Revisiting the Psychiatric Day Hospital Experience 6 Months After Discharge: How Was the Transition and What Have Clients Retained?

Psychiatric day hospitals offer intensive short-term multidisciplinary treatment. No study has examined in more depth the impact of this therapeutic experience in the life of participants and what they retained from their participation after discharge. A qualitative design using semi-structured individual interviews was completed with 18 participants of different gender, age and diagnosis, treated in a day hospital, 6 months after discharge. Interview themes addressed events and changes since discharge, learnings retained, appreciated components and suggestions. Results showed that the day hospital experience was particularly helpful to improve symptoms and relationship with self. It activated a self-transformation process that continued afterwards. Termination created for many an abrupt void. Issues at stake during the first 6 months were continuity of care, social support and putting learnings into practice. The program offered at the day hospital was generally appreciated but management of the waiting time and linkage to outpatient services needed improvement.     

Nearby inverted repeats fuse to generate acentric and dicentric palindromic chromosomes by a replication template exchange mechanism

Gene amplification plays important roles in the progression of cancer and contributes to acquired drug resistance during treatment. Amplification can initiate via dicentric palindromic chromosome production and subsequent breakage–fusion–bridge cycles. Here we show that, in fission yeast, acentric and dicentric palindromic chromosomes form by homologous recombination protein-dependent fusion of nearby inverted repeats, and that these fusions occur frequently when replication forks arrest within the inverted repeats. Genetic and molecular analyses suggest that these acentric and dicentric palindromic chromosomes arise not by previously described mechanisms, but by a replication template exchange mechanism that does not involve a DNA double-strand break. We thus propose an alternative mechanism for the generation of palindromic chromosomes dependent on replication fork arrest at closely spaced inverted repeats.     

Mutant epidermal growth factor receptor in benign, borderline, and malignant ovarian tumors

PURPOSE: Dysfunction of the epidermal growth factor (EGF) complex is essential to the growth and development of many human tumors. Overexpression of the EGF receptor (EGFR) is a characteristic finding in a considerable number of solid tumors and often signalizes poor prognosis. There is a major disagreement among researchers about both the frequency and possible clinical importance of EGFR overexpression in ovarian cancer. The type III variant of EGFR (EGFRvIII) is a mutant with a deletion. Contrary to the wild-type, it is constitutively active. EGFRvIII has not been found in normal tissue, and consequently, it is an attractive tumor-specific candidate for molecular targeted treatment. The literature dealing with this mutation in ovarian cancer has been very sparse. EXPERIMENTAL DESIGN: Tissue from 225 patients who underwent surgery for a pelvic mass was collected consecutively. The samples included 99 ovarian/peritoneal/tuba cancers, 17 ovarian borderline tumors, 66 benign ovarian tumors, 15 other cancer types, 24 normal ovarian biopsies, and 4 miscellaneous. The presence of EGFRvIII was investigated both by PCR analyses for EGFRvIII gene expression and with protein analysis by Western blots. RESULTS: None of the tissue samples was positive for the EGFRvIII mutation neither at the mRNA level nor at the protein level. CONCLUSIONS: The EGFRvIII mutation seems to be very rare in ovarian tissue. Our data indicate that EGFRvIII is not a part of the malignant phenotype in ovarian cancer and should not be pursued as a therapeutic target for treatment of this disease.     

In vivo and in vitro degradation of glucagon-like peptide-2 in humans

Glucagon-like peptide-2 (GLP-2), an intestinal product of glucagon gene expression which induces intestinal growth in mice, has been proposed as a treatment for intestinal insufficiency. GLP-2 is metabolized extensively by dipeptidyl peptidase IV (DPP-IV) in rats, but less is known about its fate in humans. Therefore, GLP-2 metabolism was investigated in healthy volunteers after 1) a 500-Cal mixed meal (n = 6), 2) iv infusion of synthetic human GLP-2 (0.8 pmol/kg x min; n = 8), 3) a sc bolus injection (400 microg; n = 9), and 4) in vitro incubation in plasma and blood (1,000 pmol/L; n = 4). GLP-2 concentrations were determined by N-terminal RIA measuring only intact GLP-2, side-viewing RIA measuring intact and degraded forms [e.g. GLP-2-(3-33) arising from DPP-IV degradation], and high performance liquid chromatography (HPLC). Meal ingestion elevated plasma GLP-2 (intact, 16 +/- 3 to 73 +/- 10 pmol/L at 90 min), and HPLC revealed two immunoreactive components: intact GLP-2 (57 +/- 2%) and GLP-2-(3-33). GLP-2 infusion increased plasma levels [intact, 9 +/- 4 to 131 +/- 11 pmol/L; total, 23 +/- 7 to 350 +/- 18 pmol/L; the differences represent GLP-2-(3-33)]. The elimination t(1/2) values were 7.2 +/- 2 min (intact GLP-2) and 27.4 +/- 5.4 min [GLP-2-(3-33)], and MCRs were 6.8 +/- 0.6 and 1.9 +/- 0.3 mL/kg x min, respectively. Subcutaneous injection increased intact GLP-2 to maximally 1,493 +/- 250 pmol/L at 45 min, whereas total GLP-2 increased to 2,793 +/- 477 pmol/L at 90 min. At 60 min, plasma contained 69 +/- 1% intact GLP-2. In vitro the t(1/2) values were 8.0 +/- 1.5 h (plasma) and 3.3 +/- 0.3 h (blood). GLP-2-(3-33) was the only degradation product identified by HPLC, and a DPP-IV inhibitor abolished the degradation of GLP-2 in vitro. We conclude that GLP-2 is extensively degraded to GLP-2-(3-33) in humans, presumably by DPP-IV. Nevertheless, 69% remains intact 1 h after GLP-2 injection, supporting the possibility of sc use in patients with intestinal insufficiency.     

