Contractile proteins in human fetoplacental vessels

OBJECTIVE: Our purpose was to compare the protein isoform composition of the contractile apparatus at different levels of the fetoplacental vessel musculature et term.STUDY DESIGN: Umbilical, chorionic, and stem villi vessel protein extracts were run on one- and two-dimensional gel electrophoresis; previously characterized human myometrium proteins were used as the smooth muscle proteins of reference.RESULTS: Fetoplacental vessel musculature exhibited a high ratio. The presence, in varying quantities, of myosin heavy chain and actin isoforms of smooth muscle type in the different vessels reflected their degree of differentiation. The presence of nonmuscle protein isoforms, particularly in stem villi vessels, indicated a certain degree of immaturity.CONCLUSIONS: The presence of smooth muscle contractile protein isoforms indicates that fetoplacental vessel musculature is highly differentiated. Regional modulation of fetoplacental blood flow could be, in part, the result of local differences in contractile apparatus protein composition.     

Public involvement in health care priority setting: an economic perspective

Background  Public involvement in health care decision making and priority setting in the UK is being promoted by recent policy initiatives. In 1993, the British Medical Association called for public consultation where rationing of services was to be undertaken. The approach to priority setting advocated by many health economists is the maximization of quality adjusted life years (QALYs). Typically, for a particular health care programme, the QALY calculation takes account of four features: (1) the number of patients receiving the programme, (2) the survival gain, (3) the gain in quality of life and, (4) the probability of treatment success. Only one feature, that relating to quality of life, is based upon public preferences. If the QALY is to be used as a tool for health care resource allocation at a societal level then it should incorporate broader societal preferences.
Methods  This study used an interview-based survey of 91 members of the general public to explore whether the traditional QALY maximization model is a good predictor of public responses to health care priority setting choices.
Results and conclusions  Many respondents did not choose consistently in line with a QALY maximization objective and were most influenced by quality of life concerns. There was little support for health care programmes that provided a prognostic improvement but left patients in relatively poor states of health. The level of respondent engagement in the survey exercise was not sensitive to the provision of supporting clinical information.     

Effects of long-term treatment with trandolapril on augmented vasoconstriction in rats with chronic heart failure

Background:

Despite the clinical relevance of angiotensin I-converting enzyme (ACE)inhibitors, their effects on impaired vascular function in patients and animals with chronic heart failure (CHF) have not been fully understood. This study was undertaken to determine whether long-term treatment with an ACE inhibitor improved the altered contractile properties of vessels from rats with CHF.

Methods and Results:

Twelve weeks after coronary artery ligation, the rats were sacrificed and the isometric tension development of thoracic aorta, pulmonary artery, and mesenteric artery with and without endothelium was examined. Contractile responses to norepinephrine and prostaglandin F₂α were augmented in endothelium-intact, but not in endothelium-denuded, thoracic aorta and pulmonary artery segments of the rat with CHF. The contractile response to angiotensin II was augmented in endothelium-denuded mesenteric artery segments of the rat with CHF, which was attenuated by indomethacin or diclofenac sodium but not by bunazosin. Trandolapril (3 mg/kg/d) was administered orally from the 2nd to 12th week after the operation. Treatment with trandolapril reversed the augmented contractile response of the rat with CHF to norepinephrine, prostaglandin F₂α, and angiotensin II almost to the levels in the sham-operated rat.

Conclusions:

The results demonstrate that an ACE inhibitor is capable of reversing altered vascular function in the rat with CHF, suggesting that vascular beds are possible sites of action for ACE inhibitors in the therapy for CHF.     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

• 1 Autoradiographic binding studies have shown that the AT₁ receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT₁ receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
• 2 While there are differences between species, AT₂ receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
• 3 Circulating AngII acts on AT₁ receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
• 4 Centrally administered AngII may act on AT₁ receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
• 5 Recent evidence shows that centrally administered AT₁ antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
• 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT₁ receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.

     

The relationships among height,penile length,and foot size

To determine whether "folk myths" regarding the relationships of penile size to body height and foot size have any basis in fact, 63 normally virilized men were studied. Height and stretched penile length were measured; shoe size was recorded and converted to foot length. Penile length was found to be statistically related to both body height and foot length, but with weak correlation coefficients. Height and foot size would not serve as practical estimators of penis length.     

