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Biomedical subjects

D J Johnson

Publications and source records attributed to D J Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1993

Acute effects of cocaine on ornithine decarboxylase activity in fetal and neonatal rat heart: evidence for cardiotoxicity.

Fetal exposure to cocaine is associated with increased perinatal cardiac risk. In the current study, we examined the effects of acute cocaine administration on ornithine decarboxylase (ODC) activity in fetal and neonatal rat heart. ODC is a key regulatory enzyme in the control of cell differentiation and growth, and rapid changes in ODC are associated with the response to cell injury. Administration of 30 mg/kg s.c. of cocaine to pregnant rats on the 20th day of gestation caused acute elevation of fetal cardiac ODC that persisted throughout the ensuing 24 h. In contrast, the same dose given directly to neonatal rats the day after birth evoked only a short-term (1-h) stimulation of ODC that was reversed by 4 h after treatment. By 4 days of age and subsequently, cocaine was unable to elicit acute stimulation of heart ODC and only evoked inhibition of enzyme activity. Elevated progesterone levels during pregnancy have been shown to sensitize the maternal myocardium to cocaine-induced catecholaminergic effects; the greater sensitivity of fetal heart ODC to cocaine, as compared to neonatal heart, supports the hypothesis that similar enhancement of fetal cardiac irritability can contribute to cocaine-induced cell damage.

Analysis of Variance↗
PubMed1993

The addition of sighs during pressure support ventilation. Is there a benefit?

The purpose of this study was to determine if sigh breaths delivered during pressure support ventilation (PSV) were beneficial in maintaining arterial oxygenation (PaO2) and pulmonary mechanics. Ten patients being weaned from mechanical ventilation in the PSV mode were studied. All patients were ventilated for 4 h without sighs, 4 h with sighs, and again for 4 h without sighs. During each 4-h period, continuous measurements of ventilatory volumes and airway pressures were accomplished. At the end of each 4-h period, an arterial blood gas determination was obtained. There were no statistically significant differences in any of the measured variables during the different periods of ventilation. We conclude that the sigh breath is of no benefit during PSV.

Adult↗
PubMed1993

Humidification in the intensive care unit. Prospective study of a new protocol utilizing heated humidification and a hygroscopic condenser humidifier.

STUDY OBJECTIVE: Determine the utility of a proposed algorithm in allowing safe, efficient humidification in mechanically ventilated patients using both a hygroscopic condenser humidifier (HCH) and heated humidifier (HH). DESIGN: A prospective study using an algorithm to chose humidification devices based on physical examination and sputum characteristics. SETTING: All patients admitted to the surgical ICU. PATIENTS: One hundred twenty consecutive patients requiring mechanical ventilation (MV) were studied. INTERVENTIONS: Patients were examined by the attending respiratory care practitioner and given either an HCH or HH. If patients demonstrated any of the following--thick or tenacious secretions, core temperature < 32 degrees C, or bloody secretions--they were given an HH. All others used an HCH. If any of the above conditions occurred during HCH use, the patient was given an HH. MEASUREMENTS AND RESULTS: Duration of ventilation, incidence of nosocomial pneumonia, ventilator circuit colonization, and mortality were determined for patients in each group. Cost of humidification devices, number of suctioning procedures per day, and volume of saline solution instilled were also recorded. Initially, 27 percent (32/120) of patients used an HH and 73 percent (88/120) used an HCH. During the study, ten patients required changing to an HH during HCH use. Patients in the HH group were more likely to have preexisting lung disease and had a longer duration of ventilation (83 +/- 21 h) and higher mortality (21 percent). Patients in the HCH group were more likely to be postoperative, had shorter durations of ventilation (38 +/- 14 h), and lower mortality (9 percent). There was no difference in the incidence of nosocomial pneumonia between the two groups (9 percent vs 6 percent) and endotracheal tube occlusion did not occur in either group. Circuit colonization was common in the HH group (64 percent) but rate in the HCH group (5 percent). Cost per day was significantly less for the HCH group ($4 vs $19.80). Patients who required a change from HCH to HH did so at a mean of 5 days. CONCLUSION: The proposed algorithm resulted in cost-efficient and safe application of humidification devices in patients in the surgical ICU.

