Monomeric M2e antigen in VesiVax® liposomes stimulates protection against type a strains of influenza comparable to liposomes with multimeric forms of M2e.

Given the interest in the ectodomain of the matrix 2 (M2e) channel protein as a target for development of a universal influenza vaccine, we examined the role of the antigen configuration of M2e in generating a protective immune response. A series of M2e mutations and a truncated M2e segment were prepared as a means of controlling the formation of monomer, dimer, and higher order multimeric forms of M2e. Each of these M2e peptides was incorporated into a liposome-based vaccine technology platform previously shown to stimulate a protective response to influenza A infection using M2e as a mixture of monomers, dimers and multimers (L-M2e1-HD/MPL). Our results using these modified forms of M2e produced 90-100% survival following lethal challenge with H1N1 (A/PR/8/34) in both inbred BALB/c and outbred Swiss Webster mice vaccinated with a truncated monomeric form of the M2 protein, M2e1-15 in liposomes. These observations show that a tetrameric configuration is not required to elicit significant protection when the M2e antigen is formulated in immunogenic liposomes and further, that the first 15 amino acids of M2e likely play a primary role in providing the protective immune response.

Diagnostic and prognostic significance of the alternatively spliced ACTN4 variant in high-grade neuroendocrine pulmonary tumours.

BACKGROUND: High-grade neuroendocrine tumours (HGNTs) of the lung manifest a wide spectrum of clinical behaviour, but no method for predicting their outcome has been established. MATERIALS AND METHODS: We newly established a monoclonal antibody specifically recognizing the product of the alternatively spliced ACTN4 transcript (namely, variant actinin-4), and used it to examine the expression of variant actinin-4 immunohistochemically in a total of 609 surgical specimens of various histological subtypes of lung cancer. RESULTS: Variant actinin-4 was expressed in 55% (96/176) of HGNTs, but in only 0.8% (3/378) of non-neuroendocrine (NE) lung cancers. The expression of variant actinin-4 was significantly associated with poorer overall survival in HGNT patients (P=0.00021, log-rank test). Multivariate analysis using the Cox proportional hazards model showed that the expression of variant actinin-4 was the most significant independent negative predictor of survival in HGNT patients (hazard ratio (HR), 2.15; P=0.00113) after the presence of lymph node metastasis (HR, 2.25; P=0.00023). CONCLUSIONS: The expression of variant actinin-4 is an independent prognostic factor for patients with HGNTs. This protein has a high affinity for filamentous actin polymers and likely promotes aggressive behaviour of cancer cells. The present clinical findings clearly support this notion.

Liposomal gD ectodomain (gD1-306) vaccine protects against HSV2 genital or rectal infection of female and male mice.

Herpes simplex virus type 2 (HSV2) is the most common causative agent of genital herpes, with infection rates as high as 1 in 6 adults. The present studies were done to evaluate the efficacy of a liposomal HSV2 gD(1-306) vaccine (L-gD(1-306)-HD) in an acute murine HSV2 infection model of intravaginal (female) or intrarectal (male or female) challenge. Two doses of L-gD(1-306)-HD containing 60 microg gD(1-306)-HD and 15 microg monophosphoryl lipid A (MPL) per dose provided protection against HSV2 intravaginal challenge (86-100% survival, P< or =0.0003 vs. control liposomes; P=0.06 vs. L-gD(1-306)-HD without MPL). Both male and female mice (BALB/c and C57BL/6) immunized with L-gD(1-306)-HD/MPL were significantly protected against HSV2 intrarectal challenge, with higher survival rates compared to controls (71-100%, P< or =0.007). L-gD(1-306)-HD/MPL also provided increased survival when compared to a liposomal peptide vaccine, L-gD(264-285)-HD/MPL (male BALB/c, P

Surgical treatment of late developmental displacement of the hip. Results after 33 years.

The outcome of displaced hips treated by Somerville and Scott's method was assessed after more than 25 years. A total of 147 patients (191 displaced hips) was reviewed which represented an overall follow-up of 65.6%. The median age at the index operation was two years. During the first five years, 25 (13%) hips showed signs of avascular change. The late development of valgus angulation of the neck, after ten years, was seen in 69 (36%) hips. Further operations were frequently necessary. Moderate to severe osteoarthritis developed at a young age in 40% of the hips. Total hip replacement or arthrodesis was necessary in 27 (14%) hips at a mean age of 36.5 years. Risk factors identified were high dislocation, open reduction, and age at the original operation. Two groups of patients were compared according to outcome. All the radiographic indices were different between the two groups after ten years, but most were similar before. It takes a generation to establish the prognosis, although some early indicators may help to predict outcome.

