Deep evolutionary origin of limb and fin regeneration.

Salamanders and lungfishes are the only sarcopterygians (lobe-finned vertebrates) capable of paired appendage regeneration, regardless of the amputation level. Among actinopterygians (ray-finned fishes), regeneration after amputation at the fin endoskeleton has only been demonstrated in polypterid fishes (Cladistia). Whether this ability evolved independently in sarcopterygians and actinopterygians or has a common origin remains unknown. Here we combine fin regeneration assays and comparative RNA-sequencing (RNA-seq) analysis of Polypterus and axolotl blastemas to provide support for a common origin of paired appendage regeneration in Osteichthyes (bony vertebrates). We show that, in addition to polypterids, regeneration after fin endoskeleton amputation occurs in extant representatives of 2 other nonteleost actinopterygians: the American paddlefish (Chondrostei) and the spotted gar (Holostei). Furthermore, we assessed regeneration in 4 teleost species and show that, with the exception of the blue gourami (Anabantidae), 3 species were capable of regenerating fins after endoskeleton amputation: the white convict and the oscar (Cichlidae), and the goldfish (Cyprinidae). Our comparative RNA-seq analysis of regenerating blastemas of axolotl and Polypterus reveals the activation of common genetic pathways and expression profiles, consistent with a shared genetic program of appendage regeneration. Comparison of RNA-seq data from early Polypterus blastema to single-cell RNA-seq data from axolotl limb bud and limb regeneration stages shows that Polypterus and axolotl share a regeneration-specific genetic program. Collectively, our findings support a deep evolutionary origin of paired appendage regeneration in Osteichthyes and provide an evolutionary framework for studies on the genetic basis of appendage regeneration.

Fins into limbs: Recent insights from sarcopterygian fish.

Limbs with digits evolved as sarcopterygian fish transitioned to a terrestrial life, giving rise to modern tetrapods. Since the Devonian, most of the sarcopterygian fish diversity became extinct, with the only surviving representatives being two coelacanth and six lungfish species. As the sister group of tetrapods, sarcopterygian fish constitute the ideal models to address questions regarding the transition of vertebrates from water to land. However, distantly related yet experimentally amenable teleost fish species have instead become the organisms of choice for geneticists and developmental biologists. Comparative studies using teleosts, such as zebrafish, have greatly enriched our knowledge on the genetic and regulatory mechanisms underlying fin development. However, their highly derived fin anatomy provides limited insights on the origin of limbs and the teleost-specific whole-genome duplication represents a further complication to comparisons of gene function and regulation. In recent years, refined morphological and behavioral studies and access to lungfish embryos and availability of genetic resources have underscored the value of nontetrapod sarcopterygians as model organisms. Here we review recent studies using lungfishes and coelacanths that shed light on various aspects of the evolution of the tetrapod limb, including the origin of the tetrapod pelvis, limb musculature, digits, locomotion, and regenerative capacity.

Comparative multidisciplinary prediction of survival in patients with advanced cancer.

PURPOSE: The expected survival of patients with metastatic cancer can significantly impact decisions regarding treatment, care setting, and future planning. We evaluated the prognostication ability of a multidisciplinary team (MDT) experienced in providing supportive care and palliative radiotherapy. METHODS: After clinical assessment of consecutive patients, survival predictions were independently made by each MDT member. Patient demographics, factors influencing predictions, and dates of death were collected. Clinical predictions of survival (CPS) were considered correct if within 30 days of actual survival (AS). Summary statistics and Kaplan-Meier estimates of overall survival were obtained. Correlations between actual and CPS were calculated using Spearman's correlation coefficient. Multivariate logistic regression analysis identified factors associated with prognostication accuracy. RESULTS: A total of 395 predictions (06/2010-07/2012) were made by eight disciplines. Average age was 68 years, 68.3 % of patients were male, and 48.4 % had lung cancer. Median AS was 87 days (95 % CI 66-102 days). Survival was over-estimated 72.4 % (286/395) of the time with r = 0.54 (p < 0.0001) for all predictions across all disciplines. In addition, 30.3 % (36/119) of radiation therapist (RTT) predictions were correct compared to 30.1 % (22/73) of nurses', 28.7 % (43/150) of physicians', and 15.1 % (8/53) of allied health (AH) providers. There were no differences in accuracy by discipline except for the RTT versus AH groups (p = 0.04). Factors most frequently cited as influencing correct predictions were Karnofsky performance status (KPS), extent of disease, and histology. KPS was the only significant variable on multivariate analysis (p ≤ 0.04). CONCLUSION: MDT members providing collaborative care for advanced cancer patients utilize similar factors in predicting survival with comparable accuracy.

