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Measuring the thermal resistance of microorganisms: selecting an appropriate test system, correcting for heat-transfer lags, and determining minimum heating times.

Errors that occur in physical systems used to evaluate the heat resistance of microorganisms are discussed: namely, (a) not knowing the test heating-medium temperature accurately, (b) using heating times that are so short that the maximum temperature reached in the test unit is significantly below the test heating-medium temperature, and (c) ignoring significant heat-transfer lags, first in the heating and later in the cooling of the test units. Procedures and methods that can be used to minimize the effect of potential test-system errors on microbial resistance data are reported. Examples are included regarding the treatment of the different types of errors. Heating and cooling lag-correction values for several commonly-used testing systems, gleaned from the published literature and from the author's experience, are listed. A method is described and illustrated regarding how we may determine (in advance of carrying out an experiment to gather enumeration or survivor-curve data), the shortest heating time--highest temperature that should be used with a specific test-unit system and microbial DT -value.

Hot Temperature↗

Ciclopirox gel for seborrheic dermatitis of the scalp.

BACKGROUND: Seborrheic dermatitis is a common inflammatory skin disorder that usually occurs in patients with pre-existing seborrhea. The etiology of seborrheic dermatitis is uncertain. Typically, sites dense with sebaceous glands support growth of the lipophilic yeast Malassezia furfur. Ciclopirox (Loprox) gel is a hydroxypyridone, broad-spectrum antifungal agent proven effective against the yeast M. furfur. OBJECTIVE: A multicenter, randomized, double-blind, vehicle controlled study of 178 subjects evaluated the efficacy of ciclopirox gel in treating seborrheic dermatitis of the scalp. METHODS: One hundred and seventy-eight subjects were randomized to apply either ciclopirox gel 0.77% twice daily, or vehicle twice daily for 28 days. Subjects' signs and symptoms of severity (erythema, scaling, pruritus and burning) were rated on a scale of 0-3 (none to severe); for inclusion, a minimum score of 4, for the sum of the individual ratings was required. Efficacy evaluations were performed at baseline, days 4, 8, 15, 22, 29, and at end-point (final visit, up to day 33). The primary efficacy variable was clinical response assessed by a global improvement, based on a scale of 0-5 (100% clearance to flare of treatment area). Changes in signs/symptoms severity scores within the target lesion were also evaluated. RESULTS: Global evaluation scores demonstrated that significantly more ciclopirox-treated subjects achieved over 75% improvement compared with vehicle at days 22, 29, and endpoint (P < 0.01). Change-from-baseline mean score for total signs and symptoms was significantly greater in ciclopirox subjects compared with vehicle subjects at the same time points as above (P < 0.001), as well as day 15 (P < 0.01). Twenty-nine percent of subjects rated ciclopirox as having excellent cosmetic acceptability. There were only mild adverse events, with the most common being burning sensation in 13% of ciclopirox subjects and 9% of vehicle subjects. CONCLUSION: Ciclopirox gel is effective and safe in the treatment of seborrheic dermatitis of the scalp.

Administration, Topical↗

Cardiac output augmentation during hypoxemia improves cerebral metabolism after hypothermic cardiopulmonary bypass.

