Israel Medical Association Journal

Background: Normal-tension glaucoma is a chronic progressive optic neuropathy of unknown etiology. Neuroimaging workup in these patients is controversial.

Objectives: To determine the value of routine neurologic and neuro-ophthalmologic evaluations in patients with NTG[1].

Methods: We conducted a retrospective review of all patients diagnosed with NTG in our institution between 2001 and 2006. Neurologic and neuro-ophthalmologic data were evaluated.

Results: Sixty-eight patients were considered suitable for the study (35 males, 33 females age range 43–90 years). Neurologic and neuro-ophthalmologic findings were normal in all of them. The computed tomography brain scan was normal in 88% and duplex carotid Doppler scan was normal in 92%.

Conclusions: Pathologic findings in neurologic and neuro-ophthalmologic assessments were uncommon in NTG. Therefore, contrary to earlier suggestions, neurologic and neuro-ophthalmologic evaluations in typical normal-tension glaucoma patients appear to have no added value.

Background: The prognostic significance of biologic markers in women with ductal carcinoma in situ is not fully understood. HER2/neu is a marker of prognostic significance that is routinely assessed in invasive cancer but its correlation with clinical outcome in DCIS[1] is still obscure.

Objectives: To evaluate the significance of HER-2/neu expression as a prognostic marker in DCIS.

Methods: Clinical and pathologic data from 84 patients treated for DCIS were analyzed. HER-2/neu expression was determined by immunohistochemical staining. Histopathologic parameters (nuclear grade, histologic subtype, necrosis, calcifications, margins) were reviewed by an experienced pathologist. Local recurrence and/or metastatic spread were used as endpoints to determine the prognostic significance of HER-2/neu expression.

Results: With a median follow-up of 94.8 months, nine recurrences were reported. Neither univariate nor multivariate analysis showed a significant correlation between HER-2/neu expression and disease recurrence or the time to disease recurrence. Although HER-2/neu expression demonstrated a significant association with high nuclear grade (P < 0.0001) and comedo subtype (P < 0.0001), there was no correlation between these histologic features and recurrence rate. The correlation between high nuclear grade and disease recurrence approached statistical significance (P = 0.07).

Conclusions: No significant association was found between HER-2/neu expression in DCIS and disease recurrence. However, HER-2/neu correlated with negative markers such as nuclear grading and comedo necrosis, and its role should therefore be investigated in larger studies.
 

[1] DCIS = ductal carcinoma in situ

Background: Adenoviral infection in children undergoing stem cell transplantation is associated with significant morbidity and mortality. Identification of adenoviral infection by polymerase chain reaction from blood facilitates accurate and rapid diagnosis and surveillance. The incidence of adenoviral infection among children undergoing SCT[1] in Israel is not known.

Objective: To estimate the incidence of adenoviral infection in pediatric SCT patients and to characterize the morbidity associated with proven infection.

Methods: Blood samples obtained weekly from children who underwent allogeneic SCT were retrospectively tested for adenovirus using standard PCR[2]. A total of 657 samples collected from 32 patients were examined. Correlation was made between the presence of adenovirus in samples and clinical records.

Results: Of the 32 patients 4 had adenoviral infection by PCR (12.5%). Clinical disease was present in all four patients concurrent with positive PCR. Gastrointestinal complaints and abnormal hepatocellular enzymes were uniformly present. One patient died due to disseminated disease. T cell depletion was a significant risk factor for adenoviral infection (P = 0.03).

Conclusions: In the patient population studied, the incidence of adenoviral infection in children undergoing SCT was 12.5%. The combination of gastrointestinal symptoms and abnormal hepatocellular enzymes should raise the suspicion of adenoviral infection, especially when occurring during the first few months after SCT. 

Background: Fracture of the scaphoid is the most common fracture of a carpal bone. Nevertheless, the diagnosis of SF[1] might be challenging. Plain X-rays that fail to demonstrate a fracture line while clinical findings suggest the existence of such a fracture is not uncommon. Currently there is no consensus in the literature as to how a clinically suspected SF should be diagnosed, immobilized and treated.

Objectives: To assess the current status of diagnosis and treatment of clinically suspected scaphoid fractures in Israeli emergency departments

Methods: We conducted a telephonic survey among orthopedic surgeons working in Israeli EDs[2] as to their approach to the diagnosis and treatment of occult SF.

