Clinical development of new treatments for diabetic macular oedema.

The benchmark treatment for diabetic macular oedema, the major cause of visual impairment in patients with diabetes mellitus, has traditionally been laser photocoagulation; however, as laser treatment does not always improve vision or even prevent further loss in many cases, several new pharmacotherapies that are injected into the vitreous for diabetic macular oedema have been successfully trialled over the past decade. Others are currently being evaluated. The two major classes of these drugs are steroids and vascular endothelial growth factor antagonists. In this article we briefly review the major clinical studies recently conducted in this field.

Herpetic necrotizing retinitis following flucinolone acetonide intravitreal implant.

PURPOSE: To report a case of herpes simplex virus-induced herpetic necrotizing retinitis after placement of a flucinolone acetonide (Retisert) intravitreal implant. DESIGN: Interventional case report. METHODS: Retrospective chart review. RESULTS: A 22-year-old male with idiopathic unilateral panuveitis since 2002 that was intolerant of systemic immunosuppressive therapy received a flucinolone acetonide implant 6 years later. Intraocular inflammation was completely quiescent until 1 year following the implant, when he developed retinitis. To the authors' knowledge, this is the first reported case of polymerase chain reaction-proven herpetic necrotizing retinitis following implantation of a Retisert device. CONCLUSIONS: Although rare, herpetic necrotizing retinitis can occur in the setting of local ocular immunosuppression with the Retisert intravitreal implant. This potential infection should be considered in the face of recurrent uveitis following Retisert implantation.

[Acquired amegakaryocytic thrombocytopenia after thymectomy in a case of pure red cell aplasia associated with thymoma].

The association of thymoma with pure red cell aplasia has been well documented, but amegakaryocytic thrombocytopenia is not a recognized paraneoplastic syndrome complicating thymoma. We report a case of thymoma-complicated pure red cell aplasia and amegakaryocytic thrombocytopenia in a 73-yr-old woman. Pure red cell aplasia was diagnosed seven months after the detection of thymoma. One year after the diagnosis of pure red cell aplasia and seven months after thymectomy, bone marrow aspiration and biopsy showed an absence of megakaryocytes, marked erythroid hypoplasia with normal myeloid series. A diagnosis of amegakaryocytic thrombocytopenia and pure red cell aplasia was made. Oral steroid maintenance therapy resulted in recovery of platelet count. She has still transfusion-dependent anemia but platelet and neutrophil counts had been maintained in normal range for more than five months, until the last follow-up. We think that autoreactive T cells may induce a clinical autoimmune response even after eradication of thymoma, and aplastic anemia as a late complication following thymectomy was described in previous cases. This patient also has to be under a close observation because of the possibility to evolve into aplastic anemia.

Efficacy of steroid therapy on adult patients with severe pneumonia.

Optimal management of steroid therapy for severe pneumonia is an urgent issue. One hundred forty-eight elderly patients enrolled in our study were treated for severe pneumonia in a university hospital in Tokyo from 1998 through 2002. Steroid drugs were given to 82 patients (55.4%), whereas 66 (44.6%) received no steroids. Based on this main division, retrospective analyses were performed with regard to patient characteristics, antimicrobial agents, use or nonuse of mechanical ventilators, and prognoses. Significant difference was not seen in age, sex, underlying disease, isolated pathogens, and artificial respirator between the steroid and nonsteroid groups. Partial pressure of oxygen in arterial blood/fraction of inspired oxygen (Pao(2)/Fio(2)) ratio was significantly lower in the steroid (227.2 +/- 96.9) compared with the nonsteroid group (271.6 +/- 86.4) (P < 0.01). Prognoses were evaluated 21 days after treatment initiation. Significant differences appeared: First, the average cure rate of patients who took steroids within 3 days after starting treatment was 62.7%, whereas the rate was 12.9% (P < 0.001) in those who did not take steroids earlier than the 4th day. The cure rate of the nonsteroid group was 39.3% (P < 0.001). Second, the total dose of steroids (methylprednisolone) given within 7 days was less in cured cases (774 +/- 749 mg) than in noncured cases (1,190 +/- 768 mg) (P < 0.05). In conclusion, steroids should be administered in the early stage after onset of pneumonia, and large doses of steroids becomes a compounding factor in the prognosis of pneumonia.

Acquired Amegakaryocytic Thrombocytopenia after Thymectomy in a Case of Pure Red Cell Aplasia Associated with Thymoma / 대한진단검사의학회지

The association of thymoma with pure red cell aplasia has been well documented, but amegakaryocytic thrombocytopenia is not a recognized paraneoplastic syndrome complicating thymoma. We report a case of thymoma-complicated pure red cell aplasia and amegakaryocytic thrombocytopenia in a 73-yr-old woman. Pure red cell aplasia was diagnosed seven months after the detection of thymoma. One year after the diagnosis of pure red cell aplasia and seven months after thymectomy, bone marrow aspiration and biopsy showed an absence of megakaryocytes, marked erythroid hypoplasia with normal myeloid series. A diagnosis of amegakaryocytic thrombocytopenia and pure red cell aplasia was made. Oral steroid maintenance therapy resulted in recovery of platelet count. She has still transfusion-dependant anemia but platelet and neutrophil counts had been maintained in normal range for more than five months, until the last follow-up. We think that autoreactive T cells may induce a clinical autoimmune response even after eradication of thymoma, and aplastic anemia as a late complication following thymectomy was described in previous cases. This patient also has to be under a close observation because of the possibility to evolve into aplastic anemia.

