Accurate portal dose measurement with a fluoroscopic electronic portal imaging device (EPID) for open and wedged beams and dynamic multileaf collimation

Measuring portal dose with an electronic portal imaging device (EPID) in external beam radiotherapy can be used to perform routine dosimetric quality control checks on linear accelerators and to verify treatments (in vivo dosimetry). An accurate method to measure portal dose images (PDIs) with a commercially available fluoroscopic EPID has been developed. The method accounts for (i) the optical 'cross talk' within the EPID structure, (ii) the spatially nonuniform EPID response and (iii) the nonlinearity of the EPID response. The method is based on a deconvolution algorithm. Measurement of the required input data is straightforward. The observed nonlinearity of the EPID response was largely due to the somewhat outdated EPID electronics. Nonlinearity corrections for more modern systems are expected to be smaller. The accuracy of the method was assessed by comparing PDIs measured with the EPID with PDIs measured with a scanning ionization chamber in a miniphantom, located at the same position as the fluorescent screen. For irradiations in open, wedged and intensity modulated 25 MV photon beams (produced with dynamic multileaf collimation) EPID and ionization chamber measurements agreed to within 1% (1 SD).     

5-Methoxypsoralen. A review of its effects in psoriasis and vitiligo

5-Methoxypsoralen, a naturally occurring linear furocoumarin, has been successfully used in combination with ultraviolet (UV) A irradiation [psoralen plus UV (PUVA)] to manage psoriasis and vitiligo. In patients and volunteers, PUVA 5-methoxypsoralen causes a dose-related increase in cutaneous photosensitivity. However, mean minimum phototoxic doses (MPD) were 30 to 50% greater with 5-methoxypsoralen than with 8-methoxypsoralen within individuals; this suggests lower photoactivity with 5-methoxypsoralen. In comparative clinical trials of parallel design, psoriasis clearance rates of > 90% or > 97% were observed in similar numbers of patients (60 to 77%) receiving oral PUVA 5-methoxypsoralen (typically 1.2 mg/kg) or oral PUVA 8-methoxypsoralen (0.6 mg/kg) treatment. Generally, 5-methoxypsoralen recipients required a greater total UVA exposure than 8-methoxypsoralen recipients to achieve end-point. However, study end-point was achieved sooner with oral or topical PUVA 5-methoxypsoralen in a small number of patients with psoriasis who received both treatments simultaneously and contralaterally. Up to 56% of patients with vitiligo achieved > 75% repigmentation with 5-methoxypsoralen (oral or topical) combined with UV irradiation (lamp or sun); the face and trunk were the most responsive areas. Lack of response to PUVA 5-methoxypsoralen treatment was observed in up to 16% of patients with psoriasis and, in 1 trial, in 22% of those with vitiligo. Lesion spreading during treatment of vitiligo was also observed in 7 (19%) patients in 1 study. The incidence and severity of adverse events was generally lower in PUVA 5-methoxypsoralen 1.2 mg/kg than in PUVA 8-methoxypsoralen 0.6 mg/kg recipients. Nausea and/or vomiting, pruritus and erythema were the most commonly reported adverse events in the short term; they occurred about 2 to 11 times more frequently in 8-methoxypsoralen than 5-methoxypsoralen recipients within clinical trials. Adverse hepatic events after oral administration of the drug were uncommon. Long term tolerability data for PUVA 5-methoxypsoralen are scarce; however, carcinogenicity was not reported during a 14-year observation period of 413 patients with psoriasis. CONCLUSION: Similar lesion clearance rates were observed with oral 5- or 8-methoxypsoralen plus UVA exposure in patients with vitiligo or psoriasis, although patients given 5-methoxypsoralen often required a greater total UV exposure than 8-methoxypsoralen recipients. The incidence of short term cutaneous and gastrointestinal adverse effects is markedly less with 5-methoxypsoralen than with 8-methoxypsoralen, which is an advantage, although the long term tolerability of 5-methoxypsoralen has yet to be fully established. Nevertheless, in appropriately selected patients, PUVA 5-methoxypsoralen therapy may be recommended as an alternative first-line systemic treatment option for the management of vitiligo or psoriasis.     

