Effect of age, ethnicity, sex, cognitive status and APOE genotype on amyloid load and the threshold for amyloid positivity.

The threshold for amyloid positivity by visual assessment on PET has been validated by comparison to amyloid load measured histopathologically and biochemically at post mortem. As such, it is now feasible to use qualitative visual assessment of amyloid positivity as an in-vivo gold standard to determine those factors which can modify the quantitative threshold for amyloid positivity. We calculated quantitative amyloid load, measured as Standardized Uptake Value Ratios (SUVRs) using [18-F]florbetaben PET scans, for 159 Hispanic and non-Hispanic participants, who had been classified clinically as Cognitively Normal (CN), Mild Cognitive Impairment (MCI) or Dementia (DEM). PET scans were visually rated as amyloid positive (A+) or negative (A-), and these judgments were used as the gold standard with which to determine (using ROC analyses) the SUVR threshold for amyloid positivity considering factors such as age, ethnicity (Hispanic versus non-Hispanic), gender, cognitive status, and apolipoprotein E ε4 carrier status. Visually rated scans were A+ for 11% of CN, 39.0% of MCI and 70% of DEM participants. The optimal SUVR threshold for A+ among all participants was 1.42 (sensitivity = 94%; specificity = 92.5%), but this quantitative threshold was higher among E4 carriers (SUVR = 1.52) than non-carriers (SUVR = 1.31). While mean SUVRs did not differ between Hispanic and non-Hispanic participants;, a statistically significant interaction term indicated that the effect of E4 carrier status on amyloid load was greater among non-Hispanics than Hispanics. Visual assessment, as the gold standard for A+, facilitates determination of the effects of various factors on quantitative thresholds for amyloid positivity. A continuous relationship was found between amyloid load and global cognitive scores, suggesting that any calculated threshold for the whole group, or a subgroup, is artefactual and that the lowest calculated threshold may be optimal for the purposes of early diagnosis and intervention.

Identification of toxicants in cinnamon-flavored electronic cigarette refill fluids.

In a prior study on electronic cigarette (EC) refill fluids, Cinnamon Ceylon was the most cytotoxic of 36 products tested. The purpose of the current study was to determine if high cytotoxicity is a general feature of cinnamon-flavored EC refill fluids and to identify the toxicant(s) in Cinnamon Ceylon. Eight cinnamon-flavored refill fluids, which were screened using the MTT assay, varied in their cytotoxicity with most being cytotoxic. Human embryonic stem cells were generally more sensitive than human adult pulmonary fibroblasts. Most products were highly volatile and produced vapors that impaired survival of cells in adjacent wells. Cinnamaldehyde (CAD), 2-methoxycinnamaldehyde (2MOCA), dipropylene glycol, and vanillin were identified in the cinnamon-flavored refill fluids using gas chromatography­mass spectrometry and high-pressure liquid chromatography (HPLC). When authentic standards of each chemical were tested using the MTT assay, only CAD and 2MOCA were highly cytotoxic. The amount of each chemical in the refill fluids was quantified using HPLC, and cytotoxicity correlated with the amount of CAD/product. Duplicate bottles of the same product were similar, but varied in their concentrations of 2MOCA. These data show that the cinnamon flavorings in refill fluids are linked to cytotoxicity, which could adversely affect EC users.

A method for rapid dose-response screening of environmental chemicals using human embryonic stem cells.

INTRODUCTION: Human embryonic stem cells (hESC) provide an invaluable model for assessing the effects of environmental chemicals and drugs on human prenatal development. However, hESC are difficult to adapt to 96-well plate screening assays, because they survive best when plated as colonies, which are difficult to count and plate accurately. The purpose of this study is to present an experimental method and analysis procedure to accomplish reliable screening of toxicants using hESC. METHODS: We present a method developed to rapidly and easily determine the number of cells in small colonies of hESC spectrophotometerically and then accurately dispense equivalent numbers of cells in 96-well plates. The MTT assay was used to evaluate plating accuracy, and the method was tested using known toxicants. RESULTS: The quality of the plate set-up and analysis procedure was evaluated with NIH plate validation and assessment software. All statistical parameters measured by the software were acceptable, and no drift or edge effects were observed. The 96-well plate MTT assay with hESC was tested by performing a dose-response screen of commercial products, which contain a variety of chemicals. The screen was done using single wells/dose, and the reliability of this method was demonstrated in a subsequent screen of the same products repeated three times. The single and triple screens were in good agreement, and NOAELs and IC(50)s could be determined from the single screen. The effects of vapor from volatile chemicals were studied, and methods to monitor and avoid vapor effects were incorporated into the assay. DISCUSSION: Our method overcomes the difficulty of using hESC for reliable quantitative 96-well plate assays. It enables rapid dose-response screening using equipment that is commonly available in laboratories that culture hESC. This method could have a broad application in studies of environmental chemicals and drugs using hESC as models of prenatal development.