Adult↗
PubMed1993

Relative efficiency of incorporation of newly synthesized elastin and collagen into aorta, pulmonary artery and pulmonary vein of growing pigs.

It is generally accepted that, once laid down in the extracellular matrix, elastin turns over only very slowly if at all. However, much of the evidence for minimal turnover of elastin comes from aortic tissue. In this study we have compared the relative synthesis rates of elastin and collagen with their relative accumulation rates in segments of aorta (AO), pulmonary artery (PA), and pulmonary vein (PV) of young, growing pigs. While rates of elastin synthesis are comparable in the AO and PA, the PA accumulates only 33% of the elastin deposited in the AO. Similarly, while the rate of elastin synthesis in the PV is 60% of that in the AO, accumulation of elastin is only 20% of that in the AO. Similar discrepancies between collagen synthesis and accumulation were seen among these three vessels. These data suggest that, at least in growing animals, the efficiency of permanent incorporation of elastin and collagen into the extracellular matrix may be an important factor in determining the final contents of these connective tissue proteins in vascular tissues.

Aging↗
PubMed1993

Splanchnic resuscitation: a strategy for preventing liver failure in sepsis.

Liver failure is commonly encountered in the critically ill, septic patient. This hepatic dysfunction occurs as a wide spectrum of abnormalities, ranging from mild chemical derangements to fulminant liver failure. The syndrome of multiple system organ system failure due to sepsis is often complicated by alterations in splanchnic/hepatic function. Knowledge of gut pathophysiology with resultant changes in substrate metabolism, synthetic function, cytokine release, and the detrimental effects on other organ systems is rapidly expanding. The functions of these pathophysiologically produced factors include extensive autocrine, paracrine, and endocrine effects. Evidence suggests that adequate resuscitation during sepsis, which is measured by systemic end-points, may result in inadequate splanchnic blood flow and oxygen delivery. The addition of serial measurements of splanchnic end-points may limit the hepatic failure encountered in multiple system organ failure due to sepsis.

Animals↗
PubMed1993

A developmentally regulated program restricting insolubilization of elastin and formation of laminae in the fetal lamb ductus arteriosus.

BACKGROUND: The ductus arteriosus (DA) is a fetal vessel in which the elastic laminae fail to assemble normally in late gestation. This feature is associated with the development of intimal cushions, structures that partially occlude the DA lumen and assure that the vessel will close completely when it constricts postnatally. EXPERIMENTAL DESIGN: We studied the fetal lamb DA at two different gestational time-points, 100 days before, and 138 days coincident with intimal cushion formation (term = 145 days) to establish the ultrastructural basis for the 'disassembly' of elastic laminae apparent on light microscopy and to determine further whether the mechanism was due to increased elastolytic activity, decreased synthesis of tropoelastin, or impaired insolubilization of tropoelastin. RESULTS: Morphometric ultrastructural analyses of tissue from the 138-day gestation fetal lambs revealed that the volume density of elastin in the DA vessel wall was only 40% of that in the aorta (Ao) and 50% of that in the pulmonary artery (PA). Moreover, only 16% of the elastin present contributed to the formation of laminae when compared to 80% in the Ao and 50% in the PA. Despite the morphologic appearance of 'fragmented' elastin, there was no evidence of increased elastolytic activity in the DA at either gestational time-point as judged by solubilization of a [3H] elastin substrate. The reduced elastin apparent was morphologically accompanied by an increase in soluble (tropo) elastin in DA compared with Ao and PA, as measured by enzyme linked immunosorbent assay, in tissue from both 100- and 138-day gestation lambs. Lack of differences in tropoelastin mRNA levels when comparing the 3 vessels suggested that the enzyme linked immunosorbent assay measurements reflected increased DA tropoelastin accumulation owing to lack of insolubilization rather than an increase in synthesis. Reduced insolubilization of newly synthesized elastin was evident in the DA compared with the Ao at 100 days gestation and in the DA compared with both Ao and PA at 138 days gestation in association with reduced desmosine levels. CONCLUSIONS: The mechanism of the decrease in tropoelastin insolubilization was unrelated to lysyl oxidase activity in the tissue and represents a unique developmental program.

