Clinical and immunological results of corneal allograft rejection

Of 111 episodes of graft rejection in 66 patients, 62 responded to therapy with graft clearing (responders); 49 did not (non-responders). Both groups were of similar age, sex, and etiology; both had a similar rate of glaucoma and a similar rate of previous grafting. In responders the graft reaction was shorter in duration (2.2 vs. 5.6 wks. p less than 0.005), and it was necessary to increase the number of glaucoma medications more often in non-responders compared to responders (41% vs. 19%, p less than 0.02). The interval from surgery to reaction was similar in responders and non-responders (18.2 vs. 13.3 mos., p greater than 0.1). An epithelial rejection line was present in 11% of responders, but was not present in non-responders (p less than 0.05). Lymphocytotoxic antibody development correlated with rejection in 16 of 64 episodes. Patients who responded to treatment were more frequently asymptomatic (p less than 0.05) or were treated earlier following the onset of symptoms compared to non-responders (p less than 0.0001).     

Combination therapy with felodipine and metoprolol compared with captopril and hydrochlorothiazide. German MC Study Group.

This study compared the antihypertensive efficacy and tolerability of a combination tablet containing the vascular-selective calcium antagonist felodipine and the beta1-selective adrenergic antagonist metoprolol, with a combination tablet of captopril-hydrochlorothiazide in a randomized, double-blind trial involving 109 patients with mild to moderate hypertension. After 2 weeks on placebo, patients with a supine diastolic blood pressure of 95-115 mm Hg were randomized to felodipine-metoprolol, 5/50 mg o.d. (Logimax) or captopril-hydrochlorothiazide, 25/25 mg o.d. (Capozide). After a further 4 weeks, there was a mandatory dose increase to felodipine-metoprolol 10/100 mg o.d., and captopril-hydrochlorothiazide, 50/25 mg o.d., and treatment then continued for a another 4 weeks. At the end of the study, felodipine-metoprolol reduced supine blood pressure significantly more than captopril-hydrochlorothiazide. The mean differences in change in supine systolic and diastolic blood pressure between treatments after 8 weeks were 5.2 and 3.4 mm Hg, respectively, in favour of felodipine-metoprolol (p<0.05). Standing blood pressure also showed trends in favour of felodipine-metoprolol. The proportion of responders was similar in both groups. Both treatments were well tolerated. Two patients treated with felodipine-metoprolol and 5 with captopril-hydrochlorothiazide discontinued treatment due to adverse events. Felodipine-metoprolol combination reduced supine blood pressure significantly more than captopril-hydrochlorothiazide with maintained tolerability.     

Liver transplantation in infants younger than 1 year of age.

OBJECTIVE: The authors report on experience with liver transplantation for infants younger than 1 year of age. SUMMARY BACKGROUND DATA: Over the last 15 years, orthotopic liver transplant has become the only lifesaving procedure available for infants with end-stage liver disease. Many transplant centers initially required infants to reach a specific weight or age to minimize morbidity and mortality. Size-appropriate infant donors also were uncommon. As a result, many children, in the first few years of life, died of their disease. The availability of reduced-size cadaveric and living-related liver transplants has offered the ability to transplant the young infant with liver failure. METHODS: The authors instituted a program to aggressively transplant infants with liver failure in the first year of life using both cadaveric and living-related liver donors. RESULTS: Between June 1991 and January 1995, 13 infants were transplanted for rapidly progressive liver failure. Infant age ranged from 4 to 11 months (mean, 7.5 months). The cause of liver failure included biliary atresia (11), alpha 1-antitrypsin deficiency (1), and liver failure secondary to echovirus 7 (1). The United Network for Organ Sharing status at the time of transplant ranged from status 4, intensive care unit bound (4 patients); status 3, hospitalized (4 patients); or status 2, failing at home (5 patients). Six patients (46%) received cadaveric whole organ (2) or segmental transplants (4). Seven patients (54%) received left lateral segment living-related transplants from parental donors. After operation, patients received cyclosporine or FK506-based immunosuppression. Three patients (23%) required four retransplants (two cadaveric for primary nonfunction; one living-related for graft thrombosis in the face of fungal infection and bile leak). Postoperative complications included primary nonfunction (15%), rejection (85%), graft vascular thrombosis (15%, two of three revascularized successfully), bacterial and fungal infections (77%), and viral infections (46%). Epstein-Barr virus-associated lymphoproliferative developed in two patients (15%). Intestinal perforation requiring reoperation developed in two patients (15%). Bile leaks requiring reoperation or transhepatic stinting or both developed in three patients (23%). Two patients died in the perioperative period (< 1 month) from a combination of primary nonfunction or graft thrombosis and sepsis. Overall survival was 85%, ranging from 11.0 months to 4.5 years. CONCLUSIONS: Orthotopic liver transplantation in infants younger than 1 year of age poses significant challenges from technical and infectious complications. Despite these barriers, overall patient survival is comparable to that of older children and adults.     

