Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic.

BACKGROUND: Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews. METHODS: All eligible women between 33 and 46 years at ≥17% lifetime risk of breast cancer and undergoing annual mammography in our service were invited to take a 5-year course of tamoxifen. Reasons for accepting (n=15) or declining (n=15) were explored using semi-structured interviews. RESULTS: Of 1279 eligible women, 136 (10.6%) decided to take tamoxifen. Women >40 years (74 out of 553 (13.4%)) and those at higher non-BRCA-associated risk were more likely to accept tamoxifen (129 out of 1109 (11.6%)). Interviews highlighted four themes surrounding decision making: perceived impact of side effects, the impact of others' experience on beliefs about tamoxifen, tamoxifen as a 'cancer drug', and daily reminder of cancer risk. CONCLUSIONS: Tamoxifen uptake was similar to previously ascertained uptake in a randomised controlled trial (IBIS-I). Concerns were similar in women who did or did not accept tamoxifen. Decision making appeared to be embedded in the experience of significant others.

Systematic review of skills transfer after surgical simulation-based training.

BACKGROUND: Simulation-based training assumes that skills are directly transferable to the patient-based setting, but few studies have correlated simulated performance with surgical performance. METHODS: A systematic search strategy was undertaken to find studies published since the last systematic review, published in 2007. Inclusion of articles was determined using a predetermined protocol, independent assessment by two reviewers and a final consensus decision. Studies that reported on the use of surgical simulation-based training and assessed the transferability of the acquired skills to a patient-based setting were included. RESULTS: Twenty-seven randomized clinical trials and seven non-randomized comparative studies were included. Fourteen studies investigated laparoscopic procedures, 13 endoscopic procedures and seven other procedures. These studies provided strong evidence that participants who reached proficiency in simulation-based training performed better in the patient-based setting than their counterparts who did not have simulation-based training. Simulation-based training was equally as effective as patient-based training for colonoscopy, laparoscopic camera navigation and endoscopic sinus surgery in the patient-based setting. CONCLUSION: These studies strengthen the evidence that simulation-based training, as part of a structured programme and incorporating predetermined proficiency levels, results in skills transfer to the operative setting.

Reduced sperm concentration in a patient from a suspected post-operative infection: a case study.

A diagnostic semen analysis should be performed as part of a couple's routine fertility investigations in order to determine sperm quality prior to managing the treatment pathway. The semen analysis report should be considered alongside clinical discussions and a review of both patients' medical history. However, whilst it is part of the standard patient pathway, a regular up-to-date review at each clinical step of a patients' journey is not always performed, which may miss potential clinical changes that could impact the most effective management of the couple. This case study reports the impact on the semen quality of a post-operative infection and hospitalisation of a male patient on a fertility management pathway.

Atypical paraneoplastic pemphigus secondary to endometrial carcinoma with no mucosal involvement.

Paraneoplastic pemphigus (PNP) is a mucocutaneous immunobullous disease associated with several types of internal malignancy. We report a case of a 78-year-old woman presenting with an atypical form of PNP associated with a recurrence of endometrial cancer. There was no involvement of the mucous membranes. Although the macroscopic and histological appearances were typical for IgA pemphigus or Sneddon-Wilkinson disease, direct immunofluorescence was positive for intercellular IgG and C3 staining. Circulating antibodies were detected to periplakin and envoplakin, but not to desmogleins 1 or 3. This case therefore meets the modified criteria for PNP. A response was seen to a combination of topical and systemic corticosteroids and acitretin, although with cyclical recurrences. These ceased after resection of her recurrent endometrial carcinoma.

The reliability and validity of the Severity of Dependence Scale for detecting cannabis dependence in psychosis.

AIMS: To determine the reliability and validity of the Severity of Dependence Scale (SDS) for detecting cannabis dependence in a large sample of in-patients with a schizophrenia spectrum disorder. DESIGN: Cross-sectional study. PARTICIPANTS: Participants were 153 in-patients with a schizophrenia spectrum disorder in Brisbane, Australia. MEASUREMENTS: Participants were administered the SDS for cannabis dependence in the past 12 months. The presence of Diagnostic and Statistical Manual Version-IV (DSM-IV) cannabis dependence in the previous 12 months was assessed using the Comprehensive International Diagnostic Interview (CIDI). FINDINGS: The SDS had high levels of internal consistency and strong construct and concurrent validity. Individuals with a score of >or = 2 on the SDS were nearly 30 times more likely to have DSM-IV cannabis dependence. The SDS was the strongest predictor of DSM-IV cannabis dependence after controlling for other predictor variables. CONCLUSIONS: The SDS is a brief, valid and reliable screen for cannabis dependence among people with psychosis.

