Acquired oculomotor paralysis: a new therapeutic approach. Apropos of 10 cases

PURPOSE: The aim of this work is to report our rehabilitation scheme and outcome in patients with acquired oculomotor palsy. PATIENTS AND METHODS: We cared for 10 patients with oculomotor palsy between January 1996 and March 1998 at the Casablanca University Hospital. Our orthoptic rehabilitation scheme was based on reinforcing the patient's sensorial potential using a prism dioper and motor capacities by soliciting vergency and version movements. RESULTS: The 10 patients (7 males, 3 females, mean age 39.5 years) had unilateral IV palsy (n =3), bilateral IV palsy (n= 1), unilateral VI palsy (n= 2), bilateral VI palsy (n= 1), partial unilateral III palsy (n= 1) and dissociated bilateral III palsy (n= 2). Mean delay to initiation of rehabilitation was 49 days and mean duration for treatment was 3 months. We achieved total recovery in 50% of the cases and partial recovery in 40%. Intermittent diplopia persisted in 10 per thousand of the cases. These results differ slightly from those in the literature where total regression is reported in about 50% of the patients after therapeutic abstention. CONCLUSION: This small series is insufficient to validate our method. The results obtained do however show that rehabilitation is safe and should be applied more widely in patients with oculomotor palsy.     

Ocular impairment during type II membranoproliferative glomerulonephritis

Membranoproliferative glomerulonephritis type II (MPGN) is characterized by dense deposits within glomerular basal membrane and Bruch's membrane which result in retinal lesions similar to drusens. We observed a 50-year-old patient with chronic renal deficiency who developed central bilateral serous retinopathy with diffuse punctiforme yellow subretinal lesions. Ophthalmoscopic and angiographic aspects led to an MPGN type II diagnosis. Specific posterior segment lesions are described during MPGN type II. Dense deposits concerned both lamina densa of glomerular basal membrane and Bruch's membrane with choriocapillaris. The main ocular complications were central serous chorioretinopathy and choroidal neovascularization. We review the clinical and evolutive aspects of this disease.     

Treatment of depression with the CRH-1-receptor antagonist R121919: endocrine changes and side effects

A dysregulation of the hypothalamus-pituitary-adrenocortical (HPA) system has been hypothesized to account for a myriad of cardinal symptoms of affective disorders. Specifically, increased CRH signalling via CRH type 1 receptors is thought to be an important factor in the pathogenesis of major depression and anxiety disorders. Consequently, a number of drugs have been developed in order to target the postulated increase in CRH/CRH 1 receptor signalling. One of these compounds, R121919, binds with high affinity to CRH1 receptors antagonising the action of CRH. R121919 was recently tested in an open-label study conceptualized as a safety and tolerability study. As part of this study, a thorough endocrine evaluation and detailed clinical laboratory analysis were assessed several times during 30 days of treatment with two different dose regimens of R121919 (5–40 mg vs. 40–80 mg) in 24 patients with a major depressive episode. During treatment with the experimental drug no serious side effects were noted. In particular, there were no adverse effects or impairment of the hypothalamic–pituitary–gonadal system, the hypothalamic–pituitary–thyroid axis, the renin–angiotensin system, prolactin or vasopressin secretion. Furthermore, no changes in the serum corticotropin and cortisol concentrations and in the responsivity of corticotropin and cortisol following a CRH stimulation test were noted. No effects of R121919 on clinical laboratory parameters including liver enzymes, EEG and ECG were observed. These results encourage the development of other CRH-1-R antagonists as a novel class of antidepressive drugs.     

Postoperative cardiac tamponade in the modern surgical era

BACKGROUND: Pericardial effusions resulting in cardiac tamponade (CT) are uncommon after open heart surgery (OHS) and are associated with significant morbidity and mortality. Characteristics and outcomes of patients who develop postoperative CT are poorly defined. Our objective was to further analyze the population at risk for developing postoperative CT, identify potential perioperative and surgical risk factors, and evaluate the impact of CT on patient outcomes. METHODS: A retrospective analysis of 4,561 consecutive patients undergoing OHS at our institution was performed. Patients with clinical suspicion of pericardial effusion following surgery were evaluated by transthoracic or transesophageal echocardiography, and clinical parameters were analyzed. RESULTS: Forty-eight (1%) of the 4,561 patients were found to have echocardiographic evidence of a moderate or large pericardial effusion, of whom 36 (74%) had evidence of CT. The mean age of the patients with CT was 61 years. Coronary artery bypass grafting (CABG) had been performed in 24% of these patients, valve +/- CABG in 73%, and other OHS procedures in 3%. The incidence of CT following CABG alone was 0.2%, whereas it was 0.6% after valve +/- CABG. Females had a higher risk for developing CT, and this occurred earlier in the postoperative period when compared with men. Aspirin, heparin, or warfarin were given to 84% of patients within 3 days of surgery. Mean time to diagnosis of CT was 10 +/- 1 days after OHS. Prior to diagnosis of CT, the maximum international normalized ratio (INR) and partial thromboplastin time (PTT) were 2.7 +/- 0.3 and 68 +/- 5 seconds, respectively. Forty-nine percent of pericardial effusions were posterior and 46% were circumferential; one-third of the effusions were considered large by echocardiography. There was one in-hospital cardiovascular death. CONCLUSIONS: CT after OHS is more common following valve surgery than CABG alone and may be related to the preoperative use of anticoagulants. Females appear to be at higher risk for developing early postoperative CT. When diagnosed and treated promptly, postoperative CT should not significantly increase mortality.     

