Genetic markers in primary open-angle glaucoma

Purpose: To investigate possible associations between genetic markers and Primary Open-Angle Glaucoma (POAG). Methods: A number of genetic markers were typed in 84 unrelated patients with POAG and compared with a random sample of healthy individuals. The markers were Transferrin, Group Specific Component, G1m (1), G1m (2) and G3m (5) Allotypes, Adenylate Kinase, Adenosin Deaminase, Glyoxalase I and Acid Phosphatase and PCR-based markers HLA-DQA1 and D1S80. Results: No significant differences were found except the strong association between the group of POAG patients and Acid Phosphatase ACP^*C allele (² = 32.86; p < 0.0001). Conclusions: Since Acid Phosphatase gene is localized to chromosome 2p23, this result could be a first comprehensive step in the localization of POAG genes.     

Evaluation of vesico-urethral and sweating function in disorders presenting with parkinsonism

Investigation of vesico-urethral and sweating function was performed in twelve patients with classical idiopathic Parkinson's disease and ten patients with parkinsonism associated with features suggestive of more extensive involvement of the nervous system, as in the Shy—Drager syndrome. The urodynamic studies revealed detrusor hyperreflexia with reduction of maximal cystometric capacity in only one patient with Parkinson's disease (8%), but in nine patients with parkinsonism associated with other features (90%). Urethral sphincter electromyography did not indicate denervation in any patient of either group. Delayed or incomplete relaxation of the urethral sphincter during micturition was observed in seven patients with Parkinson's disease (58%) and in two patients of the other group (20%). Decreased sweating responses were found in both groups of patients when compared with control subjects. Hypohidrosis was more pronounced in parkinsonism associated with other features than in Parkinson's disease. Differences in sweating between the two sides of the body were observed in both groups of patients. Although there are differences in vesico-urethral and sweating function, they do not precisely differentiate between patients with classical Parkinson's disease and those with parkinsonism associated with features suggestive of more extensive involvement of the nervous system.     

Die anomalen Fusionsbewegungen: Der senso-motorische Aspekt des anomalen Binokularsehens

Zusammenfassung Es wurde nachgewiesen, daß bei konkomitierender Esotropie außer sensorischen Folgen auch senso-motorische Folgezustände vorkommen. Sie lassen sich vor allem mit Prismen nachweisen und werden als fusionsbedingt aufgefaßt (anomale Fusionsbewegungen).Bei 30 Patienten wurden die Eigenschaften dieser Vorgänge untersucht und erklärt. Schließlich wurde der Zusammenhang zwischen den anomalen Fusionsbewegungen und schon früher von anderen Autoren beschriebenen Krankheitsbildern analysiert, die je nach der ihnen zugrundegelegten Auffassung, unter verschiedenen Namen bekannt waren.

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Anomalous fusional movements: The sensorimotor aspect of anomalous binocular vision

Summary It has been demonstrated that, besides sensory adaptation phenomena, sensorimotor phenoma may also develop in concomitant esotropia. The existence of the latter entity can be shown particularly by means of prisms and is interpreted as fusional in origin. It is therefore defined as anomalous fusional movements.The features of these anomalous fusional movements were studied in a group of 30 patients, mainly in order to investigate their finality.Correlations were evaluated between anomalous fusional movements and entities previously described by different names according to the interpretation given them by various authors.

     

Phase I evaluation of 773U82-HCl in a two-hour infusion repeated daily for three days

One of a novel series of compounds (AMAPS or arylmethylaminopropanediols), 773U82-HCl has shown significant antitumor activity inin vitro and inin vivo tumor systems, but has less animal CNS toxicity than the lead compound in the same series (crisnatol). This study was designed to evaluate the pharmacokinetics, qualitative and quantitative toxicities of 773U82-HCl and to determine the recommended phase II dose (MTD) of 773U82-HCl given as a short infusion daily for 3 days every 3 weeks. Twenty-nine patients with refractory malignancies received 79 courses over 9 dose levels during this study. Doses ranged from 50 to 1060 mg/m²d×3 days. Due to the possibility of local hemolysis with concentrations > 1.5 mg/ml, drug was administered in solutions containing 1.5 mg/ml. Because large volumes were needed at the higher dose levels, the infusion duration was increased from 2 hours to 4 hours. Mild to moderate nausea, vomiting, fatigue, dizziness and headaches were observed. Myelosuppression was the dose limiting toxicity. The recommended phase II dose and schedule was determined to be 800 mg/m²d×3d every 3 weeks. 773U82-HCl plasma concentration-time data were analyzed using a two-compartment pharmacokinetic model. The t1/2 averaged 6 hours and the total body clearance was 75.9 L/hr/m². The volume of distribution (Vdss) was large, averaging 470 L/m².Abbreviations ECG electrocardiogram - t^1/2 half-life - Vdss volume of distribution - HPLC highperformance liquid chromatography - Vd_ss steady-state volume of distribution - AUC area under the concentration × time curve - CL total body clearance - C_max peak plasma level - V_c central volume of distribution     

