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PubMed2002

Efficacy of indomethacin 0.1% and fluorometholone 0.1% on conjunctival inflammation following chronic application of antiglaucomatous drugs.

BACKGROUND: Subclinical conjunctival inflammation has been shown to have a deleterious effect on the outcome of filtering surgery. The study was designed to assess the efficacy and safety of a non-steroidal anti-inflammatory ophthalmic solution (preservative-free indomethacin 0.1%) on conjunctival inflammation following chronic application of antiglaucomatous drugs, in comparison with a steroidal ophthalmic solution (preserved fluorometholone). METHODS: Eighty-nine glaucomatous patients were included in a randomised, multicentre study comparing two parallel groups of treatment given on the basis of 1 drop 4 times daily for 1 month before filtering surgery. Patients had been treated with one or more antiglaucomatous drugs for at least 3 years. The routine antiglaucomatous treatment was continued during the study. Evaluations were carried out at baseline and after 30 days of treatment. Conjunctival inflammation was assessed under masked conditions by means of conjunctival impression analysis which determined the percentage of cells expressing HLA-DR. The ocular surface was also examined using the fluorescein test and lissamine green staining. RESULTS: Paired conjunctival impression specimens available both on day 0 (D0) and day 30 (D30) involved 49 patients. Among them, 34 eyes had a positive expression of HLA-DR at inclusion. On D30, in patients positive to HLA-DR on D0, the percentage of cells expressing HLA-DR had significantly decreased in both treatment groups: the mean reduction was 29.7% from a baseline value of 51.4% in the indomethacin group ( P=0.019) and 32.5% from a baseline value of 48.7% in the fluorometholone group ( P<0.001). There was no significant difference between groups. Seven cases of drug-related superficial punctate keratitis were observed on D30 by means of a fluorescein test: one in the indomethacin group and six in the fluorometholone group. CONCLUSION: Both anti-inflammatory eyedrops were effective in reducing subclinical conjunctival inflammation before filtering surgery. Regarding superficial punctate keratitis, the corneal tolerance of preservative-free indomethacin 0.1% eyedrops seemed to be better than that of preserved fluorometholone eyedrops.

Aged↗

PubMed2000

Structures of helical junctions in nucleic acids.

Our knowledge of the architectural principles of nucleic acid junctions has seen significant recent advances. The conformation of DNA junctions is now well understood, and this provides a new basis for the analysis of important structural elements in RNA. The most significant new data have come from X-ray crystallography of four-way DNA junctions; incidentally showing the great importance of serendipity in science, since none of the three groups had deliberately set out to crystallise a junction. Fortunately the results confirm, and of course extend, the earlier conformational studies of DNA junctions in almost every detail. This is important, because it means that these methods can be applied with greater confidence to new systems, especially in RNA. Methods like FRET, chemical probing and even the humble polyacrylamide gel can be rapid and very powerful, allowing the examination of a large number of sequence variants relatively quickly. Molecular modelling in conjunction with experiments is also a very important component of the general approach. Ultimately crystallography provides the gold standard for structural analysis, but the other, simple approaches have considerable value along the way. At the beginning of this review I suggested two simple folding principles for branched nucleic acids, and it is instructive to review these in the light of recent data. In brief, these were the tendency for pairwise coaxial stacking of helical arms, and the importance of metal ion interactions in the induction of folding. We see that both are important in a wide range of systems, both in DNA and RNA. The premier example is the four-way DNA junction, which undergoes metal ion-induced folding into the stacked X-structure that is based on coaxial stacking of arms. As in many systems, there are two alternative ways to achieve this depending on the choice of stacking partners. Recent data reveal that both forms often exist in a dynamic equilibrium, and that the relative stability of the two conformers depends upon base sequence extending a significant distance from the junction. The three-way junction has provided a good test of the folding principles. Perfect three-way (3H) DNA junctions seem to defy these principles in that they appear reluctant to undergo coaxial stacking of arms, and exhibit little change in conformation with addition of metal ions. Modelling suggests that such a junction is stereochemically constrained in an extended conformation. However, upon inclusion of a few additional base pairs at the centre (to create a 3HS2 junction for example) the additional stereochemical flexibility allows two arms to undergo coaxial stacking. Such a junction exhibits all the properties consistent with the general folding principles, with ion-induced folding into a form based on pairwise coaxial stacking of arms in one of two different conformers. The three-way junction is therefore very much the exception that proves the rule. It is instructive to compare the folding of corresponding species in DNA and RNA, where we find both similarities and differences. The RNA four-way junction can adopt a structure that is globally similar to the stacked X-structure (Duckett et al. 1995a), and the crystal structure of the DNAzyme shows that the stacked X-conformation can include one helical pair in the A-conformation (Nowakowski et al. 1999). However, modelling suggests that the juxtaposition of strands and grooves will be less satisfactory in RNA, and the higher magnesium ion concentration required to fold the RNA junction indicates a lower stability of the antiparallel form. Perhaps the biggest difference between the properties of the DNA and RNA four-way junctions is the lack of an unstacked structure at low salt concentrations for the RNA species. This clearly reflects a major difference in the electrostatic interactions in the RNA junction. In general the folding of branched DNA provides some good indications on the likely folding of the corresponding RNA species, but caution is required in making the extrapolation because the two polymers are significantly different. A number of studies point to the flexibility and malleability of branched nucleic acids, and this turns out to have particular significance in their interactions with proteins. Proteins such as the DNA junction-resolving enzymes exhibit considerable selectivity for the structure of their substrates, which is still not understood at a molecular level. Despite this, it appears to be universally true that these proteins distort the global, and in some cases at least the local, structure of the junctions. The somewhat perplexing result is that the proteins appear to distort the very property that they recognise. In general it seems that four-way DNA junctions are opened to one extent or another by interaction with proteins. (ABSTRACT TRUNCATED)

Animals↗

PubMed2002

Assessment of articular fragment displacement in acetabular fractures: a comparison of computerized tomography and plain radiographs.

