scholarly journals PROKR2 and PROK2 mutations cause isolated congenital anosmia without gonadotropic deficiency

2013 ◽  
Vol 168 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Antoine Moya-Plana ◽  
Carine Villanueva ◽  
Ollivier Laccourreye ◽  
Pierre Bonfils ◽  
Nicolas de Roux

ObjectiveIsolated congenital anosmia (ICA) is a rare phenotype defined as absent recall of any olfactory sensations since birth and the absence of any disease known to cause anosmia. Although most cases of ICA are sporadic, reports of familial cases suggest a genetic cause. ICA due to olfactory bulb agenesis and associated to hypogonadotropic hypogonadism defines Kallmann syndrome (KS), in which several gene defects have been described. In KS families, the phenotype may be restricted to ICA. We therefore hypothesized that mutations in KS genes cause ICA in patients, even in the absence of family history of reproduction disorders.Design and methodsIn 25 patients with ICA and olfactory bulb agenesis, a detailed phenotype analysis was conducted and the coding sequences of KAL1, FGFR1, FGF8, PROKR2, and PROK2 were sequenced.ResultsThree PROKR2 mutations previously described in KS and one new PROK2 mutation were found. Investigation of the families showed incomplete penetrance of these mutations.ConclusionsThis study is the first to report genetic causes of ICA and indicates that KS genes must be screened in patients with ICA. It also confirms the considerable complexity of GNRH neuron development in humans.

1977 ◽  
Vol 8 (1) ◽  
pp. 128-148 ◽  
Author(s):  
Sylvia J. Hallam

Following several discussions in recent numbers of Quaternary Research on the peopling of the Americas, this paper suggests that movements into the New World should be viewed in the wider context of subsistence, technology, and movement around the western littorals of the Pacific, resulting in the colonization not of one but of two new continents by men out of Asia. Specific points which have been raised by these recent papers are reviewed in the light of Australian, Wallacian, and East Asian data.(1) The earliness of watercraft is evidenced by chronology of the human diaspora through Wallacia and Greater Australia.(2) The simplistic nomenclature of chopper-flake traditions masks considerable complexity and technological potential, revealed in detailed Antipodean studies.(3) These traditions also have great potential for adapting to differing ecological zones, evidenced within Greater Australia; and for technological and economic innovation there, through Southeast Asia, and to Japan and the north Asian littoral.(4) The history of discovery and the nature of the evidence from Australia cannot validly be used to controvert early dates in the Americas.(5) Demographic data from Australia suggest that total commitment to a rapid-spread “bowwave” model for the peopling of new continents may be unwise.


Author(s):  
E C Wirrell ◽  
L D Hamiwka ◽  
L A Hamiwka ◽  
S Grisaru ◽  
X Wei

Objective:Posterior reversible encephalopathy syndrome (PRES) occurs most commonly in the setting of known hypertension or use of immunosuppressive agents.Design and Methods:We report four previously-well children who presented acutely with altered mentation, seizures and visual disturbances and were diagnosed with PRES.Results:Only one child had a history of gross hematuria prior to the seizure. All four were discovered to be hypertensive only after onset of their neurological symptoms, and were subsequently diagnosed with glomerulonephritis. All four had rapid resolution of neurological symptoms with adequate treatment of hypertension.Conclusions:Blood pressure must be measured promptly in all children presenting with these symptoms. If elevated, the diagnosis of PRES should be strongly considered and a workup for renal disease pursued.


2021 ◽  
Vol 9 (1) ◽  
pp. e001988
Author(s):  
K M Venkat Narayan ◽  
Dimple Kondal ◽  
Sayuko Kobes ◽  
Lisa R Staimez ◽  
Deepa Mohan ◽  
...  

