Olanzapine-associated neuroleptic malignant syndrome: Is there an overlap with the serotonin syndrome?

BACKGROUND: The neuroleptic malignant syndrome is a rare but serious condition mainly associated with antipsychotic medication. There are controversies as to whether "classical" forms of neuroleptic malignant syndrome can occur in patients given atypical antipsychotics. The serotonin syndrome is caused by drug-induced excess of intrasynaptic 5-hydroxytryptamine. The possible relationship between neuroleptic malignant syndrome and serotonin syndrome is at present in the focus of scientific interest. METHODS: This retrospective phenomenological study aims to examine the seventeen reported olanzapine - induced neuroleptic malignant syndrome cases under the light of possible overlap between neuroleptic malignant syndrome and serotonin syndrome clinical features. RESULTS: The serotonin syndrome clinical features most often reported in cases initially diagnosed as neuroleptic malignant syndrome are: fever (82%), mental status changes (82%) and diaphoresis (47%). Three out of the ten classical serotonin syndrome clinical features were concurrently observed in eleven (65%) patients and four clinical features were observed in seven (41%) patients. CONCLUSION: The results of this study show that the clinical symptoms of olanzapine-induced neuroleptic malignant syndrome and serotonin syndrome are overlapping suggesting similarities in underlying pathophysiological mechanisms.     

Irritable Bowel Syndrome Is Positively Related to Metabolic Syndrome: A Population-Based Cross-Sectional Study

Irritable bowel syndrome is a common gastrointestinal disorder that may affect dietary pattern, food digestion, and nutrient absorption. The nutrition-related factors are closely related to metabolic syndrome, implying that irritable bowel syndrome may be a potential risk factor for metabolic syndrome. However, few epidemiological studies are available which are related to this potential link. The purpose of this study is to determine whether irritable bowel syndrome is related to metabolic syndrome among middle-aged people. We designed a cross-sectional study of 1,096 subjects to evaluate the relationship between irritable bowel syndrome and metabolic syndrome and its components. Diagnosis of irritable bowel syndrome was based on the Japanese version of the Rome III Questionnaire. Metabolic syndrome was defined according to the criteria of the American Heart Association scientific statements of 2009. Dietary consumption was assessed via a validated food frequency questionnaire. Principal-components analysis was used to derive 3 major dietary patterns: “Japanese”, “sweets-fruits”, and “Izakaya (Japanese Pub) “from 39 food groups. The prevalence of irritable bowel syndrome and metabolic syndrome were 19.4% and 14.6%, respectively. No significant relationship was found between the dietary pattern factor score tertiles and irritable bowel syndrome. After adjustment for potential confounders (including dietary pattern), the odds ratio (95% confidence interval) of having metabolic syndrome and elevated triglycerides for subjects with irritable bowel syndrome as compared with non-irritable bowel syndrome are 2.01(1.13–3.55) and 1.50(1.03–2.18), respectively. Irritable bowel syndrome is significantly related to metabolic syndrome and it components. This study is the first to show that irritable bowel syndrome was significantly related to a higher prevalence of metabolic syndrome and elevated triglycerides among an adult population. The findings suggest that the treatment of irritable bowel syndrome may be a potentially beneficial factor for the prevention of metabolic syndrome. Further study is needed to clarify this association.     

X-linked dominant inherited diseases with lethality in hemizygous males

Summary X-linked dominant inheritance with lethality in hemizygous males is a rare mode of inheritance. The three best-known disorders which seem to be inherited in this way, are incontinentia pigmenti (IP) Bloch-Sulzberger, oral-facial-digital I (OFD I) syndrome, and focal dermal hypoplasia (FDH syndrome, Goltz syndrome). It is the purpose of this article to give a review of the clinical and genetic aspects of the abovementioned diseases and to add those disorders in which this mode of inheritance is discussed. These disorders are: X-linked chondrodysplasia punctata (CP), cervico-oculo-acusticus syndrome (Wildervanck syndrome, COA), congenital cataract with microcornea or slight microphthalmia, muscular dystrophy-hemizygous lethal, partial lipodystrophy with lipatrophic diabetes and hyperlipidemia, Aicardi syndrome, coxo-auricular syndrome, and Johanson-Blizzard syndrome. OTC defiency is included in the study, although there is no lethality in utero, only in the neonatal period.A critical evaluation of the current literature is carried out.     

