A randomized, double-blind phase II study evaluating cediranib versus cediranib and saracatinib in patients with relapsed metastatic clear-cell renal cancer (COSAK).

BACKGROUND: Preclinical work suggests SRC proteins have a role in the development of resistance to vascular endothelial growth factor (VEGF) targeted therapy in metastatic clear-cell renal cancer (mRCC). This hypothesis was tested in this trial using the SRC inhibitor saracatinib and the VEGF inhibitor cediranib. PATIENTS AND METHODS: Patients with disease progression after ≥1 VEGF-targeted therapy were eligible to participate in this double-blind, randomized (1:1) phase II study. The study compared the combination cediranib 30 mg once daily (o.d.) and saracatinib 175 mg o.d. (CS) (n = 69) or cediranib 45 mg o.d. and placebo o.d. (C) (n = 69). Archived tissue was used for biomarker analysis [SRC, focal adhesion kinase (FAK), von Hippel-Lindau, protein tyrosine phosphatase 1b and hypoxia-inducible factor 2α : n = 86]. The primary end point was progression-free survival (PFS) by RECIST v1.1. RESULTS: Between 2010 and 2012, 138 patients were randomized across 16 UK sites. The characteristics of the two groups were well balanced. Partial responses were seen in 13.0% for C and 14.5% for CS (P > 0.05). There was no significant difference in PFS [5.4 months (3.6-7.3 months) for C and 3.9 (2.4-5.3 months) for CS; hazard ratio (HR) 1.18 (0.94-1.48)] or overall survival (OS) [14.2 months (11.2-16.8 months) for C and 10.0 (6.7-13.2 months) for CS; HR 1.28 (1.00-1.63)]. There was no significant difference in the frequency of key adverse events, dose reductions or drug discontinuations. None of the biomarkers were prognostic for PFS or OS. FAK overexpression correlated with an OS benefit [HR 2.29 (1.09-4.82), P > 0.05], but not PFS, for CS. CONCLUSIONS: Saracatinib did not increase the efficacy of a VEGF-targeted therapy (cediranib) in this setting. Biomarker analysis did not identify consistent predictive biomarkers. CLINICALTRIALSGOV: NCT00942877.

Maternal testosterone levels are associated with C-peptide levels in the Mexican American subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study cohort.

Altered sex hormone levels are thought to play an important role in adult-onset diseases including obesity, cardiovascular disease, and diabetes. They contribute to these complex diseases through changes in their availability, which is influenced, in part, by binding proteins. Insulin resistance, which is characteristic of these diseases, along with increased insulin secretion, is a physiologic change that occurs normally during pregnancy. To determine the relationship between insulin resistance and sex hormone levels, we examined the associations of sex hormone-binding globulin (SHBG) and testosterone with measures of glycemia and insulinemia in a healthy pregnant population. We measured fasting serum SHBG and testosterone levels in 215 Hispanic mothers of Mexican ancestry from the HAPO Study cohort and tested for associations between SHBG and testosterone levels and maternal plasma glucose and C-peptide. After adjusting for confounding variables, serum total testosterone (TT) was positively associated with fasting C-peptide (0.18 µg/l higher for TT higher by 1 SD, p=0.001) and 1-h C-peptide (0.79 µg/l higher for TT higher by 1 SD, p<0.001). Free testosterone (FT) was also positively associated with fasting C-peptide (0.19 µg/l higher for FT higher by 1 SD, p<0.001), and 1-h C-peptide (0.83 µg/l higher for FT higher by 1 SD, p<0.001). Although these findings are from a single cohort, this study provides evidence for an association between testosterone and C-peptide during pregnancy in a nondiabetic Hispanic obstetric population.

Lung uptake on technetium-99m-MDP bone scan in Wegener's vasculitis.

A 99mTc-MDP bone scan was performed on a 65-yr-old woman because of joint pain. The study showed bilateral lung uptake and no abnormalities of the affected joints. Wegener's vasculitis was diagnosed. Lung uptake on bone scans has been noted in various conditions but not Wegener's vasculitis. The differential diagnosis of lung uptake on bone scan should include Wegener's vasculitis.

