A Pre-Clinical Assessment of Minocycline for Treatment of Chronic Neuropathic Pain after Spinal Cord Injury

Patients living with a spinal cord injury (SCI) often develop chronic neuropathic pain (CNP). Unfortunately, the clinically approved, current standard of treatment, gabapentin, only provides temporary pain relief. This treatment can cause numerous adverse side effects that negatively affect the daily lives of SCI patients. There is a great need for alternative, effective treatments for SCI-dependent CNP. Minocycline, an FDA-approved antibiotic, has been widely prescribed for the treatment of acne for several decades. However, recent studies demonstrate that minocycline has neuroprotective properties in several pre-clinical rodent models of CNS trauma and disease. Pre-clinical studies also show that short-term minocycline treatment can prevent the onset of CNP when delivered during the acute stage of SCI and can also transiently attenuate established CNP when delivered briefly during the chronic stage of SCI. However, the potential to abolish or attenuate CNP via long-term administration of minocycline after SCI is unknown. The purpose of this study was to investigate the potential efficacy and safety of long-term administration of minocycline to abolish or attenuate CNP following SCI. A severe spinal contusion injury was administered on adult, male, Sprague-Dawley rats. At day 29 post-injury, I initiated a three-week treatment regimen of daily administration with minocycline (50 mg/kg), gabapentin (50 mg/kg) or saline. The minocycline treatment group demonstrated a significant reduction in below-level mechanical allodynia and above- level hyperalgesia while on their treatment regimen. After a ten-day washout period of minocycline, the animals continued to demonstrate a significant reduction in below-level mechanical allodynia and above-level hyperalgesia. However, minocycline-treated animals exhibited abnormal weight gain and hepatotoxicity compared to gapabentin-treated or vehicle-treated subjects.The results support previous findings that minocycline can attenuate CNP after SCI and suggested that minocycline can also attenuate CNP via long-term delivery of minocycline after SCI (36). The data also suggested that minocycline had a lasting effect at reducing pain symptoms. However, the adverse side effects of long-term use of minocycline should not be ignored in the rodent model. Gabapentin treatment caused a significant decrease in below-level mechanical allodynia and below-level hyperalgesia during the treatment regimen. Because gabapentin treatment has an analgesic effect at the concentration I administered, the results were expected. However, I also found that gabapentin-treated animals demonstrated a sustained reduction in pain ten days after treatment withdrawal. This result was unexpected because gabapentin has a short half-life of 1.7 hours in rodents and previous studies have demonstrated that pre-drug pain levels return shortly after withdrawal of treatment. Additionally, the gabapentin-treated animals demonstrated a significant and sustained increase in rearing events compared with all other treatment groups which suggested that gabapentin treatment was not only capable of reducing pain long-term but may also significantly improve trunk stability or improve motor function recovery.

Azithromycin efficacy in treatment of Chlamydia trachomatis

Adolescents 15 – 19 years of age have the highest prevalence of Chlamydia trachomatis out of any age group, reaching 28.3% among detained youth [1]. The 2010 Center for Disease Control guidelines recommend one dose of azithromycin for the treatment of uncomplicated chlamydia infections based on 97% cure rate with azithromycin. Recent studies found an 8% or higher failure rate of azithromycin treatment in adolescents [2-5]. We conducted a prospective study beginning May, 2012 in the Harris County Juvenile Justice Center (HCJJC) medical department. Study subjects were detainees with positive urine NAAT tests for chlamydia on intake. We provided treatment with Azithromycin, completed questionnaires assessing risk factors and performed a test of cure for chlamydia three weeks after successful treatment. Those with treatment failure (positive TOC) received doxycycline for seven days. The preliminary results summarized herein are based on data collected from May 2012 to January 2013. Of the 97 youth enrolled in the study to date, 4 (4.1%) experienced treatment failure after administration of Azithromycin. Of these four patients, all were male, African-American and asymptomatic at the time of initial diagnosis and treatment. Of note, 37 (38%) patients in the cohort complained of abdominal pain with administration of Azithromycin. Results to date suggest that the efficacy of Azithromycin in our study is higher than the recent reported studies indicating a possible upper bound of Azithromycin. These results are preliminary and recruitment will continue until a sample size of 127 youth is reached.^

Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs).

