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Biomedical subjects

J S Young

Publications and source records attributed to J S Young.

At least 19 recordsLinked to original sources
PubMed2007

The origin of the skewed amplitude distribution of spontaneous excitatory junction potentials in poorly coupled smooth muscle cells.

The skewed amplitude distribution of spontaneous excitatory junction potentials (sEJPs) in the mouse vas deferens and other electrically-coupled smooth muscle syncytia has been attributed to electrically-attenuated depolarizations resulting from the spontaneous release of quantized packets of ATP acting on remote smooth muscle cells (SMCs). However, in the present investigation surface SMCs of the mouse isolated vas deferens were poorly electrically coupled, with input resistances (176+/-18 MOmega, range: 141-221 MOmega, n=4) similar to those of dissociated cells. Furthermore, the amplitude of evoked EJPs was more variable in surface compared with deeper SMCs (F test, F=17.4, P<0.0001). Using simultaneous electrophysiology and confocal microscopy to investigate these poorly-coupled cells, it is shown that alpha-latrotoxin-stimulated sEJPs correlate, in timing (median delay ranged from -30 to -57 ms, P<0.05 in all experiments, n=5) and amplitude (Pearson product moment correlation, rho>0.55 and P<0.001), with purinergic neuroeffector Ca2+ transients (NCTs) in SMCs. The temporal correlation between sEJPs of widely ranging amplitude with NCTs in the impaled SMC demonstrates that all sEJPs could arise from neurotransmitter action on the impaled cell and that the skewed distribution of sEJPs can be explained by the variable effect of packets of ATP on a single SMC. The amplitude correlation of sEJPs and NCTs argues against the attenuation of electrical signal amplitude along the length of a single SMC. The skewed sEJP amplitude distribution arising from neurotransmitter release on single SMCs is consistent with a broad neurotransmitter packet size distribution at sympathetic neuroeffector junctions.

Adenosine Triphosphate↗
PubMed2006

Changes in TRPC channel expression during postnatal development of cerebellar neurons.

In the brain, classical (canonical) transient receptor potential (TRPC) channels are thought to be involved in different aspects of neuronal development. We investigated the developmental expression profile of TRPC channels in rat cerebellum during the first 6 weeks after birth. TRPC3 expression is significantly up-regulated whereas TRPC4 and TRPC6 expression are significantly down-regulated over this period of time. TRPC3 expression is mainly found on Purkinje cells and their dendrites, suggesting that the increase in TRPC3 expression reflects development of the dendritic tree of Purkinje cells. TRPC4 expression was restricted to granule and their precursor cells. TRPC6 expression is found on Purkinje cell bodies, on mature granule cells in the internal granule cell layer (but not their precursors) and interneurons in the molecular layer. The decrease in TRPC4 expression suggests that it is required for proper granule cell development whereas the decrease in TRPC6 expression is presumably correlated with interneuron development. Moreover, we demonstrate the presence of functional TRPC channels on Purkinje cell dendrites that are activated following stimulation of metabotropic glutamate receptors. Our results reveal cell-specific expression patterns for different TRPC proteins and suggest that developmental changes in TRPC protein expression may be required for proper postnatal cerebellar development.

Animals↗
PubMed2001

Nitrate-cancrinite precipitation on quartz sand in simulated Hanford tank solutions.

Caustic NaNO3 solutions containing dissolved Al were reacted with quartz sand at 89 degrees C to simulate possible reactions between leaked nuclear waste and primary subsurface minerals at the U.S. Department of Energy's Hanford site in Washington. Nitrate-cancrinite began to precipitate onto the quartz after 2-10 days, cementing the grains together. Estimates of the equilibrium constant for the precipitation reaction differ for solutions with 0.1 or 1.0 m OH- (log Keq = 30.4 +/- 0.8 and 36.2 +/- 0.6, respectively). The difference in solubility may be attributable to more perfect crystallinity (i.e., fewer stacking faults) in the higher-pH cancrinite structure. This is supported by electron micrographs of crystal morphology and measured rates of Na volatilization under an electron beam. Precipitate crystallinity may affect radionuclide mobility, because stacking faults in the cancrinite structure can diminish its zeolitic cation exchange properties. The precipitation rate near the onset of nucleation depends on the total Al and Si concentrations in solution. The evolution of experimental Si concentrations was modeled by considering the dependence of quartz dissolution rate on AI(OH)4- activity, cancrinite precipitation, and the reduction of reactive surface area of quartz due to coverage by cancrinite.

