How spirituality is understood and taught in New Zealand medical schools.

OBJECTIVES: The objective of this research was to explore how spirituality is currently understood and taught in New Zealand Medical Schools. METHODS: A mixed methods study was carried out involving interviews (n = 14) and a survey (n = 73). The first stage of the study involved recorded semi-structured interviews of people involved in curriculum development from the Dunedin School of Medicine (n = 14); which then informed a cross-sectional self-reported electronic survey (n = 73). RESULTS: The results indicate that spirituality is regarded by many involved in medical education in New Zealand as an important part of healthcare that may be taught in medical schools, but also that there is little consensus among this group as to what the topic is about. SIGNIFICANCE OF RESULTS: These findings provide a basis for further discussion about including spirituality in medical curricula, and in particular indicate a need to develop a shared understanding of what 'spirituality' means and how it can be taught appropriately. As a highly secular country, these New Zealand findings are significant for medical education in other secular Western countries. Addressing spirituality with patients has been shown to positively impact a range of health outcomes, but how spirituality is taught in medical schools is still developing across the globe.

Perceived barriers and facilitators to physical activity in men with prostate cancer: possible influence of androgen deprivation therapy.

While physical activity is beneficial for men with prostate cancer, too few perform sufficient activity for such benefit. This study examined perceptions of men with prostate cancer of their barriers and facilitators to physical activity, and how androgen deprivation therapy (ADT) may influence these perceptions. Two focus groups were conducted, involving six ADT and eight non-ADT patients respectively. Data were transcribed verbatim and themes developed using a general inductive thematic approach. Facilitators to physical activity common to both groups of cancer survivors included clinician and spousal involvement, with pre-existing co-morbidities and increased age cited as barriers by both groups. The ADT subgroup cited personal involvement as a facilitator to physical activity, with fatigue, reduced motivation and a relative lack of specific advice from their clinician as additional barriers. The non-ADT subgroup had no additional facilitators to physical activity but cited time constraints as a barrier. These results highlight the important role that cancer clinicians and spouses play in promoting physical activity for men with prostate cancer and how ADT may influence their other facilitators and barriers. As physical activity is beneficial for prostate cancer survivors, especially those on ADT, cancer clinicians should regularly discuss physical activity with their patients.

JAK2 V617F tyrosine kinase mutation in cell lines derived from myeloproliferative disorders.

A mutation in the JH2 pseudokinase domain of the Janus kinase 2 gene (JAK2 V617F) has been described in chronic myeloproliferative disorders (MPD). We screened 79 acute myeloid leukemia (AML) cell lines and found five positive for JAK2 V617F (HEL, MB-02, MUTZ-8, SET-2, UKE-1), 4/5 with histories of MPD/MDS. While SET-2 expressed both mutant (mu) and wild-type (wt) JAK2, remaining positives carried homo-/hemizygous JAK2 mutations. Microsatellite analysis confirmed losses of heterozygosity (LOH) affecting the JAK2 region on chromosome 9p in MB-02, MUTZ-8 and UKE-1, but also in HEL, the only JAK2mu cell line lacking any reported MPD/MDS history. All five JAK2mu cell lines displayed cytogenetic hallmarks of MDS, namely losses of 5q or 7q, remarkably in 4/5 cases affecting both chromosomes. Our combined FISH and microsatellite analysis uncovered a novel mechanism to supplement mitotic recombination previously proposed to explain JAK2 LOH, namely chromosome deletion with/without selective JAK2mu amplification. Confirming the importance of the mutated JAK2 protein for growth and prevention of apoptosis, JAK2mu cell lines displayed higher sensitivities to JAK2 inhibition than JAK2wt cell lines. In summary, JAK2 V617F cell lines, derived from patients with history of MPD/MDS, represent novel research tools for elucidating the pathobiology of this JAK2 mutation.

Early clinical exposure to people who are dying: learning to care at the end of life.

BACKGROUND: The nature of medical care at the end of life and, in particular, the way in which caring is learned remain problematic for medical educators and the profession. Recent work has indicated that doctors learn to care, in an emotional and intimate way, from people who are dying. METHODS: This paper reports on the development of a programme designed for medical students in their first clinical year who spend time with a person who is dying and their family. The students are required to produce a portfolio assignment that includes a personal reflection of the experience. The findings from a phenomenological study undertaken using these personal reflections are reported. These reflections and comments are interpreted as being embedded in five key themes. RESULTS: The actual encounters differed from the medical students' anticipation of them. Students identified an emotional component to the experience; they explored their own and the patient's understandings of spirituality; they reflected on personal meanings of the encounter and they suggested ways in which they might learn to care more effectively for people who are dying. DISCUSSION: The way in which many of these students approach end-of-life care has been altered through a transformative educational experience that encouraged them to draw on their own experiences and skills. Their learning was facilitated by the writing of accounts and the discussion that each group held with teaching staff at the conclusion of the programme.

On reflection: doctors learning to care for people who are dying.

