Risk factors and outcomes of anxiety symptom trajectories in type 2 diabetes: the Fremantle Diabetes Study Phase II.

AIM: To identify determinants and outcomes of 4-year trajectories of anxiety symptoms in a community-based cohort with type 2 diabetes. METHODS: Some 1091 participants in the Fremantle Diabetes Study-Phase II with type 2 diabetes completed the Generalized Anxiety Disorder Scale at baseline and biennially for 4 years, in addition to psychological, biomedical and self-management measures. Latent growth mixture modelling identified trajectories of anxiety symptom severity, and regression models determined predictors of trajectory membership and associated outcomes. RESULTS: Two distinct groups of participants were identified: those with continuously low-no anxiety symptoms (87%) and those with improving but consistently high anxiety symptoms (elevated anxiety; 13%). Higher HbA1c and BMI, macrovascular complications and a history of generalized anxiety and/or major depressive disorder increased the risk of elevated anxiety. Elevated anxiety did not predict change in health-related outcomes over time. Elevated anxiety and depression symptoms were highly comorbid and those with both displayed the most persistent anxiety symptoms. CONCLUSIONS: A subgroup of individuals with type 2 diabetes are at risk of persistently elevated anxiety symptoms. Routine monitoring of the severity of psychological symptoms over time in this population should facilitate earlier and more intensive mood management.

Depression prevalence in Type 2 diabetes is not related to diabetes-depression symptom overlap but is related to symptom dimensions within patient self-report measures: a meta-analysis.

AIM: Depression is common in Type 2 diabetes, yet rates vary. Overlap between symptoms of depression and diabetes may account for this variability in depression prevalence rates. We examined to what extent depression prevalence was a function of the proportion of depression-diabetes symptom overlap (items within symptom dimensions) and sample characteristics. METHODS: Electronic and hand searching of published and unpublished works identified 147 eligible papers. Of 3656 screened, 147 studies (149 samples, N = 17-229 047, mean sample age 25.4-82.8 years, with 152 prevalence estimates), using 24 validated depression questionnaires were selected. Sample size, publication type, sample type, gender, age, BMI, HbA1c , depression questionnaire and prevalence rates were extracted. RESULTS: Prevalence rates ranged from 1.8% to 88% (mean = 28.30%) and were higher in younger samples, samples with higher mean HbA1c and clinic samples. Diabetes-depression symptom overlap did not affect prevalence. A higher proportion of anhedonia, cognition, cognitive, negative affect and sleep disturbance symptoms, and a lower proportion of somatic symptoms were consistently associated with higher depression prevalence. CONCLUSIONS: The lack of an overall effect of diabetes-depression symptom overlap might suggest that assessment of depression in Type 2 diabetes is generally not confounded by co-occuring symptoms. However, questionnaires with proportionally more or fewer items measuring other symptom categories were associated with higher estimates of depression prevalence. Depression measures that focus on the cardinal symptoms of depression (e.g. negative affect and cognition), limiting symptoms associated with increasing diabetes symptomatology (e.g. sleep disturbance, cognitive) may most accurately diagnose depression.

The fine needle aspiration of translocation sarcomas.

INTRODUCTION: Soft tissue sarcomas comprise a heterogeneous group of clinically aggressive cancers that are often hard to classify on limited cytological samples. "Translocation sarcomas" (TS) are a diverse subset of such cancers, different from pleomorphic sarcomas, and characterised by unique single chromosomal translocations in each sarcoma subtype. Interestingly, despite their high-grade biological behaviour, TS have deceptively monotonous and bland cytomorphology, therefore creating diagnostic issues on limited samples. MATERIALS AND METHODS: A retrospective search was conducted of the cytopathology archives of The Johns Hopkins Hospital revealing 147 translocation sarcoma cases over a 25-year period. RESULTS: The common morphological denominators for most translocation sarcomas were: hypercellularity, cellular monotony, mostly discohesive and single cells, round-to-oval or short spindled cells and a lack of necrosis. The exceptions were an inflammatory myofibroblastic tumour, in which cellular monotony was not present owing to the prominence of lymphocytes and plasma cells, and low-grade fibromyxoid sarcoma, in which the specimens were generally hypocellular. Ancillary testing, especially immunoperoxidase staining, was often required for primary lesions. CONCLUSION: Distinct morphological clues and subsequent ancillary testing (particularly immunoperoxidase staining) provide an accurate diagnosis on cytological interpretation of both, primary and recurrent/metastatic lesions.

