A lethal case of the dapsone hypersensitivity syndrome involving the myocardium.

In the Netherlands dapsone is used for the treatment of dermatitis herpetiformis, leprosy and Pneumocystis jiroveci pneumonia and prophylaxis in case of cotrimoxazole allergy. An idiosyncratic drug reaction, known as the dapsone hypersensitivity syndrome (DHS), appears in about 0.5-3.6% of persons treated with dapsone. DHS can be associated with fever, rash and systemic involvement. We present a 35-year-old woman who developed severe DHS seven weeks after starting dapsone. Six weeks after being discharged in a good clinical condition she died from fulminant myocarditis, 11 weeks after the first DHS symptoms and the discontinuation of dapsone.

Melanocyte antigen-specific antibodies cannot be used as markers for recent disease activity in patients with vitiligo.

BACKGROUND: Objective parameters to assess disease activity in non-segmental vitiligo are lacking. Melanocyte antigen-specific antibodies are frequently found in the sera of patients with vitiligo and the presence of these antibodies may correlate with disease activity. OBJECTIVE: To investigate the relationship between melanocyte antigen-specific antibodies and recent disease activity in patients with vitiligo and to evaluate the potential usefulness of this objective parameter in daily clinical practice. METHODS: The prevalence of tyrosinase, melanoma antigen recognized by T-cells-1 (MART1), melanin-concentrating hormone receptor-1 (MCHR1), gp100 and tyrosine hydroxylase (TH) antibodies was evaluated in 21 patients with non-segmental vitiligo and in 20 healthy controls. RESULTS: In 21 patients, nine (42.8%) showed antibody responses against tyrosinase, MART1, MCHR1, gp100 or TH. No antibody responses were found in the 20 controls. No correlation was found between the presence of antibodies and recent disease activity or other clinical characteristics such as age, gender, extension and duration of vitiligo. CONCLUSIONS: In this study, 42.8% of the vitiligo patients showed an antibody response to melanocyte antigen-specific antigens. However, the presence of antibodies against melanocytes did not correlate with recent disease activity or other relevant disease parameters, and for the moment screening for these antibodies in individual patients does not appear to be clinically relevant.

Low yield of routine screening for thyroid dysfunction in asymptomatic patients with vitiligo.

BACKGROUND: Nonsegmental vitiligo is considered to be an autoimmune disease and is known to be associated with other autoimmune diseases, particularly affecting the thyroid. Screening patients with nonsegmental vitiligo for thyroid function and for the presence of thyroid autoantibodies has been recommended. OBJECTIVE: To investigate the prevalence of thyroid dysfunction and thyroid peroxidase-specific (TPO) antibodies in a large cohort of patients with nonsegmental vitiligo in order to help decide whether routine screening is justified. METHODS: A total of 434 adults with nonsegmental vitiligo who were referred to our institute were enrolled. Thyroid function and anti-TPO antibody titres were assessed in those patients who had no history of thyroid disease or recent thyroid screening. RESULTS: Forty-three patients had already been diagnosed with thyroid dysfunction, and in 27 patients the general practitioner had performed a thyroid function test with negative results <3months previously. In these patients, thyroid function assessment was not repeated. The remaining 364 patients were screened for thyroid dysfunction. Overt hypothyroidism was newly diagnosed in three (0·8%) patients; subclinical disease was found in 10 (2·7%) patients and increased levels of TPO antibodies, without thyroid disease, were found in 49 (13·5%) patients. An elevated risk for thyroid disease was found among older women and in women with a positive family history of thyroid disease. CONCLUSION: The overall prevalence of thyroid dysfunction in adult patients with nonsegmental vitiligo was higher than reported in the general population. However, the number of newly diagnosed cases with overt and subclinical thyroid dysfunction in our population was low. Most patients had already been diagnosed by their general practitioner and had symptoms indicative for thyroid disease. Thyroid disease was found predominantly among older women and in subjects with a positive family history of thyroid disease. Thyroid screening including anti-TPO antibodies is advisable in these high-risk subpopulations.

A placebo-controlled, double-masked evaluation of mitomycin C in combined glaucoma and cataract procedures.

