1,25-dihydroxycholecalciferol reduces acute rejection in rat lung allotransplantation.
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Journal Article↗
Biomedical subjects
C Redaelli
Publications and source records attributed to C Redaelli.
Properties and reactivity of myoglobin reconstituted with chemically modified protohemin complexes.
The synthetic complexes protohemin-6(7)-L-arginyl-L-alanine (HM-RA) and protohemin-6(7)-L-histidine methyl ester (HM-H) were prepared by condensation of suitably protected Arg-Ala or His residues with protohemin IX. HM-RA and HM-H were used for reconstitution of apomyoglobin from horse heart, yielding the Mb-RA and Mb-H derivatives, respectively, of the protein. The spectral, binding and catalytic properties of Mb-RA and Mb-H are significantly different from those of Mb. As shown by MM and MD calculations, these differences are determined by some local structural changes around the heme which are generated by increased mobility of a key peptide segment (Phe43-Lys47), containing the residue (Lys45) that in native Mb interacts with one of the porphyrin carboxylate groups. In the reconstituted Mbs this carboxylate group is bound to the Arg-Ala or His residue and is no longer available for electrostatic interaction with Lys45. The mobility of the peptide segment near the active site allows the distal histidine to come to a closer contact with the heme, and in fact Mb-RA and Mb-H exist as an equilibrium between a high-spin form and a major low-spin, six-coordinated form containing a bis-imidazole ligated heme. The two forms are clearly distinguishable in the NMR spectra, that also show that each of them consists of a mixture of the two most stable isomers resulting from cofactor reconstitution, as also anticipated by MM and MD calculations. Exogenous ligands such as cyanide, azide, or hydrogen peroxide can displace the bound distal histidine, but their affinity is reduced. On the other hand, mobilization of the peptide chain around the heme in the reconstituted Mbs increases the accessibility of large donor molecules at the heme periphery, with respect to native Mb, where a rigid backbone limits access to the distal pocket. The increased active site accessibility of Mb-RA and Mb-H facilitates the binding and electron transfer of phenolic substrates in peroxidase-type oxidations catalyzed by the reconstituted proteins in the presence of hydrogen peroxide.
Alanine↗
High- or low-potassium solutions for the storage of abdominal and thoracic organs.
BACKGROUND: Clinically, intracellular type solutions are the most widely used solutions to preserve organs. The optimal ion composition of preservation solutions, however, is still unknown and extracellular-type solutions have frequently been superior to intracellular solutions in various experimental studies. MATERIALS AND METHODS: In this study, we measured extracellular (interstitial) electrolyte concentrations in rat livers, kidneys, hearts and lungs at 4 degrees C by means of microdialysis sampling. RESULTS: After 24 h cold ischaemia, [Na+]int and [K+]int were 104 +/- 25 mmol/l and 6.5 +/- 0.7 mmol/l in hearts, 92 +/- 12 mmol/l and 6.9 +/- 1.0 mmol/l in livers, 115 +/- 22 mmol/l and 6.3 +/- 0.9 mmol/l in kidneys and 87 +/- 17 mmol/l and 6.4 +/- 0.6 mmol/l in lungs. After preservation of organs in intracellular-type solutions, [Na+]int was significantly lower for each organ (range from 69 +/- 8 mmol/l to 73 +/- 20 mmol/l) and [K+]int was significantly higher (range from 8.0 +/- 1.7 mmol/l to 9.8 +/- 1.0 mmol/l). In no instance did the interstitial electrolyte concentration equilibrate with the intracellular electrolyte concentration. When the diffusion gradient from the vascular space to the interstitial space was calculated for Na+ and K+, a significantly higher barrier was found for K+ than for Na+ (P<0.001 and P<0.01 for hearts). CONCLUSIONS: These studies indicate that during cold storage of rat hearts, lungs, livers and kidneys, intra- and extracellular electrolytes do not equilibrate. Ion exchange stabilises at extracellular Na+ concentrations between 87 mmol/l and 115 mmol/l and K+ concentrations between 6.3 mmol/l and 6.9 mmol/l. Storage of organs in solutions with extracellular-type ion compositions might improve graft function and survival not only after lung and liver but also after heart and renal preservation.