We have investigated the in vivo safety, efficacy, and persistence of autologous Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) for the treatment of solid organ transplant (SOT) recipients at high risk for EBV-associated posttransplantation lymphoproliferative disease (PTLD). EBV-CTLs generated from 35 patients expanded with normal kinetics contained both CD8 and CD4 lymphocytes and produced significant specific killing of autologous EBV-transformed B lymphoblastoid cell lines (LCLs). Twelve SOT recipients at high risk for PTLD, or with active disease, received autologous CTL infusions without toxicity. Real-time polymerase chain reaction (PCR) monitoring of EBV-DNA showed a transient increase in plasma EBV-DNA suggestive of lysis of EBV-infected cells, although there was no consistent decrease in virus load in peripheral-blood mononuclear cells. Interferon-gamma enzyme-linked immunospot (ELISPOT) assay and tetramer analysis showed an increase in the frequency of EBV-responsive T cells, which returned to preinfusion levels after 2 to 6 months. None of the treated patients developed PTLD. One patient with liver PTLD showed a complete response, and one with ocular disease has had a partial response stable for over one year. These data are consistent with an expansion and persistence of adoptively transferred EBV-CTLs that is limited in the presence of continued immunosuppression but that nonetheless produces clinically useful antiviral activity.

Impact of medications prescribed for treatment of attention-deficit hyperactivity disorder on physical growth in children and adolescents with HIV.

OBJECTIVE: To examine the relationships between physical growth and medications prescribed for symptoms of attention-deficit hyperactivity disorder in children with HIV. METHODS: Analysis of data from children with perinatally acquired HIV (N = 2251; age 3-19 years), with and without prescriptions for stimulant and nonstimulant medications used to treat attention-deficit hyperactivity disorder, in a long-term observational study. Height and weight measurements were transformed to z scores and compared across medication groups. Changes in z scores during a 2-year interval were compared using multiple linear regression models adjusting for selected covariates. RESULTS: Participants with (n = 215) and without (n = 2036) prescriptions were shorter than expected based on US age and gender norms (p < .001). Children without prescriptions weighed less at baseline than children in the general population (p < .001) but gained height and weight at a faster rate (p < .001). Children prescribed stimulants were similar to population norms in baseline weight; their height and weight growth velocities were comparable with the general population and children without prescriptions (for weight, p = .511 and .100, respectively). Children prescribed nonstimulants had the lowest baseline height but were similar to population norms in baseline weight. Their height and weight growth velocities were comparable with the general population but significantly slower than children without prescriptions (p = .01 and .02, respectively). CONCLUSION: The use of stimulants to treat symptoms of attention-deficit hyperactivity disorder does not significantly exacerbate the potential for growth delay in children with HIV and may afford opportunities for interventions that promote physical growth. Prospective studies are needed to confirm these findings.

Role of cytochrome P450 in DNA damage produced by treatment of colon cells with 1,2-dimethylhydrazine

The study of colon cancer has taken advantage of the development of a model in animals in which tumors in the colon are easily induced by chemical treatment. When 1,2-dimethylhydrazine (DMH) is injected into rats tumor growth is observed in colon in preference to other tissues. This observation led us to investigate the Cytochrome P450 system in colon and its participation in the particular “colon sensitivity” to DMH. It has been established that the Cytochrome P450 system participates in the metabolism of DMH and the methyl carbonium product of Cytochrome P450 activation of DMH is responsible for DNA damage which is considered an initial step to carcinogenesis. The Cytochrome P450 system is a reasonable place to search for an explanation of this organotropic effect of DMH and we feel that the knowledge obtained from this study can take us closer to understanding the development of colonic malignancy. In our study we used a human colon cell line (LS174T) treated with DMH. The Cytochrome P450 system in the cells was manipulated with inducers of different isoforms of Cytochrome P450. The effect of DMH on colon cells was measured by determination of O-6-methylguanine which is a DNA adduct derived from the metabolism of this chemical and is associated with development of tumors. Our results support the hypothesis that Cytochrome P450 plays an important role in the damage to cellular DNA by DMH. This damage is increased after induction of Cytochromes P450 1A1 and 2E1. The effect of inhibition of the methyltransferase and glutathione systems on protection against DMH damage in colon demonstrated the importance of the protective role of the former and the lack of effective protection of the latter system. ^

Use of cardiac glycosides for treatment of cancer: Determinants of cancer cell sensitivity

