Mathematical modelling of Pseudomonas aeruginosa biofilm growth and treatment in the cystic fibrosis lung.

Lung failure due to chronic bacterial infection is the leading cause of death for patients with cystic fibrosis (CF). It is thought that the chronic nature of these infections is, in part, due to the increased tolerance and recalcitrant behaviour of bacteria growing as biofilms. Inhalation of silver carbene complex (SCC) antimicrobial, either encased in polymeric biodegradable particles or in aqueous form, has been proposed as a treatment. Through a coordinated experimental and mathematical modelling effort, we examine this proposed treatment of lung biofilms. Pseudomonas aeruginosa biofilms grown in a flow-cell apparatus irrigated with an artificial CF sputum medium are analysed as an in vitro model of CF lung infection. A 2D mathematical model of biofilm growth within the flow-cell is developed. Numerical simulations demonstrate that SCC inactivation by the environment is critical in aqueous SCC, but not SCC-polymer, based treatments. Polymer particle degradation rate is shown to be an important parameter that can be chosen optimally, based on environmental conditions and bacterial susceptibility.

Modeling the response of a biofilm to silver-based antimicrobial.

Biofilms are found within the lungs of patients with chronic pulmonary infections, in particular patients with cystic fibrosis, and are the major cause of morbidity and mortality for these patients. The work presented here is part of a large interdisciplinary effort to develop an effective drug delivery system and treatment strategy to kill biofilms growing in the lung. The treatment strategy exploits silver-based antimicrobials, in particular, silver carbene complexes (SCC). This manuscript presents a mathematical model describing the growth of a biofilm and predicts the response of a biofilm to several basic treatment strategies. The continuum model is composed of a set of reaction-diffusion equations for the transport of soluble components (nutrient and antimicrobial), coupled to a set of reaction-advection equations for the particulate components (living, inert, and persister bacteria, extracellular polymeric substance, and void). We explore the efficacy of delivering SCC both in an aqueous solution and in biodegradable polymer nanoparticles. Minimum bactericidal concentration (MBC) levels of antimicrobial in both free and nanoparticle-encapsulated forms are estimated. Antimicrobial treatment demonstrates a biphasic killing phenomenon, where the active bacterial population is killed quickly followed by a slower killing rate, which indicates the presence of a persister population. Finally, our results suggest that a biofilm with a ready supply of nutrient throughout its depth has fewer persister bacteria and hence may be easier to treat than one with less nutrient.

Nanoparticle deposition onto biofilms.

We develop a mathematical model of nanoparticles depositing onto and penetrating into a biofilm grown in a parallel-plate flow cell. We carry out deposition experiments in a flow cell to support the modeling. The modeling and the experiments are motivated by the potential use of polymer nanoparticles as part of a treatment strategy for killing biofilms infecting the deep passages in the lungs. In the experiments and model, a fluid carrying polymer nanoparticles is injected into a parallel-plate flow cell in which a biofilm has grown over the bottom plate. The model consists of a system of transport equations describing the deposition and diffusion of nanoparticles. Standard asymptotic techniques that exploit the aspect ratio of the flow cell are applied to reduce the model to two coupled partial differential equations. We perform numerical simulations using the reduced model. We compare the experimental observations with the simulation results to estimate the nanoparticle sticking coefficient and the diffusion coefficient of the nanoparticles in the biofilm. The distributions of nanoparticles through the thickness of the biofilm are consistent with diffusive transport, and uniform distributions through the thickness are achieved in about four hours. Nanoparticle deposition does not appear to be strongly influenced by the flow rate in the cell for the low flow rates considered.

ZNF217, a candidate breast cancer oncogene amplified at 20q13, regulates expression of the ErbB3 receptor tyrosine kinase in breast cancer cells.

