Phantom tooth pain: a new look at an old dilemma

The aim of this paper is to review the current knowledge of phantom tooth pain, a neuropathic facial pain disorder, thought to result from peripheral nerve injury. Phantom tooth pain is a deafferentation pain disorder of persistent toothache in teeth that have been denervated (usually by root canal treatment) or pain in the area formerly occupied by teeth prior to their extraction. The pain usually extends to the facial structures adjacent to tissues that have undergone deafferentation. The clinical characteristics, differential diagnosis, epidemiology, and treatment of phantom tooth pain are reviewed. Suggestions for further research include the need for controlled treatment trials and modification of current criteria. CONCLUSIONS: Phantom tooth pain has much in common with other phantom pain disorders. In the absence of controlled clinical trials specifically directed to phantom tooth pain, treatment should be guided by standards used for other neuropathic pain disorders. Revised diagnostic criteria for phantom tooth pain are proposed.     

Seroreactivity to human papillomavirus (HPV) types 16, 18, or 31 and risk of subsequent HPV infection: results from a population-based study in Costa Rica.

Whether antibodies to human papillomavirus (HPV) capsids, elicited by natural infection, are protective is unknown. This question was addressed in a population-based cohort of 7046 women in Costa Rica by examining the association between baseline seroreactivity to HPV-16, HPV-18, or HPV-31 virus-like particles and the risk of subsequent HPV infection at a follow-up visit 5-7 years after enrollment. Seropositivity to HPV-16, HPV-18, or HPV-31 was not associated with a statistically significant decreased risk of infection with the homologous HPV type [relative risk (RR) and [95% confidence interval (CI)], 0.74 (0.45-1.2), 1.5 (0.83-2.7), and 0.94 (0.48-1.8), respectively]. Seropositivity to HPV-16 or HPV-31 was not associated with a decreased risk of infection with HPV-16 or its genetically related types [RR (95% CI), 0.82 (0.61-1.1) and 0.93 (0.68-1.2), respectively]. Seropositivity to HPV-18 was not associated with a decreased risk of infection with HPV-18 or its genetically related types (RR 1.3; 95% CI 1.0-1.8). Thus, we did not observe immunity, although a protective effect from natural infection cannot be excluded because of the limits of available assays and study designs.     

Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis.

PURPOSE: Radiation-induced fibrosis (RIF) is a rare morbid complication of radiotherapy, without an established method of management. RIF treatment with a combination of pentoxifylline (PTX) and alpha-tocopherol (vitamin E; Vit E) was recently prompted by the good results of a clinical trial and an animal study. The present double-blind, placebo-controlled, monocentric study was designed to assess the efficacy of this combination in treating RIF sequelae. PATIENTS AND METHODS: Twenty-four eligible women with 29 RIF areas involving the skin and underlying tissues were enrolled from December 1998 to April 2000. These patients, previously irradiated for breast cancer, were randomly assigned to four balanced treatment groups: (A) 800 mg/d of PTX and 1,000 U/d of Vit E; (B) PTX plus placebo; (C) placebo plus Vit E; and (D) placebo-placebo. The main end point measure was the relative regression of measurable RIF surface after 6 months of treatment. Assessment was completed by depth (with ultrasonography) and associated symptom measures. RESULTS: Twenty-two patients with 27 RIF areas were analyzed at 6 months. Mean RIF surface regression was significant with combined PTX/Vit E versus double placebo (60% +/- 10% v 43% +/- 17%; P =.038). The median slope for the speed of RIF surface area and volume regression was significantly higher for group A than groups B, C, and D. All treatments were well tolerated. CONCLUSION: Six months' treatment of combined PTX/Vit E can significantly reduce superficial RIF. Synergism between PTX and Vit E is likely, as treatment with each drug alone is ineffective, but these results require confirmation in larger series.     

Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor augments antitumor immunity in some patients with metastatic non-small-cell lung carcinoma.

