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Biomedical subjects

R B Holtzman

Publications and source records attributed to R B Holtzman.

At least 19 recordsLinked to original sources
PubMed2001

Blunt innominate artery injury.

Traumatic injury to the innominate artery is a rare occurrence. A literature review reveals that penetrating wounds account for the overwhelming majority of these injuries. Fewer than 90 cases of innominate artery injury caused by blunt trauma have been documented. Over the past 12 months the trauma service successfully treated two patients with blunt injury to the innominate artery. Both cases involved high-speed motor vehicle crashes with sudden deceleration. Both patients were wearing lap and shoulder restraints and had similar associated bruising following the line of the shoulder harness. The first patient presented with a wide mediastinum on chest X-ray. Angiography revealed an innominate artery injury at the aortic arch. The second patient had a normal chest X-ray. Given the extent of soft tissue bruising from the shoulder harness he underwent a magnetic resonance angiography, which was suspicious for an innominate artery injury. Arch aortography confirmed a disruption of the innominate artery midway between its origin and its bifurcation. Both were repaired through a median sternotomy with cervical extension as necessary. Given the present technology of safety restraint devices this injury may occur with greater frequency. A "shoulder strap sign" should prompt a search for more extensive injuries.

Accidents, Traffic↗
PubMed2000

Indomethacin tocolysis and risk of necrotizing enterocolitis.

OBJECTIVE: To investigate the possible association of indomethacin tocolysis with neonatal necrotizing enterocolitis. METHODS: A case-control study was performed for the period November 1, 1997, through May 1, 1999. All cases of proven necrotizing enterocolitis were ascertained, and four controls for each case were randomly identified from all Special Care Nursery admissions before 37 weeks' gestation without necrotizing enterocolitis during that same period. RESULTS: During the 18-month period there were 24 cases of necrotizing enterocolitis out of 10,200 deliveries. Infants with necrotizing enterocolitis were more preterm (29.7 +/- 3.9 compared with 32.7 +/- 6.0 weeks; P =.03) and had lower birth weights (1453 +/- 777 compared with 1820 +/- 678 g; P =.02) compared with controls (n = 96). Respiratory distress syndrome (RDS) and sepsis were both significantly associated with an increased risk of necrotizing enterocolitis: 16 of 24 cases compared with 40 of 96 controls had RDS (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.0, 8.3) and 14 of 24 cases compared with 11 of 96 controls were septic (OR 10.8, 3.4, 95% CI 34.2). Indomethacin as a single agent was not associated with necrotizing enterocolitis (OR 1.0, 95% CI 0.2, 4.8). Using a logistic regression model, necrotizing enterocolitis was strongly associated with sepsis (adjusted OR 8.5, 95% CI 2.2, 32.5). When sepsis was removed from the model, double-agent tocolytic therapy was significantly associated with necrotizing enterocolitis (adjusted OR 6.9, 95% CI 1.1, 43.6). CONCLUSION: Tocolysis with indomethacin as a single agent was not associated with necrotizing enterocolitis in this case-control study. Combination tocolytic therapy may be a marker for subclinical infection and not causally related to necrotizing enterocolitis.

Adult↗
PubMed1998

Surfactant replacement therapy. An update on applications.

Surfactant replacement therapy has been shown to be an effective and often life-saving treatment for newborn infants with respiratory distress syndrome (RDS). This article provides the clinician with an update regarding the various other applications of surfactant replacement therapy, as well as issues related to surfactant administration for the preparations approved for use in pediatric patients.

Chemistry, Pharmaceutical↗
PubMed1993

Surfactant replacement therapy for pulmonary diseases.

