Evaluation of Two Potent and Selective PET Radioligands to Image COX-1 and COX-2 in Rhesus Monkeys.

This study assessed whether the newly developed PET radioligands 11C-PS13 and 11C-MC1 could image constitutive levels of cyclooxygenase (COX)-1 and COX-2, respectively, in rhesus monkeys. Methods: After intravenous injection of either radioligand, 24 whole-body PET scans were performed. To measure enzyme-specific uptake, scans of the 2 radioligands were also performed after administration of a nonradioactive drug preferential for either COX-1 or COX-2. Concurrent venous samples were obtained to measure parent radioligand concentrations. SUVs were calculated from 10 to 90 min. Results:11C-PS13 showed specific uptake in most organs, including spleen, gastrointestinal tract, kidneys, and brain, which was blocked by COX-1, but not COX-2, preferential inhibitors. Specific uptake of 11C-MC1 was not observed in any organ except the ovaries and possibly kidneys. Conclusion: The findings suggest that 11C-PS13 has adequate signal in monkeys to justify its extension to human subjects. In contrast, 11C-MC1 is unlikely to show significant signal in healthy humans, though it may be able to do so in inflammatory conditions.

The 5-HT1A Receptor PET Radioligand 11C-CUMI-101 Has Significant Binding to α1-Adrenoceptors in Human Cerebellum, Limiting Its Use as a Reference Region.

Prazosin, a potent and selective α1-adrenoceptor antagonist, displaces 25% of 11C-CUMI-101 ([O-methyl-11C]2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione) binding in monkey cerebellum. We sought to estimate the percentage contamination of 11C-CUMI-101 binding to α1-adrenoceptors in human cerebellum under in vivo conditions. In vitro receptor-binding techniques were used to measure α1-adrenoceptor density and the affinity of CUMI-101 for these receptors in human, monkey, and rat cerebellum. METHODS: Binding potential (maximum number of binding sites × affinity [(1/dissociation constant]) was determined using in vitro homogenate binding assays in human, monkey, and rat cerebellum. 3H-prazosin was used to determine the maximum number of binding sites, as well as the dissociation constant of 3H-prazosin and the inhibition constant of CUMI-101. RESULTS: α1-adrenoceptor density and the affinity of CUMI-101 for these receptors were similar across species. Cerebellar binding potentials were 3.7 for humans, 2.3 for monkeys, and 3.4 for rats. CONCLUSION: Reasoning by analogy, 25% of 11C-CUMI-101 uptake in human cerebellum reflects binding to α1-adrenoceptors, suggesting that the cerebellum is of limited usefulness as a reference tissue for quantification in human studies.

Review of linear epidermal nevus with oral mucosal involvement--series of five new cases.

INTRODUCTION: Linear epidermal nevi are sporadic hamartomatous alterations of the epidermis and superficial dermis that clinically appear as verrucous papules and plaques distributed in a linear pattern following Blaschko's lines. Their extent varies from unilateral involvement (nevus unius lateris) to extensive bilateral involvement (ichthyosis hystrix). Oral mucosal lesions have rarely been described. AIMS: We review the literature, focusing on the rare intraoral manifestations of linear epidermal nevus. CASE SERIES: We present a series of five new cases with oral mucosal involvement. Four cases had associated cutaneous lesions and one case had oral lesions exclusively. Histopathologic evaluation of lesional tissue in four cases showed hyperkeratosis, acanthosis, epithelial hyperplasia, and papillomatosis. Dental abnormalities, consisting of enamel hypoplasia and congenitally missing teeth, were noted in one patient adjacent to the oral lesions.

Resorbable mesh in the treatment of orbital floor fractures.

