Third Prize: Comparison of radical nephrectomy, laparoscopic microwave thermotherapy, cryotherapy, and radiofrequency ablation for destruction of experimental VX-2 renal tumors in rabbits

BACKGROUND AND PURPOSE: Currently available minimally invasive renal tumor-ablation procedures include cryotherapy, radiofrequency ablation, and microwave thermotherapy. In this study, we investigated the ability of these three approaches to destroy experimental renal tumors in rabbits. The mechanism of potential tumor metastasis was also explored. MATERIALS AND METHODS: The VX-2 tumor line is an aggressive rabbit epidermoid tumor with a high metastatic potential. An initial experiment comparing cooled-tip microwave thermotherapy with cryotherapy and radical nephrectomy for treatment of small VX-2 tumors revealed that all microwave-treated rabbits had local recurrence and that several also had diffuse intraperitoneal carcinomatosis. In view of these results, a second experiment was performed in which 45 New Zealand White rabbits were implanted laparoscopically with VX-2 xenografts underneath the kidney capsule and divided into five groups of 9 each. The test groups were microwave thermotherapy with a 3.5-mm cooled-tip probe, microwave thermotherapy with a 3.5-mm noncooled- tip probe, radiofrequency ablation with a 1.5-mm cooled-tip probe, radiofrequency ablation with a 1.5- mm non-cooled tip probe, and cryotherapy with a 2.3-mm cryoprobe. The control groups were five rabbits that were not treated, five rabbits with tumors that had the tumor pierced with a probe but were untreated, and five rabbits that underwent nephrectomy after piercing of the tumor. Treatment was initiated 5 days after tumor implantation. One month later, all animals were euthanized and autopsied. RESULTS: At 5 days after tumor implantation, laparoscopic inspection revealed no visible peritoneal metastases. At 1 month, in the cooled and non-cooled microwave-thermotherapy groups, carcinomatosis occurred in five and six of nine animals, respectively. In comparison, carcinomatosis was detected in two of nine animals in the cryotherapy group at autopsy. With respect to cooled and non-cooled radiofrequency ablation, carcinomatosis was observed in four of nine rabbits in each group. In the control groups, none of the animals with unpierced tumors exhibited carcinomatosis, while carcinomatosis was seen in two of the five rabbits with tumor violated by piercing and in three of the five rabbits that underwent immediate nephrectomy after piercing of the tumor. CONCLUSION: Carcinomatosis occurred most frequently in animals treated with microwave thermotherapy, followed by radiofrequency ablation, and lastly cryoablation. The simple act of piercing a highly aggressive tumor can result in local spread. More disconcerting, and less well understood, is why certain ablative modalities appear to increase the rate of intraperitoneal spread.     

Long-term success of sinus augmentation using a synthetic alloplast: a 20 patients, 7 years clinical report

An adverse architecture of the maxillary sinus is no longer a contraindication for implant placement. Grafting the sinus has become an accepted treatment modality. Techniques for lifting the sinuses are well documented and numerous articles have been published. The main difference between the multitude of articles seems to be the graft material used. After having used different grafts, with varying success, this article reflects the authors' impressions on one particular grafting material, a composite synthetic bone substitute. The objective of this clinical study was to evaluate the effectiveness, reliability and predictability of that synthetic graft material (Bioplant HTR). After treating 20 patients (22 sites, 56 implants), and after a follow-up period as long as 7 years, it was clinically and radiographically observed that achieved results are enhanced if this synthetic graft material is used and that its use enhances sinus augmentation outcome and predictability. It provides the patient with the benefits of implant-supported restorations in a simple, quick, cost-effective, predictable, and secure manner.     

Effects of aspirin, clopidogrel and dipyridamole administered singly and in combination on platelet and leucocyte function in normal volunteers and patients with prior ischaemic stroke

The aim of this study was to assess whether triple antiplatelet therapy is superior to dual and mono therapy in attenuating platelet and leucocyte function. Aspirin (A), clopidogrel (C), and dipyridamole (D) were administered singly and in various combinations (A, C, D, AC, AD, CD, ACD), each for two weeks (without washout) to 11 healthy subjects and to 11 patients with previous ischaemic stroke in two randomised multiway crossover trials. At the end of each two-week period platelet aggregation, platelet-leucocyte conjugate formation and leucocyte activation were measured ex vivo blinded to treatment. Platelets were stimulated with collagen; additional measurements were made with adenosine diphosphate (ADP), platelet activating factor (PAF), adrenaline and the combination of, ADP, PAF and adrenaline. Results show that in the presence of collagen, ACD was superior to all antagonists or combinations, except AC, in reducing aggregation, platelet-leucocyte conjugate formation, and monocyte activation (all p<0.05). ACD was also more potent than other treatments, except AC, in inhibiting the aggregation and platelet-monocyte conjugate formation induced by the combination of ADP, PAF and adrenaline. The effects were similar in both volunteers and stroke patients. No serious adverse events or major bleeding events occurred. Triple antiplatelet therapy did not appear to be more effective than combined aspirin and clopidogrel in moderating platelet and leucocyte function. Any additional clinical benefit provided by dipyridamole may be through other mechanisms of action.     

