Expression of the fusogenic p14 FAST protein from a replication-defective adenovirus vector does not provide a therapeutic benefit in an immunocompetent mouse model of cancer.

When injected directly into a tumor mass, adenovirus (Ad) vectors only transduce cells immediately along the injection tract. Expression of fusogenic proteins from the Ad vector can lead to syncytium formation, which efficiently spreads the therapeutic effect. Fusogenic proteins can also cause cancer cell death directly, and enhance the release of exosome-like particles containing tumor-associated antigens, which boosts the anti-tumor immune response. In this study, we have examined whether delivery of an early region 1 (E1)-deleted, replication-defective Ad vector encoding the reptilian reovirus p14 fusion-associated small transmembrane (FAST) protein can provide therapeutic efficacy in an immunocompetent mouse tumor model. A high multiplicity of infection of AdFAST is required to induce cell fusion in mouse mammary carcinoma 4T1 cells in vitro, and FAST protein expression caused a modest reduction in cell membrane integrity and metabolic activity compared with cells infected with a control vector. Cells expressing FAST protein released significantly higher quantities of exosomes. In immunocompetent Balb/C mice harboring subcutaneous 4T1 tumors, AdFAST did not induce detectable cancer cell fusion, promote tumor regression or prolong mouse survival compared with untreated mice. This study suggests that in the context of the 4T1 model, Ad-mediated FAST protein expression did not elicit a therapeutic effect.

Spatio-temporal modeling and optimization of a deformable-grating compressor for short high-energy laser pulses.

Monolithic large-scale diffraction gratings are desired to improve the performance of high-energy laser systems and scale them to higher energy, but the surface deformation of these diffraction gratings induce spatio-temporal coupling that is detrimental to the focusability and compressibility of the output pulse. A new deformable-grating-based pulse compressor architecture with optimized actuator positions has been designed to correct the spatial and temporal aberrations induced by grating wavefront errors. An integrated optical model has been built to analyze the effect of grating wavefront errors on the spatio-temporal performance of a compressor based on four deformable gratings. A 1.5-meter deformable grating has been optimized using an integrated finite-element-analysis and genetic-optimization model, leading to spatio-temporal performance similar to the baseline design with ideal gratings.

Optical Tomographic and Magnetic Resonance Imaging of Tumor Growth and Regression in Mice treated with VEGF Blockade.

Small animal imaging systems now allow researchers to non-invasively monitor the progression of diseases in living small animals and study the efficacy of drugs and treatment protocols. Magnetic resonance imaging (MRI) is an established imaging modality capable of obtaining high resolution anatomical images which are sensitive to blood volume, blood flow, and metabolic rate of oxygen. Optical tomography, on the other hand, is an emerging imaging modality, which, while much lower in spatial resolution and insensitive to blood flow, can separate the effects of oxyhemoglobin, deoxyhemoglobin, and blood volume with high temporal resolution. We illustrate how these imaging modalities can supplement each other and cross validation can be performed by applying both modalities to imaging of tumors growth & regression in mice that are treated with a vascular endothelial growth factor (VEGF) antagonist.

Autonomic dysfunction in patients with multiple sclerosis.

The disturbances of autonomic cardiovascular reflexes have already been described in patients with multiple sclerosis (MS). It seems that this disturbances are the result of reflex pathways impairment in the central nervous system. We have tested 28 patients with MS and control group of 21 healthy volunteers using a set of autonomic cardiovascular reflexes tests. In all of patients zones of demyelinization have been discovered with magnetic resonance imaging (MRI). The biggest number of abnormal results was found in respiratory sinus arrhythmia (RSA) test (60.7%) and cortical activation test (35.7%). In 11 patients we found abnormal results in 2 or more tests. Patients with abnormal results in 4 or more tests had clinical impairment of other autonomic functions (urinary bladder regulation). The results of autonomic dysfunction tests show positive correlation to the MRI findings.

Complex disorder of neuronal migration in an infant with possible congenital cytomegalovirus infection.

A ten-months-old girl was evaluated for developmental delay, increased muscle tone and seizures. CT and MRI revealed un uncommon combination of two different manifestations of neuronal migration disturbance: agyria/pachygyria and subcortical laminar heterotopia ("double cortex" syndrome). The occurrence of these two manifestations of neuronal migration dosorders in the same individual is quite unusual. The possible pathogenesis of such a complex disorder could probably be established only by histologic examination of the brain. A positive serologic reaction for cytomegalovirus in the infant at the age of 11 months and in the mother suggested but did not prove the cytomegalovirus infection in early gestation as the cause of the disorder.