Surfactant therapy has clearly been a meaningful addition to the therapeutic armamentarium in the management of premature infants with RDS. Pediatricians and others involved in the care of newborn infants should familiarize themselves with the various surfactant preparations, the indications for their use, the techniques of administration, and the possible side effects. All such care provides should also be skilled in endotracheal intubation and ventilation of neonates; recognition of the clinical and radiographic signs of RDS; and have the appropriate equipment to monitor cardiopulmonary status, oxygenation, and ventilation in these infants until transport to a tertiary care facility can be accomplished. In addition to the two current FDA-approved surfactants, several other surfactants are in various stages of evaluation. When administered to infants with established RDS, both natural and synthetic surfactants have clearly been shown to improve survival, decrease requirements for ventilatory support, and reduce the incidence of air leak complications. Although by no means conclusively demonstrated, certain infants, particularly those delivered at < 30 week gestation, may benefit from immediate treatment in the delivery room. It should be emphasized that, except under extenuating but controlled circumstances and except in the hands of an experienced physician, surfactant treatment should not be viewed as an integral part of neonatal resuscitation. Adequate treatment requires the administration of a minimum of two surfactant doses, although some infants may benefit from additional doses or treatment with an alternative preparation. Massive pulmonary hemorrhage, although rare, is observed with prophylactic and rescue treatment protocols and may result from hemorrhagic pulmonary edema due to a hemodynamically significant PDA. Currently there are no data to recommend the use of one surfactant preparation over another. The short- and long-term benefits may be similar with different products. Therefore, we must await results of trials with then necessary power (large number of subjects) and unbiased design to discern any clinically relevant differences. Results of studies directly comparing the relative efficacy of Survanta and Exosurf, conducted under the auspices of the National Institutes of Health, are expected in 1993. Multicenter trials comparing prophylactic and rescue administration of Exosurf versus CLSE and Survanta versus CLSE are currently underway. It is encouraging to note that follow-up studies up to 2 years of age do not reveal an increase in physical or neurodevelopmental handicaps, BPD, or other problems in preterm infants who received surfactant preparations either for prophylaxis or rescue therapy. Results of long-term follow-up studies, however, are not yet available.(ABSTRACT TRUNCATED AT 400 WORDS)

Bronchopulmonary Dysplasia↗
PubMed1992

Evaluation of a prostacyclin analog in prevention of pulmonary oxygen toxicity.

Prolonged exposure to high concentrations of oxygen can result in significant lung injury, although newborn animals are tolerant relative to adults. We previously reported that relative O2 tolerance in the rabbit is lost by 10 days of age, and is coincident with a decline in lung prostacyclin. In the current study we administered iloprost, a stable prostacyclin analog, by continuous infusion to maturing rabbits exposed to greater than 95% oxygen. Compared to vehicle-treated controls, iloprost-treated rabbits had significantly lower protein in bronchoalveolar lavage fluid at 84 h, a smaller percentage of neutrophils at 65 and 84 h, and lower mortality at 96 h. The partial protection against pulmonary oxygen toxicity afforded by iloprost is likely due to its membrane stabilizing effect, and its inhibitory actions on neutrophil migration, activation, production of oxygen radicals and proteolytic enzymes.

Animals↗
PubMed1992

Evaluation of a leukotriene receptor antagonist in prevention of hyperoxic lung injury in newborn rabbits.

Prolonged exposure to hyperoxia can result in significant lung injury and has been associated with the development of bronchopulmonary dysplasia. Leukotrienes (LT) recruit polymorphonuclear leukocytes (PMN) to the lung, increase vascular permeability, and have therefore been postulated to play a role in the pathogenesis of hyperoxic lung injury. This study investigates ICI 198,615 (ICI), an LTD4 and LTE4 receptor antagonist in preventing hyperoxic lung injury in newborn rabbits. Matched littermates of 7-day-old rabbits received ICI (0.1 or 1.0 microM/kg/h) or vehicle alone, were exposed to greater than 95% O2, and sacrificed after 48, 72, 84 and 96 h of exposure. Bronchoalveolar alveolar lavage fluid (BAL) of the left lung was analyzed for white cell count, differential, absolute number of PMNs, total protein, and cyclooxygenase products 6-keto-PGF1 alpha, and thromboxane B2. Lung water was quantified utilizing the right lung. Results demonstrated no significant differences between the ICI groups or between the ICI groups and controls. In conclusion, the administration of the LTD4 and LTE4 receptor antagonist ICI 198,615 was insufficient to reduce the formation of pulmonary edema, reduce mortality or attenuate hyperoxic lung injury. These experiments suggest that a number of other mediators may be involved in the hyperoxic lung injury process and that the functional inhibition of a portion of the arachidonic acid cascade was not sufficient to either prevent or attenuate hyperoxic lung injury in newborn rabbits.

