Physician burnout: contributors, consequences and solutions.

Physician burnout, a work-related syndrome involving emotional exhaustion, depersonalization and a sense of reduced personal accomplishment, is prevalent internationally. Rates of burnout symptoms that have been associated with adverse effects on patients, the healthcare workforce, costs and physician health exceed 50% in studies of both physicians-in-training and practicing physicians. This problem represents a public health crisis with negative impacts on individual physicians, patients and healthcare organizations and systems. Drivers of this epidemic are largely rooted within healthcare organizations and systems and include excessive workloads, inefficient work processes, clerical burdens, work-home conflicts, lack of input or control for physicians with respect to issues affecting their work lives, organizational support structures and leadership culture. Individual physician-level factors also play a role, with higher rates of burnout commonly reported in female and younger physicians. Effective solutions align with these drivers. For example, organizational efforts such as locally developed practice modifications and increased support for clinical work have demonstrated benefits in reducing burnout. Individually focused solutions such as mindfulness-based stress reduction and small-group programmes to promote community, connectedness and meaning have also been shown to be effective. Regardless of the specific approach taken, the problem of physician burnout is best addressed when viewed as a shared responsibility of both healthcare systems and individual physicians. Although our understanding of physician burnout has advanced considerably in recent years, many gaps in our knowledge remain. Longitudinal studies of burnout's effects and the impact of interventions on both burnout and its effects are needed, as are studies of effective solutions implemented in combination. For medicine to fulfil its mission for patients and for public health, all stakeholders in healthcare delivery must work together to develop and implement effective remedies for physician burnout.

Risk of myocardial infarction and stroke in bipolar disorder: a systematic review and exploratory meta-analysis.

OBJECTIVE: To review the evidence on and estimate the risk of myocardial infarction and stroke in bipolar disorder. METHOD: A systematic search using MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and bibliographies (1946 - May, 2013) was conducted. Case-control and cohort studies of bipolar disorder patients age 15 or older with myocardial infarction or stroke as outcomes were included. Two independent reviewers extracted data and assessed quality. Estimates of effect were summarized using random-effects meta-analysis. RESULTS: Five cohort studies including 13 115 911 participants (27 092 bipolar) were included. Due to the use of registers, different statistical methods, and inconsistent adjustment for confounders, there was significant methodological heterogeneity among studies. The exploratory meta-analysis yielded no evidence for a significant increase in the risk of myocardial infarction: [relative risk (RR): 1.09, 95% CI 0.96-1.24, P = 0.20; I(2)  = 6%]. While there was evidence of significant study heterogeneity, the risk of stroke in bipolar disorder was significantly increased (RR 1.74, 95% CI 1.29-2.35; P = 0.0003; I(2)  = 83%). CONCLUSION: There may be a differential risk of myocardial infarction and stroke in patients with bipolar disorder. Confidence in these pooled estimates was limited by the small number of studies, significant heterogeneity and dissimilar methodological features.

Systematic review with meta-analysis: highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation.

BACKGROUND: Highly selective 5-HT4 agonists have been suggested for the treatment of chronic constipation (CC). AIM: To assess the effects of highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) on patient-important clinical efficacy outcomes and safety in adults with CC. METHODS: We searched the medical literature in January 2013 using MEDLINE/Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomised, controlled trials of highly selective 5-HT4 agonists in adults with CC, with no minimum duration of therapy (maximum 12 weeks) or date limitations. Data were extracted from intention-to-treat analyses, pooled using a random-effects model, and reported as relative risk (RR), mean differences, or standardised mean differences with 95% confidence intervals (CI). RESULTS: Main outcomes included stool frequency, Patient-Assessment of Constipation Quality of Life (PAC-QOL), PAC of symptoms (PAC-SYM) and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1 velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5-HT4 agonists was superior for all outcomes: mean ≥3 spontaneous complete bowel movements (SCBM)/week (RR = 1.85; 95% CI 1.23-2.79); mean ≥1 SCBM over baseline (RR = 1.57; 95% CI 1.19, 2.06); ≥1 point improvement in PAC-QOL and PAC-SYM scores. The only active comparator trial of prucalopride and PEG3350 suggested PEG3350 is more efficacious for some end points. Adverse events were more common with highly selective 5-HT4 agonists, but were generally minor; headache was the most frequent. Most trials studied prucalopride. CONCLUSION: Demonstration of efficacy on patient-important outcomes and a favourable safety profile support the continued use and development of highly selective 5-HT4 agonists in the treatment of chronic constipation.

