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At least 91 records · Page 5Linked to original sources

Labour migration and the work permit system in the United Kingdom.

"The aim of this paper is to examine the effects of the work permit today [in the United Kingdom], using official data. It first reviews the operation of the [labor migration] system and describes the main schemes incorporated. Then, it uses data for 1984-88 to describe the general characteristics of labor immigration through the schemes. Finally, by means of a small random sample of applications and issues, it presents details on particular aspects of the immigration. It demonstrates that current labour immigration through the system is selective: most of those entering with long-term permits are highly skilled, well paid, and moving within the internal labor markets of large transnational corporations." (SUMMARY IN FRE AND SPA)

Demography↗

Tumescent technique for regional anesthesia permits lidocaine doses of 35 mg/kg for liposuction.

The tumescent technique for local anesthesia permits regional local anesthesia of the skin and subcutaneous tissues by direct infiltration. The tumescent technique uses large volumes of a dilute anesthetic solution to produce swelling and firmness of targeted areas. This investigation examines the absorption pharmacokinetics of dilute solutions of lidocaine (0.1% or 0.05%) and epinephrine (1:1,000,000) in physiologic saline following infiltration into subcutaneous fat of liposuction surgery patients. Plasma lidocaine concentrations were measured repeatedly over more than 24 hours following the infiltration. Peak plasma lidocaine levels occurred 12-14 hours after beginning the infiltration. Clinical local anesthesia is apparent for up to 18 hours, obviating the need for postoperative analgesia. Dilution of lidocaine diminishes and delays the peak plasma lidocaine concentrations, thereby reducing potential toxicity. Liposuction reduces the total amount of lidocaine absorbed systemically, but does not dramatically reduce peak plasma lidocaine levels. A safe upper limit for lidocaine dosage using the tumescent technique is estimated to be 35 mg/kg. Infiltrating a large volume of dilute epinephrine assures diffusion throughout the entire targeted area while avoiding tachycardia and hypertension. The associated vasoconstriction is so complete that there is virtually no blood loss with liposuction. The tumescent technique can be used with general anesthesia or IV sedation. However, with appropriate instrumentation and surgical method, the tumescent technique permits liposuction of large volumes of fat totally by local anesthesia, without IV sedation or narcotic analgesia.

Absorption↗

Rapid dissemination by the agent of Lyme disease in hosts that permit fulminating infection.

We determined whether the agent of Lyme disease (Borrelia burgdorferi) disseminates more rapidly following deposition in hosts that permit fulminating infection than in hosts in which infection is relatively benign. Thus, individual infected nymphal deer ticks (Ixodes dammini) were permitted to engorge on the ears of C3H mice, and the site of attachment was excised at intervals thereafter. Infection in each mouse was determined by serology and by examining previously noninfected ticks that had engorged on these mice. These results were compared with data obtained similarly by using the CD-1 strain of mice in which the agent is relatively nonpathogenic. When the site of inoculation was ablated within 2 days after the infected tick became replete, dissemination was aborted. Spirochetemia could not be demonstrated in any of these mice. We conclude that Lyme disease spirochetes disseminate from the feeding lesion of an infecting tick more rapidly in certain highly spirochete-susceptible mice than in others in which pathogenesis is less severe.

Animals↗

Two novel adenovirus vector systems permitting regulated protein expression in gene transfer experiments.

Two new adenovirus vector systems based on the tetracycline-regulated Tet-ON- (Gossen, M., et al., Science 268:1766-1769, 1995) and the RU 486-regulated progesterone antagonist (Wang, Y., et al., Proc. Natl. Acad. Sci. USA 91:8180-8184, 1994)-induced gene expression systems are described. We show that both systems permit a tight control of chloramphenicol acetyltransferase reporter gene expression in a variety of cell types, with induction levels of approximately 1,800-fold (Tet-ON system) and 600-fold (RU 486-regulated system), respectively. A significant advantage of our vector systems is that reporter protein expression can be adjusted over a wide range by varying the amount of inducer. The Tet-ON system is also shown to permit an efficient control of reporter gene expression in mice.

3T3 Cells↗

Restricting extensions to permitted licensing hours does not influence the numbers of alcohol or assault related attendances at an inner city accident and emergency department.