Results: A total of 42 orthopedic surgeons in 6 hospital EDs participated in the survey. They reported performing a mean of 2.45 ± 0.85 clinical tests, with tenderness over the snuffbox area being the sign most commonly used.  A mean of 4.38 ± 0.76 X-ray views were ordered for patients with a clinically suspected SF. The most common combination included posterior-anterior, lateral, semipronated and semisupinated oblique views. All participating surgeons reported immobilizing the wrists of patients with occult fractures in a thumb spica cast based on their clinical findings. Upon discharge from the ED patients were advised to have another diagnostic examination as follows: 29 (69%) repeated X-rays series, 18 (43%) were referred to bone scintigraphy and 2 (5%) to computed tomography; none were referred to magnetic resonance imaging.

Conclusions: No consensus was found among Israeli orthopedic surgeons working in EDs regarding the right algorithm for assessment of clinically suspected SF. There is a need for better guidelines to uniformly dictate the order and set of tests to be used in the assessment of occult fractures.

Background: The trefoils factor family is a relatively new family of peptides. Their abundant expression in the epithelial cells of the gastrointestinal tract in the normal physiological state and in various ulcerative conditions suggests an important role in mucosal defense and repair. Infection with Helicobacter pylori interferes with normal mucosal activity.

Objectives: To investigate whether H. pylori infection alters the expression of trefoils TFF1[1] and TFF2 in the gastric mucosa of patients with H. pylori-associated chronic active gastritis, positive or negative for the CagA strain.

Methods: During investigation for dyspepsia, gastric biopsies and blood samples were obtained from patients who underwent upper gastrointestinal endoscopy. Rapid urease testing, histology for determination of H. pylori-associated CAG[2] and Western analysis for TFF1 and TFF2 expression with antisera were performed. CagA state was determined using a commercial kit.

Results: TFF2 expression was significantly reduced in both groups of patients with H. pylori-associated CAG compared to healthy patients without H. pylori infection, particularly in CagA-positive patients. TFF1 expression showed a tendency of reduction (not significant) in this group only.

Conclusions: These results suggest that H. pylori-associated CAG has a deleterious effect on the expression of TFF2 in the gastric antrum. This reduced expression may contribute to the damage induced to the gastric mucosa by H. pylori.

Background: Ocular hypotony is a common unexplained feature of myotonic dystrophy type 1. Spuriously low applanation tonometric readings can be caused by thin corneas, flat corneal curvature and corneal edema.

Objectives: To determine whether structure abnormalities of the cornea cause spuriously low readings in applanation tonometry.

Methods: We utilized a TMS-2N corneal topographer, a NonconRobo SP-6000 Specular microscope and a Corneo-Gage Plus 1A Pachymeter to examine seven patients with DM1[1] and eight healthy controls. Intraocular pressure, central corneal thickness, and endothelial cell density were measured, and simulated keratometry readings were made. Cornea guttata and irregularity of corneal topography patterns were also sought.

Results: The mean intraocular pressure was 9.86 ± 1.29 mmHg for all patients (intraocular operated and non‑operated eyes) and 12.88 ± 1.89 mmHg for the controls (P = 0.000021, two-tailed t-test). Central corneal thickness was 530.57 ± 35.30 micron for all patients and 535.00 ± 39.62 micron for the controls (P = 0.75, two-tailed t-test). Endothelial cell density was 3164 ± 761 cells/mm² for all patients and 3148 ± 395 cells/mm² for the controls (P = 0.94, two-tailed t-test). Simulated keratometry readings were similar in both groups when the operated eyes were excluded. Cornea guttata and irregularity of corneal topography patterns were also noted in the study group.

Conclusions: Corneal thickness, corneal curvature and corneal hydration were within normal limits and thus were not the cause for the low applanation tonometry reading in DM1. The presence of cornea guttata and irregularity of corneal topography patterns in DM1 warrants further investigation. 

Background: Since surgical repair of tetralogy of Fallot was introduced, follow-up studies have shown that the majority of patients lead actives lives and have no subjective exercise limitation.

Objectives: To examine lung function, cardiopulmonary functional capacity and echo-Doppler assessment of pulmonary pressure in adult patients 20 years after repair of TOF.

Methods: Unselected consecutive patients performed full lung function testing, progressive cardiopulmonary exercise, and echo-Doppler assessments of pulmonary pressure.