Analysis of Variance↗
Covalently modified microperoxidases as heme-peptide models for peroxidases.
Microperoxidase-8 (MP8) and microperoxidase-9 (MP9) have been covalently modified by attachment of proline-containing residues to the amino terminal peptide chain in order to obtain new peroxidase model systems. The catalytic activities of these derivatives in the oxidation of p-cresol by hydrogen peroxide have been compared to that of MP8. The presence of steric hindrance above the heme reduces the formation rate of the catalytically active species, while the reactivity is increased when the amino group of a proline residue is close to the iron. The modification of the catalyst affects the rate of degradation processes undergone by the heme group during catalysis. A bulky aromatic group on the distal side decreases the stability of the complex because it reduces the mobility of a phenoxy radical species formed during catalysis, while the presence of proline residues increases the number of turnovers of the heme catalysts before degradation. The complex Pro2-MP8 obtained by addition of two proline residues to MP8 exhibits the best catalytic performance in terms of activity and chemical stability.
Amino Acid Sequence↗
[Liver resection for liver metastases--1998 Bern Symposium].
The increasing knowledge of the anatomy and function of the liver made the surgical resection of liver metastases currently to the therapy of choice. Although liver metastasis is an advanced stage in tumor-progression, surgery achieves the best long-term results due to a better understanding of the carcinogenesis (i.e. micrometastases) and the prognostic risk factors. This study summarizes the results of 109 resections of colorectal and non-colorectal liver metastases during a period of 59 months at our department. Four different surgical techniques (extended hepatectomy vs. segmental resection vs. atypical resection vs. biopsy) were investigated. For resections a tumour-free resection margin of at least 10 mm was always attempted to achieve. The accumulated morbidity of all techniques together was 23%. Although the morbidity was higher for extended resections (Encephalopathy 16% vs. 2.3% for segmental resections, Liver insufficiency 23% vs. 4.7%), compared to the limited resection procedures, the long-term survival improved. The overall mortality was 2.7%. Survival was higher in patients with resection of colorectal than non colorectal metastases. Our results indicate that liver resection, under observance of the anatomical and functional margins (i.e. an adequate resection margin), is the only potentially curative therapy for liver metastases. An extensive formal resection, although inducing a higher perioperative morbidity, is superior to the limited resection techniques and results in an increased long-term survival. One reason is the increased probability of co-resection of preoperatively undetected local micrometastases.
Adolescent↗
Liver nodules resembling focal nodular hyperplasia after hepatic venous thrombosis.
We report the case of focal nodular hyperplasia-like nodular hepatic lesions, that developed in the liver of a 35-year-old Caucasian female who required orthotopic liver transplantation for Budd-Chiari syndrome. The rapid development of focal nodular hyperplasia-like lesions in a severe hepatic vascular disorder and in the absence of cirrhosis may represent an additional argument in favor of the vascular origin of focal nodular hyperplasia. The pathogenesis of the nodules is not clear, but pathological arterialization of the liver in hepatic vein thrombosis may be a candidate mechanism.
Adult↗
[Surgical treatment of giant hemangiomas of the liver].
Giant liver hemangiomas are defined as hemangiomas with a diameter of more than 4 cm. They often require surgery due to bleeding tendencies or local compression. Between 1994 and 1998 we operated 11 patients with giant hemangiomas (median diameter 5.8 cm, range 4-12.5 cm). Average age was 50 years (range 23-85 years). 6 patients complained of pain, 1 patient sustained a bleeding. 7 hemangiomas were enucleated, 2 segmentally resected, 1 patient underwent a hemihepatectomy. 1 patient suffered from a bile leakage. Mortality was 0%. We conclude that clinically symptomatic liver hemangiomas can be safely resected. In a right sided localisation a enucleation has the best parenchyma sparing effect, in left sided locations a segmentectomy or bisegmentectomy can be performed with little blood loss.