OBJECTIVE: To determine the effect of restricting extensions to permitted licensing hours on the numbers of alcohol or assault related attendances at an inner city accident and emergency (A&E) department. METHODS: Prospective data collection on consecutive attendances between 17.00 and 09.00 h during three study periods: two weeks before the introduction of the restriction, two weeks immediately afterwards, and for a two week period beginning five weeks after the change. Blood alcohol concentration was measured with a pocket alcohol meter. RESULTS: Overall 56.5% of patients (n = 2836) provided a breath sample, and 28.9% (819) were positive. The proportion of patients testing positively peaked between 02.00 and 04.00 h. A very high proportion of assault cases who were tested (260) were positive (67.3%). Assault cases comprised 19.1% of all attendances between 24.00 and 04.00 h. No significant changes in the pattern of alcohol or assault related attendances followed the restriction in extensions to permitted licensing hours. CONCLUSIONS: A policy of uniform closing times of licensed premises does not influence the profile of alcohol or assault related attendances at an inner city A&E department.

Alcohol Drinking↗

Cross-bridge blocker BTS permits direct measurement of SR Ca2+ pump ATP utilization in toadfish swimbladder muscle fibers.

Because the major processes involved in muscle contraction require rapid utilization of ATP, measurement of ATP utilization can provide important insights into the mechanisms of contraction. It is necessary, however, to differentiate between the contribution made by cross-bridges and that of the sarcoplasmic reticulum (SR) Ca2+ pumps. Specific and potent SR Ca2+ pump blockers have been used in skinned fibers to permit direct measurement of cross-bridge ATP utilization. Up to now, there was no analogous cross-bridge blocker. Recently, N-benzyl-p-toluene sulfonamide (BTS) was found to suppress force generation at micromolar concentrations. We tested whether BTS could be used to block cross-bridge ATP utilization, thereby permitting direct measurement of SR Ca2+ pump ATP utilization in saponin-skinned fibers. At 25 microM, BTS virtually eliminates force and cross-bridge ATP utilization (both <4% of control value). By taking advantage of the toadfish swimbladder muscle's unique right shift in its force-Ca2+ concentration ([Ca2+]) relationship, we measured SR Ca2+ pump ATP utilization in the presence and absence of BTS. At 25 microM, BTS had no effect on SR pump ATP utilization. Hence, we used BTS to make some of the first direct measurements of ATP utilization of intact SR over a physiological range of [Ca2+]at 15 degrees C. Curve fits to SR Ca2+ pump ATP utilization vs. pCa indicate that they have much lower Hill coefficients (1.49) than that describing cross-bridge force generation vs. pCa (approximately 5). Furthermore, we found that BTS also effectively eliminates force generation in bundles of intact swimbladder muscle, suggesting that it will be an important tool for studying integrated SR function during normal motor behavior.

Adenosine Triphosphate↗

Modification to a commercial immunoradiometric assay permitting intraoperative monitoring of parathyroid hormone levels.

We describe a modification to a commercially available immunoradiometric assay which reduces the turnaround time for parathyroid hormone (PTH) measurement to 1 h and permits intraoperative monitoring during parathyroidectomy. Alterations in PTH concentrations following removal of parathyroid tissue are compared with those of calcium, ionised calcium and phosphate. PTH measurements obtained intraoperatively permit definitive conclusions about the success of the operation within 1 h of sampling, allowing re-exploitation of the gland to take place immediately if necessary.

Calcium↗

Molecular monitoring of adenovirus in peripheral blood after allogeneic bone marrow transplantation permits early diagnosis of disseminated disease.

Adenovirus (AdV) infection in the course of allogeneic stem cell transplantation (SCT) is associated with high transplant-related morbidity and mortality. Disseminated AdV disease is lethal in most instances. Early detection of AdV infection and identification of patients carrying a high risk of disseminated disease therefore remain a major challenge. In view of the large number of existing AdV types, we have established real-time polymerase chain reaction (PCR) assays permitting sensitive detection and quantification of all 51 currently known human AdV serotypes. In a series of 132 consecutive pediatric patients undergoing SCT, more than 5000 samples derived from peripheral blood (PB), stool, urine, and throat were screened for adenovirus infection by PCR during the posttransplantation period. Thirty-six patients (27%) tested positive by PCR, revealing AdV types of the subgenera A, B, C, D, and F. Except for enteritis in some patients with AdV positivity in stool, detection of the virus at sites other than PB was not associated with clinical signs of virus disease, and transplant-related mortality was not significantly different from AdV-negative patients. By contrast, 82% of patients who had detectable AdV in PB died from infectious complications (P <.001). Monitoring of PB specimens by real-time PCR permitted early diagnosis of invasive AdV infection in all instances. In patients who developed disseminated AdV disease, detection of the virus in PB preceded onset of clinical symptoms by a median of more than 3 weeks. The observation of AdV in peripheral blood may therefore serve as a basis for early initiation of preemptive antiviral treatment.

