Israel Medical Association Journal

Background: Diabetic macular edema causes visual loss in almost one-third of diabetic patients. There is currently no treatment for the accompanying cystoid foveal changes.

Objectives: To assess the clinical outcome, i.e., change in visual acuity, in patients treated with steroids for long-standing diabetic macular edema with foveal cystoid changes.

Methods: In the ophthalmology department of a tertiary care university‑affiliated medical center and the ophthalmology service of a health management organization, 46 diabetic subjects (56 eyes) who had diabetic macular edema with cystoid foveal changes received one intravitreal injection of 4 mg triamcinolone acetonide.

Results: The mean baseline (pre‑injection) visual acuity of 0.21 increased to 0.31 and 0.48 at 1 and 3 months, respectively, after which it decreased to 0.33 at 6 months. The mean intraocular pressure was 15.07 mmHg at baseline, 15.83 at day 1, gradually rising to 17.16, 18.38 and 18.57 mmHg at 1, 3 and 6 months respectively. Three patients suffered immediate visual decline after the injection.

Conclusions: Intravitreal triamcinolone acetonide may be a therapeutic option for long‑standing diabetic macular edema with foveal cystoid changes.
 

Background: Men and postmenopausal women with iron deficiency anemia are routinely evaluated to exclude a gastrointestinal source of suspected internal bleeding. Iron deficiency anemia in premenopausal women is often treated with simple iron replacement, under the assumption that the condition is due to excessive menstrual blood loss.

Objectives: To determine the yield of endoscopy evaluations in premenopausal women with iron deficiency anemia.

Methods: Upper and lower gastrointestinal endoscopic examinations were conducted in 45 premenopausal women with iron deficiency anemia not related to gynecologic or nutritional causes.

Results: Forty-three of the 45 women fulfilled the entry criteria and were enrolled. Their mean age was 35 ± 15 years and their mean hemoglobin level 9.3 ± 2.3 g/dl. Twenty‑eight upper gastrointestinal lesions were demonstrated in 24 of the 43 patients (55.8%): erosive gastritis in 12 (27.9%), erosive duodenitis in 4 (9.3%), erosive esophagitis in 3 (7.0%), hiatus hernia (with Cameron lesions) in 3 (7.0%), active duodenal ulcer in 1 (2.3%) and hyperplastic polyp (10 mm) in 1 (2.3%). Five lower gastrointestinal lesions were detected in 5 patients (16.3%): 2 (4.6%) had adenocarcinoma of the right colon, 2 (4.6%) had pedunculate adenomatous polyp > 10 mm, and 1 (2.3%) had segmental colitis (Crohn's disease). One patient (2.3%) had pathologic findings in both the upper and lower gastrointestinal tracts.

Conclusions: Our findings of a gastrointestinal source of chronic blood loss in 28 of 43 premenopausal women with iron deficiency anemia (65.1%) suggest that this population will benefit from bi‑directional endoscopic evaluations of the gastrointestinal tract.

Background: Magnetic resonance imaging is a diagnostic tool of growing importance. Since its introduction, certain medical implants, e.g., pacemakers, were considered an absolute contraindication, mainly due to the presence of ferromagnetic components and the potential for electromagnetic interference. Patients with such implants were therefore prevented from entering MRI systems and not studied by this modality. These devices are now smaller and have improved electromechanical interference protection. Recently in vitro and in vivo data showed that these devices may be scanned safely in the MRI.

Objectives: To report our initial experience with three patients with pacemakers who underwent cerebral MRI studies.

Methods: The study included patients with clear clinical indications for MRI examination and who had implanted devices shown to be safe by in vitro and in vivo animal testing. In each patient the pacemaker was programmed to pacing-off. During the scan, continuous electrocardiographic telemetry, breathing rate, pulse oximetry and symptoms were monitored. Specific absorption rate was limited to 4.0 W/kg for all sequences. Device parameters were assessed before, immediately after MRI, and 1 week later.

