• Questionnaire Design and Responsiveness in a Data Capture Tool for Student Sharing of Experiences of Statewide Clerkship Sites

      Zheng, Stephanie; Behrman, David; Agrawal, Parth; Basco, Brian; Ball, Charlotte; Rose, Jennifer; Miller, Samel; Wood, Elena (2017-03)
      Positive clerkship experiences and student performance in the clinical years has been correlated to perceived quality of education and specialty choice amongst medical students [1-3]. The Medical College of Georgia uses a distributed campus model with more than 250 clerkship rotation sites across the state and beyond, making student clerkship choices imperative to their development as physicians. We developed a survey to collect both quantitative and qualitative data from students during their clerkship years and a system to distribute that information to students. The data allowed us to evaluate the effectiveness of various question formats through responsiveness, the length of responses, and time spent on the survey. In addition to this, we looked at the number of responses per clerkship in order to see whether or not our survey was getting information about all of the 3rd year rotations. We aspire to take these findings and utilize them to expand t he program and improve the questionnaire in order to yield more responsiveness from students.
    • An Investigation of the Chronic Disease Self-Management Program - Assessing CDSMP Facilitators' Perceptions of the Program's Effect

      Hillman, L. M.; Anderson, C.; Stoodt, G.; Department of Medicine; Augusta University (2017-03)
      Chronic conditions are public health threats. The Chronic Disease Self-Management Program (CDSMP) is an evidence-based disease management program that addresses personal self-management of chronic conditions. The CDSMP involves peer trainers who instruct and assist with chronic disease preventive measures. Although disease management demonstrates promise to improving patient self-maintenance, previous researchers have not evaluated how the program affects program leaders. The purpose of this study was to discover how self-help leaders feel about the CDSM program. The overarching research question asked about perspectives that self-help leaders had toward the program. Through a narrative qualitative approach, the perceptions of peer leaders were examined to determine if the program was personally beneficial. Guided by the social cognitive theory, a purposeful convenience sample of 20 participants completed the study. The participants were practicing peer trainers in the CDSMP prog ram. Data analysis included hand coding using open and axial coding and content analysis. Study findings included themes surrounding how the CDSMP program benefits health in general as well as the management of facilitators’ own chronic diseases, health behaviors, and increased quality of life. The ability for chronic disease management leaders to experience positive effects of the program they administer may result in positive social change. This awareness can positively affect social change by enhancing an already established evidence-based community health program with stronger and better-equipped leaders.
    • Salmonella newport bacteremia in a 12-day-old infant.

      Singh, Abhijit; Wilkins, Thad; Schade, Robert R.; Department of Family Medicine (2011-03)
      In the United States, Salmonella infections (salmonellosis) cause multiple medical problems. Although the most common presenting symptom is diarrhea, bacteremia can also occur. An estimated 1.4 million cases of salmonellosis occur annually in the United States. We present a case of Salmonella bacteremia in a 12-day old infant. We discuss the presenting signs, symptoms, and management strategies for a patient younger than 28 days old (neonate) presenting with fever and diarrhea.
    • Diagnosis and management of upper gastrointestinal bleeding.

      Wilkins, Thad; Khan, Naiman; Nabh, Akash; Schade, Robert R.; Department of Family Medicine; Department of Medicine (2012-03-01)
      Upper gastrointestinal bleeding causes significant morbidity and mortality in the United States, and has been associated with increasing nonsteroidal anti-inflammatory drug use and the high prevalence of Helicobacter pylori infection in patients with peptic ulcer bleeding. Rapid assessment and resuscitation should precede the diagnostic evaluation in unstable patients with severe bleeding. Risk stratification is based on clinical assessment and endoscopic findings. Early upper endoscopy (within 24 hours of presentation) is recommended in most patients because it confirms the diagnosis and allows for targeted endoscopic treatment, including epinephrine injection, thermocoagulation, application of clips, and banding. Endoscopic therapy results in reduced morbidity, hospital stays, risk of recurrent bleeding, and need for surgery. Although administration of proton pump inhibitors does not decrease mortality, risk of rebleeding, or need for surgery, it reduces stigmata of recent hemorrhage and the need for endoscopic therapy. Despite successful endoscopic therapy, rebleeding can occur in 10 to 20 percent of patients; a second attempt at endoscopic therapy is recommended in these patients. Arteriography with embolization or surgery may be needed if there is persistent and severe bleeding.
    • Anomalous coronary artery found in the syncopal workup of an elderly man

