Whole-eye transplantation: a look into the past and vision for the future.

Blindness afflicts ~39 million people worldwide. Retinal ganglion cells are unable to regenerate, making this condition irreversible in many cases. Whole-eye transplantation (WET) provides the opportunity to replace diseased retinal ganglion cells, as well as the entire optical system and surrounding facial tissue, if necessary. Recent success in face transplantation demonstrates that this may be a promising treatment for what has been to this time an incurable condition. An animal model for WET must be established to further enhance our knowledge of nerve regeneration, immunosuppression, and technical aspects of surgery. A systematic review of the literature was performed to evaluate studies describing animal models for WET. Only articles in which the eye was completely enucleated and reimplanted were included. Study methods and results were compared. In the majority of published literature, WET can result in recovery of vision in cold-blooded vertebrates. There are a few instances in which mammalian WET models demonstrate survival of the transplanted tissue following neurovascular anastomosis and the ability to maintain brief electroretinogram activity in the new host. In this study we review in cold-blooded vertebrates and mammalian animal models for WET and discuss prospects for future research for translation to human eye transplantation.

Developmental differences of angiotensinogen mRNA in the preoptic area between spontaneously hypertensive and age-matched Wistar-Kyoto rats.

In order to know the possible involvement of the central angiotensin system in hypertension, angiotensinogen mRNA (AomRNA) levels of eight discrete brain areas were measured by Northern blot hybridization analysis in the spontaneously hypertensive rats (SHR), compared with those in age-matched normotensive Wistar-Kyoto rats (WKY). In 16-week-old SHR (hypertensive stage), AomRNA levels in the preoptic area (POA), but not in the ventromedial hypothalamus, lateral hypothalamus and mammillary body, among the hypothalamic nuclei, were higher (approximate 50%) than in WKY. There were no differences in other brain areas, such as the striatum, septum, amygdala and cerebellum between both the strains. The AomRNA levels in POA were already higher (38%) in 4-week-old SHR (prehypertensive stage) without significance, and the difference was augmented (82%) in 7-week-old SHR (evolving stage). These results suggest that the developmental changes of AomRNA levels at POA may be related in some aspect to hypertension process.

Dexamethasone down-regulates the expression of endothelin B receptor mRNA in the rat brain.

The present study was designed to examine effects of dexamethasone on the steady state level of endothelin B(ETB) receptor mRNA in in vivo the rat brain. ETB receptor mRNA was very high at the hypothalamus and cerebellum but was comparatively low at the striatum and amygdala. Dexamethasone, 1 and 7 mg/kg, i.p., markedly and dose-relatedly decreased ETB receptor mRNA level with slow onset of 8hr at the hypothalamus and cerebellum, but did not induced a marked decrease at other areas. On the contrary, dexamethasone produced an increase of ET-1 mRNA which preceded to the decrease of ETB receptor mRNA at the same brain areas. Phosphoramidon, a endothelin-converting enzyme inhibitor, did not antagonized but potentiated the effect of dexamethasone. Besides, phosphoramidon per se markedly stimulated the expression of ET-1 mRNA. The results suggested that dexamethasone down-regulates ETB receptor mRNA level at the hypothalamus and cerebellum of rat brain and these effects may be involved in the increase of ET-1 peptide gene transcription.

A case of myasthenia gravis complicated with hyperthyroidism and thymic hyperplasia in childhood.

We report here a case of myasthenia gravis complicated with hyperthyroidism and thymic hyperplasia. The patient was a 13-year-old girl with struma and hyperthyroidism which began at age 12. Two weeks following the initiation of treatment against hyperthyroidism she developed left blepharoptosis, diplopia, and dysphagia, which responded promptly to edrophonium administration. An increase of the anti-acetylcholine receptor antibody was found in the serum. A chest CT showed a large soft tissue mass in front of the ascending aorta, which was proven histopathologically as thymic hyperplasia. The patient underwent an extensive thymectomy and was placed on combination therapy with an anti-thyroid drug, glucocorticosteroid, and an anti-cholinesterase drug. Her symptoms and signs have been well controlled by this treatment. Coexistence of myasthenia gravis, hyperthyroidism, and thymic hyperplasia in childhood have never been documented in literature.