Características clínicas e identidad genérica en subtipos de trastornos de la conducta alimentaria / Clinical characteristics and gender identity among eating disordered patients subtypes

BACKGROUND: Gender identity is a relevant issue in the approach to eating disorders. AIM: To compare psychological and behavioural characteristics and traits of gender identity among women with eating disorders and its subtypes and non eating disordered female subjects. MATERIAL AND METHODS: An structured clinical interview based on the DSM-IV diagnostic criteria for eating disorders, the EAT-40 (Eating Attitudes Test), the Eating Disorders Inventory (EDI) and the Bem Sex Role Inventory (IBRS) were administered to 58 compulsive-purgative anorectics (AN/BN group), 15 restrictive anorectics (AN group), 33 patients suffering from eating disorder not otherwise identified, 33 purgative bulimics and to 82 female students without eating disorders. RESULTS: Patients with eating disorders ranked significantly higher on the EAT-40 and EDI and all its items (p < 0.001). The AN/BN group ranked significantly higher on the EDI (p < 0.001) and on Drive for thinness, Perfectionism and interpersonal distrust (p < 0.001). The AN group ranked higher on Maturity fears (p < 0.001). The BN group ranged higher on Body dissatisfaction, Ineffectiveness and Interoceptive awareness (p < 0.001). Patients with eating disorders were significantly identified with Feminine category and subjects without eating disorders with Androgynous and Undifferentiated categories on the IBRS (p = 0.002). The AN group showed the highest percentage on Feminine category and the lowest on Androgynous and Undifferentiated categories. All the groups rejected and approved feminine, masculine and neutral qualities. CONCLUSIONS: Femininity emerged as the main trait of gender identity in patients suffering from eating disorders, in contrast to androgyny, showed by healthy women.

[Gender identity and eating disorders]. / Identidad de género y trastornos de la conducta alimentaria.

BACKGROUND: A possible role of the feminine gender role in the genesis of eating disorders is possible, since most patients with these disorders are women. AIM: To compare some traits of gender identity between females with eating disorders and a control group. MATERIAL AND METHODS: An structured clinical interview based on the DSM-IV diagnostic criteria for eating disorders and the Bem Sex Role Inventory (BSRI) were administered to 63 patients that fulfilled the DSM-IV criteria for anorexia nervosa or bulimia nervosa (ED group) and 63 comparison subjects (C group). RESULTS: Forty three percent of patients in contrast with 23.8% of controls were classified within the feminine category. Likewise 19% of patients and 31.7% of controls were qualified as Androgynous; 27% of patients and 43% of controls were qualified as Undifferentiated. There were significant differences between patients and controls in 22 items of the BSRI (p < 0.01). Both groups rejected and were identified with some feminine, masculine and neutral qualities. DISCUSSION: Femininity emerged as the main trait of gender identity in patients suffering of eating disorders. In contrast, Androgyny showed by the control group could result in a better adaptability and flexibility to face difficult life circumstances.

Minimally invasive treatment for localized adenocarcinoma of the prostate: review of 1048 patients treated with ultrasound-guided palladium-103 brachytherapy.

PURPOSE: To assess the effectiveness of palladium-103 brachytherapy in stage T1 and T2 adenocarcinoma of the prostate. PATIENTS AND METHODS: The charts of 1048 patients treated between 1991 and 1999 with transperineal realtime ultrasound-guided (103)Pd (Theraseed) implants were reviewed to assess the effects on serum prostate specific antigen (PSA) values and tissue (biopsy). Of the 1048 patients, 780 had sufficient data for this report. Preoperative total androgen blockade (leuprolide and flutamide) was used selectively in patients whose prostate size was >50 cc and those whose tumors had a Gleason score of >7. RESULTS: At 1 year, 86% of the evaluable 766 patients had stable PSA concentration <1.5 ng/mL; at 5 years, 86% of the 166 patients with data available had stable PSA values <1.5 ng/mL. Biopsies were negative in 92% of the patients studied at 2 years. Patients with pretreatment PSA values <10 ng/mL had the best outcomes, and those treated with (103)Pd plus hormone ablation achieved PSA reduction more rapidly than those treated with radioisotope monotherapy. There was one disease-related death; the principal morbidity was short-term bladder and bowel irritation without permanent sequelae. Impotence occurred in approximately 15% of patients, and incontinence occurred in 5% of those who had undergone prior transurethral resection of the prostate. CONCLUSION: The technique used in this study proved effective in reducing PSA concentrations to <1.5 ng/mL and in producing negative biopsies 1 and 2 years postoperatively. These results are comparable to those of external-beam radiation therapy and radical prostatectomy while demonstrating a significant reduction in morbidity.