Cardiac glycoside compounds have traditionally been used to treat congestive heart failure. Recently, reports have suggested that cardiac glycosides may also be useful for treatment of malignant disease. Our research with oleandrin, a cardiac glycoside component of Nerium oleander, has shown it to be a potent inducer of human but not murine tumor cell apoptosis. Determinants of tumor sensitivity to cardiac glycosides were therefore studied in order to understand the species selective cytotoxic effects as well as explore differential sensitivity amongst a variety of human tumor cell lines. ^ An initial model system involved a comparison of human (BRO) to murine (B16) melanoma cells. Human BRO cells were found to express both the sensitive α3 as well as the less sensitive α1 isoform subunits of Na+,K +-ATPase while mouse B16 cells expressed only the α1 isoform. Drug uptake and inhibition of Na+,K+-ATPase activity were also different between BRO and B16 cells. Partially purified human Na+,K+-ATPase enzyme was inhibited by cardiac glycosides at a concentration that was 1000-fold less than that required to inhibit mouse B16 enzyme to the same extent. In addition, uptake of oleandrin and ouabain was 3–4 fold greater in human than murine cells. These data indicate that differential expression of Na+,K+-ATPase isoform composition in BRO and B16 cells as well as drug uptake and total enzyme activity may all be important determinants of tumor cell sensitivity to cardiac glycosides. ^ In a second model system, two in vitro cell culture model systems were investigated. The first consisted of HFU251 (low expression of Na+,K+-ATPase) and U251 (high Na+ ,K+-ATPase expression) cell lines. Also investigated were human BRO cells that had undergone stable transfection with the α1 subunit resulting in an increase in total Na+,K+-ATPase expression. Data derived from these model systems have indicated that increased expression of Na+,K+-ATPase is associated with an increased resistance to cardiac glycosides. Over-expression of Na +,K+-ATPase in tumor cells resulted in an increase of total Na+,K+-ATPase activity and, in turn, a decreased inhibition of Na+,K+-ATPase activity by cardiac glycosides. However, of interest was the observation that increased enzyme expression was also associated with an elevated basal level of glutathione (GSH) within cells. Both increased Na+,K+-ATPase activity and elevated GSH content appear to contribute to a delayed as well as diminished release of cytochrome c and caspase activation. In addition, we have noted an increased colony forming ability in cells with a high level of Na+,K+-ATPase expression. This suggests that Na+,K+-ATPase is actively involved in tumor cell growth and survival. ^

Preclinical evaluation of proteasome inhibition for the treatment of prostate cancer

Prostatic carcinoma is the most prevalent cancer detected in men. Bortezomib is the first proteasome inhibitor to undergo clinical trials for several forms of cancer. Although we know this class of agent preferentially kills cancer cells, our knowledge of proteasome inhibition mechanisms of induced death is far from complete. We investigated the effects of bortezomib on the LNCaP-Pro5 (Pro5) and PC-3-Pro4 (Pro4) human prostatic adenocarcinoma cells lines. We showed a reduction in proliferation and an increase in DNA fragmentation, caspase 3 activity, and cell surface phosphatidyl serine exposure. The bortezomib-treated tumors from both cell lines were dramatically reduced, and apoptosis was induced. There was also a reduction in proliferation in the treated tumors from both cells lines. We looked at changes in the levels of the proangiogenic factors VEGF, IL-8 and bFGF in vitro and in vivo. Although there was a reduction in the levels of VEGF produced by the Pro5 cell line and tumor due to bortezomib, no similar observations were made for the other angiogenic factors or in the Pro4 cells. We investigated the effects of bortezomib on p53 in the Pro5 cell line. Bortezomib induced strong stabilization of p53. It did not promote phosphorylation on serines 15 and 24 and p53 remained bound to its inhibitor, mdm2. Nonetheless, confocal microscopy revealed that bortezomib stimulated p53 translocation to the nucleus and enhanced p53 DNA binding, accumulation of p53-dependant transcripts, and activation of a p53-responsive reporter gene. Furthermore, stable transfectants of LNCaP-Pro5 expressing the p53 inhibitor, HPV-E6, displayed reduced bortezomib-induced p53 activation and cell death. Our data shows bortezomib to induce antitumor effects in the human Pro4 and Pro5 prostatic adenocarcinoma cell lines by the direct induction of apoptosis. The drug also causes a reduction in cell proliferation and mean vessel density while modulating the secretion of proangiogenic factors. Although we show that proteasome inhibition stimulates p53 activation via a novel mechanism in Pro5 cells, it is also toxic to p53 null cells as is seen in the Pro4 line. ^

