Efficacy and tolerability of estraderm MX, a new estradiol matrix patch

Objectives: To assess the efficacy and tolerability of a new matrix patch delivering 0.05 mg estradiol per day (Estraderm MX 50) in postmenopausal women with moderate to severe postmenopausal symptoms. Methods: A multicenter, double-blin, randomized, between-patient, placebo controlled trial in 109 postmenopausal women was carried out. Patches were applied twice weekly for 12 weeks. Patients were assessed at 4, 8 and 12 weeks of treatment. The primary efficacy variable was change from baseline in mean number of moderate to severe hot flushes (including night sweats) per 24 h during the last 2 weeks of treatment. Other variables included Kupperman Index, local and systemic tolerability. Plasma concentrations of estradiol (E2), estrone (E1) and estrone sulfate (E1S) were determined before and after treatment. Results: Estraderm MX was significantly superior to placebo (P < 0.001) in reducing mean number of moderate to severe hot flushes (including night sweats) per 24 h after 4, 8 and 12 weeks of treatment. The estimate of treatment group differences after 12 weeks was 4.2 hot flushes (95% confidence interval: 2.6–5.5). Estraderm MX also significantly reduced Kupperman Index at all time points compared to placebo (P < 0.001). Estraderm MX induced increases in mean E2, E1 and E1S plasma levels as expected (E2: baseline 2.7 pg/ml, 12 weeks 38.9 pg/ml; E1: baseline 18.8 pg/ml, 12 weeks 41.6 pg/ml; E1S: baseline 235.6 pg/ml, 12 weeks 765.1 pg/ml). Overall rates of adverse experiences were similar for Estraderm MX and placebo. The number of patients reporting skin irritation was low and similar in both groups. Conclusions: Estraderm MX 50, a new matrix patch, offers an effective and well tolerated dosage form for transdermal delivery of 0.05 mg E2 per day.     

Liminal therapy: A strategy for the complete and selective destruction of malignant tissue

The property of aerobic glycolysis commonly possessed by malignant cells points to a weakness in oxidative metabolism which has been equated in some tumours with partial uncoupling of oxidative phosphorylation. The suggestions are made, first, that this endogenous defect may account for spontaneous cell death , and, second, that its accentuation would inflict extensive tumour injury upon sensitive neoplasms. Certain drugs not in current use for the treatment of malignant disease are known to be able to interfere selectively with energy metabolism in sensitive tumours to such an extent that widespread necrotisation ensues. The drugs activate an endogenous destructive mechanism that appears to require oxygen. Liminal therapy, the maintenance of continuous destructive pressure on sensitive growths in such a manner that maximal anti-tumour activity in terms of interference with energy production is not achieved at any one time, and under conditions in which the oxygen supply is only partly depleted, is put forward as a possible means of achieving complete and selective tumour destruction .     

Cannabinoid agonist, CP 55,940, facilitates intake of palatable foods when injected into the hindbrain

Cannabinoids have been shown to influence food intake, and until recently, the neural pathways mediating these effects have remained obscure. It has been previously shown that intracerebroventricular injection of delta-9-tetrahydrocannabinol (Δ⁹-THC) causes increased consumption of palatable foods in rats, and we postulated the involvement of the hindbrain in this cannabinoid-induced food intake. Cannulated rats (both female and male groups) trained to consume sweetened condensed milk received either lateral or fourth ventricle injections of CP 55,940 and were presented with sweetened condensed milk 15 min after injection. Rats were injected over a range of doses between 100 pg and 10 μg per rat. Milk intake was recorded for a total of 3 h. Lateral ventricle injection of CP 55,940 increased milk intake at doses in the microgram range. However, CP 55,940 was effective in increasing food intake at nanogram doses when injected into the fourth ventricle. Finally, male rats appeared to be more sensitive to CP 55,940 than female rats inasmuch as milk consumption was increased at the 1 ng dose in male rats, whereas only the 10 ng dose was effective in females. These results indicate that CP 55,940 may act in the hindbrain to influence feeding behavior in rats.     

Measurement of functional ability and health status in the arthritic patient

Chronic arthritis may have great impact on the patient but also on his or her family, relatives and friends. The assessment of the consequences of chronic arthritis and the effect of therapy not only in terms of physical, but also psychological and social dimensions deserves more attention. Functional ability and health status can be measured using a questionnaire or ‘instrument’, high-lighting important aspects not quantified with more traditional measurements. In this paper, arguments to apply such instruments more frequently are given. Health status instruments can be used not only to assess beneficial but also deleterious (side-)effects of therapeutic interventions. The properties are summarized of the most frequently used instruments assessing functional ability and health status. Many of these instruments have been evaluated sufficiently for validity and reliability; their sensitivity to detect change seems to be satisfactory. Therefore it is advisable to choose an internationally accepted, frequently used instrument, reflecting the area of interest.     