Animals↗
PubMed1990

Tumor necrosis factor-alpha inhibits expression of pulmonary surfactant protein.

Tumor necrosis factor-alpha (TNF-alpha) decreased the expression of pulmonary surfactant proteins SP-A and SP-B in human pulmonary adenocarcinoma cell lines. The effect of TNF alpha on SP-A content and mRNA in the pulmonary adenocarcinoma cell line, H441-4, was concentration and time dependent. TNF alpha decreased the cellular content of SP-A to less than 10% of control 48 h after addition. TNF alpha decreased de novo synthesis of SP-A and decreased the accumulation of SP-A in media. SP-A mRNA was decreased within 12 h of addition of TNF alpha, with nearly complete loss of SP-A mRNA observed after 24 h. Inhibitory effects of TNF alpha on SP-A mRNA were dose-related with nearly complete inhibition of SP-A mRNA caused by 25 ng/ml TNF alpha. The effects of TNF alpha on SP-A were distinct from the effects of interferon gamma which increased SP-A content approximately twofold in H441-4 cells. TNF alpha also decreased the content of SP-B mRNA. In contrast to the inhibitory effect of TNF alpha on SP-A and SP-B mRNA, TNF alpha increased mRNA encoding human manganese superoxide dismutase (Mn-SOD). TNF alpha did not inhibit growth, alter cell viability or beta-actin mRNA in either cell line. These in vitro studies demonstrate the marked pretranslational inhibitory effects of the cytokine, TNF alpha, on the expression of pulmonary surfactant proteins, SP-A and SP-B. The results support the concept that macrophage-derived cytokines may control surfactant protein expression.

Blotting, Northern↗
PubMed1989

Loss of oxygen tolerance in newborn rabbits: relationship to changes in eicosanoid and antioxidant levels.

Relative tolerance of newborn animals to hyperoxia has been reported. This study investigated the age limitation of oxygen tolerance and mechanisms for its loss. Developmental changes in lungs of normoxic New Zealand rabbits were studied on days 1, 3, 4, 5, and 10 of life. These were contrasted with newborn and 7-day-old rabbits exposed to greater than 95% O2 for 65 hours. Normoxic rabbits demonstrated a decrement in bronchoalveolar lavage (BAL) 6keto-PGF1a, thromboxane B2, and lower lung catalase, total glutathione, and superoxide dismutase with maturation. Newborns were more tolerant to oxygen than 7-day-old rabbits. Oxygen exposure beginning on day 1 did not result in identifiable lung damage. Exposure beginning on day 7 resulted in microscopic evidence of injury and significant increases in BAL white cells, neutrophils and protein, and a trend toward higher BAL LTB4 compared to normoxic age-matched controls. Antioxidants were higher in the hyperoxic 7 day-olds, but remained lower than values in hyperoxic newborns. These results suggest that loss of oxygen tolerance in maturing rabbits is related to a developmental decrement in antioxidants and prostacyclin.

Animals↗
PubMed1989

Role of eicosanoids in relative oxygen tolerance of newborn rabbits.

Prolonged exposure to hyperoxia can result in significant lung injury, although newborn animals are more oxygen-tolerant than adults. Mechanisms affording tolerance to the newborn are incompletely understood. This study examined the hypothesis that eicosanoids play a significant role in newborn oxygen tolerance. One litter of term newborn albino rabbits and 15 adult rabbits were exposed to 65 hours of greater than 95% O2. An additional litter of newborns served as a normoxic control. Normoxic newborn rabbits had very high quantities of 6-keto-PGF1a and low TXB2 in bronchoalveolar lavage (BAL) fluid. Sixty-five hours of oxygen exposure in newborn rabbits produced no evidence of lung injury on light microscopy, 97% of BAL white cells were alveolar macrophages and BAL protein was low. An equal period of oxygen exposure produced significant lung injury in adult rabbits. BAL fluid from oxygen-injured adults contained a 17-fold greater percentage of PMN and 16-fold higher protein than oxygen-exposed newborns. Hyperoxic adults had significantly lower 6-keto-PGF1a, and significantly higher LTB4 and LTC4 in BAL compared to hyperoxic newborns. This study confirms the hypothesis of relative oxygen tolerance in newborn rabbits compared to adults, and suggests that this tolerance may have been afforded by higher pulmonary levels of the protective prostacyclin metabolite.