IntroductionSouth Asians (SA) and Pima Indians have high prevalence of diabetes but differ markedly in body size. We hypothesize that young SA will have higher diabetes incidence than Pima Indians at comparable body mass index (BMI) levels.Research design and methodsWe used prospective cohort data to estimate age-specific, sex, and BMI-specific diabetes incidence in SA aged 20–44 years living in India and Pakistan from the Center for Cardiometabolic Risk Reduction in South Asia Study (n=6676), and compared with Pima Indians, from Pima Indian Study (n=1852).ResultsAt baseline, SA were considerably less obese than Pima Indians (BMI (kg/m2): 24.4 vs 33.8; waist circumference (cm): 82.5 vs 107.0). Age-standardized diabetes incidence (cases/1000 person-years, 95% CI) was lower in SA than in Pima Indians (men: 14.2, 12.2–16.2 vs 37.3, 31.8–42.8; women: 14.8, 13.0–16.5 vs 46.1, 41.2–51.1). Risk of incident diabetes among 20–24-year-old Pima men and women was six times (relative risk (RR), 95% CI: 6.04, 3.30 to 12.0) and seven times (RR, 95% CI: 7.64, 3.73 to 18.2) higher as compared with SA men and women, respectively. In those with BMI <25 kg/m2, however, the risk of diabetes was over five times in SA men than in Pima Indian men. Among those with BMI ≥30 kg/m2, diabetes incidence in SA men was nearly as high as in Pima men. SA and Pima Indians had similar magnitude of association between age, sex, BMI, and insulin secretion with diabetes. The effect of family history was larger in SA, whereas that of insulin resistance was larger in Pima IndiansConclusionsIn the background of relatively low insulin resistance, higher diabetes incidence in SA is driven by poor insulin secretion in SA men. The findings call for research to improve insulin secretion in early natural history of diabetes.


1999 ◽  
Vol 123 (10) ◽  
pp. 949-951
Author(s):  
Carol S. Marshall ◽  
Denis Dwyre ◽  
Robin Eckert ◽  
Liisa Russell

Abstract A 35-year-old gravida 3, para 3 Filipino woman with a negative antibody screen, no prior history of transfusion, and no hemolytic disease of the newborn in her children suffered a massive postpartum hemorrhage requiring transfusion. A severe hemolytic transfusion reaction occurred 5 days after delivery. Subsequently, a panagglutinin on a routine antibody identification panel was identified as anti-Jk3. The patient's red blood cell phenotype was Jk(a−b−) and all of her children were Jk(a−b+), yet the antibody that formed reacted with equal strength against all Jka- or Jkb-positive cells. The rare Jk(a−b−) phenotype is more common in Polynesians. Anti-Jk3, like other Kidd system antibodies, is difficult to detect because in vivo production may be absent between provocative episodes and because these antibodies often show weak in vitro reactions. The increasing numbers of Pacific Islanders in the United States could result in more frequent encounters with this rare phenotype. Increased awareness of ethnic variability in blood phenotypes and of the capricious nature of Kidd antibodies can help pathologists and technologists deal more effectively with these cases.


2021 ◽  
Vol 49 ◽  
Author(s):  
Fábio Luiz da Cunha Brito ◽  
Eduardo Perlmann ◽  
Jéssica Naiara Voitena ◽  
Andrea Kuner ◽  
Rayssa Dias Faleiro

Background: Cryptococcosis is a systemic mycotic disease caused by encapsulated yeasts C. neoformans and C. gattii. Cryptococcus neoformans is predominantly found in soils and feces of pigeons and psittacids. Infection occurs mainly through the respiratory tract, through the inspiration of fungal propagules (basidiospores and/or desiccated yeast cells). The main lesions observed are in the nasal cavity and lungs, but in dogs, the central nervous system and eyes are widely affected. Despite some previously mentioned reports, the retrobulbar form has not been described in the literature. Therefore, the purpose of this report is to describe a case of retrobulbar cryptococcoma mimetizing a tumor in a young bitch.  Case: A 2-year-old female Labrador Retriever,  was admitted to one Veterinary Hospital with exophthalmia on the left eye for 15 days and other signs included negative retropulsion, mydriasis, and abscence of menace and pupillary reflexes. Ocular ultrasound imaging revealed a hyperecotic and heterogeneous retrobulbar mass in the mid-dorsal region compressing the optic nerve. Computed tomography of the skull showed the presence of proliferation of neoplastic tissue in a locally invasive retrobulbar region promoting      moderate rostrolateral displacement of the left ocular bulb, discrete osthelysis in maxillary bone, palatine, medial wall of the orbital bone and frontal bone, with destruction of cribiform plate adjacent to the dorsal region of the orbital wall and presence of mild contrast uptake in the region of the left olfactory bulb lobe, characterizing a picture compatible with neoplasia with malignancy and locally invasive characteristics. Exenteration and excision of part of the frontal bone were performed and histopathological examination revealed granulation with the presence of fibroblasts and  numerous typical blastoconidia of Cryptococcus neoformans. The patient was treated with Itraconazole [10 mg/kg, v.o, SID, for 90 days] and one year after diagnosis, X-ray was performed to control the lesion and radiographic aspects were within normal limits.Discussion: Cryptococcus sp. is an environmental fungus that has the potential to be pathogenic to humans and animals. Fungus present as a basidiospores in pigeon droppings. The patient described had a history of contact with free-living pigeons, making it a risk factor for the occurrence of cryptococcosis, being the possible cause of the infection. In dogs, the disease is mainly described in immunosuppressed animals, which was not the case of the patient, who presented clinical and laboratory results within the normal range and without a previous history of use of immunosuppressants. The alterations described in the computed tomography, such as destruction of the cribriform plate adjacent to the dorsal region of the left orbital wall and the presence of slight contrast uptake in the left olfactory bulb lobe region, are compatible with the main entry point for propagules of Cryptococcus sp. In the present case, no periocular and ocular alterations were observed as described in the literature, and the lesion was restricted to the retrobulbar space. Ultrasonography and computed tomography revealed a neoformation mimicking a malignant neoplasm and the diagnosis of cryptococcoma was revealed by histopathology.  Based on the present case, cytology through aspiration of retrobulbal neoformations is imperative as a diagnostic method, especially in endemic areas for fungal diseases that can mimic ocular neoplasms. Keywords: cryptococcosis, fungus, Cryptococcus sp., dog. Descritores: criptococose, fungo, Cryptococcus sp., cão.