Corticosteroids reduce postoperative morbidity after third molar surgery: a systematic review and meta-analysis.

PURPOSE: The purpose of this study was to apply meta-analytical methods to measure the effect of corticosteroids (CS) on edema, trismus, and pain at early and late postoperative periods after third molar (M3) removal. MATERIALS AND METHODS: A systematic search of the literature was carried out to identify eligible articles. The primary predictor variable was perioperative CS exposure (yes or no). The 3 outcome variables were edema, trismus, and pain assessed during the early (1-3 days) and late (>3 days) postoperative time periods. Standardized mean differences (SMD) for edema and weighted mean differences (WMD) for trismus and pain were pooled across studies. Differences between the 2 treatment groups were assessed using random effects models and metaregressions for both early and late postoperative assessments. RESULTS: Twelve trials met the inclusion criteria. Subjects receiving CS had significantly less edema during both early (SMD, 1.4; 95% confidence interval [CI], 0.6, 2.2; P < .001) and late (SMD, 1.1; 95% CI, 0.1, 2.0; P = .03) time periods after surgery and less trismus than controls during the early and late postoperative periods (early WMD, 4.1 mm; 95% CI, 2.8 mm, 5.5 mm; P < .001; late WMD, 2.7 mm; 95% CI, 0.8 mm, 4.6 mm; P = .005). Average pain levels were not significantly different between the 2 groups (early WMD, 0.4 visual analog scale [VAS]; 95% CI, -0.04 VAS, 0.9 VAS; P = .07; late WMD, 0.5 VAS; 95% CI, -0.6 VAS, 1.5 VAS; P = .4). CONCLUSIONS: The findings of this study suggest that perioperative administration of corticosteroids produces a mild to moderate reduction in edema and improvement in range of motion after M3 removal.

The diagnosis of lichen-planus-like contact dermatitis to chlorpheniramine maleate.

In spite of the common use of the diagnostic category of lichen-planus-like contact dermatitis, we were unable to find established criteria for such a condition. An atypical distribution of otherwise typical lichen planus lesions is usually considered as a feature of a lichenoid eruption. When facing unusual or unexpected clinical features, it is always advisable to consider an adverse reaction to a medical intervention as a potential option. We report a lichen-planus-like eruption occurring after contact with a topical agent containing chlorpheniramine maleate. To our knowledge, this is the first reported case of lichen-planus-like contact dermatitis associated with chlorpheniramine maleate.

New steroidal antiinflammatory antedrugs: Methyl 3,20-dioxo-9 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-1,4-pregnadiene-16 alpha-carboxylate and its 21-O-acyl derivatives.

In a continuing effort to increase local to systemic activity ratios of potent steroidal antiinflammatory antedrugs, a series of 21-O-acyl derivatives of methyl 3,20-dioxo-9 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-1,4-pregnadiene-16 alpha-carboxylate, FP16CM, were synthesized. These derivatives were evaluated for antiinflammatory activity and their adverse effects in an acute and semi-chronic croton oil-induced ear edema bioassay. Following a single topical application in the croton oil-induced ear edema bioassay, treatment with all the compounds resulted in dose-dependent inhibition of edema. From these dose-response profiles, the following ID(50) values (nmol/ear resulting in a 50% reduction of edema) were calculated: prednisolone (Pred); 454, FP16CM; 255, 21-acetate (FP16CM-acetyl); 402, 21-propionate (FP16CM-propionyl); 474, 21-valerate (FP16CM-valeryl); 446 and 21-pivalate (FP16CM-pivalyl); 219 nmol. In a 5-day semi-chronic study at the equipotent doses, the novel steroidal antedrugs did not significantly alter body weight gain, thymus weights or plasma corticosterone levels unlike the parent compound Pred. The compounds were assessed for high-affinity glucocorticoid receptor binding and glucocorticoid-mediated inhibition of nitric oxide (NO) generation in an in vitro RAW 264.7 macrophage cell culture system. Binding affinities for cytosolic glucocorticoid receptors were Pred; 85, FP16CM-acetyl; 86, FP16CM-propionyl; 169, FP16CM-valeryl; 149, FP16CM-pivalyl; 126 nM, respectively. Concomitant potencies for inhibition of NO generation by macrophages stimulated with lipopolysaccharide were Pred; 159, FP16CM-acetyl; 377, FP16CM-propionyl; 405, FP16CM-valeryl; 344, FP16CM-pivalyl; 311 nM, respectively. Collectively, results of these investigations suggest that esterification of 21-OH with various anhydrides did not improve receptor binding, inhibition of NO generation and ear edema inhibition, however, serum corticosterone level and local over systemic activities (L/S) were markedly improved.

