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Two in vitro studies assessed the potential of daptomycin (Cubicin), a newly marketed antibiotic, to affect the cytochrome P450 (CYP450) isoforms in primary cultured human hepatocytes. Both induction and inhibition of isoforms 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 were evaluated. The highest concentrations of daptomycin used in both the induction and inhibition assays were approximately eight-fold higher than the peak total drug concentration (50-60 microg/mL), or the peak free drug concentration (estimated 5-6 microg/mL), in plasma at the clinical dose regimen of 4 mg/kg qd. Results in primary human hepatocytes indicate that daptomycin, at concentrations up to 400 microg total drug/mL, demonstrated no biologically significant induction of any of the CYP450 isoform activities in comparison with the negative control or known inducers. At daptomycin concentrations up to 40 microg free drug/mL, no biologically significant inhibition of the activities of these CYP450 isoforms was observed as compared with known inhibitors. The human hepatocyte results demonstrate that daptomycin has no effects on hepatic CYP450-mediated drug metabolism and, therefore, suggest that daptomycin is unlikely to show potential for pharmacokinetic interactions with concomitantly administered drugs that are metabolized by CYP450 isoforms.

Background: The concept of immediate loading of dental implants has been researched in animal and man. High predictability with titanium screw implants can be expected under certain circumstances. Delayed loading, which is empirically based, may offer roadblocks to success in the complex case. Micromotion under a denture, retention of compromised teeth, and the necessity for multiple implant surgeries complicate the situation. The present study was undertaken to demonstrate whether in partial and fully edentulous patients, titanium screw implants may be installed and loaded within 72 hours., Methods: The study included 27 jaws (23 mandibles and 4 maxillas) in patients who refused to wear a denture or were told of the possibility of immediately loading their implants. Criteria similar to delayed loading was utilized. The patient had to have adequate volume and density for a minimum of 4 (10 mm) implants in the mandible and 6 in the maxilla, in addition to other requirements. After a thorough presurgical evaluation by the restorative dentist, a template and heat-cured/metal-reinforced provisional were fabricated. Following fixture installation, either the fixed provisional was placed or an impression was taken, and the provisional was seated within 72 hours. Once the temporary was placed, it remained until osseointegration was complete., Results: Success rates similar to those in delayed loaded cases may be expected (95%). Fewer sandblasted/acid-etched titanium screws were lost than machined titanium screws. All patients went on to completion of their original prosthetic prescription., Conclusions: Patients who are partially or fully edentulous may predictably be restored with fixed implant prostheses immediately upon fixture placement if certain parameters are met.

The alarming increase in the incidence of Gram-positive infections, including those caused by resistant bacteria, has sparked renewed interest in novel antibiotics. One such agent is daptomycin, a novel lipopeptide antibiotic with proven bactericidal activity in vitro against all clinically relevant Gram-positive bacteria. These include resistant pathogens, such as vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide intermediately susceptible Staphylococcus aureus (GISA), coagulase-negative staphylococci (CNS) and penicillin-resistant Streptococcus pneumoniae (PRSP), for which there are very few therapeutic alternatives. Daptomycin provides rapid, concentration-dependent killing and a relatively prolonged concentration-dependent post-antibiotic effect in vitro. Spontaneous acquisition of resistance to daptomycin occurs rarely. Daptomycin exhibits linear pharmacokinetics, minimal accumulation with once-daily dosing, and low plasma clearance and volume of distribution. Phase II clinical trials indicate that daptomycin at doses of 2 mg/kg q24 h and 3 mg/kg q12 h is efficacious against skin and soft tissue infections and bacteremia, respectively. In addition, results in endocarditis suggested potential efficacy with higher doses. On the basis of clinical trials to date, it appears that daptomycin has an excellent safety profile, with the incidence and nature of serious adverse events comparable to those observed with conventional therapy. Adverse events associated with other classes of antimicrobials (nephrotoxicity, local irritation, ototoxicity, hypersensitivity, and gastrointestinal effects) were uncommon with daptomycin. Minimal skeletal muscle toxicity was seen at only the highest dose tested (4 mg/kg q12 h), predicted by elevations in serum creatinine phosphokinase, and readily reversible upon discontinuation of treatment. There were no signs of toxicity in cardiac or smooth muscle. Phase II and III clinical trials are underway to evaluate daptomycin for the treatment of Gram-positive bacteremia and complicated skin and soft tissue infections, respectively. Daptomycin holds promise as a rapidly acting and highly effective antibiotic for Gram-positive infections.

