Update: severe acute respiratory syndrome--Toronto, 2003.
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Biomedical subjects
Publications and source records attributed to D Low.
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PURPOSE: The emergent use of combined modality approach (chemotherapy and radiation therapy) for the treatment of patients with cervical cancer is associated with significant gastrointestinal and genitourinary toxicity. Intensity-modulated radiation therapy (IMRT) has the potential to deliver adequate dose to the target structures while sparing the normal organs and could also allow for dose escalation to grossly enlarged metastatic lymph node in pelvic or para-aortic area without increasing gastrointestinal/genitourinary complications. We conducted a dosimetric analysis to determine if IMRT can meet these objectives in the treatment of cervical cancer. METHODS AND MATERIALS: Computed tomography scan studies of 10 patients with cervical cancer were retrieved and used as anatomic references for planning. Upon the completion of target and critical structure delineation, the imaging and contour data were transferred to both an IMRT planning system (Corvus, Nomos) and a three-dimensional planning system (Focus, CMS) on which IMRT as well as conventional planning with two- and four-field techniques were derived. Treatment planning was done on these two systems with uniform prescription, 45 Gy in 25 fractions to the uterus, the cervix, and the pelvic and para-aortic lymph nodes. Normalization was done to all IMRT plans to obtain a full coverage of the cervix with the 95% isodose curve. Dose-volume histograms were obtained for all the plans. A Student's t test was performed to compute the statistical significance. RESULTS: The volume of small bowel receiving the prescribed dose (45 Gy) with IMRT technique was as follows: four fields, 11.01 +/- 5.67%; seven fields, 15.05 +/- 6.76%; and nine fields, 13.56 +/- 5.30%. These were all significantly better than with two-field (35.58 +/- 13.84%) and four-field (34.24 +/- 17.82%) conventional techniques (p < 0.05). The fraction of rectal volume receiving a dose greater than the prescribed dose was as follows: four fields, 8.55 +/- 4.64%; seven fields, 6.37 +/- 5.19%; nine fields, 3.34 +/- 3.0%; in contrast to 84.01 +/- 18.37% with two-field and 46.37 +/- 24.97% with four-field conventional technique (p < 0.001). The fractional volume of bladder receiving the prescribed dose and higher was as follows: four fields, 30.29 +/- 4.64%; seven fields, 31.66 +/- 8.26%; and nine fields, 26.91 +/- 5.57%. It was significantly worse with the two-field (92.89 +/- 35.26%) and with the four-field (60.48 +/- 31.80%) techniques (p < 0.05). CONCLUSION: In this dosimetric study, we demonstrated that with similar target coverage, normal tissue sparing is superior with IMRT in the treatment of cervical cancer.
We studied target volume coverage and normal tissue sparing of serial tomotherapy intensity modulated radiation therapy (IMRT) and fixed-field IMRT for nasopharyngeal carcinoma (NPC), as compared with those of conventional beam arrangements. Twelve patients with NPC (T2-4N1-3M0) at Mallinckrodt Institute of Radiology underwent computed tomography simulation. Images were then transferred to a virtual simulation workstation computer for target contouring. Target gross tumor volumes (GTV) were primary nasopharyngeal tumor (GTV(NP)) with a prescription of 70 Gy, grossly enlarged cervical nodes (GTV(LN)) with a prescription of 70 Gy, and the uninvolved cervical lymphatics [designated as the clinical tumor volume (CTV)] with a prescription of 60 Gy. Critical organs, including the parotid gland, spinal cord, brain stem, mandible, and pituitary gland, were also delineated. Conventional beam arrangements were designed following the guidelines of Intergroup (SWOG, RTOG, ECOG) NPC Study 0099 in which the dose was prescribed to the central axis and the target volumes were aimed to receive the prescribed dose +/- 10%. Similar dosimetric criteria were used to assess the target volume coverage capability of IMRT. Serial tomotherapy IMRT was planned using a 0.86-cm wide multivane collimator, while a dynamic multileaf collimator system with five equally spaced fixed gantry angles was designated for fixed-beam IMRT. The fractional volume of each critical organ that received a certain predefined threshold dose was obtained from dose-volume histograms of each organ in either the three-dimensional or IMRT treatment planning computer systems. Statistical analysis (paired t-test) was used to examine statistical significance. We found that serial tomotherapy achieved similar target volume coverage as conventional techniques (97.8 +/- 2.3% vs. 98.9 +/- 1.3%). The static-field IMRT technique (five equally spaced fields) was inferior, with 92.1 +/- 8.6% fractional GTV(NP) receiving 70 Gy +/- 10% dose (P < 0.05). However, GTV(LN) coverage of 70 Gy was significantly better with both IMRT techniques (96.1 +/- 3.2%, 87.7 +/- 10.6%, and 42.2 +/- 21% for tomotherapy, fixed-field IMRT, and conventional therapy, respectively). CTV coverage of 60 Gy was also significantly better with the IMRT techniques. Parotid gland sparing was quantified by evaluating the fractional volume of parotid gland receiving more than 30 Gy; 66.6 +/- 15%, 48.3 +/- 4%, and 93 +/- 10% of the parotid volume received more than 30 Gy using tomotherapy, fixed-field IMRT, and conventional therapy, respectively (P < 0.05). Fixed-field IMRT technique had the best parotid-sparing effect despite less desirable target coverage. The pituitary gland, mandible, spinal cord, and brain stem were also better spared by both IMRT techniques. These encouraging dosimetric results substantiate the theoretical advantage of inverse-planning IMRT in the management of NPC. We showed that target coverage of the primary tumor was maintained and nodal coverage was improved, as compared with conventional beam arrangements. The ability of IMRT to spare the parotid glands is exciting, and a prospective clinical study is currently underway at our institution to address the optimal parotid dose-volume needs to be spared to prevent xerostomia and to improve the quality of life in patients with NPC.
