scholarly journals TAC3/TACR3 Mutations Reveal Preferential Activation of GnRH Release by Neurokinin B in Neonatal Life Followed by Reversal in Adulthood

2010 ◽  
Vol 31 (2) ◽  
pp. 254-255
Author(s):  
Elena Gianetti ◽  
Cintia Tusset ◽  
Sekoni D. Noel ◽  
Margaret G. Au ◽  
Andrew A. Dwyer ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Tertiary Care ◽  
Sequence Variants ◽  
Neurokinin B ◽  
Coding Sequence ◽  
Base Pair Deletion ◽  
Gnrh Release ◽  
Reproductive Life ◽  
Tertiary Care Centers

ABSTRACT Context Mutations in TAC3 and TACR3 (encoding neurokinin B and its receptor) have been identified in Turkish patients with hypogonadotropic hypogonadism (IHH), but broader populations have not yet been tested and genotype-phenotype correlations have not been established. Objective A broad cohort of normosmic IHH probands was screened for mutations in TAC3/TACR3 to evaluate the prevalence of such mutations and define the genotype/phenotype relationships. Design Sequencing of TAC3/TACR3; in vitro functional assays, neuroendocrine phenotyping. Setting Tertiary care centers world-wide. Patients or other participants 345 probands, 18 family members, 292 controls. Intervention Examination of reproductive phenotypes throughout reproductive life and pre/post therapy. Main Outcome Measure Rare sequence variants in TAC3/TACR3. Results In TACR3, 19 probands harbored 13 distinct coding sequence rare nucleotide variants (3 nonsense mutations, 6 non-synonymous, 4 synonymous [one predicted to affect splicing]). In TAC3, one homozygous single base pair deletion was identified, resulting in complete loss of the neurokinin B decapeptide. Phenotypic information was available on 16 males and 7 females with coding sequence variants in TACR3/TAC3. Of the 16 males, 15 had microphallus; none of the females had spontaneous thelarche. Seven of the 16 males and 5/7 females were assessed after discontinuation of therapy and 6/7 males and 4/5 females demonstrated evidence for reversibility of their hypogonadotropism. Conclusions Mutations in the neurokinin B pathway are relatively common as causes of hypogonadism. While the neurokinin B pathway appears essential during early sexual development, its importance in sustaining the integrity of the hypothalamic-pituitary-gonadal axis appears attenuated over time.

scholarly journals TAC3/TACR3 Mutations Reveal Preferential Activation of Gonadotropin-Releasing Hormone Release by Neurokinin B in Neonatal Life Followed by Reversal in Adulthood

2010 ◽  
Vol 95 (6) ◽  
pp. 2857-2867 ◽  
Author(s):  
Elena Gianetti ◽  
Cintia Tusset ◽  
Sekoni D. Noel ◽  
Margaret G. Au ◽  
Andrew A. Dwyer ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Tertiary Care ◽  
Sequence Variants ◽  
Neurokinin B ◽  
Coding Sequence ◽  
Base Pair Deletion ◽  
Before And After ◽  
Reproductive Life ◽  
Tertiary Care Centers

Abstract Context: Mutations in TAC3 and TACR3 (encoding neurokinin B and its receptor) have been identified in Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations have not yet been tested and genotype-phenotype correlations have not been established. Objective: A broad cohort of normosmic IHH probands was screened for mutations in TAC3/TACR3 to evaluate the prevalence of such mutations and define the genotype/phenotype relationships. Design and Setting: The study consisted of sequencing of TAC3/TACR3, in vitro functional assays, and neuroendocrine phenotyping conducted in tertiary care centers worldwide. Patients or Other Participants: 345 probands, 18 family members, and 292 controls were studied. Intervention: Reproductive phenotypes throughout reproductive life and before and after therapy were examined. Main Outcome Measure: Rare sequence variants in TAC3/TACR3 were detected. Results: In TACR3, 19 probands harbored 13 distinct coding sequence rare nucleotide variants [three nonsense mutations, six nonsynonymous, four synonymous (one predicted to affect splicing)]. In TAC3, one homozygous single base pair deletion was identified, resulting in complete loss of the neurokinin B decapeptide. Phenotypic information was available on 16 males and seven females with coding sequence variants in TACR3/TAC3. Of the 16 males, 15 had microphallus; none of the females had spontaneous thelarche. Seven of the 16 males and five of the seven females were assessed after discontinuation of therapy; six of the seven males and four of the five females demonstrated evidence for reversibility of their hypogonadotropism. Conclusions: Mutations in the neurokinin B pathway are relatively common as causes of hypogonadism. Although the neurokinin B pathway appears essential during early sexual development, its importance in sustaining the integrity of the hypothalamic-pituitary-gonadal axis appears attenuated over time.

scholarly journals Uncovering Novel Reproductive Defects in Neurokinin B Receptor Null Mice: Closing the Gap Between Mice and Men

