David C. Stanton

Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells

Androgenetic alopecia (AGA), also known as common baldness, is characterized by a marked decrease in hair follicle size, which could be related to the loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from AGA individuals for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin15 (KRT15), CD200, CD34, and integrin, α6 (ITGA6) were quantitated via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. These KRT15(hi) stem cells were maintained in bald scalp samples. However, CD200(hi)ITGA6(hi) and CD34(hi) cell populations--which both possessed a progenitor phenotype, in that they localized closely to the stem cell-rich bulge area but were larger and more proliferative than the KRT15(hi) stem cells--were markedly diminished. In functional assays, analogous CD200(hi)Itga6(hi) cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA.

Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia

Prostaglandin D2 inhibits hair growth through its receptor, GPR44, and this pathway could serve as a new target for developing treatments for male pattern baldness. A Not-So-Hairy Situation Everybody wishes his or her hair was different; curly hair wants straight locks, straight hair desires some curl. Patients with androgenetic alopecia (AGA), however, would take either one, as long as it meant having hair. AGA is a disorder that affects both men and women, leading to hair thinning and loss. Here, Garza and colleagues provide new insight into the pathogenesis of AGA, in hopes of developing new therapeutics that target specific pathways responsible for baldness. The authors first examined bald and haired scalp from five men with AGA and showed that the enzyme prostaglandin D2 (PGD2) synthase was elevated at the mRNA and protein levels in bald scalp only. In a larger group of 17 men, they confirmed that the synthase product PGD2 was also elevated in bald versus haired scalp. In mice with synchronized hair follicle cycling, Garza et al. uncovered a temporal relationship between PGD2 gene expression and hair follicle regression. The authors further found that PGD2 and a related metabolite, 15-dPGJ2, inhibited hair growth in both mice and human hair follicles, providing a crucial functional link between the prostaglandin pathway and AGA. Garza and coauthors identified the receptor GPR44 to be responsible for mediating the negative effects of PGD2. By discovering such therapeutic targets for downstream drug development, such as a topical treatment, Garza et al. may have given patients with AGA a long-awaited choice: curly or straight? Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D2 synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D2 (PGD2), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD2 levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD2 inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD2 receptor G protein (heterotrimeric guanine nucleotide)–coupled receptor 44 (GPR44), but not the PGD2 receptor 1 (PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD2 in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD2 as an inhibitor of hair growth in AGA and suggest the PGD2-GPR44 pathway as a potential target for treatment.

Outcome of surgical management of bisphosphonate-related osteonecrosis of the jaws: review of 33 surgical cases.

PURPOSE We describe our experience with surgical management of bisphosphonate-related osteonecrosis of the jaws (BRONJ). MATERIALS AND METHODS The data included 33 BRONJ cases treated surgically by a single surgeon at the Hospital of the University of Pennsylvania. RESULTS Of the 30 debridement patients, 25 (including 1 sequestrectomy patient who required formal debridement) healed completely. Of the 30 patients who underwent surgical debridement, 18 healed following this initial treatment and remained healed. Of the 4 patients requiring sequestrectomy, 3 healed after the initial treatment. Thus, 28 of 33 patients healed completely with complete mucosal coverage and elimination of pain. Four patients developed occurrence of BRONJ at a separate site. All 4 patients were treated with our surgery protocol and remain healed. Thus, 32 of 37 BRONJ occurrences have healed with our surgical debridement protocol or sequestrectomy. The follow-up range was 1 to 40 months (average 10.7). CONCLUSIONS The results of our case series have shown that surgical debridement can be successful in treating BRONJ.

Behavioral and biologic evidence of persistent high-risk behavior in an HIV primary care population.

ObjectiveTo define the prevalence of gonorrhea, chlamydial infection, and high-risk sexual behavior in an HIV primary care clinic. DesignSubjects enrolling in this cross-sectional study answered a brief interviewer-administered questionnaire and provided a urine sample for gonorrhea and chlamydia testing. SettingA large urban HIV primary care clinic. ParticipantsHIV-infected patients presenting for a scheduled medical visit from June 1997 to April 1998. Main outcome measuresPrevalence of self-reported high-risk sexual behavior and gonorrhea and chlamydial infection. ResultsOf 691 patients consenting to the study over a 10-month period, 58% reported sexual activity in the past 90 days, 7.4% reported multiple sexual partners in the past month, and 34.6% did not use a condom at last sexual encounter. Overall, 4.6% reported a history of either gonorrhea or a chlamydial infection in the past year. Of 637 giving a urine sample for testing, the prevalence of chlamydial infection was 2.4%; the prevalence of gonorrhea was 1.6%. Overall, 7.5% of those screened had either current or recent (within 1 year) gonorrhea or chlamydial infection. Current or recent gonorrhea or chlamydial infection was not associated with age, gender, HIV transmission risk, CD4 cell count, HIV viral load, symptoms, or self-reported risk behavior. ConclusionHigh-risk sexual behavior and unrecognized sexually transmitted diseases (STD) are common among HIV-infected persons followed in primary medical care. Enhanced detection of treatable STD among this population coupled with improved risk-reduction counselling may be important clinical practice measures that can curb the spread of HIV.