Animals↗
PubMed1992

Gut feeding and hepatic hemodynamics during PEEP ventilation for acute lung injury.

Mechanical ventilation with positive end-expiratory pressure (PEEP) limits hepatic blood flow (HBF) and oxygen delivery (HO2D). Early gut feeding may augment hepatic hemodynamics and avoid relative ischemia in this flow-limited environment. To examine these effects, canines were instrumented with arterial, pulmonary artery, portal, and hepatic vein catheters. Splenectomy and gastrostomy were performed and the hepatic artery and portal vein were encircled with flow probes. All animals underwent lung injury with oleic acid (0.08 ml/kg) followed by the addition of 10 cm H2O PEEP to correct shunt. One group (fed) was then given a bolus elemental feeding (1 kcal/ml, 10 ml/kg) and the Control group, sterile water. Cardiac index (CI), HBF, hepatic oxygen delivery (HO2D), and hepatic oxygen consumption (HO2C) were measured at baseline (T0), after PEEP (T1), and 1 (T2) and 2 hr (T3) after feeding. Data were tested for significant changes between time points in the same group by ANOVA and significant differences were subjected to t testing. PEEP significantly decreased CI, HBF, and HO2D compared to baseline. Subsequently, gut feeding increased HBF to baseline levels and improved HO2D. HO2C also increased but hepatic O2 extraction was unchanged. There was little change noted in the control group over this same period. We conclude that gut feeding augments HBF and HO2D in this flow-limited state and may preserve splanchnic integrity in critical illness.

Acute Disease↗
PubMed1992

Treatment of chloroquine-resistant malaria in monkeys with a drug combination that reverses resistance in vitro.

Compounds that inhibit the P-glycoprotein-related efflux mechanism of multidrug-resistant cells reverse chloroquine resistance in vitro. Hence, the co-administration of chloroquine and an efflux-blocking drug could potentially treat chloroquine-resistant malaria infections. We administered a drug combination (chloroquine and a tiapamil analogue), that has been shown to reverse chloroquine resistance in vitro, to Aotus monkeys but failed to safely clear experimentally-induced chloroquine-resistant Plasmodium falciparum parasitaemias.

Animals↗
PubMed1992

The effect of hypothermia on liver adenosine triphosphate (ATP) recovery following combined shock and ischemia.

During both hemorrhagic shock and ischemia, adenosine triphosphate (ATP) concentrations fall in liver tissue. Incomplete recovery of ATP correlates with cell death and subsequent organ dysfunction. Changes in liver ATP levels were evaluated in paired groups of rats subjected to combined hemorrhagic shock and ischemia. A second set of paired animals was studied over time with shock alone. One animal in each pair was maintained at 28 degrees C and the other at 37 degrees C. Ischemia was produced by occluding inflow to the left half of the liver, and tissue was obtained from this area in all animals studied. Adenosine triphosphate levels fell in warm and cold animals subjected to both shock and 60 minutes of ischemia but recovered more completely during reperfusion in the cold animals. Shock alone caused a steady fall in ATP levels in the warm, but not the cold rats. These biochemical changes may indicate a beneficial effect of moderate hypothermia in the management of severe liver hemorrhage requiring temporary occlusion of blood flow.

Adenosine Triphosphate↗
PubMed1992

Monoethylglycinexylidide production parallels changes in hepatic blood flow and oxygen delivery in lung injury managed with positive end-expiratory pressure.

