[Functional results and complications in the long-term follow-up after 25-gauge vitrectomy of epiretinal membrane]. / Funktionelle Ergebnisse und Komplikationen im Langzeitverlauf nach 25-Gauge-ppV bei epiretinaler Gliose.

BACKGROUND: Idiopathic epiretinal membranes can lead, among other things, to visual impairment and metamorphopsia. The treatment of choice is a pars plana vitrectomy with removal of the membrane. The improvement of visual acuity and postoperative complications have already been described in several studies. OBJECTIVE: The aim of this retrospective study is to evaluate the long-term outcome of at least 3 years. MATERIAL AND METHODS: In the period from 2011 to 2016, a total of 667 eyes underwent 25-gauge pars plana vitrectomy, membranectomy and peeling of the ILM (Internal limiting membrane) because of epiretinal membrane by the same surgeon. This study included 51 eyes from 51 patients who had returned to our clinic after at least 3 years. For the follow-up, data were collected after 3 months and then annually, if available. The mean follow-up time was 57 months (37-104 months). In the postoperative follow-up visual acuity, intraocular pressure and complications were recorded. RESULTS: Of the 51 eyes included 34 had a 25-gauge pars plana vitrectomy with phacoemulsification and artificial lens implantation, 8 eyes without phako and 9 eyes were already pseudophakic. The most common complication in the follow-up period was a persistent macular edema with 5.9% (3 eyes) and a recurrence of epiretinal membrane in 5.9% of cases. The best corrected logMar visual acuity was 0.4 (0.1-1.3; n = 51) preoperatively, at the last examination 0.23 (0-1.0; n = 51, p < 0.001). Three months postoperatively, the logMar visual acuity was 0.29 (n = 41), after 1 year 0.25 (n = 35), 2 years 0.23 (n = 29), after 3 years 0.26 (n = 29), after 4 years 0.27 (n = 27), after 5 years 0.24 (n = 17) and after 6 years 0.24 (n = 13). CONCLUSION: The 25-gauge pars plana vitrectomy is a low complication procedure for the removal of epiretinal membranes. The clearest increase in visual acuity can be seen within the first 3 months postoperatively, but then stabilizes. In the long-term follow up a change in visual acuity can also be found after more than 3 years.

The impact of calcineurin inhibitors on insulin sensitivity and insulin secretion: a randomized crossover trial in uraemic patients.

AIMS: The calcineurin inhibitors cyclosporine and tacrolimus are implicated in post-transplant complications such as new-onset diabetes after transplantation. The relative contribution of each calcineurin inhibitor to new-onset diabetes after transplantation remains unclear. We sought to compare the impact of cyclosporine and tacrolimus on glucose metabolism in humans. METHODS: Eight haemodialysis patients received 8-10 days of oral treatment followed by 5-h infusions with cyclosporine, tacrolimus and saline in a randomized, investigator-blind, crossover study. Glucose metabolism and ß-cell function was investigated through: a hyperinsulinaemic-euglycaemic clamp, an intravenous glucose tolerance test and insulin concentration time series. RESULTS: Cyclosporine and tacrolimus decreased insulin sensitivity by 22% (P = 0.02) and 13% (P = 0.048), respectively. The acute insulin response and pulsatile insulin secretion were not significantly affected by the drugs. CONCLUSION: In conclusion, 8-10 days of treatment with cyclosporine and tacrolimus impairs insulin sensitivity to a similar degree in haemodialysis patients, while acute insulin responses and pulsatile insulin secretion remain unaffected.

[25-Gauge macular surgery: comparison with and without combined phacoemulsification and artificial lens implantation]. / 25-Gauge-Makulachirurgie im Vergleich mit und ohne kombinierte Phakoemulsifikation und Kunstlinsenimplantation.

