Infliximab for chronic cystoid macular edema associated with uveitis

PURPOSE: To assess the efficacy of the anti-TNF monoclonal antibody infliximab in uveitis patients without clinically evident ocular inflammation and impaired visual acuity because of chronic cystoid macular edema (CME). DESIGN: Prospective, noncomparative, interventional case series. METHODS: Patients with refractory CME (14 eyes, mean duration of 14 months), associated with intermediate uveitis (n = 6), Adamantiades-Behcet disease (n = 2), adult-type vascular pseudotumor (n = 1), and HLAB27+-related uveitis (n = 1) received an intravenous infliximab infusion (5 mg/kg); five patients were retreated after 1 month. RESULTS: Macular thickness, measured by ocular coherence tomography, was reduced from 428 +/- 138 microm to 219 +/- 51 microm at 2 months postbaseline (P = .0001), while visual acuity increased from 0.41 +/- 0.18 to 0.83 +/- 0.17 (P < .00001). Anatomic and functional improvement was sustained at 6 months in all. No ocular or extra-ocular side effects were noted. CONCLUSION: These promising results suggest that TNF may play an important pathogenetic role in chronic CME, thus, a controlled trial is warranted.     

Behçet's disease: a new target for anti-tumour necrosis factor treatment

Beh?et's disease is a multisystemic, chronic relapsing inflammatory disease classified among the vasculitides. Recurrent mucocutaneous lesions may be the only symptoms in mild cases, but articular, ocular, vascular, and/or gastrointestinal and central nervous system involvement may occur in most of the patients. Ocular disease is the most frequent cause of morbidity leading to blindness in 25% of those affected. The various non-specific immunosuppressive drugs, used either alone or in combinations, frequently fail to control inflammation or maintain remissions. The aetiology of Beh?et's disease is unknown, however it is currently thought that a central pathogenetic role of tumour necrosis factor (TNF) in the inflammatory process is possible. Until June 2002, and according to published and anecdotal data, more than 80 patients from 10 different countries have received anti-TNF treatment. The short-term effects of the anti-TNF monoclonal antibody infliximab have been reported in several case reports and small case series, whereas the effects of etanercept have been presented in recent conferences. Preliminary results strongly suggest that infliximab is remarkably effective in inducing short-term remission of almost all manifestations of the disease, including acute, sight threatening panuveitis. A double blind, placebo controlled, one month study on the efficacy of etanercept in suppressing the mucocutaneous manifestations of the disease showed beneficial results. To date, significant side effects have not been reported. It seems that TNF block is an effective new treatment for patients with Beh?et's disease. Whether such treatment is superior to the conventional therapeutic approaches in preventing relapses and progression of the disease remains to be determined by carefully controlled studies. At least three open, long term studies, including larger numbers of patients are currently being conducted.     

13q deletion in chronic lymphocytic leukemia: characterization of E4.5, a novel chromosome condensation regulator-like guanine nucleotide exchange factor

We report the characterization of a new gene (E4.5) that maps at chromosome band 13q14.3, a chromosomal area frequently deleted in chronic lymphocytic leukemia (CLL) and in other lymphoid malignancies. E4.5 gene encodes for a 4 kb mRNA expressed in various tissues and has an open reading frame of 531 amino acids. The predicted E4.5 protein shows strong homology with the human regulator of chromosome condensation (RCC1) protein, the principal GTP exchange factor for Ran protein. The E4.5 protein contains a BTB domain in its N-terminus, a protein-protein interaction motif. Therefore, we propose that E4.5 is a new member of the RCC1-related guanine nucleotide exchange factor (GEF) family with potent interaction with other proteins and unknown function. Until now, no tumor suppressor genes have been mapped in the 13q14.3 minimal deleted region (MDR) in patients with CLL. It has been proposed that loss of the 13q14.3 MDR may contribute to lymphoid neoplasia by altering the expression/function of genes located on 13q14.3 outside the MDR. The E4.5 is one of these genes with a potential role in the pathogenesis of CLL.     

