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R S Clark

Publications and source records attributed to R S Clark.

At least 55 records · Page 3Linked to original sources
PubMed1997

The relationship between brain temperature and neutrophil accumulation after traumatic brain injury in rats.

Mild hypothermia reduces secondary damage after traumatic brain injury (TBI) in rodent models; however, the mechanisms involved in this beneficial effect remain unclear. We previously reported that TBI induces the upregulation of adhesion molecules and infiltration of neutrophils (PMN) in brain. Since PMN accumulation may be associated with the development of hyperemia and blood-brain barrier injury, we hypothesized that hypothermia would reduce acute inflammation after TBI in rats. To test this hypothesis, rats were anesthetized and subjected to TBI by controlled cortical impact to left parietal cortex. Brain temperature was controlled at 32 degrees C, 37 degrees C, or 39 degrees C (n = 8 per group) for 4 h after TBI, then rats were sacrificed and brain were harvested. Immunohistochemistries were performed on brain sections using antibodies that recognize the adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1), and PMN. PMN were also quantified using a myeloperoxidase (MPO) assay. PMN accumulation in injured brain was decreased in rats maintained at 32 degrees C vs 39 degrees C (4-fold by immunohistochemistry and 8-fold by MPO, p < 0.05). E-selectin was induced after TBI, but not attenuated by hypothermia. ICAM-1 was not up-regulated at this early time after TBI. Based on these preliminary data, we conclude that mild hypothermia reduces PMN accumulation in injured brain during the initial 4 h after TBI, without decreasing adhesion molecule expression.

Animals↗
PubMed1997

A longitudinal clinical assessment of spark erosion technology in implant-retained overdenture prostheses: a preliminary report.

STATEMENT OF PROBLEM: As adapted for the dental profession, spark erosion technology permits precise machining of retentive metal overdenture frameworks for use in implant prosthetics. PURPOSE: The resultant prostheses are retentive and provide a number of benefits offered by both conventional overdenture and fixed prosthetic designs. MATERIAL AND METHODS: Preliminary data collected from an ongoing 5-year clinical trial were reviewed to qualitatively assess the clinical results obtained from 25 spark eroded implant-retained overdenture prostheses placed in 24 subjects. RESULTS: Throughout an evaluation period of 13.33 months (range 4 to 19 months), subject responses measured by questionnaire were uniformly good. Few complications were encountered and were limited to resin denture base/tooth fractures or retentive component failures that were easily repaired. CONCLUSION: Overdenture prostheses retained by spark eroded milled frameworks offer an acceptable treatment alternative for patients undergoing dental implant therapy.

Dental Alloys↗
PubMed1997

Early neuropathologic effects of mild or moderate hypoxemia after controlled cortical impact injury in rats.

Hypoxemia has detrimental effects after traumatic brain injury (TBI) in both experimental models and humans. The purpose of this study was to determine the effect of mild or moderate hypoxemia on early histologic and motor functional outcome after controlled cortical impact (CCI) in rats. Anesthetized rats underwent CCI and were randomized to receive mild (FiO2 = 13%, n = 6), moderate (FiO2 = 11%, n = 9), or no (FiO2 = 33%, n = 6) hypoxemia for 30 min after trauma. Sham-operated rats without hypoxemia (n = 7) were used as controls. Motor function (beam balance latency) was assessed on days 0-5. Rats were killed 7 days after injury and their brains removed for assessment of survival of hippocampal neurons and contusion volume. Terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling (TUNEL) was performed on brain sections from rats killed at 6, 24, and 72 h after CCI and moderate hypoxemia to assess DNA fragmentation in situ. Mild and moderate hypoxemia augmented motor function deficits after CCI in a dose-dependent manner. Moderate hypoxemia after CCI reduced 7-day survival of CA3 neurons but not CA1 neurons vs. sham (55 [46-86] vs. 99 [95-130], p < 0.05, and 79 [63-86] vs. 101 [81-123], NS, respectively; % uninjured hemisphere, median [range]). The addition of mild or moderate hypoxemia did not increase contusion volume. TUNEL-positive neurons were seen in ipsilateral cortex and dentate gyrus at 6, 24, and 72 h after trauma, and in ipsilateral CA3 hippocampal neurons and thalamus at 24 and 72 h. Moderate hypoxemia augments CA3 neuronal death and early motor functional deficits after CCI. The pattern of DNA fragmentation in selectively vulnerable neurons suggests that apoptosis may play a role in the delayed neuronal death seen after TBI.

