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Noninvasive imaging of tumor hypoxia in rats using the 2-nitroimidazole 18F-EF5.

Tumor hypoxia is an important prognostic indicator for cancer therapy outcome. EF5 [2-(2-nitro-1[ H]-imidazol-1-yl)- N-(2,2,3,3,3-pentafluoropropyl)-acetamide] has been employed to measure tumor hypoxia in animals and humans using immunohistochemical methods. EF5 is a lipophilic molecule designed to have a very uniform biodistribution, a feature of obvious benefit for use in PET imaging. The present study represents the first demonstration of noninvasive PET imaging of rat tumors using fluorine-18 labeled EF5. Because of the small tumor size, partial volume effects may result in underestimation of concentration of the compound. Therefore, validation of the PET data was performed by gamma counting of the imaged tissue. The tumor models studied were the Morris 7777 (Q7) hepatoma (n=5) and the 9L glioma (n=2) grown subcutaneously in rats. Our previous studies have demonstrated that early passage 9L tumors are not severely hypoxic and that Q7 tumors are characterized by heterogeneous regions of tumor hypoxia (i.e., Q7 tumors are usually more hypoxic than early passage 9L tumors). The seven rats were imaged in the HEAD Penn-PET scanner at various time points after administration of 50-100 micro Ci (18)F-EF5 in 30 mg/kg carrier nonradioactive EF5. The carrier was used to ensure drug biodistribution comparable to prior studies using immunohistochemical methods. (18)F-EF5 was excreted primarily via the urinary system. Images obtained 10 min following drug administration demonstrated that the EF5 distributed evenly to all organ systems, including brain. Later images showed increased uptake in most Q7 tumors compared with muscle. Liver uptake remained relatively constant over the same time periods. Tumor to muscle ratios ranged from 0.82 to 1.73 (based on PET images at 120 min post injection) and 1.47 to 2.95 (based on gamma counts at approximately 180 min post injection). Tumors were easily visible by 60 min post injection when the final tumor to muscle ratios (based on gamma counts) were greater than 2. Neither of the 9L tumors nor the smallest Q7 tumor met this criterion, and these tumors were not seen on the PET images. These preliminary results suggest that (18)F-EF5 is a promising agent for noninvasive assessment of tumor hypoxia. Plans are underway to initiate a research project to determine the safety and preliminary evidence for the efficacy of this preparation in patients with brain tumors.

Animals↗

Transpupillary thermotherapy (TTT) for the treatment of choroidal neovascularisation.

AIM: To assess the effectiveness of transpupillary thermotherapy (TTT) for the treatment of classic and occult choroidal neovascularisation (CNV). METHOD: In a retrospective, case selected, open label trial 44 eyes of 42 patients with CNV secondary to age related macular degeneration (ARMD) were studied. 44 eyes with angiographically defined CNV were treated with diode laser (810 nm) TTT. Laser beam sizes ranged between 0.8 and 3.0 mm and power settings between 250-750 mW. Treatment was given in one area for 1 minute, the end point being no visible change, or a slight greying of the retina. Outcome was assessed with Snellen visual acuity and clinical examination; in 24/44 patients angiographic follow up was available. RESULTS: 12 predominantly classic CNV and 32 predominantly occult membranes were followed up for a mean of 6.1 months (range 2-19). Mean change in vision for classic membranes was -0.75 (SD 1.75) Snellen lines and occult membranes was -0.66 Snellen lines (2.1) (p>0.05). Predominantly classic membranes were closed in 75% (95% CI: 62.5-87.5) of eyes, remained persistent in 25% (95% CI: 12.5-37.5); no recurrences occurred. Predominantly occult membranes were closed in 78% (95% CI: 70.1-85.3) of eyes, remained persistent in 12.5% (95% CI: 6.6-18.5), and were recurrent in 5.1% (95% CI: 4.2-14.3). CONCLUSIONS: Transpupillary thermotherapy is a potential treatment for CNV. It is able to close choroidal neovascularisation while maintaining visual function in patients with classic and occult disease. Further trials of TTT are needed to compare this intervention with the natural history and other treatment modalities.

