Ethical issues in clinical neuroscience research: A patient’s perspective

A patient-centered paradigm for clinical research and medical care is presented as a solution to the problem of declining innovation and increasing costs and development time in the pipeline for new therapies. Fundamental differences in values and motivations among scientists, clinicians, industry sponsor, and patients in neurotherapeutics provide a framework for analysis of ethical conflicts and the loss of public confidence in medical research. Parkinson advocates’ views on clinical trial participation, perceived risks and benefits, placebo controls, and sham surgery are presented. These views reflect the sense of urgency and the unique perspective that comes from living with this progressive, debilitating condition full time. A patient-centered paradigm that includes authentic voices of patients as collaborators at every stage of development will help to resolve conflicts, build trust, recruit trial participants, and accelerate new therapies. Key elements are adaptive clinical trial methods and the development of information technology for the assessment of outcomes and surveillance of safety over the life cycle of a medical product. Supported by the Parkinson’s Disease Foundation, the Parkinson Pipeline Project is a grassroots group of Parkinson’s patients whose goal is to represent an authentic voice for patients in the treatment development process. This group promotes education and communication between members of the Parkinson’s community and active stakeholders in medical research, industry, and regulatory agencies. Its members are an example of a new breed of knowledgeable consumers, armed with first-hand access to research findings and reinforced by on-line connections to like-minded peers throughout the world.     

Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.     

Masculinizing sclerosing stromal tumor of the ovary during pregnancy

Sclerosing stromal cell tumors of the ovary are an uncommon neoplasm that usually does not produce hormonal imbalances. Most patients showing a hormonal effect from this lesion have had menstrual cycle disturbances. Infertility and endometrial hyperplasia have also been described. One other reported case had masculinizing effects. Other authors have documented elevated levels of both estrogenic and androgenic hormones that corrected after surgery. A case of a pregnant 27-year-old Caucasian with hirsutism on her chin and neck and a male suprapubic hair pattern is presented. Elevated androstenedione, dehydroepiandrosterone, and free testosterone levels were present. A 3-cm left ovarian mass was excised and identified as a sclerosing stromal tumor. The histologic features included a pseudolobular pattern with focal areas of sclerosis and a two-cell population of spindled and polygonal cells. Immunohistochemical studies showed a positive vimentin reaction, weakly positive desmin and muscle-specific actin stains, and a negative cytokeratin stain. Following surgery the hormone levels returned to normal and the hirsutism resolved. A normal female infant without evidence of masculinization was delivered from the patient at term.     

Evaluation of renal transplant dysfunction by duplex Doppler sonography: a prospective study and review of the literature

A disconcertingly wide variation exists in the literature as to the accuracy of duplex Doppler sonography in the detection of acute renal transplant rejection. Sensitivities range from 9% to 76%. In an attempt to explain the disparity of results, we undertook a double-blind prospective study of the accuracy of duplex Doppler ultrasound in the detection of acute rejection in renal transplants. We scanned 49 consecutive patients with a total of 65 biopsies; 46 biopsies in 33 consecutive patients were included in our study. In our population, the prevalence of acute rejection was 61% (28/46). Using a resistive index (RI) cutoff of greater than 0.90 based on the main renal artery flow pattern, the sensitivity of our test was 43%, with a 67% specificity. The positive predictive value was 67%. Our results are contrasted and compared with the published data from other groups in a critical survey of the literature. We conclude that duplex Doppler sonography alone is inadequate to evaluate acute rejection in renal transplants.     

Primary gastrointestinal lymphomas in Turkey: a retrospective analysis of clinical features and results of treatment.

Thirty-three patients with primary gastrointestinal lymphoma (GIL) followed at Ankara University Medical School have been evaluated. The most frequent locations of the disease are the small intestine (48.4%) and the stomach (39.3%). The intermediate and high grade lymphomas constitute 84.8% of the cases. The mean age of the patients with small intestinal lymphoma is 28.7 years and 47.1 years for those with gastric lymphoma. The patients treated with surgery and chemotherapy (S+CT) have a longer survival than those treated with chemotherapy (CT) alone. In conclusion: 1) Small intestinal lymphoma occurs more frequently than gastric lymphoma in our study. 2) The median age of the Turkish patients with primary GIL is approximately 10 years less than those in the Western countries. 3) The therapeutic results of S+CT are superior to those of CT in the early stages of the disease.     