Understanding the mechanisms underlying ErbB3 overexpression in breast cancer will facilitate the rational design of therapies to disrupt ErbB2-ErbB3 oncogenic function. Although ErbB3 overexpression is frequently observed in breast cancer, the factors mediating its aberrant expression are poorly understood. In particular, the ErbB3 gene is not significantly amplified, raising the question as to how ErbB3 overexpression is achieved. In this study we showed that the ZNF217 transcription factor, amplified at 20q13 in ∼20% of breast tumors, regulates ErbB3 expression. Analysis of a panel of human breast cancer cell lines (n = 50) and primary human breast tumors (n = 15) showed a strong positive correlation between ZNF217 and ErbB3 expression. Ectopic expression of ZNF217 in human mammary epithelial cells induced ErbB3 expression, whereas ZNF217 silencing in breast cancer cells resulted in decreased ErbB3 expression. Although ZNF217 has previously been linked with transcriptional repression because of its close association with C-terminal-binding protein (CtBP)1/2 repressor complexes, our results show that ZNF217 also activates gene expression. We showed that ZNF217 recruitment to the ErbB3 promoter is CtBP1/2-independent and that ZNF217 and CtBP1/2 have opposite roles in regulating ErbB3 expression. In addition, we identify ErbB3 as one of the mechanisms by which ZNF217 augments PI-3K/Akt signaling.

Covalent and noncovalent interactions mediate metabotropic glutamate receptor mGlu5 dimerization.

Some, perhaps all, G protein-coupled receptors form homo- or heterodimers. We have shown that metabotropic glutamate receptors are covalent dimers, held together by one or more disulfide bonds near the N terminus. Here we report how mutating cysteines in this region affect dimerization and function. Covalent dimerization is preserved when cysteines 57, 93, or 99 are mutated but lost with replacement at 129. Coimmunoprecipitation under nondenaturing conditions indicates that the C[129]S mutant receptor remains a dimer, via noncovalent interactions. Both C[93]S and C[129]S bind [3H]quisqualate, whereas binding to C[57]S or C[99]S mutants is absent or greatly attenuated. The C[93]S and C[129]S receptors have activity similar to wild-type when assayed by fura-2 imaging of intracellular calcium in human embryonic kidney cells or electrophysiologically in Xenopus laevis oocytes. In contrast, C[57]S or C[99]S are less active in both assays but do respond with higher glutamate concentrations in the oocyte assay. These results demonstrate that 1) covalent dimerization is not critical for mGlu5 binding or function; 2) mGlu5 remains a noncovalent dimer even in the absence of covalent dimerization; and 3) high-affinity binding requires Cys-57 and Cys-99.

Development of a screen for predicting clinical outcomes in patients with work-related upper extremity disorders.

This study prospectively examined the extent to which a set of medical, physical, ergonomic, occupational psychosocial, and individual psychosocial variables would predict clinical outcome associated with a diverse set of work-related upper extremity disorders in recently diagnosed individuals. This investigation was designed to develop a tool for use in a clinical setting to assist in identifying patients at risk for poorer outcome. Outcome was measured at 1, 3, and 12 months after completing a baseline questionnaire. Outcome status was based on a median split of a standardized composite index (symptoms, function, workdays lost, and mental health). Logistic regression indicated that predictors of poorer outcome at 1 month were: upper extremity comorbidity (risk ratio [RR], 1.58), pain severity (RR, 1.45), ergonomic risk exposure (RR, 1.07), low job support (RR, 1.03), and pain coping style (RR, 1.54). At 3 months, poorer outcome was predicted by: symptom severity (RR, 10.46), job stress (RR, 1.20), and pain coping style (RR, 1.98). The number of prior treatments/providers (RR, 1.77), past recommendation for surgery (RR, 6.43), and pain coping style were found to predict poorer outcome at 12 months. Sensitivity and specificity, respectively, for the models were 77.4% and 71.8% at 1 month, 80.6% and 82.4% at 3 months, and 80.6% and 83.3% at 12 months. The results indicate that baseline measures of ergonomic and psychosocial stress, pain severity, and pain coping style predict clinical outcome at shorter intervals, whereas number of past treatments/providers, recommendation for surgery and pain coping style predict longer-term outcome. The resulting prognostic screen provides a simple tool that assesses the multidimensional nature of work-related upper extremity disorders and predicts clinical outcome. Furthermore, the findings suggest the importance of early intervention that addresses both physical and psychosocial stressors at work. Specific recommendations to reduce the impact of observed risk factors are discussed.

IL-1 and TNF-alpha are important factors in the pathogenesis of murine recurrent herpetic stromal keratitis.

