Triglyceride (TG) concentrations >2000 mg/dL are extremely elevated and increase the risk of pancreatitis.
We characterized five cases and two kindreds and ascertained prevalence in a reference ...laboratory population.
Plasma lipids and DNA sequences of LPL, GPIHBP1, APOA5, APOC2, and LMF1 were determined in cases and two kindreds. Hypertriglyceridemia prevalence was assessed in 440,240 subjects.
Case 1 (female, age 28 years) had TG concentrations >2000 mg/dL and pancreatitis since infancy. She responded to diet and medium-chain triglycerides, but not medications. During two pregnancies, she required plasma exchange for TG control. She was a compound heterozygote for a p.G236Gfs*15 deletion and a p.G215E missense mutation at LPL, as was one sister with hypertriglyceridemia and pancreatitis during pregnancy. Her father was heterozygous for the deletion and had hypertriglyceridemia and recurrent pancreatitis. Other family members had either the missense mutation or the deletion, and had hypertriglyceridemia but no pancreatitis. In kindred 2, three preschool children had severe hypertriglyceridemia and were homozygous for a GPIHBP1 p.T108R missense mutation. Case 5 (male, age 43 years) presented with pancreatitis and TG levels >5000 mg/dL and had heterozygous GPIHBP1 p.G175R and APOC2 intron 2-4G>C mutations. On diet, fenofibrate, fish oil, and atorvastatin, his TG concentration was 2526 mg/dL, but normalized to <100 mg/dL with added pioglitazone. In our population study, 60 subjects (0.014%) of 440,240 had TG concentrations >2000 mg/dL, and 66.7% were diabetic and had elevated insulin levels.
Extreme hypertriglyceridemia is rare (0.014%); and during pregnancy, it may require plasma exchange.
•Extreme hypertriglyceridemia (>2000 mg/dL) is associated with pancreatitis.•The prevalence of this condition in a reference laboratory population is 0.01%.•Pregnancy exacerbates hypertriglyceridemia and may require plasmapheresis.•Effective therapies include a low-fat diet, medium-chain triglyceride(s) oil, fibrates, and fish oil.•The underlying molecular defects should be characterized by DNA analysis.
Sun exposure and risk of melanoma Oliveria, S A; Saraiya, M; Geller, A C ...
Archives of disease in childhood,
02/2006, Letnik:
91, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Background: As skin cancer education programmes directed to children and adolescents continue to expand, an epidemiological basis for these programmes is necessary to target efforts and plan for ...further evaluation. Aims: To summarise the epidemiological evidence on sun exposure during childhood and adolescence and melanoma risk. Methods: A literature review was conducted using Medline (1966 to December 2004) to identify articles relating to sun exposure and melanoma. The review was restricted to studies that included sun exposure information on subjects 18 years of age or younger. Results: Migrant studies generally indicate an increased melanoma risk in individuals who spent childhood in sunny geographical locations, and decreasing melanoma risk with older age at arrival. Individuals who resided in geographical locations close to the equator or close to the coast during childhood and/or adolescence have an increased melanoma risk compared to those who lived at higher latitudes or never lived near the coast. The intermittent exposure hypothesis remains controversial; some studies indicate that children and adolescents who received intermittent sun exposure during vacation, recreation, or occupation are at increased melanoma risk as adults, but more recent studies suggest intermittent exposure to have a protective effect. The majority of sunburn studies suggest a positive association between early age sunburn and subsequent risk of melanoma. Conclusion: Future research efforts should focus on: (1) clarifying the relation between sun exposure and melanoma; (2) conducting prospective studies; (3) assessing sun exposure during different time periods of life using a reliable and quantitative method; (4) obtaining information on protective measures; and (5) examining the interrelations between ability to tan, propensity to burn, skin type, history of sunburns, timing and pattern of sun exposure, number of nevi, and other host factors in the child and adolescent populations.
Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair ...functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples.
The symptoms of obsessive-compulsive disorder (OCD) are highly heterogeneous and it is unclear what is the optimal way to conceptualize this heterogeneity. This study aimed to establish a ...comprehensive symptom structure model of OCD across the lifespan using factor and network analytic techniques.
A large multinational cohort of well-characterized children, adolescents, and adults diagnosed with OCD (
= 1366) participated in the study. All completed the Dimensional Yale-Brown Obsessive-Compulsive Scale, which contains an expanded checklist of 87 distinct OCD symptoms. Exploratory and confirmatory factor analysis were used to outline empirically supported symptom dimensions, and interconnections among the resulting dimensions were established using network analysis. Associations between dimensions and sociodemographic and clinical variables were explored using structural equation modeling (SEM).
Thirteen first-order symptom dimensions emerged that could be parsimoniously reduced to eight broad dimensions, which were valid across the lifespan: Disturbing Thoughts, Incompleteness, Contamination, Hoarding, Transformation, Body Focus, Superstition, and Loss/Separation. A general OCD factor could be included in the final factor model without a significant decline in model fit according to most fit indices. Network analysis showed that Incompleteness and Disturbing Thoughts were most central (i.e. had most unique interconnections with other dimensions). SEM showed that the eight broad dimensions were differentially related to sociodemographic and clinical variables.
Future research will need to establish if this expanded hierarchical and multidimensional model can help improve our understanding of the etiology, neurobiology and treatment of OCD.
