Biomedical subjects

John A Griswold

Publications and source records attributed to John A Griswold.

15 recordsLinked to original sources

PubMed2006

Toward the improvement of image-guided interventions for minimally invasive surgery: three factors that affect performance.

OBJECTIVES: The objectives were to measure the impact of specific features of imaging devices on tasks relevant to minimally invasive surgery (MIS) and to investigate cognitive and perceptual factors in such tasks. BACKGROUND: Although image-guided interventions used in MIS provide benefits for patients, they pose drawbacks for surgeons, including degraded depth perception and reduced field of view (FOV). It is important to identify design factors that affect performance. METHOD: In two navigation experiments, observers fed a borescope through an object until it reached a target. Task completion time and object shape judgments were measured. In a motion perception experiment, observers reported the direction of a line that moved behind an aperture. A motion illusion associated with reduced FOV was measured. RESULTS: Navigation through an object was faster when a preview of the object's exterior was provided. Judgments about the object's shape were more accurate with a preview (compared with none) and with active viewing (compared with passive viewing). The motion illusion decreased with a rectangular or rotating octagonal viewing aperture (compared with circular). CONCLUSIONS: Navigation performance may be enhanced when surgeons develop a mental model of the surgical environment, when surgeons (rather than assistants) control the camera, and when the shape of the image is designed to reduce visual illusions. APPLICATION: Unintentional contact between surgical tools and healthy tissues may be reduced during MIS when (a) visual aids permit surgeons to maintain a mental model of the surgical environment, (b) images are bound by noncircular apertures, and (c) surgeons manually control the camera.

Humans↗

PubMed2006

Isolated chyle duct injury in blunt trauma.

We present a case of a patient sustaining an isolated injury to the right main branch of the cysterna chyli due to a high-speed motor vehicle accident. A 42-year-old man presented after a high-speed collision. CT revealed a collection of hypodense fluid in the gallbladder fossa, which was the clue to take him to the OR. We proceeded to laparoscopic exploration, and based on the milky white color of the fluid, identified a chyle leak. In an open fashion, the retroperitoneum was explored and the injury was identified as disruption of the right lumbar branch entering the cisterna chyli, and this was ligated with silk ties. Chyle duct injury secondary to blunt trauma is a rare finding. The use of CT imaging can identify this injury. Laparoscopy can confirm the injury. Open ligation of the injured duct is the best treatment.

Adult↗

PubMed2005

Protamine sulfate reduces the susceptibility of thermally injured mice to Pseudomonas aeruginosa infection.

BACKGROUND: In this study, we investigated the ability of protamine sulfate, at sub-bactericidal dosing, to interfere with the in vivo virulence of Pseudomonas aeruginosa (PAO1) during burn wound infection. MATERIALS AND METHODS: The study was conducted using the murine model of thermal injury. Preliminary experiments determined a protocol for administration of protamine sulfate that had no in vivo bactericidal effects. Based on this, the effect of local injection of protamine sulfate on the in vivo virulence of PAO1 was assessed using these parameters: (1) the percent mortality among PAO1-infected, thermally injured mice; (2) the local proliferation and spread of PAO1 within the infected burned tissue; (3) the systemic spread of PAO1 within thermally injured/infected mice; and (4) the local cytokine response elicited by PAO1 thermally injured/infected mice. RESULTS: Injection of protamine sulfate into the thermally injured tissue of PAO1-infected/thermally injured mice significantly decreased the percent mortality and inhibited the systemic dissemination of PAO1 microorganisms to the liver and spleen. It had no effect, however, on the ability of the bacteria to proliferate and spread within the thermally injured tissue. It also was determined that protamine sulfate was ineffective at preventing mouse death at the dose administered if injected intramuscularly instead of directly into burned tissue. Protamine sulfate reduced the expression of the proinflammatory cytokines IL-6 and LIF in the injured/infected tissue. Heparan sulfate given in conjunction with protamine sulfate returned mortality levels to those of untreated mice. CONCLUSIONS: Our results suggest that: (1) local injection of sub-bactericidal doses of protamine sulfate reduces the virulence of P. aeruginosa; (2) this effect is due to interference with the systemic rather than local spread of P. aeruginosa; and (3) local application of protamine sulfate may have potential as supportive therapy for prevention of systemic P. aeruginosa infection in severely burned patients.