Analysis of intraprostatic therapeutic effects in prostate cancer patients using [(11)C]-choline pet/ct after external-beam radiation therapy.

PURPOSE: The objective of the present study was to analyze, with relatively high sensitivity and specificity, uptake properties of [(11)C]-choline in prostate cancer patients by means of positron-emission tomography (pet)/computed tomography (ct) imaging using objectively defined pet parameters to test for statistically significant changes before, during, and after external-beam radiation therapy (ebrt) and to identify the time points at which the changes occur. METHODS: The study enrolled 11 patients with intermediate-risk prostate cancer treated with ebrt, who were followed for up to 12 months after ebrt. The [(11)C]-choline pet scans were performed before treatment (baseline); at weeks 4 and 8 of ebrt; and at 1, 2, 3, 6, and 12 months after ebrt. RESULTS: Analysis of [(11)C]-choline uptake in prostate tissue before treatment resulted in a maximum standardized uptake value (suvmax) of 4.0 ± 0.4 (n = 11) at 40 minutes after injection. During week 8 of ebrt, the suvmax declined to 2.9 ± 0.1 (n = 10, p < 0.05). At 2 and 12 months after ebrt, suvmax values were 2.3 ± 0.3 (n = 10, p < 0.01) and 2.2 ± 0.2 (n = 11, p < 0.001) respectively, indicating that, after ebrt, maximum radiotracer uptake in the prostate was significantly reduced. Similar effects were observed when analyzing the tumour:muscle ratio (tmr). The tmr declined from 7.4 ± 0.6 (n = 11) before ebrt to 6.1 ± 0.4 (n = 11, nonsignificant) during week 8 of ebrt, to 5.6 ± 0.03 (n = 11, p < 0.05) at 2 months after ebrt, and to 4.4 ± 0.4 (n = 11, p < 0.001) at 12 months after ebrt. CONCLUSIONS: Our study demonstrated that intraprostatic [(11)C]-choline uptake in the 11 analyzed prostate cancer patients significantly declined during and after ebrt. The pet parameters SUVmax and tmr also declined significantly. These effects can be detected during radiation therapy and up to 1 year after therapy. The prognostic value of these early and statistically significant changes in intraprostatic [(11)C]-choline pet avidity during and after ebrt are not yet established. Future studies are indicated to correlate changes in [(11)C]-choline uptake parameters with long-term biochemical recurrence to further evaluate [(11)C]-choline pet changes as a possible, but currently unproven, biomarker of response.

Active treatment in low-risk prostate cancer: a population-based study.

Background: Active surveillance instead of active treatment (at) is preferred for patients with low-risk prostate cancer (lr-pca), but practice varies widely. We conducted a population-based study to assess the proportion of patients who underwent at between January 2011 and December 2014, and to evaluate factors associated with at. Methods: The provincial cancer registry was linked to administrative health datasets to identify patients with lr-pca and to acquire demographic, tumour, and treatment data. The primary outcome was receipt of at during the first 12 months after diagnosis, defined as any receipt of external-beam radiotherapy, brachytherapy, radical prostatectomy, cryotherapy, or androgen deprivation. Univariate and multivariate logistic regression were used to analyze the correlation between patient and tumour factors and at. Results: Of 1565 patients with lr-pca, 554 (35.4%) underwent at within 12 months of diagnosis. Radical prostatectomy was the most common treatment (58%), followed by brachytherapy (29.6%). Younger age [odds ratio (or) 0.92; 95% confidence interval (ci): 0.91 to 0.94], lower score (≥3) on the Charlson comorbidity index (OR: 0.36; 95% ci: 0.19 to 0.68), T2 stage (or: 3.05; 95% ci: 2.03 to 4.58), higher prostate-specific antigen (psa) at diagnosis (or: 1.13; 95% ci: 1.06 to 1.21), radiation oncologist consultation (or: 3.35; 95% ci: 2.55 to 4.39), and earlier diagnosis year (2012 or: 0.46; 95% ci: 0.34 to 0.63; 2013 or: 0.45; 95% ci: 0.32 to 0.63; 2014 or: 0.33; 95% ci: 0.23 to 0.47) were associated with a higher probability of at. Conclusions: This contemporary population-based study demonstrates that approximately one third of patients with lr-pca undergo at. Patients of younger age, with less comorbidity, a higher tumour stage, higher psa, earlier year of diagnosis, and radiation oncologist consultation were more likely to undergo at. Further investigation is needed to identify strategies that could minimize overtreatment.