OBJECTIVES: Quantitatively evaluate plain radiographs, relative to computed tomography (CT) scans, for assessment of articular fragment displacement (step and gap) in displaced acetabular fractures and in canine osteotomized acetabular specimens. DESIGN: Retrospective evaluation of a consecutive series of CT scans and plain radiographs of patients with displaced acetabular fractures and canine acetabulae osteotomized to represent acetabular fractures with displacement. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Computed tomography scans and plain radiographic images of 62 consecutive patients with displaced acetabular fractures were reviewed; 20 patients met the inclusion criteria regarding location, fracture pattern, availability of plain radiographs and CT scans, and the position of the femoral head at the time of radiographic assessment. The hemipelvi of five adult mongrels underwent osteotomy of the acetabulum and similar radiographic evaluation. INTERVENTION: Three independent reviewers measured step and gap deformity on plain radiographs and CT scans utilizing a standardized measurement technique. MAIN OUTCOME MEASUREMENTS: Sensitivity and specificity of plain radiographs for detecting step and gap displacement (2 mm and 4 mm) relative to CT scans were determined. Intraclass correlation coefficient and intraobserver reliability was also calculated. For the canine specimens, sensitivities of each imaging method were determined relative to actual fragment displacement measurements. RESULTS: In the clinical images, when compared to CT, plain radiographs showed poor sensitivity at detecting step deformity (sensitivity = 25%). When analyzed by fracture type, plain radiographs were particularly poor at detecting step deformities in fractures involving a single column of the acetabulum (sensitivity = 0%). Excellent intraobserver and intraclass reliability existed among the three reviewers. Computed tomography scans were considerably more accurate in measuring step and gap displacement relative to actual measurements than plain radiographs in the canine specimens. CONCLUSIONS: 1) Plain radiographs showed poor sensitivity for the detection of step and gap deformities in patients with acetabular fractures and in osteotomized canine specimens, relative to CT scans; 2) differences between CT and plain radiographs in both specimen types were greatest with the most clinically relevant deformity-i.e., step; and 3) CT scans are essential and should continue to be used in conjunction with plain radiographs in the preoperative evaluation of displaced acetabular fractures and perhaps should be considered in the postoperative assessment of fracture reduction.

Acetabulum↗

PubMed2003

Noninvasive and invasive micropapillary (low-grade) serous carcinoma of the ovary: a clinicopathologic analysis of 135 cases.

Reports describing the behavior of micropapillary serous carcinomas (MPSCs) of the ovary have focused on those that are noninvasive. There are only very limited data on the behavior of those that are invasive. To further characterize the behavior of MPSCs, invasive versus noninvasive primary tumors were distinguished based on the presence or absence of destructive infiltrative growth. To qualify for inclusion, invasive MPSCs, like the noninvasive tumors, were required to display a micropapillary architecture and low-grade nuclei. A total of 135 cases of MPSC were identified: 96 noninvasive and 39 invasive. On follow-up, survival for 10 patients with stage I noninvasive and invasive MPSCs was 100%, and survival for women with stage II and III noninvasive and invasive MPSCs with noninvasive implants was 80%. In contrast, the 5-year and 10-year survival for patients with stage II and III noninvasive MPSCs with invasive implants was 85% and 55%, respectively. The 5-year and 10-year survival for women with invasive MPSCs and invasive implants was 55% and 45%, respectively. The median time from diagnosis to death for women with noninvasive and invasive MPSCs with invasive implants was 60 months (range 33-240 months). The indolent behavior of these low-grade carcinomas distinguishes them from conventional serous carcinomas, which are high-grade aggressive neoplasms. Five of six patients with small (<5 mm) MPSCs in whom follow-up was available presented with high stage disease. Of these five women, three are alive and well and two are alive with disease (one with invasive and one with noninvasive implants). Nearly three fourths of noninvasive MPSCs were associated with atypical proliferative serous tumors, adenofibromas, or both, and 62% of invasive MPSCs were associated with noninvasive MPSCs, atypical proliferative serous tumors, and adenofibromas, alone or in combination. In addition to the frequent mixtures of these tumor components, transitions between them were common. These data in conjunction with recent molecular genetic studies strongly suggest that MPSCs (low-grade carcinomas) arise from atypical proliferative serous tumors unlike conventional serous carcinomas (high-grade carcinomas), which appear to develop de novo. The findings provide further support for the hypothesis that there are distinct pathways of carcinogenesis for low-grade and high-grade serous carcinoma of the ovary.

Adolescent↗

PubMed2002

Sedatives for opiate withdrawal in newborn infants.

