Perceptions of underweight images: are women with anorexia nervosa perceived as attractive and healthy?

The current study examined the impact of receiving information about a woman's eating disorder status on perceptions of the woman's health and attractiveness. A total of 99 females and 84 males viewed a photo of a model who had disclosed her diagnosis of anorexia nervosa. Participants were randomly divided into three groups: model (M) group (those who were informed that the photo showed a model), eating disorders (ED) group (those who were informed that the photo showed a woman with an eating disorder), and no description control (C) group. Male and female participants in the ED group rated the woman in the photo as less healthy than did participants in the M and C groups. However, there were no differences between groups for ratings of attractiveness or the participants' desire to achieve a similar look (for females). Additionally, male participants rated the photo as less attractive than female participants had predicted. Finally, internalization of the thin ideal was a significant predictor of ratings of health and attractiveness of the woman in the photo.

Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor.

Substance P is released in the spinal cord in response to painful stimuli, but its role in nociceptive signaling remains unclear. When a conjugate of substance P and the ribosome-inactivating protein saporin was infused into the spinal cord, it was internalized and cytotoxic to lamina I spinal cord neurons that express the substance P receptor. This treatment left responses to mild noxious stimuli unchanged, but markedly attenuated responses to highly noxious stimuli and mechanical and thermal hyperalgesia. Thus, lamina I spinal cord neurons that express the substance P receptor play a pivotal role in the transmission of highly noxious stimuli and the maintenance of hyperalgesia.

Transmission of chronic nociception by spinal neurons expressing the substance P receptor.

Substance P receptor (SPR)-expressing spinal neurons were ablated with the selective cytotoxin substance P-saporin. Loss of these neurons resulted in a reduction of thermal hyperalgesia and mechanical allodynia associated with persistent neuropathic and inflammatory pain states. This loss appeared to be permanent. Responses to mildly painful stimuli and morphine analgesia were unaffected by this treatment. These results identify a target for treating persistent pain and suggest that the small population of SPR-expressing neurons in the dorsal horn of the spinal cord plays a pivotal role in the generation and maintenance of chronic neuropathic and inflammatory pain.

Production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226.

The increasing application of Ac-225 for cancer therapy indicates the potential need for its increased production and availability. The production of Ac-225 has been achieved using bremsstrahlung photons from an 18 MV medical linear accelerator (linac) to bombard a Ra-226 target. A linac dose of 2800 Gy produced about 64 microCi of Ra-225, which decays to Ac-225. This result, while consistent with the theoretical calculations, is far too low to be of practical use. A more powerful linac is required that runs at a higher current, longer pulse length and higher frequency for practical production. This process could also lead to the reduction of the nuclear waste product Ra-226.

Neonatal outcomes following planned preterm delivery in diabetic mothers.

OBJECTIVE: Women with diabetes may need elective preterm delivery due to pregnancy or diabetes related complications. The aim of this study was to describe the neonatal outcomes arising from elective preterm delivery in diabetic women. METHOD: Suitable patients were identified by the obstetric team at Hull Royal Infirmary Women and Children's Hospital and data was extracted from their case notes. 45 diabetic women with planned preterm delivery were identified within a set time frame, resulting in 48 babies. RESULTS: Of the 48 babies born, 47 survived. 36 out of 48 were delivered via caesarean section. Gestational ages ranged from 29+3 to 36+6 weeks, and 24 out of 48 (50%) had a birth weight greater than the 90th centile for gestational age.34 out of the 48 babies experienced some form of neonatal complication and were admitted to the neonatal unit. The median duration of stay in the neonatal unit was 7 days. 14 of the surviving neonates suffered from respiratory distress, although only 4 required surfactant therapy to regain respiratory function. However, the incidence of serious neonatal complications in those born after 34 weeks was shown to be low. CONCLUSIONS: Elective preterm delivery after 34 weeks had little effect on overall neonatal outcome. Therefore it could be proposed that elective preterm delivery after 34 weeks gestation may be an acceptable option in diabetic women if there are maternal or obstetric complications.