Developing predictive animal models and establishing a preclinical trials network for assessing treatment effects on cognition in schizophrenia

Animal models are an essential initial phase in the discovery of novel drugs to treat psychiatric disorders. At the sixth Measurement and Treatment Research to Improve Cognition in Schizophrenia conference, "New Approaches to Assessing and Improving Cognition in Schizophrenia," a discussion group was formed to address issues related to the development of predictive animal models of cognition that may be used as preclinical assays for putative cognitive enhancers. We identified 2 complementary approaches used to model cognitive impairments in animals. First, basic lesion/pharmacological models provide information about the particular neural substrates that may underlie different types of cognitive deficits found in schizophrenia. Findings from these studies can be mapped onto the second, more elaborate and etiologically relevant neurodevelopmental models of the disorder to ascertain which cognitive systems may be altered by early developmental insults. Particular attention must be given to the types of animal tasks used, in order to relate directly to the cognitive domains that are affected in schizophrenia patients. Importantly, the validation and standardization of the methodologies used in these preclinical assays would require the establishment of a preclinical trials network, serving as a counterpart to the recently established Treatment Units for Research on Neurocognition and Schizophrenia. The need to validate specific approaches to assess cognitive functions relevant to schizophrenia could be satisfied by a concerted effort enabled by a new funding directive from the National Institute of Mental Health with the explicit purpose of facilitating research on these models and assessing novel drug therapies that may be used to ameliorate the cognitive deficits in schizophrenia.     

Community-wide vaccination with the heptavalent pneumococcal conjugate significantly alters the microbiology of acute otitis media

BACKGROUND: Community-wide use of conjugated heptavalent pneumococcal vaccine (PCV7) in children <2 years of age could affect the microbiology of acute otitis media (AOM) in vaccinees, particularly for penicillin-nonsusceptible Streptococcus pneumoniae (PNSP). SETTING: Since Summer 2000, 94% of young children cared for by this 7-clinician, pediatric practice in rural central Kentucky received 3 or 4 doses of PCV7 in the first 18 months of life. OBJECTIVE: To determine changes in microbiology of AOM before and after community-wide routine implementation of PCV7. METHODS: Among children 7-24 months old with severe or refractory AOM, we compared 336 AOM isolates from 1992-1998 with 83 AOM isolates from 2000-2003 in children who had received 3 or 4 doses of PCV7. RESULTS: Comparing each cohort (1992-1998 versus 2000-2003), the proportion of S. pneumoniae decreased from 48% to 31% (P = 0.009; relative risk, 0.754; 95% confidence interval, 0.628-0.906), and nontypable Haemophilus influenzae increased from 41% to 56% (P = 0.01; relative risk, 1.87; 95% confidence interval, 1.15-3.04; beta-lactamase-positive, 56% versus 64%, not significant). The proportions of intermediate PNSP and resistant PNSP, respectively, were 16% and 9% versus 13% and 6% pre- and post-PCV7, respectively. Vaccine and vaccine-related serotypes, respectively, comprised 70% and 8% versus 36% and 32% of S. pneumoniae strains (P = 0.003). Post-PCV7, Gram-negative bacteria and beta-lactamase-producing organisms accounted for two-thirds and one-half of all AOM isolates, respectively. DISCUSSION: The overall proportion of S. pneumoniae isolates and vaccine serotypes in AOM were significantly reduced by community-wide use of PCV7 vaccine in our practice. The proportion of Gram-negative bacteria became 2-fold more frequent than S. pneumoniae in AOM in PCV7-vaccinated young children where PCV7 uptake was community-wide and supply was adequate.     

Anonymous oocyte donation: a follow-up analysis of donors' experiences

BACKGROUND: this study was conducted to assess oocyte donors' satisfaction after the procedure and to obtain information on base rates of various experiences associated with oocyte donation. METHODS: volunteer anonymous oocyte donors seen at a university-based IVF programs were identified (N = 54). The follow-up questionnaire asked donors to rate aspects of clinic interactions, medical procedures and experiences during and after the process, as well as expectations and level of fulfillment. RESULTS: ten individuals were lost to follow-up and 20 donors did not respond. The typical oocyte donor respondent (N = 24) was 26.5 years old, Caucasian, single with no children and had experienced some college education. Mean follow-up time was 21 months. Overall, 79% were satisfied or extremely satisfied with their experience, 42 % would be an oocyte donor again and 50% would recommend that a friend consider being an oocyte donor. Donors tolerated procedures well, but most did experience cramping and injection site pain. A significant proportion experienced anxiety and negative emotional experiences during the process. Expectations were fulfilled regarding helping another woman and sense of satisfaction, but most (87.5%) expressed the desire to know the outcome for the recipient. CONCLUSIONS: the data demonstrate that oocyte donation was a positive experience for the majority of women in the program, although emotional symptoms are normative.