Transdermal flux predictions for selected selective oestrogen receptor modulators (SERMs): Comparison with experimental results

The aim of this work was to evaluate the feasibility of delivering transdermally a series of highly lipophilic compounds (log P ~ 4–7), comprising several selective oestrogen receptor modulators and a modified testosterone (danazol). The maximum fluxes of the drugs were predicted theoretically using the modified Potts & Guy algorithm (to determine the permeability coefficient (k_p) from water) and the calculated aqueous solubilities. The correction provided by Cleek & Bunge took into account the contribution of the viable epidermal barrier to the skin permeation of highly lipophilic compounds. Experimental measurements of drug fluxes from saturated hydroalcoholic solutions were determined in vitro through excised pig skin. Overall, the predicted fluxes were in good general agreement (within a factor of 10) with the experimental results. Most of the experimental fluxes were greater than those predicted theoretically suggesting that the 70:30 v/v ethanol–water vehicle employed may have had a modest skin penetration enhancement effect. This investigation shows that the transdermal fluxes of highly lipophilic compounds can be reasonably predicted from first principles provided that the viable epidermis, underlying the stratum corneum, is included as a potentially important contributor to the skin's overall barrier function. Furthermore, the absolute values of the measured fluxes, when considered in parallel with previous clinical studies, indicate that it might be feasible to topically deliver a therapeutically useful amount of some of the compounds considered to treat cancerous breast tissue.     

重复胃镜检查的原因分析

0　引言　胃镜检查是上消化道疾病诊断的重要方法之一 .了解重复胃镜检查的原因及结果 ,有利于探讨疾病发生发展的基本规律 ,有利于发现诊断和治疗中存在的问题 ,从而提高对消化疾病的诊治水平 .1　材料和方法1.1　材料　随机抽检 1996 / 1998胃镜检查资料为调查对象7812例 ,其中行 2次以上胃镜检查者 937例 .调查内容包括性别、年龄、职业、主要症状和体征、病程、初步诊断、内镜检查时间、次数、内镜诊断、病理诊断、确诊时间 .1.2　方法　回顾性调查上述材料的临床特征 .列表统计研究对象一般情况的分布状况 ,计算各年龄段比例构成 ,各病…     

Childhood cardiac function after twin-to-twin transfusion syndrome – a 10-year follow up

Aim:  To perform a 10-year follow up of cardiac structure and function after twin-to-twin transfusion syndrome (TTTS) – a severe foetal circulatory complication associated with myocardial hypertrophy in the recipient twin.
Methods:  Cardiac dimensions, systolic and diastolic function as assessed by echocardiography including flow and tissue Doppler velocimetry in 22 healthy survivors of TTTS with a mean age of 9.6 (7.2–11.8) years.
Results:  The donor and recipient twin did not show any differences in end-diastolic ventricular size, interventricular septum thickness, diameter of right ventricular outflow tract, cardiac valves, coronary arteries or in systolic blood flow velocities. However, compared with the donors, the recipients had significantly lower E/A ratios because of lower E-waves in both mitral (−0.15 ± 0.10, p < 0.01) and tricuspid (−0.09 ± 0.07, p < 0.01) valves, indicating reduced early diastolic ventricular fillings compared with donors.
Conclusion:  At school age, twins surviving TTTS had a cardiac structure and function within normal range. There were no differences in heart structure or systolic ventricular function between twins but, compared with the donor twin, we found a reduced early diastolic function in the recipient.     

Risk factors associated with having psoriatic arthritis in patients with cutaneous psoriasis

The aim of this study was to determine if the following characteristics were associated with the presence of psoriatic arthritis in a sample of psoriasis patients: race, family history of psoriasis and psoriatic arthritis, age of onset of psoriasis, smoking, alcohol consumption and the maximum body surface area (BSA) affected by psoriasis. This was a case–control study involving 400 psoriasis patients who attended the Psoriasis and Photo‐medicine clinic in the National Skin Center of Singapore over a 1‐year period. Cases were psoriasis patients with psoriatic arthritis while controls were psoriasis patients without psoriatic arthritis. The diagnosis of psoriatic arthritis was made by rheumatologists and participants completed a self‐administered standardized questionnaire. The maximum BSA involved was determined from the case notes. Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption but was significantly associated with a family history of psoriatic arthritis (P < 0.001) and the maximum body surface involved (P = 0.05). Using multivariate analysis to control for variables, the presence of psoriatic arthritis was significantly associated with a family history of psoriatic arthritis (odds ratio [OR] = 20.5; 95% confidence interval [CI] = 2.49–169.10) and the maximum BSA involved (OR = 2.52; 95% CI = 1.33–4.75). Indian psoriatic patients were more likely to have psoriatic arthritis compared to the other races. A family history of psoriatic arthritis and a greater maximum body surface involved may be associated with having psoriatic arthritis in this study population of psoriasis patients.     

Cognitive-behavioral therapy for persistent pain: Does adherence after treatment affect outcome?

It is a tenet of cognitive behavioral treatment of persistent pain problems that ex‐patients should adhere to treatment methods over the longer term, in order to maintain and to extend treatment gains. However, no research has quantified the causal influence of adherence on short‐term outcome in this field. The aims of this study are to assess determinants of adherence to treatment recommendations in several domains, and to examine the extent to which cognitive and behavioral adherence predicts better outcome of cognitive behavioral treatment for persistent pain. Longitudinal data from a sample of 2345 persistent pain patients who attended a multicomponent treatment programme were subjected to structural equation modeling. Adherence emerged as a mediating factor linking post‐treatment and follow‐up treatment outcome, but contributed only 3% unique variance to follow‐up outcomes. Combined end‐of‐treatment outcomes and adherence factors accounted for 72% of the variance in outcome at one‐month follow‐up. Notwithstanding shortcomings in the measurement of adherence, these findings question the emphasis normally given to adherence in the maintenance of behavioral and cognitive change, and clinical implications are discussed.     

Male-male competition magnifies inbreeding depression in wild house mice

The detrimental effects of inbreeding on vertebrates are well documented for early stages of the life cycle in the laboratory. However, the consequences of inbreeding on long-term survival and reproductive success (Darwinian fitness) are uncertain for vertebrates in the wild. Here, we report direct experimental evidence for vertebrates that competition increases the harmful effects of inbreeding on offspring survival and reproduction. We compared the fitness of inbred (from full-sib matings) and outbred wild house mice (Mus domesticus) in large, seminatural enclosures. Inbred males sired only one-fifth as many surviving offspring as outbred males because of their poor competitive ability and survivorship. In laboratory conditions, inbreeding had relatively minor effects on male reproductive success and no effect on survivorship. Seminatural conditions did not increase inbreeding depression for females, probably because females were not competing for any critical resources. The overall reduction in fitness from inbreeding was 57%, which is 4.5 times as great as previous estimates from the laboratory. These results have important implications for medicine, conservation, evolutionary biology, and functional genomics.     

Thinking about vaginal microbicide testing

A vaginal microbicide could slow the spread of HIV. To date, volunteers in placebo-controlled trials of candidate microbicides have been counseled to use condoms. This does not reduce the number of volunteers exposed to possible risk, but it shifts the allotment of risk from those conducting the trial to those women who may be least able to make autonomous decisions. Alternative ways of meeting the obligation to offer volunteers active benefits are explored. Counseling the use of condoms prolongs clinical trials and could cause tens of thousands of otherwise avoidable deaths.