SEARCH · PubMed Health

Results for “Conjunctivitis, Inclusion”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,297 records · Page 72Linked to original sources

PubMed1999

CT cystography versus conventional cystography in evaluation of bladder injury.

OBJECTIVE: The objective of this study was to evaluate prospectively the use of CT cystography, using retrograde filling of the bladder with diluted iodinated contrast material, versus conventional cystography to identify bladder injury in patients with hematuria after blunt abdominal trauma. SUBJECTS AND METHODS: Inclusion criteria consisted of the adult hemodynamically stable abdominal trauma patient with hematuria referred for abdominopelvic CT and also being considered for cystography. An initial abdominopelvic CT scan using IV iodinated contrast material was obtained, as would have been done routinely in the trauma victim. A second CT scan through the pelvis was obtained after retrograde distention of the bladder with dilute iodinated contrast material. CT cystography revealing bladder injury was followed with appropriate therapy. CT cystograms not revealing injury were followed by conventional cystography. Results of patient outcome were evaluated. RESULTS: Over a 21-month period from January 1995 through September 1996, CT cystography was performed on 55 patients who presented with hematuria after blunt abdominal trauma. Five of the 55 patients had bladder injury on CT cystography. The injury in each of these five patients was confirmed intraoperatively. In the remaining 50 patients, both CT and conventional cystography did not reveal bladder injury. CONCLUSION: CT cystography is an accurate method for evaluating bladder injury in the blunt abdominal trauma victim with hematuria. CT cystography, performed in conjunction with routine CT of the abdomen and pelvis for evaluating traumatic hematuria, would therefore preclude conventional cystograms in these patients.

Abdominal Injuries↗

PubMed2003

Periodontal host modulation with antiproteinase, anti-inflammatory, and bone-sparing agents. A systematic review.

BACKGROUND: The use of modulating agents, including inhibition of matrix metalloproteinases (MMPs) with antiproteinases, blocking production of proinflammatory cytokines and prostaglandins with anti-inflammatory drugs, and inhibiting activation of osteoclasts with bone-sparing agents, has been postulated to be of therapeutic value as an adjunctive therapy to the management of chronic periodontitis. RATIONALE: The objective of this systematic review of the literature was to assess the adjunctive efficacy of antiproteinase, anti-inflammatory, and bone-sparing host-modulating agents in the treatment of gingivitis, aggressive periodontitis, and chronic periodontitis. FOCUSED QUESTIONS: 1. In patients with periodontal diseases, what is the effect of host-modulation agents, alone or combined with conventional therapy, compared to conventional therapy alone as assessed by clinical, radiographic, adverse, and patient-centered outcomes? 2. In patients with dental implants, what is the effect of host-modulation agents on implant success assessed by clinical, radiographic, adverse, and patient-centered outcomes? SEARCH PROTOCOL: MEDLINE, Embase, and the Cochrane Library databases were searched without language restrictions through April 1, 2002 for studies that used tetracycline (TET)-related matrix metalloproteinase (MMP) inhibitors, or non-steroidal anti-inflammatory drugs (NSAIDs) and bisphosphonate anti-osteolytic agents. The investigation also included hand searching of journals and contacting authors and industry experts. SELECTION CRITERIA INCLUSION CRITERIA: Only human studies (randomized controlled clinical trials, cohort studies, case-control studies, cross-sectional studies, and case series) were selected. Studies were on subjects with gingivitis, aggressive or chronic periodontitis, or dental implants. Interventions included TET-related MMP inhibitors, NSAIDs, or bisphosphonate anti-osteolytic agents. EXCLUSION CRITERIA: Studies that used MMP tissue inhibitors as diagnostic or prognostic indicators of periodontal disease or that evaluated short-term systemic antibodies or locally delivered levels of drugs with antiproteinase activity were excluded. DATA COLLECTION AND ANALYSIS: The primary outcomes for assessment were changes in bone or clinical attachment levels (CAL); secondary outcomes included clinical measures of plaque, gingival inflammation, probing depth (PD), and mobility. Summary data appropriate for meta-analysis were pooled using a weighted average and analyzed using a standardized difference; the results were checked with both fixed-effects and random-effects models. MAIN RESULTS: 1. A meta-analysis done on the studies reporting changes in CAL and PD following administration of sub-antimicrobial doses of doxycycline (SDD) in conjunction with scaling and root planing (SRP) in patients with periodontitis showed a statistically significant beneficial adjunctive effect. 2. There were insufficient data to provide meta-analyses on periodontal patients treated with other host-modulating agents; descriptive tables are included. 3. NSAIDS show promise in their ability to slow periodontal disease. 4. Preliminary data on bisphosphonate agents indicate there is a potential role for these agents in periodontitis management. 5. There are a very limited number of studies on host-modulating agents and dental implants and no analyses were possible. 6. Because the treatment methodologies and clinical variables differed considerably among the studies, it is difficult to summarize the information and identify a reliable total patient population. REVIEWERS' CONCLUSIONS: 1. Large multi-center trials are needed to evaluate the role of host-modulating agents in the treatment of periodontitis. 2. NSAIDS and bisphosphonate drugs may have a potential adjunctive role in periodontal therapy. 3. The adjunctive use of SDD with SRP is statistically more effective than SRP alone in reducing PD and in achieving CAL gain.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1984

