Future research directions in plant signal transduction mechanisms.

Photosynthesis is the ultimate driving force behind world food production. Modern agricultural practices have done much to maximize the benefits of photosynthesis through better land management and intensive crop breeding. However, enhancement in grain production is becoming increasingly dependent on biotechnology with every improvement becoming more difficult to achieve. With several crop species nearing the physical limits of grain production, more attention will be given to methods that enable farmers to consistently attain maximum yields. These efforts focus in part on how plants respond to the biotic and abiotic stresses that can significantly reduce potential yields, including the study of plant signal transduction pathways related to stress responses. Strong evidence is emerging that these pathways share many similarities to classical mammalian receptor systems including tyrosine-kinase receptors and G protein-coupled receptors. Several putative receptor-like proteins have been identified in maize and provide vast opportunities for studying plant signal transduction mechanisms. The elucidation of plant signaling pathways combined with modern technologies will not only serve to push harvest yields closer to the maximum theoretical levels but may also provide opportunities for actually increasing the theoretical maximum.

The effect of hospital volume on the in-hospital complication rate in knee replacement patients.

OBJECTIVE: To examine the effect of hospital volume on in-hospital surgical outcomes for knee replacement using six years of Medicare claims data. DATA SOURCES/STUDY SETTING: The data include inpatient claims for a 100 percent sample of Medicare patients who underwent primary knee replacement during 1985-1990. We supplemented these data with information from HCFA's denominator files, the Area Resource File, and the American Hospital Association survey files. STUDY DESIGN: We estimated the probability that a patient has an in-hospital complication in the initial hospitalization for the first primary knee replacement, using a Logit model, for three definitions of complication. The models controlled for hospital volume, other hospital characteristics, patient demographics, and patient health status. We tested for the endogeneity of hospital volume. DATA COLLECTION/EXTRACTION METHODS: A panel of two orthopaedic surgeons and two internists reviewed diagnosis codes to determine whether a complication was likely, possible, or due to anemia. After removing the few observations with bad or missing data, the final population has 295,473 observations. PRINCIPAL FINDINGS: The probability of a likely in-hospital complication declines rapidly from 53 through 107 operations per year, then levels off. Statistical tests imply that hospital volume is exogenous in this patient-level data. Complication rates increased steadily through the study period. Although obesity appeared to lower the probability of a complication, a counterintuitive result, further investigation revealed this to be an artifact of the claims data limit of listing no more than five diagnoses. Controlling for this restriction reversed the effect of obesity. CONCLUSIONS: Rather than uncontrolled expansion of knee surgery to small hospitals, decentralization to regional centers where at least about 50, and preferably about 100, operations per year are assured appears to be the optimal policy to reduce in-hospital complications.

Management of osteoarthritis of the knee by primary care physicians.

BACKGROUND: Most patients with osteoarthritis (OA) are treated by primary care physicians (in this article, primary care physicians are family physicians and general internists). OBJECTIVE: To describe and compare the self-reported practice patterns of family physicians and general internists for the evaluation and management of severe OA of the knee, including factors that might influence referral for total knee replacement. DESIGN, SETTING, AND PARTICIPANTS: A survey was developed and mailed to randomly selected community family physicians and general internists practicing in Indiana. MAIN OUTCOME MEASURE: Self-reported physician practice patterns regarding OA of the knee. RESULTS: Physical examination was the most common method of evaluating OA of the knee. Family physicians were more likely to examine for crepitation, joint stability, and quadriceps muscle strength than were general internists (P<.05). Patients with OA of the knee treated by family physicians were more likely to receive nonsteroidal anti-inflammatory drugs or oral corticosteroids and were less likely to receive aspirin, acetaminophen, or narcotics compared with patients treated by general internists. Six patient characteristics were rated as positive factors favoring a referral for possible total knee replacement, 8 characteristics were rated as negative, and 5 were rated as not a factor in the decision about referral. CONCLUSIONS: Results from this study suggest that additional research is needed to determine the evaluative techniques for OA of the knee that provide the most useful information for management decisions, the management techniques that maximize patient outcomes, and the criteria that should be used to select patients who would benefit most from referral for possible total knee replacement.