A theoretical model for the production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226.

Radium needles that were once implanted into tumours as a cancer treatment are now obsolete and constitute a radioactive waste problem, as their half-life is 1600 years. We are investigating the reduction of radium by transmutation on a small scale by bombarding Ra-226 with high-energy photons from a medical linear accelerator (linac) to produce Ra-225, which subsequently decays to Ac-225, which can be used as a generator to produce Bi-213 for use in 'targeted alpha therapy' for cancer. This paper examines the possibility of producing Ac-225 with a linac using an accurate theoretical model in which the bremsstrahlung photon spectrum at 18 MV linac electron energy is convoluted with the corresponding photonuclear cross sections of Ra-226. The total integrated yield can then be obtained and is compared with a computer simulation. This study shows that at 18 MV, the photonuclear reaction on Ra-226 can produce low activities of Ac-225 with a linac. However, a high power linac with high current, pulse length and frequency is needed to produce practical amounts of Ac-225 and a useful reduction of Ra-226.

Loss of differentiation control in transformed 3T3 T proadipocytes.

Nontransformed 3T3 T mesenchymal/proadipocyte stem cells can be readily induced to differentiate, yet previous work has shown that 3T3 T cells that are spontaneously or virally transformed not only lose their normal growth control mechanisms but also lose the ability to differentiate. Loss of growth control can be due to autocrine mechanisms in some transformed cells, but the mechanisms involved in disrupting differentiation control are poorly understood. Our goal is to further define the growth and differentiation defects that arise in neoplastically transformed cells and the mechanisms underlying those defects. For example, exogenous transforming growth factor beta and tumor necrosis factor, both of which are secreted aberrantly by some tumor cells, are known inhibitors of different steps of the normal 3T3 T adipocyte differentiation process, suggesting a potential role as autocrine factors in disrupting differentiation of transformed 3T3 T cells. In the current study we transformed 3T3 T cells in vitro with chemical or UV irradiation treatment in order to determine if the acquisition of the transformed phenotype after these treatments is also associated with loss of differentiation control as it is with spontaneously or virally transformed cells. Four chemically and two UV-treated 3T3 T cell lines were isolated from type III foci and all have been found to be tumorigenic in syngeneic animals and to have lost the ability to differentiate. Relative to the parental cell line the differentiation abilities of the transformed clones ranged from 0 to less than 5%. In this regard, we also analyzed the normal and aberrant expression of three growth factors and differentiation inhibitors in transformed cells. Both transforming growth factor alpha and beta were found to be expressed in non-transformed 3T3 T cells as determined by Northern blot analyses. In addition, both were found to be down-regulated during differentiation of 3T3 T cells. Transformed/differentiation-defective 3T3 T cells expressed varied levels of transforming growth factor alpha and beta. Three of the new transformed clones expressed particularly high levels of transforming growth factor alpha. Very low levels of tumor necrosis factor expression were found in the normal cells and the transformed cells appeared to express tumor necrosis factor at similar levels. In contrast, none of the transformed cells expressed any of the differentiation-specific genes tested (lipoprotein lipase, glycerol-3-phosphate dehydrogenase, etc.). Even a transformed clone which could undergo growth arrest but not morphological differentiation expressed no differentiation-specific genes. Together, these data suggest that neoplastic transformation in general disrupts differentiation control.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of L-10B-p-boronophenylalanine-fructose and the boron neutron capture reaction on mouse brain dopaminergic neurons.

Radiation damage to the dopamine tracts caused by enriched L-10B-p-boronophenylalanine (L-10BPA)-fructose and the boron neutron capture reaction was investigated using the mouse model. Following various treatments with L-10BPA and neutron irradiation of the head, the brain was perfusion fixed and removed; 50-microns frozen sections were cut. Dopaminergic neurons were visualized using immunohistochemistry for tyrosine hydroxylase. The administration of L-10BPA had no permanent effect on dopaminergic tracts. Neutron capture therapy with L-10BPA caused a reduction in tyrosine hydroxylase immunohistochemical activity within 4 h of irradiation, but by 48 h, this reduction reversed. No damage was observed at 120 h postirradiation.

