Oxyphil and squamous variants of medullary thyroid carcinoma

Two unusual morphologic variants of medullary thyroid carcinoma not previously described are reported. The first tumor was composed predominantly of large eosinophilic cells indistinguishable at the light microscopic level from Hürthle cells. Focal areas of conventional medullary carcinoma were also present. Electron microscopic study showed mitochondrion-rich cells containing round neurosecretory granules. Immunoreactive calcitonin and carcinoembryonic antigen (CEA) were demonstrated within most tumor cells. The second tumor had areas of typical medullary carcinoma but exhibited extensive squamous differentiation. The tumor was positive for CEA, neuron-specific enolase, and chromogranin but negative for calcitonin. Oxyphil and squamous cells must be added to the long list of cell types that have been described in medullary thyroid carcinoma.     

Risk factors for acquisition of multiply drug-resistant gram-negative bacteria

Some bacteria are naturally resistant to many antibiotics and most can become multiply resistant. Multiply resistant gram-negative bacteria have proved a particular problem over the last 30 years, but the development of new agents has lessened their significance for most clinicians. Now, however, clinical practice is threatened by the lack of new classes of antibiotics, the widespread emergence of resistance and the advent of plasmid-mediated cephalosporinases by which the spread of resistance is likely to be rapid. Increased use of prophylaxis in immunosuppressed and intensive care patients is likely to aggravate the problem, as is the use of new broad-spectrum agents in the community. More directed and restricted antibiotic use and better education of patients and prescriber are necessary to contain the problem of antibiotic resistance. Improved surveillance of sensitivity trends is essential. Many outbreaks also are associated with poor infection control techniques. The cost of outbreaks due to multiply resistant organisms and lack of compliance with infection control procedures needs to be properly studied. While many predisposing factors for the acquisition of these organisms and the development of infection are understood, the multifactorial nature of illness in many patients complicates the issue, necessitating further study of risk factors and preventative and therapeutic measures.     

Tumor targeting by an aptamer.

Aptamers are small oligonucleotides that are selected to bind tightly and specifically to a target molecule. We sought to determine whether aptamers have potential for in vivo delivery of radioisotopes or cytotoxic agents. METHODS: TTA1, an aptamer to the extracellular matrix protein tenascin-C, was prepared in fluorescent and radiolabeled forms. After in vivo administration, uptake and tumor distribution of Rhodamine Red-X-labeled aptamer was studied by fluorescence microscopy. In glioblastoma (U251) and breast cancer (MDA-MB-435) tumor xenografts, biodistribution and imaging studies were performed using TTA1 radiolabeled with (99m)Tc. Tenascin-C levels and tumor uptake were studied in a variety of additional human tumor xenografts. To assess the effect of radiometal chelate on biodistribution, mercapto-acetyl diglycine (MAG(2)) was compared with diethylenetriaminepentaacetic acid and with MAG(2)-3,400-molecular-weight PEG (PEG(3,400)). RESULTS: Intravenous injection of fluorescent aptamer TTA1 produced bright perivascular fluorescence in a xenografted human tumor within 10 min. In the ensuing 3 h, fluorescence diffused throughout the tumor. Labeled with (99m)Tc, TTA1 displayed rapid blood clearance, a half-life of less than 2 min, and rapid tumor penetration: 6% injected dose (%ID)/g at 10 min. Tumor retention was durable, with 2.7 %ID/g at 60 min and a long-lived phase that stabilized at 1 %ID/g. Rapid tumor uptake and blood clearance yielded a tumor-to-blood ratio of 50 within 3 h. Both renal and hepatic clearance pathways were observed. Using the (99m)Tc-labeled aptamer, images of glioblastoma and breast tumors were obtained by planar scintigraphy. Aptamer uptake, seen in several different human tumors, required the presence of the target protein, human tenascin-C. Modification of the MAG(2) radiometal chelator dramatically altered the uptake and clearance patterns. CONCLUSION: TTA1 is taken up by a variety of solid tumors including breast, glioblastoma, lung, and colon. Rapid uptake by tumors and rapid clearance from the blood and other nontarget tissues enables clear tumor imaging. As synthetic molecules, aptamers are readily modified in a site-specific manner. A variety of aptamer conjugates accumulate in tumors, suggesting imaging and potentially therapeutic applications.     

The pathologist's examination of the "lumpectomy"--the pathologists' view of surgical margins.

Despite the widespread conservative management of breast cancer, the pathologists' examination of these specimens is far from uniform. Pathologists sample margins differently, and even disagree on what constitutes a positive margin. This variability in the pathologic examination of the lumpectomy creates tremendous problems in analyzing the existing literature on the importance of positive margins. Herein is a discussion of the available data on the significance of margin assessment. We furthermore suggest a practical approach to examining margins with an emphasis on a functional orientation of the specimen with respect to the nipple. Only by adopting a uniform system of margin assessment can we begin to critically evaluate the importance of positive margins in segmental resections of the breast.     

