Practical guide to the Idea, Development and Exploration stages of the IDEAL Framework and Recommendations.

BACKGROUND: Evaluation of new surgical procedures is a complex process challenged by evolution of technique, operator learning curves, the possibility of variable procedural quality, and strong treatment preferences among patients and clinicians. Preliminary studies that address these issues are needed to prepare for a successful randomized trial. The IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) Framework and Recommendations provide an integrated step-by-step evaluation pathway that can help investigators achieve this. METHODS: A practical guide was developed for investigators evaluating new surgical interventions in the earlier phases before a randomized trial (corresponding to stages 1, 2a and 2b of the IDEAL Framework). The examples and practical tips included were chosen and agreed upon by consensus among authors with experience either in designing and conducting IDEAL format studies, or in helping others to design such studies. They address the most common challenges encountered by authors attempting to follow the IDEAL Recommendations. RESULTS: A decision aid has been created to help identify the IDEAL stage of an innovation from literature reports, with advice on how to design and report the IDEAL study formats discussed, along with the ethical and scientific rationale for specific recommendations. CONCLUSION: The guide helps readers and researchers to understand and implement the IDEAL Framework and Recommendations to improve the quality of evidence supporting surgical innovation.

Low-temperature plasma treatment induces DNA damage leading to necrotic cell death in primary prostate epithelial cells.

BACKGROUND: In recent years, the rapidly advancing field of low-temperature atmospheric pressure plasmas has shown considerable promise for future translational biomedical applications, including cancer therapy, through the generation of reactive oxygen and nitrogen species. METHOD: The cytopathic effect of low-temperature plasma was first verified in two commonly used prostate cell lines: BPH-1 and PC-3 cells. The study was then extended to analyse the effects in paired normal and tumour (Gleason grade 7) prostate epithelial cells cultured directly from patient tissue. Hydrogen peroxide (H2O2) and staurosporine were used as controls throughout. RESULTS: Low-temperature plasma (LTP) exposure resulted in high levels of DNA damage, a reduction in cell viability, and colony-forming ability. H2O2 formed in the culture medium was a likely facilitator of these effects. Necrosis and autophagy were recorded in primary cells, whereas cell lines exhibited apoptosis and necrosis. CONCLUSIONS: This study demonstrates that LTP treatment causes cytotoxic insult in primary prostate cells, leading to rapid necrotic cell death. It also highlights the need to study primary cultures in order to gain more realistic insight into patient response.

A single plan solution to chest wall radiotherapy with bolus?

OBJECTIVE: Radiotherapy treatments of post-mastectomy chest walls are complex, requiring treatment close to skin, necessitating bolus use. Commonly used 5- and 10-mm-thick boluses develop full skin dose, needing removal for the latter half of treatment and requiring two treatment plans to be generated. Can a thinner bolus be used for all treatment fractions, requiring only one plan? METHODS: Investigation of doses received using (A) a half-time 10-mm-thick Vaseline® bolus (current situation); (B) a brass mesh (Whiting & Davis, Attleboro Falls, MA) and (C) 3- and 5-mm Superflab™ (Mick Radio-Nuclear Instruments, Mount Vernon, NY) for 6 and 15 MV. Dosimetric measurements in Barts WT1 solid water and an anthropomorphic phantom, using ionization chambers and thermoluminescent dosemeters, were used to study the effect of different bolus regimes on the photon depth-dose curves (DDCs) and skin doses. RESULTS: Measured skin doses for the current 10-mm-thick Vaseline bolus, brass mesh and 3-mm bolus were compared (5 mm bolus has been rejected). The brass mesh has the least effect on the DDC, with changes <0.7% for depths greater than dmax. Brass mesh conforms superiorly to skin surfaces. Measurements on an anthropomorphic phantom demonstrate an increased skin dose compared with our current treatment protocol. CONCLUSION: Brass mesh has the smallest effect on the DDC, whilst sufficiently increasing surface dose. It can be removed at any fraction, based on a clinical decision, without the need for generating a new plan. Treating with one plan significantly reduces planning times. ADVANCES IN KNOWLEDGE: Quantification of skin doses required and achieved from wax-on/wax-off treatment compared with alternative available breast boluses.

Occupational exposure to potential endocrine disruptors: further development of a job exposure matrix.