Detection of Giardia lamblia cysts in non-fixed long-term stored human feces by direct immunofluorescence assay.

Giardia lamblia cysts in fecal specimens are detected by conventional morphological methods. The direct immunofluorescence monoclonal antibody assay (DFA) is also applied to detect G. lamblia cysts in feces, but little is known about the usefulness of DFA in fecal specimens stored under various conditions. The aim of the present study was to evaluate the DFA for detection of G. lamblia cysts and to compare these results with the direct smear method in long-term storage of non-fixed fecal specimens. Fecal specimens with G. lamblia cysts were stored in a refrigerator at 5 degrees C(14 samples), a freezer at -20 degrees C (9 samples), or in 3.9% formalin-saline solution at room temperature (28 samples). G. lamblia cysts were detected by DFA in all stored specimens, while they were detected in only 56% of refrigerated and 93% of frozen specimens by the direct smear method. The storage period of all samples testing negative by direct smear was more than 24 months. Many degenerated cysts were recognized by DFA when cysts were negative by the direct smear method. Our results indicate that DFA is a useful method for detecting G. lamblia cysts in fecal samples that have undergone long-term storage.

Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in Behçet's disease.

Increases in the number and activity of peripheral polymorphonuclear neutrophils (PMNs) is often found in Behçet's disease (BD), indicating that PMN may play an important role in the pathogenesis of this disorder. It has recently been reported that G-CSF and GM-CSF, a family of hematopoietic growth factors, enhance PMN activity. To explore the role of these two CSFs in BD, we first examined the chemotactic response of PMNs to these CSFs by performing a polarization assay. PMN response to G-CSF in BD patients was lower than that in controls, while PMN response to GM-CSF was similar in patients and controls. However, PMNs from BD patients showed an enhanced chemotactic response to N-formyl-L-methionyl-leucyl-phenylalanine. Thus, it is speculated that the PMNs of the patients might have already been activated in vivo by G-CSF and thus could not respond further to this agent in vitro. We examined G-CSF and GM-CSF mRNA expressions in peripheral mononuclear cells stimulated with LPS, PMA, and Con A by Northern hybridization. G-CSF mRNA expression levels in BD patients were higher than in the controls, while GM-CSF mRNA expression levels were lower than in the controls. We also examined the serum levels of the two CSFs by ELISA and EIA. However, all levels of the two CSFs in both patients and controls were not detectable, except in the case of one BD patient in the active stage of the disease, who showed high levels of G-CSF, but not of GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Time course and clinical significance of marked left axis deviation in airline pilots.

The purpose of this study was to examine the time course and evaluate the clinical significance of marked left axis deviation (LAD) in airline pilots. The study group consisted of 30 Japan Airlines' pilots with marked LAD, identified from a group of 1,700 who are now 35 years of age or older. The mean age at examination was 48.5 +/- 5.7 years [corrected] and the mean observation period was 22.6 +/- 5.6 years [corrected]. The prevalence rate of marked LAD was 1.8%. In 20%, the axis remained unchanged, and in 70%, LAD progressed either gradually or suddenly. All subjects were examined by exercise testing and 26 had echocardiograms. Two pilots (6.7%) were found to have organic heart disease (hypertension), which was much lower than the rate reported previously. In these individuals, the onset of marked LAD was noted more than 10 years before hypertension was detected. No progression to complete left bundle branch block, nor any form of AV block, was observed among these subjects. No cardiac events or death occurred during the study period.

[Diagnostic value of the transesophageal atrial pacing stress for Tl-201 myocardial SPECT].

The stress study for Tl-201 myocardial SPECT (single photon emission computed tomography) of a patient with old myocardial infarction, who had occasionally felt a chest pain for the last 8 months was performed with the transesophageal atrial pacing. The examination was fastly started and regular pacing rates were completely obtained for every pacing rate (50-100/min). In spite of a little amount of the pacing stress, the finding of stress induced ischemia and MI were obtained on this patient. This result suggests that the transesophageal atrial pacing stress might be useful for the evaluation of ischemic heart disease by Tl-201 myocardial SPECT, and is easily applied to the old and the patient with disorder of leg movement.

[A case of repetitive monomorphic ventricular tachycardia].

