Imaging features and clinical significance of perineural spread or extension of head and neck tumors

Perineural spread of head and neck tumors is a form of metastatic disease in which tumor disseminates to noncontiguous regions along the endoneurium or perineurium. Both computed tomography (CT) and magnetic resonance (MR) imaging can help detect perineural spread, although MR imaging is the modality of choice because of its multiplanar capability, its superior soft-tissue contrast, and the decreased amount of artifact from dental hardware. Perineural spread most commonly occurs in adenoid cystic carcinoma and squamous cell carcinoma. Nerve enlargement may lead to foraminal enlargement and, ultimately, to foraminal destruction, findings that are best seen at CT. Extension through the foramen ovale and involvement of the Meckel cave is best seen on coronal T1-weighted MR images, and nerve enhancement is best seen on fat-suppressed T1-weighted MR images. Other radiologic findings include obliteration of fat planes at foraminal openings, neuropathic atrophy, cavernous sinus enlargement, and replacement of the trigeminal subarachnoid cistern with soft tissue. The pathway of perineural tumor spread is predictable with knowledge of the pertinent cranial nerve anatomy; however, patients with radiologically or pathologically proved perineural spread may have normal nerve function at clinical examination. Therefore, it is imperative that the radiologist be familiar with both normal cranial nerve anatomy and the radiologic appearance and assessment of perineural tumor extension.     

A comparison of the hypolipidemic action of probucol at doses of 500 and 1000 mg/day in moderate hyperlipoproteinemia

AIM: Evaluation of effectiveness of hypolipidemic action of probucol in doses 500 and 1000 mg/day and comparison of probucol blood concentrations on the treatment month 3 and 6. MATERIALS AND METHODS: Probucol (Akrikhin, Russia) was given to 41 patients with primary hypercholesterolemia in a dose 500 mg/day. 3 months later the patients were divided into two groups. Group 1 patients exhibited a > 10% decrease in cholesterol levels and continued to take probucol in the dose 500 mg/day. Group 2 patients were crossed over to higher cholesterol dose--up to 1000 mg/day. Lipids levels were measured by enzyme tests, apoproteins--by immunoturbidimetry and immunodiffusion, probucol concentrations--by high-performance liquid chromatography. RESULTS: After 3 months of treatment, cholesterol lowered by 14.3 and 9.2% in groups 1 and 2, respectively. After 6 months, by 19.7 and 12.9%, respectively. Probucol concentrations in blood were higher after 6 months of treatment than after 3 months in both groups. No significant differences existed between the groups by probucol concentrations in 3 and 6 months. CONCLUSION: Hypolipidemic effect of probucol depended on the individual features of lipoproteins metabolic disorders rather than the drug blood concentration. Larger probucol doses fail to reduce cholesterol further.     

ATP-Citrate lyase as a target for hypolipidemic intervention. 2. Synthesis and evaluation of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids and their gamma-lactone prodrugs as inhibitors of the enzyme in vitro and in vivo

A series of (3R,5S)-omega-substituted-3-carboxy-3, 5-dihydroxyalkanoic acids have been synthesized and evaluated as inhibitors of the recombinant human form of ATP-citrate lyase. The best of these have Ki's in the 200-1000 nM range. As the corresponding thermodynamically favored gamma-lactone prodrugs, a number of compounds are able to inhibit cholesterol and fatty acid synthesis in HepG2 cells and reduce plasma triglyceride levels in vivo. The best of these, compound 77, is able to induce clear hypocholesterolemic and hypotriglyceridaemic responses when administered orally to rat and dog. These results provide evidence to support the hypothesis that compounds which inhibit ATP-citrate lyase have the potential to be a novel class of hypolipidemic agent, which possess combined hypocholesterolemic and hypotriglyceridemic activities.     

The effect of a two-week anti-orthostatic hypokinesia on the cardiac function and on the latter''s regulation in monkeys

Medical practice guidelines are being developed rapidly and advocated as a crucial component in transforming and improving the delivery of health care services. However, little is known about the ability of hospitals to institute guidelines outside of experimental settings. This article approaches guideline implementation from the viewpoint of process innovation assimilation and presents specific recommendations for organizational tactics leading to successful implementation of practice guidelines.     

