Israel Medical Association Journal

Chemokines and their receptors play regulatory roles in inflammatory reactions. Lipoprotein(a) is an atherogenic lipoprotein, however the mechanisms of its actions are not defined. Our interest in chemokines and their receptors was stimulated by the finding that incubation of Lp(a)[1] with human umbilical vein endothelial cells produced a conditioned medium that was chemotactic for human monocytes. Since infiltration of monocytes into the vessel wall is an early lesion in atherosclerosis, this finding provided a novel mechanism to explain the relationship between Lp(a) and atherosclerosis. The chemoattractant produced by HUVEC[2] was identified as CCL1/I-309, a CC chemokine previously reported to be secreted by stimulated monocytes/macrophages and T lymphocytes. CCR8, the CCL1 receptor, was identified on endothelial cells, and CCL1 was found to be a chemoattractant for these cells. Most recently we demonstrated functional CCR8 on human vascular smooth muscle cells and found that the Lp(a)-HUVEC conditioned medium is a chemoattractant for these cells. CCL1 increased metalloproteinase-2 production by HUVEC, an activity that enables these cells to remodel the vascular matrix. These studies suggest that CCR8 may play an important role in arterial wall pathology.

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[1] Lp(a) = lipoprotein(a)

[2] HUVEC = human umbilical vein endothelial cells

Background: Low density lipoprotein apheresis is used as a complementary method for treating hypercholesterolemic patients who cannot reach target LDL[1]-cholesterol levels on conventional dietary and drug treatment. The DALI system (direct absorption of lipoproteins) is the only extracorporeal LDL-removing system compatible with whole blood.

Objective: To describe our one year experience using the DALI[2] system.

Methods: LDL apheresis was used in 13 patients due to inability to reach target LDL-C levels on conventional treatment. They included seven patients with familial hypercholesterolemia, three who had adverse reactions to statins, and three patients with ischemic heart disease who did not reach LDL-C target level on medical treatment.

Results: The average triglyceride, total cholesterol, high density lipoprotein-C and LDL-C levels before and after treatment in all patients were: 170 ± 113 vs. 124 ± 91, 269 ± 74 vs. 132 ± 48, 42 ± 8 vs. 37 ± 7.9, and 196 ± 77 vs. 80 ± 52 mg/dl, respectively. Comparing the results of a subgroup of seven patients who had previously been treated with plasma exchange, it is noteworthy that while the reduction in triglyceride, total cholesterol and LDL-C are comparable, the effect on HDL[3]-C concentration was less apparent: from an average of 39.7 ± 8.7 and 23 ± 5.7 mg/dl before and after plasma exchange to an average of 43.9 ± 8.1 and 38.4 ± 7 mg/dl before and after LDL apheresis, respectively. Five patients developed treatment-related adverse events: three experienced allergic reactions manifested as shortness of breath, urticaria and facial flushing; one patient developed rhabdomyolysis, an adverse reaction that was not reported previously as a result of LDL apheresis; and one patient had myopathy with back pain. All untoward effects occurred during the first few treatment sessions.

Conclusions: LDL apheresis using the DALI system is highly efficacious for the treatment of hypercholesterolemia. It is associated with a significant number of side effects occurring during the first treatment sessions. In patients not experiencing adverse effects in the early treatment period, it is well tolerated, and can provide remarkable clinical benefit even after short-term therapy.

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Background: The Bloom syndrome gene, BLM, was mapped to 15q26.1 and its product was found to encode a RecQ DNA helicase. The Fanconi anemia complementation group C gene was mapped to chromosome 9q22.3, but its product function is not sufficiently clear. Both are recessive disorders associated with an elevated predisposition to cancer due to genomic instability. A single predominant mutation of each disorder was reported in Ashkenazi Jews: 2281delATCTGAinsTAGATTC for Bloom syndrome (BLM-ASH) and IVS4+4A®T for Fanconi anemia complementation group C.

Objectives: To provide additional verification of the mutation rate of BLM and FACC[1] in unselected Ashkenazi and non-Ashkenazi populations analyzed at the Sheba Medical Center, and to trace the origin of each mutation.

Methods: We used polymerase chain reaction to identify mutations of the relevant genomic fragments, restriction analysis and gel electrophoresis. We then applied the Pronto^TM kit to verify the results in 244 samples and there was an excellent match.

Results: A heterozygote frequency of 1:111 for BLM-ASH and 1:92 for FACC was detected in more than 4,000 participants, none of whom reported a family history of the disorders. The Pronto^TM kit confirmed all heterozygotes. Neither of the mutations was detected in 950 anonymous non-Ashkenazi Jews. The distribution pattern of parental origin differed significantly between the two carrier groups, as well as between each one and the general population.