BACKGROUND: Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. Treatments used to ameliorate symptoms and reduce morbidity include opiates, sedatives and non-pharmacological treatments. OBJECTIVES: To assess the effectiveness and safety of using a sedative compared to a non-opiate control for NAS due to withdrawal from opiates, and to determine which type of sedative is most effective and safe. SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used. This included searches of the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002) and MEDLINE 1966-2002. SELECTION CRITERIA: Trials enrolling infants with NAS born to mothers with an opiate dependence, with > 80% follow up and using random or quasi-random allocation to sedative or control. Control could include another sedative or non-pharmacological treatment. DATA COLLECTION AND ANALYSIS: Each author assessed study quality and extracted data independently. Primary outcomes included treatment failure (failure to achieve symptom control or use of additional drug treatment), seizure occurrence, mortality and neurodevelopment. Treatment effect was expressed using (RR), risk difference (RD), mean difference (MD) and weighted mean difference (WMD). Meta-analysis was performed using a fixed effect model. MAIN RESULTS: Five studies enrolling a total of 285 patients met inclusion criteria (Finnegan 1984, Kahn 1969, Kaltenbach 1986, Khoo 1995, Madden 1977); however, two (Finnegan 1984, Kaltenbach 1986) may be sequential reports that include some identical patients. Methodological concerns included the use of quasi-random rather than random patient allocation methods in three studies, and sizeable, largely unexplained differences in reported numbers allocated to each group in three studies. Phenobarbital compared to supportive care alone has not been shown to reduce treatment failure or time to regain birthweight (one study). However, the duration of supportive care required to be given to infants each day was significantly reduced (MD -162.1 minutes/day, 95% CI -249.2, -75.1). Comparing phenobarbital to diazepam, meta-analysis of two studies found that phenobarbital produced a significant reduction in treatment failure (typical RR 0.39, 95% CI 0.24, 0.62). There was no significant difference in duration of treatment or duration of hospital stay. Comparing phenobarbital with chlorpromazine, one study found no significant difference in treatment failure rate. No data for neurodevelopment were available, reported by treatment group as allocated. No trials were eligible that assessed clonidine for NAS. REVIEWER'S CONCLUSIONS: In newborn infants with NAS, there is no evidence that phenobarbital, compared with supportive care alone, reduces treatment failure; however, phenobarbital may reduce the daily duration of supportive care needed. Phenobarbital, compared to diazepam, reduces treatment failure. There is insufficient evidence to support the use of chlorpromazine or clonidine in newborn infants with NAS. Clonidine and chlorpromazine should only be used in the context of a randomised clinical trial. The results of this review, taken in conjunction with the related review, Opiate treatment for opiate withdrawal in newborn infants (Osborn 2002), indicate that treatment with opiates is the preferred initial therapy for NAS. It is hypothesised that this is particularly true for infants whose mothers have used only opiates during pregnancy. If a sedative is used, phenobarbital is preferred to diazepam. The results of an ongoing trial of the addition of phenobarbital to an opiate are awaited.

Chlorpromazine↗

PubMed2002

E. coli expression of TIMP-4 and comparative kinetic studies with TIMP-1 and TIMP-2: insights into the interactions of TIMPs and matrix metalloproteinase 2 (gelatinase A).

The inhibitory properties of TIMP-4 for matrix metalloproteinases (MMPs) were compared to those of TIMP-1 and TIMP-2. Full-length human TIMP-4 was expressed in E. coli, folded from inclusion bodies, and the active component was purified by MMP-1 affinity chromatography. Progress curve analysis of MMP inhibition by TIMP-4 indicated that association rate constants (k(on)) and inhibition constants (K(i)) were similar to those for other TIMPs ( approximately 10(5) M(-)(1) s(-)(1) and 10(-)(9)-10(-)(12) M, respectively). Dissociation rate constants (k(off)) for MMP-1 and MMP-3 determined using alpha(2)-macroglobulin to capture MMP dissociating from MMP-TIMP complexes were in good agreement with values deduced from progress curves ( approximately 10(-)(4) s(-)(1)). K(i) and k(on) for the interactions of TIMP-1, -2, and -4 with MMP-1 and -3 were shown to be pH dependent. TIMP-4 retained higher reactivity with MMPs at more acidic conditions than either TIMP-1 or TIMP-2. Molecular interactions of TIMPs and MMPs investigated by IAsys biosensor analysis highlighted different modes of interaction between proMMP-2-TIMP-2 (or TIMP-4) and active MMP-2-TIMP-2 (or TIMP-4) complexes. The observation that both active MMP-2 and inactive MMP-2 (with the active site blocked either by the propeptide or a hydroxamate inhibitor) have essentially identical affinities for TIMP-2 suggests that there are two TIMP binding sites on the hemopexin domain of MMP-2: one with high affinity that is involved in proMMP-2 or hydroxamate-inhibited MMP-2; and the other with low affinity involved in formation of the complex of active MMP-2 and TIMP-2. Similar models of interaction may apply to TIMP-4. The latter low-affinity site functions in conjunction with the active site of MMP-2 to generate a tight enzyme-inhibitor complex.

Amino Acid Sequence↗

PubMed2003

Pain associated with the sacroiliac joint region: a clinical study of 74 horses.

REASONS FOR PERFORMING STUDY: There has been no large study of horses with suspected sacroiliac (SI) joint region pain in which the clinical diagnosis has been supported by either abnormal radiopharmaceutical activity in the SI joint region or by periarticular infiltration of local anaesthetic solution. OBJECTIVES: To describe the clinical features of horses with SI joint region pain, to document the age, breed, sex, discipline, size and conformation of affected horses and to compare these with the author's (SD) normal case population and to document the results of infiltration of local anaesthetic solution around the SI joint region. METHODS: Horses were selected for inclusion in the study based upon the exclusion of other causes of lameness or poor performance, together with clinical signs suggestive of SI joint pain and abnormal radiopharmaceutical activity in the SI joint region and/or a positive response to periarticular infiltration of local anaesthetic solution. RESULTS: Sacroiliac joint region disease was identified in 74 horses between November 1997 and March 2002. Dressage and showjumping horses appeared to be at particular risk (P < 0.001). Affected horses were generally slightly older than the normal clinic population (P < 0.0001), taller at the withers (P < 0.0001) and of greater bodyweight (P < 0.01). There was a significant effect of breed (P < 0.001), with a substantially higher proportion of Warmblood horses (51%) in the SI pain group compared to the normal clinic population (29%). There was no correlation between conformation and the presence of SI joint region pain. The tubera sacrale appeared grossly symmetrical in most (95%) horses. Poor development of the epaxial muscles in the thoracolumbar region and asymmetry of the hindquarter musculature were common. Twenty-six horses (35%) showed restricted flexibility of the thoracolumbar region and 10 (16%) had an exaggerated response to pressure applied over the tubera sacrale. Fourteen horses (19%) were reluctant to stand on one hindlimb for prolonged periods. The majority of horses (75%) had a straight hindlimb flight and only 18% moved closely behind or plaited. In all horses restricted hindlimb impulsion was the predominant feature; invariably this was most obvious when the horse was ridden. Stiffness, unwillingness to work on the bit and poor quality canter were common. Sacroiliac joint region pain was seen alone (47%), or in conjunction with thoracolumbar pain (16%), hindlimb lameness (20%), forelimb lameness (7%) or a combination of problems (10%). Seventy-three horses (99%) had abnormalities of the SI joint region identified using nuclear scintigraphy. Infiltration of local anaesthetic solution around the SI joint region produced profound improvement in gait in all 34 horses in which it was performed. CONCLUSIONS AND POTENTIAL RELEVANCE: Careful clinical examination combined with scintigraphic evaluation of the SI joint region and local analgesia can enable a more definitive diagnosis of SI joint region pain than has previously been possible.