Animals↗

PubMed2005

A comparison of anterior and posterior approaches for the surgical treatment of pancreatic pseudocyst using laparoscopic cystogastrostomy.

BACKGROUND: Laparoscopic treatment of pancreatic pseudocyst allows for definitive drainage with faster recovery. Although many groups have reported their experience with an anterior approach, only a few have done so with a posterior approach. This paper compares the approaches, analyzing their potential benefits and pitfalls. MATERIALS AND METHODS: Seven females and one male underwent laparoscopic cystgastrostomy to treat pancreatic pseudocysts. The anterior approach was performed by opening the stomach anteriorly, localizing the pseudocyst ultrasonographically, draining the cyst with a needle and, via the same opening, using a stapler to form a cystgastrostomy. The posterior approach was performed by directly visualizing the posterior gastric wall and the pseudocyst, opening and draining the cyst with a needle, and using a stapler and running sutures for closure. RESULTS: All patients had gallstone pancreatitis. Cystgastrostomy via the anterior approach was used in 4 patients and via the posterior approach in 4 patients. Dense adhesions required one attempted posterior cystgastrostomy to be converted to an anterior approach. The mean age of the anterior group was 38 years (range, 18-58 years) and hospital stay was 6 days (range, 4-8 days): for the posterior group, mean age was 42 years (range, 40-44 years) and length of stay was 3 days (range, 2-4 days). CONCLUSION: Although both approaches had good results with no complications and short hospital stays, the posterior approach is safer, with a more precise cyst visualization and dissection that permits more tissue to be sent for histopathologic examination. Furthermore, the posterior approach?s larger anastomosis would seem to yield fewer occlusions, which are commonly seen with the anterior approach. The anterior approach is easier to learn, but it requires the opening of the anterior stomach and the use of ultrasound.

Adolescent↗

PubMed2005

Syndecan 1 shedding contributes to Pseudomonas aeruginosa sepsis.

The innate immune system is comprised of many components that function coordinately to prevent bacterial sepsis. However, thermal injury suppresses many of these factors, and the opportunistic pathogen Pseudomonas aeruginosa takes advantage of this condition, making it one of the leading causes of morbidity and mortality in the setting of thermal injury. P. aeruginosa is extremely efficient at colonizing burn wounds, spreading systemically, and causing sepsis, which often results in a systemic inflammatory response, multiple-organ failure, and death. The pathogenicity of P. aeruginosa is due to the arsenal of virulence factors produced by the pathogen and the immunocompromised state of the host. Syndecan 1 is a major heparan sulfate proteoglycan present on many host cells involved in thermal injury. Syndecan 1 anchored to the cell surface can be cleaved in a process termed ectodomain shedding. Syndecan 1 shedding results in the release of intact, soluble proteoglycan ectodomains that have diverse roles in innate immunity. Here we show for the first time that thermal injury results in shedding of syndecan 1 from host tissue. Our data show that syndecan 1 null mice are significantly less susceptible to P. aeruginosa infection than their wild-type counterparts, as demonstrated by (i) significantly lower mortality; (ii) absence of systemic spread of P. aeruginosa; and (iii) significant reductions in some proinflammatory cytokines. These results suggest that shed syndecan 1 plays an important role in the pathogenesis of P. aeruginosa infection of thermal injury and that syndecan 1-neutralizing agents may be effective supplements to current P. aeruginosa treatments.

Animals↗

PubMed2005

The association between Chance fractures and intra-abdominal injuries revisited: a multicenter review.

The association between Chance fractures and intra-abdominal injuries is reported to be as high as 89 per cent. Because prior studies were small series or case reports, we conducted a multicenter review to learn the true association between Chance fractures and intra-abdominal injuries as well as diagnostic trends. Trauma registry data, medical records, and radiology reports from 7 trauma centers were used to characterize 79 trauma patients with Chance fractures. Initial methods of abdominal assessment were computed tomography (CT) scan (79%), clinical examination (16%), and diagnostic peritoneal lavage (DPL) (5%). Twenty-six (33%) patients had intraabdominal injuries of which hollow viscus injuries predominated (22%). Twenty patients (25%) underwent laparotomy. The presence of an abdominal wall contusion and automobile restraint use were highly predictive of intra-abdominal injury and the need for laparotomy. The association between a Chance fracture and intra-abdominal injury is not as high as previously reported. CT scan has become the primary modality to assess the abdominal cavity of patients with Chance fractures, whereas the role of DPL has diminished.

