Linear parameters of normal and abnormal cava septi pellucidi: a post-mortem study

Anatomical variations in the dimensions of different brain structures have been correlated with clinical syndromes. This study on the parameters of normal and abnormal cavum septi pellucidi (CSP) can be of clinical significance. We obtained 479 brains from autopsied persons (310 males and 169 females, 377 normal or asymptomatic and 102 abnormal or symptomatic persons, aged 22-89 years) and observed that 110 brains (75 males and 35 females) had CSP. These cava were classified into two groups depending on the past medical histories of the autopsied person: 40 asymptomatic and 70 symptomatic cava. We have defined symptomatic cava as those in autopsied persons who had known past medical history of psychiatric or neurological disease. Asymptomatic cava were in autopsied persons who had no known past medical history of psychiatric or neurological disease. The CSP parameters (length, width, depth) of the symptomatic and asymptomatic groups were measured and were statistically analyzed. Analysis showed that the cava in the symptomatic group were significantly longer and wider. Discriminant function analysis was used to derive a mathematical formula to classify CSP into an asymptomatic or symptomatic group based on length and width measurements of the cavum.     

Recurrent posterior dislocation following primary posterior-stabilized total knee arthroplasty

In our series of 136 patients with primary total knee arthroplasty using posterior-stabilized prosthesis, a female patient with Parkinson disease developed posterior dislocation of the knee 9 months after surgery. Eventually, the dislocation became recurrent, occurring several times a day. The patient made the reposition always by herself. Two months after the first dislocation, we performed the revision of the polyethylene tibial insert and found wearing of the tibial insert's cam as an hitherto unreported cause of the mechanical instability of the total knee prosthesis.     

Clinical approach to normal intraocular pressure glaucoma

Normal intraocular pressure (IOP) glaucoma is a clinical condition characterized by pathologic optic nerve excavation and visual field impairment, defined as optic neuropathy with certain features of a disease known as glaucoma. Glaucomatous optic nerve lesion is characterized by optic disk excavation or depression, however, this feature may greatly vary. The level of IOP is considered only one of the multiple risk factors involved in the disease development. In normal IOP glaucoma, papillary lesions and visual field impairments may differ from those occurring in primary open-angle glaucoma. In modern ophthalmology, the terminology has been modified, so the term low IOP glaucoma has been replaced by the term normal IOP glaucoma. It is now believed that various factors play a role in the development of glaucomatous optic neuropathy in normal IOP glaucoma and show variable interference depending on IOP level. Additional studies are needed to define these interactions and their impact on the mechanism of glaucomatous excavation. This will hopefully pave the way to new therapeutic approaches and help in clinical decisions concerning the prognosis and treatment of individual patients.     

Lid retraction etiology

The upper lid position is abnormal if it exposes a white band of sclera between the lid margin and the upper corneal limbus while the retracted lower lid lies below the inferior corneal margin and is tethered to the orbital margin. Lid retraction is a sign of many congenital and acquired diseases and is characterised by multifactorial etiology. The aim of this study was to discuss the etiology of lid retraction divided into four categories: neurogenic, myogenic, mechanical and miscellaneous, what suggests a successful differential diagnostic and therapeutic approach.     

Importance of plasmapheresis in the treatment of paraneoplastic cerebellar degeneration

Paraneoplastic neurologic syndromes are disorders of the nervous system function caused by cancer but not due to metastatic disease, vascular or metabolic deficits, infections, nutritive deficiency, nor side effects of antineoplastic drugs or irradiation. Immunologic factors probably play the crucial role in the pathogenesis of paraneoplastic neurologic syndromes, but nonimmunologic mechanisms that include metabolic abnormalities and competition for substrate are also involved. Paraneoplastic cerebellar degeneration most commonly occurs in the setting of gynecologic cancers, but it accompanies the small-cell lung cancer too. Other tumors are infrequently associated with cerebellar degeneration. Several paraneoplastic antibodies have been identified in patients with paraneoplastic cerebellar degeneration. Their association with particular cancers may help identify an occult lesion. Anti-Yo antibodies are directed against Purkinje cell antigens and occur in patients with cerebellar degeneration who have breast cancer or gynecologic tumors. A target antigen of anti-Yo antibody is CDR2 protein that is normally expressed only in the brain and testis. Patients with paraneoplastic cerebellar degeneration present with dizziness, nausea and vomiting followed by gait instability, diplopia, gait and appendicular ataxia, dysarthria and dysphagia. Therapeutic options include tumor excision, chemotherapy and/or irradiation, and adjuvant therapy with glucocorticoids, immunoglobulins and plasmapheresis. The role of plasmapheresis in the treatment of paraneoplastic cerebellar degeneration is still uncertain. Reports of its efficacy are anecdotal. We present patient with paraneoplastic cerebellar degeneration with positive anti-Yo antibodies and tumor of the ovaries whose neurologic status significantly improved after four daily plasmaphereses, which was accompanied by a fourfold decrease in the anti-Yo antibodies titer. Further investigations are needed to define a protocol for plasmapheresis in the treatment of patients with paraneoplastic syndromes.     

Adenoviral vectors expressing siRNAs for discovery and validation of gene function

RNA interference is a powerful tool for studying gene function and for drug target discovery in diverse organisms and cell types. In mammalian systems, small interfering RNAs (siRNAs), or DNA plasmids expressing these siRNAs, have been used to down-modulate gene expression. However, inefficient transfection protocols, in particular, for primary cell types, have hampered the use of these tools in disease-relevant cellular assays. To be able to use this technology for genome-wide function screening, a more robust transduction protocol, resulting in a longer duration of the knock-down effect, is required. Here, we describe the validation of adenoviral vectors that express hairpin RNAs that are further processed to siRNAs. Infection of cell lines, or primary human cells, with these viruses leads to an efficient, sequence-specific, and prolonged reduction of the corresponding target mRNA, resulting in a reduction of the encoded protein level in the cell. For knock-down of one of the targets, GalphaS, we have measured inhibition of ligand-dependent, G-protein-coupled signaling. It is expected that this technology will prove to be of great value in target validation and target discovery efforts.