Health-Related Quality of Life During Routine Treatment with the SQ-Standardised Grass Allergy Immunotherapy Tablet: A Non-Interventional Observational Study.

BACKGROUND AND OBJECTIVE: Allergy immunotherapy (AIT) with the SQ(®) grass sublingual immunotherapy (SLIT)-tablet has been shown to be efficacious, well-tolerated and to improve disease-specific health-related quality of life (HRQoL) in controlled clinical trials. The aim of our study was to investigate HRQoL in patients with allergic rhinoconjunctivitis routinely treated with the SLIT-tablet and taking symptomatic medication as needed compared with patients treated only with symptomatic medication. METHODS: In a non-interventional, open-label study, patients treated with the SLIT-tablet were observed for about 12 months compared with patients only symptomatically treated. Patients assessed their HRQoL with the 12-Item Short Form Health Survey (SF-12) and the Rhinitis Quality of Life Questionnaire (RQLQ) in the grass pollen seasons (GPS) at baseline (GPS1, HRQoL1), after GPS1 (HRQoL2) and in the following GPS (GPS2, HRQoL3). Tolerability, compliance, symptoms and medication use were assessed in the SLIT-tablet group by the physician. RESULTS: Overall, data were analysed in 576 patients. Mean differences (±SD) in overall scores for HRQoL3 versus HRQoL1 (186 patients) of SF-12 were +11.4 ± 16.8 (SLIT-tablet) and -3.4 ± 15.7 (symptomatic medication), (p < 0.0001), and of RQLQ -1.31 ± 1.07 and +0.10 ± 0.74 (p < 0.001), and for HRQoL3 versus HRQoL2 (238 patients) of SF-12 -1.6 ± 15.3 and -10.0 ± 14.1 (p = 0.0003), and of RQLQ +0.22 ± 1.29 and +1.24 ± 1.30 (p < 0.0001). Tolerability and adherence for the SLIT-tablet were comparable with data of other non-interventional studies. CONCLUSIONS: Routine treatment with the SQ(®) grass SLIT-tablet resulted in clear improvements in disease-specific and general quality of life, while no improvements were observed in patients treated only symptomatically.

Orbitopatía de Graves: una enfermedad poco conocida por el oftalmólogo. «El presente y el futuro está en los inhibidores de citoquinas. Cómo y cuándo utilizarlas» / Graves’ ophthalmopathy: A disease little-known by the ophthalmologist. The present and future is in cytokinase inhibitors. How and when to use them

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Probiotic milk consumption in pregnancy and infancy and subsequent childhood allergic diseases.

BACKGROUND: Whether probiotics, which can influence the microbiome, prevent infant eczema or allergic disease remains an open question. Most studies have focused on high-risk infants. OBJECTIVES: We sought to assess whether consumption of probiotic milk products protects against atopic eczema, rhinoconjunctivitis, and asthma in early childhood in a large population-based pregnancy cohort (the Norwegian Mother and Child Cohort study). METHODS: We examined associations between consumption of probiotic milk products in pregnancy and infancy with questionnaire-reported atopic eczema, rhinoconjunctivitis, and asthma in 40,614 children. Relative risks (RRs) were calculated by using general linear models adjusted for potential confounders. RESULTS: Consumption of probiotic milk in pregnancy was associated with a slightly reduced relative risk (RR) of atopic eczema at 6 months (adjusted RR, 0.94; 95% CI, 0.89-0.99) and of rhinoconjunctivitis between 18 and 36 months (adjusted RR, 0.87; 95% CI, 0.78-0.98) compared with no consumption during pregnancy. Maternal history of allergic disease did not notably influence the associations. When both the mother (during pregnancy) and infant (after 6 months of age) had consumed probiotic milk, the adjusted RR of rhinoconjunctivitis was 0.80 (95% CI, 0.68-0.93) relative to no consumption by either. Probiotic milk consumption was not associated with asthma at 36 months. CONCLUSIONS: In this population-based cohort consumption of probiotic milk products was related to a reduced incidence of atopic eczema and rhinoconjunctivitis, but no association was seen for incidence of asthma by 36 months of age.

Treatment and prevention of ophthalmia neonatorum.