Is Metabolic Syndrome Predictive of Prevalence,Extent, and Risk of Coronary Artery Disease beyond Its Components? Results from the Multinational Coronary CT Angiography Evaluation for Clinical Outcome: An International Multicenter Registry (CONFIRM)

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n=690) were matched 1:1:1 to those with 1 component (n=690) and 2 components (n=690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p<0.05), while those with 2 components did not (10.5% vs 13.8%, 2.8% vs 4.5% and 1.3% vs 2.3%, respectively; p>0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p=0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p=0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome.     

Oto-facio-cervical (OFC) syndrome is a contiguous gene deletion syndrome involving EYA1: molecular analysis confirms allelism with BOR syndrome and further narrows the Duane syndrome critical region to 1 cM

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder involving hearing loss, branchial defects, ear pits and renal abnormalities. Oto-facio-cervical (OFC) syndrome is clinically similar to BOR syndrome, with clinical features in addition to those of BOR syndrome. Mutations in the EYA1 gene (localised to 8q13.3) account for nearly 70% of BOR syndrome cases exhibiting at least three of the major features. Small intragenic deletions of the 3' region of the gene have also been reported in patients with BOR syndrome. We have developed a fluorescent quantitative multiplex polymerase chain reaction for three 3' exons (7, 9 and 13) of the EYA1 gene. This dosage assay, combined with microsatellite marker analysis, has identified de novo deletions of the EYA1 gene and surrounding region in two patients with complex phenotypes involving features of BOR syndrome. One patient with OFC syndrome carried a large deletion of the EYA1 gene region, confirming that OFC syndrome is allelic with BOR syndrome. Microsatellite analysis has shown that comparison of the boundaries of this large deletion with other reported rearrangements of the region reduces the critical region for Duane syndrome (an eye movement disorder) to between markers D8S553 and D8S1797, a genetic distance of approximately 1 cM.     

Associated malformations in cases with congenital diaphragmatic hernia

The etiology of congenital diaphragmatic hernia (CDH) is unclear and its pathogenesis is controversial. Because previous reports have inconsistently noted the type and frequency of malformations associated with CDH, we assessed these associated malformations ascertained between 1979 and 2003 in 334,262 consecutive births. Of the 115 patients with the most common type of CDH, the posterolateral, or Bochdalek-type hernia, 70 (60.8%) had associated malformations. These included: chromosomal abnormalities (n = 21, 30.0%); non-chromosomal syndromes (Fryns syndrome, fetal alcohol syndrome, De Lange syndrome, CHARGE syndrome, Fraser syndrome, Goldenhar syndrome, Smith-Lemli-Opitz syndrome, multiple pterygium syndrome, Noonan syndrome, and spondylocostal dysostosis); malformation sequences (laterality sequence, ectopia cordis); malformation complexes (limb body wall complex) and non syndromic multiple congenital anomalies (MCA) (n = 30, 42.9%). Malformations of the cardiovascular system (n = 42, 27.5%), urogenital system (n = 27, 17.7%), musculoskeletal system (n = 24, 15.7%), and central nervous system (n = 15, 9.8%) were the most common other congenital malformations. We observed specific patterns of malformations associated with CDH which emphasizes the need to evaluate all patients with CDH for possible associated malformations. Geneticists and pediatricians should be aware that the malformations associated with CDH can often be classified into a recognizable malformation syndrome or pattern (57.1%).     