OBJECTIVES: The aim was to develop a new up-to-date and comprehensive job exposure matrix (JEM) for estimating exposure to potential endocrine disruptors in epidemiological research. METHODS: Chemicals with endocrine disrupting properties were identified from the literature and classified into 10 chemical groups: polycyclic aromatic hydrocarbons (PAHs), polychlorinated organic compounds, pesticides, phthalates, organic solvents, bisphenol A, alkylphenolic compounds, brominated flame retardants, metals and a miscellaneous group. Most chemical groups were divided into three to six subgroups. Focusing on the years 1996-2006, three experts scored the probability of exposure to each chemical group and subgroup for 353 job titles as "unlikely" (0), "possible" (1) or "probable" (2). Job titles with positive exposure probability scores were provided with exposure scenarios that described the reasoning behind the scores. RESULTS: Exposure to any chemical group was unlikely for 238 job titles (67%), whereas 102 (29%) job titles were classified as possibly (17%) or probably (12%) exposed to one or several endocrine disruptors. The remaining 13 job titles provided too little information to classify exposure. PAHs, pesticides, phthalates, organic solvents, alkylphenolic compounds and metals were often linked to a job title in the JEM. The remaining chemical groups were found to involve very few occupations. CONCLUSIONS: Despite some important limitations, this JEM could be a valuable tool for exposure assessment in studies on the health risks of endocrine disruptors, especially when task specific information is incorporated. The documented exposure scenarios are meant to facilitate further adjustments to the JEM to allow more widespread use.

A multi-centre retrospective cohort study comparing the efficacy, safety and cost-effectiveness of hysterectomy and uterine artery embolisation for the treatment of symptomatic uterine fibroids. The HOPEFUL study.

OBJECTIVES: To examine and compare the medium-term results of hysterectomy and uterine artery embolisation (UAE) as a treatment for symptomatic uterine fibroids with regard to safety, efficacy, special issues in the UAE group, cost-effectiveness, and women's own perspectives on the treatments. DESIGN: Data were collected locally from patients' hospital records and also from patients themselves by postal questionnaire. Questionnaire data included free-text comments and this qualitative material was analysed using constant comparison. A two-stage probabilistic decision model was designed to estimate UK NHS costs and health outcomes in terms of quality-adjusted life-years (QALYs). SETTING: Eighteen NHS hospital trusts, 17 in England and one in Scotland. PARTICIPANTS: Eligible women (972 UAE, 762 hysterectomies) who had received treatment specifically for symptomatic fibroids were identified. INTERVENTIONS: The UAE patients were treated by experienced interventional radiologists and all received their index UAE prior to the end of 2002, ensuring a minimum 2-year follow-up. The average length of follow-up was 8.6 years for the hysterectomy cohort and 4.6 years for the UAE cohort. MAIN OUTCOME MEASURES: Primary outcome measures were complication rates to assess the comparative safety of the two interventions. Secondary outcome measures related to treatment efficacy including resolution of symptoms and patient-reported satisfaction with treatment. Further efficacy outcome measures obtained in the UAE group included fibroid/uterine size shrinkage and further treatments required for unresolved fibroid symptoms. Data were also gathered on pregnancies post-UAE. RESULTS: Data were available for 1108 women (649 UAE and 459 hysterectomy). Fewer complications were experienced by women in the UAE cohort compared to the hysterectomy cohort: hysterectomy n = 120 (26.1%), UAE n = 114 (17.6%), adjusted odds ratio 0.48 [95% confidence interval (CI) 0.26 to 0.89]. When only the severe/major complications were considered, this odds ratio was reduced to 0.25 (95% CI 0.13 to 0.48). Expected general side-effects of UAE occurred in 32.7% of the UAE cohort, of which 8.9% also experienced complications. Obesity and medical co-morbidity predisposed women to complications, whereas prophylactic antibiotics appeared to protect against both complications and the expected side-effects of UAE. More women in the hysterectomy cohort reported relief from fibroid symptoms (89% versus 80% UAE, p less than 0.0001) and feeling better (81% versus 74% UAE, p less than 0.0001), but only 70% (compared with 86% UAE, p = 0.007) would recommend their treatment to a friend. In the UAE cohort, 18.3% of the women went on to receive one or more further fibroid treatments including hysterectomy (11.2%). After adjusting for differential time of follow-up, the UAE women had up to a 23% (95% CI 19 to 27%) likelihood of requiring further treatment. The free-text data indicated that many women, in both cohorts, felt that their treatment had been a complete success. In the UAE cohort there were several areas where expectations were apparently high and outcome had not fulfilled their expectations. Disappointment was expressed mainly about continuation or return of symptoms or failure to become pregnant. Many continued to have remaining questions about their treatment. The economic analysis indicated that UAE is less expensive than hysterectomy even after further treatments for unresolved or recurrent symptoms are taken into account, with little difference in QALYs between the two treatments. Younger women are exposed to the risk of recurrent fibroids and subsequent additional procedures over a longer period and consequently UAE may no longer be cost-effective. CONCLUSIONS: The study results suggest that both UAE and hysterectomy are safe. No unexpected problems were detected following UAE after a long follow-up period (average 5 years). Complications are less common for UAE than hysterectomy. The cost-effectiveness analysis favours embolisation even after taking account of complications, expected side-effects associated with the procedure and subsequent re-treatments for women with a preference for uterus preservation. It is important to improve the management of expectations following UAE, particularly regarding fertility. The data suggested that fertility and miscarriage rate are consistent with those of age-matched women with fibroids. UAE is an effective treatment for some women with fibroids and our trial supports the National Institute for Health and Clinical Excellence guidance that it should be made available as one of the options for treatment, with a possible reduction in the need for hysterectomy as the first-line treatment. Further research is needed into which women will be treated most successfully by UAE, the best method of achieving effective embolisation, advice for women who desire future fertility, the role of prophylactic antibiotics in UAE, and the effects of HRT use after UAE on recurrence of fibroid symptoms.

