Methadone maintenance therapy in liver transplantation

Cirrhosis due to chronic infection with hepatitis C virus remains by far the most common reason for liver transplantation in North America. Currently, parenteral use of street drugs is the most common means of acquiring hepatitis C. Methadone maintenance therapy is an accepted form of treatment for chronic opiate (eg, heroin) addiction and, not surprisingly, a significant proportion of methadone-treated patients have chronic hepatitis C. The feasibility of liver transplant candidacy in hepatitis patients who require methadone maintenance therapy is controversial, and some transplant centers require patients to withdraw from such therapy in order for the transplant process to move forward. Thus stable patients with end-stage cirrhosis who are receiving methadone maintenance are left in a most difficult situation: discontinue methadone and accept the side effects of withdrawal with the risk of recidivism to use of street opiates, an absolute contraindication for transplantation, or continue methadone therapy and risk exclusion from the transplant process. The issue of methadone replacement therapy in end-stage cirrhosis and the posttransplant literature on the subject are explored in this paper.     

Management of Aromatase Inhibitor-Resistant Disease with Estrogen,Selective Estrogen Receptor Down-Regulators,and Other Agents

With increased use of aromatase inhibitors (AIs) in the adjuvant and first-line metastatic settings for postmenopausal women with estrogen receptor (ER)-positive breast cancer, systemic relapse or progressive metastatic disease on AIs is an increasingly encountered clinical scenario. Overcoming resistance is a priority. Patients with AI-resistant disease represent a heterogeneous population, with diverse mechanisms of resistance dictating varied sensitivity to subsequent treatment. Cells with persistent dependence on ER signaling may be inhibited by fulvestrant, in which case dose-dependent ER downregulation and activity favor high-dose, loading schedule fulvestrant. In direct contrast, cells with long-term estrogen deprivation with adaptive estrogen hypersensitivity may be inhibited by exposure to estrogen. Cell survival by alternate growth signaling pathways may be inhibited by targeted agents. Currently missing, however, are predictive biomarkers to identify underlying resistance mechanisms and guide effective post-AI therapy for individual patients.     

Influence of substitutive ovarian steroids in the nuclear and cell body volumes of neurons in the posterodorsal medial amygdala of adult ovariectomized female rats

The volumes of the neuronal nucleus and the cell body in the left posterodorsal medial amygdala (MePD) of adult ovariectomized (OVX) female rats submitted to different hormonal therapies were studied here, aiming to reveal possible influence of substitutive sex steroids in these morphological parameters. One week following ovariectomy and at the end of treatments, brains were cut to semi-thin sections (1 μm) and stained with 1% toluidine blue for stereological estimations, carried out using the Cavalieri method and the technique of point counting. Both the volume of the neuronal nucleus and the soma showed a statistically significant difference when comparing the data among OVX females treated with vehicle (V), estradiol (EB) alone, EB plus progesterone (EB + P) or P alone [n = 5 rats in each group; one-way ANOVA test, P < 0.01 in both cases]. The Tukey test showed that OVX and EB + P treated females had higher mean neuronal nucleus and somatic volumes when compared to V (P < 0.01) or EB alone (P < 0.01). Also, OVX females treated with P alone showed larger mean neuronal nucleus and somatic volumes when compared to V (P < 0.05). These results suggest that the neuronal nucleus and the somatic volumes can be modulated by substitutive ovarian hormones administered to OVX females, for which P can lead to higher results. These findings reveal additional epigenetic actions of the sex steroids in the MePD and new neuronal morphological features in adult female rats.     