[The efficacy of function water (electrolyzed strong acid solution) on open heart surgery; postoperative mediastinitis due to methicillin-resistant Staphylococcus aureus].

Methicillin-resistant Staphylococcus aureus (MRSA) infection after cardiac surgery has recently increased. We compared the anti-inflammatory effect of an electrolyzed strong acid solution and a warm saline solution in patients with open heart surgery. These solutions were used for mediastinal irrigation before closing the sternum. Group A patients were irrigated by a warm saline solution, and group B patients were irrigated by an electrolyzed strong acid solution, administration of this water is safe, feasible, and easy for the prevention of MRSA infection. Postoperative infection was significantly decreased in the group B as compared in the group A. An electrolyzed strong acid solution may be effective on postoperative infection, particularly MRSA infection following open heart surgery.

[Successful treatment for tachyarrhythmia with ultra short acting beta-blocker during beating coronary artery bypass grafting; report of a case].

A 62-year-old man with supraventricular/ventricular tachycardia associated with myocardial infarction developed tachycardia during beating coronary artery bypass grafting (CABG). Intravenous administration of an ultra short acting beta-blocker, landiolol hydrochloride, controlled heart rate and improved tachyarrhythmia without significant change of blood pressure. Landiolol hydrochloride is effective and useful for the treatment of tachyarrhythmia during beating CABG.

Visual task performance in blind humans with retinal prosthetic implants.

A prototype electronic retinal prosthesis has been tested in three subjects. The system features an implanted retinal stimulator and an external system for image acquisition, processing, and telemetry. The subjects in general performed better than chance on psychophysical tests involving object detection, object counting, object discrimination, and direction of movement.

Closed reduction of developmental dislocation of the hip by prolonged traction.

The efficacy of traction before an attempted closed reduction for patients with developmental dislocation of the hip remains controversial. We treated 55 children (62 dislocations of the hip) by preliminary, prolonged traction for a mean of eight weeks. All were followed up for at least two years in order to observe the development of any avascular changes within the femoral head. Of the 55 children, 27 (31 dislocations) were followed up until they were over six years of age. Fifty-seven of the 62 hips (92%) showed a successful closed reduction. Only one had radiological evidence of avascular necrosis of the femoral head. Of the 31 hips which were followed up to over six years of age, 15 (48%) showed residual subluxation. Our method of prolonged preliminary traction leads to a high rate of successful closed reduction, a low incidence of avascular necrosis and a reduced need for secondary operations.

Atrial flutter after coronary artery bypass grafting: proposed mechanism as illuminated by independent predictors.

OBJECTIVE: The aim of this study was to evaluate the cause and treatment of atrial flutter after coronary artery bypass grafting (CABG). METHODS: Between July 1999 and July 2000, 96 CABGs were performed at the Cardiovascular Center of Aichi Prefectural Owari Hospital. We compared two groups of patients: those with atrial flutter after CABG (group A) and those without atrial flutter (group B). RESULTS: We treated the atrial flutter group with medication, electrical defibrillation, and overdrive pacing. Six of these cases later required radiofrequency catheter ablation (RFCA). These were all with common-type atrial flutter, treated by RFCA for the posterior isthmus, without difficulty. The frequency of direct cannulation to the coronary sinus for retrograde cardioplegia was significantly higher in group A. CONCLUSIONS: Incidence of atrial flutter after CABG was influenced by surgical damage arising from direct cannulation to the coronary sinus for retrograde cardioplegia. Preoperative viability of the myocardium (in addition to good myocardial protection during surgery) also seems to be associated with an increased likelihood of postoperative atrial flutter.

Avascular necrosis associated with fractures of the femoral neck in children: histological evaluation of core biopsies of the femoral head.

There is no well-documented effective treatment for avascular necrosis following fractures of the femoral neck in children. Six children who suffered avascular necrosis following these fractures were treated with a long period of non-weight bearing. We tried to predict the advisable period of non-weight bearing by histological finding on core biopsy taken from the femoral head and present long-term follow-up results. The time interval for the biopsy ranged from 4 to 21 months after injury. Two specimens obtained within 1 year after injury showed total necrosis. The other four specimens taken more than 1 year after injury showed partial repair. Two specimens obtained from patients who had minimally displaced fractures also revealed necrotic tissue. Four patients were initially placed non-weight bearing for over 1 year. Two patients started weight bearing immediately after surgery, and late segmental collapse occurred within 1 year. They were then placed non-weight bearing for a further period in excess of 1 year. All patients, including those who had severely displaced fractures, avoided severe collapse of the femoral head. To avoid severe collapse of the femoral head due to avascular necrosis after pediatric femoral neck fractures, a long period of non-weight bearing of at least 1 year may be recommended treatment.

