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[Spontaneous necrosis of the femoral condyle--new findings in T2-weighted spin-echo sequences and gradient-echo studies].

The spontaneous necrosis of the femur condyles might cause diagnostic problems because clinical symptoms precede the radiologic changes on conventional x-ray. MRI offers an early detection of the necrosis of the femur condyle like bone necrosis of other localisation. Nine patients were examined by T1- and T2-weighted spin echo- and by T2*-weighted gradient echo sequences. All patients had reduced signal intensity in the subchondral bone marrow on T1-w SE sequences. In three patients new findings were observed on T2-w SE and gradient echoes respectively. These findings allow better understanding in the underlying pathologic-anatomical changes.

Aged↗

HLA-A0201 positive pancreatic cell lines: new findings and discrepancies.

Pancreatic cancer is being pursued as an immunotherapy target using antigen-specific vaccine approaches activating CD8(+) CTL and CD4(+) T-helper cells. CD8(+) CTL exert their anti-tumor effects in an HLA-restricted manner and only tumor cells carrying a matched HLA class I sub-type are targets for antigen-specific CTL. In the process of characterizing CD8(+) T cell responses against pancreatic cancer, we screened a number of human pancreatic tumor cell lines for HLA-A0201 positive (HLA-A2(+)) cell lines to be used in the evaluation of CTL function. This analysis revealed some new findings and discrepancies in the literature on the HLA sub-type of some commonly used pancreatic cell lines. We found that Capan-1 cells, originally reported to be HLA-A0201(+), actually only express HLA-A010101 and HLA-A300101 and were targets for HLA-A0201-restricted CTL only after transduction with an HLA-A0201-expressing lentivirus. Panc-1 cells were found to be HLA-A0201 positive, in agreement with published reports, while CF-Pac-1 cells were found to express both HLA-A020101 and HLA-A030101. We also found a normal human pancreatic ductal epithelial cell line, HPDE, to be HLA-A0201 positive. Our findings were verified with two different sequence-based typing methods, antibody staining followed by flow cytometry analysis, and functional analysis using an HLA-A0201-restricted peptide-specific T cell response.

Base Sequence↗

Moebius syndrome: the new finding of hypertrophy of the coronoid process.

The first detailed description of congenital facial paralysis was reported by Moebius in 1888. It is characterized by either unilateral or bilateral paralysis of the facial muscles and an associated abducens palsy. The present report is of two patients with Moebius syndrome, who were also diagnosed with trismus at birth. Each patient also demonstrated bilateral hypertrophy of the coronoid process of the mandible. In effect, the zygoma obstructed the excursion of the mandible because of a "coronoid block." A three-dimensional computed tomography scan demonstrated normal temporomandibular joints but bilateral hypertrophy of the coronoid processes and micrognathia. Both patients demonstrated less than 10 mm of oral excursion. Bilateral coronoidectomies were performed through an intraoral approach. The oral excursions after surgery increased to at least 20 mm. In each of these patients, the coronoid process was enlarged relative to the zygoma, which was of normal size and configuration. The trismus was associated with blocking of the coronoid by the anterior zygoma, preventing open or full excursion of the hypoplastic mandibles. Moebius syndrome can have a variable presentation at birth. In two patients, the authors describe a new finding of hypertrophy of the coronoid process and trismus secondary to obstruction of the coronoid by the hypertrophic zygomas during oral excursions. Each patient is described, and a review of the literature is discussed.

Abnormalities, Multiple↗

Lead neuropathy. 1) Morphometry, nerve conduction, and choline acetyltransferase transport: new finding of endoneurial edema associated with segmental demyelination.

