Experiences of decision making about psychotropic medication during pregnancy and breastfeeding in women living with severe mental illness: a qualitative study.

PURPOSE: The aim of this study was to explore the experiences of women living with severe mental illnesses making decisions about psychotropic medication use in pregnancy and breastfeeding, and what helped or hindered the decision-making process. METHODS: We report on a qualitative study from 12 women who attended the pregnancy service between May 2018 and June 2019. Interviews occurred at 4-6 weeks postpartum on women with severe mental illnesses, which was nested within a larger mixed-methods study. RESULTS: Three main themes were elicited from the participants' transcriptions and included (i) the decision-making process with subthemes of shared decision-making, consistency and complete care, collaboration and clear communication, and challenges of managing medication; (ii) how information is given, with subthemes of information delivery and communication breakdown; and (iii) breastfeeding dilemmas with subthemes of lithium and breastfeeding choice and autonomy regarding breastfeeding on medication. CONCLUSION: Findings offer understanding of patients' experiences in the decision-making and use of psychotropic medication during pregnancy and breastfeeding. Women living with severe mental illnesses, such as bipolar and psychosis, face difficult medication decisions due to uncertainty around use in pregnancy, potentially causing conflict with their dual role as both persons with a diagnosed mental illness but also new mothers. The clinician needs to provide comprehensible and concise information, giving space for a woman's voice to be heard to guide them from a position of hesitancy to one of assurance. Collaboration within a multidisciplinary team and external care providers combined with consistency of care assists this process.

Nutritional status, food choices, barriers and facilitators to healthy nutrition in pregnant women with severe mental illness: a mixed methods approach.

BACKGROUND: Although widely acknowledged that adequate maternal nutrition is important for mother and baby, limited research has focussed on women with severe mental illnesses (SMI) in pregnancy. The present study reports on nutritional factors and food choices and investigates barriers and facilitators to healthy nutritional choices by pregnant women with SMI. METHODS: A prospective mixed method study was undertaken of 38 pregnant women with SMI, including a cross-sectional survey, a food frequency questionnaire and 12 postnatal qualitative interviews, with integrated analysis of all data. RESULTS: Elevated rates of obesity (35%) were found, with 82% of women having above the recommended gestational weight gain. Despite perceived knowledge, 32% of women did not meet any of the Five Food Group serving recommendations for pregnancy and consumed above-recommended levels for processed (19%) and sugar snacks (51%). Thematic analysis identified four main barriers: a discrepancy between knowledge and action, food cravings, mental health, and physical health. During pregnancy, food cravings were reported in 66% of women, psychological distress in 71% and physical distress in 37%. Screening identified 19% with potential eating disordered behaviours. Despite the challenges, several facilitators were identified and covered three themes: access to a dietitian, information delivery and support, and comprehensive care. DISCUSSION: Women with SMI in pregnancy struggle with issues of obesity, gestational weight gain, food cravings and possible eating disorder behaviours. They have additional challenges when pregnant, with management of their mental health and physical health having a direct impact. Interventional strategies in this population should incorporate findings from this research.

Effectiveness of a shared team approach between nurses and doctors for improved risk factor management in survivors of stroke: a cluster randomized controlled trial.

BACKGROUND AND PURPOSE: Limited evidence exists on the benefits of organized care for improving risk factor control in patients with stroke or transient ischaemic attack. The effectiveness of an individualized management programme in reducing absolute cardiovascular disease risk in this high-risk population was determined. METHODS: This was a prospective, multicentre, cluster-randomized controlled trial with blinded assessment of outcomes and intention-to-treat analysis. Patients hospitalized for stroke/transient ischaemic attack and aged ≥18 years were recruited from four hospitals. General practices treating recruited patients were randomized to provide either usual care or an individualized management programme comprising nurse-led education and review of care plans by stroke specialists in addition to usual care. The primary outcome was a change in cardiovascular Framingham Risk Score between baseline and 12 months. RESULTS: From January 2010 to November 2013, 156 general practices (280 patients) were randomly assigned to usual care (control) and 159 (283 patients) to the intervention. The median age was 70.1 years; 65% were male. Overall, >80% of participants were prescribed recommended secondary prevention therapies at baseline. The primary efficacy analysis comprised 533 participants, with 30 either dying or lost to follow-up. In adjusted analyses, no significant between-group difference was found in the cardiovascular risk score at 12 months (0.04, 95% confidence interval -1.7, 1.8). CONCLUSIONS: The effectiveness of an organized secondary prevention programme for stroke may be limited in patients from high-performing hospitals with regular post-discharge follow-up and communication with general practices.