Tacrolimus (FK 506)--a new therapeutic agent for severe recalcitrant psoriasis.

BACKGROUND: Psoriasis, a disease of unknown etiology, is in some patients severe, extremely debilitating, and unresponsive to conventional therapies, including UV-B, oral psoralen with long-wave UV radiation in the A range (PUVA), oral retinoids, and methotrexate. We report the results from our study of seven patients with refractory psoriasis who were treated with the new immunosuppressive drug, tacrolimus (FK 506). OBSERVATIONS: All seven patients showed a dramatic resolution of psoriasis that remained in remission as long as they received full-dose therapy. Serial skin biopsy specimens demonstrated a rapid disappearance of the inflammatory infiltrate and a slower resolution of the epidermal changes. Tacrolimus was well tolerated during the 5.5 to 14 months of observation. Side effects, including nephrotoxicity and hypertension, were controlled by appropriate modification of drug dosage. CONCLUSIONS: Tacrolimus, a new immunosuppressive agent, is effective in treating patients with severe recalcitrant psoriasis. The mechanism of its action in psoriasis is unknown, but it may be related to its ability to modulate immune function. Further studies will establish criteria for patient selection and drug dosage, to maximize efficacy of this agent in psoriasis, while minimizing its toxicity.

A double-blind study to determine the duration of action of flurbiprofen in a sustained release preparation.

This double-blind, placebo-controlled, parallel-group study proves that the duration of activity of a sustained-release preparation of flurbiprofen 200 mg covers a full 24 hour period. In a group of 24 patients with clinically active rheumatoid arthritis a statistically significant increase of pain was noted 37 hours after the last active dose. The increase in disease symptoms was inversely related to the plasma flurbiprofen levels and was rapidly reversed with one active dose of sustained release flurbiprofen.

Destructive lesions of small joints in seronegative spondylarthropathies: relation to gut inflammation.

Destructive lesions of small joints were found in 40 out of 211 patients suffering from seronegative spondylarthropathies (SpA) on whom ileocolonoscopy with biopsies of the ileum and colon were performed. The destructive lesions of small joints, radiologically only distinguishable from rheumatoid arthritis lesions by the pauciarticular and asymmetrical involvement, the rare tendency to fusion and the rare occurrence of periosteal hypertrophy, were observed more frequently in patients presenting subclinical inflammatory gut lesions, predominantly of the chronic type, than in patients without gut inflammation.

The effect of glycerol and humidity on desmosome degradation in stratum corneum.

Moisturizers are known to have occlusive, emollient and humectant properties, all of which help to alleviate the symptoms of skin xerosis. Although the biological mode of action of moisturizers is poorly understood, the recent observation that skin xerosis is associated with incomplete desmosome digestion suggests that moisturizers improve the desquamation process in such conditions. To examine the possibility that certain moisturizers act by facilitating desmosomal digestion, we investigated the ability of glycerol, a common humectant, to influence this process in stratum corneum in vitro. Examining desmosome morphology in isolated stratum corneum by electron microscopy, it was observed that the desmosomes were in more advanced stages of degradation in glycerol-treated tissue compared with control tissue. This enhanced desmosomal degradation in glycerol-treated tissue was confirmed by significant decreases in the levels of immunoreactive desmoglein 1, a marker of desmosome integrity. Desmosomal degradation was also shown to be a humidity-dependent event, being significantly reduced at low relative humidity. The effect of glycerol on desmosome digestion was emphasized further in two in vitro model systems. Firstly, glycerol increased the rate of corneocyte loss from the superficial surface of human skin biopsies in a simple desquamation assay. Secondly, measurement of the mechanical strength of sheets of stratum corneum, using an extensiometer, indicated a dramatic reduction in the intercorneocyte forces following glycerol treatment. These studies demonstrated the ability of glycerol to facilitate desmosome digestion in vitro. Extrapolating from these results, we believe that one of the major actions of moisturizers in vivo is to aid the digestion of desmosomes which are abnormally retained in the superficial layers of xerotic stratum corneum.