A pilot randomized trial comparing symptomatic vs. hemoglobin-level-driven red blood cell transfusions following hip fracture.

BACKGROUND: The indications for transfusion have never been evaluated in an adequately sized clinical trial. A pilot study was conducted to plan larger clinical trials. STUDY DESIGN AND METHODS: Hip fracture patients undergoing surgical repair who had postoperative hemoglobin levels less than 10 g per dL were randomly assigned to receive 1) symptomatic transfusion: that is, transfusion for symptoms of anemia or for a hemoglobin level that dropped below 8 g per dL or 2) threshold transfusion: that is, patients receive 1 unit of packed RBCs at the time of random assignment and as much blood as necessary to keep the hemoglobin level above 10 g per dL. Outcomes were 60-day mortality, morbidity, functional status, and place of residence. RESULTS: Among 84 eligible patients enrolled, mean (+/- SD) prerandomization hemoglobin was 9.1 (+/- 0.6) g/ dL. The median number of units transfused in the threshold transfusion group was 2 (interquartile range, = 1-2), and that in the symptomatic transfusion group was 0 (6; interquartile range, = 0-2) (p < 0.001). Mean hemoglobin levels were approximately 1 g per dL higher in the threshold group than in the symptomatic group: for example, on Day 2, 10.3 (+/- 0.9) g per dL versus 9.3 (+/- 1.2) g per dL, respectively (p < 0.001). At 60 days, death or inability to walk across the room without assistance occurred in 16 (39.0%) of the symptomatic transfusion group and 19 (45.2%) of the threshold transfusion group. Death occurred by 60 days in 5 (11.9%) of the symptomatic transfusion group and 2 (4.8%) in the threshold transfusion group (relative risk = 2.5; 95% CI, 0.5-12.2). Other outcomes were similar for the two groups. CONCLUSIONS: Symptomatic transfusion may be an effective blood-sparing protocol associated with the transfusion of appreciably fewer units of RBCs and lower mean hemoglobin levels than are associated with the threshold transfusion policy. However, it is unknown whether these two clinical strategies have comparable mortality, morbidity, or functional status. A definitive trial is needed.

Revision rates after knee replacement in the United States.

OBJECTIVES: Each year approximately 100,000 Medicare patients undergo knee replacement surgery. Patients, referring physicians, and surgeons must consider a variety of factors when deciding if knee replacement is indicated. One factor in this decision process is the likelihood of revision knee replacement after the initial surgery. This study determined the chance that a revision knee replacement will occur and which factors were associated with revision. METHODS: Data on all primary and revision knee replacements that were performed on Medicare patients during the years 1985 through 1990 were obtained. The probability that a revision knee replacement occurred was modeled from data for all patients for whom 2 full years of follow-up data were available. Two strategies for linking revisions to a particular primary knee replacement for each patient were developed. Predictive models were developed for each linking strategy. ICD-9-CM codes were used to determine hospitalizations for primary knee replacement and revision knee replacement. RESULTS: More than 200,000 hospitalizations for primary knee replacements were performed, with fewer than 3% of them requiring revision within 2 years. The following factors increase the chance of revision within 2 years of primary knee replacement: (1) male gender, (2) younger age, (3) longer length of hospital stay for the primary knee replacement, (4) more diagnoses at the primary knee replacement hospitalization, (5) unspecified arthritis type, (6) surgical complications during the primary knee replacement hospitalization, and (7) primary knee replacement performed at an urban hospital. CONCLUSIONS: Revision knee replacement is uncommon. Demographic, clinical, and process factors were related to the probability of revision knee replacement.

Differential down-regulation of alpha-2 adrenergic receptor subtypes.