Age Factors↗

PubMed1999

Modulation of neuronal and recombinant GABAA receptors by redox reagents.

1. The functional role played by the postulated disulphide bridge in gamma-aminobutyric acid type A (GABAA) receptors and its susceptibility to oxidation and reduction were studied using recombinant (murine receptor subunits expressed in human embryonic kidney cells) and rat neuronal GABAA receptors in conjunction with whole-cell and single channel patch-clamp techniques. 2. The reducing agent dithiothreitol (DTT) reversibly potentiated GABA-activated responses (IGABA) of alpha1beta1 or alpha1beta2 receptors while the oxidizing reagent 5, 5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) caused inhibition. Redox modulation of IGABA was independent of GABA concentration, membrane potential and the receptor agonist and did not affect the GABA EC50 or Hill coefficient. The endogenous antioxidant reduced glutathione (GSH) also potentiated IGABA in alpha1beta2 receptors, while both the oxidized form of DTT and glutathione (GSSG) caused small inhibitory effects. 3. Recombinant receptors composed of alpha1beta1gamma2S or alpha1beta2gamma2S were considerably less sensitive to DTT and DTNB. 4. For neuronal GABAA receptors, IGABA was enhanced by flurazepam and relatively unaffected by redox reagents. However, in cultured sympathetic neurones, nicotinic acetylcholine-activated responses were inhibited by DTT whilst in cerebellar granule neurones, NMDA-activated currents were potentiated by DTT and inhibited by DTNB. 5. Single GABA-activated ion channel currents exhibited a conductance of 16 pS for alpha1beta1 constructs. DTT did not affect the conductance or individual open time constants determined from dwell time histograms, but increased the mean open time by affecting the channel open probability without increasing the number of cell surface receptors. 6. A kinetic model of the effects of DTT and DTNB suggested that the receptor existed in equilibrium between oxidized and reduced forms. DTT increased the rate of entry into reduced receptor forms and also into desensitized states. DTNB reversed these kinetic effects. 7. Our results indicate that GABAA receptors formed by alpha and beta subunits are susceptible to regulation by redox agents. Inclusion of the gamma2 subunit in the receptor, or recording from some neuronal GABAA receptors, resulted in reduced sensitivity to DTT and DTNB. Given the suggested existence of alphabeta subunit complexes in some areas of the central nervous system together with the generation and release of endogenous redox compounds, native GABAA receptors may be subject to regulation by redox mechanisms.

Animals↗

PubMed2004

Short- and long-term outcomes of adult audiological rehabilitation.

OBJECTIVE: To examine short- and long-term subjective benefits of providing a counseling-oriented audiological rehabilitation (AR) program as an adjunct to hearing aid intervention for individuals with adult-onset hearing loss. DESIGN: One hundred six veterans (68 men and 38 women), fit binaurally with digitally programmable analog hearing aids, participated. The Communication Profile for the Hearing Impaired (CPHI; ) was administered to all participants before hearing aid fitting. Half the patients were randomly assigned to receive hearing aids alone (i.e., control); the other patients were assigned to participate in a 4-wk group AR program in conjunction with receiving hearing aids (i.e., HA + AR). At the end of the AR program, the CPHI was again administered to all participants to assess short-term benefit and at 6 mo and 1 yr after hearing aid fitting to assess long-term benefit. RESULTS: A separate repeated-measures version of the general linear model was used to examine short- and long-term benefits for the CPHI factor scores (communication importance, communication performance, adjustment, interaction, and reaction) and for individual importance ratings and scale scores. Hearing aid use improved both short- and long-term self-perception of communication performance, with no additional benefits from participation in the AR program. Consistent with the goals of a counseling-oriented AR program, differential short-term treatment effects were found for communication strategy usage, which led to differential short-term benefits for the interaction and reaction factors. Although failing to reach strict criteria for statistical significance, there was an observable difference in short-term outcomes between the two groups for the adjustment factor, with greater improvements occurring for the HA + AR group. Over the course of the year, benefits measured for the HA + AR group remained stable, whereas scores for the control group continued to increase, resulting in no differences in factor scores between groups at 1 yr after intervention. CONCLUSIONS: The finding of a short-term differential treatment benefit for AR in terms of interaction and reaction, and possibly for adjustment, was important, as better outcomes in these areas may be important in the decision to keep hearing aids. If this is the case, then the data support the inclusion of a counseling-oriented AR program. Differential treatment effects in interaction and reaction appeared to result from communication strategy use, indicating that the AR program is meeting many of its goals in this area. The lack of long-term differential effects appeared as the result of continued changes in adjustment, interaction, and reaction with continued hearing aid experience.

