[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.

[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.

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.

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.

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.

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.

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.

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.

Renal effects of brain natriuretic peptide in patients with congestive heart failure.

The effect of a continuous infusion of human brain natriuretic peptide, 2 pmol.min-1.kg-1, during 60 min was studied in nine patients with congestive heart failure and in 10 healthy control subjects. Brain natriuretic peptide increased from 1.6 to 101 pmol/l in control subjects and from 25 to 173 pmol/l in congestive heart failure during infusion. Urinary sodium excretion increased significantly in both congestive heart failure (60%) and control subjects (71%), but the absolute increase was significantly lower in congestive heart failure (27 micromol/min) than in control subjects (190 micromol/min). Urinary flow rate did not change. The lithium clearance technique was used to evaluate the segmental tubular function; the distal fractional reabsorption of sodium decreased significantly less in congestive heart failure (DFRNa: -0.8%) than in control subjects (DFRNa: -3.7%). Baseline values for glomerular filtration rate and renal plasma flow were reduced in congestive heart failure, but brain natriuretic peptide induced no significant changes between congestive heart failure and control subjects. Brain natriuretic peptide induced the same absolute increase in secondary messenger cGMP in plasma and urine in both patients and healthy subjects. It is concluded that the natriuretic response to brain natriuretic peptide infusion was impaired in patients with congestive heart failure compared with healthy subjects, and it is likely that the impaired natriuretic response was caused by a reduced responsiveness in the distal part of the nephron.

Renal effects of a urodilatin infusion in patients with liver cirrhosis, with and without ascites.

This study reports the effects of a short-term (60 min) low-dose (20 ng x kg(-1) x min(-1)) infusion of synthetic urodilatin (URO) in patients with liver cirrhosis. URO is a natriuretic peptide. A total of 15 cirrhotic patients with ascites and nine without ascites participated in a randomized, double-blind, placebo-controlled study in a crossover design. Renal hemodynamics were estimated by a clearance technique using radioactive tracers, and tubular handling of sodium was evaluated by the lithium clearance method. The renal effects of URO were characterized by a significant increase in urine sodium excretion rate (UNa) and urine flow rate (V) in the cirrhotic patients without ascites (UNa: 173%; V: 94%) and with ascites (UNa: 219%, P < 0.01; V: 42%, P < 0.01) when compared with placebo infusions. Fractional excretion of sodium increased significantly, indicating a tubular effect of URO on sodium handling. Filtration fraction, lithium clearance (a marker of end-proximal fluid delivery), and fractional excretion of lithium increased, fractional proximal tubular sodium reabsorption decreased, and absolute proximal tubular sodium reabsorption remained unchanged, suggesting increased delivery of isotonic fluid from the proximal tubule during URO infusion. In addition, a significant decrease in fractional distal tubular sodium reabsorption contributed to the natriuresis. In conclusion, URO improved sodium and urine output in cirrhotic patients with and without ascites by enhancing fluid delivery from the proximal tubules in addition to inhibiting fractional sodium reabsorption in the distal nephron.

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.

Effect of BNP on renal hemodynamics, tubular function and vasoactive hormones in humans.

The effect of a continuous infusion of human brain natriuretic peptide (BNP) was studied in 48 healthy men. The study was randomized, placebo controlled, and single blind. BNP was given in doses of 1, 2, or 4 pmol.kg-1.min-1 for 60 min, and peak values of BNP in plasma were 38, 85, and 199 pmol/l, giving increments in plasma as seen in heart or renal failure. BNP infusion increased the urinary flow rate and the excretion of sodium in a dose-dependent way. The maximal effects were +65 and +156%, respectively. GFR increased and RPF decreased, the latter in a dose-dependent manner. Blood pressure, heart rate, angiotensin II, and aldosterone were all unaffected by infusion of BNP, whereas a direct inhibition of renin secretion was seen. With the use of the lithium clearance technique, we concluded that the tubular site of action is in both the proximal and distal segments, and the major effect on sodium handling is in the distal parts of the nephron.

A new, fast and reliable radioimmunoassay of brain natriuretic peptide in human plasma. Reference values in healthy subjects and in patients with different diseases.