Depression symptoms are persistent in Type 2 diabetes: risk factors and outcomes of 5-year depression trajectories using latent class growth analysis.

AIMS: To describe the long-term trajectories of depression symptom severity in people with Type 2 diabetes, and to identify predictors and associates of these trajectories. METHODS: A community-dwelling cohort of 1201 individuals with Type 2 diabetes from the Fremantle Diabetes Study Phase II was followed for 5 years. The nine-item version of the Patient Health Questionnaire was administered annually to assess depression symptoms, and biomedical and psychosocial measures were assessed at baseline and biennially. Latent class growth analysis was used to identify classes of depression severity trajectories and associated outcomes, and logistic regression models were used to determine predictors of class membership. RESULTS: Three trajectories of depression symptoms were identified: continuously low depression symptoms (85.2%); gradually worsening symptoms that then began to improve (persistent depression - low-start; 7.3%); and gradually improving symptoms which later worsened (persistent depression - high-start; 7.5%). Younger age, being a woman, and a lifetime history of major depressive disorder, were associated with greater risk of persistent depression symptoms. Persistent depression was associated with consistently higher BMI over time, but not with changes in HbA1c or self-monitoring of blood glucose. CONCLUSIONS: A subset of individuals with Type 2 diabetes is at risk of depression symptoms that remain elevated over time. Younger, overweight individuals with a history of depression may benefit from early and intensive depression management and ongoing follow-up as part of routine Type 2 diabetes care.

Lifetime depression and anxiety increase prevalent psychological symptoms and worsen glycemic control in type 2 diabetes: The Fremantle Diabetes Study Phase II.

AIMS: To determine the contribution of lifetime major depressive disorder (L-MDD) and lifetime generalized anxiety disorder (L-GAD) to current psychological symptom severity, health behaviour and glycaemic control in type 2 diabetes. METHODS: 1285 community-dwelling people with type 2 diabetes (Fremantle Diabetes Study Phase-II; FDS2) completed the PHQ-9 and Brief Life-Time Depression Scale (BLDS) to assess current and past MDD. The Generalized Anxiety Disorder Scale (GADS) and the Generalized Anxiety Disorder Scale-Lifetime (GAD-LT), designed for FDS2, assessed current and past anxiety. Data were analysed using analysis of covariance and multiple mediation models, controlling for age, gender, marital status, and diabetes duration. RESULTS: L-MDD and L-GAD were independently associated with more severe current depression (both P<0.001) and anxiety (both P<0.001) symptoms. Mediation models revealed that, through increasing the severity of current depressive symptoms, L-MDD was associated with higher HbA1c and body mass index (BMI), greater likelihood of current smoking, and reduced self-monitoring of blood glucose (SMBG) (indirect regression path ab, all P<0.001). In combination, L-MDD+L-GAD additionally elevated the risk of higher HbA1c and worse diabetes management, by increasing the severity of current depressive symptoms (indirect regression path ab, all P<0.001). CONCLUSIONS: Lifetime depression and anxiety increase risk of more severe psychological symptoms, hyperglycaemia, and difficulties with health behaviour in type 2 diabetes. Early screening for these disorders at diabetes diagnosis may be warranted to maximize long-term health outcomes.

Olanzapine plasma concentration in a newborn.

Little is known about the use of antipsychotics in pregnancy and the corresponding plasma levels in the newborn child. We report on a woman with schizophrenia treated with olanzapine during pregnancy. Plasma levels of olanzapine were assessed both from the mother and from umbilical cord. The plasma level of the newborn (11 ng/mL) was about one third compared to the mother (range 25-34 ng/mL).The development of the fetus, delivery and the development of the child during the first six months were normal.

Molecular cloning of Soli E2: an elastase-like serine proteinase from the imported red fire ant (Solenopsis invicta).

The 4th instar larva of the imported red fire ant, Solenopsis invicta, possesses several serine proteinases, one of which, referred to as Soli E2, has been found to contain elastase-like activity. A cDNA library was constructed in lambda gt10 using Poly(A)+RNA from these larvae and a synthetic degenerate oligonucleotide probe corresponding to a sequence encoding the N-terminal of Soli E2 was utilized to screen the library. Two clones were obtained covering the entire coding region of Soli E2, and the predicted structure of this proteinase indicated that it was synthesized as a preproenzyme of 249 amino acids, which was cleaved to give the mature form of 226 residues. In addition, both clones showed identity to the N-terminal amino acid sequence obtained from Edman degradation of the mature purified proteinase. Significantly, Northern blot analysis of the different developmental stages revealed that Soli E2 was selectively expressed in the 4th instar larvae.