Adult↗
Anterior uveitis associated with Mycoplasma pneumoniae pneumonia: a case report.
The authors report a case of bilateral uveitis following Mycoplasma pneumoniae pneumonia verified by IgM and rising IgG antibodies against the organism. Uveitis is a rare manifestation of Mycoplasma pneumoniae pneumonia and since it is a common pathogen, it should be considered in the differential diagnosis, even in the absence of respiratory symptoms or neurological findings. Immunobiological hypotheses are briefly discussed.
Adult↗
Evaluation of laser doppler flowmetry for the study of benign and malignant gastric blood flow in vivo.
BACKGROUND: Tumour vascularisation is a determinant of the development of metastases. AIMS: To measure blood flow in normal stomach and gastric adenocarcinomas by laser Doppler flowmetry and correlate blood flow with vascularisation after immunohistochemical staining of resected specimens for CD31 and von Willebrand factor. PATIENTS: Twenty two undergoing resection for gastric adenocarcinoma and 10 undergoing cholecystectomy. RESULTS: Mean (SD) gastric blood flow was 208 (35) perfusion units (PU) in patients undergoing cholecystectomy and 190 (75) PU in the undiseased part of the stomach in patients with gastric adenocarcinoma. Gastric blood flow was higher in the border of gastric adenocarcinomas (322 (120) PU, p<0.01 v normal stomach) but lower in the centre (74 (27) PU, p<0.01 v normal stomach and tumour border). Blood flow was higher in tumours staged T>/=3 than in those staged T<3. Blood vessel density in normal stomach was 41 (8) stained cells/field viewed and was 1. 9-3.4 times higher in gastric adenocarcinomas. CONCLUSION: Laser Doppler flowmetry is a valuable tool for studying the pathophysiological alterations of malignant blood flow in the human stomach in vivo.
Adenocarcinoma↗
Natural interferon therapy: optic nerve ischemic damage?
The purpose of this study was the evaluation of retinal abnormalities during a treatment with natural interferon (IFN-alpha for chronic hepatitis C. Retinal hemorrhages and optic disk edema were found in a 40-year-old woman during IFN-alpha therapy. The disk edema and retinopathy resolved after the INF was discontinued. Although retinal abnormalities correlated with IFN therapy have been described recently by some authors, the pathogenesis is still unclear. Anterior ischemic optic neuropathy occurring in a patient treated with IFN is a probable complication of the therapy.
Adult↗
Microcirculation in chronic alcoholic pancreatitis: a laser Doppler flow study.
Experimental chronic pancreatitis is associated with microcirculatory disturbances but can also be induced or aggravated by perfusion changes. Microcirculatory alterations in human chronic pancreatitis are poorly defined. In this clinical study we investigated pancreatic microcirculation in the normal human pancreas and in chronic pancreatitis by laser Doppler flowmetry. Laparotomy was performed on 13 patients with nonpancreatic disease and on nine patients with chronic alcoholic pancreatitis for pancreatic head resection. Blood flow was measured over the pancreatic head, the uncinate process, over the mesenteric vein, the pancreatic corpus, and over the pancreatic tail by laser Doppler flowmetry. Blood flow was highest in the head of a normal pancreas with a mean of 436 +/- 34 perfusion units (PU), 399 +/- 43 PU in the uncinate process, 286 +/- 30 PU in the pancreatic corpus, and 351 +/- 46 PU in the tail of the pancreas. In the normal pancreas, lowest blood flow was measured over the mesenteric vein (228 +/- 23 PU). In chronic pancreatitis, blood flow in the pancreas was significantly decreased across the whole pancreas (p < 0.01). Furthermore flow-wave pattern was altered in chronic pancreatitis as compared with the normal pancreas. The normal human pancreas has a spatial variation in blood flow, correlating with the pancreatic arterial blood supply. In the chronically inflamed human pancreas, blood flow is significantly diminished, with a lower flow toward the pancreatic head.
