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Pfeiffer syndrome

Pfeiffer syndrome is a genetic disorder characterized by the premature fusion of certain bones of the skull (craniosynostosis), which prevents further growth of the skull and affects the shape of the head and face. In addition, the thumbs and big toes are broader and often shorter than normal. more...

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Many of the characteristic facial features of Pfeiffer syndrome result from the premature fusion of the skull bones. The head is unable to grow normally, which leads to bulging and wide-set eyes, an underdeveloped upper jaw, and a beaked nose. About 50 percent of children with Pfeiffer syndrome have hearing loss, and dental problems are also common. Additionally, the thumbs and big toes are broader than normal and bend away from the other digits. Unusually short fingers and toes (brachydactyly) are also common, and there may be some webbing or fusion between the digits (syndactyly).

Pfeiffer syndrome is divided into three subtypes. Type 1 or "classic" Pfeiffer syndrome has symptoms as described above. Most individuals with type 1 have normal intelligence and a normal life span. Types 2 and 3 are more severe forms of Pfeiffer syndrome, often involving problems with the nervous system. Type 2 is distinguished from type 3 by more extensive fusion of bones in the skull, leading to a "cloverleaf" shaped head.

Pfeiffer syndrome affects about 1 in 100,000 individuals.

Genetics

Mutations in the FGFR1 and FGFR2 genes cause Pfeiffer syndrome. The FGFR1 and FGFR2 genes play an important role in signaling the cell to respond to its environment, perhaps by dividing or maturing. A mutation in either gene causes prolonged signaling, which can promote early maturation of bone cells in a developing embryo and the premature fusion of bones in the skull, hands, and feet.

Type 1 Pfeiffer syndrome is caused by mutations in either the FGFR1 or FGFR2 gene. Types 2 and 3 are caused by mutations in the FGFR2 gene.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

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Better characterization of acute lung injury/ARDS using lung water - communications to the editor - Letter to the Editor
From CHEST, 3/1/04 by Frederic Michard

To the Editor:

We read with interest the study by Sakka et al (December 2002) (1) demonstrating the prognostic value of extravascular lung water (EVLW) in critically ill patients, and we would like to emphasize another potential clinical value of this parameter. In patients with pulmonary edema (defined as EVLW > 7 mL/kg), fluid restriction/depletion has been shown to improve outcome. (2) However, in patients with acute lung injury (ALI)/ARDS, the effectiveness of such a fluid conservative approach remains a subject of ongoing controversy. (3)

The radiographic criterion used in the American-European definition of ALI/ARDS showed high interobserver variability, (4) and arterial hypoxemia can be due to other disease processes than pulmonary edema. Therefore, we postulated that ALI/ARDS criteria could be inaccurate to identify patients with pulmonary edema, ie, patients who may benefit from fluid restriction/ depletion.

Seventy-five chest radiographs, blood gas measurements, and EVLW measurements done simultaneously in 37 patients receiving mechanical ventilation without evidence for left heart failure have been analyzed. The EVLW was evaluated by transpulmonary thermodilution, a technique validated against the double-indicator (thermo-dye) and the gravimetric methods. (5) Chest radiographs were analyzed independently by each author. When discrepancies were observed (21 of 75 [28%]) between individual analysis, radiographs were reanalyzed for a consensual decision.

Bilateral pulmonary infiltrates were observed in 51 instances. The Pa[O.sub.2]/fraction of inspired oxygen (FI[O.sub.2]) ratio was < 300 or 200 mm Hg in 60 instances and 44 instances, respectively. A negative and weak ([r.sup.2] = 0.27, p < 0.001) relationship was observed between Pa[O.sub.2]/FI[O.sub.2] ratio and EVLW. The ALI/ARDS criteria were fulfilled in 46 of 75 instances (61%). The EVLW was higher (11.3 [+ or -] 5.4 mL/kg vs 8.6 [+ or -] 5.2 mL/kg, p < 0.05) in the cases of ALI/ARDS (mean [+ or -] SD). However, ALI/ARDS criteria (ALI, n = 7; ARDS, n = 9) were associated with an EVLW value [less than or equal to] 7 mL/kg in 16 of 46 instances (35%) [Fig 1].

These findings suggest that a substantial number (approximately one third) of patients with ALI/ARDS criteria have no significant pulmonary edema. In this regard, EVLW measurement should be helpful to identify patients with ALI/ARDS who might benefit from fluid restriction/depletion. Clinical studies are required to confirm the value of EVLW in the decision-making process concerning fluid restriction/depletion in patients with ALI/ARDS.