Regional attitudes of generalists, specialists, and subspecialists about management of atrial fibrillation.

BACKGROUND: It is unknown whether physicians' attitudes about the management of atrial fibrillation (AF) reflect the recommendations of published guidelines. METHODS: To obtain information about physicians' attitudes about management of AF, a questionnaire was returned by 904 (20.1%) of 4500 physicians involved in managing AF (385 cardiologists, 326 internists, and 193 electrophysiologists). The cardiologists and internists were from Massachusetts or California; the electrophysiologists were from around the United States. The questionnaire called for 86 separate answers about use of resources and drug therapy for different types of AF, including recent-onset AF, paroxysmal AF, and chronic AF of less than 6 months' and more than 3 years' duration. RESULTS: Transthoracic echocardiography and thyroid function were requested by more than 90% of physicians; transesophageal echocardiography and catheterization were requested by 10% of physicians. To control ventricular response, digoxin was the overwhelming first-line therapy; calcium channel blockers were favored over beta-blockers for adjunct therapy. To prevent thromboemboli, warfarin sodium was preferred for chronic AF; warfarin or aspirin were equally considered for paroxysmal AF. In considering sinus rhythm, respondents agreed about factors determining whether to revert, the number of drug trials, and the first-line drug choice (quinidine sulfate) but disagreed about second-line antiarrhythmic drugs and whether to hospitalize the patient before initiating drug therapy. CONCLUSIONS: Physicians ranging from primary care providers to subspecialists agree on issues of AF management such as heart rate control and anticoagulation. Attitudes vary widely about issues such as antiarrhythmic drugs.

Safety and efficacy of nandrolone decanoate for treatment of wasting in patients with HIV infection.

OBJECTIVE: To evaluate the safety and efficacy of the anabolic steroid, nandrolone decanoate (Deca Durabolin) in patients with HIV wasting who are resistant to nutritional intervention. DESIGN: A 16-week open trial with subjects who had lost 5-15% of their usual body weight. SETTING: HIV/AIDS specialist ambulatory care services, both public and private, in sydney, Australia. PARTICIPANTS: Two hundred and twenty men entered the pre-therapy phase, and of these, 24 failed to gain weight and were enrolled. Seventeen subjects (81%) completed the 16-week trial. INTERVENTIONS: Pre-therapy nutritional assessment and education was conducted by the clinical dietitian. Those who failed to gain weight (10.9%) were treated with nandrolone decanoate (100 mg/ml) by deep intramuscular injection every 2 weeks for 16 weeks. MAIN OUTCOME MEASURES: Changes in weight and body composition (lean body mass, total body water and nitrogen index) were measured by anthropometry, bioelectrical impedance, and in vivo neutron activation. Changes in quality of life were assessed by the 30-item Medical Outcomes Study short form questionnaire. Changes in biochemistry, haematology and immunology were also measured. RESULTS: There were significant increases in weight (mean, 0.14 kg per week; P < 0.05) and lean body mass (mean, 3 kg by anthropometry; P < 0.005). The change in lean body mass was of similar magnitude across all measurement modalities. Quality of life parameters, especially functionality, increased significantly during the trial. No subject experienced toxicity. CONCLUSION: Nandrolone decanoate has beneficial effects on weight, lean body mass and quality of life in selected patients who have mild to moderate HIV wasting.

In vitro and preclinical targeted alpha therapy for melanoma, breast, prostate and colorectal cancers.