Risk of second primary tumors following treatment of non-small cell lung cancer

Background. The rise in survival rates along with more detailed follow-up using sophisticated imaging studies among non-small lung cancer (NSCLC) patients has led to an increased risk of second primary tumors (SPT) among these cases. Population and hospital based studies of lung cancer patients treated between 1974 and 1996 have found an increasing risk over time for the development of all cancers following treatment of non-small cell lung cancer (NSCLC). During this time the primary modalities for treatment were surgery alone, radiation alone, surgery and post-operative radiation therapy, or combinations of chemotherapy and radiation (sequentially or concurrently). There is limited information in the literature about the impact of treatment modalities on the development of second primary tumors in these patients. ^ Purpose. To investigate the impact of treatment modalities on the risk of second primary tumors in patients receiving treatment with curative intent for non-metastatic (Stage I–III) non-small cell lung cancer (NSCLC). ^ Methods. The hospital records of 1,095 NSCLC patients who were diagnosed between 1980–2001 and received treatment with curative intent at M.D. Anderson Cancer Center with surgery alone, radiation alone (with a minimum total radiation dose of at least 45Gy), surgery and post-operative radiation therapy, radiation therapy in combination with chemotherapy or surgery in combination with chemotherapy and radiation were retrospectively reviewed. A second primary malignancy was be defined as any tumor histologically different from the initial cancer, or of another anatomic location, or a tumor of the same location and histology as the initial tumor having an interval between cancers of at least five years. Only primary tumors occurring after treatment for NSCLC will qualified as second primary tumors for this study. ^ Results. The incidence of second primary tumor was 3.3%/year and the rate increased over time following treatment. The type of NSCLC treatment was not found to have a striking effect upon SPT development. Increased rates were observed in the radiation only and chemotherapy plus radiation treatment groups; but, these increases did not exceed expected random variation. Higher radiation treatment dose, patient age and weight loss prior to index NSCLC treatment were associated with higher SPT development. ^

Physician and patient determinants of the treatment of sleep difficulties in U.S. outpatient settings

The prevalence of sleep difficulties among the patients seen in the primary care settings is about 30%. This problem increases with age and is more common among females than males. Variations are noticed in prescription choices for different patients with sleep difficulties. Many factors affect a physician's prescription decision while chosen from a wide array of available medications. Both pharmacological and behavioral therapies are available for the treatment of sleep difficulties. It is important to know the impact of use of different types of prescriptions on health outcomes related to sleep difficulties. Thus the knowledge of prescription patterns among different types of patients (e.g. age, gender, race, insurance type etc.) becomes important for determining a clinical guideline. This study is designed to assist in evidence-based policymaking on understanding the variations in physician prescriptions for sleep difficulties and reasons for such variations. ^ A modified version of the model suggested by Eisenberg was used as a theoretical framework for this study to predict the factors influencing treatment of sleep difficulties. Multivariate logistic regression methods were used to analyze the 1996–2001 National Ambulatory Medical Care Survey data. ^ This study found that increased age, female gender, white race, established patients, and mental comorbidity were associated with significantly increased likelihood for prescription of some type of therapy for sleep difficulties in US outpatient settings. Patients with private insurance were associated with lower likelihood of receipt of many therapies. Psychiatrists were more likely to prescribe some kind of treatment as well as more expensive therapies for sleep difficulty as compared to other physician specialties. HMO enrolled patient visits were more likely to be associated with receipt of behavioral therapy. This study also found that 32% of patients with sleep difficulties received no type of therapy during their visits. Only 5% of the patients received behavioral therapy only. Almost three-quarters of the patients receiving some kind of medication prescription were prescribed benzodiazepines. The study results also suggest a need for wider coverage of behavioral therapy by payers in US outpatient settings. ^

Optimal frequency of Imiquimod (Aldara(RTM)) 5% cream treatment of external genital warts in immunocompetent adults. Systematic review and meta-analysis

Genital warts are a sexually transmitted disease with high prevalence in the U.S. Imiquimod 5% cream is a self-applied treatment, prescribed three-times weekly, at bedtime, for 16 weeks. The post-marketing research addressed questions of imiquimod dosing frequency. MEDLINE, Embase, and the Cochrane Library were searched for randomized trials on efficacy and safety of imiquimod 5% cream with either three-times weekly or once-daily regimens to systemically review treatment options. Efficacy was evaluated by completely cleared warts at the end of treatment, and safety - by frequency of adverse events and at least one rest period taken from treatment. Six studies were selected for the analysis, including circumcised men, uncircumcised men, and women. The once-daily compared to three-times weekly regimen did not improve the efficacy, but resulted in increased incidence of local skin reactions and events, when at least one rest period was taken from treatment. The optimal regimen is three-times weekly.^

