Biomedical subjects

G Annich

Publications and source records attributed to G Annich.

5 recordsLinked to original sources

PubMed1999

Recombinant Kunitz protease inhibitory domain of the amyloid beta-protein precursor as an anticoagulant in venovenous extracorporeal circulation in rabbits.

Investigations were performed to characterize a recombinant Kunitz protease inhibitory domain of the amyloid beta-protein precursor (rKPI) as anticoagulants. After a single intravenous infusion of wild type rKPI into dogs, its elimination fit a two compartment model with a t1/2alpha and t1/2beta of 5 and 77 min, respectively. Further investigations determined if a variant form of rKPI with 178-fold more potent anti-factor Xa activity (rKPI-DD135, Ki = 0.9 nM) could serve as an anticoagulant in a rabbit model of extracorporeal circulation using a venovenous shunt. A prospective investigation was initiated to compare standard heparin (n = 8) at 400 U/kg with different infusion concentrations of rKPI-DD135. After a single intravenous infusion of 1.89 mg/kg of rKPI-DD135 followed by a constant infusion at 0.003 (n = 3), 0.03 (n = 7), or 0.3 (n = 5) mg/kg/min, the anti-factor Xa activity of the animals' plasma rapidly reaches a steady state for the two lower infusion concentrations of the agent. All infusions of rKPI-DD135 prolong the activated clotting time with less variation than that seen with heparin administration. rKPI-DD135 anticoagulation does not prevent a drop in the platelet counts. Fibrinogen levels decrease only slightly when the circuit is anticoagulated with rKPI-DD135. rKPI-DD135 markedly prolongs the APTT, has little effect on the PT, and reduces plasma prekallikrein and plasminogen activation. The 0.3 mg/kg/min infusion concentration of rKPI-DD135 results in reduced deposition of 111Indium-labeled platelets on the circuit when compared to heparin. Last, after a steady state level is achieved, 60% of the plasma anti-factor Xa activity of rKPI-DD135 is eliminated within 60 min after stopping the infusion. These data show the rKPI-DD135 can provide single agent anticoagulation in a rabbit extracorporeal circuit. Development of short acting factor Xa inhibitors may be useful anticoagulants for cardiopulmonary bypass.

Amyloid beta-Protein Precursor↗

PubMed1998

An approach to the treatment of severe adult respiratory failure.

OBJECTIVES: The purpose of this article is to evaluate outcome in adult patients with severe respiratory failure managed with an approach using (1) limitation of end inspiratory pressure, (2) inverse ratio ventilation, (3) titration of PEEP by SvO2, (4) intermittent prone positioning, (5) limitation of FiO2, (6) diuresis, (7) transfusion, and (8) extracorporeal life support (ECLS) if patients failed to respond. PATIENTS AND METHODS: This study was designed as a retrospective review in the intensive care unit of a tertiary referral hospital. One-hundred forty-one consecutive patients with hypoxic (n = 135) or hypercarbic (n = 6) respiratory failure referred for consideration of ECLS between 1990 and 1996. Overall, initial PaO2/FiO2 (P/F) ratio was 75+/-5 (median = 66). RESULTS: Lung recovery occurred in 67% of patients and 62% survived. Forty-one patients improved without ECLS (83% survived); 100 did not and were supported with ECLS (54% survived). Survival was greater in patients cannulated within 12 hours of arrival (59%) compared with those cannulated after 12 hours (40%, P < .05). Multiple logistic regression identified age, duration of mechanical ventilation before transfer, four or more dysfunctional organs, and the requirement for ECLS as independent predictors of mortality. CONCLUSIONS: An approach that emphasizes lung protection and early implementation of extracorporeal life support is associated with high rates of survival in patients with severe respiratory failure.

Adolescent↗

PubMed1997

Effect of hyperventilation on regional cerebral blood flow in head-injured children.

OBJECTIVES: To study cerebral blood flow and cerebral oxygen consumption in severe head-injured children and also to assess the effect of hyperventilation on regional cerebral blood flow. DESIGN: Prospective cohort study. SETTING: Pediatric intensive care unit at a tertiary-level university children's hospital. PATIENTS: Twenty-three children with isolated severe brain injury, whose admission Glasgow Coma Scores were <8. INTERVENTIONS: PaCO2 was adjusted by altering minute ventilation. Cerebral metabolic measurements were made at three levels of PaCO2 (>35, 25 to 35, and <25 torr [>4.7, 3.3 to 4.7, and <3.3 kPa]) after allowing 15 mins for equilibrium. MEASUREMENTS AND MAIN RESULTS: Thirty-eight studies (each study consisting of three sets of measurements at different levels of PaCO2) were performed on 23 patients. At each level of PaCO2, the following measurements were made: xenon-enhanced computed tomography scans; cerebral blood flow; intracranial pressure; jugular venous bulb oxygen saturation; mean arterial pressure; and arterial oxygen saturation. Derived variables included: cerebral oxygen consumption; cerebral perfusion pressure; and oxygen extraction ratio. Cerebral blood flow decreased below normal after head injury (mean 49.6 +/- 14.6 mL/min/100 g). Cerebral oxygen consumption decreased out of proportion to the decrease in cerebral blood flow; cerebral oxygen consumption was only a third of the normal range (mean 1.02 +/- 0.59 mL/min/100 g). Neither cerebral blood flow nor cerebral oxygen consumption showed any relationship to time after injury, Glasgow Coma Score at the time of presentation, or intracranial pressure. The frequency of one or more regions of ischemia (defined as cerebral blood flow of <18 mL/min/100 g) was 28.9% during normocapnia. This value increased to 73.1% for PaCO2 at <25 torr. CONCLUSIONS: Severe head injury in children produced a modest decrease in cerebral blood flow but a much larger decrease in cerebral oxygen consumption. Absolute hyperemia was uncommon at any time, but measured cerebral blood flow rates were still above the metabolic requirements of most children. The clear relationship between the frequency of cerebral ischemia and hypocarbia, combined with the rarity of hyperemia, suggests that hyperventilation should be used with caution and monitored carefully in children with severe head injuries.

Adolescent↗

PubMed1996

Chronic lung disease following neonatal ventilation. I. incidence in two geographically defined populations.

The objective of this study was to compare the incidence of chronic lung disease following neonatal ventilation in two geographically defined populations. Prospective data collection was carried out over a 1 year period from March 11, 1990 to February 28, 1991 in the Trent Health Region (England) and in British Columbia, Canada. All infants < or = 32 weeks gestation and/or < or = 1500 g birthweight born to mothers normally resident in either the Trent Health Region or British Columbia were included. The main outcome measures were mortality rate, presence of chronic lung disease, days of ventilation, and oxygen used by each infant. The proportion of shortened gestation, low birthweight babies was 1.5% in Trent and 1.2% in British Columbia (957 of 63,350 births in Trent and 526 of 45,333 births in British Columbia). There were no significant differences in mean birthweight or gestation between the two cohorts, but there was a trend towards lower mortality for infants 750-1500 g birthweight in British Columbia. The incidence of chronic lung disease (using either of two definitions) was significantly higher in British Columbia, with a corresponding greater amount of respiratory care required. This occurred despite higher use of antenatal steroids and surfactant therapy in the British Columbia group. We conclude that there are important clinical and resource implications resulting from the number of ventilator and oxygen days used by the preterm population in terms of planning of neonatal services. The role of individual treatment modalities in producing differences in the incidence of chronic lung disease warrants further study in the setting of a geographically defined population.

Birth Weight↗

PubMed1993

The CRIB score.

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Birth Weight↗