The use of alisat for correction of level of lipids and their peroxidation products in blood of patients with atherosclerosis

A simple and easy assay for plasma heparin measurement (international units/ml) is described. The method is based upon the heparin neutralization and titration by polybrene. Heparin biological activity is measured first by activated partial thromboplastin time prolongment and then by means of polybrene titration: plasma heparin concentration was evaluated in international units/ml (IU/ml). The design and properties of this method are reported. Application in clinical practice of monitoring heparinization during hemodialysis is evaluated.     

Identification of marker chromosomes and translocations in man using a computerized diagnostic database and fluorescent in situ hybridization

BACKGROUND: Many species of bats have two sets of submandibular glands, principal and accessory. The accessory gland may resemble the principal one but more often shows wide morphological divergence. The free-tailed bat, Tadarida thersites, is very unusual in that it has two sets of parotid glands rather than binary submandibular glands. We studied the ultrastructure of the principal parotid gland to establish a baseline for comparison with the accessory parotid. METHODS: Two specimens of adult free-tailed bats, one male and one female, were live-trapped in western Kenya. Parotid glands were fixed for electron microscopy using a protocol expressly designed for field fixation and then embedded by conventional means. RESULTS: Histologically, the principal parotid is a typical serous gland. The secretory granules of the endpiece cells have an unusual substructure in that they contain variable numbers of lucent halos and one or several spherules. Intercalated duct cells contain a significant number of dense, serous-like granules. Striated ducts have the usual basal configuration of mitochondria and folded plasma membranes, but the supranuclear cytoplasm contains many small, dense granules, so that these ducts resemble the granular convoluted tubules found in the submandibular glands of many families of rodents. The apices of the duct cells have a peculiar contour--the luminal surfaces obliquely invaginate into the apical cytoplasm, so that in thin section the luminal membranes appear to be underlaid by a layer of vacuoles. CONCLUSION: Although the principal parotid gland of the free-tailed bat shows some distinctive, species-specific ultrastructural features, it basically is similar to the parotid gland in two other molossid bats, Tadarida brasiliensis and Molossus molossus. The distinctive features in the principal parotid gland of T. thersites might relate to its feeding on hard-bodied insects and perhaps to the production of lysozyme.     

Organization of the genetic locus for chicken myosin light chain kinase is complex: multiple proteins are encoded and exhibit differential expression and localization

We report that the genetic locus that encodes vertebrate smooth muscle and nonmuscle myosin light chain kinase (MLCK) and kinase-related protein (KRP) has a complex arrangement and a complex pattern of expression. Three proteins are encoded by 31 exons that have only one variation, that of the first exon of KRP, and the genomic locus spans approximately 100 kb of DNA. The three proteins can differ in their relative abundance and localization among tissues and with development. MLCK is a calmodulin (CaM) regulated protein kinase that phosphorylates the light chain of myosin II. The chicken has two MLCK isoforms encoded by the MLCK/KRP locus. KRP does not bind CaM and is not a protein kinase. However, KRP binds to and regulates the structure of myosin II. Thus, KRP and MLCK have the same subcellular target, the myosin II molecular motor system. We examined the tissue and cellular localization of KRP and MLCK in the chicken embryo and in adult chicken tissues. We report on the selective localization of KRP and MLCK among and within tissues and on a differential distribution of the proteins between embryonic and adult tissues. The results fill a void in our knowledge about the organization of the MLCK/KRP genetic locus, which appears to be a late evolving regulatory paradigm, and suggest an independent and complex regulation of expression of the gene products from the MLCK/KRP genetic locus that may reflect a basic principle found in other eukaryotic gene clusters that encode functionally linked proteins.     