Performance by spring and fall-calving cows grazing with full, limited, or no access to toxic Neotyphodium coenophialum-infected tall fescue.

Replacing toxic, wild-type Neotyphodium coenophialum-infected tall fescue (E+) with nontoxic, N. coenophialum-infected tall fescue (NE+) has improved cow performance, but producer acceptance of NE+ has been slow. The objective was to compare performance by spring- and fall-calving cows grazing either E+ or NE+ at different percentages of the total pasture area. Gelbvieh×Angus crossbred cows (n=178) were stratified by BW and age within calving season and allocated randomly to 1 of 14 groups representing 5 treatments for a 3-yr study: i) Fall-calving on 100% E+ (F100); ii) Spring-calving on 100% E+ (S100); iii) Fall-calving on 75% E+ and 25% NE+ (F75); iv) Spring-calving on 75% E+ and 25% NE+ (S75); and v) Spring-calving on 100% NE+ (SNE100). Groups allocated to F75 and S75 grazed E+ until approximately 28 d before breeding and weaning, then were then moved to their respective NE+ pasture area for 4 to 6 wk; those allocated to F100, S100, and SNE100 grazed their pastures throughout the entire year. Samples of tall fescue were gathered from specific cells within each pasture at the time cows were moved into that particular cell (∼1 sample/mo). Blood samples were collected from the cows at the start and end of the breeding season. Stocking rate for each treatment was 1 cow/ha. Forage IVDMD, CP, and total ergot alkaloid concentrations were affected (P<0.05) by the treatment×sampling date interaction. Hay offered, cow BW, and BCS at breeding, end of breeding, and at weaning were greater (P<0.05) from fall-calving vs. spring-calving. Cow BW at weaning was greater (P<0.05) from F75 and S75 vs. F100 and S100. The calving season×NE+ % interaction affected (P<0.05) calving rates. Preweaning calf BW gain, actual and adjusted weaning BW, ADG, sale price, and calf value at weaning were greater (P<0.05) from fall-calving vs. spring-calving and from SNE100 vs. S75 except for sale price which was greater (P<0.05) from S75 vs. SNE100. Cow concentrations of serum prolactin at breeding and serum NEFA at the end of breeding were affected (P<0.05) by the calving season×NE+ % interaction. Serum Zn and Cu concentrations from cows were affected (P<0.05) by calving season. A fall-calving season may be more desirable for cows grazing E+, resulting in greater calving rates, cow performance, and calf BW at weaning, whereas limited access to NE+ may increase calving rates, serum prolactin, and NEFA concentrations during certain times in the production cycle, particularly in spring-calving cows.

First Report of Rust Caused by Puccinia emaculata on Switchgrass in Arkansas.

