Computerized tomographic finding of saddle pulmonary embolism is associated with high mortality in cancer patients.

BACKGROUND: Large pulmonary embolism (PE) is associated with high mortality in cancer patients. Several risk stratification methods have been used in PE setting. While computer-assisted tomography (CT) is now the preferred diagnostic modality for PE, its prognostic value is not well established. METHODS: A retrospective study of patients discharged from our centre between 2000 and 2006 with a PE diagnosis identified 52 patients with thrombus in the main pulmonary artery or the right or left branch. Clinical, echocardiographic and CT data were reviewed; vital status was determined 1 month and 1 year after index event. Patients were divided into saddle (defined as main pulmonary artery thrombus) and non-saddle PE. Multivariate logistic regression was applied to predict vital status, with patient age and CT parameters as predictors. RESULTS: Eighteen out of 52 patients were found to have a saddle PE. No significant difference was found between the group characteristics, although saddle PE patients were more likely to receive thrombolytic therapy (27.8% vs 2.9%, P = 0.02) and have an echocardiogram within 30 days of PE (61.1% vs 29.4%, P = 0.03). Overall mortality at 1 month was 9.6% with no difference between groups. At 1 year, mortality rates in saddle PE were significantly higher (83.3% vs 41.2%, P = 0.004). Presence of saddle PE was associated with an odds ratio of death within 1 year of 7.41 (95% confidence interval: 1.75-31.46, P = 0.007). CONCLUSION: The relatively simple distinction of saddle versus non-saddle PE by CT findings may provide a straightforward method for risk stratification, and remains useful up to 1 year after the index event.

Posterior-stabilized and cruciate-retaining total knee replacement: a randomized study.

A randomized controlled study was done to compare the clinical, radiographic, and quality of life outcomes between posterior-stabilized and cruciate-retaining primary total knee implants. One hundred forty-three patients were enrolled in the study. Patients ranged in age from 57 to 89 years, had a primary diagnosis of osteoarthritis, and an intact functioning posterior cruciate ligament. Patients were excluded if they had a flexion contracture greater than 15 degrees, a varus deformity greater than 20 degrees, or a valgus deformity greater than 15 degrees. Patients were randomized to one of two study groups, posterior-stabilized AMK total knee implants (76 patients) or cruciate-retaining AMK total knee implants (67 patients). One hundred eight patients have had a minimum 2-year followup including 57 patients in the posterior-stabilized group and 51 patients in the cruciate-retaining group. Seventy-three patients have had a minimum 3-year followup including 37 patients in the posterior stabilized group and 36 patients in the cruciate-retaining group. The overall total Knee Society clinical rating score at 2 years averaged 157.1 points in the posterior-stabilized group and 156.5 points in the cruciate-retaining group. At 3 years, the scores averaged 156.8 points in the posterior-stabilized group and 163.5 points in the cruciate-retaining group. The range of motion component of the Knee Society score averaged 113.6 degrees for the posterior-stabilized group and 108.5 degrees for the cruciate-retaining group at 2 years, and 108.3 degrees in the cruciate-retaining group and 108.5 degrees in the posterior-stabilized group. Based on the various parameters analyzed, there were no notable differences between the groups with a posterior-stabilized and a cruciate-retaining total knee implant at 2 years. This trend seemed to be the same at 3 years.

Molecular structure of acid-etched dentin smear layers--in situ study.

It is commonly reported that acid etchants remove the smear layer, but to date, there has been no chemical evidence to support these observations. The purpose of this study was to determine the molecular structure of acid-etched carbide- and diamond-bur-created smear layers. This project tested the null hypothesis that such smear layers are totally removed with current etchants. Smear layer/demineralized/mineralized dentin interfaces were analyzed at 1- m intervals by micro-Raman spectroscopy. Features associated with the organic component were substantially broadened with loss of fine structure, and mineral peaks were clearly evident in the spectra of acid-etched smear layers. The organic features in the spectra of the EDTA-treated smear layer showed relative intensity ratios similar to demineralized dentin without contribution from the mineral phase. The disorganized collagen within the smear layer was not removed but was denatured by the acid treatment; the mineral was trapped in this gelatinous matrix and shielded from complete reaction.

Influence of additional acid etch treatment on resin cement dentin infiltration.