Results: Fifty consecutive patients (33 men, 17 women) aged 29 ± 11 years who underwent surgical repair of TOF at age 10.1 ± 10.9 years were enrolled in this study. Patients after TOF showed no restriction (forced expiratory vital capacity 80%, total lung capacity 91%) and had normal oxygen saturation (97%) and 6 minute walking distance (600 meters). Echocardiography showed normal pulmonary pressure and left ventricular ejection function (62%). Cardiopulmonary exercise testing showed mild limitation of exercise capacity with oxygen uptake at maximal effort of 75–78% predicted.

Conclusions: After corrections of TOF the study patients had normal lung function and pulmonary arterial pressure but mild limitation in their exercise capacity.
 

Background: Negative-pressure therapy for the closure of wounds, a technique to accelerate secondary wound healing, is clinically available as the V.A.C.™ system (KCI Inc, San Antonio, TX, USA). Budgetary considerations in our institution precluded widespread use of the expensive V.A.C.™ system in routine cases.

Objectives: To develop a less expensive comparably effective dressing, based on the same principles.

Methods: We used our “homemade” system to treat 15 patients with appropriate complex wounds. Their hospital charts were reviewed and assessed retrospectively. Cost analysis was performed comparing our dressing with the V.A.C.™ system.

Results: Our homemade negative-pressure wound treatment system obtained results similar to what one could expect with the V.A.C.™ System in all parameters. Complications encountered were few and minor. Cost per day using our negative-pressure system for a 10 cm² wound is about US$1, as compared to US$22, utilizing the V.A.C.™ System.

Conclusions: Our homemade negative-pressure system proved to be a good cost-effective treatment for wound closure in hospitalized patients, yielding results comparable to those of the more expensive V.A.C.™ system.
 

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.
 

Background: Acupuncture and public interest in this modality have increased over recent years in Israel and throughout the western world.

Objectives: To compare the knowledge and attitudes of physicians to medical students with regard to acupuncture.

Methods: An anonymous questionnaire was completed by internists and medical students at the Soroka Medical Center.

Results: There were 122 respondents in all, 57 of them women (46.7%). The study sample included 40 physicians (33%), 39 fifth year medical students (32%) and 43 second year medical students (35%). The majority of participants (93.4%) had never received training in acupuncture and 84.4% had never undergone acupuncture therapy themselves. In these variables there were no significant differences between the physicians and the students. The participants’ level of knowledge of acupuncture was very low, with 40% unable to answer even one question (of eight) correctly. Despite the poor level of knowledge and the lack of personal exposure to acupuncture, 90 participants (74%) believed that acupuncture has more than a placebo effect, and 57 (42%) believed it was important to include acupuncture in medical education. There were no statistically significant differences in the attitudes of physicians and medical students to acupuncture.

Conclusions: The level of knowledge and exposure of physicians and medical students to acupuncture is low. However, both groups have relatively positive attitudes to this modality as an acceptable treatment for health problems and were open to its inclusion in the medical school curriculum.

Mesenchymal stromal cells are multipotent cells capable of tissue repair and immune modulation. They are primarily found in bone marrow, but are also present in other tissues of mesenchymal origin, such as fatty tissue, muscle, tendons, etc. MSC[1] can easily be obtained by bone marrow aspiration, showing a rapid expansion in vitro. New protocols enable cell culture without the use of animal-derived sera and artificial growth factors. Avascular necroses of the bone may have different causes. AVN[2] in autoimmune and hematological diseases show a strong association with corticosteroid treatment, which is often unavoidable in severe cases. Until recently, core decompression of the affected osseous area was the standard approach. Because of their differentiation properties, easy accessibility and proliferative capacity, autologous MSCs could potentially complement AVN treatment by adding fresh “osteogenic cells” to the healing process.

There has been a paradigm shift in the treatment of rheumatoid arthritis in recent years. Early and aggressive treatment with good control of disease activity has improved the prognosis of the disease, however, there is significant variability in the response of patients to different therapeutic agents. Hence it is essential to find the predictors of response to a drug at baseline so that we can avoid the delay in achieving remission and improve the outcome. Here we review the literature on available predictors for treatment response in general and specifically for methotrexate and biological agents. We also look at specific scores or indices that can help predict the response in individual patients.

