Devoid of dentistry

Dental curricula in UK dental schools are seemingly excising ever more skills as each generation of students is trained. This has implications for the quality of education held by the latest dental graduates, and furthermore potentially for the standard of care that their patients may receive. This leaves us today somewhat nostalgic for a bygone era when dental undergraduate education was replete with a fuller repertoire.     

Comparison between true and partial hemifacial hypertrophy

Hemifacial hypertrophy (HFH) is rare and characterized by unilateral enlargement of the head and teeth. Hemifacial hypertrophy is classified as true HFH (THFH) with unilateral enlargement of the viscerocranium, and partial HFH (PHFH) in which not all structures are enlarged. We present a case of THFH and compare and contrast it with a case of PHFH. Hemifacial hypertrophy may cover a wide spectrum of defects or may involve only muscle or bone. Myohyperplasia, reported previously as a separate syndrome, may actually represent a forme fruste of PHFH or THFH. The PHFH patient lead a healthy, normal life without significant psychosocial problems and was reluctant to accept his deformity. Contrastingly, the THFH patient had significant social stigma and compromised health together with major aesthetic morbidity. Treatment planning in THFH is arduous and involves multiple modalities. Therefore, it is imperative to differentiate THFH and PHFH for better understanding and management of the condition.     

Rhinocerebral zygomycosis: an increasingly frequent challenge: update and favorable outcomes in two cases

Zygomycosis or mucormycosis is an increasingly frequent life-threatening infection caused by opportunistic fungal organisms of the class Zygomycetes. The pathognomonic feature is the presence of invasive aseptate mycelia that are larger than other filamentous fungi with the hyphae exhibiting right angle and haphazard branching. Usually classified as rhinocerebral, disseminated, and cutaneous types, this classification serves as important predictor of pathogenesis and outcome. These occur mostly in immunosuppressed patients including individuals with diabetes (43% exhibit the rhino-cerebral form) and patients with organ transplants and hematologic malignancies. Without early aggressive treatment, the disease follows a dismal and fatal course. The prognosis has not shown any appreciable change in the past 40 years with a stagnant mortality rate of 44%. We present 2 cases of rhinocerebral zygomycosis (RCZ), in a 58-year-old male and a 63-year-old female; both were poorly controlled diabetic patients with maxillary lesions suggestive of osteomyelitis. The patients were leading a near normal life with minimal discomfort or signs and symptoms of underlying mycosis. Most of the health care professionals treating these patients often overlooked the disease or recommended inadequate therapy. Despite long delays and inadequate initial therapy these patients survived with little outward morbidity. The prognosis for this condition may therefore be considered less dire than previously thought.     

Long-term outcome following radical prostatectomy for Gleason 8–10 prostatic adenocarcinoma

Purpose

Compared to low-grade disease, high-grade prostate cancers exhibit a higher rate of disease progression. As a result, there has been a trend to treat high-risk disease with methods other than surgery. The purpose of this study is to evaluate the long-term survival following radical prostatectomy (RRP) for non-metastatic Gleason 8–10 prostate adenocarcinoma (CaP).

Methods

All patients 75 years or less with Gleason 8–10 CaP that underwent RRP were identified from the SEER 18 database. Patients with metastatic disease, those who underwent other modalities of treatment, or with more than one primary cancer, were excluded. Data were analyzed for demographics, stage at presentation, treatment modality, and overall survival and cancer-specific survival.

Results

A total of 30,379 men met inclusion criteria. Mean age was 62.5 years and 82.5 % of patients were white. A total of 52.8 % of patients had T2 disease, and 73.1 % had node-negative disease, 80.2 % of patients underwent pelvic lymph node dissection, and 12.9 % underwent adjuvant radiation therapy. Overall survival for the entire cohort was 92.8, 78.6, 59.5, 38.6, and 20.0 % for 5, 10, 15, 20, and 25 years, respectively. Cancer-specific survival was 96.4, 89.5, 82.0, 72.9, and 68.8 % for 5, 10, 15, 20, and 25 years, respectively.