We present a case treated with aprindine and metoprolol combined with a DDD type pacemaker for repetitive monomorphic ventricular tachycardia. A 50-year-old man was admitted because of palpitation and near syncope attack. Electrocardiogram showed repetitive monomorphic ventricular tachycardias (RBBB LAD type) and R-R interval of about 440 msec and I degree A-V block in sinus rhythm. Electrophysiologic study disclosed that overdrive pacing in HRA suppressed ventricular tachycardias. Left ventriculography revealed a dilated left ventricular and decreased contractility. Antiarrhythmic agents such as quinidine sulfate, procainamide, disopyramide, mexiletine, lidocaine and propranolol were not effective. But, the combination of propranolol and aprindine decreased the rate of the ventricular tachycardia. With aprindine 60 mg/day and metoprolol 60 mg/day combined with the atrioventricular sequential pacing at 85/min, ventricular tachycardia completely disappeared.

Utility of the filtered bipolar esophageal lead in the diagnosis of arrhythmias.

Electrophysiologic study was performed in 25 patients with tachycardia or bradycardia attacks. The coronary sinus (CS) and filtered bipolar esophageal electrograms were recorded simultaneously to compare the phase of atrial activations. During sinus rhythm and high right atrial pacing, the esophageal and proximal CS atrial activations were nearly simultaneous but earlier by 26 +/- 5 msec on the average than the distal CS atrial activations. During reciprocating tachycardia due to reentry using a left-side accessory atrioventricular pathway for retrograde conduction the esophageal and CS atrial activations occurred earlier than the low septal right atrial activation, so the esophageal lead can be used as a substitute for the CS lead to clarify the eccentric retrograde atrial activation sequence. By using the filtered bipolar esophageal lead, the interval from Q wave on the surface electrocardiogram to the first rapid deflection in the esophageal atrial activation (Q-AESO interval) was measured in 15 patients with supra-ventricular tachycardia. All patients with reciprocating tachycardia due to reentry using a left side accessory atrioventricular pathway had Q-AESO intervals between 100 to 130 msec and four of five patients with a right side accessory atrioventricular pathway for retrograde conduction had Q-AESO intervals between 130 to 150 msec. In contrast, all patients with reentry in the atrioventricular node had Q-AESO intervals between 30 to 60 msec. The esophageal lead is also of value in the prompt diagnosis of atrial flutter and ventricular tachycardia, since the esophageal electrograms readily reveal the relationship between atrial and ventricular activations. In conclusion, the filtered bipolar esophageal lead provides a non-invasive method for the quick diagnosis of various arrhythmias.

Patterns of interruption of atrial flutter induced by rapid atrial pacing.

We evaluated the patterns of interruption of atrial flutter (AFl) induced by rapid atrial pacing in 10 patients using standard electrophysiologic techniques. We observed 3 patterns of interruption of AFl: 1) interruption resulting from block of an orthodromic wavefront within the reentry loop in 5 patients; 2) interruption when pacing impulses no longer captured all of the recording sites in the atrium during rapid atrial pacing in 2 patients, and 3) interruption with 1 echo wave after the cessation of pacing in 3 patients. These findings suggest that there are patterns of interruption of AFl other than that resulting from a simple block of an orthodromic wavefront within the reentry loop.

[The use of MPG in preventing the post-reperfusion injury of an epigastric island flap: an experimental study in rats]. / O uso de MPG na proteção da lesão pósreperfusão do retalho epigástrico em ilha: estudo experimental em rato.

The objective of this work was to study the protective effects of the free radical scavenger N2-mercaptopropionylglycine used in a rat model of reperfusion of epigastric island flaps submitted to transient occlusion of their vascular pedicles. In one group the epigastic vein of the flap was occluded for 5 hours. In the second group the epigastric artery was occluded for 21 hours and in the third group both the epigastric vein and artery were occluded for 8 hours. The scavenger or equivalent volume of saline solution was injected 10 minutes before the vascular occlusion and 10 minutes before declamping. The flap viability was assessed on the seventh day after flap reperfusion. In the three types of vascular occlusion a significant, and differential, increase of the areas of flap survival was observed. The protective effect of N2-mercaptopropionylglycine in reperfusion injuries was demonstrated.

Effects of four antiarrhythmic drugs on the induction and termination of paroxysmal supraventricular tachycardia.

