Citations

Leptin is a circulating hormone secreted by adipose and a few other tissues. The leptin receptor consists of a single transmembrane-spanning polypeptide that is present as a long physiologically important form as well as in several short isoforms. Recent studies have suggested that the anterior pituitary may have a role in the regulatory effects of leptin in animal models. To test this possibility in human pituitaries, we examined the expression of leptin and OB-R in normal and neoplastic pituitaries, and the possible functions of leptin in the pituitary were also analyzed. Leptin was present in 20–25% of anterior pituitary cells and was expressed in most normal anterior pituitary cells, including ACTH (70% of ACTH cells), GH (21%), FSH (33%), LH (29%), TSH (32%), and folliculo-stellate cells (64%), but was colocalized with very few PRL cells (3%), as detected by double labeling immunohistochemistry with two different antileptin antibodies. In addition, leptin expression was detected by RT-PCR in some pituitary tumors, including ACTH (three of four), GH (one of four), null cells (two of four), and gonadotroph (one of four) tumors as well as in normal pituitary. Immunohistochemical staining showed greater immunoreactivity for leptin in normal pituitaries compared to adenomas. Treatment of an immortalized cultured anterior pituitary cell line, HP75, with leptin stimulated pancreastatin secretion in vitro. Leptin also inhibited cell growth in the human HP75 and in the rat pituitary GH3 cell lines. Both long (OB-Rb) and common (OB-Ra) forms of the leptin receptor messenger ribonucleic acid and leptin receptor protein were expressed in normal and neoplastic anterior pituitary cells. These findings show for the first time that leptin is expressed by most human anterior pituitary cell types and that there is decreased leptin protein immunoreactivity in pituitary adenomas compared to that in normal pituitary tissues. We also show that OB-Rb is widely expressed by normal and neoplastic anterior pituitary cells, implicating an autocrine/paracrine loop in the production and regulation of leptin in the pituitary.

AbstractWe examined the specific cell types in normal human pituitaries that expressed PRL receptor (PRL-R) messenger ribonucleic acid (mRNA) by combined in situ hybridization and immunohistochemistry. The distribution of PRL-R mRNA in 28 pituitary adenomas was examined by in situ hybridization and reverse transcription-PCR in 12 cases of adenomas. In another set of experiments, 34 PRL adenomas from men, women, and bromocriptine-treated patients were analyzed for PRL-R by in situ hybridization.In the normal pituitary, PRL- and LH-producing cells had significantly more mean grain counts per cell and higher percentages of cells positive for PRL-R than GH and TSH cells. PRL-R mRNA was present in all groups of adenomas by in situ hybridization and reverse transcription-PCR. PRL adenomas had a significantly higher density of labeling compared to other adenoma types. Although there was no difference in the levels of PRL-R mRNA in PRL adenomas from men and premenopausal and postmenopausal women, patients treated with bromocriptine before pituitary surgery had significantly lower levels of PRL-R compared to all other groups. These results indicate that in the normal pituitary, PRL and LH cells have the highest level of PRL-R mRNA, whereas PRL adenomas have significantly higher levels of PRL-R mRNA than other types of adenomas, and bromocriptine treatment decreases the levels of PRL-R mRNA in PRL adenomas.

Objective To evaluate the horizontal and vertical stability of the quadrangular Le Fort I in patients with congenital cleft lip and palate. Design Prospective longitudinal study. Patients A total of 15 congenital cleft lip and palate patients treated with the maxillary quadrangular Le Fort I were enrolled. Intervention Lateral cephalometric radiographic examinations were obtained preoperatively, early postoperatively, and late postoperatively for four dental and skeletal landmarks. A questionnaire regarding patients' satisfaction with treatment and functional/cosmetic outcomes (airway, speech, mastication) was administered. Main Outcome Measures Surgical horizontal and vertical movement, late postsurgical horizontal and vertical movement, and surgical and postsurgical movement in relation to age and cleft type were evaluated using Spearman correlation coefficients, Wilcoxon signed rank tests, and Mann-Whitney tests. Results Surgical horizontal movements of all measured points showed significant changes. Significant differences of postsurgical horizontal movement were observed in younger patients versus adult patients. Significant differences of postsurgical horizontal movement were observed in unilateral cleft patients versus bilateral cleft patients. A high percentage of patients showed significant functional improvement in nasal airflow, speech, mastication, temporomandibular joint function, and mouth versus nose breathing. Conclusions The quadrangular Le Fort I is a functionally stable and a surgically predictable procedure for cleft lip and palate patients who present with midface deficiency. Patients under the age of 18 at the time of the osteotomy had a higher relapse rate than patients over 18 years of age. Younger patients who need surgery should be advised regarding the increased risk of skeletal relapse. Patients' satisfaction was high in all aesthetic- and function-related items on the questionnaire.