Targeted alpha therapy (TAT) can inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The alpha emitting radioisotopes Tb-149 and Bi-213 were chelated to cancer specific monoclonal antibodies to form alpha-immunoconjugates (AIC) against melanoma, leukaemia, prostate and colorectal cancer, and to the plasminogen activator inhibitor type-2 (PAI2) to form alpha-PAI2 (API) against breast and prostate cancer. These conjugates were found to be highly stable, specific and cytotoxic in vitro. Melanoma and breast cancer tumour growth was observed in nude mouse models for untreated controls and non-specific AIC/API at 2 days post-subcutaneous inoculation of cancer cells. Complete inhibition of melanoma and breast cancer growth was found for local injections of AIC and API, respectively. Intra-lesional TAT of established melanoma showed that all melanomas regressed with 100 microCi injections of AIC. These results point to the potential application of local and systemic TAT in the management of metastatic cancer.

Nitrogen deposition in malnourished children with cystic fibrosis.

To determine the protein nutritional status of 21 malnourished children with cystic fibrosis (CF), total body nitrogen (TBN) was measured and the results were compared with 21 control subjects. CF patients demonstrated a lower TBN (P less than 0.001). When matched for height (n = 10) or bone age (n = 13), the CF patients still had a depressed TBN/height or TBN/lean body mass (P less than 0.05). To assess nitrogen deposition during nutritional rehabilitation, repeat TBN measurements were performed on the 21 CF patients. Nitrogen deposition ranged from -230 to 550 g/y and correlated with weight velocity (r = 0.78, P less than 0.001). Increased nitrogen deposition (greater than 150 g/y) was generally associated with normal height gain (height velocity SD score greater than -2.00) and weight gain (greater than 2.0 kg/y). Decreased nitrogen deposition was associated with poor weight gain but did not preclude normal linear growth. These data suggest an important role for TBN estimations in defining protein nutritional status in children and indicate that skeletal growth can continue in the presence of minimal nitrogen deposition.

Determination of skeletal muscle and fat-free mass by nuclear and dual-energy x-ray absorptiometry methods in men and women aged 51-84 y (1-3).

BACKGROUND: Skeletal muscle mass (SMM) and fat-free mass (FFM) are important variables in nutritional studies. Accurate techniques for measuring these variables have not been thoroughly validated in elderly subjects. OBJECTIVES: The objectives of this study were to 1) compare SMM values derived from dual-energy X-ray absorptiometry (DXA) with those calculated by a nuclear method from total body potassium (TBK) and total body nitrogen (TBN) measurement (both: KN) in older subjects, and 2) assess the accuracy of FFM measurement by DXA in these subjects. DESIGN: TBK, TBN, DXA (model XR36; Norland, Fort Atkinson, WI), bioimpedance, and anthropometric measurements were performed on healthy women (n = 50) and men (n = 25) aged 51-84 y. RESULTS: Mean SMM by KN was not significantly different from SMM by DXA in either sex. SMM by KN predicted SMM by DXA with an SEE of 2.1 kg (r = 0.95, P < 0.0001 for women and men together). In the men, FFM by DXA agreed well with FFM estimated by TBK, skinfold thicknesses, bioimpedance analysis, and a multicompartment model. In women, FFM by DXA was 4-5 kg less than that by the other methods (P < 0.01). Truncal fat was related to intermethod FFM differences (r = 0.58, P < 0.0001). CONCLUSIONS: These data indicate that 1) either the nuclear or the DXA method can be applied to estimate SMM in healthy older subjects, and 2) the Norland DXA instrument significantly underestimates FFM in older women, in part, because of the influence of truncal adiposity.

Protein repletion and treatment in anorexia nervosa.

Body fat and total body nitrogen (TBN) were quantified before and after refeeding in 32 female anorexia nervosa patients and in 29 matched control subjects by using the techniques of anthropometry and in vivo neutron-capture analysis (IVNCA). Mean body weight of patients (mean body mass index; BMI, in kg/m2), 15.4 +/- 1.3, was 72.7% of that of control subjects, increasing to 89.8% of mean weight of control subjects after refeeding (mean BMI 19.0 +/- 1.2). Mean BMI of control subjects was 21.6 +/- 2.7. Compared with the control group, patients' nitrogen was initially depleted by 24.5%, increased by 18.4%, but remained 10.6% below control values (P < 0.001). Body fat was depleted by 58.4%, increased by 89.7%, but remained 21.8% below control values (P < 0.001). Thus, despite a greater initial depletion and subsequently a greater net gain, body fat remained relatively more depleted after treatment than did nitrogen and protein. Anorexia nervosa patients were shown to readily replenish protein during nutritional rehabilitation.

