Characterization of the tryptophan fluorescence and hydrodynamic properties of rat DNA polymerase beta.

We have examined the biophysical properties of DNA polymerase beta (beta-pol) in solution. Time-resolved and steady-state fluorescence were used to investigate the microenvironment of the lone tryptophanyl residue (Trp324), and a combination of sedimentation equilibrium, sedimentation velocity and fluorescence anisotropy decay measurements were used to study the hydrodynamic properties of the enzyme. Trp324 appears to be exposed to water as judged by the tryptophan emission and steady-state and lifetime quenching experiments. The fluorescence is easily quenched by a neutral quencher acrylamide (kq = 1.59 x 10(9)M-1S-1), and by a negatively charged ionic quencher, I- (kq = 1.60 x 10(9) M-1S-1), but not by a positively charged ionic quencher, Cs+ (kq = 0.2 x 10(9) M-1S-1). The fluorescence lifetime of beta-pol is best described by the sum of two exponentials with a longer lifetime component of 8.4 ns and a shorter lifetime component of 1.3 ns. Decay associated spectra (DAS) show emission maxima at 340 nm and at 345 nm for the shorter lifetime and longer lifetime components, respectively, with corresponding centers of gravity at 347 nm and 348 nm. Sedimentation equilibrium experiments show that the enzyme exists as a monomer at the KCl concentrations (> 0.05 M) studied in the absence of divalent metals. Zn2+ causes higher order aggregation, but no such aggregates are seen with Mg2+ and Mn2+. In the presence of 1 mM manganese, the average lifetime decreased approximately 10%, from 8.14 ns to 7.38 ns, with a concomitant increase of average rotational correlational time (phi) from 24 ns to 28 ns. The accessibility of the positively charged quencher (Cs+) to tryptophan also decreases approximately 50%, indicating alteration of the tryptophan microenvironment. By contrast, Mg2+ causes minor changes in fluorescence properties. The hydrodynamic shape of the intact enzyme and its single-stranded (8 kDa) and double-stranded (31 kDa) DNA binding domains were further investigated by sedimentation velocity measurements. The value of S0(20),W for the intact enzyme is 2.97 S, and the calculated axial ratio is 5.0. In contrast to the 8 kDa domain, which has a less asymmetric shape with an axial ratio of 2.3, the 31 kDa domain shows an elongated structure with an axial ratio of 5.5. These data suggest that the axial ratio of the intact enzyme may be the result of marked bending of the molecule at the flexible hinge region between the two domains.

Massive hemoptysis in cystic fibrosis.

Massive hemoptysis occurs in 5% to 7% of patients with cystic fibrosis. Approximately 11% of these patients will die within 48 hours of manifestation because of uncontrolled hemoptysis and asphyxiation. If conservative medical treatment fails to control hemoptysis, fiberoptic or rigid bronchoscopy is the least risky and most accurate method of localizing the source of hemoptysis. Acute control of hemoptysis can be obtained in up to 100% of patients with endobronchial Fogarty balloon tamponade and in up to 88% of patients with bronchial artery embolization. Emergency thoracotomy can be performed if the above fail, but only in patients with mild cystic fibrosis and adequate pulmonary reserve.

Intravenous therapy team and peripheral venous catheter-associated complications. A prospective controlled study.

A prospective controlled trial was conducted on four similar inpatient medical wards to test the hypothesis that a trained intravenous therapy (IVT) team would substantially reduce the incidence of peripheral intravenous (IV) catheter-related complications. We followed 863 IV catheters. The overall incidence of phlebitis in the ward staff-maintained IV catheters was 32% as compared with 15% for those maintained by the IVT team. The incidence of two more serious complications (cellulitis and suppurative phlebitis) was reduced tenfold from 2.1% to 0.2%. We conclude that an IVT team can substantially reduce the iatrogenic complications related to IV catheters.

The natural history of intravenous catheter-associated phlebitis.

During a controlled evaluation of an intravenous therapy (IVT) team, we had the opportunity to follow up 202 episodes of catheter-associated phlebitis. While the IVT team had a considerable effect on the incidence of phlebitis, the clinical course of this complication was not influenced. More than 40% of catheter-associated phlebitis occurred more than 24 hours after withdrawal of the catheter. Premonitory symptoms were not useful in predicting the development of phlebitis. Factors that influenced the duration of phlebitis included the patient's diagnosis and the administration of vancomycin hydrochloride. The duration of phlebitis was prolonged by delayed removal of the catheter after the development of phlebitis.

Emergency lobectomy for massive hemoptysis in cystic fibrosis.

Massive hemoptysis occurs in 50% to 70% of patients with cystic fibrosis and carries an immediate mortality of up to 32%. Cystic fibrosis is regarded by many as a disease in which thoracic operations are ill-advised. A 21-year-old woman with mild cystic fibrosis presented with unrelenting massive hemoptysis, was not helped by medical management, and underwent a successful left upper lobectomy. We suggest that thoracotomy does have a role in the management of massive hemoptysis in selected patients with cystic fibrosis. On the basis of our case and all other cases reported in the English literature, we suggest criteria for determining which patients are suitable candidates for emergency thoracotomy.

