Treating a Case of First-Episode Psychosis to Uncover Undiagnosed Obsessive Compulsive Disorder: A Case Report.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric condition characterized by the presence of obsessions, compulsions, or both. Historically OCD was associated with good insight. However, there are more categories to the degrees of insight in OCD patients, namely good, fair, poor, absent, or delusional beliefs. It is also important to note that insight can fluctuate circumstantially. We describe a rare case of first-episode psychosis of undetermined cause presenting with suicidal ideation. After continued treatment, it was discovered to be previously undiagnosed OCD with poor insight.

Implications of Introducing High-Sensitivity Cardiac Troponin T Into Clinical Practice: Data From the SWEDEHEART Registry.

BACKGROUND: Cardiac troponin is the preferred biomarker for diagnosing myocardial infarction (MI). OBJECTIVES: The aim of this study was to examine the implications of introducing high-sensitivity cardiac troponin T (hs-cTnT) into clinical practice and to define at what hs-cTnT level risk starts to increase. METHODS: We analyzed data from 48,594 patients admitted because of symptoms suggesting an acute coronary syndrome and who were entered into a large national registry. Patients were divided into Group 1, those with hs-cTnT<6 ng/l; Group 2, those with hs-cTnT 6 to 13 ng/l; Group 3, those with hs-cTnT 14 to 49 ng/l (i.e., a group in which most patients would have had a negative cardiac troponin T with older assays); and Group 4, those with hs-cTnT≥50 ng/l. RESULTS: There were 5,790 (11.9%), 6,491 (13.4%), 10,476 (21.6%), and 25,837 (53.2%) patients in Groups 1, 2, 3, and 4, respectively. In Groups 1 to 4, the proportions with MI were 2.2%, 2.6%, 18.2%, and 81.2%. There was a stepwise increase in the proportion of patients with significant coronary stenoses, left ventricular systolic dysfunction, and death during follow-up. When dividing patients into 20 groups according to hs-cTnT level, the adjusted mortality started to increase at an hs-cTnT level of 14 ng/l. CONCLUSIONS: Introducing hs-cTnT into clinical practice has led to the recognition of a large proportion of patients with minor cardiac troponin increases (14 to 49 ng/l), the majority of whom do not have MI. Although a heterogeneous group, these patients remain at high risk, and the adjusted mortality rate started to increase at the level of the 99th percentile in healthy controls.

Prognostic value of combining high sensitive troponin T and N-terminal pro B-type natriuretic peptide in chest pain patients with no persistent ST-elevation.

The aim was to examine whether high sensitive troponin T (Hs-TnT) is better than conventional troponins to risk stratify chest pain patients, in particular when applying early serial measurements or combining with natriuretic peptides. Samples were obtained on admission and after 2 h in 231 chest pain patients who were followed for a median time of 22 months. Troponin levels were determined by Hs-TnT, conventional TnT (Roche Diagnostics) and troponin I (Beckman Coulter) assays. N-terminal pro B-type natriuretic peptide (NT-proBNP) was determined by the assay from Roche Diagnostics. The combined endpoint was death, MI or heart failure. When predefined decision limits were used, Hs-TnT (14 ng/L), TnT (0.04 µg/L), and TnI (0.06 µg/L) identified 63%, 46%, and 52% of the patients with positive troponin. In those with negative TnT, Hs-TnT identified 36 patients of whom 19% had subsequent events. In those with negative TnI, Hs-TnT identified 26 patients of whom 23% had subsequent events. After adjusting for differences in baseline characteristics, both Hs-TnT and NT-proBNP were independently associated with short-term (3 months) risk of combined endpoint and long-term risk of death or MI. By combining Hs-TnT and NT-proBNP patients could be divided into low-, intermediate- and high-risk groups.

Diagnostic value of high sensitive troponin T in chest pain patients with no persistent ST-elevations.

OBJECTIVES: The aim of this study was to compare the early diagnostic value of the Roche high-sensitive troponin T (Hs-TnT) and that of conventional troponins. DESIGN: A total of 233 consecutive chest pain patients without ST-elevations were included. Hs-TnT was compared with two conventional assays (Roche troponin T [fourth generation] and Beckman Coulter Accu-TnI) on admission and at two hours. RESULTS: When acute Myocardial Infarction (MI) was defined by conventional troponins and prespecified decision limits (Hs-TnT ≥ 14 ng/l, conventional TnT ≥ 0.04 µg/l, and Accu-TnI ≥ 0.06 µg/l) were used, Hs-TnT had a higher sensitivity but a lower specificity than conventional troponins both on admission and after two hours. When the biomarkers were compared in a ROC analysis there were no significant differences with regard to AUC. When acute MI was defined by Hs-TnT, the diagnostic performance of Hs-TnT remained very high (on admission: sensitivity 96%, specificity 85%, at two hours: sensitivity 99%, specificity 83%) whereas that of conventional troponins became lower, mainly because of lower sensitivity. CONCLUSION: In conclusion, when acute MI is defined by a high sensitive troponin assay, the use of Hs-TnT improves the early diagnostic accuracy compared with conventional troponins. By measuring Hs-TnT it seems possible to exclude acute MI already within the first few hours from admission.

Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans.

OBJECTIVE: To gain insight into the function of proprotein convertase subtilisin kexin type 9 (PCSK9) in humans by establishing whether circulating levels are influenced by diurnal, dietary, and hormonal changes. METHODS AND RESULTS: We monitored circulating PCSK9 in a set of dynamic human experiments and could show that serum PCSK9 levels display a diurnal rhythm that closely parallels that of cholesterol synthesis, measured as serum lathosterol. In contrast to these marked diurnal changes in cholesterol metabolism, serum low-density lipoprotein (LDL) cholesterol levels remained stable during the diurnal cycle. Depletion of liver cholesterol by treatment with the bile acid-binding resin, cholestyramine, abolished the diurnal rhythms of both PCSK9 and lathosterol. Fasting (>18 hours) strongly reduced circulating PCSK9 and lathosterol levels, whereas serum LDL levels remained unchanged. Growth hormone, known to be increased during fasting in humans, reduced circulating PCSK9 in parallel to LDL cholesterol levels. CONCLUSIONS: Throughout the day, and in response to fasting and cholesterol depletion, circulating PCSK9 displays marked variation, presumably related to oscillations in hepatic cholesterol that modify its activity in parallel with cholesterol synthesis. In addition to this sterol-mediated regulation, additional effects on LDL receptors may be mediated by hormones directly influencing PCSK9.

Dihydropyrimidinase deficiency: Phenotype, genotype and structural consequences in 17 patients.

Dihydropyrimidinase (DHP) is the second enzyme of the pyrimidine degradation pathway and catalyses the ring opening of 5,6-dihydrouracil and 5,6-dihydrothymine. To date, only 11 individuals have been reported suffering from a complete DHP deficiency. Here, we report on the clinical, biochemical and molecular findings of 17 newly identified DHP deficient patients as well as the analysis of the mutations in a three-dimensional framework. Patients presented mainly with neurological and gastrointestinal abnormalities and markedly elevated levels of 5,6-dihydrouracil and 5,6-dihydrothymine in plasma, cerebrospinal fluid and urine. Analysis of DPYS, encoding DHP, showed nine missense mutations, two nonsense mutations, two deletions and one splice-site mutation. Seventy-one percent of the mutations were located at exons 5-8, representing 41% of the coding sequence. Heterologous expression of 11 mutant enzymes in Escherichia coli showed that all but two missense mutations yielded mutant DHP proteins without significant activity. Only DHP enzymes containing the mutations p.R302Q and p.T343A possessed a residual activity of 3.9% and 49%, respectively. The crystal structure of human DHP indicated that the point mutations p.R490C, p.R302Q and p.V364M affect the oligomerization of the enzyme. In contrast, p.M70T, p.D81G, p.L337P and p.T343A affect regions near the di-zinc centre and the substrate binding site. The p.S379R and p.L7V mutations were likely to cause structural destabilization and protein misfolding. Four mutations were identified in multiple unrelated DHP patients, indicating that DHP deficiency may be more common than anticipated.

Growth hormone induces low-density lipoprotein clearance but not bile acid synthesis in humans.

OBJECTIVE: Growth hormone (GH) induces hepatic low-density lipoprotein (LDL) receptors and lowers plasma cholesterol. We characterized the influence of GH treatment on plasma LDL clearance in normal humans and investigated the relative role of LDL receptor (LDLR) activity and stimulation of bile acid synthesis in subjects with different LDLR expression. METHODS AND RESULTS: Plasma clearance of autologous 125I-LDL was measured before and during 3 weeks of treatment with GH (0.1 IU/kg per day) in 9 healthy young males. Plasma LDL cholesterol was reduced by 13% and the fractional catabolic rate of LDL increased by 27%. More marked changes were seen in a patient with hypopituitarism substituted with GH (0.07 IU/kg per day) for 3 months. In a second study, GH dose-dependently reduced LDL cholesterol and increased Lp(a) levels in 3 groups of males: younger and elderly healthy subjects and heterozygous familial hypercholesterolemia (FH). No effect on bile acid synthesis measured by the plasma marker 7alpha-hydroxy-4-cholesten-3-one was observed. In an LDLR-deficient FH homozygote, LDL cholesterol was not affected by GH. CONCLUSIONS: GH treatment reduces plasma LDL cholesterol by inducing LDL clearance. In humans, LDLR expression is a prerequisite for this effect, whereas it is not related to stimulation of bile acid synthesis.