Adenoviridae↗

Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice.

INTRODUCTION: Our goal was to generate xenograft mouse models of human breast cancer based on luciferase-expressing MDA-MB-231 tumor cells that would provide rapid mammary tumor growth; produce metastasis to clinically relevant tissues such as lymph nodes, lung, and bone; and permit sensitive in vivo detection of both primary and secondary tumor sites by bioluminescent imaging. METHOD: Two clonal cell sublines of human MDA-MB-231 cells that stably expressed firefly luciferase were isolated following transfection of the parental cells with luciferase cDNA. Each subline was passaged once or twice in vivo to enhance primary tumor growth and to increase metastasis. The resulting luciferase-expressing D3H1 and D3H2LN cells were analyzed for long-term bioluminescent stability, primary tumor growth, and distal metastasis to lymph nodes, lungs, bone and soft tissues by bioluminescent imaging. Cells were injected into the mammary fat pad of nude and nude-beige mice or were delivered systemically via intracardiac injection. Metastasis was also evaluated by ex vivo imaging and histologic analysis postmortem. RESULTS: The D3H1 and D3H2LN cell lines exhibited long-term stable luciferase expression for up to 4-6 months of accumulative tumor growth time in vivo. Bioluminescent imaging quantified primary mammary fat pad tumor development and detected early spontaneous lymph node metastasis in vivo. Increased frequency of spontaneous lymph node metastasis was observed with D3H2LN tumors as compared with D3H1 tumors. With postmortem ex vivo imaging, we detected additional lung micrometastasis in mice with D3H2LN mammary tumors. Subsequent histologic evaluation of tissue sections from lymph nodes and lung lobes confirmed spontaneous tumor metastasis at these sites. Following intracardiac injection of the MDA-MB-231-luc tumor cells, early metastasis to skeletal tissues, lymph nodes, brain and various visceral organs was detected. Weekly in vivo imaging data permitted longitudinal analysis of metastasis at multiple sites simultaneously. Ex vivo imaging data from sampled tissues verified both skeletal and multiple soft tissue tumor metastasis. CONCLUSION: This study characterized two new bioluminescent MDA-MB-231-luc human breast carcinoma cell lines with enhanced tumor growth and widespread metastasis in mice. Their application to current xenograft models of breast cancer offers rapid and highly sensitive detection options for preclinical assessment of anticancer therapies in vivo.

Animals↗

Preclinical evaluation of a novel intracerebral microinjection instrument permitting electrophysiologically guided delivery of therapeutics.

OBJECTIVE: This series of studies was designed to evaluate the function of a new neurosurgical instrument for precision injection of therapeutics within the central nervous system. METHODS: An intracerebral microinjection instrument was designed to 1) allow multiple injections to be placed in three-dimensional space within a target structure from a single proximal brain penetration, 2) incur minimal injury at the site of injection, 3) enable accurate microvolume injections, and 4) permit electrophysiological recording during the injection procedure. Rats received injections of fluorescent microspheres or suspensions of labeled cells to test instrument function and level of induced trauma. A rodent model of stroke was used to test the instrument's ability to record electrocorticograms or somatosensory evoked potentials from normal and damaged tissue. RESULTS: Microliter volumes of fluorescent microspheres were accurately placed at predetermined sites within the rat striatum. Reactive gliosis was markedly reduced using the intracerebral microinjection instrument when compared with standard cannulas. In a stroke model, electrophysiological recording with the instrument allowed discrimination between viable and nonviable ischemic tissue, and function of pathways or circuits was assessed using evoked potentials. Embryonic stem cells grafted immediately after electrophysiological recordings demonstrated robust long-term survival. CONCLUSION: The intracerebral microinjection instrument enables electrophysiologically guided microinjection of therapeutics to target areas with exquisite accuracy while incurring minimal local trauma and reactive gliosis at the injection site. The instrument also permits minimally invasive, multiple injections to be disseminated in three-dimensional space within the target region from a single proximal penetration of the brain.