OBJECTIVE: To compare three laboratory screening protocols for the detection of methicillin-resistant Staphylococcus aureus (MRSA) from surveillance specimens (mannitol-salt agar containing 2 microg/mL of oxacillin [MSA-2], mannitol-salt agar containing 4 microg/mL of oxacillin [MSA-4], and a broth-containing protocol as recommended by the American Society for Microbiology [M-ASM]). DESIGN: Blinded comparative laboratory study and cost analysis. SETTING: University-affiliated microbiology laboratory. METHODS: Outcome measurements included rate of detection of MRSA-positive specimens and patients, turnaround time, and media and technologist costs. All MRSA culture swabs obtained from any patient site from November 1998 to April 1999 were included. RESULTS: The M-ASM protocol detected between 19.1% and 32.0% more MRSA-positive specimens and between 13.3% and 23.3% more MRSA-positive patients per surveillance event than the MSA-4 and MSA-2 protocols, respectively. There was no difference in positive-culture reporting time between the M-ASM and MSA4 protocols. The broth-containing protocol was 2- to 2.5-fold more expensive than the simpler protocols, taking into account media and laboratory personnel costs. CONCLUSIONS: It remains to be determined whether it is cost beneficial for a hospital to adopt the M-ASM, as the potential cost of MRSA transmission from unidentified MRSA-colonized patients is unknown. A broth-containing protocol should be considered the gold standard in future studies examining newer MRSA screening protocols
A reliable measurement of the thermal expansion coefficient (alpha) value is required to achieve a positive thermal mismatch between metal and porcelain for porcelain-fused to metal crowns. Heating rate and specimen conditions may significantly influence the alpha value and the effects of these factors were studied. Commercially pure cast titanium rods, 'as cast' and sandblasted, were heated at various conditions. According to this study, the discrepancy of alpha values between heating and cooling conditions was insignificant when the heating (cooling) rate was reduced to 1 degrees C min(-1). It was revealed that alpha values obtained from 1 degrees C min(-1) cooling rates should be utilized. Dental porcelain with an alpha value lower than 8.5 x 10(-6) degrees C will be suitable for titanium-ceramic applications.
This case report presents the relatively uncommon occurrence of a maxillary second premolar with 3 root canals. The possibility of additional root canals should be considered even in teeth with a low frequency of abnormal root canal anatomy. Sound knowledge of root canal anatomy, critical interpretation of radiographs, and high-magnification examination are essential elements of success in complicated root canal therapy.
Measurement of the elastic modulus (E) of investment materials has been difficult because of their low strength. However, these values are essential for engineering simulation and there are many methods available to assess the elasticity of materials. The present study compared two different methods with one of the methods being non-destructive in nature and can be used for specimens prepared for other tests. Two different types of investment materials were selected, gypsum-and phosphate-bonded. Method 1 is a traditional three-point bending test. Twelve rectangular bars with dimension of (70 x 9 x 3 mm) were prepared and placed on supports 56.8 mm apart. The test was conducted at a cross-head speed of 1 mm/min by use of a universal testing machine. The load applied to the test specimen and the corresponding deflection were measured until the specimen fractured. The E value was calculated from a linear part of the stress-strain plot. Method 2 is an ultra micro-indentation system to determine near surface properties of materials with nanometer resolution. The measurement procedure was programmed such that the specimens were indented with an initial contact force of 5 mN then followed by a maximum force of 500 mN. Measurement consisted of 10 indentations conducted with a spherical stainless steel indenter (R = 250 microm) that were equally spaced (500 microm). The E value rose asymptotically with depth of penetration and would approach the three-point bending test value at approximately four time's maximum contact depth for both materials. Both methods are practical ways of measuring the E of investment materials.