Staging of non-small cell bronchogenic carcinoma. Relationship of the clinical evaluation to organ scans.

Organ scans are generally performed on patients with bronchogenic carcinoma only when clinical evaluation is suspicious for metastases. However, it is not clear whether the clinical abnormalities will direct attention to the single organ which should be scanned, or if all three organs (bone, brain, liver) should be evaluated if any clinical abnormality is present. We investigated the use of triple organ radionuclide scanning and computerized tomography (CT) of the brain in the initial staging of patients with non-small cell bronchogenic carcinoma with no obvious metastases. Of 122 patients with newly diagnosed lung cancer, 53 met our criteria for further study. Thirty-three (62 percent) of these had at least one clinical abnormality suggestive of metastasis. Bone scanning detected metastases in seven (21 percent) and head CT in two additional patients (6 percent). Brain and liver scanning had no yield. In only five of these nine patients did the clinical abnormality direct attention to the organ with detectable metastases. Twenty of the 53 (38 percent) patients had a negative routine clinical evaluation, yet bone scanning showed metastases in three (15 percent). We concluded that clinical abnormalities are not specific for the organ in which metastases may be detected, so three scans (bone, liver, CT of the brain) should be obtained if there is any suspicion of metastasis based on history, physical examination, and laboratory tests. The value of bone scanning in clinically normal patients deserves further study.

Reduction of anti-inflammatory drug costs with newer aspirin formulations.

Anti-inflammatory/analgesic drugs account for a large proportion of prescriptions and prescribing costs, particularly for ambulatory patients. Although aspirin is highly effective, 95% of anti-inflammatory/analgesic prescriptions have been for the newer, more expensive alternatives. Recently two newer aspirin formulations were made available on our hospital's formulary. Subsequently aspirin prescribing rose from 5% to 14.5% (P less than 0.0005), and mean pharmacy costs for anti-inflammatory analgesics fell 5.9% over a 7-month period (P less than 0.025). This decline in costs interrupted a historic trend toward increased prescription costs and was accomplished with minimal effort or hospital resources. Increased availability and familiarity with these newer aspirin formulations may substantially reduce costs for the health care system.

Influence of simple computerized feedback on prescription charges in an ambulatory clinic. A randomized clinical trial.

Pharmaceuticals account for a significant portion of health care costs and are an important target for attempts at cost reductions. While many techniques have been shown effective, most are resource-intensive, have demonstrated fatigue after the intervention is ceased, and have been directed at specific items rather than total charges. The authors designed a computerized program to feed back prescription charges. The intervention is easy to execute, inexpensive, and can be maintained indefinitely. The intervention was performed in a randomized, prospective, controlled trial with the medical residents of a large county hospital. The goal was to reduce total prescribing charges and produce a meaningful financial result. The intervention reduced the mean charge for a prescription by 6.7% (P less than 0.025), but with a long latent period and minimal impact on resident knowledge of drug charges. Significant differences were seen only at the end of the study. The program was viewed positively by the residents. The low cost of the intervention yielded a benefit-to-cost ratio in excess of 50:1. Because of computerization and ongoing patient and resident randomization at the study hospital, added costs of this randomized trial in terms of computer time and research assistance were less than $1,000.

Actobindin induces the accumulation of actin dimers that neither nucleate polymerization nor self-associate.

Actobindin purified from Acanthamoeba castellanii inhibits the nucleation, but not the elongation, phase of actin polymerization. Previously, we had speculated that actobindin, which can simultaneously bind two actin monomers (Bubb, M.R., Lewis, M.S., and Korn, E.D. (1991) J. Biol. Chem. 266, 3820-3826), might preferentially interact with small oligomers and inhibit their ability to elongate (Lambooy, P.K., and Korn, E.D. (1988) J. Biol. Chem. 263, 12836-12843). In the accompanying paper (Bubb, M.R., Lewis, M.S., and Korn, E.D. (1994) J. Biol. Chem. 269, 25587-25591), we show that under non-polymerizing conditions, actobindin binds to covalently cross-linked actin dimers with higher affinity than to two actin monomers. The sedimentation velocity and fluorescence anisotropy experiments described in this paper show that actobindin prevents the formation of actin oligomers larger than an actin dimer under conditions in which, in the absence of actobindin, actin rapidly polymerizes to F-actin with no detectable small oligomers. Moreover, the molar concentration of actin dimer formed in the presence of actobindin can exceed the total actobindin concentration. These results indicate that actobindin does not form a stable complex with native actin dimer but, rather, causes the accumulation of dimers that are unable to nucleate polymerization or self-associate.

A randomized controlled trial of academic group practice. Improving the operation of the medicine clinic.

