Israel Medical Association Journal

Background: Recent evidence suggests that olfaction is impaired in patients with pseudotumor cerebri (PTC).

Objectives: To measure suprathreshold olfactory function by using the University of Pennsylvania Smell Identification Test (UPSIT), assessing its usefulness for routine clinical use.

Methods: Forty PTC patients underwent USPIT olfactory testing.

Results: Twenty-nine out of 40 (73%) PTC patients (36 women, 4 men; mean age 34 years) had reduced suprathreshold smell sensation according to UPSIT scores: 19 (47%) had mild microsmia, 9 (23%) had moderate microsmia, and one (3%) was classified as having severe microsmia. The mean UPSIT score of all patients was 32.4 (95% confidence interval 31.4–33.4). Multivariate regression analysis found that UPSIT scores were not related to disease activity, disease duration, initial intracranial pressure (ICP), or visual function.

Conclusions: Many PTC patients have reduced suprathreshold olfactory dysfunction that can be discovered by UPSIT, a rapidly administered smell test, which is suitable for clinical office use.

Background: There is little evidence about awareness and functional outcome of hip fracture-related falls among patients with a history of recurrent falling.

Objectives: To measure the awareness of recurrent falling in patients and to compare their functional outcomes with those who suffered hip fracture after a sporadic isolated fall.

Methods: A prospective comparative study of patients after a hip fracture-related fall was conducted. Awareness of falls was measured and functional outcome was assessed by total and motor Functional Independence Measure (FIM) score changes and efficiency and scores at admission and on discharge.

Results: Of 97 eligible participants, 49 (50.5%) were recurrent fallers. Of these recurrent falls, 19 (38.8%) were not reported, 16 (32.7%) were reported but no action was taken, and 7 (14.3%) were reported and a partial assessment performed. A full assessment was performed in only 7 cases (14.3%). FIM scores on admission and discharge were significantly higher in once-fallers. A multiple linear regression analysis showed that being a once-faller was independently associated with higher total FIM at admission (β coefficient = 0.290, P = 0.004), higher motor FIM at admission (β coefficient = 0.295, P = 0.003), higher total FIM at discharge (β Coefficient = 0.264, P = 0.009), and higher motor FIM at discharge (β coefficient = 0.230, P = 0.023).

Conclusions: Awareness of the syndrome of recurrent falling is extremely low. Recurrent falls before a hip fracture-related fall is associated with substantial loss of functional independence. Being a recurrent faller adversely affects rehabilitation outcome of hip fracture patients.

Background: Weight loss surgery is the most effective treatment for obesity, and it reduces cardiovascular and cancer risk through poorly understood mechanisms. MicroRNAs (miRNAs) are short RNA molecules that regulate the stability and translation of many mRNAs. We hypothesized that levels of specific circulating miRNAs are altered following surgery and may contribute to lower cancer risk.

Objectives: To investigate the change of miRNA following surgery.

Methods: All patients underwent gastric “sleeve operation”. RNA was isolated from sera of 21 patients (14 men, 7 women) before and 3 months after surgery. Sera were combined into two pools, which served for cDNA library construction followed by miSeq sequencing. The levels of candidate miRNAs were validated in the individual samples by QRT-PCR.

Results: Serum miR-122 was significantly up-regulated 3 months post-bariatric surgery in sera of patients, whose endothelial function had greatly improved. In addition, serum miR-122 levels correlated positively with endothelial function as measured by FMD. The changes in miR-122 levels from pre-surgery to 3 months post-surgery also tended to correlate with the respective changes in FMD.

Conclusions: The serum miR-122/miR-451 ratio may serve as a marker for endothelial function in obese patients. miR-122 is the dominant miRNA in the liver and a known tumor suppressor. Our findings suggest a role for circulating miR-122 in the maintenance of vascular endothelial cells (VECs) and in the prevention of cancer. Further studies are required to elucidate the mechanism of its secretion into circulation and its absorption by VECs, as well as its relevant cellular targets.

Background: Systemic CD11b+ cells have been associated with several cardiac diseases, such as chronic heart failure.

Objectives: To assess the levels of circulating CD11b+ cells and pro-inflammatory cytokines in cardiomyopathy induced by chronic adrenergic stimulation.

Methods: Male Lewis rats were injected with low doses of isoproterenol (isoprel) for 3 months. Cardiac parameters were tested by echocardiography. The percentage of CD11b+ cells was tested by flow cytometry. The levels of inflammatory cytokines in the sera were determined by an inflammation array, and the expression levels of cardiac interleukin-1 (IL-1) receptors were analyzed by real-time polymerase chain reactions. Cardiac fibrosis and inflammation were determined by histological analysis.

Results: Chronic isoprel administration resulted in increased heart rate, cardiac hypertrophy, elevated cardiac peri-vascular fibrosis, reduced fractional shortening, and increased heart weight per body weight ratio compared to control animals. This clinical presentation was associated with accumulation of CD11b+ cells in the spleen with no concomitant cardiac inflammation. Cardiac dysfunction was also associated with elevated sera levels of IL-1 alpha and over expression of cardiac IL-1 receptor type 2.