Aged↗

Stability of randomly amplified polymorphic DNA fingerprinting in genotyping clinical isolates of Helicobacter pylori.

AIM: H pylori genomes are highly diversified. This project was designed to genotype H pylori isolates by the polymerase chain reaction (PCR)-based randomly amplified polymorphic DNA (RAPD) fingerprinting technique and to verify its stability by Southern blotting and DNA sequencing. METHODS: Clinical isolates of H pylori were cultured from gastric antra and cardia of 73 individuals, and genomic DNA was prepared for each isolate. RAPD was carried out under optimized conditions. 23S rDNA was regarded as an internal control, and a 361 bp rDNA fragment (RDF) was used as a probe to screen the RAPD products by Southern blotting. Ten RDFs from different clinical isolates and the flanking regions (both upstream and downstream) of four RDFs were amplified and sequenced. RESULTS: H pylori isolates from different individuals had different RAPD profiles, but the profiles for isolates cultured from different gastric sites of a given individual were identical in all but one case. Isolates from 27 individuals were RDF positive by Southern blotting. Sequences of the RDFs and their flanking regions were almost the same between the RDF positive and negative isolates as determined by Southern blotting. There was no binding site for random PCR primer inside the sequences. CONCLUSION: RAPD is very useful in genotyping H pylori grossly on a large scale. However, it seems unstable in amplification of low yield fragments, especially those that do not appear as visible bands on the agarose gel stained with EB, since the primer is partially matched to the template.

Blotting, Southern↗

Helicobacter pylori in patients can be killed by visible light.

BACKGROUND: Helicobacter pylori colonizes the mucus layer of the human stomach and may cause peptic ulcer and adenocarcinoma. Novel antimicrobial approaches are sought due to the occurrence of antibiotic resistance and consequent treatment failure. We report here that H. pylori is susceptible to inactivation by blue light. STUDY DESIGN/MATERIALS AND METHODS: A controlled, prospective, blinded, trial of endoscopically delivered blue light to eradicate H. pylori in regions of the gastric antrum, in 10 patients between the ages of 21 and 80 who tested positive for H. pylori. Light (405 nm) (40 J/cm2) was delivered to a 1-cm diameter spot in the gastric antrum via optical fiber passed through the endoscope and weighed biopsies were taken from treated and control spots and colonies quantitatively cultured. RESULTS: Blue light killed 5 logs of bacteria in vitro. The mean reduction in H. pylori colonies per gram tissue between treated and control spots was 91% (7.4+/-4.8 x 10(6) vs. 8.1+/-1.9 x 10(7), two-tailed P < 0.0001). Some patients had reductions approaching 99%. No differences were observed on histological examination of light-treated and control gastric tissue. CONCLUSION: Blue light phototherapy may represent a novel approach to eradication of H. pylori, particularly, in patients who have failed standard antibiotic treatment.

Adult↗

A pilot study to derive clinical variables for selective chest radiography in blunt trauma patients.

STUDY OBJECTIVE: The goal of this pilot study was to determine whether clinical criteria can identify blunt trauma patients with significant acute intrathoracic injury on chest radiograph. METHODS: From January 2003 to May 2004, adult blunt trauma patients who received chest radiographs were prospectively enrolled at 2 urban trauma centers. Exclusion criteria were age less than 15 years, penetrating trauma, trauma more than 72 hours before presentation, isolated head trauma, and Glasgow Coma Scale score less than 14. Before chest radiograph viewing, providers recorded the following data: mechanism of injury, vital signs including oxygen saturation, patient symptoms, intoxication, distracting injuries, and the presence or finding of visible chest wall injury, chest palpation tenderness, pain on lateral chest compression, crepitus, and abnormal chest auscultation. Significant acute intrathoracic injury was defined as pneumothorax, hemothorax, aortic injury, 2 or more rib fractures, sternal fracture, or pulmonary contusion by blinded radiologist chest radiograph interpretation. RESULTS: Of the 507 enrolled patients, 15 patients were excluded because chest radiograph was not performed. Significant acute intrathoracic injury was confirmed in 31 of 492 (6.3%) patients. Palpation tenderness and chest pain had the highest sensitivity (90%) as individual criteria for significant acute intrathoracic injury, and hypoxia had the highest specificity (97%). The combination of palpation tenderness and hypoxia identified all significant acute intrathoracic injury with the following screening performance with 95% confidence intervals (CIs): sensitivity 100% (95% CI 91% to 100%); specificity 50% (95% CI 45% to 54%); positive predictive value 12% (95% CI 9% to 17%); and negative predictive value 100% (95% CI 99% to 100%). CONCLUSION: In this small sample, the combination of palpation tenderness and hypoxia identified all blunt trauma patients with significant acute intrathoracic injury while potentially eliminating the need for 46% of chest radiographs.