      Oommen, Ronnie; Wilkins, Thad; Chen, Stephen Y; Arora, Vishal; Department of Family Medicine; Department of Medicine; Department of Cardiology (2012-07)
      Syncope, defined as a transient loss of consciousness, is seen in 1% of all visits to emergency departments and urgent care clinics in the United States. Syncope is categorized as cardiogenic, neurologic, or psychogenic. Anomalies of the coronary arteries are rare, and anomalous coronary arteries present as syncope more often in the young than in the elderly; syncope rarely occurs in patients 65 years of age and older. There are 2 major variants of coronary anomalies. In the first variant, the left main coronary artery arises from the right aortic sinus. In the second variant, the right coronary artery arises from the left aortic sinus. The risk of sudden death is higher in patients with the left coronary artery arising from the right aortic sinus. We present a case of an anomalous coronary artery discovered during the syncopal workup in a 66-year-old man because no such cases have been published in the United States. We will discuss the management of anomalous coronary arteries as well as a systematic approach to the diagnosis and management of syncope.
    • Accelerated Growth Plate Mineralization and Foreshortened Proximal Limb Bones in Fetuin-A Knockout Mice

      Seto, Jong; Busse, Bjorn; Gupta, Himadri S.; Schafer, Cora; Krauss, Stefanie; Dunlop, John W. C.; Masic, Admir; Kerschnitzki, Michael; Zaslansky, Paul; Boesecke, Peter; et al. (2012-10-16)
      The plasma protein fetuin-A/alpha2-HS-glycoprotein (genetic symbol Ahsg) is a systemic inhibitor of extraskeletal mineralization, which is best underscored by the excessive mineral deposition found in various tissues of fetuin-A deficient mice on the calcification-prone genetic background DBA/2. Fetuin-A is known to accumulate in the bone matrix thus an effect of fetuin-A on skeletal mineralization is expected. We examined the bones of fetuin-A deficient mice maintained on a C57BL/6 genetic background to avoid bone disease secondary to renal calcification. Here, we show that fetuin-A deficient mice display normal trabecular bone mass in the spine, but increased cortical thickness in the femur. Bone material properties, as well as mineral and collagen characteristics of cortical bone were unaffected by the absence of fetuin-A. In contrast, the long bones especially proximal limb bones were severely stunted in fetuin-A deficient mice compared to wildtype littermates, resulting in increased biomechanical stability of fetuin-A deficient femora in three-point-bending tests. Elevated backscattered electron signal intensities reflected an increased mineral content in the growth plates of fetuin-A deficient long bones, corroborating its physiological role as an inhibitor of excessive mineralization in the growth plate cartilage matrix - a site of vigorous physiological mineralization. We show that in the case of fetuin-A deficiency, active mineralization inhibition is a necessity for proper long bone growth.
    • Asymptomatic Severe Hypocalcemia Secondary to Vitamin D Deficiency in an Elderly Patient

      Aldasouqi, Saleh; Glassy, Crystal M.; Glassy, Matthew S.; Treska, Anxhela; Caldwell-McMillan, Molly; Gossain, Ved; Department of Medicine (2011-11-2)
    • Rac1 Activation Driven by 14-3-3f Dimerization Promotes Prostate Cancer Cell-Matrix Interactions, Motility and Transendothelial Migration

      Goc, Anna; Abdalla, Maha; Al-Azayzih, Ahmad; Somanath, Payaningal R.; Department of Medicine (2012-07-13)
      14-3-3 proteins are ubiquitously expressed dimeric adaptor proteins that have emerged as key mediators of many cell signaling pathways in multiple cell types. Its effects are mainly mediated by binding to selective phosphoserine/threonine proteins. The importance of 14-3-3 proteins in cancer have only started to become apparent and its exact role in cancer progression as well as the mechanisms by which 14-3-3 proteins mediate cancer cell function remain unknown. While protein 14-3-3s is widely accepted as a tumor suppressor, 14-3-3f, b and c isoforms have been shown to have tumor promoting effects. Despite the importance of 14-3-3 family in mediating various cell processes, the exact role and mechanism of 14-3-3f remain unexplored. In the current study, we investigated the role of protein 14-3-3f in prostate cancer cell motility and transendothelial migration using biochemical, molecular biology and electric cell-substrate impedance sensing approaches as well as cell based functional assays. Our study indicated that expression with wild-type protein 14-3-3f significantly enhanced Rac activity in PC3 cells. In contrast, expression of dimer-resistant mutant of protein 14-3-3f (DM-14-3-3) inhibited Rac activity and associated phosphorylation of p21 activated kinase-1 and 2. Expression with wild-type 14-3-3f or constitutively active Rac1 enhanced extracellular matrix recognition, lamellipodia formation, cell migration and trans-endothelial migration by PC3 cells. In contrast, expression with DM 14-3-3f or DN-Rac1 in PC3 cells significantly inhibited these cell functions. Our results demonstrate for the first time that 14-3-3f enhances prostate cancer cell-matrix interactions, motility and transendothelial migration in vitro via activation of Rac1-GTPase and is an important target for therapeutic interventions for prostate cancer.
    • Association between Genetic Variants in DNA and Histone Methylation and Telomere Length