Abdominal Injuries↗

PubMed2005

Treatment of isolated penetrating flank trauma.

We present our experience during the past 5 years with isolated penetrating flank trauma. We examined the evaluation process, treatment plan, length of stay, outcome, and complications of patients with isolated penetrating injuries to the flank. There were four patient groups: 1) laparotomy (n = 5); 2) local wound exploration (n = 1); 3) laparoscopy (n = 8); and 4) observation and triple contrast CT scan (n = 9). All patients were male. The mean length of stay was 15 days for group 1, one day for group 2, two days in group 3, and 1.5 days in group 4. Three patients had diaphragmatic injuries, which were repaired laparoscopically. One patient with local wound exploration re-presented with a diaphragm hernia. A negative triple contrast CT scan resulted in no subsequent intervention. There were no missed injuries or complications from CT scan + observation or from diagnostic laparoscopy. We believe that laparoscopy may emerge as a useful adjunct in the treatment of patients with flank trauma. We present an algorithm for the management of penetrating flank trauma.

Abdominal Injuries↗

PubMed2004

Cytokine induction by the P. aeruginosa quorum sensing system during thermal injury.

INTRODUCTION: Pseudomonas aeruginosa causes serious infections in severely burned patients due to its ability to produce numerous virulence factors. The production of most of these factors is controlled by the cell-to-cell communication system called quorum sensing (QS). We have recently shown that several proinflammatory and hematopoietic cytokines are produced during infection of the burn wound with P. aeruginosa strain PAO1. Most of these cytokines were not produced during either thermal injury or P. aeruginosa infection alone. MATERIALS AND METHODS AND RESULTS: In this study, we tried to determine if the QS systems play a role in the production of cytokines during P. aeruginosa infection of burn wounds. This was accomplished using the murine model of thermal injury, the P. aeruginosa strain PAO1 and its QS defective mutant (PAO-JP2), and the Multi-probe RNase protection assay. The mRNA for TNF-alpha, IL-6, TGF-beta, and G-CSF was detected within the skin of PAO1 infected/thermally injured mice. In contrast, the expression of these cytokines was not detected in PAO-JP2 infected/thermally injured mice. In comparison with the parent strain, PAO-JP2 was not defective either in its growth or in its spread within the thermally injured skin. A complementation experiment, using a plasmid that carries the intact QS gene, was conducted to confirm these results. In the presence of the complementing plasmid, PAO-JP2 produced the mRNA for the above cytokines. CONCLUSIONS: These results suggest that: 1) the QS system is involved in the induction of cytokine expression during P. aeruginosa infection of burn wounds; and 2) this effect may be caused by either a component of the QS system or a QS-controlled virulence factor.

Animals↗

PubMed2004

Heterogeneity in the effect of albumin and other resuscitation fluids on intracellular oxygen free radical production.

BACKGROUND: We hypothesized that by studying a suspension of a single cell type in various resuscitation fluids, we could compare their effects on parameters associated with cell death. METHODS: Jurkat cells were suspended in resuscitation fluids. Using flow cytometry, light scatter, phosphatidylserine translocation, propidium iodide uptake, and intracellular H2O2 production were measured. RESULTS: Buffer (pH, 7.4) and albumin added to Ringer's lactate inhibited the adverse changes, including intracellular oxygen free radical production. Oxygen free radical production was variable within the cell population and inhibited by albumin but not other colloids or crystalloids. This correlated well with the ability of albumin to enhance metabolic activity. A flavoprotein inhibitor blocked H2O2 production, suggesting that mitochondria are the source of the H2O2 and the variability. CONCLUSION: Oxygen free radical inhibition by albumin could explain both its beneficial and its harmful effects.

Albumins↗

PubMed2004

Analysis of quorum sensing-deficient clinical isolates of Pseudomonas aeruginosa.