The regulation of G protein-coupled receptor expression is important in the physiology of an organism and can occur at any of the steps between gene transcription to turnover of the receptor protein itself. Agonist stimulation causes receptor desensitization, which is characterized by a rapid reduction in response to the agonist. Down-regulation often occurs after prolonged agonist treatment and is manifested as a decrease in receptor density. Short term desensitization results from a rapid (in minutes) and reversible uncoupling of the receptor-G protein complex, followed by sequestration and/or internalization of receptors from the cell surface. Receptors are not degraded as removal of agonist rapidly restores receptor function. Down-regulation, on the other hand, displays a much longer time-course (hours to days) and is characterized by a decrease in receptor density as determined by radioligand binding. Removal of agonist will only slowly reverse down-regulation, because new receptor synthesis is required in most cases (1;2). The mechanism of receptor down-regulation is not well understood, but may include an accelerated rate of removal of receptors, a decrease in the rate of appearance of receptors, or both. Our previous studies have shown significant differences in the concentration of agonist required to produce down-regulation of alpha-2 adrenergic receptor subtypes (3;4). Here we review the mechanisms and molecular determinants for receptor down-regulation as well as our own data exploring the subtype-specific differences in alpha-2 receptor down-regulation. We find that the extent and time-course of agonist-induced down-regulation occurs in a similar fashion regardless of the receptor subtype or the cell line in which it is expressed. The mechanism for receptor down-regulation in all cases is an increase in the rate of receptor disappearance.

Patient outcomes after knee replacement.

A prospective, observational cohort investigation was performed to help understand the impact of knee replacement on patients with knee osteoarthritis in community practice. Of those, 291 patients (330 knees) were eligible and willing to participate. Forty-eight orthopaedic surgeons referred 563 patients from 25 institutions within the state of Indiana. Demographics, patient completed health status, satisfaction, independent radiographic measures, surgeon reported intraoperative factors, hospital discharge factors, and independent physical examinations were recorded. A minimum 2-year followup was obtained in 92% of the patients. At followup, 88% were satisfied, 3% were neutral, and 9% were dissatisfied with the results of their knee surgery. The physical composite score improved from 27.4 +/- 0.4 (range, 13.3-50.3) to 37.7 +/- 0.7 (range, 12.9-61.3) at two years. Maximal improvement in physical composite score was seen in patients who had their surgery performed in institutions that performed greater than 50 knee replacements per year in patients with Medicare insurance; who had a better mental health status at baseline; who had surgery performed on Monday, Friday, or Saturday; who were older; who were treated with a posterior cruciate sparing device; and who had worse preoperative function. A lower likelihood of complications were found with surgeons who performed greater than 20 knee replacements per year; midweek surgeries; in patients with more severe preoperative knee dysfunction; patients with fewer comorbidities; patients with less preoperative stiffness; patients being treated by younger surgeons; and in patients undergoing unilateral knee replacement. Among voluntarily participating physicians, knee replacement can be a highly effective medical technology with high levels of patient satisfaction and low rates of complications.

Mechanism of down-regulation of alpha-2 adrenergic receptor subtypes.

Long-term exposure to agonist down-regulates receptor expression for many G protein-coupled receptors. This decrease in receptor density could occur through either an increase in receptor degradation or a decrease in receptor synthesis. We studied the mechanism of down-regulation of the alpha-2A and alpha-2B adrenergic receptor subtypes transfected into the Chinese hamster ovary cell line as well as the alpha-2A receptor endogenous to the HT29 cell line. The rate constants for receptor appearance and disappearance were calculated from the recovery of receptor expression after irreversible inactivation of the existing receptor population with an alkylating agent. In the presence of the agonist norepinephrine, the receptor subtypes in all three cell lines down-regulated to about 50% with a half-time of 2.5 hr. When recovering in the presence of norepinephrine after irreversible inactivation, the rate of receptor degradation increased approximately 2-fold for all three cell lines with little change in the rate of synthesis. During this recovery, the transfected alpha-2A receptor exhibited a half-life of 3.0 hr, which agrees with the 2.7-hr half-time of down-regulation in the presence of norepinephrine. In contrast, the transfected alpha-2B receptor and the endogenous alpha-2A receptor had a half-life of 1.2 hr and 8.9 hr, respectively. For only the endogenous alpha-2A receptor, pertussis toxin increased the half-time of down-regulation to 9.8 hr, similar to the 8.9-hr receptor half-life in the presence of norepinephrine during recovery after irreversible inactivation. Our results indicate that the mechanism of down-regulation of the alpha-2A and -2B adrenergic receptor subtypes is an increase in the rate of receptor degradation.