Background— Ejection fraction (EF) as a marker of left ventricular (LV) dysfunction and the appropriate thresholds for diagnosing severe or mild/moderate LV dysfunction in mitral regurgitation are doubted and poorly followed in clinical practice. We aimed at assessing the role of EF in a large registry of organic mitral regurgitation to objectively establish thresholds for various degrees of LV dysfunction and to analyze whether mitral surgery remains beneficial in those subsets of patients. Methods and Results— We investigated the relation between EF and mortality in 1875 patients with mitral regurgitation due to flail leaflets in sinus rhythm (65±13 years; median EF, 66% [60%–71%]) enrolled in the Mitral Regurgitation International Database (MIDA) registry. With EF <60%, mortality after diagnosis increased precipitously under medical management (adjusted hazard ratio [HR], 1.59 [1.19–2.12]) and during the entire follow-up (adjusted HR, 1.51 [1.22–1.87]). Severe LV dysfunction, if defined by EF <30%, would affect a minuscule number of patients (0.3%). Conversely, EF <45% was more frequent (2.9%) and was associated with considerable mortality under medical management (adjusted HR, 2.43 [1.50–3.95]) and during the entire follow-up (adjusted HR, 2.46 [1.67–3.61]). The group with EF of 45% to 60% represented a large proportion of patients (23%), exhibited rarely overt symptoms, and had higher mortality compared with EF >60%. Above 60%, no EF threshold further determined survival. The benefit of surgery remained considerable in the groups with EF <45% (adjusted HR, 0.28 [0.17–0.56]) and with EF of 45% to 60% (adjusted HR, 0.34 [0.21–0.64]). Conclusions— EF is valuable in defining presence and severity of LV dysfunction in organic mitral regurgitation. Patients with EF <45% have severe LV dysfunction, catastrophic outcome under medical management, and should not be denied surgery. Although there is no survival gain with EF ranges >60%, with EF dropping <60%, mortality increases precipitously and prompt surgical referral is critical to outcome.

Key Points Imatinib improves outcomes for adults with Ph+ ALL at least in part by facilitating allogeneic stem cell transplant. Allogeneic hematopoietic stem cell transplant is not dispensible in Ph+ ALL in the imatinib era.

Background and purposeTrochlear headaches are a recently recognized cause of headache, of which both primary and inflammatory subtypes are recognized. The clinical features, long‐term prognosis and optimal treatment strategy have not been well defined.MethodsA cohort of 25 patients with trochlear headache seen at the Mayo Clinic between 10 July 2007 and 28 June 2012 were identified.ResultsThe diagnosis of trochlear headache was not recognized by the referring neurologist or ophthalmologist in any case. Patients most often presented with a new daily from onset headache (n = 22, 88%). The most characteristic headache syndrome was reported as continuous, achy, periorbital pain associated with photophobia and aggravation by eye movement, especially reading. Individuals with a prior history of migraine were likely to have associated nausea and experience trochlear migraine. Amongst individuals with trochleitis, 5/12 (41.6%) had an identified secondary mechanism. Treatment responses were generally, but not invariably, favorable to dexamethasone/lidocaine injections near the trochlea. At a median follow‐up of 34 months (range 0–68), 10/25 (40%) of the cohort had experienced complete remission.ConclusionsTrochlear headaches are poorly recognized, have characteristic clinical features, and often require serial injections to optimize the treatment outcome. The identification of trochleitis should prompt neuroimaging to look for a secondary cause.