Rapid detection of heparin-induced platelet antibodies with particle gel immunoassay (ID-HPF4)

Early and acute diagnosis is needed to prevent thromboembolic complications in heparin-induced thrombocytopenia. We developed a particle agglutination assay that allows the detection of such antibodies within 20 min.

Use of laser flare photometry to assess and monitor inflammation in uveitis.

PURPOSE: Laser flare photometry (LFP) is a new quantitative method for the evaluation of aqueous flare, making flare the only inflammatory parameter that can be evaluated precisely and objectively. The aim of this study was to characterize the inflammatory pattern of acute human leukocyte antigen-B27 (HLA-B27)-related anterior uveitis and to determine further clinical use and limitations of LFP in posterior inflammation. METHODS: In the first part of the study, 78 episodes of HLA-B27-related acute anterior uveitis were analyzed to determine mean pretreatment (initial) flare, mean flare evolution, need for additional periocular steroids, and mean duration of an episode. In the second part of the study, the use of LFP was further tested in posterior inflammation, first by analyzing the predictive value of a subclinical LFP-detected flare increase for disease recrudescence in posterior scleritis, and then by exploring clinical applications for LFP in posterior uveitis, where LFP was essential either in the establishment of a diagnosis or in guiding therapeutic decisions. RESULTS: Mean initial flare in HLA-B27-related acute anterior uveitis was 160 +/- 22 photons/msec, and mean duration of an episode was 18.5 +/- 15 days. A 50% and 90% flare reduction occurred after 2 and 8 days, respectively. In posterior scleritis, LFP was accurate in monitoring response to systemic steroid therapy and a small flare increase was predictive for disease recrudescence in five of six cases (predictive value 0.83, sensitivity 100%). In posterior uveitis, LFP was sensitive to monitor systemic treatments and to establish a diagnosis in unclear cases by measuring the effect of a selective therapy (therapeutic trial) on the flare level. CONCLUSION: In acute anterior HLA-B27-associated uveitis, LFP represented a potential improvement in management by allowing precise adjustment of therapy. In uveitis of the posterior segment, our data confirm the validity of LFP to monitor response and adjust systemic therapy and to detect disease recurrence in patients with a sufficient pretreatment level of associated blood-aqueous barrier disruption (flare).

Sensitivity of laser flare photometry to monitor inflammation in uveitis of the posterior segment.

PURPOSE: Laser flare photometry is a new quantitative method for evaluating aqueous flare, making flare the only inflammatory parameter that can be evaluated precisely and objectively. The validity of the method already has been demonstrated in anterior segment inflammation. The aim of this study is to assess the validity and limitations of the method to quantify and monitor inflammation in uveitis with predominant involvement of the posterior segment. METHODS: Five well-defined conditions with uveitis predominant in the posterior segment were analyzed in this study: Behçet uveitis, pars planitis, posterior sarcoidosis, posterior pole toxoplasmosis, and birdshot chorioretinopathy. (1) Mean initial (pretreatment) flare was determined; (2) in the patients needing systemic steroid therapy, introduction of therapy was correlated with evoluting laser flare photometry; and (3) in patients with quiescent disease, the predictive value of a defined subclinical photometry-detected flare rise for disease recrudescence was analyzed. RESULTS: Initial pretreatment flare was 331.8 +/- 47.7 photon counts per millisecond (ph/msecond) (mean +/- standard error of the mean) for Behçet uveitis, 15.6 +/- 1.3 ph/msecond for pars planitis, 26.9 +/- 4.6 ph/msecond for posterior sarcoidosis, 7.5 +/- 1.0 ph/msecond for posterior pole toxoplasmosis, 5.8 +/- 0.7 ph/msecond for birdshot chorioretinopathy, and 4.7 +/- 0.1 ph/msecond for a group of 88 control eyes. A significant flare reduction after start of steroid therapy was seen in Behçet uveitis (78% reduction), sarcoidosis (44.8%), and pars planitis (51%), but not in toxoplasmosis or in birdshot. A small flare rise had a predictive value for disease recrudescence in 27/35 patients (predictive value, 0.77; sensitivity rate, 100%). The level of associated blood-aqueous barrier disruption for reliable follow-up of posterior uveitis was empirically determined to be 13 to 15 ph/msecond. CONCLUSION: Laser flare photometry was found to be very sensitive to monitor inflammation in uveitis of the posterior segment as long as a sufficient level of associated blood-aqueous barrier disruption (flare) was present.

