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J M O'Brien

Publications and source records attributed to J M O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1997

In vitro efficacy of carboplatin and hyperthermia in a murine retinoblastoma cell line.

PURPOSE: To determine the cell-killing activity of varying doses of carboplatin, graded hyperthermia, and the combination of carboplatin and hyperthermia in the treatment of a transgenic murine retinoblastoma cell line. METHODS: Replicate cell wells (more than six wells per dose point) from an established transgenic murine retinoblastoma cell line (Rb-6) were exposed to a single application of hyperthermia for 15, 30, 60, and 120 minutes at temperatures of 37 degrees C (control), 40 degrees C, and 43 degrees C. Carboplatin dose response treatment was studied at doses of 2000, 1000, 500, 400, 300, 200, 100, and 50 ng per well. Combined treatment studies used these carboplatin dosages with each of the graded hyperthermia exposure temperatures at each exposure time. At 24 hours, all wells were pulsed with 3H-thymidine for 24 hours, washed three times, harvested, and counted. Raw counts (3H-thymidine) were fitted to a linear regression model to calculate the lethal dose for 50% (LD50) of cells. RESULTS: The LD50 for carboplatin exposure at 37 degrees C occurred at 542 ng. The LD50 for hyperthermia at 40 degrees C occurred at 90 minutes and at 43 degrees C it occurred at 62 minutes. Combined hyperthermia and carboplatin exposure yielded a synergistic interaction with an LD50 of 327 ng at 43 degrees C for 30 minutes. Determination of a thermal enhancement ratio yielded an enhancement range of 1.1 to 25.8. CONCLUSIONS: The synergistic cytocidal interaction of heat and carboplatin in a transgenic murine retinoblastoma cell line has been established in this study. The increased thermal enhancement ratio documents the potential utility of combined treatment applications in reducing treatment levels of single-modality therapy, potentially allowing for a decrease in treatment-related morbidity.

Animals↗
PubMed1996

Radiation therapy and ferromagnetic hyperthermia in the treatment of murine transgenic retinoblastoma.

BACKGROUND: Combined modality therapy for childhood retinoblastoma holds the potential of decreasing treatment-related morbidity while maintaining excellent tumor control rates. OBJECTIVE: To evaluate the efficacy of external beam radiation therapy (EBRT), ferromagnetic hyperthermia (FMH), and the combination of both modalities in the control of ocular tumors in a transgenic murine model of retinoblastoma. METHODS: One hundred sixty-six mouse eyes from 4-week-old animals transgenically positive for simian virus 40 large T antigen were treated with a total dose of 10, 15, 20, 30, 40, 45, or 50 Gy of EBRT in 5-Gy fractions twice daily, with 48 degrees C or 54 degrees C FMH for 20 minutes, or with combined EBRT at 10 or 30 Gy and 48 degrees C or 54 degrees C FMH for 20 minutes. Serial histologic sections, obtained 8 weeks after treatment, were examined for the presence of tumor. RESULTS: The tumor control dose for 50% of eyes (TCD50) treated with EBRT occurred at 27.6 Gy. Ferromagnetic hyperthermia at 48 degrees C cured 30% (6/20) of eyes, while 54 degrees C FMH resulted in a 100% (20/20) cure rate. Combined treatment with 48 degrees C FMH and EBRT exhibited a TCD50 at 3.3 Gy. The thermal enhancement ratio was 8.4. Ferromagnetic hyperthermia at 54 degrees C exhibited tumor cure in all animals, but 25% of eyes were lost owing to secondary treatment complications. CONCLUSIONS: This represents the first documentation of tumor control via EBRT, ocular FMH, and a combination of these treatment modalities in this murine transgenic retinoblastoma model. The extent of treatment synergy in this model suggests that combined treatment application may allow a reduction in total ocular and periocular radiation dose while maintaining excellent local tumor control.

Animals↗
PubMed1996

Local carboplatin and radiation therapy in the treatment of murine transgenic retinoblastoma.

