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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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Looking at transpulmonary thermodilution curves: the cross-talk phenomenon
From CHEST, 8/1/04 by Frederic Michard

Transpulmonary thermodilution has been shown to be an easy and reliable technique for hemodynamic monitoring in critically ill patients and is being used increasingly. (1-4) After injection of a cold saline solution bolus via a central venous catheter, a thermistor-tipped arterial catheter (usually femoral) is connected to a specific monitor (PiCCOplus; Pulsion Medical Systems; Munich, Germany), which records the downstream temperature changes, ie, a transpulmonary thermodilution curve. The mathematical analysis of the curve allows the computation of cardiac output, heart blood volume (global end-diastolic volume), and an estimation of extravascular lung water. (1-4)

Recently, the mere observation of the transpulmonary thermodilution curve has been shown to be useful to detect and monitor right-to-left intracardiac shunting. (5) Indeed, in case of right-to-left intracardiac shunt, one part of the cold indicator passes through the atrial septum and rapidly reaches the arterial thermistor. As a result, the thermodilution curve appears prematurely and becomes biphasic with two humps ("camel" curve). (5)

I would like to report such a camel thermodilution curve that was not related to a right-to-left intracardiac shunt. This curve was recorded in a patient with septic shock instrumented with a right femoral thermistor-tipped arterial catheter and a right femoral venous catheter. Both catheters were of the same length (20 cm). When the cold saline solution was injected through the femoral venous line, the transpulmonary thermodilution curve was highly suggestive of right-to-left intracardiac shunting (Fig 1). However, the patient was not hypoxemic and contrast echocardiography as well as color Doppler imaging did not reveal any intracardiac shunt. Because both arterial and venous femoral catheters were on the same side and of the same length, it was hypothesized that the high concentration of cold indicator at the site of injection (the tip of the venous catheter) may induce significant temperature changes in the femoral artery, ie, at the level of the arterial catheter tip equipped with a thermistor (cross-talk phenomenon). To confirm this hypothesis, central venous injections were also performed through an internal jugular line. In this case, the shape of the transpulmonary thermodilution curve was normal (Fig 1).

[FIGURE 1 OMITTED]

Looking at transpulmonary thermodilution curves can be very useful to diagnose intracardiac shunts. (5) However, a cross-talk phenomenon may result in a double-hump thermodilution curve wrongly suggestive of right-to-left intracardiac shunting. Therefore, the use of venous and thermistor-tipped arterial catheters on the same side and of the same length should be avoided in patients monitored with transpulmonary thermodilution.

Frederic Michard, MD, PhD

Massachusetts General Hospital-Harvard Medical School

Boston, MA

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 and Critical Care, Massachusetts General Hospital-Harvard Medical School, 55 Fruit St, Boston, MA 02114; e-mail: fmichard@partners.org

REFERENCES

(1) 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

(2) Sakka SG, Reinhart K, Meier-Hellmann A. Comparison of pulmonary artery and arterial thermodilution cardiac output in critically ill patients. Intensive Care Med 1999; 25:843-846

(3) Michard F, Alaya S, Zarka V, et al. Global end-diastolic volume as an indicator of cardiac preload in patients with septic shock. Chest 2003; 124:1900-1908

(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

(5) Michard F, Alaya S, Medkour F. Monitoring right to left intracardiac shunt in acute respiratory distress syndrome. Crit Care Med 2004; 32:308-309

COPYRIGHT 2004 American College of Chest Physicians
COPYRIGHT 2004 Gale Group

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