A UK multicentre retrospective cohort study comparing hysterectomy and uterine artery embolisation for the treatment of symptomatic uterine fibroids (HOPEFUL study): main results on medium-term safety and efficacy.

OBJECTIVES: Comparison of medium-term safety and efficacy of hysterectomy and uterine artery embolisation (UAE) for symptomatic uterine fibroids. DESIGN: Multicentre retrospective cohort. SETTING: 18 UK NHS hospital trusts. PARTICIPANTS: Four hundred and fifty nine women who had hysterectomy within a national audit during 12 months from October 1994 (VALUE study) (average follow up of 8.6 years) and 649 women receiving UAE from 1996 to 2002 (average follow up of 4.6 years). METHODS: Clinical data from existing hospital records and patient completed postal questionnaires. MAIN OUTCOME MEASURES: Complication rates, side effects of embolisation, satisfaction with treatment, relief from symptoms and requirement for further fibroid treatment. RESULTS: Fewer complications were experienced by women receiving UAE (19 versus 26% hysterectomy, P = 0.001), the adjusted odds ratio for UAE versus hysterectomy was 0.48 (95% CI 0.26-0.89). One-third of women undergoing UAE experienced anticipated general side effects associated with the procedure. More women in the hysterectomy cohort reported relief from fibroid symptoms (95 versus 85%, P < 0.0001) and feeling better (96 versus 84%, P < 0.0001), but only 85% would recommend the treatment to a friend compared with 91% in the UAE arm (P = 0.007). There was a 23% (95% CI 19-27%) chance of requiring further treatment for fibroids after UAE. Twenty-seven women who had had UAE reported 37 pregnancies after treatment resulting in 19 live births. CONCLUSIONS: UAE results in fewer complications than hysterectomy. Side effects after embolisation should be anticipated, and almost one-quarter of women having UAE were likely to require further treatment for fibroid symptoms. Both treatments appear to be safe and effective over the medium term, and the choice of treatment may be a matter of personal preference for each individual woman.

Uterine artery embolisation or hysterectomy for the treatment of symptomatic uterine fibroids: a cost-utility analysis of the HOPEFUL study.

