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Biomedical subjects

Christopher J Hogan

Publications and source records attributed to Christopher J Hogan.

14 recordsLinked to original sources

Experimental investigation of nanoparticle dispersion by beads milling with centrifugal bead separation.

A new type of beads mill for dispersing nanoparticles into liquids has been developed. The bead mill utilizes centrifugation to separate beads from nanoparticle suspensions and allows for the use of small sized beads (i.e. 15-30 microm in diameter). The performance of the beads mill in dispersing a suspension of titanium dioxide nanoparticle with 15 nm primary particles was evaluated experimentally. Dynamic light scattering was used to measure titania particle size distributions over time during the milling process, and bead sizes in the 15-100 microm range were used. It was found that larger beads (50-100 microm) were not capable of fully dispersing nanoparticles, and particles reagglomerated after long milling times. Smaller beads (15-30 microm) were capable of dispersing nanoparticles, and a sharp peak around 15 nm in the titania size distribution was visible when smaller beads were used. Because nanoparticle collisions with smaller beads have lower impact energy, it was found by X-ray diffraction and transmission electron microscopy that changes in nanoparticle crystallinity and morphology are minimized when smaller beads are used. Furthermore, inductively-coupled plasma spectroscopy was used to determine the level of bead contamination in the nanoparticle suspension during milling, and it was found that smaller beads are less likely to fragment and contaminate nanoparticle suspensions. The new type of beads mill is capable of effectively dispersing nanoparticle suspensions and will be extremely useful in future nanoparticle research.

Microscopy, Electron, Transmission↗

Charge reduced electrospray size spectrometry of mega- and gigadalton complexes: whole viruses and virus fragments.

The ability to analyze and identify large macromolecular complexes whose molecular weight is beyond the analyzable range of mass spectrometry is of great interest. The size of such complexes makes them suitable for analysis via mobility size spectrometry. In this work, charge reduced electrospray size spectrometry was used for the analysis of bacteriophage viruses with total molecular masses ranging from 3.6 MDa up to the gigadalton range. The electrospray source used was operated in "cone jet" mode with a mean droplet diameter of 170.56 nm. Bacteriophage MS2 was found to have a mobility diameter of 24.13 +/- 0.06 nm and remain highly viable after the electrospray process. Larger bacteriophages T2 and T4 have lengths greater than the diameter of the electrospray jet and droplets; thus, they could not be completely enclosed and were found to fragment at the virus capsid head-tail noncovalent interface during either the jet formation or jet breakup process. No viable T2 or T4 virions were detectable after being electrosprayed. While the exact mechanism of fragmentation could not be determined, it is proposed here that macromolecular fragmentation at noncovalent interfaces occurs due to mechanically and electrically induced stresses during jet formation and jet breakup. Bacteriophage T4 capsid heads were found to be statistically significantly larger than bacteriophage T2 capsid heads, with a mean peak diameter of 88.32 +/- 1.02 nm for T4 and 87.03 +/- 0.18 nm for T2. While capsid head fragments were detectable, tail and tail-fiber fragments could not be detected by size spectrometric analysis. This is attributed to the fact that the contractile tails of bacteriophage T2 and T4 virions mechanically deform to a varying degree while confined within the smaller jet and droplets. Further evidence of contractile tail deformation during the electrospray process was found by measuring the size spectrum of bacteriophage lambda, which has a noncontractile tail. Bacteriophage lambda had two distinct peaks in its size spectrum, one corresponding to the capsid head and the other corresponding to the tail fragment. Size spectrometry was also used for rapid quantification of virus concentrations, thus demonstrating its full capabilities in the analysis of large macromolecular complexes.

Bacteriophages↗

High-pressure injection injuries to the upper extremity: a review of the literature.

