A novel deletion of approximately 27 kb including the beta-globin gene and the locus control region 3'HS-1 regulatory sequence: beta zero- thalassemia or hereditary persistence of fetal hemoglobin?

A novel deletion of approximately 27 kb with the 5' breakpoint 1.5 to 2.2 kb upstream of the beta-globin gene, and the 3' breakpoint approximately 24 kb downstream of the beta-globin gene, has been found in five members of two families from Southeast Asia (Vietnam and Cambodia). Six members of another family from China, previously reported from our laboratory, have also been shown to carry this deletion. The patients presented with mild hypochromia and microcytosis, a hemoglobin (Hb) A2 level of approximately 4.0%, and a markedly increased, heterocellularly distributed, Hb F level (14.0 to 26.0%). In vitro globin-chain synthesis showed a mild imbalance with appreciable gamma-chain compensation (alpha/beta + gamma ratio of 1.46). The 3' end of this deletion includes the 3'HS-1, and we hypothesize that removal of this region results in the loss of its gamma-globin gene-silencing effect, which causes a markedly elevated Hb F level with a modest increase in Hb A2 levels, unlike the situation in other deletional beta zero-thalassemias. The possible influence of particular sequence variations in the locus control region 5'HS-2 and the G gamma promoter, present on the chromosome with this deletion, on the overall gamma-globin gene should also be considered.     

Quantitation of three types of gamma chain of HbF by high pressure liquid chromatography; application of this method to the HbF of patients with sickle cell anemia or the S-HPFH condition

A modification of a high pressure liquid chromatographic (HPLC) procedure is described that enables the complete separation and quantitation of the A gamma T, A gamma I, and G gamma chains in human fetal hemoglobin. The method, which is fast and accurate, requires 5 to 2000 micrograms Hb F. The purity of the Hb F is not essential and admixture of up to 70% adult Hb does not interfere with the determination. The method has been applied to the Hb F of 64 Black SS patients and 7 persons with the Hb S-HPFH (G gamma A gamma type) conditions. (A) Both "adult" G gamma to A gamma (2:3) and "newborn" G gamma to A gamma (3:2) ratios were observed in adult SS patients, 8 yr and older. Only 12% of the SS patients had the "newborn" ratio. This high G gamma to A gamma ratio may be due to a modification of the genetic switch mechanism that regulates the change of this ratio after birth. (B) Intermediate G gamma to A gamma ratios were only found in young SS patients, 5 yr of age or less. The results suggest a delayed switch of the newborn leads to adult ratio in sickle cell anemia. (C) The A gamma T chain was present in only 6% of all SS patients. One patient is homozygous for this variant chain. (D) Three of the 7 subjects with Hb S-HPFH were positive for the A gamma T chain. Its percentage was low, which suggests that the A gamma T chain gene is in trans of the HPFH determinant. (E) Quantitation of the three gamma chain types is also possible in the Hb F from Hb S heterozygotes with (nearly) normal Hb F levels. Such an analysis is useful for an evaluation of genetic conditions involving variations in the production of (different types of) Hb F.     

Early identification of non‐remission in first‐episode psychosis in a two‐year outcome study

Simonsen E, Friis S, Opjordsmoen S, Mortensen EL, Haahr U, Melle I, Joa I, Johannessen JO, Larsen TK, Røssberg JI, Rund BR, Vaglum P, McGlashan TH. Early identification of non‐remission in first‐episode psychosis in a two‐year outcome study. Objective: To identify predictors of non‐remission in first‐episode, non‐affective psychosis. Method: During 4 years, we recruited 301 patients consecutively. Information about first remission at 3 months was available for 299 and at 2 years for 293 cases. Symptomatic and social outcomes were assessed at 3 months, 1 and 2 years. Results: One hundred and twenty‐nine patients (43%) remained psychotic at 3 months and 48 patients (16.4%) remained psychotic over 2 years. When we compared premorbid and baseline data for the three groups, the non‐remitted (n = 48), remitted for <6 months (n = 38) and for more than 6 months (n = 207), duration of untreated psychosis (DUP) was the only variable that significantly differentiated the groups (median DUP: 25.5, 14.4 and 6.0 weeks, respectively). Three months univariate predictors of non‐remission were being single, longer DUP, core schizophrenia, and less excitative and more negative symptoms at baseline. Two‐year predictors were younger age, being single and male, deteriorating premorbid social functioning, longer DUP and core schizophrenia. In multivariate analyses DUP, negative and excitative symptoms predicted non‐remission at 3 months, but only DUP predicted at 2 years. Conclusion: Long DUP predicted both 3 month and 2‐year non‐remission rates in first‐episode psychosis.     

Infusions of albumin increase free fraction of naproxen in healthy volunteers: a randomized crossover study

Background: In vitro and in vivo studies have indicated that stabilizers present in pharmaceutical‐grade albumin influence the albumin‐binding capacity for highly protein‐bound drugs. However, the half‐life of the stabilizers and the quantitative effect have been difficult to determine. Method: A randomized crossover study including six healthy volunteers was performed. The study subjects received 750 mg of oral naproxen 2 h before the study. They were randomized to receive either 100 ml of 20% albumin or 100 ml of Ringer's acetate solution intravenously. Frequent blood samples were obtained. The experiment was repeated 4 weeks later with the alternate solution. The serum samples were analysed to determine the concentrations of albumin, N‐acetyl‐dl ‐tryptophan, caprylate, and naproxen. Results: The free fraction of naproxen increased significantly after the infusion of albumin (P<0.05). The increase was concurrent with the appearance of N‐acetyl‐dl ‐tryptophan and caprylate in serum. The free fraction of naproxen declined rapidly after the albumin infusion was completed. N‐acetyl‐dl ‐tryptophan had a half‐life of approximately 30 min. The half‐life of caprylate was <15 min. Conclusion: A transfusion of albumin results in an increase in the free fraction of naproxen. The transient increase in free‐fraction naproxen decreased together with the detectable levels of the stabilizers N‐acetyl‐dl ‐tryptophan and caprylate. N‐acetyl‐dl ‐tryptophan and caprylate have a short half‐life in serum.     