      Kim, Sangmi; Parks, Christine G.; Xu, Zongli; Carswell, Gleta; DeRoo, Lisa A.; Sandler, Dale P.; Taylor, Jack A.; Department of Medicine (2012-07-11)
      Telomere length, a biomarker of aging and age-related diseases, exhibits wide variation between individuals. Common genetic variation may explain some of the individual differences in telomere length. To date, however, only a few genetic variants have been identified in the previous genome-wide association studies. As emerging data suggest epigenetic regulation of telomere length, we investigated 72 single nucleotide polymorphisms (SNPs) in 46 genes that involve DNA and histone methylation as well as telomerase and telomere-binding proteins and DNA damage response. Genotyping and quantification of telomere length were performed in blood samples from 989 non-Hispanic white participants of the Sister Study, a prospective cohort of women aged 35–74 years. The association of each SNP with logarithmically-transformed relative telomere length was estimated using multivariate linear regression. Six SNPs were associated with relative telomere length in blood cells with p-values<0.05 (uncorrected for multiple comparisons). The minor alleles of BHMT rs3733890 G>A (p = 0.041), MTRR rs2966952 C>T (p = 0.002) and EHMT2 rs558702 G>A (p = 0.008) were associated with shorter telomeres, while minor alleles of ATM rs1801516 G>A (p = 0.031), MTR rs1805087 A>G (p = 0.038) and PRMT8 rs12299470 G>A (p = 0.019) were associated with longer telomeres. Five of these SNPs are located in genes coding for proteins involved in DNA and histone methylation. Our results are consistent with recent findings that chromatin structure is epigenetically regulated and may influence the genomic integrity of telomeric region and telomere length maintenance. Larger studies with greater coverage of the genes implicated in DNA methylation and histone modifications are warranted to replicate these findings.
    • Plerixafor Salvage Is Safe and Effective in Hard-to-Mobilize Patients Undergoing Chemotherapy and Filgrastim-Based Peripheral Blood Progenitor Cell Mobilization

      Awan, Farrukh T.; Kochuparambil, S. Thomas; DeRemer, David; Cumpston, Aaron; Craig, Michael; Jillella, Anand; Hamadani, Mehdi; Department of Medicine; Department of Pharmacology and Toxicology (2012-04-10)
      The combination of filgrastim (G-CSF) and plerixafor is currently approved for mobilizing peripheral blood progenitor cells in patients with non-Hodgkin lymphoma and multiple myeloma undergoing autologous peripheral blood hematopoietic cell transplantation. However, chemotherapy and G-CSF-based mobilization remains a widely used strategy for peripheral blood progenitor cell collection. In this paper we describe our experience from two North American transplant centers in a series of patients who received salvage plerixafor while failing chemotherapy and G-CSF mobilization. Patients received a median of two doses of plerixafor salvage upon failure to mobilize adequate number of peripheral blood progenitor cells at neutrophil recovery. The use of plerixafor was associated with a 2.4-fold increase in peripheral blood CD34+ cell count and 3.9-fold increase in total CD34+ cell yield. All patients were able to collect â ¥2 Ã 106 CD34+â cells/kg with this approach. These results were more pronounced in patients with a higher CD34+ cell count at the time of the first plerixafor dose. Interestingly, peripheral blood white blood cell count was not shown to correlate with a response to plerixafor. Our results provide safety and efficacy data for the use of plerixafor in patients who are destined to fail chemomobilization.
    • Carcinomatous Meningitis: The Natural History of Successfully Treated Metastatic Bladder Cancer

