In-vivo monitoring of acute DSS-Colitis using Colonoscopy, high resolution Ultrasound and bench-top Magnetic Resonance Imaging in Mice.

OBJECTIVE: The aim of this study was to establish and evaluate (colour Doppler-) high-resolution-ultrasound (hrUS) and bench-top magnetic resonance imaging (btMRI) as new methods to monitor experimental colitis. MATERIALS AND METHODS: hrUS, btMRI and endoscopy were performed in mice without colitis (n = 15), in mice with acute colitis (n = 14) and in mice with acute colitis and simultaneous treatment with infliximab (n = 19). RESULTS: Determination of colon wall thickness using hrUS (32 MHz) and measurement of the cross-sectional colonic areas by btMRI allowed discrimination between the treatment groups (mean a vs. b vs. c - btMRI: 922 vs. 2051 vs. 1472 pixel, hrUS: 0.26 vs. 0.45 vs. 0.31 mm). btMRI, endoscopy, hrUS and colour Doppler-hrUS correlated to histological scoring (p < 0.05), while endoscopy and btMRI correlated to post-mortem colon length (p < 0.05). CONCLUSIONS: The innovative in vivo techniques btMRI and hrUS are safe and technically feasible. They differentiate between distinct grades of colitis in an experimental setting, and correlate with established post-mortem parameters. In addition to endoscopic procedures, these techniques provide information regarding colon wall thickness and perfusion. Depending on the availability of these techniques, their application increases the value of in vivo monitoring in experimental acute colitis in small rodents. KEY POINTS: • Improved in vivo monitoring might balance interindividual differences in murine colitis. • In monitoring murine colitis, btMRI and hrUS are safe and technically feasible. • Very short examination times underline the usefulness especially of hrUS. • Results of btMRI and hrUS correlate with endoscopic and post-mortem findings.

Mechanistic analysis of PLGA/HPMC-based in-situ forming implants for periodontitis treatment.

In-situ forming implant formulations based on poly(lactic-co-glycolic acid) (PLGA), acetyltributyl citrate (ATBC), minocycline HCl, N-methyl pyrrolidone (NMP) and optionally hydroxypropyl methylcellulose (HPMC) were prepared and thoroughly characterized in vitro. This includes electron paramagnetic resonance (EPR), nuclear magnetic resonance ((1)H NMR), mass change and drug release measurements under different conditions, optical microscopy, size exclusion chromatography (SEC) as well as antibacterial activity tests using gingival crevicular fluid samples from periodontal pockets of periodontitis patients. Based on these results, deeper insight into the physico-chemical phenomena involved in implant formation and the control of drug release could be gained. For instance, the effects of adding HPMC to the formulations, resulting in improved implant adherence and reduced swelling, could be explained. Importantly, the in-situ formed implants effectively hindered the growth of bacteria present in the patients' periodontal pockets. Interestingly, the systems were more effectively hindering the growth of pathogenic bacterial strains (e.g., Fusobacterium nucleatum) than that of strains with a lower pathogenic potential (e.g., Streptococcus salivarius). In vivo, such a preferential action against the pathogenic bacteria can be expected to give a chance to the healthy flora to re-colonize the periodontal pockets.

In-situ forming composite implants for periodontitis treatment: How the formulation determines system performance.