Animals↗

A study of criteria permitting the use of plastinated specimens for light and electron microscopy.

Plastination permits the preservation of anatomical specimens in a physical state approaching that of the living condition. We studied the possibility of using silicone plastinated fragments of spleen and pancreas for optical and electron microscopy, and found that with an adequate fixation protocol, plastinated specimens can be used for both light microscopy and ultrastructural studies. Deplastination with sodium methoxide permitted production of clean sections. Artifacts produced by plastination/deplastination could be nearly eliminated by glutaraldehyde/formaldehyde fixation. The (Biodur) silicone S10 polymer is transparent and stable in an electron beam, and plastinated tissues can be contrasted or colored similar to tissues embedded in Epon 812. In addition to being very life-like, plastinated tissues are stable and easy to handle. They can also be used for electron and light microscopic studies. This technique may also allow retrospective epidemiological studies of archived pathology specimens.

Animals↗

Acid Rain Program: general provisions and permits, allowance system, continuous emissions monitoring, excess emissions and administrative appeals--EPA. Final rule.

Title IV of the Clean Air Act (the Act), as amended November 15, 1990, requires the Environmental Protection Agency (EPA or Agency) to establish an Acid Rain Program to reduce the adverse effects of acidic deposition. To implement this statutory mandate, the Acid Rain Program requirements will be codified in seven regulations. This action delineates all or portions of five final regulations that were initially proposed December 3, 1991: General Provisions and Permits; the Allowance System; Continuous Emissions Monitoring; Excess Emissions Penalties; and Administrative Appeals. (The administrative appeals procedures were originally proposed as a subpart of the permits rule; EPA has decided to remove it from part 72 and place it in a separate part 78.) In addition to the final rules, this action includes a brief overview of the acid rain problem, summaries of major provisions of the proposed rules, the public's comments on these proposals, and summaries of the major changes that have been made in this final rule. DATES: These rules become effective February 10, 1993. The incorporation by reference of certain publications listed in the regulations is approved by the Director of the Federal Register as of February 10, 1993.

Acid Rain↗

Drug Enforcement Administration--Records and reports of registrants; central recordkeeping permits. Final rule.

This rule amends 1304.04(a) of Title 21 of the Code of Federal Regulations by eliminating Central Recordkeeping Permits but still provides a means whereby qualified registrants will be able to keep certain required records at a central location. The amendment will establish a simplified notification system in lieu of requiring a central recordkeeping permit necessary under current regulations.

Drug and Narcotic Control↗

Consolidated permit regulations and hazardous waste management system: Environmental Protection Agency. Notice of issuance of regulation interpretation memorandum.

The Environmental Protection Agency (EPA) is issuing today a Regulation Interpretation Memorandum (RIM) which provides official interpretation of the issue of whether a generator who accumulates hazardous waste pursuant to 40 CFR 262.34, may qualify for interim status after November 19, 1980. This issue arose when the requirements for submitting a Part A permit application (one of the prerequisites to qualifying for interim status) were amended on November 19, 1980. The provisions interpreted today are part of the Consolidated Permit Regulations promulgated under Subtitle C of the Solid Waste Disposal Act, as amended by the Resource Conservation and Recovery Act, as amended (RCRA).

Refuse Disposal↗

A Phase I trial of pulse calcitriol in patients with refractory malignancies: pulse dosing permits substantial dose escalation.

BACKGROUND: Calcitriol is the principal biologically active metabolite of vitamin D. Calcitriol's activity against many neoplasms is well documented, but calcitriol's therapeutic application has been hampered by predictable hypercalcemia when it is given daily. Because laboratory data has suggested that intermittent exposure to high levels of calcitriol may be sufficient to produce antiproliferative effects, the authors developed a Phase I trial to determine the maximal tolerated dose, dose-limiting toxicity, and the pharmacokinetic profile of calcitriol given weekly by mouth. METHODS: Patients with refractory malignancies were enrolled for 4 weeks of treatment followed by 4 weeks of observation. Reenrollment at a higher dose level was permitted for patients who had evidence of response or stable disease and no Grade 3 or greater toxicity. The starting dose was 0.06 microg/kg. RESULTS: Fifteen patients received 20 cycles of therapy. Doses up to 2.8 microg/kg of calcitriol weekly produced no dose-limiting toxicity. While peak levels and the area under the serum concentration-time curve of calcitriol increased in a linear fashion at lower doses, saturable absorption was observed at doses above 0.48 microg/kg. Doses of 0.48 microg/kg and above produced mean peak calcitriol levels of 1625 pg/mL, approximately 25-fold greater than top normal levels and well within the therapeutic range suggested by in vitro experiments. Eight patients experienced self-limiting Grade 1 hypercalcemia. CONCLUSIONS: Weekly dosing of oral calcitriol permitted substantial dose escalation with minimal toxicity. Peak serum calcitriol levels were in the predicted therapeutic range. A dose of 0.5 microg/kg was selected for evaluation in Phase II studies.