Characteristics of calcaneal bone infarction: an MR imaging investigation

Objective. Bone infarction (BI) of the calcaneus is an uncommon entity which has received little mention in the recent literature. In this paper, we review the MR images of six calcanei with BI, which demonstrate a pattern of presentation that may explain the etiology of BI at this unusual location. Design. A retrospective review was performed of the transcribed reports of the foot or ankle MR examinations at our institution. MR images of examinations with any marrow signal abnormality were reviewed for presence of BI and its distribution. Patients. Based on MRI criteria, four patients had calcaneal BI (none biopsy proven); they ranged in age from 37 to 51 years old. Two patients were diagnosed with systemic lupus erythematosus, one with fibrositis, and another with polymyositis. All were treated with corticosteroids. Results. Six calcanei (in four patients) contained a region of calcaneal BI. In five of the six, the lesions were entirely or predominantly located in the posterior half of the calcaneus. Conclusion. Two theories are proposed which may explain why BI predominantly occurs in the posterior half of the calcaneus. First, the convergence of the recurrent intraosseous calcaneal vessels may occasionally produce the equivalent of a single dominant vessel that is more prone to vascular accidents. Secondly, the region between the recurrent and the epiphyseal vessels may act as a watershed zone, increasing its susceptibility to ischemia.     

Cell death in ischemic,reperfused porcine hearts: A histochemical and functional study

Summary The temporal development of infarcts was histochemically and functionally determined in porcine hearts. In one series of experiments (22 pigs), the distal third of the left anterior descending coronary artery (LAD) was transiently occluded for periods between 20 and 90 min and was reperfused for another 24h. At the end of the experiments, the infarcted myocardium of four tissue slices was determined with a tetrazolium stain and related to the risk region which was delineated by a fluorescent dye. Infarcts started to develop in the ischemic septum and the subendocardial layer of the free anterior wall between 20 and 35 min of ischemia. Thereafter, infarctions progressed rapidly from the inner towards the outer layer at risk. The jeopardized anterior left ventricular wall became almost completely infarcted within 60 min of ischemia. In a second series of experiments (10 pigs) recovery of systolic shortening was studied with implanted ultrasonic crystals over 3 weeks of reperfusion. At the end of the experiments, systolic shortening was about 75% of baseline level when ischemia had lasted between 20 and 35 min. Almost no recovery was observed when the occlusion time lasted 45 to 60 min. This study suggests that the assessment of myocardial infarction with a tetrazolium stain after 24 h of reperfusion corresponds very well with functional recovery after 3 weeks of reperfusion. Furthermore, determination of regional myocardial function of the ischemic, reperfused segment in the chronic stage may be considered an additional tool to evaluate therapeutic effects on infarct size in this model.The study was supported by a grant of Deutsche Forschungsgemeinschaft (DFG) Sonderforschungsbereich 330 Organprotektion Göttingen.This paper contains parts of the Habilitationsschrift of Dr. H. H. Klein.     

