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.

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.

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.

Keratoacanthoma.

Keratoacanthoma is a benign epithelial tumor with a close resemblance to squamous-cell carcinoma both clinically and histologically. Both the pathologic status and treatment of keratoacanthoma are controversial.

Nonexcisional therapy for benign skin lesions.

Benign skin lesions are commonly seen and treated in the physician's office using standard equipment. These simple techniques may be easily learned and can and should be effectively employed by plastic surgeons.

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.

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.

Aesthetic considerations and the pediatric population.

Aesthetic surgery is the natural evolution of reconstructive surgery done to improve a patient's form in addition to function. This becomes especially critical in the pediatric age group in which patients are constantly evolving and their concepts of self-esteem and body image are so fragile.

Surgical treatment of acne scars.

Dermatologists and their plastic surgical colleagues treating acne vulgaris and its sequelae have an effective arsenal of anti-acne preparations to inhibit and avoid many of the long-term, cosmetically deforming effects of severe inflammatory acne. It is incumbent upon the physician participating in the care of the early and late sequelae of acne vulgaris to provide timely surgical therapy for those lesions requiring surgical drainage, extraction, or scar revision, while maintaining appropriate medical therapy for those areas of the skin still at risk to develop active disease.

Skin morphology and function.

Proper understanding of the cause, nature, and treatment of diseases affecting the skin requires an intimate knowledge of the anatomy and physiology of normal as well as pathologic skin. This article thus lays the groundwork for the discussions of specific pathologic conditions that follow in this issue.

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.

Management of residual cranial vault deformities.

The aims of calvarial reconstruction are to restore anesthetic contour and to provide protection for the underlying central nervous system structures. The authors present their algorithm of reconstructive options. Important considerations are the anatomic location of the defect and the duration since the original injury.

Nonepidermal and appendageal skin tumors.

This article reviews the essential clinical and pathologic features of a number of tumors of the dermis and epidermal appendages to help improve the clinician's skill at formulating preoperative differential diagnoses, assessing the need for treatment, and determining appropriate follow-up. In addition, it attempts to alert the practitioner to a number of heritable and systemic conditions that may be signalled by the presence of cutaneous tumors.

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.

Early surgical management of coronal synostosis.

Craniofacial surgery aims to allow proper expansion of the brain and the creation of an acceptable appearance. Early surgery represents an important means to attain these goals, with the choice of surgical technique being as critical as timing.

Mons pubis as a donor site for split-thickness skin grafts.

It is extremely important that a donor graft site be selected with attention to the type of graft needed as well as the specific patient's needs and lifestyle. While it is inevitable that any donor site heals with altered pigmentation and texture, we feel that by using a combination of several time-honored techniques in this well-concealed donor site, we have achieved long-term aesthetic results of the transfer of skin grafts from a hair-bearing area.

V-Y advancement of a subcutaneous pedicle in vermilion lip reconstruction.

We present three patients with lip cancer in whom the classic wedge excision would have resulted in an inordinate loss of tissue and possible compromise in shape and function. Without sacrificing the primary principle of adequately removing the cancer, the authors were able to excise the lesion and reconstruct the defect by means of a subcutaneous pedicle that might otherwise have been discarded with the usual wedge resection. There is a slight tendency for the healed skin flap to exhibit trapdoor scarring; however, in the older age group, in whom this technique has its greatest applicability, this has not been a permanent problem. This one-stage method of closing lip defects using subcutaneous pedicle flaps has the additional advantages of easy execution and minimal morbidity.

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.

Cartilage warping: an experimental model.

Cadaveric cartilage was cut into blocks with a newly devised cartilage cutter. Over one-hundred pieces of cartilage were used to define a kinetics curve of cartilage warping. Kinetics curves were developed for a control group of cartilage blocks placed in saline-soaked gauze (n = 46). In addition, kinetics curves were developed for cartilage placed in hypotonic saline (n = 14), hypertonic saline (n = 14), and cyanoacrylate glue (n = 6). Photographs of all groups were taken at timed intervals in order to plot the cartilage warping. It was found that pieces of cartilage which were cut peripherally (n = 6) warped twice as much as those cut centrally (n = 40). This was significant to p = 0.001. Within 15 minutes, centrally cut pieces of cartilage warped to approximately 90 percent of their end warpage; on the other hand, peripherally cut pieces of cartilage required 30 minutes to warp 90 percent of their destined warpage. The variables used did not significantly alter the kinetics curves as compared with control.