BACKGROUND: With the surgical methods continuously developed in recent years, macular surgery has become an increasingly less traumatic procedure for the eye. For patients with additional lens opacification, a 1-stage procedure with combined cataract surgery is recommended. OBJECTIVE: The aim of this retrospective study was to record the functional results and complications after elective macular surgery with and without combined phacoemulsification and artificial lens implantation. MATERIAL AND METHODS: The retrospective study included all patients who were operated on with a pars plana vitrectomy (ppV; 25 gauge) for epiretinal membrane, macular hole or vitreoretinal traction between 2010 and 2016 and who had a follow-up period of at least 3 months. The functional results and possible risk factors as well as complications that occurred were then recorded. RESULTS: A total of 781 eyes were identified of which 517 (66%) had a phacoemulsification and artificial lens implantation with a 25-gauge vitrectomy, membranectomy, ILM peeling and SF6 gas or air tamponade. The mean follow-up time was 17 months. The mean logMAR visual acuity was 0.59 preoperatively and 0.4 postoperatively. From 64 phacic eyes which did not receive a combined phacoemulsification and artificial lens implantation 40 (62.5%) required phacoemulsification and artificial lens implantation within 13.6 months due to complicated cataract, 18 even within 6 months. In terms of complications, there were comparable results between ppV alone and the combined operation, particularly with respect to an IOL dislocation or iris capture. CONCLUSION: Overall elective macular surgery is a procedure with few complications both without and above all with combined phacoemulsification and artificial lens implantation. Therefore, a combined operation makes sense in terms of surgical management and postoperative rehabilitation, especially in times of a pandemic with limited surgical resources.

Transcriptional profiles in urine during acute rejection, bacteriuria, CMV infection and stable graft function after renal transplantation.

Acute rejection remains an important cause of renal allograft dysfunction and the need for accurate diagnosis is essential to treat transplant recipients successfully. Molecular markers in urine may serve as a diagnostic tool in acute rejection, but controversy still exists regarding the uniqueness of these biomarkers. We measured mRNA of perforin (PRF), granzyme B (GZMB) and granulysin (GNLY) normalized to cyclophilin B in urine specimens from 24 renal allograft recipients with acute rejection, 12 with bacteriuria, 11 with cytomegalovirus (CMV) infections and 17 controls with stable graft function. Measurements were performed using a real-time polymerase chain reaction assay. mRNA levels (means [95% CI]) for all three markers were significantly higher in recipients with acute rejection compared with controls: PRF (0.23 [0.12-0.42] versus 0.04 [0.02-0.07] P<0.001), GZMB (0.14 [0.09-0.23] versus 0.05 [0.03-0.08] P=0.003), GNLY (0.24 [0.14-0.41] versus 0.06 [0.03-0.11] P=0.001). GZMB and GNLY levels during acute rejection were significantly higher when compared with bacteriuria (P=0.011 and P=0.005 respectively), and PRF level during acute rejection was significantly elevated compared with CMV infection (P=0.015). No significant difference was found when comparing marker levels during bacteriuria and CMV infection to controls. Urinary mRNA levels of PRF, GZMB and GNLY are significantly elevated during acute rejection but not during bacteriuria or CMV infections when compared with recipients with stable graft function. The ability to differentiate acute rejection from bacteriuria and CMV infections was only present for some of the markers, that is why careful consideration should be given before applying this technique to clinical practice.

Intragraft mRNA cytotoxic molecule expression in renal allograft recipients.