A variety of materials have been used to reconstruct defects of the orbital floor. Autogenous materials such as bone and cartilage have the obvious drawback of the necessary donor site, whereas alloplastic implants carry the potential risk of infection, particularly when in communication with the maxillary sinus. Consequently, there has been interest in the use of resorbable alloplastic material that acts as a barrier until completely degraded. In this series, a total of 12 patients with orbital defects larger than 1 cm2 were treated by the placement of a resorbable mesh plate of polyglycolic and polylactic acid (Lactosorb). Of the total of 12 patients treated, 3 were lost to follow-up. Of the remaining 9 patients, the mean follow-up was 6 months, with the longest follow-up being 15 months and the shortest 1 month. Two patients developed enophthalmos. In each case, this measured 2 mm using Hertel exophthalmometry, and was present in the early postoperative period (less than 1 month). The cause of the enophthalmos in both patients was found to be a technical error in placement of the mesh. One patient developed an inflammatory reaction along the infraorbital rim requiring implant removal. This occurred at 7 months. From the above series, it is concluded that resorbable mesh is an acceptable material for reconstruction of the orbital floor in selected patients. It is believed that larger floor defects are better suited for nonresorbable alloplastic reconstruction, and that placement of the mesh over the infraorbital rim is unnecessary and places the patient at risk for a local inflammatory reaction.

Compartmentalized bone regeneration of cranial defects with biodegradable barriers: an animal model.

In bony defects of the cranium, bone healing may be complicated by prolapse of surrounding tissue into the defect. This tissue acts as an impediment to prevent the migration of osteogenic cells, leading to impaired bone formation. It has been previously shown that a membrane placed over the bony defect inhibits the connective tissue cells from entering the wound and theoretically improves bone formation. The use of a proven resorbable material, Lactosorb, is used in this animal model and has shown a significant increase in autogenous bony formation. The majority of previous work was accomplished with nonresorbable material that resulted in foreign body formation. This paper is unique because resorbable material in the animal model is relatively inexpensive and easy to use and has allowed successful autogenous bony regeneration.

The use of resorbable spacers for nasal spreader grafts.

The concept and technique of the use of resorbable synthetic material for nasal spreader grafts are presented. The material is felt to be particularly useful in revision rhinoplasty, in which the likelihood of internal valve collapse is high and the septum (the most common source of material for spreader grafts) often has already been harvested. The material used is a commercially available polymer of polylactic and polyglycolic acid, Lactosorb. It is supplied as a mesh sheet that can be cut to an appropriate size for spreader grafts. Although the material absorbs after approximately 12 months, it is believed that this is sufficient time for the upper lateral cartilages to be stabilized by fibrosis in their new position and to maintain the appropriate internal valve angle. This material was used on 10 patients with valvular collapse undergoing secondary rhinoplasty. In follow-up observations ranging from 12 to 18 months, there has been no recurrence of airway obstruction.

Visual loss associated with fibrous dysplasia of the anterior skull base. Case report and review of the literature.

The authors present a case of visual loss associated with fibrous dysplasia of the anterior skull base and the surgical management of this case. Preoperative computerized tomography scanning in this patient demonstrated a patent optic foramen and a rapidly growing cystic mass within the orbit, which was responsible for the patient's visual loss. A literature review revealed that this case is typical, in that cystic mass lesions of various types are frequently responsible for visual loss associated with fibrous dysplasia. The authors did not find significant evidence in the literature to support the notion that visual loss associated with fibrous dysplasia is the result of progressive optic canal stenosis, thus raising questions about the value of prophylactic optic canal decompression. Instead, as demonstrated by this case and those uncovered in the literature review, most instances of visual loss result from the rapid growth of mass lesions of cystic fibrous dysplasia, mucoceles, or hemorrhage. Findings of the literature review and the present case of fibrous dysplasia of the anterior skull base support a role for extensive surgical resection in these cases and indicate a need for additional prospective analysis of a larger number of patients with this disease.

Nonsyndromic cleft lip and palate is not associated with cancer or other birth defects.

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is one of the most common human malformations with an average prevalence of 1 in 1,000 live births. The cause(s) of NSCLP remain unclear as the relative roles of genes, of the environment, and/or of chance alone are unknown. The purpose of this study was to evaluate the potential role of environmental factors in the cause of NSCLP, to determine if other birth defects aggregate in families with at least one individual affected with NSCLP, and to investigate the frequency of cancer in the first- and second-degree relatives of NSCLP index-cases. Included in this study were 196 index-cases and their families. Information pertaining to environmental factors and pedigree information was obtained on each family. Analysis showed that no single environmental factor could explain the occurrence of NSCLP in this population. The frequency of other birth defects in these families was 1.2%, which is not increased over that in the general population. One hundred seven cancers were reported in 72 of the 196 families included in the study. The frequency of cancer was not significantly increased in the first- or second-degree relatives of the NSCLP index cases or in those families with a positive family history of NSCLP. No childhood or adult cancers were reported in any of the 196 NSCLP index cases.