Epididymal specific, selenium-independent GPX5 protects cells from oxidative stress-induced lipid peroxidation and DNA mutation.

STUDY QUESTION: Can selenium (Se) independent, epididymal-specific glutathione peroxidase 5 (GPX5) protect CHO-K1 cells from oxidative damage and, more specifically, from lipid peroxidation and DNA mutation? SUMMARY ANSWER: CHO-K1 cells expressing GPX5 have increased resistance to oxidative challenge and, more specifically, decreased levels of lipid peroxidation and decreased levels of the downstream DNA lesion 8-oxo-7,8-dihydroguanine (8-oxodG) compared with control cells. WHAT IS KNOWN ALREADY: GPX5 associates with sperm during transit of the epididymis, and has been postulated to protect sperm from peroxide-mediated attack. However, its function as an active glutathione peroxidase has been questioned due to substitution of the classical selenocysteine residue at its active site. Indirect evidence for a functional role for GPX5 has been provided by in vivo studies, in particular from the GPX5 knockout mouse whereby offspring sired by GPX5(-/-) males have a higher rate of spontaneous abortion and developmental defects, attributed to increased oxidative injury (8-oxodG) to sperm DNA, but only when the GPX5(-/-) males are over 1 year of age. Interestingly, we have previously shown severely reduced levels of GPX5 in humans. STUDY DESIGN, SIZE, DURATION: To look more directly at its role in protection against oxidative damage, we have used an in vitro system, generating a CHO-K1 mammalian cell line expressing recombinant rat GPX5. PARTICIPANTS/MATERIALS, SETTING, METHODS: We have used the recombinant CHO-K1 cells to determine whether GPX5 is able to protect these cells from an administered oxidative challenge, using a range of approaches. We compared the viability of GPX5-expressing cells with control cells by both MTT and trypan blue exclusion assays. We next investigated whether GPX5 protects the cells specifically from lipid peroxidation, by using the fluorescent reporter molecule C11-BODIPY(581/591), and thus from downstream DNA mutation, by comparing levels of the DNA lesion 8-oxodG. We also investigated whether GPX5 can be transferred to rat sperm via epididymosomes. MAIN RESULTS AND THE ROLE OF CHANCE: GPX5-expressing CHO-K1 cells had increased viability compared with control cells following oxidative challenge (P < 0.005). We also found that GPX5-expressing CHO-K1 cells had significantly lower levels of C11-BODIPY(581/591) oxidation, and hence lipid peroxidation, compared with control cells. Levels of 8-oxodG DNA damage were also markedly lower in the nuclei of GPX5-expressing cells than in control cells. Finally, we showed that GPX5 can be transferred to rat sperm via epididymosomes. LIMITATIONS, REASONS FOR CAUTION: GPX5 is not active in glutathione peroxidase assays using H2O2 as the substrate. However, the related non-mammalian Se-independent GPXs show preference for electron donors other than glutathione, with a number utilizing thioredoxin as a reducing equivalent. Hence, the in vitro activity of GPX5 needs to be assessed using a range of alternative substrates and electron donors. GPX5 is secreted by the epididymis and associates with the sperm plasma membrane. We showed that this transfer can occur via epididymosomes; however, the mechanism for transfer and the identity of a potential binding partner in the sperm membrane needs to be determined. Finally, our study utilized an in vitro system that needs to be translated to human sperm. WIDER IMPLICATIONS OF THE FINDINGS: Our study supports an important role for GPX5 as an antioxidant, possibly acting as a phospholipid hydroperoxidase and participating in the maintenance of cell and DNA integrity.

Does salvage and tranexamic acid reduce the need for blood transfusion in revision hip surgery?

We carried out a retrospective case-control study in 80 patients who underwent a revision total hip replacement. Group A (40 patients) received tranexamic acid and intra-operative cell salvage. Group B (40 patients) was a matched control group and did not receive this management. Each group was divided into four subgroups: revision of both components, revision of both components with bone grafting, revision of the acetabular component with or without bone graft, and revision of the femoral component with or without bone graft. In group A the total number of units transfused was 52, compared with 139 in group B, representing a reduction in blood usage of 62.5%. The mean amount of blood transfused from cell salvage in each group was 858 ml (113 to 2100), 477 ml (0 to 2680), 228 ml (75 to 315) and 464 ml (120 to 1125), respectively. There was a significant difference in the amount of blood returned between the groups (p < 0.0001). In group A, 22 patients needed transfusion and in group B, 37 (p < 0.0001). A cost analysis calculation showed a total revenue saving of pounds sterling 70 000 and a potential saving throughout our facility of pounds sterling 318 288 per year. Our results show that a significant reduction in blood transfusion can be made using combined cell salvage and tranexamic acid in revision surgery of the hip.

