Israel Medical Association Journal

Background: Upper eyelid blepharoplasty surgery is one of the most common plastic surgeries. Khat is used topically to reduce tissue edema.

Objectives: To evaluate the effect of topical khat administration after eyelid surgery on postoperative healing.

Methods: Our prospective comparative study included 24 patients who underwent upper eyelid blepharoplasty or ptosis surgery between 2019 and 2020. Patients were randomly assigned to 48 hours of cold dressing with frozen khat leaves and frozen peas dressing (common practice). Postoperative photographs of the eyes were evaluated for the degree of ecchymosis and edema on postoperative days (PODs) 1, 3, and 7 by three blinded observers. Measures included tissue swelling and hemorrhage on PODs 1, 3, and 7.

Results: The mean age of the cohort was 67 ± 7 years; 17 females (71%). Khat application was associated with lower postoperative ecchymosis at each time point. Females had lower levels of postoperative ecchymosis on POD 7 (P = 0.07). Eyelid edema was more pronounced in the khat group on PODs 1 and 3, but this was reversed on POD 7. There was good agreement among all three observers in grading ecchymosis and edema (P < 0.001).

Conclusions: The use of khat was associated with less tissue ecchymosis after oculoplastic surgery, although this was not statistically significant even following sub-population analysis. The outcome can be attributed to the active ingredients of cathinone and cathine, which cause vasoconstriction and lipolysis, and to the anti-inflammatory and anti-oxidative flavonoids and phenolic compounds. These encouraging preliminary findings warrant additional studies on a biochemical/cellular level.

Background: The distribution of pathology and clinical characteristics of lacrimal gland diseases are different in different areas of the world.

Objectives: To evaluate the incidence rate, patient characteristics, and indications for surgical intervention of lacrimal gland lesions in a tertiary care center in Israel.

Methods: All biopsied or surgically removed lacrimal gland lesions at the Goldschleger Eye Institute from 2009 to 2015 were identified. The following data were collected: age, gender, indications for surgical intervention, diagnosis, treatment, and prognosis.

Results: We evaluated 28 lacrimal gland biopsies from 26 patients (11 men, 15 women). Mean age at biopsy was 47.5 years old. The most common presenting symptoms were: eyelid swollenness (57.14%), ptosis (32.14%), and proptosis (10.71%). All patients underwent computed tomography and magnetic resonance imaging. In 28 cases, infiltrations of the lacrimal gland were found. In nine cases infiltration of muscles or orbital extension were found. The most common pathologies were non-specified inflammation (44.82%), lymphoma (20.68%), and immunoglobulin G4-related disease (10.34%). The treatment was diverse according to the patient diagnosis. Prognosis of lacrimal gland disease was good; however, in five patients the systemic disease progressed.

Conclusions: Lesions of the lacrimal gland comprise a wide variety of pathological findings that require different treatment strategies. Lacrimal gland biopsies enable physicians to precisely recognize the pathology; therefore, it is important to consider this surgical method in any patient with lesions in the lacrimal gland.

Background: Targeted anti-tumor necrosis factor-alpha (TNFα) therapy in patients with rheumatoid arthritis (RA) has resulted in dramatic improvement in the course of the disease and prognosis. One of the features of RA is hyperplasia of synovial cells, particularly RA synovial fibroblasts (RA-SF), caused partially by impaired apoptosis of RA-SF cells. It has been shown that TNFα may inhibit apoptosis in RA-SF cells and this process may be reversed by the use of TNFα antagonists.

Objectives: To determine the influence of etanercept, an anti-TNFα agent, on sFas (CD 95) receptor.

Methods: We analyzed serum levels of sFaS and TNFα in a group of 26 patients with high RA disease activity who were selected to start treatment with etanercept. Assessment of sFas receptor and TNFα levels was performed before and 6 months after treatment with etanercept.

Results: Treatment with etanercept resulted in increased TNFα levels (log TNFα 0.602 vs. 1.17, P < 0.05) but no change in sFas levels (log sFas 3.17 vs. 3.11, P = 0.37). As expected, treatment resulted in significant reduction in both disease activity and levels of inflammatory markers.

Conclusions: Etanercept may increase TNFα levels in patients with RA. We also speculate that the Fas pathway is not the main apoptotic pathway in patients with RA treated with etenercept, since sFas, a marker of apoptotic activity, remained unchanged and was not influenced by disease activity and concomitant treatment. 

The autoimmune lymphoproliferative syndrome is a recently described human disorder that affects lymphocyte programmed cell death (apoptosis).

Recent studies have implicated the dying cell as a potential reservoir of modified autoantigens that may initiate and drive systemic autoimmunity in susceptible hosts. The uridine-rich small nuclear ribonucleoprotein complex is a common target for autoantibodies present in the serum of patients with systemic lupus erythematosus and SLE[1]-overlap syndromes. Four modifications occurring in this complex during apoptosis have been described to date: the caspase-mediated cleavage of the U1-70K protein, the U1 RNA and the Sm-F protein, and the association with hyperphosphorylated SR proteins. In addition, the U1 snRNP[2] complex has been shown to translocate from its normal subcellular localization to apoptotic bodies near the surface of cells undergoing apoptosis. This redistribution might facilitate exposure of the modified components of the U1 snRNP complex to the immune system when the clearance of apoptotic cell remnants is somehow disturbed. The modifications in the U1 snRNP components during apoptosis might represent the initial epitopes to which an immune response is generated and may be the trigger for the production of autoantibodies to this complex in patients with SLE or SLE-overlap syndromes. Therefore, it can be hypothesized that the exposure of elevated levels of apoptotically modified U1 snRNP to the immune system of a genetically susceptible individual might lead to the breaking of immunologic tolerance towards the U1 snRNP complex.

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Background: The neurosteroids dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) have been reported to possess neuroprotective as well as anti-tumoral activity in vitro and in vivo.

Objectives: To compare the effect of the two neurohor­mones on cell viability in primary whole-brain fetal mouse culture and isolated neuronal culture, as well as in a human neuroblastoma cell line (SK-N-SH).

Methods: Cell viability and cell proliferation were deter­mined with the neutral red and ³H-thymidine uptake methods, Apoptosis in propidium iodide-stained neuroblastoma cells was determined using flow cytometry.

Results: DHEA (1 nM-10 ìM) decreased the viability of selected primary neuronal cells (33-95% after 24 and 72 hours) but not of whole-brain cultured cells (neuron+glia). DHEAS did not significantly modify cell viability in either primary culture. In a human neuroblastoma cell line, DHEA (1 nM- 1 ìM) decreased ³H-thymidine uptake (30-60%) and cell viability (23-52%) after 24 hours. DHEAS did not significantly modify, or only slightly stimulated, cell viability and uptake of  ³H-thymidine (132% of controls). The combination of DHEA and DHEAS neutralized the toxic effect of DHEA in both primary neuronal culture and neuroblastoma cell line. Flow cytometric analysis of DNA fragmentation in neuroblastoma cells treated with 100 nM DHEA/DHEAS for 24 hours showed an increase in apoptotic events (31.9% and 26.3%. respec­tively, vs. control 2.54%).

Conclusions: Our results do not confirm a neuroprotective role for DHEA and suggest that DHEA and DHEAS have a differential role: DHEA possesses a neurotoxic (expressed only in isolated neurons) and anti-proliferative effect DHEAS demonstrates only a slight neuroprotective effect.