In vivo observations of hydraulic stiffening in the canine femoral head.

The role that intertrabecular contents and their boundary conditions have on the dynamic mechanical response of canine femoral heads was investigated in vivo. Femoral heads from paired intact hind limbs of canine specimens were subjected to a sinusoidal strain excitation at physiologic frequencies, in the cranio-caudal direction. The fluid boundary conditions for the contralateral limbs were changed by predrilling through the lateral femoral cortex and into the femoral neck. The drilling procedure did not invade the head itself. This femoral head fluid boundary alteration reduced the stiffness by 19 percent for testing at 1 Hz. The results of this study demonstrate that fluid stiffening occurs in vivo as previously observed ex vivo.

Demographic variation in the rate of knee replacement: a multi-year analysis.

OBJECTIVE: The aim of this study is to describe the practice variation of knee replacements (KRs) in the elderly ( > or = 65) over time from 1985-1990 in terms of the number of primary, bilateral, and revision KRs; the extent of large area variation in performance rates; and the degree to which demographic variables are the determinants of area rates. DATA SOURCES/STUDY SETTING: Data analyzed are from every hospital in the United States that performed a KR on a Medicare patient during the study period. Data were obtained from the MEDPAR, HISKEW, and denominator files of the Medicare Statistical System. STUDY DESIGN: This is a cohort study of all Medicare beneficiaries who received a KR between 1985 and 1990. The dependent variable in the analyses was the count of the KRs performed in each area. DATA COLLECTION/EXTRACTION METHODS: This is a population-based sample of Medicare enrollees in the United States. All hospitalizations for Medicare-reimbursed KRs were included in the initial data set. Exclusion criteria were used to identify the Medicare covered population with a definite KR. These criteria resulted in 7.3 percent exclusions and a final set of 414,079 KR hospitalizations. PRINCIPAL FINDINGS: The number of Medicare-funded KRs increased in each of the study years corresponding to an annual rate of increase of 18.45 percent. The likelihood of receiving a KR was a function of age, gender, and race. For each year, KRs were almost-twice as likely to be performed on women than on men. The odds of whites getting the surgery were over 1.5 times greater than for blacks. Even after adjusting for demographic factors, significant regional variation remained. CONCLUSIONS: Much about area variation and the rate of growth in KR rates remains unexplained. For answers to emerge, better data and different types of studies are required.

Prosthetic component failures in hip arthroplasty surgery.

A survey was conducted of the entire membership of the American Association of Hip and Knee Surgeons to determine their experience with total hip arthroplasty (THA) device-related failures. Forty-seven percent of the membership reviewed their preceding 5-year clinical experience and returned the survey instrument. The aggregate 5-year volume encompassed experience with more than 60,000 hip arthroplasties. The median 5-year experience per respondent was 200 metal-based sockets and 214 metal stems. The frequency distribution of the number of hip arthroplasties per respondent was skewed to the right, with fewer surgeons reporting the higher volumes of arthroplasties. In aggregate, 60,115 of the acetabular components used were metal backed. Nonmetal acetabular component usage totaled 3,219. Complete polyethylene failure was defined as fracture or complete wear through of the polyethylene portion of the component. Complete polyethylene failure was seen in 172 metal-backed sockets (29/10,000). Seventy-seven all-polyethylene sockets had complete polyethylene failure (239/10,100). A total of 87 THAs were revised for modular acetabular dissociations for a dissociation rate of 15/10,000. In aggregate, 64,483 metal-stemmed components were used. Femoral stem fractures occurred in 172 for a rate of 27/10,000. A total of 56,965 metallic femoral components were reported as being modular. Dissociation between the femoral head and neck was uncommonly seen (3/10,000). Use of ceramic femoral heads was low (5,023); however, a total of 11 ceramic head fractures were revised in the 5-year period for a failure rate of 22/10,000. The risks of catastrophic prosthetic THA failure are low but vary according to hip component and the manufacturer of the part.