Regulation of oxytocin production by purified adult rat Leydig cells in vitro: effects of LH, testosterone and lipoproteins.

The aim of the present study was to determine whether LH stimulates oxytocin production by adult rat Leydig cells directly or indirectly via testosterone. Purified adult rat Leydig cells were cultured in the presence or absence of 0.1 ng/ml LH or 1, 10 or 100 ng/ml testosterone for 22 h. Culture medium was collected at 2-hourly intervals and assayed for oxytocin and testosterone. In the presence of LH, Leydig cells produced significantly higher levels of both testosterone (basal production 1.4 +/- 0.13 ng, LH-stimulated 4.1 +/- 0.13 ng/10(6) cells per 2 h) and oxytocin (basal production 8.3 +/- 1.2 pg, LH-stimulated 20.2 +/- 1.3 pg/10(6) cells per 2 h). Testosterone also stimulated oxytocin secretion. However, the increase was smaller compared with that seen with LH and was not found to be dose-dependent. Furthermore, testosterone production was only significantly increased by LH during the first 10 h of the 22-h culture period whereas LH stimulated oxytocin production throughout the whole culture period. To further determine the effect of LH on oxytocin production, cultures were performed in the presence of LH and/or 400 microM aminoglutethimide. In the presence of aminoglutethimide both the basal and LH-stimulated production of testosterone was significantly reduced. However, in the same cultures aminoglutethimide did not alter either the basal or LH-stimulated production of oxytocin. These data show that LH does not act via testosterone to stimulate oxytocin production and therefore acts directly or by some alternative indirect mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of germ cell complement on the presence of oxytocin in the interstitial and seminiferous tubule fluid of the rat testis.

In the rat testis oxytocin has been localized to the Leydig cells, and these cells have been shown to produce oxytocin in vitro. The present study was performed to determine whether oxytocin is present in the interstitial fluid (IF) and seminiferous tubule fluid (TF) of the rat and whether concentrations of the peptide vary within the two compartments following germ cell destruction. In order to destroy germ cells adult male rats were anaesthetized and their scrotal regions placed in a water bath at 43 degrees C for 20 min. Control animals were subjected to anaesthesia alone. Groups of 6 animals were killed 3, 7 and 21 days after heat treatment and their testes removed for histological examination or fluid extraction. IF and TF were separated and the oxytocin content of the fluids measured by radioimmunoassay. Immunoreactive oxytocin was detected in both the IF (100 +/- 11 pg/ml) and TF (27 +/- 4 pg/ml) of control rats and this immunoreactivity co-eluted with the authentic peptide following HPLC. Three days after heat treatment IF levels of oxytocin were significantly reduced but TF levels of the peptide were significantly increased. These changes were associated with a lack of pachytene spermatocytes in the histological sections. Seven and 21 days after heat treatment the levels of oxytocin in the IF and TF were not significantly different from control levels. Similar changes in IF and TF oxytocin levels were seen in a second experiment when pachytene spermatocytes were removed using the testicular toxicant methoxyacetic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

The potential use of sperm antigens as targets for immunocontraception; past, present and future.

Immunocontraception, and in particular the targeting of antibodies to gamete-specific antigens implicated in sperm egg binding and fertilisation, offers an attractive approach to the growing global problem of overpopulation. Such an idea is not new; indeed several immunocontraception trials, using animal model systems, have been reported in recent years and a number are reviewed here. However, the results of these studies have been largely disappointing. We believe that two fundamental flaws attribute to the poor success of most of these preliminary immunocontraceptive trials. Firstly, loss of fertility has invariably been used as the assay. This presupposes that immuno-neutralisation of a single, gamete-specific antigen will be sufficient to cause a significant reduction in fertility; however, recent data suggests that such a premise may not be well-founded for a number of reasons. Secondly, and arguably the most important flaw, is the almost universal, but largely inappropriate, use of systemic immunisation as the sole route of antigen delivery. Whilst systemic immunisation regimes may lead to high serum IgG levels, these levels do not correlate with specific antibody levels in the reproductive tract or with contraceptive efficacy. Hence, an alternative antigen delivery approach is required which will induce an effective local immune response in the reproductive tract. Here we discuss the ways in which this might be achieved.

Highly selective targeting of ovarian cancer with the photosensitizer PEG-m-THPC in a rat model.