Animals↗
PubMed1989

Axillobrachial artery bypass grafting with in situ cephalic vein for axillary artery occlusion: a case report.

The cephalic vein has been reported to be a suitable vascular conduit for arterial reconstructive surgery, but its use remains controversial. When used for lower extremity revascularization, its use has been complicated by elongation and dilation. Its use for upper extremity revascularization has only been rarely reported. This article represents the first published use of the cephalic vein with the in situ technique for upper extremity occlusive disease. This technique may avoid some of the complications noted when used in the reverse fashion.

Arm↗
PubMed1989

Perinatal management of meconium staining of the amniotic fluid.

The pathogenesis of meconium passage and the pathophysiology of meconium aspiration are reviewed. Intrapartum and neonatal strategies for the prevention of meconium aspiration syndrome are presented in historical perspective, and newer interventions are appraised.

Amniotic Fluid↗
PubMed1988

Failure of non-selective inhibition of arachidonic acid metabolism to ameliorate hyperoxic lung injury.

We have previously reported that bronchoalveolar lavage fluid cyclo-oxygenase products of arachidonic acid (AA) metabolism increase prior to the development of significant hyperoxic lung injury. To further assess the role of AA metabolites in the development of hyperoxic lung injury, we have utilized this same model of hyperoxic lung injury and administered either indomethacin (an inhibitor of the cyclo-oxygenase pathway of AA metabolism) or dexamethasone (inhibitor of AA release). A total of 46 adult rabbits were exposed to greater than 95% oxygen for 65 hours. Fourteen animals were given either 2 or 3 mg/kg/day indomethacin, 7 served as controls: 18 animals were given either 0.5 or 1.0 mg/kg/day of dexamethasone, 7 served as controls. The surviving animals were sacrificed after 65 hours of hyperoxia and bronchoalveolar lavage of the left lung was done; the right lung was examined by light microscopy. Treatment with indomethacin or dexamethasone failed to ameliorate the hyperoxic lung injury process. However, in both the indomethacin and dexamethasone treatment groups, significant suppression of 6-keto-PGF1 alpha, a PGI2 metabolite, was observed. Some suppression of TXB2 production was observed, but there was no evidence of any decrease in leukotriene production. We postulate that failure to ameliorate hyperoxic lung injury with either indomethacin or dexamethasone therapy was related to significant suppression of PGI2, a potentially protective AA metabolite, and/or to failure to significantly decrease production of potential pathogenic participants, such as TXA2 or LTB4.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1986

The estimation and potential radiobiological significance of the intake of 228Ra by early Ra dial workers in Illinois.

We made radiochemical determinations of 226Ra and the 228Ra-decay product, 228Th, in samples of bone from former Ra dial workers who belonged to a major cohort of Ra-exposed persons under study for health effects at our institution. Most of the former workers were long-term residents of two communities supplied with drinking water containing elevated natural levels of 228Ra and 226Ra, so determinations also were made of radioactivity in samples of bone from long-term residents not occupationally exposed to Ra. The 228Th activity of the bones of the former workers, after correction for the presence of natural radioactivity, showed that some had significant occupational intakes of 228Ra, contrary to published reports that 228Ra was never used by the Illinois company that had employed the cohort of early workers. For 14 workers hired in the years 1920-23, the calculated ratio of the occupational intake of 228Ra to 226Ra activity averaged 0.15 (coefficient of variation 0.65), whereas for three workers hired in 1924, it was not significantly different from zero (mean 0.05, coefficient of variation 1.5). The risk of radiogenic cancer for the typical worker hired before 1924 may have been nearly twice that incurred in the absence of the 228Ra component of the Ra intakes.

Adult↗