Blood Flow Velocity↗
Prolongation of allograft survival by 1,25-dihydroxyvitamin D3.
BACKGROUND: 1,25-Dihydroxyvitamin D3, the hormonal form of vitamin D, is now believed to play a significant role in the immune responses, both in vitro and in vivo, preventing the development of several autoimmune diseases. These studies suggest that 1,25-dihydroxyvitamin D3 may be effective in prolonging allograph survival. METHODS: To test the hypothesis that 1,25-dihydroxyvitamin D3 would prolong allograft survival, neonatal heart grafts were transplanted to allogeneic recipients receiving either 19-nor-1,25-dihydroxyvitamin D2 (200 ng/day) or 1,25-dihydroxyvitamin D3 (50 ng/mouse/day) orally through the diet. The efficacy of 1,25-dihydroxyvitamin D3 in prolonging graft survival in a vascularized model was determined by heterotopic ACI to Lewis heart transplants. RESULTS: The provision of exogenous 1,25-dihydroxyvitamin D3 or an analog, 19-nor-1,25-dihydroxyvitamin D2, to mice markedly prolonged the survival of neonatal mouse heart allografts. Similar results were obtained with a vascularized heterotopic heart transplant model in rats. Cyclosporine at a maximum 25 mg/kg dose for mice proved less effective than 1,25-dihydroxyvitamin D3. Graft survival in mice differing at class I and class II loci (B10.A(4R) --> C57BL/10) increased from 13.0+/-1.1 days to 51.0+/-5.6 days and was significantly better than cyclosporine monotherapy (33.2+/-3.6). Rat heart survival in a high responder strain combination (ACI --> Lewis) increased from 6.2+/-0.3 to 25.2+/-2.8 days. The increased survival of the transplants brought about with 1,25-dihydroxyvitamin D3 was not accompanied by hypercalcemia in rats. CONCLUSION: These results suggest that 1,25-dihydroxyvitamin D3 can be used as an effective agent in preventing graft rejection.
Animals↗
1,25-Dihydroxyvitamin D3 prolongs graft survival without compromising host resistance to infection or bone mineral density.
BACKGROUND: Recently, we have shown that 1,25-dihydroxyvitamin D3 prolongs graft survival in mice and rats when the donor and recipient differ at two or more major histocompatability loci. Among the most serious side effects encountered with the currently available transplantation antirejection drugs are an increased susceptibility to infection and decreased bone mineralization. Our results suggest that 1,25-dihydroxyvitamin D3 prolongs graft survival without these side effects of bone loss and susceptibility to infection. METHODS: We compared the ability of 1,25-dihydroxyvitamin D3-treated, nontreated, or cyclosporine (CsA)-treated mice to resist infection with Candida albicans and herpes simplex virus-1. To determine bone density, femurs were collected from nontreated, 1,25-dihydroxyvitamin D3-treated (50 ng/mouse/day), or CsA-treated (25 mg/kg/day) mice, and bone ash was determined. RESULTS: Here we show that 1,25-dihydroxyvitamin D3 treatment does not increase the susceptibility of the host to fungal or viral infection. Furthermore, CsA causes bone loss, whereas 1,25-dihydroxyvitamin D3 actually increases bone mass. CONCLUSIONS: The use of 1,25-dihydroxyvitamin D3 and its analogs to increase transplant survival will avoid bone loss and opportunistic infection, two important disadvantages of the most widely used transplant antirejection drugs--CsA and the glucocorticoids.
Animals↗
Role of thromboxane and leukotriene B4 in patients with acute respiratory distress syndrome after oesophagectomy.