Physical activity and quality of life in older adults: Influence of health status and self-efficacy

Background: Physical activity has been positively linked to quality of life (QOL) in older adults. Measures of health status and global well-being represent common methods of assessing QOL outcomes, yet little has been done to determine the nature of the relationship of these outcomes with physical activity.Purpose: We examined the roles played by physical activity, health status, and self-efficacy in global QOL (satisfaction with life) in a sample of older Black and White women.Method: Participants (N = 249, M age = 68.12 years) completed multiple indicators of physical activity, self-efficacy, health status, and QOL at baseline of a 24-month prospective trial. Structural equation modeling examined the fit of 3 models of the physical activity and QOL relationship.Results: Analyses indicated that relationships between physical activity and QOL, self-efficacy and QOL were all indirect. Specifically, physical activity influenced self-efficacy and QOL through physical and mental health status, which in turn influenced global QOL.Conclusions: Our findings support a social cognitives model of physical activity’s relationship with QOL. Subsequent tests of hypothesized relationships across time are recommended. Funding for this study was provided by the National Institute on Aging (Grant AG 20118). We extend our sincere appreciation to April Bell for all of her efforts on this project.     

Prematurity Stereotyping by Mothers of Premature Infants

Previous research has experimentally documented a prematuritystereotype in college students and mothers of full-term infants.The present investigation extends the scope of earlier studiesto mothers of premature infants. Thirty-two mothers of prematureinfants viewed four videotapes of 9-month-old full-term infants,each labeled either full-term or premature and either male orfemale. When infants were labeled premature the mothers perceivedthem as littler, finer featured, weaker, more passive, and slowerthan infants labeled full-term. The mothers also perceived labeledboys as bigger than labeled girls. Differences in stereotypingbetween the mothers in this study and both mothers of full-terminfants and college students are identified and discussed. Resultssuggest that mothers of premature infants expect deficits inpremature infants' physical development but not in prematureinfants' mental or social development. The likely sources andpossible self-fulfilling nature of these biased perceptionsare considered     

Suppression by Trypanosoma brucei of anaphylaxis-mediated ion transport in the small intestine of rats.

The hypothesis that failure of hosts infected with Trypanosoma brucei to express type 1 hypersensitivity is related to this parasite's ability to down-regulate IgE production, and not to an innate lack of allergenicity of T. brucei antigens, was tested by studying anaphylaxis-induced changes in net epithelial ion transport in rats. Transport changes were quantified electrophysiologically in vitro, as a change in transmural short-circuit current when sensitized intestine was challenged with homologous antigen. Rats injected parenterally with trypanosome antigen elicited intestinal anaphylaxis in response to antigenic challenge, whereas the intestine of rats infected with T. brucei failed to respond. Infection with T. brucei also suppressed the anaphylactic response in rats sensitized to and challenged with ovalbumin and T. spiralis-derived antigens. In these cases suppression was related to the ability of T. brucei to block production of IgE, and not to the physiological failure of the epithelial response. However, in rats sensitized by infection with T. spiralis, neither the anaphylactic response nor IgE production were inhibited by T. brucei. Furthermore, intestinal mastocytosis normally associated with trichinosis was unaffected by the trypanosome infection. Results support the conclusion that the failure to express anaphylaxis in T. brucei-infected rats is due to the inhibition of IgE production and not to the lack of allergenicity of trypanosome antigens.     

The effect of venous flow alterations upon patency of rat femoral vein anastomoses.

The rat femoral vein has become a standard model for laboratory training in microvascular anastomotic technique as well as for research investigations into factors affecting venous patency. This study examined the short-term patency (1 and 7 days) of rat vein anastomoses. The influences upon patency of epigastric flap creation and distal femoral vessel ligation (epigastric flow only) were explored. In a separate experiment, blood flow from the femoral vein was determined through catheter collection of venous efflux; the influences of island epigastric flap creation and distal femoral ligation on flow rates were explored. It was found that 82% of basic femoral vein anastomoses were patent at one day, while 100% of anastomoses associated with an epigastric flap and ligated/transected distal femoral vessel circulation (creating a low-tension anastomosis) were patent (P less than 0.01). With distal femoral vessel ligation and no transection (normal tension at the repair), anastomoses were patent in 90% of the veins when an epigastric flap was also raised, and in 60% when a flap was not created. When a flap was raised without disturbing the distal femoral circulation, vein patency was 75% at one day. When the vein anastomosis was performed with distal femoral vein ligation, the patency rate was 50%. All veins patent at 1 day were also patent at 7 days post-op; 96% of veins clotted at 1 day were found to be patent at 7 days. The venous efflux was not found to vary significantly when an epigastric flap was raised.(ABSTRACT TRUNCATED AT 250 WORDS)