Immunization of cows with ferric enterobactin receptor from coliform bacteria

The serum and milk immunoglobulin (Ig) G responses of lactating dairy cows were determined following immunization with ferric enterobactin receptor FepA. Escherichia coli 471 was cultured in iron-depleted medium, and outer membrane proteins were extracted by 2% N-lauroylsarcosine sodium salt and 2% Triton X-100. The FepA was isolated from the outer membrane proteins by ion-exchange chromatography. Twenty cows were assigned to four treatment groups of 5 cows blocked by breed and days in milk. Treatment groups were vaccinated with 100 micrograms of FepA, 500 micrograms of FepA, Escherichia coli J5 bacterin, or sterile phosphate-buffered saline. Primary immunization was at approximately 200 d in milk, and booster immunizations were given 14 and 28 d later. Serum and whey IgG titers to FepA in cows vaccinated with FepA were significantly higher than those from cows vaccinated with either E. coli J5 bacterin or phosphate-buffered saline. Serum and whey IgG titers to FepA were elevated by 14 d in cows vaccinated with FepA. Significant differences were not observed between doses of FepA. The degree of cross-reactivity of purified IgG from cows vaccinated with FepA to E. coli and Klebsiella pneumoniae isolates was significantly higher than that to a control isolate that lacked FepA production. Immunization with FepA elicited an immunological response in serum and milk.     

Calcitropic peptides: neural perspectives

In mammals and higher vertebrates, calcitropic peptides are produced by peripheral endocrine glands: the parathyroid gland (PTH), thyroid or ultimobranchial gland (calcitonin) and the anterior pituitary gland (growth hormone and prolactin). These hormones are, however, also found in the neural tissues of lower vertebrates and invertebrates that lack these endocrine organs, suggesting that neural tissue may be an ancestral site of calcitropic peptide synthesis. Indeed, the demonstration of CNS receptors for these calcitropic peptides and their induction of neurological actions suggest that these hormones arose as neuropeptides. Neural and neuroendocrine roles of some of these calcitropic hormones (calcitonin and parathyroid hormone) and related peptides (calcitonin gene related peptide, stanniocalcin and parathyroid hormone related peptide) are thus the focus of this review.     

A prospective study to assess the frequency of familial clustering of congenital bicuspid aortic valve

Subspecific typing of clinical meningococcal strains is important in the investigation of outbreaks and for disease surveillance. Serogrouping, typing, and subtyping of strains currently require isolation of a meningococcus from one or more clinical specimens. However, the increasing widespread practice of preadmission administration of parenteral antibiotics has resulted in a decrease in the frequency of positive cultures obtained from blood and cerebrospinal fluid. Confirmation of meningococcal disease can be obtained by meningococcus-specific PCR from both cerebrospinal fluid (H. Ni et al., Lancet 340:1432-1434, 1992) and peripheral blood (J. Newcombe et al., J. Clin. Microbiol. 34:1637-1640, 1996) specimens. However, current PCR protocols do not yield epidemiologically useful typing information. We report here the use of PCR-single-stranded confirmational polymorphism (PCR-SSCP) analysis to amplify and type meningococcal DNA present in clinical specimens. PCR-SSCP analysis with the VR1 region of the Neisseria meningitidis porA gene as the target produced unique banding patterns for each serosubtype. Direct PCR-SSCP of clinical specimens can therefore provide typing data that can be used to investigate the epidemiology of clusters of cases and outbreaks and for disease surveillance in situations in which culture of patient specimens proves negative.     

