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Biomedical subjects

P C Rimensberger

Publications and source records attributed to P C Rimensberger.

At least 19 recordsLinked to original sources

Somato-sympathetic vasoconstriction to intranasal fluid administration with consecutive decrease in nasal nitric oxide.

AIM: Patients suffering from non-allergic chronic rhinosinusitis (NACRS) increasingly use intranasal saline sprays. They report better nasal comfort. METHODS: In order to better understand this phenomenon, we studied intranasal laser Doppler flowmetry (LDF) and nasal nitric oxide (NO) variations evoked by local administration of saline, histamine, N-acetylcysteine (NAC) and lidocaine at room temperature (22 degrees C). RESULTS: There was a significant (P < 0.05) 14 +/- 3.8% decrease in LDF signal after 30 s, which lasted for 60-90 s, for all the substances applied at 22 degrees C. This pharmaco-independent vasoconstriction was further studied in patients under general anaesthesia (GA), with saline at 37 degrees C and after intranasal adrenaline treatment. While GA did not influence the vasoconstriction, saline at 37 degrees C and adrenaline pre-treatment abolished it. Nasal NO is influenced by vasoconstriction. Therefore we investigated, whether the observed vasoconstriction also changes nasal NO. A significant (P < 0.001) 8.03 +/- 0.59% decrease in nasal NO was recorded 60 s after administration of all the substances, and under GA after 22 degrees C saline application. This NO decrease was absent after intranasal adrenaline pre-treatment. An additional experiment tested the effect of nose blowing on nasal NO concentration. We registered an NO decrease with a similar pattern than observed with the other substances. CONCLUSIONS: Intranasal fluid nebulization at 22 degrees C induces a sympathetic mediated, transient vasoconstrictor reflex response. This somato-sympathetic vasoconstriction induces a decrease in nasal NO. Both could be related to the subjective comfort experienced by NACRS patients using intranasal saline sprays.

Acetylcysteine↗

Aerosolized iloprost induces a mild but sustained inhibition of platelet aggregation.

Pathological studies have revealed that one of the main features encountered in the pulmonary vasculature of patients with pulmonary hypertension is the presence of thrombotic lesions. Open pilot studies have indicated that aerosolized iloprost may have beneficial effects in patients with pulmonary hypertension. The effects of aerosolized iloprost on platelet function and plasma cyclic adenosine monophosphate (cAMP) were studied. Platelet aggregation and plasma cAMP were measured at baseline, 30 min, 4 and 6 h after inhalation of 15 microg iloprost in 10 healthy volunteers. Maximal platelet aggregation in response to adenosine diphosphate (ADP) (2 and 6 micromol x L(-1)), collagen (2.5 and 5 microg x mL(-1)), epinephrine (1.25 and 5 micromol x L(-1)) and arachidonic acid (0.5 mg x mL(-1)) was measured. Platelet aggregation was significantly inhibited at 30 min in response to ADP (2 and 6 micromol x L(-1), epinephrine (1.25 and 5 micromol x L(-1)) and collagen (2.5 microg x mL(-1)). It was still inhibited at 4 h in response to the same agents, but normalized at 6 h. cAMP increased at 30 min, from 27.3+/-1.2 to 31.8+/-1.2 nmol x L(-1), remained increased at 4 h (29.2+/-1.3 nmol x L(-1)) and normalized at 6 h (27.4+/-1.1 nmol x L(-1)). Aerosolized iloprost induced a mild but sustained inhibition of platelet aggregation. Platelet aggregation inhibition may be one of the mechanisms which explains the beneficial effect of repeated inhalation of iloprost in pulmonary hypertension.

Administration, Inhalation↗

Inhaled nitric oxide versus aerosolized iloprost in secondary pulmonary hypertension in children with congenital heart disease: vasodilator capacity and cellular mechanisms.