Aluminum↗
PubMed2001

Assessing aggregate and cumulative pesticide risks using a probabilistic model.

Determining aggregate and cumulative risks from exposures to pesticides presents a number of challenges. The analysis must capture the correlations in residues that occur from both additive and exclusionary processes in the use of pesticides. The analysis also requires a quantitative mechanism for evaluating risks associated with exposures to mixtures of pesticides. This paper presents an analysis of aggregate exposures and risks associated with exposures to a pesticide, Alpha, and the cumulative exposure to and risk from three pesticides, Alpha, Beta, and Gamma. The cumulative risks are evaluated by determining the systemic (absorbed) doses that result from inhalation, dermal, and oral exposures to the pesticides. A 'relative toxicity' model is used to evaluate cumulative risks. The assessment of cumulative exposure was performed using the LifeLine Version 1.0. The model simulates pesticide exposure using an individual-based approach where daily exposures are evaluated for each person, season, and location.

Administration, Cutaneous↗
PubMed2001

Relative effectiveness of kinetic analysis vs single point readings for classifying environmental samples based on community-level physiological profiles (CLPP).

The relative effectiveness of average-well-color-development-normalized single-point absorbance readings (AWCD) vs the kinetic parameters mu(m), lambda, A, and integral (AREA) of the modified Gompertz equation fit to the color development curve resulting from reduction of a redox sensitive dye from microbial respiration of 95 separate sole carbon sources in microplate wells was compared for a dilution series of rhizosphere samples from hydroponically grown wheat and potato ranging in inoculum densities of 1 x 10(4)-4 x 10(6) cells ml-1. Patterns generated with each parameter were analyzed using principal component analysis (PCA) and discriminant function analysis (DFA) to test relative resolving power. Samples of equivalent cell density (undiluted samples) were correctly classified by rhizosphere type for all parameters based on DFA analysis of the first five PC scores. Analysis of undiluted and 1:4 diluted samples resulted in misclassification of at least two of the wheat samples for all parameters except the AWCD normalized (0.50 abs. units) data, and analysis of undiluted, 1:4, and 1:16 diluted samples resulted in misclassification for all parameter types. Ordination of samples along the first principal component (PC) was correlated to inoculum density in analyses performed on all of the kinetic parameters, but no such influence was seen for AWCD-derived results. The carbon sources responsible for classification differed among the variable types with the exception of AREA and A, which were strongly correlated. These results indicate that the use of kinetic parameters for pattern analysis in CLPP may provide some additional information, but only if the influence of inoculum density is carefully considered.

Carbon↗
PubMed2001

The "July phenomenon" and the care of the severely injured patient: fact or fiction?

BACKGROUND: The "July phenomenon," a common belief in medical academia, refers to purported errors, inefficiency, and negative outcomes during the summertime transition of the house staff. We hypothesized that care in a trauma service is consistent throughout the year and that the July phenomenon therefore is a myth. METHODS: The records of adults admitted to a trauma service between July 1994 and September 1999 were evaluated. The care of and outcomes for patients admitted in July and August were compared with those of patients admitted in April and May. RESULTS: Nine hundred seventeen patients were evaluated over 5 years. Patients were well matched by the Injury Severity Score, the Glasgow Coma Score, by mechanism, and by survival probability. Patients admitted in the spring were significantly older, by a mean of 5.1 years. Length of stay and intensive care unit stay were similar. Emergency department times were similar, as were resuscitation times, infection rates, and hospital costs. The mortality of patients was similar between the 2 times. CONCLUSIONS: There was no evidence of an increase in negative outcomes early in the academic year compared with the end of the academic year. We believe that a systematic approach to the diagnosis, resuscitation, and treatment of trauma prevented a July phenomenon.

Academic Medical Centers↗
PubMed2001

Pilot study of electrical stimulation on median nerve in comatose severe brain injured patients: 3-month outcome.