Drug effects on clinical laboratory tests

Drugs and xenobiotics can affect clinical laboratory test results either by interfering with the analytical systems themselves, or by influencing endogenous constituents. National and international bodies have brought widespread recognition to this problem and have proposed protocols for its thorough scientific study. In this survey the authors discuss studies in their laboratories concerning the effects of drugs on thousands of patients undergoing a routine clinical screen. A database is described for storing both patient information and a detailed analysis of the published literature on drug effects. Analytical interferences in clinical tests must be examined in validating the procedure. However, highly specific analytical techniques are increasingly helping to reduce such interferences. Biological effects can be classified as physiological, pharmacological or toxicological. In some cases, biological effects can be used to advantage in monitoring treatment by potentially hazardous drugs, such as the cardiac glycosides. The requirement for a well-defined reference population for each drug and for access to all clinical and medical data for each patient is discussed. The need for greater awareness of the influence of drugs on clinical laboratory results is considered, together with the suggestion that the health professions should try to exploit such effects in monitoring possible toxicity problems, in defining genetic constitution and in designing medication programmes.     

Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.     

几种中西药抗人实验模拟运动病效果观察

目的 :选用中药“治晕灵”的主要成分生姜、明天麻等六味草药煎成汤剂、或半量汤剂配西药脑益嗪、山莨菪碱各1 4临床常用量配成复方中西药制剂 ,与目前常用抗晕药晕海宁等中、西药的药效进行比较 ,看中药制剂或中西药复方制剂是否具有较好的抗运动病效果。方法 :选 7名敏感被试者 (女性 ,19～ 2 1岁 ) ,用旋转刺激诱发运动病至出现恶心。按拉丁方设计 ,与安慰剂 (淀粉 10 0mg)及晕海宁 (5 0mg)进行对比 ,分别观察了生姜合剂 (30ml)、晕可平 (30ml)、山莨菪碱 (10mg)、脑益嗪 (2 5mg)及上述复方中西药制剂口服后的运动病耐力。结果 :与安慰剂比较 ,晕海宁、山莨菪碱、脑益嗪、晕可平、生姜合剂、复方中西药制剂分别使运动病耐力提高 5 .4%、7.5 %、5 .9%、7.4%、32 .3 %、2 0 .4% ;生姜合剂效果较优 ,除口服时有辛辣味外 ,无明显的副作用。复方中西药制剂各成分未显示协同作用 ,而只是简单的作用相加。结论 :生姜合剂具有较好的抗运动病作用     

Assessment of vascularity in breast carcinoma by computer-assisted video analysis (CAVA) and its association with axillary lymph node status

Case-control methodology was used to evaluate the significance of vascularity in small breast carcinomas with regard to the presence or absence of axillary lymph node metastases. Vascularity was assessed in 32 axillary node positive primary breast tumours (LN+ve) less than 2 cm in size and compared with 56 control axillary node negative primary tumours (LN–ve), which were matched for histological type and grade and tumour size. This study design employed computer-assisted video analysis (CAVA) to assess the total blood vessel perimeter (BVP), total blood vessel area (BVA), and total blood vessel density (BVD) throughout a tissue section that encompassed an entire cross section of the tumour and its immediate periphery. The BVA and BVD in these tumours were not significantly different between LN+ve and LN–ve groups. The LN–ve carcinomas had, on average, a significantly (P < 0.05) higher total BVP (3355 µm/mm²) than LN+ve tumours (2771 µm/mm²). 'Hot spot' areas were also independently assessed by two pathologists and the same areas measured by CAVA. A strong correlation (P < 0.001) between the two methods of assessment of BVD of the neovascular 'hot spots' was found; however, no association with axillary lymph node metastasis was found using either method of assessment. In conclusion, vascularity assessed by either blood vessel density or blood vessel size in primary invasive breast cancers less than 2 cm in diameter showed no association with axillary lymph node metastasis; in fact a negative association was found with total BVP of whole tumour sections and BVD in 'hot spots' using CAVA. Further, this study has established a computer-assisted method of quantifying vascularity in solid neoplasms and is a positive step towards a standardised approach to this diverse and methodologically variable area.