In May 2007, switchgrass (Panicum virgatum L.) cv. Alamo and a breeding line, OSU-NSL 2001-1, were planted at the Arkansas Agricultural Research and Extension Center, Fayetteville. In August 2008, a high incidence of dark brown-to-black rectangular foliar lesions delineated by major veins was observed throughout plots of both lines. Lesions covered 25% to nearly 100% of total leaf tissue. Similar symptoms were also observed on unknown switchgrass cultivars in Benton County in northwest Arkansas and in St. Francis County in east-central Arkansas, suggesting that the disease was widely distributed throughout the state. The pathogen produced epiphyllous and adaxial masses of dark brown-to-black telia from erumpent fissures on leaf surfaces. Dark brown teliospores were observed under magnification and were two-celled, oblong to ellipsoid, and 33 ± 3.5 µm long with an apical cell width of 17.5 ± 2.7 µm and basal cell width of 16.2 ± 2.8 µm (reported as mean ± standard deviation, n = 25). Pedicles were colorless to light brown and measured 25.4 ± 9.2 µm (n = 25). In June 2009, at the Fayetteville Research and Extension Center, several second-year stands of switchgrass developed amphigenous and adaxial foliar lesions containing urediniospores. The uredia were globose and finely echinulate, measuring 23.1 ± 2.2 µm (n = 25) with brown cell walls. Teliospore and urediniospore morphology from all collections was consistent with Puccinia emaculata Schw. (2). Genomic DNA was extracted from a representative infected leaf of cv. Alamo, collected in Fayetteville, AR in June 2009, and amplified by PCR with primer sets PRITS1F (3) and ITS4B (1), which amplified an 803-bp fragment of rDNA encoding the first internal transcribed spacer (ITS1), 5.8S subunit, and second internal transcribed spacer (ITS2). The fragment was cloned into pGEM T Easy (Promega Corp, Madison, WI) and sequenced. A BLAST search of GenBank revealed that the fragment was most similar to the rDNA of P. emaculata (GenBank Accession No. EU915294.1; 755 of 758 bases matching; 99% identity) previously reported as a pathogen on switchgrass in Tennessee (3). The incidence and severity of rust on the widely planted switchgrass cv. Alamo is considerable cause for concern as efforts are made to increase acreage and production. Climatic conditions in St. Francis County are generally consistent with locations in Tennessee where switchgrass rust was previously reported (3). However, northwest Arkansas represents the eastern edge of the southwestern United States, suggesting that P. emaculata may affect switchgrass in geographically diverse areas of the United States. To our knowledge, this study represents the first report of rust on switchgrass in Arkansas. Managing this disease will be an important consideration for large-scale switchgrass cultivation in the state. References: (1) M. Gardes and T. D. Bruns. Mol. Ecol. 2:113, 1993. (2) P. Ramachar and G. Cummins. Mycopathol. Mycol. Appl. 25:7, 1965. (3) J. Zale et al. Plant. Dis. 92:1710, 2008.

Effects of fescue type and sampling date on the nitrogen disappearance kinetics of autumn-stockpiled tall fescue.

Two tall fescue [Lolium arundinaceum (Schreb.) Darbysh] forages, one an experimental host plant/endophyte association containing a novel endophyte that produces low or nil concentrations of ergot alkaloids (HM4) and the other a typical association of Kentucky 31 tall fescue and the wild-type endophyte (Neotyphodium coenophialum; E+), were autumn-stockpiled following late-summer clipping and fertilization with 56 kg/ha of N to assess N partitioning and ruminal disappearance kinetics of N for these autumn-stockpiled tall fescue forages. Beginning on December 4, 2003, sixteen 361 +/- 56.4-kg replacement dairy heifers were stratified by weight and breeding, and assigned to one of four 1.6-ha pastures (2 each of E+ and HM4) that were strip-grazed throughout the winter. Pastures were sampled before grazing was initiated (December 4), each time heifers were allowed access to a fresh pasture strip (December 26, January 15, and February 4), and when the study was terminated (February 26). Generally, fescue type and the fescue type x sampling date interaction exhibited only minor effects on total forage N, or partitioning of N within the cell solubles or the cell wall. For pregrazed forages, concentrations of N and N partitioned within the cell solubles both declined in a strongly linear relationship with sampling dates. In contrast, concentrations of cell-wall-associated N changed in erratic and often higher-ordered relationships with time, but the magnitude of these responses generally was limited. Unlike the partitioning of N within cell-wall and cell-soluble fractions, kinetic characteristics of ruminal N disappearance frequently exhibited interactions of fescue type and sampling date. For pregrazed forages, these included interactions for all response variables, and for postgrazed forages, fractions B and C, as well as rumen degradable protein. Ruminal disappearance rate for pregrazed E+ and HM4 exhibited quadratic (range = 0.057 to 0.082/h) and cubic (range = 0.057 to 0.075/h) relationships with time, respectively. For postgrazed E+ and HM4 forages, ruminal disappearance rate was unaffected (mean = 0.066/h) or only tended to be affected by sampling date (mean = 0.065/h), respectively. Concentrations of rumen degradable protein exhibited various curvilinear relationships with sampling dates, but disappearance was consistently extensive, and the overall range was relatively narrow (71.3 to 78.9% of N). These findings suggest that ruminal disappearance of N for autumn-stockpiled tall fescue forages remains extensive throughout the winter months and is only affected minimally by fescue type, sampling date, and grazing status.

