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Biomedical subjects

R Rich

Publications and source records attributed to R Rich.

At least 19 recordsLinked to original sources

Rationale and dose-finding studies of the combination of irinotecan and a taxane on a weekly schedule.

Cisplatin (Platinol)-based chemotherapy has been the standard systemic therapy for both non-small-cell and small-cell lung cancer for the past 2 decades, though the efficacy and benefit remain modest. Recently, several novel agents have been introduced that have single-agent activity comparable to cisplatin and offer the possibility of improved therapy for lung cancer. Camptothecin and taxane derivatives are associated with both different mechanisms of action and nonhematologic toxicities, and have demonstrated additive or synergistic activity when used in combination in preclinical studies. We review pertinent clinical studies of these agents in lung cancer and present our experience in combining irinotecan (Camptosar, CPT-11) with taxanes on a weekly schedule in dose-finding and efficacy studies. When chemotherapy is delivered for 4 consecutive weeks followed by a 2-week rest, hematologic toxicity is dose limiting and most prominent during weeks 3 and 4. Dose intensification is feasible if the schedule is modified so the chemotherapy is given on days 1 and 8, with cycles repeated every 3 weeks. The most common nonhematologic toxicities remain asthenia, neuropathy, and diarrhea. Future studies will explore and better define the role of these drug combinations in the treatment of lung cancer.

Adult↗

Intraocular pressure-raising potential of 1.0% rimexolone in patients responding to corticosteroids.

OBJECTIVE: To compare the intraocular pressure (IOP) elevating potential of 1.0% rimexolone and 0.1% fluorometholone alcohol ophthalmic suspensions in patients known to have responded to corticosteroids. DESIGN: In a double-masked, randomized, single-eye, crossover protocol, corticosteroid responsiveness initially was verified in 40 asymptomatic known steroid responders by challenge with either 0.1% dexamethasone sodium phosphate or 1.0% prednisolone acetate for up to 6 weeks. After a 1-month medication washout, subjects randomly received either rimexolone or fluorometholone for 6 weeks. Medications were again discontinued for 1 month, and subjects then received the alternate drug for 6 weeks. RESULTS: There was no significant difference between rimexolone and fluorometholone in the number of subjects demonstrating a 10-mm Hg increase in IOP or in the mean number of weeks required to achieve a 10-mm Hg response. Responses occurred in significantly more subjects receiving dexamethasone sodium phosphate (P = .001) or prednisolone acetate (P < .001) and in a significantly shorter interval than in subjects receiving rimexolone. CONCLUSIONS: Rimexolone has a low IOP-elevating potential, comparable to that of fluorometholone and less than that of dexamethasone sodium phosphate and prednisolone acetate.

Administration, Topical↗

Povidone-iodine for ophthalmia neonatorum prophylaxis.

PURPOSE: The agents currently used to prevent ophthalmia neonatorum are less than optimal, with reports indicating evidence of bacterial resistance, ineffectiveness, and toxicity. Povidone-iodine ophthalmic solution, which has been shown to be effective in the preoperative preparation of the eye, generates no resistance, is an effective antimicrobial agent, and has low toxicity. We evaluated the effectiveness and safety of povidone-iodine for ophthalmia neonatorum prophylaxis. METHODS: A bacterial culture was taken from the conjunctiva of each eye of 100 infants within 30 minutes of birth. A drop of 2.5% povidone-iodine solution was then placed on one eye, while the other eye received either one drop of silver nitrate 1% ophthalmic solution or 0.5% erythromycin ointment. Conjunctival bacterial cultures were again taken two to four hours after birth. At each culture and at 24 hours after birth, the eyes were examined for toxic changes. To measure the effectiveness of the medications, the number of bacterial colony-forming units and species from each culture was compared. RESULTS: All three agents significantly reduced the number of colony-forming units, but povidone-iodine caused the most significant decrease. The number of species was reduced significantly by povidone-iodine (P = .00051) and silver nitrate (P = .007), with povidone-iodine yielding the most significant decrease. Erythromycin did not significantly reduce the number of species. Silver nitrate demonstrated more ocular toxicity at the 24-hour determination point than did either of the other two medications (P < .001). CONCLUSIONS: Povidone-iodine 2.5% ophthalmic solution is an effective antibacterial agent on the conjunctiva of newborns and causes less toxicity than silver nitrate.