QUESTION: In my office I occasionally see neonates with conjunctivitis. What are the current recommendations for ocular prophylaxis at birth? Do topical antibiotics alone provide adequate treatment of neonatal conjunctivitis? When is systemic therapy indicated? ANSWER: All infants should receive ocular prophylaxis at birth to prevent gonococcal ophthalmia. Neonates presenting with signs of conjunctivitis should have a conjunctival swab sent for Gram stain and culture. If Gram-negative diplococci are present on the Gram stain results, the infants and their parents should be treated immediately for presumed gonorrhea. Infants with chlamydial infection should be treated with oral antibiotics. Most of all other forms of bacterial conjunctivitis can be treated with topical antibiotics, with the exception of Pseudomonas infection. Infants should be followed during their treatment and upon completion of therapy to ensure resolution of symptoms. For cases in which sexually transmitted bacteria are implicated, the mothers and their sexual partners should be treated.

Conjuntivite neonatal com ênfase na sua prevenção / Neonatal conjunctivitis with emphasis on its prevention

Nos últimos tempos, a necessidade da utilização de medicamentos para prevenção da conjuntivite neonatal (CN) passou a ser questionada em alguns países desenvolvidos, devido ao elevado nível de assistência pré-natal. Ao contrário, no Brasil, embora não haja dados oficiais sobre sua ocorrência, vários trabalhos recentes comprovam elevada prevalência da infecção genital em mulheres em idade fértil e em gestantes. Isso, aliado ao fato de que o índice de transmissão da infecção genital por clamídia e gonococo, da mãe infectada para o recém-nascido é de 30 a 50 por cento, leva à conclusão de que a profilaxia medicamentosa está mais que justificada. A CN implica em importante potencial de complicações locais e sistêmicas, além da necessidade de exames laboratoriais para seu diagnóstico etiológico. Por isso, constitui importante problema de saúde pública, negligenciado no Brasil, onde não há padronização do método de prevenção. Embora o uso do nitrato de prata pareça ainda ser o método oficial, seu uso tem sido questionado devido à incompleta proteção contra clamídia, principal agente da conjuntivite neonatal nos dias atuais, e pela frequente ocorrência de conjuntivite química. Por isso, tem sido substituído por outros agentes, como a eritromicina, a tetraciclina, além de outros antibióticos. A superioridade da Iodopovidona em relação a esses antibióticos, nos vários quesitos analisados, tem sugerido que esse é o mais adequado entre os produtos, testados até o momento, para prevenção da CN.

Nowadays the use of drugs for prevention of neonatal conjunctivitis (NC) has been questioned in some developed countries, due to the high level of prenatal care. In Brazil, although no official data on the occurrence of NC is available, several recent studies has shown high prevalence of genital infection in childbearing age and pregnant women. This, coupled with the 30 percent to 50 percent transmission rate of genital chlamydia and gonococcus from mother to newborn, leads to the conclusion that chemoprophylaxis is justified. The potential for local and systemic complications and the need for laboratory tests for its diagnosis have made NC an important public health problem, overlooked in Brazil, where there is no standardization of the method of prevention. Although the use of silver nitrate still appears to be the official method, it has been questioned due to incomplete protection against chlamydia, nowadays the leading agent of NC, and by the frequent occurrence of chemical conjunctivitis. So, it has been replaced by other agents such as erythromycin, tetracycline and other antibiotics. The advantages of povidone-iodine compared to these agents in the various items analyzed, has suggested that it is the best, among the products tested so far, for the prevention of NC.

Successful treatment of Stevens-Johnson syndrome with steroid pulse therapy at disease onset.