Long-term follow-up of treated dental phobics.

Behavioural treatment programmes have been shown repeatedly to be effective in alleviating dental anxiety but few studies have provided long-term follow-ups. In this study, dentally anxious Ss who had completed a 4-session behavioural group programme were followed up for periods between 1 and 4 years after successful completion of treatment. It was hypothesized that dental visit satisfaction would be associated with regular dental attendance. 88% of Ss contacted agreed to cooperate; of these, 70% were still maintaining regular check-ups. There were no differences between regular and irregular attenders in terms of age, gender, education, marital status, degree of pre-treatment avoidance or time elapsed since completion of the programme. However, Ss who did not see their dentists regularly were more likely to have shown higher levels of anxiety immediately after completing the programme, less concordance between the subjective and overt behavioural aspects of anxiety and to have experienced more invasive than non-invasive procedures than the others. It was argued that dentally anxious individuals are not a homogeneous group and that a better understanding of their individual differences would lead to the development of more efficacious treatment procedures.

Oregon State University's Steer-a-Year program: integrating classroom learning and hands-on experience.

The Steer-a-Year course is designed to provide classroom and hands-on experience, industry-student interaction, and student group problem-solving opportunities. It is a cooperative agreement between the Department of Animal Sciences and the Oregon Cattlemen's and Cattlewomen's Associations. Steers are donated to the program by beef producers, fed a high concentrate ration to a target BW and condition, and marketed as either carcass or retail beef. After feed and management expenses are deducted, the Department of Animal Sciences retains one-half of the profit to be used for beef facilities improvements, and the other half is distributed to the donor's choice of either the Oregon Cattlemen's or Cattlewomen's Association. Approximately 30 steers have been donated to the program annually each of the past eight years. The donor receives updates regarding steer performance during the feeding period and carcass data following harvest of the animal. Students and instructors feed and manage the steers. The instructor uses classroom time to provide information to enable students to make informed management decisions. Officers are elected from within the class each term. Student officers are responsible for ensuring that cattle are managed and fed appropriately, and they lead the class in writing and sending producer updates. An evolving facet of the program is processing and marketing. Steers are sold locally through the Clark Meat Science Center. Students are encouraged to participate in a separate course in which they process the steers into retail product. In this manner, students can be involved in procurement, management, processing, and marketing. The course is challenging for the instructor since it requires management of lecture material, cattle health and feeding, producer and employee rapport, and student participation to ensure annual success of the program in terms of student learning and public relations. The course is very well received by students, most of whom have labeled it as a great learning experience.

Effects of supplementing prairie hay with corn and soybean meal on intake, digestion, and ruminal measurements by beef steers.

Prairie hay supplemented with various amounts of corn and soybean meal was fed to steers in two experiments. Effects of supplementation on hay OM intake, digestion, and ruminal fermentation and kinetics were measured. A preliminary study was conducted to attain accurate values for OM intake and digestibility of prairie hay to be used in ration formulation using the NRC (1996) level 1 model. Ten steers (284 +/- 9 kg) given ad libitum access to chopped prairie hay (75% NDF, 6% CP) were supplemented with dry-rolled corn (0.75% of BW/d) plus soybean meal (0.25% of BW/d). Hay OM intake was 1.85% of BW and hay OM digestibility was 48%. Based on results from the preliminary study, eight ruminally cannulated beef steers (317 +/- 25 kg) received a sequence of eight different supplementation combinations (2 x 4 factorial arrangement of treatments). These supplements consisted of dry-rolled corn at either 0 or 0.75% of BW (DM basis) daily combined with one of four amounts of added soybean meal to provide between 0 and 1.3 g of degradable intake protein (DIP)/kg of BW. After supplements had been fed for 10 d, feces were collected for 4 d. Intake of hay and total OM increased quadratically (P < 0.01) in response to added DIP with or without supplemental corn. Hay OM digestibility increased quadratically (P = 0.03) as DIP was added when corn was fed in the supplement. Intake of digestible OM was greater (P < 0.01) with than without corn supplementation. Increasing DIP increased (P < 0.01) digestible OM intake regardless of whether corn was fed. Inadequate ruminally degraded protein in grain-based supplements decreased forage intake, digestibility, and energy intake of cattle fed low-quality prairie hay. Providing adequate supplemental DIP to meet total diet DIP needs seemed to overcome negative associative effects typically found from supplementing low-quality forages with large quantities of low-protein, high-starch feeds.