The effect of thalidomide and supidimide on endotoxin-induced uveitis in rats.

BACKGROUND: Endotoxin-induced uveitis (EIU) is an animal model of ocular inflammation, produced by footpad injection of endotoxin (lipopolysaccharide, LPS) to mimic the human disease of acute anterior uveitis, that is useful for testing new anti-inflammatory therapy. The purpose of this study was to test the anti-inflammatory effect on EIU of thalidomide and one of its derivatives, supidimide. METHODS: EIU was produced in rats by hind foot-pad injection of LPS (100 micrograms/animal). Animals were killed 20 h after LPS injection. Inflammation was evaluated by anterior chamber determination of proteins and cells. RESULTS: A dosage of 400 mg/kg per day of thalidomide was efficient in reducing inflammation whether given in three doses (at -24 h, -4 h and +4 h relative to LPS challenge = THAL-1; p < 0.001 for proteins and cells), in two doses (-4 h and +4 h = THAL-2; p < 0.001 for proteins, p < or = 0.012 for cells) or in one dose (at +4 h = late THAL; p < 0.001 for proteins, p < or = 0.02 for cells). A dosage of 300 mg/kg per day of thalidomide was still efficient (p < or = 0.023 for proteins, p < or = 0.06 for cells), but 150 mg/kg per day had no effect on inflammation. Supidimide (400 mg/kg per day) had some anti-inflammatory effect (p < or = 0.053 for proteins, p < or = 0.06 for cells). CONCLUSION: High-dose thalidomide had a potent anti-inflammatory effect in EIU, but lower doses were not sufficient to reduce inflammation. At similar high doses, supidimide had some effect on EIU but was less effective than thalidomide.

[Quantitative measurement of inflammation in HLA-B27 acute anterior uveitis using the Kowa FC-100 laser flare-cell meter]. / Mesure quantitative de l'inflammation dans l'uvéite antérieure aiguë (UAA) HLA-B27 à l'aide du laser flare-cell meter Kowa FC-1000.

PURPOSE: LFP represents a major gain of sensitivity over slit-lamp evaluation of aqueous flare, allowing to detect subclinical changes of flare both in low grade and high grade flare situations. It is now possible to exactly quantify anterior chamber inflammation and determine inflammatory patterns. The purpose of this study was to determine the mean initial and evolutionary flare in AAU and the mean duration of an AAU episode. PATIENTS AND METHODS: Since 1990 routine LFP follow-up of inflammation in uveitis patients is performed by the same technician with a Kowa FC-1000 laser flare-cell meter. The standard treatment for AAU was to begin with hourly topical 1% prednisolone acetate drops during the day and ointment at night and mydriatic drops. In case of a flare rise or persistence of the initial high flare after 48 hours a periocular injection of betamethasone (4 mg) was added to the topical therapy. End of an episode was defined as a flare under 8 photons/ms. RESULTS: Mean initial flare was 160.7 +/- 22 ph/ms (n = 61). Mean duration of an AAU episode was 18.5 +/- 15 days and evolution of mean flare showed that 50% flare reduction occurred on day 2 of therapy and 90% reduction on day 8. With our treatment protocol 14% of non complicated AAU needed an additional periocular steroid injection. CONCLUSION: LFP represents a major improvement in the management of AAU patients by allowing precise adjustment of therapy and favors good patient compliance because of the numbered evidence of disease recovery.

[Indications and complications of systemic corticosteroid therapy in treatment of uveitis]. / Indications et complications de la corticothérapie systémique dans le traitement des uvéites.