Adult↗

Correlation of eggshell strength and Salmonella enteritidis contamination of commercial shell eggs.

Shell quality has been identified as a heritable trait that can be manipulated by genetic selection. Previous research has concluded that many methods of determining shell quality produce variable results. With the development of newer, more precise measuring technologies, shell strength can now be assessed in a consistent, objective fashion. A research project was conducted to determine what role shell strength might play in affecting external Salmonella Enteritidis contamination of egg contents. Visibly clean eggs were collected from an in-line shell egg-processing facility at the accumulator. Eggs were inoculated by dipping in a concentrated suspension of nalidixic acid-resistant Salmonella Enteritidis. After storage, eggs were assessed for shell strength and both external and internal Salmonella Enteritidis contamination. In the first study, there was a significant difference (P < 0.05) in shell strength among the three replicates. No differences between treatments were found for shell strength or Salmonella Enteritidis contamination of contents. In the second study, there were no replicate differences for any of the monitored factors. When rinsate and content samples were enriched, 100% of the rinsates were positive for Salmonella Enteritidis. No content samples were shown to be contaminated with Salmonella Enteritidis during direct plating, but 3 to 5% of the samples from each replicate were positive after enrichment. Correlation analysis of the results from each study found only weak correlations between shell strength and Salmonella Enteritidis contamination on eggshell surface or contents. Within the range of shell strengths recorded in this study, the correlation analysis suggests that shell strength does not play a major role in Salmonella Enteritidis contamination. Further work with eggs that represent a greater range of shell strengths could provide a clearer indication of the interaction of shell strength and Salmonella Enteritidis contamination.

Animals↗

Heritable aspects of dysplastic breast glandular tissue (DY).

Breast parenchymal patterns, as visible on mammograms, are determined by the relative amount of radio-dense, glandular dysplastic tissue DY). High percentages of DY are related to higher breast cancer risk. Previous studies reported heritable influences on DY of 32-67%, depending on the family relationship that was studied. depending on the family relationship that was studied. We assessed heritability in 466 sister-, 25 dizygotic twin- and 26 monozygotic twin-pairs participating in a population-based breast cancer screening program; the DOM project (Diagnostic Investigation Mamma Carcinoma). The heritability was estimated for non-twin sisters, dizygotic and monozygotic twins seperately by computing correlations between siblings from the dichotomous DY-score (high risk versus low risk). This was done using methods based on the number of shared genes per sibtype. Heritability estimates were 38, 34 and 88% for sisters, dizygotic twins and monozygotic twins respectively. Heritability estimates from models that combine monozygotic twins with dizygotic twins or sisters indicated that combine monozygotic twins with dizygotic twins or sisters indicated that dominant gene effects, genetic interactions or gene-environment effects could be involved. Parity appeared to have an effect on the heritabile influence with estimates ranging from 90% in sisters that were both nulliparous, to 2% in sisterpairs discordant for nulliparity. These result indicate a substantial genetic influence on DY, but with a possible modifying ability of other factors, such as parity.

Adult↗

The nutritional status of a rural community in KwaZulu-Natal, South Africa: the Ndunakazi project.