Visual and electrical evoked response recorded from subdural electrodes implanted above the visual cortex in normal dogs under two methods of anesthesia.

Sensitive methods are required to record electrical evoked potentials over the visual cortex to evaluate the efficacy and safety of a retinal prosthesis before it can be implanted on the retinal surface of patients afflicted by outer retinal diseases. This study was designed to examine subdural electrodes as a mean to evaluate cortical evoked potentials in response to light and electrical stimulation of the retina in three dogs under two methods of anesthesia-halothane and propofol. Results showed that subdural electrodes could be stabilized over the visual cortex for several (3-5) months, and that they were 6.95 times more sensitive than subdermal electrodes in recording cortical visual evoked potentials (VEPs) and 4.31 times more sensitive in recording cortical electrical evoked potentials under both methods of anesthesia. The waveforms' shape changed for each electrode in the subdural array during 6/6 (100%) and 20/38 (52%) multi-channel recording sessions under halothane and propofol, respectively. This change could point to a cortical retinotopic organization versus hierarchical organization of different cortical areas for a given retinal stimulus. In summary, subdural electrodes show promising results for recording visual and electrical evoked responses (EERs) and thus for evaluation of the retinal prosthesis.

Detection of genes expressed in primary colon cancers by in situ hybridisation: overexpression of RACK 1.

AIMS: The isolation of various genes that are expressed in a region specific manner is considered useful for research in molecular pathology. In situ hybridisation (ISH) was used in a screening procedure to isolate these genes efficiently, using colon cancer as a model. METHODS: Suppression subtractive hybridisation (SSH) between colon cancer tissue samples and corresponding non-cancerous tissues was performed. Genes showing high expression in the cancers were selected using macro-DNA array analysis. As a final screening procedure, conventional ISH was performed to isolate genes expressed specifically in colon cancers. RESULTS: Sixty nine clones were selected by SSH and macro-DNA array analyses. These clones were then analysed by ISH to examine their expression patterns. ISH screening revealed that all the clones screened showed more intense signals in colon cancers than in non-cancerous tissues. Among them, RACK 1, which is a protein kinase C receptor and a homologue of the G protein beta subunit, was expressed intensely in colon cancer cells. RACK 1 expression was evaluated in multiple samples by ISH, and the results confirmed that RACK 1 was universally overexpressed in cells of all 11 colon cancers examined. CONCLUSIONS: Many genes, including RACK 1, expressed in colon cancer cells can be isolated efficiently by this method, and their precise expression pattern can be evaluated. These results indicate that ISH is an excellent technique for systemic screening of genes expressed in a region specific manner.

Reliability of the Severin classification in the assessment of developmental dysplasia of the hip.

This study was undertaken to investigate the reliability of Severin's classification at various ages, and to determine whether the reliability is improved by careful measurement rather than subjective assessment. The radiographs taken at ages 6, 10 and 16 years of 20 randomly selected patients treated for developmental dysplasia of the hip were graded by six observers on two separate occasions using parameters measured according to Severin's criteria. In addition, four of these observers regraded the same radiographs using subjective assessment without measurements being made on two other separate occasions. Agreements between and within observers were evaluated using the weighted Cohen's kappa statistic for each age group. Intraobserver reliability was good, there being a close association between the measured and the subjectively observed ratings. This accords with the subjective nature of this classification. The interobserver reliability was found to be poor although it improved when direct measurements were made. Overall agreement between observers improves as patient age increases. It is concluded that comparisons between different observers using the Severin classification system are not reliable. However, a single investigator comparing treatment modalities in the same study allowing for individual bias in assessing deformity and subluxation would produce reliable results.

Diplopia after limited macular translocation surgery.