Retention properties of a split-shaft threaded post: cut at different apical lengths.

The retention of the post to the root of an endodontically treated tooth is critical for a successful restoration. Modification of the post length to accommodate a specific clinical situation is common. This study compared the retention of No. 1 and No. 2 Flexi-Post restorations shortened apically from 1 to 5 mm with that reported for full-length control No. 1 and No. 2 Flexi-Post dowels. The experimental material was divided into 10 groups with 10 samples in each group. Retentive values were recorded in pounds with a universal testing machine. Analysis of variance with a Tukey-Student range, multiple-comparison test showed no statistical differences from apical reductions of 1, 2, 3, and 5 mm including the full-length control Flexi-Post No. 1 system. With 4 mm of apical shortening statistically greater retention was recorded. No statistical differences resulted with apical reductions of 1 to 4 mm or with the full-length control Flexi-Post No. 2 system, but 5 mm of apical shortening caused significantly less retention.     

Analysis of premature ventricular counts in long term ECG following myocardial infarction.

Frequent and recurrent ventricular premature beats (VPB's) are considered to be associated with a higher risk of sudden cardiac death, particularly for survivors of myocardial infarction (MI). The distribution of VPB's has a large probability mass at zero, and a very heavy right hand tail. In this research, we fitted a model to VPB for patients for which VPB was present. The model was fitted on the basis of a relatively large data set on MI survivors in Israel. The model was fitted by a method which is based on the generalized linear model. This method, which was introduced by Zeger and Liang, is designed for longitudinal data and uses the quasi-likelihood concept. No specific assumptions are required on the shape of the distribution of the dependent variable. The results indicate that the model fits the data quite well but underestimates the very extreme high values. This research demonstrates the applicability of generalized linear models for longitudinal non-Gaussian data. Such data often arise in medical studies. The study also points out the distributional properties of VPB counts. In particular, it shows their associations with simple clinical and epidemiological variables, and with certain time periods during the day.     

Epidural block for obstetrics: Comparison of bolus injection of local anesthetic with gravity flow technique

Study Objective: To test the hypothesis that slow administration of local anesthetic into the epidural space by gravity flow reduces the incidence of signs and symptoms of unintended injection.

Design: Prospective, randomized study.

Setting: Teaching hospital.

Patients: 600 ASA physical status I and II parturients scheduled for labor and delivery or elective cesarean section.

Interventions: After identification of the epidural space with pulsations of an air-fluid column, parturients for vaginal delivery (n = 380) were randomized to receive a test dose of 3 ml 3% 2-chloroprocaine with epinephrine 20 μg, two doses of 7 ml bupivacaine 0.03 % with sufentanil 1 μg/ml and epinephrine 2 μg/ml by either gravity flow (Group 1) given over 30 seconds or by bolus injection (Group 2) given over 5 seconds through the epidural needle; parturients for Cesarean delivery (n = 220) were randomized to receive a test dose and two doses of 6 ml lidocaine 2 % with sufentanil 1 μg/ml and epinephrine 2 μg/ml by either gravity flow or by bolus injection through the epidural needle. Changes in maternal heart rate (HR) and blood pressure, signs of intravascular injection, and adverse effects of epidural bupivacaine-sufentanil were recorded after each dose.

Measurements and Main Results: Gravity flow administration (Group 1) was associated with a smaller increase in mean maternal HR (p < 0.001), less hypotension (p < 0.01), sedation (p < 0.01), nausea (p = 0.01), and segmental spread (p < 0.0001) than were corresponding doses given by traditional bolus injection (Group 1) for vaginal or Cesarean deliveries. The incidence of systemic toxicity was zero of 300 (0%) with gravity flow and 4 of 300 (1.3%) by bolus injection, p = 0.12, Fisher's exact test. No patient in either group had an accidental intrathecal injection.

Conclusion: Gravity flow administration of local anesthetic-opioid solution during epidural block for obstetrics was associated with fewer signs of systemic drug absorption and cardiovascular perturbations than was the traditional bolus injection. This study supports the current opinion that slow administration of local anesthetic during epidural black contributes to fewer adverse events.