The gene expression of the cytotoxic T-cell molecules perforin, granzyme B and Fas ligand are associated with acute rejection in renal allograft recipients. Several immune mechanisms are linked to severe systemic inflammation in brain-dead organ donors. We examined the mRNA expression of these T-cell activation biomarkers in donor kidney biopsies to evaluate if they could separate living from deceased donors and primary graft function from delayed graft function or acute rejection in the early post transplantation period. We obtained 139 cadaveric and 19 living donor kidney core biopsies post reperfusion and 78 renal allograft biopsies taken because of graft dysfunction. RNA was isolated from tissue samples and mRNA encoding perforin, granzyme B or Fas ligand and a constitutively expressed cyclophilin B, a reference gene, was measured with the use of real-time quantitative polymerase chain reaction assay, and the levels of expression was correlated with allograft status. We did not find statistically significant differences in gene expression of perforin, granzyme B or Fas ligand among deceased and living donor kidneys and the mRNA expression of these cytotoxic molecules in donor kidney biopsies did not distinguish primary allograft function or early acute rejection. Significant differences were found between acute rejection (n=17) and zero-hour samples and acute rejection and non-rejection (n=41) samples for all 3 measured transcripts. No significant difference was found between acute borderline rejection (n=16) and non-rejection samples. In conclusion, effector molecules secreted by cytotoxic T lymphocytes were not activated in deceased donor kidneys and the genes did not classify the post-transplant course.

The granule exocytosis and Fas/FasLigand pathways at the time of transplantation and during borderline and acute rejection of human renal allografts.

Cytotoxic lymphocytes induce target cell death by the granule exocytosis mechanism in which perforin and granzyme B induce target cell lysis, and ligation of the Fas-FasLigand, which results in apoptosis. The purpose was to detect the level of activation of cytolytic pathways at the time of renal transplantation and during acute rejection. We investigated 119 biopsies obtained at transplantation from 100 deceased donor allografts and 19 living donor allografts as well as 45 allograft biopsy specimens collected from recipients because of a clinical suspicion of an acute rejection episode. Total RNA was isolated and transcribed to cDNA. To measure mRNA encoding perforin, granzyme B, and FasLigand by real-time quantitative, polymerase chain reaction we used oligonucleotide primers in a LightCycler equipment with cyclophilin B as the housekeeping gene. At the time of transplantation, the transcript expression levels of perforin and granzyme B were the same in the biopsies from deceased and living donors. During acute rejection episodes (n = 10), perforin (P < .01), and granzyme B levels (P < .05) were significantly up-regulated. In cases of suspected rejection (n = 12), both the clinical picture and the effector gene responses were heterogeneous. The FasLigand expression was up-regulated during acute rejection episodes (n = 8) compared with the time of transplantation, but the change was not significant. In conclusion, brain death did not seem to influence the granule exocytosis pathway in the kidney. The cytolytic effector pathways are up-regulated in renal allograft tissue in acute rejection episodes.

Metabolism and action of urodilatin infusion in healthy volunteers.

OBJECTIVES: The objective of this investigation was to study both the pharmacokinetics and renal pharmacodynamic properties of intravenously infused urodilatin in human beings. METHODS: Twelve healthy subjects received a short-term infusion (90 minutes) of urodilatin and placebo with a graded infusion rate (from 7.5 to 15 to 30 ng.kg body weight-1.min-1) in a randomized, double-blind, crossover study design. The renal parameters were evaluated by clearance technique with the use of 51Cr-ethylenediaminetetraacetic acid, 125I-hippuran, and lithium. Urodilatin concentrations were determined by a radioimmunoassay with a urodilatin-specific antibody. RESULTS: Kinetics were characterized by a high apparent volume of distribution (43.7 +/- 11.2 L), a high total body clearance (5383 +/- 581 ml/min), and a short plasma half-life (5.57 +/- 0.8 minutes). The maximal plasma urodilatin level was 177.2 +/- 25.8 pmol/L. Less than 1% of total infused urodilatin was recovered in urine. Urodilatin significantly increased glomerular filtration rate (urodilatin, 7.0%, versus placebo, -1.9%; p < 0.05), reduced effective renal plasma flow (urodilatin, -17%, versus placebo, -3%; p < 0.01), increased fractional excretion of sodium (urodilatin, 137%, versus placebo, 27%; p < 0.05), and increased urine flow rate (urodilatin, 46%, versus placebo, -15%; p < 0.01). Fractional excretion of lithium did not change. Mean blood pressure decreased and vasoactive hormone levels remained unchanged or increased. CONCLUSION: The natriuretic and diuretic effects of urodilatin closely followed the profile of urodilatin concentration in plasma. A major part of the synthetic urodilatin was removed from circulation by a route other than filtration through the glomeruli.