Aged↗

PubMed1997

Clinical experience with epidural cooling for spinal cord protection during thoracic and thoracoabdominal aneurysm repair.

PURPOSE: This report summarizes our experience with epidural cooling (EC) to achieve regional spinal cord hypothermia and thereby decrease the risk of spinal cord ischemic injury during the course of descending thoracic aneurysm (TA) and thoracoabdominal aneurysm (TAA) repair. METHODS: During the interval July 1993 to Dec. 1995, 70 patients underwent TA (n = 9, 13%) or TAA (n = 61) (type I, 24 [34%], type II, 11 [15%], type III, 26 [37%]) repair using the EC technique. The latter was accomplished by continuous infusion of normal saline (4 degrees C) into a T11-12 epidural catheter; an intrathecal catheter was placed at the L3-4 level for monitoring of cerebrospinal fluid temperature (CSFT) and pressure (CSFP). All operations (one exception, atriofemoral bypass) were performed with the clamp-and-sew technique, and 50% of patients had preservation of intercostal vessels at proximal or distal anastomoses (30%) or by separate inclusion button (20%). Neurologic outcome was compared with a published predictive model for the incidence of neurologic deficits after TAA repair and with a matched (Type IV excluded) consecutive, control group (n = 55) who underwent TAA repair in the period 1990 to 1993 before use of EC. RESULTS: EC was successful in all patients, with a 1442 +/- 718 ml mean (range, 200 to 3500 ml) volume of infusate; CSFT was reduced to a mean of 24 degrees +/- 3 degrees C during aortic cross-clamping with maintenance of core temperature of 34 degrees +/- 0.8 +/- C. Mean CSFP increased from baseline values of 13 +/- 8 mm Hg to 31 +/- 6 mm Hg during cross-clamp. Seven patients (10%) died within 60 days of surgery, but all survived long enough for evaluation of neurologic deficits. The EC group and control group were well-matched with respect to mean age, incidence of acute presentations/aortic dissection/aneurysm rupture, TAA type distribution, and aortic cross-clamp times. Two lower extremity neurologic deficits (2.9%) were observed in the EC patients and 13 (23%) in the control group (p < 0.0001). Observed and predicted deficits in the EC patients were 2.9% and 20.0% (p = 0.001), and for the control group 23% and 17.8% (p = 0.48). In considering EC and control patients (n = 115), variables associated with postoperative neurologic deficit were prolonged (> 60 min) visceral aortic cross-clamp time (relative risk, 4.4; 95% CI, 1.2 to 16.5; p = 0.02) and lack of epidural cooling (relative risk, 9.8; 95% CI, 2 to 48; p = 0.005). CONCLUSION: EC is a safe and effective technique to increase the ischemic tolerance of the spinal cord during TA or TAA repair. When used in conjunction with a clamp-and-sew technique and a strategy of selective intercostal reanastomosis, EC has significantly reduced the incidence of neurologic deficits after TAA repair.

Adult↗

PubMed1994

Use of polymerase chain amplification reaction for the detection of adenoviruses in ocular swab specimens.

PURPOSE: To evaluate the application of polymerase chain reaction (PCR) methodology as a potential diagnostic tool for the detection of adenovirus DNA in ocular swab samples. METHODS: Oligonucleotides derived from the adenovirus hexon gene were used to amplify a 306-base pair (bp) product by PCR. Radiolabeled oligonucleotides derived from sequences within the amplified product were used as specific probes. Specificity was determined against DNA of 13 adenovirus serotypes (types 1 to 11, inclusive, and types 19 and 37) and from nonadenoviral DNAs. Limits of detection were determined by PCR amplification of known amounts of purified adenovirus serotype 2 DNA. The assay was tested on 107 ocular swab samples and correlated to results obtained from tissue culture and a commercial immunoassay (Adenoclone). RESULTS: The 306-bp PCR product was amplified from all adenovirus serotypes tested, but not from negative control DNAs. As little as 15 fg of adenovirus type 2 DNA could be detected by PCR and ethidium bromide stain. Using a simplified sample preparation procedure, 46 of 58 adenovirus culture-positive but Adenoclone-negative swabs were positive by PCR (79% sensitivity). All (11 of 11) Adenoclone-positive clinical eye swabs tested were positive by PCR (100% sensitivity). Only 1 of 38 nonadenoviral ocular swab samples was positive by PCR (97% specificity). CONCLUSIONS: PCR appeared to be highly suitable for the diagnosis of adenovirus in ocular swabs, offering important improvements in speed over tissue culture isolation and in sensitivity over immunoassay.

Acute Disease↗

PubMed2003

[Patellar tendon-bone autograft reconstruction of the anterior cruciate ligament for advanced-stage chronic anterior laxity: is an extra-articular plasty necessary? A prospective randomized study of 100 patients with five year follow-up].

