Israel Medical Association Journal

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.

Background: The most common and most serious complication of varicella (chickenpox) in adults is pneumonia, which can lead to severe respiratory failure. Varicella pneumonia is associated with considerable morbidity and even death.

Objectives: To summarize our experience with varicella pneumonia in terms of clinical, laboratory and radiological characteristics as well as risk factors, management and outcome.

Methods: We conducted a retrospective cohort survey in our facility from 1995 to 2008.

Results: Our cohort comprised 21 patients with varicella pneumonia, of whom 19 (90%) were men; their mean age was 35 ± 10.5 years. Nineteen patients (90%) were Bedouins and 18 (86%) were smokers. Eleven (52%) were admitted to the Medical Intensive Care Unit; 3 of them required mechanical ventilation and the remaining 10 (48%) were admitted to the general medical ward. Median length of stay was 6 ± 7.7 days. Hypoxemia and elevated lactate dehydrogenase on admission were associated with respiratory failure. Radiological manifestations were variable and nine patients exhibited characteristic findings. All but one patient were treated with acyclovir. All patients fully recovered.

Conclusions: In southern Israel varicella pneumonia is primarily a disease of young male Bedouins who are smokers. Severity ranges from mild disease to severe, resulting at times in respiratory failure requiring mechanical ventilation. Prognosis is favorable with complete recovery.

There are isolated cases of physicians who murdered their patients. However, never had a single physician personally supervised the mass murder of hundreds of thousands of individuals, until Dr. Irmfried Eberl. Commander of the Nazi death camp Treblinka, he killed both the ill and those he considered "a disease to his nation." At age 32 Dr. Eberl established Treblinka, where he was responsible for the killing of approximately 280,000 individuals within a few weeks. The position of camp commandant was earned following his success as head of two psychiatric hospitals in Germany where he coordinated the murder of thousands of mentally ill Jews and non-Jews within the context of the euthanasia program. However, few in medicine have heard of him or the harm he caused to the ethical practice of the profession and to human rights.

Background: Early-onset neonatal sepsis is a major cause of morbidity and mortality among newborn infants.

Objectives: To determine the incidence, type of pathogens and resistance to antibiotics among newborns with early-onset neonatal sepsis, and to identify the risk factors predisposing infants to resistant pathogens in order to reevaluate antibiotic regimens appropriate for resistant bacteria in these high risk neonates.

Methods: We retrospectively studied maternal and neonatal variables of 73 term and near-term infants and 30 preterm infants, born over a period of 10.5 years and exhibiting early-onset neonatal sepsis (positive blood cultures in the first 72 hours of life).

Results: Predominant pathogens in term and near-term infants were gram-positive compared with gram-negative organisms (mostly Escherichia coli) in preterm infants. Mothers of infants with antibiotic-resistant organisms were more likely to have prolonged rupture of membranes and prolonged hospitalization before delivery and to be treated with antibiotics. No trends towards more resistant strains of pathogens were recorded over the 10.5 years of the study period.

Conclusions: Early-onset neonatal sepsis in term infants differs in bacterial species from that in preterm infants, with predominantly gram-positive organisms in term and near-term infants and gram-negative organisms in preterms. Rates of bacterial resistance to the combination of ampicillin and gentamicin, though higher among infants born to mothers with prolonged hospitalization who had been treated with antibiotics, still remained very low in our department. Thus, it seems that our classic antibiotic regimen is still appropriate for both term and preterm newborns.
 

Background: Long QT syndrome is an inherited cardiac disease, associated with malignant arrhythmias and sudden cardiac death.

Objectives: To map and identify the gene responsible for LQTS[1] in an Israeli family.

Methods: A large family was screened for LQTS after one of them was successfully resuscitated from ventricular fibrillation. The DNA was examined for suspicious loci by whole genome screening and the coding region of the LQT2 gene was sequenced.