Periodontitis is the primary cause of tooth loss in adults and a very wide-spread disease. Recently, composite implants, based on a drug release rate controlling polymer and an adhesive polymer, have been proposed for an efficient local drug treatment. However, the processes involved in implant formation and the control of drug release in these composite systems are complex and the relationships between the systems' composition and the implants' performance are yet unclear. In this study, advanced characterization techniques (e.g., electron paramagnetic resonance, EPR) were applied to better understand the in-situ forming implants based on: (i) different types of poly(lactic-co-glycolic acid) (PLGA) as drug release rate controlling polymers; (ii) hydroxypropyl methylcellulose (HPMC) as adhesive polymer; and (iii) doxycycline or metronidazole as drugs. Interestingly, HPMC addition to shorter chain PLGA slightly slows down drug release, whereas in the case of longer chain PLGA the release rate substantially increases. This opposite impact on drug release was rather surprising, since the only difference in the formulations was the polymer molecular weight of the PLGA. Based on the physico-chemical analyses, the underlying mechanisms could be explained as follows: since longer chain PLGA is more hydrophobic than shorter chain PLGA, the addition of HPMC leads to a much more pronounced facilitation of water penetration into the system (as evidenced by EPR). This and the higher polymer lipophilicity result in more rapid PLGA precipitation and a more porous inner implant structure. Consequently, drug release is accelerated. In contrast, water penetration into formulations based on shorter chain PLGA is rather similar in the presence and absence of HPMC and the resulting implants are much less porous than those based on longer chain PLGA.

Hierarchy of characteristics associated with depressive symptoms in an urban elderly sample.

In contrast to the uncertainty about the prevalence and importance of late-life depressive disorders, a consistent pattern of risk factors for depressive symptoms has been shown by studies using the Center for Epidemiologic Studies Depression Scale (CES-D). The authors surveyed a representative sample of 2,137 elderly community residents with the CES-D and found a hierarchy of characteristics associated with substantial levels of depressive symptoms: illness, disability, isolation, bereavement, and poverty. If these findings are confirmed by prospective studies, addressing modifiable factors in the emergence, persistence, and remission of depressive symptoms might extend the independent survival of older adults.

Calibration of saccades in infants.

Prism induced shift of fixation was measured in 12 cooperative patients utilizing electro-oculography. These recordings were compared with a voluntary shift in fixation of the same eye. No differences were noted when comparing voluntary movements with prism induced movements. Trial of the prism induced eye movement for calibration in a group of 10 infants has shown it can be used successfully.

Double elevator palsy.

Of 15 patients with monocular limitation of elevation, six had no deviation in primary gaze while the remaining nine had hypotropia of the involved eye. Twelve of 15 patients had restriction to upgaze on forced duction testing. Eleven of these 12 had normal upward saccadic velocity, which suggested normal elevator function. Four patients had reduced saccadic velocity, which indicated true elevator weakness. Superior rectus muscle paresis alone could account for limited elevation and would reduce upward saccadic speed. Patients with a diagnosis of "double elevator palsy" only infrequently (about one quarter of cases) have palsy of an elevator muscle and may have only a single elevator palsy. The identification of a true elevator weakness is most important in planning management.

Saccadic velocity studies in superior oblique palsy.

Eighteen patients (21 eyes) with superior oblique palsy had vertical saccadic velocity measurements in primary gaze, adduction, and abduction. No noticeable difference was found when upward saccades were compared with downward saccades in all fields of gaze. Thus, saccadic velocity studies would not be helpful in the diagnosis of superior oblique palsy.

Saccades with limited downward gaze.

Fourteen patients with monocular limitation of downward gaze had vertical saccadic velocity measurements. Patients with orbital floor fracture and endocrine ophthalmopathy were excluded from the group. In four cases (29%), the difference between upward downward saccadic velocities was 20% or less. These patients were not thought to have any evidence of inferior rectus muscle paresis. In ten cases (71%), the difference between upward and downward saccades varied between 46% to 275% (average, 115%), upward saccades being more rapid in each case. These cases were all believed to have moderate to great inferior rectus muscle palsy. In one subject with a lidocaine hydrochloride-induced inferior rectus muscle palsy, upward saccades were 135% faster than downward saccades. These findings were compared with those in patients with monocular limitation of elevation, and the surgical management was reviewed.

The adjustable Harada-Ito procedure.

In four patients with superior oblique palsy, symptomatic excyclotorsion was present without a substantial vertical deviation. Surgery of anteriorizing and lateralizing the anterior fibers of the superior oblique tendon on an adjustable suture was performed (adjustable Harada-Ito procedure). the morning after surgery, adjustment of the suture was made to eliminate the torsional deviation. The suture was loosened when an overcorrection was present and was tightened when an undercorrection was present. Follow-up varied from two to 20 months. All patients remained free of torsional symptoms and no vertical deviation was induced. In addition, the eyes operated on had no limitation of elevation in adduction. The technique allows the surgeon to more exactly adjust the advanced fibers of the superior oblique tendon so as to minimize or eliminate the excyclotorsion and eliminate symptomatic complaints.

