Safety and efficacy of intratracheal recombinant human Clara cell protein in a newborn piglet model of acute lung injury.

Despite the widespread use of exogenous surfactant, acute and chronic lung injury continues to be a major cause of morbidity in preterm infants. CC10 is a protein produced by Clara cells that inhibits phospholipase A2 and has anti-inflammatory and antifibrotic properties. We studied whether intratracheal (IT) recombinant human Clara cell protein (rhCC10) could safely minimize lung injury in a newborn piglet model of acute lung injury.

Pulmonary antioxidant enzyme activity during early development: Effect of ventilation.

OBJECTIVE: To examine the effect of tidal liquid ventilation (TLV) and conventional gas ventilation (GV) on the pulmonary antioxidant enzyme (AOE) activity in two groups of preterm lambs at 110 and 120 days of gestation and to compare these results to age-matched fetal controls. DESIGN: Experimental, prospective, randomized, controlled study. SETTING: School of medicine, department of physiology.

Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human CuZn superoxide dismutase.

Objective: To examine whether treatment of premature infants with intratracheal recombinant human CuZn superoxide dismutase (r-h CuZnSOD) reduces bronchopulmonary dysplasia and improves pulmonary outcome at 1 year corrected age.

Design: Three hundred two premature infants (600-1200 g birth weight) treated with exogenous surfactant at birth for respiratory distress syndrome were randomized to receive either intratracheal r-h CuZnSOD (5 mg/kg in 2 mL/kg saline) or placebo every 48 hours (as long as intubation was required) for up to 1 month of age. Short-term, as well as longer-term pulmonary outcome was assessed.

Effects of granulocyte colony-stimulating factor on hyperoxia-induced lung injury in newborn piglets.

Granulocyte colony-stimulating factor (G-CSF) increases the concentration and activation of neutrophils in the peripheral blood and has been used to prevent late-onset infection in premature infants. However, if G-CSF also augmented the inflammatory response in the lung, the incidence and severity of acute and chronic lung injury might be expected to increase. Using a newborn piglet model of acute lung injury, we examined the effects of rhG-CSF (recombinant-metHuG-CSF) on lung injury.

Effects of variable concentrations of inhaled nitric oxide and oxygen on the lungs of newborn piglets.

We previously demonstrated that inhalation of high concentrations of nitric oxide (iNO) and oxygen for 48 hr causes significant lung injury in newborn piglets. To determine if these effects persist at lower concentrations, groups of newborn piglets were mechanically ventilated for 48 hr with (study 1) constant O(2) (90-100%) and decreasing iNO (100-2 ppm) or (study 2) constant iNO (50 ppm) and decreasing O(2) (95-30%). Bronchoalveolar lavage (BAL) fluid was assayed for surfactant function, and markers of lung inflammation and physiologic parameters were monitored.

Hyperoxia inhibits oxidant-induced apoptosis in lung epithelial cells.

It has previously been shown that hyperoxia induces nonapoptotic cell death in cultured lung epithelial cells, whereas hydrogen peroxide (H(2)O(2)) and paraquat cause apoptosis. To test whether pathways leading to oxidative apoptosis in epithelial cells are sensitive to molecular O(2), A549 cells were exposed to 95% O(2) prior to exposure to lethal concentrations of H(2)O(2). The extent of H(2)O(2)-induced apoptosis was significantly reduced in cells preexposed to hyperoxia compared with room-air controls.

Inherited coagulopathies in OB/GYN.

There is an increased risk of venous thrombosis in women with inherited plasma protein coagulopathies (thrombophilias). Although a general screening for thrombophilia is impractical, risk assessment based on identification of other hypercoagulable states-such as a personal or family history of venous thrombosis-can identify patients who may benefit from testing. Those patients testing positive for thrombophilia need to be counseled regarding the implications of oral contraceptive use, hormone replacement therapy, use of selective estrogen receptor modulators, and pregnancy.

Hyperoxia-induced cell death in the lung--the correlation of apoptosis, necrosis, and inflammation.

Prolonged exposure to hyperoxia causes tissue damage in many organs and tissues. Since the entire surface area of lung epithelium is directly exposed to O2 and other inhaled agents, hyperoxia leads to the development of both acute and chronic lung injuries. These pathologic changes in the lung can also be seen in acute lung injury (ALI) in response to other agents.

Hyperoxia in cell culture. A non-apoptotic programmed cell death.

Here we discuss the morphological features and our current understanding of the pathways involved in non-apoptotic cell death from O2 toxicity. Preliminary data on hyperoxic signaling indicate that NF-kappa B translocation (and presumptive activation) is not a result of the p42/p44 MAPK pathway, but a likely downstream consequence of activation of the JNK pathway. Our observations suggest the existence of multiple signal transduction pathways in hyperoxia-induced cell death: one involved in the stress response which appears to be NF-kappa B-dependent and another in cell death.