Hydrocortisone 17-butyrate (Locoid) 0.1% fatty cream versus desonide (Apolar) 0.1% ointment in the treatment of patients suffering from atopic dermatitis.

A randomized, double-blind, left-right study to compare the therapeutic efficacy and the cosmetic acceptability of the new hydrocortisone 17-butyrate (Locoid) 0.1% fatty cream application form with desonide (Apolar) 0.1% ointment was performed in thirty patients suffering from moderate to severe atopic dermatitis. The medications were applied to symmetrical, bilateral skin lesions twice daily for 4 weeks. Both treatments effected highly significant reductions of the score values for the severity of all clinical skin parameters assessed. Score reductions were, however, more pronounced on Locoid-treated sides than on Apolar-treated sides both after 2 and 4 weeks of therapy. It appeared further that clinical efficacy of treatment at completion of the study was also in favour of Locoid-treated sides, indicating that Locoid fatty cream is more effective than Apolar ointment. No serious side-effects were reported during the study. The expressed patient preferences with respect to cosmetic acceptability of treatments were significantly in favour of Locoid fatty cream, indicating that patients preferred the use of this new galenic formulation over an ointment formulation. It is concluded that the new application form of Locoid, a fatty cream, is a useful and beneficial addition to topical corticosteroid therapy, which will promote patient compliance in a wide range of corticosteroid-responsive skin diseases.

Clinical comparison of alclometasone dipropionate and desonide ointments (0.05%) in the management of psoriasis.

This was a double-blind, randomized, parallel-groups comparison of alclometasone dipropionate and desonide ointments (0.05%) applied twice daily without occlusion for 3 weeks by patients with moderate to severe psoriasis. Data from thirty-three patients in each group showed that both treatments produced rapid amelioration of erythema, induration, and, especially, scaling; substantial improvement was evident after 1 week and continued thereafter. Differences between the groups were not statistically significant, but trends consistently favoured alclometasone. No adverse drug reaction occurred.

Comparison of the effect of phenylbutazone, desonide and cyclophosphamide on four types of experimental pleurisy.

The action of phenylbutazone, a non-steroid anti-inflammatory drug, desonide, a corticosteroid, and cyclophosphamide, an immunosuppressant agent, was studied on four types of experimental pleurisy: carrageenan-pleurisy in rats; passive reversed Arthus pleurisy in rats; Bordetella pertussis-delayed hypersensitivity pleurisy in rats and PPD (purified protein derivative)--delayed hypersensitivity pleurisy in guinea-pigs. For each compound, the action on the exudate and on the number of the different categories of leucocytes in the inflammation focus was evaluated. In carrageenan-inflammation, phenylbutazone reduced the oedema and the number of neutrophils and macrophages. Its favourable effect on exudative events in Arthus--and B. pertussis--reactions was not accompanied by high modifications at the cellular level. With the exception of PPD-pleurisy, desonide reduced the three other reactions. Its action related to the exudate and the various leucocyte types, except in the Arthus reaction in which only the number of neutrophils was decreased. The effect of cyclophosphamide was mainly in B. pertussis pleurisy in which it resulted in a decrease of oedema and a reduction in the number of mononuclears. For each compound, correlations between the effect on exudative and cellular phenomena are discussed.

[Effect of a corticosteroid additive on the result of local therapy of bacterial superinfection in tinea pedis intertriginosa]. / Der Einfluss eines Kortikosteroidzusatzes auf das Ergebnis der Lokalbehandlung der bakteriell superinfizierten Tinea pedum intertriginosa.

Sixty cases of tinea pedum intertriginosa were topically treated in a double-blind trial. In 34 cases a cream was used, which contained 5-chloro-8-hydroxyquinoline, gentamycin and fluprednyliden-21-acetate. In 26 cases a cream was used, which contained 5-chloro-8-hydroxyquinoline and gentamycin alone. Treatment was continued over three weeks. In weekly intervalls mycological, bacteriological and clinical controls were performed, which showed that the steroid-component had no disadvantageous effect on the course of infection. In contrast the steroid containing preparation proved to be slightly superior.

Action of phenylbutazone, cyclophosphamide and prednacinolone on pleurisy due to Bordetella pertussis hypersensitivity in the rat.

Phenylbutazone, cyclophosphamide and prednacinolone acetonide, administered around the period of challenge reduced the exudate of pleurisy due to Bordetella pertussis hypersensitivity in the rat. The results on the leukocytes of the exudate are different depending on the class of product studied. Phenylbutazone only slightly reduced the number of mononuclears cells. Both the immunosuppressive and the corticoid induced a clear decrease in the total leukocyte number. But, while prednacinolone effects were nearly equally distributed among mononuclears and polynuclears, cyclophosphamide was mainly active on mononuclears.