Adult↗

Genes that permit or prevent infections.

In addition to heritable immunodeficiencies and polygenic susceptibility, acquisition genes and resistance genes are important genetic determinants of infectious diseases. Normal forms of acquisition genes permit entry of microorganisms into cells; mutations prevent entry. Normal forms of resistance genes prevent infections; mutations permit infections. The Genome Project has resulted in a growing list of each type. The current lists support important clinical principles. Many, if not most, pathogens readily enter cells unless prevented by antisepsis, blocking, and sterile techniques. Many, if not most, infections occur primarily in persons with heritable mutations of resistance genes.

Communicable Diseases↗

Thoracic massage permits use of echocardiography in unanesthetized rats.

PURPOSE: The objective of the study reported here was to investigate whether massage-like stroking of the thorax and cranial portion of the abdomen might relax unanesthetized rats sufficiently to permit in vivo echocardiography. METHODS: Nine-month-old spontaneously hypertensive rats (SHR) were first conditioned to being held by hand for 10 to 15 min twice a day for seven to 10 days. During each session, the animal was placed in supine position, and the thorax and cranial abdominal area were gently stroked (approx. 5 cm/s, 12 to 14 times/min). After the conditioning period, echocardiography was initiated. We obtained serial transthoracic two-dimensional (2-D) and M-mode echocardiograms from nine-month-old SHR that were treated with isoproterenol (60 mg/kg of body weight, s.c., x 1, followed by 30 mg/kg/d x3), and from old (20 to 24 months old) SHR, studied when labored breathing, suggestive of heart failure, was evident (SHR-F). Measurements included end-diastolic volume (EDV) and end-systolic volume (ESV). RESULTS: In the isoproterenol-treated SHR, mean +/- SD echocardiographically derived EDV (2-D, 0.29 +/- 0.05; M-mode, 0.28 +/- 0.01 ml) was not significantly different from volume at necropsy (0.33 +/- 0.04 ml). Measurements of EDV and ESV by use of M-mode and 2-D echocardiography were significantly correlated (EDV R2 = 0.48, P = 0.05; ESV R2 = 0.39, P = 0.02). Echocardiography revealed pleuropericardial effusions (4/6), atrial thrombi (5/6), and left and right ventricular enlargement (6/6). The EDV and ESV were increased fivefold (P < 0.01) and threefold (P < 0.05), respectively, versus values for SHR not in heart failure (SHR-NF). Left ventricular ejection fraction of hearts from SHR-F was markedly decreased, compared with that in SHR-NF (44 +/- 7 versus 74 +/- 2%, respectively; P < 0.05). The presence or absence of left atrial thrombi and fluid in the thoracic cavity was confirmed at necropsy in SHR-F and SHR-NF. CONCLUSION: Thoracic massage permits use of echocardiography in unanesthetized rats, thereby providing a simple, non-invasive technique for assessment of cardiac structure and function in rats without the potentially adverse effects of anesthesia.

Anesthesia↗

[Color-coded duplex sonography of liver tumors. Does the blood supply permit a conclusion on staging?].

Real-time ultrasonography is a sensitive screening method in patients with suspected liver tumors. However, sonomorphology does not differentiate between benign and malignant tumors. In a prospective study we examined patients with liver tumors with color-coded duplex ultrasonography to find out whether the perfusion status of the liver tumor permits a differential diagnosis. A total of 108 patients with liver tumors were included, and the results of color-coded duplex sonography were compared with histology, MRI and CT. No correlation was seen between the final diagnosis and the perfusion pattern. The vascular status visualized by color-coded duplex ultrasonography does not permit differentiation between benign and malignant liver tumors.

Adolescent↗