PURPOSE OF THE STUDY: This prospective randomized study was conducted to analyze the anatomic and functional impact of an extra-articular lateral plasty associated with patellar tendon-bone autograft in anterior cruciate ligament reconstruction. MATERIAL AND METHODS: A consecutive series of 100 patients with grade II (Noyes classification) chronic anterior laxity confirmed on stress x-rays were included in the study. All patients had a positive Trillat-Lachman test, a direct anterior drawer at 90 degrees flexion confirmed on the lateral x-ray, and an instrumental differential laxity greater than 5 mm (manual arthrometry, Medmetric KT1000). Mean patient age was 27 years (range 16-29 years) and time from the accident to ligamentoplasty was 29 months (range 3-156 months). In the operating theater, the patients were assigned at random to two groups. Group 1 (50 patients) underwent arthroscopic free patellar tendon-bone autograft reconstruction of the anterior cruciate ligament. In the second group (50 patients) the same reconstruction was further supported by a lateral extra-articular plasty using the quadriceps tendon. All patients were followed prospectively. At 58 months follow-up (none of the patients were lost to follow-up) residual laxity (Medmetric KT1000) was noted and functional outcome was assessed using the IKDC criteria. The Aglietti method was used to assess the position of the drill holes. RESULTS: The two groups were strictly identical at inclusion. At last follow-up, the statistical analysis did not reveal any significant difference between the groups for subjective outcome, joint motion, instrumental residual laxity, meniscal stock, or radiological changes. The overall IKDC score was A or B in 80% of the patients in group 1 and 88% of the patients in group 2. Delay to resumed sports activities (about 12 months) was also equivalent in the two groups with a trend towards lower intensity and sports producing less stress on the knee. A minimally positive pivot test with no effect on stability was observed in 4 patients in group 1 (intra-articular plasty alone) and in 2 patients in group 2 (intra- and extra-articular plasty). 16% of the insufficient results (IKDC C and D) were related to repeated tears (n=8, 6 patients in group 1 and 2 patients in group 2, p=0.268), and failure (n=8, 4 in each group) due to defective motion and pain. Repeated tears were strongly correlated with incorrect drill hole position in the tibia (p=0.01) or femur (p=0.024). Despite the stabilization, radiological remodeling was observed in 31% of the patients in both groups. DISCUSSION: The results in this consecutive series of patients demonstrated the good results obtained with intra-articular ligamentoplasy using the mid third of the patellar tendon. The rate of repeated tears or minimally positive pivot tests was higher in group 1 with intra-articular plasty alone but did not reach statistical significance and was generally related to a technical error in positioning the autograft, making it difficult to draw any conclusion concerning the anatomic superiority of mixed plasty. CONCLUSION: At the current follow-up of 5 years, this study was unable to demonstrate any advantage of systematic conjunction of an extra-articular lateral support for advanced chronic anterior laxity of the knee treated by a free patellar tendon graft.

Adolescent↗

PubMed2001

The use of PVP-iodine as an adjunct to non-surgical treatment of chronic periodontitis.

OBJECTIVE: The present study was performed to assess the effect of topically-applied PVP-iodine, used as an adjunct both during basic non-surgical therapy and at re-treatment during the long-term maintenance of patients with advanced periodontal disease. MATERIAL AND METHODS: 223 patients with advanced destructive periodontitis were recruited. The participants met the following inclusion criteria: (i) a minimum of 8 non-molar teeth, (ii) probing pocket depth of > or = 6 mm at > or = 2 teeth in each dentate quadrant, and radiographic bone loss exceeding 40% at the same teeth. A baseline I examination included assessment of plaque, gingivitis, probing pocket depth (PPD), probing attachment level (PAL) and radiographic bone height (RxBL). Following baseline I, the patients were stratified into 2 treatment groups; 2 subjects out of 3 were included in a control group and 1 in a test group. All participants, on an individual basis, received a case presentation and were instructed in proper self-performed plaque control measures. Non-surgical therapy was performed by the use of an ultrasonic device. The instrumentation in the test group was combined with the administration of 0.1% PVP-iodine. All subjects were recalled for comprehensive examinations 3, 6 and 12 months (baseline II) after baseline I and then after 3, 5 and 13 years of maintenance therapy. PAL determinations were performed annually. Subjects (losers) who at the re-examinations after 1, 2 and 3 years of maintenance demonstrated an annual further loss of PAL > or = 2 mm at > or = 4 teeth were exited from the study and referred for re-treatment. There were 9 losers in the test and 31 in the control group. In addition, 8 subjects in the test and 25 subjects in the control group withdrew from the trial for reasons unrelated to the study. These 73 subjects were not included in the data presentation from the various examinations. RESULTS: It was demonstrated that non-surgical periodontal therapy resulted in (i) improved gingival conditions, (ii) reduced PPD, (iii) gain in PAL. It was also documented that the topical application of 0.1% PVP-iodine in conjunction with the mechanical root debridement established conditions which further improved the outcome of therapy. This was evidenced by the fact that at the 3, 6, and 12 months re-examinations after baseline I, the test group had significantly lower mean PPD values and significantly more gain of PAL than the control group. During the 12 years of SPT, it was possible for most subjects in both groups to maintain shallow pockets and to avoid marked further loss of PAL. There were, however, a larger number of losers in the control than in the test group. CONCLUSION: PVP-iodine, topically applied during subgingival instrumentation, may improve the outcome of non-surgical periodontal therapy.

Administration, Topical↗

PubMed1996

Expression of keratohyalin-trichohyalin hybrid granules in molluscum contagiosum.

BACKGROUND: Recently, in the filiform papillae epithelium of mouse dorsal tongue, we showed the presence of hybrid granules in which filaggrin and trichohyalin were both present, but physically segregated. Further, trichohyalin was also detected in scattered granular cells of a number of hyperplastic skin diseases. METHODS: The epidermis infected with molluscum contagiosum virus (MCV) was studied by conventional electron microscopy in conjunction with light and electron-microscopic immunohistochemistry, using both antifilaggrin and antitrichohyalin antibodies as probes. RESULTS: We found that the granular cells of MCV-infected epidermis contained both filaggrin and trichohyalin. Subsequent electron-microscopic examination showed that the granular cells contained morphologically heterogeneous granules that appeared to be composed of discrete areas of distinct electron densities. Double-labeling, using antibodies to filaggrin and trichohyalin, clearly indicated that filaggrin and trichohyalin were both present in the hybrid granules and that the electron-dense regions contained trichohyalin while the more electron-lucent regions contained filaggrin. CONCLUSIONS: The expression of trichohyalin was a common feature observed in the epidermis from a heterogenous group of hyperplastic conditions, including MCV infection. This finding has led us to speculate that trichohyalin may be specifically or preferentially involved in interacting with the hyperproliferation-related keratin pair (K6/K16), whereas the function of filaggrin is more closely linked to the skin-type keratin pair (K1/K10) that are normal keratins found in the differentiated epidermis.