Establishment of genital tract infection in the CF-1 mouse by intravaginal inoculation of a human oculogenital isolate of Chlamydia trachomatis.

A human oculogenital strain of Chlamydia trachomatis was instilled intravaginally in the outbred CF-1 mouse to establish cervical infection. The mice were neither hormonally nor immunologically manipulated before inoculation. Duration of chlamydial excretion varied from two to ten days. In the culture-positive animals, IgG and IgM antibody titers were elevated in 38% and 17%, respectively. Neither intracytoplasmic inclusions nor elementary bodies of C. trachomatis were detected in genital tissues. Infection was limited primarily to the cervix and only rarely extended into the uterus. Chlamydial infection could only be established during specific periods of the estrus cycle (metestrus-2, diestrus, and proestrus; P less than .001), stages when leukocytes are present in the vaginal smear. Thus, chlamydial infection of the cervix is cycle-dependent in the mouse. In summary, infection of the cervix of the mouse has been established with a human oculogenital strain of C. trachomatis and may be useful as a model of human chlamydial cervicitis.

Animals↗

PubMed2006

Decompressive craniectomy in pediatric patients with traumatic brain injury with intractable elevated intracranial pressure.

BACKGROUND: Care of pediatric traumatic brain injury (TBI) has placed emphasis on maximizing cerebral perfusion to prevent ischemia and reperfusion injury. A subset of patients with TBI will continue to have refractory intracranial pressure (ICP) elevation despite aggressive therapy including ventriculostomy, pentobarbital coma, hypertonic saline, and diuretics. Decompressive craniectomy (DC) is a controversial treatment of severe TBI. It is our hypothesis that DC can enhance survival and minimize secondary brain injury in this patient subset. METHODS: Patients younger than 20 years treated at a level I regional trauma center between November 2001 and November 2004, who met inclusion criteria for the Brain Trauma Foundation TBI-trac clinical database were included. All patients with a mechanism of injury consistent with TBI and Glasgow Coma Scale score of less than 9 for at least 6 hours after resuscitation and who did not die in the emergency department are entered into a clinical database. Patients who arrived at the study hospital more than 24 hours after injury are excluded. RESULTS: There were 30 patients with TBI identified. The mean Glasgow Coma Scale score at presentation was 8 with a range of 3 to 13. Six patients underwent DC for intractable elevated ICP. Of 6 patient's postoperative ICP, 5 were less than 20 mm Hg. One patient required a return to the operating room where further débridement of brain was performed. All patients who received a DC survived and were discharged to a TBI rehabilitation facility. CONCLUSION: Although this is a small sample, DC should be considered in patients with TBI with refractory elevated ICP. Long-term follow-up of this patient population should consist of neuropsychiatric evaluation in conjunction with measurement of social function.

Adolescent↗

PubMed2004

Impact of Vitamin E supplementation on lipoprotein peroxidation and composition in Type 1 diabetic patients treated with Atorvastatin.

OBJECTIVE: To investigate the impact of Vitamin E on lipids and peroxidation during statin treatment. RESEARCH DESIGN AND METHODS: T1DM patients with high cholesterol received Atorvastatin 20mg with either placebo (group AP, n = 11) or d-alpha-tocopherol 750 IU (group AE, n = 11) daily. They were monitored for blood biochemistry, low-density lipoprotein (LDL) subfractions and lipid peroxidation at inclusion and after 3 and 6 months. RESULTS: Serum cholesterol and triglycerides decreased to the same extent (29 and 21% respectively) in both groups. Serum tocopherol decreased by 18% in AP and increased by 50% in AE (P < 0.0001, between-group comparison by repeated measures ANOVA) but relative to lipids it increased by 15% in AP and by 100% in AE. Copper-induced production of thiobarbituric reactive substances in the LDL + VLDL fraction increased by 18% in AP and did not change in AE (P = 0.02). The lagtime for the production of fluorescent products was prolonged by 13 min only in group AE (P = 0.028). Plasma malondialdehyde decreased by 35% in both groups (P = 0.002) but not when adjusted for lipids. CONCLUSIONS: In T1DM Vitamin E supplements do not affect the lowering of lipids and plasma malondialdehyde achieved by Atorvastatin. They reverse the increase of in vitro peroxidation caused by Atorvastatin but do not achieve the decreases observed in patients not receiving lipid-lowering drugs. These results indicate that the antioxidant effect of Vitamin E is attenuated when given in conjunction with this statin.

