Treating Suicidal Thoughts and Behaviors Within an Emotional Disorders Framework: Acceptability and Feasibility of the Unified Protocol in an Inpatient Setting.

We provide a theoretical rationale for applying a transdiagnostic, shared mechanism treatment (the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders [UP]) to suicidal thoughts and behaviors. We also present results from a proof of concept study examining the feasibility and acceptability of adding a modified UP to treatment as usual (TAU) in an inpatient setting for individuals reporting a recent suicide attempt or active suicidal ideation. Participants ( N = 12) were randomly assigned to receive UP + TAU or TAU alone. Findings indicate good feasibility and acceptability of the adjunctive intervention. Among participants who were responsive to contact attempts postdischarge ( n = 6), there were no observable differences in suicidal thoughts or behaviors during a 6-month follow-up. This application represents a promising initial extension of a cognitive-behavioral, emotion-focused treatment to suicidal individuals within an inpatient setting. Future studies adequately powered to speak to efficacy of the modified UP intervention are warranted.

The association between nonsuicidal self-injury and the emotional disorders: A meta-analytic review.

Existing research supports a relationship between nonsuicidal self-injury (NSSI) and the emotional disorders (i.e., anxiety, mood, and related disorders). The aim of this investigation was to conduct a meta-analysis of the associations between NSSI and the emotional disorders, and evaluate the quality of evidence supporting this relationship. A literature search was conducted from database inception through June 2014, and two reviewers independently determined the eligibility and quality of studies. A total of 56 articles providing data on engagement in NSSI among individuals with and without emotional disorders met eligibility criteria. Compared to those without an emotional disorder, individuals with an emotional disorder were more likely to report engagement in NSSI (OR=1.75, 95% CI: 1.49, 2.06). This increase of risk of NSSI was shown for each disorder subgroup, with the exceptions of bipolar disorder and social anxiety disorder. The largest associations were observed for panic and post-traumatic stress disorder; however, the risk of NSSI did not differ significantly across disorders. The quality of evidence was variable due to inconsistent methodological factors (e.g., adjustment for confounding variables, NSSI assessment). Overall, these findings provide evidence for a relationship between NSSI and the emotional disorders, and support conceptualizations of NSSI as transdiagnostic.

Factors that distinguish college students with depressive symptoms with and without suicidal thoughts.

BACKGROUND: Suicide among college students is a significant public health concern. Although suicidality is linked to depression, not all depressed college students experience suicidal ideation (SI). The primary aim of this study was to determine potential factors that may distinguish college students with depressive symptoms with and without SI. METHODS: A total of 287 undergraduate college students with substantial depressive symptoms (Beck Depression Inventory [BDI] total score >13) with and without SI were compared across psychiatric and functional outcome variables. Independent sample t tests were conducted for each outcome variable using the suicide item of the BDI as a dichotomous (ie, zero vs nonzero score) grouping variable. RESULTS: Relative to students with substantial depressive symptoms without SI, those with SI were more symptomatic overall, having significantly higher levels of depressive symptoms, hopelessness, and anxiety. However, contrary to our expectations, nonsuicidal and suicidal students did not differ on measures of everyday functioning (ie, cognitive and physical functioning and grade point average). CONCLUSIONS: Our findings suggest that SI among college students is associated with increased subjective distress but may not adversely impact physical or cognitive functioning or academic performance.

Folates and S-adenosylmethionine for major depressive disorder.

Interest in nonpharmaceutical supplements for treating major depressive disorder (MDD) has increased significantly, both among patients and among clinicians during the past decades. Despite the large array of antidepressants (ADs) available, many patients continue to experience relatively modest response and remission rates, in addition to a burden of side effects that can hinder treatment compliance and acceptability. In this article, we review the literature on folates and S-adenosylmethionine (SAMe), 2 natural compounds linked in the 1-carbon cycle metabolic pathway, for which substantial evidence supports their involvement in mood disorders. Background information, efficacy data, proposed mechanisms of action, and side effects are reviewed. Based on existing data, supplementation with SAMe, as well as with various formulations of folates, appears to be efficacious and well tolerated in reducing depressive symptoms. Compared with other forms of folates, 5-methyltetrahydrofolate (L-methylfolate or 5-MTHF) may represent a preferable treatment option for MDD given its greater bioavailability in patients with a genetic polymorphism, and the lower risk of specific side effects associated with folic acid. Although further randomized controlled trials in this area appear warranted, SAMe and L-methylfolate may represent a useful addition to the AD armamentarium.