PURPOSE: Systemic steroids is often the first choice of immunosuppressive therapy for severe endogenous uveitis. The aim of this study was to analyse the indications of steroid therapy, complications and side-effects. PATIENTS AND METHODS: Charts from all patients that received oral steroid therapy were reviewed for this purpose and a questionnaire was sent out to all patients to record their subjective complaints. RESULTS: From January 1990 to March 1993, 63 out of the 435 new patients seen at the uveitis clinic received oral prednisone. In 4 cases severe complications occurred that did however not lead to discontinuation of therapy. In 2 cases of intolerance cyclosporine (CsA) had to be added to the treatment regimen to lower the steroid doses and in one case steroids had to be stopped because of intolerance. The questionnaire showed a high rate of subjective side-effects to steroids. CONCLUSIONS: In our collective oral steroids were associated with complications, intolerance and side-effects in a high proportion of cases. It is important to explain the possible side-effects to the patient before starting the therapy. The preventable collateral effects like weight gain and decalcification should be addressed by diet recommendations and modern calcium sparing therapy.

Evaluation of laser flare-cell photometry in the appraisal and management of intraocular inflammation in uveitis.

BACKGROUND: Laser flare-cell photometry enables objective and quantitative measurement of anterior chamber inflammation. Systematic data currently are used mainly for clinical research; few are yet available in uveitis. The authors prospectively studied the amount, duration, and pattern of inflammation for well-defined uveitic conditions and evaluated the potential usefulness of laser flare-cell photometry in uveitis. METHODS: Mean initial flare was calculated in HLA-B27-positive acute anterior uveitis, acute herpes zoster uveitis, acute retinal necrosis (ARN), Fuchs heterochromic cyclitis, intermediate uveitis (pars planitis-type), posterior sarcoidosis, posterior pole toxoplasmosis, and birdshot chorioretinopathy. Evolution of aqueous flare and cells was analyzed for acute anterior uveitis, ARN, and pars planitis treated for cystoid macular edema (CME), all of which received a standardized therapy. RESULTS: Blood-aqueous barrier disruption was very pronounced in acute anterior uveitis (170.2 +/- 33 photons/msecond), ARN (177.4 +/- 88 photons/msecond), moderate in posterior sarcoidosis (38.1 +/- 11 photons/msecond), acute zoster uveitis (25.8 +/- 6.1 photons/msecond), and pars planitis (19.1 +/- 2.9 photons/msecond) but only minimal in Fuchs heterochromic cyclitis (10.2 +/- 3.5 photons/msecond), toxoplasmosis (9.0 +/- 1.2 photons/msecond) and birdshot chorioretinopathy (5.7 +/- 1.1 photons/msecond). For acute anterior uveitis, ARN, and pars planitis with CME, the inflammatory patterns were determined. The potential of laser flare-cell photometry for precise follow-up and adjustment of therapy was illustrated in cases of anterior and posterior uveitis. CONCLUSION: The authors' findings show that laser flare-cell photometry allows quantitative assessment of inflammation in uveitis and contributes to improved management of patients with uveitis.

Epidemiological characteristics of uveitis in Switzerland.

Since January 1990, data from uveitis patients have been systematically stored in a computer data bank. During the period from January 1990 to March 1993, 435 new patients (185 female and 250 male, mean age 43 years; range 6-92) were seen at the Uveitis Clinic of the Hôpital Jules Gonin. These 435 patients (630 eyes) were subdivided into anterior uveitis (268 patients--62%), intermediate uveitis (47 patients--11%), posterior uveitis (89 patients--20%) and panuveitis (31 patients--7%). The incidence of uveitis for the referral area considered was calculated to be 17 per 100,000 inhabitants per year. A specific diagnosis was found in 312 cases (72%). The most frequently diagnosed entities were HLA-B27-associated acute anterior uveitis (67 cases--15.4%), uveitis associated with acute herpes zoster ophthalmicus (40 cases--9.2%), toxoplasmosis (39 cases--9%), typical pars planitis (29 cases--6.7%), sarcoidosis (29 cases--6.7%), Fuchs' heterochromic cyclitis (27 cases--6.2%), herpetic anterior uveitis (21 cases--4.8%) and acute retinal necrosis (11 cases--2.5%). Incidence and distribution of most disease entities correspond to those of other European series.

Dexamethasone versus diclofenac sodium eyedrops to treat inflammation after cataract surgery.

