Working time directive shift patterns may improve care.
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Emergency Service, Hospital↗
Biomedical subjects
S Bolton
Publications and source records attributed to S Bolton.
Properties of neurons in the trigeminal nucleus caudalis responding to noxious dural and facial stimulation.
Extracellular single unit recordings were made in the rat trigeminal nucleus caudalis (Vc) from cells with Adelta and C-fibre latency responding to electrical stimulation of the thinned cranium overlying the middle meningeal artery (MMA). The neurons had an ipsilateral facial receptive field (FRF) that mainly extended over areas innervated by the first and second division of the trigeminal nerve but in some cases also included areas innervated by the third division of the trigeminal nerve. No wind-up of either long latency C-fibre or short latency Adelta responses was seen during trains of electrical stimulation. Sensitisation of mechanical stimulation of the FRF could also not be observed at any time during dural stimulation. In contrast, extracellular single unit recordings in the Vc activated by electrical stimulation of the facial skin resulted in a significant wind-up response of long latency response in six of ten cells studied. The facial-elicited wind-up response was significantly enhanced, 18 min after the electrical stimulation protocol was started, indicating that the process of wind-up had generated central excitability. The findings in this study demonstrate a clear difference between the effects of electrical stimulation of cutaneous and non-cutaneous inputs. In the trigeminal system, this has implications for the study of pathways such as those involved in headache, where it is believed that an enhanced dural input to the Vc may generate central sensitisation and partly explain the hyperalgesia and allodynia reported by patients.
Afferent Pathways↗
Dynamics of Saturn's magnetosphere from MIMI during Cassini's orbital insertion.
The Magnetospheric Imaging Instrument (MIMI) onboard the Cassini spacecraft observed the saturnian magnetosphere from January 2004 until Saturn orbit insertion (SOI) on 1 July 2004. The MIMI sensors observed frequent energetic particle activity in interplanetary space for several months before SOI. When the imaging sensor was switched to its energetic neutral atom (ENA) operating mode on 20 February 2004, at approximately 10(3) times Saturn's radius RS (0.43 astronomical units), a weak but persistent signal was observed from the magnetosphere. About 10 days before SOI, the magnetosphere exhibited a day-night asymmetry that varied with an approximately 11-hour periodicity. Once Cassini entered the magnetosphere, in situ measurements showed high concentrations of H+, H2+, O+, OH+, and H2O+ and low concentrations of N+. The radial dependence of ion intensity profiles implies neutral gas densities sufficient to produce high loss rates of trapped ions from the middle and inner magnetosphere. ENA imaging has revealed a radiation belt that resides inward of the D ring and is probably the result of double charge exchange between the main radiation belt and the upper layers of Saturn's exosphere.
Atmosphere↗
Composition and dynamics of plasma in Saturn's magnetosphere.
During Cassini's initial orbit, we observed a dynamic magnetosphere composed primarily of a complex mixture of water-derived atomic and molecular ions. We have identified four distinct regions characterized by differences in both bulk plasma properties and ion composition. Protons are the dominant species outside about 9 RS (where RS is the radial distance from the center of Saturn), whereas inside, the plasma consists primarily of a corotating comet-like mix of water-derived ions with approximately 3% N+. Over the A and B rings, we found an ionosphere in which O2+ and O+ are dominant, which suggests the possible existence of a layer of O2 gas similar to the atmospheres of Europa and Ganymede.
Atmosphere↗
Diversity among three novel groups of hyperthermophilic deep-sea Thermococcus species from three sites in the northeastern Pacific Ocean.
Eight new strains of deep-sea hyperthermophilic sulfur reducers were isolated from hydrothermal vent fields at 9 degrees 50'N East Pacific Rise (EPR) and at the Cleft and CoAxial segments along the Juan de Fuca Ridge (JdFR). 16S rRNA gene sequence analysis showed that each strain belongs to the genus Thermococcus. Restriction fragment length polymorphism patterns of the 16S/23S rRNA intergenic spacer region revealed that these isolates fell into three groups: those from the EPR, those from fluid and rock sources on the JdFR, and those isolated from Paralvinella spp. polychaete vent worms from the JdFR. The optimum-temperature specific growth rates and the temperature ranges for growth were significantly higher and broader for those strains isolated from worms relative to those isolated from low-temperature diffuse hydrothermal fluids. Furthermore, the worm-derived isolates generally produced a larger array of proteases and amylases based on zymogram analyses. The zymogram patterns also changed with growth temperature suggesting that these organisms alter their lytic protein suites in response to changes in temperature. This study suggests that there is significant phenotypic diversity in Thermococcus that is not apparent from their highly conserved 16S rRNA nucleotide sequences.