Modelling the global competing risks of a potential interaction between injectable hormonal contraception and HIV risk

Background:Some, but not all, observational studies have suggested an increase in the risk of HIV acquisition for women using injectable hormonal contraception (IHC). Methods:We used country-level data to explore the effects of reducing IHC use on the number of HIV infections, the number of live births and the resulting net consequences on AIDS deaths and maternal mortality for each country. Results:High IHC use coincides with high HIV incidence primarily in southern and eastern Africa. If IHC increases the risk of HIV acquisition, this could generate 27 000–130 000 infections per year globally, 87–88% of which occur in this region. Reducing IHC use could result in fewer HIV infections but also a substantial increase in live births and maternal mortality in countries with high IHC use, high birth rates and high maternal mortality: mainly southern and eastern Africa, South-East Asia, and Central and South America. For most countries, the net impact of reducing IHC use on maternal and AIDS-related deaths is dependent on the magnitude of the assumed IHC–HIV interaction. Conclusions:If IHC use increases HIV acquisition risk, reducing IHC could reduce new HIV infections; however, this must be balanced against other important consequences, including unintended pregnancy, which impacts maternal and infant mortality. Unless the true effect size approaches a relative risk of 2.19, it is unlikely that reductions in IHC could result in public health benefit, with the possible exception of those countries in southern Africa with the largest HIV epidemics.

Synovial chondromatosis with cranial extension

Synovial chondromatosis is a benign arthropathy characterized by metaplasia in synovial membranes that can produce detached particles of cartilage. It occurs most often in the knee, hip, and elbow but has been reported in the temporomandibular joint. This is a rare presentation of synovial chondromatosis with glenoid fossa erosion and cranial extension.

Use of bioresorbable plating systems in paediatric mandible fractures

AIM The aim of this study is to retrospectively evaluate the use of bioresorbable plating systems in the rigid fixation of paediatric mandible fractures. PATIENTS AND METHODS Our series consists of fifteen paediatric patients (11 male, 4 female, average age 8.13 years) with mandible fractures of varying severity treated with bioresorbable plates over a 54-month period at our institution. Fractures of the ramus, body, parasymphysis, and symphysis were treated by one surgeon with open reduction and internal fixation with 1.5 mm and 2 mm resorbable plates and monocortical screws, using 3 different plating systems, each with differing polymer concentrations of polyglycolic and poly-L-lactic acid. The patients were followed with respect to the following clinical categories: fracture location, postoperative occlusion, maximum interincisal opening (MIO), segmental mobility at the fracture site, and any abnormal swelling at the operative site. RESULTS Our data shows a stable occlusion and maximum interincisal opening of thirty millimetres or greater was achieved in 14 of 15 patients seen in follow up, with 8 patients having an MIO of 40 mm or greater. No segmental mobility noted at any of the fracture sites. Thirteen patients had no postoperative sequelae or implant related complications. Two patients developed a seroma-like collection at the operative site. Postoperative films starting at 1 year showed significant bony osseous fill where the previous screw sites were located. CONCLUSIONS In our case series we found that the use of resorbable polyglycolic and poly-L-lactic acid plating systems when combined with a brief postoperative period of intermaxillary fixation is an effective method of internal fixation for mandibular fractures in the paediatric population.

Common dental and orofacial trauma: evaluation and management

This article reviews common dental and orofacial traumatic injuries, and provides a broad overview and general principles of the diagnosis and management of common dental and orofacial injuries. Such knowledge will aid the physician in recognition and assessment of injury, proper treatment, and appropriate referral to the specialist. Although many of these injuries warrant appropriate consultation, a sound understanding of assessment and treatment protocol is important.

Recurrent Lower Lip Swelling in a 62-Year-Old African American Female

A 62-year-old African American female presented to the mergency department complaining of lower lip swelling or 4 days. She reported that the swelling had increased in ize over the 4 days prior to presentation. One month prior he had similar swelling and was evaluated by her primary hysician. At that time, treatment with penicillin and warm ompresses had resulted in spontaneous purulent drainage f the swelling. She denied fever, chills, nausea, vomiting, ightheadedness, dizziness, or trauma at the time of the mergency department visit. The patient also reported that he began noticing similar lesions 3 years ago. She initially

Acquired arteriovenous fistula associated with traumatic oroantral fistula: Endovascular treatment

Oroantral fistulas are pathologic connections between the oral cavity and the maxillary sinus. Arteriovenous fistulas are abnormal connections between an artery and a vein with no intervening capillary network.