Analysis of swainsonine and its early metabolic precursors in cultures of Metarhizium anisopliae

We examined the separate and combined effects of hypohydration level and exercise intensity on aldosterone (ALD) and arginine vasopressin (AVP) responses during exercise-heat stress. Nine heat acclimated men performed 50 min of treadmill exercise in a warm room (30 degrees C dry bulb (DB), 50% relative humidity (RH) at 25%, 45% and 65% VO2max when euhydrated and when hypohydrated by 3% and 5% of body weight. Blood samples were drawn at rest and at 20 min of exercise. ALD and AVP increased (P < 0.05) in a graded manner with hypohydration level, and this effect persisted during exercise-heat stress. High intensity exercise produced greater ALD and AVP increases than low intensity exercise. ALD responses during exercise were independent of hypohydration level. AVP responses were closely related to osmolality (N = 6 of 7 subjects; r = 0.51 to r = 0.98; average r = 0.84) despite varying hydration, exercise intensity, or core temperature. We conclude that: 1) ALD and AVP increase in a graded manner with hypohydration, and this effect persists during exercise-heat stress; 2) ALD and AVP increases elicited by exercise are greater during high intensity than low intensity exercise; 3) Hypohydration and exercise intensity have additive effects on ALD: and 4) AVP responses are closely coupled to osmolality.     

The rim sign in hepatic abscess: case report and review of the literature

We studied a previously healthy patient who presented with a 3-wk history of fever, flu-like symptoms and abdominal pain. METHODS: Blood cultures were positive for Escherichia coli. A computed tomography (CT) scan revealed a 2-cm low-density focus in the right hepatic lobe. A technetium-99m-mebrofenin scan showed a photopenic area in the right hepatic lobe surrounded by a rim of activity greater than the adjacent parenchymal activity. RESULTS: Gallbladder visualization was normal and the diagnosis of hepatic abscess was made. CT-guided percutaneous drainage of the lesion yielded six cc of pus, the culture of which grew E. coli, Prevotella and Bacteroides fragilis. Drainage and a 6-wk course of intravenous antibiotics were followed by clinical improvement and resolution of the abscess by CT. CONCLUSION: The rim sign and its possible mechanism of causation in hepatic abscess are discussed in this report, together with a review of the literature.     

Novastan (brand of argatroban): a small-molecule, direct thrombin inhibitor

Because of the unsatisfactory options available for safe and effective antithrombotic therapy, recent, intense research and development efforts have focused on direct, or site-directed, thrombin inhibitors. Argatroban is a small-molecule, reversible, direct thrombin inhibitor selective for the catalytic site of the thrombin molecule. Argatroban's molecular properties (small molecule; fast, selective, and reversible inhibition of the thrombin catalytic site; and similar in vitro potency for inhibiting both clot-bound and soluble thrombin) offer the potential for significant antithrombotic efficacy with minimal systemic anticoagulant effects. Its clinical pharmacologic properties offer the potential for minimal risk of bleeding, very rapid achievement of therapeutic antithrombotic efficacy, predictable dose response, and rapid restoration of the hemostatic systems to baseline on termination of intravenous infusion. The intravenous agent Novastan (brand of argatroban) is currently approved for clinical use in Japan for the treatment of peripheral arterial occlusive disease. Novastan is in advanced clinical development in North and South America for several indications, including (1) anticoagulant/antithrombotic therapy in heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia, and thrombosis syndrome (HITTS); and (2) adjunctive therapy to thrombolytic agents in acute myocardial infarction. Results from these trials are projected to be available by early 1997.     

Clinical quality measurement. Comparing chart review and automated methodologies

OBJECTIVES: This study investigates the use of data from automated systems within a large managed care plan to create indicators of clinical quality. METHODS: Measures from the first year of Health Plan Employer Data and Information Set, HEDIS 2.0, are used to compare chart review and automated analysis methodologies. The contributions of various data systems in creating clinical quality measures are evaluated. RESULTS: Chart review data usually are better for creating clinical quality indicators, although the level of agreement between the two methodologies often is quite high. Computerized patient record systems are found to be the most reliable automated data source, and automated claims are found to be the least reliable. This study's findings suggest that automated encounter systems may provide relatively reliable data. CONCLUSIONS: Managed care plans may not want to rely on automated data alone for clinical quality measurement. The results reported here support the use of combined methodologies such as the "hybrid" method, which utilizes both automated and chart-review data.