OBJECTIVES: The purpose of this review was to identify the relative impact of injected material, location of injury, time to debridement, injection pressure, infection, and the use of adjuvant steroid medication upon the need for amputation after high-pressure injection injuries to the upper extremity. DATA SOURCES AND STUDY SELECTION: A Medline literature search extending from 1966 to December 2003 was performed, referencing the key words "high-pressure injection injury," "grease gun injury," "paint gun injury," "pressure gun injury," and "high-pressure injection." The results were limited to the English language and to reports involving human subjects. Each abstract was reviewed to confirm that the described injury had occurred in the upper extremity and that it had truly been a high-pressure injection. The reference pages from each of the papers were reviewed to identify additional reports of high-pressure injection injury. Manuscripts describing injuries resulting from hand held syringes or other low-pressure mechanisms were excluded. DATA EXTRACTION: All of the manuscripts were analyzed to identify the clinical outcome, age, hand dominance, site of injection, substance injected, injection pressure, elapsed time to wide debridement, use of steroids, and incidence of infection. These variables were subjected to a Pearson chi test to determine their impact upon the need for amputation. RESULTS: Four hundred thirty-five cases of high-pressure injection injury to the upper extremity were identified. The amputation rate after these injuries was 30%. The location of the injury and the material injected contributed significantly to the need for amputation. For injections of paint, paint thinner, gasoline, oil, or jet fuel (organic solvents), the amputation risk was lower if wide surgical debridement occurred within 6 hours of injury. Steroids did not impact the amputation rate or incidence of infection. The presence of infection did not affect the incidence of amputation. CONCLUSIONS: The risk of amputation after high-pressure injection injury to the upper extremity is highest with organic solvent injection into the fingers. Injections into the thumb or palm result in a much lower frequency of tissue loss. Emergent surgical debridement reduces the amputation risk after injections of organic solvents. From the available data, no conclusions could be reached regarding functional outcomes, other than amputation, after high-pressure injection injury.

Forearm Injuries↗

Posttraumatic proximal interphalangeal joint flexion contractures.

Normal motion of the proximal interphalangeal joint requires bony support, intact articular surfaces, unimpeded tendon gliding, and uncompromised integrity of the collateral ligaments and volar plate. Deficiency in any one of these structural requirements can lead to a loss of finger joint motion and decreased hand function. Once finger extension is lost, options include nonsurgical or surgical treatment. Nonsurgical treatment such as splinting or serial casting should be tried before attempting surgical intervention. When severe flexion deformity exists or the vascular status of the finger has been compromised, arthrodesis or amputation should be undertaken instead of procedures to regain motion. Surgical options for regaining motion include external fixators and open surgical release. Although they can lead to improved extension at the proximal interphalangeal joint, external fixators carry a risk of reduced finger flexion and pin site infection. Most clinical series of patients who have undergone surgical release document improvement in flexion contracture between 25 degrees to 30 degrees and a shift of the flexion/extension arc into a more functional range. Close follow-up after surgery is warranted, with frequent physical therapy and splinting.

Contracture↗

The utility of microvascular perfusion assessment in heart failure: a pilot study.

BACKGROUND: The evaluation of heart failure is routinely based on subjective patient symptoms and physician examination. We propose the noninvasive evaluation of microvascular and global perfusion can objectify heart failure severity and provide additional prognostic information. METHODS: A prospective, observational pilot study of patients previously stratified into New York Heart Association (NYHA) heart failure classes and who after a routine cardiology clinic evaluation were felt to be at their stable baseline state. Measurements included: thoracic impedance (Zo), hypothenar tissue hemoglobin oxygen saturation (StO2), and Zo-derived cardiac index (CI). To determine if adverse outcomes (hospitalization or death) occurred, patients or their families were contacted 6 months after enrollment and their charts reviewed. Monitor values between the NYHA classes were compared using analysis of variance. Values of those who later developed adverse outcomes were compared to patients who remained stable using a Student t-test (P < .05 considered significant). A Kaplan-Meier survival curve was used to describe the adverse outcome rate over time, and a Cox's proportional hazards model was used to relate perfusion values to adverse outcomes. RESULTS: There were no differences in CI (P = .08), Zo (P = .38), or StO2 (P = .14) found between NYHA classes (n = 46). After 6 months, 6 patients required hospitalization for heart failure and 1 died. This group had lower StO2 values compared with the stable group (P = .015). The time course of the adverse events was found not to be due to chance alone when evaluated using a Kaplan-Meier curve and the StO2 was significantly associated with time to adverse outcome (P < .05). CONCLUSIONS: Outpatient heart failure patients who later develop adverse outcomes have significantly lower StO2 values than those who remain stable. This suggests cardiac performance in stable heart failure patients may be better reflected at the microvascular level using measures such as StO2 as opposed to a global level using the physical exam or impedance cardiography. StO2 may serve as a predictor for future adverse events and as an adjunct to current evaluation techniques.