BACKGROUND: Hypothermic circulatory arrest (HCA) impairs cerebral oxygen delivery (CDO2) and cerebral oxygen consumption (CMRO2), which are further reduced by perioperative hypoxemia. This study investigates if continuous hypothermic low-flow cardiopulmonary bypass (HLF) or intermittent hypothermic low-flow cardiopulmonary bypass (IHLF) can prevent reductions in CDO2 and CMRO2 during hypoxemia. METHODS: Eighteen neonatal piglets, cooled to 16 degrees to 18 degrees C with cardiopulmonary bypass (CPB), were randomly assigned into three groups: HCA, HLF (50 cc.kg(-1).min(-1)), or IHLF (1 minute of HLF for every 15 minutes of HCA). After 60 minutes of hypothermia, normothermic CPB (100 cc.kg(-1).min(-1)) was established and cerebral perfusion data measured at hyperoxemia (PaO2 150 to 250 mm Hg), hypoxemia (PaO2 50 to 60 mm Hg), and severe hypoxemia (PaO2 30 to 40 mm Hg), and with increased CPB flow (200 cc.kg(-1).min(-1)) during severe hypoxemia. RESULTS: The CMRO2 (in mL O2.100 g(-1).min(-1)) was lower after HCA (2.5 +/- 0.3), compared with HLF (4.1 +/- 0.5, p = 0.02) and IHLF (6.2 +/- 0.8, p = 0.002). Within groups, the change from hyperoxemia to severe hypoxemia resulted in decreased CMRO2: HCA (1.3 +/- 0.2, p = 0.004), HLF (3.0 +/- 0.5, p = 0.01), and IHLF (2.9 +/- 0.5, p = 0.01). During severe hypoxemia, increasing CPB flow (from 100 cc.kg(-1).min(-1) to 200 cc.kg(-1).min(-1)) improved CMRO2: HCA (1.9 +/- 0.5, p = 0.05), HLF (4.2 +/- 0.5, p = 0.05), and IHLF (7.4 +/- 0.5, p = 0.04). CONCLUSIONS: Hypoxemia reduces CDO2 and CMRO2 despite the method of hypothermic CPB. Increased CPB flow during hypoxemia can restore both CDO2 and CMRO2 to values found with hyperoxemia and slower CPB flows. Augmenting cardiac output during periods of perioperative hypoxemia may prevent cerebral injury after exposure to hypothermic cardiopulmonary bypass.

Animals↗

Model-independent analysis of the orientation of fluorescent probes with restricted mobility in muscle fibers.

The orientation of proteins in ordered biological samples can be investigated using steady-state polarized fluorescence from probes conjugated to the protein. A general limitation of this approach is that the probes typically exhibit rapid orientational motion ("wobble") with respect to the protein backbone. Here we present a method for characterizing the extent of this wobble and for removing its effects from the available information about the static orientational distribution of the probes. The analysis depends on four assumptions: 1) the probe wobble is fast compared with the nanosecond time scale of its excited-state decay; 2) the orientational distributions of the absorption and emission transition dipole moments are cylindrically symmetrical about a common axis c fixed in the protein; 3) protein motions are negligible during the excited-state decay; 4) the distribution of c is cylindrically symmetrical about the director of the experimental sample. In a muscle fiber, the director is the fiber axis, F. All of the information on the orientational order of the probe that is available from measurements of linearly polarized fluorescence is contained in five independent polarized fluorescence intensities measured with excitation and emission polarizers parallel or perpendicular to F and with the propagation axis of the detected fluorescence parallel or perpendicular to that of the excitation. The analysis then yields the average second-rank and fourth-rank order parameters ( and ) of the angular distribution of c relative to F, and and , the average second-rank order parameters of the angular distribution for wobble of the absorption and emission transition dipole moments relative to c. The method can also be applied to other cylindrically ordered systems such as oriented lipid bilayer membranes and to processes slower than fluorescence that may be observed using longer-lived optically excited states.

Animals↗

Melting and burning solids into liquids and gases.

We propose a novel technique for melting and burning solid materials, including the simulation of the resulting liquid and gas. The solid is simulated with traditional mesh-based techniques (triangles or tetrahedra) which enable robust handling of both deformable and rigid objects, collision and self-collision, rolling, friction, stacking, etc. The subsequently created liquid or gas is simulated with modern grid-based techniques, including vorticity confinement and the particle level set method. The main advantage of our method is that state-of-the-art techniques are used for both the solid and the fluid without compromising simulation quality when coupling them together or converting one into the other. For example, we avoid modeling solids as Eulerian grid-based fluids with high viscosity or viscoelasticity, which would preclude the handling of thin shells, self-collision, rolling, etc. Thus, our method allows one to achieve new effects while still using their favorite algorithms (and implementations) for simulating both solids and fluids, whereas other coupling algorithms require major algorithm and implementation overhauls and still fail to produce rich coupling effects (e.g., melting and burning solids).

Algorithms↗

Health promotion and the use of Gpass in Scotland.