The evaluation of a rapid in situ HIV confirmation test in a programme with a high failure rate of the WHO HIV two-test diagnostic algorithm.

BACKGROUND: Concerns about false-positive HIV results led to a review of testing procedures used in a Médecins Sans Frontières (MSF) HIV programme in Bukavu, eastern Democratic Republic of Congo. In addition to the WHO HIV rapid diagnostic test algorithm (RDT) (two positive RDTs alone for HIV diagnosis) used in voluntary counselling and testing (VCT) sites we evaluated in situ a practical field-based confirmation test against western blot WB. In addition, we aimed to determine the false-positive rate of the WHO two-test algorithm compared with our adapted protocol including confirmation testing, and whether weakly reactive compared with strongly reactive rapid test results were more likely to be false positives. METHODOLOGY/PRINCIPAL FINDINGS: 2864 clients presenting to MSF VCT centres in Bukavu during January to May 2006 were tested using Determine HIV-1/2 and UniGold HIV rapid tests in parallel by nurse counsellors. Plasma samples on 229 clients confirmed as double RDT positive by laboratory retesting were further tested using both WB and the Orgenics Immunocomb Combfirm HIV confirmation test (OIC-HIV). Of these, 24 samples were negative or indeterminate by WB representing a false-positive rate of the WHO two-test algorithm of 10.5% (95%CI 6.6-15.2). 17 of the 229 samples were weakly positive on rapid testing and all were negative or indeterminate by WB. The false-positive rate fell to 3.3% (95%CI 1.3-6.7) when only strong-positive rapid test results were considered. Agreement between OIC-HIV and WB was 99.1% (95%CI 96.9-99.9%) with no false OIC-HIV positives if stringent criteria for positive OIC-HIV diagnoses were used. CONCLUSIONS: The WHO HIV two-test diagnostic algorithm produced an unacceptably high level of false-positive diagnoses in our setting, especially if results were weakly positive. The most probable causes of the false-positive results were serological cross-reactivity or non-specific immune reactivity. Our findings show that the OIC-HIV confirmation test is practical and effective in field contexts. We propose that all double-positive HIV RDT samples should undergo further testing to confirm HIV seropositivity until the accuracy of the RDT testing algorithm has been established at programme level.

A re-appraisal of the burden of infectious disease in New Zealand: aggregate estimates of morbidity and mortality.

AIM: To assess the aggregate burden of infectious disease in New Zealand in terms of mortality and hospital admissions. METHODS: New Zealand mortality records for the years 1980-1998, and hospital discharges for the period 1988-2000, were re-analysed using a recoding of ICD-9 codes to estimate the aggregate burden of infectious disease. The recoding scheme was modified, as in an earlier analysis, from that developed by Centers for Disease Control and Prevention. RESULTS: Following recoding, the proportion of deaths attributable to infectious disease increased from 0.7% of deaths to 6.6% of deaths. Likewise recoding of hospital discharges showed an increase in the proportion due to infectious disease from 2.2% to 12.6%, second only to "complications of pregnancy, childbirth and the puerperium". Over the study period infectious disease mortality rates have showed little decline, and there has been a nearly 60% increase in infectious disease hospital discharge rates. CONCLUSIONS: The findings confirm and extend those of an earlier study, indicating the substantial burden of disease that is still attributable to infectious disease in New Zealand. The burden remains inequitable.

Increased levels of phosphatidylinositol 3-kinase activity in colorectal tumors.

BACKGROUND: Phosphatidylinositol 3-kinase (PI 3-kinase), an enzyme that phosphorylates inositol phospholipids at the D-3 position of the inositol ring, has been implicated in the signaling pathways regulating cell growth by virtue of its activation in response to various mitogenic stimuli. In spite of the considerable attention PI 3-kinase has received with regard to its possible role in the mitogenic pathways in hematopoietic malignancies, there are few reports of investigations into PI 3-kinase activity in solid tumors. METHODS: Colorectal tumor tissue and normal-appearing colonic mucosa from the same patients were homogenized and solubilized and adjusted to equal protein levels. PI 3-kinase then was immunoprecipitated from 200 microg of the solubilized tissue using a polyclonal antibody to the p85 subunit of PI 3-kinase. PI 3-kinase activity was assessed using phosphatidylinositol as the substrate and the assay product analyzed by thin-layer chromatography. Phosphorylation of phosphatidylinositol in the D-3 position was confirmed by high performance liquid chromatography analysis of deacylated and deglycerated products. RESULTS: Thirty-two of the 37 tumors tested (86%) demonstrated increased PI 3-kinase activity compared with normal-appearing mucosa from the same patients (overall mean increase+/-standard error of the mean=3.8+/-0.6-fold; P < 0.05, Student's t test for paired data). The frequency and extent of increased PI 3-kinase enzyme activity in tumors did not correlate with clinical parameters or the presence of oncogenic ras mutations. CONCLUSIONS: In this study colorectal tumors exhibited enhanced PI 3-kinase activity compared with normal colonic mucosa, raising the possibility that PI 3-kinase may be a potential target for new strategies for the treatment of colorectal carcinoma.