BACKGROUND: Combined modality therapy in the treatment of retinoblastoma may decrease treatment-related morbidity and second tumor-associated mortality, while maintaining excellent tumor control rates. OBJECTIVE: To evaluate tumor control and potential synergy between intravitreally delivered carboplatin and external beam radiation therapy (EBRT), using a transgenic murine model of spontaneous heritable retinoblastoma. METHODS: Sixty-six mouse eyes from 4-week-old transgenic mice positive for the simian virus 40 large T antigen were evaluated. Thirty-three mice were treated with 5 intravitreal injections of carboplatin (ranging from 0.1-4.0 micrograms) combined with concurrent bilateral EBRT (ranging from 10-30 Gy) delivered in twice daily 5-Gy fractions. All eyes were followed up for treatment complications. Twelve weeks following final treatment, all eyes were enucleated, serial histologic sections obtained, and the eyes examined for the presence of retinoblastoma. RESULTS: No eye treated with 0.1 microgram of carboplatin and EBRT exhibited tumor control. Three (75%) of 4 mice receiving 1.0 microgram of carboplatin combined with 10-Gy EBRT had complete tumor control. Four (100%) of 4 mice receiving 1.0 microgram of carboplatin combined with 30-Gy EBRT had complete tumor control. Nine (100%) of 9 mice receiving 4.0 micrograms of carboplatin in combination with EBRT had complete tumor control. The chemotherapeutic enhancement ratio ranged from 1.07 to 3.24. CONCLUSIONS: Combined administration of intravitreal carboplatin and EBRT enhances local tumor control in murine retinoblastoma. Combining these treatment modalities may allow tumor control in selected patients with retinoblastoma while decreasing treatment-related morbidity and the mutagenic risks associated with radiation and systemic chemotherapy.

Animals↗
PubMed1996

The management of placenta percreta: conservative and operative strategies.

OBJECTIVE: Our purpose was to assess preferences for the management of placenta percreta and identify aspects of care related to an improved outcome. STUDY DESIGN: Both an analysis of a questionnaire issued to members of the Society of Perinatal Obstetricians and a retrospective study at our institution were used to obtain case histories of women with placenta percreta during a recent 3-year period. RESULTS: Fifty-five of the 109 cases (50%) reported by members of the Society of Perinatal Obstetricians were suspected ante partum. Complications associated with this disorder included uterine rupture (3 cases), transfusion of > 10 units (44 cases, 40%), ureteral ligation or fistula formation (5 cases each, 5%), infection (31 cases, 28%), perinatal death (10 cases, 9%), and maternal death (8 cases, 7%). Management options included surgical removal of the uterus and involved tissues (101 cases, 93%) and conservative treatment with the placenta left in situ after delivery (8 cases, 7%). More members of the Society of Perinatal Obstetricians responding to our survey opted for conservative management if adjacent tissues were involved (69% with extension into the bladder or gastrointestinal tract) compared with 31% when the percreta was confined to the uterus, p < 0.001. Conservative therapy was also associated with less blood loss in reported cases (median units red blood cells transfused, 0 vs 7, p = 0.003). Two of the three cases of placenta percreta at our institution were identified ante partum. The third case represents the first reported with antepartum identification of percreta followed by deliberate conservative treatment. CONCLUSIONS: With greater involvement of surrounding tissues, conservative treatment was preferred in hemodynamically stable patients. If surgical excision of the placenta is attempted or necessary, physicians experienced in pelvic dissection must be involved because of the frequency of maternal morbidity and mortality.

Adult↗
PubMed1996

Local carboplatin therapy in transgenic murine retinoblastoma.

PURPOSE: To determine the efficacy and toxicity associated with intraocular delivery of carboplatin in the treatment of murine transgenic hereditary retinoblastoma. METHODS: Forty-eight transgenic BLH-SV40 Tag retinoblastoma mice were administered five intravitreal injections of carboplatin in one eye. After 12 weeks, the eyes were examined histopathologically to evaluate tumor burden. Twelve rabbits were administered intravitreal injections of carboplatin in one eye, after which they underwent serial electroretinography. All experimental and control eyes were obtained for histopathology and electron microscopy. RESULTS: A dose-dependent inhibition of intraocular tumor growth by carboplatin was observed in transgenic retinoblastoma mice. Tumor development was inhibited in 50% of the mouse eyes at doses of 1.4 micrograms. In rabbits, retinal toxicity resulted when intravitreal injections of carboplatin were administered at doses of 10 micrograms or higher. CONCLUSIONS: Local delivery of carboplatin in serial doses effectively inhibits intraocular tumor growth in a dose-dependent manner in transgenic murine retinoblastoma.