OBJECTIVE: To identify how computerised practices using Gpass software (General Practice Administration System for Scotland), currently implement the new health promotion regulations. DESIGN: Postal questionnaire to all Gpass practices in Scotland. Data were gathered on types and methods of recording health promotion data, Read code selection, health education given and intended methods of data analysis. Questionnaire results were compared with data from an Electronic Questionnaire analysing actual data recorded on practice computers. RESULTS: Overall response rate: 64.6%, 94.8% of the responding practices have been approved for health promotion band three. Most practices (94.5%) use their computer for data collection, 63.6% of practices use a manual data capture form and 28.8% use computer data capture methods. Methods of collecting patient data and selection of Read codes for computer data entry are variable. Most practices use one method of data collection; a significant minority use multiple methods or more than one Read code to record the same item. The recording of health promotion on computer has increased greatly since the introduction of the new regulations: the current levels of recording are alcohol history (26.3%), blood pressure reading (57.6%), smoking (35.4%), exercise (7.1%), weight (21.4%) and height (16.4%). Most practices (94.3%) intend using Gpass for data analysis. CONCLUSION: Methods of collecting and recording health promotion data differ greatly between practices, with variable standardisation of health promotion codes and differing use of appropriate elements of the Gpass software.

Adult↗

The use of live three-dimensional Doppler echocardiography in the measurement of cardiac output: an in vivo animal study.

OBJECTIVES: The purpose of this study was to investigate whether cardiac output (CO) could be accurately computed from live three-dimensional (3-D) Doppler echocardiographic data in an acute open-chested animal preparation. BACKGROUND: The accurate measurement of CO is important in both patient management and research. Current methods use invasive pulmonary artery catheters or two-dimensional (2-D) echocardiography or esophageal aortic Doppler measures, with the inherent risks and inaccuracies of these techniques. METHODS: Seventeen juvenile, open-chested pigs were studied before undergoing a separate cardiopulmonary bypass procedure. Live 3-D Doppler echocardiography images of the left ventricular outflow tract and aortic valve were obtained by epicardial scanning, using a Philips Medical Systems (Andover, Massachusetts) Sonos 7500 Live 3-D Echo system with a 2.5-MHz probe. Simultaneous CO measurements were obtained from an ultrasonic flow probe placed around the aortic root. Subsequent offline processing using custom software computed the CO from the digital 3-D Doppler DICOM data, and this was compared to the gold standard of the aortic flow probe measurements. RESULTS: One hundred forty-three individual CO measurements were taken from 16 pigs, one being excluded because of severe aortic regurgitation. There was good correlation between the 3-D Doppler and flow probe methods of CO measurement (y = 1.1x - 9.82, R(2) = 0.93). CONCLUSIONS: In this acute animal preparation, live 3-D Doppler echocardiographic data allowed for accurate assessment of CO as compared to the ultrasonic flow probe measurement.

Animals↗

Effect of freezing parameters (freeze cycle and thaw process) on tissue destruction following renal cryoablation.

BACKGROUND AND PURPOSE: Renal cryoablation is a successful nephron-sparing treatment alternative for selected patients with small renal tumors. The purpose of this study was to compare the effects of the number of freeze cycles (one v two) and the thaw process (active v passive) on renal tissue following cryodestruction. MATERIALS AND METHODS: Sixteen female mongrel dogs (19.9 +/- 2.1 kg) were randomly divided into four groups and underwent transabdominal laparoscopic access by standard techniques. Tissue freezing was performed using argon gas following interstitial cryoprobe (3 mm) placement into the upper and lower poles of the left kidney. Single active (SA), single passive (SP) double active (DA) or double passive (DP) 15-minute treatment cycle(s) were carried out via the CRYOcare Cryosurgical Unit (Endocare, Irving, CA) on eight kidneys each. An active thaw process with helium gas or a passive thaw process was initiated after each freeze period. The cryoprobe was removed when the temperature reached 0 degrees C. Four weeks following cryosurgery, animals were sacrificed, and the renal tissue was evaluated grossly and histologically. RESULTS: Interstitial cryoprobe temperatures decreased from 31.3 degrees C +/- 1.4 degrees C to -142 degrees C +/- 1.0 degrees C following the 15-minute freeze cycle. The temperature reached 0 degrees C significantly faster following active thaw than with the passive process (2.13 +/- 0.24 min/freeze cycle and 15.18 +/- 2.97 min/freeze cycle, respectively; P < 0.0001). Grossly, each lesion consisted of a central area of necrosis surrounded by a rim of white tissue. On microscopic examination, each lesion consisted of a central area of liquefaction necrosis (LN) surrounded by various degrees of fibrosis and granulation tissue admixed with residual parenchyma. The size of the LN was significantly different in tissues subjected to double and single freeze cycles when compared across both thaw processes (active and passive). There was no significant difference in the overall lesion volume following DA, DP, SA, or SP. CONCLUSIONS: Renal cryodestruction via laparoscopic access achieves complete tissue ablation without complications. The double freeze cycle produced significantly larger areas of LN than the single freeze regardless of the thaw process. The type of thaw process did not affect the amount of tissue damage. Utilizing a double 15-minute freeze cycle with the faster active thaw process will effectively cryoablate renal tissue as well as significantly reduce overall operative time.