Frequency and clinico-pathological associations of ras mutations in colorectal cancer in the Victorian population.

BACKGROUND: Mutations in the oncogene ras occur in 20-50% of colorectal cancers. The presence of these mutations allows screening tests to be developed based on the identification of mutant DNA in cells derived from cancers. A study of the prevalence and clinicopathological associations of ras mutations was undertaken. METHODS: The frequency of mutations in codons 12 and 13 of the K-ras gene was investigated in 103 colorectal carcinomas using restriction fragment length polymorphism. RESULTS: Mutations were detected in 32% (33/103) of the tumours, predominantly in codon 12 (25/33). No mutations were detected in normal-appearing mucosa from the same patients. CONCLUSIONS: Analysis of the frequency of ras mutations compared with various independent clinical variables revealed a sex-linked relationship between the presence of a ras mutation and nodal status but no correlation with any other clinical parameter was found. The findings suggest that screening tests based on ras mutation detection may lack sensitivity because of the presence of mutations in only 32% of tumours.

Chromosomal transmission bias in laboratory hybrids between wild strains of the two European subspecies of house mice.

Laboratory crosses between wild strains of the two European house mouse subspecies Mus musculus domesticus (2n = 34) and M. m. musculus (2n = 40) were performed to analyze the selective processes involved in the non-introgression of centromeric regions of Robertsonian (Rb) fusions in the Danish hybrid zone. The chromosomal analysis of 226 backcross progeny from 22 reciprocal crosses showed that the segregation of the three Rb fusions present did not significantly differ from Mendelian expectations. However, a significant negative correlation was found between Rb transmission rates and the average litter sizes of the F1 pairs. Among the different models of selection discussed, the most likely one supported the existence of two opposing selective factors resulting in an overall compensation of chromosomal types in the backcross progeny. A two-phase selective process involving embryo competition was postulated with non-Rb carriers being favored during pre-implantation but disadvantaged after implantation. Such balanced selective pressures acting on musculus non-Rb centromeres are compatible with the steep slope and off-centered position of the chromosomal cline observed in the Danish hybrid zone. These results suggested that these selective factors may be more related to centromere origin (musculus or domesticus) than to centromere structure (Rb or non-Rb).

Genomic incompatibilities in the hybrid zone between house mice in Denmark: evidence from steep and non-coincident chromosomal clines for Robertsonian fusions.

The pattern of chromosomal variation is investigated in house mice from the Danish hybrid zone between the translocation-prone Mus musculus domesticus and the chromosomally conservative M. m. musculus. The cytogenetic analysis confirmed the non-introgression of three pairs of Robertsonian (Rb) fusions from M. m. domesticus into the M. m. musculus genome. The geographic distribution of two of these Rb fusions was shown to follow staggered chromosomal clines which increased in steepness the closer they were to the centre of the hybrid zone as defined by allozymes. Analysis of alternate hypotheses suggests that chromosomal differentiation of the Danish domesticus occurred after contact was established with musculus. The staggering of the clines would reflect the order of arrival of the Rb fusions into the hybrid zone. Several models with different processes of underdominance of the chromosomal heterozygotes are discussed to account for the difference in width between clines. A selective model with increasing levels of genomic underdominance due to interaction with a progressively enriched musculus genome provides the best fit for the observed pattern. Selection against Rb fusions with little effect on the recombination of linked allozyme markers supports the view that no reduction in gene flow due to chromosomal heterozygosity is yet apparent through the hybrid zone and that only the centromeric segments of the Rb fusions are incompatible with the musculus genome.

Selective venous catheterization in the evaluation of hyperandrogenism.

