Three-dimensional ultrashort echo time (3D UTE) MRI of Achilles tendon at 4.7T MRI with comparison to conventional sequences in an experimental murine model of spondyloarthropathy.

BACKGROUND: Due to the very short T2 of its components, the normal anatomy of Achilles enthesis is impossible to define with "conventional" long echo time (TE) T2 sequences. However, this is a common site affected by rheumatologic disease. Early abnormalities related to inflammatory processes are impossible to detect in this location. PURPOSE: To assess the feasibility of a 3D-UTE (ultrashort echo time) sequence to evaluate normal and pathological Achilles entheses, determining both anterior fibrocartilaginous and posterior collagenic portions at 4.7T, in a rat model of spondyloarthropathy (SpA) with histological correlation. To assess whether this sequence detects SpA enthesopathy prior to long TE T2 sequences, enabling disease monitoring. STUDY TYPE: Prospective case-control study. ANIMAL MODEL: Twelve immunocompetent Wistar male rats imaged before (controls); the model was induced in eight rats (16 tendons) imaged at day 6, day 13, and day 21 with regular sacrifice for ex vivo imaging and histological correlation. FIELD STRENGTH: 4.7T Bruker Biospec Systems. 3D balanced steady-state free precession (bSSFP) and 3D-UTE sequences, performed at baseline (day 0, n = 12 animals / 24 tendons), day 6 (n = 8/16), 13 (n = 4/8), and day 21 (n = 2/4). ASSESSMENT: Visual analysis and signal intensity measurements (signal to noise ratio, SNR) of both bSSFP and UTE images were performed by two independent musculoskeletal radiologists at different locations of the Achilles enthesis and preinsertional area. STATISTICAL TESTS: Normal and pathological rat values were compared by Wilcoxon signed-rank tests, as well as interobserver differences. MRI findings were compared against histological data. RESULTS: The 3D-UTE sequence identified the anterior fibrocartilage and posterior collagenic areas of Achilles entheses in all cases. Visual analysis and signal intensity measurements distinguished SpA-affected entheses from healthy ones at days 6 and 13 (P = 0.002 and P = 0.006, respectively). Neither the normal anatomy of the enthesis nor its pathological pattern could be identified on T2 bSSFP sequences. DATA CONCLUSION: Unlike bSSFP T2 sequences, 3D-UTE sequences enable visualization of normal enthesis anatomy and early detection of abnormalities in pathological conditions. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:127-135.

Reproducibility of low-dose stereography measurements of femoral torsion after IM nailing of femoral shaft fractures and in intact femurs.

INTRODUCTION: Rotational malunion is a complication of intramedullary (IM) nailing for femur fractures. Symptoms can appear with 15° or more of axial deformity. None of the currently available measurement methods have a satisfactory reliability/irradiation ratio. The purpose of this study was to study the reproducibility of measuring femoral torsion with an EOS(®) low-dose stereography (LDX) system. HYPOTHESIS: LDX is a reproducible method for measuring post-traumatic femoral torsion. MATERIAL AND METHODS: The intra- and inter-observer reproducibility was studied in 45 patients who had a femoral fracture treated by IM nailing. Both the injured and contralateral healthy femurs were modelled. Bland-Altman plots were used to analyze the measurements made by three different observers (two orthopedic surgeons and one radiologist). For a given comparison, the interval between the upper limit of agreement (ULA) and lower limit of agreement (LLA) had to be within [-5°; 5°] for the examination to qualify as reproducible. Measurements were made by three observers (A, B, C) on the injured and healthy femur. RESULTS: With the fractured femurs (n=39), the intra-observer [LLA; ULA] interval was [-16.295; 12.977]; it was [-18.475; 16.744] for the A-B pairing, [-13.316; 13.532] for the B-C pairing and [-17.839; 19.355] for the A-C pairing. With the healthy femurs (n=37), the intra-observer [LLA; ULA] interval was [-7.909; 7.88]; it was [-11.924; 11.639] for the A-B pairing, [-12.654; 11.93] for the B-C pairing and [-11; 12.009] for the A-C pairing. DISCUSSION: The [LLA; ULA] intervals were greater than the [-5; +5] interval in all cases. LDX reproducibility is not sufficient for measuring femoral torsion after fracture or in healthy femurs. Observer experience, cohort size and the perfectible image quality are likely sources of bias. Conversely, the use of Bland-Altman plots and the multidisciplinary training of observers are major strengths of this study. Reproducibility will likely improve as the software is developed further and the image acquisition improves.