The treatment of A and V patterns by monocular surgery.

Eleven patients with "A" or "V" pattern strabismus and the absence of notable oblique muscles overactions, were operated on, using the technique of monocular vertical displacement of the horizontal rectus muscles. The average correction of the A or V pattern was 16.5 delta. Subjective torsional complaints were not reported by any of the patients. Torsion was measured postoperatively with the Maddox rod, Maddox wing, and amblyoscope. The average torsional measurement, at least one month postoperatively, was 1.6 degrees with a range of 0 degrees to 7 degrees. It was concluded that monocular vertical displacement of the horizontal rectus muscles can result in satisfactory correction of the A or V pattern and produces no substantial postoperative torsional symptoms or substantial measured torsion at both distance and near fixation.

A model for eye muscle surgery.

An inexpensive model for demonstrating and practicing strabismus surgery is described here. The figure-of-8 technique, adjustable rectus recession and resection surgery, and various types of conjunctival closure have been performed on the model. The model can also be helpful in demonstrating and practicing typical recession, resection, advancement, tucking, and marginal myotomy procedures to residents in ophthalmology.

Adjustable rectus muscle recession surgery. A follow-up study.

Fifty-six patients underwent an adjustable rectus muscle recession procedure. This procedure permits the surgeon to enhance or diminish the amount of muscle recession on the evening after surgery or the first postoperative day if cover-testing indicates an inappropriate amount of undercorrection or overcorrection. The adjustable rectus muscle recession technique seems to be a practical and effective means to change the strabismic deviation postoperatively. The procedure requires patient cooperation and is most suitable for patients age 15 years and older. The procedure has been effective in altering the angle of deviation, and this alteration has been stable during the follow-up period in most cases. In this initial series, the reoperation rate was low, postoperative alignment was excellent, and complications were minimal.

Restrictive factors in strabismus.

Either muscle weakness (paresis) or mechanical restrictions can account for diminished ocular rotation. In practice, restrictions are more commonly seen. The forced duction test, differential intraocular pressure measurement and saccadic velocity studies can all assist in documenting the presence of restriction. Restrictions frequently occur with orbital floor fracture, endocrine ophthalmopathy and Brown's syndrome, and following multiple stabismus procedures, orbital or retinal detachment surgery, or muscle transposition surgery. They also occur as a result of antagonist muscle contracture after rectus muscle palsy or they may be due to orbital tumor or inflammation.

Saccadic velocity measurements in internuclear ophthalmoplegia.

Five patients with internuclear ophthalmoplegia had horizontal saccades measured by electro-oculography. In all patients, abduction saccadic velocities were normal while adduction saccades were slowed either binocularly or monocularly. In one patient, adduction saccades were reduced in velocity, even though full adduction was present. Saccadic velocity measurements may be helpful in diagnosing internuclear ophthalmoplegia, especially in the early or subclinical case. As bilateral internuclear ophthalmoplegia frequently suggests multiple sclerosis, prolonged examination with more sophisticated and difficult diagnostic tests is avoided.

Treatment of unilateral acute sixth-nerve palsy with botulinum toxin.

We studied 29 consecutive patients with acute unilateral sixth-nerve palsy, who received botulinum toxin injection to the antagonist medial rectus muscle. The average interval between onset of palsy and treatment was 40 days and the mean follow-up from the last injection was 14 months. Before treatment, esotropia in the primary position ranged from 12 to 45 prism diopters and limitation to abduction in the affected eye ranged from -2 (approximately 15 degrees lateral to midline) to -6 (15 degrees nasal to midline). After treatment, 22 of 29 patients (76%) had complete recovery of motility as determined by version testing. Of the seven patients with a residual abduction deficit, two had fusion in the primary position, three had fusion with prismatic correction, and two patients required subsequent surgery. Botulinum toxin injection seems to be an effective treatment option in cases of acute unilateral sixth-nerve palsy.