Evolution of techniques for ultrasound-guided palladium 103 brachytherapy in 950 patients with prostate cancer.

PURPOSE: Brachytherapy is an effective, low-morbidity, cost-effective treatment for adenocarcinoma of the prostate. Although both iodine 125 and palladium 103 have been used extensively over the last 14 years, 103Pd (Theraseed) provides a more rapid initial dose and therefore better control of higher Gleason grade tumors. We assessed a highly refined methodology for 103Pd brachytherapy in patients with prostate cancer and compared outcomes before and after making adjustments in technique. MATERIALS AND METHODS: Standard brachytherapy techniques were modified to include combination of preplanning with real-time adjustment, placing all needles at once to minimize prostate movement, using monitored anesthesia control sedation during preoperative volume study and cystoscopy, and several other small but important changes. Charts were reviewed from 950 patients treated with 103Pd implants from 1991 through 1999. Prostate-specific antigen (PSA) and biopsy data before and after 1993 were compared for 733 patients whose data qualified for analysis. RESULTS: At 1 and 5 years after treatment, 85-88% of patients had stable PSA <1.5 ng/mL. Biopsies were negative in 90-94% at 2 years. CONCLUSION: The modification in techniques provides positive results that remain stable over time.

Outpatient ultrasound-guided palladium 103 brachytherapy for localized adenocarcinoma of the prostate: a preliminary report of 434 patients.

OBJECTIVES: To assess the effectiveness of palladium 103 (Pd-103) brachytherapy in Stage T1 and T2 adenocarcinoma of the prostate. METHODS: Charts of 474 patients treated between 1991 and 1996 with transperineal real-time ultrasound-guided Pd-103 implants were reviewed to assess post-treatment prostate-specific antigen (PSA) levels and follow-up biopsy results. Of 474 patients, 434 had sufficient data for this report. The implant technique used allows precise placement of seeds and accurate dose delivery of the entire prostate. Preoperative neoadjuvant leuprolide (Lupron) and flutamide (Eulexin) were given selectively to reduce prostate size greater than 50 cc and for Gleason grade lesions greater than 7. RESULTS: Of 434 patients, successful cancer control was demonstrated in 81% of patients by a decrease in PSA levels to less than 1.5 ng/mL at 1 year. Biopsies were negative in 88% of patients 1 year after the procedure and in 89% at 2 years. Analysis of the data suggests that patients with pretreatment PSA levels less than 10 ng/mL had the best outcomes. There were no disease-related deaths; the predominant morbidity was short-term bladder and bowel irritation without permanent sequelae. Incontinence occurred in less than 5% of patients who had undergone prior transurethral resection of the prostate. Impotence occurred in less than 15% of patients. CONCLUSIONS: The technique used in this study proved effective in reducing PSA levels to less than 1.5 ng/mL and in producing negative biopsies 1 and 2 years postoperatively. Results are comparable to external-beam radiation therapy, demonstrating a significant reduction in morbidity.

[Eating disorders in adolescents: clinical and epidemiological aspects]. / Trastornos del hábito del comer en adolescentes: aspectos clínicos y epidemiológicos.