Bisphosphonate therapy for unresectable symptomatic benign bone tumors: a long-term prospective study of tolerance and efficacy.

OBJECTIVES: To evaluate the long-term tolerance of bisphosphonates proposed as an alternative therapeutic option for symptomatic unresectable benign bone tumors and to evaluate the long-term efficacy of this treatment. METHODS: From March 2007 to March 2011, patients with unresectable symptomatic benign bone tumors were consecutively included in this institutional review board-approved study and treated with bisphosphonates. Prospectively long-term follow-up is reported. The study endpoints were to describe the long-term tolerance, the clinical evolution of pain for each patient and the radiological success defined as a complete disappearance of inflammation and ossification of the bone lesion. All complications and side effects were recorded. RESULTS: Eight patients (mean age 16 years; range 7-42) with various tumor subtypes were included: aneurysmal bone cysts (N=5), Langerhans cell histiocytosis (N=1), osteoblastoma (N=1), and a giant cell tumor (N=1). Tumors were located in cervical (N=4) or thoracic (N=1) vertebrae, femoral shaft (N=1), acetabulum (N=1) and sacrum (N=1). Mean number of bisphosphonate cycles was 3 (range: 1-6) over a median period of 10 months. The median clinical and imaging follow-up period was 21 months (6 to 63 months). No severe complications due to treatment or lesion recurrence were reported. Pain disappeared within 6 weeks of the first cycle for all but one patient. Ossification of the bone lesion was observed for all patients but one, complete for two and partial for the five others. CONCLUSIONS: Bisphosphonates appear to be an effective option without adverse effects for the non-operative management of symptomatic benign bone tumors.

Radiologically guided percutaneous cryotherapy for soft tissue tumours: A promising treatment.

Studies of percutaneous cryotherapy in the treatment of benign or malignant soft tissue tumours are rare and mainly involve small populations. Nevertheless, results show cryotherapy's potential in terms of local control of tumours, analgesic efficacy, reduced intra- and postoperative complications, and reduction in the length of convalescence after the procedure. The objective of this update is to set out the short-term prospects for this technique in the treatment of soft tissue tumours, so that it may be more widely offered in these indications.

Quality control of colonoscopy procedures: a prospective validated method for the evaluation of professional practices applicable to all endoscopic units.

OBJECTIVES: To produce valid information, an evaluation of professional practices has to assess the quality of all practices before, during and after the procedure under study. Several auditing techniques have been proposed for colonoscopy. The purpose of this work is to describe a straightforward original validated method for the prospective evaluation of professional practices in the field of colonoscopy applicable in all endoscopy units without increasing the staff work load. METHODS: Pertinent quality-control criteria (14 items) were identified by the endoscopists at the Cochin Hospital and were compatible with: findings in the available literature; guidelines proposed by the Superior Health Authority; and application in any endoscopy unit. Prospective routine data were collected and the methodology validated by evaluating 50 colonoscopies every quarter for one year. RESULTS: The relevance of the criteria was assessed using data collected during four separate periods. The standard checklist was complete for 57% of the colonoscopy procedures. The colonoscopy procedure was appropriate according to national guidelines in 94% of cases. These observations were particularly noteworthy: the quality of the colonic preparation was insufficient for 9% of the procedures; complete colonoscopy was achieved for 93% of patients; and 0.38 adenomas and 0.045 carcinomas were identified per colonoscopy. CONCLUSION: This simple and reproducible method can be used for valid quality-control audits in all endoscopy units. In France, unit-wide application of this method enables endoscopists to validate 100 of the 250 points required for continuous medical training. This is a quality-control tool that can be applied annually, using a random month to evaluate any changes in routine practices.

Inputs to nucleus pontis caudalis from adjacent trigeminal areas.