新生儿毛细血管渗漏综合征危险因素分析

目的:了解新生儿发生毛细血管渗漏综合征(CLS)的相关危险因素。方法:对620例新生儿进行回顾性分析,采用Logistic回归模型分析毛细血管渗漏综合症发生的危险因素。结果:620例新生儿中有168例诊断为CLS,单因素分析显示严重感染、呼吸窘迫综合征、早产、重度窒息、发病前低体温对新生儿CLS的发生有影响(P<0.05),经多元Logistic回归分析显示严重感染、呼吸窘迫综合征、早产是发生CLS的独立危险因素(P<0.05)。结论:严重感染、呼吸窘迫综合征、早产是发生CLS的独立危险因素。     

Effects of the histone deacetylase inhibitor ITF2357 in autoinflammatory syndromes

We explored the effects of the oral histone deacetylase (HDAC) inhibitor ITF2357 in patients with autoinflammatory syndrome. In this prospective open-label pilot study, eight patients were enrolled; one patient with tumor necrosis factor receptor-associated periodic syndrome (TRAPS), three patients with hyper-IgD and periodic fever syndrome (HIDS) and four patients with Schnitzler syndrome were closely followed during 90 d of ITF2357 treatment. Three patients with Schnitzler syndrome and one TRAPS patient experienced a partial remission. In four patients, there was no effect. In HIDS patients, there was a tendency toward a higher attack frequency and increasing attack severity. In two patients (one TRAPS and one HIDS), we observed a decrease of acute-phase response without signs of clinical improvement. One patient with Schnitzler syndrome showed a partial response despite an ongoing acute-phase response. In conclusion, ITF2357 monotherapy was able to induce partial response only in patients with Schnitzler syndrome and no response in patients with HIDS.     

先天性心脏病相关综合征的遗传学研究

先天性心脏病(congenitalheartdisease,CHD)是儿科常见的疾病,现已发现约有300多种临床综合征伴有CHD.对Alagille综合征、CHARGE联合征、Holt-Oram综合征、Noonan综合征、Turner综合征、VACTERL联合征、Williams综合征、22q11缺失综合征和13、18、21三体综合征与CHD相关流行病学、临床表型、遗传病因和诊断及其再发风险进行了综述,为产前和产后临床诊断,了解疾病预后和再发概率提供资料.     

Cytogenetics of genetic counseling patients in Pelotas, Rio Grande do Sul, Brazil

From 1986 to 2002, we examined the chromosomal composition of 916 patients attended by two genetic counseling services in the city of Pelotas, in the Brazilian State of Rio Grande do Sul, to determine the genetic causes of their disturbances. Patterns of G-banding using trypsin and Giemsa (GTG) and C-banding using barium and Giemsa (CBG) were studied using phytohemagglutinin M-stimulated lymphocytes cultured from peripheral blood. Among the patients, 110 had Down's syndrome, 7 had Edward's syndrome, 4 had Patau's syndrome, 29 had Turner's syndrome, 5 had Klinefelter's syndrome, and 3 had "cri-du-chat" syndrome. Abnormal chromosomes were observed in 29.3% of the patients. Most of these (56.3%) were numerical abnormalities, with the remaining being structural variants.     

Langer-Giedion syndrome associated with submucous cleft palate

We report a 4-year-old girl with characteristic features of the Langer-Giedion syndrome (trichorhinophalangeal syndrome type II) who also had submucous cleft palate. When she underwent a palatoplasty, a diagnosis of Langer-Giedion syndrome was made because of the characteristic facial features, multiple exostoses, and partial deletion of the long arm of chromosome 8. This is the first case of trichorhinophalangeal syndrome associated with cleft palate. We review the clinical alterations of trichorhinophalangeal syndromes and differential diagnosis of Langer-Giedion syndrome from trichorhinophalangeal syndrome type I and hereditary multiple exostoses. We also describe the importance of trichorhinophalangeal syndrome in plastic surgery.     