Patient outcomes following unicompartmental or bicompartmental knee arthroplasty. A meta-analysis.

The purpose of this study was to summarize the literature describing patient outcomes following unicompartmental and bicompartmental knee arthroplasty. Original studies were included in this meta-analysis if they enrolled 10 or more patients at the time of an initial knee arthroplasty and measured patient outcomes using a global knee rating scale. Forty-six studies on unicompartmental prostheses and 18 studies on bicompartmental prostheses met these criteria. For unicompartmental studies, the total number of enrolled patients was 2,391, with a mean enrollment of 47 patients and a mean follow-up period of 4.6 years. The mean patient age was 66 years; 67% were women, 75% had osteoarthritis, and 16% underwent bilateral knee arthroplasty. The mean postoperative global rating scale score was 80.9. The overall complication rate was 18.5% and the revision rate was 9.2%. Studies published after 1987 reported better outcomes, but also tended to enroll older patients and patients with osteoarthritis and higher preoperative knee rating scores. For bicompartmental studies, the total number of enrolled patients was 884, with a mean enrollment of 44 patients and a mean follow-up period of 3.6 years. The mean patient age was 61 years; 79% were women, 31% had osteoarthritis, and 29% underwent a bilateral arthroplasty. The mean postoperative global rating scale score was 78.3. The overall complication rate was 30% and the revision rate was 7.2%. Although bicompartmental studies reported lower mean postoperative global rating scale scores, these studies tended to enroll patients with worse preoperative knee rating scores. Recent improvements in patient outcomes following unicompartmental knee arthroplasty appear to be due, at least partially, to changes in patient selection criteria. Patient outcomes appear to be worse for bicompartmental arthroplasties than for other prosthetic designs; however, patients enrolled in these studies had more poorly functioning knees before surgery and actually had greater absolute improvements in global knee rating scores.

A biomechanical comparison of techniques of flexor tendon repair.

Achieving satisfactory digital motion after suturing severed flexor tendons remains a challenge. Although a suture technique proposed by Savage is stronger in vitro than a true Kessler repair, the Savage technique has not been previously tested in vivo. We repaired 96 severed canine tendons using either of two modifications of the Kessler technique or the Savage technique. The tensile strength of these repairs were compared at 0, 1, 3, and 6 weeks after suturing. The Savage technique provided a significantly stronger repair than the "suture locking" method in vitro and at 1 and 3 weeks after repair. We found no significant differences between the tensile strengths of the Kessler-Tajima and suture-locking methods at any time.

Tricompartmental knee replacement. A comparison of orthopaedic surgeons' self reported performance rates with surgical indications, contraindications, and expected outcomes. Knee Replacement Patient Outcomes Research Team.

The chance of a person with osteoarthritis of the knee receiving a knee replacement is highly variable. To understand better the reasons for this variation, all practicing orthopaedists in Indiana were surveyed about their management of severe knee osteoarthritis and their perception of tricompartmental knee replacement as a therapeutic option. Their perceptions of indications and outcomes of knee replacement were compared with the self reported annual number of patients for whom they performed (or referred to other surgeons for) tricompartmental knee replacements. A completed survey was returned by 220 (79%) of the 280 orthopaedists surveyed; analyses were limited to the 188 respondents who had cared for at least one patient with osteoarthritis of the knee in the prior 2 weeks (mean = 13). These surgeons reported performing (or referring patients for) a mean of 31 knee replacements in the prior year (SD 45, median 21, range 0-480 knee replacements). There was strong agreement (> 95%) among respondents for seven (21%) of 33 surgical indications and contraindications, and more general agreement (> 60%) for 21 (64%). In the five factors (15%) for which there was disagreement, there was no consistent relationship between opinions and self reported knee replacement performance rate. Surgeons reporting more knee replacements had significantly higher estimates of pain relief and functional improvement following surgery, and lower estimates of prosthesis infection and failure rates. When all responses were considered together, four decision factors correlated independently with the performance of more knee replacements, but these four factors explained only 24% of the variation in self reported knee replacement performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Deliberations on the dissemination of PORT products: translating research findings into improved patient outcomes.