Conclusions: CD11b+ systemic levels and IL-1 signaling are associated with cardiomyopathy induced by chronic adrenergic stimulation. Further studies are needed to define the role of systemic immunomodulation in this cardiomyopathy.

 

Background: Holocaust survivors report a much higher prevalence of osteoporosis and fracture in the hip joint compared to those who were not Holocaust survivors.

Objective: To evaluate whether being a Holocaust survivor could affect the functional outcome of hip fracture in patients 64 years of age and older undergoing rehabilitation.

Methods: A retrospective cohort study compromising 140 consecutive hip fracture patients was conducted in a geriatric and rehabilitation department of a university-affiliated hospital. Being a Holocaust survivor was based on registry data. Functional outcome was assessed by the Functional Independence Measure (FIM)TM at admission and discharge from the rehabilitation ward. Data were analyzed by t-test, chi-square test, and linear regression analysis. 

Results: Total and motor FIM scores at admission (P = 0.004 and P = 0.006, respectively) and total and motor FIM gain scores at discharge (P = 0.008 and P = 0.004 respectively) were significantly higher in non-Holocaust survivors compared with Holocaust survivors. A linear regression analysis showed that being a Holocaust survivor was predictive of lower total FIM scores at discharge (β = -0.17, P = 0.004).

Conclusion: Hip fracture in Holocaust survivors showed lower total, motor FIM and gain scores at discharge compared to non-Holocaust survivor patients. These results suggest that being a Holocaust survivor could adversely affect the rehabilitation outcome following fracture of the hip and internal fixation. 

 

Background: Both cigarette smoking and chronic kidney disease (CKD) are linked to cardiovascular morbidity and development of atherosclerosis. However, the relationship between cigarette smoking and renal function is not clearly understood. 

Objectives: To investigate the relationship between cigarette smoking and renal function, and determine whether the intensity of cigarette smoking influences renal function.

Methods: We conducted a retrospective analysis of subjects attending the screening center at the Rabin Medical Center. Subjects were classified as smokers, non-smokers and past smokers. Renal function was evaluated by means of the CKD-EPI equation for estimating glomerular filtration rate (eGFR). Multivariate and gender-based analyses were performed.

Results: The study population comprised 24,081 participants, of whom 3958 (17%) were classified current smokers, and 20,123 non-smokers of whom 4523 were classified as past smokers. Current smokers presented a higher eGFR compared to the non-smoking group (100.8 vs. 98.7, P < 0.001) as well as higher rates of proteinuria (15.3% vs. 9.3%, P < 0.001). The difference in eGFR between smokers and non-smokers was more significant in males than in females. Past smokers had the lowest eGFR of all groups, this difference remained significant after age adjustments (P = 0.005). 

Conclusions: Cigarette smoking is associated with higher eGFR compared to non-smoking. This difference was more pronounced in males than females, implying a gender-based difference. The higher prevalence of proteinuria in smokers suggests a mechanism of hyperfiltration, which might result in future progressive renal damage.

 

Background: Neurolathyrism is a toxic nutritional disorder caused by consumption of the grass pea, Lathyrus sativus. The disease, which manifests as an acute or insidiously evolving spastic paraparesis, continues to occur throughout Africa and Asia. Research on this disease is limited, and to our knowledge no imaging studies of patients with neurolathyrism have been published. 

Objectives: To better localize the site of damage in neurolathyrism using advanced imaging methods. 

Methods: Three male patients, immigrants from Ethiopia, were included in the study. All had a history of arrested spastic paraparesis that had evolved before their emigration from Ethiopia, and a past history of exposure to grass pea without any other cause. Functional magnetic resonance imaging (fMRI) included simple motor tasks to evaluate cortical motor areas. Anatomic scans included diffusion tensor imaging (DTI) to evaluate the corticospinal tracts.

Results: In all patients clear activation was found in motor regions and the patients’ activity pattern was qualitatively similar to that in control subjects. In one patient in whom clinical symptoms were asymmetric, an asymmetric activity pattern in M1 was identified. DTI analysis identified intact corticospinal tracts connecting the pons and the primary motor regions, similar to control subjects. 

Conclusions: Advanced neuroimaging clearly identified well-functioning motor regions and tracts in neurolathyrism patients, suggesting a spinal etiology.

 

Background: Androgen deprivation therapy (ADT) added to radiation therapy (RT) in intermediate to high risk prostate cancer negatively impacts quality of life. 

Objectives: To compare health-related quality of life (HR-QOL) in patients receiving combined RT with and without ADT 

Methods: The study population comprised patients treated with definitive RT for prostate cancer who completed the Expanded Prostate Cancer Index Composite-26 form between 3 and 24 months after completing RT. Covariance and a stepwise backward logistic regression model was used. 

Results: Data were available for 143 patients who received RT+ADT and 70 who received RT alone. The sexual function and hormonal vitality scores of patients receiving RT+ADT were significantly lower than those receiving RT alone (P < 0.0001). Patients with only compulsory school education had significantly lower sexual function scores than patients with university level education (P ≤ 0.005). Patients with depression had significantly lower hormonal vitality scores than those without depression (P ≤ 0.0001). 