Animal performance and economic comparison of novel and toxic endophyte tall fescues to cool-season annuals.

Increased costs of annual establishment of small grain pasture associated with fuel, machinery, and labor are eroding the profitability of stocker cattle enterprises. Interest has therefore increased in development of cool-season perennial grasses that are persistent and high quality. This study occurred on 24 ha (divided into thirty 0.81-ha paddocks) located at the University of Arkansas Division of Agriculture Livestock and Forestry Branch Station, near Batesville. Two tall fescue (Festuca arundinacea Schreb.) cultivars infected with novel endophytes (NE), Jesup infected with AR542 endophyte (Jesup AR542), and HiMag infected with Number 11 endophyte (HM11) were established in September 2002. Jesup AR542 and HM11 were compared with endemic endophyte Kentucky 31 (KY-31) tall fescue; wheat (Triticum aestivum L.) and cereal rye (WR, Secale cereale L.) planted in September 2003, 2004, and 2005; and annual ryegrass [RG, Lolium perenne L. ssp. multiflorum (Lam.) Husnot] planted in September 2004 and 2005. Each year, 3 steers (3.7 steers/ha) were placed on each pasture for fall and winter grazing, and 5 steers (6.2 steers/ha) were placed on each pasture for spring grazing. Animal performance is presented by year in the presence of a year x treatment interaction (P < 0.01). Body weight gain per hectare of steers grazing NE tall fescue was greater (P < 0.01) than those of KY-31 and WR during 2003 to 2004, whereas in 2004 to 2005, BW gain per hectare of steers grazing NE and RG did not differ (P < or = 0.29) and was greater (P < 0.01) than that of WR, which was greater (P < 0.01) than that of KY-31. During 2005 to 2006, BW gain per hectare was greater (P < 0.01) for steers grazing RG than those of NE and WR, which did not differ (P > or = 0.14). Body weight gain per hectare was least (P < 0.01) for steers grazing KY-31. Average net return of NE tall fescue was greater (P < 0.01) than KY-31, but profitability of NE did not consistently differ from cool-season annuals. Across the 3-yr study, NE tall fescue produced net returns per hectare of $219; this level of profitability would require 4 yr for a new planting of NE tall fescue to break even. Novel endophyte tall fescues offer potential benefits related to decreased risk of stand establishment of annual forage crops, longer growing season, and acceptable animal performance.

Effects of fescue type and sampling date on the ruminal disappearance kinetics of autumn-stockpiled tall fescue.

Two tall fescue (Festuca arundinacea Schreb.) forages, one an experimental host plant/endophyte association containing a novel endophyte (HM4) that produces low or nil concentrations of ergot alkaloids, and the other a typical association of Kentucky 31 tall fescue and the wild-type endophyte (Neotyphodium coenophialum; E+), were autumn-stockpiled following late-summer clipping and fertilization with 56 kg/ha of N to assess the nutritive value and ruminal disappearance kinetics of autumn-stockpiled tall fescue forages. Beginning on December 4, 2003, sixteen 361 +/- 56.4-kg replacement dairy heifers were stratified by weight and breeding and assigned to one of four 1.6-ha pastures (2 each of E+ and HM4) that were strip-grazed throughout the winter. Pastures were sampled before grazing was initiated (December 4), each time heifers were allowed access to a fresh strip (December 26, January 15, and February 4), and when the study was terminated (February 26). For fiber components, there were no interactions between fescue type and sampling date for either pregrazed or postgrazed forages. Over sampling dates, neutral detergent fiber (NDF; 56.5 to 67.8%), acid detergent fiber (27.7 to 34.9%), hemicellulose (28.8 to 34.0%), cellulose (25.0 to 28.1%), and lignin (3.61 to 10.05%) varied with sampling date, but patterns were almost exclusively curvilinear with time. Ruminal disappearance rate of dry matter (DM) was not affected by any treatment factor (overall mean for both pregrazed and postgrazed forages = 0.050 h(- 1)); similar responses were observed for NDF disappearance (overall mean = 0.048 h(- 1)). Interactions of fescue type and sampling date were observed for both pregrazed and postgrazed forages with respect to effective ruminal disappearance of DM; however, estimates were relatively high for all forages (overall mean = 64.0%). Effective disappearance of NDF was relatively extensive for all forages (overall mean = 55.4% of NDF). Based on the results of this trial, the endophyte status of stockpiled tall fescue forages had little practical effect on forage nutritive value and kinetics of ruminal DM or NDF disappearance. Overall, autumn-stockpiled tall fescue forages would appear to be a legitimate and lower cost alternative to harvested forages, and appear to possess suitable nutritional characteristics for developing dairy heifers in the Ozark Highlands.

