Molecular Diagnostics and In Utero Therapeutics for Orofacial Clefts.

Orofacial clefts and their management impose a substantial burden on patients, on their families, and on the health system. Under the current standard of care, affected patients are subjected to a lifelong journey of corrective surgeries and multidisciplinary management to replace bone and soft tissues, as well as restore esthetics and physiologic functions while restoring self-esteem and psychological health. Hence, a better understanding of the dynamic interplay of molecular signaling pathways at critical phases of palate development is necessary to pioneer novel prenatal interventions. Such pathways include transforming growth factor-ß (Tgfß), sonic hedgehog (Shh), wingless-integrated site (Wnt)/ß-catenin, bone morphogenetic protein (Bmp), and fibroblast growth factor (Fgf) and its associated receptors, among others. Here, we summarize commonly used surgical methods used to correct cleft defects postnatally. We also review the advances made in prenatal diagnostics of clefts through imaging and genomics and the various in utero surgical corrections that have been attempted thus far. An overview of how key mediators of signaling that drive palatogenesis are emphasized in the context of the framework and rationale for the development and testing of therapeutics in animal model systems and in humans is provided. The pros and cons of in utero therapies that can potentially restore molecular homeostasis needed for the proper growth and fusion of palatal shelves are presented. The theme advanced throughout this review is the need to develop preclinical molecular therapies that could ultimately be translated into human trials that can correct orofacial clefts at earlier stages of development.

Temporomandibular disorders: clinical and laboratory analyses for risk assessment of criteria for surgical therapy, a pilot study.

Temporomandibular disorder (TMD) is a broad category involving dysfunction of the skeletomuscular structures of the head and neck, and the temporomandibular joint (TMJ). A total of 66 patients, 54 with TMD, participated in this study. Group 1 (G1) had 31 patients suffering from early to intermediate stage disease, and no prior surgeries. G1 patients had arthrotomy/meniscectomy performed on the diseased joint(s). Group 2 (G2) consisted of 23 patients with late stage disease. All G2 patients had previously had unsuccessful TMJ surgery and were treated with either a partial or total joint prosthesis. Group 3 (G3) consisted of 12 patients who were clinically and radiographically asymptomatic. Medical histories including inflammatory bowel disease, headaches, vertigo, tinnitus and anemia, as well as surgical tonsillectomies, appendectomies and cholecystectomies, were significantly greater in G1 and G2 when compared to G3. Serological testing included HLA subtype, positive (ANA) antinuclear antibody, erythrocyte sedimentation rate (ESR), anemia profile, hormonal levels of prolactin and estradiol, and rheumatoid factor (RF). HLA frequencies, as well as some serological analyses, were significantly different among the three groups. These findings suggest that surgical failure may be secondary to autoimmune dysfunction with a predisposition to multisystem disease. The utilization of genetic markers, serological testing, and thorough medical and surgical histories should allow the clinician to determine which patients are potentially better surgical risk candidates for treatment of TMD.

Ultra-rapid cycling bipolar affective disorder following a closed-head injury.

A young adult with no prior history of affective disease suffered the onset of a rapid cycling bipolar illness, marginally responsive to psychotropic medications, following a mild closed-head injury, and persisting after the cognitive effects of the injury had resolved. A concurrence of findings on the neurological examination, neurobehavioural examination, SPECT scan, EEG and neuropsychological test battery suggested the presence of a diffuse cerebral injury with a predominance of left frontotemporal findings. This case demonstrates that a severe and disabling mood disorder may follow a mild head injury, and that its course may be independent of cognitive impairment and recovery.

Ultrastructural localization of gonadotropin and luteinizing hormone releasing hormone in the pituitary gland of a teleost fish (the platyfish).

Immunoreactive luteinizing hormone releasing hormone (irLHRH) and immunoreactive gonadotropin (irGtH) are demonstrated in the pituitary gland of a teleost fish (Xiphophorus maculatus, the platyfish) at the ultrastructural level. Using a immunoperoxidase procedure, irGtH and irLHRH are specifically localized over the secretory granules of both gonadotropes and some cells of the pars intermedia (PI). All other pituitary cell types lack immunoreactive material. A concept of LHRH receptors on gonadotrope granules is discussed and a new function for a class of PI cells is suggested.

Identification of luteinizing hormone-releasing hormone (LH-RH) in the brain and pituitary gland of a fish by immunocytochemistry.

For the first time immunoreactive luteinizing hormone-releasing hormone (LH-RH) is demonstrated in both the brain and pituitary gland of a teleost (Xiphophorus maculatus) using an immunoperoxidase procedure. It is specifically localized in the perikarya and their axons of the ventral telencephalon and nucleus lateralis tuberis and within and between the gonadotrops and within some cells of the pars intermedia. These immunoreactions are extinguished when antiserum to LH-RH is preincubated with LH-RH antigen but not with neurohypophysial hormones.