Clinical results after en block double lung transplantation with direct bronchial revascularization. The first three and a half years' experience in Denmark

En-bloc double lung transplantation with tracheal anastomosis and direct revascularization of the bronchial arteries to the left internal mammary artery has been carried out in Denmark since June 1992. Forty-seven patients (32 with alfa-1 antitrypsin deficiency, 11 with chronic obstructive pulmonary disease, two with cystic fibrosis and two with primary pulmonary hypertension), 25 men and 22 women, average age 39 years (17-64 years), have received their first double-lung transplant with bronchial artery revascularization. Arteriography of the internal mammary artery and bronchial arteries was performed in 42 (89%) of the patients from 1-150 days after the operation. Successful bronchial artery revascularization was demonstrated arteriographically in 40 patients, in two patients the arteriography failed to show bronchial artery revascularization. Arteriography was not performed in five patients due to early complications and death. Bronchoscopy showed rapid, uncomplicated airway healing in 42 patients. Mucosal necrosis under the tracheal anastomosis was found in three patients, and severe obstructive endobronchial growth of the fungus Aspergillus fumigatus was diagnosed in the last two patients. The one- and two-year survival is 83% (Kaplan-Meier). Eleven patients are dead, five due to pulmonary causes and six due to extra-pulmonary causes. Pulmonary function became normal in nearly all surviving patients between three to six months after the transplantation. In conclusion, en-bloc double-lung transplantation with bronchial artery vascularization has shown good short-term results, and the one- and two-year survival gives hope that a successful bronchial artery revascularization will improve the long-term survival following lung transplantation.     

Topical reversion at the HIS1 locus of Saccharomyces cerevisiae. A tale of three mutants

Mutants of the HIS1 locus of the yeast Saccharomyces cerevisiae are suitable reporters for spontaneous reversion events because most reversions are topical, that is, within the locus itself. Thirteen mutations of his1-1 now have been identified with respect to base sequence. Revertants of three mutants and their spontaneous reversion rates are presented: (1) a chain termination mutation (his1-208, née his1-1) that does not revert by mutations of tRNA loci and reverts only by intracodonic suppression; (2) a missense mutation (his1-798, née his1-7) that can revert by intragenic suppression by base substitutions of any sort, including a back mutation as well as one three-base deletion; and (3) a -1 frameshift mutation (his1-434, née his1-19) that only reverts topically by +1 back mutation, +1 intragenic suppression, or a -2 deletion. Often the +1 insertion is accompanied by base substitution events at one or both ends of a run of A's. Missense suppressors of his1-798 are either feeders or nonfeeders, and at four different locations within the locus, a single base substitution encoding an amino acid alteration will suffice to turn the nonfeeder phenotype into a feeder phenotype. Late-appearing revertants of his1-798 were found to be slowly growing leaky mutants rather than a manifestation of adaptive mutagenesis. Spontaneous revertants of his1-208 and his1-434 produced no late-arising colonies.     

Ancient gene duplication and differential gene flow in plastid lineages: the GroEL/Cpn60 example

BACKGROUND: The course of Crohn's disease is characterised by the occurrence of intestinal complications such as strictures, intra-abdominal fistulas, or abscesses. Standard diagnostic procedures may fail to show these complications, in particular fistulas. AIMS: To test the value of transabdominal bowel sonography (T) for the detection of intestinal complications in Crohn's disease. METHODS: T was prospectively performed in 213 patients with Crohn's disease in a university based inflammatory bowel disease referral centre. Thirty three underwent resective bowel surgery and were included in this study. The accuracy of T to detect strictures, intra-abdominal fistulas, or abscesses was compared with surgical and pathological findings. RESULTS: T was able to identify strictures in 22/22 patients and to exclude it in 10/11 patients (100% sensitivity, 91% specificity). Fistulas were correctly identified in 20/23 patients and excluded in 9/10 patients (87% sensitivity, 90% specificity). Intra-abdominal abscesses were correctly detected in 9/9 patients and excluded in 22/24 patients (100% sensitivity, 92% specificity). CONCLUSIONS: In experienced hands T is an accurate method for the detection of intestinal complications in Crohn's disease. T is thus recommended as a primary investigative method for evaluation of severe Crohn's disease.     