PRIMARY OBJECTIVE: To determine if electrical stimulation (ES) benefits (waking time, 3-month outcomes) treated coma patients. RESEARCH DESIGN: Double blind randomized-controlled study. METHODS AND PROCEDURES: Ten coma patients; six treatment and four controls, using the 'Respond Select' by EMPI. EXPERIMENTAL INTERVENTIONS: Treatment group received radial nerve ES applied in 300 ms intermittent pulses at 40 Hz, 15-20m A 8 hours a day up to 14 days of coma; control group received sham stimulation. MAIN OUTCOMES AND RESULTS: ES group emerged from coma mean 2 days earlier than controls, although this result was not statistically significant. At 3 months post-injury, there was no group difference in Glasgow Outcome Scale, although the ES group had improved function over controls as measured by the FIM/FAM (mean of 114 and 64.5, respectively, n.s.). CONCLUSIONS: These data show an interesting trend, although statistical power was limited in this small pilot study, suggesting the need for a larger trial.

Adult↗
PubMed2001

Outpatient laparoscopic cholecystectomy: patient outcomes after implementation of a clinical pathway.

OBJECTIVE: To determine the success of a clinical pathway for outpatient laparoscopic cholecystectomy (LC) in an academic health center, and to assess the impact of pathway implementation on same-day discharge rates, safety, patient satisfaction, and resource utilization. SUMMARY BACKGROUND DATA: Laparoscopic cholecystectomy is reported to be safe for patients and acceptable as an outpatient procedure. Whether this experience can be translated to an academic health center or larger hospital is uncertain. Clinical pathways guide the care of specific patient populations with the goal of enhancing patient care while optimizing resource utilization. The effectiveness of these pathways in achieving their goals is not well studied. METHODS: During a 12-month period beginning April 1, 1999, all patients eligible for an elective LC (n = 177) participated in a clinical pathway developed to transition LC to an outpatient procedure. These were compared with all patients undergoing elective LC (n = 208) in the 15 months immediately before pathway implementation. Successful same-day discharges, reasons for postoperative admission, readmission rates, complications, deaths, and patient satisfaction were compared. Average length of stay and total hospital costs were calculated and compared. RESULTS: After pathway implementation, the proportion of same-day discharges increased significantly, from 21% to 72%. Unplanned postoperative admissions decreased as experience with the pathway increased. Patient characteristics, need for readmission, complications, and deaths were not different between the groups. Patients surveyed were highly satisfied with their care. Resource utilization declined, resulting in more available inpatient beds and substantial cost savings. CONCLUSIONS: Implementation of a clinical pathway for outpatient LC was successful, safe, and satisfying for patients. Converting LC to an outpatient procedure resulted in a significant reduction in medical resource use, including a decreased length of stay and total cost of care.

Academic Medical Centers↗
PubMed2001

Laparotomy potentiates cytokine release and impairs pulmonary function after hemorrhage and resuscitation in mice.

BACKGROUND: The two-hit theory has emerged as a mechanism to explain the development of organ failure after traumatic injury. We evaluated the effects of exploratory laparotomy (EL) as a second hit on mice after hemorrhage and resuscitation (H/R). Our hypothesis was that mice exposed to prior H/R would demonstrate more evidence of acute lung injury (ALI), as well as an augmented cytokine response, than mice exposed to H/R or EL alone. METHODS: Three groups of mice were examined. Mice undergoing H/R alone were labeled as the H/R group. Mice undergoing sham H/R (cannulation but no hemorrhage), followed 5 days later by EL, were labeled as the EL group; and mice undergoing H/R, followed 5 days later by an EL, were labeled as the H/R + EL, or two-hit, group. Respiratory function was determined by using whole-body plethysmography and lung gas diffusion. Serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assayed at 1 and 4 hours after the injury stimuli. RESULTS: Evaluation of the change in pulmonary function after 24 hours demonstrated that EL alone induces a significant decrease in pulmonary function, whereas two-hit mice did not exhibit a potentiated response. Alveolar function was significantly degraded in the EL group compared with all other groups (p < 0.0001). TNF-alpha did not change after any injury at any time. However, evaluation of IL-6 levels demonstrated a substantial increase after H/R, EL, and H/R + EL compared with baseline and at 1 hour. Comparison of the three groups at 4 hours did not demonstrate any differences in serum concentrations of IL-6. Histologic evaluation lungs demonstrated that the most severe lung injury was seen in the EL mice. CONCLUSION: It would appear that serum TNF-alpha has little impact on the pathogenesis of ALI after EL, whereas serum IL-6 may be more important. Exploratory laparotomy resulted in a significant change in pulmonary function. Contrary to our initial hypothesis, two-hit mice did not demonstrate more evidence of ALI and, in fact, demonstrated less lung injury than EL mice.