PURPOSE: To better understand the role of interleukin (IL)-1 and tumor necrosis factor (NF)alpha in recurrent herpetic stromal keratitis (HSK), the cytokine content and the effects of anti-cytokine antibodies on mouse corneas with the disease were examined. METHODS: Competitive reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent analyses of IL-1alpha and TNF-alpha content were performed on corneas removed 3, 5, 7, 10, 14, and 21 days after latently infected NIH mice were irradiated with UV-B light to reactivate herpes simplex virus (HSV). In separate experiments, mice were injected with anti-IL-1 or anti-TNF-a antibodies 1 day before and 7 days after reactivation. RESULTS: UV-B irradiation stimulated an increase in corneal IL-la mRNA in reactivated (virus shedding) mice. This increase persisted longer and was higher than in UV-B irradiated uninfected control animals. IL-1alpha and TNF-alpha protein in corneas of reactivated mice was significantly elevated on days 3 to 10 compared with day 0 levels, and exceeded levels in control corneas on the same days. Anti-IL-1 and anti-TNF-alpha antibody administration both resulted in significantly decreased virus-induced corneal opacity between 7 and 21 days after UV-B exposure. CONCLUSIONS: IL-1alpha and TNF-alpha are upregulated in corneas in mice experiencing recurrent HSK. Abrogation of virus-induced corneal disease by anti-cytokine antibodies suggests that these cytokines play important roles in the pathogenesis of recurrent disease. Therefore, neutralization of specific proinflammatory cytokines may have potential therapeutic value.

Metabolic activation of dacarbazine by human cytochromes P450: the role of CYP1A1, CYP1A2, and CYP2E1.

Dacarbazine (DTIC), a widely used anticancer agent, is inactive until metabolized in the liver by cytochromes P450 to form the reactive N-demethylated species 5-[3-hydroxymethyl-3-methyl-triazen-1-yl]-imidazole-4-carboxamide (HMMTIC) and 5-[3-methyl-triazen-1-yl]-imidazole-4-carboxamide (MTIC). The modest activity of DTIC in the treatment of cancer patients has been attributed in part to lower activity of cytochromes P450 (P450) in humans when compared with rodents. Importantly, the particular P450 isoforms involved in the activation pathway have not been reported. We now report that the DTIC N-demethylation involved in MTIC formation by human liver microsomes is catalyzed by CYP1A1, CYP1A2, and CYP2E1. The most potent inhibitors of DTIC N-demethylation were alpha-naphthoflavone (CYP1A1 and CYP1A2), quercetin (CYP1A2), chlorzoxazone (CYP1A2 and CYP2E1), and di-sulfiram (CYP2E1). Antihuman CYP1A2 antiserum also inhibited DTIC N-demethylation. DTIC N-demethylation in a panel of 10 human liver microsome preparations was correlated with the catalytic activities for CYP1A2 (ethoxyresorufin O-deethylation and caffeine N3-demethylation) in the absence of alpha-naphthoflavone and with the catalytic activities for CYP2E1 (chlorzoxazone 6-hydroxylations) in the presence of alpha-naphthoflavone. DTIC metabolism was catalyzed by recombinant human CYP1A1, CYP1A2, and CYP2E1. The Km (Vmax) values for metabolism of DTIC by recombinant human CYP1A1 and CYP1A2 were 595 microM (0.684 nmol/min/mg protein) and 659 microM (1.74 nmol/min/mg protein), respectively. The CYP2E1 Km value exceeded 2.8 mM. Thus, we conclude that (a) CYP1A2 is the predominant P450 that catalyzes DTIC hepatic metabolism; (b) CYP2E1 contributes to hepatic DTIC metabolism at higher substrate concentrations; and (c) CYP1A1 catalyzes extrahepatic metabolism of DTIC.

Effect of additional cobalt, copper, manganese, and zinc on reproduction and milk yield of lactating dairy cows receiving bovine somatotropin.

The objective of this study was to determine whether organically complexed Co, Cu, Mn, and Zn would improve the reproductive performance and milk and milk component production in lactating dairy cows that began receiving bovine somatotropin in the ninth week of lactation. Holstein (n = 50) and Jersey (n = 10) cows were blocked by breed, lactation number, and incidence of retained fetal membranes. Two diets assigned within blocks and fed from parturition until 154 d of lactation were control or control supplemented daily with 26 mg of Co as Co glucoheptonate, 125 mg of Cu as Cu-Lys, 199 mg of Mn as Mn-Met, and 359 mg of Zn as Zn-Met. Cows were fitted with electronic pressure-sensing devices in the second week of lactation for detection of estrus. Ovarian structures were determined via transrectal ultrasonography at 7-d intervals from parturition until observation of the first corpus luteum. Blood samples were taken at 7-d intervals and analyzed for plasma concentrations of progesterone, insulin, and urea nitrogen. Onset of luteal activity was identified by progesterone concentrations > or = 1 ng/ml. Retained fetal membranes increased days to first estrus (detected via electronic estrous detection), first luteal activity, and first corpus luteum in control cows but not in supplemented cows. Days to first observed estrus were greater for control cows than for supplemented cows. Days to first service, days open, days from first service to conception, services per conception, milk yield, milk components, and somatic cell counts were similar for control and supplemented cows. Supplementation with complexed trace minerals effectively reduced days to first estrus.