Proton therapy versus intensity modulated x-ray therapy in the treatment of prostate cancer: Estimating secondary cancer risks

External beam radiation therapy is used to treat nearly half of the more than 200,000 new cases of prostate cancer diagnosed in the United States each year. During a radiation therapy treatment, healthy tissues in the path of the therapeutic beam are exposed to high doses. In addition, the whole body is exposed to a low-dose bath of unwanted scatter radiation from the pelvis and leakage radiation from the treatment unit. As a result, survivors of radiation therapy for prostate cancer face an elevated risk of developing a radiogenic second cancer. Recently, proton therapy has been shown to reduce the dose delivered by the therapeutic beam to normal tissues during treatment compared to intensity modulated x-ray therapy (IMXT, the current standard of care). However, the magnitude of stray radiation doses from proton therapy, and their impact on this incidence of radiogenic second cancers, was not known. ^ The risk of a radiogenic second cancer following proton therapy for prostate cancer relative to IMXT was determined for 3 patients of large, median, and small anatomical stature. Doses delivered to healthy tissues from the therapeutic beam were obtained from treatment planning system calculations. Stray doses from IMXT were taken from the literature, while stray doses from proton therapy were simulated using a Monte Carlo model of a passive scattering treatment unit and an anthropomorphic phantom. Baseline risk models were taken from the Biological Effects of Ionizing Radiation VII report. A sensitivity analysis was conducted to characterize the uncertainty of risk calculations to uncertainties in the risk model, the relative biological effectiveness (RBE) of neutrons for carcinogenesis, and inter-patient anatomical variations. ^ The risk projections revealed that proton therapy carries a lower risk for radiogenic second cancer incidence following prostate irradiation compared to IMXT. The sensitivity analysis revealed that the results of the risk analysis depended only weakly on uncertainties in the risk model and inter-patient variations. Second cancer risks were sensitive to changes in the RBE of neutrons. However, the findings of the study were qualitatively consistent for all patient sizes and risk models considered, and for all neutron RBE values less than 100. ^

The high cost of inappropriate empiric treatment of presumed Clostridium difficile-associated diarrhea

The Center for Disease Control and Prevention (CDC) estimates that more than 2 million patients annually acquire an infection while hospitalized in U.S. hospitals for other health problems, and that 88,000 die as a direct or indirect result of these infections. Infection with Clostridium difficile is the most important common cause of health care associated infectious diarrhea in industrialized countries. The purpose of this study was to explore the cost of current treatment practice of beginning empiric metronidazole treatment for hospitalized patients with diarrhea prior to identification of an infectious agent. The records of 70 hospitalized patients were retrospectively analyzed to determine the pharmacologic treatment, laboratory testing, and radiographic studies ordered and the median cost for each of these was determined. All patients in the study were tested for C. difficile and concurrently started on empiric metronidazole. The median direct cost for metronidazole was $7.25 per patient (95% CI 5.00, 12.721). The median direct cost for laboratory charges was $468.00 (95% CI 339.26, 552.58) and for radiology the median direct cost was $970.00 (95% CI 738.00, 3406.91). Indirect costs, which are far greater than direct costs, were not studied. At St. Luke's, if every hospitalized patient with diarrhea was empirically treated with metronidazole at a median cost of $7.25, the annual direct cost is estimated to be over $9,000.00 plus uncalculated indirect costs. In the U.S., the estimated annual direct cost may be as much as $21,750,000.00, plus indirect costs. ^ An unexpected and significant finding of this study was the inconsistency in testing and treatment of patients with health care associated diarrhea. A best-practice model for C. difficile testing and treatment was not found in the literature review. In addition to the cost savings gained by not routinely beginning empiric treatment with metronidazole, significant savings and improvement in patient care may result from a more consistent approach to the diagnosis and treatment of all patients with health care associated diarrhea. A decision tree model for C. difficile testing and treatment is proposed, but further research is needed to evaluate the decision arms before a validated best practice model can be proposed. ^

A simplified protocol for the treatment of acute radiation overexposures from sources external to the body

