Israel Medical Association Journal

Abstract

Background: Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations.

Objectives: To confirm previous observations on the association of homozygosity for the TT MTHFR genotype with B12 deficiency and endothelial dysfunction, and to investigate whether patients with B12 deficiency should be tested for 677MTHFR genotype.

Methods: We enrolled 100 individuals with B12 deficiency, tested them for the MTHFR C677T polymorphism and measured their homocysteine levels. Forearm endothelial function was checked in 23 B12-deficient individuals (13 with TT MTHFR genotype and 10 with CT or CC genotypes). Flow-mediated dilatation (FMD) was tested after short-term treatment with B12 and folic acid in 12 TT MTHFR homozygotes.

Results: Frequency of the TT MTHFR genotype was 28/100 (28%), compared with 47/313 (15%) in a previously published cohort of individuals with normal B12 levels (P = 0.005). Mean homocysteine level was 21.2 ± 16 mM among TT homozygotes as compared to 12.3 ± 5.6 mM in individuals with the CC or CT genotype (P = 0.008). FMD was abnormal (£ 6%) in 9/13 TT individuals with B12 deficiency (69%), and was still abnormal in 7/12 of those tested 6 weeks after B12 and folic treatment (58%).

Conclusions: Among individuals with B12 deficiency, the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid. Based on our findings we suggest that B12 deficiency should be tested for MTHFR polymorphism to identify potential vascular abnormalities and increased cardiovascular risk. 

Abstract

Background: Renal hemangiomas are rare benign tumors seldom distinguished from malignant tumors preoperatively.

Objectives: To describe the Memorial Sloan-Kettering Cancer Center (MSKCC) experience with diagnosing and treating renal hemangiomas, and to explore possible clinical and radiologic features that can aid in diagnosing renal hemangiomas preoperatively.

Methods: Patients with renal hemangiomas treated at MSKCC were identified in our prospectively collected renal tumor database. Descriptive statistics were used to describe the patient characteristics and the tumor characteristics. All available preoperative imaging studies were reviewed to assess common findings and explore possible characteristics distinguishing benign hemangiomas from malignant renal tumors preoperatively.

Results: Of 6341 patients in our database 15 were identified. Eleven (73%) were males, median age at diagnosis was 53.3 years, and the affected side was evenly distributed. All but two patients were treated surgically. The mean decrease in estimated glomerular filtration rate (eGFR) after surgery was 36.3%; one patient had an abnormal presurgical eGFR and only two patients had a normal eGFR after surgery. We could not identify radiographic features that would make preoperative diagnosis certain, but we did identify features characteristic of hepatic hemangiomas that were also present in some of the renal hemangiomas.

Conclusions: Most renal hemangiomas cannot be distinguished from other common renal cortical tumors preoperatively. In select cases a renal biopsy can identify this benign lesion and the deleterious effects of extirpative surgery can be avoided.

Background: Gaucher disease is the most prevalent inherited disorder among Ashkenazi Jews (carrier frequency of about 6%) and six mutations account for about 96% of their mutant alleles. Two mutations, N370S and R496H, have been reported only in mildly affected or asymptomatic patients, Due to the rarity of R496H, it was recommended that it be excluded from screening programs. 

Objectives: To verify the frequency and trace the origin of Gaucher mutations in screened individuals whose Ashkenazi ethnicity was confirmed by the birthplace of their grandparents.

Methods: We conducted a retrospective analysis of the screened results for the period 2006–2011. Mutations were identified by restriction analysis, Tag-It^TM detection system, Pronto® diagnostic kit and Nanogen technology (NanoChip® 400).

Results: The heterozygote frequency of eight mutations was estimated in a cohort of 16,910 alleles. Two mutations, N370S and R496H, were the most frequent in our population. However, while the occurrence of N370S carriers was similar to other reports (1:19.4), that of R496H carriers was considerably elevated (1:207). Examination of the screened individuals' ethnicity showed a significant difference in the distribution pattern of the country of origin between the carriers of these two mutations.

Conclusions: The origin pattern differences between the two groups of heterozygotes might reflect a separate geographic region of introduction for various mutations. As a result, secondary subgroups could be formed within the Ashkenazi population. This might clarify the dissimilarities in the occurrence of R496H mutation reported by various centers. 