Morphometric and pathologic studies along the length of the peripheral nervous system were obtained in groups of rats fed 4% lead carbonate for 3 and 6 months and in match-fed controls. The number and diameter histograms of L6 cytons of spinal ganglia and of myelinated fibers of proximal and distal portions of peroneal and sural nerve were not significantly different from the control groups. On the other hand, segmental demyelination occurred approximately as frequently in proximal as in distal parts of nerves. At 3 months approximately 1/3 of teased myelinated fibers showed changes of segmental demyelination (Condition C), or of remyelination after segmental demyelination (Condition F) or of both segmental demyelination and of remyelination (Condition D), while at 6 months more than 4/5ths of fibers showed these changes. As expected, regression lines of axonal area on number of lamellae of myelin, were less steep in nerves of rats fed on lead for 6 months as compared to controls. Axonal transport of choline acetyltransferase in lead neuropathy did not differ from that in control rats. As expected from the studies of others, conduction velocity of myelinated fibers of caudal nerve were low. A new finding was the often quite striking increase of transverse fascicular area of peripheral nerves. This was due to edema which appeared to develop at about the time of onset os segmental demyelination. Although the edema may be an epiphenomenon, it could be an important observation bearing on the development of lead neuropathy. It would be important to know next whether or not the blood nerve barrier is altered in lead neuropathy.

Animals↗

[New findings on the structure of normal blood vessels according to rastral electron microscopy data].

Under rastral electron microscopic study were the internal surface of the aorta of 48 humans from 2 weeks to 75 years of age, the large cutaneous vein of the shank in 14 humans from 12 to 58 years of age, the femoral artery and vein in 8 mongrel dogs. It was established that the internal surface of blood vessels was not a smooth-walled cylinder but a structure with a complicated relief. The microrelief of the internal surface is formed of subendothelially disposed collagenous-elastic formations and configuration of the endothelial cells cytoplasm. It consists of folds of the first and second order, which make the internal square surface of the blood vessels 3-4 times larger. There are some peculiar features in the structure of the internal surface of arteries and veins which, to the author's opinion, might be due to differences in the structure of collagenous-elastic constructions of the wall of these vessels. Certain developmental changes of the internal surface of the aorta are described. The authors believe that the special microrelief of the internal surface of blood vessels is of particular significance for hemodynamics, the exchange of substances between the blood and vascular wall and for the thrombus formation. These new findings should be presented in manuals and textbooks on anatomy, histology and embryology.

Adolescent↗

New findings on the structure-phototoxicity relationship and photostability of fluoroquinolones with various substituents at position 1.

The present study examined the phototoxicities of a series of 7-(3-aminopyrrolidinyl) quinolones containing various substituents at position 1 (in which the substituent at R8 is a hydrogen or a halogen) by use of a mouse model. For the 7-(3-aminopyrrolidinyl) quinolones with a halogen atom at position 8, well-known substituent groups such as a cyclopropyl, an ethyl, or a difluorophenyl at position 1 were found to be responsible for severe phototoxicity. However, when an aminodifluorophenyl or an isoxazolyl group was placed at position 1, even 8-halogeno quinolones were found to be mildly phototoxic. This is the first report of 8-halogeno quinolones that are not severely phototoxic. Two structurally similar 8-chloro quinolones (the 1-aminodifluorophenyl 8-chloro quinolone and the 1-difluorophenyl 8-chloro quinolone) were investigated further. The former was mildly phototoxic; the latter was severely phototoxic. We demonstrate that these two 8-chloro quinolones have practically the same areas under the concentration-time curves from 0 to 4 h in auricular tissue, suggesting that the mild phototoxicity is not due to pharmacokinetic instability. The rates of UV photodegradation of these compounds were also measured. We found that these two quinolones photodegrade at similar rates, suggesting that the mild phototoxicity is not attained through increased photostability. In conclusion, the phototoxic potentials of fluoroquinolones are influenced not only by the substituent at position 8 but also by that at position 1 (a new finding from this study). We also discovered a mildly phototoxic 8-chloro quinolone which did not have increased photostability.

Animals↗

New findings in phase transitions of spinel Li1.07Mn1.93O4-delta studied by transmission electron microscopy.

