Changes in early psychosis service provision: a file audit

OBJECTIVE: To measure change in services provided to young people with first-episode psychosis following the introduction of specialized early psychosis teams and staff training. METHOD: A standardized tool was developed to audit services provided to young people with first-episode psychosis. The tool initially comprised 27 clinical indicators measuring aspects of optimal care derived from the Australian clinical guidelines for early psychosis. The first 12 months of treatment, as documented in the case records, were audited for all young people receiving their first treatment for psychosis during a 6-month period prior to the introduction of these service developments (n = 47). These subjects were compared with those who received treatment after the implementation of service development strategies (n = 70). A comparison was also made within the second group, between those receiving some treatment from a specialized early psychosis team and those being exclusively treated by other services. RESULTS: Inter-rater reliability was achieved for 24 of the 27 indicators. Improvements were found on 10 indicators which measured psychosocial interventions, prescribing practices, family interventions and continuity of care. There was no significant deterioration on any of the indicators. Clients who attended early psychosis teams were significantly more likely to receive psychoeducation. CONCLUSIONS: The services increased their provision of "guideline concordant" care for early psychosis. The audit proved useful to monitor performance, to demonstrate improvements in care and to identify those areas of service provision and documentation in need of improvement.     

6-Hydroxymelatonin protects against cyanide induced oxidative stress in rat brain homogenates

Both 6-hydroxymelatonin and N-acetyl-N-formyl-5-methoxykynurenamine are photodegradants and enzymatic metabolites of melatonin and are known to retain equipotent activity against potassium cyanide-induced superoxide generation compared to melatonin. It is not clear whether one or both of these metabolites is responsible for this effect. The present study therefore investigates the possible manner in which 6-hydroxymelatonin protects against oxidative stress induced by cyanide in rat brain homogenates. We examined the ability of 6-hydroxymelatonin to scavenge KCN-induced superoxide anion generation as well as lipid peroxidation. In addition, we also examined the effect of this indole on lactate dehydrogenase activity (LDH) as well as mitochondrial electron transport using dichlorophenol-indophenol as an electron acceptor. The results of this study show that 6-hydroxymelatonin significantly reduces KCN-induced superoxide anion generation, which is accompanied by a commensurate reduction in lipid peroxidation. Partial reversal of the KCN-induced reduction in mitochondrial electron transport is accompanied by a similar reversal of mitochondrial LDH activity blunted by KCN. It can thus be proposed that 6-hydroxymelatonin is potentially neuroprotective against KCN-induced neurotoxicity.     

Spinal neuronal responses to urinary bladder stimulation in rats with corticosterone or aldosterone onto the amygdala

Elevating glucocorticoids in the amygdala produces colorectal hypersensitivity through activation of lumbosacral spinal neurons. The aim of this study was to determine if descending modulation from the amygdala affects spinal processing of input from urinary bladder afferents. Fischer-344 rats received cholesterol (inactive control)-, corticosterone-, or aldosterone-containing micropellets placed stereotaxically on the dorsal margin of the left and right amygdala (n = 10 for each group). Seven days after amygdaloid implantation, extracellular potentials of single L6-S1 spinal neurons were examined for the responses to graded (0.5-2.0 ml, 20 s) urinary bladder distension (UBD). Spontaneous activity of neurons with excitatory responses to UBD in aldosterone-implanted rats [11.0 +/- 1.7 (SE) imp/s], but not in corticosterone-implanted rats, was higher than in the cholesterol-implanted group (6.6 +/- 1.1 imp/s, P < 0.05). Noxious UBD (1.5 ml) produced a greater excitatory response (21.6 +/- 2.6 imp/s) in aldosterone-implanted rats compared with cholesterol- or corticosterone-implanted rats (15.1 +/- 1.5 and 13.6 +/- 1.4 imp/s; P < 0.05). In contrast, the duration of excitatory responses to UBD in corticosterone-implanted rats (38.5 +/- 3.4 imp/s) was significantly longer than those in the aldosterone or control groups (26.8 +/- 1.8 and 24.7 +/- 1.5 imp/s). Neurons with low thresholds for excitatory responses to UBD were seen more frequently in aldosterone-implanted rats than in corticosterone or cholesterol treated rats (74 vs. 44% and 39%, P < 0.05). No difference in somatic field properties of spinal neurons responsive or nonresponsive to UBD was found among the three groups. These findings suggest that both mineralocorticoid- and glucocorticoid-mediated mechanisms in the amygdala are involved in descending modulation to lumbosacral spinal neurons receiving inputs from the urinary bladder; and this mechanism may play a role in the activation and maintenance of primary central sensitization to noxious visceral stimuli.     