PURPOSE: The purpose of this study was to compare the penetration of a resin cement into dentin surfaces pretreated with self-etching primer with or without conventional acid etch. MATERIALS AND METHODS: Dentin surfaces of 8 unerupted human third molars were treated with self-etch primer (Panavia 21; Kuraray Co, Ltd, Osaka, Japan) with or without conventional acid etch treatment. A resin cement (Panavia 21) was applied according to manufacturer's instructions. Dentin/resin cement interface sections from each tooth were examined with light microscopy and scanning electron microscopy. In the light microscopy sections, exposed protein at the dentin/cement interface was stained a distinct red with Goldner's trichrome. RESULTS: The resin cement did not penetrate the depth of the zone of demineralized dentin when the self-etch primer was used in combination with conventional acid etch treatment. Inadequate resin cement penetration leaves a substantial area of exposed protein at the dentin/cement interface. In contrast, there was complete resin cement diffusion throughout the demineralized dentin when the self-etch primer was used without acid etching. CONCLUSIONS: Combining conventional acid etch treatment with a self-etching primer/resin cement system resulted in incomplete resin cement penetration and exposed protein at the dentin/cement interface.

Interfacial chemistry of the dentin/adhesive bond.

To date, the dentin/adhesive (d/a) bond has primarily been studied by morphologic analysis in conjunction with bond strength measurement. Although these analyses have enhanced our understanding, numerous questions about the chemistry have not been answered. The purpose of this study was to determine, at the molecular level, quantitative differences in the composition of the d/a interface formed under "wet" bonding conditions. The occlusal one-third of the crown was removed from 10 extracted, unerupted human third molars. The prepared dentin surfaces were treated, per manufacturers' instructions, with either Single Bond (3M) or One-Step adhesive (Bisco). Three-micron-thick sections of the d/a interface were cut and stained with Goldner trichrome for light microscopy. Companion slabs were analyzed with micro-Raman spectroscopy; the sample was placed at the focus of a 100x microscope objective, and spectra were acquired at 1-microm intervals across the d/a interface. Reference spectra were collected on model compounds of type I collagen and adhesive; the relative ratios of the integrated intensities of spectral features from adhesive and collagen were determined and plotted as a function of wt% adhesive. The same ratios were determined for the interface samples; by comparing these ratios with the calibration curve generated from the model compounds, we determined the percent of adhesive as a function of spatial position across the d/a interface. The relative percent of Single Bond adhesive was < 50% throughout more than half of the hybrid layer; One Step adhesive was > or = 50% throughout most of the hybrid. The results from this study provide the first direct chemical evidence of phase separation in a dentin adhesive and its detrimental effect on the dentin/adhesive bond.

Morphology of azurophil lysosomes in polymorphonuclear leukocytes from humans with rapidly progressive periodontitis.

Previous investigations have shown that subjects with rapidly progressive periodontitis (RPP), an early-onset aggressive form of periodontitis, have polymorphonuclear leukocytes (PMNs) with increased intracellular levels of beta-glucuronidase, a characteristic enzyme of azurophil lysosomes. The current study attempted to account for that increase. Ten healthy controls and 10 otherwise healthy subjects with RPP participated. PMNs from peripheral blood were separated, fixed and reacted for peroxidase to identify azurophil lysosomes. Using transmission electron microscopy, 20 PMNs per subject were photographed at 10,000x. Photographs were subsequently digitized and analyzed by computer. RPP PMNs had a higher percentage of the area of the cell profile occupied by azurophil lysosomes compared to control subjects' PMNs. The RPP subjects also had greater absolute numbers of azurophil lysosomes per cell. Lysosome shape was assessed visually. There were no differences between RPP and control groups for lysosome shape, with the majority of lysosomes in each group exhibiting a round or oval shape. RPP lysosomes did exhibit a significantly greater mean size.

Cardiotoxicity in patients receiving transtuzumab (Herceptin): primary toxicity, synergistic or sequential stress, or surveillance artifact?

Human epidermal growth factor receptor-2 (HER2) is a member of the epidermal growth factor receptor family, which produces factors that are considered to be important mediators of cell growth. Overexpression of HER2, which occurs in approximately 25% to 30% of human breast cancers, has fostered considerable interest in innovative therapeutic modalities designed to target tumor cells demonstrating such overexpression. Trastuzumab (Herceptin; Genentech, San Francisco, CA), a humanized monoclonal antibody developed to target the HER2 receptor, is the most widely studied example of such a modality. In early clinical studies with trastuzumab, cardiomyopathy was observed with a clinical expression similar to that seen with the anthracyclines (ie, a potentially progressive decrease in cardiac systolic function). A number of possible explanations for this cardiotoxicity are explored in this report. The first is that trastuzumab has inherent toxicity. This consideration has some theoretical interest, since fetal myocardial cells exhibit HER2 receptors and the adult myocardium expresses HER3 receptors. A second possibility is that sequential stresses following doxorubicin administration contribute to cardiac dysfunction. A third explanation is that observational artifacts lead to an overestimation of trastuzumab cardiotoxicity. Approaches for additional study of the extent and severity of trastuzumab cardiotoxicity are briefly addressed.