BACKGROUND: Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each. METHODS AND RESULTS: A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng. kg(-1). min(-1) for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48+/-0.38 to 0.27+/-0.16 (P:<0.001). Similarly, iloprost decreased the ratio from 0.49+/-0.38 to 0.26+/-0.11 (P:<0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6+/-11.9 to 34.7+/-21.4 nmol/L during iNO (P:<0.01), and plasma cAMP increased from 55.7+/-22.9 to 65.1+/-21.2 nmol/L during iloprost inhalation (P:<0.05). CONCLUSIONS: In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.

Administration, Inhalation↗

Hypothesis for generation of the unstable Hb Bucuresti (beta 42 Phe-->Leu) mutation.

INTRODUCTION: Unstable hemoglobin disorders are characterized by a congenital, mostly familial chronic hemolytic anemia with episodes of severe hemolysis during febrile illnesses. Usually, isopropanol and heat stability tests lead to the diagnosis which is confirmed by protein and gene sequencing. Generation of the mutations is still a subject of controversy. PATIENT, MATERIALS AND METHODS: We describe a 6-year-old Swiss child with congenital hemolytic anemia and a negative family history. Hemoglobin was studied by IEF, HPLC reverse phase chromatography, heat stability and isopropranol tests. DNA was sequenced in both coding and non-coding strands. RESULTS: An unstable Hb was diagnosed on the basis of positive heat stability and isopropranol tests. The TTT-->TTG mutation at codon 42 corresponding to a Phe-->Leu substitution was found on DNA sequencing. Paternity was confirmed indicating that we are dealing with a new mutation. CONCLUSION: So far, three different mutations at codon 42 of the beta-chain, and two at the corresponding position of the alpha-chain have been described, all leading to a hemolytic anemia. These mutations can either represent random phenomena occurring at an important location in the heme pocket, or may be secondary to the two highly homologous zones present in this region. These homologous zones may indicate a hot spot for point mutations created by abnormal crossing over or formation of loops, and an imperfect DNA repair process.

Amino Acid Substitution↗

Acute symptomatic hyponatremia and cerebral salt wasting after head injury: an important clinical entity.

Hyponatremia is a well known complication of traumatic and nontraumatic cerebral injury, often related to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Nonetheless, it also can be associated with a different entity, the syndrome of cerebral salt wasting (CSW). The authors report the case of a 4.5-year-old boy presenting with major head injury who at day 6 after admission had generalized tonic-clonic seizures caused by severe acute hyponatremia (serum sodium level, 119 mmol/L) and signs of dehydration. Despite initial isotonic rehydration, hyponatremia persisted because of excessive renal salt losses and concomitant enormous water losses, necessitating increasing amounts of sodium, up to 160 mmol/kg/d, and large amounts of intravenous fluids, up to 27 L/d. Highly increased levels of atrial natriuretic peptide (ANP) confirmed the diagnosis of CSW. The occurrence of a CSW has to be recognized early in the clinical course for adequate treatment and remains one of the important differential diagnosis of SIADH in hyponatremic states in patients with cerebral disorders, especially after head injury.

Acute Disease↗

Long term inhalation of iloprost in a child with primary pulmonary hypertension: an alternative to continuous infusion.

Primary pulmonary hypertension is a rare disease in childhood associated with a poor prognosis. However, during the past 10 years, pulmonary vasodilator treatment has somewhat improved its prognosis. Long term continuous infusion of prostacyclin (epoprostenol) has been shown to improve physical capacity and to reduce mortality in primary and secondary pulmonary hypertension. It has been reported in adults that daily repetitive inhalation of iloprost, a prostacyclin analogue, seems also suitable for long term therapy of pulmonary hypertension. Repetitive inhalation of iloprost was administered to a 5 year old boy with severe primary pulmonary hypertension. He showed continuous clinical improvement without any side effects over the three years of treatment. This treatment may offer an alternative to continuous intravenous prostacyclin infusion and obviates the need for a permanent central venous catheter.