PURPOSE: To evaluate the visual prognosis of patients with Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), followed by general and topical high-dose corticosteroids administration from disease onset. DESIGN: Prospective, observational case series. METHODS: Between May 1, 2003 and June 30, 2005, we enrolled 5 patients with SJS or TEN with ocular complications at the acute stage. Intravenous pulse therapy with methylprednisolone (steroid pulse therapy; 500 or 1000 mg/day for 3 to 4 days) was initiated within 4 days from disease onset. Topically, 0.1% betamethasone was applied over 5 times daily for at least 2 weeks. Visual acuity (VA) and slit-lamp microscopic appearance 1 year from disease onset were evaluated. RESULTS: At the first examination, corneal or conjunctival epithelial defects and pseudomembranous conjunctivitis were present in all cases. Skin eruptions dramatically improved after steroid pulse therapy. Although ocular inflammation increased for several days, pseudomembranes disappeared and corneal and conjunctival epithelium regenerated within 6 weeks. At the chronic stage, all eyes had clear corneas with the palisades of Vogt (POV), implying the presence of corneal epithelial stem cells. Best-corrected VA was 20/20 or better in all eyes. Five eyes showed superficial punctate keratopathy. No eye had cicatricial changes except for 1 with slight fornix shortening. No significant adverse effects of steroid occurred during all clinical courses. CONCLUSIONS: Steroid pulse therapy at disease onset is of great therapeutic importance in preventing ocular complications. Topical betamethasone also shows great promise for preventing corneal epithelial stem cell loss in the limbal region and cicatricial changes.

Oral supplementation with L-lysine did not prevent upper respiratory infection in a shelter population of cats.

Cats in animal shelters are highly susceptible to infection by feline herpesvirus (FHV) by virtue of their stress and close proximity to other cats. Animal shelters take several different approaches to prevent FHV-related upper respiratory infections (URIs), including empirically treating all cats with L-lysine, a supplement believed to prevent the replication of FHV and, therefore, manifestations of herpesvirus infections. In this study we tested oral supplementation of L-lysine as a means to prevent URIs. One hundred and forty-four cats were treated with L-lysine in a small amount of canned food once daily. A 'no treatment' group of 147 cats received no lysine during the course of the study. The development of conjunctivitis or URI was tracked between the two groups. In all measures, there was no effect between the two groups, suggesting that lysine was not able to prevent URI or conjunctivitis in our shelter situation. Cats entering shelters encounter stressors that may make them more susceptible to FHV reactivation or infection. Infection control and control of fomite transmission are also key to keeping cats healthy in a group housing situation. The finding that lysine did not prevent URI in this animal shelter suggests that shelters may better use their resources by finding ways to decrease stress among their feline population, focusing on proper infection control measures, and limiting fomite transmission of disease.

Clinical efficacy and safety of preseasonal sublingual immunotherapy with grass pollen carbamylated allergoid in rhinitic patients. A double-blind, placebo-controlled study / Eficacia clínica y seguridad de la inmunoterapia sublingual preestacional con polen de gramíneas con alergoide carbamilado en pacientes con rinitis alérgica. Estudio a doble ciego controlado por placebo

Background: The aim of this study was to confirm the clinical efficacy and safety of a preseasonal sublingual immunotherapy (SLIT) in a group of allergic patients with seasonal rhinoconjunctivitis with or without mild intermittent or mild persistent asthma. The immunotherapy was administered through the oral mucosa with a monomeric carbamylated allergoid (allergoid SLIT) for grass pollens. A secondary endpoint was to evaluate the effect of the allergoid SLIT on nasal reactivity. Methods and results: A single-center, randomized, double-blind, placebo-controlled study was performed. Patients were selected and randomly allocated to two groups: one group received active treatment (allergoid SLIT) for 2 years and the other received placebo. Both groups received the necessary drug treatment throughout the trial. Thirty-three outpatients (20 men and 13 women, mean age: 30 years; range: 19-43) attending our center were enrolled in the study. Symptoms and medications were scored on diary cards during the pollen season. An allergen nasal challenge was performed at baseline and after 2 years of SLIT to evaluate nasal reactivity. Because the clinical scores were non-normally distributed, the Mann-Whitney and the Chi-square tests for intergroup comparisons and the Wilcoxon test for intragroup comparisons were used. The results were evaluated after 1 and 2 years of treatment. Between the first and second years of treatment, no changes in the scores for the placebo group were found, while for the active vaccine group significant decreases were found in rhinorrhea (p < 0.03), sneezing (p < 0.03), and conjunctivitis (p < 0.02). Symptom scores after nasal challenge decreased (p < 0.03) after 2 years' treatment. Nasal steroid use significantly decreased in the active treatment group during May and June in both the years of treatment (p < 0.02). Only two mild local adverse events were reported in the active group and none was reported in the placebo group. Conclusions: The results of this study show that the allergoid SLIT is safe and effective in decreasing symptom scores and drug use in rhinitic patients allergic to grass pollen