Adult↗

PubMed1995

Mechanisms of selective long-term potentiation of excitatory synapses in stratum oriens/alveus interneurons of rat hippocampal slices.

1. We investigated long-term potentiation (LTP) of synaptic transmission in different populations of interneurons in the CA1 region of rat hippocampal slices using whole cell recordings. We elicited excitatory postsynaptic currents (EPSCs) in interneurons located in stratum oriens near the alveus (O/A) or in stratum lacunosum-moleculare near the stratum radiatum border (L-M) by electrical stimulation of nearby axons in stratum oriens and radiatum, respectively. 2. High-frequency stimulation (100 Hz, 1 s) of axons in conjunction with postsynaptic depolarization (to -20 mV) increased the peak amplitude of test EPSCs elicited at -80 mV in O/A interneurons. The mean peak amplitude of EPSCs was significantly potentiated relative to the control period at 10 min (39 +/- 7% increase, mean +/- SE; n = 11 cells) and 30 min (30 +/- 1% increase; n = 5 cells) after tetanization. Similar stimulation did not produce potentiation of EPSCs in L-M interneurons (n = 7 cells). 3. This selective LTP in O/A interneurons was reversibly blocked by the N-methyl-D-aspartate receptor antagonist (+/-)2-amino-5-phosphonopentanoic acid (AP-5). Tetanization in the presence of 25 microM AP-5 did not increase the amplitude of EPSCs (8 cells). After washout of AP-5 (4 cells), a second tetanization resulted in long-term potentiation of EPSCs. 4. LTP was dependent on the activation of metabotropic glutamate receptors. The peak amplitude of EPSCs was not increased 5-10 or 15-20 min after tetanization during bath application of the metabotropic glutamate receptor antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (500 microM) (n = 5 cells). 5. Inclusion of the Ca2+ chelator 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA; 25 mM) in the patch pipette blocked LTP in O/A interneurons. In five cells recorded with BAPTA-containing electrodes, the mean peak amplitude was not significantly increased after tetanization. Thus a rise in postsynaptic intracellular Ca2+ appeared necessary for the induction of LTP in these interneurons. 6. Incubation of slices with the inhibitor of nitric oxide synthase N omega-nitro-L-arginine methyl ester (100 microM) before and throughout the recording session also blocked the increase in EPSC amplitude at 5-10 min (5 cells) and 15-20 min (3 cells) after tetanization. NO synthesis may therefore be necessary for LTP in O/A interneurons. 7. These results suggest that LTP of excitatory synapses is selectively produced in O/A but not L-M interneurons, and that this LTP shares similar characteristics with LTP in hippocampal CA1 pyramidal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMedDate not supplied

The efficacy of various bone augmentation procedures for dental implants: a Cochrane systematic review of randomized controlled clinical trials.

PURPOSE: To test (a) whether and when bone augmentation procedures are necessary and (b) which is the most effective augmentation technique for specific clinical indications. Trials were divided into 3 categories: (1) major vertical or horizontal bone augmentation (or both); (2) implants placed in extraction sockets; (3) fenestrated implants. MATERIALS AND METHODS: An exhaustive search was conducted for all randomized controlled clinical trials (RCTs) comparing different techniques and materials for augmenting bone for implant treatment reporting the outcome of implant therapy at least to abutment connection. No language restriction was applied. The last electronic search was conducted on October 1, 2005. RESULTS: Thirteen RCTs of 30 potentially eligible trials reporting the outcome of 332 patients were suitable for inclusion. Six trials evaluated techniques for vertical and/or horizontal bone augmentation. Four trials evaluated techniques of bone grafting for implants placed in extraction sockets, and 3 trials evaluated techniques to treat fenestrated implants. CONCLUSIONS: Major bone grafting procedures of extremely resorbed mandibles may not be justified. Bone substitutes may replace autogenous bone for sinus lift procedures of extremely atrophic sinuses. Both guided bone regeneration procedures and distraction osteogenesis can be used to augment bone vertically, but it is unclear which is the most efficient. It is unclear whether augmentation procedures are needed at immediate single implants placed in fresh extraction sockets; however, sites treated with barrier + Bio-Oss showed a higher position of the gingival margin than sites treated with barriers alone. More bone was regenerated around fenestrated implants with nonresorbable barriers than without barriers; however, it remains unclear whether such bone is of benefit to the patient. Bone morphogenetic proteins may enhance bone formation around implants grafted with Bio-Oss, but there was no reliable evidence supporting the efficacy of other active agents, such as platelet-rich plasma, in conjunction with implant treatment.

