Structure and compositional analysis of aluminum oxyhydroxide adsorbed pertussis vaccine.

PURPOSE: The goal of this study was to characterize an acellular pertussis vaccine (Tdap) containing genetically modified pertussis toxin (gdPT) and TLR agonist adsorbed to AlOOH adjuvant. METHODS: Several analytical tools including nanoDSF, FTIR, and LD were used to examine the conformation of novel gdPT and the composition of AlOOH adjuvant formulations adsorbed to pertussis vaccine. RESULTS: DLS particle size results were 9.3 nm and 320 nm for gdPT. For pertussis toxoid (PT), the DLS particle size results were larger at ~440 nm. After adsorption to AlOOH, which was driven by the protein antigen, the size distribution ranged from 3.5 to 22 µm. Two thermal transitions were observed by DSC for gdPT at 70 °C and 102 °C. The main thermal transition was confirmed to be at 72 °C by nanoDSF. All three vaccine formulations showed one thermal transition: Tdap-AlOOH had a thermal transition of 74.6 °C, Tdap-E6020-AlOOH had a thermal transition at 74.2 °C, and Tdap-CpG-AlOOH had a thermal transition at 77.0 °C. Analysis of pertussis toxin (PTx) and gdPT was also performed by FTIR spectroscopy for the purpose of comparison. The second derivative of the FTIR spectra showed an additional feature for PTx at 1685 cm-1 compared to gdPT. The antigen's amide I and II regions were largely unchanged after adsorption to AlOOH adjuvant as shown by FTIR, suggesting that there were no significant changes in the secondary structure. CONCLUSION: gdPT conformation was successfully characterized using an array of analytical methods. All three Tdap formulations have similar thermal stability as shown by nanoDSF, similar size distribution as shown by LD, and similar overall secondary structure as shown by FTIR. In-line particle sizing and IR can be used as in-process characterization tools to monitor consistency of adsorbed vaccine and to confirm product identity.

Identity, Structure and Compositional Analysis of Aluminum Phosphate Adsorbed Pediatric Quadrivalent and Pentavalent Vaccines.

PURPOSE: The goal of this study is to set an empirical baseline to map the structure-function relation of the antigens from the commercialized vaccine products. METHODS: To study the structural changes of protein antigens after adsorption several analytical tools including DLS, FTIR, Fluorescence, LD, and SEM have been used. RESULTS: All antigens have shown wide range of hydrodynamic diameter from 7 nm to 182 nm. Upon adjuvantation, the size distribution has become narrow, ranging from 10 to 12 µm, and has been driven by the derived diameter of aluminum phosphate (AlPO4) adjuvant. Further to examine size and morphology of adsorbed antigens, SEM has been used. The SEM results have demonstrated that the AlPO4 adjuvant suspension and adsorbed proteins consist of submicron particles that form a continuous porous surface. Diphtheria Toxoid (DT), Tetanus Toxoid (TT), and chemically-modified Filamentous Haemagglutinin (FHA) have shown surface adsorption to AlPO4. Secondary structure alpha-helix and beta-sheet content of DT and TT has increased after adsorption to AlPO4 adjuvant as shown by FTIR, whereas no significant changes were noted for other protein antigens. The results from Intrinsic Fluorescence have shown a structural rearrangement in DT and TT, consistent with the FTIR results. Multivalent vaccine product identity has been determined by FTIR as unique fingerprint spectrum. CONCLUSION: The globular proteins such as DT and TT have shown changes in secondary structure upon adsorption to AlPO4, whereas fibrillar protein FHA has not been affected by adsorption. FTIR can be used as a lean technique to confirm product identity at different manufacturing sites.

Interstitial tissue pressure associated with dental injections: a clinical study.

OBJECTIVES: The purpose was to measure the interstitial fluid pressure generated from tissue resistance during administration of local anesthetic solution at 4 anatomic locations within the oral cavity and to determine whether differences in soft tissue density affect interstitial fluid pressure when anesthetic solution is administered at a fixed flow rate. METHOD AND MATERIALS: A computer-controlled local anesthetic delivery device (CompuFlo, Milestone Scientific) that records and stores pressure data during a subcutaneous injection was used. Subjects consisted of adult patients seeking routine dental care that required local anesthesia. A total of 200 injections were administered and fluid pressure readings recorded. Injections were divided into 4 groups of 50: group 1--intraligamentary injections (PDL); group 2--palatal injection, anterior middle superior alveolar nerve block; group 3--supraperiosteal buccal infiltrations, and group 4--inferior alveolar nerve blocks. For all injections 1 cartridge (1.8 mL) of lidocaine containing 1:100,000 concentration of epinephrine was administered at a fixed flow rate of 0.005 mL/sec. RESULTS: One-way analysis of variance (ANOVA) revealed that the data were statistically significant (P < .001), with corresponding mean values as follows: group 1, 293.98 psi; group 2, 68.16 psi; group 3, 11.50 psi, and group 4, 9.76 psi (F-ratio of 2371.933). Groups 1 and 2 were different from all other groups; groups 3 and 4 were not statistically different from each other. CONCLUSION: Interstitial resistance to fluid pressure can be measured during administration of 4 different local anesthetic injections used in dentistry. Based on fluid pressure and tissue resistance characteristics, a soft tissue density classification was defined.