Pseudomonas aeruginosa produces multiple virulence factors and causes different types of infections. Previous clinical studies identified P. aeruginosa isolates that lack individual virulence factors. However, the impact of losing several virulence factors simultaneously on the in vivo virulence of P. aeruginosa is not completely understood. The P. aeruginosa cell-to-cell communication system, or quorum sensing (QS), controls the production of several virulence factors. Animal studies using constructed QS mutants indicated that loss of the QS system severely impacts the virulence of P. aeruginosa. In this study, we tried to determine if deficiency within the QS system compromises the ability of P. aeruginosa to establish infections in humans. We have identified five QS-deficient strains through screening 200 isolates from patients with urinary tract, lower respiratory tract and wound infections. These strains lacked LasB and LasA activities and produced either no or very low levels of the autoinducers N-(3-oxododecanoyl) homoserine lactone and N-butyryl homoserine lactone. PCR analysis revealed that three isolates contained all four QS genes (lasI, lasR, rhlI and rhlR) while two isolates lacked both the lasR and rhlR genes. We also examined the five isolates for other virulence factors. The isolates produced variable levels of exotoxin A and, with one exception, were deficient in pyocyanin production. One isolate produced the type III secretion system (TTSS) effector proteins ExoS and ExoT, two isolates produced ExoT only and two isolates produced no TTSS proteins. The isolates produced weak to moderate biofilms on abiotic surfaces. Analysis of the patients' data revealed that two of the isolates represented a single strain that was isolated twice from the same patient within a 1 month interval. One QS-deficient clinical isolate (CI-1) lacked all tested virulence factors and produced a weak biofilm. These results suggest that naturally occurring QS-deficient strains of P. aeruginosa do occur and are capable of causing infections; and, that besides the known virulence factors, additional factors may contribute to the ability of certain strains such as CI-1 to establish an infection.

4-Butyrolactone↗

PubMed2004

Pseudomonas aeruginosa autoinducer enters and functions in mammalian cells.

Quorum sensing (QS) is a cell density-dependent signaling mechanism used by many bacteria to control gene expression. Several recent reports indicate that the signaling molecules (autoinducers) that mediate QS in Pseudomonas aeruginosa may also modulate gene expression in host cells; however, the mechanisms are largely unknown. Here we show that two P. aeruginosa autoinducers, N-3-oxododecanoyl-homoserine lactone and N-butyryl-homoserine lactone, can both enter eukaryotic cells and activate artificial chimeric transcription factors based on their cognate transcriptional activators, LasR and RhlR, respectively. The autoinducers promoted nuclear localization of chimeric proteins containing the full LasR or RhlR coding region, and the LasR-based proteins were capable of activating transcription of a LasR-dependent luciferase gene. Responsiveness to autoinducer required the N-terminal autoinducer-binding domains of LasR and RhlR. Truncated proteins consisting of only the C-terminal helix-turn-helix DNA-binding domains of both proteins attached to a nuclear localization signal efficiently translocated to the nucleus in the absence of autoinducer, and truncated LasR-based proteins functioned as constitutively active transcription factors. Chimeric LasR proteins were only activated by their cognate autoinducer ligand and not by N-butyryl-L-homoserine lactone. These data provide evidence that autoinducer molecules from human pathogens can enter mammalian cells and suggest that autoinducers may influence gene expression in host cells by interacting with and activating as-yet-unidentified endogenous proteins.

4-Butyrolactone↗

PubMed2002

Anti-ETA IgG neutralizes the effects of Pseudomonas aeruginosa exotoxin A.

BACKGROUND: The opportunistic pathogen Pseudomonas aeruginosa causes severe infections in immunocompromised hosts. Among P. aeruginosa-infected burn patients, mortality may reach as high as 50%. Due to their immunocompromised status, burn patients may benefit from passive immunotherapy against infection. As a potential multivalent immunoglobulin therapy, specific polyclonal antibodies against four P. aeruginosa virulence factors, including exotoxin A (ETA), were prepared. MATERIALS AND METHODS AND RESULTS: In this study, we analyzed the ability of ETA antibody (ETA-Ab) to neutralize the in vivo effects of ETA. Adult mice injected with purified ETA suffered 100% mortality. The cytosolic DNA of their hepatocytes was fragmented, indicating ETA induction of apoptosis. In addition, multiprobe RNase protection assays showed that ETA upregulates the expression of the genes for proinflammatory cytokines as well as apoptosis genes in the livers of ETA-injected mice. Treatment with ETA-Ab prior to ETA injection prevented mortality, ETA-induced hepatocyte DNA fragmentation, and upregulation of the cytokine and apoptosis-related genes. The role of ETA during P. aeruginosa infection of the burn wound was examined by determining the in vivo virulence of P. aeruginosa PA103 and its isogenic, ETA-deficient mutant PA103Omega::toxA using the thermally injured mouse model. The lethality, local spread, and systemic spread of PA103Omega::toxA were significantly reduced compared to PA103. CONCLUSION: These results suggest that (1) ETA induces apoptosis in hepatocytes, (2) specific cytokines are produced in response to ETA, (3) ETA-Ab neutralizes these effects, and (4) ETA contributes to the spread of P. aeruginosa during burn wound infection.