Adult↗

Reconstruction of the ulnar collateral ligament of the thumb metacarpophalangeal joint: a cadaver study.

PURPOSE: The purpose of this study was to compare the stiffness and strength of the native ulnar collateral ligament with 4 methods of static ulnar collateral ligament (UCL) reconstruction at the thumb metacarpophalangeal (MCP) joint. METHODS: Eleven fresh-frozen cadaver specimens were amputated at the carpometacarpal and interphalangeal joints and all soft tissues were removed except for the extensor pollicis brevis tendon, the proper and accessory collateral ligaments, and the volar plate. Each thumb metacarpal was potted in cement and the native UCL was loaded to failure at 30 degrees of MCP flexion. Ulnar collateral ligament reconstructions as described by Strandell, Osterman, Fairhurst, and a modification of the Glickel procedure then were performed. Each specimen was again loaded to failure and the moment at failure, stiffness, and angle at failure were calculated. RESULTS: None of the reconstructions duplicated the strength or stiffness of the native UCL. The modification of the Glickel procedure with interference knot fixation had a significantly higher moment at failure and was significantly stiffer than any of the other procedures. The differences in strength and stiffness between the Strandell, Osterman, and Fairhurst reconstructions were not statistically significant. There were no significant differences in angle at failure for any of the reconstructions. CONCLUSIONS: No static ligament reconstruction restores the normal stability characteristics of the thumb UCL. The anatomic reconstruction of the UCL with interference knot fixation of the tendon graft has far better strength and stiffness than any of the other reconstructions tested. These characteristics may allow for early motion at the MCP joint.

Cadaver↗

Three cast techniques for the treatment of extra-articular metacarpal fractures. Comparison of short-term outcomes and final fracture alignments.

BACKGROUND: Most extra-articular metacarpal fractures can be managed nonoperatively. While the conventional wisdom is that the metacarpophalangeal joint should be immobilized in a position of flexion, alternative methods for cast immobilization have been described. The purpose of this study was to retrospectively evaluate three methods of closed treatment; specifically, we investigated whether the position of immobilization of the metacarpophalangeal joint or the absence of a range of motion of the interphalangeal joints affected the short-term outcome or fracture alignment. METHODS: Between November 2000 and April 2004, extra-articular metacarpal fractures were immobilized for five weeks in one of three ways: with the metacarpophalangeal joints in flexion and full interphalangeal joint motion permitted (Group 1); with the metacarpophalangeal joints in extension and full interphalangeal joint motion permitted (Group 2); and with the metacarpophalangeal joints in flexion, the interphalangeal joints in extension, and no interphalangeal joint motion permitted (Group 3). Radiographs and the range of motion were evaluated at five weeks after application of the cast, and the range of motion and grip strength were assessed at nine weeks. RESULTS: Two hundred and sixty-three patients met the inclusion criteria. At five weeks, there was no difference among the treatment methods with regard to the range of motion or the maintenance of fracture reduction. At nine weeks, there was no significant difference with regard to the range of motion or grip strength. CONCLUSIONS: When immobilization was discontinued by five weeks, the position of the metacarpophalangeal joints and the absence or presence of interphalangeal joint motion during the immobilization had little effect on motion, grip strength, or fracture alignment. This finding contradicts the conventional teaching that the metacarpophalangeal joint must be immobilized in flexion to prevent long-term loss of joint extension. Patient comfort, ease of application, and the surgeon's familiarity with the technique should influence the choice of immobilization. LEVEL OF EVIDENCE: Therapeutic Level III.