This report outlines the activities undertaken by the Inter-PORT Dissemination work group during its first 2 years of operation. The work group's initial purpose was to assist the individual PORTs in developing their plans for both disseminating research findings and evaluating the effectiveness of these strategies. However, it became quickly apparent that in a discipline little more than a decade old, a commonly understood vocabulary had yet to be adopted. Even the term "dissemination" held different meaning for different constituencies. Consequently, the work group has tried to encourage the development of both a definitional framework and a set of common data elements of importance to all dissemination programs. The work group has analogously attempted to agree on minimum standards of methodologic rigor as a starting point for coordination of evaluations across PORTs. To help determine the potential for further coordination, a matrix of each individual PORT's target audiences, intervention strategies, and evaluation designs has been constructed. Much remains to be learned before we can know with any certainty how best to translate research findings into useful behavior change and improved patient outcomes. Our goal is that the efforts of the work group will serve to catalyze this process.

Patient outcomes following tricompartmental total knee replacement. A meta-analysis.

OBJECTIVE: To provide estimates of patient outcomes following tricompartmental knee replacement and to examine variation in outcomes due to patient and prosthesis characteristics. DATA SOURCES: English-language articles identified through a computerized literature search and bibliography review. STUDY SELECTION: Studies were included if they enrolled 10 or more patients at the time of initial knee replacement and measured patient outcomes using a global knee-rating scale. DATA EXTRACTION: Each study was subjected to a blinded qualitative assessment and unblinded abstraction of patient characteristics, surgical techniques, and outcomes. DATA SYNTHESIS: A total of 130 studies reporting patient outcomes on 154 cohorts satisfied inclusion criteria. The total number of enrolled patients was 9879 with a mean enrollment of 64.1 patients. The mean follow-up was 4.1 years. The mean patient age was 65.0 years, 71.7% of patients were women, 62.6% had osteoarthritis, and 26.6% underwent bilateral knee replacement. Global rating scale scores improved by 100% for the typical enrolled patient, and 89.3% of patients reported good or excellent outcomes. Anatomic classification of the prosthesis, percentage of enrolled patients with osteoarthritis, publication year, and number of enrolled patients explained 27% of the variation in reported mean postoperative global rating scale scores. The weighted mean complication rate was 18.1%, and the mean mortality rate per year of follow-up was 1.5%. The overall rate of revision during 4.1 years was 3.8%. CONCLUSIONS: Tricompartmental knee replacement was a safe and effective procedure for the patients reported in these studies. The knee pathology and the type of prosthesis were significant predictors of outcomes. Limitations in the reporting style of these articles severely constrain the ability to explore variation in outcomes due to study, patient, or prosthesis characteristics and restrict their generalizability.

Molecular determinants of the alpha-2D adrenergic receptor subtype.

The alpha-2 adrenergic receptor in the bovine pineal gland and the rodent homologues of the human alpha-2-C10 receptor express alpha-2D subtype pharmacological characteristics. The alpha-2 adrenergic receptor in the chicken pineal expresses characteristics similar to the alpha-2A subtype found in human and pig. The rodent receptors (alpha-2D) contain a serine residue at position 201 whereas the human and porcine receptors (alpha-2A) have a cysteine at this position. Our results indicate that the bovine pineal receptor has a serine at position 201, supporting the alpha-2D classification. However, the chicken pineal receptor also contains a serine at position 201 suggesting that other amino acids may be responsible for the differences in pharmacological characteristics.

Unicompartmental knee arthroplasty. A multicenter investigation with long-term follow-up evaluation.

Nonmental-backed, cemented, unicompartmental knee arthroplasty has a survivorship rate in this multicenter investigation at ten years of 91.4% (+/- 2.8). High levels of patient weight were associated with increased need for revision arthroplasty. Overall, men had a lower revision rate (2.4%) compared with women (3.9%). Valgus postoperative alignment was minimally associated with progression of disease as a cause for revision. No difference in revision rates between medial and lateral compartmental arthroplasty was noted. The theoretical clinical benefits of the use of metal-backed tibial components will need to be reevaluated in light of these findings.