OBJECTIVES: To assess the nutritional status of six month to 11 year old rural Black children and their mothers as a first phase in a nutrition intervention project. DESIGN: Cross sectional study. SETTING: A rural African community +/- 60 km northwest of Durban, KwaZulu-Natal, South Africa. SUBJECTS: A random sample of 127 mothers and 105 pre-school and 131 primary school children were selected from this community. MAIN OUTCOME MEASURES: Anthropometric (height and weight), biochemical and dietary and socio-demographic information was collected. RESULTS: Among the pre-schoolers anaemia was present in 23.8%, iron deficiency in 19.8%, while marginal vitamin A deficiency was observed in 44.9%. Urinary iodine levels indicated moderate iodine deficiency in 31.8% and severe iodine deficiency in 9.1%. In primary school children the prevalence of anaemia was 22%, while marginal vitamin A deficiency was observed in 50.8%. Moderate iodine deficiency was observed in 37.9% of primary school children while 13.6% presented with severe iodine deficiency. The prevalence of goitre in this group was 22.1%. Almost 22% of mothers were anaemic and 18.9% were iron deficient. Only 1.6% of mothers were marginally vitamin A deficient. An enlarged thyroid was observed in 26.7% of mothers of which 17.3% were palpable and 9.4% visible. Of mothers 43.4% were overweight while 33.8% were obese. CONCLUSION: The rural community in KwaZulu-Natal, showed a high prevalence of anaemia, marginal vitamin A deficiency and iodine deficiency. The information gathered during this cross sectional study served as a basis to plan and implement an intervention study aimed at addressing the nutritional deficiencies.

Adult↗

Role of high-resolution pinhole tomography in the evaluation of thyroid abnormalities.

The present study was undertaken to evaluate the contribution of pinhole-single photon emission computed tomography (P-SPECT) to scintigraphy of the thyroid gland. Thirty-six patients, referred for thyroid scintigraphy because of palpatory or ultrasonographic findings, were studied after intravenous administration of technetium-99m pertechnetate (222 MBq) using a rectilinear scanner and a single-headed rotating gamma camera equipped with a pinhole collimator. P-SPECT study was acquired on a 128 x 128 matrix, in 30 projections over 180 degrees and an acquisition time of 40 seconds per step. After transaxial reconstruction, coronal slices were compared with planar views obtained by the scanner. The size of the thyroid gland obtained by P-SPECT matched the life-size image of a rectilinear scan, and it clearly delineated the shape and borders of two huge multinodular glands. Its major contribution was in its improved resolution. Pinhole-SPECT identified 21 foci not visualized on planar views, 19 cold lesions, and 2 "warm" nodules embedded in normal tissue of 13 patients. Furthermore, it clearly delineated 18 discrete ill-defined nodules of 13 patients, (single in 4 patients and multiple in 9 patients): 16 cold lesions, and 2 hot foci. When a distinct palpable nodule was present, whether cold (22 lesions) or hot (2 foci), SPECT was of no additional diagnostic value. However, when the palpable nodule was a toxic one, the contralateral suppressed lobe was visible on SPECT only. Two ultrasonographic findings, of 3- and 5-mm in diameter, were neither identified on planar views nor on P-SPECT. In conclusion, P-SPECT of the thyroid gland improves delineation of huge multinodular glands and detection of small nodules (within the resolution of the camera) that could otherwise have been overlooked on planar views of a thyroid scanner. It allows for definition of tracer uptake in tiny discrete nodules and in multinodular goiter, and is a better guide to the physician in fine-needle aspiration of the cold areas.

Female↗

Retrospective intermodality registration techniques for images of the head: surface-based versus volume-based.