OBJECTIVE: To compare in female adolescents clinical and epidemiological aspects of eating disorders. METHODS: Three hundred schoolgirls, university students and young girls with weight problems who did not score within the pathological range of the Eating attitudes test (EAT-40) (group S), one hundred and thirty eight schoolgirls, university students and young girls with weight problems who scored within the pathological range of the EAT-40 (group SC) and one hundred eating disordered patients (group THC) were given the Eating disorders inventory (EDI). RESULTS: The EAT-26 emerged as an abbreviated and trustful instrument. The scores on the EAT-40 and EDI were lower in group S, intermedial in group SC and higher in group THC. The same statistically significant differences (p < 0.001) were observed on Interoceptive awareness. Bulimia, Ineffectiveness and Maturity fears. Diet (EAT-40-Factor I) (90%) and EDI-Drive for thinness (87%) had the highest sensitivity. CONCLUSIONS: The EAT-26, EAT-40 and EDI were useful to confirm an eating disorder. On one hand, the profile of the eating disordered patients and the adolescents at risk was characterized by a high Drive for thinness and Body dissatisfaction and on the other, by a low Interoceptive awareness. Diet and Drive for thinness may be helpful for screening large non-clinical groups to predict an eating disorder. Finally, the importance of the nutrition assessment and primary prevention is emphasized.

Iridium-192 interstitial implant and external beam radiation therapy in the management of squamous cell carcinomas of the tonsil and soft palate.

PURPOSE: To evaluate the results, techniques, indications and complications of interstitial brachytherapy in the management of squamous cell carcinomas of the tonsil and soft palate, we reviewed the Stanford University Medical School experience with this modality. METHODS AND MATERIALS: Between May 1975 and January 1990, 37 patients with squamous cell carcinomas of the Tonsillo-Palatine region were treated with a combination of external beam irradiation and a removable Iridium-192 interstitial implant. The mean age of these patients was 56. Twenty-two were males and 15 were females. The stage distribution included four patients with Stage I, 5 with Stage II, 10 with Stage III, and 18 with Stage IV cancers. Thirty-two percent (12/37) of these patients had T3 or T4 lesions. Forty-nine percent (18/37) had stage N2 or N3 cervical lymphadenopathy. All 37 patients received initial external beam irradiation to the primary, bilateral necks, and supraclavicular region (mean dose: 5400 cGy, range 4000-6600). Eighteen patients (49%) also received neck dissections. All 37 patients received an interstitial Irridium-192 implant using a combination intraoral swage and external looping technique. The mean dose was 2700 cGy (range 2000-4000 cGy) to an average volume of 24 cc (range 5-81). RESULTS: Local control was obtained in 95% (35/37) of the patients. Eighty-seven percent (32/37) of the patients have remained disease-free in the neck. Nine patients have developed second primary lesions, and one developed pulmonary metastasis. Fifteen patients have died (6 succumbed to their cancers, 6 to second primaries, 2 to intercurrent disease, 1 from an unknown cause). The actuarial freedom from relapse is 75%, and overall survival is 64% at 5 years, with a mean follow up of 43 months (range 5-110). Complications were limited to one case of osteoradionecrosis of the mandible and one tonsillar ulcer. Functional and esthetic integrity was preserved in most of these patients. CONCLUSION: Iridium-192 interstitial implant boost combined with external beam radiation therapy is a safe and effective therapy in the management of locally advanced carcinomas of the tonsil and soft palate.

Hodgkin's disease with bulky mediastinal involvement: effective management with combined modality therapy.

PURPOSE: To assess results, complications, treatment techniques, and patterns of failure in patients with bulky mediastinal Hodgkin's disease treated with combined modality therapy. METHODS AND MATERIALS: Between 1980 and 1988, 48 patients with Hodgkin's disease who had large mediastinal masses were treated at Stanford University. All patients were staged with clinical studies which included computed tomographic scans of the chest and bipedal lymphograms. Initially, 10 patients underwent staging laparotomy and splenectomy, subsequently all patients were staged by clinical criteria alone. Mediastinal mass ratios ranged from .35 to .85 (mean .46). The majority of patients had at least one site of extralymphatic extension (E-lesion) within the chest. Combined modality therapy included MOPP (prednisone deleted after mediastinal irradiation) in 15, ABVD in 14, and PAVe in 19 patients. All patients received mantle irradiation (mean dose 44 Gy) but only patients with abdominal disease received subdiaphragmatic irradiation. RESULTS: The actuarial survival and freedom from relapse were 84% and 88% at 9 years. There was an intrathoracic component of failure in all seven patients who either failed to achieve an initial complete response or who experienced a relapse after a complete response. Both patients who experienced a relapse after a complete response achieved durable second responses with subsequent chemotherapy. Two of five patients who failed to achieve an initial complete response were treated successfully with alternative chemotherapy. CONCLUSIONS: Routine combined modality therapy is the treatment of choice for patients with Hodgkin's disease who have large mediastinal masses.