Effective laser ablation of bone based on the absorption characteristics of water and proteins.

BACKGROUND: Collateral thermal damage and residual char formation have severely limited the use of conventional lasers in the surgical preparation of bony tissue. Thermal damage from lasers can be minimized by selecting a wavelength that is strongly absorbed and by reducing the laser pulse duration. In contrast to the fixed wavelengths and microsecond pulse intervals of conventional lasers, the Vanderbilt free electron laser (FEL) can be set at wavelengths ranging from 2.1 to 9.8 microm, and the pulse duration can be reduced to a series of 1 to 2 picosecond (ps) micropulses delivered in succession over intervals of 4 microsecond macropulses. The purpose of this study was to compare the morphologic and chemical changes induced in the near-surface region of bone following exposure to the FEL at 3.0, 6.1, and 6.45 microm wavelengths. The selected wavelengths coincide with the vibrational modes of proteins and water within bone. METHODS: Under general anesthesia, laser incisions were made in the tibias of 14 skeletally mature rabbits. Laser parameters included 22.5+/-2.5 mJ/pulse delivered in individual 4 microsecond macropulses at a repetition rate of 30 Hz, focused to 200 microm and 500 microm spot sizes. Laser incisions were made using a computer-assisted surgical program, and control incisions were created with a bone saw. Rabbits were euthanized after the final incision, tibias recovered, and non-decalcified specimens processed for light microscopy. Separate samples were prepared for FTIR (Fourier transform infrared) photoacoustic spectroscopic analysis. RESULTS: The light microscopy sections of the ablation defects created at the differing wavelengths showed similar features, i.e., 2 zones of collateral damage, a zone generally < 10 mm of extensive thermal damage, and a wider zone of empty lacunae. In comparing treated and untreated surfaces, the spectral differences were limited to a relative decrease in intensity of the amide II and III absorption peaks in all laser-treated surfaces. CONCLUSIONS: Spectroscopic and histologic results indicated minimal thermal damage to bone ablated at 3.0, 6.1, and 6.45 microm wavelengths using the FEL (Fourier transform infrared) at the specified parameters. The FTIR photoacoustic spectroscopic results suggest that the char layer is limited to an area less than approximately 6 microm from the surface.

Unprotected protein at the dentin-adhesive interface.

OBJECTIVE: With dental bonding systems that require acid etching of dentin, inadequate adhesive penetration can leave exposed collagen at the dentin-adhesive interface. The exposed collagen could be degraded by bacterial proteases, compromising the integrity of the dentin-adhesive bond and, ultimately, the restoration. The purpose of this study was to develop a nondestructive staining technique to identify exposed collagenous protein at the dentin-adhesive interface. METHOD AND MATERIALS: The following adhesives were placed, according to manufacturer's instructions, on dentin cut from 15 human third molars: Scotchbond Multi-Purpose, Scotchbond Multi-Purpose Plus, and 3M Single Bond. Light microscopic sections of native dentin-adhesive interfaces of each tooth were cut and stained with Goldner's trichrome. This reagent stained exposed protein in the sections a distinct red-orange. RESULTS: Exposed protein was identified at the dentin-adhesive interface with each of the adhesives. Corollary scanning electron microscopic examination confirmed the presence of exposed protein, i.e., protein that was removed by sodium hypochlorite, at the interface. Sites of exposed protein that were clearly identified in the light microscopic sections were obscured in the transmission electron microscopic sections. CONCLUSION: In vitro identification of inadequacies in the dentin-adhesive bond is the first step in determining sites that may be vulnerable to premature breakdown under clinical conditions.

Spectroscopic and morphologic characterization of the dentin/ adhesive interface.

The potential environmental risks associated with mercury release have forced many European countries to ban the use of dental amalgam. Alternative materials such as composite resins do not provide the clinical function for the length of time characteristically associated with dental amalgam. The weak link in the composite restoration is the dentin/adhesive bond. The purpose of this study was to correlate morphologic characterization of the dentin/adhesive bond with chemical analyses using micro-Fourier transform infrared and micro-Raman spectroscopy. A commercial dental adhesive was placed on dentin substrates cut from extracted, unerupted human third molars. Sections of the dentin/adhesive interface were investigated using infrared radiation produced at the Aladdin synchrotron source; visible radiation from a Kr+ laser was used for the micro-Raman spectroscopy. Sections of the dentin/adhesive interface, differentially stained to identify protein, mineral, and adhesive, were examined using light microscopy. Due to its limited spatial resolution and the unknown sample thickness the infrared results cannot be used quantitatively in determining the extent of diffusion. The results from the micro-Raman spectroscopy and light microscopy indicate exposed protein at the dentin/adhesive interface. Using a laser that reduces background fluorescence, the micro-Raman spectroscopy provides quantitative chemical and morphologic information on the dentin/adhesive interface. The staining procedure is sensitive to sites of pure protein and thus, complements the Raman results. © 1999 Society of Photo-Optical Instrumentation Engineers.