We compared the postoperative anti-inflammatory effect of diclofenac sodium 0.1% and dexamethasone phosphate 0.1% in a prospective, randomized, double-masked pilot study. Anterior chamber inflammation was evaluated by measuring aqueous flare and cells with a laser flare-cell meter at one, three, 12, 30, and 60 days after cataract surgery. Flare values in the two groups did not significantly differ at any time, nor did aqueous cell counts at one, three, 12, and 60 days after surgery. At 30 days, however, cell count was significantly lower in the diclofenac group. Diclofenac sodium seems to be as potent as dexamethasone phosphate, as good as anti-inflammatory agent, and may replace corticosteroid therapy after cataract surgery.

Epidemiology of uveitis in Switzerland.

During the period from January 1990 to December 1993, 558 new patients (250 female and 308 male, mean age 44 years; range 5-92) were seen at the Uveitis Clinic of the Hopital Jules Gonin. These 558 patients (740 eyes) were subdivided into anterior uveitis (343 patients-61%), intermediate uveitis (57 patients-10%), posterior uveitis (118 patients-21 %) and panuveitis (40 patients-7%). The incidence of uveitis for the referral area considered was calculated to be 17.5 per 100,000 inhabitants per year. A specific diagnosis was found in 386 cases (69%). The most frequently diagnosed entities were HLA-B27-associated acute anterior uveitis (89 cases-15.9%), uveitis associated with acute herpes zoster ophthalmicus (54 cases-9.7%), toxoplasmosis (53 cases-9.5%), sarcoidosis (33 cases-5.9%), typical pars planitis (31 cases-5.6%), Fuchs' heterochromic cyclitis (30 cases-5.4%), herpetic anterior uveitis (23 cases-4.1 %) and acute retinal necrosis (13 cases-2.3%). Incidence and distribution of most disease entities correspond to those of other European and American series.

Fluorodeoxyglucose cell incorporation as an index of cell proliferation: evaluation of accuracy in cell culture.

The use of fluorodeoxyglucose (FDG) and positron emission tomography (PET) is recognized as an accurate tool for the specific diagnosis and staging of cancer. It has also been proposed for the monitoring of anticancer therapy. FDG cell incorporation reflects glycolytic activity whereas inhibition of cell proliferation corresponds to an efficient cancer treatment. The relationship between FDG incorporation and cell proliferation has yet to be demonstrated. Therefore, we aimed to correlate the effects of the toxic agents bleomycin and unlabelled meta-iodobenzylguanidine (mIBG) on cellular metabolism and proliferation. We determined the in vitro metabolic and cytotoxic effects of bleomycin and mIBG by measuring the incorporation of fluorine-18 FDG (%UFDG) and hydrogen-3 thymidine (%UTHY) in cells of the human premonocytic line U937 in the presence of increasing concentrations of these agents. Proliferation rate of these cells was studied by means of limiting dilution analysis. %UTHY appeared more sensitive to bleomycin or mIBG-mediated cell injury than %UFDG. After 1 h of exposure to 0.5 microM bleomycin, %UTHY was significantly reduced to 62.0% +/- 10.4% of control value whereas %UFDG remained unchanged (91.6% +/- 5.3%). Similar results were obtained after 1 h of exposure to increasing concentrations of mIBG (1 microM to 1 mM). After 20 h of exposure to bleomycin, %UTHY and %UFDG were significantly reduced as a function of concentration. After 20 h of exposure to mIBG, a transient increase in %UFDG up to 149.3% +/- 11.2% with 50 microM mIBG was further followed by a reduction to 20.1% +/- 6.7% with 0.5 mM (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Anterior segment inflammation in cataract operation: comparison of intraocular lens implanted in the lens capsule and in the sulcus]. / La barrière hémato-aqueuse après opération de cataracte: comparison de l'implantation dans le sac capsulaire et dans le sulcus.

Intracapsular implantation of an intraocular lens (IOL) after cataract extraction is considered to be more "physiologic" than sulcus implantation. Using a laser flare-cell meter, we measured the degree of anterior segment inflammation in 24 eyes with an IOL implanted in the sulcus and 14 eyes with an IOL implanted "in the bag." All patients were followed for 1 year. The mean flare value was significantly lower in the bag-implanted eyes than in the sulcus-implanted eyes 1 day (p = 0.009) and 3 days (p = 0.012) after surgery; no significant difference in degree of flare was found between the groups after that time. At 1 year the sulcus-implanted group was found to have slightly higher flare values than a control group of 34 unoperated patients matched for age. Although this difference was statistically significant (p = 0.012), it should not be considered clinically relevant.

