Synchronization of the G1/S transition in response to corneal debridement.

PURPOSE: This study's intention was to examine the progression of ocular surface epithelium through the G1/S transition of the cell cycle after corneal epithelial debridement. METHODS: Three-millimeter debridements were made in central rat cornea and allowed to heal 4 to 48 hours in vivo. Unwounded contralateral eyes served as controls. Two hours before the animals were killed, 5-bromo-2-deoxyuridine (BrdU) was injected to detect S-phase cells. Incorporated BrdU was visualized by indirect immunofluorescence microscopy, and expression of G1 cell-cycle markers cyclins D and E was examined by indirect immunofluorescence and immunoblotting. RESULTS: The number of BrdU-labeled cells in conjunctival, limbal, and peripheral epithelium peaked at 28 hours after wounding (3.9-, 4.5-, and 3.2-fold increases, respectively). In unwounded eyes, cyclin D showed diffuse cytoplasmic localization with occasional basal cells exhibiting a nuclear localization, while anti-cyclin E showed intense localization in limbal and conjunctival basal cells but only minimal labeling in corneal epithelium. Within 8 to 12 hours after wounding, the nuclei of most corneal basal cells outside the wound area were bound intensely by anti-cyclins D and E. Immunoblotting revealed that cyclin D and E protein levels increased 4.5- and 12.1-fold after wounding, respectively. Epithelium migrating into the wound area did not incorporate BrdU and did not exhibit nuclear localization of cyclins D and E. CONCLUSIONS: Corneal epithelial debridement stimulates basal cells outside the wound area to synchronously enter the cell cycle. However, cells migrating to cover the wound area do not progress through the cell cycle. These data suggest a compartmentalization of the proliferative and migratory phases of wound repair.     

Qualitative research methodology in the exploration of patients' perceptions of participating in a genetic research program

The success of genetic research studies depend on patients' willingness to participate. It is thus important to explore the attitudes of individuals that participate in such studies. This study used qualitative methods to explore how individuals with inherited retinal degenerative disorders (RDD) perceived participating in genetic research and subsequently receiving mutation results. Individual interviews were conducted with all the individuals in the Cape Town Metropolitan area who had received mutation results after participating in a genetic research program (4 individuals). Although experiences differed significantly, the study revealed that the participants had positive attitudes towards participating in the RDD research program. This study illustrates the importance of using qualitative methods in ophthalmic populations to explore important issues.     

Primary piggyback implantation using the Tecnis ZM900 multifocal intraocular lens: case series

PURPOSE: To assess the postoperative outcomes of primary piggyback implantation using the Tecnis ZM900 multifocal intraocular lens (IOL) (Advanced Medical Optics). SETTING: Hospital Oftalmológico de Brasília, Brasília, Brazil. METHODS: Patients who had phacoemulsification with primary piggyback IOL implantation were analyzed prospectively. In all cases, a Tecnis ZM900 multifocal IOL was implanted in the capsular bag and a second silicone IOL was implanted in the ciliary sulcus. Information collected included near and distance uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), and the spherical equivalent (SE) before and after the surgery. RESULTS: Twenty eyes of 12 patients were included in the study. They were followed for 6 months. The mean preoperative distance UCVA was 20/400. At the last follow-up (6 months), the mean distance UCVA was 20/29, significantly better than before referral (P<.001). The mean preoperative SE was +6.35 diopters (D) +/- 2.25 (SD). Six months after surgery, the mean SE was -0.25 +/- 0.40 D (range -1.00 to +0.50 D), significantly better than before referral (P<.001). No patient lost lines of BCVA after surgery. At the last follow-up, 90% of the eyes achieved a near UCVA of J1 and 83.3% of patients were spectacle independent for near and distance vision. A second refractive procedure was performed in 2 eyes. CONCLUSIONS: Primary piggyback implantation using the Tecnis ZM900 multifocal IOL was a simple, safe, and accurate option for patients with high hyperopia who wanted to reduce their dependency on spectacles.     

Tear osmolality and ferning patterns in postmenopausal women.

PURPOSE: To compare tear osmolality and ferning patterns in postmenopausal women (PMW) with and without dry eye symptoms. METHODS: Thirty-seven healthy PMW (>50 years of age), not on hormone replacement therapy, were categorized as being symptomatic or asymptomatic of dry eye based on their responses to an Allergan "Single-Item Score Dry Eye Questionnaire" (SIDEQ). They subsequently completed the Allergan "Ocular Surface Disease Index" (OSDI) questionnaire. Tear samples were collected from participants to evaluate osmolality and ferning patterns. A novel freezing point depression osmometer (Advanced Instruments Inc., Model 3100 Tear Osmometer), was used to measure the osmolality of the tear film. The tear ferning test was performed and evaluated for the quality of ferning based on the Rolando grading system. RESULTS: SIDEQ responses revealed 21 symptomatic and 16 asymptomatic participants. The OSDI total score was 6.5 +/- 5.9 for the non-dry-eyed (NDE) group and 25.7 +/- 12.4 for the dry-eyed (DE) group. The subscores for the DE group were significantly greater than the NDE group (p < 0.001). Osmolality values in DE individuals were significantly different from NDE (328.1 +/- 20.8 vs. 315.1 +/- 11.3 mOsm/kg; p = 0.02). Fifty percent of the DE participants showed type II ferning patterns and 29% of the DE participants showed type III ferning patterns, whereas the NDE participants showed either type I (44%) or II (66%) ferning patterns. There was a significant difference between the DE and NDE participants for the ferning patterns (p = 0.019). There was no significant correlation between tear osmolality and tear ferning (DE: r = 0.12; p > 0.05, NDE: r = -0.17; p > 0.05). CONCLUSIONS: Osmolality in mild and moderately DE PMW is higher than in NDE PMW and tear ferning is a rapid, simple, noninvasive laboratory procedure that indicates altered tear quality in PMW with symptoms of dry eye.     