Journal Article↗
Association of prostate size with urinary morbidity following mixed conformal neutron and photon irradiation.
PURPOSE: This study was designed to characterize the relationship between the observed rate of postradiation genitourinary (GU) complications and the prostate gland size. METHODS AND MATERIALS: Two hundred seventy-three patients received conformal neutron and photon irradiation to the prostate seminal vesicles. Data on post-treatment urinary morbidity were collected and examined in relationship to a number of clinical and technical factors. RESULTS: With a median follow-up of 30 months (range 7-61), the 4-year rate of Grade 2 or higher GU complications was 21%. On univariate analysis, the risk of complications was significantly associated with prostate size and neutron beam arrangement. On multivariate analysis, only the prostate size was significantly associated with the risk of GU morbidity. Patients with a preradiation prostate volume more than 74 cc had a two and a half fold increase in the risk of complications compared to patients with smaller glands. CONCLUSION: Patients with an enlarged prostate have a significantly higher risk of chronic GU complications. Although these data were obtained for patients receiving combined neutron and photon irradiation, it is likely that these data would also be applicable for those patients receiving photon irradiation as well. These observations may add an additional rationale for the study of preirradiation hormonal treatment.
Black or African American↗
Postneoadjuvant hormone PSA levels and prognosis in locally advanced prostate cancer.
OBJECTIVES: To determine whether the response to hormonal therapy before radiation predicts the rate of biochemical relapse in patients with locally advanced prostate cancer. METHODS: Between October 1991 and December 1997, 105 patients with locally advanced adenocarcinoma of the prostate received radiotherapy in two dose-escalation studies. Sixty-seven patients received neoadjuvant hormonal therapy. The mean and median duration of hormonal therapy before radiotherapy was 4 months each. All treatments were designed using three-dimensional conformal therapy. The total dose to the gross tumor volume ranged from 73 to 87 Gy in 2 Gy per fraction photon equivalent dose. The median follow-up time was 30 months (range 1 to 66). RESULTS: The median prostate-specific antigen (PSA) nadir after neoadjuvant hormonal therapy but before radiotherapy was 1.7 ng/mL (range less than 0.05 to 71.2). The median nadir after radiation for patients who did and did not receive neoadjuvant androgen deprivation was 0.25 ng/mL (range less than 0.05 to 6.2) and 1.35 ng/mL (range 0.08 to 10), respectively. Median time to achieve nadir was 6 months (range 1 to 42) with and 12 months (range 1 to 48) without hormonal therapy. There was no significant difference in the rate of biochemical failure for patients with a posthormone (before irradiation) PSA nadir less than 1 ng/mL versus 1 ng/mL or greater (overall P = 0.9). However, there was a significant difference in biochemical no evidence of disease rates between those with a PSA nadir less than 1 ng/mL and those with a PSA nadir of 1 ng/mL or greater after radiation (63% versus 22% at 3 years, overall P <0.001). CONCLUSIONS: Our data showed that the initial response to hormonal therapy before radiation, as indicated by the PSA level, did not impact on the rate of recurrence. However, the time to reach nadir and the absolute nadir level achieved were lower in patients who did receive hormonal therapy.
Actuarial Analysis↗
Independence and statistical inference in clinical trial designs: a tutorial review.
The requirements for statistical approaches to the design, analysis, and interpretation of experimental data are now accepted by the scientific community. This is of particular importance in medical studies where public health consequences are of concern. Investigators in the clinical sciences should be cognizant of statistical principles in general, but should always be wary of the pursuing their own analyses and engage statisticians for data analysis whenever possible. Examples of circumstances that require statistical evaluation not found in textbooks and not always obvious to the lay person are pervasive. Incorrect statistical evaluation and analyses in such situations will result in erroneous and potentially serious misleading interpretation of clinical data. Although a statistician may not be responsible for any misinterpretations in such unfortunate circumstances, the quote often cited about statisticians and "damned liars" may appear to be more truth than fable. This article is a tutorial review and describes a common misuse of clinical data resulting in an apparently large sample size derived from a small number of patients. This mistake is a consequence of ignoring the dependency of results, treating multiple observations from a single patient as independent observations.