Growth rate and physiology of steers grazing tall fescue inoculated with novel endophytes.

Cattle grazing tall fescue (Festuca arundinacea Schreb.) often develop fescue toxicosis. This condition is thought to be caused by ergot alkaloids produced by the endophyte Neotyphodium coenophialum. Endophytes from wild tall fescue plants, which do not produce ergot alkaloids, were transferred into the endophyte-free tall fescue germplasm, HiMag. The novel associations also lacked the ability to produce ergot alkaloids. Our objective was to determine whether cattle grazing these novel endophyte associations showed signs of fescue toxicosis. At the Fayetteville, Arkansas location, tester steers (n = 72) were assigned to one of four pasture treatments: endophyte-free HiMag tall fescue (HiMag-); 'Kentucky-31' tall fescue infected with its native, toxic endophyte (KY+); and two novel endophyte-infected tall fescue associations, HiMag4 and HiMag9. At the Mount Vernon, Missouri location, steers (n = 54) were used to test three of the four cultivars (HiMag9 was not tested). Ergot alkaloid concentrations in the forage of HiMag4 and HiMag9 were low or undetectable. Respiration rate, rectal temperature, ADG, and hair scores were measured during the grazing period. Blood was collected via jugular venipuncture and used for prolactin, aspartate aminotransferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), cholesterol, triglyceride, and creatinine analysis. Weight gains by steers grazing HiMag4 and HiMag9 did not differ from those of steers grazing HiMag-, but were greater than gains (P < 0.05) by steers on the KY+ treatment. Steers grazing KY+ had higher (P < 0.05) respiration rates, rectal temperatures, and hair scores than did steers grazing novel endophyte and HiMag- pastures. Prolactin, ALP, cholesterol, LDH, and triglycerides all were suppressed (P < 0.05) in steers grazing KY+ compared with steers grazing novel endophyte and HiMag- pastures. Steers grazing the novel endophyte tall fescues did not suffer from the decreased weight gains and toxicities associated with fescue toxicosis, resulting in enhanced animal production.

Use of a rat model to evaluate tall fescue seed infected with introduced strains of Neotyphodium coenophialum.

Experimental cultivars of the pasture grass tall fescue are infected with unique strains of the fungal endophyte Neotyphodium coenophialum, which produce low concentrations of ergot alkaloids. A rat model was evaluated as a tool for rapid, initial screening of experimental cultivars considered to be nontoxic. Rats were fed diets that included seed from experimental cultivars of tall fescue with introduced strains of N. coenophialum and a toxic control diet containing seed of the cultivar Kentucky 31 (KY31), with its endemic strain of N. coenophialum. Rats were preconditioned to a nontoxic diet and then fed treatment diets for 13 days with 5 days at thermoneutrality (21 degrees C) followed by 8 days under heat stress (31 degrees C). For most of the 13-day treatment period, rats fed KY31 exhibited depressed daily intake compared to those fed diets of cultivars with introduced endophytes (P < 0.05). In addition, rats fed KY31 exhibited significantly less weight than rats on other diets after heat treatment was imposed. For all initial trials and repeated trials, total intake and total gain calculated at the end of each trial were the most consistent indicators of toxicity.

Ischemic stroke outcome: racial differences in the trial of danaparoid in acute stroke (TOAST).