Anti-inflammatory effect of diclofenac drops after argon laser trabeculoplasty.

Using a laser flare-cell meter, the anti-inflammatory effect of diclofenac sodium drops was evaluated after argon laser trabeculoplasty in a double-masked placebo-controlled study. Fifty-three eyes with pseudoexfoliative (43 eyes) or pigmentary glaucoma (10 eyes) were randomly assigned to treatment (n = 27) or placebo (n = 26) groups. Diclofenac (0.1%) or placebo drops were administered once before and after trabeculoplasty and then four times daily for a total of 4 days. Visual acuity, intraocular pressure, and anterior chamber flare, measured with the laser flare-cell meter, were evaluated before trabeculoplasty, 3 and 6 hours after trabeculoplasty, and 1, 2, 4, 7, and 14 days after trabeculoplasty. Flare increase after argon laser trabeculoplasty was completely blocked by 0.1% topical diclofenac and the mean of maximal flare increases was reduced significantly in the diclofenac group. Therefore, 0.1% diclofenac drops represent a very efficient anti-inflammatory therapy after argon laser trabeculoplasty.

Aqueous humor analysis after Nd:YAG laser capsulotomy with the laser flare-cell meter.

Using the laser flare-cell meter (Kowa FC-1000), we conducted a prospective study analyzing the effect of Nd:YAG posterior capsulotomy on the quantity of aqueous particles, aqueous flare, and intraocular pressure in 65 eyes (58 patients). Aqueous particles increased at six hours, followed by flare rise which was significant at 18 hours after capsulotomy. Only 22 eyes (34%) had a significant flare rise over prelaser values. Anti-inflammatory therapy was necessary in only one patient. The mean intraocular pressure value did not rise significantly after capsulotomy. Acute intraocular hypertension (AIOHT) (> 7 mm Hg increase) occurred between three and six hours after laser therapy in 12 patients (19%), was related in time to particle rise, and always responded to a single dose of acetazolamide. Acute intraocular hypertension was strongly correlated with elevated aqueous particles (P < .0001) and somewhat correlated with flare rise (P < .036), but was not correlated with the intraocular lens position (bag or sulcus fixation). Our findings strongly suggest that trabecular meshwork clogging by debris generated by the capsulotomy is the mechanism at the origin of AIOHT.

[Anti-inflammatory effect of topical diclofenac sodium (Voltarène Ophta) after argon laser trabeculoplasty: preliminary results of a prospective double-blind method]. / Effet anti-inflammatoire du diclofenac sodium topique (Voltarène Ophta) après trabéculoplastie au laser argon (TLA): résultats préliminaires d'une étude prospective en double-insu.

Using the laser flare-cell meter (LFMC), we have previously determined the intensity and pattern of post-ALT ocular inflammation. Inflammation peak occurs 48 hours after ALT and clinically relevant inflammation is seen in 100% of pigmentary glaucomas (PIG), 75% of pseudoexfoliative glaucomas (PEXG) but only in 25% of primary open angle glaucomas (POAG). We also showed that topical diclofenac reduced inflammation in all 17 treated patients. Prostaglandins are thought to play a major role in ALT-inflammation and it is therefore logical to assume that NSAID are effective in that situation and will probably advantageously replace corticosteroids. In order to assess the anti-inflammatory effect of diclofenac drops (Voltaren Ophtha) we included a total of 37 PIG or PEXG (19 in the diclofenac and 18 in the placebo group) scheduled for ALT in prospective randomized placebo-controlled study. Visual acuity, tonometry, and LFCM flare measure were performed before, 3, 6 hours, 1, 2, 4, 7, 14 days after ALT. Topical diclofenac or placebo was given before and after ALT and then QID for a total of 4 days. Mean maximal flare increase was significantly less in the diclofenac group than in the placebo group (4.6 +/- 3.8 ph/msec v. 17.4 +/- 19 ph/msec; p less than 0.01). Flare increase compared to pre-ALT values was significant at 1 and 2 days after ALT in the placebo group only (p less than 0.02; p less than 0.05); no significant flare increase occurred in the diclofenac group.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diclofenac-dexamethasone combination in treatment of postoperative inflammation: prospective double-blind study]. / Association diclofenac-dexamethasone dans le traitement de l'inflammation postopératoire: étude prospective en double-insu.