Adolescent↗

Loxoscelism: old obstacles, new directions.

Loxosceles spiders have a worldwide distribution and are considered one of the most medically important groups of spiders. Envenomation (loxoscelism) can result in dermonecrosis and, less commonly, a systemic illness that can be fatal. The mechanism of venom action is multifactorial and incompletely understood. The characteristic dermonecrotic lesion results from the direct effects of the venom on the cellular and basal membrane components, as well as the extracellular matrix. The initial interaction between the venom and tissues causes complement activation, migration of polymorphic neutrophils, liberation of proteolytic enzymes, cytokine and chemokine release, platelet aggregation, and blood flow alterations that result in edema and ischemia, with development of necrosis. There is no definitive treatment for loxoscelism. However, animal model studies suggest the potential value of specific antivenom to decrease lesion size and limit systemic illness even when such administration is delayed.

Animals↗

Changes in radiocarpal loading characteristics after proximal row carpectomy.

PURPOSE: To document the changes in wrist loading that occur after proximal row carpectomy in a cadaver model. METHODS: The normal radioulnar carpal pressure distributions of 7 cadaver wrists were measured using super-low-pressure-sensitive film. Proximal row carpectomies were performed and the loading characteristics re-evaluated. RESULTS: In the lunate fossa the contact area increased 37%, the average contact pressure increased 57%, and the location of the contact moved radially 5.5 mm. With wrist motion between 40 degrees of extension and 20 degrees of flexion the volar/dorsal excursion of the lunate fossa contact point increased by 108%. CONCLUSIONS: Significant changes in radiocarpal loading occur after proximal row carpectomy. The increased radiocarpal excursion with wrist motion may explain the low incidence of radiocapitate arthritis in patients who have had proximal row carpectomy.

Biomechanical Phenomena↗

The development of diabetes in E2f1/E2f2 mutant mice reveals important roles for bone marrow-derived cells in preventing islet cell loss.

Our studies of mice deficient for the E2F1 and E2F2 transcription factors have revealed essential roles for these proteins in the cell cycle control of pancreatic exocrine cells and the regulation of pancreatic beta cell maintenance. Pancreatic exocrine cells in E2f1-/-E2f2 mutant mice become increasingly polyploid with age, coinciding with severe exocrine atrophy. Furthermore, mice deficient for both E2F1 and E2F2 develop nonautoimmune, insulin-dependent diabetes with high penetrance. Surprisingly, transplantation of wild-type bone marrow can prevent or rescue diabetes in E2f1-/-E2f2-/-mice. We hypothesize that exocrine degeneration results in a destructive environment for beta cells, which can be alleviated by restoration of the hematopoietic system that is also defective in E2f1-/-E2f2-/-mice The demonstration that beta cell maintenance under conditions of stress is influenced by bone marrow-derived cells may provide important insight into the design of therapies to boost islet mass and function in diabetic patients.

Animals↗

Defective gene expression, S phase progression, and maturation during hematopoiesis in E2F1/E2F2 mutant mice.

E2F plays critical roles in cell cycle progression by regulating the expression of genes involved in nucleotide synthesis, DNA replication, and cell cycle control. We show that the combined loss of E2F1 and E2F2 in mice leads to profound cell-autonomous defects in the hematopoietic development of multiple cell lineages. E2F2 mutant mice show erythroid maturation defects that are comparable with those observed in patients with megaloblastic anemia. Importantly, hematopoietic defects observed in E2F1/E2F2 double-knockout (DKO) mice appear to result from impeded S phase progression in hematopoietic progenitor cells. During DKO B-cell maturation, differentiation beyond the large pre-BII-cell stage is defective, presumably due to failed cell cycle exit, and the cells undergo apoptosis. However, apoptosis appears to be the consequence of failed maturation, not the cause. Despite the accumulation of hematopoietic progenitor cells in S phase, the combined loss of E2F1 and E2F2 results in significantly decreased expression and activities of several E2F target genes including cyclin A2. Our results indicate specific roles for E2F1 and E2F2 in the induction of E2F target genes, which contribute to efficient expansion and maturation of hematopoietic progenitor cells. Thus, E2F1 and E2F2 play essential and redundant roles in the proper coordination of cell cycle progression with differentiation which is necessary for efficient hematopoiesis.

