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1.
Transl Androl Urol ; 13(2): 320-330, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38481863

ABSTRACT

Background and Objective: Coronavirus disease 2019 (COVID-19) necessitated a transition to virtual education which limits hands-on opportunities and student engagement. To adapt, a pilot study investigating clay modeling as an alternative educational tool for medical students was incorporated in a virtual and in-person sub-internship for prospective urology applicants. We aim to review the literature supporting the use of clay modeling in medical education as well as describe our experience with the activity as a way to engage trainees and evaluate early surgical skills. Methods: The current literature on clay modeling in medical and early surgical education was reviewed using multiple search queries in PubMed. A total of thirteen publications were identified and analyzed, with zero articles specifically discussing urological anatomy or surgery. The pilot study was conducted through the traditional in-person sub-internship as well as through a novel virtual sub-internship at a single academic U.S. Urology residency program. Students were instructed to create a three-dimensional model of a genitourinary organ using modeling clay. Anonymized surveys were collected. Responses of virtual and in-person students were compared. Key Content and Findings: Clay modeling has been shown in the literature to be beneficial in medical and early surgical education through the use of active learning. Twenty-five total virtual (N=6) and in-person (N=19) students participated in the clay modeling activity. Survey ratings were mixed, with 100% positive responses amongst the virtual group in the areas of "relevance" and "creatively challenging" compared to the in-person cohort, 31.6% of whom responded positively to "relevance" and 47.4% for "creatively challenging" respectively. Overall, students responded positively for the exercise being "creatively challenging" (n=15, 60%) and "enjoyable" (n=16, 64%). Positive results echoed the student perspectives described in the current literature on clay modeling. Conclusions: Clay modeling has previously been used in the in-person classroom setting as a learning supplement or replacement for dissection classes but has not been previously described for use in the virtual learning environment or within the field of Urology. With ongoing need to develop novel teaching modalities, clay modeling may be a unique tool to enhance learning, and evaluate technical skill, and boost engagement for medical trainees.

2.
Urol Pract ; 7(4): 279-284, 2020 Jul.
Article in English | MEDLINE | ID: mdl-37317423

ABSTRACT

INTRODUCTION: AUA guidelines recommend periprocedural antibacterial prophylaxis for high risk patients undergoing in-office cystoscopy. We sought to determine if implementation of a simple quality improvement protocol could increase guideline compliance. METHODS: As part of a quality improvement initiative, 4 simple changes were incorporated into our practice for in-office cystoscopy, including creation of a "yes/no" checklist to identify high risk patients, checklist review and electronic antibiotics order placed by urology provider, immediate nurse directed administration of single doses of the most common recommended antibiotics, and review of the checklist and antibiotic administration during the preprocedural time-out. We retrospectively compared antibiotic adherence in patients 3 months before and 3 months after implementation of the intervention. Data collected included age, gender, indication for procedure, type of procedure and high risk status. RESULTS: A total of 307 patients were included in the study (157 before implementation and 150 after implementation of the protocol). In the pre-intervention group 120 patients (76.4%) were considered high risk and should have been administered antibiotic prophylaxis, although only 38 (31.7%) actually received it. In the post-intervention group 104 patients (69.3%) were considered high risk and should have been given antibiotic prophylaxis, and 84 (80.8%) actually received it. Overall, this quality improvement initiative resulted in a 49.1% increase in appropriate antibiotic administration (p <0.0001). CONCLUSIONS: Implementation of a simple 4-step quality improvement initiative resulted in a significant increase in the administration of appropriate antibiotics for in-office cystoscopy.