We have studied prospectively the clinical course and serum concentrations of thromboxane B2 (TxB2) and leukotriene B4 (LTB4) in patients developing adult respiratory distress syndrome (ARDS) after oesophagectomy. The clinical course was assessed according to a validated ARDS score, and intra- and postoperative measurements of TxB2 and LTB4 in pre- and post-pulmonary blood were performed in 18 patients undergoing oesophagectomy for oesophageal carcinoma and 11 control patients undergoing thoracotomy and pulmonary resection. Six of 18 patients undergoing oesophagectomy, but no control patient, developed ARDS. The ARDS score was highest on day 8 after operation. Only patients with ARDS had a significant postoperative increase in post-pulmonary, but not pre-pulmonary, TxB2 concentrations (P < 0.05 vs patients without ARDS). This study provides evidence that TxA2, originating from the lungs, was associated with the development of ARDS after oesophageal resection. In view of the high incidence of ARDS after oesophagectomy (10-30%), prophylactic treatment of patients undergoing oesophageal resection with clinically applicable thromboxane synthetase inhibitors may be warranted.
Adult↗
Unilateral retinal vasculitis associated with hairy cell leukaemia: immunogenetic study.
This report describes a case of retinal vasculitis which occurred in hairy cell leukaemia and was localized only in the right eye. An immunogenetic study investigates the possible genetic association between vascular uveitis and hairy cell leukaemia.
Adult↗
Iris cyst in aphakic patient: improvement of visual acuity after excision.
Postsurgical or spontaneous iris cyst is a rare finding. Unfortunately, all treatments are complicated and the results may be disappointing. We report a case of postsurgical iris cyst treated by sector iridectomy with satisfactory recovery of visual acuity.
Aged↗
First clinical experience with fundus rotation gastroplasty as a substitute for the oesophagus.
BACKGROUND: Leakage of oesophagogastric anastomosis has been associated with poor perfusion of the gastric tube. The authors recently developed a new form of gastroplasty, preserving not only the arterial arcade along the greater curvature, but also the lesser curvature. In this study their first clinical experience with that gastric tube is reported. METHODS: Thirty-five patients undergoing either oesophagectomy or laryngopharyngo-oesophagectomy for malignant lesions and substitution of the oesophagus with a funds rotation gastroplasty were included. Patient outcome, including anastomotic leak, hospital mortality and morbidity rates, were studied prospectively. RESULTS: Hospital mortality rate was one of 35 and anastomotic leak (one minor, one moderate) was found in two patients with no subsequent mortality. Further major morbidity included pulmonary dysfunction in the form of acute respiratory distress syndrome (ARDS) in seven patients. Mean (s.e.m.) hospital stay was 27(19) days, and 21(9) days in patients who did not develop ARDS. CONCLUSION: Fundus rotation is a new method of gastroplasty that allows safe anastomosis of the tube with the remaining oesophagus or pharynx and is associated with a low leak rate even at high cervical levels.
Adenocarcinoma↗
Splanchnic microcirculatory changes during CO2 laparoscopy.
BACKGROUND: Splanchnic macrocirculatory changes during high-pressure CO2 pneumoperitoneum include a decrease in mesenteric arterial blood flow, and decreased gastric perfusion with a drop in gastric pH in experimental studies. Microcirculatory changes in abdominal organs under clinical conditions with a low pressure CO2 pneumoperitoneum are unknown. STUDY DESIGN: In 18 patients undergoing routine laparoscopy with a CO2 pneumoperitoneum (7 symptomatic cholecystolithiasis, 3 acute cholecystitis, and 8 acute appendicitis) gastric, duodenal, jejunal, colonic, hepatic, and peritoneal blood flow was measured with a custom-made laser Doppler flow probe at an intra-abdominal pressure of 0, 10, and 15 mm Hg. RESULTS: Intra-abdominal pressure elevation from 10 mm Hg to 15 mm Hg significantly decreased the blood flow in the stomach by 40 percent to 54 percent, the jejunum by 32 percent, the colon by 44 percent, the liver by 39 percent, the parietal peritoneum by 60 percent, and the duodenum by 11 percent. Splanchnic blood flow decreased with operative time at a constant intra-arterial pressure (r = 0.88, p < 0.0001). CONCLUSIONS: From our study, we concluded that laparoscopic procedures with a CO2 pneumoperitoneum should be performed at a pressure of 10 mm Hg or lower to avoid splanchnic microcirculatory disturbances.
Adolescent↗