Recent studies suggest that the nucleus pontis caudalis (nPontc) plays a role in patterning mastication through interactions with the adjacent lateral tegmentum. In this study, we used in vitro intracellular recording and staining to describe the basic membrane properties and morphology of nPontc neurones and to further explore interactions with adjacent structures, using coronal sections of the brainstem of 78 rats, aged 9-28 days. Neurones were large, with dendrites that spread in all directions, and about 64% fired tonically even in the absence of synaptic inputs. Tonic neurones were predominant in the centre of the nucleus. Electrical stimulation of all regions of the nPontc produced mixed excitatory and inhibitory effects on interneurones of lateral tegmental nuclei. Focal inactivation of the dorsal nPontc with injections of tetrodotoxin also had mixed effects on the spontaneous firing of both interneurones and motoneurones but similar injections in the ventral nPontc produced mostly increases of firing. Sixty-five percent of nPontc neurones received synaptic inputs from the lateral tegmental areas and most of these (68%) were excitatory and mediated by glutamatergic receptors. Inhibitory postsynaptic potentials were mediated by GABA(A) or glycinergic receptors. Although most responses occurred at relatively long latencies (> 2 ms), they could follow relatively high-frequency stimulation (> 50 Hz). Excitatory and inhibitory connections between ipsi- and contralateral nPontc neurones were also documented, which could contribute to bilateral coordination of jaw movements. This study provides evidence that the nPontc exerts both tonic and phasic influences on the premotor components of the masticatory central pattern generator.

Long-term cholinergic enhancement of evoked potentials in rat hindlimb somatosensory cortex displays characteristics of long-term potentiation.

Pairing a cutaneous electrical stimulus of the hind-paw with stimulation of the basal forebrain produces long-term cholinergic enhancement of the responsiveness to a tactile stimulus. A short period of pairing (20 trials) increased the area of the two main components of the evoked potential by 37.1 +/- 13.5% (+/- SEM) and 37.9 +/- 6.8%, respectively. The effects lasted for the duration of the experiment (> 2 h). The enhancement could be blocked by either MK-801, an NMDA receptor antagonist or by L-NAME, a nitric-oxide-synthase inhibitor when they were given prior to pairing. Control experiments with skin stimulation alone and basal forebrain stimulation alone had only small long-term effects (approximately 10%) on the size of the evoked potential. Thus, long-term cholinergic enhancement, attributable to disinhibition and increased release of acetylcholine in the cortex during neuronal excitation by other sources, and so named because it is blocked by atropine, may be a form of long-term potentiation. The existence of such a mechanism for the control of cortical neuronal plasticity identifies the basal forebrain as a powerful modulator of long-lasting changes in cortical neuronal excitability.

In vitro immunization of patient T cells with autologous bone marrow antigen presenting cells pulsed with tumor lysates.

Presentation of cell-associated antigen to T cells is a critical event in the initiation of an anti-tumor immune response but it appears to often be deficient or limiting. Here we report an experimental system for stimulation of human T lymphocytes using autologous antigen presenting cells (APCs) and autologous tumor cells. Two types of APCs were prepared from human bone marrow: MC and DC. MC were produced by using GM-CSF and SCF. DC were obtained with the same cytokines plus IL-4. DC and MC were generated in parallel from the same patients and their phenotypes and capacities to prime T lymphocytes were analyzed and compared. MC were CD14+, CD1a-, CD33+ and HLA-DR+. Two populations of DC were defined: immature DC were uniformly CD1a-; mature DC expressed CD1a, CD80, CD86, HLA-DR, CD54 and CD58 but lacked surface CD14. Stimulation of autologous T lymphocytes was studied by measuring their proliferation and cytotoxic function. In more than 80% of our experiments the proliferation of autologous T lymphocytes cocultured with APC pulsed or not with tumor cell lysates was higher than that of T cells cultured alone. DC were more effective than MC in stimulating proliferation of lymphocytes. The capacity of a patient's autologous bone marrow-derived APC to stimulate T cells when exposed to autologous tumor cell lysates suggest that such antigen-exposed APC may be useful in specific anti-tumor immunotherapy protocols.