Effect of pethidine administered during the first stage of labor on the acid-base status at birth

OBJECTIVE: To evaluate the association between the use of pethidine during the first stage of labor and the presence, type and timing of acidosis in the newborn at birth. STUDY DESIGN: Secondary data analysis of a randomized controlled trial, which included term singleton pregnancies diagnosed with dystocia and requiring active management of labor. Women were randomized to receive either 100 mg of pethidine or placebo. Statistical analyses were performed using chi(2) or Fisher's exact tests for proportions and multiple linear regression for continuous outcomes. RESULTS: Three hundred and eighty-three pregnant women with a valid arterial blood cord sample were included in the final analysis. Lower pH and bicarbonate levels, as well as higher pCO(2) levels were found in the pethidide group. A higher incidence of acidosis was found in the pethidine group (pH<7.12 OR: 8.59 95% C.I. 3.29, 22.46). The highest frequency of acidosis was encountered when pethidine-delivery interval was 5 h. CONCLUSION: Pethidine use during the first stage of labor was associated with an increased risk of acidosis at birth.     

Steroid hormones and leiomyomas

The sex steroid hormones play an important role in myoma maintenance and growth as evidenced by clinical, molecular, biological, and pharmacological models. It is hoped that the next phase of research will elucidate better the mechanisms through which these hormones modulate myoma growth and how they interact with the as yet unidentified other factors that play a role in myoma development and growth.     

Adjuvant therapy for HER2+ breast cancer: practice, perception, and toxicity

Multiple adjuvant regimens are used for HER2+ breast cancer, but experience in routine practice is not reported. We evaluated whether oncologists' perceptions of these regimens matches clinical experience. We surveyed Wisconsin medical oncologists throughout the state regarding factors impacting selection of TCH (docetaxel, carboplatin, and trastuzumab) or anthracycline-based therapy. We also reviewed 200 cases of HER2+ breast cancer treated at the University of Wisconsin and the Marshfield Clinic and collected data on patient and tumor characteristics, chemotherapy regimen, and toxicities. Two-thirds of surveyed oncologists prefer anthracycline-based therapy, particularly for node-positive cancers. However, TCH was preferred for early-stage (T1a-bN0) tumors. Half of oncologists use prophylactic G-CSF with TCH. In the 200 cases reviewed at our centers, acute toxicity occurred more frequently with TCH. There were fewer dose modifications or delays for AC-TH (doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab) than TCH (31% vs. 47%, P?=?0.07), possibly due to higher use of prophylactic G-CSF with AC-TH (77% vs. 34% with TCH, P?相似文献   

Incidence and risk factors for axillary web syndrome after breast cancer surgery

The objective of the study is to estimate the incidence and risk factors of axillary web syndrome (AWS) in early postoperative period (45 days). From the prospective cohort of women undergoing breast cancer surgery, we collected the variables related to patient characteristics, treatment, tumor, and postoperative complications. We performed bivariate and logistic regression. A total of 193 patients are included with a mean age of 58.26 years, majority of which are women who are overweight or obese (72.3%). The incidence of AWS was 28.1%. The presence of pain in the ipsilateral upper-limb associated with AWS was reported in 5.4% of the patients, and the shoulder joint restriction was observed in 11.4%. When controlling for confounding between AWS and the factors that showed statistical significance in bivariate analysis, the variables that explain the occurrence of the AWS were the type of axillary surgery, where women who underwent sentinel lymph node biopsy showed 68% less risk compared with those that underwent axillary lymphadenectomy (AL) (RR = 0.32; 95% CI, 0.13−0.79; P value = 0.014) and numbness in the arm after an injury of the intercostobrachial nerve, which is 3.19 times the risk of the AWS (RR = 3.19; 95% CI, 1.40−7.29, P value = 0.006). From the above findings, we concluded that the incidence of AWS was 28.1%, and it was associated with AL and numbness in the arm after injury of the intercostobrachial nerve.     

Adverse events in cancer genetic testing: medical, ethical, legal, and financial implications

ABSTRACT: Cancer genetic counseling and testing are now integral services in progressive cancer care. There has been much debate over whether these services should be delivered by providers with specialized training in genetics or by all clinicians. Adverse outcomes resulting from cancer genetic counseling and testing performed by clinicians without specialization in genetics have been reported, but formal documentation is sparse. In this review, we present a series of national cases illustrating major patterns of errors in cancer genetic counseling and testing and the resulting impact on medical liability, health care costs, and the patients and their families.