The importance of angiogenesis in ovarian cancer

Advanced stage ovarian cancer has a high rate of recurrence even after surgery followed by chemotherapy combining carboplatin and a taxane. New strategies are currently under way to combat this situation and one of the most promising ones is based on the knowledge that angiogenesis, the mechanism of formation of new blood vessels coupled with the degradation of the extracellular matrix for metalloproteinases, could be crucial in the development of this tumor. The principal molecule implicated in angiogenesis process of ovarian cancer is the vascular endothelial growth factor (VEGF). Several studies are now in progress to clarify its role as a diagnostic tool or its therapeutic implication. Presently, there is no indication for the use of VEGF in a preliminary diagnosis seeing that an increase in levels can be seen in both benign and malignant ovarian conditions. VEGF is also responsible for an increase in vascular permeability and is directly related to symptoms such as ascites and pleural effusion, both of which are frequent in ovarian cancer. Several papers have analised the role of VEGF as a prognostic factor and some of them do confirm VEGF as an independent prognostic factor in ovarian cancer. VEGF and the metalloproteinase system coupled with angiogenesis are currently being evaluated as therapeutic targets but no positive results have yet to be seen in this field.      

A phase I study of 5-fluorouracil, leucovorin and levamisole

 Purpose: The activity of 5-fluorouracil (5-FU) against colon cancer is enhanced by leucovorin and the combination of 5-FU and levamisole has activity in the adjuvant treatment of colonic malignancies. The combination of 5-FU with both leucovorin and levamisole may provide additional benefit in the treatment of colon cancer. Methods: A phase I study to assess qualitative and quantitative toxicities of this three-drug combination and to determine a dose for further phase II testing was undertaken. The role of levamisole as an immunomodulator was also assessed. Results: A group of 38 patients with incurable etastatic malignancies received 119 cycles of treatment at eight dose levels. 5-FU (375 mg/m² per day) and leucovorin (200 mg/m² per day) were administered intravenously (days 1–5). Levamisole was administered orally (days 1–3 and 15–17) at doses from 30 to 470 mg/m² per day. Patients received both 5FU/leucovorin and 5-FU/leucovorin/levamisole in random order for their initial two cycles. All subsequent treatments were with the three-drug combination. Toxicities included nausea, vomiting, stomatitis, thrombocytopenia and granulocytopenia. Diarrhea was the dose-limiting toxicity at 470 mg/m² per day levamisole. The addition of levamisole resulted in more toxicity than 5-FU and leucovorin alone. No clinical responses were seen with this regimen. The addition of levamisole resulted in more immunomodulation than 5-FU and leucovorin alone as evidenced by release of neopterin from monocytes. Conclusion: With this schedule and dose of 5-FU and leucovorin, the maximum tolerated dose of levamisole was 354 mg/m². However, given the lack of response and the absence of dose-dependent immunomodulation, this may not be the appropriate dose for further phase 11 studies. Received: 20 October 1995 / Accepted: 16 June 1996     

Splenectomy during primary and secondary cytoreductive surgery for epithelial ovarian carcinoma

Scarabelli C, Gallo A, Campagnutta E, Carbone A. Splenectomy during primary and secondary cytoreductive surgery for epithelial ovarian carcinoma. Int J Gynecol Cancer 1998; 8 : 215–221.
Splenectomy is occasionally indicated to achieve optimal cytoreduction during surgery for epithelial ovarian cancer. Between January 1989 and December 1996, 40 epithelial ovarian cancer patients underwent splenectomy: 14 patients during primary surgery and 26 during secondary cytoreductive surgery. Splenectomy was performed for tumor reduction in 34 patients (85 %) and for iatrogenic injury in six patients (15%). The spleen was removed because of parenchymal splenic metastases in nine patients (22.5 %), significant hilar and/or capsular disease in 10 patients (25 %), and perisplenic disease in 15 patients (37.5%). The histopathological diagnosis of the resected spleens showed microscopic hilar disease in four patients who had the spleen removed because of iatrogenic injury and no disease in only two patients. Splenectomy could be carried out with an acceptable morbidity. Left-sided pleural effusion was the most frequent complication. The estimated two-year survival rate for patients who underwent splenectomy during primary surgery with no residual disease and <2 cm intraperitoneal residual disease was 83% and 42%, respectively. Nine of these patients (64.3%) had recurrent disease. The median time to recurrence was 11 months (range 5–18). The estimated two-year survival rate for patients who underwent splenectomy during secondary surgery with no residual disease and <2 cm intraperitoneal residual disease was 78% and 24%, respectively. The estimated three-year survival rate was 0% for all these patients. The results of the present study show that splenectomy, if necessary to achieve optimal debulking, should be considered in previously untreated patients with no intraperitoneal residual disease and in patients with late (>1 year) recurrent disease.