Effect of supplemental dietary vitamin E and zinc on reproductive performance of dairy cows and heifers fed excess iron.

We tested the hypothesis that the incidence of retained fetal membranes could be reduced by limiting oxidative stress. Sixty-four primigravid heifers (56 Holstein and 8 Jersey) and 80 multiparous cows (64 Holstein and 16 Jersey) were used. A combination of vitamin E or Zn and Fe was fed in a 2 x 2 x 2 factorial arrangement during the last 42 d prepartum. Amounts of supplements per animal were 1000 IU of vitamin E (d, l alpha-tocopheryl acetate), 0.8 g of Zn (Zn-Met and ZnSO4), and 12 g of Fe (FeSO4.7H2O) for Holsteins and 9 g for Jerseys. Neither vitamin E nor Zn directly affected the incidence of retained fetal membranes, but plasma alpha-tocopherol was lower when fetal membranes were retained > 12 h or when vitamin E was not supplemented. Iron had no direct negative effects on reproductive performance, but cows receiving additional Fe had lower unsaturated iron-binding capacity, which, in turn, was also lower in cows that retained fetal membranes. Days to first observed estrus were reduced by supplementation with either vitamin E or Zn. Vitamin E reduced days to first artificial insemination (AI) and tended to reduce days open. Supplemental Zn tended to reduce days to first AI but did not affect days open. Milk production during the first 12 wk and AI per conception were not affected by supplementation with either vitamin E or Zn. Both vitamin E and Zn reduced days to first observed estrus, indicating improved reproductive health during the early postpartum period.

Efficacy of a recombinant glycoprotein D subunit vaccine on the development of primary and recurrent ocular infection with herpes simplex virus type 1 in mice.

The protective efficacy of a glycoprotein D subunit vaccine (gD2 SB AS4) was evaluated in a mouse model of human recurrent herpetic stromal keratitis (HSK). When administered before primary infection, gD2 SB AS4 protected mice against corneal pathology, mortality, and latency resulting from ocular viral challenge with herpes simplex virus type 1 (HSV-1) McKrae strain. In addition, gD2 SB AS4 significantly decreased postreactivation corneal disease. A control vaccine, gD2 alum, protected against acute ocular infection only. When administered after primary infection, gD2 SB AS4 vaccination decreased postreactivation ocular shedding but had no other significant effects. Vaccination with gD2 SB AS4 was associated with high anti-gD antibody responses and low delayed-type hypersensitivity responses. These results have identified a prophylactic vaccine, gD2 SB AS4, with activity against acute and recurrent HSK in mice and emphasize the need for vaccine evaluation in both primary and recurrent ocular herpetic disease models.

A comparison of recurrent and primary herpes simplex keratitis in NIH inbred mice.

Herpes simplex virus (HSV) infection is one of the leading causes of corneal blindness. This study compared the clinical, virologic, and immunopathologic features of primary and recurrent murine models of herpes simplex keratitis (HSK) in the National Institutes of Health (NIH) inbred mouse strain. Primary infection resulted in multiple epithelial dendrites, followed by diffuse stromal opacification, symptoms that do not mimic what is seen in human HSK. In contrast, recurrent infection presented clinical features that included microdendrites, focal stromal opacities, disciform endotheliitis, and corneal neovascularization, which were similar to those observed in human disease. Immunohistochemical characterizations indicated that the number and duration of T cells and macrophages in recurrent HSK resemble those observed in primary disease. Results also indicated that the amount of infectious virus detected in the cornea during primary and recurrent disease was similar. However, when corneas were stained for HSV-1 antigens, mice with primary HSK displayed diffuse HSV antigen expression throughout the cornea, whereas HSV antigens were more focally distributed in recurrent disease. These data suggest that the clinical differences between the recurrent and primary herpetic keratitis may, in part, reflect the different distribution of HSV-1 antigens within the cornea.