Palliative radiotherapy for women with breast cancer.

AIMS: Palliative radiotherapy (PRT) plays an important role in women with metastatic breast cancer. However, not all cancer patients with an indication for PRT receive it. The aim of this study was to measure the use of PRT for women who have died of breast cancer in the Canadian province of Alberta, and to identify factors that might affect this use. MATERIALS AND METHODS: All women who died of breast cancer in Alberta between 2000 and 2004 were identified from the Alberta Cancer Registry. PRT, defined as any radiotherapy given with palliative intent, was abstracted from the radiotherapy databases of the treatment facilities of the Alberta Cancer Board (ACB). The variables evaluated were: age at death, regional health authority (RHA), driving distance to nearest radiotherapy facility, receipt of initial treatment at an ACB facility, receipt of radiotherapy as part if initial treatment, residence in a city with an ACB facility, residence in a city with radiotherapy facilities or visiting radiation oncologists, median household income, and municipality population. Backwards stepwise logistic regression was used to determine the final set of predictor variables for the use of PRT. RESULTS: In total, 1906 women were identified as having died of breast cancer between 2000 and 2004, inclusive. Of these, 50.4% received at least one course of PRT. Factors associated with not receiving PRT in the final multiple logistic regression model for women who lived outside of the cities with radiotherapy facilities were: age>75 years, community size>10,000, median income<$47,000, and residence in RHA 4. For women living in cities with radiotherapy facilities, only age was significant. CONCLUSIONS: There are many factors that influence the receipt of PRT in Alberta that are unrelated to patient need. The education of physicians and patients, as well as the establishment of more radiotherapy facilities, will help to improve the use of PRT.

Chart-recorded psychiatric diagnoses in women giving birth in California in 1992.

OBJECTIVE: Although major advances have been made in the diagnosis and treatment of mental disorders in primary care, few population-based investigations have focused on the obstetrical sector. This study examines the occurrence of chart-recorded psychiatric discharge diagnoses among all women delivering in California hospitals in 1992. METHOD: The authors undertook an archival analysis of the California Health Information for Policy Project data set, which consists of linked hospital discharge and birth certificate data for 580,282 deliveries. Frequencies of ICD-9 psychiatric diagnoses were ascertained. RESULTS: Among all women delivering, 1.5% received psychiatric or substance use diagnoses. Of diagnoses recorded, 75% were substance use disorders, 21% were classified generically as "mental disorder of pregnancy," and other psychiatric disorders accounted for 4%. CONCLUSIONS: The occurrence of psychiatric diagnoses in these women is markedly lower than expected, suggesting an underreporting of psychiatric disorders at delivery. Further investigations into the detection of mental disorders in the obstetrical sector are needed.

Relationships between calcium and phosphorus homeostasis, parathyroid hormone levels, bone aluminum, and bone histomorphometry in patients on maintenance hemodialysis.

Serum biochemistry related to calcium and phosphorus homeostasis and parathyroid function was studied together with bone histomorphometry after double-labeling with tetracycline and staining for aluminum in 17 patients without symptoms of bone disease, treated with maintenance hemodialysis for at least 6 months. A close correlation was found between the serum level of parathyroid hormone (PTH) and bone resorption surfaces and bone formation rates, both at tissue and basic multicellular unit (BMU) levels. The patients could be divided into a high turnover group with a normal mineralization process and a low turnover group with markedly defective mineralization. The second group was further characterized by lower PTH and higher fractional aluminum-stained trabecular bone surfaces. For the whole patient material, the fractional aluminum-stained surfaces related inversely to tetracycline-labeled surfaces and to bone formation rates at both BMU and tissue levels, but not to the time on dialysis or to the cumulative ingested amount of aluminum hydroxide. The data provide evidence that PTH or PTH-related factors, besides activating bone remodeling, directly enhance bone formation in dialysis patients and that aluminum incorporation into bone is associated with a progressive disturbance of bone mineralization.

Blood viscosity and peripheral vascular resistance in patients with untreated essential hypertension.