The pharmacokinetics of p-Boronophenylalanine.fructose in human patients with glioma and metastatic melanoma.

PURPOSE: To study the biodistribution of p-Boronophenylalanine in patients undergoing surgery for intracranial tumors or metastatic melanoma. METHODS AND MATERIALS: D,L-p-Boronophenylalanine was administered as boronophenylalanine.fructose in an intravenous bolus 1-4 h before the operation. Blood samples were collected for 24 h from the time of administration of the compound, and the blood boron elimination parameters were determined. For the glioma patients tumor samples were obtained and skin, dura, periosteum, and surrounding brain samples were collected whenever possible. For the metastatic melanoma patients tumor, fat, skin, and muscle were collected. Determination of the boron content was performed using inductively coupled plasma-atomic emission spectrometry. Twelve melanoma patients and six glioma patients participated in the study. The melanoma patients included four cases of cutaneous metastatic melanoma, six cases of metastatic melanoma to the lymph nodes and two cases of cerebral metastasis. RESULTS: The results for the metastatic melanoma patients are encouraging with an average tumor:blood boron concentration ratio and standard deviation of about 4.4 +/- 3.2 and a maximum value of 10 for the cerebral metastasis. The glioma patients involved high grade glioma for which the tumor:blood ratio was 2.2 +/- 1.2. CONCLUSION: The tumor:blood ratios for melanoma fulfil requirements for epithermal boron neutron capture therapy for cerebral melanoma metastases, whereas those for high grade glioma do not.

Hypolipidemic arylthioalkanoic acids.

A series of arylthioalkanoic acids related to probucol was studied for hypolipidemic activity. Homologation of the alkyl side chain led to marked changes in the serum cholesterol and serum triglyceride lowering activity in rats with the best combination of properties appearing in compound 7, 2-[3,5-di-tert-butyl-4-hydroxyphenyl)thio]hexanoic acid. Modification of the ring substitution failed to improve the activity despite the empirical observation that lipophilic substitution was necessary. Removal of the phenolic hydroxyl produced compound 23 with properties similar to 7 but of somewhat lower activity. Replacement of the sulfur by oxygen increased the toxicity of the series. Resolution of racemic 7 did not change the activity of the compound. The LD50 in mice of 7 was between 5000 and 10 000 mg/kg and compound 7 has been submitted for human clinical evaluation.

Factors determining maintenance of sinus rhythm after chronic atrial fibrillation with left atrial dilatation.

Successful therapy of atrial fibrillation (AF) has been reportedly influenced by a variety of factors including patient age, type of underlying heart disease, duration of arrhythmia, left ventricular function and left atrial (LA) size. To determine which of these factors are associated with maintenance of sinus rhythm after conversion, 43 patients with symptomatic chronic AF in the setting of a dilated left atrium (greater than or equal to 45 mm, range 45 to 78) were followed for at least 6 months after the return of sinus rhythm. Class IA drugs, IC drugs or amiodarone were used for therapy. Life table analysis showed sinus rhythm to be maintained in 81% for 6 months, 79% for 12 months and 60% for 24 months. Factors positively associated with success were conversion with drug therapy alone, duration of chronic AF less than or equal to 1 year, absence of mitral valve disease and LA dimension less than or equal to 60 mm (all p less than 0.05). Patient age, left ventricular function and presence of coronary disease were not associated with outcome. Thus, patients with moderate LA dilatation (45 to 60 mm) and a short duration of chronic AF can often be maintained in sinus rhythm, especially if they convert with pharmacologic intervention alone.

