Background: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account.
Methods: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs.
Results: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed. 相似文献
In Italy mifepristone is not yet marketed. Gynaecologists in our hospital asked to use this medication as a less traumatic
method for voluntary abortions. We followed the standard procedure defined by the Italian Health Ministry (IMH) for purchasing
drugs from abroad but encountered several unexpected barriers. Starting from this case, this paper is aimed at identifying
these barriers which we found to be not only professional, but also ethical, religious and moral. 相似文献
We have prospectively evaluated the skin changes that occurred in ten patients who were undergoing immunotherapy with interleukin 2 (IL-2) and autologous lymphokine-activated killer cells to treat cancer. Serial skin biopsy specimens were obtained before therapy (baseline), during IL-2 administration, and during IL-2/lymphokine-activated killer cell infusion. All patients developed an eruption that was characterized by macular erythema, with burning and pruritus of the skin. It began after two or three days of IL-2 infusion and was usually localized to the head and neck; it occasionally became generalized (ie, erythroderma). The eruption resolved with desquamation within 48 to 72 hours after cessation of infusion of IL-2. Histologically, the changes were not specific. The only consistent immunohistological finding noted was the presence of DR+/Leu-4+ lymphoid cells surrounding blood vessels in the papillary dermis, with fewer of these cells in the epidermis. There was no difference between the clinical or histological features of the eruption that occurred with IL-2 alone and that which occurred with IL-2 and lymphokine-activated killer cell infusion, suggesting that the cutaneous effects were mediated by IL-2 alone. 相似文献
Stapled hemorrhoidopexy is widely accepted to treat hemorrhoids, but serious complications have been reported. In this prospective
audit, we correlated clinical outcome with pathological findings. From January 2003 to April 2007, 94 patients underwent hemorrhoidopexy.
Macroscopic appearance of the specimen (shape, size, and depth) was recorded. Microscopically, the presence of columnar, transitional,
and squamous epithelium, the involvement of circular/longitudinal smooth muscle, and features of mucosal prolapse were assessed.
Clinical outcome was evaluated by a validated questionnaire. Postoperative pain, secretion, and bleeding durations were 12.7 +/− 10.6,
5.6 +/− 9.6, and 6.3 +/− 8.4 days. Patient’s return to work averaged 16.7 +/− 10.7 days. Fissure, skin tags, and anal strictures
were observed in 23.4%. Seven patients experienced pain for a significantly longer period of time. All specimens contained
columnar mucosa, but 29.8% contained columnar and transitional epithelium and 12.8% contained columnar, anal transitional,
and stratified squamous epithelium. Smooth muscle was observed in 62.7%. Pain was significantly increased if transitional
epithelium was present in the specimen. No correlation or differences were observed if smooth muscle was present, although
postoperative bleeding was more frequent. Hemorrhoidopexy is safe and effective. The specimen should always be sent for pathology
examination. Only columnar epithelium should be present and, although the presence of smooth muscle does not influence the
outcome in terms of functional results, its presence may play a role in postoperative bleeding.
Presented as poster at the Digestive Disease Week, May 2007, Washington, USA 相似文献
Background Recently, it has been demonstrated that surgical treatment of hemorrhoids in a day-care basis is possible and safe. The aim
of this study was to compare the Longo stapled hemorrhoidopexy (SH) and the Milligan–Morgan hemorrhoidectomy (MMH).
Methods One hundred seventy one patients (95 cases in SH group and 76 cases in MMH group) entered the study: 83 cases were III degree
hemorrhoids, 88 IV degree. A priori and a post hoc power analysis were performed. Results, prospectively collected, were compared
using chi squared test and student t test. Visual analog scale was used for pain evaluation. Postoperative pain, duration of pain, wound secretion, bleeding,
resumption of a normal lifestyle, and postoperative complication were evaluated.
Results Surgical time was 28.41 ± 10.78 for MMH and 28.30 ± 13.28 min in SH (P = 0.94). Postoperative pain was not different between MMH and SH during the first two postoperative days (4.73 ± 2.91 vs
5.1 ± 3.048; P = 0.4), during the following 6 days, patients treated with SH had less pain (4.63 ± 2.04 in MMH vs 3.60 ± 2.35 in SH; P = 0.006). In the SH group, seven patients needed further hospital stay for complicated course. SH showed higher incidence
of anal fissure compared with MMH (6.3% vs 0%; P = 0.025) but no differences in urinary retention, anal stricture, urgency, or anal hemorrhage.
Conclusions This study confirms that SH is associated with less postoperative pain and shorter postoperative symptoms, compared with MMH.
SH may be a viable addition to the therapy for hemorrhoids with some advantages in early postoperative pain and some disadvantages
in postoperative complications and costs. 相似文献
Summary: Purpose: Gangliogliomas (GGs) are neuronal-glial tumors highly associated with epilepsy. We hypothesized that the expression of select gene families including neurotransmitter receptor subunits and growth factors would be distinct in neurons and astrocytes within GG compared with adjacent cortex and that these changes would yield insights into seizure onset and lesion formation. Methods: Candidate gene expression was defined in single immunohistochemically labeled neurons and astrocytes microdissected from GG specimens compared with neurons and astrocytes microdissected from morphologically intact cortex adjacent to the GG or normal control cortex. Results: Differential expression of 16 genes including glutamate transporter (EAAC1) and receptor (NMDA2C, mGluR5), growth factor (hepatocyte growth factor), and receptor (platelet derived growth factor receptor β, fibroblast growth factor receptor 3) mRNAs was detected in GG neurons compared with control neurons. In astrocytes, altered expression of p75NGF, mGluR3, TGFβ3 and Glt-1 mRNAs was detected. Nestin mRNA, a gene that exhibits enhanced expression in balloon cell cortical dysplasia, was increased in GG neurons. Because of the morphological similarities between GG and cortical dysplasia, we show that there is activation of the mTOR cascade in GG as evidenced by enhanced expression of phospho-p70S6kinase and phosphoribosomal S6 proteins. Conclusion: We find differential candidate gene expression in neurons and astrocytes in GG compared with adjacent cortex and show that there is activation of the mTOR pathway. These changes highlight pathways that may be pivotal for epileptogenesis and lesion growth. 相似文献