      Tadepalli, S.; Coleman, Teresa; Hackett, Ladawn A.; Liles, G.B.; Department of Medicine; Department of Pathology (2011-08-24)
      Carcinomatous meningitis due to bladder cancer is a rare entity reported only in case reports. Optimal therapy is thus poorly defined with earlier cases reporting an unsuccessful outcome. Here we report a case of late carcinomatous meningitis secondary to transitional cell carcinoma (TCC) of the bladder occurring in a patient in complete remission. He was successfully treated with intrathecal methotrexate and whole brain irradiation and experienced prolonged survival after treatment. With modern chemotherapy increasing complete remissions and survival rates in patients with TCC, more and more patients are being reported with carcinomatous meningitis. We raise the question of whether central nervous system prophylaxis should be considered in patients with TCC achieving a complete remission to chemotherapy in the metastatic setting.
    • Improved Immunodetection of Endogenous α-Synuclein

      Lee, Byung Rho; Kamitani, Tetsu; Department of Medicine; Center for Molecular Chaperone/Radiobiology & Cancer Virology (2011-08-19)
      α-Synuclein is a key molecule in understanding the pathogenesis of neurodegenerative α-synucleinopathies such as Parkinson's disease. Despite extensive research, however, its precise function remains unclear partly because of a difficulty in immunoblotting detection of endogenous α-synuclein. This difficulty has largely restricted the progress for α-synucleinopathy research. Here, we report that α-synuclein monomers tend to easily detach from blotted membranes, resulting in no or very poor detection. To prevent this detachment, a mild fixation of blotted membranes with paraformaldehyde was applied to the immunoblotting method. Amazingly, this fixation led to clear and strong detection of endogenous α-synuclein, which has been undetectable by a conventional immunoblotting method. Specifically, we were able to detect endogenous α-synuclein in various human cell lines, including SH-SY5Y, HEK293, HL60, HeLa, K562, A375, and Daoy, and a mouse cell line B16 as well as in several mouse tissues such as the spleen and kidney. Moreover, it should be noted that we could clearly detect endogenous α-synuclein phosphorylated at Ser-129 in several human cell lines. Thus, in some tissues and cultured cells, endogenous α-synuclein becomes easily detectable by simply fixing the blotted membranes. This improved immunoblotting method will allow us to detect previously undetectable endogenous α-synuclein, thereby facilitating α-synuclein research.
    • Mild Functional Ischemic Mitral Regurgitation Following Acute Coronary Syndrome: A Retrospective Study

      Pant, Sadip; Neupane, Pritam; Pant, Om Biju; Paudel, Raju; Kumar, M. P. Kavin; Vijayashankar, C. S.; Shrestha, Rajendra Man; Department of Pulmonary and Critical Care (2011-04)
      Background:: Ischemic mitral regurgitation is a frequent complication of acute coronary syndrome. It primarily occurs in patients with a prior myocardial infarction but also may be seen with acute ischemia, a setting in which the MR typically resolves after the ischemia resolves. The vast majority of patients have â functionalâ ischemic MR. In these individuals, the papillary muscles, chordae, and valve leaflets are normal. However, the leaflets do not coapt and restricted leaflet motion is frequently noted on echocardiography. Ischemic mitral regurgitation indicates a poor prognosis after acute myocardial infarction. This study addresses the clinical characteristics of patients of acute coronary syndrome with mild functional ischemic mitral regurgitation and its impact on immediate in-hospital cardiovascular outcomes and death.
    • PROTEIN SYNTHESIS IN PANCREAS OF FASTED PIGEONS

      Black, Owen; Webster, Paul D.; Department of Medicine; Department of Cellular Biology and Anatomy (1973-04-1)
      The regulation of protein synthesis in the pigeon has been studied by comparing the capability of cell-free amino acid incorporating systems of membrane-bound and membrane-free polysomes prepared from fasted and fed birds. New methods were developed for isolating polysomes since techniques used for other tissues did not provide quantitative recovery of polysomal RNA. The sucrose gradient profile of polysomes from pigeon pancreas showed a predominance of trisome species. Although initiation factors are present on polysomes, it was found that polysomes in cell-free systems would not initiate protein synthesis without exogenous initiation factors. This suggested the presence of an inhibitor or regulator of protein synthesis. These studies show that fasting resulted in: (a) decreased amounts of polysomes; (b) disaggregation of polysomes to monosomes; (c) decreased capability of polysomes to synthesize nascent peptides and to initiate additional synthesis, apparently not related to concentration of initiation factors.
    • The effect of student training on accuracy of completion of death certificates.