PURPOSE: We demonstrated that vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor immunity in multiple murine models and patients with metastatic melanoma. To test whether this vaccination strategy enhances antitumor immunity in patients with metastatic non-small-cell lung cancer (NSCLC), we conducted a phase I clinical trial. PATIENTS AND METHODS: Resected metastases were processed to single-cell suspension, infected with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines consisted of 1 x 10(6), 4 x 10(6), or 1 x 10(7) cells, depending on overall yield, and were administered intradermally and subcutaneously at weekly and biweekly intervals. RESULTS: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 513 ng/10(6) cells/24 h. Toxicities were restricted to grade 1 to 2 local skin reactions. Nine patients were withdrawn early because of rapid disease progression. Vaccination elicited dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates in 18 of 25 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransfected tumor cells in 18 of 22 patients. Metastatic lesions resected after vaccination showed T lymphocyte and plasma cell infiltrates with tumor necrosis in three of six patients. Two patients surgically rendered as having no evidence of disease at enrollment remain free of disease at 43 and 42 months. Five patients showed stable disease durations of 33, 19, 12, 10, and 3 months. One mixed response was observed. CONCLUSION: Vaccination with irradiated autologous NSCLC cells engineered to secrete GM-CSF enhances antitumor immunity in some patients with metastatic NSCLC.     

Intracytoplasmic injection of fresh and cryopreserved testicular spermatozoa in patients with nonobstructive azoospermia—a comparative study

Objective: To compare the outcome of intracytoplasmic sperm injection (ICSI) with fresh and frozen-thawed testicular spermatozoa in patients with nonobstructive azoospermia.Design: Retrospective analysis of consecutive ICSI cycles.Setting: In Vitro Fertilization Unit, Assaf Harofeh Medical Center.Patient(s): Eighteen with nonobstructive azoospermia in whom testicular sperm was found after testicular sperm extraction.Intervention(s): Testicular sperm retrieval, cryopreservation, and ICSI with fresh or frozenthawed testicular spermatozoa.Main Outcome Measure(s): Two-pronuclear fertilization; embryo cleavage rates, mean number of embryos transferred per cycle, and their relative quality, embryo implantation, clinical pregnancy, and ongoing pregnancy rates (PRs) per ET.Result(s): No statistically significant differences were noted in all parameters examined between ICSI cycles with fresh or cryopreserved testicular spermatozoa from the same nine patients and comparing all ICSI cycles performed; with fresh (25 cycles) and thawed (14 cycles) testicular spermatozoa, respectively: two-pronuclear fertilization, 47% versus 44%; embryo cleavage rates, 94% versus 89%; implantation rates, 9% versus 11%; and clinical PR, 26% versus 27%. The delivery or ongoing PR using fresh sperm was better (21% versus 9%), but the difference did not reach statistical significance. The cumulative clinical PRs and ongoing PRs per testicular sperm extraction procedure were 36% and 24%, respectively.Conclusion(s): Testicular sperm cryopreservation using a simple freezing protocol is promising in patients with nonobstructive azoospermia augmenting the overall success achieved after surgical sperm retrieval. (Fertility Sterility 1997;68:892-7. C 1997 by American Society for Reproductive Medicine.)     

Fabry disease and vascular risk factors: future strategies for patient-based studies and the knockout murine model

Fabry disease is secondary to deficiency of the lysosomal enzyme α-galactosidase A, leading to altered glycosphingolipid metabolism and accumulation that is often associated with endothelial dysfunction. Current evidence suggests that there is impairment of the vascular nitric oxide pathway, with abnormalities evident in the cerebral circulation and in the dermal vasculature of patients with Fabry disease. Some of these findings have been confirmed in a mouse model of Fabry disease. The murine model, however, allows investigation of Fabry disease at a non-clinical level and a near complete investigation of biological processes within an affected tissue. This is of particular utility in allowing gene expression analysis of clinically inaccessible tissues such as the aorta.
Conclusion: Future developments in array technology for proteins and DNA single nucleotide polymorphism analysis, together with gene expression microarray analysis, may open a new chapter in our understanding of the biology of lysosomal storage disorders.     

