Outcome measurement in the correction of mandibular asymmetry.

This study related clinical assessments of the severity of mandibular asymmetry with computerized measurements, obtained by digitizing mandibular outlines from standardized facial photographs. Four ratios were calculated: area (size), compactness (shape), perimeter (length of outline), and moment (center of area). When comparing clinical severity with computer assessment, significant correlations were observed; those for area and compactness were the highest. Sixteen patients subsequently underwent corrective surgery, and their ratios were used to relate the degree of improvement to the original severity of the asymmetry. The posttreatment ratios were also used to audit the outcome, comparing the patients' scores as a group with results previously obtained from patients with normal symmetry and mild asymmetry. Posttreatment outcomes were significantly different from the normal outline group but were comparable with outcomes of patients with mild mandibular asymmetry. The system provided a sensitive, noninvasive method of assessing treatment change and could be useful in providing an objective means of quantifying treatment outcomes.     

Reversible changes in cerebral activity associated with acidosis in preterm neonates

Murdoch Eaton DG, Wertheim D, Oozeer R, Dubowitz LMS, Dubowitz V. Reversible changes in cerebral activity associated with acidosis in preterm neonates. Acta Paediatr 1994;83:486–92. Stockholm. ISSN 0803–5253
Computerized online EEG monitoring in ventilated preterm infants less than 32 weeks' gestation enabled evaluation of the effect of acidosis on cerebral function. All episodes of acidosis were found to be associated with changes in the levels of cerebral activity. In 21 of the 32 episodes, EEG activity returned to pre-acidosis levels after therapeutic intervention. The duration of EEG abnormality was related to the severity of acidosis. However, the time to recovery of the EEG after therapeutic procedures was not related to duration of the EEG change.     

Comparative antitumor effects of hormonal ablation, estrogen agonist, estrogen cytotoxic derivative, and antiestrogen in the PAIII rat prostatic adenocarcinoma.

The effects of hormonal ablation, estrogen, estrogen-derived cytotoxic agent, and estrogen antagonist therapies used clinically were evaluated on in vitro colony formation, in vivo growth, and lymphatic and pulmonary metastasis of the PAIII tumor. Ventral prostatic and seminal vesicle weights were evaluated in the same animals to assess androgen-related responses. Estradiol, estramustine phosphate, and testosterone had no effects on PAIII colony formation in vitro. Castration, hypophysectomy, estradiol benzoate, and estramustine phosphate treatment of PAIII-bearing Lobund Wistar rats produced significant (P less than 0.05) regression of male accessory sex organs. Of these treatments, only hypophysectomy had significant (P less than 0.05) inhibitory effects on primary PAIII growth and lymphatic and pulmonary metastasis. LY117018 [6-hydroxy-2-(p-hydroxyphenyl)benzo(b)thien-3-yl-p-2-(l-pyrrolidin yl)ethoxy phenyl ketone] has antiestrogenic activity but produces no significant agonist responses. LY117018 had no effect upon PAIII colony formation in vitro. Following s.c. implantation of PAIII cells, LY117018 (2.0, 10.0, or 20.0 mg/kg s.c.) had no effect on primary tumor growth in the tail. In vitro LY117018 administration produced marked antimetastatic effects. In a dose-dependent manner, LY117018 inhibited PAIII metastasis to the gluteal (97%) and iliac lymph nodes (88%) (P less than 0.05 for both). LY117018 also maximally inhibited pulmonary metastasis by 86% (P less than 0.05). Maximal regression of 42% for ventral prostatic and 35% for seminal vesicle weights were also seen after LY117018 administration (P less than 0.05 for both). Co-administration of estradiol benzoate had no antagonistic effect upon the antitumor responses produced by LY117018. The mechanism of action of LY117018 is not known. The failure of estradiol benzoate to affect PAIII growth and metastasis supports the contention that the responses to LY117018 are not attributable to simple antagonism of estrogen action. LY117018 may be exerting its antitumor effects through autocrine, paracrine, or endocrine mechanisms. LY117018 represents a class of agents with potential utility in treating metastatic cancer of the prostate.     

Phase I trial and clinical pharmacological evaluation of 10-ethyl-10-deazaaminopterin in adult patients with advanced cancer