Irreversible corneal decompensation in patients treated with topical dorzolamide.

PURPOSE: To describe irreversible corneal decompensation after topical dorzolamide hydrochloride (Trusopt; Merck and Co, Inc, West Point, Pennsylvania) therapy in nine patients who had histories consistent with corneal endothelial compromise. METHOD: Multicenter review of patients' charts. RESULTS: Nine eyes of nine patients developed overt corneal decompensation after starting topical dorzolamide, a condition that did not resolve with drug cessation. This occurred after 3 to 20 weeks (mean, 7.8) of therapy. All nine patients had undergone intraocular surgery. Eight patients had undergone cataract surgery; three were aphakic and three had posterior chamber intraocular lenses. Two patients had anterior chamber intraocular lenses and also had undergone trabeculectomies. Four patients had undergone penetrating keratoplasties, each case complicated by episodes of corneal allograft rejection that were successfully treated. Two patients had asymptomatic Fuchs endothelial dystrophy. Seven patients have since undergone successful penetrating keratoplasties. CONCLUSION: The reports suggest that dorzolamide can cause irreversible corneal edema in a subset of glaucoma patients with endothelial compromise. The findings suggest a rationale for research into the long-term effects of dorzolamide on the corneal endothelium.

[HCV RNA clearance after treatment with interferon-alpha in chronic hemodialysis patients with or without coinfection by HGV/HGBV-C]. / Clairance de l'ARN du VHC après traitement par interféron alpha chez des hémodialysés chroniques avec ou sans coinfection par le VHG/VHGB-C.

Patients on maintenance hemodialysis are frequently infected with hepatitis C virus (HCV). The long-term effect of alpha interferon therapy has not yet been assessed, or the influence of co-infection with the newly discovered hepatitis G/hepatitis GB virus-C (HGV/HGBV-C) upon therapy outcome. Eleven anti-HCV and HCV RNA-positive hemodialysis patients, 3 of whom had HGV/HGBV-C infection were given 3 mega-units of alpha 2b recombinant interferon subcutaneously 3 times weekly for six months. The mean follow-up after cessation of therapy was 24 +/- 8 months (range: 18-30 months). Sustained serum HCV RNA clearance, as assessed by PCR analysis, occurred in 5/11 patients (45.5%). Two had received a cadaveric kidney transplant at 16 and 18 months post-treatment and were treated by immunosuppressive therapy; HCV RNA remained undetectable in both serum and a liver biopsy. HCV was eradicated in 3 of the 6 patients infected with HCV genotype 1b, which is less sensitive to alpha-interferon than other HCV genotypes. Among the 3 patients infected with both HCV and HGV/HGBV-C, alpha-interferon cleared the HCV RNA from one patient, but not the HGV/HGBV-C RNA. In view of the high rate of HCV eradication after alpha-interferon therapy and its fair tolerance, we suggest that HCV RNA-positive dialysis patients should be treated before transplantation, regardless of their aminotransferase levels or liver histological score, since alpha interferon therapy after renal allografting is associated with an unacceptable rate of renal failure. Our preliminary data indicate that HGV/HGBV-C does not interfere with sustained HCV RNA clearance.

A phase I trial of repeated tumour-infiltrating lymphocyte (TIL) infusion in metastatic melanoma.

The aim of the protocol was to evaluate the side-effects induced by repeated tumour-infiltrating lymphocyte (TIL) infusions in patients with metastatic melanoma (MM). Patients were to receive four TIL infusions at given intervals: every 3 weeks (two patients), every 2 weeks (3 patients) and weekly (4 patients). All patients were evaluated and received a total of 34 TIL infusions. The total number of TILs administered varied from 0.65 to 2.34 x 10(11) cells. TIL phenotypes were predominantly CD8+ (two patients), CD4+ (4 patients), CD4+ then CD8+ (two patients) or CD56+ (two patient). Autocytotoxicity was only observed for one culture. Six patients presented at least one WHO grade 3 side-effect: hypotension (5 patients), dyspnoea (two patients), fever (one patient), fatigue (one patient), chills (two patients), diarrhoea (one patient), agitation (one patient), locoregional pain (two patients). Hypotension was constantly seen in patients who were given TILs every week. Two cases of minor pericarditis were recorded. No objective response to treatment was observed; 1 stable disease occurred in one patient and progression in eight. However, five patients presented a partial response on a tumour site for 1-4 months. Three patients presented signs of inflammation or softening at one tumour site. Plasma tumour necrosis factor alpha (TNF-alpha) levels were increased 1.2- to 22-fold after TIL infusion. TILs could be produced in sufficient quantity to perform this study, so repetitive infusions of TIL became possible on a weekly basis. However, no objective response was observed even when TIL infusions were performed weekly. An increase in circulating TNF-alpha was noted after TIL infusion.