Animals↗

Manipulation of neuronal nitric oxide synthase within the paraventricular nucleus using adenovirus and antisense technology.

Congestive heart failure (CHF) is characterized by impaired cardiovascular reflexes and increased neurohumoral drive. The long-term sympatho-excitation increases the progression and risk of mortality during CHF. The paraventricular nucleus (PVN) of the hypothalamus is a very important central site for integration of sympathetic outflow and cardiovascular function. Within the PVN, nitric oxide (NO), mainly generated by neuronal nitric oxide synthase (nNOS), functions in inhibitory regulation of sympathetic outflow. Our previous study has indicated that in rats with experimental heart failure, the NO mechanism within the PVN is attenuated. We hypothesize that this alteration may contribute to the sympatho-excitation commonly observed in CHF. To investigate the role of NO within the PVN in sympathetic dysfunction in CHF, we have manipulated nNOS expression using adenoviral gene transfer of nNOS or nNOS antisense. These techniques have allowed us to observe the effects of alterations in nNOS on sympathetic outflow and cardiovascular function. In this chapter, we describe the methods for delivering nNOS adenoviral vector or nNOS antisense into the PVN using microinjection, as well as the protocols for detecting nNOS expression after these manipulations, using Western blot, NADPH-diaphorase staining, and immunofluorescent staining.

Adenoviridae↗

Polyamine-stimulated growth of cultured rat urinary bladder epithelial cells.

A technique for isolating and establishing long-term cultures of rat urinary bladder epithelium has been devised. Cells isolated and cultured by this method have been grown for 12 weeks without subculturing. Rat bladder epithelial cells require the addition of putrescine, spermine, and spermidine to attain maximum growth and long-term survival. Monolayer cultures have been subcultured and carried through five passages.

Animals↗

Disseminated Mycoplasma orale infection in a patient with common variable immunodeficiency syndrome.

Human infection with Mycoplasma species other than M. pneumoniae are infrequent, but may be encountered in patients with immunodeficiencies. We report a patient with combined variable immunodeficiency that developed multiple abscesses and destructive bone disease caused by M. orale, an organism generally considered to be non-pathogenic. Molecular laboratory methods, 16S rRNA sequence analysis, were used to detect the organism directly in the surgical specimen and confirmed following isolating of the organism. This case demonstrates the importance of molecular technology in the diagnosis of difficult infectious disease problems.

Administration, Oral↗

Benzene exposures during gasoline loading at bulk marketing terminals.

A study was conducted at 20 gasoline bulk marketing terminals to determine benzene exposure levels to both Gulf and outside carrier personnel operating at these facilities. Emphasis was placed on breathing zone samples of short duration during loading of trucks at the rack. Racks utilizing various methods of product transfer were surveyed. From the results of the study, it can be seen that the largest employee exposure to benzene occurs at facilities utilizing top loading without vapor recovery. Exposures during loading can exceed 0.5 ppm for an eight-hour time-weighted average.

Air Pollutants↗

[Respiratory effects of epidural anesthesia and anesthetic level obtained in patients for cesarean section].