PTPN11 gene analysis in 74 Brazilian patients with Noonan syndrome or Noonan-like phenotype

Mutations in the PTPN11 gene are known to cause a large fraction of the cases of Noonan syndrome. The objective of this study was to determine the PTPN11 gene mutation rate in a cohort of clinically well-characterized Brazilian patients with Noonan or Noonan-like syndromes and to study the genotype-phenotype correlation. Fifty probands with Noonan syndrome ascertained according to well-established diagnostic criteria, 3 with LEOPARD syndrome, 5 with Noonan-like/multiple giant cell lesion syndrome, and 3 with neurofibromatosis/ Noonan were enrolled in this study. Mutational analysis was performed using denaturing high-performance liquid chromatography (DHPLC) followed by sequencing of amplicons with an aberrant elution profile. We detected missense mutations in the PTPN11 gene in 21 probands with Noonan syndrome (42%), in all 3 patients with LEOPARD syndrome, and in 1 case with Noonan-like/multiple giant cell lesion syndrome. One patient with neurofibromatosis-Noonan syndrome had a mutation in both the PTPN11 and NF1 genes. The only anomalies that reached statistical significance when comparing probands with and without mutations were the hematological abnormalities. Our data confirms that Noonan syndrome is a genetically heterogeneous disorder, with mutations in the PTPN11 gene responsible for roughly 50% of the cases. A definitive genotype-phenotype correlation has not been established, but the T73I mutation seems to predispose to a myeloproliferative disorder. Regarding Noonan-like syndromes, mutation of the PTPN11 gene is the main causal factor in LEOPARD syndrome, and it also plays a role in neurofibromatosis-Noonan syndrome. Noonan- like/multiple giant cell lesion syndrome, part of the spectrum of Noonan syndrome, is also heterogeneous.     

Persistent Rotating Shift-Work Exposure Accelerates Development of Metabolic Syndrome among Middle-Aged Female Employees: A Five-Year Follow-Up

Limited follow-up studies are available as to whether special job-types, such as day-night rotating shift work, contribute to the progression of metabolic syndrome among female industrial employees. A retrospective cohort study on the development of metabolic syndrome was conducted by utilizing health examination records for a five-year interval. The records of 387 female employees without metabolic syndrome at baseline were used for the analysis. Data analyzed included age, metabolic syndrome components, insulin resistance status, lifestyle factors, and job-types. The initial mean age of subjects was 32.8 yrs. Abnormal rates at baseline, including metabolic syndrome components and insulin resistance, were all significantly higher among the 34 female workers with metabolic syndrome outcome. Also, the persistent rotating shift-work exposure rates and five-year change of metabolic syndrome component measurements were significantly unfavorable for subjects with metabolic syndrome outcome. After controlling for the potential confounders, significant raised risks were found in the female worker with persistent rotating shift-work exposure (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.3–9.0 vs. day workers) and in smokers (OR, 5.4; 95% CI, 1.1–25.8 vs. non-smokers). At the same time, the female workers initially with one or two metabolic syndrome components had a 4.6-fold (95% CI, 1.3–17.0) and 12.7-fold (95% CI, 3.2–50.1), respectively, increased risk of progressing to metabolic syndrome within five years. In conclusion, persistent day-night rotating shift work, smoking, and baseline metabolic syndrome components associate with the progression toward metabolic syndrome for middle-aged female workers. (Author correspondence: pchen@ntu.edu.tw, gphinx@gmail.com).     

Hepatogenic polyglobulinemias and polycythemias]

The authors distinguish three kinds of hepatogenous polyglobulia: Polycythaemia caused by Budd-Chiari syndrome, polycythaemia caused by a Mosse syndrome (cirrhosis without liver venous thrombosis) and polyglobulia caused by liver tumours. In all three cases the same mechanism is likely to induce polycythaemia or polyglobulia respectively. In addition to the three cases of the Mosse syndrome published in 1966, the present paper deals with three cases of Budd-Chiari syndrome. Twice the Budd-Chiari syndrome was followed by a polycythaemia, once a Budd-Chiari syndrome was developed in the course of a polycythaemia vera.     