      Degani, Adil T; Patel, Rajendrakumar M; Smith, Betsy E; Grimsley, Edwin; Section of Pulmonary & Critical Care Medicine, Department of Medicine, Medical College of Georgia (2010-02-18)
      BACKGROUND: Death certificates are an invaluable source of statistical and medical information, as well as important legal documents. However, few physicians receive formal training on how to accurately complete them. PURPOSE: To determine if a simple intervention can improve the accuracy of death certificate completion by medical students. METHODS: Participants included all third year medical students undergoing their core Internal Medicine rotation at Mercer University School of Medicine at the Medical Center of Central Georgia. Participation was voluntary and participants completed an approved informed consent. Students were presented a tutorial from the National Association of Medical Examiners website. They were asked to complete a death certificate both before and after the tutorial along with subjective questionnaires. The primary outcome measurement was the difference in scores pre- and post-tutorial. RESULTS: The mean score before the tutorial was 11.75 (+/-3.20) and the mean score post-tutorial was 18.85 (+/-2.56), indicating an increase in scores. The mean difference in pre- and post-tutorial scores was significant (t = 20.39, p < 0.0001). CONCLUSIONS: We found that using a tutorial to teach students how to correctly complete a death certificate was effective.
    • Impact of clinical pharmacy services on renal transplant recipients' adherence and outcomes.

      Chisholm-Burns, Marie A; Spivey, Christina A; Garrett, Charlene; McGinty, Herbert; Mulloy, Laura L; Department of Medicine (2009-11-20)
      The purpose of this article is to provide a description of a clinical pharmacy services program implemented in a renal transplant clinic to improve medication access and adherence as well as health and economic outcomes among renal transplant recipients (RTRs). Following a team-based planning process and an informal survey of RTRs, a clinical pharmacy service intervention was implemented in the Medical College of Georgia renal transplant clinic. As part of the intervention, a clinical pharmacist reviewed and optimized medication therapy, provided instructions on how to take medication, and assisted with enrollment into medication assistance programs. Significant differences were found between RTRs who did and did not receive clinical pharmacy services on measures of adherence, health, economics, and quality of life. Clinical pharmacy services, as described in this article, have a positive impact on renal transplant recipients' medication adherence, health and economic outcomes, and health-related quality of life. The findings described here suggest that clinical pharmacy services are a viable and effective option for improving care for RTRs in an outpatient clinic setting.
    • Can novel Apo A-I polymorphisms be responsible for low HDL in South Asian immigrants?

      Dodani, Sunita; Dong, Yanbin; Zhu, Haidong; George, Varghese; Department of Medicine (2010-03-19)
      Coronary artery disease (CAD) is the leading cause of death in the world. Even though its rates have decreased worldwide over the past 30 years, event rates are still high in South Asians. South Asians are known to have low high-density lipoprotein (HDL) levels. The objective of this study was to identify Apolipoprotein A-I (Apo A-I) polymorphisms, the main protein component of HDL and explore its association with low HDL levels in South Asians. A pilot study on 30 South Asians was conducted and 12-h fasting samples for C-reactive protein, total cholesterol, HDL, low-density lipoprotein (LDL), triglycerides, Lipoprotein (a), Insulin, glucose levels, DNA extraction, and sequencing of Apo A-I gene were done. DNA sequencing revealed six novel Apo A-I single nucleotide polymorphisms (SNPs) in South Asians, one of which (rs 35293760, C938T) was significantly associated with low (<40 mg/dl) HDL levels (P = 0.004). The association was also seen with total cholesterol (P = 0.026) and LDL levels (P = 0.032). This pilot work has highlighted some of the gene-environment associations that could be responsible for low HDL and may be excess CAD in South Asians. Further larger studies are required to explore and uncover these associations that could be responsible for excess CAD risk in South Asians.
    • Symptomatic hypercalcemia in a patient with chronic tophaceous gout: a case report.

