Features and Outcomes of Methamphetamine-associated Pulmonary Arterial Hypertension.

RATIONALE: Although amphetamines are recognized as "likely" agents to cause drug- and toxin-associated pulmonary arterial hypertension (PAH), (meth)amphetamine-associated PAH (Meth-APAH) has not been well described. OBJECTIVES: To prospectively characterize the clinical presentation, histopathology, and outcomes of Meth-APAH compared with those of idiopathic PAH (iPAH). METHODS: We performed a prospective cohort study of patients with Meth-APAH and iPAH presenting to the Stanford University Pulmonary Hypertension Program between 2003 and 2015. Clinical, pulmonary angiography, histopathology, and outcomes data were compared. We used data from the Healthcare Cost and Utilization Project to estimate the epidemiology of PAH in (meth)amphetamine users hospitalized in California. MEASUREMENTS AND MAIN RESULTS: The study sample included 90 patients with Meth-APAH and 97 patients with iPAH. Patients with Meth-APAH were less likely to be female, but similar in age, body mass index, and 6-minute-walk distance to patients with iPAH. Patients with Meth-APAH reported more advanced heart failure symptoms, had significantly higher right atrial pressure (12.7 ± 6.8 vs. 9.8 ± 5.1 mm Hg; P = 0.001), and had lower stroke volume index (22.2 ± 7.1 vs. 25.5 ± 8.7 ml/m2; P = 0.01). Event-free survival in Meth-APAH was 64.2%, 47.2%, and 25% at 2.5, 5, and 10 years, respectively, representing more than double the risk of clinical worsening or death compared with iPAH (hazard ratio, 2.04; 95% confidence interval, 1.28-3.25; P = 0.003) independent of confounders. California data demonstrated a 2.6-fold increase in risk of PAH diagnosis in hospitalized (meth)amphetamine users. CONCLUSIONS: Meth-APAH is a severe and progressive form of PAH with poor outcomes. Future studies should focus on mechanisms of disease and potential therapeutic considerations.

Tongue Flap for Keratinized Soft Tissue Coverage Around Dental Implants: A Case Report and Discussion.

The tongue flap is a hardy flap that is routinely utilized by oral and maxillofacial surgeons to cover intraoral defects. It has not been previously described as a method for keratinized soft tissue coverage in conjunction with dental implant placement. In this article, we describe use of a tongue flap in the closure of a chronic anterior maxillary dehiscence and to provide keratinized soft tissue coverage for anterior dental implants.

Pseudoaneurysm of the Greater Palatine Vessel Following Subepithelial Connective Tissue Graft.

Subepithelial gingival connective tissue grafts are a common surgical procedure performed in periodontal and implant surgery. This versatile procedure has many indications including tooth root coverage, thickening of gingiva, and improvement of the quality of the crestal gingiva. Several techniques have been described for graft harvest from the palate. Reported complications from these techniques include pain, inflammation, bleeding, flap necrosis, and infection in the donor site. We report a previously unpublished complication following subepithelial gingival connective tissue graft from the palate: pseudoaneurysm of the greater palatine vessel.

Dental radiation dosimetric maps from intensity-modulated radiation therapy planning for head and neck cancers.

BACKGROUND: The purpose of this study was to create dental radiation maps to calculate the mean dose to individual teeth, maxilla and mandible using intensity-modulated radiation therapy (IMRT). METHODS: Eighteen common clinical settings were chosen. Radiation plans were extracted, and each tooth was contoured at its junction with the gingiva and labeled based on the Universal/American numbering system. RESULTS: All patients were treated with prescribed doses of 50-70 Gy in 1.66-2 Gy/fraction. Patients receiving mean doses >50 Gy to the teeth, mandible, and maxilla included those with advanced tumors of the oral cavity and gross lymphadenopathy of level 1b. CONCLUSION: We believe this to be the first study generating dosimetric maps of estimated doses to each tooth and each third of the mandible and the maxilla for common examples of head and neck cancer faced by radiation oncologists. Adoption of these dental maps may help improve clinical workflow efficiency.