Animals↗
PubMed2000

Hemorrhage and resuscitation induce delayed inflammation and pulmonary dysfunction in mice.

BACKGROUND: It is well known that hemorrhagic shock induces inflammatory changes. Our objective was to study the histologic and biochemical changes in the lung and evaluate alterations in respiratory function after hemorrhage and resuscitation (H/R) in mice. METHODS: After 30 min of hemorrhagic shock, mice were resuscitated with shed blood to restore mean arterial blood pressure to baseline. A sham group was anesthetized and instrumented for 30 min, but did not undergo hemorrhage. Myeloperoxidase (MPO) levels were measured and histologic analysis was performed on lung tissue. Pulmonary function was evaluated using whole-body plethysmography (WBP) 1, 3, and 5 days postprocedure. Alveolar function was evaluated by measuring carbon monoxide uptake via gas chromatography 5 days after H/R. RESULTS: Five days after H/R, mice exposed to shock had significantly higher lung MPO levels and showed greater histologic evidence of lung injury. Airway resistance (Penh) in the sham mice was 0.91 +/- 0.06 versus 1.21 +/- 0.09 in the hemorrhage group (P < 0.01). Alveolar function was significantly decreased in the H/R group (70.8 +/- 3.6%) compared with shams (81.6 +/- 1.8%) (P < 0.05). CONCLUSIONS: Hemorrhage and resuscitation cause delayed biochemical, histologic, and physiologic changes in the lung. These were marked by increased lung MPO, increased neutrophils, and decreased alveolar function. The alterations of pulmonary function and structure were most severe 5 days after H/R.

Animals↗
PubMed2000

Sodium nitroprusside mitigates oleic acid-induced acute lung injury.

BACKGROUND: Acute lung injury (ALI) is associated with pulmonary hypertension, intrapulmonary shunting, and increased microvascular permeability, leading to altered oxygenation capacity. Oleic acid (OA) creates a significant ALI that physiologically mimics human adult respiratory distress syndrome (ARDS). It has been hypothesized that pulmonary vasodilatation may improve ALI. Studies in our laboratory using this model and nitric oxide (NO) have shown that NO inhalation is detrimental and worsens the effects of OA. We studied the effect of pretreatment with a potent vasodilator, sodium nitroprusside (SNP), on ALI induced by OA in an isolated lung model. We hypothesized that pretreatment with SNP will worsen pulmonary hypertension and oxygenation in OA-induced ALI, similar to the effects seen with inhaled NO in this model. METHODS: Rabbit heart lung blocks were isolated, flushed in vivo, harvested, immediately perfused with whole blood, and ventilated with 50% oxygen. Pulmonary artery pressure was determined every 15 seconds for 90 minutes of perfusion. Oxygenation was determined by blood gas analysis of pulmonary venous effluent at 0, 20, 40, 60, and 90 minutes after initiation of OA infusion. Four groups were studied: saline control (SC), oleic acid control (OAC; 20-minute infusion of 50% OA/ethanol into pulmonary circulation), SNP control (NPC; 10 microg/ kg/min SNP infused without subsequent OA infusion), and SNP treatment (NPRx); 10 microg/kg/min SNP infused before OA/ethanol. Pulmonary artery pressure (PAP), oxygenation (arterio-venous oxygen difference [AVO2], compliance (CPL), and wet/dry lung weight were determined. RESULTS: No significant differences were found between the NPRx group and SC. Pretreatment with SNP eliminated the detrimental effects of OA infusion. CONCLUSIONS: Contrary to our hypothesis, pretreatment with SNP eliminates the decrease in oxygenation and increase in lung weight, and ameliorates pulmonary hypertension in our isolated lung model of OA-induced ALI.

Animals↗
PubMed2000

Photopolymers in orthopedics: characterization of novel crosslinked polyanhydrides.

Novel, high modulus, degradable polymers were prepared from methacrylated anhydride monomers of tricarballylic acid (MTCA) and pyromellitylimidoalanine (MPMA-ala). Kinetic studies indicate that the time scale of photopolymerization of MTCA (< 30 s) is suitable for in vivo applications. Additionally, the tensile modulus of copolymers of these novel monomers with methacrylic anhydride (MA) ranged from 0.8 to 2.1 GPa, which lies between the modulus of trabecular and cortical bone. Degradation studies indicate that the copolymers of MTCA and MPMA-ala with MA are initially surface degrading, which is important to maintaining polymer strength through the degradation process. Monomers such as these that can be rapidly polymerized using ultraviolet or blue light into high modulus degradable materials have great potential in orthopedics.