OBJECTIVES: The viscosity of blood is increased in patients with essential hypertension. The aim of the present study was to investigate the importance of the different variables of blood rheology to total peripheral resistance, and to elucidate whether inappropriate regulation of the formation of erythropoietin could be important. DESIGN: Nineteen consecutive patients with untreated essential hypertension were examined and compared with a group of matched healthy volunteers. METHODS: The haemorheologic variables were assessed by rotational viscometry and the haemodynamic variables by bioimpedance cardiography. The serum concentrations of erythropoietin were determined by radioimmunoassay. RESULTS: The whole blood viscosity and peripheral resistance index were elevated in the hypertensive group. The two variables were positively correlated with each other (r = 0.68, P = 0.0015). The plasma viscosity and erythrocyte aggregation tendency were increased and the erythrocyte deformability, measured as fluidity, was decreased in the hypertensive patients. In the male subpopulation (n = 12) the aggregation tendency was positively, and the deformability negatively, correlated with body mass index. The serum concentrations of erythropoietin were equal in the two groups. CONCLUSIONS: The increased total peripheral resistance in patients with essential hypertension may in part be explained by an increased blood viscosity, but the possibility of an opposite cause-effect relationship must also be taken into consideration. The haemorheological abnormalities observed in the present patients cannot be explained by high serum levels of erythropoietin.

Cytomegalovirus disease is not a major risk factor for ischemic heart disease after renal transplantation.

BACKGROUND: It has been suggested that cytomegalovirus infection increases the risk of ischemic heart disease. Both cytomegalovirus and ischemic heart disease are common after renal transplantation, suggesting a possible causal association in this population. METHODS AND PATIENTS: We studied 1004 consecutive renal transplants with no prior history of ischemic heart disease and grafts that functioned at least 12 months. We performed univariate and multivariate analyses to examine the effect of cytomegalovirus disease and other risk factors (measured during the first posttransplant year) on the development of primary ischemic heart disease events after the first posttransplant year. RESULTS: More than 1 year after transplantation, 116 patients (11.6%) experienced their first ischemic event (75 myocardial infarction, 12 percutaneous angioplasty, 18 bypass grafting, and 11 deaths). Patients with ischemic heart disease were more likely to have known risk factors (age, diabetes, smoking, hypercholesterolemia, systolic blood pressure, low serum albumin, and acute rejections). However, the incidence of cytomegalovirus disease was not different for those with or without ischemic heart disease (36.2% vs. 31.1%). Moreover, a similar proportion of those with and without ischemic heart disease (19.8% vs. 15.5%) had a rise in cytomegalovirus antibodies during follow-up. By multivariate analysis, risk factors for ischemic heart disease (P<0.05) were age, diabetes, smoking, low serum albumin, and two or more acute rejections during the first year. Cytomegalovirus disease was not associated with ischemic heart disease events: unadjusted relative risk=1.14 (95% confidence interval 0.78-1.67, P=0.485). After adjusting for multiple risk factors, the relative risk was 0.91 (0.60-1.37, P=0.657). CONCLUSION: These data suggest that cytomegalovirus disease is not a significant risk factor for the development of primary ischemic heart disease after renal transplantation.

The use of pretransplant erythropoietin to normalize hemoglobin levels has no deleterious effects on renal transplantation outcome.

BACKGROUND: The aim of this study was to establish the outcome of renal transplantation in patients given pretransplant erythropoietin (EPO) treatment targeted at reaching a normal hemoglobin concentration (Hb), compared to those given EPO-treatment aimed at maintaining subnormal Hb. METHODS: A total of 416 patients from Scandinavian countries and with renal anaemia were enrolled to examine the effects of increasing Hb from a subnormal level (90-120 g/liter) to a normal level (135-160 g/liter) by EPO treatment. Half of the patients were randomized to have their Hb increased, with the other half randomized to maintain a subnormal Hb. Thirty-two patients from the normal Hb group and 24 patients from the subnormal group received a renal graft during the study period. The outcomes of these transplantations were examined prospectively for 6 months. RESULTS: Preoperative Hb levels were 143+/-17 and 121+/-14 g/liter in the two groups, respectively (P<0.0001). The Hb remained higher in the normal Hb group during the first 2 weeks after transplantation. The percentage of patients requiring postoperative blood transfusions in the normal Hb group was 16%, compared with 50% in the subnormal group (P<0.01). No statistically significant difference in the proportion of functioning grafts or in the serum creatinine levels could be detected. No correlation between EPO treatment and creatinine levels after transplantation was found. The frequency of adverse events was similar in the two groups. CONCLUSIONS: EPO treatment aimed at reaching a normal Hb in renal transplant recipients reduces the postoperative requirement for blood transfusions and has no deleterious effects on kidney graft function.

Intravenous diazoxide therapy in hypertensive crisis.