A minimal motor domain from chicken skeletal muscle myosin.

The myosin head (S1) consists of a wide, globular region that contains the actin- and nucleotide-binding sites and an alpha-helical, extended region that is stabilized by the presence of two classes of light chains. The essential light chain abuts the globular domain, whereas the regulatory light chain lies near the head-rod junction of myosin. Removal of the essential light chain by a mild denaturant exposes the underlying heavy chain to proteolysis by chymotrypsin. The cleaved fragment, or "motor domain" (MD), migrates as a single band on SDS-polyacrylamide gel electrophoresis, with a slightly greater mobility than S1 prepared by papain or chymotrypsin. Three-dimensional image analysis of actin filaments decorated with MD reveals a structure similar to S1, but shorter by an amount consistent with the absence of a light chain-binding domain. The actin-activated MgATPase activity of MD is similar to that of S1 in Vmax and Km. But the ability of MD to move actin filaments in a motility assay is considerably reduced relative to S1. We conclude that the globular, active site region of the myosin head is a stable, independently folded domain with intrinsic motor activity, but the coupling efficiency between ATP hydrolysis and movement declines markedly as the light chain binding region is truncated.

Quantitative coronary arteriography and its assessment of atherosclerosis. Part I. Examining the independent variables.

BACKGROUND: Previous work has demonstrated that quantitative coronary arteriography (QCA) can accurately measure phantom images to within +/- 0.1 mm and has been accepted as a reliable and reproducible method of measuring human coronary artery disease (CAD). Assessment of CAD by QCA involves the measurement of numerous variables, which are currently required to calculate stenosis flow reserve (SFR). METHODS AND RESULTS: In this study 1040 stenotic lesions were analyzed by two well-accepted methods with demonstrated accuracy and reproducibility. These methods measure percent diameter stenosis (%DS), absolute diameter, percent area stenosis, length, as well as entry and exit angles to and from a stenotic coronary artery lesion respectively. Based upon these results, the mean +/- standard deviations and range seen in CAD were determined for each of these independent variables. This study demonstrated that atherosclerotic coronary artery lesions do not appear to exceed an entry angle of -39 degrees, and exit angle of +35 degrees, or an absolute length of 4.84 cm when accurately measured by QCA. It was also noted that, once percent diameter stenosis exceeded 89% (regardless of the visual estimate) or percent area stenosis exceeds 99%, coronary arteries become completely occluded as measured by QCA. CONCLUSIONS: While previously suspected that once certain critical limits are exceeded in the deposit of cholesterol and calcium within the coronary artery, the artery will close, this study demonstrated by QCA what the limitations in human coronary arteries appear to be. These limits may be in part due to turbulent factors resulting in platelet activation or local mediators from endothelium of the coronary artery.

Late doxorubicin-associated cardiotoxicity in children. The possible role of intercurrent viral infection.

BACKGROUND: The most frequently encountered doxorubicin related cardiac toxicity is a dose-related myocardial dysfunction occurring 1-6 months after chemotherapy. Recently, late cardiotoxicity has been the focus of interest. This paper explores the possibility that acute intercurrent viral illness may trigger late cardiotoxicity. METHODS: Thirty selected pediatric patients were followed for changes in their echocardiographically measured fractional shortening (FS) for 2-10 years after completion of their doxorubicin chemotherapy. They were divided according to the dose of doxorubicin they received (< 300 mg/m2 or > or = 300 mg/m2) and to whether the manifestations of an acute intercurrent viral illness during the observation period were documented. Eleven patients experienced such infections. RESULTS: Changes in FS demonstrated two different responses. The usual response to doxorubicin was a gradual, dose-related fall in FS, followed by recovery; while the second response included an unexpected, late, sudden decrease in FS. Four patients in the low dose subgroup experienced an acute intercurrent viral illness, but none of these demonstrated the unexpected decrease. Of the seven patients who acquired such illness in the high dose subgroup, five demonstrated the sudden, late decrease in FS, with two of them developing severe, reversible congestive heart failure. CONCLUSIONS: The most likely explanation for the late, sudden decrease in FS is an additional stress in patients who already have sustained subclinical cardiac damage as a result of their doxorubicin chemotherapy. An acute intercurrent viral illness may have triggered late cardiac dysfunction in some of these patients.