Mechanical ventilation with high levels of positive end-expiratory pressure (PEEP) decreases hepatic blood flow (HBF) and hepatic oxygen delivery (HO2D). Noninvasive methods of detecting decreased HBF might prevent hepatic ischemia and dysfunction. Monoethylglycinexylidide (MEGX) is a hepatic metabolite of lidocaine, used clinically to determine graft function following hepatic transplantation. In order to test the hypothesis that MEGX production would be affected by changes in hepatic hemodynamics associated with lung injury, 12 dogs were instrumented with femoral and pulmonary artery catheters. Splenectomy was performed and the portal and hepatic veins cannulated. The hepatic artery and portal vein were encircled with flow probes. Lung injury was induced in six animals (INJURED group) with oleic acid (0.08 mL/kg) and 10 cm H2O PEEP was added to correct subsequent shunt. Levels of MEGX were measured 15 minutes after injection of intravenous lidocaine (1 mg/kg). Levels of HBF, HO2D, and MEGX were measured at BASELINE, after lung injury (INJURY time point), and after addition of PEEP (PEEP time point). CONTROL animals (n = 6) were studied at the same time points but without lung injury or PEEP. Hepatic blood flow and hepatic oxygen delivery were significantly decreased after lung injury and further decreased after PEEP. Levels of MEGX were unchanged in the CONTROL group but were significantly reduced by lung injury and PEEP in the INJURED group. Decreased MEGX production may be a useful clinical indicator of reduced hepatic flow and oxygen supply in critical illness.

Animals↗
PubMed1992

Cost and complications during in-hospital transport of critically ill patients: a prospective cohort study.

We prospectively studied transport of a group of 100 surgery/trauma patients and a matched control group in the ICU. APACHE II scores for the two groups were 23 +/- 6 and 20 +/- 8. During transport both groups had ECG, heart rate, blood pressure, and oxygen saturation continuously monitored. We also determined the cost and results of transport for those patients requiring diagnostic testing. There were six diagnostic tests performed: CT scan of the abdomen (39%), CT scan of the head (31%), CT scan of the chest (8%), CT scan of the cervical spine (4%), angiography (14%), and tomography (4%). Average transport time was 74 +/- 16 minutes with a range of 20-225 minutes. Physiologic changes defined as a BP +/- 20 mm Hg, heart rate +/- 20 beats/min, respiratory rate +/- 5 breaths/min, or oxygen saturation +/- 5% for 5 minutes duration occurred in 66% of transported patients and 60% of ICU patients. There were no differences in arterial blood gas levels before and during transport. In 39% of transports, the results of diagnostic testing produced a change in patient management within 48 hours. Abdominal CT scanning and angiography were associated with the highest percentage of tests leading to a management change (51% and 57%). The average charge to the patient was $612.00 and the average cost to the hospital $452.00. Our results suggest that while physiologic changes are frequent during transport, they are also frequent in ICU patients as a consequence of the severity of illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Laboratory and clinical evaluation of the impact Uni-Vent 750 portable ventilator.

BACKGROUND: Transportation of critically ill, mechanically ventilated patients from intensive care units for diagnostic and therapeutic procedures has become common in the last decade. Maintenance of adequate oxygenation and ventilation during transport is essential. We evaluated the Impact Uni-Vent 750 portable ventilator in the laboratory and in the clinical arena to determine its usefulness during inhospital transport. MATERIALS & METHODS: In the laboratory, we determined the Uni-Vent 750's ability to assure tidal volume (VT) delivery in the face of decreasing compliance of a test lung and tested the alarm systems. Using a two-compartment lung model modified to simulate spontaneous breathing, we also evaluated the responsiveness of the demand valve. The clinical evaluation was accomplished by comparing arterial blood gas values and ventilator settings in the intensive care unit before transport to those during transport. RESULTS: As lung compliance was reduced from 0.1 to 0.02 mL/cm H2O [1.0 to 0.20 L/kPa], a slight, statistically insignificant decrease in delivered tidal volume was observed. All alarm systems operated according to manufacturer's specifications. The demand valve triggered appropriately with PEEP from 0 to 20 cm H2O [0 to 1.96 kPa]. Sensitivity settings less than -6 cm H2O [-0.59 kPa] sometimes resulted in inability to trigger the demand valve. During patient transport, arterial blood gas values and ventilator settings were comparable to those observed in the ICU. Because an FIO2 of 1.0 was used during transport, mean (SD) PaO2 was significantly greater 89 (26) vs 341 (78) [11.8 (3.5) vs 45.3 (10.4) kPa]. CONCLUSIONS: The Uni-Vent 750 is a reliable transport ventilator, capable of maintaining adequate oxygenation and ventilation in a majority of mechanically ventilated patients. The Uni-Vent 750's ability to (1) provide CMV, AMV, and SIMV; (2) provide low and high pressure alarms; and (3) provide PEEP compensation is unique among portable ventilators.