Humane care is an essential component of the doctor's role at the end of life. Over the last 20 years, there has been a steady global increase in the extent and variety of medical teaching about the care of people who are dying. In some countries, palliative medicine is now recognised as a discrete medical specialty. Rightly, much emphasis has been placed on symptom management, communication skills and ethical issues. But rarely does the concept of care, or how doctors learn to care, emerge in the medical literature. The concept of "care" is usually defined as a professional behaviour: attending to a patient's needs. Yet, the concept of care also requires a professional commitment on a more holistic level. To care is to be receptive to and responsible for others. This is care motivated by true empathy: a concern for the patient's well-being that comes from a sensitive identification with the patient's situation. This paper reports some of the findings from an interpretive phenomenological study involving 10 doctors and their experiences of learning to care for people who were dying. The doctors came from differing medical disciplines and had varying levels of experience. During the interviews the doctors retrospectively identified "turning points" at which they first perceived some notion of what it means to care for someone who is dying. The doctors often used poignant language when recollecting the strong feelings associated with these critical incidents. They felt that their training had been inadequate in preparing them for such care. The article asks whether their medical education had adequately prepared these doctors for this key element of their work. It recommends ways in which practitioners may be better prepared to care for people who are dying.

Characterization of the inhibitory effect of boiled rice on intestinal chloride secretion in guinea pig crypt cells.

BACKGROUND & AIMS: When rice is incorporated into oral rehydration therapy for patients with secretory diarrhea, clinical outcomes improve. We have shown that a factor purified from boiled rice (RF) blocks the secretory response of intestinal crypt cells to adenosine 3',5'-cyclic monophosphate (cAMP). Now we report that the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the cellular target for this rice inhibitor. METHODS: We used RF, the same previously described extract prepared from boiled rice, to assess chloride channel activation in vitro, measuring (1) cell volume regulation of guinea pig intestinal crypt epithelial cell suspensions using standard Coulter counter technology, (2) transepithelial chloride current in monolayers of T84 cells mounted in Ussing chambers, and (3) whole-cell and single-channel currents using the patch-clamp technique in cells transfected to express CFTR. RESULTS: RF inhibited activation by cAMP of CFTR chloride channels in all experimental preparations; RF did not block volume-stimulated Cl- secretion, suggesting that its effect might be specific for CFTR chloride channels. RF inhibited transepithelial cAMP-stimulated Cl- current in T84 cells and inhibited forskolin (i.e., cAMP)-induced current in cells transfected with CFTR. Excised patch and single-channel patch-clamp recordings supported the view that the response was a direct effect on CFTR rather than on cAMP signal transduction. CONCLUSIONS: RF exerts a specific inhibitory effect on CFTR chloride channels, blocking activation from the luminal surface of the cell and reversing established activation. Many major diarrheal states are based on cAMP-induced CFTR activation, leading to excessive gut secretion; our findings could have clinical relevance.

Inhibition of intestinal secretion by rice.

Rates of stool output are reduced when cooked rice is incorporated into oral rehydration solutions. We found that a fraction extracted from rice inhibited the response of intestinal epithelial crypt cells to adenosine 3'5'-cyclic monophosphate, a major intracellular mediator of secretion. This response to rice was seen as an inhibition of cell shrinkage and of chloride efflux in fresh suspended guinea pig crypt cells. The active fraction was of low molecular weight (< 1.5 kDa), hydrophobic, and not a peptide or glycoprotein. It may be chloride-channel blocker.

Endotoxin-induced release of interleukin-6 from rat medial basal hypothalami.

Interleukin-6 (IL-6) is an inflammatory cytokine that stimulates T-cell activation and B-cell differentiation. We recently reported that picomolar concentrations of IL-6 stimulated PRL, GH, and LH release in vitro. These data suggested that IL-6 may function as a hypothalamic releasing factor for anterior pituitary hormones. Medial basal hypothalami (MBH) were incubated for 60-90 min in Krebs-Ringer bicarbonate buffer supplemented with 0.025% BSA, and the conditioned medium was assayed for IL-6 concentrations by the 7TD1 cell growth factor assay. It was found that MBH released IL-6 in vitro. Although depolarizing concentrations of K+ (56 mM) did not increase IL-6 release, somatostatin release from the MBH was increased significantly. The bacterial endotoxin lipopolysaccharide (LPS; 1-100 ng/ml) induced significant increases in IL-6 release from the MBH. The presence of IL-6 in the hypothalamus suggested a possible role for this cytokine in the regulation of neuropeptide release; however, the release of somatostatin was not affected by 20 ng/ml IL-6. Comparison studies of neural and neuroendocrine tissues revealed that the anterior and posterior pituitaries released larger amounts of bioactive IL-6 than the MBH or parietal cortex during a 4-h incubation; induction of IL-6 release by endotoxin occurred only in the anterior pituitary and hypothalamus. IL-6 mRNA was detectable in the MBH and anterior pituitary tissue after a 4-h incubation; however, no IL-6 mRNA was detectable in freshly isolated tissues. LPS (100 ng/ml) and (Bu)2cAMP (1 mM) increased IL-6 mRNA accumulation in and IL-6 release from the MBH and anterior pituitary. These data suggest that the MBH synthesizes and releases IL-6 via a nonneuronal source in vitro.