Animals↗

Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice.

Over the past decade xenotransplantation systems have been used with increasing success to gain a better understanding of human cells that are able to initiate and maintain the hematopoietic system in vivo. The nonobese diabetic/severe combined immunodeficiency (SCID) mouse has been a particularly useful model. Human cells capable of hematopoietic repopulation in this mouse, termed SCID-repopulating cells, have been assumed to represent the most primitive elements of the hematopoietic system, responsible for long-term maintenance of hematopoiesis. However, we demonstrate that SCID-repopulating cells present in the CD34(+) cell fraction of cord blood can be segregated into subpopulations with distinct repopulation characteristics. CD34(+)/CD38(+) progenitors can repopulate recipients rapidly, but can only maintain the graft for 12 weeks or less and have no secondary repopulation potential. Conversely, the more primitive CD34(+)/CD38(-) subpopulation repopulates recipients more gradually, can maintain the graft for at least 20 weeks, and contains cells with serial repopulation potential throughout the engraftment period. Additionally, a much higher frequency of T cell precursors are found among SCID-repopulating cells in the CD34(+)/CD38(-) subpopulation. These findings demonstrate that cells with variable repopulation potential comprise the human CD34(+) population and that short- and long-term potential of human precursors can be evaluated in the mouse model.

ADP-ribosyl Cyclase↗

Transplantation of ex vivo expanded cord blood.

Umbilical cord blood (CB) from unrelated donors is increasingly used to restore hematopoiesis after myeloablative therapy. CB transplants are associated with higher rates of delayed and failed engraftment than are bone marrow transplants, particularly for adult patients. We studied the ex vivo expansion of CB in an attempt to improve time to engraftment and reduce the graft failure rate in the recipients. In this feasibility study, 37 patients (25 adults, 12 children) with hematologic malignancies (n = 34) or breast cancer (n = 3) received high-dose therapy followed by unrelated allogeneic CB transplantation. A fraction of each patient's CB allograft was CD34-selected and cultured ex vivo for 10 days prior to transplantation in defined media with stem cell factor, granulocyte colony-stimulating factor, and megakaryocyte growth and differentiation factor. The remainder of the CB graft was infused without further manipulation. Two sequential cohorts of patients were accrued to the study. The first cohort had 40% and the second cohort had 60% of their CB graft expanded. Patients received a median of 0.99 x 10(7) total nucleated cells (expanded plus unexpanded) per kilogram. The median time to engraftment of neutrophils was 28 days (range, 15-49 days) and of platelets was 106 days (range, 38-345 days). All evaluable patients who were followed for 28 days or longer achieved engraftment of neutrophils. Grade III/IV acute GVHD was documented in 40% and extensive chronic GVHD in 63% of patients. At a median follow-up of 30 months, 13 (35%) of 37 of patients survived. This study demonstrates that the CD34 selection and ex vivo expansion of CB prior to transplantation of CB is feasible. Additional accrual will be required to assess the clinical efficacy of expanded CB progenitors.

Adolescent↗

Treatment of complex regional pain syndrome of the lower extremity.

Complex regional pain syndrome, formerly known as reflex sympathetic dystrophy or causalgia, is a difficult therapeutic problem for the orthopaedic surgeon treating an affected lower extremity. Despite many divergent and often conflicting theories, the cause of the severe pain, alterations in regional blood flow, and edema is unknown. Interventions that have proved successful for treating similar conditions in the arm and hand frequently do not relieve pain similarly in the lower extremity. Common treatment regimens target individual components of this symptom complex, namely, sympathetic or afferent nerve hyperactivity, vasomotor instability, or regional osteoporosis. Despite widespread use of some of these treatments, few controlled clinical trials quantify their effectiveness. This challenging syndrome is best managed by a multidisciplinary team, including chronic pain management specialists, physical therapists, and orthopaedic surgeons.

Complex Regional Pain Syndromes↗