Analysis of Variance↗
PubMed1997

Interleukin-6 and interleukin-10 in cerebrospinal fluid after severe traumatic brain injury in children.

Cytokines may play an important role in the pathophysiology of traumatic brain injury (TBI) in children. Interleukin-6 (IL-6) is a proinflammatory cyotkine that plays a role in regenerative processes within the central nervous system (CNS), whereas interleukin-10 (IL-10) is an antiinflammatory cytokine. Both have been measured in serum and cerebrospinal fluid (CSF) as an index of the degree of inflammation in diseases, including sepsis and meningitis. We hypothesized that both IL-6 and IL-10 would be increased in the CSF of children after severe TBI. Fifteen children who sustained severe TBI (Glascow Coma Score [GCS] < or = 7) were studied. Standard neurointensive care was provided. Ventricular CSF collected the first 3 days after TBI was analyzed for IL-6 and IL-10 concentrations by ELISA. Controls were 20 children who were evaluated for meningitis with diagnostic lumbar puncture subsequently found to have no CSF pleocytosis and negative cultures. IL-6 was increased in children after TBI versus controls on all days studied (day 1, 3158.2 +/- 621.8 pg/ml; day 2, 1111.6 +/- 337.0 pg/ml; day 3, 826.7 +/- 193.5 pg/ml vs. 20.6 +/- 5.8 pg/ml, p < 0.0001, Mann-Whitney Rank Sum). IL-10 was increased in children after TBI vs controls on all days studied (day 1, 47.2 +/- 12.9 pg/ml; day 2, 21.0 +/- 6.7 pg/ml; day 3, 15.5 +/- 5.9 pg/ml vs. 8.9 +/- 7.5 pg/ml, p < 0.01). Increased IL-10 concentrations were independently associated with age < 4 years and mortality (p = 0.004 and 0.04, respectively, multivariate linear model). This study demonstrates that IL-6 is increased after TBI in children to levels similar to those reported in adults and is the first to show that IL-10 is increased in CSF of humans after TBI. These data suggest that there may be an age-dependent production of IL-10 after TBI in children.

Adolescent↗
PubMed1997

The effect of brain temperature on acute inflammation after traumatic brain injury in rats.

The effect of varying brain temperature on neutrophil accumulation in brain and the expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1) on cerebrovascular endothelium after controlled cortical impact (CCI) was studied in rats. Sprague Dawley rats were anesthetized and subjected to CCI to the left parietal cortex. Ten minutes after CCI, brain temperature was modulated and maintained at 32 degrees C, 37 degrees C, or 39 degrees C (n = 8 per group) for 4 h. Rats were then decapitated and immunohistochemistry on brain sections was performed using monoclonal antibodies (MoAb) that recognize neutrophils (RP-3), ICAM-1 (TM-8, Athena Neurosciences), or MoAb that react with E-selectin (La-Roche). Each of these markers was quantified in 100 x fields. Neutrophil accumulation was also quantified with myeloperoxidase (MPO) assay. Absolute neutrophil count (ANC) was measured in blood samples before and 1 h and 4 h after CCI. Neutrophil accumulation in injured brain was decreased in rats maintained at 32 degrees C vs 39 degrees C (4-fold difference as assessed by immunohistochemistry, p < 0.05; 8-fold difference as assessed by MPO assay, p < 0.05). Peripheral blood ANC was not affected by temperature. E-selectin was induced on cerebrovascular endothelium after CCI (p < 0.05), but was only decreased modestly at 32 degrees C versus 39 degrees C (p = 0.11). ICAM-1 was not upregulated on cerebrovascular endothelium at this early time following CCI. Neutrophil accumulation is directly dependent on brain temperature during the initial 4 h after CCI. This appears to be mediated by mechanisms other than effects of temperature on E-selectin or ICAM-1 expression or systemic ANC.

Animals↗
PubMed1997

Cerebrospinal fluid adenosine concentration and uncoupling of cerebral blood flow and oxidative metabolism after severe head injury in humans.