Collateral blood supply through the ophthalmic artery: a steal phenomenon analyzed by color Doppler imaging

OBJECTIVE: This study aimed to evaluate the retrobulbar circulatory effects of reversed ophthalmic artery flow (ROAF) on the ophthalmic artery branches by means of color Doppler imaging. DESIGN: The design was a case-controlled study. PARTICIPANTS: Among 56 consecutive patients with severe (>70% stenosis) occlusive carotid artery disease, 15 patients (26.8%) with ROAF were identified. The control group consisted of 15 patients with similar degrees of carotid artery stenosis and forward ophthalmic artery flow. INTERVENTION: Arteriography and measurement of the retrobulbar hemodynamic parameters with color Doppler imaging were performed. MAIN OUTCOME MEASURES: Blood flow velocities and resistive index in the ophthalmic, central retinal, and temporal short posterior ciliary arteries were measured. RESULTS: Arteriography confirmed the diagnosis of ROAF in all 15 patients. There was no patient with ROAF diagnosed by arteriography and not diagnosed by color Doppler imaging. The frequency of bilateral severe occlusive carotid artery disease was significantly higher in the ROAF group (40%) compared to the control group (6.6%) (P = 0.04). Patients with ROAF showed significantly reduced vascular resistance in the ophthalmic artery (P = 0.03), higher vascular resistance, and lower blood flow velocities in the central retinal and temporal short posterior ciliary arteries (P < 0.05). CONCLUSION: This study suggests that patients with ROAF show a steal phenomenon, characterized by a shunt to the low-resistance intracranial circuit and reduction of retrobulbar blood flow.     

Heterogeneity of the T cell response to immunodominant determinants within hen eggwhite lysozyme of individual syngeneic hybrid F1 mice: implications for autoimmunity and infection

Hybrid F1 mice derived from inbred parental mouse strains are extensively used as animal models of human autoimmune diseases and transplantation. It is generally believed that with regard to immunologic studies, hybrid F1 mice behave in a consistent manner, equivalent to any other inbred mouse strain. In this study, we report that in comparison to inbred parental strains, individual hybrid F1 mice revealed a broad heterogeneity of proliferative response to the immunodominant determinants within hen eggwhite lysozyme (HEL). Of five parental strains tested, individual mice of three strains responding to only a few dominant HEL determinants (B6, BALB/c, and B10.PL) showed quite homogeneous patterns of response, whereas two mouse strains responsive to several determinants of HEL revealed either relative homogeneity (CBA/J mice) or heterogeneity (SJL mice) of response. However, in SJL mice, responses to major, dominant determinants of HEL were quite consistent. On the contrary, regardless of the consistency of response of parental strains, all three of F1 mice [[B6 x BALB/c]F1, [B6 x CBA/J]F1, and [SJL x B10.PL]F1] revealed significantly greater heterogeneity of response, which even involved the major, dominant determinants of HEL. We attribute the above heterogeneity of response to the competitive as well as aleatory nature of the interaction between various factors, including the coexistence of different MHC (parental as well as hybrid MHC) molecules, determinant capture, and the T cell repertoire. These results have important implications for studies on autoimmunity, infection, and vaccine design in human populations, where heterozygosity is the norm rather than the exception.     

Evidence for a Turner syndrome locus or loci at Xp11.2-p22.1

Turner syndrome is the complex human phenotype associated with complete or partial monosomy X. Principle features of Turner syndrome include short stature, ovarian failure, and a variety of other anatomic and physiological abnormalities, such as webbed neck, lymphedema, cardiovascular and renal anomalies, hypertension, and autoimmune thyroid disease. We studied 28 apparently nonmosaic subjects with partial deletions of Xp, in order to map loci responsible for various components of the Turner syndrome phenotype. Subjects were carefully evaluated for the presence or absence of Turner syndrome features, and their deletions were mapped by FISH with a panel of Xp markers. Using a statistical method to examine genotype/phenotype correlations, we mapped one or more Turner syndrome traits to a critical region in Xp11.2-p22.1. These traits included short stature, ovarian failure, high-arched palate, and autoimmune thyroid disease. The results are useful for genetic counseling of individuals with partial monosomy X. Study of additional subjects should refine the localization of Turner syndrome loci and provide a rational basis for exploration of candidate genes.