OBJECTIVES: To evaluate the relative cost-effectiveness of uterine artery embolisation (UAE) and hysterectomy in women with symptomatic uterine fibroids from the perspective of the UK NHS. DESIGN: Cost-utility analysis. SETTING: Eighteen UK NHS hospital trusts. POPULATION OR SAMPLE Women who underwent UAE (n= 649; average follow up of 8.6 years) or hysterectomy (n= 459; average follow up of 4.6 years) for the treatments of symptomatic fibroids. METHODS: A probabilistic decision model was carried out based on data from a large comparative cohort and the literature. The two interventions were evaluated over the time horizon from the initial procedure to menopause. Extensive sensitivity analysis was carried out to test model assumptions and parameter uncertainties. MAIN OUTCOME MEASURES: Costs of procedures and complications and quality of life expressed as quality-adjusted life years (QALYs). RESULTS: Overall, UAE was associated with lower mean cost (2536 pounds sterling versus 3282 pounds sterling) and a small reduction in quality of life (8.203 versus 8.241 QALYs) when compared with hysterectomy. However, when the quality of life associated with the conservation of the uterus was incorporated in the model, UAE was shown to be the dominant strategy--lower costs and greater QALYs. CONCLUSIONS: UAE is a less expensive option to the health service compared with hysterectomy, even when the costs of repeat procedures and associated complications are factored in. The quality of life implications in the short term are also predicted to favour UAE; however, this advantage may be eroded over time as women undergo additional procedures to deal with recurrent fibroids. Given the hysterectomy is the current standard treatment for symptomatic fibroids, offering women UAE as an alternative treatment for fibroids is likely to be highly cost-effective for those women who prefer uterus-conserving treatment.

Spatial and temporal operation of the Scotia Sea ecosystem: a review of large-scale links in a krill centred food web.

The Scotia Sea ecosystem is a major component of the circumpolar Southern Ocean system, where productivity and predator demand for prey are high. The eastward-flowing Antarctic Circumpolar Current (ACC) and waters from the Weddell-Scotia Confluence dominate the physics of the Scotia Sea, leading to a strong advective flow, intense eddy activity and mixing. There is also strong seasonality, manifest by the changing irradiance and sea ice cover, which leads to shorter summers in the south. Summer phytoplankton blooms, which at times can cover an area of more than 0.5 million km2, probably result from the mixing of micronutrients into surface waters through the flow of the ACC over the Scotia Arc. This production is consumed by a range of species including Antarctic krill, which are the major prey item of large seabird and marine mammal populations. The flow of the ACC is steered north by the Scotia Arc, pushing polar water to lower latitudes, carrying with it krill during spring and summer, which subsidize food webs around South Georgia and the northern Scotia Arc. There is also marked interannual variability in winter sea ice distribution and sea surface temperatures that is linked to southern hemisphere-scale climate processes such as the El Niño-Southern Oscillation. This variation affects regional primary and secondary production and influences biogeochemical cycles. It also affects krill population dynamics and dispersal, which in turn impacts higher trophic level predator foraging, breeding performance and population dynamics. The ecosystem has also been highly perturbed as a result of harvesting over the last two centuries and significant ecological changes have also occurred in response to rapid regional warming during the second half of the twentieth century. This combination of historical perturbation and rapid regional change highlights that the Scotia Sea ecosystem is likely to show significant change over the next two to three decades, which may result in major ecological shifts.

A synthesis of growth rates in marine epipelagic invertebrate zooplankton.