OBJECTIVE: Uncoupling of cerebral blood flow (CBF) and oxidative metabolism is observed after severe head injury in comatose patients; however, the mechanism(s) involved remain undefined. Adenosine can produce cerebral vasodilation and reduce neuronal activity and is a possible mediator of uncoupling. We hypothesized that cerebrospinal fluid (CSF) adenosine concentrations would be increased during uncoupling of CBF and oxidative metabolism, defined as a narrow arterio-jugular venous oxygen difference [D(a-v)O2 4 vol%] after head injury. METHODS: Adenosine concentrations were measured using fluorescent-based high-pressure liquid chromatography in 67 CSF samples obtained from 13 comatose (Glasgow Coma Scale score 7) adult patients who sustained a severe closed head injury. At the time each sample was obtained, CBF was measured by the xenon-133 method, and blood samples were obtained for determination of D(a-v)O2. RESULTS: CSF adenosine concentration was negatively associated with D(a-v)O2 (P < 0.05, generalized multivariate linear regression model). In addition, CSF adenosine concentration was increased when D(a-v)O2 was 4 versus > 4 vol% (38.5 [3.2-306.3] versus 14.0 [2.7-795.5] nmol/L, respectively, median [range]; P < 0.025) and in patients who died versus survivors (40.1 [6.9-306.3] versus 12.9 [2.7-795.5] nmol/L, respectively, median [range]; P < 0.001). CONCLUSION: The association between increased CSF adenosine concentration and a reduction in global cross-brain extraction of oxygen supports a regulatory role for adenosine in the complex balance between CBF and oxidative and nonoxidative metabolism severe head injury in humans.

Adenosine↗
PubMed1997

Validation of microsatellite markers for routine horse parentage testing.

A parallel testing of 4803 routine Quarter Horse parentage cases, using 15 loci of blood group and protein polymorphisms (blood typing) and 11 loci of dinucleotide repeat microsatellites (DNA typing), validated DNA markers for horse pedigree verification. For the 26 loci, taken together, the theoretical effectiveness of detecting incorrect parentage was 99.999%, making it extremely unlikely that false parentage would fail to be recognized. The tests identified incorrect parentage assignment for 95 offspring (2% of cases). Despite fewer loci, DNA typing was as effective as blood typing and, in parentage exclusion cases, provided more systems to substantiate the genetic incompatibility. Five offspring presented potential genetic incompatibilities with their parents in only a single microsatellite system, but the parentage exclusions could not be confirmed with discordant results at additional loci. Two of these five incompatibilities could be explained as consequences of a null allele and three as fragment size increases or decreases (putative mutations). Provided that an exclusion assignment was based on at least two systems of genetic incompatibility, such rare genetic events did not lead to false exclusions. Notwithstanding the near 100% effectiveness estimations for either typing panel alone to identify incorrect parentage, this validation test showed an actual effectiveness of 97.3% for blood typing and 98.2% for DNA typing. The DNA-based test, however, may feasibly achieve higher efficacy than reported here by adding selected systems to the parentage test panel.

Alleles↗
PubMed1996

Antibodies against Mac-1 attenuate neutrophil accumulation after traumatic brain injury in rats.

Neutrophils (PMN) accumulate and are associated with cerebrovascular disturbances after experimental traumatic or ischemic brain injury, and meningitis. We hypothesized that posttraumatic PMN accumulation in brain is mediated by the PMN adhesion receptor Mac-1 (CD11b/CD18). Anesthetized rats were randomized to receive 2 mg/kg intravenously of murine monoclonal antibody to rat Mac-1 (1-B6) or anti-Mac-1 F(ab)2' [1-B6F(ab)2'] fragment (Repligen Corp., Cambridge, MA). Control rats were treated with isotype matched control antibody. Rats were subjected to percussive trauma to the right parietal cortex 30 min after treatment. Rats were killed 24 h posttrauma, and PMN accumulation was assessed by myeloperoxidase (MPO) activity. The presence of 1-B6F(ab)2' bound to PMN in brain after trauma was assessed by immunohistochemistry. Complete blood cell counts were obtained before treatment and 24 h after trauma. Brain MPO activity was reduced by 43% in the 1-B6-treated rats vs. controls (0.31 +/- 0.09 vs 0.55 +/- 0.10 U/g, n = 6/group, p = 0.013) and by 34% in the 1-B6F(ab)2'-treated rats vs. controls (0.43 +/- 0.10 vs. 0.65 +/- 0.09 U/g, n = 6/group, p = 0.006). Systemic neutropenia developed in the 1-B6-treated rats (absolute PMN count decreased by 73% vs. baseline) but not in rats treated with 1-B6F(ab)2' (absolute PMN count increased by 26 and 25% vs. baseline in treated and controls, respectively). Immunohistochemical staining showed 1-B6F(ab)2' on the surface of infiltrated PMN 24 h after trauma. Mac-1 mediates posttraumatic PMN accumulation in brain. This accumulation can be attenuated by 34%, without reducing circulating PMN, using an anti-Mac-1 F(ab)2' fragment; however, some PMN coated with 1-B6F(ab)2' still infiltrate into traumatized tissue. These results are similar to those reported in models of cerebral ischemia, and suggest the participation of multiple PMN adhesion pathways after ischemic and traumatic brain injury.