Alveolar Ridge Augmentation↗

PubMed2003

Progress in the treatment of aneurysms of the distal aortic arch: approach through median sternotomy.

AIM: A review of past and current operative procedures for the treatment of aneurysms of the distal aortic arch is presented in conjunction with a series of 43 patients. In this study, distal aortic arch aneurysm refers to an aneurysm involving at least the origin of the left subclavian artery, but not extending beyond the left common carotid artery. We excluded dissection aneurysm and extended aneurysm to the descending thoracic aorta from this study. METHODS: Between January, 1985, and March, 2000, 43 consecutive patients (37 males, 6 females; mean age 67.5 years) underwent repair of aneurysms of the distal aortic arch. The approach to the aneurysm was through a left thoracotomy in 4 patients and a median sternotomy in 39 patients, including an additional left thoracotomy continued to a median sternotomy in 2 patients. The supportive methods during surgery were left heart bypass using a centrifugal pump in 4 patients (LHB group), cardiopulmonary bypass with selective cerebral perfusion in 11 patients (SCP group), and cardiopulmonary bypass with continuous retrograde cerebral perfusion in 28 patients (RCP group). In the RCP group, the "aortic no-touch technique" was applied in 21 patients. The operative methods were patch closure in 4 patients, graft replacement of the distal arch using the inclusion technique in 14 patients, and total arch replacement using the exclusion technique in 25 patients. RESULTS: There were 5 hospital deaths: 1 patient in the LHB group, intractable bleeding; 1 patient in the SCP group, rupture of the distal anastomosis; 3 patients in the RCP group, stroke, rupture of the dissection arising from the distal anastomosis, and perioperative myocardial infarction. Stroke occurred in 1 patient (25%) with LHB, 3 patients (27.2%) with SCP, and 1 patient (3.6%) with RCP. Among the postoperative survivors, a new onset of left recurrent nerve palsy occurred in 2 patients (66.7%) with LHB, 1 patient (10%) with SCP, and in 1 patient (4%) with RCP. No neurological injury or left recurrent nerve palsy occurred in the patients who underwent the "aortic no-touch technique". CONCLUSION: Total arch replacement with the graft exclusion technique under profound hypothermic circulatory arrest using RCP through the median sternotomy is a promising surgical treatment for atherosclerotic distal aortic arch aneurysm. The "aortic no-touch technique" further improved the surgical results of the distal aortic arch aneurysm.

Aged↗

PubMed1975

Ultrastructural and immunohistochemical studies in five cases of Argentine hemorrhagic fever.

Ultrastructural and immunohistochemical studies on tissues from five patients with Argentine hemorrhagic fever revealed previously undetected lesions caused by the viral infection. Two types of particle were seen in the cells of all organs examined. The particles had some characteristics similar to those described for arenaviruses. However, the virus-like particles were intracellular, had a single membrane, and apparently originated by a process of budding into the endoplasmic reticulum cisternae. Intranuclear bodies and three types of cytopolasmic change were observed in conjunction with the virus-like particles; Antigenic determinants of Junin virus were demonstrated in cells of all organs examined. Immunohistochemical experiments also indicated alterations in the cellular mechanisms of protein synthesis. Until now the pathogenesis of human diseases produced by arenaviruses has not been established. The results of this study suggest that in Argentine hemorrhagic fever the virus is responsible for a direct pathogenic action.

Adult↗

PubMed2003

Quality of life in patients with a pituitary adenoma.

A validated quality of life (QOL) measure, the SF-36 questionnaire, was used to assess patients' perception of the impact of a pituitary adenoma, prior to treatment, on his or her physical and mental functioning. Of 270 new patients evaluated for pituitary disease at the University of Virginia Pituitary Clinic, 168 met the criteria for inclusion (pituitary hormone hypersecretion and/or pituitary adenoma) into this prospective study. Results of the SF-26 questionnaire in 36 patients with acromegaly, 42 patients with Cushing's disease, 39 patients with a prolactinoma and 51 patients with a non functioning macroadenoma prior to treatment were compared with those of the normal population; a comparison of results among patients with different types of pituitary adenomas was also performed. Patients with a pituitary adenoma had a significantly decreased QOL compared with the normal population in both physical and mental measures (p < 0.05). There were different degrees of perceived impairment depending on the type of pituitary adenoma. Patients with acromegaly had impairment in measures of physical function while patient with Cushing's disease had impairment in all but one measures compared with the normal population and with patients with other types of pituitary adenomas. Patients with a prolactinoma had impairment in mental measures and patients with a non-functioning adenoma had impairment in both physical and mental measures compared with the normal population. Patients with a pituitary adenoma have an impaired quality of life that should be routinely assessed in conjunction with endocrine and anatomic studies before and after treatment.