Maxillary nerve block--a new approach using a computer-controlled anesthetic delivery system for maxillary sinus elevation procedure. A prospective study.

OBJECTIVE: The maxillary (or second division) nerve block is an effective method of achieving profound anesthesia of a hemimaxilla. This block can be used for procedures involving the maxillary sinus, including the maxillary sinus elevation procedure. The purpose of this study was to evaluate a computer-controlled anesthetic delivery system (Wand) for maxillary nerve block injection to attain maxillary sinus anesthesia for sinus floor elevation procedure. METHOD AND MATERIALS: The study population consisted of 61 healthy adult patients, ranging in age from 40 to 72 years (mean 45 years), who received 76 maxillary nerve blocks (17 having both right and left maxillary blocks) by means of the Wand system via the greater palatine nerve approach, for sinus floor elevation procedure. Two patients (3%) were excluded from the study due to the inability to negotiate the greater palatine foramen. For each block, two cartridges of 2% lidocaine hydrochloride with adrenaline (1:100,000) were administered, using a 27-gauge--long needle. After ensuring the anesthetized areas (waiting time 2.5 minutes), the sinus elevation procedure was performed. Parameters recorded were the success or failure of anesthesia, positive (blood) aspiration, bony obstructions in the greater palatine canal, and complications. RESULTS: The use of this technique increased the ability to more easily locate the greater palatine foramen. A local infiltration (at the incisor region) was needed in 13 (17%) of the blocks, and seven (9.2%) sites required an extra infraorbital block injection in addition to the maxillary nerve block. One block had a positive aspiration. There were no bony obstructions demonstrated in the canal interfering with the injection, and no complications were recorded. CONCLUSION: The Wand appears to offer a number of advantages over the hand-held syringe when the greater palatine block technique for the maxillary nerve block is used. It is suggested that, when indicated, and with the required knowledge and respect for the associated anatomy, this technique should be considered with greater ease and more confidence.

Deceleration energy and change in velocity on impact: key factors in fatal versus potentially survivable motor vehicle crash (mvc) aortic injuries (AI): the role of associated injuries as determinants of outcome.

OBJECTIVE: To examine the difference in force mechanisms between fatal and potentially survivable MVC aortic injuries (AI) compared to non-AI severe thoracic injuries (ST). METHODS: Of 324 autopsied MVC driver or front seat passenger fatalities (1997-2000), there were 43 fatal AI (36 scene deaths, 7 hospital deaths) and 5 additional AI survivors. RESULTS: Of the 48 AI, there was only a 42% survival for those reaching hospital alive. 80% of AI survivors had isthmus lesions and all had no or minimal brain injury (GCS >= 13), no cardiac injury and only 20% ribs 1-4 fx or shock; of AI non-survivors reaching hospital alive, 67% had GCS <= 12, 50% cardiac injury, 83% ribs 1-4 fx and 83% shock; AI scene deaths had 78% severe brain injury, 56% cardiac injury, 69% lung injury and 78% ribs 1-4 fx. Quantifying forces in AI scene mortality: the Instantaneous Velocity on Impact of the subject vehicle (delta V1) and the Impact Energy Dissipated (IE) on the subject vehicle (V1) in joules demonstrated a linear regression in fatal car MVC AIs: Energy dissipated (joules) = -56.65 x (delta V1)(2) + 15972 x delta V1 - 454661, r(2) = 0.83. However, for 27 patients with non-AI but severe thoracic (ST) injury (AIS>=3), the relationship of IE to delta V1 had a linear regression of Energy dissipated (joules) = -5.0787 x (delta V1)(2) + 4282.1 x delta V1 - 57182 1, r(2) = 0.84, with the slope difference between the regression for AI scene deaths and that of ST and AI survivors being significant (p<0.05). Based on these relationships, a Critical Zone limited by MVC Impact Energy level of 336000 joules and a delta V1 of 64 kph appears to be the limit of potential survivability in MVCs producing aortic injuries. All AI above these thresholds died. In contrast, ST had greater use of seatbelts (AI 10% vs all ST 60%) and airbags (AI 50% vs all ST 72%), and an 83% survival. CONCLUSION: The data suggest different mechanisms of force delivery and injury patterns in fatal vs potentially survivable AI, and vs ST MVCs. They suggest that an approach to improving vehicle safety measures for AI may involve better safety devices and mechanisms for reducing that fraction of Impact Energy dissipated on V1 for a given delta V1 which is focused on the upper portion of the subject's thoracic cage between the levels of ribs1-8.

The National Pharmaceutical Stockpile Program: an overview and perspective for the Pacific Islands.

The National Pharmaceutical Stockpile (NSP) program was created as a national resource and is an essential response component of the Centers for Disease Control and Prevention's (CDC's) larger Bioterrorism Preparedness and Response Initiative. The role of the NPS program is to maintain a national repository of life-saving pharmaceuticals and medical supplies that can be delivered to communities in the event of a biological or chemical terrorist attack or an event involving mass casualties. The NPS is to be a re-supply and backup mechanism to state and local emergency response. Before a decision is made to deploy NPS assets, CDC will collaborate with local, state, and federal officials to determine the nature and extent of the event. Once the federal decision to deploy NPS assets is made, CDC's NPS program will arrange for delivery of assets to reach the affected area within 12 hours.