Early posterior vitreous detachment is associated with LAMA5 dominant mutation

Background: Extracellular matrix molecular components, previously linked to multisystem syndromes include collagens, fibrillins and laminins. Recently, we described a novel multisystem syndrome caused by the c.9418G>A p.(V3140M) mutation in the laminin alpha-5 (LAMA5) gene, which affects connective tissues of all organs and apparatus in a three generation family. In the same family, we have also reported a myopic trait, which, however, was linked to the Prolyl 4-hydroxylase subunit alpha-2 (P4HA2) gene. Results of investigation on vitreous changes and their pathogenesis are reported in the present study.Materials and Methods: Nineteen family individuals underwent complete ophthalmic examination including best-corrected visual acuity (BCVA), fundus examination, fundus photography, intraocular pressure measurement, axial length measurement using ocular biometry, Goldmann visual field examination, standard electroretinogram, SD-OCT. Segregation analysis of LAMA5 and P4HA2 mutations was performed in enrolled members.Results: The vitreous alterations fully segregated with LAMA5 mutation in both young and adult family members. Slight reduction of retinal thickness and peripheral retinal degeneration in only two patients were reported.Conclusions: In this work we showed that PVD is a common trait of LAMA5 multisystem syndrome, therefore occurring as an age-unrelated trait. We hypothesize that the p.(V3140M) mutation results in a reduction of retinal inner limiting membrane (ILM) stability, leading to a derangement in the macromolecular structure of the vitreous gel, and PVD. Further investigations will be necessary to elucidate the role of wild type and mutated LAMA5 in the pathogenesis of PVD.     

A case of primary lymphoma of the rectum

The Authors describe a case of primary rectal lymphoma. The primitive involvement of this area is infrequent. The Authors emphasize the difficulty of preoperative diagnosis. The therapeutic approach should allow for correct staging which is only obtained by means of diagnostic studies aimed at excluding multicentric localisation. Sensitivity to radiotherapy has led the Authors to propose it as primary treatment, at least in stage I; surgery must be considered elective in stage II or in cases of need. Chemotherapy is indicated alone or in association with radiotherapy or surgery.     

Transesophageal echocardiography-guided cardioversion of atrial fibrillation. Selection of a low-risk group for immediate cardioversion.

INTRODUCTION: In patients (pts) with atrial fibrillation (AF) of more than 48 hours' duration, electrical cardioversion (ECV) should only be performed after 3 weeks of effective anticoagulation. Transesophageal echocardiography (TEE) allows earlier ECV; however, despite exclusion of thrombi in the atrium and left atrial appendage (LAA), cases of thromboembolism related to ECV have been documented in AF. To define a low-risk group for cardioversion without previous anticoagulation, pts were selected for immediate ECV if no thrombi or dynamic spontaneous echo contrast (auto-contrast) were found after TEE and if LAA velocity was more than 0.25 m/sec. METHODS AND RESULTS: We performed TEE in 31 consecutive pts referred for ECV for AF of more than 48 hours' duration and without previous anticoagulation. After TEE the pts eligible for immediate ECV began anticoagulation with low molecular weight heparin (enoxaparin), subcutaneously in therapeutic doses, together with warfarin immediately before cardioversion. Enoxaparin was continued until an INR of over 2 was reached. Based on the TEE findings, the pts were divided in 2 groups: immediate ECV, group A, 20 pts with a mean age of 62 +/- 13 years, 6 female; and conventional therapy with warfarin before ECV, group B, 11 pts, mean age of 67 +/- 10 years (p < 0.05), 2 female. None of the pts in either group had mitral stenosis or previous episodes of thromboembolism. The mean transverse diameter of the left atrium in the 31 pts was 47 +/- 4.5 mm, without statistically significant differences between the 2 groups. Of the 11 pts in group B, 3 had a thrombus in the LAA, 6 dynamic spontaneous echo contrast and the remainder LAA velocities of less than 0.25 m/sec. ECV was achieved in all the pts, with no complications. Oral anticoagulation was maintained for at least a month. At one month, sinus rhythm was maintained in 75% of group A and 45% of group B (p < 0.01). CONCLUSION: In pts with AF of more than 48 hours' duration and no previous history of thromboembolism, the use of our exclusion criteria during TEE enabled stratification of a low-risk population for immediate ECV, which was accomplished effectively and safely in 2/3 of the pts. This strategy is associated with early symptomatic improvement, and may contribute to maintenance of sinus rhythm after one month, which was significantly better than in the pts who had prolonged therapy with warfarin before ECV, despite the differences found in age and left ventricular function.     

Dilating guide wire: use of a new ultra-low-profile percutaneous transluminal coronary angioplasty system

The following case reports represent two examples using the newly released Dilating Guide Wire. The balloon-wire system is specifically designed to be used as a steerable percutaneous transluminal coronary angioplasty (PTCA) guide wire. It can be utilized as a predilatation device in combination with a standard PTCA dilating balloon or as a free-standing dilatation catheter. As applied to the following situations, predilatation proved to be an effective time- and step-saving approach when confronting severely stenosed coronary artery lesions.     

Long-term results of laryngotracheal resection for benign stenosis.