Adult↗
PubMed1991

The effect of low dose dopamine on gut hemodynamics during PEEP ventilation for acute lung injury.

Mechanical ventilation with positive end-expiratory pressure (PEEP) diminishes gut and hepatic blood flow and redistributes cardiac output away from the splanchnic circulation. This flow-limited environment can aggravate underlying hypoperfusion and ischemia in the postinjury setting. To examine the effects of low dose dopamine on a lung injury PEEP model of gut hypoperfusion, six anesthetized, splenectomized canines were instrumented with arterial, pulmonary artery, portal vein, and hepatic vein catheters. Electromagnetic flow probes were placed around the hepatic artery and portal vein for continuous flow measurements. Gut and hepatic blood flow, oxygen delivery, oxygen consumption, and extraction ratio were calculated at four time points: baseline, 1 hr after lung injury with oleic acid, 1 hr after ventilation with 10 cm H2O PEEP, and 1 hr after the continuous infusion of dopamine. Portal flow and gut oxygen delivery fell significantly with the infusion of PEEP. These values returned to near baseline levels with the addition of dopamine. Gut oxygen extraction increased from 16 +/- 2% to 35 +/- 3% with PEEP but returned to near baseline with dopamine (20 +/- 4%, P less than 0.01 compared to PEEP). We conclude that dopamine improves blood flow and oxygen delivery to the gut in this flow-limited model. This may preserve splanchnic physiology during PEEP ventilation for acute lung injury.

Animals↗
PubMed1990

Pattern of accumulation of elastin and the level of mRNA for elastin in aortic tissue of growing chickens.

Synthesis and accumulation of elastin in many elastic tissues begins in the last third of fetal development, reaches a maximum shortly after birth, and then declines rapidly. For the aorta of the chick and the pig and the ligamentum nuchae and lung of the sheep, it has been shown that increased levels of elastin production with fetal development are correlated with increased levels of elastin mRNA in the tissue, measured both by cell-free translation and by hybridization to cDNA probes. In this study we examine the relationship between insoluble elastin accumulation and message levels for tropoelastin in aortic tissue of chickens during posthatching development and growth. Whether evaluated by cell-free translation or by dot blot hybridization, steady state levels of tropoelastin message increase to a maximum at 2 weeks after hatching, and then fall rapidly with further development and growth. This pattern correlates well with production of insoluble elastin by the aorta, determined either by direct measurements of synthesis or by rate of accumulation of insoluble elastin. The data indicate that the major site of regulation of elastin production is pretranslational throughout the entire period of development and growth of the chicken aorta.

Animals↗
PubMed1990

Toward cultural/ecological perspectives on schooling and achievement in African- and Asian-American children.

The review acknowledges that research on the family and its contribution to achievement in ethnic minority children is important. Past research and theorizing suggest the need for new directions, however. For example, research in educational achievement predicts educational failure for African-American students and educational success for Asian-American students. Little differentiation is made either among African-Americans or among Asian-Americans of different cultural, language, immigration, and economic backgrounds. The theory and design of research on family and educational achievement have been influenced by prevailing societal stereotypes. Research and policy implications of this review include the need to move toward cultural/ecological theories of achievement socialization and development.

Achievement↗