Photodynamic therapy (PDT) uses light to activate a photosensitizer that has been absorbed or retained preferentially by cancer cells after systemic administration. The first pegylated photosensitizer, tetrakis-(m-methoxypolyethylene glycol) derivative of 7,8-dihydro-5,10,15,20-tetrakis(3-hydroxyphenyl)-21,23-[H]-porphyrin (PEG-m-THPC), was evaluated to target selectively unresectable pelvic ovarian cancer bulks. Our goals were two-fold: (1) to establish an ovarian cancer model suitable for the development of debulking techniques and (2) to characterize the pharmacokinetics and tumor selectivity of PEG-m-THPC by fluorescence microscopy. NuTu-19 ovarian cancer cells were injected into the caudal part of the right psoas muscle of Fisher rats. Five weeks later, 30 mg/kg body weight of PEG-m-THPC was injected intravenously. Necropsy was performed between 4 and 10 days following drug application, and fluorescence of the tumor and various abdominal organs was measured. All rats developed bulky pelvic tumors with an average diameter of 2.6 cm (+/- 0.6 SD). Tumor masses were encompassing and infiltrating pelvic organs in a similar manner to ovarian cancers in humans. Fluorescence of cancer tissue was maximal 8-10 days following drug application. At 8 days, the tumor-to-tissue ratio was 40:1 (+/- 12 SE) for most abdominal organs. We conclude that this tumor model may be used for the study of new pelvic debulking techniques, and that the tumor selectivity of PEG-m-THPC is exceptionally high 8 days after drug application. Based on these data, we are currently developing a PDT-based minimally invasive debulking technique for advanced ovarian cancer.

Stereotactic fine needle aspiration biopsy (SFNB) of breast: preliminary results in Perth with the TRC mammotest machine. Cytological aspects.

Stereotactic fine needle aspiration biopsy (SFNB) was carried out on 404 mammographically detected impalpable breast lesions from 389 women between October 1988 and January 1990. Seventy-three lesions were excised, and 38 were carcinomas. Thirty-six of the 38 carcinomas had been diagnosed as atypical, suspicious or malignant by cytology; in the remaining 2 only fat and fibrous tissue were present in smears. The sensitivity of cytological diagnosis in detecting malignancy was therefore 94.8% (36 of 38 cases). A cytological diagnosis of malignancy was made in 23 cases (5.7%) and in 5 (1.2%) the findings were suspicious of malignancy. All of these were confirmed as carcinoma histologically; the predictive value of a positive cytological diagnosis was therefore 100%. In 32 cases (7.9%) the cytological findings were atypical but inconclusive. Twenty-three of these lesions were excised, and 8 proved to be carcinoma (34.8%). No case assessed radiologically and cytologically as benign has subsequently proven to be malignant. Twenty-two of 28 cases of invasive carcinoma were given an unequivocal cytological diagnosis of malignancy; 2 were suspicious of malignancy, and in 3 the findings were atypical but inconclusive. Of the 10 pure duct carcinoma-in-situ (DCIS) lesions, (26.3% of the cancers) 1 was diagnosed cytologically as malignant, 3 as suspicious of malignancy, and 5 as atypical. The sensitivity of SFNB in detecting DCIS lesions was therefore similar to invasive carcinomas, but cases of DCIS were more likely to be given a suspicious or atypical diagnosis rather than a definite diagnosis of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS)

MHC Class II positive cells and T cells in the equine endometrium throughout the oestrous cycle.

The quantity and distribution of MHC Class II positive cells and T cells in the equine endometrium was investigated throughout the oestrous cycle. Significantly more MHC Class II positive cells were detected in the stratum compactum and stratum spongiosum of endometria from naturally cycling mares during the follicular than during the luteal phase of the oestrous cycle. Significantly more T cells were also detected in the stratum compactum, but not stratum spongiosum, of these mares during the follicular phase. Furthermore, there was a marked increase in the number of MHC Class II positive cells and T cells in the endometria of ovariectomised mares treated with oestradiol compared with progesterone. An increase in the expression of MHC Class II antigen by endometrial epithelial cells was also observed in mares treated with oestradiol and in some naturally cycling mares during the follicular phase.

Detection of tetanus toxoid-specific memory T cells in equine lymph nodes but not in peripheral blood.

The use of tetanus toxoid as a recall antigen to investigate equine immune responses would be, in theory, a useful and cost-effective model in vitro. However, by using various regimens for culturing peripheral blood mononuclear cells from horses previously immunised with toxoid no proliferative response to the antigen was obtained in vitro, whereas lymph node mononuclear cells from the same animals proliferated significantly in response to it. The lack of response by the peripheral blood mononuclear cells was not due to the presence of a suppressive factor but to a lack of recognition of the antigen by the T cells of the peripheral blood.