Plasmid-encoded fimbriae (Pef) expressed by Salmonella typhimurium mediate adhesion to mouse intestinal epithelium. The pef operon shares features with the Escherichia coli pyelonephritis-associated pilus (pap) operon, which is under methylation-dependent transcriptional regulation. These features include conserved DNA GATC box sites in the upstream regulatory region as well as homologues of the PapI and PapB regulatory proteins. Unlike Pap fimbriae, which are expressed in a variety of laboratory media, Pef fimbriae were expressed only in acidic, rich broth under standing culture conditions. Analysis of S. typhimurium grown under these conditions indicated that Pef production was regulated by a phase variation mechanism, in which the bacterial population was skewed between fimbrial expression (phase ON) and non-expression (phase OFF) states. Leucine-responsive regulatory protein (Lrp) and DNA adenine methylase (Dam) were required for pef transcription. In contrast, the histone-like protein (H-NS) and the stationary-phase sigma factor (RpoS) repressed pef transcription. Methylation of the pef GATC II site appeared to be required for pef fimbrial expression based on analysis of a GCTC II mutant that did not express Pef fimbriae. Analysis of the DNA methylation states of pef GATC sites indicated that, under acidic growth conditions, which induced Pef production, most GATC I sites were non-methylated, whereas GATC II and GATC X were predominantly methylated. The methylation protection at GATC I and GATC II was dependent upon Lrp and was modulated by PefI. Together, these results indicate that Pef production is regulated by DNA methylation, which is the first example of methylation-dependent gene regulation outside of E. coli.
OBJECTIVES: The aim of the present study was to establish a statistical model between thermal expansion values of investments and dimensional accuracy of cast titanium full crowns. METHODS: Thermal expansion (TE) measurements were made on cylindrical specimens (5O x 20 mm) dried to constant mass and full crown wax patterns were prepared from metal dies having the same design. Castings were made using a one-chamber high-pressure casting machine. Dimensional accuracy of the cast crowns was expressed by the discrepancy (micron) between the wax pattern and a casting prepared from the same die. A simple least squares linear regression analysis was made on data accumulated over the last five years. RESULTS: A high correlation coefficient (R = 0.87) was found between dimensional accuracy (Y) and thermal expansion value (X), and the accuracy was predicted by a formula Y = 1040.50X - 1004.45 microns. For zero discrepancy, a thermal expansion of 0.97% was required. SIGNIFICANCE: The dimensional accuracy expressed as the discrepancy between wax pattern and casting is easy to understand and less confusing than the traditional percentage value. The crown accuracy was highly predictable (R = 0.87) from the thermal expansion value of investments determined under controlled laboratory measuring conditions. New investments being released for titanium casting can be under constant modification. For this, regular monitoring of their TE behaviour is essential and use of the same batch is preferable for expansion measurement and crown accuracy assessment.
Recent work by our group has shown that an exopolysaccharide (EPS)-producing starter pair, Streptococcus thermophilus MR-1C and Lactobacillus delbrueckii subsp. bulgaricus MR-1R, can significantly increase moisture retention in low-fat mozzarella (D. B. Perry, D. J. McMahon, and C. J. Oberg, J. Dairy Sci. 80:799-805, 1997). The objectives of this study were to determine whether MR-1C, MR-1R, or both of these strains are required for enhanced moisture retention and to establish the role of EPS in this phenomenon. Analysis of low-fat mozzarella made with different combinations of MR-1C, MR-1R, and the non-EPS-producing starter culture strains S. thermophilus TA061 and Lactobacillus helveticus LH100 showed that S. thermophilus MR-1C was responsible for the increased cheese moisture level. To investigate the role of the S. thermophilus MR-1C EPS in cheese moisture retention, the epsE gene in this bacterium was inactivated by gene replacement. Low-fat mozzarella made with L. helveticus LH100 plus the non-EPS-producing mutant S. thermophilus DM10 had a significantly lower moisture content than did cheese made with strains LH100 and MR-1C, which confirmed that the MR-1C capsular EPS was responsible for the water-binding properties of this bacterium in cheese. Chemical analysis of the S. thermophilus MR-1C EPS indicated that the polymer has a novel basic repeating unit composed of D-galactose, L-rhamnose, and L-fucose in a ratio of 5:2:1.
