DNA vaccines: an active immunization strategy for prostate cancer

Immunotherapy is currently being investigated as a treatment for patients with asymptomatic, recurrent prostate cancer manifested only by a rising prostate-specific antigen (PSA) level. Several different approaches to active immunization against antigens found on cancer cells have been explored. Immunization with DNA overcomes many of the obstacles noted in previous studies. Injection of plasmid DNA encoding a xenogeneic differentiation antigen (prostate-specific membrane antigen [PSMA]) is a potent means to induce antibody and T-cell responses to these otherwise poorly immunogenic self proteins. Use of the xenogeneic DNA (ie, human PSMA DNA injected into mouse) has been shown to be an absolute requirement to overcome immunologic tolerance. We are currently conducting a phase I trial of human and mouse PSMA DNA vaccines in patients with recurrent prostate cancer, based on preclinical experiments described below.     

Clinical approaches to osseous metastases in prostate cancer

BACKGROUND: Prostate cancer is unique among solid tumors in its proclivity to metastasize primarily to bone. Osseous metastases pose a formidable health threat to patients with metastatic disease, putting them at risk for pain, marrow crowding, fracture, and other sequelae. Treatments directed against bone disease have the potential both to palliate pain and to increase survival. CONCLUSIONS: A number of agents exist that have the potential to palliate the effects of osseous metastases and should be routinely applied in the clinical care of the patient with advanced prostate cancer. These include hormones, bone-seeking radiopharmaceuticals, chemotherapy, and bisphosphonates. Strategies under investigation aim to eradicate bone disease, and not merely palliate symptoms. These approaches combine those listed above with tumor-directed targeting of osseous disease and manipulation of the biology that underlies the cancer's relationship to bone.     

Prostate cancer: a dynamic illness with shifting targets

Despite high response rates and palliative clinical benefits, androgen ablation does not cure advanced prostate cancer because of the inevitable emergence of resistant cells. Many new therapies under development for prostate cancer target pathways and molecules that contribute to the growth and survival of these cells. The rational and effective use of targeted therapies to eradicate resistant populations of tumour cells should be grounded on the premise that prostate cancer is a dynamic disease that evolves as it progresses, and that specific molecular determinants mediating sensitivity and resistance may be relevant only during specific states of the disease. Directed approaches must account for this changing dynamic so that clinical outcomes may be improved.     

A pilot study of irinotecan (CPT-11) as single-agent therapy in patients with locally advanced or metastatic esophageal carcinoma

BACKGROUND AND AIMS. This study assessed the efficacy and safety of irinotecan (CPT-11) in the treatment of patients with unresectable esophageal carcinoma. PATIENTS AND METHODS. Ten patients with esophageal squamous cell carcinoma (SCC) and three with adenocarcinoma (AC) were treated with CPT-11. Eight of the 13 patients were pretreated by surgery, radio-, or chemotherapy. CPT-11 was administered in repeated 6-week cycles consisting of CPT-11 once weekly for 4 weeks, followed by a 2-week rest. The starting dose of CPT-11 was 125 mg/m(2) given intravenously over 60 min; subsequent doses were adjusted based on tolerance and toxicity. Nine patients were evaluable for response. RESULTS. Two patients showed a partial response (one SCC, one AC) and two others disease stabilization (one SCC, one AC). The mean time to progression was 3.8 months. Mean survival since study entry was 6.1 months. In the 103 administrations we observed grade 3 or 4 toxicity on six occasions with diarrhea, five with neutropenia, and one with nausea and vomiting. Toxicity required dose reductions in five patients; in two of these patients treatment was stopped because of severe toxicity. No treatment related deaths occurred. CONCLUSION. CPT-11 as single-agent therapy is modestly effective against squamous cell cancer of the esophagus.     

Fetal and neonatal neurologic case histories: assessment of brain disorders in the context of fetal-maternal-placental disease. Part 1: Fetal neurologic consultations in the context of antepartum events and prenatal brain development

The pediatric neurologist can contribute to a fetal diagnostic service that includes the maternal-fetal specialist as well as placental and pediatric pathologists, neonatologists, neurosurgeons, geneticists, and other pediatric subspecialists. Selected case histories of patients who presented to our fetal neurology service illustrate the wide spectrum of disease entities that are highly dependent on the time during gestation, location of brain injury, and the direct as well as indirect effects of fetal/maternal/placental disease processes on brain maturation. The pediatric neurologist has the opportunity to provide an important consultative role, bridging prenatal to neonatal life and integrating medical and ethical concerns for the child in the context of the family.     