Anhydrides↗
PubMed2000

Persistent occult hypoperfusion is associated with a significant increase in infection rate and mortality in major trauma patients.

OBJECTIVE: To investigate the hypothesis that occult hypoperfusion (OH) is associated with infectious episodes in major trauma patients. METHODS: Data were collected prospectively on all adult trauma patients admitted to the Surgical/Trauma Intensive Care Unit from November of 1996 to December of 1998. Treatment was managed by a single physician according to a defined resuscitation protocol directed at correcting OH (lactic acid [LA] > 2.4 mmol/L). RESULTS: Of a total of 381 consecutive patients, 118 never developed OH and 263 patients exhibited OH. Seventeen patients were excluded because their LA never corrected, and they all subsequently died. One hundred seventy-six infectious episodes occurred in 97 of the 364 patients remaining. The infection rate in patients with no elevation of LA was 13.6% (n = 118) compared with 12.7% (n = 110) in patients whose LA corrected by 12 hours, 40.5% (n = 79; p < 0.01 compared with all other groups) in patients whose LA corrected between 12 and 24 hours, and 65.9% (n = 57; p < 0.01 compared with all other groups) in patients who corrected after 24 hours. Among the patients with infections, there were 276 infection sites with 42% of infections involving the lung and 21% involving bacteremia. There was no difference in proportion of infections occurring at each site between groups. The mortality rate of patients who developed infections was 7.9% versus 1.9% in patients without infections (p < 0.05). Of the patients who developed infections, 69.8% versus 25.8% (p < 0.001) did not have their lactate levels normalized within 12 hours of emergency room admission. Logistic regression demonstrated that both the Injury Severity Score and OH > 12 hours were independently predictive of infection. CONCLUSION: A clear increase in infections occurred in patients with OH whose lactate levels did not correct by 12 hours, with an associated increase in length of stay, days in surgical/trauma intensive care unit, hospital charges, and mortality.

Acidosis, Lactic↗
PubMed2000

Occult hypoperfusion is associated with increased morbidity in patients undergoing early femur fracture fixation.

BACKGROUND: The presence of persistent occult hypoperfusion (OH) is associated with higher morbidity and mortality rates after trauma. Early femur fracture fixation in trauma patients with multiple injuries is associated with decreased morbidity and mortality. Association of OH and incidence of postoperative complications after intramedullary (IM) fixation in patients with femur fractures was investigated. METHODS: A retrospective study design was used. All patients with femur fractures admitted to the trauma service of a Level I trauma center between January 1, 1995, and August 1, 1998, who were older than 18 years of age and who had IM fracture fixation within 24 hours of admission and serum lactate determinations on admission and at proscribed intervals, were included in the study. Patients with lactic acid levels > or = 2.5 mmol/L were determined to have OH. No patients had clinical signs of shock (hypotension, tachycardia, decreased urine output) on transfer to the operating room. Complete resuscitation was defined as a lactic acid level < 2.5 mmol/L. Patients were divided into two groups based on presence/absence of OH determined from the lactic acid level immediately before surgery. The incidence of all postoperative organ complications was recorded, and complication rates were compared between groups. Total hospital costs were also compared. RESULTS: One hundred seventy-seven patients with femur fractures were admitted to the trauma service during this period. Seventy-nine patients met initial criteria for inclusion in the study. Further review excluded 32 patients. Occult hypoperfusion was present in 20 patients before early IM fixation (group 2). Twenty-seven patients were completely resuscitated before early IM fixation (group 1). Injury Severity Scores were similar in both groups. Group 2 had 35 complications in 20 patients, and group 1 had 11 complications in 27 patients. A significant difference was found in incidence of postoperative complications in group 1 (20%) versus group 2 (50%). Group 2 also had a significantly higher proportion of postoperative infections than group 1 (72% vs. 28%, respectively) and higher total hospital costs ($46,469 vs. $23,139). CONCLUSION: The presence of OH in trauma patients undergoing early IM fixation of a femur fracture is associated with a twofold higher incidence of postoperative complications. Clinical judgment, not surgical dogma, should guide the timing of IM fixation in these patients. Identifying and correcting OH through relatively simple resuscitative measures may be advantageous in reducing morbidity in the patient with multiple injuries.

Adult↗