The impact of overnight wear on the risk of contact lens-associated ulcerative keratitis.

OBJECTIVE: To assess the relative risk of contact lens-associated ulcerative keratitis by lens type and related lens-wearing behavior. DESIGN: Case-control study. SETTING/PARTICIPANTS: Forty practice-based case patients with contact lens-associated ulcerative keratitis and 180 control patients matched to the case patients' dispensing practitioner and date of contact lens prescription. RESULTS: Compared with users of daily-wear soft lenses, users of disposable soft contact lenses had a 13.33-fold (95% confidence interval [CI], 5.35 to 33.20) excess risk of ulcerative keratitis. However, after adjusting for overnight wear, the excess risk associated with disposable contact lenses is reduced to 3.21 (95% CI, 1.22 to 14.36). Overall, overnight wear of contact lenses conferred an 8.25-fold excess risk (95% CI, 3.33 to 25.58) of ulcerative keratitis after controlling for lens type. No protective effect of standard compared with substandard lens hygiene was found. The risk of ulcerative keratitis attributable to overnight wear was estimated at 49% for users of daily-wear lenses and 74% for users of lenses approved for overnight wear. CONCLUSION: Overnight wear of contact lenses is the overwhelming risk factor for ulcerative keratitis among contact lens users. We estimate that 49% to 74% of cases of contact lens-associated ulcerative keratitis could be prevented by eliminating overnight wear.

A randomized trial of intraocular lens fixation techniques with penetrating keratoplasty.

PURPOSE: Pseudophakic corneal edema is the principal indication for penetrating keratoplasty in the United States. Currently, three techniques of intraocular lens (IOL) fixation during penetrating keratoplasty for this condition are commonly used--flexible anterior chamber IOL (AC IOL) implantation, iris suture fixation of a posterior chamber IOL (PC IOL), and transscleral suture fixation of a PC IOL. This study represents the first prospective, randomized comparison of these three techniques. METHODS: One hundred seventy-six consecutive patients with pseudophakic corneal edema who underwent penetrating keratoplasty with IOL exchange were randomized to one of the three implantation techniques. Standardized evaluations were performed at baseline and at 6, 12, and 18 months postoperatively. Life-table analysis provided cumulative risk estimates for specific complications. RESULTS: Randomization produced comparable groups at baseline. The cumulative risk of macular edema was significantly less for the iris fixation cohort than for either the AC IOL or scleral fixation group. A complications index was constructed based on the major adverse outcomes of glaucoma escalation, cystoid macular edema, IOL dislocation, and graft failure. A significantly lower risk of complication was found for iris compared with scleral fixation of PC IOLs. CONCLUSION: The authors conclude that transscleral fixation of the PC IOL at the time of penetrating keratoplasty for pseudophakic corneal edema is associated with a greater risk of adverse outcome than iris fixation of a PC IOL.

The increased risk of ulcerative keratitis among disposable soft contact lens users.