Retrograde bilateral ovarian-adrenal vein catheterization was carried out in 16 patients with plasma testosterone levels exceeding 1.4 ng/ml (4.85 nmol/l). While pelvic ultrasonography and computerized axial tomographic scan failed to locate the androgen-producing ovarian tumors, catheterization led to a diagnosis of occult ovarian tumor in 5 patients, based on the observation of an abnormally-high and unilateral ovarian-peripheral vein testosterone gradient, which was subsequently confirmed histopathologically. In one case, unilateral elevation of the adrenal-peripheral vein testosterone gradient was found, complementing the ultrasonographic finding of an adrenal mass and confirming the diagnosis of a virilizing adrenal tumor. In the other 10 patients, gradient analysis ruled out an androgen-producing tumor, leading to the identification of nontumoral hyperandrogeny, such as a severe form of the polycystic ovary syndrome in the 6 premenopausal patients and of ovarian stromal and hilus cell hyperplasia in the 4 menopausal patients. In conclusion, appropriate indication of selective catheterization may considerably reduce the need for exploratory surgery and may help in selecting the adequate surgical approach.

Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia.

Thirty late-onset adrenal hyperplasia patients consulting for isolated hirsutism were randomly divided into two groups; group 1 (n = 16) was treated with hydrocortisone in order to suppress androgen adrenal secretion, and group 2 (n = 14) received cyproterone acetate (CPA) antiandrogen therapy to inhibit peripheral androgen activity. The clinical and hormonal effects of each type of treatment were evaluated. Before treatment, the clinical and hormonal profiles of the two patient groups did not differ significantly. Excellent clinical evolution in terms of the regression of hirsutism was observed in the CPA-treated patients (54% decrease in the clinical score in 1 yr), in contrast with the slight decrease in hirsutism (26%) after hydrocortisone treatment. In hydrocortisone-treated patients, plasma androgen decreased to normal levels: testosterone from 3.05 +/- 1.45 to 1.46 +/- 0.42 nmol/L and delta 4-androstenedione from 13.6 +/- 4.1 to 6.33 +/- 1.47 nmol/L. Conversely, in CPA-treated patients, only a slight decrease in testosterone from 2.98 +/- 1.98 to 2.29 +/- 0.64 nmol/L and in delta 4-androstenedione from 12.9 +/- 5.9 to 9.86 +/- 2.23 nmol/L was observed. This slight decrease in plasma androgens contrasts with the rapid clinical improvement after CPA. These results emphasize the importance of peripheral receptivity to androgens in the clinical expression of hyperandrogenism. Moreover, they indicate that peripheral antiandrogen therapy may be more appropriate in late-onset adrenal hyperplasia patients than conventional adrenal inhibition using cortisone therapy.

Prolactin secretion in benign breast diseases.

In order to evaluate the importance of prolactin in the pathogenesis of benign breast diseases (BBD), serum prolactin (PRL) levels were determined before and during a TRH challenge test in 50 patients affected by various BBD studied during the luteal phase of their cycle. They were compared to 15 normal women also studied during the luteal phase. In all the subjects estradiol (E2) and progesterone (P) were also measured. The patients were studied as a total group and in different subgroups according to the type of their disease, before and after 3 months of treatment with a potent progestin, lynestrenol. No significant differences appeared between any group of patients and the control group either on the basal prolactin secretion or on its dynamic secretory pattern after TRH injection before and during treatment. The only significant difference observed between patients and controls was the progesterone values, respectively 6.86 +/- 0.9 ng/ml and 21.2 +/- 1.4 ng/ml. It can therefore be concluded that benign breast diseases are more likely to be related to an inadequate luteal phase than to any abnormality of prolactin secretion.

Hypocalcaemic effect of WR-2721, S-2 (3-aminopropylamino) ethyl-phosphorothioic acid in an anuric haemodialysis patient.

The radio- and chemoprotective agent, S-2 (3-aminopropylamino) ethyl-phosphorothioic acid (WR-2721) has been reported to lower hypercalcaemia in patients with cancer, probably by increased renal calcium excretion and decreased parathyroid hormone (PTH) secretion and bone calcium resorption. The present study reports the first clinical use of WR-2721 in an anuric haemodialysis patient with severe secondary hyperparathyroidism. The drug was administered intravenously at different doses, i.e. 150, 300, and 500 mg/m2. The infusion was followed by a striking decrease of plasma immunoreactive (i) PTH within 30 min. The nadir of the iPTH decrease was reached at 60 min and was followed by a steady return to previous values. Serum ionised calcium decreased more progressively from 1.55 mmol/l initially to 1.30 mmol/l at 4 h after the 300-mg dose, remained at that level at 24 h, but rose again to pre-infusion values after 48 h. The extent and duration of the decrease in plasma iPTH and ionised calcium were dose-dependent. The circulating iPTH at 24 h was inversely related to the corresponding plasma ionised calcium concentration and had risen above preinfusion values at that time. Plasma concentrations of three other hormones, i.e. renin, insulin, and prolactin, were not affected by the administration of WR-2721. In conclusion, WR-2721 can induce a decrease in serum ionised calcium in the absence of any excretory kidney function. The rapid effect of the drug on circulating iPTH supports the notion of an interference with PTH secretion or catabolism.