Plasma cell gingivitis related to the use of herbal toothpaste.

Plasma cell gingivitis is an uncommon condition, characterised by a sharply demarcated, erythematous and oedematous gingivitis, often extending to the mucogingival junction. The condition is generally considered to be a manifestation of hypersensitivity, but often no antigenic agent can be identified. This report describes a case of plasma cell gingivitis, apparently associated with the use of a herbal toothpaste.

Gonadotropin-releasing hormone-stimulated phosphoinositide hydrolysis in the anterior pituitary. Modulation by protein kinase C but not by cyclic nucleotides.

Gonadotropin-releasing hormone (GnRH) produces a rapid and concentration-dependent hydrolysis of polyphosphoinositides in rat anterior pituitary cells in culture. Evaluation of the action of the decapeptide by measurement of [3H]-inositol phosphates and of prelabeled phosphoinositides demonstrated an effect on phosphatidylinositol-4,5-bis-phosphate and phosphatidylinositol-4-phosphate earlier than on phosphatidylinositol. The receptor antagonist [D-pGlu1,D-Phe2,D-Trp3,6]-luteinizing hormone-releasing hormone blocked the effect of GnRH on [3H]-inositol phosphate production. Protein kinase C activators attenuated GnRH-induced phosphoinositide hydrolysis, while neither cyclic AMP analogs nor cyclic GMP analogs were effective. These results indicate that phosphoinositide hydrolysis represents an important postreceptor transducing mechanism for GnRH action at the gonadotroph and that protein kinase C (but not cyclic nucleotides) may exert a negative feedback control on GnRH receptor-coupling mechanisms.

Effects of iodine deficiency and high-fat diet on N-nitrosomethylurea-induced mammary cancers in rats.

The effects of an altered content of dietary iodine and fat on the development of N-nitrosomethylurea-induced mammary tumors in rats were studied and correlated with thyroid and pituitary function studies. In three separate experiments, animals fed a semisynthetic diet containing 11.8% fat had an earlier time of tumor appearance and greater tumor burden than did controls maintained on a diet containing 4.6% fat. These diet-associated changes were markedly inhibited by ovariectomy, indicating that the tumor growth was hormone responsive. We examined the possibility that the diet with increased fat content enhanced tumor growth through alterations in prolactin metabolism but could find no consistent elevation in serum prolactin and no increase in pituitary prolactin synthesis in vitro. Our data further showed that rats on an iodine-deficient form of the high-fat diet had no greater tumor growth than did animals receiving an iodine-supplemented form of the same diet. We conclude from these results that iodine deficiency does not promote mammary tumorigenesis. An incidental finding of great interest was that ovariectomy led to a highly significant depression of thyroid-stimulating hormone production in vitro. This suggests that estrogens may directly influence thyroid-stimulating hormone synthesis in vivo and thus contribute to the sex-related differences in thyroid physiology.

Effect of prolactin on dopamine synthesis in medial basal hypothalamus: evidence for a short loop feedback.

Several procedures were utilized to study the effects of prolactin on dopamine synthesis in the medial basal hypothalamus of the rat. Elevation of serum prolactin was produced by the administration of trifluoperazine (5 mg/kg, i.p.) and resulted in a significant increase in the conversion of [3',5'-3H]tyrosine to dopamine when measured in slices of medial basal hypothalamus and striatum. Hypophysectomy abolished this effect of trifluoperazine in the medial basal hypothalamus but not in the striatum. In addition, the synthesis of dopamine was significantly elevated in slices of medial basal hypothalamus obtained from rats bearing pituitary tumor implants that secreted microgram quantities of prolactin. In contrast, the in vitro synthesis of dopamine in the striatum of such rats was increased by the secretory products in one tumor line but decreased in another compared to that observed in control animals. It is suggested that the ability of prolactin to accelerate the synthesis of dopamine in the medial basal hypothalamus might constitute a short loop feedback system that finely regulates prolactin secretion.

Control of prolactin secretion by the hypothalamic catecholamines.

The neuroendocrine control of prolactin secretion is very complex. Even though the hypothalamus exerts a profound inhibitory influence upon the secretion of this hormone, the mechanism(s) involved is poorly understood. The cerebrospinal fluid seems to be becoming increasingly important as regards neuroendocrine regulatory mechanisms involving prolactin. Pharmacological agents such as apomorphine and many of the ergot alkaloids are very effective inhibitors of the secretion of prolactin. Still other pharmacological agents such as DMPEA, alpha-methyldopa, reserpine, and certain of the phenothiazines are very effective in causing a stimulation of prolactin secretion.