3.
J Sex Med ; 16(1): 137-144, 2019 01.
Article in English | MEDLINE | ID: mdl-30509506

ABSTRACT

BACKGROUND: Despite the known nephrotoxicity of gentamicin, in 2008 the American Urological Association recommended a weight-based gentamicin dose of 5 mg/kg for antimicrobial prophylaxis during urologic prosthetic surgery. AIM: To identify and characterize rates of acute kidney injury (AKI) in urologic prosthetic surgery, both before and after the implementation of weight-based gentamicin dosing. METHODS: We performed a single-institution retrospective study of patients receiving perioperative gentamicin during implant, revision, salvage, or explant of inflatable penile prostheses, malleable penile prostheses, or artificial urinary sphincters between the years 2000 and 2017. Patients were stratified into 2 groups, based on administration of either weight-based gentamicin (5 mg/kg or 2-3 mg/kg in cases of poor renal function) or standard-dose gentamicin (80 mg). Patient characteristics and perioperative outcomes were identified. Patients with available preoperative and postoperative (≤7 days) serum creatinine values were included. AKI was defined by Kidney Disease: Improving Global Outcomes criteria. Comparative analyses were performed between groups. MAIN OUTCOME MEASURE: Our primary outcome was incidence of AKI, with secondary outcomes including device infection rate and length of stay. RESULTS: Of the 415 urologic prosthetic surgeries performed during the study period, 124 met inclusion criteria with paired preoperative and postoperative serum creatinine values. 57 received weight-based gentamicin (median dose 5.06 mg/kg, interquartile range [IQR] 3.96-5.94) and 67 received standard-dose gentamicin (median dose 1.07 mg/kg, IQR 1.04-1.06), P < .001. There were no significant differences in preoperative renal function or comorbidities between groups; however, the weight-based group was older (median age 64.0 years, IQR 60.0-68.5) compared with the standard-dose group (median age 61.0 years, IQR 55.0-66.0), P = .01, and comprised fewer explant cases (1.8%, 1 of 57) than the standard-dose group (13.4%, 9 of 67), P = .02. The AKI rate was significantly higher in the weight-based group (15.8%, 9 of 57) compared with the standard-dose group (3.0%, 2 o67), P = .02. Device infection rate was similar between groups (5.3%, 3/56 vs 5.2%, 3 of 58), P = 1.00. CLINICAL IMPLICATIONS: Our data suggest weight-based perioperative gentamicin prophylaxis may be associated with an increased AKI risk, without noticeably improving infection rates. STRENGTH & LIMITATIONS: Strengths of our study include the Veterans Affairs population analyzed, as well as rigorous inclusion criteria that allowed for a sensitive assessment of postoperative renal function. Limitations include the retrospective design and small sample size. CONCLUSION: Weight-based gentamicin dosing may warrant closer perioperative monitoring of renal function, and merits larger investigations to further elucidate risks and benefits. Moore RH, Anele UA, Krzastek SC. Potential Association of Weight-Based Gentamicin with Increased Acute Kidney Injury in Urologic Prosthetic Surgery. J Sex Med 2019;16:137-144.


Subject(s)
Acute Kidney Injury/epidemiology , Anti-Bacterial Agents/administration & dosage , Gentamicins/administration & dosage , Penile Prosthesis , Urologic Surgical Procedures/methods , Aged , Anti-Bacterial Agents/adverse effects , Body Weight , Gentamicins/adverse effects , Humans , Incidence , Male , Middle Aged , Postoperative Period , Retrospective Studies , Risk Factors , Urologic Surgical Procedures/adverse effects
4.
Respir Res ; 19(1): 213, 2018 Nov 06.
Article in English | MEDLINE | ID: mdl-30400950

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is chronic fibrosing pneumonia with an unpredictable natural disease history. Functional respiratory imaging (FRI) has potential to better characterize this disease. The aim of this study was to identify FRI parameters, which predict FVC decline in patients with IPF. METHODS: An IPF-cohort (treated with pamrevlumab for 48 weeks) was retrospectively studied using FRI. Serial CT's were compared from 66 subjects. Post-hoc analysis was performed using FRI, FVC and mixed effects models. RESULTS: Lung volumes, determined by FRI, correlated with FVC (lower lung volumes with lower FVC) (R2 = 0.61, p < 0.001). A negative correlation was observed between specific image based airway radius (siRADaw) at total lung capacity (TLC) and FVC (R2 = 0.18, p < 0.001). Changes in FVC correlated significantly with changes in lung volumes (R2 = 0.18, p < 0.001) and siRADaw (R2 = 0.15, p = 0.002) at week 24 and 48, with siRADaw being more sensitive to change than FVC. Loss in lobe volumes (R2 = 0.33, p < 0.001), increasing fibrotic tissue (R2 = 0.33, p < 0.001) and airway radius (R2 = 0.28, p < 0.001) at TLC correlated with changes in FVC but these changes already occur in the lower lobes when FVC is still considered normal. CONCLUSION: This study indicates that FRI is a superior tool than FVC in capturing of early and clinically relevant, disease progression in a regional manner.