Administration, Inhalation↗

Management of preterm infants with intracardiac thrombi: use of thrombolytic agents.

Improvement in neonatal care has led to improvements in survival and patient outcome in preterm infants; however, this improved survival has been associated with the development of secondary complications, such as catheter-associated intravascular and intracardiac thrombus formation with a non-negligible morbidity and mortality. The sick preterm infant is at high risk of catheter-related thrombus formation because of the combination of a high prothrombotic activity, low levels of natural anticoagulants, and various imbalances in the fibrinolytic systems. Based on clinical experience in adults and children, and several neonatal case reports demonstrating the efficacy and tolerability of specific thrombolytic treatment, this approach should be recommended as a first choice treatment in the premature infant with intracardiac or intravascular thrombosis. The thrombolytic agents of choice are urokinase or tissue plasminogen activator (tPA); however, none of them have proven to be superior to the other in terms of efficacy or tolerability, either in adult patients or premature infants. In the past, it has been suggested that newborn infants may require higher doses of thrombolytic agents than adults for effective systemic thrombolysis; however, based on more recent in vitro studies, it seems unlikely that this is true. Nevertheless, systemic (high dose) fibrinolysis is of concern as premature neonates present an increased risk of cerebral haemorrhage during the first weeks of life; therefore, low dose treatment has been proposed with, if possible, direct infusion of the fibrinolytic agent into, or close to, the thrombus. This approach has proven to be efficient and well tolerated in several small case series of newborn and preterm infants. Recommended doses are 1000 to 3000 U/kg/h for urokinase or 0.01 to 0.05 mg/kg/h for tPA. A systemic proteolytic state will not be induced by this low dose; however, specific monitoring of fibrinogen plasma levels has to be recommended. Fibrinogen levels should remain above 100 mg/dL during low dose treatment. Lower levels of fibrinogen will indicate the presence of an unwanted systemic fibrinolytic state. After successful thrombolysis, a follow-up treatment, preferentially with low-molecular-weight heparin for neonates at adjusted doses, should be instituted for at least 6 weeks in the absence of any persisting thrombophilic factor. A longer course (3 to 6 months) of anticoagulation therapy is recommended when thrombophilic factors (i.e. hereditary thrombophilia or central venous catheter still in place) are present. Furthermore, it is recommended that any neonate with thrombosis should be evaluated for hereditary thrombophilia later in life.

Fibrinolytic Agents↗

Noninvasive pressure support ventilation for acute respiratory failure in children.

Noninvasive ventilation is becoming widely accepted not only for treatment of chronic but also acute respiratory failure of various aetiology in children. However, thus far, there is only empirical evidence that this treatment is safe and effective in improving oxygenation and alveolar ventilation and in obviating endotracheal intubation in many cases. With this limited experience it is difficult to define the ideal candidate who will respond to a noninvasive ventilation trial. Infants and small children are at high risk of developing respiratory fatigue and, consecutively, respiratory failure due to structural and functional properties of their developing respiratory system. This may justify early noninvasive pressure support ventilation as soon as clinical signs of impending respiratory failure develop and before physiological evidence of acute respiratory failure with respiratory acidosis and/or hypoxaemia are present. For the success of noninvasive ventilation in the acute care setting, the correct choice and adaptation of the patient-machine interface and the delivery system are crucial. Furthermore, medical and nursing staff must be familiar with child-specific respiratory physiology and mechanics. Well controlled randomised prospective trials in children presenting with acute respiratory failure will be needed to evaluate the treatment's effectiveness and safety, and to better define the patient likely to benefit from this alternative method of respiratory support.

Acute Disease↗

Lung recruitment and lung volume maintenance: a strategy for improving oxygenation and preventing lung injury during both conventional mechanical ventilation and high-frequency oscillation.