Moisture content of vital vs endodontically treated teeth.

The moisture content of vital and endodontically treated teeth was compared in matched pairs of contralateral human teeth extracted for prosthodontic reasons. Samples from each tooth were weighed then placed in an oven to remove the unbound water from the dentin. Weighing was carried out daily until a constant weight was achieved for three days. The moisture content was then calculated and expressed as a percentage of the initial sample weight. It was found that vital dentin had a moisture content of 12.35% whilst dentin from endodontically treated teeth had a moisture content of 12.10%. These results indicated that there was no significant difference in the moisture content between endodontically treated teeth and vital teeth.

Pins for direct restorations.

Self-threading dentine pins permit the retention of large complex direct restorations but there are problems associated with their placement. Strain and crazing of dentine following pin insertion and pulpal and lateral perforations are common. Perforations can be avoided by operator awareness of tooth morphology. Strain and crazing has been found to be minimized by unscrewing the pin slightly after insertion, by using pins with a tap thread, and by using the smallest pin possible. Twist drill form and dulling affects the pin channel shape which in turn influences pin seating. A lack of standardization of pin and twist drill diameter and length has been implicated as the cause of poor pin retention. Manufacturers, in an attempt to standardize the depth of penetration of pins, have incorporated shoulders at the midpoint of the pin, which has met with varying success. More research in the area of limiting pin penetration is necessary, as well as attempts to improve the quality control of pin and twist drill manufacture.

Efficacy of tunnel restorations in the removal of caries.

Tunnel restorations have been advocated as a conservative treatment modality for early carious lesions. However, the question arises as to quantity of dentin that remains within the marginal ridge above the tunnel path. In this experiment, extracted maxillary premolars with early carious lesions were sectioned and photographed. Measurements taken from tracings of the projected slides revealed that no dentin remained within the marginal ridge, irrespective of the direction of the tunnel path. These measurements indicate that the tunnel restoration is not a satisfactory treatment for proximal caries. The position of caries precludes the cutting of a tunnel preparation that leaves sufficient dentin under the marginal ridge, unless the bulk of enamel caries is left untouched.

Salvage, with arthrodesis, in intractable diabetic neuropathic arthropathy of the foot and ankle.

Twenty-nine patients who had diabetic neuropathic arthropathy of the foot and ankle were managed with open reduction and arthrodesis of various joints. Rigid internal fixation was used in all but four patients, who had external fixation. All patients had severe instability or a fixed deformity that precluded successful treatment with bracing. The sites of the fracture-dislocations or the neuropathic dislocations were the ankle in twenty-one patients, the subtalar joint in six, and the transverse tarsal joint in two. The ankle-brachial Doppler indices of these patients averaged 0.86 (range, 0.55 to 1.14). The involved extremities were graded at the initial evaluations according to the Wagner classification system for neuropathic ulceration. The grade was 0 in fourteen patients, I in seven, II in two, and III in six. A tibiocalcaneal arthrodesis was performed after a talectomy in eleven patients; a tibiotalar arthrodesis, in eight; a triple arthrodesis, in six; a pantalar arthrodesis, in two; and a tibiotalocalcaneal arthrodesis, in two. Postoperatively, all patients remained non-weight-bearing and wore a below-the-knee plaster cast for two months. Weight-bearing was then begun with the leg in a total-contact plaster cast, and use of the cast was continued for a mean of five months (range, four to fourteen months). Thereafter, a polypropylene ankle-foot orthosis was used permanently. The most recent evaluation of the patients was performed at an average of forty-two months (range, fourteen to sixty-eight months) after the arthrodesis. There were twenty complications in nineteen of the twenty-nine patients, and there were nine pseudarthroses (six tibiocalcaneal, one tibiotalar, and two talonavicular). However, seven of the pseudarthroses were clinically stable. In these patients, the arthrodesis was performed as an alternative to amputation, and salvage was successful in twenty-seven (93 per cent) of the twenty-nine patients.

Tunnel restorations versus class II restorations for small proximal lesions: a comparison of tooth strengths.

An increased emphasis on the preservation of tooth structure has led to alternative cavity designs for early proximal caries. The tunnel restoration (which preserves the marginal ridge) and a conservative Class II composite resin restoration were compared in vitro for effects on tooth strength with nondestructive and destructive tests. The tunnel restoration, which is generally thought to be the more conservative of the two techniques, was actually more damaging, as shown by the stiffness, load at fracture, and proximity to the pulp.

Pantalar and tibiotalocalcaneal arthrodesis for post-traumatic osteoarthrosis of the ankle and hindfoot.