OBJECTIVE: We report the long-term results of our 16-year experience with laryngotracheal resection for benign stenosis. METHODS: Between 1991 and 2006, 35 consecutive patients (19 males, 16 females) underwent laryngotracheal resection for subglottic postintubation (32) or idiopathic (3) stenosis. Mean age was 43 years (range 14-71). At the time of surgery 13 patients presented with tracheostomy and 7 with a Dumon stent. The upper limit of the stenosis was from 0.6 to 1.5 cm below the vocal cords. The length of airway resection ranged between 1.5 and 6 cm. Suprahyoid release was performed in two patients and pericardial release in one. Nine patients had psychiatric and/or neurological post-coma disorders. Mean follow-up is over 5 years (61 months; range 3-194). RESULTS: There was no perioperative mortality. Thirty patients (85.7%) had excellent or good anatomic and functional results. Four patients (11.4%) presented restenosis at a distance of 25-110 days from the operation. Restenosis was successfully treated by endoscopic procedures in all four patients. One patient (2.9%) presented anastomotic dehiscence that required temporary tracheostomy closed after 1 year with no sequelae. Three patients (8.4%) had wound infection. Long-term follow-up was uneventful also in patients who had early complications. CONCLUSIONS: Long-term follow-up confirms that laryngotracheal resection is the definitive curative treatment for benign subglottic stenosis. Surgical complications can be successfully managed by non-operative procedures. Despite the occurrence of early complications, excellent and stable results can still be obtained at long term.     

Murder, insanity, and medical expert witnesses.

Recent advances in the ability to study brain anatomy and function and attempts to link these findings with human behavior have captured the attention of the legal system. This had led to the increasing use of the "neurological defense" to support a plea of not guilty by reason of insanity. This article explores the history of the insanity defense and explores the role of the medical expert witnesses in integrating clinical and laboratory findings, eg, computed tomographic scans, magnetic resonance scans, and single-photon emission computed tomographic scans. Three cases involving murder and brain dysfunction are discussed: the first case involves a subarachnoid hemorrhage resulting in visual perceptual and memory impairment; the second case, a diagnosis of Alzheimer's disease; and the third case, the controverted diagnosis of complex partial seizures in a serial killer.     

CD16 surface molecules regulate the cytolytic function of CD3CD16+ human natural killer cells

Monoclonal (IgG) antibodies (MAbs) directed to CD16 molecules efficiently induced lysis of the IgG-binding P815 target cells. A similar effect was observed with selected anti-CD2 MAbs. While combinations of 2 appropriate anti-CD2 MAbs were required for induction of T lymphocyte activation, single stimulatory anti-CD2 MAbs were sufficient for inducing cytolytic function in CD3- CD16+ lymphocytes. In order to study possible regulatory mechanisms existing in the process of activation and induction of the cytolytic machinery of CD3- CD16+ effector cells, we utilized the anti-CD16 OKNK MAb. Being of IgM isotype, the OKNK MAb does not allow cross-linking between CD3- D16+ lymphocytes and target cells. Pre-treatment of effector cells with OKNK MAb sharply inhibited the target cell lysis induced by either anti-CD16 (IgG) MAbs or stimulatory anti-CD2 MAb. Moreover, a strong inhibitory activity of PHA-induced target cell lysis and even of "spontaneous" lysis (at high effector:target ratio) was observed. In contrast, in CD3+ CD16+ clones, OKNK MAb selectively inhibited the cell triggering induced by anti-CD16 MAbs (but not by anti-CD3, anti-CD2 MAbs or PHA). Our data indicate that CD16 receptor molecules expressed by CD3- CD16+ lymphocytes down-regulate cell responses to anti-CD2 MAbs or PHA, and then exert a regulatory role in the cytolytic function of these cells.     

Self class I molecules protect normal cells from lysis mediated by autologous natural killer cells

The surface expression of given HLA class I alleles protects target cells from lysis mediated by natural killer (NK) clones specific for these (or related) alleles. We could define two groups of NK clones specifically recognizing either Cw4 and related C alleles (“group 1”) or Cw3 and related C alleles (“group 2”), respectively. Monoclonal antibodies (mAb) to class I molecules should interfere with the interaction between NK receptors and class I molecules, thus resulting in lysis of protected target cells. However, none of the numerous available mAb to class I molecules had this effect. Therefore, we attempted to select new mAb on the basis of their ability to induce lysis of Cw4- or Cw3-protected lymphoblastoid cell lines by “group 1” or “group 2” NK clones, respectively. From mice immunized with phytohemagglutinin (PHA)-activated lymphocytes expressing either Cw3 or Cw4 alleles, two mAb were selected, the 6A4 (IgG1) and the A6-136 (IgM), on the basis of their ability to induce lysis of protected target cell. Both mAb immunoprecipitated molecules which, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gave two bands of 45 and 12 kDa, typical of the class I heavy chain and β2 microglobulin, respectively. It has been proposed (but not proven), that self major histocompatibility complex class I molecules protect normal cells from autologous NK cell lysis. Thus, we used the 6A4 and A6-136 mAb to assess this possibility directly. Cw4-specific (“group 1”) and Cw3-specific (“group 2”) NK clones were isolated from donors expressing the corresponding (or related) protective C alleles. None of these clones lysed autologous PHA-induced blasts, used as target cells. However, addition of the F(ab′)₂ of 6A4 mAb or the A6-136 mAb resulted in lysis of autologous target cells by “group 1” or “group 2” NK clones, respectively. These data provide direct evidence that the expression of class I molecules protects normal cells from lysis by autologous NK cells.