Postocclusive transcutaneous oximetry in followup assessment of tibial nonunion and healed tibia fractures

Transcutaneous oximetry measurements were performed on 25 limbs in 25 patients with clinical and radiographic nonunion, and compared with data obtained from patients with healed tibia fractures and a control group of nonfractured extremities. A technique of "stress testing" vascular inflow patterns by temporary occlusion of arterial inflow was utilized to accentuate differences in perfusion not apparent at rest between normal limbs and those with inflow impairment. Changes in postocclusive hyperemic response were monitored by changes in transcutaneous oxygen detected by sensors placed over the dorsum of the foot, at the fracture site, over the anterior compartment, and at the chest. No statistically significant differences were found between the control group and the group of united tibia fractures. Analysis of results using the unpaired Student's t-test demonstrated statistically significant differences between the control and nonunion groups at each limb site tested (p less than 0.05). The prolonged oxygen recovery time values found in more than half the limbs with nonunion are consistent with the presence of impaired oxygenation following physiologic stress. The impairment of oxygenation appears to be on a perfusion basis and reflects the limited capacity of many limbs with tibial nonunion to respond to experimental ischemia with immediate compensatory hyperemia. Clinical relevance: This technique is a feasible method for serially assessing the regional oxygenation of a limb, and substantiates ischemia as a possible factor in the genesis of tibial nonunion.     

Differential expression of hla antigen of HLA anigens on human B-cell lines of normal and malignant origin: A consequence of immune surveillance or a phenotypic vestige of the progenitor cells?

Pairs of BL-derived cell lines and in vitro EBV-transformed LCLs, derived from the same patient, were compared for the expression of MHC class-I antigenic determinants as shown both by monoclonal antibody (MAb) binding and by sensitivity to HLA-specific CTL clones. BL lines expressed all polymorphic determinants tested at a lower level than the corresponding LCLs, as indicated by the binding of the MAbs AUF 5.13 (anti-HLA A3,A11), GS 142.1 (anti-HLA A1), GS 114.1 (anti-HLA A24), GSP 35.1 (anti-HLA A2,A28), GSP 55.1 (anti-HLA A25,A32), TER MA32 (anti-HLA A32), GSP 145.2 (anti-HLA B27), B27 M.1 (anti-HLA B27,B7) and GSP 8.1 (anti-HLA B8). The difference was most pronounced for HLA A11 and least for B27,A1 and B8 with intermediate differences for the other specificities. The BL lines were also less sensitive to lysis by HLA-specific CTL clones directed to the same and to additional antigens. The polymorphic determinants detected by the AUF 5.13 and GSP 35.1. MAbs were expressed at a lower level in resting T and B cells compared to mitogen- and EBV-induced blasts. An analogous change in the expression of polymorphic determinants was observed in EBV-converted sublines of originally EBV-negative BLs that have become more "LCL-like" after conversion. The appearance of B-cell activation markers was paralleled by the up-regulation of both the serologically defined and the CTL-target epitopes. The findings suggest that the low expression of HLA determinants on the BL cells is a phenotypic vestige of the normal BL precursor.     

"Weber's law" for position: unconfounding the role of separation and eccentricity

Bisection thresholds are approximately proportional to the separation/eccentricity of the targets. This "Weber's law" for position has been invoked over the past century. It is the separation of the reference targets, or their eccentricity which determines the threshold? In previous studies separation and eccentricity are confounded. In the present report we have pitted separation against eccentricity. Bisection thresholds were measured for stimuli presented on an isoeccentric arc, so that separation could be varied while holding the eccentricity of the test lines constant. We used a 5-fold range of separations from 2-10 deg. In this regime, the present results provide strong evidence against Weber's law. When separation is varied but eccentricity held constant, there is no Weber's law. Rather the thresholds are approximately constant. Our results suggest that the judgement of the separation of widely separated objects is similar to a distance measurement using a ruler on the cortex, in that the error of measurement is independent of the separation between objects. The results imply that when we attempt to gauge the distance between widely separated objects it is unlikely that we do so on the basis of the outputs of large spatial filters; rather it appears that we make such judgements by estimating the cortical distance which separates the targets of interest.