OBJECTIVE: To determine whether using a small tidal volume (5 ml/kg) ventilation following sustained inflation with positive endexpiratory pressure (PEEP) set above the critical closing pressure (CCP) allows oxygenation equally well and induces as little lung damage as high-frequency oscillation following sustained inflation with a continuous distending pressure (CDP) slightly above the CCP of the lung. MATERIAL AND METHODS: Twelve surfactant-depleted adult New Zealand rabbits were ventilated for 4 h after being randomly assigned to one of two groups: group 1, conventional mechanical ventilation, tidal volume 5 ml/kg, sustained inflation followed by PEEP > CCP; group 2, high-frequency oscillation, sustained inflation followed by CDP > CCP. RESULTS: In both groups oxygenation improved substantially after sustained inflation (P < 0.05) and remained stable over 4 h of ventilation without any differences between the groups. Histologically, both groups showed only little airway injury to bronchioles, alveolar ducts, and alveolar airspace, with no difference between the two groups. Myeloperoxidase content in homogenized lung tissue, as a marker of leukocyte infiltration, was equivalent in the two groups. CONCLUSIONS: We conclude that a volume recruitment strategy during small tidal volume ventilation and maintaining lung volumes above lung closing is as protective as that of high-frequency oscillation at similar lung volumes in this model of lung injury

Animals↗

First intention high-frequency oscillation with early lung volume optimization improves pulmonary outcome in very low birth weight infants with respiratory distress syndrome.

OBJECTIVES: The lack of decline in chronic lung disease of prematurity despite the generalized use of surfactant and alternative modes of ventilation such as high-frequency oscillation (HFO) has been attributed to some misunderstanding of how HFO has to be used. We used a new ventilatory strategy in very low birth weight (VLBW) infants, by initiating HFO immediately after intubation and attempting early lung volume optimization before surfactant was administered. STUDY DESIGN: The outcome of 32 VLBW infants, managed with first intention HFO over a period of 24 months (September 1, 1996 and August 31, 1998) was compared by chart review with 39 historical controls, consecutively managed with conventional mechanical ventilation (CMV) over a period of 24 months (January 1, 1994 and December 31, 1995). SETTING: An 11-bed tertiary care pediatric and neonatal intensive care unit of a university teaching hospital. RESULTS: The 2 groups of patients were similar in demographic distribution of birth weight, gestational age, race, and gender. Patients on first intention HFO were ventilator-dependent (median [95% confidence interval]: 5 [3-6] vs 14 [6-23] days) and oxygen-dependent (12 [4-17] vs 51 [20-60] days) for a shorter time than patients on CMV. The incidence of chronic lung disease at 36 weeks of gestational age was significantly lower in the HFO group compared with the CMV group (0% vs 34%). CONCLUSIONS: First intention HFO with early lung volume optimization shortened the need for respiratory support and improved pulmonary outcome of VLBW infants with respiratory distress syndrome significantly.

Drug Combinations↗

Local low-dose urokinase treatment of acquired intracardiac thrombi in preterm infants.

We report three cases of intracardiac thrombi in preterm infants of very low birth weight, in whom local low-dose urokinase treatment achieved complete thrombolysis without any signs of systemic fibrinolytic activity or side-effects. This new treatment strategy seems to be safe, requires minimal monitoring of fibrinolytic activity, and may be a new option for thrombolysis in high-risk patients such as premature infants, patients recently operated on, and patients presenting with other contra-indications for systemic fibrinolytic therapy.

Female↗

Pulmonary artery catheter placement under transoesophageal echocardiography guidance.

Despite correct positioning pulmonary artery catheters may be displaced accidentally. Repositioning may prove to be difficult, especially when high pulmonary artery pressures are present. After failure of usual placement methods, transoesophageal echocardiography was used to guide repositioning of a displaced Swan-Ganz catheter in the early postoperative course after cardiac surgery in a child. This technique proved to be useful in visualizing intracardiac catheter orientation and facilitating pulmonary artery catheter placement at bedside, avoiding transportation of a haemodynamically unstable patient.