Pneumonic plague pathogenesis and immunity in Brown Norway rats.

The Brown Norway rat was recently described as a bubonic plague model that closely mimics human disease. We therefore evaluated the Brown Norway rat as an alternative small animal model for pneumonic plague and characterized both the efficacy and potency of vaccine candidates. When infected by intranasal instillation, these rats rapidly developed fatal pneumonic plague within 2 to 4 days of infection. Plague disease was characterized by severe alveolar edema and vascular hemorrhage in the lung in addition to fulminant necrotizing pneumonia caused by massive bacterial replication and inflammation. Twenty-four hours before death, animals developed systemic disease with an apparent delayed inflammatory response. We evaluated the ability of the protective antigen, LcrV, and a mutant derivative, V10, to protect these rats from pneumonic plague. Both were highly effective vaccines because complete protection was observed at challenge doses of 7500 LD(50). Antibody analyses suggested stronger potency of V10 immune sera compared with LcrV in the passive transfer of immunity to bubonic plague, with multiple neutralizing epitopes in LcrV. Taken together, these data demonstrate the effectiveness of inhibiting type III secretion in the prevention of pneumonic plague in rats and reveal critical contributions from both the cellular and humoral immune systems. Thus, the Brown Norway rat is an appealing alternative small animal model for the study of pneumonic plague pathogenesis and immunity.

Congenital granular cell lesion of the tongue: a report of two cases and review of the literature.

The congenital granular cell lesion most commonly occurs on the maxillary or mandibular alveolus of neonates. Extra-alveolar congenital granular cell lesion is exceptionally rare, with only 10 cases reported. Two additional cases occurring on the tongue are presented with a description of the clinical, histopathologic, and immunohistochemical features. The differential diagnosis is discussed, and the literature reviewed.

Peritoneal Coccidioidomycosis: a Rare Case Report and Review of the Literature.

Coccidioidomycosis is a fungal infection endemic to the southwestern United States that typically causes a self-limited pulmonary illness. Extrapulmonary dissemination is extremely rare and typically localized to the skin, bone, and meninges. The gastrointestinal system has generally been thought to be spared from this disease. This report describes a patient who was initially diagnosed with pulmonary coccidioidomycosis with mediastinal lymphadenopathy and skin dissemination. Ten months after completion of treatment, he presented with nonspecific abdominal pain and diffuse musculoskeletal and constitutional symptoms. Radiographic imaging revealed near resolution of previously noted thoracic findings but new peritoneal thickening and enhancement suggestive of peritoneal carcinomatosis. Laparoscopic biopsies confirmed Coccidioides immitis by culture and histology without evidence of other abnormalities. This case is unique for several reasons. It is one of a relatively small number of cases that describes a diagnosis of peritoneal coccidioidomycosis and the first case identified in which a healthy patient developed extensive peritoneal disease in spite of near-complete resolution of pulmonary and skin manifestations after appropriate treatment. This case underscores the complexity of this disease and motivates more investigation into pathophysiology and treatment considerations of coccidioidomycosis in the gastrointestinal system. We will review the risk factors associated with dissemination, the interpretation of serologies, the characteristics of patients with peritoneal involvement, and finally, the current treatment guidelines.

Amino acid residues 196-225 of LcrV represent a plague protective epitope.

LcrV, a protein that resides at the tip of the type III secretion needles of Yersinia pestis, is the single most important plague protective antigen. Earlier work reported monoclonal antibody MAb 7.3, which binds a conformational epitope of LcrV and protects experimental animals against lethal plague challenge. By screening monoclonal antibodies directed against LcrV for their ability to protect immunized mice against bubonic plague challenge, we examined here the possibility of additional protective epitopes. MAb BA5 protected animals against plague, neutralized the Y. pestis type III secretion pathway and promoted opsonophagocytic clearance of bacteria in blood. LcrV residues 196-225 were necessary and sufficient for MAb BA5 binding. Compared to full-length LcrV, a variant lacking its residues 196-225 retained the ability of eliciting plague protection. These results identify LcrV residues 196-225 as a linear epitope that is recognized by the murine immune system to confer plague protection.