Change in the cycle of circadian strabismus.

PURPOSE/METHODS: We observed a change in the typical circadian, 24-hour pattern of strabismus (esotropia) in a 2-year-old patient. Methods used include study of the history of the deviation pattern, observation, and measurement of the deviation on the day after travel and six weeks later. RESULTS/CONCLUSIONS: The patient responded to standard recession-resection surgery with a straight eye position daily, through three months of follow-up. Rapid travel over six time zones probably caused the change in the circadian pattern of strabismus.

Strabismus and pseudostrabismus with retrolental fibroplasia.

Three patients with temporal displacement of the macular secondary to retrolental fibroplasia had true strabismus in associations with amblyopia and pseudostrabismus related to a large, positive angle kappa. In one case, a headturn associated with the neutral point of nystagmus was also a presenting problem. Ocular deviation was measured by the light reflex test and the prism cover test, with particular attention paid to adequate cosmetic alignment. Large amounts of prism placed before the fixating eye resulted in loss of visual acuity, while eyes placed in a parallel position by surgical means may not appear to be straight. Thus, surgery can result in parallel ocular alignment while prismatic therapy may be required to center the pupillary light reflex and to provide satisfactory cosmetic appearance.

Horizontal saccadic velocities in Duane's syndrome.

Horizontal ocular saccadic velocities were measured by electro-oculography in 33 patients with Duane's syndrome. In 28 patients with limited abduction associated with retraction on adduction (Type 1), abduction saccadic velocity was markedly reduced while adduct-on saccades were moderately slow. In three patients with exotropia and good abduction but associated limited adduction and retraction on adduction (Type 2), abduction velocity was good, while adduction saccadic speed was slow. In two patients with limited abduction and adduction with retraction on adduction (Type 3), abduction and adduction saccadic velocity was appreciably slow. Ocular electromyographic testing selected patients indicated that slow abduction saccades could be explained by absence of lateral rectus muscle recruitment, while slow adduction saccadic speed could be explained by paradoxical innervation of the lateral rectus muscle.

Redox potential measurements of plasma in patients undergoing coronary artery bypass graft and its clinical significance.

The apparent redox potentials (Em) of plasma as a marker of oxidant injury during coronary artery bypass graft (CABG) is determined, and their clinical significance is discussed. We measured plasma Em of normal volunteers (n = 20) and samples drawn at different time points from patients undergoing elective CABG (n = 60) directly and by adding 5 microl (20 mM) oxidants or reductants with known redox potential to plasma (95 microl), using a micro Pt/AgCl combination redox electrode. The Em value stays elevated up to 30 min during the surgery, after the administration of protamine it came down toward a more reduced state. Similar changes are seen with the lactate pyruvate ratio. Smaller changes of Em than normal are observed in plasma samples from patients treated with Aprotinin (antiprotease), Carmeda (heparin-coated) circuit and aspirin reflecting their protective effect. Redox potential (Em) measurements appear to be effective and useful in monitoring redox shifts wherever oxidative stress needs to be monitored.

The O'Connor cinch revisited.

The modified O'Connor cinch operation is a useful, but little used, adjustable resection operation. For increased understanding of its shortening and adjustment characteristics, a standard cinch was performed in animals and patients with strabismus. Animal studies showed that, as each strand of the cinch was removed, a small, relatively equal release of the cinch effect occurred. Measurement of the shortening obtained in patients with strabismus showed a consistent resection effect of about 4 mm. Review of 17 cases in which the cinch was used as part of the surgical treatment showed the technique to be adjustable by reducing the overcorrection in 6 cases. Ten to 20 prism dioptres of reduction in the deviation was obtained with adjustment of the cinch on the first postoperative day. All 17 cases had satisfactory adjustment. The largest residual deviation was 12 prism dioptres.