Faculty Bibliography

Background: Contiguous gene deletion of the Wilms tumor gene (WT1) is associated with two well described syndromes; Denys-Drash (DDS) and Frasier (FS). Both are associated with nephropathy and ambiguous genitalia and have overlapping clinical and molecular features (1). The known risk of Wilms tumors in DDS and gonadoblastomas in FS patients requires tumor surveillance.Case report: We evaluated a newborn with ambiguous genitalia, intact Mullerian structures (uterus) and small bilateral perivesicular gonads with a 46,XY (SRY+) karyotype. The physical exam revealed labia with clitoromegaly (1.2 cm in length). There were separate uretheral and vaginal openings with no urogenital sinus. Labs in the early neonatal period (Quest Diagnostics: all male references) revealed 17-OH-Progesterone 96 (<420 ng/dL), testosterone 133 (2-23 ng/dL; tanner 1), DHEAS 441 (73-367 ug/dL), inhibin A <1 (<21 pg/mL; prepubertal), inhibin B 35 (<161 pg/mL; 3-9 years old), and AMH 3.7 (87.3-243 ng/mL; 1-6 years old). After a joint discussion with the family, geneticist, endocrinologist, and psychologist the infant was assigned a female gender. Based on the phenotype (ambiguous genitalia, pre and postnatal hydronephrosis, and genitourinary abnormalities), the exon and exon-intron boundaries were sequenced. A missense mutation leading to the substitution of lysine for glutamine at position 369 of the WT1 protein (Q369K) in exon 8 was found to be consistent with Denys-Drash syndrome. At seven months of age the patient underwent a clitoroplasty and gonadectomy. Bilateral gonadoblastomas were found in an indeterminate left gonad and a right testis. In addition, the patient had bilateral grade 2-3 vesicoureteral reflux and progressed to end stage renal failure at 11 months of age (creatinine 1.4mg/dl). Consequently, the patient has secondary hyperparathyroidism with PTH 691 (12-65 pg/mL), calcium 7.2 (8-10.4 mg/dL), and phosphorus 7 (2.7-4.5 mg/dL). The patient's most recent renal ultrasound does not show evidence of a Wilms tumor (2).Conclusion: This is one of the earliest cases of bilateral gonadoblastoma reported in DDS. This case highlights the importance of early gonadectomy at the time of diagnosis of the WT1 gene mutation as these tumors have potential for malignant transformation

OBJECTIVE:To examine change in health-related quality of life in association with clinical outcomes of neuropsychiatric events in systemic lupus erythematosus (SLE). METHODS:An international study evaluated newly diagnosed SLE patients for neuropsychiatric events attributed to SLE and non-SLE causes. The outcome of events was determined by a physician-completed seven-point scale and compared with patient-completed Short Form 36 (SF-36) health survey questionnaires. Statistical analysis used linear mixed-effects regression models with patient-specific random effects. RESULTS:274 patients (92% female; 68% Caucasian), from a cohort of 1400, had one or more neuropsychiatric event in which the interval between assessments was 12.3 ± 2 months. The overall difference in change between visits in mental component summary (MCS) scores of the SF-36 was significant (p<0.0001) following adjustments for gender, ethnicity, centre and previous score. A consistent improvement in neuropsychiatric status (N=295) was associated with an increase in the mean (SD) adjusted MCS score of 3.66 (0.89) in SF-36 scores. Between paired visits when the neuropsychiatric status consistently deteriorated (N=30), the adjusted MCS score decreased by 4.00 (1.96). For the physical component summary scores the corresponding changes were +1.73 (0.71) and -0.62 (1.58) (p<0.05), respectively. Changes in SF-36 subscales were in the same direction (p<0.05; with the exception of role physical). Sensitivity analyses confirmed these findings. Adjustment for age, education, medications, SLE disease activity, organ damage, disease duration, attribution and characteristics of neuropsychiatric events did not substantially alter the results. CONCLUSION/CONCLUSIONS:Changes in SF-36 summary and subscale scores, in particular those related to mental health, are strongly associated with the clinical outcome of neuropsychiatric events in SLE patients.