10-Ethyl-10-deazaaminopterin (10-EDAM) is an analogue of methotrexate with improved preclinical anticancer activity, more selective entry, and greater conversion to polyglutamate forms in neoplastic cells. In this Phase I trial, we have treated 62 adults with advanced solid tumors, giving 10-EDAM i.v. on either a weekly x 3 schedule (35 patients) or a weekly schedule (27 patients). The dosage levels ranged from 5 to 120 mg/m2. The toxicity observed with 10-EDAM was qualitatively similar to that of methotrexate. Oral mucositis was the dose-limiting toxicity; diarrhea, skin rash, leukopenia, thrombocytopenia, and mild elevations of serum glutamic-oxaloacetic transaminase, prothrombin, and partial thromboplastin times were also observed, but were not dose limiting. A weekly dosage of 80 mg/m2 with escalation or attenuation in accordance with patient tolerance, or 100 mg/m2 weekly for 3 weeks, followed by a 2-week "rest period" are recommended for Phase II assessment. 10-EDAM produced partial remissions in three patients with non-small cell lung cancer and one patient with breast cancer lasting 6, 40+, 26+, and 15 months, respectively. Pharmacokinetic studies carried out at the 5, 30, and 100 mg/m2 dosage levels demonstrated the drug to have a triphasic disappearance from plasma. Elimination was independent of dose over the range tested, with mean plasma half-lives of: alpha = 12.9 min, beta = 1.5 h, and gamma = 11.9 h. Cumulative urinary excretion of the drug ranged from 13 to 55% of the administered dose (mean = 33%); 88% of the urinary drug appeared within the first 4 h following drug administration. The pharmacokinetic behavior of the first and second weekly dosages were consistent within a given patient. The metabolites 7-hydroxy-10-EDAM, and 10-ethyl-10-deaza-2,4-diamino-pteroic acid were demonstrated in the plasma and urine of treated patients. In studies of tissue homogenates from two patients with skin metastases, more extensive retention of the drug and of its polyglutamates was observed in the breast cancer metastases than in the metastases from a kidney cancer or in normal skin.     

Swainsonine induced modification of N-linked oligosaccharides on human phagocytic cell formyl peptide chemotactic receptors

Swainsonine, a Golgi mannosidase II inhibitor, causes a 15,000 dalton decrease in the apparent molecular weight of formyl peptide chemotactic receptor (FPCR) synthesized by three types of human phagocytic cells (differentiated HL-60 cells, differentiated U-937 cells, and cultured human macrophages derived from peripheral blood monocytes). This indicates that some of the asparagine-linked (N-linked) oligosaccharide of FPCR is of the complex type. Studies with endoglycosidase F and endoglycosidase H show that unaltered FPCR contains both complex and high mannose content N-linked oligosaccharide chains, and that FPCR synthesized in the presence of swainsonine contains only high mannose N-linked oligosaccharide chains. Cycloheximide prevents the swainsonine effect on FPCR molecular weight. This shows that swainsonine only affects the carbohydrate structure of FPCR which is newly synthesized in the presence of swainsonine. Since swainsonine decreases the molecular weight of FPCR from human peripheral blood monocytes in culture, these cells must be synthesizing new FPCR. The abnormally low molecular weight FPCR synthesized in the presence of swainsonine is converted to the normal, higher molecular weight form of FPCR when swainsonine is removed from the culture. This occurs even when new protein synthesis is inhibited by cycloheximide. This requires that previously synthesized, swainsonine-affected FPCR at the cell surface must come in contact with Golgi enzymes which complete the processing of the abnormal, high mannose oligosaccharide. This implies a potential Golgi-related repair mechanism for altered or "damaged" cell surface receptors.     

The Effects of Similarity in Sexual Excitation,Inhibition, and Mood on Sexual Arousal Problems and Sexual Satisfaction in Newlywed Couples

IntroductionDespite the importance of sexuality for romantic relationships, there has been little research attention to individual differences and dyadic variables, including couple similarity, and their association with sexual problems and satisfaction.AimThe current study examined the effects of the propensity for sexual inhibition and sexual excitation scales (SIS/SES) and the effects of different mood states on sexuality (Mood and Sexuality Questionnaire [MSQ]), at both the individual and the dyad level, on sexual arousal problems and sexual satisfaction.MethodsSimilarity in SIS/SES and MSQ was measured in a nonclinical sample of 35 newlywed couples and operationally defined as the within‐couple, z‐transformed correlations between the two partners' item responses.Main Outcome MeasuresSexual arousal problems were assessed using self‐report measures (Demographic and Sexual History Questionnaire) and focused on the past 3 months. Sexual satisfaction was assessed using the Global Measure of Sexual Satisfaction.ResultsRegression analyses revealed that greater similarity in the effects of anxiety and stress on sexuality was associated with more reported sexual arousal problems of wives. In contrast, the husbands' sexual arousal problems were related only to their own higher SIS1 scores. Higher SES scores predicted lower sexual satisfaction for both husbands and wives. Wives who reported strong positive mood effects on their sexuality indicated greater sexual satisfaction, while husbands who were more similar to their wives in the effect of positive moods on sexuality indicated greater sexual satisfaction.ConclusionsThe findings show that, above and beyond one's own sexual propensities, similarity in various aspects of sexuality predicts sexual problems (more so in women) and sexual satisfaction (in both men and women). Lykins AD, Janssen E, Newhouse S, Heiman JR, and Rafaeli E. The effects of similarity in sexual excitation, inhibition, and mood on sexual arousal problems and sexual satisfaction in newlywed couples. J Sex Med 2012;9:1360–1366.