Adenosine relaxation in small retinal arterioles requires functional Na-K pumps and K(ATP) channels

PURPOSE: To study the effect of Na-K pump and K(ATP) channel inhibition on the diameter and the adenosine-induced vasodilation of small retinal arterioles. METHODS: Thirty isolated porcine arterioles with a diameter of approximately 70 microm were mounted in a double-barrelled pipette system placed in an organ bath, and diameter changes were studied under isobaric no-flow conditions. After an equilibration period, the arterioles were incubated with the Na-K pump inhibitors ouabain and low K(+) medium or the K(ATP) channel inhibitor glibenclamide, and spontaneous diameter changes were studied. Subsequently, the arterioles were precontracted and the adenosine concentration response curve was measured with and without the presence of inhibitors. RESULTS: Inhibition of the Na-K pump elicited a significant decrease in the spontaneous diameter of the vessels (P = 0.047), whereas no change in the spontaneous diameter was induced by inhibition of the K(ATP) channels (P = 0.754). Inhibition of the Na-K pump with ouabain or with low K(+) medium, as well as inhibition of the K(ATP) channels with glibenclamide, both diminished the adenosine induced vasodilation (P = 0.003, P = 0.01, and P = 0.003, respectively). CONCLUSION: The adenosine-induced vasodilation of small retinal arterioles involves the K(ATP) channels and the Na-K pump. Changes in the metabolism of adenosine as well as the activity of the K(ATP) channels or the Na-K pump can be expected to influence the retinal blood flow.     

Bradykinin relaxation in small porcine retinal arterioles

PURPOSE: To study changes in the spontaneous diameter of small retinal arterioles and bradykinin (BK)-induced vasodilation during inhibition of the synthesis of nitric oxide (NO), prostaglandins (PGs), and cytochrome P450 2C8/9-dependent endothelial-derived hyperpolarizing factor (EDHF). METHODS: Forty-eight isolated porcine arterioles with a diameter of approximately 70 microm were mounted in a double-barreled pipette system placed in an organ bath, and diameter changes were studied under isobaric conditions. After an equilibration period, the arterioles were incubated with inhibitors of the synthesis of NO, PGs, or cytochrome P450 2C8/9-dependent EDHF, and spontaneous diameter changes were studied. Subsequently, the arterioles were precontracted, and the diameter was assessed after addition of BK in cumulative concentrations. RESULTS: Inhibition of NOS elicited a significant decrease in the spontaneous diameter of the vessels (P = 0.028), whereas no change in the spontaneous diameter was induced by inhibition of PG or cytochrome P450 2C8/9 dependent EDHF synthesis (P = 0.35 and P = 0.75, respectively). The vasodilating effect of BK was decreased by inhibition of NO (P = 0.002) but not by inhibition of prostaglandin or cytochrome P450 2C8/9-dependent EDHF synthesis (P = 0.82 and P = 0.94, respectively). CONCLUSIONS: The results suggest the presence of a spontaneous release of NO, which keeps the retinal microcirculation dilated under normal conditions. The finding of BK-induced relaxation being dependent on the NO synthase (NOS), but not on PGs or cytochrome P450 2C8/9-dependent EDHF may be of importance for understanding the microcirculatory effects of pharmacologic compounds affecting the BK metabolism, such as angiotensin-converting enzyme (ACE) inhibitors.     

Renal ischemia-reperfusion injury in the rat is prevented by a novel immune modulation therapy

BACKGROUND: Vasogen Inc.'s (Mississauga, Ontario, Canada) immune modulation therapy (IMT) is a therapy in which cells from the patient's own blood are modified by ex vivo exposure to specific physicochemical stressors, including oxidation, ultraviolet (UV) light, and an elevated temperature. The therapy has been shown to have a beneficial effect in models of inflammation and vascular diseases. This study tested the hypothesis that IMT can prevent renal ischemia-reperfusion (I/R) injury in rats. METHODS: Whole blood was collected from syngeneic age-matched donors by cardiac puncture. It was treated with a combination of controlled physiochemical stressors consisting of elevated temperature, a gas mixture of medical oxygen containing ozone, and UV light. The treated blood (150 microL) was injected in the gluteal muscle. Control animals received the same volume of untreated blood or physiological saline. Transient (45 or 60 minutes) left-renal ischemia was produced with simultaneous contralateral nephrectomy in treated and control spontaneously hypertensive rats (SHR). Young and old male and female rats were studied. Plasma creatinine, diuresis, and the survival rates of each group were compared. Renal apoptosis-necrosis was estimated by DNA laddering, histology, and in situ terminal deoxynucleotidyl transferase assay. mRNA levels of several regulators of apoptosis-regeneration were determined in control and postischemic kidneys by Northern blotting. RESULTS: IMT pretreatment of SHR significantly reduced renal I/R injury compared with equivalent placebo treatments consisting of untreated blood- or saline-injected SHR, as evidenced by a significant increase of the survival rate curves in young and old male SHR, which correlated with 24-hour postischemic diuresis. The increases in plasma creatinine following renal I/R were significantly lower in IMT-treated young male and old female SHR compared with saline or untreated blood-injected controls. Dilution analysis showed that the protective effect of treated blood was lost by dilution. Loss of epithelial cells was reduced in IMT-treated rats, with a significant decline in the peak of apoptosis 12 hours after acute ischemic renal injury. IMT did not modify the pattern of mRNA levels of several genes involved in the inflammation and regeneration processes. CONCLUSION: Our data demonstrate that IMT prevents the destruction of kidney tissue and the resulting animal death caused by renal I/R injury.