OBJECTIVES: (1) To describe a new protocol using nonopioid medications (clonidine, lorazepam, trazodone, and a stimulant) to successfully complete outpatient opioid detoxification, (2) to determine clinical and demographic characteristics of patients who successfully complete an outpatient opioid detoxification, and (3) to determine the safety and clinical utility of the use of this combination of medications in the treatment of opioid withdrawal. METHODS: In a posthoc evaluation study in a New York State-licensed outpatient detoxification unit of a substance abuse treatment facility, 223 heroin-dependent adults presenting for treatment were provided outpatient opioid detoxification. In the course of the opioid detoxification protocol of the facility, patients received clonidine, lorazepam, trazodone, and either a stimulant (methylphenidate or modafinil) or no stimulant, in combination on a daily basis. At each daily visit, signs and symptoms were assessed, and medications and dosing instructions were given for the following 24 hours. On completion of the detoxification protocol, patients were induced with oral naltrexone. RESULTS: Overall, 61.0% (136) of the patients in this study successfully completed the outpatient detoxification protocol and were induced with naltrexone. Pretreatment demographic variables that predicted successful treatment included full-time employment, family support, private medical insurance, and referral by an employee assistance program. About 77% of patients with good prognosis successfully completed outpatient detoxification treatment. The addition of a stimulant improved patient retention and reduced the incidence of hypotension. CONCLUSIONS: The outpatient detoxification of opioid-dependent patients without the use of opioids has traditionally led to such high drop out rates that most clinical programs do not even consider the option. This makes it difficult to induce patients with opioid antagonists such as oral naltrexone or sustained release naltrexone. We describe a protocol here that leads to excellent rates of successful detoxification. This nonopioid detoxification methodology permits induction of naltrexone without the delay experienced in opioid-based titrations, and it thus facilitates the use of opioid antagonists for sustained abstinence, enhanced aftercare treatment outcomes, and opioid-free recovery.

OBJECTIVE: This project sought to describe unmet needs among patients reported with hepatitis C in New York City. DESIGN: From the New York City Health Department's hepatitis C surveillance database, we randomly selected patients whose positive hepatitis C test was in April or May 2005. In 2006, we interviewed patients by telephone and collected information from their clinicians or by medical record review. SETTING: New York City. PARTICIPANTS: We interviewed 180 of the 387 eligible patients and collected information from clinicians for 145 of the 180 patients. MAIN OUTCOME MEASURES: These included whether patients had understood their clinicians' explanation of their hepatitis C diagnosis, if they had been counseled about not drinking alcohol, information about support group attendance, vaccination against hepatitis A and B, health status, treatment, and other factors. RESULTS: Of the 180 patients, 7% stated that they had not understood their clinicians' explanation of their hepatitis C diagnosis, and 26% said that they had not been counseled about avoiding alcohol. Among the 90% of patients who had not attended a hepatitis support group, 31% were interested in attending. Among the 145 patients with information from clinicians, at least 28% were susceptible to hepatitis A and 18% to hepatitis B. CONCLUSIONS: This hepatitis C surveillance project, with information from patients and clinicians, illustrates a valuable use of a chronic hepatitis C surveillance system. The patients described here had several unmet needs, including hepatitis A and B vaccination, basic information about the virus, support groups, and counseling about preventing further liver damage and preventing transmission to others. Relatively simple and affordable health department activities can address these needs, improving quality of life and decreasing the likelihood of liver disease progression.

While the long-term goal is to develop highly effective AIDS vaccines, first generation vaccines may be only partially effective. Other HIV prevention modalities such as preexposure prophylaxis with antiretrovirals (PrEP) may have limited efficacy as well. The combined administration of vaccine and PrEP (VAXPREP), however, may have a synergistic effect leading to an overall benefit that is greater than the sum of the individual effects. We propose two test-of-concept trial designs for an AIDS vaccine plus oral or topical ARV. In one design, evidence that PrEP reduces the risk of HIV acquisition is assumed to justify offering it to all participants. A two-arm study comparing PrEP alone to VAXPREP is proposed in which 30 to 60 incident infections are observed to assess the additional benefit of vaccination on risk of infection and setpoint viral load. The demonstrated superiority of VAXPREP does not imply vaccine alone is efficacious. Similarly, the lack of superiority does not imply vaccine alone is ineffective, as antagonism could exist between vaccine and PrEP. In the other design, PrEP is assumed not to be in general use. A 2 x 2 factorial design is proposed in which high-risk individuals are randomized to one of four arms: placebo vaccine given with placebo PrEP, placebo vaccine given with PrEP, vaccine given with placebo PrEP, or VAXPREP. Between 60 and 210 infections are required to detect a benefit of vaccination with or without PrEP on risk of HIV acquisition or setpoint viral load, with fewer infections needed when synergy is present

Communications to the public often lacked clarity. Because health officials and journalists used the phrase 'bodily fluids' instead of specifying semen, blood and vaginal secretions, many people feared they could contract AIDS from toilet seats or drinking fountains.\n

According to Jenny, it is often hard for a physician to realize that a parent may be lying about a child's symptoms or treatment.