Animals↗
PubMed1996

Combining cyclosporin with chemotherapy controls intraocular retinoblastoma without requiring radiation.

Chemotherapy without radiation has not controlled most intraocular retinoblastoma, perhaps because of the common high expression of multidrug resistance P-glycoprotein that we found in retinoblastoma. Cyclosporin blocks P-glycoprotein-induced efflux of vincristine and teniposide in vitro, and possibly modulates responses to carboplatin. To avoid eye irradiation in bilateral retinoblastoma patients with RB1 germline mutations, which incurs a high second malignancy rate, we added cyclosporin A to a vincristine-teniposide-carboplatin protocol and consolidated chemotherapy responses with focal therapy. We scored patients requiring irradiation, enucleation, or focal ablation of central vision as failures. In 21 study patients, the overall relapse-free rate at a median follow-up of 3.3 years was 76%, with a rate of 92% for newly diagnosed and 50% for previously treated, relapsed retinoblastoma. Our results for the most unfavorable tumors with vitreous seeds (86% at 3.5 years) are better than published success rates of irradiation for similar tumors, or irradiation with the same chemotherapy without cyclosporin (45% at 2. 6 years). These results also exceeded our historic success rate with similar chemotherapy without cyclosporin, focal therapy, and/or radiation in 19 equivalently poor-risk patients (relapse-free rate 37% at a median follow-up of 5.6 years, P = 0.032), 16 of whom were previously untreated (relapse-free rate also 37%, P = 0.012). A better outcome occurred with higher cyclosporin blood levels and projected tissue exposure. Cyclosporin did not enhance the usual chemotoxicity. This clinical study suggests that cyclosporin improves the long-term response of retinoblastoma to chemotherapy, possibly by more than one mechanism.

Antineoplastic Agents↗
PubMed1995

Taxol and colchicine increase LPS-induced pro-IL-1 beta production, but do not increase IL-1 beta secretion. A role for microtubules in the regulation of IL-1 beta production.

IL-1 beta is a proinflammatory cytokine secreted chiefly by monocytes and macrophages. Currently, much of its mechanism of processing and secretion is poorly understood, but there is increasing evidence that the microtubule system may be involved. For example, it is known that taxol and colchicine, two drugs that affect microtubule structure and function, increase LPS-induced IL-1 beta release. However, it is not known whether these drugs affect the synthesis of the 31-kDa precursor (pro-IL-1 beta) or the processing and release of mature IL-1 beta. To test this, an assay was used that allowed for the temporal separation of IL-1 beta synthesis and release. The addition of taxol or colchicine to the secretory phase of the assay resulted in no significant change in IL-1 beta release. However, when these drugs were added to the stimulus for IL-1 beta production, there was a significant increase in both IL-1 beta release and total IL-1 beta production, as measured by ELISA. These findings indicate that taxol and colchicine increase LPS-induced IL-1 beta release by an increase in the production of the precursor molecule. Thus, it is unlikely that microtubules are involved in the IL-1 beta secretory machinery in any significant manner, but they do play a role in the regulation of pro-IL-1 beta production.