Results: None of the patients was pacemaker dependent. During the MRI study, no device movement was felt by the patients and no episodes of inappropriate inhibition or rapid activation of pacing were observed during the scan. At device interrogation here were no significant differences in device parameters pre-, post-, and 1 week after MRI. Image quality was unremarkable in all imaging sequences used and was not influenced by the presence of the pacemaker.

Conclusion: Given appropriate precautions, MRI can be safely performed in patients with a selected permanent pacemaker. This may have significant implications for current MRI contraindications.  

Background: Intramural duodenal hematoma generates partial or complete obstruction that develops slowly and progressively with a consequent delay in diagnosis. Many diagnostic and therapeutic measures remain debatable and justify a review of current management policy.

Objectives: To highlight the diagnostic and therapeutic steps in pediatric IDH[1].

Methods: The records of 12 children with post-traumatic IDH who were treated in the Hillel Yaffe Medical Center between 1986 and 2000 were retrospectively reviewed. Three of them had clotting disorders and were excluded. The interval between their admission and diagnosis as well as the therapeutic decisions were evaluated and analyzed.

Results: Nine children were treated for IDH. The interval between admission and diagnosis ranged from 24 hours to 6 days. Five children had associated traumatic pancreatitis. Initially, all the children were conservatively treated. In seven the hematoma resolved after 9–20 days. Two children were operated upon because the obstruction failed to resolve. All nine children recovered without permanent complications.

Conclusions: Intramural duodenal hematoma has many clinical and therapeutic puzzling aspects. Bicycle handlebar, road accidents and sports trauma are the main etiologic factors in children, but child abuse should be kept in mind. Associated traumatic pancreatitis is common. Gastroduodenal endoscopy may be useful to clarify doubtful cases. Pediatric surgeons should increase awareness regarding IDH in order to reduce delay in diagnosis and the need for surgical decompression.

Background: Cardiovascular disease is now well established as a multifactorial disease. In a given individual, the level of cardiovascular risk is due to the interaction between genetic and environmental components. The BIP cohort comprised 3000 patients with cardiovascular disease who were tested for the benefits of bezafibrate treatment. This cohort has the data for the lipid profile of each individual, fibrinogen, Insulin, as well as clinical, demographic and lifestyle parameters

Objectives: To genotype up to 64 variable sites in 36 genes in the BIP cohort. The genes tested in this assay are involved in pathways implicated in the development and progression of atherosclerotic plaques, lipid and homocystein metabolism, blood pressure regulation, thrombosis, rennin-angiotensin system, platelet aggregation, and leukocyte adhesion.

Methods:  DNA was extracted from 1000 Israeli patients from the BIP cohort. A multilocus assay, developed by the Roche Molecular System, was used for genotyping. Allele frequencies for some of the markers were compared to the published frequencies in a healthy population (the French Stanislas cohort, n=1480).

Results: Among the 26 comparable alleles checked in the two cohorts, 16 allele frequencies were significantly different from the healthy French population: ApoE (E3, E2, E4), ApoB (71ile), ApoC (3482T, 455C, 1100T, 3175G, 3206G), CETP (405val), ACE (Del), AGT (235thr), ELAM (128arg); p<0001 and LPL (93G, 291Ser, 447ter); p < 005.

Conclusions: Although a comparable healthy Israeli population study is needed for more precise interpretation of these results, frequency differences in these polymorphic alleles, associated with lipid metabolism, renin-angiotensin system and leukocyte adhesion mechanism, between CVD patients and healthy individuals nevertheless implicate these candidate genes as predisposing for CVD.lic safety.
 

Background: Thyroidectomy for goiter is a common surgical procedure performed in most hospitals in Israel. Both general and ear, nose and throat surgeons are familiar with thyroidectomy for cervical goiters. In about 1–15% of thyroidectomies, the goiter is intrathoracic and requires somewhat different management. This topic has not been reviewed in the literature recently.