Acute renal failure complicating nonfulminant hepatitis A

PURPOSE: To compare the orbital blood flow velocities of patients with long-standing ocular hypertension and patients with primary open-angle glaucoma. METHODS: Twenty patients with ocular hypertension were recruited from our clinic and underwent color Doppler imaging evaluation of their retrobulbar vessels. The blood flow velocities and resistance index of their central retinal artery, temporal short posterior ciliary artery, and ophthalmic artery were compared with those of 20 glaucoma patients individually matched for age and level of the highest untreated intraocular pressure ever recorded. RESULTS: Glaucoma patients had significantly lower peak systolic velocity and end-diastolic velocity than did patients with ocular hypertension in their central retinal artery (p < 0.001). No significant difference between the groups was observed in the other vessels studied. CONCLUSIONS: Glaucoma patients had lower blood flow velocity in the central retinal artery compared with that of ocular hypertension patients of similar age and level of untreated intraocular pressure. This might be important in the development of glaucomatous damage in those patients.     

Dual regulation of the Na+/H(+)-exchange in rat peritoneal mast cells: role of protein kinase C and calcium on pHi regulation and histamine release

1. The purpose of this study was to compare the actions of phorbol 12-myristate 13-acetate (PMA) and ionomycin on Na+/H+ exchange activation and histamine release to that of compound 48/80 in order to study the possible relationship between pHi and secretion of histamine in rat peritoneal mast cells. 2. Resting pHi in mast cells suspended in a bicarbonate-free physiological salt solution amounted to 6.73 +/- 0.05 (mean +/- s.d., n = 52). 3. PMA (20 nM) induced a substantial but rather slow increase in pHi. This response was very sensitive to inhibition by staurosporine, very sensitive to inhibition by 5-(N,N-hexamethylene)amiloride (HMA), insensitive to the absence of extracellular calcium (without EGTA), and sensitive to partial depletion of intracellular calcium with EGTA. 4. Ionomycin (1 microM) induced a biphasic change in pHi that was sensitive to inhibition by HMA, insensitive to staurosporine. In the absence of extracellular calcium using EGTA, the biphasic response disappeared, leaving only a slow, and diminished change in pHi. 5. The effects of ionomycin and PMA on pHi were additive. 6. Addition of the secretagogue compound 48/80 (1 microgram ml-1) increased pHi, substantially, delta pHi amounting to 0.29 +/- 0.05 pH-units (n = 4). The biphasic pHi-response was insensitive to the absence of extracellular calcium (without EGTA). The initial fast response in pHi was, however, inhibited by HMA, not staurosporine. 7. The finding that staurosporine and HMA each inhibited approximately half of the compound 48/80-induced pHi-response, whereas both inhibitors completely abolished the compound 48/80-induced pHi-response seems to indicate that two independent pathways for the activation of the Na+/H+ exchange were stimulated by compound 48/80. 8. The histamine release induced via both PKC activation (using PMA) and calcium (using ionomycin) were much larger than the sum of each activation pathway, whereas in the absence of extracellular calcium using EGTA, the histamine release in response to PMA and ionomycin was completely abolished. 9. The compound 48/80-induced histamine release was partially sensitive to inhibition by HMA (approximately 30% inhibition) and partially sensitive to inhibition by staurosporine (approximately 50% inhibition). Preincubation with staurosporine and HMA before stimulation with compound 48/80 showed the same degree of inhibition as observed after staurosporine alone, even though this combination of drugs completely inhibited the pHi-response. Furthermore, compound 48/80-induced histamine release was not dependent on the presence of extracellular calcium (with and without EGTA). 10. In spite of the similarities in second messenger pathways for pHi regulation and histamine release, it is, however, not very likely that these two processes are directly related. It is, however, possible, that an increase in pHi plays a permissive, rather than an essential role for histamine release in rat peritoneal mast cells. This hypothesis was supported by the finding that preincubation with the Na+/H+ exchange-inhibitor HMA inhibited 30% of the compound 48/80-induced histamine secretion.     

Paternal origin of trisomy 21 following intracytoplasmic sperm injection (ICSI)

One important aspect in the debate on the genetic risks associated with intracytoplasmic sperm injection (ICSI) is the possible increased rate of chromosomal abnormalities in resulting pregnancies. ICSI was performed in a 27 year old man with asthenoteratozoospermia and his 25 year old wife. There was a spontaneous miscarriage at 9 weeks of gestation. Cytogenetic investigation revealed trisomy 21. Analysis of two polymorphic microsatellite markers showed that the additional chromosome was paternal. This is in contrast to the fact that the vast majority of trisomic concepti are maternal in origin. Identifying the parent of origin in trisomic conceptions achieved by ICSI may reveal whether ICSI is associated with an increased risk of paternally derived aneuploidy.     