Antecedentes: El objetivo de este estudio fue confirmar, en un grupo de pacientes alérgicos con rinoconjuntivitis estacional con y sin asma leve intermitente o leve persistente, la eficacia clínica y la seguridad de una inmunoterapia (IT) sublingual preestacional a través de la mucosa bucal realizada con un alergoide monomérico carbamilado (alergoide SLIT) para el tratamiento de la alergia al polen de las gramíneas. El fin secundario era evaluar el efecto que el alergoide SLIT tiene en la reactividad de la mucosa nasal. Métodos y Resultados. Se trató de un estudio comparativo doble ciego, aleatorio, controlado con placebo, realizado en un único centro. Los pacientes fueron seleccionados y asignados al azar en dos grupos: a un grupo se le administró el tratamiento activo (alergoide SLIT) durante dos años y al otro se le administró placebo. Ambos grupos recibieron el tratamiento farmacológico necesario durante todo el estudio. Se inscribieron en el estudio treinta y tres pacientes externos (20 hombres y 13 mujeres, edad promedio 30 años; entre 19-43) que asistían a nuestro centro. Durante la estación polínica, se registraron en el diario de los pacientes los síntomas y la medicación. Se expuso a los pacientes al alergeno al inicio del estudio y también al cabo de dos años de la IT para evaluar la reactividad de la mucosa nasal. Debido a que los resultados clínicos no estaban distribuidos de manera normal, se utilizaron las pruebas de Mann Whitney y de Chi cuadrado para comparar los grupos entre sí y la prueba de Wilcoxon para la comparación intragrupal. Los resultados se evaluaron después de uno y de dos años de tratamiento. Entre el primer y segundo año de tratamiento no hubo cambios en los resultados del grupo tratado con placebo, mientras que en el grupo que recibió la vacuna activa disminuyeron significativamente la rinorrea (p<0.03), los estornudos (p<0.03) y la conjuntivitis (p<0.02). Los resultados de los pacientes sintomáticos disminuyeron (p<0.03) luego de la prueba nasal después de dos años de tratamiento. El uso de esteroides nasales disminuyó significativamente en el grupo activo durante los meses de mayo y junio en los dos años de tratamiento (p<0.02). Se informaron únicamente dos casos de efectos adversos locales leves en el grupo activo y ninguno en el grupo placebo. Conclusiones: los resultados del estudio muestran que el alergoide SLIT es seguro y efectivo para disminuir no sólo los síntomas en pacientes riníticos alérgicos al polen de las gramíneas sino también el uso de medicamentos por parte de estos pacientes

Allergic diseases and atopic sensitization in children related to farming and anthroposophic lifestyle--the PARSIFAL study.

BACKGROUND: The prevalence of allergic diseases has increased rapidly in recent decades, particularly in children. For adequate prevention it is important not only to identify risk factors, but also possible protective factors. The aim of this study was to compare the prevalence of allergic diseases and sensitization between farm children, children in anthroposophic families, and reference children, with the aim to identify factors that may protect against allergic disease. METHODS: The study was of cross-sectional design and included 14,893 children, aged 5-13 years, from farm families, anthroposophic families (recruited from Steiner schools) and reference children in Austria, Germany, The Netherlands, Sweden and Switzerland. A detailed questionnaire was completed and allergen-specific IgE was measured in blood. RESULTS: Growing up on a farm was found to have a protective effect against all outcomes studied, both self-reported, such as rhinoconjunctivitis, wheezing, atopic eczema and asthma and sensitization (allergen specific IgE > or = 0.35 kU/l). The adjusted odds ratio (OR) for current rhinoconjunctivitis symptoms was 0.50 (95% confidence interval (CI) 0.38-0.65) and for atopic sensitization 0.53 (95% CI 0.42-0.67) for the farm children compared to their references. The prevalence of allergic symptoms and sensitization was also lower among Steiner school children compared to reference children, but the difference was less pronounced and not as consistent between countries, adjusted OR for current rhinoconjunctivitis symptoms was 0.69 (95% CI 0.56-0.86) and for atopic sensitization 0.73 (95% CI 0.58-0.92). CONCLUSIONS: This study indicates that growing up on a farm, and to a lesser extent leading an anthroposophic life style may confer protection from both sensitization and allergic diseases in childhood.