2019 ◽  
Vol 104 (12) ◽  
pp. 5915-5922
Author(s):  
Aditya S Shirali ◽  
James X Wu ◽  
Catherine Y Zhu ◽  
Alfonso Ocampo ◽  
Chi-Hong Tseng ◽  
...  

Abstract Context Serum levels of procalcitonin (PCT), a protein produced by the thyroid C cells under physiologic conditions, are high during sepsis. Objective To assess the test performance of serum PCT in predicting bacterial sepsis and septic shock in patients with hypothyroidism compared with those who have euthyroidism. Design and Methods This retrospective study evaluated patients with no history of thyroid dysfunction (euthyroid), primary hypothyroidism [medical hypothyroidism (MH)], and postsurgical hypothyroidism from total thyroidectomy (TT) identified from a prospectively maintained database who had PCT testing from 2005 to 2018. Quick Sequential Organ Failure Assessment score ≥ 2 or positive bacterial cultures identified bacterial sepsis, and a mean arterial pressure less than 65 mm Hg or a vasopressor requirement defined septic shock. Sensitivity and specificity of PCT for evaluation of bacterial sepsis and septic shock were measured. Results We identified 217 euthyroid patients, 197 patients with MH, and 84 patients with TT. Bacterial sepsis was found in 98 (45.2%), 92 (46.7%), and 36 (42.9%) of these patients, respectively (P > 0.05). Septic shock was identified in 13 (6.0%), 13 (6.6%), and 5 (6.0%) patients (P > 0.05), respectively. With use of a PCT cutoff of 0.5 µg/L for bacterial sepsis, the sensitivity was 59%, 61%, and 53% (P > 0.05) and specificity was 81%, 77%, and 81% (P > 0.05) for the diagnosis of bacterial sepsis in euthyroid, MH, and TT patients, respectively. With use of a PCT cutoff of 2.0 µg/L for septic shock, the sensitivity was 46%, 62%, and 63% (P > 0.05) and specificity was 86%, 82%, and 91% (P > 0.05) for the diagnosis of septic shock in these patients, respectively. Conclusions Despite the thyroidal origin of PCT, hypothyroidism did not affect the diagnostic performance of serum PCT levels in predicting bacterial sepsis or septic shock.