OBJECTIVE: To determine racial differences in baseline stroke risk factors and other measures in the Trial of ORG 10172 in Acute Stroke Therapy (TOAST). Differences in these factors could influence response to acute stroke therapy and overall stroke outcome. METHODS: The authors compared baseline demographic, medical, stroke, physical examination, CT, laboratory, and neurologic factors among 292 African-American and 801 white patients who enrolled in the TOAST study. TOAST compared danaparoid (ORG 10172) with placebo among acute ischemic stroke patients who were treated within 24 hours of stroke onset. RESULTS: African-Americans were younger and more frequently had hypertension, diabetes mellitus, congestive heart failure, and prior strokes. In addition, African-Americans had higher mean diastolic blood pressure, more lacunar strokes, and more severe prestroke disability. There were no significant differences between African-Americans and white patients in outcomes at 7 days, overall number of adverse experiences, or occurrence of serious bleeds or hemorrhagic transformations. However, there was a trend toward a higher rate of favorable outcomes in white patients at 7 days. There was no significant difference in very favorable outcome at 3 months between African-American and white patients, but significantly more white patients had favorable outcome at 3 months. CONCLUSION: Although African-Americans possess a number of factors that should predict higher rates of poor stroke outcome after acute therapy, they have the capacity to respond similarly to white patients after acute stroke therapy. Perhaps younger age and presence of lacunar infarction are stronger predictors of good outcomes than was appreciated previously.

ELISA for the detection of antibodies to Ebola viruses.

EIAs for IgG and IgM antibodies directed against Ebola (EBO) viral antigens have been developed and evaluated using sera of animals and humans surviving infection with EBO viruses. The IgM capture assay detected anti-EBO (subtype Reston) antibodies in the sera of 5 of 5 experimentally infected animals at the time they succumbed to lethal infections. IgM antibodies were also detected in the serum of a human who was infected with EBO (subtype Reston) during a postmortem examination of an infected monkey. The antibody was detectable as early as day 6 after infection in experimentally infected animals and persisted for <90 days. The IgG response was less rapid; however, it persisted for >400 days in 3 animals who survived infection, and it persisted for approximately 10 years after infection in the sera of 2 humans. Although these data are limited by the number of sera available for verification, the IgM assay seems to have great promise as a diagnostic tool. Furthermore the long-term persistence of the IgG antibodies measured by this test strongly suggests that the ELISA will be useful in field investigations of EBO virus.

The effect of physician characteristics on compliance with adult preventive care guidelines.

BACKGROUND AND OBJECTIVES: This study identified physician characteristics and attitudes related to self-reported compliance with adult prevention guidelines. METHODS: A questionnaire was mailed to family practice and internal medicine residents and faculty at the University of Iowa (n = 209). The questionnaire's 78 items fell into seven categories, including physician demographics, history-taking practices, counseling practices, self-perceived effectiveness in changing patient behavior, beliefs about preventive care, knowledge about preventive care, and perceived barriers to the delivery of preventive care. RESULTS: Compliance with history-taking recommendations was independently associated with high knowledge scores, female physician gender, and high self-perceived effectiveness in changing patient behavior. The only factor that was independently associated with counseling efforts was self-perceived effectiveness in changing patient behavior. CONCLUSIONS: Factors that were independently associated with self-reported preventive care efforts include female physician gender, knowledge about preventive care guidelines, and perceived effectiveness in changing patient behavior. After controlling for these factors, other variables such as lack of time, lack of reminder systems, attitudes about preventive care, and amount of formal preventive care education were not related to self-reported compliance with counseling and history-taking recommendations.

Hysterectomy and myomectomy by laparotomy.

Hysterectomy provides definitive treatment for uterine fibroids. Surgery should be offered to women whose fibroids are symptomatic; it is not indicated on the basis of uterine size alone. Myomectomy is an option for those wishing to preserve uterine function. The prospects for successful pregnancy following myomectomy are encouraging, although there is a significant risk of the later recurrence of fibroids. Laparotomy remains the most appropriate surgical approach for large fibroids, although vaginal, rather than abdominal, hysterectomy may be suitable for some women whose uteri do not exceed a 12-14 week gestation size. There is some evidence that the morbidity of abdominal procedures increases with very large uteri. Uterine shrinkage with GnRH analogues may facilitate vaginal hysterectomy and be useful prior to abdominal hysterectomy or myomectomy for very large fibroids, although cost-effectiveness for its use with abdominal procedures has not been demonstrated.