The electrophysiological effects of antiarrhythmic drugs were tested in 36 patients with recurrent paroxysmal supraventricular tachycardia (PSVT), 25 of whom had accessory pathway reentrant tachycardia (APRT) and 11 A-V nodal reentrant tachycardia (AVNRT; 10 of the slow-fast type one of the fast-slow type). The test drugs were procainamide (used in 19 patients), verapamil (in 27), disopyramide (in 31), and propranolol (in 15). The drugs were tested for their ability to terminate episodes of PSVT as well as to inhibit their induction. Procainamide had an inhibitory effect on APRT in nine of 12 patients (75%) and terminated episodes of APRT in seven of 11 patients (63.6%); in all of them V-A block was responsible for the termination. In four of six patients (66.7%) with slow-fast AVNRT and in one patient with fast-slow AVNRT, inhibition of the induction of tachycardia attacks was noted after procainamide. Termination of AVNRT was seen in the same number of patients. Verapamil inhibited the induction of APRT in 12 of 18 patients (66.7%) and terminated episodes of APRT in 10 of 16 patients (62.5%), all by A-V block. In six of eight patients (75%) with slow-fast AVNRT, inhibition of the induction as well as termination of tachycardia were noted after verapamil. Disopyramide had an inhibitory effect on APRT in seven of 23 patients (30.4%) and terminated APRT in five of 21 patients (23.8%) by V-A block, while AVNRT (all slow-fast type) was terminated in only one of eight patients (12.5%) by disopyramide. Disopyramide was less effective than previously reported. This could be attributed to a relatively low dosage and slow infusion speed. Propranolol inhibited the induction of APRT and terminated episodes of APRT in only one of 10 patients (10%). In two of four patients (50%) with slow-fast AVNRT, an inhibitory effect by propranolol was noted, but termination was seen in only one patients.

Study on the genesis of the double potential recorded in the high right atrium in atrial flutter and its role in the reentry circuit of atrial flutter.

To investigate the genesis of the double potential (DP), which is two separate waves, and its role in the reentry circuit of atrial flutter (AF), we performed overdrive pacing (ODP) from the high right atrium (HRA) in six cases of spontaneous AF in which the DP was recorded in the HRA. In four of the six cases, when the DP was arbitrarily designated D1 and D2, D1 and D2 showed progressive fusion during ODP. In addition, the D1 return cycle, immediately after the termination of ODP, corresponded to the AF cycle, and the D2 return cycle corresponded to the pacing cycle. This may indicate that the DP is caused by the collision of two directional waves. Furthermore, it is suggested that the HRA plays an important role in preventing a possible shortcutting of reentry waves and in stabilizing the reentry circuit of AF.

AV nodal reentrant tachycardia with Mahaim fiber conduction.

Paroxysmal tachycardia with widened QRS complexes was found in a 46-year-old woman. In sinus rhythm, the patient had electrocardiographic evidence of type B preexcitation with a left bundle branch block pattern. The resting PR interval (160 msec) and A-H interval (100 msec) were within normal limits, but the H-V interval (10 msec) was abnormally short. Programmed atrial extrastimuli at progressively shorter coupling intervals resulted in sudden prolongation of the A-H interval from 120 msec to 250 msec, and the His bundle activities became incorporated just after initiation of the QRS complexes. The QRS morphology was changed but the change was minimal, and atrial echo beats or sustained tachycardia with wide and preexcited QRS complexes were elicited. It is postulated that the site of reentry is within the AV node with preexcitation occurring as the result of conduction in an anomalous nodoventricular pathway.

Shift of atrial reentrant tachycardia with transient entrainment to an uncommon and a common type of atrial flutter.

Atrial reentrant tachycardia (ART) which demonstrated transient entrainment shifted to an uncommon type of atrial flutter (AF) with premature atrial stimulation, and then returned to ART spontaneously. Subsequently, this ART shifted to a common type of AF by rapid atrial pacing, which was further transformed into an uncommon type of AF and finally terminated by rapid atrial pacing. The mechanism of AF in clinical cases is still controversial, but in this case, AF, both uncommon and common types, is considered due to macro-reentry within the atria. To explain the shift of ART to AF and mutual transformation between common and uncommon type of AF, we made a schematic figure of reentry loop within the atria of ART and AF.