Acromegaly↗

PubMedDate not supplied

[Keller-Brandes operation: long-term outcome in young patients with hallux valgus].

PURPOSE: Aim of this retrospective study was to analyse the long term results (10-16 years) after Keller-Brandes' operation for correction of hallux valgus in the younger patient. METHODS: From 1980 to 1986 fifty-one patients (77 feet) at the age of 40 years or younger at the time of surgery (19-40 years, [symbol: see text] 34 years), were operated according to a resection-arthroplasty at our institution. 24 patients (37 feet) were evaluated retrospectively after 10 to 16 years (median: 13 years) in respect to their clinical outcome. Radiological evaluation was performed preoperatively in 23 feet and in 34 feet at follow up. Analysis was performed using a standardized questionnaire based on the HMIS-Score of the American Foot and Ankle Society, an additional clinical score, weight-bearing radiographs, the patient's record and clinical investigation inclusive pedobarographic analysis. RESULTS: Seventy-six % of the patients revealed very good or good subjective overall results. The HMIS-Score revealed excellent or good results in only 57%. Cosmetic was rated very good or good in 64%, 70% of the patients were painfree. Average ROM of the MTP I-joint ranged from 25 degrees flexion to 45 degrees extension. Radiological analysis at follow up: hallux valgus angle-correction: 28 degrees to 19 degrees, no change of the intermetatarsal angle (11 degrees), proximal shift of sesamoids: 9.4 mm to 14.4 mm, neoarticulation gap: 0-2 mm in 23 feet and 3-5 mm in 11 feet, arthritis of IP-joint: 82%: none; 18%: moderate; correction of sesamoid position: 1.7 to 1.4. Metatarsalgia was observed in 27% (10 feet). CONCLUSION: Lateral weight transfer to the lesser metatarsal heads is caused by defunction of the great toe postoperatively which may lead to metatarsalgia (transfer-metatarsalgia). Besides pain relief younger patients require satisfying functional and cosmetic long-term results. To be capable of meeting these requirements, adequate joint preserving procedures like basal or distal metatarsal osteotomies conjuncted with soft tissue procedures should be preferred in respect to the grade of the deformity.

Adult↗

PubMed2006

Analysis of the kinestatic charge detection system as a high detective quantum efficiency electronic portal imaging device.

Megavoltage x-ray imaging suffers from reduced image quality due to low differential x-ray attenuation and large Compton scatter compared with kilovoltage imaging. Notwithstanding this, electronic portal imaging devices (EPIDs) are now widely used in portal verification in radiotherapy as they offer significant advantages over film, including immediate digital imaging and superior contrast range. However video-camera-based EPIDs (VEPIDs) are limited by problems of low light collection efficiency and significant light scatter, leading to reduced contrast and spatial resolution. Indirect and direct detection-based flat-panel EPIDs have been developed to overcome these limitations. While flat-panel image quality has been reported to exceed that achieved with portal film, these systems have detective quantum efficiency (DQE) limited by the thin detection medium and are sensitive to radiation damage to peripheral read-out electronics. An alternative technology for high-quality portal imaging is presented here: kinesatic charge detection (KCD). The KCD is a scanning tri-electrode ion-chamber containing high-pressure noble gas (xenon at 100 atm) used in conjunction with a strip-collimated photon beam. The chamber is scanned across the patient, and an external electric field is used to regulate the cation drift velocity. By matching the scanning velocity with that of the cation (i.e., ion) drift velocity, the cations remain static in the object frame of reference, allowing temporal integration of the signal. The KCD offers several advantages as a portal imaging system. It has a thick detector geometry with an active detection depth of 6.1 cm, compared to the sub-millimeter thickness of the phosphor layer in conventional phosphor screens, leading to an order of magnitude advantage in quantum efficiency (>0.3). The unique principle of and the use of the scanning strip-collimated x-ray beam provide further integration of charges in time, reduced scatter, and a significantly reduced imaging dose, enhancing the imaging signal-to-noise ratio (SNR) and leading to high DQE. While thick detectors usually suffer from reduced spatial resolution, the KCD provides good spatial resolution due to high gas pressure that limits the spread of scattered electrons, and a strip-collimated beam that significantly reduces the inclusion of scatter in the imaging signal. A 10 cm wide small-field-of-view (SFOV) prototype of the KCD is presented with a complete analysis of its imaging performance. Measurements of modulation transfer function (MTF), noise power spectrum (NPS), and DQE were in good agreement with Monte Carlo simulations. Imaging signal loss from recombination within the KCD chamber was measured at different gas pressures, ion drift velocities, and strip-collimation widths. Image quality for the prototype KCD was also observed with anthropomorphic phantom imaging in comparison with various commercial and research portal imaging systems, including VEPID, flat-panel imager, and conventional and high contrast film systems. KCD-based imaging provided very good contrast and good spatial resolution at very low imaging dose (0.1 cGy per image). For the prototype KCD, measurements yielded DQE(0)=0.19 and DQE(1 cy/mm)=0.004.