Preoperative radiochemotherapy and radical surgery in comparison with radical surgery alone. A prospective, multicentric, randomized DOSAK study of advanced squamous cell carcinoma of the oral cavity and the oropharynx (a 3-year follow-up).

A multicentric, randomized study of squamous cell carcinoma (SCC) of the oral cavity and the oropharynx has been undertaken by DOSAK. The results after radical surgery alone have been compared with the results of combined preoperative radiochemotherapy followed by radical surgery. Patients with primary (biopsy proven) SCC of the oral cavity or the oropharynx with tumor nodes metastasis (TNM) stages T2-4, N0-3, M0 were included in the study. A total of 141 patients were treated by radical surgery alone, whereas 127 patients were treated by radical surgery preceded by preoperative radiochemotherapy. The preoperative treatment consisted of conventionally fractioned irradiation on the primary and the regional lymph nodes with a total dose of 36 Gy (5 x 2 Gy per week) and low-dose cisplatin chemotherapy with 5 x 12.5 mg cisplatin per m2 of body surface during the first week of treatment. Radical surgery according to the DOSAK definitions (DOSAK, 1982) was performed after a delay of 10-14 days. During the follow-up period, 28.2% of all patients suffered from locoregional recurrence, and 27.2% of the patients died. The percentages were higher after radical surgery alone for locoregional recurrence (31% and 15.6%) and for death (28% and 18.6%). The life-table analysis showed improved survival rates of 4.5% after 1 year and 8.3% after 2 years in the group of patients treated with combined therapy. The demonstrated improvement appeared to be significant with the Gehan-Wilcoxon test as well as with the log rank test below a P value of 5%.

[Effect of various ablation levels on endothelial density in the enucleated pig eye. Experimental study with the 193 nm Excimer laser]. / Einfluss unterschiedlicher Ablationstiefen auf die Endothelzelldichte am enukleierten Schweineauge. Experimentelle Untersuchung mit dem 193-nm-Excimerlaser.

UNLABELLED: The effects of deep excimer laser ablations on the corneal endothelial cell count are still unknown. MATERIALS AND METHODS: In an in-vitro study the endothelial cell counts of 125 pig corneas were examined after excimer laser ablation. Five groups of 25 eyes reach, one control group and four groups with 3, 10, 20, and 35 D of ablation were examined. After the laser treatment, a corneoscleral disc was prepared and stored for up 5 days in an organ culture medium. The endothelial cell density of 5 corneas in each group was measured in a period of 5 days with a phase contrast microscope. RESULTS: Significant cell loss, 13-25%, was measured in each group after 5 days. There were no significant differences between the ablated corneas and the control group. CONCLUSION: Deep excimer laser ablations do not significantly reduce the endothelial cell count.

Ulcerative pododermatitis in free-ranging African elephant (Loxodonta africana) in the Kruger National Park.

The occurrence of severe lameness in adult African elephant bulls in a shrub Mopane (Colophospermum mopane) ecosystem was investigated. Large ulcers in the soles of at least one front foot were seen in each of the recorded cases. Microscopically, the lesion can be described as a severe, chronic-active, ulcerative, bacterial pododermatitis (complicated by hypersensitivity/septic vasculitis). A variety of bacteria were isolated from these lesions as well as from regional lymph nodes. Streptococcus agalactiae was the most consistent isolate, while Dichelobacter nodosus, the only organism known to be involved with foot disease in domestic ruminants, was isolated from two cases. Contributory factors such as body mass, portal of entry and origin of potential pathogens may have predisposed to the development of the lesions.

The prevalence of intestinal Salmonella infection in horses submitted for necropsy.