Effects of implants on daily gains of steers wintered on dormant native tallgrass prairie, subsequent performance, and carcass characteristics.

Fall-weaned crossbred steer calves (n = 300; 184 +/- 2.9 kg) received either no implant (Control) or were implanted with Synovex-C (SC = 10 mg estradiol benzoate + 100 mg progesterone), Synovex-S (SS = 20 mg estradiol benzoate + 200 mg progesterone), or Revalor-G (RG = 8 mg estradiol-17beta + 40 mg trenbolone acetate) to determine the effects of implants on weight gain during winter grazing on dormant tallgrass prairie, subsequent grazing and finishing performance, and carcass characteristics. Steers grazed two dormant tallgrass prairie pastures from October 16, 1996, until March 29, 1997 (164 d), and received 1.36 kg/d of a 25% CP supplement that supplied 100 mg of monensin/steer. Following winter grazing, all steers were implanted with Ralgro (36 mg zeranol) and grazed a common tallgrass prairie pasture until July 17 (110 d). After summer grazing, all steers were implanted with Revalor-S (24 mg estradiol-17beta + 120 mg trenbolone acetate), and winter implant treatment groups were equally allotted to four feedlot pens. Steers were harvested November 17, 1997, after a 123-d finishing period. Daily gains during the winter grazing phase averaged .28, .32, .32, or .35 kg/d, respectively, for Control, SC, SS, or RG steers and were greater (P < .01) for implanted steers than for Controls. Summer daily gains were similar (1.05 +/- .016 kg/d; P > or = .61) for all treatment groups. Feedlot daily gains were also similar (1.67 +/- .034 kg/d; P > or = .21), with implanted steers weighing 14 kg more than Control steers (P = .05) at harvest, despite similar management during summer grazing and feedlot phases. Control steers tended (P = .06) to have lower yield grades. There were no differences (P = .99) in marbling between implanted and nonimplanted steers. Steers implanted during the wintering phase had increased skeletal and overall (P < .01) carcass maturities compared with nonimplanted steers, which resulted in more "B" and "C" maturity carcasses. Because carcass maturity score affects quality grade, the increased maturities of implanted steers resulted in a $9.04 decrease in carcass value/100 kg (P < .01) compared with Controls. The results of this study indicate that growth-promoting implants are efficacious for cattle wintered on dormant native range despite low daily gains. This increased weight is maintained through the summer grazing and feedlot phases; however, the benefit of the increased weight may be offset by decreased carcass quality grade and value due to increased carcass maturity.

Performance of light vs heavy steers grazing Plains Old World bluestem at three stocking rates.