Cerebrovascular disease in type 1A glycogen storage disease.

Glycogen storage diseases are a group of genetic disorders involving pathways for storage of glycogen and its utilization to maintain blood glucose. Clinical manifestations include hypoglycaemia, hepatomegaly, delayed adolescence and hyperlipidaemia. Hyperlipidaemia is frequent and patients surviving long enough are thought to be at increased risk of atherosclerosis. However, no cases have previously been reported. Presented is a 27-year-old male with glycogen storage disease type 1A who sustained a pontine infarction due to basilar artery stenosis. It is believed the cause of this infarction was accelerated atherosclerosis. This is of major significance to those with this disease process who are now surviving into their third and later decades due to improved management of this condition.

A re-evaluation of sperm protein 17 (Sp17) indicates a regulatory role in an A-kinase anchoring protein complex, rather than a unique role in sperm-zona pellucida binding.

Sp17 was originally proposed to be a sperm-specific protein and thought to play a role in sperm-egg interactions by binding to the zona pellucida via two conserved heparin-binding motifs. However, more recent data indicate that it may be expressed more widely, both in tumours and in normal somatic tissues. The complete nucleotide and deduced amino acid sequences of human Sp17 transcripts are reported and it is shown that they are expressed in a wide range of tissues, albeit at a much lower expression than in the testis. On the basis of the extremely high sequence conservation throughout the N-terminal half of Sp17, and the presence within this region of an A-kinase anchoring protein (AKAP)-binding motif, it is postulated that the proposed role of Sp17 in zona pellucida binding is unlikely to be its principal function.

Listeria rhomboencephalitis.

Listeria rhomboencephalitis is a rare form of listeriosis which is frequently not diagnosed before death. We here describe an instance in an apparently healthy immunocompetent lady which responded to appropriate therapy. Treatment with intravenous ampicillin with or without an aminoglycoside antibiotic should be instituted early if the patient is to survive.

Mammalian sperm-egg recognition: does fertilin beta have a major role to play?

The advent of simple in vitro fertilisation techniques has provided the reproductive biologist with an invaluable system for assaying sperm fertilising ability. In particular, they provide a useful way of identifying and characterising gamete-specific proteins that play a role in sperm-egg interactions, and in recent years, a growing number of sperm surface proteins have been identified that appear to be involved in these processes. Fertilin beta was one of the first sperm membrane proteins to be implicated in egg interactions and it has been proposed that this is mediated by means of binding of its disintegrin-like domain to cognate integrin receptors on the egg plasma membrane. A recent paper in Science by Cho and colleagues [Cho et al. 1998. Fertilisation defects in sperm from mice lacking fertilin beta. Science 281: 1857-1859 (Ref. 1)] provides preliminary data on a fertilin beta knockout mouse. Whilst fertilin beta null males had greatly reduced fertility, somewhat surprisingly, this could be largely attributed to causes other than impaired binding to the egg plasma membrane.

Thoracic intervertebral disc protrusion with spinal cord compression.

Four patients presenting with spinal cord compression and spinal nerve root irritation are described. The clinical and radiological features are described and the contribution of CT scanning to accurate diagnosis of this condition is highlighted. Review of the literature indicates that the natural history of this disorder is one of steadily progressive neurological dysfunction. Surgical decompression of the lesion, although hazardous, is the only therapeutic option. Brief comment is made on the neurosurgical approaches currently in vogue.

The gene for the human tMDC I sperm surface protein is non-functional: implications for its proposed role in mammalian sperm-egg recognition.

The sperm surface antigen tMDC I (also known as cyritestin) has been proposed to play a role in sperm-egg binding in the mouse via an interaction between its disintegrin-like domain and an integrin receptor on the oolemma plasma membrane. Here we report the cloning and sequence of human tMDC I transcripts and show that they are non-functional, owing to the presence of a variety of deletions, insertions and in-frame termination codons. The absence of a tMDC I protein is further supported by the lack of immunoreactivity on Western blots of human testis and sperm extracts probed with macaque (Macaca fascicularis) and human anti-tMDC I antisera.

Peripheral neuropathy with gammopathy responding to plasmapheresis.

Two patients with subacute sensorimotor peripheral neuropathy were found to have benign gammopathies. They both responded to treatment by plasmapheresis. We suggest that a vigorous search for a paraprotein should be made in all undiagnosed patients presenting with peripheral neuropathy, including electrophoresis with isoelectric focusing. Plasmapheresis may be a treatment modality that should be explored in such cases.