We present the most extensive study to date of globally compiled and analysed weight-specific growth rates in marine epi-pelagic invertebrate metazoan zooplankton. Using specified selection criteria, we analyse growth rates from a variety of zooplanktonic taxa, including both holo- and mero-planktonic forms, from over 110 published studies. Nine principal taxonomic groups are considered, the copepods (number of individual data points (n) = 2,528); crustaceans other than copepods (n = 253); cnidarians (n = 77); ctenophores (n = 27); chaetognaths (n = 87); pteropods (n = 8); polychaetes (n = 12); thaliaceans (n = 88); and larvaceans (n = 91). The copepods are further examined by subdividing them into broadcasters or sac-spawning species, and as nauplii (N1-N6), copepodites (C1-C5) and adults (C6). For each taxonomic group relationships between growth, temperature and body weight are examined using a variety of methods. Weight-specific growth tends to increase with increasing temperature and with decreasing body weight in the crustacean group. Growth does not relate to body weight in the case of chaetognaths and larvaceans, but does increase with temperature. In the cnidarian and ctenophore groups growth does not relate to temperature, but is negatively related to body size. For the thaliceans growth increases with both increasing body weight and temperature. In the entire broadcasting copepod data set, weight-specific growth increases with increasing temperature and decreasing body weight. In sac-spawners, growth increases with increasing temperature, and increases with decreasing body weight at temperatures below 20 degrees C, but decreases with body weight at temperatures above this. Comparison between the different taxa shows important differences and similarities. Our extensive synthesis of data generally confirms that larvaceans, pteropods, cnidarians and ctenophores have rates of weight-specific growth that are typically greater than the copepods, chaetognaths and other crustaceans of similar carbon weight. For the cnidarians, ctenophores and larvaceans growth rates are almost always greater than the general relationship describing copepod growth, and are also at the upper limits or beyond the maximum rates for copepods of a similar weight. For the pteropods, growth rates are generally greater than those of copepods, although the data set was limited to a single carnivorous species in a single study (i.e. Clione limacina). The thaliaceans have the highest growth rates for animals with body weights greater than around 1 mg C ind-1, with rates of up to 2.1 d-1 for Pegea bicaudata. Whilst the larvaceans can achieve rates of 2 d-1 in warm tropical waters (28 degrees C), and as high as > 3 d-1 for < 0.2 mg C individual-1 animals of Oikopleura diocia. These are possibly the highest rates every recorded in epi-pelagic metazoans. Reasons for the differences between taxonomic groups are discussed in relation to intrinsic and extrinsic factors and limitations. The importance of this investigation not only lies in it being the most comprehensive overview of patterns of growth to date, but because the data set highlight the gaps in measurements and current knowledge. We examine the inadequacies in the current data sets, and in the methods being used to measure growth and production. Most of the data are for animals collected from coastal and estuarine waters, and it is clear that for a fuller understanding there is an urgent need for work in the open ocean, and for investigations outside temperate regions. There is also a need to explore the role of food availability, and how food concentrations in incubations, and under food saturation, relate to those experienced in the natural environment.

Menstrual cycle effects on hypothalamic dopamine receptor function in women with a history of puerperal bipolar disorder.

Neuroendocrine challenge tests of hypothalamic dopamine receptor function in the early postpartum period suggest that the sensitivity of these receptors is increased in women with a history of bipolar disorder after childbirth. We tested the hypothesis that, in women predisposed to bipolar disorder in the puerperium, hypothalamic dopamine receptor function is more sensitive to changes in circulating ovarian hormone concentrations than in women without such histories. Eight fully recovered and drug-free women who had had at least one episode of bipolar illness following childbirth were compared with nine normal controls. Growth hormone (GH) responses to apomorphine (APO 0.005 mg s.c.) were measured in the early follicular phase, when plasma concentrations of ovarian hormones are low, and in the mid-luteal phase, when they are relatively high. The recovered bipolar subjects and the controls did not differ from each other in their follicular and midluteal oestrogen and progesterone concentrations. In the midluteal phase, both groups had increased oestrogen and progesterone levels. The recovered bipolar subjects did not differ from controls in baseline concentrations of GH in either of the menstrual phases. The APO-GH responses of the two groups did not differ in the follicular phase, but in the midluteal phase, when female sex steroids are relatively increased, the recovered group had significantly enhanced APO-GH responses [MANOVA for repeated measures: (i) area under the curve, group by phase effect: p < 0.04; (ii) GH peak rise after APO, group by phase effect: p < 0.056] and the responses were not related to concurrent measures of mood. The results of this small study of women predisposed to bipolar disorder in the puerperium shows an increased dopaminergic receptor sensitivity in the luteal phase of the menstrual cycle. It suggests that their dopaminergic systems have increased sensitivity to changes in circulating female sex steroids. This may be aetiologically relevant to the pathogenesis of puerperal bipolar disorder.

Benzodiazepines and related drugs for insomnia in palliative care.