Body positions and esophageal sphincter pressures in obese patients during anesthesia

Background: The lower esophageal sphincter (LES) and the upper esophageal sphincter (UES) play a central role in preventing regurgitation and aspiration. The aim of the present study was to evaluate the UES, LES and barrier pressures (BP) in obese patients before and during anesthesia in different body positions. Methods: Using high‐resolution solid‐state manometry, we studied 17 patients (27–63 years) with a BMI≥35 kg/m² who were undergoing a laparoscopic bariatric surgery before and after anesthesia induction. Before anesthesia, the subjects were placed in the supine position, in the reverse Trendelenburg position (+20°) and in the Trendelenburg position (?20°). Thereafter, anesthesia was induced with remifentanil and propofol and maintained with remifentanil and sevoflurane, and the recordings in the different positions were repeated. Results: Before anesthesia, there were no differences in UES pressure in the different positions but compared with the other positions, it increased during the reverse Trendelenburg during anesthesia. LES pressure decreased in all body positions during anesthesia. The LES pressure increased during the Trendelenburg position before but not during anesthesia. The BP remained positive in all body positions both before and during anesthesia. Conclusion: LES pressure increased during the Trendelenburg position before anesthesia. This effect was abolished during anesthesia. LES and BPs decreased during anesthesia but remained positive in all patients regardless of the body position.     

Clinical epidemiologic first-episode psychosis: 1-year outcome and predictors

OBJECTIVE: To describe 1-year outcome in a large clinical epidemiologic sample of first-episode psychosis and its predictors. METHOD: A total of 301 patients with first-episode psychosis from four healthcare sectors in Norway and Denmark receiving common assessments and standardized treatment were evaluated at baseline, at 3 months, and at 1 year. RESULTS: Substantial clinical and social improvements occurred within the first 3 months. At 1-year 66% were in remission, 11% in relapse, and 23% continuously psychotic. Female gender and better premorbid functioning were predictive of less severe negative symptoms. Shorter DUP was predictive for shorter time to remission, stable remission, less severe positive symptoms, and better social functioning. Female gender, better premorbid social functioning and more education also contributed to a better social functioning. CONCLUSION: This first-episode sample, being well treated, may be typical of the early course of schizophrenia in contemporary centers.     

Early detection of the first episode of schizophrenia and suicidal behavior

OBJECTIVE: The suicide rate in schizophrenia is high, with the risk being highest early in the course. The rate of suicide attempts before treatment onset is also high and is often the event leading up to first treatment contact. A previous report showed that the duration of untreated psychosis can be reduced through an early detection program, and that the reduction was associated with lower symptom levels at treatment initiation. Treatment programs that bring first-episode patients into treatment at lower symptom levels can have the potential to reduce risk for suicide attempts. METHOD: The authors examined consecutive patients with nonorganic, nonaffective psychosis who sought initial treatment at psychiatric treatment units in four catchment areas: two that had an early detection program and two that did not. RESULTS: The rate of severe suicidality (plans or attempts) was significantly higher in subjects from communities without the early detection program relative to those from early detection communities, even after adjustments for known predictors of suicidality. CONCLUSION: Early detection programs that bring patients into treatment at lower symptom levels may reduce suicidality risk at first treatment contact.     

The development of subjective quality of life over the first 2 years in first-episode psychosis

The main aim of this study was to examine changes in subjective quality of life (general s-QoL) in patients with first-episode psychosis from baseline to 2 years follow-up. A total of 201 of 252 patients had full quality of life assessment at both baseline and at 2 years. Repeated measure analyses of variance were done to evaluate the development over time, and multiple linear regression analyses to evaluate predictors of change. These patients with a first-episode psychosis showed a significant improvement in general s-QoL during the first 2 years of treatment. Improvements in general s-QoL were associated with increase in excitative symptoms and with improvements in depressive symptoms, global functioning, level of daily activities, level of social activities, and perceived general health.     

Personality traits as prospective predictors of suicide attempts

Objective: To examine higher order personality factors of negative affectivity (NA) and disinhibition (DIS), as well as lower order facets of impulsivity, as prospective predictors of suicide attempts in a predominantly personality disordered sample. Method: Data were analyzed from 701 participants of the Collaborative Longitudinal Personality Disorders Study with available follow‐up data for up to 7 years. Cox proportional hazards regression analyses was used to examine NA and DIS, and facets of impulsivity (e.g. urgency, lack of perseverance, lack of premeditation and sensation seeking), as prospective predictors of suicide attempts. Results: NA, DIS and all facets of impulsivity except for sensation seeking were significant in univariate analyses. In multivariate models which included sex, childhood sexual abuse, course of major depressive disorder and substance use disorders, only NA and lack of premeditation remained significant in predicting suicide attempts. DIS and the remaining impulsivity facets were not significant. Conclusion: NA emerged as a stronger and more robust predictor of suicide attempts than DIS and impulsivity, and warrants greater attention in suicide risk assessment. Distinguishing between facets of impulsivity is important for clinical risk assessment.