Animals↗
PubMed1995

Efficacy of outpatient induction with low-dose intravaginal prostaglandin E2: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Our purpose was to determine whether a protocol for outpatient induction is safe and effective for initiating labor. STUDY DESIGN: A randomized, double-blind, placebo-controlled trial was performed with 100 low-risk patients having well-dated pregnancies. Women with a Bishop score < or = 6 at 38 to 40 weeks' gestation were administered either 2 mg of intravaginal prostaglandin E2 gel or placebo for 5 consecutive days as outpatients while undergoing fetal monitoring. RESULTS: The median interval from randomization to delivery was 4 days in the prostaglandin E2 group (range 0 to 28 days) versus 10 days in the placebo group (range 0 to 26 days, p = 0.002). Twenty-seven of 50 patients (54%) in the prostaglandin E2 group were admitted for labor during the dosing interval compared with 10 placebo-treated patients (20%, p = 0.001). The mean gestational age at delivery was significantly reduced in the treatment group (39.9 +/- 1.0 weeks vs 40.5 +/- 0.99 weeks, p = 0.003) as was the incidence of postdates pregnancy (40% vs 66%, p = 0.016). Hyperstimulation was observed in one prostaglandin E2-treated patient, but no intervention was required. CONCLUSIONS: Outpatient low-dose prostaglandin E2 gel administration is effective for initiating labor in patients with an unfavorable cervix and appears safe if performed with adequate monitoring.

Administration, Intravaginal↗
PubMed1995

The use of a modified vaginal pouch for the diagnosis and management of premature rupture of the membranes.

A modified Reality vaginal pouch (Wisconsin Pharmacal, Jackson, Wis.) was effective in assessing membrane integrity in patients evaluated for suspected premature rupture of the membranes and was useful for collecting fluid in patients requiring pulmonary maturity studies. This technique does not alter the incidence of infection and is beneficial in the management of selected patients.

Amniotic Fluid↗
PubMed1995

Daily antenatal testing in women with severe preeclampsia.

OBJECTIVE: Our purpose was to determine whether daily antenatal testing in the expectant management of severe preeclampsia remote from term prevents stillbirth or neonatal compromise at birth. STUDY DESIGN: We reviewed the medical records of 68 women with severe preeclampsia remote from term who underwent expectant management with daily fetal testing until delivery. On admission each patient had reassuring nonstress testing (absence of persistent severe variable or late decelerations), biophysical profile (> or = 6), and amniotic fluid volume (> or = 2 cm maximal vertical pocket before 32 weeks or amniotic fluid index > or = 5 after 32 weeks). RESULTS: There were no stillbirths. Twenty-one patients (31%) had nonreassuring testing necessitating delivery. Two neonatal deaths occurred as a result of complications of prematurity. There were no statistical differences in the cord arterial pH (p = 0.93) or in the 1- and 5-minute Apgar scores (p = 0.18 and p = 0.88, respectively) between those with normal and abnormal antenatal testing. CONCLUSIONS: Because optimizing neonatal outcome is the only reason to prolong pregnancy in women with severe preeclampsia, confirmation of fetal well-being is mandatory. Because neither stillbirths nor fetal compromise at birth occurred in patients undergoing daily antenatal testing, we recommend daily testing in patients with severe preeclampsia managed expectantly.

Adolescent↗
PubMed1995

Early versus late amniotomy for labor induction: a randomized trial.

OBJECTIVE: Our purpose was to determine the impact of early and late amniotomy on labor induction with continuous oxytocin infusion at term. STUDY DESIGN: A total of 209 women admitted for labor induction were randomized to early or late amniotomy. The early amniotomy group (n = 106) had membranes ruptured as soon as it was deemed safe and feasible. The late amniotomy group (n = 103) had membrane rupture performed at > or = 5 cm dilatation. The first 103 women received a continuous oxytocin infusion with incremental adjustments at 60-minute intervals as required. The next 106 women had adjustments every 30 minutes as required. Statistical analysis was confined to concurrent groups. RESULTS: Early amniotomy was associated with shorter labor (13.3 vs 17.8 hours, p = 0.001), chorioamnionitis (22.6% vs 6.8%, p = 0.002), and significant fetal umbilical cord compression (12.3% vs 2.9%, p = 0.017). The benefit regarding shortening of labor was limited to women having oxytocin increments every 30 minutes as required (13.3 vs 17.8 hours, p = 0.001). Alternatively, the increase in chorioamnionitis was confined to the 60-minute group (39% vs 11%, p < 0.001), which also demonstrated a trend toward increased moderate and severe variable decelerations (19.6% vs 6.4%, p = 0.08). CONCLUSIONS: When a protocol of 60-minute increments in oxytocin infusion rate is desired, amniotomy should be performed late in labor to reduce chorioamnionitis and significant umbilical cord compression. Alternatively, if early amniotomy is necessary, oxytocin should be adjusted every 30 minutes as tolerated.