The primary objective of this study is to perform a blinded evaluation of two groups of retrospective image registration techniques, using as a gold standard a prospective marker-based registration method, and to compare the performance of one group with the other. These techniques have already been evaluated individually [27]. In this paper, however, we find that by grouping the techniques as volume based or surface based, we can make some interesting conclusions which were not visible in the earlier study. In order to ensure blindness, all retrospective registrations were performed by participants who had no knowledge of the gold-standard results until after their results had been submitted. Image volumes of three modalities: X-ray computed tomography (CT), magnetic resonance (MR), and positron emission tomography (PET) were obtained from patients undergoing neurosurgery at Vanderbilt University Medical Center on whom bone-implanted fiducial markers were mounted. These volumes had all traces of the markers removed and were provided via the Internet to project collaborators outside Vanderbilt, who then performed retrospective registrations on the volumes, calculating transformations from CT to MR and/or from PET to MR. These investigators communicated their transformations, again via the Internet, to Vanderbilt, where the accuracy of each registration was evaluated. In this evaluation, the accuracy is measured at multiple volumes of interest (VOI's). Our results indicate that the volume-based techniques in this study tended to give substantially more accurate and reliable results than the surface-based ones for the CT-to-MR registration tasks, and slightly more accurate results for the PET-to-MR tasks. Analysis of these results revealed that the rotational component of error was more pronounced for the surface-based group. It was also apparent that all of the registration techniques we examined have the potential to produce satisfactory results much of the time, but that visual inspection is necessary to guard against large errors.

Algorithms↗

Preoperative systemic chemotherapy followed by adjuvant postoperative intraperitoneal therapy for gastric cancer: a University of Southern California pilot program.

PURPOSE: A clinical trial for patients with gastric cancer amenable to curative resection was undertaken to determine feasibility and response to preoperative systemic chemotherapy followed by postoperative intraperitoneal (IP) chemotherapy. METHODS AND MATERIALS: Thirty-eight patients with resectable gastric tumor received two cycles of protracted intravenous (IV)-infusion fluorouracil (5FU), 200 mg/m2/d, for 3 weeks with weekly IV leucovorin 20 mg/m2 and IV cisplatin 100 mg/m2 days 1 and 29. Resection of the gastric tumor followed within 3 weeks of completion of systemic chemotherapy. Those who had all visible tumor removed with clear margins received two cycles of IP floxuridine 3,000 mg (total dose) per day for 3 days and IP cisplatin 200 mg/m2 with IV sodium thiosulfate on the fourth day of IP therapy. RESULTS: Thirty-seven of 38 patients (97%) received two cycles of systemic chemotherapy. Thirty-five of 38 patients (92%) underwent laparotomy for gastric tumor resection. Thirty-three patients (87%) had gastric resections performed; 29 (76%) had all visible tumor removed with microscopically negative margins. No operative mortality was encountered. Twenty-six patients (68%) received IP treatment. IV neoadjuvant treatment was well tolerated and resulted in 68% of the patients reporting improvement in abdominal pain, 45% objective remissions by computed tomography (CT), 38% objective remissions by gastroscopy and biopsy, and 8% had complete surgical pathologic response. Neutropenic sepsis during the IP treatment phase contributed to the only treatment-related death. Four of 29 completely resected patients (14%) have had tumor recurrence. The median follow-up time of patients remaining alive is now 19 months. The median survival for 38 patients entered onto this protocol has not been reached at 17+ months. CONCLUSION: This novel approach to the treatment of adenocarcinoma of the stomach is feasible. The neoadjuvant systemic therapy results in significant primary tumor regression. The determination of whether systemic or IP components of the program contribute to decreased recurrence or increased survival awaits a prospectively randomized clinical trial.

Adenocarcinoma↗

Results 28 months following transpupillary thermotherapy for classic and occult choroidal neovascularization in patients with age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To report the outcome of patients 28 months following treatment with transpupillary thermotherapy (TTT) for classic and occult choroidal neovascularization (CNV) secondary to age-related macular degeneration. PATIENTS AND METHODS: A nonrandomized pilot trial of 36 eyes of 33 patients was performed. Eyes with angiographically defined CNV, 11 predominantly classical and 25 predominantly occult, were treated with large spot diode laser (810 nm) TTT for 1 minute, the end point being no or minimal visible change. Outcome was assessed with best-corrected LogMAR visual acuity, clinical examination, and fluorescein angiography. RESULTS: Patients were observed for a mean of 28.7 months (range, 18 to 40 months). The mean change in LogMAR visual acuity for predominantly classic membranes was -1.91 (standard deviation [SD] = 4.3) and 5 of 11 (45.5%) eyes had a loss of 3 or more LogMAR lines. Predominantly classic membranes were closed in 9 of 11 eyes and stabilized in 2 of 11 eyes. The mean change in LogMAR visual acuity for predominantly occult membranes was -1.48 (SD = 6.3) and 10 of 25 (40%) patients had a loss of 3 lines or more. Predominantly occult CNV was stabilized in 25 of 25 cases, and recurrence developed in 2 of 25 cases; one of the latter developed classic CNV. CONCLUSIONS: The medium-term results for patients treated with TTT for both occult and classic CNV show good stability, with little visual loss and few recurrences. These data confirm the original findings of this study.