BACKGROUND: Insomnia, a subjective complaint of poor sleep and associated impairment in daytime function, is a common problem. Currently, benzodiazepines are the most used pharmacological treatment for this complaint. They are considered helpful for occasional short-term use up to four weeks but longer term use is not advised due to potential problems regarding tolerance, dosing escalation, psychological addiction and physical dependence. There is no consensus on their utility in patients with progressive incurable conditions who may require assistance with sleep for many weeks as their condition deteriorates. OBJECTIVES: To assess the effectiveness and safety of benzodiazepines or benzodiazepine receptor agonists such as Zolpidem, Zopiclone and Zaleplon for insomnia in palliative care. SEARCH STRATEGY: Several electronic databases were searched including Cochrane PaPaS Group specialized register, Cochrane Library Issue 4, 2001, MEDLINE, EMBASE, BNI plus, CINAHL, BIOLOGICAL ABSTRACTS, PSYCINFO, CANCERLIT, HEALTHSTAR, WEB OF SCIENCE, SIGLE, Dissertation Abstracts, ZETOC and the MetaRegister of ongoing trials. These were searched from 1960 to 2001 or as much of this range as possible. Additional articles were sought by handsearching reference lists in standard textbooks and reviews in the field and by contacting academic centres in palliative care and pharmaceutical companies. There were no language restrictions. SELECTION CRITERIA: Studies considered for inclusion were randomized controlled trials of adult patients in any setting, receiving palliative care or suffering an incurable progressive medical condition. (For example, cancers, AIDS, Motor Neurone Disease, Multiple Sclerosis, Parkinson's Disease, Chronic Obstructive Pulmonary Disease). There had to be an explicit complaint of insomnia in study participants, diagnosed by any of the three main classification systems (DSM-IV (APA 1994), ICSD (AASD 1990) or ICD (WHO 1992)), or as described in the study if it involved a subjective complaint of poor sleep. Studies had to compare a benzodiazepine or Zolpidem or Zopiclone or Zaleplon with placebo or active control for the treatment of insomnia. Any duration of therapy were considered. DATA COLLECTION AND ANALYSIS: Abstracts were independently inspected by both reviewers, full papers were obtained where necessary. Where there was uncertainty advice was sought by a third (PW). Data extraction and quality assessments were undertaken independently by both reviewers. MAIN RESULTS: No randomized controlled trials were identified meeting the a priori inclusion criteria. Thirty-seven studies were considered but all were excluded from the review. REVIEWER'S CONCLUSIONS: Despite a comprehensive search no evidence from randomized controlled trials was identified. It was not possible to draw any conclusions regarding the use of benzodiazepines in palliative care.

External quality assessment of techniques for the detection of drugs of abuse in urine.

Five chromatographic and six immunoassay techniques were compared using data reported by 131 participants in the UK National External Quality Assessment Scheme for Drugs of Abuse in Urine. Twenty five samples were studied containing none or one of three concentrations of amphetamine, barbiturates, benzodiazepines, benzoylecgonine, methadone and morphine. Technique sensitivity and specificity achieved with realistic clinical samples of 25 mL vol were assessed as the percentage of true positive and true negative tests, respectively. Thin-layer chromatography was inadequate for the detection of several analytes, the sensitivity for 0.5 mg/L of benzoylecgonine being < 30%, and for 1.5 mg/L of amphetamine < 86%. Gas chromatography with mass spectrometry was significantly less sensitive than other techniques for the detection of 0.5 mg/L of benzoylecgonine (71%) and 1.5 mg/L of morphine (88%). High-performance liquid chromatography was the most sensitive for amphetamine. Immunoassays performed well when operating above their specified cut-off concentrations but, because they are directed to quinalbarbitone showed reduced cross-reactivity with amylobarbitone, the barbiturate more commonly prescribed in the UK.

A blood spot assay for apo A1 and B lipoproteins and the apo B/A1 ratio.

A study of conditions for the elution of apo A1 and B lipoproteins from dried blood spots has led to the development of an apo B/A1 ratio assay with results for dried blood spots which are comparable with serum assays. This assay has been developed to be suitable for large scale population screening. The concept of measuring ratios for co-eluting blood constituents improves the accuracy and precision of blood spot assays and opens up the possibility that patients could take their own blood sample and send it to the laboratory by post.

Increased sensitivity of dopamine receptors and recurrence of affective psychosis after childbirth.