PURPOSE: Full macular translocation surgery relocates the fovea away from choroidal neovascularization, inducing significant postoperative torsional diplopia. In "limited macular translocation," a saline-induced retinal detachment is followed by scleral imbrication with mattress sutures and spontaneous retinal reattachment. In this study, diplopia was characterized in patients treated with limited macular translocation. METHODS: Two surgeons performed retinal translocation surgery on 250 patients over an 18-month time span. The extent and direction of the retinal translocation, and the amount and location of scleral imbrication, were recorded. All patients complaining of diplopia were referred for ocular motility evaluation and treatment. RESULTS: Thirteen (5.2%) patients complained of occasional or constant diplopia. Imbricating sutures were placed supero-temporally in all cases. Inferior foveal translocation ranged from 200 to 2115 microm (median, 1750 microm). Visual acuity ranged from 20/40 to 20/400 in the operated eye. Prism-and-cover testing underestimated the strabismus when compared with subjective testing. In 3 patients, there was no shift on alternate-cover testing despite binocular diplopia. Excyclotorsion ranged from 0 degrees to 16 degrees. Diplopia resolved in 10 cases with prism; 3 required an occlusive filter for distortion or aniseikonia. One patient underwent successful strabismus surgery to eliminate dependence on prism glasses. CONCLUSIONS: Limited macular translocation only rarely produces symptomatic diplopia. Suprisingly, traditional prism-and-cover testing does not reliably quantify the misalignment. This may result from the combination of a persistent macular scotoma and a repositioned fovea relative to the peripheral retina. Prism therapy is generally satisfactory in the absence of retinal distortion or aniseikonia.

Effective nasal limited macular translocation.

PURPOSE: To describe a case of effective foveal displacement toward the optic disk (nasal limited macular translocation) in a patient with a large subfoveal choroidal neovascularization secondary to age-related macular degeneration. METHODS: Case report. RESULTS: A 77-year-old white man presented with decreased vision of 20/400 due to subfoveal predominantly occult CNV secondary to age-related macular degeneration in the left eye. The CNV, measuring 9 Macular Photocoagulation Study disk areas in size, was centered temporally relative to the fovea with a minimum desired translocation of 650 microm for nasal macular translocation. The patient underwent nasal LMT with punctate retinotomy and temporal chorioscleral infolding, followed by postoperative head-positioning on his right side. Effective LMT was achieved with a postoperative nasal foveal displacement of 1400 microm. The entire CNV was ablated with laser photocoagulation postoperatively. His vision improved to 20/40 6 months postoperatively. CONCLUSION: Nasal LMT is feasible and may be considered in patients with subfoveal CNV centered temporally relative to the fovea.

Transient formed visual hallucinations following macular translocation for subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: To report the occurrence of transient formed visual hallucinations following macular translocation. METHODS: Two case reports. RESULTS: Two white women aged 84 and 83 years with bilateral age-related macular degeneration and unilateral subfoveal choroidal neovascularization underwent macular translocation with punctate retinotomy (limited macular translocation) and chorioscleral infolding in the eye with neovascularization. They complained of formed visual hallucinations which began within 24 hours following macular translocation and ceased 7 and 3 days postoperatively, respectively. Their symptoms occurred in the presence of normal cognition, orientation and insight, were not associated with other psychiatric symptoms, and were characteristic of Charles Bonnet syndrome (CBS). CONCLUSION: The temporary deliberate retinal detachment and/or poor vision following macular translocation may be associated with postoperative CBS, and this report extends the spectrum of conditions associated with CBS.

Macular translocation: unifying concepts, terminology, and classification.

PURPOSE: To describe some unifying concepts, terminology, and classification of macular translocation so as to facilitate communication within the scientific community. METHODS: A panel of ophthalmologists with expertise in macular translocation reviewed available data and developed some unifying concepts, terminology, and classification of macular translocation. RESULTS: Macular translocation may be defined as any surgery that has a primary goal of relocating the central neurosensory retina or fovea intraoperatively or postoperatively specifically for the management of macular disease. It may be classified according to the size of the retinotomy and, where applicable, the technique of chorioscleral shortening used. The direction of macular translocation is denoted by the movement of the neurosensory macula relative to the underlying tissues. Effective macular translocation may be defined as successful intraoperative or postoperative relocation of the fovea overlying a subfoveal lesion to an area outside the border of the lesion. The concepts of minimum desired translocation and median postoperative foveal displacement can give some useful idea of the likelihood of effective macular translocation before surgery. CONCLUSIONS: Use of a common standardized terminology for macular translocation will facilitate communication within the scientific community and enhance further research in this area. However, the definitions, terms, classification, and concepts concerning macular translocation are likely to continue to evolve as macular translocation undergoes further modifications and refinements.