Animals↗
PubMed1996

Cerebrospinal fluid and plasma nitrite and nitrate concentrations after head injury in humans.

OBJECTIVES: To measure cerebrospinal fluid and plasma nitrite and nitrate concentrations as indicators of nitric oxide production in adults after severe closed-head injury. To determine if there is an association between cerebrospinal fluid and plasma nitrite and nitrate concentrations, and cerebral blood flow, arterio-jugular oxygen content difference, injury severity, and outcome after severe closed-head injury. DESIGN: A prospective, clinical study. SETTING: Multidisciplinary intensive care unit. PATIENTS: Fifteen comatose (Glasgow Coma Scale score of < or = 7) adult patients with severe closed-head injury were studied during the prospective, randomized evaluation of the effect of moderate hypothermia (32 degrees C for 24 hrs) on neurologic outcome after closed-head injury. Seven patients were in the hypothermic group and eight patients were in the normothermic treatment group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were examined sequentially, every 12 hrs for 2 days. Intraventricular cerebrospinal fluid was assayed for nitrite and nitrate concentrations. Cerebral blood flow was measured by the 133xenon intravenous method. Simultaneous blood samples were obtained for measurements of arterio-jugular oxygen content difference and plasma nitrite and nitrate concentrations. Cerebral metabolic rate for oxygen was calculated. Cerebrospinal fluid nitrite and nitrate concentrations were highest at 30 to 42 hrs vs. 6 to 18, 18 to 30, and 42 to 54 hrs (26.4 +/- 3.3 vs. 17.3 +/- 2.1, 20.0 +/- 2.2, and 18.8 +/- 2.4 microM, respectively, p < .05). There was no difference over time in plasma nitrite and nitrate concentrations. Cerebral blood flow was increased and arterio-jugular oxygen content difference was reduced at 18 to 30, 30 to 42, and 42 to 54 hrs vs. 6 to 18 hrs (p < .05). At 30 to 42 hrs, cerebrospinal fluid nitrite and nitrate concentrations were 80% higher in patients who died vs. survivors (36.4 +/- 3.2 vs. 20.2 +/- 3.6, p < .05). Using a generalized, multivariate, linear regression model, both plasma nitrite and nitrate concentrations and injury Severity Score independently predicted cerebrospinal fluid nitrite and nitrate concentrations (p < .00001 and p = .0053, respectively). Cerebral blood flow and arterio-jugular oxygen content difference were not associated with cerebrospinal fluid or plasma nitrite and nitrate concentrations using this model. Cerebrospinal fluid nitrite and nitrate concentrations were increased over time in hypothermic vs. normothermic patients. But, where this difference occurred could not be determined by multiple comparisons (p = .03). The hypothermic patients had lower admission Glasgow Coma Scale scores than normothermic patients (p = .04) and tended to have higher injury Severity Scores (p = .09). CONCLUSIONS: Increases in cerebrospinal fluid nitrite and nitrate concentrations peaked at 30 to 42 hrs after severe closed-head injury. This increase in cerebrospinal fluid nitrite and nitrate concentrations was greater in nonsurvivors. Also, cerebrospinal fluid and plasma nitrite and nitrate concentrations were associated with injury Severity Score, suggesting that increased nitric oxide production in the brain is associated with injury severity and death. Hypothermia did not prevent the increase in cerebrospinal fluid nitrite and nitrate concentrations. Further study is required to determine the source of this increase in cerebrospinal fluid nitrite and nitrate concentrations and to further define the relationship to outcome and the effect of hypothermia on this process.

Adult↗
PubMed1996

Mild posttraumatic hypothermia reduces mortality after severe controlled cortical impact in rats.