PURPOSE: This study was performed to determine if adjunctive use of mitomycin C (MMC) would increase the success of combined phacoemulsification, intraocular lens implantation, and trabeculectomy surgery with releasable sutures. METHODS: Seventy-two eyes with cataract and glaucoma, requiring surgery for decreased vision, uncontrolled intraocular pressure, or to obtain a better view of the optic nerve, were randomized to receive a 2.5-minute subconjunctival exposure to either MMC (0.5 mg/ml) or placebo balanced salt solution. Postoperative evaluations at 3, 6, and 12 months were performed by a masked observer who recorded visual acuity, intraocular pressure, glaucoma medications, presence of filtering blebs, and complications. Endothelial cell counts were measured before and 3 months after surgery. RESULTS: The MMC group had significantly greater reduction in mean intraocular pressure through the first 12 months of follow-up (7.05-7.65 mmHg versus 2.62-3.84 mmHg; P = 0.001-0.028). In addition, through the first 6 months of follow-up, the MMC group required significantly fewer medications (0.4-0.5 versus 1.1-1.2; P = 0.002-0.004). Requirements for additional glaucoma surgery were less in the MMC group (4/ 36) than in the placebo group (7/35) (P = 0.301). Filtering blebs were significantly larger at 6 and 12 months (P = 0.002 and P = 0.001, respectively), and would leaks were more common (P = 0.101) in the MMC group. The mean decrease in endothelial cell count at month 3 was slightly, although not significantly, greater in the MMC treatment group (206.9 versus 91.3 cells/mm2* P = 0.377). CONCLUSION: The increased success of the glaucoma procedure in the MMC group together with relatively minor toxicity, suggests its use is beneficial in combined glaucoma-cataract surgery.

The effect of nutrient limitation on styrene metabolism in Pseudomonas putida CA-3.

Styrene degradation in Pseudomonas putida CA-3 has previously been shown to be subject to catabolite repression in batch culture. We report here on the catabolite-repressing effects of succinate and glutamate and the effects of a limiting inorganic-nutrient concentration on the styrene degradation pathway of P. putida CA-3 in a chemostat culture at low growth rates (0.05 h-1). Oxidation of styrene and the presence of styrene oxide isomerase and phenylacetaldehyde dehydrogenase activities were used as a measure of the expression of the styrene degradation pathway. Both glutamate and succinate failed to repress the styrene degradation ability under growth conditions of carbon and energy limitation. Lower levels of enzyme activities of the styrene degradation pathway were seen in cells grown on styrene or phenylacetic acid (PAA) under conditions of both ammonia and sulfate limitation than were seen under carbon and energy limitation. Cells grown on PAA under continuous culture oxidize styrene and styrene oxide and possess styrene oxide isomerase and NAD(+)-dependent phenylacetaldehyde dehydrogenase activities. Catabolite repression of styrene metabolism was observed in cells grown on styrene or PAA in the presence of growth-saturating (nonlimiting) concentrations of succinate or glutamate under sulfate limitation.

Catabolite repression of the toluene degradation pathway in Pseudomonas putida harboring pWW0 under various conditions of nutrient limitation in chemostat culture.

In earlier studies, the pathway of toluene and m- and p-xylene degradation (TOL pathway) in Pseudomonas putida (pWW0) was found to be subject to catabolite repression when the strain was grown at the maximal rate on glucose or succinate in the presence of an inducer. This report describes catabolite repression of the TOL pathway by succinate in chemostat cultures run at a low dilution rate (D = 0.05 h-1) under different conditions of inorganic-nutrient limitation. The activity of benzylalcohol dehydrogenase (BADH) in cell extracts was used as a measure of the expression of the TOL upper pathway. When cells were grown in the presence of 10 to 15 mM succinate under conditions of phosphate or sulfate limitation, the BADH activity in response to the nonmetabolizable inducer o-xylene was less than 2% of that of cells grown under conditions of succinate limitation. Less repression was found under conditions of ammonium or oxygen limitation (2 to 10% and 20 to 35%, respectively, of the BADH levels under succinate limitation). The BADH expression levels determined under the different growth conditions appeared to correlate well with the mRNA transcript levels from the upper pathway promoter (Pu), which indicates that repression was due to a blockage at the transcriptional level. The meta-cleavage pathway was found to be less susceptible to catabolite repression. The results obtained suggest that the occurrence of catabolite repression is related to a high-energy status of the cells rather than to a high growth rate or directly to the presence of growth-saturating concentrations of a primary carbon and energy source.

Surgical management of a long-standing subfoveal neovascular membrane secondary to ocular histoplasmosis.

Subretinal neovascular membranes located under the fovea typically lead to significant visual loss. Laser treatment has been limited due to the anatomic location of the neovascular process, but surgical removal has been reported with promising results. We surgically removed a long-standing, presumed ocular histoplasmosis syndrome (POHS) subfoveal neovascular membrane that had been present for 10 months in a patient's only functional eye, with unexpected good results. This case suggests that the good visual outcomes achieved by surgically excising smaller subfoveal neovascular membranes early in their natural history also can be achieved in selected patients with more chronic and severe subfoveal neovascular processes.

Temporal arteritis. Aggressive treatment prevents visual complications.

Visual loss is the most common complication of temporal arteritis when the disease is misdiagnosed or undertreated, yet treatment recommendations vary among different medical disciplines. In this article, Dr Wind presents a case report and information from the medical literature illustrating different treatment regimens and visual outcomes in patients with temporal arteritis.

Effects of Ca++ depletion on lens equatorial currents in frog lenses.