Conclusions: These findings as well as the absence of the mutations in non-Ashkenazi Jews suggest that: a) the mutations originated in the Israelite population that was exiled from Palestine by the Roman Empire in 70 AD and settled in Europe (Ashkenazi), in contrast to those who remained; and b) the difference in origin distribution of the BS[2] and FACC mutations can be explained by either a secondary migration of a subgroup with a subsequent genetic drift, or a separate geographic region of introduction for each mutation.

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[1] FACC = Fanconi anemia complementation group C

Background: Epidemiological studies in different parts of the world have revealed controversial results on the association between hepatitis C virus infection and non-Hodgkin’s lymphoma. This discrepancy suggests that HCV[1] lymphotropism or its effect on host lymphocytes may be influenced by regional and racial factors, as well as by genomic variations.

Objective: To determine the prevalence of HCV infection in patients with lymphoproliferative disorders diagnosed and treated in our institute in Israel.

Methods: A total of 212 consecutive patients (95 males and 117 females) treated in our hematology outpatient clinic between August 1997 and September 1999 was screened for anti-HCV antibodies and hepatitis B surface antigen. HCV infection was confirmed by the presence of HCV RNA in the serum. The prevalence of HCV in patients with lymphoproliferative disorders was compared to a control group of patients with myeloproliferative disorders and myelodysplastic syndromes.

Results: HCV infection was more prevalent in the group of LPD[2] patients than in the control group, but this finding was not statistically significant. The prevalence of HCV among LPD patients was 7.8%, while that in the group with myeloproliferative and myelodysplastic disorders was 1.19% and in the general population 0.64%. Among the different classes of LPD, a significant association with HCV infection was established only in patients with diffuse large B cell lymphoma. Furthermore, HCV infection was significantly more prevalent than HBV infection in the LPD group, but not in the myeloproliferative and myelodysplastic disorders group.

Conclusions: Our finding of a significant association between HCV infection and diffuse large B cell lymphoma leads us to suggest that anti-HCV antibodies be performed routinely in such subjects.  

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 [1]LPD = lymphoproliferative disorders

[2] HCV = hepatitis C virus

Background: Each winter influenza activity is a major cause of morbidity and mortality both in Israel and worldwide.

Objectives: To identify the influenza viruses active in Israel during the winter season and to assess the extent of influenza morbidity.

Methods: Information was collected on a population of 18,684 individuals enrolled in two community clinics in central Israel. It included the total number of visits for acute respiratory infection – including influenza and influenza-like illness (ARI/flu-like) – during a 20 week surveillance period (23 November 1997 to 27 March 1998) and the percent of influenza virus isolates in nasopharyngeal specimens from a sample of patients with ARI/flu-like collected on a weekly basis during the same period.

Results: A total of 5,947 visits for ARI/flu-like were recorded among 18,684 enrolled patients in two community clinics (18.1%). The progressive increase in the number of visits for ARI/flu-like reached a peak on week 2/98 with 597 visits and a rate of 31.95 visits per 1,000 population. After this, a decrease to the initial values was evident by week 12/98. Most affected patients were in the age groups 5–14 and 65 years and over, with a rate of 733.5 and 605.3 visits per 1,000 population, respectively. Influenza virus was isolated from 92 of the 426 nasopharyngeal specimens (21.6%). The most commonly detected strain was A/Sydney/5/97(H₃N₂) like (77.2%). The peak rate of isolates was recorded at the beginning of January (01/98).

Conclusions: A/Sydney/5/97(H₃N₂) like-strain was the dominant influenza virus. Its presence did not prevent the simultaneous activity of influenza A/H₁N₁ virus. The dynamic of the clinical disease as expressed by the weekly visit rate for ARI/flu-like was similar to the temporal pattern of the virological findings. The extent of morbidity suggests moderate epidemic activity.
 

Background: A mass influx of immigrants from the former Soviet Union to western countries and Israel followed the demise of the Soviet Bloc at the beginning of the 1990s. It was expected that these immigrants would have a higher morbidity and mortality rate similar to that in Russia.

Objectives: To measure and compare self-reported diseases, subjective health and health services utilization of a representative sample of veteran Israeli Jews and immigrants from the former USSR.

Methods: A cross-sectional survey of Israeli adults was performed by telephone interviews. The survey included 793 Israeli Jews, of whom 124 were immigrants from the former USSR who arrived in Israel after 1989 (response rate 52%).

Results: The immigrants reported a higher rate of diseases and sub-optimal health after adjustment for other variables. However, no excess in health services utilization was reported. A time trend of reporting sub-optimal subjective health was observed: the longer the immigrants spent in Israel the more their reporting patterns resembled those of immigrants who arrived in Israel before 1970. Those who arrived after 1994 more frequently reported having a chronic disease.

Conclusions: Acculturation seems to have been the main effect on the immigrants' health, together with a healthy migrant effect at the beginning of the 1990s. The immigrants' health was worse in the later years of the immigration wave, partially reflecting the poor state of health in Russia compared to Israel.
 