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1498-1508 ◽  
Author(s):  
Jasmine J. Yang ◽  
Claudia S. Caligioni ◽  
Yee-Ming Chan ◽  
Stephanie B. Seminara
Keyword(s):  
Pubertal Development ◽  
Hypogonadotropic Hypogonadism ◽  
Corpora Lutea ◽  
Wild Type ◽  
Neurokinin B ◽  
Gnrh Release ◽  
Estrous Cyclicity ◽  
Closing The Gap ◽  
Deficient Mice ◽  
Robust Response

Patients bearing mutations in TAC3 and TACR3 (which encode neurokinin B and its receptor, respectively) have sexual infantilism and infertility due to GnRH deficiency. In contrast, Tacr3−/− mice have previously been reported to be fertile. Because of this apparent phenotypic discordance between mice and men bearing disabling mutations in Tacr3/TACR3, Tacr3 null mice were phenotyped with close attention to pubertal development, estrous cyclicity, and fertility. Tacr3−/− mice demonstrated normal timing of preputial separation and day of first estrus, markers of sexual maturation. However, at postnatal d 60, Tacr3−/− males had significantly smaller testes and lower FSH levels than their wild-type littermates. Tacr3−/− females had lower uterine weights and abnormal estrous cyclicity. Approximately half of Tacr3−/− females had no detectable corpora lutea on ovarian histology at postnatal d 60. Despite this apparent ovulatory defect, all Tacr3−/− females achieved fertility when mated. However, Tacr3−/− females were subfertile, having both reduced numbers of litters and pups per litter. The subfertility of these animals was not due to a primary ovarian defect, because they demonstrated a robust response to exogenous gonadotropins. Thus, although capable of fertility, Tacr3-deficient mice have central reproductive defects. The remarkable ability of acyclic female Tacr3 null mice to achieve fertility is reminiscent of the reversal of hypogonadotropic hypogonadism seen in a high proportion of human patients bearing mutations in TACR3. Tacr3 mice are a useful model to examine the mechanisms by which neurokinin B signaling modulates GnRH release.

scholarly journals 124. Six-year Longitudinal Analysis of an Inpatient Infectious Diseases Telemedicine Service at a Community Hospital

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S191-S192
Author(s):  
Nupur Gupta ◽  
Adit B Sanghvi ◽  
John Mellors ◽  
Rima Abdel-Massih
Keyword(s):  
Infectious Disease ◽  
Tertiary Care ◽  
Medical Officer ◽  
Rural Hospital ◽  
Hospital Length Of Stay ◽  
Observation Study ◽  
Patient Acuity ◽  
Telemedicine Service ◽  
Tertiary Care Centers ◽  
Over Time

Abstract Background Telemedicine (TM) has emerged as a viable solution to extend infectious disease (ID) expertise to communities without access to this specialty.1 TM allows clinicians in rural settings to connect with specialists at distant sites and provide the best care for their patients, often eliminating the need for hospital transfers. Here, we describe the experience from one of the longest standing inpatient Tele-ID consult services using live audio-video (AV) visits with the assistance of a telepresenter. Methods Longitudinal data were collected from a 126-bed rural hospital in Pennsylvania that had no access to ID consultation before 2014. Live AV consults during business hours began in 2014 and telephonic physician to physician consults were made available 24/7. All ID consult data were extracted from the hospital electronic health record between 2014 to 2019. Key outcomes assessed included the number of consult encounters, total hospital length of stay (LOS), discharges to home, transfer to tertiary care centers, and readmission rates at 30 days. Results Most consulted patients were Caucasians, and females with an average age of 64.7 years (Table 1). The number of unique consult encounters increased annually from 111 in 2014 to 469 in 2019 (Table 1). The Charlson Comorbidity Score and Elixhauser Comorbidity Index also increased each year beginning in 2016 (Table 1). By contrast, LOS decreased each year as did the 30-day readmission rate (Table 2). Most patients were not transferred (average 89.4% over 6 years) to tertiary care centers and more than half were discharged to home each year (Table 2). Conclusion This longitudinal 6-year observation study of an inpatient TM ID service at a rural hospital showed remarkable annual growth in consult encounters (total growth >400%). Despite increasing patient acuity, overall hospital LOS decreased over time (10.2 to 8.2 days). Patient transfers to tertiary care centers remained low (average 10.5% over 6 years) as did 30-day readmissions (average 16.3% over 6 years). The majority of patients were discharged to home (average 61.3% over 6 years). These findings show that a rural inpatient TM ID consult service can expand over time and is an effective alternative for hospitals without access to ID expertise. Disclosures John Mellors, MD, Abound Bio (Shareholder)Accelevir Diagnostics (Consultant)Co-Crystal Pharmaceuticals (Shareholder)Gilead (Consultant, Grant/Research Support)Merck (Consultant) Rima Abdel-Massih, MD, Infectious Disease Connect (Shareholder, Other Financial or Material Support, Chief Medical Officer)

scholarly journals Surgical outcome of primary intradural spinal arachnoid cysts: a series of 10 cases

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Essam Abdelhameed ◽  
Ahmed Ali Morsy
Keyword(s):  
Tertiary Care ◽  
Outer Wall ◽  
Arachnoid Cysts ◽  
Neurophysiological Monitoring ◽  
Japanese Orthopedic Association ◽  
Common Location ◽  
Before And After ◽  
Microsurgical Resection ◽  
Tertiary Care Centers ◽  
Intradural Arachnoid Cysts