Previous controlled studies on contact lens-associated ulcerative keratitis were performed before the widespread use of disposable contact lenses. Therefore, a controlled study was undertaken to determine the relative risk of ulcerative keratitis among users of disposable soft contact lenses compared with the risk among users of other lens types. Forty-six consecutive cases of contact lens-associated ulcerative keratitis were identified between January 1990 and June 1992 at a corneal specialty practice in western Michigan. Five controls, matched to each case patient according to the dispensing data and prescribing practitioner, were obtained for 42 cases (91%). Users of daily-wear rigid gas-permeable lenses had the lowest risk of developing ulcerative keratitis. Relative to users of daily-wear soft contact lenses, users of extended-wear soft contact lens had an age-adjusted and sex-adjusted relative risk of 1.87 (95% confidence interval, 0.61 to 5.71). Disposable soft contact lens users had the highest risk of developing ulcerative keratitis, with an adjusted relative risk of 14.16 (95% confidence interval, 5.47 to 37.63) compared with daily-wear soft contact lens users and 7.66 (95% confidence interval, 2.27 to 25.83) compared with conventional extended-wear soft contact lens users.

[Should subdivision of regressive ischemic colitis be envisaged?]. / Faut-il envisager un démembrement des colites ischémiques régressives?

The term "regressive ischemic colitis" is generally accepted and refers to acute hemorrhagic colitis which may occur at any age and recovers spontaneously in most cases, sometimes leaving colonic stenosis due to scarring. Critical analysis of the literature reveals that there is no formal diagnostic criterion for this condition and no real proof that the mechanism is ischemic, particularly in young subjects who have no vascular disorder or hemodynamic triggering factor. The number of clinical, radiological, endoscopic and even histological similarities between regressive ischemic colitis and some forms of infectious colitis, particularly due to enterohemorrhagic E. coli O157:H7 and hemorrhagic colitis due to penicillin derivatives and non-steroid anti-inflammatory drugs is also striking. These observations logically lead us to wonder whether the term "regressive ischemic colitis" does really correspond to a well-defined entity rather than to a group of acute colitis of miscellaneous etiology but with many common features.

[Pregnant seropositive drug addicts]. / La toxicomane séropositive enceinte.

Understanding actual experiences of sexuality and pregnancy in HIV positive drug addicts is essential for the prevention of AIDS dissemination. A rigorous organization and a coherent therapeutic project are needed for pregnancy supervision (pregnancy being carried on in over 50 percent of cases), for psychological preparation to the recognition of foetus reality and birth, and for newborn follow up to prevent his abandonment. The specific problems of pregnancy, seropositivity and drug addiction should be taken into account at the same time. The intervention of a voluntary, motivated and polyvalent team and a hospital opening towards outreach workers are two essential conditions of success.

["Spontaneous" ischemic colitis: infectious or medicamentous colitis? 25 cases]. / Colite ischémique "spontanée": colite infectieuse ou médicamenteuse? 25 observations.

The diagnosis of non-gangrenous ischaemic colitis is difficult to assert when histological findings are not specific and when no precipitating cardiovascular event can be found. The constant absence of relapse after the initial episode suggests that an extraneous triggering event is involved. We have studied retrospectively 25 cases of spontaneous ischaemic colitis, looking for a non-haemodynamic triggering event. At the onset of colitis 9 patients had been taking non-steroidal anti-inflammatory drugs or antibiotics for 2 weeks or less. In 3 other patients colitis was associated with Escherichia coli O157:H7 infection. Striking clinical, endoscopic and histological similarities exist between ischaemic colitis on the one hand and colitis caused by absorption of non-steroidal anti-inflammatory drugs or ampicillin and the colitis reported in E. coli O157:H7 infection on the other hand. Non-steroidal anti-inflammatory drugs and E. coli O157:H7 intestinal infection, possibly facilitated by an antibiotic treatment with e.g. ampicillin, could be either non-haemodynamic triggering factors for ischaemic colitis, or responsible per se for a transient acute colitis with the same characteristics as ischaemic colitis.

Acanthamoeba keratitis associated with disposable contact lenses.

Two patients developed Acanthamoeba keratitis associated with the use of disposable extended-wear hydrogel contact lenses. Both patients removed, irrigated, and reinserted the contact lenses without disinfecting them. One patient wore the lenses on a daily basis, rinsed the lenses in tap water, stored them overnight, and discarded them weekly. Both infections were treated successfully. In a third patient, Acanthamoeba species was cultured from two pairs of disposable lenses that had been stored in cases rinsed with well water. Potential benefits from disposable contact lens wear are negated when patients do not comply with a continuous wearing schedule.