Live weight gains of light and heavy calves grazing Plains Old World bluestem at three stocking rates were evaluated during the summers of 1997 and 1998. Initial weights of mixed-breed light-weight steers (LHT) were 141 SD = 17 kg (n = 214) in 1997 and 160 SD = 23 kg (n = 193) in 1998. Initial weights of mixed-breed heavy steers (HWT) were 265 SD = 17 kg (n = 115) in 1997 and 248 SD = 13 kg (n = 126) in 1998. Initial stocking rates for both sizes of steers were as follows: light, 392 kg of live weight/ha; moderate, 504 kg of live weight/ha (increased to 616 kg live weight/ha in 1998); and heavy, 840 kg of live weight/ ha. Averaged gain and gain/hectare are reported as stocking rate by steer type within year. Heavy steers had greater ADG than LHT steers during both years. Forage intake, expressed as a percentage of BW, was greater (P = 0.05) for LHT (3.1%) than for HWT (2.8%) calves. Grazing time (min/d; 1998 only) was greater (P = 0.05) for LHT (665) than for HWT (624) steers. Forage CP and in vivo digestible organic matter (DOM) were slightly greater (P < 0.05) in pastures grazed by HWT vs LHT cattle. Gain/hectare was greater (P < 0.05) for LHT than for HWT calves at all three stocking rates during both years. A linear decline in ADG was observed (P < 0.07) as stocking rates increased for HWT steers in 1997 and LHT steers in 1998. However, ADG did not decline with increasing stocking rate for LHT calves during 1997 or HWT calves during 1998. Forage intake was not different among stocking rates in either 1997 or 1998. Grazing time was greatest (P < 0.05) for steers in the moderate and heavy stocking rates. Forage in vivo DOM decreased (P < 0.05) as stocking rate increased. Both LHT and HWT steers had lower (P < 0.05) ADG at all three stocking rates during 1998 compared with 1997. Despite lower ADG, LHT steers had greater gain/hectare than HWT steers during both 1997 and 1998.

Pretanned leather shavings in a supplement mixture for steers: I. In situ and in vitro disappearance, ruminal fermentation, and organic matter, nitrogen, and fiber digestion.

Two digestion studies were conducted to evaluate the use of pretanned leather shavings as a component of a protein supplement. In Exp. 1, the in situ and in vitro disappearance of pretanned leather shavings and soybean meal was evaluated. Results revealed that less than 18.4% of the pretanned leather shavings was solubilized and disappeared when exposed to McDougall's buffer for 48 h, but there was 90.0% disappearance with 48-h exposure to a .1 N HCl/pepsin treatment and 97.0% disappearance with exposure to a two-stage digestion. In situ disappearance following 72 h in the rumen allowed 6.8% disappearance. Thus, leather shavings seem to be relatively indigestible in the rumen, but postruminal digestion may be possible. In Exp. 2, six Angus x Holstein steers, fitted with ruminal and duodenal cannulas, were used in a replicated 3 x 3 Latin square to evaluate ruminal and digestion effects of the following supplements combined with fescue hay at 1.7% of BW (DM basis): no supplementation (control); supplementation intraruminally with soybean meal at .07% of BW (as-fed basis); and supplementation intraruminally with a combination of soybean meal and pretanned leather shavings (17:8 ratio) at .05% of BW (isonitrogenous to soybean meal; as-fed basis). Ruminal fluid passage rate was greater and fluid turnover time was shorter in steers fed leather shavings than in those fed soybean meal (P = .10). Ruminal pH was lower (P = .04) for supplemented steers than for control steers and ruminal NH3 N concentration was greater (P = .01) in steers fed soybean meal than in those fed leather shavings. Total VFA concentration was increased (P = .02) by supplementation. Supplementation with soybean meal increased (P < .05) ruminal molar proportions of butyrate, valerate, and isovalerate compared with leather shavings. Duodenal OM flow and OM disappearing in the intestines were increased by supplementation (P < .10), but not by the type of supplement fed (P > .10). Ruminal digestion of OM and total tract OM digestion were unaffected (P > .10) by supplementation and the type of supplement fed. Flow and digestion of NDF were unaffected (P > .10) by the treatments. Flow of N and the quantity of N disappearing in the intestines were increased (P < .05) by supplementation but did not differ (P > .10) between supplementation groups. Microbial N flow, N utilization for net microbial protein synthesis, and ruminal N disappearance were unaffected (P > .10) by supplementation and the type of supplement provided. Combining pretanned leather shavings with soybean meal seemed to have no deleterious effects on digestion or fermentation and to allow for escape of some N to the lower tract.

