soluble pyrophosphate and the copolymer, or to the dentifrice containing soluble pyrophosphate but without the copolymer, or to a placebo dentifrice that did not contain an anticalculus ingredient. The results of the three-month calculus examination indicated that the dentifrice containing soluble pyrophosphate and the copolymer provided a 33.66% reduction in supragingival calculus formation after an oral prophylaxis as compared to the placebo dentifrice. This reduction was statistically significant at the 99 percent level of confidence. The results of the six-month calculus examination indicated that the dentifrice containing the soluble pyrophosphate and the copolymer provided a 36.10% reduction in supragingival calculus formation after an oral prophylaxis, as compared to the placebo dentifrice. This reduction was also statistically significant at the 99% level of confidence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The lateral limited thoracotomy incision: standard for pulmonary operations.

Four hundred sixty-eight consecutive thoracotomies for which the lateral limited thoracotomy incision was used are reviewed (1978 to 1988). The limited incision is a lateral muscle-splitting incision with preservation of the latissimus dorsi, splitting of the serratus anterior, and cutting of only the intercostal muscles without rib resection. Patients were designated unsuitable for operation if (1) biopsy-proved distant metastasis existed, (2) mediastinoscopy revealed extranodal metastasis, or (3) severe respiratory compromise resulted in shortness of breath at rest with a forced expiratory volume in 1 second of less than 0.75 L (four patients). Mean patient age was 60.9 (+/- 15.7) years. Surgical procedures included lobectomy (n = 317), pneumonectomy (n = 41), wedge resection (n = 82), resections of blebs or bullae (n = 17), thoracotomy and biopsy for unresectable lesion (n = 6), and decortication (n = 5). Pathologic analysis revealed 354 malignant tumors, 102 benign lesions, and 12 carcinoids. The perioperative mortality rate was 0.85% (4/468) and major morbidity was present in 2.9% (14/468). Mean operative time was 73.1 (+/- 32.2) minutes with a blood loss resulting in a mean decrease of the hematocrit value of 2.6 (+/- 2.5) gm; three patients were given a total of 7 units of blood. Most patients do not require a stay in the intensive care unit postoperatively (less than 10%). Hospital stay postoperatively was a mean of 6.1 (+/- 2.9 days. The limited incision is a significant factor in decreasing operative time, blood loss, postoperative pain and morbidity, and cost.

Aged

Distal splenorenal shunt: standard procedure for elective and emergency treatment of bleeding esophageal varices.

The distal splenorenal shunt has been advocated for patients with bleeding esophageal varices because it is a selective shunt which decompresses the varices while preserving hepatic flow. The procedure appeared sound physiologically and since 1976, the distal splenorenal shunt has been our procedure of choice for both emergency and elective situations. Our series of 43 patients included 6 patients in Child's class A, 18 in Child's class B, and 19 in Child's class C. The operative mortality rate was 4.7 percent (2 of 43 patients) and there were 34 long-term survivors (79 percent). Use of modern cardiovascular techniques is an essential facet of the surgeon's technical ability to achieve low morbidity and mortality rates. In the present series, the average blood loss was 440 ml and the average operative time, 2 1/2 hours. The distal splenorenal shunt can be performed for emergency and elective therapy of bleeding esophageal varices with a low incidence of complications and death and excellent long-term quality of life.

Adolescent

Persistent hemorrhagic gastritis in a patient with portal hypertension and esophagogastric varices: the role of portal decompressive surgery.

Our patient, with cirrhosis, portal hypertension, varices, and chronic gastrointestinal bleeding from hemorrhagic gastritis, illustrates an important therapeutic principle. Since the gastritis is related to vascular changes and congestion of the stomach wall secondary to increased portal pressure, and not inflammation, measures aimed at local healing or surgical removal of the bleeding area fail. One must attempt to lower portal pressure with drugs such as propranolol and/or undertake portal decompressive surgery.

Aged

Saphenous vein coronary bypass graft revisited.