A new, fast and reliable radioimmunoassay for measurement of brain natriuretic peptide (BNP) in human plasma has been developed and its application is reported in healthy subjects and in patients with congestive heart failure, chronic renal failure, liver cirrhosis and essential hypertension. The antibody was raised in rabbits, the tracer was made by the iodogen method and polyethylene glycol was used for separation of free and bound tracer. BNP was extracted from plasma using Sep-Pak C18 cartridges. The recovery of unlabelled BNP added to plasma was 77.5 +/- 6.2% (mean +/- SD). The detection limit in plasma was 0.55 pmol l-1. No cross-reactivity existed with the natriuretic peptides ANP, CNP or urodilatin. In 124 healthy subjects the mean BNP was 1.8 +/- 1.0 pmol l-1 (SD), range 0.6-5.5. BNP increased slightly with age, was higher in women than men and had no circadian rhythm. In eight patients with congestive heart failure the median BNP level was 30.5 pmol l-1, range 3.9-65.3. In 14 patients with chronic renal failure the median BNP level was 50.5 pmol l-1, range 10.9-219.8 before dialysis, and 38.0 pmol l-1, range 9.4-180.0 immediately following dialysis. In 25 patients with liver cirrhosis the median BNP value was 7.8 pmol l-1, range 1.2-43.1. There was no difference between patients with or without ascites. In 18 medically treated patients with essential hypertension the median BNP level was 5.0 pmol l-1, range 1.2-45.5 pmol l-1.

[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.

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.

The steroid-sparing effect of long-term plasmapheresis in pemphigus: an update.

Glucocorticoids and immunosuppressive agents can induce remission in most pemphigus patients, but mortality remains at 5 to 15% as a result of side effects. We reviewed the adjunctive effect of long-term plasmapheresis in 8 pemphigus patients. Four cases had been resistant to conventional therapy. One or 2 large-volume plasmapheresis treatments were given monthly over 5 to 141 months. All patients, were in clinical remission within 2 months. Relapses seldom occurred: the patients stayed in remission 90% (40-94) (median, ranges) of the period. In all cases the daily dose of glucocorticoid was reduced. The prednisone level could be decreased from 38 (15-80) mg/day to 7.5 (2.5-35) mg/day (p = 0.002). The overall level of other immunosuppressive agents remained unchanged, except in 1 patient for whom cyclosporine was introduced. This indicates that long-term plasmapheresis could have a steroid-sparing effect and clinical efficacy in pemphigus.

Development of a urodilatin-specific antibody and radioimmunoassay for urodilatin in human urine.

Urodilatin (URO) (95-126) is a renal-derived natriuretic peptide that is isolated only from human urine. This study describes the development of a URO-specific antibody and a RIA for URO in urine. At present, there is no commonly available URO-specific antibody. We produced a URO-specific antibody without cross-reactivity with atrial natriuretic peptide (ANP) analogs by immunization of rabbits with the URO (95-126) peptide and subsequent purification of the resulting URO antiserum with affinity chromatography with CNBr-activated Sepharose 4B. The urine samples were ethanol-extracted before assay. The CVs were 6.7% (intraassay) and 14.1% (interassay). This study reports the circadian urinary excretion of URO in 24 healthy subjects with seven sampling periods per 24 h.

Effect of urodilatin infusion on renal haemodynamics, tubular function and vasoactive hormones.

1. The renal efficacy of urodilatin in humans has only been partly investigated. It is unknown whether intravenously infused urodilatin has an effect on sodium reabsorption in both the proximal and distal part of the nephron. 2. Twelve healthy subjects participated in this double-blind, placebo-controlled study in a cross-over design. They received, in a randomized order, a short term (60 min) infusion of urodilatin in three different doses (10, 20 and 40 ng min-1 kg-1 of body weight) and placebo. Renal haemodynamics were estimated by clearance technique with radioactive tracers, and proximal tubular handling of sodium was evaluated by lithium clearance. 3. The 20 ng min-1 kg-1 dose increased the urinary sodium excretion and urinary flow rate compared with the effects of placebo. It increased the glomerular filtration rate and decreased the effective renal plasma flow. In addition, the dose increased the lithium clearance compared with placebo, but did not significantly change the fractional excretion of lithium. On the other hand, it markedly decreased the distal fractional reabsorption of sodium. It also had a suppressive effect on renin secretion. The systemic arterial blood pressure was unchanged, but the dose increased the pulse rate and the haematocrit. The highest dose (40 ng min-1 kg-1) induced a wide variation in the natriuretic and diuretic responses, probably due to a blood-pressure-lowering effect. 4. We conclude, that the urodilatin dose of 20 ng min-1 kg-1 of body weight was most efficacious in this short-term infusion study, and that it had potent natriuretic and diuretic qualities, probably due to stimulation of the glomerular filtration rate and inhibition of sodium reabsorption in the distal part of the nephron.