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: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12–24 months in most reports.

Objectives: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up.

Methods: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1, 4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed.

Results: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0–4 and 4–7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G).

Conclusions: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.

 

Background: Non-mobilized peripheral blood contains mostly committed cells with limited numbers of early progenitors. Objectives: To enrich functional progenitor cells from healthy donors and ischemic heart disease patients by short-term culture of mononuclear cells with defined culture conditions.

Methods: Mononuclear cells obtained from healthy donors and ischemic heart disease patients were cultured for 7 days in a cytokine cocktail. We tested the multilineage differentiation capacities and phenotype of cultured cells.

Results: The short-term culture (7 days) of all study groups with a defined cytokine cocktail resulted in two distinct cell populations (adherent and non-adherent) that differed in their differentiation capacities as well as their cell surface markers. Cultured adherent cells showed higher differentiation potential and expressed endothelial and mesenchymal fibroblast-like surface markers as compared to fresh non-cultured mononuclear cells. The non-adherent cell fraction demonstrated high numbers of colony-forming units, indicating a higher differentiation potential of hematopoietic lineage.

Conclusions: This study proved the feasibility of increasing limited numbers of multipotent progenitor cells obtained from the non-mobilized peripheral blood of healthy donors and ischemic patients. Moreover, we found that each of the two enriched subpopulations (adherent and non-adherent) has a different differentiation potential (mesenchymal, endothelial and hematopoietic).

Background: The primary diagnosis of functional dyspepsia (FD) is made on the basis of typical symptoms and by excluding organic gastrointestinal diseases that cause dyspeptic symptoms. However, there is difficulty reaching a diagnosis in FD.

Objectives: To assess the efficiency of the Usefulness Index (UI) test and history-taking in diagnosing FD.

Methods: A study on acute abdominal pain conducted by the World Organizati­on of Gast­roentero­logy Research Committee (OMGE) included 1333 patients presenting with acute abdo­minal pain. The clinical history-taking variables (n=23) for each pa­tient were recorded in detail using a prede­fined structured data collection sheet, and the collected data were compared with the final diagnoses.

Results: The most signifi­cant clinical history-taking variables of FD in univa­riate analysis were risk ratio (RR): location of pain at diagnosis (RR = 5.7), location of initial pain (RR = 6.5), previous similar pain (RR = 4.0), duration of pain (RR = 2.9), previous abdominal surgery (RR = 4.1), previous abdominal diseases (RR = 4.0), and previous indigestion (RR = 3.1). T­he sensi­tivity of the physicians’ initial de­cisi­on in detecting FD was 0.44, speci­fi­city 0.99 and effi­ciency 0.98; UI was 0.19 and RR 195.3. In the stepwise multivariate logistic regression analysis, the independent predictors of FD were the physicians’ initial decision (RR = 266.4), location of initial pain (RR = 3.4), duration of pain (RR = 3.1), previous abdominal surgery (RR = 3.7), previous indigestion (RR = 2.2) and vomiting (RR = 2.0).

Conclusions: The patients with upper abdominal pain initially and a previous history of abdominal surgery and indigestion tended to be at risk for FD. In these patients the UI test could help the clinician differentiate FD from other diagnoses of acute abdominal pain.

Objectives: To evaluate the predictive value of V/Q scanning in patients with impaired renal function.

Methods: We assessed all patients with impaired renal function who underwent V/Q scanning. The patients studied included those who also had CTPA (group 1) and those who did not (group 2). We recorded the results of V/Q scanning, chest X-rays, CTPA, D-dimer levels, ultrasound of deep veins, and clinical probability for PE (Wells' score) in group 1. CTPA results were considered true results. Anticoagulant treatment was documented in all the patients.

Results: Of the 45 patients in group 1, 12 (22%) had positive CTPA for PE. The positive predictive value (PPV) for patients with high probability results on V/Q scanning for PE was 30%. Restricting results to D-dimer levels ≥ 1000 ng/ml added little to this value. Restricting results to Wells’ score ≥ 7 resulted in 72% PPV. The negative predictive values for low or moderate probability were ~79 % and ~67% respectively. Of the 95 patients in group 2, all those with high probability for PE were treated with anticoagulants.