Adolescent↗

Lung recruitment during small tidal volume ventilation allows minimal positive end-expiratory pressure without augmenting lung injury.

OBJECTIVES: Ventilation with positive end-expiratory pressure (PEEP) above the inflection point (P(inf)) has been shown to reduce lung injury by recruiting previously closed alveolar regions; however, it carries the risk of hyperinflating the lungs. The present study examined the hypothesis that a new strategy of recruiting the lung with a sustained inflation (SI), followed by ventilation with small tidal volumes, would allow the maintenance of low PEEP levels ( P(inf). MEASUREMENTS AND MAIN RESULTS: In groups 2 and 4, static compliance decreased after ventilation (p < .01). Histologically, group 2 (PEEP < P(inf) without SI) showed significantly greater injury of small airways, but not of terminal respiratory units, compared with group 1. Group 3 (PEEP < P(inf) after a SI), but not group 4, showed significantly less injury of small airways and terminal respiratory units compared with group 2. CONCLUSIONS: We conclude that small tidal volume ventilation after a recruitment maneuver allows ventilation on the deflation limb of the pressure/volume curve of the lungs at a PEEP < P(inf). This strategy a) minimizes lung injury as well as, or better than, use of PEEP > P(inf), and b) ensures a lower PEEP, which may minimize the detrimental consequences of high lung volume ventilation.

Analysis of Variance↗

The open lung during small tidal volume ventilation: concepts of recruitment and "optimal" positive end-expiratory pressure.

OBJECTIVES: To test the hypotheses that during small tidal volume ventilation (5 mL/kg) deliberate volume recruitment maneuvers allow expansion of atelectatic lung units and that a high positive end-expiratory pressure (PEEP) above the lower inflection point of the pressure/volume (PV) curve is not necessarily required to maintain recruited lung volume in acute lung injury. DESIGN: Prospective, randomized, controlled animal study. SETTING: An animal laboratory in a university setting. SUBJECTS: Adult New-Zealand rabbits. INTERVENTIONS: We studied a) the relationship of dynamic loops during intermittent positive pressure ventilation to the quasi-static PV curve, and b) the effect of lung recruitment on oxygenation, end-expiratory lung volume (EELV), and dynamic compliance in two groups (n = 4 per group) of lung-injured animals (lung lavage model): 1) the sustained inflation group, which received ventilation after a recruitment maneuver (sustained inflation); and 2) the control group, which received ventilation without any lung recruitment. MEASUREMENTS AND MAIN RESULTS: In the presence of PV hysteresis, a single sustained inflation to 30 cm H2O boosted the ventilatory cycle onto the deflation limb of the PV curve. This resulted in a significant increase in EELV, oxygenation, and dynamic compliance despite equal PEEP levels used before and after the recruitment maneuver. Furthermore, after a single sustained inflation, oxygenation remained high over 4 hrs of ventilation when a PEEP above the critical closing pressure of the lungs, defined as "optimal" PEEP, was used and was significantly higher compared with that in the control group ventilated at equal PEEP without preceding lung recruitment. CONCLUSIONS: The observation that ventilation occurs on the deflation limb of the tidal cycle-specific PV curve allows placement of the ventilatory cycle, by means of a recruitment maneuver, onto the deflation limb of the PV envelope of the optimally recruited lung. This strategy ensures sufficient lung volume recruitment to maintain the lungs during the tidal cycle while using relatively low airway pressures.

Analysis of Variance↗

Treatment of a persistent postoperative chylothorax with somatostatin.

Chylothorax is a rare but potentially serious complication of pediatric cardiac operations. We report the case of a 4-month-old boy who underwent a Senning procedure for correction of D-transposition of the great vessels. A persistent postoperative chylothorax developed, necessitating continuous drainage, despite conservative treatment over 3 weeks. Thereafter, continuous somatostatin infusion for 14 days led to the reduction and finally cessation of chyle production. This treatment allowed early enteral feeding and avoided further surgical intervention.

Chyle↗