Obesity,Metabolic Syndrome and Risk of Atrial Fibrillation: A Swedish,Prospective Cohort Study

AimWe aimed to investigate whether different measures of obesity could similarly predict atrial fibrillation, and whether the atrial fibrillation risk associated with obesity is dependent on presence of metabolic syndrome.ResultsDuring a mean follow-up of 13.6 years, 285 incident atrial fibrillation cases were recorded. One standard deviation increment of each obesity measure was associated with increased atrial fibrillation risk as: body mass index 1.25 (1.12 – 1.40), waist circumference 1.35 (1.19 – 1.54) and sagittal abdominal diameter 1.28 (1.14 – 1.44). Compared to normal weight subjects without metabolic syndrome, increased atrial fibrillation risk was noted for overweight subjects with metabolic syndrome, 1.67 (1.16 – 2.41), obese subjects without metabolic syndrome, 1.75 (1.11 – 2.74) and obese subjects with metabolic syndrome, 1.92 (1.34 – 2.74). Compared to subjects with normal waist circumference without metabolic syndrome, subjects with elevated waist circumference and metabolic syndrome suffered increased atrial fibrillation risk, 2.03 (1.44 – 2.87).ConclusionsBody mass index, waist circumference and sagittal abdominal diameter could similarly predict atrial fibrillation. Obesity was associated with an increased atrial fibrillation risk regardless of metabolic syndrome, whereas overweight and elevated waist circumference was associated with increased atrial fibrillation risk only if metabolic syndrome was present.     

Thrombocytopenia-absent radius (tar) syndrome: a case with agenesis of corpus callosum, hypoplasia of cerebellar vermis and horseshoe kidney

The thrombocytopenia-absent radius (TAR) syndrome (MIM 274000) is a congenital malformation syndrome characterised by bilateral absence of the radii with present thumbs, hypomegakaryocytic thrombocytopenia and a number of additional features including skeletal and cardiac anomalies. Mental retardation, reported in about 7% of patients, is usually secondary to intracranial hemorrhage. In 1994 there was a single report of a girl with TAR syndrome and hypoplasia of the cerebellar vermis and corpus callosum and in 2003 another case of TAR syndrome with cerebellar dysgenesis has been reported. In 2000 there was first report of horseshoe kidney in association with TAR syndrome followed by a clinical study of 34 cases with TAR syndrome in 2002 where horseshoe kidney was noted in two cases. Here we report of a girl with TAR syndrome, severe mental retardation, agenesis of corpus callosum, hypoplasia of cerebellar vermis and horseshoe kidney. There is no previous report of a child with TAR syndrome and all those associated anomalies in the same patient.     

Down syndrome rates and relaxed selection at older maternal ages.

Preferential survival in older mothers of fetuses with Down syndrome has been proposed as contributing to the maternal-age effect of this condition. If correct, this provocative hypothesis, which may be termed "relaxed selection," has major implications for approaches to prevention of Down syndrome live births in older women. Several predictions of this hypothesis are examined here by comparisons of parental ages among various populations. These revealed that: (1) mean maternal age of Down syndrome live births is slightly lower than that of Down syndrome spontaneous fetal deaths; (2) mean maternal age of those with mutant D/21 translocation Down syndrome is about the same as that of controls; (3) the ages of Down syndrome mothers who have Down syndrome live births is slightly lower than ages of Down syndrome mothers who have unaffected live births; and (4) in recent data on 47, +21 cases in which the extra chromosome 21 is of paternal origin, the mean maternal ages are 4-5 years lower than the maternal ages of cases of maternal origin (in contrast to earlier reports). All of these observations are contrary to the hypothesis that relaxed selection contributes significantly to the maternal-age association of Down syndrome. If there is any effect of relaxed selection, it is likely to be very weak and/or act primarily upon abortions that occur before recognition of pregnancy.     

Prenatal and postnatal prevalence of Turner's syndrome: a registry study.