To establish a benchmark for the clinical efficacy of PTCA and the IMA graft in our institution, the data from 79 patients who underwent isolated SVBG to the LAD between July, 1971, and December, 1984, were analyzed. Follow-up averaged 96.16 months/patient. Actuarial freedom from reoperation was 100% at 12 months, 95% at 60 months, and 89.4% at 120 months. Actuarial freedom from cardiac death was 100% at 12 months, 94% at 60 months, and 87% at 120 months. Actuarial freedom from an LAD graft failure myocardial event was 100% at 12 month, 94% at 60 months, and 77% at 120 months. Our SVBG failure rate did increase from 1.2%/year during the first 5 years to 3.4%/year during the second 5 years. We are presently selectively employing IMA grafts to the LAD. Our results with the SVBG and the palliative nature of all coronary artery bypass graft procedures remove the imperative to always use the IMA. Individual patient considerations such as age, clinical stability, IMA flow, and the residual anatomy for the potential reoperation are important considerations.

Actuarial Analysis

Scientific presentations. What to do and what not to do.

An effective scientific presentation requires skill, experience, and effort. In planning the presentation, a skilled speaker first forms clear conclusions through analysis of the data, then tailors the details of the proof of these conclusions to the interests and background of the audience. The facts and conclusions are presented in a practiced, specific, clear, and logical manner. It is not the topic or the data alone, but the sympathetic and strategic communication of the material to a particular audience that makes a meaningful presentation.

Audiovisual Aids

Growth hormone-releasing factor induces c-fos expression in cultured primary pituitary cells.

GH-releasing factor (GRF) and somatostatin regulates the secretion and biosynthesis of GH as well as the proliferation of GH-producing cells. In order to further characterize the mitogenic effect of GRF, we studied the expression of the proto-oncogene c-fos in primary pituitary cells. Maximal induction of c-fos mRNA was observed 20-60 min after stimulation with 5 nM GRF, returning to basal levels after 2 h. Somatostatin-14 (5 nM) partially inhibited the GRF induced c-fos expression. Forskolin and phorbol 12, 13 dibutyrate induced c-fos gene in cultured primary pituitary cells with similar kinetics. Transcription of the fos gene was accompanied by biosynthesis of the fos protein. Indirect immunofluorescence using a fos specific antibody, showed exclusive nuclear localization of the fos protein. These data demonstrate that GRF and somatostatin, in addition to regulating GH secretion and somatotroph proliferation, can also regulate the expression of c-fos proto-oncogene in primary somatotrophs.

Animals

Abdominal and right thoracotomy approach as standard procedure for esophagogastrectomy with low morbidity.

A series of recent articles advocate that blunt esophagectomy through neck and abdominal incisions has superior perioperative results to esophagogastrectomy via thoracotomy and abdominal approach. This prompted a review of a personal series of 40 consecutive esophagogastrectomies performed between July 1978 and December 1985. Diseases included squamous cell cancer in 15 patients, adenocarcinoma in 22, Barrett's esophagus with cancer in two, and fibromyomatoses in one. The approach was en bloc resection through an abdominal incision and right thoracotomy; a cervical incision and anastomosis was added for proximal lesions. All anastomoses were hand-sewn interrupted suture technique. Perioperative results were superior to those reported for blunt esophagectomy. Mortality was zero, no anastomotic leaks occurred, and no major pulmonary complications were seen. Four of the 40 patients required blood transfusions that totaled 8 units. Average preoperative hematocrit value was 38.9% +/- 5.44% (standard deviation) and postoperative hematocrit value was 35.57% +/- 6.06% (standard deviation). Average operating time was three hours and 26 minutes +/- 41.43 minutes and hospital stay was 11.1 +/- 4.62 days (standard deviation). Three patients required transient anastomotic dilations. It is concluded that esophagogastric en bloc resection which uses an abdominal and right thoracic approach can be accomplished with a low morbidity and mortality. A limited thoracic incision, double-lumen endotracheal tube, and self-retaining retraction on the lung minimized pulmonary trauma and respiratory problems were not a factor.

Aged

c-fos expression is neither sufficient nor obligatory for differentiation of monomyelocytes to macrophages.

The c-fos gene is rapidly and transiently expressed when human U-937 and HL-60 leukemia cells are induced to differentiate to macrophages. We show that the expression of c-fos is controlled primarily at the transcriptional level. c-fos mRNA is very labile, with a half-life of less than 30 min. Superinduction of c-fos in the presence of cycloheximide occurs primarily because of stabilization of c-fos mRNA. When U-937 cells are serum-stimulated or treated with diacylglycerol, a c-kinase agonist, c-fos is transiently expressed to high levels; however, the cells fail to differentiate to macrophages. Furthermore, HL-60 cell variants resistant to TPA can be induced to differentiate to macrophages in the absence of detectable c-fos expression.