Functional genetic identification of PRP1, an ABC transporter superfamily member conferring pentamidine resistance in Leishmania major

Pentamidine (PEN) is a second-line agent in the treatment of leishmaniasis whose mode of action and resistance is not well understood. Here, we used a genetic strategy to search for loci able to mediate PEN resistance (PENr) when overexpressed in Leishmania major. A shuttle cosmid library containing genomic DNA inserts was transfected into wild-type promastigotes and screened for PEN-resistant transfectants. Two different cosmids identifying the same locus were found, which differed from other known Leishmania drug resistance genes. The PENr gene was mapped by deletion and transposon mutagenesis to an open reading frame (ORF) belonging to the P-glycoprotein (PGP)/MRP ATP-binding cassette (ABC) transporter superfamily that we named pentamidine resistance protein 1 (PRP1). The predicted PRP1 protein encodes 1,807 amino acids with the typical dimeric structure involving 10 transmembrane domains and two nucleotide-binding domains (NBDs). PRP1-mediated PENr could be reversed by verapamil and PRP1 overexpressors showed cross-resistance to trivalent antimony but not to pentavalent antimony (glucantime). Although the degree of PENr was modest (1.7- to 3.7-fold), this may be significant in clinical drug resistance given the marginal efficacy of PEN against Leishmania.     

Effect of gonadotropin-releasing hormone agonist and medroxyprogesterone acetate on calcium metabolism: a prospective, randomized, double-blind, placebo-controlled, crossover trial

OBJECTIVE: The purpose of this study was to prospectively compare the effectiveness of administering medroxyprogesterone acetate (MPA; 20 mg/d) in either the first (protocol A) or last (protocol B) 12-week period as well as a 6-month course of the GnRH agonist (GnRH-a; leuprolide acetate; 1 mg/d, SC) on calcium (Ca) metabolism. DESIGN: Prospective, randomized, double-blind, placebo-controlled, crossover trial. SETTING: Clinical research center, university hospital. PATIENT(S): Twenty women were randomized into protocol A or B, received either MPA or placebo along with GnRH-a, and were then crossed over at 12 weeks to placebo or MPA, for the final 12-week interval of GnRH-a therapy. INTERVENTION(S): Collection of serum and urine samples and measurement of bone density.Sex hormone, calcitropic hormone, and bone density studies were performed at baseline and at 12 and 24 weeks. RESULT(S): In both protocol A and B, LH and E(2) levels declined by 79%-81% and 83%-90% of the baseline, respectively, at 12 and 24 weeks. Serum Ca, phosphorus, alkaline phosphatase, and osteocalcin; 2-h fasting and 24-h urinary Ca excretion; and urinary hydroxyproline levels all increased significantly during GnRH-a treatment alone. Estimated Ca balance decreased significantly during GnRH-a treatment alone. The addition of MPA attenuated the increases in phosphorus, alkaline phosphatase, osteocalcin, and 2-h fasting and 24-h urinary Ca excretion, and the decrease in estimated Ca balance. Comparison of phase order demonstrated that MPA prevented 24-h urinary Ca excretion and urinary hydroxyproline loss and decline in estimated Ca balance when it was added back during the second 12 weeks (protocol B) but not during the first 12 weeks (protocol A). CONCLUSION (S): We conclude that sequential MPA appears to reverse in part the negative effects of GnRH-a on calcitropic hormones and estimated Ca balance.     

Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function

OBJECTIVE: We have previously reported a reduced incidence of preeclampsia in women who were at risk and were taking vitamin C (1000 mg/d) and vitamin E (400 IU/d) supplements. In this study, we determined whether supplementation in the same cohort was associated with an improvement in indices of placental dysfunction and oxidative stress toward values determined in women who were at low risk of preeclampsia. STUDY DESIGN: Seventy-nine women who were at high risk and who were taking vitamin supplements and 81 who were taking placebos were compared with 32 women who were at low risk and who were not taking supplements who were studied simultaneously. RESULTS: Indices of oxidative stress and placental function were abnormal in the placebo group. When the placebo group was compared with the women who were at low risk, ascorbic acid, plasminogen activator inhibitor-2, and placenta growth factor concentrations were decreased; and 8-epi-prostaglandin F(2alpha),leptin, and the plasminogen activator inhibitor-1/-2 ratio were increased. In the group that received vitamin supplements, ascorbic acid, 8-epi-prostaglandin F(2alpha), leptin, and plasminogen activator inhibitor-1/-2 values were similar to women who were at low risk. CONCLUSION: Antioxidant supplementation in women who were at risk of preeclampsia was associated with improvement in biochemical indices of the disease.     

What is a 'normal' midwife?

When you look through job advertisements these days, there are many different titles for midwifery roles. From Consultant to Research & Development Midwife, breastfeeding specialist to Sure Start ... it makes me wonder what has happened to the 'normal' midwife. Last year (June 2001) we had a focus on Normal Birth--this time we are asking, what is a 'normal' midwife? What skills does she/he have? What does she/he do to keep things 'normal'? A clinical midwife, a researcher, an educationalist and a consumer give us their views.