Adolescent↗
PubMed1995

The impact of initiating a human immunodeficiency virus screening program in an urban obstetric population.

OBJECTIVE: Our purpose was to describe the incidence of human immunodeficiency virus infection and to assess the cost/benefit ratio of universal antenatal human immunodeficiency virus screening. STUDY DESIGN: Medical records of women in this urban obstetrics population, from the years 1988 to 1993, were examined. The incidence of known human immunodeficiency virus seropositivity at delivery was determined. The costs of performing human immunodeficiency virus screening, evaluating the disease status, and administering therapy were calculated. These costs were compared with an averaged cost for care and follow-up of infants infected through vertical transmission. RESULTS: The incidence of known human immunodeficiency virus seropositivity at delivery approximately doubled since the initiation of a human immunodeficiency virus screening program (0.26% to 0.48%). Obstetric screening added an approximate $100,000 to medical costs. The calculated cost of pediatric follow-up of human immunodeficiency virus-seropositive infants for the first 18 months was estimated at $344,355. In our population, with universal screening and zidovudine therapy, the medical costs could be reduced by $175,500 per year. CONCLUSION: A program of voluntary human immunodeficiency virus screening increases the incidence of known human immunodeficiency virus infection. Offering screening and follow-up to all pregnant patients in an urban setting is both cost-effective and medically beneficial.

Adult↗
PubMed1995

Efficacy of unanesthetized spiral computed tomography scanning in initial evaluation of childhood leukocoria.

PURPOSE: To evaluate the use of spiral/helical computed tomography (CT) in the preoperative evaluation of pediatric leukocoria. METHODS: A total of 34 patient charts and imaging studies were reviewed from a consecutive series of children referred with the diagnosis of presumed retinoblastoma. Of these patients, 31 had a confirmed diagnosis of retinoblastoma. Three patients had simulating lesions, including one patient with persistent hyperplastic primary vitreous and two with Coats disease. RESULTS: In all patients, a diagnosis of intraocular retinoblastoma could be established or excluded at the same clinical level by spiral CT as by conventional CT. Spiral CT of the eye, orbit, and midline structures was performed without a requirement for patient anesthesia. This technique resulted in a reduced volume of contrast material required for evaluation of the central nervous system and a small decrease in total radiation exposure. There was an attendant reduction in the amount of monitoring equipment required and the necessity for attending anesthesia staff. CONCLUSIONS: The primary advantage of spiral CT is reduced anesthesia risk in small children. In addition, this technique provides necessary clinical information with a reduction in image acquisition time, monitoring equipment, and monitoring staff.

Anesthesia↗
PubMed1995

Infections, inflammations, and immune-mediated orbital disease.

In recent months, many authors have described distinct surgical approaches to orbital decompression in thyroid ophthalmopathy. Comparison of outcomes data should allow the surgeon to decide on the best approach to orbital decompression in an individual patient. Patients with thyroid-associated lid retraction may also benefit from approaches that allow for postoperative suture adjustment, because alignment of the lids can be particularly challenging in these patients. The clinical evaluation of patients with thyroid disease has evolved with the recognition that magnetic resonance T2 relaxation time prolongation may correlate with an inflammatory disease phase and, perhaps, with improved response to medical management. Medical management of orbital inflammation and infection should be tailored to the specific disease process and, in many cases of infection, to the age of the patient.

Adolescent↗
PubMed1995

Common skin problems of infancy, childhood, and adolescence.

Common dermatological problems as a frequent presenting complaint are stratified by infancy, childhood, and adolescence. The common manifestations and questions asked by parents are discussed. Both infectious and noninfectious rashes are included. Convenient treatment modalities are listed.

Acne Vulgaris↗