Computer-Aided Design↗

PubMedDate not supplied

Cytoplasmic lipid bodies in eosinophils: central roles in eicosanoid generation.

BACKGROUND: Lipid bodies are lipid-rich cytoplasmic inclusions which form in diverse cell types, including eosinophils. Lipid body numbers increase in vivo in leukocytes participating in inflammatory processes. Our interest in lipid bodies relates to the roles that these structures play in arachidonate metabolism by eosinophils and other leukocytes involved in inflammation. METHODS: Specific agonists, platelet-activating factor (PAF), two cis-unsaturated fatty acids (arachidonic and oleic acids) and a diglyceride (1-oleyl-2-acetyl-glycerol (OAG)), were used to stimulate lipid body formation in human eosinophils. Lipid bodies were enumerated and eosinophils were stimulated with submaximal calcium ionophore to generate leukotriene C4 (LTC4), which was quantitated by immunoassay. RESULTS: Lipid body formation was rapidly inducible in eosinophils by specific intracellular signaling pathways. PAF, the two cis-unsaturated fatty acids and OAG each stimulated lipid body formation in eosinophils. Increased numbers of lipid bodies correlated quantitatively with the 'priming' response of eosinophils to form enhanced amounts of the 5-lipoxygenase-derived eicosanoid, LTC4. CONCLUSION: Lipid bodies in eosinophils function as intracellular domains that are both depots of esterified arachidonate and sites at which regulated enymatic events relevant to arachidonate metabolism can occur. In conjunction with our findings that key eicosanoid-forming enzzymes, including cyclooxygenase, 5- and 15-lipoxygenase and LTC4 synthase, are localized at lipid bodies in eosinophils, the finding that induction of lipid body formation correlated quantitatively with enhanced LTC4 production indicate that lipid bodies are structurally distinct, inducible, non-nuclear sites for enhanced synthesis of paracrine eicosanoid mediators of inflammation.

Cells, Cultured↗

PubMed2002

A systematic review on the clinical efficacy of subgingival debridement in the treatment of chronic periodontitis.

OBJECTIVE: The purpose of this study was to perform a systematic review of the literature and to evaluate, in patients with chronic periodontitis, what the effect is of subgingival debridement (SGD), in terms of bleeding on probing, pocket depth and probing attachment level. MATERIAL AND METHODS: An electronic search of the Cochrane Oral Health Group specialized register and MEDLINE were performed using specific search terms to identify studies assessing in patients with chronic periodontitis the effect of subgingival debridement with regard to clinical outcomes. This was performed on titles registered up to 2001. The only papers included were those which utilized data based on the patient as unit of observation. RESULTS: The searches identified 702 abstracts. Titles and abstracts were independently screened by two reviewers (G.A.W. & M.F.T.) to identify publications that met specific inclusion criteria. The agreement between the two reviewers was assessed. The kappa score for agreement was 0.80. Review of these abstracts resulted in 114 publications for detailed review. Finally, 26 papers which met the criteria of eligibility were independently selected by the two reviewers. The kappa score for agreement on this decision was 0.92. Disagreement regarding inclusion of both abstracts and full papers was resolved by discussion between the reviewers. No randomized controlled trials (RCT) could be retrieved that were specifically designed to answer the question formulated at the outset of this systematic review. From the 10 controlled studies, four provide a definitive 'yes' that SGD is effective with regard to clinical outcomes. In the one study where subgingival debridement was not supported by oral hygiene instruction, the paper provided a definitive 'no'. The weighted mean of attachment gain of SGD in pockets initially >or=5 mm was 0.64 mm as compared with 0.37 mm for supragingival plaque control only (SPC). The reduction of pocket depth was 0.59 mm and 1.18 mm for SPC and SGD, respectively. Of the 18 papers that provided only information on the effect of treatment as compared with the baseline values, eight showed SGD to be beneficial with regard to clinical attachment level change while the remaining 10 provided no such an analysis. The weighted mean of this effect was a 0.74-mm gain of attachment as a result of treatment in pockets initially >or= 4 mm. CONCLUSIONS: In patients with chronic periodontitis, subgingival debridement (in conjunction with supragingival plaque control) is an effective treatment in reducing probing pocket depth and improving the clinical attachment level. In fact it is more effective than supragingival plaque control alone.