Results: Nine family members, 6 males and 3 females, age (median and interquartile range) 26 years (13, 46), who were characterized by a unique T wave pattern were diagnosed as carrying the mutant gene. The LQTS-causing gene was mapped to chromosome 7 with the A614V mutation. All of the affected members in the family were correctly identified by electrocardiogram. Corrected QT duration was inversely associated with age in the affected family members and decreased with age.
Conclusions: Careful inspection of the ECG can correctly identify LQTS in some families. Genetic analysis is needed to confirm the diagnosis and enable the correct therapy in this disease

Background: Dedicated, organ-specific screening clinics have been shown to significantly reduce cancer morbidity and mortality.

Objectives: To establish a dedicated clinic for Clalit Health Service patients at high risk for hereditary gastrointestinal cancer and to provide them with clinical and genetic counseling, diagnostic screening and follow–up.

Results: During the 3 years of the clinic's activity, 634 high risk families, including 3804 at-risk relatives, were evaluated. The most common conditions were hereditary colorectal syndromes, Lynch syndrome (n=259), undefined young-onset or familial colorectal cancer (n=214), familial adenomatous polyposis (n=55), and others (n=106). They entered follow-up protocols and 52 underwent surgical procedures.

Conclusions: Consistent public and professional education is needed to increase awareness of hereditary colorectal cancer and the possibility of family screening, early diagnosis and therapy. The public health services – i.e., the four health management organizations – should provide genetic testing for these patients who, at present, are required to pay for almost all of these available but costly tests. Dedicated colorectal surgical units are needed to provide the specialized therapeutic procedures needed by patients with familial colorectal cancer. Our future plans include adding psychosocial support for these at-risk patients and their families as well as preventive lifestyle and dietary intervention. 

For centuries skin pigmentation has played a major societal role. Genetic disorders of skin pigmentation have therefore always evoked the curiosity of both laypersons and physicians. Normal skin pigmentation is a complex process that begins with the synthesis of melanin within the melanocytes, followed by its transfer to neighboring keratinocytes where it is translocated to the upper pole of the nucleus and degraded as the keratinocyte undergoes terminal differentiation. Mutations in various genes involved in melanocyte migration during embryogenesis, melanin synthesis and melanosomal function and transfer have been shown to cause pigmentation disorders. In the present review, we discuss normal skin pigmentation and the genetic underpinning of selected disorders of hypo- and hyperpigmentation.

The question of who discovered insulin is controversial. One of the scientists working on pancreas extracts was Nicolae Paulescu, the so-called Forgotten Man. In addition to his scientific research he was also active in politics. He was the father of the virulent antisemitic fascist movement “Garda de Fer” in Romania; he raved against the “Jewish Peril,” claimed in his writings that the Jews are a genetically degenerate people trying to cheat and poison the Rumanian people by alcoholism, and more. His name came up in 2003 when Romanian diabetologists initiated a move to honor him. But voices rose in protest, claiming that persons who incite hatred, support persecution and genocide and distort science as their political tools cannot be accepted or rewarded. The protesters won.

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD[1] development in women are limited and conflicting.

Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel.

Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age ≤ 65 years. DNA samples from 235 women served as the control.

Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 ± 7.0 years vs. 48.3 ± 7.5 and 46.3 ± 7.7 years, respectively, P = 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P = 0.037) and Ashkenazi control subjects (23.3%, P = 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 50 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12–13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P = 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI[2] 0.189–1.114) and in women of other origins, 5.84 (95%CI 1.76–19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR[3] 1.42, 95%CI 1.06–1.89).

Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.

Background The temporal behavior of the coronary microcirculation in acute myocardial infarction may affect outcome. Diastolic deceleration time and early systolic flow reversal derived from coronary artery blood flow velocity patterns reflect microcirculatory function.

Objectives To assess left anterior descending coronary artery flow velocity patterns using Doppler transthoracic echocardiography after primary percutaneous coronary intervention, in patients with anterior AMI[1].