Subject(s)
Disease Progression , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/physiopathology , Tomography, X-Ray Computed/methods , Vital Capacity/physiology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Tidal Volume/physiology , Tomography, X-Ray Computed/standards
5.
Case Rep Urol ; 2018: 3479202, 2018.
Article in English | MEDLINE | ID: mdl-30631633

ABSTRACT

Despite the known nephrotoxicity of gentamicin, in 2008 the American Urological Association published guidelines recommending single high-dose weight-based gentamicin prophylaxis of 5 mg/kg for procedures involving urologic prostheses. These guidelines are based on the theoretical renal safety and improved antimicrobial activity of a single large dose of gentamicin. However, the risk of nephrotoxicity after weight-based gentamicin prophylaxis specifically in penile prosthetic surgery has never been established with evidence-based studies. This is of special concern in light of the known high rates of preexisting conditions in this specific population. Therefore, in order to expose potential safety issues, we present three cases of postoperative acute kidney injury following weight-based gentamicin prophylaxis after implantation of inflatable penile prostheses.

6.
Lupus ; 19(6): 727-33, 2010 May.
Article in English | MEDLINE | ID: mdl-20118158

ABSTRACT

The objectives of the present study were (1) to clarify and quantify the relationship between age and disease duration with the rate of change in disease activity over time in patients with systemic lupus erythematosus (SLE) and (2) to explore other possible factors associated with this rate of change. To this end, SLE patients from LUMINA were studied if they had at least three visits in which disease activity (Systemic Lupus Activity Measure-Revised [SLAM-R]) had been ascertained. Variables associated with the rate (slope) of change in disease activity (obtained by regressing the SLAM-R score against the length of time from diagnosis to visit date) were examined by univariable and multivariable analyses. Five hundred and forty two of the 632 patients had at least three SLAM-R score. In multivariable analyses, Whites exhibited the fastest decline in disease activity, Texan Hispanics exhibited the slowest, trailed by the African Americans. Longer disease duration and HLA-DRB1*1503 positivity were associated with a slower decline whereas a greater number of American College of Rheumatology criteria and abnormal laboratory parameters (white blood cell counts, hematocrit and serum creatinine) were associated with a faster decline. These findings complement existing knowledge on SLE disease activity and are potentially useful to clinicians managing these patients.


Subject(s)
Disease Progression , Ethnicity , Lupus Erythematosus, Systemic/physiopathology , Cohort Studies , Female , Humans , Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/pathology , Male , Severity of Illness Index , Socioeconomic Factors
8.
Cell Signal ; 19(8): 1733-44, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17467235

ABSTRACT

The GIT proteins, GIT1 and GIT2, are GTPase-activating proteins for the ADP-ribosylation factor family of small GTP-binding proteins, but also serve as adaptors to link signaling proteins to distinct cellular locations. One role for GIT proteins is to link the PIX family of Rho guanine nucleotide exchange factors and their binding partners, the p21-activated protein kinases, to remodeling focal adhesions by interacting with the focal adhesion adaptor protein paxillin. We here identified the C-terminal domain of GIT1 responsible for paxillin binding. Combining structural and mutational analyses, we show that this region folds into an anti-parallel four-helix domain highly reminiscent to the focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK). Our results suggest that the GIT1 FAT-homology (FAH) domain and FAT bind the paxillin LD4 motif quite similarly. Since only a small fraction of GIT1 is bound to paxillin under normal conditions, regulation of paxillin binding was explored. Although paxillin binding to the FAT domain of FAK is regulated by tyrosine phosphorylation within this domain, we find that tyrosine phosphorylation of the FAH domain GIT1 is not involved in regulating binding to paxillin. Instead, we find that mutations within the FAH domain may alter binding to paxillin that has been phosphorylated within the LD4 motif. Thus, despite apparent structural similarity in their FAT domains, GIT1 and FAK binding to paxillin is differentially regulated.