Phase transitions and the related phase identifications at different temperatures for spinel Li(1.07)Mn(1.93)O(4-delta) crystals have been studied by transmission electron microscopy. The preliminary results clearly show the existence of at least two types of low-temperature phase: monoclinic and orthorhombic. Oxygen deficiency may raise the phase-transition temperature for the high-temperature (HT) cubic to low-temperature (LT) tetragonal, monoclinic, or orthorhombic phases. When the oxygen deficiency delta is very close to zero, the transition temperature is below room temperature (RT). Therefore, only the HT cubic spinel is observed at RT. When delta=0.182, the transition temperature is higher than RT, so the structures of the LT phases can be studied at RT. This study reveals the structural relationships between the LT phase and the HT phase. These relationships can be summarized as follows: (1) Two orthogonal cubic [440](Cubic)(*) and [440](Cubic)(*) reciprocal vectors are divided into two parts by {220} and {220} super reflections, respectively. This situation resembles the structures caused by correlated tilting and/or distortion of the octahedra in perovskites. (2) One of the cubic <440>Cubic(*) reciprocal vectors is divided into three parts by weak super-reflections. This situation resembles the modulated structure caused by the charge- and orbital-ordering in the perovskite La(1/3)Ca(2/3)MnO(3) of the space group Pnma. (3) One of the cubic <440>(Cubic)(*) reciprocal vectors, e.g. [440](Cubic)(*), is divided into three parts by stronger super-reflections, at the same time some strong reflections of the cubic spinel, e.g. (111)(Cubic)=(320)(Ortho)/2 disappear, indicating that there is a phase transition containing atomic movement. Items (2) and (3) are new findings in the present work.

Journal Article↗

Magnetic resonance imaging in 300 cases of placenta accreta: surgical correlation of new findings.

BACKGROUND: To establish the usefulness of placental magnetic resonance in patients with a diagnosis of placenta accreta through the correlation of diagnostic images and surgical findings. METHODS: Three hundred patients with ultrasound signs of placenta accreta were studied. In 252 patients, magnetic resonance imaging (MRI) was performed in a closed 1.5 T-resonator, and in 48 patients, open 0.23 T-set was used. T1 and T2 slices in the three planes were performed, and placental invasion was classified in depth levels and topographic areas in relation to the posterior vesical wall. The final degree of invasion was established during surgery according to clinical and anatomical criteria. The information obtained with MRI was analyzed, thus establishing its relevance to the change in surgical technique. RESULTS: In 286 cases, MRI provided topographic information of placental invasion, and in 90 patients, it modified invasion levels. Undiagnosed parametrium extent was determined in 11 cases, and 11 other cases were reclassified as placenta previa. Changes in conduct following MRI study included: recommendation to modify surgery date at week 35, recommendation for prophylactic ureteral catheterization, recommendation for the use of intraoperative blood salvage, possibility of approach through Pfannenstiel incision, probability of segmental myometrial approach, probability of aortic clamping, need to investigate subclinical disseminated intravascular coagulation, need of posterior pelvic dissection, and the possibility of uterine conservation. CONCLUSIONS: Magnetic resonance imaging turned out to be essential to define the topography and area of placental invasion. New findings modified surgical tactic and technique, allowing a reduction in historical morbidity and a significant increase in conservative surgeries.

Adolescent↗

Synovial fluid features and their relations to osteoarthritis severity: new findings from sequential studies.

