Challenges With the Jaw in a Day Technique.

Purpose: The Jaw in a Day (JIAD) procedure allows for complete primary reconstruction of bone and teeth during the same operation as tumor resection. We reviewed 12 cases, the largest published case series of the JIAD procedure, and discussed both the prosthodontic and surgical considerations.

Materials And Methods: A multi-institutional retrospective chart review was completed to identify patients undergoing the JIAD procedure.

Fibular Reconstruction of the Maxilla and Mandible with Immediate Implant-Supported Prosthetic Rehabilitation: Jaw in a Day.

The fibula free flap is a workhorse flap used to reconstruct ablative, osseous defects in the upper and lower jaws. Traditionally, the fibula free flap is inset into the defect freehand; dental implants are placed secondarily; and final prosthetic rehabilitation often occurs more than 1 year after ablative surgery. Virtual surgical planning and rapid prototyping of cutting guides and guide stents for head and neck reconstruction have facilitated improved accuracy in fibular transfer.

Pharmacokinetics and tolerability of the new second-generation nonnucleoside reverse- transcriptase inhibitor KM-023 in healthy subjects.

Background: KM-023 is a new second-generation nonnucleoside reverse-transcriptase inhibitor that is under development for the treatment of human immunodeficiency virus (HIV) type 1 infection.

Objective: This study determined KM-023 tolerability and pharmacokinetic characteristics in healthy subjects.

Materials And Methods: A randomized, double-blinded, placebo-controlled, dose-escalation study was conducted in 80 healthy South Korean male volunteers.

Burkholdines from Burkholderia ambifaria: antifungal agents and possible virulence factors.

Burkholdines are cyclic lipopeptides with unusual antifungal potency, making them promising leads as a new class of antifungal agents. However, a recent report using knockout mutagenesis indicates that these and related compounds, such as occidiofungins, xylocandins, and cepacidines, may also be synonymous with the long-known hemolytic virulence factors found in diverse Burkholderia isolates. Because of their possible roles in causing Burkholderia infections or curing fungal infections, it is important to fully define their structures and biological activities using pure compounds.

Burkholdines 1097 and 1229, potent antifungal peptides from Burkholderia ambifaria 2.2N.

Potent antifungal cyclic lipopeptides, burkholdines (Bk), were isolated from a culture of Burkholderia ambifaria 2.2N. Bk-1229 (1) and Bk-1097 (2) are octapeptides comprised of nonproteinogenic amino acids, including beta-hydroxytyrosine, beta-hydroxyasparagine, and a new fatty acyl amino acid.

Heterobiaryl human immunodeficiency virus entry inhibitors.

Previously disclosed HIV (human immunodeficiency virus) attachment inhibitors, exemplified by BMS 806 (formally BMS378806, 1), are characterized by a substituted indole or azaindole ring linked to a benzoylpiperazine via a ketoamide or sulfonamide group. In the present report, we describe the discovery of a novel series of potent HIV entry inhibitors in which the indole or azaindole ring of previous inhibitors is replaced by a heterobiaryl group. Several of these analogues exhibited IC(50) values of less than 5 nM in a pseudotyped antiviral assay, and compound 13k was demonstrated to exhibit potency and selectivity similar to those of 1 against a panel of clinical viral isolates.

Design and synthesis of human immunodeficiency virus entry inhibitors: sulfonamide as an isostere for the alpha-ketoamide group.

The crystal structures of many tertiary alpha-ketoamides reveal an orthogonal arrangement of the two carbonyl groups. Based on the hypothesis that the alpha-ketoamide HIV attachment inhibitor BMS 806 (formally BMS378806, 26) might bind to its gp120 target via a similar conformation, we designed and synthesized a series of analogs in which the ketoamide group is replaced by an isosteric sulfonamide group. The most potent of these analogs, 14i, demonstrated antiviral potency comparable to 26 in the M33 pseudotyped antiviral assay.

Second virial coefficient determination of a therapeutic peptide by self-interaction chromatography.

Self-interaction of macromolecules has been shown to play an important role in a number of physical processes, including crystallization, solubility, viscosity, and aggregation. Peptide self-interaction is not as well studied as for larger proteins, but should play an equally important role. The osmotic second virial coefficient, B, can be used to quantify peptide and protein self-interaction.

Development of HIV fusion inhibitors.

In the past 25 years, the worldwide AIDS epidemic has grown such that roughly 38 million people were estimated to be living with the disease worldwide at the end of 2003. The introduction of antiretroviral-based therapies, beginning in 1987, has enabled many to live with HIV as a chronic, rather than terminal, disease. However, the emergence and spread of drug-resistant strains highlights the continued need for new therapies with novel modes of action.

The PICNIC approach to regional care networks.

PICNIC is a pioneering project to develop an architecture for next generation regional healthcare networks. This paper gives an overview of the project and some of the reasoning behind the interrelated technical and business choices.

Large-scale manufacture of peptide therapeutics by chemical synthesis.

The large-scale commercial production of a 36-amino-acid peptide by chemical synthesis has been demonstrated in the development of enfuvirtide (T-20 or Fuzeon), a first-in-class membrane fusion inhibitor for the treatment of HIV. The rationale behind route selection and the scale-up of the process used to manufacture enfuvirtide are discussed.