Hypersensitivity reactions to carboplatin administration are common but not always severe: a 10-year experience

We have retrospectively evaluated and characterized the hypersensitivity reactions associated with carboplatin administration in ovarian cancer patients treated mainly on an outpatient basis at the Laikon Hospital from 1988 to 1998. A total of 240 patients, who had never been exposed to platinum compounds previously, received carboplatin plus cyclophosphamide (n = 58) or paclitaxel (n = 136) intravenously, and intraperitoneal carboplatin plus intravenous cyclophosphamide (n = 46). The median number of carboplatin courses was 6 (range 3-12) and 5 (range 4-6) for the intravenous and intraperitoneal treatment regimens, respectively. Thirty-two of 194 patients (16%) who were on intravenous carboplatin treatment developed symptoms compatible with a hypersensitivity reaction to carboplatin, that was always verified by manifestation of at least similar symptoms on rechallenging. In contrast, in the group of 46 patients on intraperitoneal carboplatin treatment, no hypersensitivity reaction was ever noticed. Hypersensitivity reactions always occurred after administration of the first 4 intravenous courses of carboplatin; 4, 19, 4, and 5 reactions occurred at the 5th, 6th, 7th, and 8th courses, respectively. These reactions could be distinguished in: (a) mild hypersensitivity reactions in 20 of 194 patients, which manifested as itching (20 patients) and small area erythema plus erythema of the palms and soles (12 patients), occurring either during intravenous injection when most of the drug scheduled had been administered, or within 3 days, and (b) in severe reactions in 12 of 194 patients, which manifested acutely as itching, diffuse erythroderma, rigor, facial swelling, throat and chest tightness, tachycardia (12 patients) and bronchospasm (2 patients), and hypertension or hypotension in 8 and 4 patients, respectively. With appropriate symptomatic management, discontinuation of carboplatin treatment was not required in patients with mild hypersensitivity reactions, but none of the 12 patients with severe reactions was able to receive a full subsequent dose of carboplatin on rechallenging. However, in 4 of these 12 patients carboplatin was replaced by cisplatin, which was given for 4-6 courses without side effects. These findings indicate that although hypersensitivity reactions are common in general, occurring in almost 1 of every 6 patients treated intravenously with carboplatin, their clinical picture is variable, leading to discontinuation of treatment in only 6% of patients. This is not the case when the intraperitoneal route of carboplatin administration is used when indicated.     

Gamma-knife radiosurgery for trigeminal neuralgia

Gamma knife was installed at the PD Hinduja National Hospital and Medical Research Centre, Mumbai, India, in January 1997. In the first year of gamma-knife radiosurgery to January 1998, we treated 110 patients, of whom six had medically refractory trigeminal neuralgia. Seven treatments were administered to this group of six patients (one had bilateral neuralgia). This report evaluates the effectiveness of radiosurgery treatment in these patients. The median age of the patients was 56 years and there were five males and one female. Following Leksell stereotactic frame fixation, a magnetic resonance imaging scan was done in all. The Leksell gamma plan was used for planning. A radiosurgery dose of 70–80 Gy was delivered to the trigeminal root entry zone, 2–4 mm anterior to the junction of the pons and trigeminal nerve with a single 4 mm collimator helmet. Complete pain relief was achieved in four patients. Two had partial relief. No patient developed any radiosurgery related morbidity during the follow-up period of 5–16 months. Radiosurgery seems to be an effective approach for medically or surgically refractory trigeminal neuralgia.     

Comparison of haemodynamic effects of nifedipine and molsidomine in patients with coronary artery disease

Summary The haemodynamic effects of oral nifedipine 20 mg and molsidomine 4 mg were compared in 24 patients with coronary artery disease.Molsidomine unlike nifedipine caused a significant fall in mean pulmonary artery pressure and left ventricular end-diastolic pressure. Both drugs caused a significant and comparable reduction in systolic and diastolic blood pressure. Although only nifedipine significantly reduced systemic vascular resistance the difference between the drugs was not significant. The heart rate was significantly increased by nifedipine but not by molsidomine. The ejection phase indices were all increased by molsidomine and the increment in the mean normalized systolic ejection rate was significantly greater than that due to nifedipine. The left ventricular end-systolic volume index decreased significantly after molsidomine but not nifedipine.Neither drug significantly affected left ventricular end diastolic volume index, stroke volume index, maximal rate of rise of left ventricular pressure or left ventricular stroke work index.