Calcitriol

Proto-oncogene fos: an inducible multifaceted gene.

Proto-oncogene fos, which is expressed during cell growth and cell differentiation and development, is a multifaceted gene. The viral homolog, v-fos, was identified as the resident transforming gene of FBJ-murine osteosarcoma virus, which induces bone tumors in mice. Owing to an in-frame deletion during the biogenesis of the v-fos gene, the products of viral and cellular fos proteins differ at their C-termini. Despite different C-termini, both fos proteins are nuclear in their location and can transform fibroblasts in vitro. However, transformation by the c-fos gene requires removal of a 67-base pair sequence from the 3' noncoding domain. Proto-oncogene fos is a highly inducible gene in response to a variety of growth factors and differentiation-specific inducers. The expression of the fos gene is not modulated during the cell cycle.

Animals

Proto-oncogene fos: an inducible gene.

Proto-oncogene fos is a multifaceted gene, which is expressed during cell growth, cell differentiation, and development. The viral homologue, v-fos, was identified as the resident transforming gene of FBJ-murine osteosarcoma virus which induces bone tumors in mice. Due to an in-fram deletion during the biogenesis of the v-fos gene, the products of viral and cellular fos proteins differ at their C-termini. Despite different C-termini, both fas proteins are nuclear in their location, and can transform fibroblasts in vitro. However, transformation by c-fos gene requires removal of a 67 base pair sequence from the 3' non-coding domain. Proto-oncogene fos is a highly inducible gene in response to a variety of growth factors and differentiation-specific inducers. The transcriptional enhancer and the inducible element of the fos gene have been mapped along with sequences in the 3' non-coding domain which may influence the stability of the c-fos transcripts. The c-fos gene transcription is regulated by positively and negatively acting cellular factors.

Gene Expression Regulation

Long-term experience with mitral valve replacement: an evolving strategy for prosthesis selection.

MVR was examined in 181 patients undergoing 188 consecutive operations during a 12 1/2-year observation time. Hospital mortality for MVR without aortic valve disease was 7 of 156 or 4.5% and was independent of the valve type employed and the presence of coronary artery pathology. Late cardiac mortality in isolated MVR was significantly greater in those patients receiving a Starr-Edward 6120 prosthesis when compared to those receiving an MPX. The presence of coronary artery pathology, however, defines the patient subgroup with the poorest late survival. Tissue durability has not significantly altered late survival after MPX. However, the actuarial analysis of tissue failure reveals important increases in tissue failure incidence 5 years after placement. Although MPX is our prosthesis of choice for MVR, limited tissue durability creates an important subgroup for judicious use of a mechanical prosthesis. We conclude that no valve type should be championed as "the valve" for all patients undergoing MVR. The selection of a valve for MVR remains a difficult judgment which must be tempered by the patients age, history of previous operations, severity of his present illness, and the feasibility of a second MVR.

Adult

Rapid induction of the expression of proto-oncogene fos during human monocytic differentiation.

The differentiation into macrophages of the monocytic cell line U-937 or the monomyelocytic cell line HL-60 induced by phorbol esters is accompanied by a rapid induction of the expression of the proto-oncogene c-fos. Maximal levels of c-fos gene transcripts accumulate within 20-30 min following induction. By 2 hr, the c-fos-specific mRNA level drops 5 to 10 fold below that detected at 30 min after induction. The concentration of c-fos mRNA remains unchanged for the next 5 days, at which time over 99% of the viable precursor cells are converted to adherent macrophages. c-fos protein can be detected within 20 min of induction, reaching maximal levels by 40-60 min. Little or no c-fos protein is detected by 120-150 min after induction, even though c-fos mRNA remains detectable. Presence of cycloheximide leads to superinduction of c-fos mRNA transcripts. No c-fos gene transcripts are detected when the HL-60 cell line is induced with Me2SO to differentiate to granulocytes. A role for the c-fos protein is envisaged in the monocyte differentiation pathway.

Cell Differentiation