Ocular damage during HIV infection at the University Hospital Center of Casablanca. (Apropos of 400 cases)

The objective of this study was to report ocular manifestations in Moroccan patients infected with HIV/AIDS. 400 patients were surveyed retrospectively from 1993 to 1998 as part of a co-operative study undertaken by the departments of infectious diseases and ophtalmology of the Casablanca Teaching Hospital. Of the 400 patients, 127 had an infection of the posterior segment and 7 showed signs of a palpebral infection. We also found 44 cases of opportunist retinal infections, dominated by the Cytomegalovirus (CMV) (18 cases). Our sample study indicates an intermediary position between western countries where the widespread use of the tritherapy has increased the life expectancy of patients and sub-Saharan Africa where epidemiological data are still characterised by high mortality and increasing endemic disease.     

Treatment with a CRH-1-receptor antagonist (R121919) does not affect weight or plasma leptin concentration in patients with major depression

Weight gain during treatment with psychotropic drugs is frequently observed and is assumed to be responsible for non-compliance and for an elevated risk to develop a number of somatic co-morbidities including cardiovascular disorders and type 2 diabetes. Absence of weight inducing effects is therefore a major objective for the development of new compounds. Recently, R121919, the first corticotropin releasing hormone receptor 1 (CRH1R) antagonist, was tested in major depression. Clinical efficacy, safety, and tolerability of this compound could be demonstrated. Since CRH is discussed to be involved in the regulation of appetite and weight, directly and via interaction with leptin, CRH1R antagonists are suspected to influence body weight. Effects of 30 days of treatment with the CRH1R antagonist R121919 on weight and leptin levels in 20 patients suffering from major depression were investigated. No significant weight changes during treatment with R121919 were observed. Furthermore, noeffects on plasma leptin concentrations were found. We conclude that treatment with the CRH1R antagonist R121919 does not affect weight or plasma leptin concentrations in patients with major depression. Together with previous findings indicating safety, tolerability, and clinical efficacy CRH1R antagonists are highly promising as a new treatment option in depression.     

Pretreatment cystatin C in children with malignancy: can it predict chemotherapy-induced glomerular filtration rate reduction during the induction phase?

BACKGROUND: Monitoring of kidney function is essential during chemotherapy. Serum creatinine is of limited value in early detection of renal insufficiency. The cystatin C level has been proved to be a good marker for detection of mild reduction in glomerular filtration rate. PURPOSE: To evaluate the validity of the pretreatment serum cystatin C level in predicting significant reduction of the glomerular filtration rate during the induction phase of chemotherapy. PATIENTS AND METHODS: Serum levels of cystatin C and creatinine and corrected creatinine clearance were assessed in 34 children with different types of malignancy just before the start of chemotherapy and again in 33 of them 1 month later. Patients were compared with 14 healthy controls of matched age and sex. RESULTS: Before chemotherapy, all patients when compared with controls had normal levels of cystatin C (P = 0.1) and creatinine (P = 0.62) and normal corrected creatinine clearance (P = 0.76). One month after chemotherapy, patients showed a significant increase in their cystatin C levels (P < 0.001) and a significant decrease in their corrected creatinine clearance (P < 0.001). However, creatinine levels did not change significantly (P = 0.65). Corrected creatinine clearance negatively correlated significantly with both cystatin C and creatinine levels (r = -0.622, P < 0.001; r = -0.346, P = 0.045, respectively) before chemotherapy and also 1 month after chemotherapy (r = -0.577, P < 0.001; r = -0.45, P = 0.009, respectively). When pretreatment levels of cystatin C and creatinine were used to predict patients who developed a reduction in corrected creatinine clearance of more than 20% after therapy, only the cystatin C level was statistically significant (P = 0.03). A cutoff point of 0.57 mg/L with sensitivity of 77.8%, specificity of 63%, and overall accuracy of 74% was suggested. CONCLUSIONS: Children with malignant diseases develop significant reduction in their glomerular filtration rate during the induction phase of chemotherapy, although their serum creatinine level may not change significantly. Cystatin C, as a more sensitive marker than creatinine for the assessment of glomerular filtration rate, can be used to predict patients who would have a higher risk of renal impairment during the induction phase of chemotherapy and who thus would require more frequent renal function assessment to consider adjustment of the chemotherapy dose if indicated.     

Development of a HPLC method for the determination of cyclosporin-A in rat blood and plasma using naproxen as an internal standard

An isocratic reversed phase high-performance liquid chromatographic (HPLC) method with ultraviolet detection at 205 nm has been developed for the determination of cyclosporin-A (CyA) in rat blood and plasma. Naproxen was successfully used as an internal standard. Blood or plasma samples were pretreated by liquid–liquid extraction with diethyl ether. The ether extract was evaporated and the residue was reconstituted in acetonitrile–0.04 M monobasic potassium phosphate buffer (pH 2.5) solvent mixture. After washing with n-hexane, 30 μl of the reconstituted solution was injected into HPLC system. Good chromatographic separation between CyA and internal standard peaks was achieved by using a stainless steel analytical column packed with 4 μm Nova-Pak Phenyl material. The system was operated at 75 °C using a mobile phase consisting of acetonitrile–0.04 M monobasic potassium phosphate (pH 2.5) (65:35 v/v) at a flow rate of 1 ml/min. The calibration curve for CyA in rat blood was linear over the tested concentration range of 0.0033–0.0166 M with a correlation coefficient of 0.989. For rat plasma, the range of the concentrations tested were between 0.002 and 0.0166 M and showed linearity with a correlation coefficient of 0.953. The intra- and inter-run precision and accuracy results were 1.24–21.87 and 3.1–12.23%, respectively. The low volume of blood or plasma needed (200 μl), simplicity of the extraction process, short run time (5 min) and low injection volume (30 μl) make this method suitable for quick and routine analysis.