Conclusions: The addition of ADT to RT is responsible for decrements in quality of life in the sexual and hormonal vitality domains, which is further compounded by lack of education and depression. This underlines the need to improve education, identify and treat depression, and develop strategies to improve the quality of life of patients receiving combination therapy. 

 

Background: Erectile dysfunction (ED), a common problem in males of all ages, can be of organic, psychogenic or combined etiology. Organic ED is mainly caused by vascular and neurological disorders. One of the available tests for differentiating organic from inorganic ED is measuring penile tumescence and rigidity during the REM phase of sleep. However, this test lacks the ability to differentiate between a vascular and non-vascular cause of organic ED. 

Objectives: To compare the results of the EndoPAT test and the nocturnal penile tumescence (NPT) test in patients with erectile dysfunction.

Methods: Twenty patients with ED were recruited for the study. Each participant was evaluated by the SHIM score, RigiScan during polysomnography, and two EndoPAT tests (at the beginning and end of the study).

Results: Seventeen patients had SHIM score ≤ 21; 4 of them had organic ED with a mean EndoPAT score of 1.49, significantly lower than the 1.93 mean EndoPAT score of the 11 patients in the psychogenic ED group (P = 0.047). Two participants had a neurological impairment (spinal trauma and herniated disk). The average SHIM score in the vascular organic group was 6.25 points as compared to 11.69 for the psychogenic group (P = 0.027). The positive predictive value was 43% and the negative predictive value 90%.

Conclusions: EndoPAT could be helpful in excluding organic ED.

 

Background: Pain, fatigue and functional disability are common key outcomes in most rheumatologic disorders. While many studies have assessed the outcomes of specific disease states, few have compared the outcomes of various rheumatic diseases.

Objectives: To assess how the intensity and rating of pain, fatigue and functional disability vary among groups of patients with various rheumatic disorders receiving standard care. 

Methods: In a cross-sectional study conducted in a hospital-based rheumatology unit, standard clinical and laboratory data were obtained and all patients filled out questionnaires on pain, fatigue and daily function. The analysis concentrated on visual analogue scales (VAS) using specific statistical methods.

Results: A total of 618 visits of 383 patients with inflammatory as well as non-inflammatory rheumatic disorders were analyzed. Fibromyalgia patients had significantly higher VAS scores compared to all other groups. On the other hand, patients with polymyalgia rheumatica demonstrated significantly lower VAS scores compared to all other groups of patients. Patients with psoriatic arthritis also demonstrated relatively low VAS scores. VAS scores were lower in patients with inflammatory disorders as compared to patients with non-inflammatory disorders.

Conclusions: Our results suggest a spectrum of outcome intensity in various rheumatic disorders receiving standard care, ranging from fibromyalgia patients who report distinctive severity to patients with inflammatory disorders who are doing relatively well as compared to patients with non-inflammatory disorders. The findings emphasize the need to explore the underlying mechanisms of pain and fatigue in patients with non-inflammatory rheumatic disorders. 

 

Background: Obesity causes specific sexual problems, including diminished sexual desire, poor performance and avoidance of sexual encounters.

Objectives: To systematically evaluate the effect of bariatric surgery on patients' sexual function as compared to their preoperative status.

Methods: Bariatric surgery candidates were given a validated sexual function questionnaire the day before surgery and again 1 year after surgery. Females were polled with the Female Sexual Function Index (FSFI) and males with the Brief Sexual Function Inventory (BSFI). Statistical analysis was performed to elucidate differences in response to the questionnaires.

Results: The study population included 34 females and 14 males. Mean age and body mass index (BMI) were 40.2 ± 10.2 years and 43.4 ± 5.3 kg/m2, respectively. Postoperative BMI was 31.4 ± 4.9 kg/m2 (P < 0.001). Laparoscopic sleeve gastrectomy was performed in 36 patients and laparoscopic Roux-y gastric bypass in 12. In females, the FSFI index rose significantly from 24 to 30 (P = 0.006), indicating increased sexual performance and satisfaction. In males the BSFI increased from 40.2 to 43.9 but did not reach statistical significance (P = 0.08). However, general satisfaction, desire and erection were each significantly improved within the BSFI.

Conclusions: In addition to the well-documented medical and quality-of-life benefits of bariatric surgery, there is also clear improvement in patients' sexual function, both physical and psychosexual.

 

Background: Childhood attention deficit hyperactivity disorder (ADHD) is a chronic health problem with significant risk for long-term morbidity in adulthood.

Objectives: We examined long-term outcomes of ADHD in a population-based sample of childhood ADHD cases prospectively assessed as adults.

Methods: Long-term outcomes for 70 adults who were diagnosed with ADHD during childhood were examined and compared with data on the general population.

Results: Most subjects admitted to persistence of ADHD-related symptoms in adulthood, despite discontinuation of regular medical treatment and follow-up. Areas most severely affected by past and ongoing symptoms included driving performance and incidence of motor vehicle accidents, and rates of marriage stability over time. Relatively unaffected were occupational and academic achievements and military service. 

Conclusions: There is a need for outreach and better services for adults who were previously diagnosed with ADHD. 

 

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.