The combination of the vibrating probe measuring the outward equatorial current (J) with microelectrodes measuring PD and the response to injected current provides one of the best means of relating macro findings of lens currents to the micro data that have been reported using the patch clamp technique. In standard frog Ringers solution the equatorial current appears to be a relatively pure K+ current with a reversal potential of -95 mV. This agrees with the reversal potential of the 45 pS K+ channel. When Ca++ is removed from the medium bathing the lens the input resistance (R) decreases, the PD becomes less negative and the current J increases. This process can be reversed by adding Ca++ or Mn++ to the Ca++ deficient medium. When all Ca++ is removed from the medium by adding EGTA in the absence of Ca++, the increase in J is less than expected. However, if Na+ is replaced by TMA in the Ca++ depleted EGTA medium the current is seven times as great. These changes are consistent with those found in non-selective cation channels in the absence of Ca++.

Effect of ouabain on lens equatorial currents.

The equatorial potassium current measured with the vibrating probe is a segment of the potassium electrical loop. The equatorial current, J, was measured simultaneously with the PD and with the response to an injected current, I. The injection of sufficient inward current, I, made the PD more negative and increased the electrical gradient so that the current J became zero. The PD at which this occurs (PDJ-0) is the reversal potential. Following treatment with ouabain, the PD and PDJ-0 both become less negative. Since the driving force for the current, J, is equal to the difference between PD and PDJ-0, J may increase, stay the same or decrease depending on the relative changes in PD and PDJ-0. In the presence of ouabain, the PDJ-0 changes in parallel with or more rapidly than the PD.

Equatorial potassium currents in lenses.

Earlier work with the vibrating probe demonstrated the existence of outward potassium currents at the equator and inward sodium currents at the optical poles of the lens. By adding microelectrodes to the system, it is possible to relate steady currents (J) to the potential difference (PD) measured with a microelectrode. By injecting an outward current (I), it is possible to determine resistances and also the PD at which the steady outward potassium current becomes zero (PDJ = 0). At this PD the concentration gradient for potassium efflux and the electrical gradient for potassium influx are balanced so that there is no net flow of potassium across the membranes associated with the production of J. The PDJ = 0 for 18 rat lenses was 86 mV and that for 12 frogs lenses was -95 mV. This agrees with the potassium equilibrium potential and provides strong evidence to support the view that the outward equatorial current, J, is a potassium current. With the injection of outward current, I, the PD becomes more negative, the outward equatorial current, J, decreases, and the inward current at the optical poles increases. This suggests that there are separate electrical loops for K+ and Na+ that are partially linked by the Na, K-pump. Using Ohm's law, it is possible to calculate the input resistance (R = delta PD/I), the resistance related to the production of J (RJ = delta PD/delta J), and the effect of the combined resistances (delta J/I). The driving force for J can be estimated (PDJ = 0-PD). The relationships among currents, voltages and resistance can be used to determine the characteristics of the membranes that are associated with the outward potassium current observed at the equator. The effects of graded deformation of the lens were determined. The effects were reversible. The sites of inward and outward currents were not altered. Following deformation, the equatorial current, J, increased, and the PD became less negative. The PDJ = 0 remains the same so the ratio of K+ concentrations across the membrane responsible for J is unchanged. Therefore, the decrease in PD is ascribed to an increase in Na+ permeance with a resultant increase in driving force accounting for the increase in J.

Pulsed Doppler assessment of left ventricular diastolic filling in coronary artery disease before and immediately after coronary angioplasty.

To determine if left ventricular (LV) diastolic filling abnormalities are detectable by Doppler echocardiography in patients with coronary artery disease (CAD), 34 patients with CAD and 24 normal, age-matched control subjects underwent mitral valve pulsed Doppler examination. At catheterization, all CAD patients had typical angina, at least 70% diameter narrowing of 1 major coronary artery, ejection fraction of 50% or more and no valvular heart disease. Seventeen CAD patients underwent coronary angioplasty and had a Doppler examination 1 day before and 1 day after the procedure. Doppler diastolic time intervals, peak velocities at rapid filling (E velocity), atrial contraction (A velocity) and the ratio peak E/peak A velocities were measured. The following areas under the Doppler velocity envelope and their percentage of the total area were calculated: first third of diastole (0.33 area), triangular area under the peak E velocity (E area), and triangular area under the peak A velocity (A area). Patients with CAD and normal subjects were significantly different (p less than 0.01) in peak E velocity (CAD 0.60 +/- 0.12 m/s, normal 0.68 +/- 0.12 m/s), peak A velocity (CAD 0.59 +/- 0.12 m/s, normal 0.48 +/- 0.11 m/s), ratio peak E/peak A velocities (CAD 1.0 +/- 0.27, normal 1.5 +/- 0.32), A area (CAD 0.052 +/- 0.015 m, normal 0.036 +/- 0.010 m), ratio E area/A area (CAD 1.7 +/- 0.53, normal 2.5 +/- 0.69), and all area fractions. In the CAD patients who had undergone coronary angioplasty, no differences were found in any Doppler index before and immediately after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)