Sorsby fundus dystrophy: Insights from the past and looking to the future

Sorsby fundus dystrophy (SFD), an autosomal dominant, fully penetrant, degenerative disease of the macula, is manifested by symptoms of night blindness or sudden loss of visual acuity, usually in the third to fourth decades of life due to choroidal neovascularization (CNV). SFD is caused by specific mutations in the Tissue Inhibitor of Metalloproteinase-3, (TIMP3) gene. The predominant histo-pathological feature in the eyes of patients with SFD are confluent 20–30 m thick, amorphous deposits found between the basement membrane of the retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch's membrane. SFD is a rare disease but it has generated significant interest because it closely resembles the exudative or “wet” form of the more common age-related macular degeneration (AMD). In addition, in both SFD and AMD donor eyes, sub-retinal deposits have been shown to accumulate TIMP3 protein. Understanding the molecular functions of wild-type and mutant TIMP3 will provide significant insights into the patho-physiology of SFD and perhaps AMD. This review summarizes the current knowledge on TIMP3 and how mutations in TIMP3 cause SFD to provide insights into how we can study this disease going forward. Findings from these studies could have potential therapeutic implications for both SFD and AMD.     

Subtype determination of soma-dendritic α2-autoreceptors in slices of rat locus coeruleus

The aim of the study was to subclassify the soma-dendritic α₂-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average rate of 1 Hz. The selective α₂-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential discharge with IC₅₀ values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the right by phentolamine (0.15 μM) and rauwolscine (0.15 μM) but not by prazosin (1 μM). Apparent K _d values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent K _d values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 μM) suppressed the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored firing with EC₅₀ values of 120 and 250 nM, respectively. Prazosin (1 μM) again was ineffective. All three antagonist affinity estimates – against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the presence of oxaprotiline) – yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even at a concentration of 1 μM. These findings identify the soma-dendritic α₂-autoreceptors of the LC as the rat variant of the α_2A/D-adrenoceptor, i.e. α_2D. Not only presynaptic but also soma-dendritic α₂-autoreceptors may at least predominantly be α_2A/D throughout the nervous system. Received: 3 March 1997 / Accepted: 21 April 1997     

Recurrent Cervical Abscess Due to Pyriform Sinus Fistula-A Case Report

The pyriform sinus fistula is rare congenital anomaly of either third or fourth branchial pouch, which most frequently presented itself by recurrent episodes of neck abscess for long time. Majority of patients with this anomaly presented with symptoms before 10 years and it is more common than has previously been commonly found on leftside (93%). Clinically high index of suspicion, cannulation of the tract under general anaesthesia, Direct laryngoscopy and fistulogram have freequently been successful in identifying the presence of these embryological remnants. Surgical exploration of sinus tract with its total excision, guided with cannula inside its lumen is the definitive treatment.     

In Hungary,the Old Medical Ethics Meets the New

Medical ethics in Hungary has finally moved beyond arguments over tipping and bribes to discussions of euthanasia, confidentiality, truth-telling and informed consent. Ethics committees have been formed at the local and national level, and medical schools are beginning to take seriously the systematic teaching of medical ethics. In some quarters, however, old attitudes persist. Among older doctors paternalism reigns supreme, and lawmakers continue to ignore international ethical guidelines.     

The patella and tibial condyle position after combined and after closing wedge high tibial osteotomy

