Intraocular involvement in multifocal fibrosclerosis

OBJECTIVE: To report the clinical and histopathologic findings of intraocular involvement in a patient with multifocal fibrosclerosis and the response of the patient's choroidal masses to external beam radiotherapy. DESIGN: Case report with clinicopathologic correlation of enucleated eyes. METHODS: The patient was studied by clinical observation, contact B- and A-scan ultrasonography, orbital magnetic resonance imaging, fluorescein angiography, indocyanine green angiography, choroidal biopsy, and gross and histopathologic examination of the enucleated eyes. Tissue obtained at an earlier laparotomy was also reviewed. External beam radiotherapy was used when high-dose corticosteroid and low-dose methotrexate therapy failed to decrease the size of the choroidal masses or improve the patient's vision. MAIN OUTCOME MEASURES: Changes in the clinical and ultrasonographic size of the choroidal masses, the clinical appearance of these masses, and the patient's visual acuity in response to external beam radiotherapy were monitored premortem. Histopathologic findings in the enucleated eyes were compared with the changes in previous abdominal and choroidal biopsy specimens and with tissue alterations reported in multifocal fibrosclerosis. RESULTS: Biopsy of the choroidal mass revealed a fibrosclerosing process similar to that found in the abdomen. The patient received external beam radiotherapy with disappearance of the masses. Fibrosclerosing changes similar to those seen in the abdomen were observed replacing the choroid in the enucleated eyes. CONCLUSIONS: Multifocal fibrosclerosis may involve the choroid with histopathologic changes similar to those that have been described in other locations in the body. External beam radiotherapy may be an effective treatment for intraocular involvement by multifocal fibrosclerosis.     

19S IgM rheumatoid factor-7S IgG rheumatoid factor immune complexes isolated in sera of patients with juvenile rheumatoid arthritis

19S IgM rheumatoid factors (RF) and hidden 19S IgM RF have been associated with increased disease activity in juvenile rheumatoid arthritis (JRA). Recently, immune complexes (IC) were isolated from JRA sera by several methods which demonstrated the presence of 19S IgM RF. The present study evaluates 25 JRA patients' sera by separation on a Sepharose 4B column to which were bound F(ab')2 fragments of goat IgG antihuman IgM antibody to separate IgM-containing IC. The columns were sequentially eluted with 1 M ammonia and 0.1 M glycine-HCl buffer, pH 3.0. The isolated fractions were assayed for 19S IgM RF and 7S IgM RF by ELISA, IgG levels by immunodiffusion, and by preparative isoelectric focusing. The ammonia eluate from the alpha HIgM column revealed IgG, 19S IgM RF in six patients, and IgM RF in four patients. All were polyarticular-onset JRA patients. In the glycine-HCl eluate of sera, 19S IgM RF and IgG were also detected in 15 patients, all six seropositive, polyarticular-onset, six seronegative, polyarticular-onset, and three pauciarticular-onset patients. Significant 7S IgG RF titers were demonstrated in the glycine-HCl eluates of six patients, five seropositive, polyarticular-onset patients, and one seronegative, polyarticular-onset patient. Analysis by preparative isoelectric focusing of the IgM RF and IgG RF positive ammonia and glycine-HCl eluates showed IgM RF throughout the pH range (4-10), but the highest amount of IgM RF was in the pH range 4.0-5.5. Significant IgG RF titers were detected only in this restricted spectrotypic area of pH 4.0-5.5.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aqueous outflow pathway imaging in the rabbit with fluorescein and indocyanine green

PURPOSE: The purpose of this study was to visualise the rabbit aqueous outflow pathway using a numeric imaging system with ICG and fluorescein injection in the anterior chamber. MATERIAL AND METHODS: We performed a simultaneous injection of Indocyanin Green (ICG) and Fluorescein into the anterior chamber of rabbit eyes. Using a digital camera, we took several sequenced pictures to visualize the distribution of the dyes within the outflow pathway. We observed the dynamics of the outflow over time. RESULTS: In the early phases, the shape of the outflow canal around the limbus was clearly seen. Several collecting veins close to the recti muscles were also identified. There was only slight fluorescein leakage during the early phases, allowing adequate visualization of the morphology of the outflow system. In the late phases, the sclera was stained with the fluorescein, and no details were thus visible. The ICG dye allowed better recognition of the fine details of the outflow structure. CONCLUSION: This method was relatively simple, safe and precise, and allowed us to visualise the details of the outflow pathways in the rabbit eyes. These results could be of great value in further evaluating the outcome of filtering surgeries in animal models.     