Antioxidant status of dairy cows supplemented prepartum with vitamin E and selenium.

Possible relationships among dietary antioxidants, oxidative status, and placental retention were investigated in periparturient dairy cows. During 6 wk prepartum, 16 cows each were given daily by capsule 1000 IU of vitamin E, 3 mg of Se, both vitamin E and Se, or neither (control). alpha-Tocopherol in serum and fast-acting antioxidants in plasma increased, but, in red blood cells, thiobarbituric acid-reactive substances decreased during the last 6 wk before parturition in cows given vitamin E. These measurements were unaffected by supplementation of Se. Cows that had retained placenta > or = 12 h had lower fast-acting antioxidants in plasma and glutathione peroxidase in red blood cells up to 2 wk before calving than did cows that shed fetal membranes in < 12 h. Results suggest that inadequate dietary antioxidants may increase oxidative stress, production of lipid peroxides, and incidence of retained fetal membranes in dairy cows.

A structural and functional comparison of the latency-associated transcript promoters of herpes simplex virus type 1 strains KOS and McKrae.

The promoters of the latency-associated transcripts (LATs) of herpes simplex virus type 1 (HSV-1) strains KOS and McKrae were compared to examine their influence upon the reactivation phenotypes of these two strains. Unlike strain KOS, McKrae is readily reactivable using in vivo reactivation models. We found greater than 96% sequence conservation between KOS and McKrae in the LATs promoter region, and both promoters showed equivalent basal and inducible activities. An inter-strain recombinant (termed MK13) was constructed in which the LATs promoter of HSV-1 McKrae was recombined into the background of HSV-1 strain KOS. In a murine u.v. light-induced reactivation model, virus shedding was detected by eye swabbing in two of 44 (5%) mice infected with KOS, 20 of 42 (48%) mice infected with McKrae and none of 45 (0%) mice infected with MK13. These data show that the LATs promoters of these viruses are structurally and functionally similar and that transfer of the LATs promoter from McKrae into KOS is insufficient to confer a reactivatable phenotype.

In vivo characterization of site-directed mutations in the promoter of the herpes simplex virus type 1 latency-associated transcripts.

Transient expression assays in PC12 cells showed that the cAMP response element (CRE) and the TATA box of the herpes simplex virus type 1 latency-associated transcripts (LATs) promoter are essential for basal expression. Recombinant viruses were generated containing site-specific mutations in these motifs. The abilities of these recombinants to replicate, express LATs and reactivate from latency were compared with wild-type and marker-rescued viruses in a murine ocular model. The acute replication of these TATA and CRE mutant viruses was at a level equivalent to their respective marker-rescued viruses. The reactivation of virus was unaffected by mutation in the TATA box as compared with wild-type or marker-rescued viruses. In situ hybridization of TATA box mutant virus-infected ganglia, however, showed threefold fewer LAT-positive neurons than wild-type virus-infected ganglia, with consistently weaker hybridization signals. Thus, this TATA box is required for normal expression of the LATs but not for efficient reactivation. The LATs CRE mutant reactivated with slightly but reproducibly reduced frequency and delayed kinetics relative to marker-rescued virus. By in situ hybridization, however, the percentage and intensity of LATs-positive neurons were found to be comparable for the CRE mutant- and wild-type virus-infected ganglia, suggesting that the CRE is dispensable for abundant LATs expression but that a reactivation function of the LATs may depend upon the presence of the CRE. Finally, using a modified assay for examining the timing of reactivation, we showed that the induction of viral reactivation by addition of exogenous cAMP can occur independently of the LATs.

Corneal Langerhans cell dynamics after herpes simplex virus reactivation.