We report on a de novo constitutional rearrangement involving the long arm of chromosome 7 in a second trimester fetus with the karyotype of 46,XX, inv dup del (7)(pter-q36::q36-q21.2:) pat. Both a large duplication (q21.2-q36) and a small deletion (within q36) were confirmed by FISH studies. DNA analysis on the family showed that the abnormal chromosome was derived from a single paternal homolog. A mechanism is proposed in light of this finding. The phenotype at autopsy was consistent with reported cases of similar duplications in chromosome 7 in that hydrocephalus, a depressed nasal bridge, low set ears, microretrognathia and a short neck were present.

The predictability of branemark implants has been well documented. High success rates in the maxilla and mandible in fully and partially edentulous patients can be expected. A host of factors may be attributed to the etiology of fixture loss. However, the quality of bone stands out as the single greatest determinant in fixture loss. Types I, II, and III bone offer good strength. Type IV bone has a thin cortex and poor medullary strength with low trabecular density. Ninety percent of 1,054 implants placed were in Types I, II, and III bone. Only 3% of these fixtures were lost; of the 10% of the fixtures placed in Type IV bone, 35% failed. Presurgical determination of Type IV bone may be one method to decrease implant failure.

Four patients, ages 14-17, who demonstrated characteristics of juvenile periodontitis, underwent antibiotic and surgical therapy to control microbial etiologic factors. No occlusal equilibration or bone grafting techniques were employed. Subsequent to treatment, all four patients demonstrated decreased pocket depths and mobility on teeth associated with vertical osseous defects. Osseous repair was evident on postoperative radiographs. Reentry procedures, on one patient, confirmed that osseous repair had occurred in 2- to 3-wall, 3-wall, hemi-circumferential and furcal defects. If infection and inflammation are controlled, it appears that the potential for osseous repair in juvenile periodontitis patients is greater than has been thought.

Practitioners often have delayed responses to the problems involved with complications. This was especially true in the first years of endosseous implantology. Eventually, hindsight becomes insight. This maturation is a necessary and normal process. It can be enhanced by careful documentation of the procedures and process of care such as numerous clinical photographs during treatment, and treating patients with several members of the team present (example: the prosthodontist scrubbing with the surgeon on very early or complex cases.) It is possible to improve the quality of care. Postsurgical case management conferences are invaluable. It is also important that each team member not only see his or her own role, but also the responsibility to see that the entire treatment is adequately done. Each individual must have a sense of responsibility for the management of the entire case. It is important that the practitioner not take a defensive posture regarding his or her own treatment. Reformatted computerized tomography (CT) including radiographic bone density measurement (Houncefield units) can be very valuable in determining bone quality and anatomy and will provide insight into where and where not to place fixtures. In the event of a complication, it is important that it be recognized early that it not be "covered up" and that the damage be contained and prevented from causing a secondary complication and further morbidity to the patient.

Detection of high blood pressure can be a major public health service contribution by the dental profession. The pioneer program at Fairleigh Dickinson University, in conjunction with the Bergen County Health Department and the Bergen County Dental Society, is encouraging dentists to participate in the National High Blood Pressure Program. Participants are urged to measure the blood pressures of all their adolescent and adult patients and to refer those with sustained elevated readings to their physicians, preferably by the arrangements of appointments.