Proteolytic enzymes from larvae of the fire ant, Solenopsis invicta. Isolation and characterization of four serine endopeptidases.

The imported red fire ant (Solenopsis invicta) is a problematic pest in the Southern United States. The stages of development for these ants are as follows: egg, 1st, 2nd, 3rd, and 4th instar larvae, prepupae, pupae, and adult. The 4th instar larvae plays an important role in the survival of the colony in that it is totally responsible for the digestion of solid foods and the source of nutrients for the queen and adult workers. In our studies we have been successful in purifying and characterizing four proteinases from the 4th instar larvae. Based on substrate specificity, they appear to represent two chymotrypsin-like and two elastase-like proteinases. These are referred to as Soli C1, Soli C2, Soli E1, and Soli E2, with molecular masses of 25, 28, 23, and 24 kDa, respectively, based on SDS-PAGE. All enzymes were inhibited by diisopropyl fluorophosphate, a general serine class inhibitor. Various synthetic substrates with either Phe or Val in the P1 position, were readily cleaved by Soli C1/C2 or E1/E2, respectively. Each enzyme has been characterized as to pH optimum, pH stability, isoelectrofocusing and susceptibility to inhibition by a broad range of natural and synthetic proteinase inhibitors. Such compounds may prove useful for the development of insecticides to control fire ant infestation.

The response of implanted dual chamber pacemakers to 50 Hz extraneous electrical interference.

Twenty-two patients with dual chamber pacemakers with interchangeable lead configuration were exposed to 50 Hz electromagnetic interference. Current, at corporeal levels from 0-600 microA, was applied between electrodes on shoulders and feet using a bedside injection unit. Pacemaker behavior was monitored with telemetered event markers and intracardiac electrograms. In bipolar mode, noise reversion mode was induced in all except two Medtronic units at high (> 170 microA) levels of corporeal current. In the Intermedics, Siemens Pacesetter, and Telectronics models, onset of noise reversion mode was preceded by a window of inappropriate function, characterized by rate acceleration due to atrial malsensing, or pacemaker inhibition due to ventricular malsensing. In unipolar mode, pacemaker malfunction occurred at much lower current levels. Inappropriate behavior preceded the onset of protective noise reversion mode. During current injection, all pacemakers could be interrogated and reprogrammed, and intracardiac telemetry was reliably obtained except in two Medtronic units at high current levels. No pacemaker was reset by the electrical interference, and no cross-talk was seen. Use of bipolar mode confers a high degree of protection from extraneous electrical interference, but in unipolar mode pacemakers may be inhibited by small amounts of corporeal current, potentially encountered in every day life. The current injection unit allows safe, controllable, and quantifiable investigation of the effects of the electric field induced by a current on implanted pacemakers. Telemetry of annotated intracardiac signals during electromagnetic interference clarifies observations of pacemaker acceleration and inhibition.

The effect of exercise and heart rate on fibrinolytic activity.

The effect of heart rate on plasma fibrinolytic activity was investigated in nine patients with dual chamber cardiac pacemakers before and after 10 min of stimulated tachycardia to 123 beats/min. The results were compared to seven volunteers who performed submaximal exercise to 90% target heart rate and to five of the seven who underwent a second period of exercise to a heart rate of 120 beats/min. During submaximal exercise (mean heart rate 152 beats/min) the median ECLT fell from 248 min (interquartile range 147.5-305) to 90 (55-202) P less than 0.01 and t-PA:Ag increased from 6.1 ng/ml (3.92-7.95) to 9.3 (8.45-12.7), P less than 0.025. PAI and PAI-1:Ag fell from 12.0 IU/ml (5.85-15.5) to 4.1 (1.85-11.67), P less than 0.01, and 9.7 ng/ml (2.8-10.6) to 6.7 (2.1-9.9), P less than 0.01 respectively. A lower level of exercise to 120 beats/min resulted in a reduction in ECLT from 215 min (167.5-228.5) to 135 (116-154), P = 0.05 and an increase in t-PA:Ag from 4 ng/ml (3.07-4.45) to 5.0 (3.3-5.22) P less than 0.05. PAI and PAI-1:Ag fell from 7.6 IU/ml (3.27-8.5) to 7.1 (2.77-7.4) and from 7.7 ng/ml (6.0-7.92) to 6.4 (4.8-7.3) respectively but these changes were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)