Pretanned leather shavings in a supplement mixture for steers: II. Digesta kinetics, ruminal fermentation, and grazing behavior in steers grazing dormant wheatgrass pasture.

Twelve ruminally cannulated steers (Angus x Holstein; average initial BW = 533 +/- 3.28 kg) were randomly allotted to one of three treatments (four steers/treatment) to evaluate the use of pretanned leather shavings as a component of a protein supplement for steers grazing dormant intermediate wheatgrass (Thinopyrum intermedium Host). Steers were allotted to one of three treatments: 1) no supplement (control); 2) supplementation intraruminally at 0700 with soybean meal at .2% of BW (as-fed basis); 3) supplementation intraruminally with soybean meal and pretanned leather shavings (17:8 ratio, respectively) at .16% of BW (as-fed basis). Supplements were formulated so that intakes were isonitrogenous and were placed intraruminally once daily (0700). Sampling periods were conducted February 3 to 16 and February 17 to March 5, 1995. In situ organic matter disappearance of the soybean meal supplement was greater (P > .05) than that of the leather shavings supplement at all incubation times (1, 3, 6, 9, 12, 24, and 48 h). Data suggested that pretanned leather shavings within the leather shavings supplement were only 25% degradable within the rumen. Forage OM intake (control = 12.7, soybean meal = 12.7, and leather shavings = 13.4 g/kg of BW), grazing time, and grazing efficiency were not altered (P > .10) by supplementation or type of supplement provided but did increase between the February and March samplings. Total intake was increased (P = .09) with supplementation and reflected the addition of the protein supplements. Particulate and fluid passage estimates were unaffected (P > .10) by the supplements; however, gastrointestinal fill increased (P = .01) between the February and March samplings. Ruminal pH was lower (P = .04) and ruminal NH3 N concentration was greater (P = .02) for supplemented steers than for control steers, and supplementation treatments did not differ (P > .10). Total VFA concentrations were increased (P = .01) by supplementation but were not affected by type of supplement provided (P > .10). Ruminal molar proportions of acetate and propionate and the ratio of these two VFA did not differ (P > .10) between supplementation types. Nonetheless, supplementation increased molar proportions of butyrate (P = .04), valerate (P = .02), and isovalerate (P = .05), and leather shavings supplementation increased (P = .10) isobutyrate proportions over those in steers supplemented with soybean meal. Combining pretanned leather shavings with soybean meal seemed to have no deleterious effects on forage intake, digesta passage, grazing behavior, or ruminal fermentation and seemed to provide effects similar to those of soybean meal alone.

Evaluation of perennial ryegrass straw as a forage source for ruminants.

Two experiments were conducted to evaluate perennial ryegrass straw as a forage source for ruminants. Experiment 1 evaluated digestion and physiological variables in steers offered perennial ryegrass straw containing increasing levels of ergot alkaloid, lolitrem B. Sixteen ruminally cannulated Angus x Hereford steers (231+/-2 kg BW) were blocked by weight and assigned randomly to one of four treatments. Steers were provided perennial ryegrass straw at 120% of the previous 5-d average intake. Before straw feeding, soybean meal was provided (0.1% BW; CP basis) to meet the estimated requirement for degradable intake protein. Low (L) and high (H) lolitrem B straws (<100 and 1,550 ppb, respectively; DM basis) were used to formulate treatment diets: 100% L; 67% L:33% H; 33% L:67% H; 100% H (DM basis). Intake and digestibility of DM and OM, and ruminal pH, total VFA, and NH3-N were not affected by increasing lolitrem B concentration. Ruminal indigestible ADF (IADF) fill increased linearly (P = 0.01) and IADF passage rate decreased linearly (P = 0.04) as lolitrem B increased. Experiment 2 evaluated performance and production by 72 Angus x Hereford cows (539+/-5 kg BW) consuming perennial ryegrass straw containing increasing lolitrem B during the last third of gestation. Cows were blocked by body condition score and randomly assigned to one of three treatments. Cows were provided perennial ryegrass straw ad libitum and supplemented with soybean meal (0.1% BW; CP basis) to meet the estimated requirement for degradable intake protein. Mixtures of a L and H lolitrem B straw (467 and 2,017 ppb, respectively) were used to formulate treatment diets: 100% L, 50% L:50% H, 100% H (DM basis). Thirteen of 24 cows on the 100% H treatment exhibited signs of ryegrass staggers and were removed from the study; nevertheless, lolitrem B concentration did not influence pre- or postcalving weight or body condition score change. These data suggest that feeding perennial ryegrass straw containing up to 1,550 ppb lolitrem B (DM basis) did not adversely affect nutrient digestion or physiological response variables in steers. However, providing straw with a lolitrem B concentration of approximately 2,000 ppb (DM basis) resulted in 54% of cows exhibiting signs of ryegrass staggers. These data suggest that blending straws with a high (>2,000 ppb) and low (<500 ppb) concentration of lolitrem B can be a successful management practice.