A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies

Malignancies associated with latent Epstein-Barr virus (EBV) are resistant to nucleoside-type antiviral agents because the viral enzyme target of these antiviral drugs, thymidine kinase (TK), is not expressed. Short-chain fatty acids, such as butyrate, induce EBV-TK expression in latently infected B cells. As butyrate has been shown to sensitize EBV(+) lymphoma cells in vitro to apoptosis induced by ganciclovir, arginine butyrate in combination with ganciclovir was administered in 15 patients with refractory EBV(+) lymphoid malignancies to evaluate the drug combination for toxicity, pharmacokinetics, and clinical responses. Ganciclovir was administered twice daily at standard doses, and arginine butyrate was administered by continuous infusion in an intrapatient dose escalation, from 500 mg/(kg/day) escalating to 2000 mg/(kg/day), as tolerated, for a 21-day cycle. The MTD for arginine butyrate in combination with ganciclovir was established as 1000 mg/(kg/day). Ten of 15 patients showed significant antitumor responses, with 4 CRs and 6 PRs within one treatment cycle. Complications from rapid tumor lysis occurred in 3 patients. Reversible somnolence or stupor occurred in 3 patients at arginine butyrate doses of greater than 1000 mg/(kg/day). The combination of arginine butyrate and ganciclovir was reasonably well-tolerated and appears to have significant biologic activity in vivo in EBV(+) lymphoid malignancies which are refractory to other regimens.     

The effect of H2-receptor antagonist premedication on the duration of vecuronium-induced neuromuscular blockade in postpartum patients

The clinical duration of vecuronium was measured in two groups of postpartum patients undergoing elective tubal ligation. Ten patients received no premedication and ten others ranitidine 150 mg orally the morning of surgery. The mean duration of action of vecuronium was 57.2 +/- 9.9 min in the unmedicated patients and 54.0 +/- 12.9 min in the ranitidine treated patients. These values were significantly greater than the mean value for nonpregnant control patients (35.3 +/- 8.4 min) but indistinguishable from the mean value for cimetidine pretreated patients (63.0 +/- 17.6 min) reported previously. The combined results of the previous and present studies provide convincing evidence that the clinical duration of vecuronium-induced neuromuscular blockade is significantly longer in the postpartum patient and independent of cimetidine or ranitidine pretreatment.     

Prevention and treatment of pressure ulcers/injuries: The protocol for the second update of the international Clinical Practice Guideline 2019

Aim

The European Pressure Ulcer Advisory Panel, the Pan Pacific Pressure Injury Alliance, and the National Pressure Ulcer Advisory Panel are updating the ‘Prevention and Treatment of Pressure Ulcers: Clinical Practice Guideline’ (CPG) in 2019. The aim of this contribution is to summarize and to discuss the guideline development protocol for the 2019 update.

Metabolically controlled reperfusion in acute myocardial infarction: should the polarizing solution be given subselectively?

BACKGROUND: In working rat hearts, metabolic support of injured tissue enhances recovery after acute myocardial infarction. Clinical experience with a systemic "polarizing solution" supports this claim. OBJECTIVES: In a dog model of ischemia/reperfusion, we tested the feasibility of subselectively supplying adapted metabolic substrates before instituting blood reperfusion. METHODS: Thirty-five dogs underwent ligation of the proximal left anterior descending artery and collaterals for 90 minutes. The animals were randomly assigned to receive direct blood reperfusion (Group I), intracoronary glucose, insulin, and potassium (Group II), or intracoronary glucose, insulin, and potassium plus propionyl-L-carnitine (PLC) (Group III). After 30 minutes of artificial reperfusion, prograde blood flow was resumed in groups II and III. A routine necropsy was performed 3 to 5 days later. Primary endpoints were severe arrhythmias, death, markers of infarct size, and specific histologic features. RESULTS: We excluded 4 dogs for technical reasons and 2 others for preexisting cardiomyopathy. In the remaining 29 animals, large apical infarctions were documented ventriculographically during arterial ligation. One dog died of irreversible ventricular fibrillation during the initial ischemic period, and 9/28 dogs (32.1%) died during early reperfusion. Ventricular fibrillation was more common with 10% (versus 5%) dextrose concentrations and was eliminated by PLC. Irreversibly injured (versus jeopardized) areas of myocardium were more common in Group III (85.9 19.3%) than in Groups I and II (16.9 10.8%). CONCLUSION: Subselective infusion of metabolically supportive solutions during acute myocardial infarction is technically feasible. To prevent osmotic endothelial damage, the perfusate must have a low (< 5%) dextrose content.