Topical prophylaxis of conjunctivitis induced by high-dose cytosine arabinoside.

We investigated the efficacy of dexamethasone plus diclofenac eye drops as prophylaxis for conjunctivitis induced by high-dose (HD) cytarabine (Ara-C). Sixty patients were randomized to receive either dexamethasone (group A, n=29) or dexamethasone plus diclofenac (group B, n=31). Conjunctivitis was experienced by 13/29 (45%) patients in group A, and 4/31 (13%) patients in group B (p

Efficacy of diclofenac versus dexamethasone for treatment after strabismus surgery.

OBJECTIVE: To compare the efficacy of topical diclofenac sodium 0.1% versus dexamethasone 0.1% on the conjunctival healing process and on intraocular pressure (IOP) after strabismus surgery. DESIGN: A randomized clinical trial. PARTICIPANTS: Forty consecutive pediatric patients who underwent strabismus surgery. INTERVENTION: The patients were assigned before surgery to receive topical diclofenac 0.1% (study group, 20 patients) or dexamethasone 0.1% (control group, 20 patients) from immediately after surgery to up to 4 weeks after surgery (both combined with chloramphenicol 0.2%, polymyxin B sulfate 2500 U). MAIN OUTCOME MEASURES: Between-group comparison of five parameters: patient discomfort, conjunctival chemosis, inflammation, gap, and intraocular pressure (IOP) at 1, 2, and 4 weeks after surgery. RESULTS: At postoperative week 2, the diclofenac-treated group showed significantly less patient discomfort and less conjunctival inflammation, edema, and gap than the dexamethasone group (P: = 0.003, P: = 0.04, P: = 0.02, P: = 0. 001, respectively). At week 4, the study patients continued to show less discomfort and conjunctival gap (P: = 0.02). The dexamethasone group showed a significant change in IOP between the preoperative and the fourth postoperative week (P: = 0.001 in the right eye, P: = 0.0005 in the left eye) and an increased prevalence of higher IOP during the fourth postoperative week (P: = 0.01 in the right eye, P: = 0.02 in the left eye). Thirty-eight percent of the dexamethasone group showed an increase in IOP to more than 21 mmHg during the four postoperative weeks. No increase in IOP was noted in the diclofenac group. CONCLUSIONS: Topical diclofenac is superior to dexamethasone for each of the five postoperative parameters examined. Its maximal effect occurred at 2 weeks after surgery, without an increase in IOP or in local subconjunctival hemorrhage.

Acyclovir for the prevention of recurrent herpes simplex virus eye disease. Herpetic Eye Disease Study Group.

BACKGROUND: Long-term treatment with antiviral agents has been shown to prevent recurrences of genital and orofacial herpes simplex virus (HSV) disease, but it is uncertain whether prophylactic treatment can prevent recurrences of ocular HSV disease. METHODS: We randomly assigned 703 immunocompetent patients who had had ocular HSV disease within the preceding year to receive 400 mg of acyclovir or placebo orally twice daily. The study outcomes were the rates of development of ocular or nonocular HSV disease during a 12-month treatment period and a 6-month observation period. RESULTS: The cumulative probability of a recurrence of any type of ocular HSV disease during the 12-month treatment period was 19 percent in the acyclovir group and 32 percent in the placebo group (P<0.001). Among the 337 patients with a history of stromal keratitis, the most common serious form of ocular HSV disease, the cumulative probability of recurrent stromal keratitis was 14 percent in the acyclovir group and 28 percent in the placebo group (P=0.005). The cumulative probability of a recurrence of nonocular (primarily orofacial) HSV disease was also lower in the acyclovir group than in the placebo group (19 percent vs. 36 percent, P<0.001). There was no rebound in the rate of HSV disease in the six months after treatment with acyclovir was stopped. CONCLUSIONS: After the resolution of ocular HSV disease, 12 months of treatment with acyclovir reduces the rate of recurrent ocular HSV disease and orofacial HSV disease. Long-term antiviral prophylaxis is most important for patients with a history of HSV stromal keratitis, since it can prevent additional episodes and potential loss of vision.