Occipito-cervical fusion in rheumatoid arthritis.

Between 1977 and 1988 twenty-five patients with rheumatoid arthritis involving the cervical spine were treated by an occipito-cervical fusion. Twenty-two patients are included in this study. The main indications for surgery were intractable pain and progressive neural impairment. The operative procedure consisted of an H-bone graft fixed with steel wire in 19 cases, fusion of occiput-C2 six times and of occiput-C3 thirteen times. A Hartshill-Ransford (5, 12) loop was used in three cases: occiput-C3 twice and occiput-C7 once. The mean duration of follow-up was 3 years 8 months in 17 patients. Improvement of symptoms and signs was achieved in 88%. There were 2 post-operative deaths. The high rate of pseudarthrosis in our series was confirmed by several authors. The loop technique provides a more stable fixation and will be our technique of choice in the future.

Using guided imagery to reduce pain and anxiety.

Guided imagery is a therapeutic technique that allows a person to use his or her own imagination to connect their body and mind to achieve desirable outcomes such as decreased pain perception and reduced anxiety. This article describes the use and application of guided imagery for clients in the home and the benefits to the agency. A step-by-step approach to teaching clients how to use guided imagery is included.

The role of the polycystic ovary syndrome susceptibility locus D19S884 allele 8 in maternal glycemia and fetal size.

CONTEXT: The high incidence of insulin resistance, type 2 diabetes, and metabolic syndrome in Western societies and their impact on quality of life emphasize the importance of identifying underlying susceptibility loci for metabolic diseases. The polycystic ovary syndrome (PCOS) susceptibility locus D19S884 allele 8 (A8) is associated with measures of insulin resistance, beta-cell dysfunction, and other metabolic phenotypes in PCOS families. We now investigate the role of D19S884 A8 in pregnancy. OBJECTIVE: Using the multiethnic Hyperglycemia and Adverse Pregnancy Outcome cohort, we assessed the associations of D19S884 A8 with measures of maternal glycemia and fetal size. DESIGN: We tested for association of maternal D19S884 A8 with maternal outcomes (fasting, 1-h, and 2-h plasma glucose, and fasting and 1-h C-peptide from an oral glucose tolerance test) and fetal and maternal D19S884 A8 with fetal outcomes (birth weight, length, head circumference, sum of skin folds, fat mass, cord C-peptide, and 2-h neonatal plasma glucose). SUBJECTS: We analyzed 4424 Caucasian mothers and 3347 offspring of northern European ancestry, 1957 Thai mothers and 2089 offspring from Bangkok, 1208 Afro-Caribbean mothers and 1209 offspring from Barbados, and 774 Hispanic mothers and 762 offspring from Bellflower, California. RESULTS: After adjusting for confounding variables and multiple testing, neither maternal nor fetal D19S884 A8 showed significant evidence for association with any of the outcomes tested. CONCLUSIONS: The PCOS susceptibility locus, D19S884 A8, is not a major factor contributing to glycemia during pregnancy or fetal size in a general obstetric population.