Subject(s)
Adaptor Proteins, Signal Transducing/chemistry , Adaptor Proteins, Signal Transducing/metabolism , Cell Cycle Proteins/chemistry , Cell Cycle Proteins/metabolism , Focal Adhesions/metabolism , Paxillin/metabolism , Adaptor Proteins, Signal Transducing/genetics , Amino Acid Motifs , Amino Acid Sequence , Animals , Binding Sites , COS Cells , Cell Cycle Proteins/genetics , Cell Line , Chlorocebus aethiops , Humans , Models, Molecular , Molecular Sequence Data , Point Mutation , Protein Binding , Protein Structure, Tertiary , Sequence Homology, Amino Acid
9.
Rheumatology (Oxford) ; 46(4): 683-9, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17132694

ABSTRACT

OBJECTIVES: To determine the factors predictive of new or worsening proteinuria in a large multiethnic cohort of patients with systemic lupus erythematosus (SLE). METHODS: Five hundred and twenty-nine SLE patients from a multiethnic US cohort [LUpus in MInorities: NAture versus Nurture (LUMINA)] were evaluated for new or worsening proteinuria using the categories of the Systemic Lupus Activity Measure-Revised: (1), normal; (2), trace or 1+ proteinuria on the dipstick; (3), 2-3+ proteinuria and (4), > or =4+ proteinuria. A rise in urinary protein was considered a positive event visit. Basic demographic and socioeconomic variables were assessed at baseline (T0). Clinical and immunological variables including disease features, activity, duration, comorbidities (such as hypertension and diabetes), medications and autoantibodies were assessed at the visit preceding a positive event visit. Selected HLA-DR and HLA-DQ alleles, and FCGR receptor polymorphisms were assessed. Data were analysed using logistic regression analyses and generalized estimating equations. RESULTS: There were 243 patients (59.1% of 93 Texan Hispanics, 37.0% of 100 Puerto Rican Hispanics, 58.0% of 181 African Americans and 29.7% of 155 Caucasians) with new or worsening proteinuria, and 364 positive events in 2801 visits. Younger age [Odds ratio (OR) = 1.013, 95% confidence limits (CL) = 1.001-1.024, P < 0.0334], anti-dsDNA (OR = 1.554, CL = 1.149-2.100, P < 0.0042), and HLA-DRB1*1503 (OR = 1.746, 95% CL = 1.573-2.2673, P < 0.0103) were found to independently predict the occurrence of new or worsening proteinuria. CONCLUSION: The factors predictive of new or worsening proteinuria include traditional factors associated with lupus nephritis, such as age and anti-dsDNA, as well as HLA-DRB1*1503, which has not been previously described in association with lupus nephritis, new or worsening proteinuria.


Subject(s)
Lupus Nephritis/etiology , Proteinuria/etiology , Adult , Black or African American , Age Factors , Antibodies, Antinuclear/blood , DNA/immunology , Disease Progression , Female , Genetic Predisposition to Disease , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Hispanic or Latino , Humans , Lupus Erythematosus, Systemic/ethnology , Lupus Erythematosus, Systemic/genetics , Lupus Nephritis/ethnology , Lupus Nephritis/genetics , Male , Middle Aged , Proteinuria/ethnology , Proteinuria/genetics , Risk Factors , Severity of Illness Index , Socioeconomic Factors , United States/epidemiology , White People
10.
Ann Rheum Dis ; 65(9): 1168-74, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16905579

ABSTRACT

AIM: To ascertain the predictive factors of high levels of disease activity in systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Patients with SLE (American College of Radiology criteria), aged >or=16 years, with disease duration 10). A basic multivariable model (including age, sex, ethnicity, health insurance, social support, abnormal illness-related behaviours, helplessness and prior disease activity) was first examined. Additional models were built by including other variables. RESULTS: 554 patients (100 Hispanics from Texas, 94 Hispanics from Puerto Rico, 199 African Americans, 161 Caucasians) and 2366 visits were analysed; 47% of the patients and 29% of the visits met the definition of high disease activity (more common among African Americans (72.0%) and Hispanics from Texas (71.3%) than among Caucasians (43.9%) and Hispanics from Puerto Rico (31.9%)). Variables found to predict high levels of disease activity were Hispanic (from Texas) and African American ethnicities, lack of health insurance, helplessness, abnormal illness-related behaviours and poor social support; age was negatively associated with high levels of disease activity. African admixture and anti-double-stranded DNA antibodies also predicted high levels of disease activity, as did prior disease activity. None of the human leucocyte antigen variables were retained in the models. CONCLUSIONS: Socioeconomic-demographic (age, ethnicity, health insurance), behavioural and psychological variables are important mediators of high levels of disease activity in SLE during its course. Interventions aimed at modifiable factors may improve the outcomes of SLE.