Cell Differentiation↗

PubMed1999

The role of ipratropium bromide in the emergency management of acute asthma exacerbation: a metaanalysis of randomized clinical trials.

STUDY OBJECTIVE: This study was conducted to determine whether the addition of inhaled ipratropium to inhaled beta-agonist therapy is effective in the treatment of adults with acute asthma exacerbation. METHODS: Published reports of randomized, controlled trials assessing the use of ipratropium and beta-agonists in asthma were identified by a search of the MEDLINE, EMBASE, CINAHL, Biological Abstracts on CD, the Cochrane Library, and Current Contents databases. Bibliographies from identified studies and from review articles were manually searched. Published and unpublished reports in English, French, and Italian were identified and assessed for inclusion in the metaanalysis. Randomized, double-blind, placebo-controlled trials were selected in which ipratropium was used as adjunctive therapy to beta-agonists in adult patients with acute asthma exacerbation presenting to a hospital emergency department or similar acute care setting. Data were extracted independently by 2 reviewers. For eligible trials, the mean percent change in peak expiratory flow rate (PEFR), or forced expiratory volume in one second (FEV1), and their SDs were assessed in the ipratropium-treated and control groups. The effect of ipratropium on hospitalization rates and adverse effects were also analyzed. RESULTS: Data from 10 studies, reporting on a total of 1,377 patients with asthma, were pooled using a weighted average method. Compared with placebo, the use of ipratropium was associated with a pooled 7.3% improvement in FEV1 (95% confidence interval [CI] 3.8% to 10.9%), corresponding to an absolute improvement in FEV1 in the ipratropium/ beta-agonist group, which was 100 mL (95% CI 50 to 149 mL) above that seen for the group that received beta-agonist without ipratropium. Similarly, the pooled estimate of treatment effect in trials that reported data as PEFR was 22.1% (95% CI 11.0% to 33.2%), corresponding to an absolute peak expiratory flow improvement of 32 L/min (95% CI 16 to 47 L/min) in favor of the ipratropium/ beta-agonist combination group. When these data were combined using effect size as a common measure, the use of ipratropium was associated with a summary effect size of.38 (95% CI.27 to.48). Effect sizes were negatively correlated with baseline mean expiratory flows, suggesting that studies enrolling patients with more severe airflow obstruction showed greater absolute benefits of combination bronchodilator therapy. For the 3 trials reporting hospital admission data (n=1,031), patients receiving ipratropium had a relative risk of hospitalization of .73 (95% CI.53 to .99). The use of ipratropium was not associated with any severe adverse effects when used in conjunction with beta2 -agonists. CONCLUSION: There is a modest statistical improvement in airflow obstruction when ipratropium is used as an adjunctive treatment to beta2 -agonists for the treatment of acute asthma exacerbation. Although the clinical significance of this improvement in airflow obstruction remains unclear, it would seem reasonable to recommend the use of combination ipratropium/ beta-agonist therapy in acute adult asthmatic exacerbations, since the addition of ipratropium seemed to provide physiologic evidence of benefit without risk of adverse effects.

Acute Disease↗

PubMed2000

Anterior ocular infections: an overview of pathophysiology and treatment.

OBJECTIVE: To provide a review of the pathophysiology and treatment of anterior ocular infections. DATA SOURCE: A MEDLINE search (from 1970 to October 1998) as well as a review of the tertiary literature was performed to identify pertinent literature on pathophysiology and treatment of ocular infections. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Relevant studies were selected for discussion in the article. DATA SYNTHESIS: Ocular infections are common and vary from self-limiting to sight-threatening. Infections occur in different eye structures; presentation and treatment vary accordingly. Infections can occur when tissues of the eye are exposed to pathogens not normally present, when the eye is damaged, allowing pathogens to overcome the natural defenses of the eye, or in immunosuppressed patients where normal flora may become opportunistic. In deciding on appropriate treatment, both the causative pathogen and the structure(s) affected must be considered. The most likely pathogen can often be determined based on clinical signs and symptoms, patient history, or, in some cases, may need to be determined microbiologically. Differences in drug absorption, penetration, and availability to the various structures of the eye affect treatment decisions. Severity of infection, efficacy and safety of medication, and cost/benefit ratios must be taken into consideration in choosing the proper pharmacologic management of various ocular infections. CONCLUSIONS: Treatment of ocular infections depends on knowledge of the pathophysiology and drug disposition at the site of infection. An understanding of the current concepts surrounding the management of the anterior ocular infections presented will aid in the provision of optimal patient care.

Anterior Chamber↗

PubMed2004

Review of guidelines for good practice in decision-analytic modelling in health technology assessment.

