Definitive or exploratory periodontal experimentation: an overview of the literature

Definitive and exploratory randomized controlled trials (RCTs) have different goals as well as different design and analysis characteristics. The goal of definitive studies is to provide unequivocal evidence of a treatment's tangible benefit to the patient; a pre-trial-specified hypothesis is tested by use of a pre-trial-specified method. The goal of exploratory studies is to elucidate biological treatment mechanisms, to identify promising treatments, and to generate hypotheses for definitive studies: multiple hypotheses are evaluated to extract as much information from the data as possible. The purposes of this study were: (1) to survey selected design and analysis characteristics of randomized controlled periodontal trials published between 1988 and 1992 (n = 86), and (2) to classify trials as exploratory or definitive studies. The periodontal RCTs surveyed were typical of exploratory studies whose primary goal was to elucidate biological treatment mechanisms. Trial reports indicated the testing of multiple hypotheses (> or = 6 hypothesis tests in 70 of the 86 trials) on a variety of biological markers (86 out of 86 trials). The sample size (< or = 30 subjects in 67 out of 86 trials), duration (< or = 6 months in 65 out of 86 trials), and design and analysis characteristics (e.g., an absence of masking in 57 out of 86 trials) were also typical of exploratory studies which strive to obtain quick answers (short duration) at a low cost (small sample size; accept bias for increased efficiency and a lower cost). No definitive trials were identified. Promising, biologically active, treatments identified in exploratory trials should be evaluated in definitive studies where the primary goal is the procurement of unequivocal evidence of a treatment's tangible benefit to the patient. The costs and benefits of conducting definitive periodontal RCTs to provide such evidence should be investigated.     

One-stage sternal stenting with homograft bone after cardiac operation in pediatric patients

Low cardiac output after open heart operations in neonates and infants carries a high mortality. Delayed sternal closure may be life-saving but may prolong hospital stay and increase costs. To circumvent these issues, we shaped homograft bone and interposed it between the sternal edges to allow primary wound closure in 2 pediatric patients. Midterm results are satisfactory.     

Trabeculectomy function after cataract extraction

OBJECTIVE: To examine the effect of cataract extraction (CE) after trabeculectomy on intraocular pressure (IOP) control. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: A total of 115 consecutive patients who underwent extracapsular CE (N = 58) or phacoemulsification (N = 57) with intraocular lens (IOL) placement after trabeculectomy were studied. INTERVENTION: Cataract extraction with IOL after trabeculectomy was performed. MAIN OUTCOME MEASURES: Preoperative, intraoperative, and postoperative factors were evaluated for association with loss of IOP control requiring additional medications, bleb needling, or further glaucoma surgery, using Kaplan-Meier survival analysis and Cox multivariate proportional hazards survival regression. RESULTS: After mean postoperative follow-up of 21.1 +/- 14.3 months, additional glaucoma medication or needling of the filtering bleb to maintain IOP control was required in 35 eyes (30.4%) and was significantly associated with intraoperative iris manipulation and early postoperative peak IOP greater than 25 mmHg. Additional glaucoma surgery was eventually required in 11 eyes (9.6%) and was significantly associated with age of 50 years or younger, preoperative IOP greater than 10 mmHg, and early postoperative peak IOP greater than 25 mmHg. The cumulative proportion of patients who did not require reoperation for glaucoma was 93% and 90% at 1 and 2 years, respectively. The mean IOP at last visit had increased 1.6 mmHg above the pre-CE level and did not vary significantly after the first postoperative month. The median interval from CE to the addition of glaucoma medication or bleb needling was 1.6 months (within 3 months in 20 of 33 eyes) and that from nonsurgical intervention to further glaucoma surgery was 3.6 months (before the 7th postoperative month in 6 of 11 eyes). Of 19 eyes with hypotony (IOP < or = 6 mmHg) before CE, 11 eyes remained hypotonous after CE despite an increase in the mean IOP from 4.6 to 7.5 mmHg. CONCLUSIONS: When CE is performed after trabeculectomy, age of 50 years or younger, preoperative IOP greater than 10 mmHg, intraoperative iris manipulation, and early postoperative IOP greater than 25 mmHg are associated with worsened postoperative IOP control. Most bleb failures occur soon after CE. Resolution of pre-existing hypotony after CE is unpredictable.     

Detection of optic disc changes with Glaucoma-Scope probability maps

Before use of cardiovascular surgical techniques and procedures in humans, many experiments, e.g., hypothermic circulatory arrest and cardiopulmonary bypass using the heart-lung machine, have been performed in the dog. As a consequence experimental canine cardiovascular surgery is highly developed. This has not resulted in the routine performance of open heart surgery in veterinary medicine, probably because of the high costs. Cardiovascular surgery in the dog is generally limited to interventions not depending on hypothermic circulatory arrest or cardiopulmonary bypass. The clinical cardiovascular surgery in dogs can be divided into routine and more specialized interventions. The first category includes correction of peritoneopericardial diaphragmatic hernia, pericardial fenestration in dogs with pericardial effusion, treatment of persistent right aortic arch, and patent ductus closure. The specialized interventions include dilation of pulmonic and aortic stenoses and pacemaker implantation. The diagnosis and surgical treatment of such diseases is described. New developments in cardiovascular surgical treatment that can be expected include catheter techniques for occlusion of shunts and dilations using balloons, because the financial costs of these procedures are not prohibitive.     