Objective: To evaluate the clinical presentation, preoperative workup, surgical complications and risk of malignancy in retrosternal goiters.

Methods: We retrospectively reviewed the records of 75 patients who underwent thyroidectomy for retrosternal goiter in the General Thoracic Surgical Department of our institution during a 15 year period, January 1990 to January 2005.

Results: All the patients (41 women and 34 men) were symptomatic at presentation, with choking and dyspnea being the most common complaint. Computerized tomography scan of the neck and chest were obtained before the operation in 71 patients (95%). Ten patients (13%) had a previous partial thyroidectomy. A cervical approach was used in 68 patients (91%). Seven patients (9%) required median sternotomy to complete the operation. One patient (1.3%) died from postoperative respiratory failure. Transient recurrent laryngeal nerve palsy occurred in 5 patients (7%) and permanent RLNP[1] in 3 (4%). The incidence of transient and permanent hypoparathyroidism was 10% and 2.6% respectively. Sixty-six lesions (88%) were benign and 9 (12%) were malignant.

Conclusions: Choking and dyspnea are the most common presenting symptoms of retrosternal goiter. CT scan is an important component of the preoperative evaluation and operative planning. Surgical removal of the thyroid is the treatment of choice and most patients have symptomatic improvement following the operation. Since a substernal thyroidectomy may be technically different from cervical thyroidectomy, a surgical team familiar with its unique pitfalls should perform the procedure.

Three decades have elapsed since the inception of Level I trauma centers as the final link in the trauma system "chain of survival".

Dirofilariasis is a parasitic disease of domestic and wild animals that occasionally appears in humans.

Background: Phototherapy is considered the standard of care for neonatal jaundice. However, its short term cardiorespiratory effects have not been studied thoroughly.

Objectives: To assess the cardiorespiratory effect of phototherapy during sleep in term infants with physiologic jaundice.

Methods: We performed two polysomnography studies during 3 hours sleep in 10 healthy term infants with physiologic jaundice; each infant served as his/her own control. The first study was performed just prior to phototherapy and the second study during phototherapy 24 hours later. Heart and respiratory rates, type and duration of apneas, and arterial oxygen saturation were analyzed during active and quiet sleep.

Results: Term infants (gestational age 38.6 ± 1.4 weeks, birth weight 3.2 ± 0.5 kg) underwent the two polysomnography studies within a short time interval and had a comparable bilrubin level (3.6 ± 0.8 and 4.5 ± 0.8 days; 14.5 ± 1.4 and 13.8 ± 2.1 mg/dl, P = NS, respectively). There was no difference in sleeping time or the fraction of active and quiet sleep before or during phototherapy. During active sleep under phototherapy there was a significant decrease in respiratory rate and increase in heart rate (54.3 ± 10.3 vs. 49.1 ± 10.8 breaths/minute, and 125.9 ± 11.7 vs. 129.7 ± 15.3 beats/minute, respectively, P < 0.05), as well as a decrease in respiratory effort in response to apnea. These effects were not found during quiet sleep. Phototherapy had no significant effect on oxygen saturation, apnea rate or periodic breathing in either sleep state. No clinical significant apnea or bradycardia occurred.

Conclusions: Phototherapy affected the cardiorespiratory activity during active sleep but not during quiet sleep in term infants with physiologic jaundice. These effects do not seem to have clinical significance in "real-life" conditions.

Background: Ischemic mitral regurgitation is associated with reduced survival after coronary artery bypass surgery.

Objectives: To compare long-term survival among patients undergoing coronary surgery for reduced left ventricular function and severe ischemic MR[1] in whom the valve was either repaired, replaced, or no intervention was performed.