A phase I/II study of high-dose cyclophosphamide,cisplatin, and thioTEPA followed by autologous bone marrow and granulocyte colony-stimulating factor-primed peripheral-blood progenitor cells in patients with advanced malignancies

 The purpose of the present study was to determine the maximally tolerated dose of thioTEPA given with fixed high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous bone marrow (ABM) with or without granulocyte colonystimulating factor (G-CSF)-primed peripheral-blood progenitor cells (PBPCs) in patients with advanced malignancies. Patients were required to have histologically documented malignancies and adequate renal, hepatic, pulmonary, and cardiac function. CPA was given at 1,875 mg/m² per day as a 1-h i.v. infusion for 3 consecutive days, and cDDP was given at 55 mg/m² per day as a 24-h continuous i.v. infusion over 3 days concurrently with CPA. ThioTEPA was given once as a 1-h i.v. infusion (300–900 mg/m²) either following (the first 13 patients) or prior to CPA and cDDP. In all, 31 patients received PBPCs. A total of 46 patients were treated. There were 6 deaths among the 15 patients who did not receive PBPCs (13 received thioTEPA following CPA and cDDP). Among the other 31 patients who received PBPCs (all of whom also received thioTEPA prior to CPA and cDDP), there were 4 deaths, all involving patients with refractory ovarian carcinoma. The main toxicities were mucositis, esophagitis, hepatotoxicity, and nephrotoxicity. The median time required to achieve an absolute neutrophil count of 500 μl was 10 days (range, 9–12 days) for those who received PBPCs and 15 days (range, 15–34 days) for those who did not receive PBPCs. Altogether, 47% of the major organ toxicities (grades 3 and 4 renal, hepatic, and cardiac toxicities) occurred among the 15 patients who did not receive PBPCs, although these patients received thioTEPA at the lowest 2 dose levels. There were 3 complete responses and 22 partial responses among 35 evaluable patients (overall response rate, 71%), with the median duration of response being 3.5 months (range, 2–17 months). The maximally tolerated dose of thioTEPA was 600 mg/m² given as a 1-h i.v. infusion on the day prior to CPA and cDDP administration. The combination of high-dose CPA, cDDP, and thioTEPA is a well-tolerated regimen when thioTEPA is given prior to CPA and cDDP and when the combination also includes PBPCs in addition to ABM. This regimen is active in a variety of malignancies. Received: 15 February 1995/Accepted: 22 May 1995     

Influence of Paternal 252Cf Neutron Exposure on Abnormal Sperm, Embryonal Lethality, and Liver Tumorigenesis in the F1 Offspring of Mice

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to the development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with ²⁵²Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or 3 months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) ( P < 0.01). In the 100 cGy group, 6 of 39 (15%) mice had lesions. At 3 months after irradiation abnormal sperm and embryonal lethality were not significantly increased. The incidences of liver tumors in male offspring from the 50 cGy, 100 cGy and 200 cGy groups were 6 of 20 (30%), 5 of 22 (23%) and 1 of 19 (5%), respectively, which are not significantly increased compared with the control. It is concluded that increased hepatic tumor risk in the F₁ generation may be caused by genetic transmission of hepatoma-associated trait(s) induced by ²⁵²Cf neutron irradiation.     

Acid gastroesophageal reflux in the child with intubation, artificial respiration and continuous nutrition. Apropos of 28 cases

Continuous monitoring of distal oesophageal pH and oesophagoscopy were performed in 28 children aged 15 days to 12 years (mean: 14 months) intubated and ventilated for bronchiolitis (7), pneumonia (8), epiglotitis (2), neurological distress (8), whooping cough (2) or recurrent apneic spells (1). Esophageal pH was studied 2-8 days (mean: 2 days) after intubation; its duration was 12-23 h 50 min (M: 22 h). An abnormal gastroesophageal reflux was presumed when the percent of total monitoring time during which the esophageal pH fell below 4.0 was above 5.2%. The esophagoscopy was carried out on the day following the pH monitoring. All children were in the supine position and fed a pH 7 diet infused continuously with a nasogastric tube; 15 children were under pancuronium. An abnormal gastroesophageal reflux was found in 4 children, associated with a benign esophagitis in 2. A benign esophagitis without gastroesophageal reflux was found in 3 cases. One child had a peptic ulcer of the bulb without gastroesophageal reflux nor oesophagitis. 21 children had no abnormality. Only one of the 15 children under pancuronium had an abnormal gastroesophageal reflux. We conclude that in intubated children fed continuously with a nasogastric tube, gastroesophageal reflux is unfrequent and, when present, appears to have little consequences.     

Drug therapy in childhood hypertension

Indian Journal of Pediatrics -     

A predictive index of cure versus no cure in advanced ovarian carcinoma patients—Replacement of second-look laparotomy as a diagnostic test

Three hundred forty-two Stage III and IV epithelial ovarian carcinoma patients received cytoreductive surgery followed by Adriamycin and cisplatin, 50 mg/m2 each, q 4 weeks for 9 courses. One hundred ninety-seven were clinically NED at completion of treatment and 173 of these 197 had a second-look laparotomy. One hundred twenty had persistent disease. Fifty-three were second-look negative and had no further treatment. Thirty of these latter patients relapsed--all (with one exception) within 2 years. Those not relapsing after negative second-look are considered "cured" (median follow-up 42 months, range 24-68 months) and all others "failures." Stage was a significant predictor of treatment failure--there were no Stage IV "cures." In Stage III patients, age and largest residual tumor diameter post initial surgery were significant predictors of failure. Performance status was marginally significant. In our series, any patient with Stage IV disease or Stage III disease with at least two of the following three poor prognostic factors had a chance of cure of 2.2% (2 "cures" out of 90 patients): age greater than 60 years, macroscopic residual initially, or initial performance status of 2 or 3. Under normal circumstances a second-look procedure to identify persistent disease in this group of patients does not appear justified.