Consumption of fatty fish from the Baltic Sea and PCB in whole venous blood, plasma and cord blood from delivering women in the Aland/Turku archipelago

The present study aimed to assess the role of fish consumption for the body burden of polychlorinated biphenyls (PCBs) in mothers living in the Aland and Turku archipelago in Finland. The overall objective was to investigate whether there exists an appropriate population for a full-scale prospective study on PCB-related developmental effects in infants. Concentrations of the four major PCBs were determined in whole venous blood and cord blood from 30 delivering mothers, of which 20 subjects consumed fatty fish from the Baltic Sea (2.5-12.5 meals per month) and the remaining 10 mothers did not. The concentrations of CB-118, CB-138, CB-153, and CB-180 in cord blood were generally two- to threefold lower than in whole blood from the mothers, but strong correlations were observed between PCBs in the two matrices (r = .67-.80). Neither the venous blood nor cord blood concentrations of PCBs, however, were correlated with stated fish intake. Moreover, the concentration of CB-153 in plasma was only weakly associated with fish intake, and the level of organic mercury in erythrocytes was not correlated with fish intake at all. The present results of CB-153 concentrations in women's blood are lower than those reported in other recent investigations. A reasonable contributing explanation is the rapid decline during the last decades of PCB in Baltic Sea fish, which has resulted in less impact of fish intake on the body burdens of PCB in relatively young women (median 30 yr in the present study) as compared with older females. The relatively low PCB levels in blood taken together with the low number of yearly deliveries in the archipelago population makes it an inappropriate study base for a prospective study of PCB-related health effects in infants.     

New bioelectrical impedance formula for patients with respiratory insufficiency: comparison to dual-energy X-ray absorptiometry

Malnutrition in patients with severe respiratory insufficiency can lead to severe complications, justifying the use of objective nutritional assessment techniques, such as bioelectrical impedance analysis (BIA), which is an easy, noninvasive method of measuring body composition. The purpose of this study was to develop, and validate against dual-energy X-ray absorptiometry (DXA), a BIA formula to predict fat-free mass (FFM) specific for patients with chronic severe respiratory insufficiency. Seventy-five ambulatory patients (15 females and 60 males) with severe chronic respiratory insufficiency (obstructive and restrictive) aged 63.6+/-19.2 yrs (mean+/-SD), in a stable pulmonary and cardiac condition for > or = 2 months, were measured simultaneously with BIA and DXA. Patients younger than 45 yrs of age and with a body mass index > or = 32 kg x m(-2) were excluded. The best-fitting multiple regression equation to predict FFM = -6.06 +/- (height x 0.283) +/- (weight x 0.207) - (resistance x 0.024) +/- (sex (males=1, females=0) x 4.036), gave a correlation coefficient of r=0.952, slope+/-SEM 0.902+/-0.034, standard error of the estimate 1.670, and p<0.0001. The mean difference for FFM was 0.2+/-2.3 kg (mean+/-SD) and percentage fat mass was -0.7+/-3.8%. These results suggest that the bioelectrical impedance analysis formula specific to patients with severe respiratory insufficiency give a better correlation and smaller mean differences than 12 different bioelectrical impedance analysis formulae described in the medical literature. A prediction equation, validated against dual-energy X-ray absorptiometry and based on subjects with similar clinical characteristics, is more applicable to the patients with respiratory insufficiency than a formula developed for healthy subjects.     

Measles virus-induced autoimmune reactions against brain antigen

Recovery from viral infection is a result of very complex interactions between specific and nonspecific immune reactions and the infectious agent. A variety of immune mechanisms are undoubtedly important factors in this event and operate together in overcoming the infectious process. However, despite much available information about these viral defense mechanisms, it has proved remarkably difficult to assign a determinative role in vivo to any single antiviral immunological mechanism in recovery from a single viral disease, particularly since the immune response to the virus itself may frequently contribute to the pathology of the disease. Furthermore, if virus-induced immune responses are also directed against normal host components, this may set the stage for an autoimmune disease. In this context acute measles encephalomyelitis is of interest since in this disease autoimmune reactions against brain antigens have been observed and considered of pathogenetic importance. In this short review, virological and immunological findings of measles virus infections in a rat model in relation to autoimmune reactions will be presented and the mechanisms by which measles virus may alter host reactivity against self-antigens discussed.