In a prospective randomized double masked study including 40 patients we evaluated the anti-inflammatory effect of a combination of dexamethasone acetate 0.1% + diclofenac 0.1% drops compared to dexamethasone acetate 0.1% + placebo drops, after ECCE + posterior chamber lens implantation. Anterior chamber (AC) flare and cells were measured with the laser flare-cell meter Kowa FC-1000. The group receiving the dexamethasone-diclofenac combination showed a more rapid decrease of AC flare which was significant at days D3 (P less than 0.003) and D12 (p less than 0.028). The reduction of AC cells was comparable in both groups, showing however a strong tendency toward a lower cell count in the group receiving diclofenac at days D12 and D30 (p less than 0.08). Tolerance of diclofenac was good and comparable to the placebo.

[Comparison of the effects of trabeculoplasty using the Nd-YAG laser and the argon laser]. / Comparaison des effets de la trabéculoplastie effectuée avec le laser Nd-YAG et le laser argon.

We compared the effect of Argon Laser trabeculoplasty (ALT) and Nd-YAG-Laser trabeculoplasty (YLT) on inflammation and intraocular pressure (IOP). Twenty-two patients scheduled for bilateral trabeculoplasty were treated with an Argon laser in one eye and with Nd-YAG laser in the controlateral eye. Visual acuity, IOP and anterior chamber inflammation (measured with the laser flare-cell meter) were controlled at 0, 3, 6, 18 hours, 2, 4, 7, 14, 30, 90 and 180 days after trabeculoplasty. Our results showed a similar pressure lowering effect in both groups (-24.5 +/- 23% after YLT versus -32.9 +/- 16.3% after ALT at 90 days post-laser; p = 0.26). The anterior chamber inflammation was delayed and more important in the ALT-group (inflammation peaked at 24.8 hours after YLT versus 44.5 hours after ALT; p = 0.034) (maximal mean flare increase: 19.4 +/- 12 pH/msec. after ALT, versus 16.1 +/- 11.4 ph/msec. after YLT). All eyes with inflammation were successfully treated with topical diclofenac QID (Voltaren Ophtha), a nonsteroidal anti-inflammatory agent. YLT is a safe and effective alternative technique to perform laser trabeculoplasty, which is especially useful in poorly pigmented angles where ALT is known to be less effective.

Inflammation patterns after laser trabeculoplasty measured with the laser flare meter.

Anterior chamber inflammation was measured in 71 eyes after argon laser trabeculoplasty with the laser flare-cell meter (Kowa FC-1000). Visual acuity, tonometry, and laser flare measurement were performed before and 3, 6, and 18 hours and 2, 4, 7, 14, 30, and 90 days after argon laser trabeculoplasty. Anterior chamber inflammation peaked 2 days after argon laser trabeculoplasty. Forty-nine percent of the eyes showed significant inflammation, with a flare increase of more than 10 photon counts per millisecond over prelaser values. Inflammation was significantly more frequent in pseudoexfoliative glaucoma (69%) and pigmentary glaucoma (100%) than in primary open angle glaucoma (23%). Post-argon laser trabeculoplasty relative pressure decrease was significantly more important in the group of patients with inflammation than in the group without inflammation in the early and late follow-up periods. Topical nonsteroidal anti-inflammatory treatment (diclofenac sodium) was needed in 17 patients, who readily responded to treatment within 72 hours.

[Tyndallometry of the anterior chamber with the Kowa FC-100 Laser FLare-Cell Meter]. / Tyndallométrie de la chambre antérieure avec le Laser Flare-Cell Meter Kowa FC-1000.

The laser flare-cell meter measures the scattered light intensity of a He-Ne laser in the aqueous of the anterior chamber. It allows a reliable quantitative determination of the flare and the number of cells in the aqueous humor. The aqueous flare intensities are significantly decreased by short-acting mydriatic agents such as 0.5% tropicamide and phenylephrine. Diurnal variations and an increase of the aqueous flare with increasing age were demonstrated.