Colony Count, Microbial↗

Complete heart block in a child with varicella.

A case of varicella myocarditis in a previously healthy 6-year-old child was reviewed. The patient presented with third-degree heart block and shock as the sole manifestation of her cardiac involvement. Bradyarrhythmias required temporary transvenous pacing. Intravenous acyclovir was used. The patient recovered without permanent sequelae. The natural history, clinical presentation, and treatment of varicella myocarditis are reviewed.

Acyclovir↗

Comparative efficacies of ciprofloxacin, pefloxacin, and vancomycin in combination with rifampin in a rat model of methicillin-resistant Staphylococcus aureus chronic osteomyelitis.

The efficacies of the quinolones ciprofloxacin and pefloxacin alone and in combination with rifampin were compared with those of vancomycin alone and in combination with rifampin in a rat model of chronic osteomyelitis caused by methicillin-resistant Staphylococcus aureus. Neither the quinolones nor vancomycin alone was effective in reducing titers of organisms in bone after therapy, while rifampin alone was effective. All combination regimens with rifampin were more effective than the regimen with rifampin alone was, although these differences did not achieve statistical significance. Rifampin-resistant isolates were detected rarely. Quinolone-rifampin combination regimens may offer a nonparenteral option for the treatment of chronic osteomyelitis caused by methicillin-resistant S. aureus.

Animals↗

Microbiological and clinical significance of a new property of defective lysis in clinical strains of pneumococci.

A pneumococcal isolate that caused relapsing meningitis in a patient infected with human immunodeficiency virus (HIV) was found to display an unusual response to penicillin--rapid death but a striking lack of cellular lysis. This lytic defect was also detected in all four pneumococcal isolates from three additional HIV-infected patients and in more than half of the clinical isolates from patients with bacteremia. In a rabbit model of meningitis, the lysis-defective strain remained cryptic, with a delay of 5 h in the onset of leukocytosis in cerebrospinal fluid. A marked burst of leukocytosis was associated with ampicillin-induced lysis of a lysis-sensitive strain but not of a lysis-defective strain. Pneumococcal clinical isolates have different lytic responses to penicillin; defective lysis may adversely affect the course of meningitis, an observation suggesting that autolysins play a role in modulating infectious diseases.

Acquired Immunodeficiency Syndrome↗

Growth of the conjunctival fornix and orbital margin in term and premature infants.

Knowledge of the growth of the neonatal conjunctival fornix and anterior orbit will aid development of neonatal prosthetic conformers and conjunctival sensors for oxygen determinations, as well as help define orbital malformation syndromes. These data are not available in any prospective series in the literature. The authors studied 55 premature and term neonates and determined horizontal and vertical dimensions of the conjunctival fornix and orbital margin and palpebral fissure width. Each of the ocular parameters had statistically significant correlation coefficients in relation to weight and gestational age (P less than 0.05). Linear regression analysis showed significant relationships which predict conjunctival fornix, orbital margin, and palpebral fissure dimensions from body weight (P less than 0.05). Statistically significant correlation coefficients and linear regression relationships were found for horizontal, but not vertical, diameter measurements of the conjunctival fornix in relation to orbital margin and palpebral fissure dimensions (P less than 0.01).

Birth Weight↗

Nonsteroidal anti-inflammatory agents in the therapy for experimental pneumococcal meningitis.

An increased inflammatory mass in the subarachnoid space during bacterial meningitis may correlate with a poor outcome of disease. Using a rabbit model of pneumococcal meningitis, we sought to reduce this inflammatory process. The ability of the pneumococcal cell wall to cause death and to generate leukocytosis and abnormal chemistry in cerebrospinal fluid was prevented when animals were treated with inhibitors of cyclooxygenase pathway of arachidonate metabolism. Bacterial lysis by ampicillin led to release of cell wall that caused a significant, transient increase in meningeal inflammation. This inflammatory burst was also prevented by administering cyclooxygenase inhibitors concurrently with the antibiotic.