Classic and occult submucous cleft palates: a histopathologic analysis.

OBJECTIVE: Although classic and occult submucous clefts have been well described with respect to clinical features and endoscopic findings, there is a paucity of information regarding the histologic characteristics of the midline palatal area and its role in the clefting process. This preliminary study describes the histopathologic features of classic and occult submucosal clefts. DESIGN: Twenty-eight patients with classic submucous cleft (12 patients) and occult submucous cleft (16 patients) were available for study. Histopathologic evaluation of two biopsies from each patient (muscular uvulae biopsy; levator muscle bundle biopsy) was performed. RESULTS: Submucosal fibrosis with relatively dense collagen deposition was noted in both the musculus uvulae and levator muscle bundle biopsy sites. Individual myocytes and myocyte fascicles were entrapped and encased by fibrotic tissue, resulting in disruption of the fascicular organization. Most fascicles were disrupted by intervening dense collagen bands within and interposed between the fascicles. The myocytes had an atrophic or hypoplastic appearance with cross-sectional diameters ranging from 42% to 61% (mean reduction, 53%) less than those expected for myocytes from normal palates. There was fascicular disorganization with intermixing of longitudinally and cross-sectionally oriented myocyte groups. Minor salivary glands were affected as well with increased collagen deposition between and within lobules of salivary gland tissue. CONCLUSIONS: This histopathologic study indicates that significant fibrosis is present within submucosal cleft regions and is associated with myocyte atrophy or hypoplasia. The relatively dense fibrosis appears to be a well-organized, chronic process and is present in the absence of significant chronic inflammation. In addition, there is myocyte fascicular disorganization with a haphazard arrangement. This disorderly arrangement may imply that there is a failure of resorption of the epithelial/mesenchymal tissue during palatine shelf closure with retention of mesenchymal tissue that contains the insertion of the velopharyngeal musculature apparatus.

Cleft lip with or without cleft palate: effect of family history on reproductive planning, surgical timing, and parental stress.

OBJECTIVE: This study tested whether the presence of a family history of nonsyndromic cleft lip with or without cleft palate (NSCLP) lessens the negative impact on reproductive planning, decreases treatment anxiety, and relieves parental stress when there is a recurrent cleft. DESIGN: Sixty-one participating families, retrospectively ascertained through their children with NSCLP, were divided into two groups: those with a family history of clefting and those in which only the proband was affected. SETTING: Each family completed a questionnaire either at their home or during a clinic visit. PARTICIPANTS: Questionnaires were distributed to 117 families with an NSCLP child. Of these 117, 49 (42%) had another family member with NSCLP and 68 (58%) had no prior history of clefting. Sixty-one (52%) families returned the questionnaire and were categorized by family history. MAIN OUTCOME MEASURES: The Parenting Stress Index and the Hollingshead Index of Social Position were included with family and medical history questions in the 137-item questionnaire. RESULTS: The reproductive plans of the two groups were quite similar and were not dependent on the families' actual or perceived recurrence risks of NSCLP. The majority (85%) of the children with NSCLP underwent surgical closure at the recommended age. The two groups did not significantly differ on any score on the Parenting Stress Index, indicating a similar parental stress level between the groups. CONCLUSIONS: These findings suggest that family history does not significantly influence reproductive plans, timing of cleft repair, or stress of parents of a child with NSCLP. Further, these results indicate a need for additional psychosocial study of this population.

The team approach in the management of congenital and acquired deformities.

This article provides a summary of practices and guidelines for the design and methods used to form interdisciplinary medical teams. Education and organizational resources are discussed with regard to children with congenital anomalies, specifically craniofacial and cleft lip and palate deformities. The team format is recommended to maximize efficiencies and assure a continuum of care in the evolving managed care environment.