Cardiac diastolic function in pediatric patients receiving doxorubicin.

The purpose of the study was to compare systolic and diastolic function in pediatric patients treated with doxorubicin. Left ventricular function was evaluated in 61 children prior to and following chemotherapy. None had clinical evidence of cardiac decompensation prior to treatment. All received relatively low cumulative doses of doxorubicin; the majority received the drug by continuous infusion. Systolic function was estimated using fractional shortening; diastolic function was estimated using A wave velocity, E wave velocity, E to A ratio, and deceleration time. There was a small but significant decline in systolic cardiac function as estimated from changes in fractional shortening that could not be appreciated in any of the measured parameters of diastolic function. A variety of reasons that could be responsible for the absence of significant changes in diastolic function are discussed. For the present, estimations of systolic function are preferred over the studied parameters of diastolic function in the evaluation of cardiac status in pediatric patients receiving doxorubicin containing regimens.

Cardiac emergencies in the cancer patient.

Cardiac emergencies may be encountered during the management of patients with cancer, both in those with underlying cardiovascular disease and those with no previous history of cardiac problems. Both surgical and medical cancer treatment modalities may exacerbate preexisting cardiac conditions. Some antineoplastic agents can adversely affect the coronary arteries, myocardium, or pericardium. It has also been recognized that cardiac damage due to radiotherapy and chemotherapy may become clinically significant many years after therapy has been completed. Treatment of urgent cardiac problems in the cancer patient may differ from that recommended for other patient groups, since many cancer patients are not ideal candidates for some of the newer cardiac agents. Management of these conditions must therefore be tailored to the individual patient.

Nodus migrans: the case of the migrating knot.

Flow-directed pulmonary artery catheters provide important information regarding intravascular volume status, cardiac function and vascular resistance. We describe an unusual complication of pulmonary artery catheterization in which a knot formed at the distal end was torn away from the catheter body and migrated from its original position in the right subclavian vein to a distal branch of the right pulmonary artery. Careful attention to insertion and withdrawal techniques could prevent this potentially serious complication.

Postoperative atrial fibrillation in cancer surgery: preoperative risks and clinical outcome.

Postoperative atrial fibrillation (AF) is a recognized complication of cancer surgery. The purpose of this study was to define preoperative risk factors for AF, and to evaluate the clinical significance of the arrhythmia. We reviewed the medical records of 43 patients with postoperative AF admitted to the surgical intensive care unit (SICU). All patients were older than 60 years, 79% had a history of cigarette smoking, and 44% had hypertension. AF occurred an average of 2.8 days following surgery, and lasted an average of 2.1 days. No significant complications developed, and there were no long-term sequelae. This study suggests that, in cancer patients, postoperative AF is a disease of elderly patients. In addition the arrhythmia appears to be a relatively transient and benign phenomenon. Prolonged monitoring in an intensive care setting may not be necessary for asymptomatic, hemodynamically stable patients.

Using quantitative coronary arteriography to redefine SPECT sensitivity and specificity.

Previous studies looking at the sensitivity, specificity, and predictive accuracy of single photon emission computed tomography (SPECT) have been based upon the results obtained by visual interpretation of coronary arteriograms. Since the results of visual and quantitative determination of percent diameter stenosis have been shown to be statistically different, the results obtained from SPECT imaging when compared to quantitative methods for assessing coronary artery disease would be expected to provide a more correct assessment of sensitivity, specificity, and predictive accuracy. To determine the "true" sensitivity, specificity, and predictive accuracy of SPECT in diagnosing coronary artery disease, this study compared the results obtained in 44 SPECT images (20 thallium and 24 teboroxime) with the results obtained when quantitative coronary arteriography was used to analyze the coronary arteriograms. These 44 cases were then compared against 8 different definitions of significant coronary artery disease, varying from 30 to 80%, to yield 352 comparisons. The maximum specificity and predictive accuracy was found when 45% diameter stenosis was used to define the presence or absence of significant disease. At 45% diameter stenosis, SPECT imaging demonstrated an 86% sensitivity, 78% specificity, and 94% predictive accuracy with only 6% false positives. In 100% of the cases where 45% diameter stenosis was used to define the presence of disease and exercise failed to demonstrate ST segment changes or angina, when SPECT imaging demonstrated a perfusion defect(s), quantitative coronary arteriography agreed with SPECT imaging results.(ABSTRACT TRUNCATED AT 250 WORDS)