Ampicillin↗

Induction of pulmonary inflammation by components of the pneumococcal cell surface.

Using a rabbit model of experimental pneumonitis, the components on the surface of the pneumococcus that incite pulmonary inflammation were identified. Rabbits were challenged intratracheally with live pneumococci, capsular polysaccharide, purified cell walls, or cell wall subcomponents. Leukocytosis and elevation of protein concentration was quantitated in bronchial lavage fluid during the first 24 h after challenge. Of the pneumococcal surface components tested, cell wall preparations had the highest specific activity in inducing inflammation; abnormalities in bronchial lavage fluid cytochemistry appeared rapidly and in a dose-dependent manner. Cell wall building blocks and the products of penicillin-induced hydrolysis of the cell wall were also highly inflammatory, indicating that inflammation can be generated by disruption of the cell wall during lysis of bacteria by beta-lactam antibiotics. Administration of inhibitors of arachidonic acid metabolism suggested that inhibition of the lipoxygenase pathway reduced inflammation associated with cell walls. We propose that pulmonary inflammation during pneumococcal pneumonia arises in large part from the interaction of the bacterial cell wall with complement and noncomplement-mediated host defenses.

Animals↗

Filamentous hemagglutinin and pertussis toxin promote adherence of Bordetella pertussis to cilia.

Bordetella pertussis adheres specifically to the cilia of respiratory epithelial cells. This ability to adhere is characteristic of virulent organisms. In order to define the contribution of various virulence factors of B. pertussis to the process of adherence, mutants deficient in single virulence factors were tested for the ability to adhere to rabbit cilia in vitro and in vivo. Two protective antigens were found to be critical to the process of adherence: filamentous hemagglutinin and pertussis toxin.

Animals↗

Treatment of advanced non-Hodgkin's lymphoma with vincristine infusion.

Twenty-five patients with a variety of histologic types of advanced non-Hodgkin's lymphoma refractory to previous chemotherapy were entered into a trial of vincristine infusion. Patients received 5-day courses of vincristine 0.25 mg/m2/day by continuous intravenous infusion after an initial 0.5 mg intravenous bolus injection. Courses were repeated every 3 weeks. Objective responses were observed in nine patients (36%), all of whom had previously received vincristine given by conventional bolus injection. A complete response occurred in a patient with diffuse mixed histiocytic lymphocytic lymphoma, and partial responses were observed in eight patients with the following histologic types: diffuse poorly differentiated lymphocytic (4); nodular poorly differentiated lymphocytic (2); diffuse mixed histiocytic lymphocytic (1); and diffuse histiocytic (1). Duration of response lasted from 1.2 to 16.2 months (mean, 4.4 months). The principal complication of therapy was mild-to-moderate neurotoxicity; this occurred in 12 patients (48%) who received a total of 54 courses of vincristine infusion. Hematologic toxicity was minimal and nausea/vomiting did not occur. Vincristine infusion may afford palliation for patients with advanced non-Hodgkin's lymphomas who have become refractory to standard chemotherapeutic regimens even if they have received prior vincristine by conventional bolus injection. These data suggest the possibility of enhancing the therapeutic efficacy of vincristine in the treatment of non-Hodgkin's lymphoma by use of an infusion technique.

Adult↗

Anticoagulation in urologic surgery.

The present report describes a pilot project to apply the principle of minidose heparinization to patients undergoing prostatectomy, comparing a control group of 50 prostatectomies treated in conventional fashion to a study group of 43 prostatectomies treated with minidose heparinization. Results of the study indicate that perioperative minidose heparinization in patients undergoing prostatectomy is associated with longer hospitalization, greater need for blood transfusion, greater degree of immediate and delayed postoperative bleeding, and a higher incidence of "rebound" pulmonary embolization after cessation of heparin, than in patients treated in conventional fashion.

Heparin↗