In order to determine the optimal level of epidural anesthesia, the author examined respiratory function of 138 full-term pregnant women in sitting and supine positions without anesthesia, and in supine position under epidural anesthesia prior to the cesarean section. Vital capacity (VC) increased in the sitting position in comparison with supine position because expiratory reserve volume (ERV) and tidal volume (TV) increased. In contrast, %FFV1.0, peak expiratory flow (PEF) and V75 decreased as uterus shifted anteriorly in the sitting position. Under the epidural anesthesia with T4-T6 analgesic, TV showed a relative increase resulting in an increase in VC. This was due to lateral displacement of the uterus alleviating the depression of diaphragm. Epidural anesthesia with levels C8-T3 caused a reduction in inspiratory reserve volume (IRV) and ERV which in turn resulted in a decrease in VC and PaCO2. This change depended on the paralysis of respiratory muscles and the dyspneic feeling of patient. Generally %FFV1.0 and the data related to flow volume curve decreased under epidural anesthesia. In conclusion, epidural anesthesia with T4-T6 levels accompanied a sufficient analgesic efficacy and respiratory function comparable with that in the sitting position without anesthesia, therefore this was considered to be a method of choice for cesarean section.

Adult↗

Sensory-mechanical relationships during high-intensity, constant-work-rate exercise in COPD.

During constant-work-rate exercise in chronic obstructive pulmonary disease, dyspnea increases steeply once inspiratory reserve volume (IRV) falls to a critical level that prevents further expansion of tidal volume (Vt). We studied the effects of this mechanical restriction on the quality and intensity of exertional dyspnea and examined the impact of an anticholinergic bronchodilator. In a randomized, double-blind, crossover study, 18 patients with chronic obstructive pulmonary disease (forced expiratory volume in 1 s = 40 +/- 3%predicted; mean +/- SE) inhaled tiotropium 18 mug or placebo once daily for 7-10 days each. Pulmonary function tests and symptom-limited cycle exercise at 75% of each patient's maximal work capacity were performed 2 h after dosing. Dyspnea intensity (Borg scale), operating lung volumes, breathing pattern, and esophageal pressure (n = 11) were measured during exercise. Dynamic hyperinflation reached its maximal value early in exercise and was associated with only mild increases in dyspnea intensity and the effort-displacement ratio, which is defined as the ratio between tidal swings of esophageal pressure (expressed relative to maximum inspiratory pressure) and Vt (expressed relative to predicted vital capacity). After a minimal IRV of 0.5 +/- 0.1 liter was reached, both dyspnea and the effort-displacement ratio rose steeply until an intolerable level was reached. Tiotropium did not alter dyspnea-IRV relationships, but the increase in resting and exercise inspiratory capacity was associated with an improved effort-displacement ratio throughout exercise. Once a critically low IRV was reached during exercise, dyspnea rose with the disparity between respiratory effort and the Vt response. Changes in dyspnea intensity after tiotropium were positively correlated with changes in this index of neuromechanical coupling.

Administration, Inhalation↗

The detour extra-anatomic stent--a permanent solution for benign and malignant ureteric obstruction?

OBJECTIVES: We describe our experience of the Detour extra-anatomic stent (EAS) (Mentor-Porgés, UK) for permanent bypass of complete upper urinary tract obstruction. The self-retaining expanded polytetrafluoroethylene-silicone tube, placed in the kidney using a percutaneous route, is tunnelled under the skin and sutured into the bladder to establish extra-anatomical urinary drainage. METHODS: From April 2002 to November 2005, a total of nine Detour stents were inserted into eight patients; one patient needed bilateral stent insertions. The causes for ureteric obstruction were persistent malignant disease in three and complicated benign disease in five patients. RESULTS: To date, four of five patients with benign disease are alive; one died unexpectedly of metastatic malignancy. The only stent-related complications were infection and haematuria. The two patients with malignancy have subsequently died, but there were no urinary drainage problems for their second and third years of life, respectively. CONCLUSIONS: The preliminary data presented here suggest that the Detour EAS offers a permanent and minimally invasive method to establish internalisation of urinary drainage to bypass complete ureteric obstructions for which conventional stenting has failed, open surgery has been tried and failed or was not considered feasible, and long-term nephrostomy drainage was not favoured.

Adult↗

Intraoperative radiotherapy for breast cancer.