Adult↗

PubMed2000

Inclusion of S-sepharose beads in the culture medium significantly improves recovery of secreted rBPI(21) from transfected CHO-K1 cells.

rBPI(23), a recombinant N-terminal fragment of human bactericidal/permeability-increasing protein (BPI), kills gram-negative bacteria and binds endotoxin. rBPI(21), a variant, in which cysteine 132 is changed to alanine, retains the activities of rBPI(23). Initial attempts using conventional ion-exchange chromatography to purify rBPI(23) from culture supernatants of transfected CHO-K1 cells resulted in lower than expected yields. Also, ELISA of supernatants from CHO-K1 transfectants expressing rBPI(23) or rBPI(21) yielded variable signals. Results from pulse-chase experiments using [(35)S]methionine had indicated that rBPI(23) could not be detected in the culture medium by 7 h of chase, suggesting that these proteins were degraded and/or bound to cells, media components, or vessel surfaces. To address these issues, we developed a novel process whereby sterile S-Sepharose beads were added directly to the cell culture medium. For attached cells, the beads were added to confluent cultures with serum-free medium for the expression phase, while for suspension-adapted cells, beads were added at the beginning of culture growth. The S-Sepharose was then separated from cells and media and washed, and BPI was eluted with high-salt buffer. This approach yielded up to a 50-fold improvement in recovery of rBPI(23) and rBPI(21) from roller bottles, shake flasks, and 2-liter fermenters. It also resulted in improved detection and quantitation of secreted rBPI(23) and rBPI(21) by ELISA. Results of competition binding studies with iodinated rBPI(21) in conjunction with unlabeled rBPI(21) and rBPI(23) or with heparin demonstrated that these proteins bound specifically and with high affinity to heparan-containing sites on the surface of the CHO-K1 cells. We conclude that the S-Sepharose included in the culture medium captures the BPI protein products as they are secreted and protects them from degradation and/or irreversible binding to cell surfaces. This method has been scaled up to a manufacturing process in large (2750 liter) fermenters for pharmaceutical production.

Animals↗

PubMed2001

Liposome-mediated DNA vaccination: the effect of vesicle composition.

Liposome-entrapped DNA has been shown to enhance the potency of DNA vaccines, possibly by facilitating uptake of the plasmid by antigen-presenting cells (APC). In this paper, we have investigated the influence of the liposomal composition and surface charge on such potency. Plasmid DNA pRc/CMV HBS encoding the S (small) region of hepatitis B surface antigen was entrapped within cationic liposomes of various compositions and surface charges with high efficiency (88-97% of the amount used) by the dehydration-rehydration method that generates dehydration-rehydration vesicles (DRV). Cryo-electron microscopy revealed that DNA-containing DRV (DRV(DNA)) were multilamellar. In immunisation studies, female Balb/c mice were given two to four intramuscular injections of 10 microg naked or liposome-entrapped pRc/CMV HBS and bled at time intervals. Results indicate that the lipid composition of the DRV(DNA) influences the strength of the humoural response (immunoglobulin (Ig)G subclasses) with inclusion of dioleoyl phosphatidylethanolamine (DOPE) or phosphatidylethanolamine (PE) in the liposomal structure contributing to greater responses. DRV(DNA) in which the DOPE or PE were omitted or substituted with cholesterol led to significant reduction of humoural responses against the encoded antigen. Replacing phosphatidylcholine (PC) in the DRV(DNA) with the high-melting distearoyl phosphatidylcholine also contributed to lower responses. In other experiments, IgG responses were monitored in mice immunised with pRc/CMV HBS entrapped in DRV composed of PC and DOPE as before but incorporating increasing amounts of DOTAP (1-16 micromol). Maximal IgG responses were observed at 10 weeks after the first of four injections and suggested a trend of higher responses when 4 or 8 micromol DOTAP was present in the DRV(DNA) formulation. Cell-mediated immunity (measured in terms of endogenous antigen-specific splenic interferon-gamma) in mice immunised with pRc/CMV HBS entrapped in liposomes composed of PC, DOPE and DOTAP (16:8:4 molar ratio) was much greater than in animals treated with naked plasmid. These results indicate that liposome-mediated DNA immunisation is more effective than the use of naked DNA, and also suggest that the presence of fusogenic phosphatidylethanolamine in DRV in conjunction with a low-melting phosphatidylcholine and an appropriate content of cationic lipid might contribute to more effective liposomal DNA vaccines. The notion that liposomes improve immune responses to the plasmid-encoded vaccine by facilitating the latter's uptake by APC was supported by the observation that in Balb/c mice injected intramuscularly with liposome-entrapped pCMV. Enhanced green fluorescent protein, expression of the gene in terms of fluorescence intensity in the draining lymph nodes, was much greater than in animals treated with the naked plasmid.