Algorithms for the treatment of cleft lip and palate.

Developing standardized outcomes and algorithms of treatment is a constantly evolving task. This article examines four variables in this process: cleft type, operative technique, surgical experience, and timing. Input from international cleft lip and palate programs regarding techniques and treatment modalities provide a dynamic tool for assessment and the development of guidelines in the treatment of the cleft lip and palate patient.

Applications of distraction osteogenesis. Part I.

Distraction osteogenesis (DO) of facial bones is a recent development in the treatment of pediatric patients. The use of DO in current clinical practice of pediatric reconstructive surgery is primarily limited to severe deformities of the lower jaw, most of which are congenital in nature. Clinical experience with DO for early facial deformities remains limited, and no authoritative works are currently available to guide clinicians in the techniques or indications for DO of the facial skeleton.

Congenital syndromes associated with nonmelanoma skin cancer.

Syndromes associated with nonmelanoma skin cancer are part of a group of inherited disorders characterized by a wide variety of clinical manifestations including palmar and plantar pitting, calcification of the dura, jaw cysts, and skeletal abnormalities. The syndromes have in common skin lesions progressing to basal or squamous cell cancers. In addition to skin tumors, bone and visceral tumors are common. Early diagnosis, genetic counseling, and treatment of skin lesions are appropriate tools for the management of patients with these syndromes. Surgical procedures generally involve total resection combined with reconstructive efforts.

Caution: prenatal clubfoot can be both a transient and a late-onset phenomenon.

Clubfoot (talipes equinovarus) is a common orthopaedic malformation that can be accurately diagnosed prenatally. The study was conducted to investigate possible in utero visualization of transient and late-onset clubfoot. Early (13-16 weeks' gestation) prenatal transvaginal sonographic diagnosis of clubfoot deformity was made in 36 cases during the study period. Only those cases where follow-up examination revealed different sonographic findings were considered. The results showed that seven cases of transient (as well as relapsing) clubfoot were identified. In 4 of 7 cases, the clubfoot resolved (all after more than 10 min of observation) during the same examination. In the fifth and sixth cases, it initially resolved, later reappearing in follow-up examinations (20 and 22 weeks' gestation). In the seventh case, the clubfoot persisted for two consecutive examinations (2 weeks apart each) and later disappeared. In addition, six late-onset (22-24 weeks' gestation) clubfoot cases were identified during the study period. Although infrequent, in utero clubfoot can be both a transient and a late-onset phenomenon. Over- and under-diagnosis are potential hazards in these situations.

An algorithm for management of residual posttraumatic calvarial defects in adults.

For the discussion of options in late reconstruction of residual posttraumatic calvarial defects in adults, the calvaria is divided into three reconstructive zones. Zone 1 comprises the frontal sinus region and the contour of the supraorbital brow; Zone 2 comprises the smooth, cosmetically visible prehairline forehead; Zone 3 comprises the posthairline area and the calvaria. The particular reconstructive requirements (autogenous bone versus alloplastic material) of each zone are described and illustrated with clinical cases. The merits of bone from various donor sites and those of alloplastic material are discussed. The authors present an algorithm of reconstructive choices for residual posttraumatic calvarial defects in adults based on the nature of the defect and the aesthetic reconstructive zone.

Orbital hemorrhage during rhinoplasty.

The most common complication of rhinoplasty is perioperative and postoperative hemorrhage. We present two patients who experienced intraoperative orbital hemorrhage during rhinoplasty. Patients with a history of previous nasal trauma, because of scarring/altered anatomy, may be more prone to this serious complication. A precise and well-placed osteotomy must be done to avoid aberrant anatomy and complications. The proposed mechanism for orbital hemorrhage is shearing or tearing of fibrovascular scar tissue involving the angular vessels during the surgical dissection. Prompt recognition and management of an orbital hemorrhage during or following rhinoplasty is necessary to prevent possible ocular injury and loss of vision. A management algorithm for orbital hemorrhage is presented along with a discussion of surgical techniques to prevent this complication. Surgeons performing rhinoplasty should be cognizant of this type of intraoperative complication along with its medical and surgical management.