Aged↗

Cone-beam computed tomography with a flat-panel imager: initial performance characterization.

The development and performance of a system for x-ray cone-beam computed tomography (CBCT) using an indirect-detection flat-panel imager (FPI) is presented. Developed as a bench-top prototype for initial investigation of FPI-based CBCT for bone and soft-tissue localization in radiotherapy, the system provides fully three-dimensional volumetric image data from projections acquired during a single rotation. The system employs a 512 x 512 active matrix of a-Si:H thin-film transistors and photodiodes in combination with a luminescent phosphor. Tomographic imaging performance is quantified in terms of response uniformity, response linearity, voxel noise, noise-power spectrum (NPS), and modulation transfer function (MTF), each in comparison to the performance measured on a conventional CT scanner. For the geometry employed and the objects considered, response is uniform to within 2% and linear within 1%. Voxel noise, at a level of approximately 20 HU, is comparable to the conventional CT scanner. NPS and MTF results highlight the frequency-dependent transfer characteristics, confirming that the CBCT system can provide high spatial resolution and does not suffer greatly from additive noise levels. For larger objects and/or low exposures, additive noise levels must be reduced to maintain high performance. Imaging studies of a low-contrast phantom and a small animal (a euthanized rat) qualitatively demonstrate excellent soft-tissue visibility and high spatial resolution. Image quality appears comparable or superior to that of the conventional scanner. These quantitative and qualitative results clearly demonstrate the potential of CBCT systems based upon flat-panel imagers. Advances in FPI technology (e.g., improved x-ray converters and enhanced electronics) are anticipated to allow high-performance FPI-based CBCT for medical imaging. General and specific requirements of kilovoltage CBCT systems are discussed, and the applicability of FPI-based CBCT systems to tomographic localization and image-guidance for radiotherapy is considered.

Animals↗

Fine particulate chemical composition and light extinction at Meadview, AZ.

The concentration of fine particulate nitrate, sulfate, and carbonaceous material was measured for 12-hr day-night samples using diffusion denuder samplers during the Project Measurement of Haze and Visibility Effects (MOHAVE) July to August 1992 Summer Intensive study at Meadview, AZ, just west of Grand Canyon National Park. Organic material was measured by several techniques. Only the diffusion denuder method measured the semivolatile organic material. Fine particulate sulfate and nitrate (using denuder technology) determined by various groups agreed. Based on the various collocated measurements obtained during the Project MOHAVE study, the precision of the major fine particulate species was +/- 0.6 microg/m3 organic material, +/- 0.3 microg/m3 ammonium sulfate, and +/- 0.07 microg/m3 ammonium nitrate. Data were also available on fine particulate crustal material, fine and coarse particulate mass from the Interagency Monitoring of Protected Visual Environments sampling system, and relative humidity (RH), light absorption, particle scattering, and light extinction measurements from Project MOHAVE. An extinction budget was obtained using mass scattering coefficients estimated from particle size distribution data. Literature data were used to estimate the change in the mass scattering coefficients for the measured species as a function of RH and for the absorption of light by elemental carbon. Fine particulate organic material was the principal particulate contributor to light extinction during the study period, with fine particulate sulfate as the second most important contributor. During periods of highest light extinction, contributions from fine particulate organic material, sulfate, and light-absorbing carbon dominated the extinction of light by particles. Particle light extinction was dominated by sulfate and organic material during periods of lowest light extinction. Combination of the extinction data and chemical mass balance analysis of sulfur oxides sources in the region indicate that the major anthropogenic contributors to light extinction were from the Los Angeles, CA, and Las Vegas, NV, urban areas. Mohave Power Project associated secondary sulfate was a negligible contributor to light extinction.