Animals↗

PubMed2002

Accumulation of cytoplasmic lipid droplets in bovine embryos and cryotolerance of embryos developed in different culture systems using serum-free or serum-containing media.

In this study, the quantitative fluctuation of cytoplasmic lipid droplets (LD) and cryotolerance were investigated in bovine embryos derived from in vitro-matured (IVM) and in vitro-fertilized (IVF) oocytes developed in different culture systems using serum-free or serum-containing media. The serum-free cultures were grown using IVMD101 medium in conjunction with bovine cumulus/granulosa cell (BCGC) cocultures or IVD101 medium without BCGC cocultures, and the serum-containing cultures were grown in the presence of BCGC cocultures using HPM199 medium supplemented with 5% calf serum (HPM199 + CS). Large numbers of sudanophilic LD were present in the cytoplasm of bovine embryos from 2-cell to hatched blastocyst stages, and the number and size differed between the embryos cultured in serum-free and serum-supplemented media. In the embryos cultured in HPM199 + CS, large (2-6 microm in diameter) sudanophilic LD increased significantly from the morula to the blastocyst stages. Throughout the embryonic development, the embryos developed in serum-free cultures with and without BCGC cocultures had numerous sudanophilic LD, but most of these droplets were small (<2 microm in diameter) and large LD were less numerous than those embryos cultured in HPM199 + CS. Giant LD (>6 microm in diameter) were frequently observed in morulae and blastocysts (including early blastocysts) developed in HPM199 + CS. Electron microscopic observations demonstrated that large LD were abundant in the cytoplasm of trophoblast and embryonic (inner cell mass) cells of blastocysts cultured in HPM199 + CS. These large LD were identified as osmophilic LD, an indication that these lipid inclusions contained a significant proportion of unsaturated lipids. Many elongated mitochondria were found in embryos developed in IVMD101 and IVD101 at the morula and early blastocyst stages, whereas many of the mitochondria in the morulae developed in HPM199 + CS were of an immature form such as spherical or ovoid shape. The survival and hatching rates of embryos (morulae, early blastocysts, and blastocysts) produced in serum-free media (both IVMD101 and IVD101) after post-thaw culture were superior to those of embryos produced in serum-containing medium. These results showed that bovine embryos cultured in serum-containing medium abnormally accumulated cytoplasmic lipids into their cytoplasm and the excess accumulation of cytoplasmic LD in embryos may affect the cryotolerance of embryos.

Animals↗

PubMed2004

Effect of processing and formulation variables on the stability of a salt of a weakly basic drug candidate.

The effect of some processing and formulation variables on the stability of tablets containing a crystalline salt of a triazine derivative was studied. The salt has a relatively low melting point and a low microenvironmental pH due to the weakly basic nature of the parent compound (pKa = 4.0). This compound decomposes through acid-catalyzed hydrolysis. A full factorial design was used to study the effect of three variables on tablet stability: aqueous wet granulation, ball milling of the salt and filler prior to manufacturing, and the inclusion of sodium carbonate in the formulation as a pH modifier. In addition to the factorial design experiments, a batch of tablets was prepared by wet granulation, using sodium bicarbonate as the pH modifier. Stability of the drug in tablets was evaluated at 40 degrees C/75% relative humidity (RH) and at 40 degrees C/ambient humidity. Stability of tablets was adversely affected by wet granulation. However, stability was greatly improved by wet granulation in the presence of sodium carbonate. While sodium carbonate enhanced drug stability in the tablets, regardless of the manufacturing process, wet granulated tablets were more stable than tablets containing sodium carbonate and prepared without wet granulation. Similarly prepared tablets by using sodium bicarbonate were remarkably less stable compared with those containing sodium carbonate. The use of sodium bicarbonate as a pH modifier resulted in only marginal enhancement of tablet stability, suggesting that a higher microenvironmental pH than that provided by sodium bicarbonate is needed to maximize stability. Despite the low lattice energy of the salt and the potential for disruption of salt crystallinity by mechanical stress, milling did not appear to have an adverse effect on tablet stability under the current experimental conditions. This study shows that selection of the proper manufacturing process, in conjunction with the appropriate pH modifier, could be critical to dosage form stability.

Chemistry, Pharmaceutical↗