Frederic Michard, MD, PhD

Veronique Zarka, MD

Sami Alaya, MD

Bicetre Hospital

Paris Sod Medical School

Le Kremlin Bicetre, France

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org).

Correspondence to: Frederic Michard, MD, PhD, Department of Anesthesia & Critical Care, Massachusetts General Hospital-Harvard Medical School, 55 Fruit St, Boston, MA 02114-2696; e-mail: fmichard@rcn.com

REFERENCES

(1) Sakka SC, Klein M, Reinhart K, et al. Prognostic value of extravascular lung water in critically ill patients. Chest 2002; 122:2080-2086

(2) Mitchell JP, Schuller D, Calandrino FS, et al. Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization. Am Rev Respir Dis 1992; 145:990-998

(3) Matthay MA. Clinical measurement of pulmonary edema. Chest 2002; 122:1877-1879

(4) Meade MO, Cook RJ, Guvatt GH, et al. Interobserver variation in interpreting chest radiographs for the diagnosis of acute respiratory distress syndrome. Am J Respir Crit Care Med 2000; 161:85-90

(5) Michard F, Perel A. Management of circulatory and respiratory failure using less invasive hemodynamic monitoring. In: Vincent JL, ed. Yearbook of intensive care and emergency medicine. Berlin, Germany: Springer, 2003; 508-520

To the Editor:

We appreciate the correspondence by Michard and colleagues with reference to our article on the prognostic value of extravascular lung water (EVLW) in critically ill patients. (1) They address an important issue as to whether EVLW should be a criterion in the definition of acute lung injury (ALI) or ARDS.

Currently, oxygenation index (Pa[O.sub.2]/fraction of inspired oxygen [FI[O.sub.2]] ratio) is part of the ALI/ARDS criteria. Although relatively easy to obtain in critically ill patients, Pa[O.sub.2]/FI[O.sub.2] ratio as marker of pulmonary edema has been questioned. In their letter, Michard et al report data from 37 critically ill patients on the reliability of Pa[O.sub.2]/FI[O.sub.2] ratio as evaluated by EVLW. In their analysis, only 65% of patients fulfilling the ALI/ARDS criteria had pulmonary edema (as defined by EVLW > 7 mL/kg). Since thus approximately one third of patients with ALI/ARDS were ascribed to have no significant pulmonary edema, the authors suggest that EVLW may be more helpful to identity, patients with ALI/ARDS.

We also feel that EVLW might be a valuable criterion for ALI/ARDS. However, EVLW > 7 mL/kg was uniformly considered as marker of pulmonary edema in their analysis. Nevertheless, appropriate cut-off values for ALI and ARDS have to be established for both entities in prospective trials before EVLW can be added to ALI/ARDS criteria.

Currently, data on EVLW-based fluid management in critically ill patients are still limited. So far, using EVLW to guide the management of patients with both cardiac and noncardiac pulmonary edema (ARDS) has been shown to reduce the duration of mechanical ventilation, length of stay in the ICU, and potential intensive care costs. (2) Moreover, EVLW-guided therapy also reduced mortality in patients with congestive heart Failure and ARDS. (3)

Further studies on the value of EVLW in critically ill patients are highly warranted, ie, for potential implementation in scoring systems or as part of ARDS/ALI criteria. We re-emphasize the need to perform appropriate prospective trials in the future, especially since determination of EVLW has become possible by a simplified approach based on the single transpulmonary thermodilution technique. (4)

Samir Sakka, MD, PhD, DEAA

Magdalena Klein

Jena, Germany

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org).

Correspondence to: Samir Sakka, MD, PhD, DEAA, Klinik fur Anasthesiologie und Intensivtherapie, Friedrich-Schiller-Universitaet, Bachstr. 18, D-07740 Jena, Germany; e-mail: Samir. Sakka@med.uni-jena.de

REFERENCES

(1) Sakka SG, Klein M, Reinhart K, et al. Prognostic value of extravascular lung water in critically ill patients. Chest 2002; 122:2080-2086

(2) Mitchell JP, Schuller D, Calandrino FS, et al. Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization. Am Rev Respir Dis 1992; 145:990-998

(3) Eisenberg PR, Hansbrough JR, Anderson D, et al. A prospective study of lung water measurements during patient management in an intensive care unit. Am Rev Respir Dis 1987; 136:662-668

(4) Sakka SG, Ruhl CC, Pfeiffer UJ, et al. Assessment of cardiac preload and extravascular lung water by single transpulmonary thermodilution. Intensive Care Med 2000; 26:180-187

COPYRIGHT 2004 American College of Chest Physicians
COPYRIGHT 2004 Gale Group

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