Ninety-one doses of diazoxide were administered intravenously to 41 patients with hypertensive crises. Diastolic blood pressure was reduced from an average of 139 to 98 mm Hg within 10 minutes. On the basis of a retrospective analysis of the response of diastolic blood pressure, it was possible to determine within 10 minutes of injection whether a second dose would be required. Therapy was judged to be effective in 38 of 41 patients; 35 percent of injections were ineffective. Concomitant administration of furosemide was not shown to have a beneficial antihypertensive effect. Mean blood urea nitrogen was 59.5 mg/100 ml initially and was not significantly different 2 weeks after therapy. None of the patients demonstrated clinical evidence of diazoxide-induced deterioration of coronary circulation. Electrocardiograms obtained 2 weeks after diazoxide therapy failed to show evidence of new ischemic changes. Only 9 percent of patients complained of side effects, and these were transient and relatively innocuous. It is concluded that diazoxide is both safe and efficacious in the management of hypertensive crises.

"True" mycotic aneurysm of a renal artery allograft.

A 60-year-old white man sustained a rupture of the renal artery 6 weeks after a cadaveric kidney transplantation. The bleeding site was repaired, and culture of the hematoma showed an isolated growth of Candida albicans. Blood and urine cultures were negative. Systemic antifungal therapy was initiated. Bleeding from the renal artery recurred, eventually requiring removal of the transplanted kidney. Histopathology of the resected specimen showed budding yeast in the wall of the renal artery, but no evidence of fungal invasion of the kidney. The patient received 6 weeks of amphotericin B therapy and currently remains on hemodialysis therapy.

Comparing methods for monitoring serum creatinine to predict late renal allograft failure.

Few studies have systematically investigated what changes in chronic renal allograft function best predict subsequent graft failure, when these changes occur, and whether they occur soon enough to allow possible intervention. We collected serum creatinine values (mean, 183 +/- 75 values/patient) measured over a maximum follow-up of 22 years in 101 consecutive renal transplant recipients (excluding creatinine levels from periods of acute rejection). We determined the dates of first decline in inverse creatinine (Delta1/Cr; < -20%, -30%, -40%, -50%, and -70%), declines in estimated creatinine clearance (CCr; <55, 45, 35, 25, and 15 mL/min), and declines in measured slope of 1/Cr over time. We used time-dependent covariates in Cox proportional hazards analyses to determine the relative effect of each renal function parameter on outcomes while adjusting for other risk factors. The best predictor of subsequent graft failure was Delta1/Cr. Delta1/Cr less than -40% first occurred at a median of 1.28 years after transplantation in 73 patients, and 67 patients went on to have graft failure a median of 3.28 years after Delta1/Cr less than -40%. The independent relative risk for graft failure attributable to Delta1/Cr less than -40% was 5.91 (95% confidence interval, 3.25 to 10.8; P < 0.0001). A decline in CCr, eg, less than 45 mL/min, also was a strong predictor of subsequent graft failure. Conversely, declines in allograft function estimated from slopes of 1/Cr were poor predictors of graft failure. In analysis limited to patients followed up for 2.5 years or less, Delta1/Cr continued to predict graft failure, suggesting that Delta1/Cr will be a useful predictor in populations with shorter follow-up. If confirmed in other populations, eg, patients treated with calcineurin inhibitors, this simple marker of chronic allograft dysfunction may prove to be a practical tool for defining patients at high risk for late graft failure.

TTX blocks baclofen-induced phase shifts of the mammalian circadian pacemaker in vitro.

The mammalian circadian pacemaker, located in the suprachiasmatic nucleus (SCN), expresses 24-h rhythms when isolated in vitro. The GABA(A) agonist, muscimol, induces phase advances during the mid-subjective day, while the GABA(B) agonist, baclofen, induces both daytime phase advances and nighttime phase delays. Here, we present evidence that tetrodotoxin (TTX) completely blocks baclofen-induced phase shifts in vitro, but does not block in vitro phase advances induced by muscimol. These results suggest that GABA(A), but not GABA(B), receptors are located on SCN pacemaker cells.

Crystal inhibition: the effects of polyanions on calcium oxalate crystal growth.

