Cytostatic and immunosuppressive treatment of ocular Beh?et syndrome

Ocular symptoms of Beh?et's syndrome in 16 patients and the results of cytostatic and immunosuppressive therapy with cyclosporin A (6 patients), chlorambucil (6 patients), and a combination of cyclophosphamide and procarbacin (4 patients) are described. The clinical course and therapeutic outcome were compared to the patients' visual acuity and the duration of the disease prior to institution of cytostatic therapy. Average follow-up was 4.6 years, maximum 9 years. The principal ocular symptom in all patients was hemorrhagic, occlusive periphlebitis. Other symptoms, in descending order of frequency, were chorioretinitis, iridocyclitis, complicated cataract, secondary glaucoma and exudative retinal detachment. The patients in whom cytostatic therapy was instituted no later than 6 months after onset of the disease showed an improvement in or stabilization of visual acuity, as well as a clear reduction in signs of intraocular inflammation and frequency of recurrence. No improvement in visual acuity or ocular symptoms was achieved in cases where the disease was very advanced, despite cytostatic-immunosuppressive therapy. The results support early institution of immunosuppressive therapy in cases with Beh?et's syndrome where severe, irreversible damage has not yet occurred and in which vision is threatened in both eyes. However, due consideration must be given to the potential risks of immunosuppressive therapy, in particular the risk of a malignant tumor.     

D-[3H]galactose incorporation into glycogen in retinal cone cells

Previous studies have shown that bovine retinas incubated with [3H]galactose incorporated it, unmodified, into large molecules. Light and electron microscope autoradiography showed a significant proportion of the label to be in cone inner segments, and pulse-chase studies showed it was subsequently transported to the synaptic pedicles. In this report, evidence is presented to show that the galactose-labelled macromolecules are resistant to hydrolysis by proteolytic enzymes, testicular hyaluronidase, chondroitinase ABC, beta-glucosidase and beta-glucuronidase, but are readily degraded by alpha-amylase and beta-galactosidase, and to a lesser extent by beta-amylase. Treatment with alpha-amylase also leads to specific removal of radioactivity from cone inner segments and pedicles, as judged by light-microscopic autoradiography. These studies appear to indicate that the cone-specific galactose label is in glycogen or glycogen-like molecules.     

Four years' experience with a clinical intervention program: cost avoidance and impact of a clinical coordinator

Four years of data are reported on the drug cost avoidance and the net cost savings associated with a clinical pharmacy intervention program. In 1986 the pharmacy department at a 324-bed nonprofit community medical center began a clinical intervention program by adding one full-time equivalent for providing clinical services. A new clinical pharmacist position was created in 1988. A reorganization in 1989 resulted in further increases in staffing, including the creation of a clinical coordinator position to oversee the intervention program, and in administrative time. Staff pharmacists self-report a broad range of interventions on a clinical documentation form. During the period 1986-1989, monthly data on the number of types of interventions recommended, the percentage of recommendations accepted by the medical staff, and drug cost avoidance were tabulated. Cost avoidance was calculated by subtracting the cost of therapy ordered by the physician from the cost of therapy initiated as a result of the intervention. Net drug cost savings were calculated by subtracting from cost avoidance the cost of pharmacist time required for performing the interventions. The average number of interventions per month ranged from 170 in 1986 to 292 in 1990. During an 18-month period before the clinical coordinator was added, average monthly cost avoidance and net savings were $4932 and $3739, respectively. Average monthly cost avoidance increased to $6244 and savings to $4644 in a 12-month period after the clinical coordinator was added. A four-year study of a clinical intervention program showed that the dollar value and impact outlasted the initial success expected for such programs.     

The Relationship Between Quantitative MRI and Neuropsychological Functioning in Temporal Lobe Epilepsy

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.     

Lines of Murine Oligodendroglial Precursor Cells Immortalized by an Activated neu Tyrosine Kinase Show Distinct Degrees of Interaction with Axons In Vitro and In Vivo

Replication-defective retroviruses expressing the t- neu oncogene, or a hybrid protein with the neu tyrosine kinase linked to the external region of the human epidermal growth factor receptor ( egfr-neu ), were used to establish lines of murine oligodendroglial precursor cells. Differentiation of the t- neu lines into myelin-associated glycoprotein (MAG)-positive oligodendrocytes was induced by dibutyryl cAMP, and the egfr-neu line showed limited differentiation in vitro upon withdrawal of epidermal growth factor. Cerebellar granule cell neurons expressed mitogens for the cell lines. Upon transplantation into demyelinated lesions, t- neu line cells engaged with the demyelinated axons whereas the egfr-neu line cells differentiated further and ensheathed the axons. These cell lines thus interact with neurons in vitro and in vivo and can be used as tools to define the molecules involved in different stages of neuron-glia interaction.     

Molluskizid wirksame Spiro-α-methylen-γ-butyrolactone

α-Methylene-γ-butyrolactones with Molluscicidal Activity The α-methylene-γ-butyrolactones 1-28 were tested in vitro for molluscicidal activity against Biomphalaria glabrata. The racemic compound 25 shows the best activity. The synthesis was carried out by modified Reformatzky reaction of the corresponding carbonyl compounds and bromomethylacrylic acid ethyl ester. 7-10, 17 and 22-27 have been synthesized for the first time.     

A phase I/II study of continuous infusion suramin in patients with hormone-refractory prostate cancer : toxicity and response

 Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin’s activity in hormone-refractory prostate cancer. Received: 9 June 1995/Accepted: 18 March 1996