Air Pollutants↗

Endoscope-assisted brain surgery: part 1--evolution, basic concept, and current technique.

RATIONALE: The evolution of neurosurgical techniques indicates the effort to reduce surgery-related traumatization of patients. The reduction of traumatization contributes to better postoperative outcomes. The improvement of diagnostic imaging techniques facilitates not only the precise localization of lesions but also the accurate determination of topographical relations of specific lesions to individual anatomic variations of intracranial structures. This precision of diagnostic imaging should be used to perform individual surgical procedures through so-called keyhole approaches. Keyhole craniotomies are afflicted with a reduction of light intensity in the depth of the operating field, and they provide rather narrow viewing angles. Thus, objects located directly opposite the approach entrance are more visible than those in the shadow of the microscope beam. These two deficiencies of keyhole craniotomies can be compensated for by the intraoperative use of rigid rod lens endoscopes, the shaft of which remains easily controllable through the surgical microscope. CONCEPT: Endoscope-assisted microsurgery, like all routine microsurgical procedures, is performed with both hands; the endoscope is fixed in its desired position via a mechanical arm to the headholder. Because of their superior optical quality and maneuverability, only rigid lens scopes are used for endoscope-assisted brain microsurgery. There are five ways of observing the endoscopic and microscopic images at the same time: 1) observation of the microscopic image through the oculars of the microscope and observation of the endoscopic image on a video screen placed in front of the surgeon, 2) observation of the microscopic image through the oculars of the microscope and display of the endoscopic image on a head-mounted LCD screen, 3) projection of both microscopic and endoscopic images on one screen in a picture-in-picture mode, 4) projection of both microscopic and endoscopic images into specially designed microscope oculars, and 5) transmission of both microscopic and endoscopic images into a head-mounted LCD screen. DISCUSSION: With the knowledge of almost all individual anatomic and pathoanatomic details of a specific patient, it is possible to target the individual lesion through a keyhole approach using the particular anatomic windows. As the light intensity and the depiction of important anatomic details are improved by the intraoperative use of lens scopes, endoscope-assisted microsurgery during keyhole approaches may provide maximum efficiency to remove the lesion, maximum safety for the patient, and minimum invasiveness.

Brain↗

Evolution and regression of pancreatic calcification in chronic pancreatitis. A prospective long-term study of 107 patients.

Pancreatic calcifications are virtually pathognomonic of chronic pancreatitis and develop in up to 90% of patients with alcoholic chronic pancreatitis in series with long-term results. We investigated the natural course of pancreatic calcification in a prospective longitudinal study over the past 23 yr. All patients were studied at regular intervals with particular regard to etiology, clinical findings, surgery, pancreatic function, and pancreatic calcification visible by x-ray (e.g., film series in three projections centered on the pancreas). We evaluated the findings of 107 patients with x-ray documentation of pancreatic calcification in at least three film series over a period of 4 yr or longer. Eighty-four patients had alcoholic chronic pancreatitis (group A) and 23 patients had nonalcoholic chronic pancreatitis (group B). Four hundred seventy-two film series of group A and one hundred forty-two film series of group B were reviewed independently by two expert teams. Both series were graded according to a score system in terms of intensity and distribution of pancreatic calcification (correlation of grading r = 0.91). The duration of calcification averaged 10 yr in group A and 12.6 yr in group B. Similar dynamic changes of pancreatic calcification were noted in groups A and B. Chronologically, three phases of evolution could be distinguished. After an initial increase (phase 1), greater than 50% of cases reached a plateau of stationary calcification (phase 2). Approximately one-third of cases showed a marked decrease of calcification in late phases of chronic pancreatitis (phase 3). Dissolution of pancreatic stones was related primarily to duration of chronic pancreatitis (duration of calcification and marked pancreatic dysfunction), and occurred frequently (but not exclusively) in patients after ductal drainage procedures. These results indicate that spontaneous dissolution of pancreatic stones is a rather common biologic phenomenon. The factors responsible for dissolution of stones remain to be elucidated.