Methods: Eighty patients with severe left ventricular dysfunction and severe MR underwent coronary bypass surgery. The mean age of the patients was 65 years (range 42–82), and 63 (79%) were male. Sixty-three (79%) were in preoperative NYHA functional class III-IV (mean NYHA 3.3), and 26 (32%) were operated on an urgent/emergent basis. Coronary artery bypass surgery was performed in all patients. The mitral valve was repaired in 38 and replaced in 14, and in 28 there was no intervention. The clinical profile was similar in the three groups, although patients undergoing repair were slightly younger.

Results: Operative mortality was 15% (8%, 14%, and 25% for the repair, replacement and no intervention respectively; not significant). Long-term follow up was 100% complete, for a mean of 38 months (range 2–92). Twenty-nine patients (57%) were in NYHA I-II (mean NYHA 2.3). Among the surgery survivors, late survival was improved in the repair group compared to the other groups (P < 0.05). Predictors for late mortality were non-repair of the mitral valve, residual MR, and stroke (P = 0.005).

Conclusions: Patients with severe ischemic cardiomyopathy and severe MR undergoing coronary bypass surgery should have a mitral procedure at the time of surgery. Mitral valve repair offers a survival advantage as compared to replacement or no intervention on the valve. Patients with residual MR had the worst results.

Background: During the last decade, Israel, a country with low tuberculosis rates, absorbed some 900,000 new immigrants from TB[1]-endemic countries.

Objectives: To analyze the specific impact of our screening procedures on active TB among children in Israel.

Methods: We conducted a retrospective analysis of epidemiologic and clinical data of all children (aged 0–17) with TB notified to the Ministry of Health between 1990 and 1999.

Results: There were 479 children with TB (male/female ratio 1.36). Most cases (81.8%) were foreign born, predominantly (88.2%) immigrants from Ethiopia and, therefore, huge differences existed in TB incidence rates according to countries of origin. Some 80% were diagnosed within 3 years of arrival, mainly due to active case-finding. Pulmonary TB, with infiltrates on chest X-ray, was found in 49.5%. Extra-pulmonary TB sites were: intra-thoracic lymphadenitis (31.1%), extra-thoracic lymphadenitis (12.5%), bones (3.6%), pleura (1.3%), meninges (1%), and others (1%). Seventy percent had a tuberculin skin test reaction ≥10 mm in size. Two (non-immigrant) children died of TB meningitis.

Conclusions: Most of the pediatric TB cases occurred in recent immigrants and were diagnosed within 3 years of immigration. These data support our policy of active case-finding among new immigrants from Ethiopia and extensive contact evaluation for all TB cases.

Background: The 5 year survival rate in patients with advanced epithelial ovarian cancer is 25–40% and treatment is mainly palliative once the disease recurs.

Objectives: To determine the time to progression, overall survival and toxicity of 1 year maintenance treatment with carboplatin in women with advanced EOC[1] after achieving complete remission with platinum‑based combination chemotherapy.

Methods: Twenty-two women with epithelial ovarian cancer stage III-IV previously treated with platinum‑based combinations who had achieved complete remission evidenced by symptoms, pelvic examination, computerized tomography and serum CA-125, were assigned to the study protocol consisting of: carboplatin of AUC=6, three cycles every 2 months, followed by two cycles once every 3 months for a total of five courses over 1 year.

Results: Median follow‑up in the 22 patients was 83 months (range 18–133 months), median disease‑free survival was 36 months (range 2.5–126.4, 95% confidence interval 16.39–56.34). The 5 year survival was 59.7% with a mean overall survival of 83 months (range 18–133, 95% CI[2] 39.11-127.29). Eleven patients have relapsed and died, 11 are alive, 6 are still in complete remission, and 5 are alive with recurrent disease. Grade III-IV toxicity was shown in some of the patients, anemia in 9%, thrombocytopenia in 9%, fatigue in 4.5%, and hypersensitivity in 4.5%.

Conclusions: A 1 year extension of treatment with a single‑agent carboplatin, administered to women with advanced EOC who had achieved complete recovery on platinum‑based chemotherapy as their first‑line therapy, has an acceptable toxicity. The disease-free survival and overall survival values noted in this study are encouraging and warrant further investigation.