2015 ◽  
Vol 16 (2) ◽  
pp. 83-88
Author(s):  
Muhammad Hafizur Rahman ◽  
Liaquat Ali

Objective: To explore lipid abnormalities in normoglycemic first-degree diabetic relatives (FDRs) and prediabetic and diabetic subjects in the natural history of diabetes.Research design and methods: Thirty six impaired fasting glucose (IFG), 61 isolated impaired glucose tolerance (I-IGT), 64 combined IFG-IGT, 73 diabetic, and 32 FDRs along with 57 normoglycemic healthy controls without family history of diabetes in 1st degree relatives, were selected purposively following 2003 ADA cut-off values and 2006 WHO/IDF grouping. Anthropometry and blood pressure of the subjects were taken. Fasting and 2-h plasma glucose and HbA1C were measured. Fasting plasma triglyceride, total cholesterol and HDL cholesterol were measured by enzymatic colorimetric method.Results: Serum triglyceride was higher in IFG, I-IGT, IFG-IGT, diabetic and FDRs compared to Control [145 (59- 307), 128 (66-584), 166 (68-764), 161 (69-750) and 130 (81-281) vs. 108 (47-219) mg/dl, P<0.01, P<0.01, P<0.001, P<0.001 and P<0.05]. Total cholesterol was raised in IFG-IGT and diabetes compared to Control [185 (105-310), 185 (123-326) vs. 171 (101-235) mg/dl, P<0.05] and FDRs. But HDL did not differ among the groups. Prevalence of metabolic syndrome was higher in IFG, I-IGT, IFG-IGT and diabetes and FDRs than Control [55%, 38%, 57%, 58% and 36% vs. 15%, P<0.001, P<0.01, P<0.001, P<0.001 and P<0.05] and also in IFGIGT and diabetic compared to I-IGT and FDRs (P<0.05).Conclusions: Higher prevalence of metabolic syndrome and raised serum triglyceride is seen among diabetic, prediabetic and 1st degree diabetic-relatives. Total cholesterol and non-HDL cholesterol is raised only in IFG-IGT and diabetes, the more decompensated glycemic states.J MEDICINE July 2015; 16 (2) : 83-88


1999 ◽  
Vol 5 (4) ◽  
pp. 201-204
Author(s):  
Elshami M. Elamin, MD ◽  
Farida Khan, MD ◽  
Ernest Lieber, MD

2013 ◽  
Vol 2 (2) ◽  
pp. 14 ◽  
Author(s):  
Padraic Fleming ◽  
Sinead O'Neill ◽  
Miriam Owens ◽  
Therese Mooney ◽  
Patricia Fitzpatrick

<em>Background</em>. To determine why women skip rounds and factors influencing return of previous non attenders (PNAs) to breast screening. <em></em><br /><em>Design and methods</em>. Retrospective, quantitative, structured questionnaire posted to 2500 women. First PNAs did not attend their first screening appointment in 2007/2008 but then attended in 2010; First Controls first attended in 2010 without missed previous appointments. Women who attended screening in 2006 or earlier then skipped a round but returned in 2010 were Subsequent PNAs; Subsequent Controls attended all appointments.<br /><em>Results</em>. More First Controls than First PNAs had family history of cancer (72.7% <em>vs</em> 63.2%; P=0.003); breast cancer (31.3% <em>vs</em> 24.8%; P=0.04). More PNAs lived rurally; more First PNAs had 3rd level education (33.2% <em>vs</em> 23.6%; P=0.002) and fewer had private insurance than First Controls (57.7% <em>vs</em> 64.8%; P=0.04). Excellent/good health was reported in First PNAs and First Controls (82.9% <em>vs</em> 83.2%), but fewer Subsequent PNAs than Subsequent Controls (72.7% <em>vs</em> 84.9%; P=0.000). Common considerations at time of missed appointment were<em> had mammogram elsewhere</em> (33% First PNA) and <em>postponed to next round</em> (16% First PNA, 18.8% Subsequent PNA). Considerations when returning to screening were similar for First PNAs and Subsequent PNAs: <em>I am older </em>(35.4%, 29.6%), <em>I made sure I remembered</em> (29%, 23.6%), <em>could reschedule</em> (17.6%, 20.6%), <em>illness of more concern</em> (16.5%, 19%). More First PNAs stated <em>my family/friends advised</em> (22.3% <em>vs</em> 15.2%) or<em> my GP</em> (12.6% <em>vs</em> 4.6%) <em>advised me to attend</em>, h<em>eard good things about BreastCheck</em> (28.8% <em>vs</em> 13.6%).<br /><em>Conclusions</em>. Intermittent attenders do not fit socio-demographic patterns of non-attenders; GP recommendation and word of mouth were important in women’s return to screening. Fear and anxiety seem to act as a screening facilitator rather than an inhibitor.<br />


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