Latanoprost-associated recurrent herpes simplex keratitis

PURPOSE/METHOD: We present a case of a patient who developed recurrent epithelial herpes simplex keratitis after starting treatment with latanoprost. Her ophthalmic history was only remarkable for a past episode of herpetic keratitis 21 years previously. RESULTS/CONCLUSIONS: Episodes of herpetic keratitis were under remission only when latanoprost was discontinued. No recurrences of herpes simplex keratitis have been observed since then. Latanoprost usage might be associated with recurrent episodes of herpes simplex keratitis in patients with previous history of ocular herpes simplex virus infection.     

Peripheral multineuritis pointing at systemic sarcoidosis

We report a patient with a peripheral neuropathy as the first symptom of sarcoidosis. The systemic illness was proved by the presence of typic granulomes in the bone marrow. The fact that sarcoidosis is the cause for the neuropathy is supported by the temporary relation and by the good response of all clinical picture to the corticosteroid therapy.Sarcoid neuropathy can rarely be the presenting feature of sarcoidosis.     

Down-regulation of retroviral transgene expression during differentiation of progenitor-derived dendritic cells

OBJECTIVE: Hematopoietic progenitor cells are a promising source for generation of genetically modified dendritic cells. A prerequisite for using these cells in therapeutic approaches is stable vector-mediated transgene expression during and after cell maturation. We investigated the expression of enhanced green fluorescence protein (EGFP) mediated by retroviral vectors in dendritic cells and other hematopoietic cells differentiated in vitro. MATERIAL AND METHODS: CD34(+) cells were efficiently transduced with retroviral vector constructs known to mediate different expression levels due to distinct cis-acting elements. EGFP(+) cells were purified by cell sorting and differentiated to monocytes, granulocytes, dendritic cells, and erythrocytes. Coexpression of EGFP and cell type-specific markers was analyzed by flow cytometry. RESULTS: Transgene expression from various retroviral vectors was silenced exclusively in dendritic cells, but not in other mature myeloid cells. Loss of EGFP was most pronounced in cells initially displaying low expression levels. This was confirmed by using a retroviral vector coding for a variant of EGFP with significantly reduced half-life. In contrast, a majority of dendritic cells showed stable expression when a self-inactivating retroviral construct using an internal cytomegalovirus promotor was used. CONCLUSIONS: We suggest that expression from the retroviral long terminal repeat is silenced during dendritic cell differentiation in vitro. High levels of stable transgene product in progenitor cells may mask a loss of expression. An improvement of retroviral vectors mediating stable transgenic expression is necessary for therapeutic approaches using gene-modified dendritic cells.     

Variability of results of cavernous nerve stimulation during radical prostatectomy

PURPOSE: We assess the reliability of intraoperative cavernous nerve stimulation for producing an erectile response during radical prostatectomy. MATERIALS AND METHODS: In 61 patients cavernous nerve function was assessed during radical retropubic prostatectomy using a CaverMap nerve stimulator. Control stimulation was also performed before and after prostatic dissection by placing the nerve stimulator tip on the anterior bladder wall. An increase in penile circumference measured by the device was considered a tumescence response while any measurable detumescence was also categorized. RESULTS: Patient age ranged 43 to 72 years (mean 59.8). Before apical dissection 41% and 46% had tumescence, 31% and 21% had detumescence, and 28% and 33% had no response with stimulation of the neurovascular bundle and anterior bladder wall, respectively. After dissection 42% and 25% had tumescence, 16% and 18% had detumescence, and 42% and 57% had no response with stimulation of the neurovascular bundle and anterior bladder wall, respectively. CONCLUSIONS: A response to neurovascular bundle stimulation using this device does not necessarily correlate with the precise anatomical location of the cavernous nerves. There is considerable background variability related to anesthesia, surgical manipulation and other undefined factors that may cause minor but measurable changes in penile circumference.     

