Israel Medical Association Journal

Background: Orofacial clefts are the most common craniofacial congenital malformations, with significant anatomic, ethnical, racial and gender differences.

Objectives: To investigate the prevalence, distribution and characteristic features of various types of non-syndromic clefts among Israeli Jews and Arabs.

Methods: We conducted a retrospective multi-center survey in 13 major hospitals in Israel for the period 1993–2005. To obtain the true prevalence and detailed clinical characteristics, data on liveborn infants with non-syndromic clefts were obtained from the Ministry of Health's National Birth Defect Registry and completed by chart reviews in the 13 surveyed hospitals.

Conclusions: The prevalence of non-syndromic clefts was 7.00/10,000 live births. The markedly higher rate in Arabs is related to the high rate of consanguinity. Both very young and old maternal age represents a higher risk of clefts in their offspring. 

Background: The "obesity paradox" is defined as an inverse association of good health, survival and obesity. Usually in healthy persons the more obese you are the more metabolic complications you have; however, thin patients with chronic obstructive pulmonary disease (COPD) have more cardiovascular complications and a higher mortality rate.

Objectives: To explore whether atherosclerosis and peripheral artery disease (PAD) contribute to the higher morbidity and mortality of patients with COPD.

Methods: This prospective study included 87 patients with chronic COPD who were treated in the pulmonary outpatient clinic; all signed a consent form before enrollment. We documented their lung function (FEV1%), body mass index (BMI) and ankle brachial index (ABI). The primary endpoints were to find an association between atherosclerosis and BMI in patients with COPD, and between atherosclerosis and severity of lung disease.

Results: Average ABI[1] was 1.01 ± 0.20, BMI[2] was 29.33 ± 7.48 kg/m2, and the abdominal circumference was 107.34 ± 18.87 cm. A positive correlation was found between BMI and ABI (P = 0.001) and between abdominal circumference and ABI (P = 0.000). Patients with peripheral artery disease were older (73.6 ± 11.5 vs. 68.1 ± 11.6 years old, P = 0.04), were thinner (average BMI 25.5 ± 6.2 vs. 31.06 ± 7.3, P = 0.001), and had a lower abdominal circumference (97.7 ± 18.3 vs. 111.7 ± 17.5 cm, P = 0.001). No such difference was observed for years of smoking. Male PAD patients with COPD had a lower BMI (25.2 ± 5.6 vs. 29.9 ± 7.4, P = 0.016), and their abdominal circumference was smaller (96.1 ± 18.0 vs. 110.2 ± 16.5 cm, P = 0.004). Female PAD patients with COPD had a lower BMI (26.3 ± 8.2 vs. 33.1 ± 7.0, P = 0.045), but their abdominal circumference was not different from females without PAD (102.0 ± 19.7 vs. 114.0 ± 19.4 cm, P = 0.162). Patients with PAD had a worse lung disease (FEV1% 34 ± 8% vs. 45 ± 16%, P = 0.01). During the 1 year of follow-up five patients died: two PAD patients due to acute myocardial infarction and three non-PAD patients died from pulmonary insufficiency (two patients) and pulmonary emboli (one patient).

Discussion: We found that COPD patients with PAD were older and thinner and had a lower abdominal circumference and a more progressive lung disease. Extensive atherosclerosis in patients with COPD may partly explain the “obesity paradox” observed in patients with COPD.

Background: High sensitivity C-reactive protein, a marker of inflammation, has been proposed to stratify coronary artery disease risk and is lowered by HMG-CoA reductase (statin) therapy. However, the reproducibility of persistently elevated hs-CRP[1] levels and association with other markers of inflammation in patients with stable CAD[2] on aggressive statin therapy is unknown.

Objectives: To determine the reproducibility of hs-CRP levels measured within 2 weeks in patients with documented CAD with stable symptoms and to identify associations with other markers of inflammation.

Methods: Levels of hs-CRP were measured twice within 14 days (7 ± 4) in 23 patients (22 males and 1 female, average age 66 ± 10 years) with stable CAD and hs-CRP ≥ 2.0 mg/L but ≤ 10 mg/L at visit 1. All patients had received statins for cholesterol management (low density lipoprotein-cholesterol 84 ± 25 mg/dl) with no dose change for > 3 months. None had a history or evidence of malignancy, chronic infection or inflammation, or recent trauma. There was no change in medications between visits 1 and 2, and no patient reported a change in symptoms or general health during this interval. White blood cell count and pro- and anti-inflammatory cytokines were measured at both visits.

Results: hs-CRP levels tended to be lower at visit 2 (median 2.4 mg/L, range 0.8–11 mg/L) than at visit 1 (median 3.3 mg/L, range 2.0–9.7 mg/L; P = 0.1793). However, between the two visits hs-CRP levels decreased by more than 1.0 mg/L in 10 patients and increased by more than 1.0 mg/L in 4 patients. Changes in hs-CRP levels were unrelated to changes in levels of white blood cells (P = 0.4353). Of the cytokines tested, only the anti-inflammatory cytokine interleukin-1 receptor antagonist and the pro-inflammatory cytokine interleukin-8 were above lower limits of detection, but there were no correlations between changes in these values and changes in hs-CRP (both P > 0.5).

Conclusions: In stable CAD patients on aggressive statin therapy, hs-CRP levels may fluctuate over brief periods in the absence of changes in health, cardiac symptom status and medications, and without corroboration with other measures of inflammation. Accordingly, elevated hs-CRP levels should be interpreted with caution in this setting.

Experimental and clinical data suggest a causal relationship between immunological and inflammatory processes and heart failure. Inflammatory processes may be involved in the pathogenesis of heart failure and may play a role in the progression of ventricular dysfunction. In the last decade several immunological methods were developed that tried to address these questions and overcome the inflammatory and immunological insults. We hope that the present review will increase awareness of new treatment options and encourage researchers and physicians to investigate this novel approach to treat patients with heart failure.
 

Ten years ago we published a review updating current knowledge on heart failure. We summarized that heart failure is a neuro-humoral and inflammatory syndrome, and that pro-inflammatory cytokines are involved in cardiac depression and in the complex syndrome of heart failure. We suggested that understanding the involvement of these cytokines may enable us to reverse cardiac depression and heart failure. Now we know that there are several mechanisms involved in this syndrome, including inflammation, nitric oxide-dependent pathways, apoptosis, reactive oxygen species, and mitochondrial energy metabolism. This review will focus on the up-to-date mechanistic aspects of heart failure, including clinical trials that have contributed to our better understanding of this entity.

Inherited forms of proteinuria constitute a rare and heterogeneous group of diseases, the most prominent of which is glomerular dysfunction, which leads to proteinuria. Investigation of the genetic background underlying these diseases has provided significant data on the normal operation of the glomerular filter. Among the different components of the glomerulus, the podocyte slit diaphragm is considered the main source for genetically derived protein alteration, which leads in turn to proteinuria. Investigation of the different proteins revealed that the lack of nephrin and podocin is the leading cause of several inherited forms of proteinuria. It was also proposed that the lack of podocin is linked to cardiac anomalies. This review suggests that the absence of slit diaphragm proteins and the open zipper phenomenon are associated with cardiac anomalies.