Methods Patterns of flow velocity patterns of the LAD[2] were obtained using transthoracic echocardiography-Doppler in 31 consecutive patients who presented with anterior AMI. Measurements were done at 6 hours, 36–48 hours, and 5 days after successful PPCI[3]. Measurements of DDT[4] and pressure half times (Pt½), as well as observation for ESFR[5] were performed.

Results In the first 2 days following PPCI, the average DDT, 600 ± 340 msec, were shorter than on day 5, 807 ± 332 msec (P < 0.012). FVP[6] in the first 2 days were dynamic and bidirectional: from short DDT (< 600 msec) to long DDT (> 600 msec) and vice versa. On day 5 most DDTs became longer. Pt½ at 6 hours was not different than at day 2 (174 ± 96 vs. 193 ± 99 msec, P = NS) and became longer on day 5 (235 ± 98 msec, p = 0.012). Bidirectional patterns were also observed in the ESFR in 6 patients (19%) at baseline, in 4 (13%) at 36 hours, and in 2 (6.5%) on day 5 after PPCI.

Background: Occult breast cancer without clinically or mammographically detectable breast tumor is an uncommon presentation.

Objectives: To assess the role of breast MRI in women with metastatic carcinoma and an occult primary, and to define the MRI characteristics of the primary breast tumor.

Methods: This retrospective study evaluated 20 women with metastatic carcinoma of unknown origin who underwent breast MRI between 2000 and 2006. Four women were excluded, leaving 16 in the study group. Probability of malignancy was assessed according to BIRADS classification. MRI performance in detecting lesions and evaluating disease extent was assessed, with the gold standard being surgical or biopsy pathology.

Results: MRI detected suspicious lesions in 15 patients. Lesion size ranged from 0.4 to 7 cm (median 1.5 cm). MRI detected a single lesion in 6 patients (40%), multifocal disease in 3 (20%), multicentric disease in 4 (27%), and bilateral breast lesions in 2 (13%). In 13 patients MRI depicted the primary breast cancer. Initial treatment was surgical in nine; MRI correctly estimated disease extent in 6 (67%), underestimated disease extent in 1 (11%), and overestimated it in 2 (22%). Four patients had biopsy followed by chemotherapy; one had multicentric disease and one had multifocal disease. MR findings were false positive in two patients and false negative in one.

Conclusions: MRI is sensitive in detecting the primary tumor and beneficial in assessing tumor extent. Small size and multiple foci are common features. We suggest that bilateral breast MRI be part of the evaluation of women with metastatic carcinoma and an occult primary.
 

Background: Parental fear and misconceptions about fever are widespread in western society. Ethnicity and sociodemographic factors have been suggested as contributing factors.

Objectives: To test the hypothesis that undue parental concern about fever is less in traditional than in western cultural-ethnic groups.

Methods: Bedouin (traditional society) and Jewish (western society) parents of children aged 0–5 years with fever were interviewed in a pediatric emergency unit. Interviews were conducted in the parents' most fluent language (Hebrew or Arabic). A quantitative variable (a 9 item “fever phobia” scale) was constructed.

Results: The parents of 101 Jewish and 100 Bedouin children were interviewed. More Bedouin parents were unemployed, had less formal education and had more and younger children than the Jewish parents. Parents of both groups expressed erroneous beliefs and practices about fever; quantitative but not qualitative differences in fever phobia variables were documented. Compared with their Jewish counterparts, more Bedouin parents believed that fever may cause brain damage and death, administered antipyretic medications for temperature ≤ 38ºC and at excessive doses, and consulted a physician within 24 hours even when the child had no signs of illness other than fever (all P values < 0.001). The mean fever phobia score was higher in the Bedouin than in the Jewish group (P < 0.001). By multivariate analysis, only the cultural-ethnic origin correlated with fever phobia.

Conclusions: A higher degree of fever phobia was found among parents belonging to the traditional Bedouin group as compared to western society parents.