[Gender role and anorexia nervosa]. / Roles genéricos y anorexia nerviosa.

The gender role is defined; its physiognomy, adopted by women since the occurrence of the Industrial Revolution, and the intricate status that characterizes the present feminine role are described. Finally, a psychosocial approach of anorexia nervosa is made. This disorder is considered as a paradigm of the present ambiguity of the femininity concept likely to become a transactional phenomenon between sexual identities.

Roles genéricos y anorexia nerviosa. / [Gender role and anorexia nervosa]

The gender role is defined; its physiognomy, adopted by women since the occurrence of the Industrial Revolution, and the intricate status that characterizes the present feminine role are described. Finally, a psychosocial approach of anorexia nervosa is made. This disorder is considered as a paradigm of the present ambiguity of the femininity concept likely to become a transactional phenomenon between sexual identities.

Roles genéricos y anorexia nerviosa. / [Gender role and anorexia nervosa]

The gender role is defined; its physiognomy, adopted by women since the occurrence of the Industrial Revolution, and the intricate status that characterizes the present feminine role are described. Finally, a psychosocial approach of anorexia nervosa is made. This disorder is considered as a paradigm of the present ambiguity of the femininity concept likely to become a transactional phenomenon between sexual identities.

Radiation therapy in the management of bulky mediastinal Hodgkin's disease.

From July 1981 to July 1985, 20 patients with bulky mediastinal Hodgkin's Disease (maximum mediastinal width divided by the maximum intrathoracic diameter for a mediastinal mass ratio (MMR) greater than 0.33 were treated at Stanford University with definitive radiation therapy alone. The majority of these patients were selected to receive radiation therapy because they had the more favorable characteristics of minimal extralymphatic involvement, mediastinal masses that were superior and central in location, and a MMR less than or equal to 0.50. All 20 patients were laparotomy staged, and 17 received some radiation to the mantle before laparotomy. Seventeen patients had pathologic stage (PS) II disease (13 PS IIA, 4 PS IIB), two had PS IIISA, and one had PS IB. Eleven patients (55%) had extralymphatic involvement. All patients were irradiated to the mantle field using a shrinking field technique (mediastinal dose, 4400 to 5500 cGy, mean 4990 cGy). After completion of the mantle, all patients with good clinical responses received infradiaphragmatic radiation. Treatment complications included two cases of mild radiation pneumonitis, five of hypothyroidism, five of localized Herpes zoster, one of amenorrhea, one of non-Hodgkin's lymphoma, and one of sepsis. Four patients relapsed. All had an intrathoracic component to their failure. All four patients were salvaged with MOP(P) chemotherapy and are currently alive and free of disease. For the entire group, the actuarial freedom from relapse is 80% at 7 years and the survival is 100%. Median follow-up time is 67 months. The authors conclude that radiation therapy alone is effective in the management of selected patients with Hodgkin's disease who have extensive mediastinal involvement, even when the MMR exceeds 1/3.

Neurology referral patterns.

To examine the indications for referral of patients to neurologists, a survey was conducted of 88 such referrals by general internists in an HMO. In approximately one third of all referrals, the neurologist's advice regarding diagnosis and treatment was of minor or no importance. Instead, such referrals were often responsive to patient and family demands or focused upon the necessity for neuroimaging, even when the likely diagnosis and required treatment were already evident. Referral rates in HMO practice are strongly influenced by the practice styles of primary care providers. The authors conclude that a case manager ("gatekeeper") mechanism in competitive medical plans that excludes patient self-referrals may have a greater effect upon total (and surgical) specialty care, compared with the volume of services provided by medical specialists such as neurologists.

Cytomegalovirus polyradiculoneuropathy in acquired immune deficiency syndrome.

A 34-year-old homosexual man with acquired immune deficiency syndrome developed extraocular muscle deficits, chorioretinitis, and paraplegia without sensory symptoms. EMG showed severe diffuse denervation, but only mildly slowed nerve conduction velocities, in both legs. Meningitis persisted for 6 weeks and was exacerbated prior to the patient's death. Necropsy revealed subpial and subependymal cytomegalovirus (CMV) infection. Histology of ventral roots demonstrated proximal CMV infection and massive fiber loss. In this immunosuppressed patient, CMV caused a severe motor polyradiculopathy by selective destruction of the motor neurons of ventral spinal roots and motor cranial nerves.