Israel Medical Association Journal

Background: Primary pulmonary hypertension is a rare disorder, characterized by progressive pulmonary hypertension and right heart failure. It may be familial or sporadic. Mutations in bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor-beta receptor superfamily of receptors, underlie many cases of the disorder.

Objectives: To perform molecular analysis of a patient with familial PPH[1] and provide her and her family with suitable genetic counseling.

Methods: DNA was extracted from 10 ml whole blood, and the BMPR2 gene was screened for mutations. Individual exons were amplified by polymerase chain reaction and sequenced. Mutation confirmation and molecular characterization of additional family members was performed using restriction enzyme analysis followed by appropriate genetic counseling.

Results: We identified a novel T to C missense mutation expected to result in substitution of arginine for a conserved cysteine in the ligand-binding domain of BMPR2. Screening of family members demonstrated the presence of the mutation in the father and a younger asymptomatic sister of the index patient.

Conclusions: Molecular diagnosis in PPH allows for identification of at-risk family members and raises the option of earlier diagnosis and possibly instituting earlier treatment in affected individuals. However, molecular screening of asymptomatic family members raises difficult ethical questions that can only be resolved by conducting large multicenter prospective studies in BMPR2 carriers.

Sepsis is an infection-induced inflammatory syndrome that results in a complex network of adaptive and maladaptive alterations in homeostatic mechanisms. Severe sepsis, defined as sepsis associated with acute organ failure, is a serious disease with a mortality rate of 30–50%. The coagulation system, through complex interactions, has an important role in the final outcome of the sepsis-induced inflammatory cascade. A fine and delicate balance that normally exists between anticoagulant mechanisms and the procoagulant response is altered in sepsis. Activated protein C, an endogenous vitamin K-dependent anticoagulant, plays a major role in the down-regulation of the procoagulant arm. It also possesses anti-inflammatory properties. Endothelial damage during sepsis impairs the endothelium-dependent activation of protein C, thus shifting the balance towards thrombosis. This shift may contribute to the development of sepsis-related multi-organ failure. Evidence suggesting that activation of the coagulation system may contribute to sepsis-related morbidity and mortality has led to extensive research attempting to correct the hemostatic defects seen in septic patients. Indeed, a recent randomized controlled trial demonstrated a reduction in overall mortality in patients with severe sepsis treated with APC[1]. In this review we discuss the pathogenesis of the coagulopathy of sepsis, as well as the new therapeutic approaches aimed at correcting the defects in the coagulation system.

Pressure sores are a well-recognized problem, with an etiology that is multifactorial and not solely a consequence of pressure itself. Malnutrition is one of the factors involved, namely low calorie and protein intake. Mainly elderly patients, patients after hip fracture, but also patients after trauma, burns or extended surgery require additional nutritional support to reduce the possibility of pressure ulcers developing. Evidence has shown the efficacy of percutaneous endoscopic gastrostomy in elderly patients with malnutrition and dementia. Nutritional support should include sufficient calories, protein, fat, carbohydrates, vitamins and minerals. Arginine is the main amino acid required and is essential for collagen deposition and wound healing. Vitamin A and zinc should be added to nutritional support.

Background: inflammation is an important feature of atherosclerotic lesions and increased production of the actuephase reactant. The contribution of coagulation factor to the development of coronary artery disease has not yet been clearly established.

Objective: To test whether C-reactive protein, fibrinogen and antithrombin-III are associated with angiograpic CAD, history of myocardial infarction and extensive atherosclerotic involvement.

Methods: Blood samples were tested for CRP, fibrinogen and AT-III levels from 219 individuals undergoing coronary angiography.

Results: CRP was higher in patients with CAD (0.95 + 1.31, n=180, vs. 0.39 + 0.61 mg/dl, n=39, P<0.0001) and in those with a history of MI (1.07 + 1.64, n=96, vs. 0.65 + 0.72 mg/dl, n=84, P<0.05) than in control subjects. The patients who developed unstable angina had higher CRP levels than the patients with stable CAD (2.07 + 2/38, n=7, vs. 0.80 + 1.13 mg/dl, n=173, P<0.001).

Fibrinogen was significantly higher in patients with CAD (298 + 108 vs. 258 + 63 mg/dl, P<0.01). In patients with CAD, mean AT-III value was less than in patients without CAD, but this difference was found in CRP, fibrinogen and AT-III values among the patients with single, double or triple vessel disease.

Conclusion: CRP is elevated in patients with CAD and a history of MI. Elevated levels of CRP at the time of hospital admission is a predictive value for future ischemic events.

There is an association between higher levels of fibrinogen and CAD. The association of AT-III levels with CAD needs testing in further studies.
 

Background: Previous reports on the behavior of procalcitonin blood levels in diverse clinical conditions suggest that it is part of the activation of cellular immunity and is another acute-phase reactant.

Objective: To compare procalcitonin with C-reactive protein, a well-known acute-phase reactant, in a series of acutely febrile pediatric patients and to review recent literature on procalcitonin.

Methods: Procalcitonin and CRP levels were evaluated in 38 blood samples of pediatric patients who were admitted to the Dana Children’s Hospital for evaluation of unexplained fever or for sepsis work-up.

Results: The parallelism between procalcitonin and CRP was found to be highly significant (P<0.01).

Conclusion: The rise of procalcitonin blood levels in febrile pediatric patients suggests that it is part of the acute-phase reaction, parallel with the CRP reaction.