Data Interpretation, Statistical↗
Impact of postprostatectomy prostate-specific antigen nadir on outcomes following salvage radiotherapy.
OBJECTIVES: To evaluate the relationship between the postprostatectomy prostate-specific antigen (PSA) nadir and the outcome of patients treated with salvage radiotherapy. METHODS: Seventy-eight patients received definitive external beam radiation for recurrence following radical prostatectomy (RP). The PSA nadir was undetectable in 41 patients (less than 0.05 ng/mL). All patients received salvage radiotherapy (median dose 66 Gy) for a median of 19 months (range 2 to 149) following prostatectomy. The median follow-up time was 25 months (range 1 to 59) from the date of completion of radiation. RESULTS: Among patients having an undetectable or detectable postoperative PSA, 78% and 68% were free of disease, respectively, at the last follow-up. At 3 years, the disease-free survival rates were 65% and 60%, respectively (P = 0.6). Overall, the disease-free survival rate at 3 years was 78% in patients with a PSA level 2 ng/mL or less at the time of radiotherapy compared to 31% with a PSA greater than 2 ng/mL (P < 0.0001). CONCLUSIONS: Many patients who never achieve an undetectable postprostatectomy PSA level may still be salvaged with therapeutic radiotherapy. The best predictor of a favorable outcome is a low (2 ng/mL or less) PSA level at the time of radiation.
Disease-Free Survival↗
Is it necessary to take small blend samples to assess drug uniformity?
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Evaluation Studies as Topic↗
Distinguishing borderline personality disorder from bipolar disorder: differential diagnosis and implications.
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Adult↗
Primary closure of choledochotomy using CO2 laser: comparison with suture closure.
This study was designed to compare laser welding to suture closure of the common bile duct (CBD). A 12 mm linear choledochotomy was closed in 12 mongrel dogs using tissue welding low-energy CO2 laser. Tissue welding was accomplished at 5.0 w/cm2 for 120 sec. Twelve similar mongrel dogs (control) were treated with CBD closure using 5/0 Vicryl (polyglactin 910, Ethicon, Inc., Somerville, NJ) interrupted simple stitches. All animals were sacrificed at six weeks. Gross and histologic evaluation of the choledochotomy site were performed. There were no statistical differences in parameters of comparison in the two groups. These parameters were pre- and post-treatment measurements of liver function tests, stenosis, and dehiscence. However, it must be noted that there was a 33% (4/12) incidence of dehiscence and death in the CO2 laser welded choledochorrhaphy. This result, although not statistically significant, is clinically significant. We conclude that the tensile strength of CO2 laser welded CBDs must be optimized and that these results are preliminary and still unreliable to recommend for clinical adaptability.
Animals↗
A floating controlled-release drug delivery system: in vitro-in vivo evaluation.
A novel floating controlled-release drug delivery system was formulated in an effort increase the gastric retention time of the dosage form and to control drug release. The buoyancy was attributed to air and oil entrapped in the agar gel network. A floating controlled-release 300-mg theophylline tablet having a density of 0.67 was prepared and compared in vitro and in vivo to Theo-dur. The in vitro release rate of the floating tablet was slower. In vivo scintigraphic studies for a floating and a heavy nonfloating tablet, under fasting and nonfasting conditions, showed that the presence of food significantly increased the gastric retention time for both tablets, and tablet density did not appear to make a difference in the gastric retention time. However, the positions of the floating and nonfloating tablets in the stomach were very different. Bioavailability studies in human volunteers under both fasting and nonfasting conditions showed results comparable to those with Theo-dur. The floating controlled-release theophylline tablet maintained constant theophylline levels of about 2 mg/mL for 24 hr, which may be attributable to the release from the agar gel matrix and the buoyancy of the tablet in the stomach.
Biological Availability↗
Physical characterization and dissolution properties of ibuprofen: Eudragit coprecipitates.