      Sachdeva, Alok; Goeckeritz, Bruce E; Oliver, Alyce M; Department of Medicine (2008-08-21)
      ABSTRACT: Hypercalcemia has been widely associated with granulomatous processes. This is due to enhanced extra-renal conversion of calcidiol to calcitriol by activated macrophages within the granuloma. Symptomatic hypercalcemia due to granulomatous disorders is not common, with the incidence in sarcoidosis ranging from 10-20%. Large aggregates of monosodium urate crystals in patients with longstanding chronic tophaceous gout can serve as the inciting antigen for the development of granuloma, but hypercalcemia has not been described in this context. We report a case of symptomatic hypercalcemia due to gouty tophi induced granulomatous inflammation. Long term treatment with immunosuppressants, in addition to bisphosphonates and uric acid lowering therapy, has led to stabilization of serum calcium levels and other lab parameters indicative of granulomatous burden.
    • The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome.

      Pedersen-White, Jennifer R; Chorich, Lynn P; Bick, David P; Sherins, Richard J; Layman, Lawrence C; Department of Medicine; Department of Obstetrics and Gynecology; Department of Obstetrics and Gynecology; Institute of Molecular Medicine and Genetics; Institute of Neuroscience (2008-06-23)
      Idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are clinically and genetically heterogeneous disorders caused by a deficiency of gonadotrophin-releasing hormone (GnRH). Mutations in three genes--KAL1, GNRHR and FGFR1--account for 15-20% of all causes of IHH/KS. Nearly all mutations are point mutations identified by traditional PCR-based DNA sequencing. The relatively new method of multiplex ligation-dependent probe amplification (MLPA) has been successful for detecting intragenic deletions in other genetic diseases. We hypothesized that MLPA would detect intragenic deletions in approximately 15-20% of our cohort of IHH/KS patients. Fifty-four IHH/KS patients were studied for KAL1 deletions and 100 were studied for an autosomal panel of FGFR1, GNRH1, GNRHR, GPR54 and NELF gene deletions. Of all male and female subjects screened, 4/54 (7.4%) had KAL1 deletions. If only anosmic males were considered, 4/33 (12.1%) had KAL1 deletions. No deletions were identified in any of the autosomal genes in 100 IHH/KS patients. We believe this to be the first study to use MLPA to identify intragenic deletions in IHH/KS patients. Our results indicate approximately 12% of KS males have KAL1 deletions, but intragenic deletions of the FGFR1, GNRH1, GNRHR, GPR54 and NELF genes are uncommon in IHH/KS.
    • 8-Cl-Adenosine enhances 1,25-dihydroxyvitamin D3-induced growth inhibition without affecting 1,25-dihydroxyvitamin D3-stimulated differentiation of primary mouse epidermal keratinocytes.

      Bollag, Wendy B; Zhong, Xiaofeng; Josephson, Sarah; Department of Medicine; Department of Cellular Biology and Anatomy; Institute of Molecular Medicine and Genetics (2004-08-10)
      BACKGROUND: Epidermal keratinocytes continuously proliferate and differentiate to form the mechanical and water permeability barrier that makes terrestrial life possible. In certain skin diseases, these processes become dysregulated, resulting in abnormal barrier formation. In particular, skin diseases such as psoriasis, actinic keratosis and basal and squamous cell carcinomas are characterized by hyperproliferation and aberrant or absent differentiation of epidermal keratinocytes. We previously demonstrated that 8-Cl-adenosine (8-Cl-Ado) can induce keratinocyte growth arrest without inducing differentiation. RESULTS: To determine if this agent might be useful in treating hyperproliferative skin disorders, we investigated whether 8-Cl-Ado could enhance the ability of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], a known keratinocyte differentiating agent and a clinical treatment for psoriasis, to inhibit keratinocyte growth. We found that low concentrations of 8-Cl-Ado and 1,25(OH)2D3 appeared to act additively to reduce proliferation of primary mouse epidermal keratinocytes. However, another agent (transforming growth factor-beta) that triggers growth arrest without inducing differentiation also coincidentally inhibits differentiation elicited by other agents; inhibition of differentiation is suboptimal for treating skin disorders, as differentiation is often already reduced. Thus, we determined whether 8-Cl-Ado also decreased keratinocyte differentiation induced by 1,25(OH)2D3, as measured using the early and late differentiation markers, keratin 1 protein levels and transglutaminase activity, respectively. 8-Cl-Ado did not affect 1,25(OH)2D3-stimulated keratin 1 protein expression or transglutaminase activity. CONCLUSIONS: Our results suggest that 8-Cl-Ado might be useful in combination with differentiating agents for the treatment of hyperproliferative disorders of the skin.