Adolescent↗

Relation of interleukin-6, C-reactive protein, and the prothrombotic state to transesophageal echocardiographic findings in atrial fibrillation.

Atrial fibrillation (AF) is a major cause of morbidity and mortality from stroke due to thromboembolism from the fibrillating left atrium, including its appendage. We hypothesized that indexes of inflammation (as indicated by C-reactive protein and interleukin-6) and indexes of the prothrombotic state in AF that represent platelet activation (soluble P-selectin levels), endothelial damage or dysfunction (von Willebrand factor), coagulation (tissue factor and fibrinogen), and hemorrheology (plasma viscosity and hematocrit) would be related to the presence of thromboembolic predictors on transesophageal echocardiography in patients with long-term AF. To test this hypothesis, we recruited 37 patients with long-term AF who were receiving warfarin therapy with an international normalized ratio of > or =2.0 for > or =3 weeks before transesophageal echocardiography. Twenty-two patients had dense spontaneous echo contrast (SEC) visible in the left atrium or left atrial appendage, 10 had complex atheromatous plaque in the descending aorta, 11 had peak left atrial appendage velocities < or =0.2 m/s, and 3 had thrombus visible in the left atrial appendage. Twenty-eight patients had > or =1 transesophageal echocardiographic (TEE) risk factor for thromboembolism. Plasma levels of C-reactive protein (p = 0.03) and soluble P-selectin (p = 0.04) and hematocrit (p = 0.004) were higher among patients with AF with dense SEC than among those without. No significant associations were found for other TEE risk factors. Hematocrit was the only variable significantly associated with the presence of > or =1 TEE risk factor among patients with AF (p = 0.007) and the only independent associate of dense SEC after multivariate analysis (relative risk 1.4, 95% confidence interval 1.1 to 1.6) per 1% increase in hematocrit (p = 0.003, r(2) = 0.22). Although hematocrit was the only independent associate of dense SEC and > or =1 TEE risk factor, significant associations between dense SEC and the 2 indexes, C-reactive protein and soluble P-selectin, may indicate that mechanisms other than stasis are present with dense SEC. These observations support an "inflammatory hypothesis" in the pathogenesis of SEC that may have implications for thrombogenesis in AF.

Aged↗

The forum of ESRD networks: past, present and future.

The increasing visibility and credibility of the Forum of ESRD Networks in the national ESRD landscape is due, in large part, to the Forum's longstanding and unwavering advocacy for improved ESRD patient outcomes through the application of continuous quality improvement methodologies and the development of a data infrastructure which encompasses a universal patient sample. This advocacy is untainted by the agenda of any single professional constituency, and its success is limited only by the commitment that all stakeholders (payers, providers, and patients) have to the process. The data infrastructure, SIMS-VISION, is almost a reality, and has the potential to significantly improve the quality of care through the provision of provider-specific profiles to drive quality improvement. The application of quality improvement principles themselves will take longer, and requires the commitment of facility medical directors, whom the Forum hopes to reach through its collaborative education project with the RPA. Through its clearinghouse activities, the Forum hopes to foster evidence-based medicine, increasing provider awareness of clinical practice guidelines and other literature which may improve the quality of patient care. The Forum's strategic plans for achieving its goals closely parallel the recommendations of the President's Advisory Commission on Consumer Protection and Quality in the Health Care Industry, and emphasize not only the information infrastructure, quality measuring/reporting, and evidence-based medicine, but also enhancing patient participation, building partnerships, and facilitating education and research. The Forum's strategic plan, as reconfigured according to the President's Advisory Commission domains, has been endorsed by the Renal Coalition as the national renal quality agenda, and the Coalition's constituent organizations are exploring projects and funding sources to achieve some of these goals as well.

Data Collection↗