Abstract Background Primary intradural spinal arachnoid cysts are rare pathologies of uncertain etiology and variable presentation from no symptoms to myelopathy or radiculopathy according to cord or root compression. MRI with diffusion and contrast differentiates them from many pathologies. There is a lot of debate regarding when to treat and how to treat such rare pathologies. Objective We present a series of 10 primary intradural arachnoid cysts and evaluate outcome after surgery. Methods This retrospective study includes patients having primary intradural spinal arachnoid cysts operated in two tertiary care centers from October 2012 till October 2019. Symptomatic cysts were subjected to microsurgical resection or outer wall excision and inner wall marsupialization under neurophysiological monitoring. The Japanese Orthopedic Association Score was used for clinical evaluation while MRI with contrast and diffusion was used for radiological evaluation before and after surgery. Results This series included 10 patients, 4 males and 6 females, with mean age of 40 years. Pain was the most common presentation. The most common location was dorsal thoracic region. Total excision was achieved in 2 cases and marsupialization in 8 cases. All symptoms improved either completely or partially after surgery. No neurological deterioration or recurrence was reported during the follow-up period in this series. Conclusion Treatment of symptomatic primary intradural spinal arachnoid cysts should be microsurgical resection, when the cyst is adherent to the cord, microscopic fenestration can be safe and effective.

scholarly journals Perception about Etiology of Epilepsy and Help-Seeking Behavior in Patients with Epilepsy

2021 ◽  
Author(s):  
Gautam Das ◽  
Samar Biswas ◽  
Souvik Dubey ◽  
Durjoy Lahiri ◽  
Biman Kanti Ray ◽  
...  
Keyword(s):  
Help Seeking ◽  
Tertiary Care ◽  
Epileptic Seizures ◽  
Treatment Seeking ◽  
Professional Help ◽  
Epileptic Patients ◽  
Seeking Behavior ◽  
Tertiary Care Centers ◽  
Patients With Epilepsy

Abstract Objectives Patients with epilepsy and their family have diverse beliefs about the cause of their illness that generally determine their treatment-seeking behavior. In this study, our aim was to find out different beliefs about epilepsy that lead to different help-seeking patterns, which act as barrier to the intended modern medical management of epilepsy. Materials and Methods One hundred and fifty consecutive consenting patients accompanied by a reliable informant/family member fulfilling the International Classification of Epileptic Seizures (ICES), simplified version, were included. Demographic and clinical data of all the eligible subjects was collected. Perceived cause of illness and help-seeking pattern were explored from patient/informant by administering proper instruments. Results Respondents identified varied causes of epilepsy and explored multiple help-seeking options before reaching tertiary care centers. We observed that, generally, epileptic patients/relatives who had belief in causes like supernatural causes sought help from nonprofessional personnel and those attributed their symptom to bodily pathology had professional help-seeking. Conclusions The belief in supernatural causes not being conformed to the biomedical models of the epileptic disorders increases the treatment gap.

scholarly journals A national study of choanal atresia in tertiary care centers in Canada – part I: clinical presentation

2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Josee Paradis ◽  
Agnieszka Dzioba ◽  
Hamdy El-Hakim ◽  
Paul Hong ◽  
Frederick K. Kozak ◽  
...  
Keyword(s):  
Respiratory Distress ◽  
Clinical Presentation ◽  
Tertiary Care ◽  
Choanal Atresia ◽  
Case Series ◽  
Retrospective Chart Review ◽  
National Study ◽  
Feeding Difficulties ◽  
Presenting Symptoms ◽  
Tertiary Care Centers

Abstract Background To evaluate the clinical presentation of choanal atresia (CA) in tertiary centers across Canada. Methods Multi-centre case series involving six tertiary care pediatric hospitals across Canada. Retrospective chart review of patients born between 1980 and 2010 diagnosed with CA at a participating center. Results The health charts of 215 patients (59.6% female) with CA were reviewed and included in this study. The mean age of patients at time of CA presentation was 0.4 months (range 0.1 to 7.2 months) for bilateral CA and 37.8 months (range 0.1 to 164.1 months) for unilateral cases. The most common presenting symptoms for bilateral CA in decreasing order were respiratory distress (96.4%), feeding difficulties (68.2%), and rhinorrhea (65.5%), and for unilateral cases in decreasing order were rhinorrhea (92.0%), feeding difficulties (24.7%), and respiratory distress (18.0%). For the majority of patients (73.2%), the obstruction comprised mixed bony and membranous tissue, with only 10.5% presenting with a purely membranous obstruction. Familial history of CA was confirmed in only 3.3% of cases. One half of patients with CA presented with one or more associated anomalies and 30.6% had a syndrome. Conclusions The present investigation is the first national multi-institutional study evaluating the clinical presentation of CA over three decades. The present cohort of CA patients presented with a breadth of co-morbidities with highly variable presentations, with bilateral cases being more severely affected than unilateral cases. Further investigation into hereditary linkages to CA development is warranted. Graphical abstract

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