Clinical implications of radionecrosis to the head and neck surgeon

Radiation necrosis is one of the most serious complications in the treatment of malignancies of the head and neck. As radiotherapy becomes more frequently used as a primary modality and in combination with chemotherapy and surgery, the head and neck surgeon needs to be able to prevent and recognize the often subtle signs and symptoms of radiation necrosis. The symptoms of necrosis can mimic the recurrence of cancer, which presents a diagnostic dilemma, because aggressive surgical biopsy may worsen necrosis and contribute to the formation of a fistula. This review provides a brief discussion of the diagnostic and treatment options for osteoradionecrosis and chondroradionecrosis in the head and neck.     

Effects of abstinence and smoking on information processing in adolescent smokers

RATIONALE: Although adolescent smokers appear to display some of the hallmark features of dependence, the biological and behavioral effects of smoking in this population are poorly understood. OBJECTIVES: This study aimed to define empirically the effects of abstinence and smoking in adolescent smokers, using indices validated in adult smokers. METHODS: Subjects were 16 young novice smokers (five male, 11 female), ages 14-18 years. A modified Stroop task measured the ability to inhibit attention to smoking-related cues; the classic Stroop task measured the ability to inhibit a pre-potent response (i.e. reading a word); a rapid information processing (RIP) task measured vigilance. RESULTS: Abstinence increased and smoking decreased the intrusiveness of smoking cues. Parallel effects were seen in commission errors on the RIP task. These effects were restricted to heavier smokers (>11 cigarettes/day). Subjective withdrawal effects predicted the intrusiveness of smoking words during abstinence. The number of cigarettes smoked per day predicted the beneficial effect of smoking on the classic as well as modified Stroop tasks. The physiological effects of abstinence and smoking predicted RIP performance. CONCLUSIONS: Abstinence impairs and smoking improves inhibitory information processing in young novice smokers in a manner similar to adult smokers. Daily frequency of smoking is a critical moderator of these effects.     

Fetal and neonatal neurologic consultations: identifying brain disorders in the context of fetal-maternal-placental disease

Pediatric neurologists provide an important consultative role for the fetus or neonate with a suspected brain disorder. Although most consultations are initiated after birth, neonatal neurologic dysfunction may be reflective of fetal brain damage or maldevelopment. Maternal or placental/cord disease states can predispose the fetus or neonate to brain disorders during the antepartum, intrapartum, or early postpartum periods. Neurologists must therefore consider maternal, placental, and fetal conditions on which a neonatal encephalopathy may be superimposed, with or without recent brain injury. This review suggests how the pediatric neurologist can contribute more effectively to fetal and neonatal neurologic evaluations regarding etiologies and mechanisms of brain injury; their role will enhance diagnostic services composed of maternal-fetal specialists, placental and pediatric pathologists, neonatologists, neurosurgeons, geneticists, and other pediatric subspecialists. Selected examples of structural markers during fetal life, and functional markers during neonatal life, illustrate the wide spectrum of disease states that are highly dependent on the timing and location of brain injury. The pediatric neurologist has the opportunity to integrate these complementary lines of investigation into a responsive consultative opinion, which is both medically accurate and ethical, responsible to the welfare of the mother and child.     

Evaluation of an Online Platform for Cancer Patient Self-reporting of Chemotherapy Toxicities

The current mechanism for monitoring toxicity symptoms in cancer trials depends on a complex paper-based process. Electronic collection of patient-reported outcomes (PROs) may be more efficient and accurate. An online PRO platform was created including a simple data entry interface, real-time report generation, and an alert system to e-mail clinicians when patients self-report serious toxicities. Feasibility assessment involving 180 chemotherapy patients demonstrated high levels of use at up to 40 follow-up clinic visits per patient over 16 months (85% of patients at any given visit), with high levels of patient and clinician acceptance and satisfaction (>95%). Alerts were used as the basis for delayed chemotherapy treatments, dose modifications, and scheduling changes. These results demonstrate that online patient-reporting is a feasible strategy for chemotherapy toxicity symptom monitoring, and may improve safety and satisfaction with care. Ongoing multi-center research will evaluate the impact of this approach on clinical and administrative outcomes.     

Current topics in nail surgery

BACKGROUND: Nail surgery can be performed in an office-based dermatology practice with a limited amount of specialized equipment and training. Several excellent reviews have been published in recent years that detail the techniques of nail surgery for both the novice and the experienced practitioner. OBJECTIVE: In this article recent developments in nail surgery are discussed. Topics that are treated include the general principles of nail surgery, including epidemiologic issues, studies of nail anatomy, instrumentation, and anesthesia. The reconstruction of injuries and congenital defects involving the nail is explained, and the role of the hand surgeon clarified. Appropriate removal of tumours and cysts is considered, with special attention to the management of malignant lesions. The controversy regarding more or less conservative management of melanonychia striata is addressed, and the need for early diagnosis of subungual melanoma is emphasized. Other topics are surgical management of ingrown nails and onychomycosis. Newer areas of nail surgery, such as laser surgery of the nail, psychodermatology of the nail, and the role of primary care physicians in simple nail surgery are also examined.