The global regulator Lrp plays a central role as both a repressor and an activator in Pap phase variation. Unlike most other members of the Lrp regulon such as ilvIH, activation of papBA transcription requires the coregulator PapI and is methylation dependent. We developed a two-color genetic screen to identify Lrp mutations that inhibit Pap phase variation but still activate ilvIH transcription, reasoning that such mutations might identify PapI binding or methylation-responsive domains. Amino acid substitutions in Lrp at position 126, 133, or 134 greatly reduced the rate of Pap switching from phase off to phase on but had much smaller effects on ilvIH transcription. In vitro analyses indicated that the T134A and E133G Lrp variants maintained affinities for pap and ilvIH DNAs similar to those of wild-type Lrp. In addition, both mutant Lrp's were as responsive to PapI as wild-type Lrp, evidenced by an increase in affinity for pap Lrp binding sites 4, 5, and 6. Thus, in vitro analyses did not reveal the step(s) in Pap phase variation where these Lrp mutants were inhibited. In vivo analyses showed that both the T134A and E133G Lrp mutants activated transcription of a phase-on-locked pap derivative containing a mutation in Lrp binding site 3. Further studies indicated that the T134A Lrp mutant was blocked in a step in Pap phase variation that does not involve PapI. Our data suggest that these mutant Lrp's are defective in a previously unidentified interaction required for the switch from the phase-off to the phase-on pap transcription state.
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PURPOSE: Long-term bowel function after right hemicolectomy (RHC), extended right hemicolectomy (ERHC), left hemicolectomy (LHC), sigmoid colectomy (SC), and anterior resection (AR) was evaluated. METHOD: Three hundred fifteen patients (52.3 percent) replied to a questionnaire on stool frequency, fecal continence, and defecation problems. All patients had undergone surgery at least one year before questionnaire was sent to them. Patients with anastomotic leaks and recurrences were excluded. RESULTS: Stool frequency was one to two bowel movements per day in 78 percent of patients after RHC, 75 percent after ERHC, 57.6 percent after LHC, 64.3 percent after SC, and only 44.8 percent after AR (P = 0.01). Continence affected lifestyle in 32 percent of patients after AR, but affected only up to 11.5 percent of patients who had had more proximal resections (P = 0.001). Defecation problems occurred in less than 15.4 percent after RHC, ERHC, and LHC but were encountered more frequently after SC (25 percent) and AR (28.4 percent; P = 0.009). CONCLUSIONS: Problems with postoperative bowel function were appreciably more common after SC and AR.
Expression of the pyelonephritis-associated pilus (pap) operon in Escherichia coli is regulated by a complex epigenetic phase-variation mechanism involving the formation of differential DNA-methylation patterns. This review discusses how DNA-methylation patterns are formed by protein-DNA interactions and how methylation patterns, in turn, control pap gene expression.
BACKGROUND: Although expandable esophageal endoprostheses may be easier to insert and are associated with fewer procedure-related perforations, data comparing clinical results with these stents to those obtained with conventional prostheses are sparse. METHODS: We reviewed the records of all patients undergoing esophageal stent placement at our institution between October 1983 and July 1995 to define relative risks, clinical results, and need for reintervention prior to death, contrasting conventional to a variety of expandable esophageal endoprostheses. RESULTS: Over the period of review, 47 patients had conventional prostheses (CP) and 38 had expandable prostheses (EP) placed. Fifteen of 44 patients with CP and 14 of 38 with EP for malignancy also had esophago-airway fistulas. Insertion complications, prestent and poststent dysphagia scores, and complete fistula occlusion rates were comparable. Subacute complications were higher in the patients receiving EP (80%) than in those receiving CP (60%), possibly related to the prospective accumulation of data in patients receiving EP. Survival data were virtually identical and approximated 3 months for either group. CONCLUSIONS: Although both CP and EP improve dysphagia and occlude tracheoesophageal fistulae, patients ill enough to require a prosthesis do poorly regardless of prosthesis design. Moreover, although EP may be easier to insert than CP, stent- and patient-related problems persist and may require additional intervention.
The lobar variation in carbon tetrachloride-induced liver damage in the rat has been assessed by use of a systematic random sampling protocol and quantitative morphometry. A random inter-animal lobar variation in severity of damage was apparent, in contrast with the results obtained previously in which sampling bias, small animal numbers, and lack of fully quantitative measurement were apparent. The route of administration (oral vs. i.p.) did not influence these findings.