Multiple protein: protein interactions between the snRNP common core proteins.

The snRNP core proteins (B, D3, D2, D1, E, F, and G) assemble with snRNA and form the snRNP core particle with a suggested stoichiometry of B2[D1, D2(E, F, G)2]D3. The newly synthesized snRNP core proteins are stored in the cytoplasm in three RNA-free complexes of (1) B at 2S-6S; (2) [D1, D2(E, F, G)2] at 6S; and (3) (B, D3, and 69 kDa) at 20S. The snRNP proteins assemble stepwise with snRNAs that appear transiently in the cytoplasm before returning to the nucleus as mature snRNP particles.

Treatment of vulvar varicosities by injection-compression sclerotherapy.

Background: Techniques of injection-compression sclerotherapy of lower extremity varicosities can be applied to treat patients with symptomatic vulvar varicosities.

Objective: To effectively use injection-compression sclerotherapy to treat patients with symptomatic vulvar varicosities.

Methods: Injection of vulvar varicosities with a 1% solution of sodium tetradecyl sulfate and subsequent compression therapy with the V2-Supporter was used to treat seven patients with symptoms of vaginal pressure, swelling, and pain.

Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome.

Objectives: To examine the safety and pharmacokinetics of multiple intratracheal (IT) doses of recombinant human CuZn superoxide dismutase (rhSOD) in premature infants with respiratory distress syndrome who are at risk for developing bronchopulmonary dysplasia (BPD). Methods. Thirty-three infants (700 to 1300 g) were randomized and blindly received saline, 2.

Safety and pharmacokinetics of recombinant human superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome.

Objective: As a first step in the evaluation of recombinant human CuZn superoxide dismutase (rhSOD) in the prevention of neonatal lung injury, safety and pharmacokinetics of intratracheally (IT) administered rhSOD were studied.

Methods: Twenty-six preterm infants weighing 750 to 1250 g with respiratory distress syndrome were studied in three sequential groups (placebo, 0.5, and 5 mg/kg).

Regulation of PNMT gene promoter constructs transfected into the TE 671 human medulloblastoma cell line.

The human medulloblastoma TE 671 cell line has been evaluated as a model for studying expression of transiently transfected phenylethanolamine N-methyltransferase (PNMT) promoter-fusion gene constructs. Because TE 671 cells are one of few continuous lines exhibiting a neuronal phenotype, possess both nicotinic and muscarinic ligand binding properties, and express PNMT mRNA, they represent a likely candidate system for study of cholinergic-regulated PNMT gene expression. When transfected with constructs containing from 0.

External laryngocele: an unusual cause of respiratory distress in a newborn.

Congenital laryngoceles are rare causes of respiratory distress in the newborn. We report a case of airway compromise in a two day old newborn boy secondary to a solitary giant external laryngocele. No internal component or other laryngeal pathology was found.

Pharmacologic interactions of exogenous lung surfactant and recombinant human Cu/Zn superoxide dismutase.

The effect of exogenous surfactant on the pharmacokinetics of intratracheally administered recombinant human superoxide dismutase (rhSOD) was studied. Five groups of rats received the following intratracheally: 1 mL/kg of saline; 5 or 25 mg/kg of rhSOD; or 4 mL/kg of exogenous surfactant followed in 30 min by 5 or 25 mg/kg of rhSOD. Animals were killed at 24, 48, and 72 h, and serum, bronchoalveolar lavage, and lung tissue were analyzed for rhSOD.

Herpetic whitlow with bacterial abscess.

The herpetic whitlow should be treated nonoperatively. However, a difficult therapeutic dilemma occurs when a whitlow is seen with an established bacterial abscess. We report a case of an adult whose first herpetic whitlow was complicated by secondary periungual abscesses that progressed despite intravenous antimicrobial therapy.

Partial lacerations of median and ulnar nerves.

Twelve patients with sharp distal partial median and ulnar nerve lacerations were treated within 2 weeks of injury by end-to-end repair of the lacerated fascicular groups. After an average follow-up of 21 months, the results, based on the British Medical Research Council Rating Scale, were good: S = 3.81 and M = 4.

Meeting an expanding educational role for ambulatory care services.

The mid-1980s have been marked by a growing shift in the locus of health care delivery: from the in-patient setting to ambulatory care programs. As a result of cost containment strategies--exemplified by the diagnosis related group method for hospital reimbursement--the ambulatory care network has assumed responsibility for many patients with advanced or complicated diseases. This increased responsibility is in addition to preventive services, health maintenance, and routine care of acute and chronic conditions.