Phase I trial of alpha-tocopherol effects on 13-cis-retinoic acid toxicity.

BACKGROUND: Retinoids are under intensive study for the treatment and prevention of cancer. Substantial dose-related toxicities of retinoids are a major obstacle to this work. In a recent retrospective analysis of combined 13-cis-retinoic acid (13cRA) and alpha-tocopherol (AT) in myelodysplasia, 13cRA toxicity was reduced significantly and 13cRA activity was enhanced. These results suggested the need for prospective testing of this new combination. This trial tested the hypotheses that At can reduce toxicity of high-dose 13cRA and does not interfere with 13cRA absorption/activity as reflected by reduced 13cRA serum levels. PATIENTS AND METHODS: This was a phase I trial design in which patients received fixed-dose 13cRA (100 mg/m2/d) plus escalating-dose AT (beginning at 800 IU/d, increased 400 IU/d each month until 2000 IU/d). We collected toxicity data every four weeks from self-report forms, clinical examinations and laboratory studies. AT effects on 13cRA toxicity were determined by comparing maximum toxicity at lowest AT dose with that at highest AT dose. We also measured serum levels of both agents every four weeks. RESULTS: Of the 45 patients registered, 36 had cancer (active or prior history), 9 had premalignant lesions. Thirty-nine patients could be evaluated for initial-course toxicity; 31 for final course toxicity. Median time on treatment (all patients) was four months (range, 1-9 months); a total of 223 month-long courses of treatment were given. Eighteen percent of patients (7/39) developed grade 3 or 4 toxicity in the initial course. The rates of increase and decrease in 13cRA toxicity associated with increasing AT doses were similar: 36% decreased (11/31), 32% increased (10/31) (P = 0.84). At did not reduce 13cRA serum levels. After initial increases of mean AT plasma levels (17.9 micrograms/ ml at baseline to 45.4 micrograms/ml after first four-week course), subsequent AT plasma increases (< 2-fold) did not keep pace with increased AT doses (2-3-fold). No major activity occurred in the 21 patients with active refractory cancer. The complete response rate in patients with premalignant head-and-neck or lung lesions was 77.8% (7/9), which included two patients previously refractory to 13cRA alone. CONCLUSION: Although escalating doses of AT did not reduce 13cRA toxicity, the rate of initial-course (including 800 IU/d of AT) high-grade toxicity was substantially lower than that typical of high-dose 13cRA-alone and similar to that typical of low-dose 13cRA-alone. Indeed, a trial of 13cRA-alone followed by 13cRA plus AT may have detected a significant toxicity difference. We did not design such a trial out of ethical concern for known side effects of high-dose 13cRA. The increase in AT serum levels was not proportional with increasing doses of AT, which may explain the lack of a dose-response effect of AT on 13cRA toxicity. Previous trials have established that 13cRA has an approximate 10% complete response rate in oral premalignancy. Our small trial's 77.8% complete response rate in premalignant lesions suggests that AT may enhance 13cRA clinical activity. Future trials of 13cRA plus AT are needed to define this combinations toxicity profile, clinical activity and pharmacokinetics.

Personal defense sprays: effects and management of exposure.

BACKGROUND: Most personal defense sprays contain o-chlorobenzylidene malononitrile (CS), w-chloroacetophenone (CN), oleoresin capsicum (OC), or a combination of these ingredients as the active agent. They are designed to incapacitate by causing acute ocular irritation, lacrimation, conjunctivitis, blepharospasm, and mild to moderate respiratory distress. METHODS: To assess the ocular effects of sprays containing OC as the active agent. Snellen visual acuities and anterior segment appearances of 22 police officers were determined before and after spray exposure. To assess the effects of OC spray contamination on soft contact lenses, four brands of lenses were sprayed and cleaned twice with an alcohol-based cleaner. Gas chromatography was used to search for residual OC in the lenses. RESULTS: All officers experienced intense blepharospasm, lacrimation, conjunctivitis, and incapacitation as the result of spray exposure. Acute effects lasted about 5 to 10 min, with relatively complete recovery occurring in about 30 to 60 min. All had significant conjunctivitis, and some had water-drop-shaped corneal defects that stained with fluorescein. These defects resolved within 24 hours without treatment. OC residue was found to be present in the soft lenses that had been sprayed and cleaned twice. CONCLUSIONS: Optometrists can manage uncomplicated spray exposure patients by directing at-home irrigation with water, and following up with an in-office examination. Soft lenses contaminated by OC spray should be discarded.