Specimens from the ileum, colon and rectum were aseptically collected from 50 consecutive horse carcases submitted for necropsy to the Department of Pathology, Faculty of Veterinary Science, University of Pretoria. These were bacteriologically examined for the presence of Salmonella. Seventeen of these were positive for Salmonella at one or more sites. Serotyping of the isolates revealed a dominance of Salmonella Hayindogo in these horses.

Major depression: a breakdown in sense of coherence?

The relationship between major depression and the salutogenic construct of sense of coherence was investigated. The Sense of Coherence scale and the Beck Depression Inventory were administered to 50 patients diagnosed with major depressive disorder and to 50 control subjects. Significant negative correlations were found between scores on Depression and total scores on the Sense of Coherence scale as well as all three of its subscales (Comprehensibility, Manageability, and Meaningfulness). A significant positive correlation was found between scores on the Sense of Coherence scale and age. Of the three subscales, a low score on Meaningfulness was the best predictor of scores on Depression.

When the wind goes out of the sail - declining recovery expectations in the first weeks of back pain.

BACKGROUND: Expectations for recovery are a known predictor for returning to work. Most studies seem to conclude that the higher the expectancy the better the outcome. However, the development of expectations over time is rarely researched and experimental studies show that realistic expectations rather than high expectancies are the most adaptive. This study aims to explore patterns of stability and change in expectations for recovery during the first weeks of a back-pain episode and how these patterns relate to other psychological variables and outcome. METHODS: The study included 496 volunteer patients seeking treatment for work-related, acute back pain. The participants were measured with self-report scales of depression, fear of pain, life impact of pain, catastrophizing and expectations for recovery at two time points. A follow-up focusing on recovery and return to work was conducted 3 months later. A cluster analysis was conducted, categorizing the data on the trajectories of recovery expectations. RESULTS: Cluster analysis revealed four clusters regarding the development of expectations for recovery during a 2-week period after pain onset. Three out of four clusters showed stability in their expectations as well as corresponding levels of proximal psychological factors. The fourth cluster showed increases in distress and a decrease in expectations for recovery. This cluster also has poor odds ratios for returning to work and recovery. CONCLUSION: Decreases in expectancies for recovery seem as important as baseline values in terms of outcome, which has clinical and theoretical implications.

Cyclosporin and tacrolimus impair insulin secretion and transcriptional regulation in INS-1E beta-cells.

BACKGROUND AND PURPOSE: Introducing the calcineurin inhibitors cyclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) decrease survival rates. EXPERIMENTAL APPROACH: We sought, in a beta-cell culture model, to elucidate the pathogenic mechanisms behind NODAT and the relative contribution of the calcineurin inhibitors. INS-1E cells were incubated at basal and stimulatory glucose concentrations, while exposed to pharmacologically relevant doses of CsA, Tac and vehicle for 6 or 24 h. RESULTS: Tac inhibited basal (P < 0.05), but not glucose-stimulated insulin secretion (GSIS) after 6 h of exposure. After 24 h, both agents inhibited basal and GSIS (P < 0.05). Calcineurin phosphatase activity was decreased by both drugs during all conditions. Apoptosis was only seen with CsA treatment, which also induced a slight suppression of calcineurin and insulin mRNA, as well as increased levels of the sterol receptor element binding protein (SREBP)-1c, a transcription factor thought to suppress genes essential for beta-cell function and induce insulin resistance. Expression levels of nuclear factor of activated T-cells (NFAT)-c1, -c2, -c3 and -c4 were not decreased notably by either drug. CONCLUSIONS AND IMPLICATIONS: Tac had acute inhibitory effects on basal insulin secretion, but prolonged exposure (24 h) to Tac or CsA revealed similar suppression of insulin secretion. These prolonged effects were mirrored by a total inhibition of calcineurin activity in beta-cells. CsA showed greater inhibition of beta-cell survival and transcriptional markers, essential for beta-cell function.

Commonly used reference genes are actively regulated in in vitro stimulated lymphocytes.