Subject(s)
Lupus Erythematosus, Systemic/diagnosis , Adolescent , Adult , Black or African American , Age Factors , Epidemiologic Methods , Female , Hispanic or Latino , Humans , Lupus Erythematosus, Systemic/ethnology , Lupus Erythematosus, Systemic/rehabilitation , Male , Prognosis , Severity of Illness Index , Sick Role , Social Support , Socioeconomic Factors , White People
12.
Lupus ; 15(1): 26-31, 2006.
Article in English | MEDLINE | ID: mdl-16482742

ABSTRACT

Renal involvement in systemic lupus erythematosus (SLE) is more frequent in minorities. We examined whether genetic or socioeconomic status (SES) explain these disparities in a large multiethnic (Hispanics from Texas and Puerto Rico, African Americans and Caucasians) SLE cohort. Renal involvement was defined as WHO Class II-V and/or proteinuria (> 0.5 g/24 h or 3+) attributable to SLE and/or abnormal urinary sediment, proteinuria 2+, elevated serum creatinine/ decreased creatinine clearance twice, 6 months apart present any time over the course of the disease. Ancestry informative markers (AIMS) were used to define the admixture proportions in each patient and group. Logistic regression models were examined to determine the percentage variance (R2) in renal involvement related to ethnicity that is explained by socio-economic status (SES) and admixture (adjusting for age, gender and disease duration, basic model). Four-hundred and fifty-nine (out of 575) patients were included; renal involvement occurred in 44.6% Texas Hispanics, 11.3% Puerto Rico Hispanics, 45.8% African Americans, 18.3% Caucasians. SES accounted for 14.5% of the variance due to ethnicity (after adjusting for basic model variables), admixture 36.8% and both, 12.2%; 45.9% of the variance remained unexplained. Alternative models for decreased glomerula filtration rate and end-stage renal disease were comparable in the distribution of the explanatory variables. Our data indicate that genetic factors appear to be more important than SES in explaining the ethnic disparities in the occurrence of renal involvement.


Subject(s)
Black or African American , Hispanic or Latino , Lupus Erythematosus, Systemic/ethnology , Proteinuria/etiology , White People , Adult , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/psychology , Male , Proteinuria/ethnology , Proteinuria/physiopathology , Risk Factors , Socioeconomic Factors , United States/epidemiology
13.
Ann Rheum Dis ; 65(6): 785-90, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16269429

ABSTRACT

BACKGROUND: Osteonecrosis is common in systemic lupus erythematosus (SLE) and often disabling. The role of glucocorticoids in its development is well known. OBJECTIVE: To explore other possible risk factors for osteonecrosis in SLE. METHODS: A nested matched case-control study undertaken in the context of a large, longitudinal, multiethnic lupus cohort (LUMINA), currently formed of 571 SLE patients meeting American College of Rheumatology criteria. All those developing symptomatic osteonecrosis after the diagnosis of SLE were considered cases. Two controls matched for age, disease duration, ethnicity, and centre were selected for each case. Cases and controls were compared by univariable analyses using selected variables. Variables with p<0.10 and those thought clinically relevant were entered into conditional logistic regression models including either the average dose or the highest dose of glucocorticoids, with osteonecrosis as the dependent variable. RESULTS: 32 cases were identified and 59 matched controls selected (in five cases only one control could be found). By univariable analyses, both groups were largely comparable for socioeconomic-demographic, clinical, and laboratory variables. Cases were less exposed to hydroxychloroquine (as assessed by the percentage of exposure time) (p = 0.026), used higher doses of glucocorticoids (average and highest doses) (p = 0.011 and 0.001, respectively), and received cytotoxic drugs more often (p = 0.015). In the multivariable analyses only cytotoxic drug use (both models) and the highest dose of glucocorticoids remained associated with the occurrence of osteonecrosis. CONCLUSIONS: Cytotoxic drug use is a risk factor for the development of symptomatic osteonecrosis in SLE patients, along with glucocorticoids. No definite protective factors were identified.