OBJECTIVES: To identify existing guidelines and develop a synthesised guideline plus accompanying checklist. In addition to provide guidance on key theoretical, methodological and practical issues and consider the implications of this research for what might be expected of future decision-analytic models. DATA SOURCES: Electronic databases. REVIEW METHODS: A systematic review of existing good practice guidelines was undertaken to identify and summarise guidelines currently available for assessing the quality of decision-analytic models that have been undertaken for health technology assessment. A synthesised good practice guidance and accompanying checklist was developed. Two specific methods areas in decision modelling were considered. The first method's topic is the identification of parameter estimates from published literature. Parameter searches were developed and piloted using a case-study model. The second topic relates to bias in parameter estimates; that is, how to adjust estimates of treatment effect from observational studies where there are risks of selection bias. A systematic literature review was conducted to identify those studies looking at quantification of bias in parameter estimates and the implication of this bias. RESULTS: Fifteen studies met the inclusion criteria and were reviewed and consolidated into a single set of brief statements of good practice. From this, a checklist was developed and applied to three independent decision-analytic models. Although the checklist provided excellent guidance on some key issues for model evaluation, it was too general to pick up on the specific nuances of each model. The searches that were developed helped to identify important data for inclusion in the model. However, the quality of life searches proved to be problematic: the published search filters did not focus on those measures specific to cost-effectiveness analysis and although the strategies developed as part of this project were more successful few data were found. Of the 11 studies meeting the criteria on the effect of selection bias, five concluded that a non-randomised trial design is associated with bias and six studies found 'similar' estimates of treatment effects from observational studies or non-randomised clinical trials and randomised controlled trials (RCTs). One purpose of developing the synthesised guideline and checklist was to provide a framework for critical appraisal by the various parties involved in the health technology assessment process. First, the guideline and checklist can be used by groups that are reviewing other analysts' models and, secondly, the guideline and checklist could be used by the various analysts as they develop their models (to use it as a check on how they are developing and reporting their analyses). The Expert Advisory Group (EAG) that was convened to discuss the potential role of the guidance and checklist felt that, in general, the guidance and checklist would be a useful tool, although the checklist is not meant to be used exclusively to determine a model's quality, and so should not be used as a substitute for critical appraisal. CONCLUSIONS: The review of current guidelines showed that although authors may provide a consistent message regarding some aspects of modelling, in other areas conflicting attributes are presented in different guidelines. In general, the checklist appears to perform well, in terms of identifying those aspects of the model that should be of particular concern to the reader. The checklist cannot, however, provide answers to the appropriateness of the model structure and structural assumptions, as these may be seen as a general problem with generic checklists and do not reflect any shortcoming with the synthesised guidance and checklist developed here. The assessment of the checklist, as well as feedback from the EAG, indicated the importance of its use in conjunction with a more general checklist or guidelines on economic evaluation. Further methods research into the following areas would be valuable: the quantification of selection bias in non-controlled studies and in controlled observational studies; the level of bias in the different non-RCT study designs; a comparison of results from RCTs with those from other non-randomised studies; assessment of the strengths and weaknesses of alternative ways to adjust for bias in a decision model; and how to prioritise searching for parameter estimates.

Benchmarking↗

PubMed2005

Sedatives for opiate withdrawal in newborn infants.

BACKGROUND: Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. Treatments used to ameliorate symptoms and reduce morbidity include opiates, sedatives and non-pharmacological treatments. OBJECTIVES: To assess the effectiveness and safety of using a sedative compared to a non-opiate control for NAS due to withdrawal from opiates, and to determine which type of sedative is most effective and safe. SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used. This update included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005), MEDLINE 1966-March 2005 and abstracts of conference proceedings. SELECTION CRITERIA: Trials enrolling infants with NAS born to mothers with an opiate dependence, with > 80% follow up and using random or quasi-random allocation to sedative or control. Control could include another sedative or non-pharmacological treatment. DATA COLLECTION AND ANALYSIS: Each author assessed study quality and extracted data independently. Primary outcomes included treatment failure (failure to achieve symptom control or use of additional drug treatment), seizure occurrence, mortality and neurodevelopment. Treatment effect was expressed using (RR), risk difference (RD), mean difference (MD) and weighted mean difference (WMD). Meta-analysis was performed using a fixed effect model. MAIN RESULTS: Six studies enrolling a total of 305 patients met inclusion criteria (Coyle 2002; Finnegan 1984; Kahn 1969; Kaltenbach 1986; Khoo 1995; Madden 1977); however, two (Finnegan 1984; Kaltenbach 1986) may be sequential reports that include some identical patients. Methodological concerns included the use of quasi-random allocation methods in four studies, and sizeable, largely unexplained differences in reported numbers allocated to each group in three studies. Phenobarbitone compared to supportive care alone has not been shown to reduce treatment failure or time to regain birthweight (one study). However, the duration of supportive care given to infants was significantly reduced (MD -162.1 mins/day, 95% CI -249.2, -75.1). Comparing phenobarbitone to diazepam, meta-analysis of two studies found phenobarbitone produced a significant reduction in treatment failure (typical RR 0.39, 95% CI 0.24, 0.62). There was no significant difference in duration of treatment or hospital stay. Comparing phenobarbitone with chlorpromazine, one study found no significant difference in treatment failure rate. No data for neurodevelopment reported by treatment group of allocation were available. No trials were eligible that assessed clonidine for NAS. In infants treated with an opiate, a small quasi-random study reported a reduced severity of withdrawal. Infants were weaned from an opiate more quickly which allowed earlier hospital discharge and reduced hospital costs. These findings may reflect the low dose of opiate used for initial treatment and the policy of discharging infants home on phenobarbitone but not morphine. AUTHORS' CONCLUSIONS: In newborn infants with NAS, there is no evidence that phenobarbitone compared with supportive care alone reduces treatment failure; however, phenobarbitone may reduce the daily duration of supportive care needed. Phenobarbitone, compared to diazepam, reduces treatment failure. In infants treated with an opiate, the addition of phenobarbitone may reduce withdrawal severity. Further trials are required to determine if this finding is applicable when a higher initial dose of opiate is used, and determine the effects of phenobabritone on infant development. There is insufficient evidence to support the use of chlorpromazine or clonidine in newborn infants with NAS. Clonidine and chlorpromazine should only be used in the context of a randomised clinical trial. This review should be taken in conjunction with the review "Opiate treatment for opiate withdrawal in newborn infants" (Osborn 2002a) which indicates that an opiate is the preferred initial therapy for NAS.

Chlorpromazine↗