OBJECTIVE--To study prevalence of Turner''s syndrome in Denmark and to assess validity of prenatal diagnosis. DESIGN--Study of data on prenatal and postnatal Turner''s syndrome in Danish Cytogenetic Central Register. SUBJECTS--All registered Turner''s syndrome karyotypes (100 prenatal cases and 215 postnatal cases) during 1970-93. MAIN OUTCOME MEASURES--Prevalence of Turner''s syndrome karyotypes among prenatally tested fetuses and Turner''s syndrome among liveborn infants. RESULTS--Among infant girls, prevalence of Turner''s syndrome was 32/100,000. Among female fetuses tested by amniocentesis, prevalence of Turner''s syndrome karyotypes was 176/100,000 (relative risk of syndrome, 6.74 compared with prevalence among untested pregnancies). Among female fetuses tested by chorion villus sampling, prevalence of syndrome karyotypes was 392/100,000 (relative risk, 16.8). We excluded prenatal tests referred because of results of ultrasound scanning: among fetuses tested by amniocentesis revised relative risk was 5.68, while revised relative risk among fetuses tested by chorion villus sampling was 13.3. For 29 fetuses with prenatal diagnosis of possible Turner''s syndrome, pregnancy was allowed to continue and 24 children were live born. Thirteen of these children were karyotyped postnatally, and diagnosis of Turner''s syndrome had to be revised for eight, seven being normal girls and one boy. This gives tentative predictive value of amniocentesis in diagnosing Turner''s syndrome of between 21% and 67%. There was no significant relation between mother''s age and risk of Turner''s syndrome. CONCLUSIONS--Discrepancy between prenatal and postnatal prevalence of Turner''s syndrome challenges specificity of prenatal examination in diagnosing Turner''s syndrome.     

南宁地区唐氏综合征患者的细胞遗传学研究

为了探讨中国南宁地区唐氏综合征患者染色体核型分布及其特点, 对广西壮族自治区妇幼保健院1994年以来的500例疑似唐氏综合征(Down syndrome, DS)患者进行外周血染色体核型分析, 130例确诊为DS患者。其中, 单纯型21-三体为86.15%(112/130); 易位型为8.46%(11/130); 嵌合型为5.39%(7/130)。在单纯型21-三体中性别比为女∶男=1∶1.8; 93.08% 的唐氏综合征患儿由年轻母亲(<35岁)所生, 另有6.92% 由高龄产妇所生。结果表明, 南宁地区86% 以上唐氏综合征患者的染色体核型是单纯型21-三体, 男性唐氏综合征患儿明显高于女性患儿。     

Preliminary investigation of lethally toxic sera of sudden infant death syndrome victims and neutralisation by commercially available immunoglobulins and adult sera

The aim of the study was to test the hypotheses (i) that sudden infant death syndrome sera are toxic to 11-day old chick embryos and (ii) that such a toxicity can be counteracted by immunoglobulin or adult sera. Serum samples from 11 SIDS victims and five controls were tested for lethal toxicity in the chick embryo bioassay. Five serum samples were used to challenge chick embryos injected with the following: sudden infant death syndrome serum plus Hank's balanced salt solution; Hank's balanced salt solution alone; sudden infant death syndrome serum plus 3% w/v commercial immunoglobulin; sudden infant death syndrome serum plus 6% w/v immunoglobulin; sudden infant death syndrome serum plus pooled sera of 40 healthy adults. Results obtained revealed that Hank's balanced salt solution, the pooled adult serum and the commercial immunoglobulin were all non-lethal, in the chick embryo test system. By contrast. 10 sudden infant death syndrome victims yielded sera containing lethal levels of toxin(s) compared to 2/5 controls which was statistically significant (P < 0.05, Fischer's exact test). In the tests of sudden infant death syndrome serum plus immunoglobulin or pooled adult serum, the lethality of sudden infant death syndrome serum was abolished in all cases. The reduction in toxicity of individual sudden infant death syndrome serum plus immunoglobulin or pooled adult serum was often statistically significant (P<0.05-P<0.00005, Fischer's exact test). We conclude that lethal levels of toxin are present in sudden infant death syndrome sera and that they can be neutralised by normal immune serum. These results indicate that passive immunisation is a potential treatment to protect babies considered at risk from sudden infant death syndrome.