Subject(s)
Ethnicity , Lupus Erythematosus, Systemic/ethnology , Osteonecrosis/etiology , Adult , Black or African American , Antibiotics, Antineoplastic/adverse effects , Antibiotics, Antineoplastic/therapeutic use , Drug Administration Schedule , Drug Therapy, Combination , Epidemiologic Methods , Female , Glucocorticoids/therapeutic use , Hispanic or Latino , Humans , Hydroxychloroquine/therapeutic use , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Male , United States , White People
15.
Rheumatology (Oxford) ; 44(10): 1303-7, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16030085

ABSTRACT

OBJECTIVE: To determine the relationship between the presence of antiphospholipid (aPL) antibodies, hydroxychloroquine use and the occurrence of thrombotic events in patients with systemic lupus erythematosus (SLE). METHODS: Four hundred and forty-two SLE patients from the LUMINA (Lupus in Minorities: Nature vs Nurture) cohort, a multiethnic (Hispanics from Texas, n = 99 and Puerto Rico, n = 36; African Americans, n = 172; and Caucasians, n = 135) cohort, were studied by generalized estimating equation (GEE) to determine the relationship between antiphospholipid (aPL) antibodies (measured as IgG and IgM aPL antibodies and/or the lupus anticoagulant) at enrolment or historically prior to enrolment, hydroxychloroquine use (ever) and the occurrence of thrombotic (central and/or peripheral, arterial and/or venous) events after adjusting for known and possible confounders [socioeconomic-demographic features, smoking, disease activity and damage, serum cholesterol levels, anti-oxidized low-density lipoprotein IgG and IgM antibodies, and high-sensitivity (hs) C-reactive protein]. Postanalysis correlation between aPL and anticardiolipin (aCL) assays was attempted by performing aCL assays on random samples of patients whose aPL status was known. RESULTS: A number of clinical variables were significant in the univariable analyses; however, in the multivariable GEE analyses, only smoking [odds ratio (OR) 2.777, 95% confidence interval (CI) 1.317-5.852] and disease activity as measured by the SLAM (Systemic Lupus Activity Measure) (OR 1.099; 95% CI 1.053-1.147) were significant. In particular, hydroxychloroquine use, which appeared to be protective against thrombotic events in the univariable analyses, was not retained in the multivariable analyses. aPL antibodies were not significant in either analysis. Few additional aPL-positive patients emerged from the validation study. CONCLUSIONS: Smoking and disease activity emerged as important determinants in the occurrence of thrombotic events in our patients. Comprehensive treatment strategies should be directed to both smoking cessation and control of disease activity in patients with SLE.


Subject(s)
Lupus Erythematosus, Systemic/complications , Thrombosis/etiology , Antibodies, Antiphospholipid/blood , Antirheumatic Agents/therapeutic use , Epidemiologic Methods , Female , Humans , Hydroxychloroquine/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/ethnology , Male , Severity of Illness Index , Smoking/adverse effects , Thrombosis/ethnology , Thrombosis/immunology
16.
Cell Signal ; 16(9): 1001-11, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15212761

ABSTRACT

GIT proteins are GTPase-activating proteins (GAPs) for ADP-ribosylation factor (ARF) small GTP-binding proteins, and interact with the PIX family of Rac1/Cdc42 guanine nucleotide exchange factors. GIT and PIX transiently localize p21-activated protein kinases (PAKs) to remodeling focal adhesions through binding to paxillin. To understand the role of these interactions, the association of GIT and PIX proteins was examined in detail. Two separable binding interactions link GIT and PIX proteins, GIT and PIX proteins each dimerize and a beta-PIX fragment containing the GIT-binding region failed to inhibit the association of the GIT and PIX proteins. Endogenous GIT and PIX co-fractionate at a very high molecular size. Purified 6xHis-tagged beta-PIX from Sf9 cells co-expressing untagged GIT1 yields recombinant GIT1/beta-PIX complexes that have equal amounts of beta-PIX and GIT1 and co-fractionate at the same large size as native GIT/PIX complexes. Thus, GIT and PIX proteins are tightly associated as a multimeric nexus capable of linking together important signaling molecules, including PAKs.