Postoperative radiotherapy, which forms part of breast-conserving therapy, may not need to encompass the whole breast. Apart from the consumption of huge resources and patients' time, postoperative radiotherapy deters many women from receiving the benefits of breast-conserving surgery, forcing them to choose a mastectomy instead. If radiotherapy could be given in the operating theatre immediately after surgery, many of these disadvantages could be overcome. One striking fact about local recurrence after breast-conserving surgery is that most occurs in the area of breast immediately next to the primary tumour; this is despite the finding that two-thirds of mastectomy samples have microscopic tumours distributed throughout the breast, even when radiotherapy is omitted. Thus, only the area adjacent to the tumour may need treatment with radiotherapy. On the basis of this premise, clinical scientists have used new technology to administer radiotherapy to the area at greatest risk of local recurrence, with the aim of completing the whole local treatment in one sitting. In this review, we have elaborated on the rationale and different methods of delivery of intraoperative radiotherapy. If this approach is validated by the results of current randomised trials, it could save time, money, and breasts.

Breast Neoplasms↗

Quantitative estimation of attenuation in ultrasound video images: correlation with histology in diffuse liver disease.

RATIONALE AND OBJECTIVES: To determine the relationship between the attenuation of backscatter intensity in B-scan images of the liver and diffuse liver disease in order to assess the usefulness of this method in providing quantitative objective characterization of diffuse liver diseases in general and in fatty liver in particular. METHODS: Twenty-four healthy volunteers and 28 patients with elevated liver enzyme levels who underwent liver biopsy were included in this study. An automatic far-field slope (FFS) algorithm that estimates the decrease in amplitude of the backscattered echo as a function of beam depth was implemented on the noncompensated image that was acquired on a commercial phased-array ultrasound system fitted to a custom-built interface card. The images were processed at a work-station. All scans were acquired repeatedly, read, and graded blindly by experienced ultrasound radiologists. Histology obtained via needle biopsy was reviewed without knowledge of the ultrasound findings. RESULTS: Analysis of the FFS data for fatty infiltration in all patient groups yielded a sensitivity of 67%, a specificity of 77%, a positive predictive value (PPV) of 77%, negative predictive value (NPV) of 67%, and an accuracy of 71%. The mean score of the ultrasound reviewers showed a sensitivity of 82%, a specificity of 66%, a PPV% of 68%, an NPV of 81%, and an accuracy of 72%. Normal FFS values (false-negative) were found in five patients with proved fatty infiltration. All of these patients had coexistent moderate to severe hepatic inflammation. However, FFS data in patients with uncomplicated (pure) fatty infiltration revealed a sensitivity of 100%, a specificity of 80%, a PPV of 89%, an NPV of 100%, and an accuracy of 92%. The best ultrasound score yielded a sensitivity of 100%, a specificity of 60%, a PPV of 80%, an NPV of 100%, and an accuracy of 85% in the same patients. CONCLUSIONS: The data demonstrate an excellent sensitivity (100%) of the FFS values in patients with uncomplicated fatty infiltration. This was also the only group of patients in whom the FFS score was superior to the radiologists' best score. The FFS method can be used as a tool to follow up the response to a clinical or research treatment and to obtain standardization of pattern interpretation independently of the individual reader.

Adolescent↗

Pilot clinical trial of 18F-fluorodeoxyglucose positron-emission mammography in the surgical management of breast cancer.

BACKGROUND: High-resolution positron-emission mammography (PEM) is a new device, which allows the imaging of breast tissue. A prospective study was performed to assess the accuracy of PEM in newly diagnosed breast cancer patients. METHODS: In a prospective multicenter study, 44 women with confirmed breast cancers were imaged with a high-resolution PEM scanner (Naviscan PET Systems, Rockville, MD) with 18F-fluorodeoxyglucose. The images were blindly evaluated and were compared with final pathology. RESULTS: The majority of the index lesions were seen on PEM (89%, 39/44). PEM detected 4 of 5 incidental breast cancers, 3 of which were not seen by any other imaging modalities. Of 19 patients undergoing breast-conserving surgery, PEM correctly predicted 6 of 8 (75%) patients with positive margins and 100% (11/11) with negative margins. CONCLUSION: The current PEM device shows promise in detecting breast malignancies and may assist in the planning of adequate partial mastectomy procedures to better ensure negative margins.

Adult↗