Experimental transmission of a plasmacytoid leukemia of chinook salmon, Oncorhynchus tshawytscha.

A plasmacytoid leukemia of chinook salmon, Oncorhynchus tshawytscha, has recently been recognized in seawater netpens in British Columbia, Canada. The disease has occurred at several sites and has caused high mortality. Plasmacytoid leukemia is characterized by a generalized invasion of visceral tissues and the orbit of the eye by plasmacytoid cells. The disease was experimentally transmitted to healthy chinook salmon by i.p. injection of kidney tissue homogenates, but transmission with a cell-free filtrate was equivocal. In another experiment, chinook salmon, coho salmon, O. kisutch, sockeye salmon, O. nerka, rainbow trout, O. mykiss (or Salmo gairdneri), and Atlantic salmon, Salmo salar, were given injections of a tissue homogenate from affected chinook salmon. Ten wk after exposure, plasmacytoid leukemia was observed in all of the sockeye salmon and chinook salmon, one of ten Atlantic salmon, and none of the rainbow trout. Seven of the ten coho salmon examined at 10 wk had lesions suggestive of early development or a mild form of the disease. Multifocal areas of proliferating cells resembling plasmablasts were observed in the visceral fat, and the kidneys exhibited mild to moderate hyperplasia of the hematopoietic interstitium. Our studies support the hypothesis of an infectious etiology for plasmacytoid leukemia, but the agent, perhaps an oncogenic virus, has yet to be detected.

The influence of gender, handedness and head-turn on auditory asymmetries.

Subjects performed dichotic tasks with their heads turned 90 degrees to the left, 90 degrees to the right, and straight ahead. In Experiment 1 the stimuli were digits and the subjects varied in both sex and handedness. Right-handedness males showed a significant right-ear advantage under the head-right and head-straight conditions, while left-handed males and both right- and left-handed females failed to show any consistent ear asymmetries. In Experiment 2 the stimuli were melodies and the subjects were all right-handed. Head-turn had no significant influence on the results, and only the males showed a significant left-ear advantage. Overall, the results confirm previous findings that sex and handedness may influence auditory asymmetries, but fail to reveal systematic effects of head turn.

Myotonia as a side effect of diuretic action.

1. Commonly used loop diuretics produce side effects in man which are similar to chemically induced myotonia. These diuretics have structural affinity with known myotonic agents. 2. We have observed EMG myotonia in vivo in leg muscles of rats treated with intravenous frusemide. 3. In the presence of several different diuretics, rat isolated diaphragm, soleus and extensor digitorum longus muscles as well as frog sartorius muscles produce typically myotonic contractions with relaxation times up to several seconds. 4. Intracellular recording of action potentials from diuretic-treated muscles reveals long lasting after-discharges following a brief electrical stimulus, again typical of chemically induced myotonia. 5. Having demonstrated a myotonic action of several diuretics we suggest a need for caution in using these drugs in persons with hereditary myotonia and a need to be aware of possible provocation of myotonia in subclinical cases. Myopathies and neuropathies which are known to result from chronic exposure to myotonic agents also need to be considered. 6. In our study, the diuretic, acetazolamide, unmasked subthreshold myotonia. This seems to be at variance with reports of its usefulness in the treatment of myotonia. 7. Diuretics should probably not be employed in the treatment of herbicide intoxication where their myotonic activity would be expected to add to the known myotonic activity of the herbicide.

Purification, partial sequences and properties of chicken insulin-like growth factors.

Insulin-like growth factor-I (IGF-I) and IGF-II have been purified to homogeneity from chicken serum as a step towards the characterization of the roles for these peptides in the growth process. Chicken IGF-I had about half the efficacy of bovine/human IGF-I in a bioassay and in radioimmunoassays with bovine IGF-I as radioligand. Chicken IGF-II competed for the binding of bovine IGF-II to cell receptors while chicken IGF-I reacted minimally in this IGF-II radioreceptor assay. Further evidence of homology was obtained by N-terminal sequence analysis of the first 31 and 35 amino acids of chicken IGF-I and IGF-II respectively. Chicken IGF-I had the same N-terminal as human IGF-I, with the exception of the substitution of serine for asparagine at residue 26. Chicken IGF-II had a unique N-terminal tetrapeptide Tyr-Gly-Thr-Ala, but from residues 5-30 the sequence was identical to that reported for residues 6-31 of human IGF-II. Substitutions also occurred corresponding to residues 32, 33, 35 and 36 of human IGF-II. A variant form of chicken IGF-II that had the same N-terminal pentapeptide as human IGF-II was also detected.