Twenty-one patients had a unilateral extended arthrodesis of the ankle and hindfoot (a tibiotalocalcaneal procedure in thirteen patients and a pantalar procedure in eight) for post-traumatic osteoarthrosis or deformity, or both. The operation was performed through a transfibular extended lateral approach, and autogenous bone graft and rigid internal fixation was used. A final alignment of 0 to 5 degrees of valgus, 0 to 5 degrees of calcaneus, and external rotation equal to that of the contralateral side was sought. Subjective and objective evaluation, including a personal interview, physical examination, and radiographic and dynamic pedobarographic analysis, was performed at a mean interval of thirty-two months (range, twenty-four to fifty-four months) after the operation. A solid fusion was achieved in eighteen (86 per cent) of the twenty-one patients. There were five malunions (24 per cent) and two superficial wound problems (10 per cent). Of the seventeen patients who were not retired from work, eleven returned to work: nine to an occupation that involved standing and two to a sedentary occupation. Although seventeen (81 per cent) of the twenty-one patients reported that they were much improved, twenty (95 per cent) had some pain, and most benefited from modifications in shoe-wear. Patients who had had a tibiotalocalcaneal arthrodesis were more mobile and functioned at a higher level than those who had had a pantalar arthrodesis. Extended arthrodesis of the ankle and hindfoot is a complex, technically demanding procedure, and should be regarded as a salvage operation capable of producing a satisfactory result and usually providing a reasonable alternative to amputation.

The total-contact cast for management of neuropathic plantar ulceration of the foot.

Seventy-one neuropathic ulcers of the foot in sixty-six patients were treated with the use of a total-contact cast. The ulcers had been present for an average of five months (range, one to twenty-nine months) and were graded according to the Wagner classification; only patients who had grade-I or grade-II lesions were treated with a total-contact cast. The diameter of the ulcer averaged 3.5 centimeters (range, 1.5 to 15.5 centimeters). Sixty-four (90 per cent) of seventy-one ulcers were healed at a mean of five and one-half weeks (range, one to fourteen weeks). A deep infection developed in two patients during treatment. Twenty-two ulcers (31 per cent) recurred within eighteen months after initial healing; nineteen (86 per cent) of them healed after an average of two weeks in a second cast. Recurrent ulceration was usually associated with an underlying fixed deformity or osseous prominence. The total-contact cast provided safe, reliable, and cost-effective treatment for patients who had neuropathic ulcers of the foot.

Tunnel restorations: a review.

Conventional cavity designs are coming under increased scrutiny because of an increased emphasis on preservation of tooth substance. The tunnel restoration when used with glass ionomer, may overcome some of the disadvantages of conventional cavity preparations. Justification for the use of the tunnel restoration is from a limited number of short-term clinical observations and destructive laboratory testing of marginal ridge strength. The technique is not without shortcomings. Long-term clinical and nondestructive laboratory trials examining the strength of teeth with tunnel restorations should be undertaken prior to its acceptance as a replacement for techniques in which the marginal ridge is removed.

[Computer tomography and spinal angiography in the diagnosis of spinal angioma]. / Ein Beitrag der Computertomographie und der spinalen Angiographie zur Diagnostik eines Wirbelangioms.

The computer tomographic and angiographic features of spinal angiomas are described. The authors observed 21 cases and, on the basis of this material, they deal with the clinical features, radiological appearances, disease patterns, forms of treatment, and prognosis. CT and angiography produce a fairly uniform and typical appearance, permitting diagnosis before therapy. Problems in differential diagnosis and errors in interpretation are enumerated.

[Congenital cysts and teratomas in the sacrococcygeal region. Report of 2 cases]. / Kongenitale Zysten und Teratome in der Sakrokokzygealgegend. Darstellung von zwei Fällen.

Developmental abnormalities in the embryo may lead to tumours in the sacro-coccygeal area, so-called sacral cysts and the teratomas (5, 7). At birth they are caudal tumours of variable size covered with thin, stretched skin. Blood vessels can be seen through the skin, particularly in the mid-line. One gains the impression that the stretched skin could burst at any moment. It is assumed that these teratomas derive from the pluripotent cells of Hensen's node and then grow in front of the coccyx (2). They grow and spread in various directions, particularly in a dorsal and caudal direction extra-rectally and, to a lesser extent, into the pelvis in a pre-sacral position. The classification of these tumours depends on their spread. The spread and localisation of these tumours may cause stenosis of elongation of the rectum and displacement of small and large bowel and of the bladder.