Amiodarone for maintenance of sinus rhythm after conversion of atrial fibrillation in the setting of a dilated left atrium.

Previous reports suggest that the finding of left atrial (LA) dilatation (greater than 45 mm) by echocardiography identifies patients not likely to maintain sinus rhythm after conversion of atrial fibrillation (AF). However, these studies antedate the availability of amiodarone, an antiarrhythmic agent that reportedly is effective in patients with AF in whom other drug therapy has failed. To analyze the relation between LA size and the ability to maintain sinus rhythm with amiodarone therapy, 28 patients, aged 32 to 87 years (mean 61), with an LA dimension greater than 45 mm (range 46 to 78, mean 57) were studied. Thirteen patients (46%) had valvular heart disease, 10 (36%) dilated cardiomyopathy and 5 (18%) miscellaneous disorders. In 25 patients (89%) quinidine therapy had failed. After therapy with amiodarone, sinus rhythm returned in all patients and was maintained. Therapy was judged completely successful in 10 patients (alive and still in sinus rhythm with at least 1 year of follow-up), partially successful in 11 (maintaining sinus rhythm for at least 6 months before a change in status) and failed in 7. Completely successful therapy was accomplished in 9 of 18 patients with an LA dimension between 46 and 60 mm, but in only 1 of 10 patients with an LA dimension greater than 60 mm (p less than 0.05). Thus, patients with LA dimensions between 46 and 60 mm who are significantly compromised by AF can often be maintained in sinus rhythm with amiodarone therapy. However, in patients with larger LA dimensions. AF is likely to return despite aggressive antiarrhythmic therapy with amiodarone, a drug with potentially serious side effects.

In vitro testing of the leukaemia monoclonal antibody WM-53 labeled with alpha and beta emitting radioisotopes.

We report the preparation and testing of a new alpha emitting radio-immunoconjugate (RIC) against acute myeloid leukaemia (AML) using CD33 positive monoclonal antibody WM-53 (specific for HL-60 cell line). Using cyclic anhydride of diethylenetriaminepentacetic acid (cDTPAa) as chelator, antibody was labeled with 213Bi (alpha), 149Tb (alpha), 153Sm (beta) and 152Tb (positron). In vitro testing showed high labeling efficiency (90-95%) and stability (11-19% leaching) with immunoreactivity virtually the same before and after labeling. DNA synthesis data and MTS cell survival were compared for all RICs. Only the alpha emitter was found to be capable of inhibiting DNA synthesis and had selective cell kill with activity as low as 2-3 microCi. The high stability and outstanding cytotoxicity of the 213Bi conjugate provides the basis for targeted alpha therapy for the control of metastatic and disseminated cancer such as AML.

Failure of ambulatory electrocardiographic monitoring to predict results of programmed electrical stimulation. Studies in patients with clinical ventricular tachyarrhythmias.

To test for an association between the results of ambulatory electrocardiographic monitoring (AEM) and programmed electrical stimulation (PES), or whether other factors better predict the results of PES, 57 patients (36 male and 21 female patients) presenting with either ventricular fibrillation (49 percent; 28/57) or sustained ventricular tachycardia (51 percent; 29/57) were studied. Each patient underwent AEM and PES using up to three ventricular extrastimuli. Sixty-three percent (36/57) had coronary disease; and of these, ventricular tachycardia was present during AEM in 64 percent (23/36) and induced by PES in 78 percent (28/36). With the addition of patients with other cardiac diagnoses, the results were 58 percent (33/57) and 60 percent (34/57), respectively. No AEM variable was positively associated with inducible ventricular tachycardia, including frequency of ventricular premature depolarizations, multiformity, couplets, or ventricular tachycardia. Clinical variables positively associated with inducible ventricular tachycardia were coronary disease, previous myocardial infarction, left ventricular dysfunction, male sex, and a history of recurrent arrhythmia. Therefore, clinical characteristics are more useful for predicting the results of PES than information derived from AEM.