Expression of oncogene products, anti-oncogene products and oncofetal antigens in intraductal papillary-mucinous neoplasm of the pancreas

A few previous studies have demonstrated the expression or mutations of oncogenes and anti-oncogenes as well as that of oncofetal antigens in intraductal papillary-mucinous neoplasm of the pancreas. In this study, we have investigated the immunohistochemical expression of oncogene (ras and c-erbB-2) and anti-oncogene (p53 and retinoblastoma [Rb]) products and oncofetal antigens (CEA, CA19-9 and DUPAN-2) in nine such tumours of the pancreas. In normal pancreas (5 cases), the Rb gene product and CA19-9 were expressed in all cases, while ras and c-erbB-2 gene products, p53 protein, CEA and DUPAN-2 were not expressed. In intraductal papillary-mucinous tumours (n = 9), ras, c-erbB-2, p53 and Rb gene products were present in 4/9 (44%), 7/9 (78%), 0.9 (0%) and 6/9 (67%) cases, respectively. CEA, CA19-9 and DUPAN-2 were expressed in 8/9 (89%), 9/9 (100%) and 2/9 (22%) cases respectively. In invasive ductal adenocarcinoma of the pancrease (7 cases), ras, c-erbB-2, p53 and Rb gene products were expressed in 3/7 (43%), 6/7 (86%), 2/7 (29%) and 3/ & (43%) cases respectively. CEA, CA19-9 and DUPAN-2 were expressed in 7/7 (100%), 7/7 (100%) and 6/7 (86%) cases, respectively. The extent and intensity of the expression of these antigens was greater in invasive ductal adenocarcinomas. These data suggest that activation of ras and c-erbB-2 oncogenes and inactivation of Rb anti-oncogene may contribute to the development and progression of intraductal papillary-mucinous tumours of the pancreas and that there is neo-expression of CEA and DUPAN-2 during the development and progression of these tumours.     

Mathematical modelling of the growth processes in the developing chick wing bud

This paper illustrates how a simple geometric model resembling the shape of the chick wing bud at an early growth stage can be mathematically expanded to simulate subsequent growth characteristics of the developing bud. The model was tested against several sets of experimental data and gave an acceptable representation of growth over the range considered. Representing growth patterns in this form enables the determination of differential growth characteristics in different parts of the bud and provides boundary constraints which will play an important part in the eventual evaluation of internal growth mechanisms.     

The mechanism of hyperlipidaemia in the nephrotic syndrome

The mechanism of hyperlipidaemia in the nephrotic syndrome has not been fully established. We propose that it results from hypoalbuminaemia due to inhibition of the reaction catalysed by lecithin cholesterol acyltransferase converting cholesterol of high density lipoproteins to cholesterol esters and to an inhibition of high density lipoprotein particle formation from very low density lipoproteins due to reduced activity of lipoprotein lipase.     

Development of a non-linear finite element modelling of the below-knee prosthetic socket interface

A non-linear finite element model has been established to predict the pressure and shear stress distribution at the limb-socket interface in below-knee amputees with consideration of the skin-liner interface friction and slip. In this model, the limb tissue and socket liner were respectively meshed into 954 and 450 three-dimensional eight-node isoparametric brick elements, based on measurements of an individual's amputated limb surface; the bone was meshed into three-dimensional six-node triangular prism elements, based on radiographic measurements of the individual's residual limb. The socket shell was assumed to be a rigid boundary. An important feature of this model is the use of 450 interface elements (ABAQUS INTER4) which mimic the interface friction condition. The results indicate that a maximum pressure of 226 kPa, shear stress of 53 kPa and less than 4 mm slip exist at the skin-liner interface when the full body weight of 800 N is applied to the limb. The results also show that the coefficient of friction is a very sensitive parameter in determining the interface pressures, shear stresses and slip. With the growth of coefficient of friction, the shear stresses will increase, while the pressure and slip will decrease.     

脑转移瘤同期加量混合调强放疗与调强放疗的剂量学比较

目的:探讨同时运用三维适形与调强的混合调强放疗（Hybrid-IMRT）与调强放疗（IMRT）用于脑转移瘤同期加量的剂量学差异。方法:选取20例进行头颅放疗的患者，分别设计Hybrid-IMRT计划和IMRT计划。Hybrid-IMRT计划包括全脑行三维适形（两野对穿）3 600 cGy/20 F、脑转移灶行IMRT同期加量至5 000 cGy/20 F；IMRT计划全程运用IMRT给予全脑照射3 600 cGy/20 F、脑转移灶5 000 cGy/20 F。在满足临床要求的前提下，比较两组计划靶区的均匀性指数、适形度指数、平均剂量和机器跳数，危及器官脑干、视神经、晶体、视交叉、眼球的最大剂量和平均剂量。结果:两种计划均能满足临床要求。Hybrid-IMRT计划的PGTV均匀性优于IMRT计划（P<0.001）；Hybrid-IMRT计划的脑干、视交叉、左右晶体的最大剂量与平均剂量，左右眼球的平均剂量以及左右视神经的最大剂量均低于IMRT计划（P<0.05）；Hybrid-IMRT计划的机器跳数比IMRT计划减少了约70%（P<0.001）。结论:两种计划均能满足临床要求，Hybrid-IMRT计划相较IMRT计划靶区剂量更加均匀，治疗时间缩短，也能更好地保护危及器官。     

Psychological reactions in patients with early rheumatoid arthritis

We report the interaction of RA and psychological factors over 2 years in a group of 89 patients with newly established disease. Short-time outcome regarding physical features was fairly good. Disease activity decreased, and disability evaluated by HAQ remained at a low level. Psychological distress as measured by the depression and anxiety subscales of SCL 90 (Symptom Check List) was not very pronounced and not related to disease state factors. A slight decrease of anxiety was recorded after 2 years. A new adjustment test was applied. It contained 13 items focused mainly on negative illness effects such as loss of independence, feelings of guilt, and change of social and leisure time activities. Three factors (regret of lost life values, dysphoric mood, and acceptance) explained 48% of the variance of the 13 items. The validity of the test was acceptable. The patients' degree of adjustment changed slowly or not at all during the 2 years.