Nicotine intake in smokers increases following a single dose of haloperidol.

The effects of oral haloperidol on nicotine intake, subjective measures of craving and smoking satisfaction were compared with placebo in light-to-moderate smokers from a post-prandial cigarette and during the subsequent hour of unrestricted smoking. Subjects smoked significantly more, as measured by blood nicotine levels, when they had received haloperidol, although there was no difference between haloperidol and placebo on any subjective measures. These findings may be interpreted to reflect a compensatory increase in smoking in order to obtain the usual nicotine reward. Having achieved usual levels of reward, subjects did not experience a decrease in subjective measures of smoking satisfaction or an increase in nicotine craving.

Effects of nicotine and amphetamine on latent inhibition in human subjects.

Latent inhibition (LI) is a phenomenon in which repeated non-reinforced exposure to a stimulus retards subsequent conditioning to that stimulus; it reflects a process whereby irrelevant stimuli become ignored, and has been the subject of study concerning attentional abnormalities in schizophrenia. Low doses of the indirect dopamine (DA) agonists, amphetamine and nicotine, disrupt LI in the rat. These drugs are believed to disrupt LI via DA release in the nucleus accumbens; LI in amphetamine- and nicotine-treated rats is reinstated by administration of the DA antagonist haloperidol. In human subjects, low doses of amphetamine abolish LI, and more recently haloperidol has been shown to potentiate LI. The present study investigated the effects of nicotine on LI in human subjects, and also attempted to replicate the abolition of LI by amphetamine. Nicotine failed to affect LI when administered either subcutaneously or by cigarette smoking. LI was, however, abolished in a group of subjects given 5 mg amphetamine 90 min before testing. Supplementary analyses of the data pooled from all three experiments showed that, in contrast to an earlier report, LI was no weaker in smokers than in nonsmokers.

Does post-withdrawal cue exposure improve outcome in opiate addiction? A controlled trial.

A controlled trial studied whether cue exposure prevented relapse in opiate addiction. Subjects were randomly allocated to one of two inpatient treatment settings: a drug dependence unit with a special 10 week program and 4 weeks in a behavioural/general treatment unit without such a program. In each setting, following drug-withdrawal, subjects had either cue exposure for at least six sessions over 3 weeks, or a control condition. Subjects were followed up twice, at about 6 weeks and 6 months post-treatment. 186 subjects were randomly allocated; 69 were assessed post-detoxification, and of these 43 completed cue exposure or control treatments. Cue exposure and control subjects did not differ in cue reactivity. This was evaluated post-treatment for cue exposure subjects and at a comparable time point for controls. All groups showed a significant decrement in cue-elicited craving, withdrawal responses and negative mood. Cue exposure and control subjects did not differ at either of the two follow up interviews.

Craving and drug reward: a comparison of methadone and clonidine in detoxifying opiate addicts.

Based upon findings relating to the reinstatement of responding from the animal laboratory, the present study investigated whether methadone, a synthetic opiate, would prime the desire to use heroin for its pleasant effect (i.e. for positive reinforcement) compared to clonidine, a non-opiate drug, in detoxifying opiate addicts (n = 16). In-patient opiate addicts were tested at maximum withdrawal and minimal withdrawal, and self-reported desire to use heroin (i) for its pleasant effect (positive craving) and (ii) to alleviate an unpleasant feeling or mood (negative craving) was recorded before drug administration, immediately after drug administration and on 4 further occasions, 15 min apart. In addition, self-reported rating of opiate withdrawal symptoms were also recorded. Although elevated in the methadone group, the difference between methadone and clonidine groups in positive craving did not reach statistical significance. Interpretation of the data is complicated by elevated baselines of positive craving in the methadone group at minimum withdrawal. Measures of negative craving and self-reported withdrawal symptoms showed a similar pattern of decline, and were significantly correlated at maximum withdrawal, thereby providing evidence from substance misusers themselves that the constructs of positive and negative reinforcement can be differentiated.

Parent training skills and methadone maintenance: clinical opportunities and challenges.