Acoustic reflectometry profiles of endotracheal and esophageal intubation

BACKGROUND: Acoustic reflectometry can be used to create a "one-dimensional image" of a cavity, such as the airway and lung, with the image displayed as an area-length curve. This pilot study was undertaken to determine whether acoustic reflectometry could be used to distinguish between an endotracheal and an esophageal intubation. METHODS: Ten adult patients underwent general endotracheal anesthesia and neuromuscular blockade. The reflectometer wavetube was attached to an endotracheal tube, and a reflectometric profile was obtained of the endotracheal tube and the airway and lung cavity. After confirmation of tracheal intubation, a second endotracheal tube was placed in the esophagus. After four breaths were administered, a reflectometric profile of the endotracheal tube-esophagus cavity was obtained. RESULTS: The acoustic reflectometric profiles for tracheal and esophageal intubation profiles were distinctive and characteristic. For an endotracheal tube-airway cavity, the profile shows a constant cross-sectional area throughout the length of the endotracheal tube, followed by a rapid rise in the area past the carina. For an esophageal intubation, the profile shows constant cross-sectional area throughout the length of the endotracheal tube, followed by a sudden decrease in the cross-sectional area to zero. CONCLUSIONS: In this pilot study, acoustic reflectometry within seconds, and without resort to capnography, was able to generate characteristic and distinctive area-length profiles for both endotracheal and esophageal intubation. Acoustic reflectometry may have a role in the emergency imaging of the airway, and in the immediate detection of esophageal intubations, particularly in cases of cardiopulmonary arrest in which the usual techniques for confirmation of breathing tube placement fail.     

Vascular and neoplastic risk in a large cohort of patients with polycythemia vera.

PURPOSE: The clinical course of polycythemia vera is often complicated by thrombosis as well as by the possible transition to myeloid metaplasia with myelofibrosis or acute myeloid leukemia. The aim of this study was to assess the rate of these complications in subjects receiving currently recommended treatments. PATIENTS AND METHODS: Overall, 1,638 patients from 12 countries were enrolled onto a large, prospective multicenter project aimed at describing the clinical history of polycythemia vera for the following outcomes: survival, the cumulative rate of cardiovascular death and thrombosis, the cumulative rate of leukemia, myelodysplasia, and myelofibrosis. The mean duration of the disease at entry and the duration of the follow-up were 4.9 and 2.7 years, respectively. RESULTS: The overall mortality rate of 3.7 deaths per 100 persons per year resulted from a moderate risk of cardiovascular death and a high risk of death from noncardiovascular causes (mainly hematologic transformations). Age older than 65 years and a positive history of thrombosis were the most important predictors of cardiovascular events. Antiplatelet therapy, but not cytoreductive treatment, was significantly associated with a lower risk of cardiovascular events. We found a consistent association between age and risk of leukemia, and between duration of the disease with risk of myelofibrosis. CONCLUSION: The European Collaboration on Low-Dose Aspirin in Polycythemia Vera study documents that large international collaborative studies are feasible in this field, in which few epidemiologic data are available. The persistently high mortality rate from hematologic malignancies characterizes the unmet therapeutic need of polycythemic patients and suggests a priority for future studies in this disease.     

Markers of past infection with simian virus 40 (SV40) and risk of incident non-Hodgkin lymphoma in a Maryland cohort.

Simian virus 40 (SV40) genome sequences have been detected in human non-Hodgkin lymphoma (NHL) tissues, and past infection with SV40 may be a risk factor for NHL. We conducted a population-based nested case-control study to investigate the association between serum antibodies to SV40 and incident NHL. Two research serum banks were established in Washington County, MD, with >45,000 volunteers contributing blood samples collected in 1974 and 1989. Incident cases of NHL diagnosed through 2002 (n = 170) were identified among participants by linkage to population-based cancer registries. Two controls were matched to each case (n = 340) on age, sex, and date of blood draw. Circulating immunoglobulin G antibodies to SV40 were measured using virus-like particle (VLP) ELISA. Positive samples were tested for cross-reactivity with JC virus (JCV) and BK virus (BKV) through competitive inhibition assays. Associations between SV40 antibody seropositivity and NHL were estimated using conditional logistic regression. Whereas SV40 antibodies were detected by VLP ELISA in 15% of cases and 10% of controls [matched odds ratio (OR), 1.97; 95% confidence interval (95% CI), 1.03-3.76], the SV40 reactivity of 85% of the SV40 antibody-positive sera was decreased by adsorption with BKV and/or JCV VLPs. Antibodies specific for SV40 (not cross-reactive) were identified in only 1.8% of cases and 1.6% of controls (OR, 1.51; 95% CI, 0.41-5.52). Our findings suggest that past infection with SV40 is not associated with an increased risk of developing NHL.