OBJECTIVE: Many factors are involved in the osteoarthritic process. It is not yet known which are initiators, promoters or simply results. Thus, we have evaluated some of those potentially important factors in osteoarthritis (OA) as observed sequentially for the first time in synovial fluids. DESIGN: Synovial fluids (SF) obtained between 1992-2002 were all routinely evaluated for gross appearance, leukocyte counts and microscopic examination of wet drop preparations. We used regular and polarized light and alizarin red s stains. We separated out all OA patients, then we looked for patients who had more than two synovial fluid analyses to get sequential information. Time between first and final aspiration ranged from 2 to 7 (3.6+/-1.6) years and number of analyses per patients from 3 to 6 (3.3+/-0.7). We related synovial fluid crystals, fibrils and white blood cell count (WBC) to age, sex, disease duration and radiographic assessment according to the Kellgren-Lawrence radiographic rating system. RESULTS: Of 4523 synovial fluid examinations, we found 855 in patients with knee OA; 330 patients with adequate clinical details for comparison were included in our study. Twenty-six patients (one woman and 25 men) had sequentially examined SF. We found that 52% of those OA patients with effusions studied had crystals identified in their synovial fluid. Twenty-one percent of all the patients had CPPD crystals, 47% had hydroxyapatite, also called basic calcium phosphate (BCP) crystals and 16% had both types of crystals. Microscopically identifiable fibrils were found in 60% of SF. In sequentially examined patients, CPPD crystals and apatite (BCP) were found in 19% and 23%, respectively, at the first aspiration and, in 34% and 58% at the final aspiration. Fibrils were seen in 54% at first examination and 85% later. Apatite and fibrils showed more significant correlation with time (r=0.51,r =0.92) than did CPPD (r=0.32). SF WBC correlated only with CPPD crystals and did not increase with OA duration or severity. CPPD, apatite and fibrils all correlated with higher radiographic grades of OA. CONCLUSIONS: As noted before CPPD and apatite crystals were more common in patients with more severe OA. New findings are that our sequential cases showed that there were some patients with no crystals at onset but that crystals appeared with progression of the disease. Fibril presence in SF also correlated with progression of the disease.

Aged↗

Bile acid signaling to the nucleus: finding new connections in the transcriptional regulation of metabolic pathways.

Recent findings indicate that the function of metabolically relevant genes is finely regulated at the level of gene transcription. Disturbances of these regulatory pathways often lead to metabolic unbalance and to the onset of socially relevant diseases, i.e. diabetes, metabolic syndrome, atherosclerosis and cardiovascular diseases. The ability of lipid metabolites, such as fatty acids and oxysterols, to signal to cells and tissues and to affect gene transcription by activating specific nuclear receptors has been known since several years. Bile acids have been known in the past as cholesterol end products, purely acting as detergents. Only recently new biological properties of bile acids as signaling molecules have been disclosed and appreciated. In this review, we will describe how bile acids can regulate their own synthesis and other metabolic pathways (i.e. glucose metabolism) by modulating gene transcription through multiple mechanisms. These findings also open new perspectives towards the exploitation of bile acid metabolism as a pharmacological target.

Animals↗

New findings in the chromosome 13 long-arm deletion syndrome and retinoblastoma.

New clinical and pathologic findings in patients with deletion of the long arm of chromosome 13 (13q-) include optic nerve hypoplasia and retinal dysplasia. Fibroblasts derived from patients with a 13q- syndrome with and without retinoblastoma, as well as from familial and sporadic retinoblastoma, are a useful model for the study of genetic susceptibility to the development of spontaneous and radiation-induced cancers. Fibroblasts from patients with hereditary retinoblastoma appear more radiosensitive than fibroblasts from patients with sporadic retinoblastoma or normal control patients.

Abnormalities, Multiple↗

[Diabetic nephropathy: new findings on pathogenesis and therapy].

The authors describe the new factors (genetic, haemodynamic and metabolic) which are involved in the pathogenesis and therapy of diabetic nephropathy. The treatment must be based especially on strict control of glycaemia, decrease in arterial blood pressure, beneficial effect of low-protein diet, reduction of body weight and smoking prevention. The combination of the presented therapeutic procedures can slow down the progression of nephropathy and approximate it to the process of natural ageing.

Diabetes Mellitus↗

[New findings and experiences in the field of malignant hyperthermia].