Children raised in substance abusing families show high rates of behavioural and emotional problems, in particular oppositional, defiant and non-compliant behaviours. While a range of social and individual factors correlate with poor parenting, it is often the quality of the parent-child relationship that mediates the effects of most other risk factors on child development. By addressing this relationship using behavioural family interventions, child behaviour problems have been reduced in multiple problem families. However, there has been little attempt to systematically evaluate such programs in substance abusing families. It is argued that methadone replacement programs provide a window of opportunity to deliver well-validated parent training programs that enhance the quality of parent-child relations. However, it is likely that such programs would need to be medium to long term and address issues beyond parent child relationships. How such interventions may be delivered and evaluated is discussed.

14C-labeled microcystin-LR administered to Atlantic salmon via intraperitoneal injection provides in vivo evidence for covalent binding of microcystin-LR in salmon livers.

The tissue distribution and clearance of radiolabeled microcystin-LR administered to Atlantic salmon via i.p. injection has been re-examined using uniformly 14C-labeled toxin. Significant differences were found to exist between these results and those obtained when fish received an i.p. injection of tritium-labeled dihydromicrocystin-LR. In addition, MeOH liver extracts were assayed by both phosphatase assay and 14C counts and the results compared with the total levels of incorporation determined by digestion and subsequent 14C counting of the same live tissues. An attempt to investigate the metabolism and to document the putative products was also undertaken. It was found that microcystin-LR was extensively metabolized to compounds that are more polar than the parent compound.

Bioaccumulation and clearance of microcystins from salt water mussels, Mytilus edulis, and in vivo evidence for covalently bound microcystins in mussel tissues.

Over a period of 3 days saltwater mussels, Mytilus edulis, were fed a cyanobacteria, Microcystis aeruginosa, that contained a high concentration of microcystins. The mussels were killed on a periodic basis over the course of 2 months. Mussels were also collected at two sites were high levels of microcystins in tissues had been noted. A strategy based on the chemically unique nature of the C20 beta-amino acid, (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6- dienoic acid (Adda), portion of the microcystins was used in conjunction with a protein phosphatase (PPase) assay to analyse for both covalently bound microcystins and free microcystins in the mussel tissues. The mussel PPase assay results were compared with the Lemieux oxidation gas chromatography-mass spectrometry (GCMS) analysis. Less than 0.1% of the total microcystin burden in the mussel tissue was found to be extractable with MeOH. Thus, direct evidence was provided for the existence of covalently bound microcystins in mussel tissues in vivo. The mussels rapidly cleared the covalently bound microcystins when transferred to untreated seawater. Within 4 days the total microcystin burden dropped from a high of 336.9 (+/- 45.8) micrograms/g wet tissue to 11.3 (+/- 2.6) micrograms/g. After 4 days postexposure until completion of the experiment the total levels remained below the detection limits of the GCMS method. The levels of free microcystins, extracted with MeOH and detected by the PPase assay, fell from 204 ng/g wet tissue to a residual 14 ng/g over a 53 day postexposure period. Presumably the bound microcystin present in the mussel tissue exists as a covalent complex with the PP-1 and PP-2A enzymes. We conclude that in any shellfish monitoring program it is the total tissue microcystin burden that needs to be considered.

Chronic intravenous administration of lentinan to the rhesus monkey.

The prolonged effects of overdosage with lentinan in the rhesus monkey are associated with foam cell reactions in lung, liver, kidney, spleen, lymph nodes and bone marrow and with varying degrees of vasculitis and associated reactions. A dose level of 0.5 mg/kg/day was without adverse effect.

Preliminary analysis of the polypeptides of the salmon leukemia virus (SLV) and evidence for development of a bimodal viremia following SLV infection.

A retrovirus, known as salmon leukemia virus (SLV), was purified from farm-reared chinook salmon (Oncorhynchus tshawytscha) with plasmacytoid leukemia (PL). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of purified SLV revealed the presence of 9 virus-associated polypeptides with molecular weights from 82 kDa to 15 kDa. Endoglycosidase digestion and alcian blue staining of viral polypeptides separated by SDS-PAGE, and immunoprecipitation experiments using hyperimmune antisera suggest that the non-glycosylated 27 kDa polypeptide may represent a capsid-associated protein and the 82 kDa glycoprotein may represent an envelope-associated protein, which appears to be composed of a 67 kDa protein moiety. Fish injected with PL-positive tissue homgenate developed a bimodal viremia, as indicated by the presence of cell-free, virus-associated reverse transcriptase activity and SLV in serum of fish from 1 to 3 wk post-injection and again from 7 wk on through the rest of the study. If horizontal transmission of SLV and PL occurs in infected chinook salmon, it is most likely to occur after the second viremic period begins.