Background: Advanced glycation end products, formed by the non-enzymatic glycation of proteins with reducing sugars, are thought to play a pathogenetic role in the vascular complications of diabetes, uremia and atherosclerosis. β2-microglobulin is a major constituent of amyloid fibrils in dialysis-related amyloidosis. AGE[1]-modified β2m[2] has been found in amyloid deposits of long-term hemodialysis patients. AGE-modified β2m has also been shown to enhance chemotaxis and increase tumor necrosis factor-alpha and interleukin-1 beta secretion by circulating and tissue monocytes/macrophages.

Objectives: To investigate the effect of AGE-modified β2m and AGE-human serum albumin on TNF-α[3] and IL-1β[4] secretion by human peritoneal macrophages derived from patients on continuous ambulatory peritoneal dialysis.

Methods: Human PMØ[5] were isolated from peritoneal dialysis effluent of stable CAPD[6] patients and were incubated for 24 hours with AGE-modified β2m, β2m, AGE-HSA[7], HSA or lipopolysaccharide. TNF-α or IL-1β secretion was measured by enzyme-linked immunosorbent assay in cell-free culture supernatants.

Results: Both AGE-modified β2m and AGE-HSA significantly increased TNF-α and IL-1β secretion by human PMØ in a dose-dependent manner (50–200 μg/ml). In contrast, β2m or HSA had no such stimulatory effect on TNF-α secretion but had a small significant increase in IL-1β secretion.

Conclusions: AGE-modified β2m promotes in vitro TNF-α and IL-1β secretion by human PMØ of CAPD patients. Activation of these macrophages by AGE-modified β2m may be a contributory factor to the morphologic changes and altered permeability of the peritoneal membrane in long-term CAPD. 

Background: Sentinel lymph node mapping is the standard of care for patients with malignant melanoma and breast cancer. Recently, SLN[1] mapping was introduced to the field of gastric cancer.

Objectives: To evaluate SLN mapping in patients with gastric cancer.

Methods: In 43 patients with gastric cancer, open intraoperative subserosal dye injection in four opposing peritumoral points was used. Ten minutes following dye injection, stained LNs were located, marked and examined postoperatively from the surgical specimen.

Results: SLN mapping was performed in 43 with gastric cancer; 782 lymph nodes were harvested and evaluated. SLNs were stained in 34 of the patients (79.1%) with a mean of 2.85 SLNs per patient. The false negative rate was 20.9%, the positive predictive value 100%, the negative predictive value 78.6% and the sensitivity 86.9%.

Conclusions: SLN mapping in patients with gastric cancer is feasible and easy to perform. SLN mapping may mainly affect the extent of lymph node dissection, and to a lesser degree gastric resection. However, more data are needed.

The pulmonary microbiology is a dominant element in cystic fibrosis and the main cause of death. Contemporary consensus accords an exclusive role in this to a single microorganism, Pseudomonas aeruginosa. The evidence convincingly shows that the microbiology consists of a multiplicity of species living in perpetual interaction and in a variety of forms – planktonic, sessile, anaerobic – and in organized communities as microcosms, biofilms and ecosystem. This compound microbiology, the essence of the pulmonary disease, is of necessity exposed to constant influence both from without (the air) and within (via the blood), leading to a perpetual state of flux with consequent impact on the clinical course. It is perhaps significant that to date, most or all microbiologic studies were probably conducted, classically, with inert instruments (glass? plastic?), whereas in real life the CF[1] microbiology lives in “test-tubes” of live mucosa with which it maintains a permanent “cross-talk.” The difference to microbial life between these two media may well be very important. It therefore justifies study and may be far-reaching in its effect. There is persuasive argument to strive for a novel holistic view of the totality of the complex microbiology of CF, and to initiate fresh concepts, strategies and methods.