Quantitative polymerase chain reaction (Q-PCR) studies of urine sediments have demonstrated an increased expression of cytotoxin genes during episodes of acute rejection of renal allografts. To compensate for differences in initial sample size and cDNA preparation, standard Q-PCR experiments involve normalization to a reference gene. Although stable expression of reference genes is a prerequisite for any Q-PCR analysis, commonly used reference genes have demonstrated a varying expression across tissues and various stimuli. In this study, cellular expression of several reference genes was investigated in a mixed lymphocyte reaction as a model of gene expression during alloreactive T-lymphocyte activation and acute rejection. Gene expression was quantified using Q-PCR, normalized to cell counts obtained by DNA quantification and corrected for cell polyploidy using flow cytometry. Examined reference genes were 18S rRNA, beta-actin (ACTB), hydroxymethylbilane synthase (HMBS), hypoxanthine phosphoribosyltransferase (HPRT1) and peptidylprolyle isomerase B (PPIB). This study also examined two novel T-lymphocyte-specific reference genes: CD3E and CD8B. HMBS and HPRT were 18.8- and 7.4-fold upregulated, respectively, ACTB was 5.3-fold upregulated, PPIB was 3.2-fold upregulated while 18S rRNA remained stably expressed. The T-lymphocyte-specific reference gene CD3E remained stable while CD8B was upregulated 2.3-fold. In conclusion, several commonly used reference genes were actively regulated during alloreactive T-lymphocyte activation. Additionally, we introduce two stable T-lymphocyte-specific reference genes that might be useful in a Q-PCR analysis of T-lymphocyte-specific cytotoxin genes in urine sediments, as they overcome the contribution of reference gene mRNA from cells irrelevant for diagnosis.

Cytomegalovirus infection in renal transplant recipients.

We have retrospectively analyzed the incidence of cytomegalovirus (CMV) infection in 250 consecutive renal allograft transplants performed in 244 recipients. The mean follow-up was 35.1+/-25.4 months. Immunosuppression was cyclosporine- or tacrolimus-based triple therapy. CMV infection prophylaxis with ganciclovir for 3 months post transplant was prescribed in CMV-seronegative recipients of allografts from seropositive donors (D+R-) and in all recipients treated with OKT3. CMV antigenemia was monitored by the pp65-antigen assay. Thirteen of 57 D+R- recipients (22.8%) developed CMV antigenemia. One recipient had a breakthrough of CMV antigenemia during ganciclovir prophylaxis; 12 D+R- recipients developed CMV antigenemia 147.5+/-173.8 days after transplantation. Four of 13 (30.7%) D+R- recipients had asymptomatic CMV infection, 8 (61.6%) had CMV infection with non-specific symptoms including fever, and 1 (7.7%) developed CMV pneumonia. Six of 13 (46.1%) D+R- patients had been treated with intensified immunosuppressive therapy before CMV infection. In the low-risk CMV groups (D+R+; D-R+; D-R-), 28 recipients (14.5%) developed CMV antigenemia 42.5+/-15.2 days post transplantation. Ten of the 28 (35.7%) recipients had asymptomatic CMV infection, 17 (60.7%) developed CMV infection with non-specific symptoms, and 1 (3.6%) developed CMV pneumonia. Twenty-one of 28 (75.0%) had intensified immunosuppressive therapy before CMV infection. In conclusion, ganciclovir prophylaxis diminished and delayed the onset of CMV infection but did not totally prevent it from occurring in D+R- renal transplant recipients. Clinicians should be vigilant to the possibility of CMV infection in both seronegative and seropositive recipients, especially after anti-rejection therapy.

An unusual case of malignant hyperpyrexia. First reported case in a South African negro.

A case of malignant hyperpyrexia with unusual features in a South African negro child is described. The diagnosis was confirmed by the clinical presentation and laboratory investigations. Aspects of treatment and subsequent successful anaesthetic management are discussed.