Electrical burn injuries in children

Aim: Electrical burns account for up to 10% of burns admissions worldwide. Although a potentially serious mechanism of injury in children, there exists limited Australian data. This study aimed to describe the epidemiology, presentation, management and complications of electrical burn injuries in children. Methods: We performed a retrospective case note review of all children under 16 years of age with electrical burns admitted to the New South Wales Paediatric Burns Centre over an 8‐year, 2‐month study period between November 1995 and December 2003. Results: Twenty‐two cases were identified. The mean age at presentation was 7.6 years (range 8 months to 14.3 years). Eighty‐six percent of cases were sustained from a Low Voltage (<1000 W) power source and 55% occurred in males. The total body surface area burnt ranged from 0.5% to 35% with an average of 4%. Fourteen children had their burns managed non‐operatively, but eight required various surgical procedures ranging from local debridement and primary closure to full‐thickness skin grafting. The average length of hospital stay was 6 days (range 1–58 days). Complications occurred in 4 of the 22 patients (18%) and included wound infections, acute renal failure because of myoglobinuria, permanent electrocardiogram changes and long‐term paraesthesia. Three patients (14%) suffered continued morbidity because of scarring, amputation and psychological disturbance. There was no mortality. Conclusions: Electrical injury was an infrequent but potentially serious cause of injury in children. Minor injuries were successfully managed non‐operatively. Neurological sequelae, cardiac arrhythmias and renal failure remain serious complications in up to 20% of cases.     

Fat-to-glucose interconversion by hydrodynamic transfer of two glyoxylate cycle enzyme genes

The glyoxylate cycle, which is well characterized in higher plants and some microorganisms but not in vertebrates, is able to bypass the citric acid cycle to achieve fat-to-carbohydrate interconversion. In this context, the hydrodynamic transfer of two glyoxylate cycle enzymes, such as isocytrate lyase (ICL) and malate synthase (MS), could accomplish the shift of using fat for the synthesis of glucose. Therefore, 20 mice weighing 23.37 ± 0.96 g were hydrodinamically gene transferred by administering into the tail vein a bolus with ICL and MS. After 36 hours, body weight, plasma glucose, respiratory quotient and energy expenditure were measured. The respiratory quotient was increased by gene transfer, which suggests that a higher carbohydrate/lipid ratio is oxidized in such animals. This application could help, if adequate protocols are designed, to induce fat utilization for glucose synthesis, which might be eventually useful to reduce body fat depots in situations of obesity and diabetes.     

Transepithelial paracellular leakiness induced by chronic phorbol ester exposure correlates with polyp-like foci and redistribution of protein kinase C-alpha

Although exposure of LLC-PK1 epithelial cell sheets to phorbol esters (TPA) causes a near immediate and total decrease of transepithelial electrical resistance (TER), continuation of exposure for 3 to 4 days results in a tachyphylactic response as TER begins to return to control levels. Recovery of TER is maximal by 5 to 6 days, but reaches only 70 to 80% of control level. A reciprocal change in the transepithelial flux of D-mannitol indicates that the TER decrease is indicative of an increase in tight junction permeability. Exposure of cell sheets to TPA for several days also results in the appearance of multilayered polyp- like foci (PLFs) across the otherwise one cell layer thick cell sheets. The pattern of penetration of the electron dense dye, ruthenium red, from the apical surface, across the tight junction and into the lateral intercellular space indicates that the tight junctions of the cell sheet become uniformly leaky after acute exposure to TPA. However, when exposure is continued for several days, only the junctions of cells in the PLFs manifest leakiness. The decrease in TER following acute TPA exposure correlates with the translocation of protein kinase C-alpha (PKC alpha) into a membrane-associated compartment. With exposure of several days, only a trace of PKC alpha is visible by Western immunoblot, and this is in the membrane-associated compartment. Immunofluorescent microscopy indicates that the trace of PKC alpha seen in the Western immunoblots is ascribable distinctly to cells of the PLFs. Monolayer areas between PLFs show no discernible immunofluorescent signal. The data therefore indicate that tight junction barrier function may be restored in certain areas by the down regulation of PKC alpha from the membrane-associated compartment. Failure to down regulate may result in the paracellular leakiness and abnormal cell architecture of the PLFs. Possible implications of this model for in vivo epithelial tumor promotion are discussed.