Evidence for separate effects of U73122 on phospholipase C and calcium channels in human platelets

U73122 ((1-[6-(( 17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)exyl]-1H-p yrrole-2,5-dione)) is generally used as a selective inhibitor of phospholipase C (PLC) and the related rise in cytosolic Ca2+. Recently, by using hepatocytes, it was suggested that its action sites are different for PLC activation and increase in Ca2+ concentration. To verify whether U73122 has different sites for inhibiting PLC activation and calcium responses in human platelets, aggregation, Mn2+ influx, cytosolic Ca2+ increase and PLC activation were studied in response to thrombin and the synthetic agonist of the thromboxane receptor U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F2alpha). With both agonists, U73122 inhibited aggregation, Mn2+ influx and the enhancement of cytosolic calcium at concentrations of 2 microM or lower, while 10 microM was necessary to inhibit PLC activation. Our results suggested that U73122 is much more active in antagonizing Ca2+ channels, both the intracellular ones, which are activated by formation of inositol 1,4,5 P3 and those present on plasma membrane, than in reducing the activation of PLC.     

Molecular mechanisms of transforming growth factor-beta signaling

The present experiments examined the effects of posttraining intrahippocampal injections of the degradative enzyme-resistant methylcarbamyl analog of the bioactive phospholipid platelet-activating factor (mc-PAF) and the platelet-activating factor (PAF) receptor antagonists BN52021 and BN 50730 on memory in male Long-Evans rats trained in a hidden platform version of the Morris water maze. Following an eight-trial training session, rats received a unilateral intrahippocampal injection of mc-PAF (0.5, 1.0, or 2.0 microgram/0.5 microliter), lyso-PAF (1.0 microgram/0.5 microliter), the cell surface PAF receptor antagonist BN 52021 (0.25, 0.5, or 1.0 micrigram/0.5 microliter/, the intracellular PAF receptor antagonist BN 50730 (2.0, 5.0, or 10.0 microgram/0.5 microliter), or vehicle (50% DMSO in 0.9% saline; 0.5 microliter). On a retention test conducted 24 h after training, the escape latencies of rats administered mc-PAF (1.0 or 2.0 microgram) were significantly lower than those of the vehicle-injected controls, demonstrating a memory-enhancing effect of mc-PAF. Injections of lyso-PAF, a structurally similar metabolite of PAF, had no influence on memory, indicating that the memory-enhancing effect of mc-PAF is not caused by membrane perturbation by the phospholipid. The retention test escape latencies of rats administered BN 52021 (0.5 microgram) and BN 50730 (5.0 or 10 microgram) were significantly higher than those of the controls, indicating a memory impairing effect of both PAF antagonists. When mc-PAF, BN 52021, or BN 50730 was administered 2 h posttraining, no effect on retention was observed, indicating a time-dependent effect of the neuroactive substances on memory storage. The findings suggest a role for endogenous PAF in hippocampal-dependent memory processes.     

The evaluation of lyophilized polymer matrices for administering recombinant human bone morphogenetic protein-2

Novel unitary devices, prepared by lyophilization of viscous solutions of sodium carboxymethylcellulose (CMC) and methylcellulose (MC), were evaluated as sustained-release delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2). In vitro characterization of the unitary devices, which contained rhBMP-2-loaded poly (d,l lactide-co-glycolide) (PLGA) bioerodible particles (BEPs), was conducted over a 2-month period. Determinations included buffer uptake, mass and molecular weight loss and rhBMP-2 release from the unitary devices. CMC devices imbibed approximately 16 times their weight of buffer, while with MC, equilibrium uptake was approximately 6 times the dry weight of the devices. Overall mass loss percentages were approximately 55 and 35%, respectively, for CMC and MC devices. rhBMP-2 release from the devices was essentially a triphasic process: an initial phase during which "free" protein (rhBMP-2 present on the surface and within the pores of the PLGA BEPs) was released, a lag period during which no release was discerned, and then release of "bound" rhBMP-2 (protein adsorbed to the BEPs). The release of bound protein correlated with the mass loss of the polymer which began after 3 weeks. Release from the unitary devices was lower than that from the BEPs alone, due to a retardation effect of the gelled CMC/MC polymers. In rabbits in which full-thickness cranial bone defects were created, the implants were well tolerated and induced significant new bone growth during an 8-week evaluation period. The CMC devices appear to have induced bone earlier (at 2 weeks), but this did not affect eventual 8-week results. CMC devices without rhBMP-2 appeared to provide some bone conduction, in contrast to the blank MC devices.     

The preparation and characterization of porous carbons for hydrogen storage

Porous carbon materials with a cylindrical pore structure were prepared using ordered mesoporous silica as a removable template. To investigate the effect of the structural and textural properties of the products on hydrogen adsorption capacity, different carbon precursors and synthetic methods were used in their preparation. All of the carbon materials prepared showed a well-defined pore structure with a high surface area irrespective of the carbon precursor used in the preparation. Hydrogen adsorption tests indicated that the capacity of the materials for hydrogen adsorption was highly dependent on total surface area and the pore structure. Based on the N₂ sorption results, the total surface area was directly correlated with the hydrogen adsorption capacity.     

Interaction of humic acid salts with drug preparations

The use of natural polymers that form complexes with drug preparations is promising in the development of drugs of new generation. The possibility of complex formation on the interaction of humic acid salts with papaverine, benzohexonium, and B-group vitamins was demonstrated by calorimetric and potentiometric titration. These interactions can occur between the charged groups of a humic acid macroanion and the positively charged centers of drug molecules. The degree of binding of drug preparations by a natural polymer macromolecule can be determined by the charge and the structure of their molecules.