Subject(s)
Cell Cycle Proteins/metabolism , GTPase-Activating Proteins/metabolism , Guanine Nucleotide Exchange Factors/metabolism , Phosphoproteins/metabolism , Animals , Cell Cycle Proteins/genetics , Cell Line , GTPase-Activating Proteins/genetics , Guanine Nucleotide Exchange Factors/genetics , Haplorhini , Humans , Macromolecular Substances/chemistry , Macromolecular Substances/metabolism , Mutagenesis , Phosphoproteins/genetics , Protein Binding , Rats , Recombinant Fusion Proteins/isolation & purification , Recombinant Fusion Proteins/metabolism , Rho Guanine Nucleotide Exchange Factors , Transfection , cdc42 GTP-Binding Protein/metabolism , rac1 GTP-Binding Protein/metabolism
17.
Rheumatology (Oxford) ; 43(2): 202-5, 2004 Feb.
Article in English | MEDLINE | ID: mdl-12923289

ABSTRACT

OBJECTIVE: To examine the predictors of damage in a multiethnic cohort of systemic lupus erythematosus (SLE) patients with a specific focus on damage at baseline. PATIENTS AND METHODS: SLE patients from a multiethnic US (Hispanic, African-American and Caucasian) cohort (LUMINA: Lupus in Minority populations, Nature versus nurture) were included if they had > or =6 months of follow-up in the cohort. Damage was measured with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). The dependent variable was the change in SDI score between study visits. Predictors were from the preceding visit. Variables known to affect damage accrual in SLE were included in the analyses. RESULTS: Three hundred and fifty-two patients (82 Hispanics, 153 African-Americans and 117 Caucasians) representing 1795 patient visits were included. Previous damage was found to be a significant predictor of subsequent damage accrual (P < 0.0001). Other variables predictive of subsequent damage accrual were disease activity (P < 0.0001), older age (P = 0.041) and use of corticosteroids (P = 0.0048). CONCLUSIONS: Once damage occurs in SLE, further damage is expected to occur. This is more likely to be the case if disease activity persists. These data have clinical implications for the management of SLE patients.


Subject(s)
Lupus Erythematosus, Systemic/ethnology , Adult , Black or African American , Cohort Studies , Disease Progression , Female , Hispanic or Latino , Humans , Lupus Erythematosus, Systemic/pathology , Male , Middle Aged , Risk Factors , Severity of Illness Index , United States , White People
18.
Lupus ; 11(3): 152-60, 2002.
Article in English | MEDLINE | ID: mdl-12004788

ABSTRACT

The purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95% confidence limits (CL) = 1.07-6.87, P < 0.04) and African-American ethnicities (OR = 3.13, 95% CL = 1.21-8.09, P < 0.02), not married or living together (OR = 3.45, 95% CL = 1.69-7.69, P < 0.0003), higher SLAM score (OR = 1.11, 95% CL = 1.02-1.19, P < 0.007), anti-dsDNA (OR = 3.14, 95% CL = 1.50-6.57, P < 0.0001) and anti-RNP (OR = 4.24, CL = 1.98-9.07, P < 0.0001) antibodies were shown to be significant predictors of the occurrence of LN. Repeated analyses excluding the patients with missing HLA data showed that absence of HLA-DQB1*0201 was also a significant predictor for the occurrence of LN (OR = 2.34, CL = 1.13-5.26, P < 0.04). In conclusion, LN occurred significantly more often in Hispanics and African-Americans with SLE. Sociodemographic, clinical and immunologic/immunogenetic factors seem to be predictive of LN occurring after the diagnosis of SLE has been made.