Effect of calcitriol in the control of plasma calcium after parathyroidectomy. A placebo-controlled, double-blind study in chronic hemodialysis patients.

Severe, prolonged hypocalcemia in observed in some, but not all, hemodialysis patients after parathyroidectomy performed because of uncontrolled hyperparathyroidism. The aim of the present study was to investigate whether calcitriol and calcium supplementation in the immediate period after parathyroidectomy (days 1-14) was of more help in the control of plasma calcium than calcium supplementation alone. Fourteen hemodialysis patients were enrolled in a prospective, randomized, double-blind and placebo-controlled study. From the day after parathyroidectomy, 7 patients received calcitriol and the remaining 7 a placebo using incremental doses adjusted to the degree of hypocalcemia (up to 4 micrograms/day for calcitriol). Plasma calcium, phosphorus, alkaline phosphatase and immunoreactive parathyroid hormone levels before parathyroidectomy were comparable in both patients groups, as was the lowest plasma calcium achieved after parathyroidectomy. The decrease in plasma calcium after parathyroidectomy was related to plasma alkaline phosphatase and to the number of osteoclasts and osteoblasts on bone biopsy surface before parathyroidectomy. The mean decrement of plasma calcium (days 3-9) as compared to that before parathyroidectomy was less pronounced in calcitriol-treated than in placebo-treated patients (0.25 +/- 0.06 versus 0.45 +/- 0.05 mM, mean +/- SEM, p less than 0.025). Treatment with placebo was interrupted before day 14 because of persistent severe hypocalcemia in 4 of 7 patients, whereas calcitriol treatment was continued in all 7 patients up to 14 days. Patients on calcitriol treatment required less mean calcium supplements (days 1-9) than patients receiving placebo (37.4 +/- 3.2 versus 49.4 +/- 3.7 g, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnostic and therapeutic problems in a severe case of hyperparathyroidism with renal insufficiency]. / Les difficultés diagnostiques et thérapeutiques dans un cas d'hyperparathyroïdie sévère avec insuffisance rénale.

It may sometimes be difficult to distinguish primary from secondary hyperparathyroidism when advanced renal failure coexists. We report here the case of a patient with end-stage renal failure who had severe hyperparathyroidism. Cervical exploration revealed only the presence of four parathyroid glands normal in size and histological appearance which were removed. Because the existence of severe hyperparathyroidism had been firmly established based on biochemical and radiological evidence, the diagnosis of primary hyperparathyroidism due to an ectopic adenoma became obvious. Digital angiography and computerized tomography were then carried out. The results of angiography were inconclusive but computerized tomography revealed and precisely localized a mediastinal adenoma which was subsequently removed via sternotomy. The existence of a hypoparathyroid state was confirmed over the following two months. Reimplantation of parathyroid fragments which had been cryopreserved during the first operation, was then performed with success.

In vivo effects of progestins on prolactin secretion.

To assess a possible inhibitory effect of progestins on PRL secretion, serum PRL and estradiol levels were determined in 13 women with hyperprolactinemia due to a pituitary microadenoma before and after 3 months of treatment with a potent progestin, lynestrenol. PRL levels also were assessed during a TRH challenge test before and after treatment. Results were compared to those obtained in 10 normal women studied during the early follicular phase of their menstrual cycle and at the end of 3 months of treatment. The PRL response to TRH was blunted in patients before lynestrenol therapy. After therapy, basal serum PRL levels were significantly decreased, and the response to TRH was almost abolished. No change occurred in the normal women. The estradiol level was 80.5 +/- 7.5 (+/- SEM) pg/ml in patients before treatment and decreased to 29.2 +/- 5.0 pg/ml after therapy. Therefore, lynestrenol, a potent 19-nortestosterone derivative, exhibits in vivo an anti-PRL effect that could be related to its antiestrogenic and/or androgenic activities.