We conducted a controlled trial of the adoption of a group-practice model within an academic department of medicine. Ongoing randomization yielded similar groups of patients and residents. To determine the effect of the intervention on medicine-clinic operation, we monitored the hospital outpatient activity of 28 residents and 2299 patients during an 11-month study period. The group-practice clinics generated 20% more patient encounters per month than did the traditional, control clinics (328 vs 273 encounters), primarily because twice as many voluntary, overflow clinic sessions were scheduled (20.2 vs 9.7 sessions). Yet, because group-practice registration was decentralized, patients spent 15% less time in completing scheduled visits (93.2 vs 109.9 minutes). Regular utilizers of the group practices made 7% more scheduled clinic visits on average (3.27 vs 3.05 visits), but 39% fewer walk-in visits (0.14 vs 0.23 visits). Hospital-wide, continuity of care was not affected. We conclude that adoption of a group-practice model at our institution improved clinic productivity, enhanced patient flow, and decreased unscheduled clinic visits.

Effect of an academic group practice on patient show rates: a randomized controlled trial.

Ambulatory medical clinics at academic centers are reputed to be expensive, inefficient, and poorly regarded by the medical residents who staff them. In an effort to address these problems, some centers have reorganized their traditional clinics into group practices. These group practices are thought to be more effective for teaching and providing services than are the traditional clinics. This is a report on the results of a study in which the authors reorganized two of four firm clinics into group practices in order to test the influence of the organizational changes on the various aspects of ambulatory care. During this controlled prospective trial of the group practice model, higher show rates were observed for patients in the group practices than in the traditional clinics (70% vs 65%, P less than 0.0005). The possible reasons for the higher rates are discussed.

Academic group practice. The patient's perspective.

The effect upon patient satisfaction of a reorganization of a traditional medical clinic into a group practice model was examined in a controlled trial in which both patients and physicians were randomized. The group practice model, unlike the traditional clinic, provided decentralized registration, 5 days/week clinic coverage, and night/weekend phone coverage. Residents worked in small groups with an attending physician, a nurse practitioner, and a receptionist. This reorganization resulted in a substantial decrease in charges and utilization for patients in the experimental group. A panel of 302 patients was interviewed prior to the reorganization and 1 year later. Patients in the experimental groups perceived improvements in access to their physicians as well as decreases in clinic waiting time and decreases in the lag time between requesting and obtaining an appointment. General health perceptions and other satisfaction measures were unchanged. The authors conclude that a group practice organization can result in decreased patient charges without substantially altering patient satisfaction.

The cost implications of academic group practice. A randomized controlled trial.

We evaluated the reorganization of a general medical clinic into several group practices, using equivalent groups of patients and physicians in a randomized controlled trial. The group practice, unlike the traditional clinic, provided decentralized registration, clinic coverage five days a week, and telephone coverage at night and on weekends. Residents worked in small groups with an attending physician, nurse practitioner, and receptionist. All financial activity involving a sample of 2299 patients was followed during the 11-month intervention. The total hospital charges per patient were 26 percent lower for the patients seen in the group practice than for those seen in the traditional clinic (P = 0.003). This difference was primarily attributable to inpatient charges, which were 27 percent lower per patient hospitalized (P = 0.004). The mean length of stay was 8.3 days among group-practice patients and 10.5 days among traditional-clinic patients (P = 0.011). We conclude that organizational changes to improve outpatient access and to integrate inpatient and outpatient services can decrease medical charges.

Academic group practice. The physicians' view.

In order to evaluate physician response to the reorganization of a traditional medical clinic into a group practice model, a randomized controlled trial was conducted using equivalent groups of patients and physicians. The group practice model, unlike the traditional clinic, provided decentralized registration, 5 days/week clinic coverage, and night/weekend phone coverage. Residents worked in small groups with an attending physician, nurse practitioner, staff nurse, and receptionist. A panel of 50 medical residents was interviewed prior to the reorganization and 1 year later. Residents in the experimental groups perceived improvements in the ancillary staff, placed a higher value on informal discussion of patient management problems, and were more satisfied with the outpatient experience. Moreover, residents in the group practices were more likely to voluntarily schedule additional clinic sessions to accommodate their patients. No change was noted in their career choices. We conclude that reorganization of a traditional medical clinic into a group practice model can result in increased physician satisfaction although it may not have a major impact on long-term career goals.

Capreomycin kinetics in renal impairment and clearance by hemodialysis.

The single-dose kinetics of capreomycin are described for 12 renal patients and seven healthy control subjects. Creatinine clearances (CrCl) ranged from zero to 121 ml/min. After single-dose intravenous infusions, mean +/- SD capreomycin clearance values (L/kg/h x 10(-2)) were 0.558 +/- 0.160 for the dialysis group (n = 4, CrCl = 1.4 +/- 1.9), 1.77 +/- 0.45 for the moderate renal group (n = 3, CrCl = 25 +/- 5), 2.82 +/- 1.52 for the mild renal group (n = 4, CrCl = 46 +/- 5), and 5.73 +/- 1.54 for the normal renal group (n = 7, CrCl = 109 +/- 11); p less than 0.01, using analysis of variance. The correlation between capreomycin clearance and CrCl was r = 0.90. Hemodialysis cleared clinically significant amounts of capreomycin. These data imply that capreomycin maintenance doses need to be reduced for renal patients.