The effect of posttraumatic hypothermia (brain temperature controlled at 32 degrees C for 4 h) on mortality after severe controlled cortical impact (CCI) was studied in rats. Four posttraumatic brain temperatures were compared: 37 degrees C (n = 10), 36 degrees C (n = 4), 32 degrees C (n = 10), and uncontrolled (UC; n = 6). Rats were anesthetized and subjected to severe CCI (4.0-m/s velocity, 3.0-mm depth) to the exposed left parietal cortex. At 10 min posttrauma the rats were cooled or maintained at their target brain temperature, using external cooling or warming. Brain temperature in the UC group was recorded but not regulated, and rectal temperature was maintained at 37 +/- 0.5 degrees C. After 4 h, rats were rewarmed over a 1-h period to 37 degrees C, extubated, and observed for 24 h. In the 37 and 36 degree C groups, 24-h mortality was 50% (37 degrees C = 5/10, 36 degrees C = 2/4). In the 32 degree C group, 24-h mortality was 10% (1/10). In the UC group, brain temperature was 35.4 +/- 0.6 degrees C during the 4-h treatment period and 24-h mortality was 0% (0/6). Mortality was higher in groups with brain temperatures > or = 36 degrees C versus those with brain temperatures < 36 degrees C (50 vs. 6%, respectively; p < 0.05). Additionally, electroencephalograms (EEG) were recorded in subsets of each temperature group and the percentage of time that the EEG was suppressed (isoelectric) was determined. Percentage of EEG suppression was greater in the hypothermic (32 degrees C, n = 6; UC, n = 4) groups than in the normothermic (36 degrees C, n = 3; 37 degrees C, n = 6) groups (23.3 +/- 14.3 vs. 1.2 +/- 3.1%, respectively; p < 0.05). Posttraumatic hypothermia suppressed EEG during treatment and reduced mortality after severe CCI. The threshold for this protective effect appears to be a brain temperature < 36 degrees C. Thus, even mild hypothermia may be beneficial after severe brain trauma.

Animals↗
PubMed1996

Inducible nitric oxide synthase expression in cerebrovascular smooth muscle and neutrophils after traumatic brain injury in immature rats.

The inflammatory response after traumatic brain injury (TBI) includes cytokine production, leukocyte infiltration, and microglial activation. Production of nitric oxide by inducible nitric oxide synthase (iNOS) occurs during acute inflammation outside of the CNS and in models of cerebral ischemia, and therefore may contribute to the inflammatory response after TBI. The purpose of this study was to localize and define the time course of iNOS expression after TBI in the immature rat. Immature Wistar rats (age 3.5-4.5 wk) were anesthetized and subjected to percussive trauma to the right parietal cortex. Nontraumatized rats were used as controls (n = 7). At 2, 24, 48, or 168 h (n = 3/group) posttrauma rats were killed by perfusion fixation. Brains were removed, frozen, sectioned, immunostained with antibodies against iNOS and glial fibrillary acidic protein (GFAP, a marker specific for astrocytes), and imaged using fluorescent detection systems. There was no detectable expression of iNOS in control brains. At 2h, minimal cerebrovascular iNOS expression was seen in the peritrauma area. At 24 and 48 h, there was marked peritrauma cerebrovascular iNOS expression that appeared to be restricted to vascular smooth muscle cells and infiltrated leukocytes. Further dual-immunolabeling showed that the leukocytes expressing iNOS were predominantly neutrophils. At 168 h, iNOS expression was no longer detectable. iNOS was not detectable in GFAP-positive cells. The prominent expression of iNOS protein after TBI in cerebrovascular smooth muscle cells and infiltrated neutrophils suggests that iNOS may play a role in cerebrovascular disturbances and secondary brain injury after trauma.

Animals↗
PubMed1995

Severe controlled cortical impact in rats: assessment of cerebral edema, blood flow, and contusion volume.