Ibuprofen:Eudragit coprecipitates were prepared in 10:3 ratios and their physical properties and related dissolution characteristics were determined. The Eudragit polymers used for the studies were three anionics (Eudragit L100, Eudragit L100-55, and Eudragit S-100), one anionic:cationic mixture used in a 1:1 ratio (Eudragit S100 + E100), and four zwitterionics (Eudragits RL 100, RS 100, RSPM, and RLPM). Physical characterizations were made using qualitative and quantitative X-ray diffractometry, IR spectrophotometry, and differential scanning calorimetry (DSC). Except for Eudragit S100 + E100 coprecipitates, no sizeable interaction at a molecular level was detected between the drug and the polymer. The crystalline structure of the drug was slightly modified in the coprecipitates. Regardless of the lack of interaction, dissolution of ibuprofen was retarded from all the coprecipitates studied (except Eudragit L100), especially in the pH 6.8 to 7.5 media in which the drug is freely soluble. The dissolution rate constants of the coprecipitates, calculated using Higuchi equation, demonstrated that dissolution decreased in the order of anionics greater than zwitterionic greater than anionic + cationic mixtures. The data obtained suggest that the release mechanisms involved are the swelling and slower dissolution of the polymer matrix relative to precipitated ibuprofen. The coprecipitates possess improved flow properties compared with ibuprofen with the exception of Eudragit RLPM and Eudragit RSPM. Eudragit coprecipitates can be useful tools in preparing ibuprofen sustained-release tablets. The coprecipitation technique used is simple and minimizes the use of organic solvents.
Acrylic Resins↗
A comprehensive method validation strategy for bioanalytical applications in the pharmaceutical industry--1. Experimental considerations.
The method validation strategy described consists of four components which are the prevalidation, validation proper, study proper and statistical analyses. These components constitute the platform upon which to evaluate the reliability and reproducibility of a bioanalytical method. Consideration has been given to emulate the study proper conditions to understand the method's limitations and performance expectations. The validation strategy will be presented in two papers. This first paper will describe the overall validation strategy, and the second paper will discuss the statistical analyses and data interpretation.
Drug Industry↗
A comprehensive method validation strategy for bioanalytical applications in the pharmaceutical industry--2. Statistical analyses.
The first paper in this two-part series described [Lang and Bolton, J. Pharm. Biomed. Anal. 9, 357-361 (1991)] an overall validation strategy for bioanalytical methods. This second paper focuses on the statistical analyses performed on the validation data that will allow the analyst to evaluate the reliability and reproducibility of a bioanalytical method. Based on the validation results, acceptance criteria for the quality control concentrations are established and used during the study proper to determine if the analytical run is valid. After analysing the clinical study samples and accepting the analytical runs, the quality control results are incorporated into databases to update their acceptance limits. This continuous validation process enables the analyst to monitor the method's performance over time and be confident that accurate sample concentrations are being reported. It is important to emphasize that the statistical analyses of the data provide information that should be considered from a practical point of view by the analyst. The analyst should use sound judgement in evaluating the reliability of the method.
Analysis of Variance↗
Particle size and content uniformity.
The requirements of the USP Content Uniformity test are translated into physical and mathematical parameters. Assuming spherical particle sizes with a log normal distribution, the mean particle size and particle size distribution required to insure a high probability of passing the content uniformity test are calculated. On the basis of these calculations it is shown that satisfactory tablets of low doses cannot be manufactured from a drug that does not meet certain particle size distribution specifications. It is recommended that particle size specifications for low dose drugs include a requirement for a limit to size distribution.
Particle Size↗
Stability of morphine sulfate in Cormed III (Kalex) intravenous bags.
The stability of various concentrations of morphine sulfate solution stored in Cormed III (Kalex) i.v. bags at two temperatures was investigated. Solutions of morphine sulfate 0.5, 15, 30, and 60 mg/mL were prepared under a horizontal-laminar-airflow hood with 0.9% sodium chloride solution and placed into 100-mL Kalex bags. Two bags were prepared for each concentration; one was stored at 5 degrees C and the other at 37 degrees C. Samples were analyzed in triplicate by high-performance liquid chromatography on days 0, 2, 5, 9, and 14. All morphine sulfate solutions were stable for 14 days at 37 degrees C, and the 0.5-, 15-, and 30-mg/mL solutions were stable for 14 days at 5 degrees C. However, the 60-mg/mL solution stored at 5 degrees C was found to contain 57% of the actual initial concentration on day 9 and 51% on day 14; the decrease coincided with the appearance of a white precipitate. Beginning on day 5, all the solutions displayed a light brown color that darkened as the study proceeded. This qualitative change was not associated with any change in morphine concentration. Solutions of morphine sulfate 0.5 to 60 mg/mL stored at 5 or 37 degrees C were stable for 14 days in Kalex bags, except for 60-mg/mL solutions stored at 5 degrees C for nine days or longer.
Chromatography, High Pressure Liquid↗