Conclusions

Although historically underutilized in patients with poorly differentiated disease, radical prostatectomy provides excellent long-term survival and should be offered to healthy patients.     

Bradykinin induces NO and PGF2α production via B2 receptor activation from cultured porcine basilar arterial endothelial cells

Our previous in vitro study demonstrated that bradykinin (BK) induced relaxation and contraction of porcine basilar artery (PBA) mediated via activation of endothelial B₂ receptors. The main relaxing and contracting factors appeared to be nitric oxide (NO) and prostaglandin (PG) H₂, respectively, but not thromboxane A₂. After obtaining these findings, we succeeded in cultivating endothelial cells isolated from the PBA. Although PGH₂ has different functionally active isoforms, including PGD₂, PGE₂, and PGF_2α, we have not yet clarified which of them is responsible for BK-induced contraction. Therefore, we attempted to quantify NO and PG production from cultured porcine basilar arterial endothelial cells (PBAECs) and to identify which of the PGs was involved in this contraction. The cultured PBAECs produced NO spontaneously, and BK enhanced this production in a concentration-dependent manner. The NO synthase inhibitor Nω-nitro-l-arginine (L-NNA) and the B₂ receptor antagonist HOE-140, but not the B₁ receptor antagonist des-Arg⁹, [Leu⁸]-BK, completely abolished it. In a functional study, PGD₂, PGE₂, and PGF_2α induced concentration-dependent contractions in isolated porcine basilar arterial rings, the order of maximum contraction being PGF_2α?>?PGE₂?>?PGD₂. The cultured PBAECs produced PGD₂, PGE₂, and PGF_2α spontaneously, and BK significantly enhanced the production of PGF_2α, but not that of PGD₂ and PGE₂. The B₂, but not B₁, antagonist completely abolished the BK-enhanced production of PGF_2α. These results suggest that BK induces production of NO and PGF_2α simultaneously from PBAECs via B₂ receptor activation.     

PDGF and TGF-β promote tenascin-C expression in subepithelial myofibroblasts and contribute to intestinal mucosal protection in mice

Background and Purpose: Tenascin-C (TnC) is a multi-domain extracellular matrix glycoprotein that is expressed at a high level during embryogenesis but is almost absent during normal postnatal life. This multi-domain complex molecule is reported to associate with both pro-inflammatory and anti-inflammatory signalling cascades. In this study, we examined how TnC modulated intestinal inflammation.Experimental Approach: TnC pathophysiology was evaluated in cultures of rat intestinal subepithelial myofibroblasts (ISEMF) and intestinal epithelial cells. Wild-type and TnC(−/−) mice were treated with dextran sodium sulfate (DSS) to induce colitis.Key Results: DSS-induced colitis in mice markedly increased TnC in the damaged mucosal areas and up-regulated mRNA for TnC, pro-inflammatory cytokines and growth factors (PDGF-B and TGF-β1). In addition, 2,4,6-trinitrobenzene sulfonic acid-induced colitis and SAMP1/Yit mice, a model of spontaneous Crohn''s disease, also exhibited increased mucosal TnC in colon and ilea respectively. PDGF receptor-α (PDGFRα) positive ISEMF were the primary TnC-producing cells in colon tissues. Accordingly, ISEMF collected from the rat colon constitutively expressed both TnC and PDGFRα. PDGF-BB and TGF-β1 up-regulated both TnC mRNA and protein levels in ISEMF. Knock-down of TnC gene increased susceptibility to DSS-induced colitis, compared with TnC(+/+) littermates. TnC(−/−) mice showed marked abrasion of intestinal mucosal barrier and increased inflammatory scores. Moreover, TnC accelerated both trans-well migration and wound healing in epithelial cells.Conclusions and Implications: The pharmacological profiles of PDGF-BB and TGF-β in colitis tissues and ISEMF suggest that increased TnC production during inflammation contributed to epithelial cell migration, remodelling and protection of intestinal barriers.