The inhibition of calcium oxalate crystal growth by the glycosaminoglycans, chondroitin sulphates and heparin, by the low-molecular-weight heparin analogue pentosan polysulphate and by Tamm-Horsfall glycoprotein extracted from human urine, was measured by using a seeded crystal procedure and compared with the inhibition by pyrophosphate. It was found that the most pronounced inhibition was obtained with the polyanions with the highest charge density, i.e., heparin and pentosan polysulphate. Tamm-Horsfall glycoprotein caused an inhibition of a similar magnitude as urinary chondroitin sulphates. Urinary polyanions with a high affinity to Sepharose 4B were more efficient inhibitors than those with a low or no affinity to the gel. It is concluded that urinary polyanions are important inhibitors of calcium oxalate crystal growth and that the potency of inhibition increases with the charge density.

Binding of glycosaminoglycan inhibitors to calcium oxalate crystals in relation to ionic strength.

Several inhibitors of calcium oxalate crystallization have been identified and shown to exhibit quantitative and qualitative differences in efficacy. Glycosaminoglycans are potent inhibitors of crystal growth and aggregation, and the efficiency seems to increase with an increasing charge density. In order to investigate the mechanism of inhibition, we performed binding experiments of radioactivity labelled heparin, chondroitin sulphate and the low-molecular mass heparin analogue pentosan polysulphate to calcium oxalate crystals and subsequent displacements by increasing the amounts of non-radioactive ligands or increasing ionic strength. Ligands with a high charge density bound more readily and with a seemingly higher affinity than ligands with a low charge density, but were also more susceptible to displacement when the ionic strength was increased. It is concluded that a higher affinity to the crystals may be the reason why highly charged glycosaminoglycans are more efficient inhibitors of calcium oxalate crystal growth.

Neurotoxicity associated with ceftazidime therapy in geriatric patients with renal dysfunction.

Ceftazidime, a beta-lactamase-stable, third-generation cephalosporin, is widely used for the treatment of serious gram-negative infections. Neurotoxicity has rarely been associated with the drug; however, two of our patients developed ceftazidime-induced neurotoxicity that produced confusion, disorientation, agitation, generalized weakness, and myoclonus. In both patients these symptoms cleared with either discontinuation or reduction of the dosage of ceftazidime. This emphasizes the importance of adjusting the dosage of ceftazidime in patients with renal insufficiency.

Decreased blood viscosity and serum levels of erythropoietin after anti-hypertensive treatment with amlodipine or metoprolol: results of a cross-over study.

The increased viscosity of blood of hypertensive patients can be assumed to be a risk factor for the development of cardiovascular diseases. The aim of the present study was to elucidate whether anti-hypertensive treatment has any impact on blood rheology. Twenty patients with previously untreated hypertension who consecutively attended our outpatient hypertension clinic were included in this prospective, open, cross-over study. The patients were randomly selected to treatment with amlodipine or metoprolol. The anti-hypertensive therapy was switched after 4 months. Haemorheological and haemodynamic variables were measured with rotational viscometry and impedance cardiography, respectively. Fifteen and 16 patients could be evaluated after amlodipine or metoprolol treatment respectively. The mean blood pressure (BP) decreased from 159 +/- 22/105 +/- 7 to 139 +/- 21/91 +/- 6 mm Hg on amlodipine and from 162 +/- 22/104 +/- 5 to 145 +/- 24/90 +/- 8 mm Hg on metoprolol therapy. After amlodipine treatment, the total peripheral resistance index decreased whereas metoprolol treatment was accompanied by a decrease in the cardiac index. Decreases in whole blood viscosity, haematocrit and serum erythropoietin were found after amlodipine as well as metoprolol treatment. After amlodipine the plasma viscosity decreased and the erythrocyte deformability increased in the majority of patients. Plasma fibrinogen decreased after metoprolol treatment. Despite the differences in haemodynamic mechanisms underlying the decrease in BP, amlodipine and metoprolol exert beneficial effects on blood viscosity. Haemodilution and a decrease in serum erythropoietin may be factors underlying this decrease in blood viscosity.

Isolation of haemorphin-related peptides from filter membranes collected in connection with haemofiltration of human subjects.

This paper describes the extraction and isolation from dialysis filters of two peptides containing the opioid active sequence haemorphin-7. The filter devices were obtained from uraemic patients subjected to haemofiltration. Following acidic extraction of the filter membranes the peptides were purified by size-exclusion, ion-exchange chromatography and finally by reversed-phase chromatography using different columns and different chromatographic systems. The purification was guided by radioimmunoassay and the structure of the final products was elucidated by N-terminal sequencing and fast-atom bombardment mass spectrometry as well as micro-electrospray mass spectrometry. The isolated peptides were suggested to be identical to fragments 1-41 and 32-41 of the beta-chain of human haemoglobin.