Background: Erysipelas is a skin infection generally caused by group A streptococci. Although penicillin is the drug of choice, some physicians tend to treat erysipelas with antibiotics other than penicillin.

Objectives: To define the pattern of antibiotic use, factors affecting antibiotic selection, and outcome of patients treated with penicillin versus those treated with other antimicrobial agents.

Methods: A retrospective review of charts of adult patients with discharge diagnosis of erysipelas was conducted for the years 1993-1996.

Results: The study group comprised 365 patients (median age 67 years). In 76% of the cases infection involved the leg/s. Predisposing condition/s were present in 82% of cases. Microorganisms were isolated from blood cultures in only 6 of 176 cases (3%), and Streptococcus spp. was recovered in four of these six patients. Cultures from skin specimens were positive in 3 of 23 cases. Penicillin alone was given to 164 patients (45%). Other antibiotics were more commonly used in the second half of the study period (P < 0.0001) in patients with underlying conditions (P = 0.06) and in those hospitalized in the dermatology ward (P< 0.0001). Hospitalization was significantly shorter in the penicillin group (P= 0.004). There were no in-hospital deaths.

Conclusions: We found no advantage in using antibiotics other than penicillin for treating erysipelas. The low yield of skin and blood cultures and their marginal impact on manage­ment, as well as the excellent outcome suggest that this infection can probably be treated empirically on an outpatient basis.
 

Background: The method of midline Iaparotomy incision and closure remains a complex surgical problem.

Objective: To compare the mechanical properties at the interface of midline laparotomy incision made by scalpel versus electrocutting current in rats.

Methods: A sharp midline laparotomy incision was made in 60 Wistar female rats using a scalpel or electrocautery to open the fascia. The fascial and skin wounds were closed separately with a continuous nylon. Fascial specimens were analyzed for mechanical properties at the midline incision using a loading machine. The load-extension curve was recorded during tensile loading at a steady extension rate of 15 mm/mm.

Results: There was no statistically significant difference between the two groups in either wound-bursting force (PPEAK) or the strain energy spent until the point of measured PPEAK. Each load-extension curve showed a characteristic pattern in all rats. Tissue stiffness was greater in the scalpel group than in the electrocautery group (P= 0.02). Correlations were found between tissue stiffness and strain energy, between tissue stiffness and bursting force, and between bursting force and strain energy.

Conclusions: While tissue stiffness was greater when a scalpel was used compared to electrocutting to incise the midline abdominal fascia in rats, there was no difference in the bursing force required to disrupt the wound.

Background: Complementary medicine incorporates several methods of treatment, all of which aim to promote the health and quality of life of the patient. Public interest and demand for complementary medicine services have increased in recent years in Israel, as they have throughout the western world.

Objective: To characterize patients attending the Com­plementary Medicine Clinic in southern Israel at the completion of its first 2 years of operation.

Methods: Data for 398 patients selected at random from 4,400 patients treated in the clinic were collected retroactively from the patientsq' charts.

Results: Of those who visited the clinic, 68% were women with an average age of 49 years. Patients attending the clinic had higher rates of hypertension (20%), diabetes (6%) and heart disease (7%) than the general population of patients insured at the Clalit Health Services in the southern region. In addition to musculoskeletal problems (47%), the other most common complaint was emotional problems (13%) such as tension and anxiety. Acupuncture and Shiatsu were the most commonly used types of treatment (61%). Homeopathy was used by 7%. Among patients with musculoskeletal problems, there were significantly more men than women (P= 0.02). The mean age was higher (P= 0.07). And more of them were referred by friends or family (P= 0.06) than those with other problems.

Conclusions: Characterizing patients attending a com­plementary medicine clinic is imporant for the planning of marketing and resource management, and can assist primary care physicians in decisions regarding the referral of patients to this type of healthcare.

Background: Lower urinary tract symptoms are highly prevalent in older men, have been shown to affect men’s quality of life, and may be associated with more serious outcomes.

Objectives: To determine the prevalence of LUTS among men aged 50 years or older registered at family practice centers in Israel and to assess the effect of these complaints on different aspects of their life.

Methods: In a random sample cohort of men aged 50 years and older, fluent in Hebrew, drawn from those registered in four family clinics in Israel, patients identified with LUTS were interviewed by phone using a structured questionnaire.

Results: The prevalence of LUTS in our study was 21%. Less than a third of these patients had low severity LUTS (28%), 59% were rated moderate, and 13% had severe symptoms. Age had a positive correlation with the severity of LUTS, and increasing severity of symptoms had a negative effect on the daily function and quality of life of patients.

Conclusions: Our community-based study shows that LUTS is a common finding among men above the age of 50 (21%) and has a significant negative effect on their quality of life and daily function. Knowledge of these data should make primary care physicians more aware of this common problem and thus improve the treatment and quality of life of these patients by better identification and prompt treatment.