Controlled cortical impact (CCI) is a contemporary model of experimental cerebral contusion. We examined the cerebrovascular and neuropathologic effects of a severe CCI in rats. The utility of magnetic resonance imaging (MRI) for the assessment of contusion volume after severe CCI was also established. Severe CCI (3.0 mm depth, 4 m/sec velocity) to the left (L) parietal cortex was produced in anesthetized (isoflurane/N2O/O2), intubated, and mechanically ventilated male Sprague-Dawley rats (n = 58). Physiologic parameters were controlled. The time course of alterations in edema [L-R% brain water (% BW) in 3-mm coronal sections through injured and contralateral hemispheres, wet-dry weight] was evaluated at 2 h, 24 h, 48 h, and 7 days posttrauma. Local cerebral blood flow (ICBF, measured in 8 structures in each hemisphere by autoradiography) was evaluated at 2 h, 24 h, and 7 days. Contusion volume (measured by histology and image analysis) was assessed at 14 days and measured in 6 rats by both MRI and histology. The survival rate after severe CCI was 96.2%. The L-R difference in % BW increased to 1.69 +/- 0.18% at 2 h, 3.00 +/- 0.08% at 24 h, 2.69 +/- 0.09% at 48 h, and 0.94 +/- 0.21% at 7 days. These values all differed from the control (p < 0.05). The % BW was greater at 24 h and 48 h than at 2 h and 7 days (p < 0.05). Marked reductions in ICBF were limited to structures in the injured hemisphere and were observed in the parietal cortex (2 and 24 h), subcortical white matter (2 and 24 h), and hippocampus (2 h), (p < 0.05) vs control rats. In the contusion core, ICBF was 19.4 +/- 8.8 mL 100 g-1 min-1 at 24 h (p = 0.011 vs normal). Necrosis was seen in large portions of the parietal cortex and subcortical white matter, and portions of the hippocampus and thalamus. Contusion volume was 47.8 +/- 9.2 mm3, which represented 14.4 +/- 2.1% of the traumatized hemisphere. Estimates of contusion volume by MRI and histology were closely correlated (r = 0.941, p < 0.017). Severe CCI in rats is accompanied by contusion, reproducible edema, and marked hypoperfusion, involving over 14% of the injured hemisphere, and can be produced with minimal mortality. T2-weighted MRI successfully and noninvasively identifies contusion volume in this model.

Animals↗
PubMed1994

Neutrophil accumulation after traumatic brain injury in rats: comparison of weight drop and controlled cortical impact models.

Previous work in our laboratory and others using the weight drop (WD) model of traumatic brain injury (TBI) has shown that neutrophils accumulate in brain tissue during the initial 24 h posttrauma as measured by myeloperoxidase (MPO) activity and immunohistochemistry. This study compares the acute inflammatory response to TBI over time, as measured by MPO activity, in the WD and controlled cortical impact (CCI) models. Anesthetized adult Sprague-Dawley rats were traumatized using WD (10-g weight dropped 5 cm) or CCI (4 m/sec, 2.5 mm depth). At 2, 24, 48, or 168 h after trauma, rats (n = 4-5/group at each time) were anesthetized and killed, the brains were removed, and 6-mm coronal slices from traumatized and contralateral hemispheres were assayed for MPO activity. Nontraumatized rats (n = 4) served as controls. Three additional rats underwent a more severe CCI (3 mm depth) with MPO activity assayed at 24 h. A separate group of rats (n = 6) was subjected to WD trauma and killed at 2 weeks after injury for analysis of lesion volume. MPO activity in the traumatized hemisphere was demonstrated at 24 and 48 h in both the WD (0.3152 +/- 0.0472 and 0.3017 +/- 0.0228 U/g, respectively, p < 0.05 vs controls) and CCI (0.1866 +/- 0.0225 and 0.1937 +/- 0.0772 U/g, respectively, p < 0.05 vs controls) models. MPO activity was below the sensitivity of the assay in the control, 2 h, and 168 h groups in both models.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Spark erosion implant-supported overdentures: clinical and laboratory techniques.

Overdentures can be utilized effectively in treatment plans involving implants. Usually soft tissue support is necessary, which requires a conventional denture base. Implant-supported overdentures do not require conventional denture base extension unless necessitated by functional or esthetic considerations. With fixed-detachable hybrid dentures, flanges can often interfere with home care procedures. Spark erosion overdentures meet the requirements for esthetics, phonetics, retention, and support and also allow accessibility for proper patient oral hygiene. This article reviews the advantages and disadvantages of the spark erosion overdenture and provides guidelines for the fabrication of this type of prosthesis.

Dental Implants↗
PubMed1991

Structure-activity studies on triazolothienodiazepine derivatives as platelet-activating factor antagonists.

A series of triazolodiazepines was synthesized and evaluated for anti-platelet activating factor (PAF) activities. Structure-activity relationship (SAR) studies on this series revealed that the introduction of a methyl group into the 8-position of the thienodiazepine nucleus can lead to a lengthening of the duration of action. Introduction of a methyl group produced an asymmetric center and the enantiomers so formed were separated with an optical resolving column. In the in vitro assay system, the (+)-isomers displayed 50-200 times more potent anti-PAF activity than the (-)-isomers. After comparison of toxicology and pharmacokinetics, (+)-6-(2-chlorophenyl)-3- cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4' ,3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (35(+)-isomer, E6123) was selected from among the compounds synthesized as a candidate for clinical study.

Animals↗