Subject(s)
Ethnicity , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Nephritis/complications , Lupus Nephritis/epidemiology , Black or African American , Autoantibodies/immunology , Cohort Studies , Female , HLA-D Antigens/immunology , Hispanic or Latino , Humans , Logistic Models , Lupus Nephritis/ethnology , Lupus Nephritis/immunology , Male , Odds Ratio , Risk Factors , Survival Analysis , White People
19.
Med Sci Sports Exerc ; 33(11): 1803-10, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11689728

ABSTRACT

PURPOSE: Previous studies among young pitchers have focused on the frequency and description of elbow injuries. The purpose of this study was to evaluate the frequency of elbow and shoulder complaints in young pitchers and to identify the associations between pitch types, pitch volume, and other risk factors for these conditions. METHODS: A prospective cohort study of 298 youth pitchers was conducted over two seasons. Each participant was contacted via telephone after each game pitched to identify arm complaints. Generalized estimating equations were used to assess associations between arm complaints and independent variables. RESULTS: The frequency of elbow pain was 26%; that of shoulder pain, 32%. Risk factors for elbow pain were increased age, increased weight, decreased height, lifting weights during the season, playing baseball outside the league, decreased self-satisfaction, arm fatigue during the game pitched, and throwing fewer than 300 or more than 600 pitches during the season. Risk factors for shoulder pain included decreased satisfaction, arm fatigue during the game pitched, throwing more than 75 pitches in a game, and throwing fewer than 300 pitches during the season. CONCLUSION: Arm complaints are common, with nearly half of the subjects reporting pain. The factors associated with elbow and shoulder pain were different, suggesting differing etiologies. Developmental factors may be important in both. To lower the risk of pain at both locations, young pitchers probably should not throw more than 75 pitches in a game. Other recommendations are to remove pitchers from a game if they demonstrate arm fatigue and limit pitching in nonleague games.


Subject(s)
Arthralgia/epidemiology , Athletic Injuries/epidemiology , Baseball/injuries , Elbow Injuries , Shoulder Pain/epidemiology , Alabama/epidemiology , Arm Injuries/epidemiology , Baseball/physiology , Biomechanical Phenomena , Child , Functional Laterality , Humans , Longitudinal Studies , Physical Education and Training/methods , Risk Factors , Task Performance and Analysis , Time Factors
20.
Spinal Cord ; 39(11): 571-6, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11641806

ABSTRACT

STUDY DESIGN: A matched case-control study. OBJECTIVES: To clarify the influence of urine specific gravity and drinking water quality on the formation of urinary stones in persons with spinal cord injury (SCI). SETTING: A rehabilitation center within a university hospital. METHODS: Between 1992 and 1998, 63 stone cases (31 kidney, 27 bladder, and five both) and 289 age-duration-matched controls were recruited from a cohort of SCI patients enrolled in an on-going longitudinal study. Data on urine specific gravity and other characteristics of study participants were retrieved from the database and medical charts. Community water supply information was provided by the Alabama Department of Environmental Management. Multivariable conditional logistic regression analysis was performed to evaluate the association with stone formation. RESULTS: SCI individuals who had urinary stones were more likely than control subjects to use indwelling catheters and have decreased renal function. The occurrence of stones was not significantly related to gender, race, severity of injury, urinary tract infection, nor urine pH. After controlling for the potential confounding from other factors, a continuously increasing stone occurrence with increasing specific gravity was observed (P=0.05); this association was stronger for kidney (odds Ratio [OR]=1.8 per 0.010 g/cm(3)) versus bladder stones (OR=1.2) and for recurrent (OR=2.0) versus first stones (OR=1.5). Increased water hardness was not significantly associated with a decreased stone occurrence. CONCLUSIONS: Study results suggest that maintaining urine specific gravity below a certain level might reduce the occurrence of urinary stones. This could be easily achieved by using a dipstick for self-feedback along with appropriate fluid intake. For persons with SCI who are at an increased risk of a devastating stone disease, this prophylactic approach could be very cost-effective; however, this requires further confirmation.


Subject(s)
Spinal Cord Injuries/urine , Urinary Calculi/etiology , Urinary Calculi/urine , Water Supply/analysis , Adult , Calcium Carbonate/analysis , Case-Control Studies , Confidence Intervals , Drinking , Female , Humans , Logistic Models , Longitudinal Studies , Male , Middle Aged , Odds Ratio , Specific Gravity
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