Medroxyprogesterone acetate with Zoladex for long-term treatment of fibroids: effects on bone density and patient acceptability.

A randomized trial was carried out to investigate the effect of 12 months administration of the gonadotrophin-releasing hormone agonist (GnRHa) Zoladex in combination with either placebo or medroxyprogesterone acetate (MPA) from the third month. Bone density, markers of bone resorption, symptoms and uterine volume were monitored in 24 women with symptomatic fibroids or menstrual problems. A total of 21 women were recruited to act as controls for the assessment of bone parameters. Vasomotor side-effects were reduced significantly in the MPA-treated group. The reduction in uterine volume in women with fibroids was not impaired by the addition of MPA. The bone markers osteocalcin and alkaline phosphatase were assessed in plasma, and the cross-links pyridinoline and deoxypyridinoline measured in urine. Changes in these markers are reported which suggest increases in bone resorption during the period of observation. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry at the spine and forearm. The net reduction in BMD at the spine in the treated groups was 4.30 +/- 0.59% at 6 months and 7.50 +/- 0.78% at 1 year, with no change in the control group. No change was seen in forearm BMD. No protective effect was observed when MPA was added. At 1 year after the completion of treatment, BMD remained significantly below baseline, and this has implications for the prolonged use of GnRHa.

A medical audit and patient survey of hysterectomies performed for menstrual disorders.

The aim of the study was to carry out an audit of 283 hysterectomies performed for menstrual disorders over a one year period, and to determine the satisfaction of the women concerned towards their treatment. The medical records of these patients were examined, and they were each sent a questionnaire, 69% of which were completed and returned. The most common presenting symptoms were menorrhagia and dysmenorrhoea. In 53% of cases no clinical abnormality was postulated and in 31% of cases no pathological abnormality was found. The preoperative clinical and pathological diagnoses were in agreement for 59% of patients. Over 90% of women were satisfied with the management of their case by their GP and the gynaecology outpatient clinic. The use of patient-controlled analgesia systems was associated with better post-operative pain relief than intramuscular injections. Thirteen percent of patients required blood transfusion; 21% suffered some form of postoperative complication, most of which were minor. Ninety-four percent of the women were pleased that they had undergone hysterectomy, and 76% wished that they had had the operation sooner. It was concluded that hysterectomy is perceived positively by patients and should not necessarily be considered as a last resort treatment for menstrual disorders.

Endophyte infection effects on stomatal conductance, osmotic adjustment and drought recovery of tall fescue.

Presence of the endophytic; fungus Acremonium coenophialum Morgan-Jones and Gams in tall fescue (Festuca artuidinacea- Sehreb.) enhances host persistence in drought-prone environments. However, the physiological mechanism is not well understood. We investigated the influence of endophyte infection and water deficit on osmotic adjustment, stomatal conductance, tiller survival and leaf elongation rate of genotype GA87-122 and cv. Kentucky-31 (KY31) of tall fescue. Plants were grown in a greenhouse in pots containing fine-silty topsoil (experiment 1) or sand (experiment 2). In expt 1, endophyte-infected (EI) and endophyte-free (EF) isolines of GA87-122 were exposed to two drought preconditioning cycles, after which all pots were re-watered and osmotic adjustment determined. Osmotic adjustment was -0.46 and -0.51 MPa in El leaf blades and tiller bases and -0.29 and -0.13 MPa in EF leaf blades and tiller bases, respectively. In expt 2, EI and EF GA87-122 and KY31 Mere exposed to severe drought after two preconditioning cycles, then re-watered. During the second preconditioning drying cycle of KY31, stomatal conductance tended to be lower in EI than in EF plants, but the difference was significant (P⩽ 0-05) only at two sampling times. Shoot tissues osmotically adjusted 0.17-0.31 MPa more in EI than in EF plants. Tiller survival and leaf elongation rates were higher (P⩽ 0.05) in preconditioned EI than in EF plants. Basal-zone osmotic adjustment was correlated with tiller survival rate in GA87-122 and KY31 (r = 0.87, P⩽ 0.01 for both). Enhanced osmotic adjustment in the meristematic and growing zone might account far improved survival of tillers by facilitating protection of the apical meristem.