High tibial osteotomy changes the patella and tibial condyle position, which makes the subsequent total knee replacement technically demanding. From 1 January 1993 to 31 December 2000, combined osteotomy [After the first osteotomy made 2 cm distally to the joint line, a bone wedge is removed based laterally. Its tip ends at the center of the tibial condyle (half bone wedge). The distal part of the tibia is placed into the valgus position and the half bone wedge is placed into the gap opened medially.] was performed on 103 knees and closing wedge osteotomy was performed on 47 consecutive knees. Eighty combined (group A) and 41 closing wedge (group B) osteotomy were studied. All knees were assessed radiologically before surgery, in the 10th postoperative week, in the 12th postoperative month and at the time of the final follow-up (in group A—66.15 months, in group B—66.61 months). We examined the change of the femorotibial angle, of the patellar height according to the method of Insall and Salvati, of the tibial slope angle according to the method of Bonnin, of the tibial condylar offset according to the method of Yoshida and of the distance between the lateral tibial plateau and the top of the fibular head. In group A and B, the recurrence of the varus deformity was not noted and valgus alignment did not increase in any case. In group-A, the Insall–Salvati ratio remained unchanged in 65% of knees. The tibial slope angle decreased in both groups. There was correlation between the change of the tibial condylar offset and the angle of the correction in both groups. There was correlation between the change of the distance between the lateral tibial plateau and the top of the fibular head. After combined osteotomy, the transposition of the tibial condyle and the decrease of the distance between the lateral tibial plateau and the top of the fibular head was less than after closing wedge osteotomy, although the average angle of correction was more after combined osteotomy (11.835°), than after closing wedge osteotomy (9.465°). Theoretically, the recurrence of the varus deformity, the increase of the valgus alignment and (in majority of cases) the shortening of the patellar tendon do not compromise the likelihood of successful conversion to the subsequent total knee replacement, either after combined or after closing wedge osteotomy. The combined osteotomy does not lead to considerable transposition of the tibial condyle and to considerable lateral tibial bone loss; therefore, theoretically, the combined osteotomy does not impair the subsequent total knee replacement.     

Cardiovascular effects of the calcium sensitizer, levosimendan, in heart failure induced by rapid pacing in the presence of aortic constriction.

1. The haemodynamic effects of a novel cardiotonic drug, levosimendan, which has both calcium-sensitizing and phosphodiesterase III (PDE III) inhibitory properties, were studied in conscious dogs in which heart failure had been induced by prolonged cardiac pacing in the presence of aortic constriction. These effects were compared with those in sham-operated dogs with essentially normal cardiac function. 2. Eighteen mongrel dogs were instrumented for the measurement of left ventricular pressure (LVSP, LVEDP) and contractile function (dP/dt; dP/dt/P). In twelve dogs a balloon catheter, positioned in the thoracic aorta, was inflated producing an approximate 60% reduction in effective aortic diameter. Twenty min later rapid ventricular pacing (240 beats mean-1) was commenced and maintained for 48 h by means of a bipolar pacing electrode introduced into the right ventricle. This electrode served also for recording changes in the endocardial electrogram in the absence of pacing. Six of these dogs were used to evaluate the haemodynamic changes of pacing-induced heart failure; a further six of these dogs the haemodynamic changes elicited by levosimendan under these conditions. Six sham-operated dogs (group 2) served as controls. 3. In six dogs (group 1) the haemodynamic alterations were assessed after the development of heart failure. In the presence of aortic constriction, 48 h continuous rapid cardiac pacing resulted in a marked deterioration in left ventricular function which remained stable for at least 48 h after cessation of pacing. Thus, there was a marked reduction in LVSP (15%), +dP/dtmax (35%), -dP/dtmax (36%) and also in dP/dt/P (29%), whereas LVEDP was increased considerably (from 6.4 +/- 1.4 to 20.0 +/- 2.2 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Incidence over 10% of premature deliveries in Hungary (based on the experience in Borsod-Abaúj-Zemplń County)

The incidence over 10% of premature delivery in Hungary was studied. The cause which motivated this work was the fact that despite of several preventive and therapeutic measures the incidence e.g. in BAZ county surpassed even the average of the country. Professors of clinics in different countries of Europe as well as medical societies dealing with this question have been consulted about the matter of whether it was sufficient to consider a neonate a premature infant and the delivery a premature one solely on the basis of birth weight (under 2.500 g). Data of BAZ county proved that this determination was misleading and proposals are made concerning the modification on the basis of the examinations of the authors.     

Development and results of valve replacement surgery at the Városmajor Clinic 1976-1990 (retorospective clinical analysis)]

In Hungary valve replacement is still a major indication for heart surgery in adults. In the Cardiovascular Surgical Clinic of Semmelweis Medical University of Budapest from 1976 to 1990 2435 patients were operated for valve disease. Majority of the cases had single (aortic n = 856, mitral n = 912) or double (aortic + mitral n = 513) valve replacement. Over this 15 years period there have been many alterations in patients characteristics and surgical technique as well. In spite of the increasing mean age of patients the operative mortality has decreased (in the last 5 years period it was 2.7%, 5.5% and 7.9% in the three groups respectively). At the same time the number of patients requiring valve re-replacement or combined valve + coronary procedure has increased. The use of bioprosthetic valves has fallen below 10 percent from the 60--80 percent observed between 1976--1980. The analysis showes excellent surgical results in the field of valve replacement in Hungary.