PURPOSE: The authors investigated the progressive changes in the distribution of corneal Langerhans cells (LC) after reactivation of latent herpes simplex virus type 1 (HSV-1) in mice. METHODS: After corneal inoculation of National Institutes of Health inbred mice with HSV-1 and the establishment of latency, viral reactivation was induced by irradiating the ocular surface with 250 mJ/cm2 of ultraviolet B (UV-B) light. RESULTS: Subsequent viral replication in the cornea was followed by the migration of the LC toward the paracentral and central corneal epithelium. These areas are normally devoid of LC. The number of LC in the paracentral and central regions of the eye reached a peak at day 14 post-UV-B irradiation. After UV-B irradiation of mice latently infected with HSV-1, the development of corneal stromal opacification and neovascularization closely followed the migration of LC toward the central cornea and paralleled the influx of T-cells into the corneal stroma. This pattern was not observed in irradiated uninfected mice. CONCLUSIONS: LC migrate centrally in the corneal epithelium after viral reactivation. There is a direct correlation between the number of LC in the cornea and the degree of persistent stromal opacification.

Reactivation of latent herpes simplex virus by excimer laser photokeratectomy.

We tested whether excimer laser photorefractive and phototherapeutic keratectomy may reactivate latent herpes simplex and cause recurrent keratitis in mice. Two of ten latently infected mice that were treated with ten excimer laser pulses to the corneal epithelium shed herpes simplex virus type 1, as did four of ten mice that were treated with 50 excimer laser pulses. Ocular shedding of herpes simplex virus was detected in four of ten mice that were treated with ethylenediamine-tetraacetic acid (EDTA) scraping of the corneal epithelium without laser keratectomy, and in six of ten mice on which combined EDTA-facilitated epithelial removal was performed followed by the application of ten excimer laser pulses. In both EDTA-treated groups, viral shedding was prolonged and 18 of 20 mice developed marked corneal opacification or neovascularization, or both. Corneal photoablation with the excimer laser may induce reactivation of latent herpes simplex virus, even in mice with clear and smooth-appearing corneas, and should be considered in the differential diagnosis of humans with persistent corneal epithelial defects after refractive or therapeutic excimer procedures.

Luque interpeduncular segmental fixation of the lumbosacral spine.

Interpeduncular segmental fixation of the lumbar and lumbosacral spine with Luque screws and plates is becoming increasingly popular. In this retrospective study, 52 consecutive patients treated with this technique were followed for 16 to 44 months (average, 21). Indications for surgical arthrodesis included lumbar instability from degenerative disease (16 cases), spondylolisthesis (25 cases), pseudarthrosis (eight cases), fracture (two cases), and tumor (one case). Fusion with instrumentation spanned one level in nine patients, two in 38 patients, three in four patients, and four in one patient. Patients wore a rigid lumbar orthosis for an average of six months (range, two to 16). Ten complications occurred in nine patients: two superficial wound infections, four neurologic complications, three loosened screws, and one broken screw. An overall fusion rate of 96% was achieved; pseudarthrosis is suspected in one case and failed arthrodesis secondary to trauma in a second patient. At four months postoperatively, solid unions had resulted in most of the cases, as seen roentgenographically. All patients reported decreased back pain; however, one patient is addicted to narcotics. Twenty-five of the 29 patients employed were able to return to work at an average of six months postoperatively.

The medical evaluation of elderly patients with major depression.

Elderly patients hospitalized for management of major depression frequently have an extensive medical evaluation to determine if physical illness is masquerading as, or serving as the precipitating event for, the depression. The purpose of this study was to determine the incidence of newly discovered medical problems and the yield of various diagnostic modalities in such elderly depressed patients. Of 100 depressed geropsychiatric inpatients, the most frequent new diagnoses included: electrolyte abnormalities (6 patients), bacteriuria (13), medication reactions (7), exacerbation of previous thyroid disease (6), new thyroid function abnormalities (3), and renal failure, Parkinson's Disease, and chronic obstructive lung disease (2 each). One patient had a cerebellar hemangioblastoma, and 4 had acute illnesses. A workup including CBC, blood chemistries, urinalysis, and thyroid function tests frequently yielded abnormal results. When used as screening tests, head CT scanning, electroencephalography, and chest radiography did not affect management. We conclude that elderly depressed patients have a high prevalence of undiscovered physical illnesses, but that history, physical examination, and simple laboratory evaluation may be sufficient to guide their workups.

Lateral and medial epicondylitis of the elbow.

Tennis elbow is a common condition, with the extensor carpi radialis brevis attachment being the usual site of pain. Conservative care including decreased activity, ice, nonsteroidal anti-inflammatory medications, and muscle strengthening will help most people. The small percentage of cases that require surgery usually benefit from debridement of the damaged portion of the extensor carpi radialis brevis attachment. The postoperative course must include muscle strengthening and a gradual return to activity.