Ovarian suppression with the gonadotrophin-releasing hormone agonist goserelin (Zoladex) in management of the premenstrual tension syndrome.

The objective of this study was to determine the effectiveness of ovarian suppression by a GnRH agonist analogue in 32 women with prospectively confirmed severe premenstrual tension. The design was a randomized, double-blind study comparing goserelin 3.6 mg with placebo, both given as a monthly s.c. injection for 3 months. Self-assessment was by daily visual analogue scales (VAS) for anxiety and depression, daily quantitative symptom rating for breast discomfort, swelling, irritability, tension, depression and by monthly Hospital Anxiety and Depression (HAD) scales. Of the 16 women in each group, 15 completed active and 12 completed placebo therapy. Median symptom scores for whole cycles showed a significant reduction of breast discomfort and swelling during active treatment, with no significant improvement in psychological symptoms. Analysis by cycle phase showed that for individual subjects, pre-treatment differences in VAS scores for anxiety and depression were abolished in a significantly greater proportion of actively treated cycles. Within-group comparisons showed a marked placebo effect and, comparing the two groups, differences reached significance only during treatment cycle 1 and the first post-treatment cycle for anxiety with no significant differences for depression. It was concluded that while suppression of ovarian activity with a gonadotrophin-releasing hormone analogue dampens down cyclical mood swings, it has a more marked effect on the physical components of the premenstrual syndrome. Results reconfirm the positive role of placebo in the management of this condition.

Treatment with the gonadotrophin releasing hormone-agonist goserelin before hysterectomy for uterine fibroids.

OBJECTIVE: To investigate the effect of the gonadotrophin releasing hormone (GnRH)-agonist goserelin, given by monthly subcutaneous injection for three months prior to total abdominal hysterectomy for uterine leiomyomata, on the pre-operative symptoms, difficulty of operation and operative blood loss. DESIGN: Randomised placebo-controlled study. SETTING: Patients were recruited from the gynaecological outpatient departments from hospitals in Edinburgh, Glasgow and Newcastle. SUBJECTS: Seventy-one premenopausal women with uterine leiomyomata who were on the waiting list for hysterectomy. INTERVENTIONS: After the presence of leiomyomata was confirmed using ultrasonography, the women were randomised to receive either the GnRH-agonist goserelin by monthly subcutaneous injection or a sham injection for three months prior to operation. At the monthly visits, patients were asked about treatment related symptoms, fibroid related symptoms, and their bleeding patterns. Blood was taken for haematological assessment. MAIN OUTCOME MEASURES: Haemoglobin concentrations at recruitment, at operation and post-operatively, pre-operative symptoms, operative difficulty and blood loss and post-operative complications. RESULTS: Treatment with goserelin induced amenorrhoea in over 80% of the women, and this was associated with a significant rise in haemoglobin level. At the time of operation, fibroid related symptoms were less in the goserelin group than in the placebo group. The hysterectomy was technically easier and the median (range) operative blood loss was significantly lower in the goserelin group compared with the placebo group (187 (60-600) ml vs 308 (118-1000) ml respectively; P < 0.05, Wilcoxon signed rank test). There was no difference between the two groups in the duration of hospital stay or the frequency of post-operative complications. The fibroids were smaller at the time of operation in the goserelin group, and more women treated with goserelin were able to have their operations through a transverse incision. CONCLUSIONS: This study demonstrates the benefits of goserelin in women having total abdominal hysterectomy for uterine leiomyomata.

Oral teratoma (epignathus) with intracranial extension: a report of two cases.

Epignathi are unusual congenital tumours presenting as oropharyngeal masses, often resulting in rapid asphyxia following birth. Occasionally, intracranial extension of the tumour is present, and two such cases are described. The presence of this complication, diagnosable by ultrasound examination, indicates that aggressive surgical treatment is inappropriate.