Background
Cognitive‐behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs) are recommended treatments for pediatric obsessive‐compulsive disorder (OCD), but their relative efficacy and ...acceptability have not been comprehensively examined. Further, it remains unclear whether the efficacy of in‐person CBT is conserved when delivered in other formats, such as over telephone/webcam or as Internet‐delivered CBT (ICBT).
Methods
PubMed, PsycINFO, trial registries, and previous systematic reviews were searched for randomized controlled trials (RCTs) comparing CBT (in‐person, webcam/telephone‐delivered, or ICBT) or SRIs with control conditions or each other. Network meta‐analyses were conducted to examine efficacy (post‐treatment Children's Yale‐Brown Obsessive Compulsive Scale) and acceptability (treatment discontinuation). Confidence in effect estimates was evaluated with CINeMA (Confidence in Network Meta‐Analysis).
Results
Thirty eligible RCTs and 35 contrasts comprising 2,057 youth with OCD were identified. In‐person CBT was significantly more efficacious than ICBT, waitlist, relaxation training, and pill placebo (MD range: 3.95–11.10; CINeMA estimate of confidence: moderate) but did not differ significantly from CBT delivered via webcam/telephone (MD: 0.85 −2.51, 4.21; moderate), SRIs (MD: 3.07 −0.07, 6.20; low), or the combination of in‐person CBT and SRIs (MD: −1.20 −5.29, 2.91; low). SRIs were significantly more efficacious than pill placebo (MD: 4.59 2.70, 6.48; low) and waitlist (MD: 8.03 4.24, 11.82; moderate). No significant differences for acceptability emerged, but confidence in estimates was low.
Conclusions
In‐person CBT and SRIs produce clear benefits compared to waitlist and pill placebo and should be integral parts of the clinical management of pediatric OCD, with in‐person CBT overall having a stronger evidence base. The combination of in‐person CBT and SRIs may be most efficacious, but few studies hinder firm conclusions. The efficacy of CBT appears conserved when delivered via webcam/telephone, while more trials evaluating ICBT are needed.
The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results.
We randomly ...assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy.
At 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, genotype-guided group minus clinically guided group, -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy.
Genotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657.).
Context. NGC 3532 is an extremely rich open cluster embedded in the Galactic disc, hitherto lacking a comprehensive, documented membership list. Aims. We provide membership probabilities from new ...radial velocity observations of solar-type and low-mass stars in NGC 3532, in part as a prelude to a subsequent study of stellar rotation in the cluster. Methods. Using extant optical and infra-red photometry we constructed a preliminary photometric membership catalogue, consisting of 2230 dwarf and turn-off stars. We selected 1060 of these for observation with the AAOmega spectrograph at the 3.9 m-Anglo-Australian Telescope and 391 stars for observations with the Hydra-South spectrograph at the 4 m Victor Blanco Telescope, obtaining spectroscopic observations over a decade for 145 stars. We measured radial velocities for our targets through cross-correlation with model spectra and standard stars, and supplemented them with radial velocities for 433 additional stars from the literature. We also measured log g, Teff, and Fe/H from the AAOmega spectra. Results. The radial velocity distribution emerging from the observations is centred at 5.43 ± 0.04 km s−1 and has a width (standard deviation) of 1.46 km s−1. Together with proper motions from Gaia DR2 we find 660 exclusive members, of which five are likely binary members. The members are distributed across the whole cluster sequence, from giant stars to M dwarfs, making NGC 3532 one of the richest Galactic open clusters known to date, on par with the Pleiades. From further spectroscopic analysis of 153 dwarf members we find the metallicity to be marginally sub-solar, with Fe/H = −0.07 ± 0.10. We confirm the extremely low reddening of the cluster, EB − V = 0.034 ± 0.012 mag, despite its location near the Galactic plane. Exploiting trigonometric parallax measurements from Gaia DR2 we find a distance of 48435−30 484 − 30 + 35 $ 484^{+35}_{-30} $ pc (m − M)0 = 8.42 ± 0.14 mag. Based on the membership we provide an empirical cluster sequence in multiple photometric passbands. A comparison of the photometry of the measured cluster members with several recent model isochrones enables us to confirm the 300 Myr cluster age. However, all of the models evince departures from the cluster sequence in particular regions, especially in the lower mass range.
Objective: To compare (1) visual estimation of postpartum blood loss with estimation using a specifically designed blood collection drape and (2) the drape estimate with a measurement of blood loss ...by photospectrometry.
Methods: A randomized controlled study was performed with 123 women delivered at the District Hospital, Belgaum, India. The women were randomized to visual or drape estimation of blood loss. A subsample of 10 drape estimates was compared with photospectrometry results.
Results: The visual estimate of blood loss was 33% less than the drape estimate. The interclass correlation of the drape estimate to photospectrometry measurement was 0.92.
Conclusion: Drape estimation of blood loss is more accurate than visual estimation and may have particular utility in the developing world. Prompt detection of postpartum hemorrhage may reduce maternal morbidity and mortality in low-resource settings.
The work of liver stem cell biologists, largely carried out in rodent models, has now started to manifest in human investigations and applications. We can now recognize complex regenerative processes ...in tissue specimens that had only been suspected for decades, but we also struggle to describe what we see in human tissues in a way that takes into account the findings from the animal investigations, using a language derived from species not, in fact, so much like our own. This international group of liver pathologists and hepatologists, most of whom are actively engaged in both clinical work and scientific research, seeks to arrive at a consensus on nomenclature for normal human livers and human reactive lesions that can facilitate more rapid advancement of our field. (HEPATOLOGY 2004; 39:1739–1745.)
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