ADP Ribose Transferases↗

PubMed2002

Heuristic haptic texture for surgical simulations.

Generation of credible force feedback renderings adds the sense of touch crucial for the development of a realistic virtual surgical environment. However, a number of difficulties must be overcome before this can be achieved. One of the problems is the paucity of data on the in-vivo tissue compliance properties needed to generate acceptable output forces. Without this "haptic texture," the sense of touch component remains relatively primitive and unrealistic. Current research in the quantitative analysis of biomechanics of living tissue, including collection of in-vivo tissue compliance data using specialized sensors, has made tremendous progress. However, integration of all facets of biomechanical data in order to transfer them into haptic texture remains a very difficult problem. For this reason, we are attempting to create a library of heuristic haptic textures of anatomical structures. The library of heuristic haptic textures will capture the expert's sense of feel for selected anatomical structures and will be used to convey the sense of touch for surgical training simulations. Once the techniques for converting biomechanical data into haptic texture become more robust, this library can be used as a benchmark to verify theoretical computational models used for generating output forces in haptic devices.

Biomechanical Phenomena↗

PubMed2002

Volumetric virtual body structures.

Understanding the visuospatial aspects of anatomic structures is one of the most important goals of gross anatomy. Creation of realistic three-dimensional structures of human anatomy has thus been a goal of medical doctors and computer scientists. In this paper, we describe a PC/NT based system in which a user can easily select anatomical structures to be created, along with the chosen connected structures. The system then constructs a three-dimensional volumetric model, a virtual body structure, slice-by-slide. Once the virtual structure is assembled it is possible to "walk" through the volume with coronal, sagittal, and transverse views, or at any angle. The dynamic nature of the system is unique in that it allows for real time choice of volumetric body structures to be created, their rapid generation, and the ability to manipulate the resulting visualization.

Anatomy, Regional↗

PubMedDate not supplied

Role of free hemoglobin in 8-iso prostaglandin F2-alpha synthesis in chronic renal failure and its impact on CD163-Hb scavenger receptor and on coronary artery endothelium.

Free hemoglobin (Hb) during autoxidation increases 8-iso-prostaglandin-F2-alpha (8-isoprostane) formation in vitro. Because 8-isoprostane and plasma Hb are elevated in chronic renal failure (CRF), we evaluated the role of Hb in this isoprostane synthesis in vivo. By monitoring correlations between Hb, haptoglobin (Hp), CD163-Hb-scavenger receptor, and 8-isoprostane that is known to induce CD163 shedding, we examined whether 8-isoprostane blocks Hb catabolism in CRF. Additionally, by studying the effect of 8-isoprostane on human coronary artery endothelium (HCAEC) in vitro and its impact on intercellular adhesion molecule-1 (ICAM-1) in vivo, we tested its role in promotion of cardiovascular events in CRF. Twenty-two never-dialyzed CRF patients and 18 control patients were screened for renal function, plasma and urine 8-isoprostane, and plasma Hb, Hp, thiobarbituric-acid-reactants (TBARS), C-reactive-protein (CRP), and soluble (s) ICAM-1 and sCD163. HCAEC exposed to 8-isoprostane were tested for ICAM-1 and apoptosis. In CRF, urine 8-isoprostane was significantly elevated and correlated with free-Hb and TBARS. The increased free-Hb, Hp, and sCD163 in CRF suggested 8-isoprostane-mediated suppression of Hb catabolism through CD163 receptor shedding. 8-Isoprostane enhanced ICAM-1 expression and apoptosis in HCAEC. CRF patients showed elevated sICAM-1. In conclusion, free-Hb, via 8-isoprostane, paradoxically blocks its own catabolism. Free-Hb and/or 8-isoprostane may intensify cardiovascular events in CRF.

Albuminuria↗