Conclusions: Patients with impaired renal function and high probability for PE on V/Q scanning had very low PPV for PE. Due to the lack of CTPA studies, patients with high probability for PE on V/Q scanning were treated with anticoagulants.

Objectives: To evaluate the effect of vitamin D analogues on cardiac function and fibrosis in an animal model of cardiorenal syndrome.

Methods: Unilateral nephrectomy was performed and myocardial infarction induced in rats. Rats were treated with vitamin D receptor activator (VDRA, paricalcitol, 40 ng/250 g x 3/week) versus a vehicle. A third group of animals, which served as the control, underwent sham surgery and received no treatment. After 4 weeks of treatment, cardiac function and fibrosis were assessed by trans-thoracic echo and histology, respectively. As a parameter of systemic inflammation, previously shown to be altered in acute coronary syndrome, T regulatory (Treg) cell levels were measured by flow cytometry. Renal dysfunction was documented by standard laboratory tests.

Results: After 4 weeks of treatment, no significant improvement in cardiac function parameters was noted following VDRA administration. VDRA treatment did not significantly alter Treg cell systemic levels. Consistently, despite a trend toward less extent of myocardial fibrosis, we found no clear beneficial effects of VDRA on myocardial tissue inflammation and remodeling.

Conclusions: Vitamin D treatment showed no beneficial effects on cardiac function parameters and fibrosis in an animal model of cardiorenal syndrome. 

Objectives: To assess whether a new herbal-based potentially wake-promoting beverage is effective in counteracting somnolence and reduced post-lunch performance.

Methods: Thirty healthy volunteers were studied on three different days at the sleep clinic. On each visit they ate a standard lunch at noontime, followed by a drink of "Wake up®," 50 mg caffeine, or a placebo in a cross-over double-blind regimen. At 30 and 120 minutes post-drinking, they underwent a battery of tests to determine the effects of the beverage. These included: a) a subjective assessment of alertness and performance based on a visual analog scale, and b) objective function tests: the immediate word recall test, the digit symbol substitution test (DSST), and hemodynamic measurements. The results of the three visits were compared using one-way analysis of variance, with P < 0.05 considered statistically significant.

Results: In all performance tests, subjective vigilance and effectiveness assessment, both Wake up® and caffeine were significantly superior to placebo 30 minutes after lunch. However, at 2 hours after lunch, performance had deteriorated in those who drank the caffeine-containing drink, while Wake up® was superior to both caffeine and placebo. Blood pressure and pulse were higher 2 hours after caffeine ingestion, compared to both Wake up® and placebo.

Conclusions: These results suggest that a single dose of Wake up® is effective in counteracting the somnolence and reduced performance during the post-lunch hours. In the current study it had no adverse hemodynamic consequences.

Objectives: To describe the outcomes of radical prostatectomy as perceived by the patients, and their ways of coping with them.

Methods: We conducted a qualitative study of 22 men with localized prostatic cancer 1 year after surgery. The key questions related to the effect of the disease and the surgery on their lives and their view on the value of the surgery.

Results: The surgery was perceived as a necessary solution for the diagnosed cancer. All the participants suffered from varying degrees of urinary incontinence and erectile dysfunction. Urinary incontinence caused severe suffering. The impaired sexual ability affected relations with partners and led to feelings of shame and guilt and a decreased sense of self-esteem. In retrospect, the participants still viewed the surgery as a life-saving procedure. Faith in the surgeon contributed to their affirmation of the decision to undergo surgery despite the difficulties.

Conclusions: Patients were prepared to suffer the inevitable physical and psychological sequelae of radical prostatectomy because they believed the surgery to be a definitive solution for cancer. Surgeons advising patients with localized prostatic cancer on treatment options should address these difficult issues and provide psychological support, either themselves or in collaboration with professionals.