New publications on malignant hyperthermia (MH), with direct clinical importance, are reported. Since even in the recent past patients have died from MH in spite of therapy with dantrolene, the effectiveness of dantrolene is discussed in particular. Atypical clinical pictures of MH are presented. Special psychiatric syndromes (malignant neuroleptic syndrome and acute febrile catatonia), rhabdomyolysis with myoglobinuria following strenuous exercise or exposure to heat are mentioned, as these disorders appear to be related to MH, in that they are hypermetabolic syndromes implying a muscle membrane dysfunction. The role of slow calcium channel blockers and 5-hydroxytryptamine antagonists as prophylactic or therapeutic agents in MH is discussed. A schedule describing how to diagnose, treat and prevent MH, considering recent advances, is presented.

Anesthesia↗

[Annular pancreas: new findings?].

Four cases of anular pancreas are described and compared with the latest references in the literature. It is considered that new anatomic and surgical findings arising from recent studies permit early presurgical diagnosis and give better results with rational surgery.

Adolescent↗

New classes of antihypertensive drugs and new findings with established agents.

Research on antihypertensive drugs not only provides new information on presently used agents but also leads to the introduction of exciting new compounds. Several important clinical trials involving currently available drugs have been published recently. Angiotensin-converting enzyme inhibitors improved survival in patients with milder degrees of congestive heart failure, which indicates that they have become the cornerstone of treatment for this condition. Angiotensin-converting enzyme inhibitors delayed or prevented the development of diabetic proteinuria (> 200 micrograms/min) in a placebo-controlled randomized trial. Further, enalapril was more effective than metoprolol in reducing the rate of decline in renal function in patients with type I diabetes. Calcium channel blockers protected against acute renal failure in patients after renal transplantation in two separate studies. Calcium channel blockers were shown to promote natriuresis, with negative sodium balance the same as that associated with thiazide diuretics. The voltage-dependent calcium channel has been cloned, and the binding sites of the three classes of calcium channel blockers are now known. beta-Blockers and thiazide diuretics were the drug treatments in the Systolic Hypertension in the Elderly Program trial and in the Swedish Trial in Old Patients with Hypertension study (patients 65 to 85 years). In both investigations, stroke and cardiovascular events were significantly reduced by these conventional inexpensive agents. Clonidine was found to lower blood pressure primarily by its interaction with the imidazole receptor rather than the alpha 2 receptor. Elucidation of the imidazole receptor promises to shed light on physiologic mechanisms as well as lead to the introduction of new agents, such as moxonidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

C-peptide: new findings and therapeutic implications in diabetes.

In contrast to earlier views, new data indicate that proinsulin C-peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. C-peptide in nanomolar concentrations binds specifically to cell membranes, probably to a G-protein coupled receptor. Ca(2+)- and MAP-kinase dependent signalling pathways are activated, resulting in stimulation of Na(+), K(+)-ATPase and endothelial nitric oxide (NO) synthase, two enzyme systems known to be deficient in diabetes. C-peptide may also interact synergistically with insulin signal transduction. Studies in intact animals and in patients with type 1 diabetes have demonstrated multifaceted effects. Thus, C-peptide administration in streptozotocin-diabetic animals results in normalization of diabetes-induced glomerular hyperfiltration, reduction of urinary albumin excretion and diminished glomerular expansion. The former two effects have also been observed in type 1 diabetes patients given C-peptide in replacement dose for up to 3 months. Peripheral nerve function and structure are likewise influenced by C-peptide administration; sensory and motor nerve conduction velocities increase and nerve structural changes are diminished or reversed in diabetic rats. In patients with type 1 diabetes, beneficial effects have been demonstrated on sensory nerve conduction velocity, vibration perception and autonomic nerve function. C-peptide also augments blood flow in several tissues in type 1 diabetes via its stimulation of endothelial NO release, emphasizing a role for C-peptide in maintaining vascular homeostasis. Continued research is needed to establish whether, among the hormones from the islets of Langerhans, C-peptide is the ugly duckling that--nearly 40 years after its discovery--may prove to be an endogenous peptide hormone of importance in the treatment of diabetic long-term complications.

Animals↗