FLAG (fludarabine, cytarabine, G-CSF) as a second line therapy for acute lymphoblastic leukemia with myeloid antigen expression: in vitro and in vivo effects.

Thirteen consecutive adult patients with primary refractory (n = 5) or relapsed (n = 8) acute lymphoblastic leukemia (ALL) were treated by an induction schedule (FLAG) consisting of Fludarabine (30 mg/sqm/d) plus high dose Cytarabine (HD-ara-C: 2 g/sqm/d) (d 1-5) and G-CSF (from d O to polymorphonuclear recovery). Patients achieving complete remission (CR) were administered a second FLAG course as consolidation and were then submitted to an individualized program of post-remission therapy, depending on the patient's age and performance status. CR was achieved in 8/12 evaluable cases (67%). The median CR duration was 22.5 w. CR attainment was significantly related to the co-expression of lymphoid and myeloid antigens. ALL/My+ patients achieved CR in 6/6 evaluable cases vs. 2/6 for ALL/My+. In vitro 3H ara-C incorporation into cellular DNA resulted significantly increased by Fludarabine (in 7/9 tested cases) and, furthermore, by the association of Fludarabine G-CSF in 5 evaluable ALL/My+ cases; in contrast, no effect of G-CSF addition to Fludarabine was observed in 4 ALL/My. Myelosuppression was observed in all patients: the median time to neutrophils > 0.5 x 10(9)/1 was 16.3 d (range 13-22) and 16.2 d (range 9-29) to platelets > 20 x 10(9)/1. Nonhematological toxicity was minimal. In conclusion, FLAG is an active and tolerable combination in refractory ALL, particularly in cases with myeloid antigen expression where G-CSF appears to improve efficacy, probably increasing ara-C incorporation into the DNA of leukemic cells.

Randomized trial of silver nitrate, erythromycin, and no eye prophylaxis for the prevention of conjunctivitis among newborns not at risk for gonococcal ophthalmitis. Eye Prophylaxis Study Group.

OBJECTIVE: To compare the efficacy of commonly used forms of eye prophylaxis for newborns with no prophylaxis in the prevention of nongonococcal conjunctivitis. DESIGN: Randomized doubly masked clinical trial. SETTING: University of Washington Hospital and affiliated clinics, Seattle, between 1985 and 1990. SUBJECTS: The medical records of 8499 women were evaluated for possible participation; 2577 were eligible. Of the 758 enrolled, the infants of 630 were evaluable. INTERVENTION: Comparison of silver nitrate, erythromycin, and no eye prophylaxis given at birth for the prevention of conjunctivitis. MAIN OUTCOME MEASURES: Conjunctivitis during the first 60 days of life and nasolacrimal duct patency in the first 2 days of life. RESULTS: The frequency of impatent tear ducts at the 30- to 48-hour examination did not differ significantly by prophylaxis group. Among the 630 infants randomized and observed, 109 (17%) developed mild conjunctivitis. Sixty-nine (63%) of the cases appeared during the first 2 weeks of life. After 2 months of observation, infants allocated to silver nitrate eye prophylaxis at birth had a 39% lower rate of conjunctivitis (hazard ratio = 0.61, 95% confidence interval = 0.39 to 0.97), and those allocated to erythromycin had a 31% lower rate of conjunctivitis (hazard ratio = 0.69, 95% confidence interval = 0.44 to 1.07), than did those allocated to no prophylaxis. CONCLUSION: Silver nitrate eye prophylaxis caused no sustained deleterious effects and even provided some benefit to infants born to women without Neisseria gonorrhoeae. However, the effect was modest and against microorganisms of low virulence. The results suggest that parental choice of a prophylaxis agent including no prophylaxis is reasonable for women receiving prenatal care and who are screened for sexually transmitted diseases during pregnancy.