Background: The presence of anti-cyclic citrullinated peptide autoantibody is highly specific for rheumatoid arthritis. Certain HLA-DR4 (HLA-DRB1*04) alleles, also known as the "shared epitope," are associated with increased susceptibility to RA[1]. In addition, these alleles may also have relevance for disease outcome. Anti-CCP[2] antibody positivity has been associated with the presence of HLA-DR4 alleles in patients with RA. However, there is little information available regarding any relationship between quantitative anti-CCP production (serum anti-CCP concentrations) and the shared epitope.

Objectives: To determine the association between anti-CCP antibody production and various HLA-DRB1 alleles.

Methods: Serum anti-CCP, rheumatoid factor and C-reactive protein levels were assessed in 53 RA patients. All these patients underwent HLA-DRB1 genotyping.

Results: Of the 53 patients 33 (62%) were positive for anti-CCP antibody. We found significant correlations between anti-CCP and RF[3] positivity (chi-square = 6.717, P < 0.01), as well as between anti-CCP and HLA-DRB1*04 positivity (chi-square = 5.828, P < 0.01). There was no correlation between RF positivity and serum levels, CRP[4] serum levels and HLA-DRB1*04 positivity. When quantitatively comparing serum anti-CCP levels with shared epitope positivity, patients carrying one or two copies of HLA-DRB1*04 alleles had significantly higher anti-CCP concentrations (530.0 ± 182.6 U/ml) compared to DRB1*04-negative patients (56.8 ± 27.4 U/ml) (P < 0.01). There was no difference in serum anti-CCP antibody concentrations between patients carrying only one HLA-DRB1*01 allele but no HLA-DRB1*04 allele (12.0 ± 8.6 U/ml) in comparison to SE[5]-negative patients (76.8 ± 56.2 U/ml). Regarding non-SE HLA-DRB1 genotypes, all 6 patients (100%) carrying DRB1*15 alleles and 6 of 7 (85%) patients carrying DRB1*13 were anti-CCP positive. In addition, patients with HLA-DRB1*13 (282.5 ± 23.8 U/ml) and DRB1*15 (398.7 ± 76.2 U/ml) produced significantly more anti-CCP than did any other non-SE HLA-DRB1 subtypes (P < 0.01).

Conclusions: There is significant association between anti-CCP and RF, as well as between anti-CCP and SE positivity in RA. In addition, the presence of one or two copies of HLA-DRB1*04 alleles has been associated with higher serum anti-CCP antibody levels. Thus, patients carrying HLA-DRB1*04 alleles exhibited an overall tenfold increase in serum anti-CCP antibody levels in comparison to HLA-DRB1*04-negative subjects. Increased anti-CCP production may also be associated with other non-SE HLA-DRB1 genotypes, such as DRB1*13 or DRB1*15. In reports by other investigators, both anti-CCP concentrations

Background: Non-operative management of blunt splenic trauma is the preferred option in hemodynamically stable patients.

Objectives: To identify predictors for the successful non-operative management of patients with blunt splenic trauma.

Methods: The study group comprised consecutive patients admitted with the diagnosis of blunt splenic trauma to the Department of Surgery, Hadassah-Hebrew University Medical Center in Jerusalem over a 3 year period. Prospectively recorded were hemodynamic status, computed tomography grade of splenic tear, presence and extent of extra-abdominal injury, number of red blood cell units transfused, and outcome. Hemodynamic instability and the severity of associated injuries were used to determine the need for splenectomy. Hemodynamically stable patients without an indication for laparotomy were admitted to the Intensive Care Unit and monitored.

Results: There were 64 adults (45 males, mean age 30.2 years) who met the inclusion criteria. On univariate analysis the 13 patients (20.3%) who underwent immediate splenectomy were more likely to have lower admission systolic blood pressure (P = 0.001), Glasgow Coma Scale < 8 (P = 0.02), and injury to at least three extra-abdominal regions (P = 0.06). Nine of the 52 patients (17.3%) who were successfully treated non-operatively suffered from grade ≥4 splenic tear. Multivariate analysis identified admission systolic BP[1] (odds ratio 1.04) and associated injury to less than three extra-abdominal regions (OD[2] 8.03) as predictors for the success of non-operative management, while the need for blood transfusion was a strong predictor (OR 66.67) for splenectomy.

Conclusions: Admission systolic blood pressure and limited extra-abdominal injury can be used to identify patients with blunt splenic trauma who do not require splenectomy and can be safely monitored outside an ICU[3] environment.