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.     

Severely comminuted distal radial fracture as an unsolved problem: complications associated with external fixation and pins and plaster techniques

Seventy-six patients with severely comminuted distal radial fractures were treated at two institutions, of which the overwhelming majority were Frykman class VIII. Fifteen fractures were open. Thirty patients were seen at the University Hospital; 17 had pins and plaster and 13 had external fixation. Forty-six patients were seen at Kaiser Hospital; all had pins and plaster treatment. The complication rate for those with pins and plaster at the University Hospital was 53%; the complication for external fixation rate was 62%. The affiliated-hospital complication rate was 52%. All patients with ipsilateral forearm shaft and carpal fractures developed a nonunion of the carpal fracture. Few patients maintained anatomic reduction, and many had significant intra-articular malalignment. External fixation with threaded half pins did not obviate pin problems in our series. These methods may help manage severely comminuted distal radial fractures, but complications should be anticipated and alternative treatment considered, especially when ipsilateral carpal or forearm shaft fractures are present.     

Acute carpal tunnel syndrome caused by pigmented villonodular synovitis of the wrist

An 89-year-old woman developed an acute carpal tunnel syndrome secondary to hemarthrosis associated with pigmented villonodular synovitis of the wrist. Pigmented villonodular synovitis is rare in a patient of this age and is an unusual cause of carpal tunnel syndrome.     

Comminuted intraarticular fractures of the distal radius

The comminuted intraarticular fracture of the distal radius requires early, accurate reduction of the articular surfaces and sustained restoration of anatomic position. The most commonly employed methods are pins and plaster, external fixation, percutaneous pinning, and open reduction and internal fixation. There are pitfalls, advantages, and disadvantages inherent in each method. Careful preoperative analysis of individual patients and fractures determines the therapeutic options.     

Developments in treatment of primary irresectable rectal cancer

Abstract The treatment options for primary irresectable rectal cancers are discussed. Assessment of tumour stage is the first step for an appropriate choice of treatment. Following a diagnosis of rectal cancer, a vast array of diagnostic procedures is available to determine its stage, and thereby its best treatment options. From the many (new) diagnostic options the merits and drawbacks are discussed. If a diagnosis of irresectability is made, further treatment options should include radiotherapy in most cases, some aspects of timing and application, i.e. intra-operative treatment are discussed. Chemotherapy options are manifold, the results are discussed and some new options are explored.     

Comminuted distal radius fractures.

Comminuted displaced fractures of the distal end of the radius pose a significant treatment challenge. The goal of treatment is to restore functional, painless motion of the wrist and fingers. Although satisfactory results correlate to a large extent with obtaining and maintaining normal anatomy, excessive distraction and a flexed wrist position with external fixation cause more harm than good, even if the anatomy is restored.