When compared to other types of occupational injuries, radiation overexposure events are somewhat rare, so health care providers may not be familiar with the actual clinical care to be provided when such an event occurs. Radiation overexposure treatment decisions are predicated on the amount of radiation dose received, which is a value many health care providers may not have the knowledge or expertise to either calculate or even estimate. Even the different units of measure for radiation exposure and dose received can be a source of confusion. The prompt treatment of radiation overexposure victims could be enhanced and facilitated through the creation of a single, simple protocol that consists of the various means of dose measurement and estimation, correlated to the corresponding appropriate clinical care measures. This culminating experience will assemble essential information currently maintained in disparate references to create a single, simplified protocol to facilitate the treatment of victims of acute external radiation overexposure. ^

The imaging and dosimetric capabilities of a CT/MR-suitable, anatomically adaptive, shielded intracavitary brachytherapy applicator for the treatment of cervical cancer

Introduction. Investigations into the shortcomings of current intracavitary brachytherapy (ICBT) technology has lead us to design an Anatomically Adaptive Applicator (A3). The goal of this work was to design and characterize the imaging and dosimetric capabilities of this device. The A3 design incorporates a single shield that can both rotate and translate within the colpostat. We hypothesized that this feature, coupled with specific A3 component construction materials and imaging techniques, would facilitate artifact-free CT and MR image acquisition. In addition, by shaping the delivered dose distribution via the A3 movable shield, dose delivered to the rectum will be less compared to equivalent treatments utilizing current state-of-the-art ICBT applicators. ^ Method and materials. A method was developed to facilitate an artifact-free CT imaging protocol that used a "step-and-shoot" technique: pausing the scanner midway through the scan and moving the A 3 shield out of the path of the beam. The A3 CT imaging capabilities were demonstrated acquiring images of a phantom that positioned the A3 and FW applicators in a clinically-applicable geometry. Artifact-free MRI imaging was achieved by utilizing MRI-compatible ovoid components and pulse-sequences that minimize susceptibility artifacts. Artifacts were qualitatively compared, in a clinical setup. For the dosimetric study, Monte-Carlo (MC) models of the A3 and FW (shielded and unshielded) applicators were validated. These models were incorporated into a MC model of one cervical cancer patient ICBT insertion, using 192Ir (mHDR v2 source). The A3 shield's rotation and translation was adjusted for each dwell position to minimize dose to the rectum. Superposition of dose to rectum for all A3 dwell sources (4 per ovoid) was applied to obtain a comparison of equivalent FW treatments. Rectal dose-volume histograms (absolute and HDR/PDR biologically effective dose (BED)) and BED to 2 cc (BED2cc ) were determined for all applicators and compared. ^ Results. Using a "step-and-shoot" CT scanning method and MR compliant materials and optimized pulse-sequences, images of the A 3 were nearly artifact-free for both modalities. The A3 reduced BED2cc by 18.5% and 7.2% for a PDR treatment and 22.4% and 8.7% for a HDR treatment compared to treatments delivered using an uFW and sFW applicator, respectively. ^ Conclusions. The novel design of the A3 facilitated nearly artifact-free image quality for both CT and MR clinical imaging protocols. The design also facilitated a reduction in BED to the rectum compared to equivalent ICBT treatments delivered using current, state-of-the-art applicators. ^

Symposium for dental treatment of medically complex children: Practice based culminating experience a continuing education course

The purpose of this Continuing Education Course is to provide oral health professionals with information to address the unique dental needs of medically complex children. The objective is to train dentists to treat special needs patients so these children have more access to oral healthcare. ^ Under the auspice of Dell Children Hospital of Austin, Lisa Jacob DDS MS is administering this Continuing Education Course for dentists and dental staff from the 46 counties of central Texas served by the hospital.^ Needs assessment was determined through a survey questionnaire to collect data about the number of special needs patients seen by general dentists in Central Texas.^ In recent years, an increasing number of continuing education courses have been developed to help dentists learn techniques for providing dentistry in more understanding ways to patients with special needs. Dentists and dental staff are trained to provide care specifically in dentistry, regardless of who the patient is. This means dentists can perform a clinical examination, carry out procedures to diagnose and treat oral diseases, and provide restorations such as fillings and crowns. ^ Four prominent speakers will provide an instructional tool to address the need for dentists to increase their competence and comfort level in caring for individuals with developmental disabilities. Each speaker will address one of the most frequently encountered cases of medically complex children. The four topics selected by Dr. Lisa Jacob are Cancer, Mental Disability, Downs Syndrome, and Craniofacial Syndromes.^ The public health implications of this continuing education course are presented in providing dental service to this underserved population. When general dentist turn away patients with special needs because of lack of knowledge to treat them, these patients will, more than likely, postpone or abandon needed dental visits because of difficulties reaching pediatric dentists who may not be available in certain areas.^