Background: Ethiopian immigration to Israel was initiated in 1981. Most immigrants were rural dwellers who migrated first to Addis Ababa or Gondar, where they waited for eligibility status from Israel to leave Ethiopia. Soon after arriving in Israel, all immigrants were offered screening tests for human immunodeficiency virus (HIV) and syphilis.

Objectives: To evaluate the association of age, gender, marital status and length of time spent in urban areas in Ethiopia with the prevalence of HIV and syphilis seropositivity.

Methods: All adult Ethiopian immigrants who arrived at the Jerusalem immigration center between 1999 and 2002 and consented to HIV and syphilis screening tests were interviewed.

Results: Altogether, 678 immigrants (51% females) were screened; 39 (5.8 %) were seropositive for HIV and 33 (4.9%) for syphilis. The length of time the immigrants spent in Ethiopian cities before leaving for Israel was significantly associated with HIV: odds ratio (OR) 2.76, 95% confidence interval (CI) 1.13–6.71, and syphilis seropositivity  OR 3.87, 95%CI  1.56–9.62.

Conclusions: The length of transit time Ethiopian immigrants from rural areas spend in Ethiopian cities is significantly associated with HIV and syphilis seropositivity. Efforts should be made to shorten this time in order to reduce the risk of infection

Background: Coronary slow flow phenomenon (CSFP) is a functional and structural disease that is diagnosed by coronary angiogram.    



Objectives: To evaluate the possible association between CSFP and small artery elasticity in an effort to understand the pathogenesis of CSFP.

Methods: The study population comprised 12 patients with normal coronary arteries and CSFP and 12 with normal coronary arteries without CSFP. We measured conjugated diene formation at 234 nm during low density lipoprotein (LDL) oxidation, as well as platelet aggregation. We estimated, non-invasively, arterial elasticity parameters. Mann-Whitney non-parametric test was used to compare differences between the groups. Data are presented as mean ± standard deviation.

Results: Waist circumference was 99.2 ± 8.8 cm and 114.9 ± 10.5 cm in the normal flow and CSFP groups, respectively (P = 0.003). Four patients in the CSFP group and 1 in the normal flow group had type 2 diabetes. Area under the curve in the oral glucose tolerance test was 22% higher in the CSFP than in the normal group (P = 0.04). There was no difference in systolic and diastolic blood pressure, plasma concentrations of total cholesterol, triglycerides, high density lipoprotein, LDL and platelet aggregation parameters between the groups. Lag time required until initiation of LDL oxidation in the presence of CuSO₄ was 17% longer (P = 0.02) and homocysteine fasting plasma concentration was 81% lower (P = 0.05) in the normal flow group. Large artery elasticity was the same in both groups. Small artery elasticity was 5 ± 1.5 ml/mmHgx100 in normal flow subjects and 6.1 ± 1.9 ml/mmHgx100 in the CSFP patients (P = 0.02).

Conclusions: Patients with CSFP had more metabolic derangements. Arterial stiffness was not increased in CSFP.

Objectives: To identify possible risk factors associated with a decreased level of care for osteoporosis among patients presenting acutely with the major types of fragility fractures, but also among patients who remain undertreated following their discharge.

Methods: We conducted a retrospective questionnaire-based cohort study. We searched our databases for patients admitted acutely with proximal humerus, distal forearm, thoracolumbar spine, and proximal femur fractures. A questionnaire was used to evaluate osteoporotic care including a referral to DEXA and any associated prescribed medication.

Results: The study group included 114 patients or their caregivers. The osteoporosis care rate rose from 56.1% (n=64) before admission to 71% (n=81) at follow-up. Significant risk factors associated with a decreased care rate prior to admission were the presence of fewer than three comorbidities, and a combination of male gender and young age. Continued neglect at follow-up was associated with the opposite risk factors, such as older age, multiple comorbidities, and polypharmacy. An additional finding was that treated patients had a significantly increased likelihood of presenting with vertebral fractures.

Conclusions: While the association of osteoporosis with the elderly may decrease its screening rates among younger and healthier patients, fragility fractures may be viewed as “end-stage” bone disease, rendering osteoporotic care inefficient.