OBJECTIVE: To test the hypothesis that affective psychosis after childbirth is associated with an altered sensitivity to dopaminergic stimulation. DESIGN: Prospective study of pregnant women at high risk of developing an affective psychosis after childbirth. Clinical assessments in pregnancy and after delivery were made by using a semistructured interview (schedule for affective disorders and schizophrenia) and psychiatric illnesses were categorised according to operational criteria (research diagnostic criteria). SETTING: Obstetric and psychiatric departments in and around Greater London. SUBJECTS: 29 pregnant women with a history of bipolar or schizoaffective psychosis and 47 control pregnant women. Of these, 16 from each group participated in a growth hormone challenge test and the results for 15 women in each group were analysed. INTERVENTIONS: On the fourth day postpartum women participating in the hormone challenge test were given a subcutaneous injection of a small dose (0.005 mg/kg) of the dopamine agonist apomorphine. MAIN OUTCOME MEASURES: Growth hormone secretion in response to apomorphine as an index of the functional state of hypothalamic dopamine receptors. RESULTS: Eight of the 15 women at risk of psychosis subsequently had a recurrence of illness (five bipolar, one schizomanic, and two major depressive illnesses); these women had significantly greater growth hormone responses to apomorphine than the seven at risk women who remained well and the 15 controls, and there were no significant differences between groups in average baseline growth hormone concentrations. The mean (SD) concentrations for women with recurrence, women at risk who remained well, and control women respectively were: average baseline concentrations 1.06 (1.14), 1.44 (1.39), and 0.90 (1.34) mU/l; peak increase in concentrations 13.68 (12.95), 3.46 (4.68), and 3.40 (3.83) mU/l (between group difference p less than 0.05); average increase in concentrations 6.74 (7.01), 1.78 (3.39), and 1.40 (2.05) mU/l (p less than 0.05). CONCLUSIONS: The onset of affective psychosis after childbirth was associated with increased sensitivity of dopamine receptors in the hypothalamus and possibly elsewhere in the brain. Such changes may be triggered by the sharp fall in circulating oestrogen concentrations after delivery.

Cause-specific mortality among physicians with differing life-styles.

We compare the mortality experience of medical school graduates from Loma Linda University (LLU [n = 4342]) and the University of Southern California (USC [n = 2832]) with each other and with that of contemporaneous, white, American men. When compared with US white men from the general population, both USC and LLU graduates had below expected deaths for all causes (USC, standardized mortality ratio [SMR] = 76; LLU, SMR = 56), although deaths due to cerebrovascular disease, airplane accidents, and suicides were elevated for USC (SMRs = 132, 360, and 218, respectively). The LLU graduates had a risk similar to that of the USC graduates for fatal cancer, with a mortality ratio (MR) of 0.92 (95% confidence interval, 0.67 to 1.26); but half the risk of fatal atherosclerotic disease, with MRs of 0.58 (0.46 to 0.73) and 0.66 (0.43 to 0.99) for coronary and cerebrovascular disease, respectively; and three times the risk of fatal airplane accidents. The overall mortality rate of LLU physicians was only 75% as high as that of the USC physicians and only 56% as high as that of the US male population at large. We attribute this reduced mortality mainly to the low cardiovascular mortality rates, which may be accounted for by the life-style of the substantial proportion of Seventh-day Adventists among LLU graduates.

Radioisotopic pulmonary lobectomy: feasibility study in dogs.

In search for an alternate treatment for inoperable cancer of the lung in humans, we investigated the possibility that introduction of radioactive material into a selected lobe of the canine lung would effectively destroy that lobe without systemic effects or radiation injury to adjacent organs. Ten million ion exchange microspheres labeled with 740 MBq of phosphorus-32 (32P) were injected through a catheter placed in a selected lobar branch of a pulmonary artery in 12 anesthetized dogs. Six additional dogs served as controls and received 10 million microspheres not labeled with 32P. Organs were harvested from 1 wk to 12 mo after injection and examined grossly and histologically. There was progressive organization and contraction of each necrosed 32P treated lobe which was reduced to a scarred remnant by 12 mo, whereas only minimal inflammatory changes occurred in controls. Of the 32P injected dose, 94% remained in injected lobe, 4%-5% in nontargeted lobes and less than 0.08% in blood. Radioactivity in liver, kidneys, spleen, heart, and bone marrow was less than 0.1% for each organ. Thus, large doses of radiation in the order of 1,500 Gy can be effectively delivered to a selected lobe to produce a "radioisotopic pulmonary lobectomy."

Radiotherapy in benign orbital disease. II: Ophthalmic Graves' disease and orbital histiocytosis X.

Ophthalmic Graves' disease and histiocytosis X involving the orbit are occasionally refractory to treatment, so that vision may be threatened. In these situations megavoltage external beam radiotherapy should be employed, and the indications for this treatment are discussed. A highly accurate technique is described, using precise planning with information obtained from high definition CT scans, a complete patient head shell for immobilisation, and modern megavoltage radiotherapy treatment machines. As a result the dose to the lens is minimised (to a maximum of 10% of the prescribed dose), and late morbidity will be small. Two cases are described to illustrate this procedure and the response to treatment.