Acute stroke: usefulness of early CT findings before thrombolytic therapy

PURPOSE: Three-dimensional conformal radiotherapy (3D-CRT) has been associated with a reduction in acute and late toxicity among patients treated for localized prostatic cancer. The purpose of this study is to assess the acute and late toxicity of 3D-CRT delivered to patients in the postprostatectomy setting and to analyze which factors predict for durable biochemical control in this group of patients. METHODS AND MATERIALS: Between 1988 and 1994, 42 patients were treated after prostatectomy with three-dimensional conformal radiotherapy. The median time from prostatectomy to radiotherapy was 11 months. Indications for treatment included a rising serum PSA level in 28 patients (65%) and positive surgical margins without a rising PSA level in 14 (35%). Twenty-five patients (60%) had pathologic stage T3 disease, and 32 (74%) had tumor at or close to the surgical margins. The median dose was 64.8 Gy, and the median follow-up time was 2 years. RESULTS: 3D-CRT in the postprostatectomy setting was well tolerated. Three patients (7%) experienced Grade II acute genitourinary toxicity and nine patients (21%) experienced Grade II acute gastrointestinal toxicity during treatment. No patient experienced Grade III or higher acute morbidity. The 2-year actuarial risk for Grade II late genitourinary and gastrointestinal late complications were 5 and 9%, respectively. In patients with existing incontinence, the incidence of worsening stress incontinence 6 months after treatment was 17%, which resolved within 12 months to its preradiotherapy level in four of six cases (66%). The overall 2-year postirradiation PSA relapse-free survival rate was 53%. The 2-year PSA relapse-free survival was 66% for patients with undetectable PSA levels in the immediate postoperative period compared to 26% for those with detectable levels of PSA after surgery (p < 0.006). Furthermore, for patients with preradiotherapy PSA levels of < or = 1.0 ng/ml, the 2-year PSA relapse-free survival was 74% compared to 17% of those with preradiotherapy PSA levels of > 1.0 ng/ml (p < 0.002). The resection margin status, presence of seminal vesicle involvement, Gleason score, and the preprostatectomy PSA level did not impact on PSA relapse-free survival. A Cox proportional hazards regression analysis demonstrated that a preradiotherapy PSA value of > 1 ng/ml (p < 0.002) was the most important covariate predicting for a rising PSA after radiotherapy. CONCLUSIONS: After prostatectomy, three-dimensional conformal radiotherapy is associated with minimal treatment-related morbidity. Patients with postprostatectomy, preradiotherapy PSA levels < or = 1.0 ng/ml, and those patients who had undetectable PSA levels in the immediate postoperative period are more likely to benefit from local adjuvant therapy.     

A retrospective epidemiological analysis of non-accidental head injury in children in Scotland over a 15 year period

We have made a simple 15-year retrospective epidemiological study of a part of South Moravia, district Breclav, on the basis of genetic documentation of 245 congenital defects and 28 spontaneous abortions. The whole area was worked up by computer-geographical methods, and the occurrence of congenital defects was compared both in areas of severe chronic air pollution and in less contamined areas. There were three municipal areas, Mikulov, Breclav-Postorná, Velké Bilovice and their surroundings, in which an increased number of congenital defects was recorded. In the municipal area of Breclav-Postorná there was also a greater occurrence of organic solvents and phosphoric acid and a significantly higher occurrence of spontaneous abortions and at the same time a higher occurrence of heart defects.     

Radiological assessment of a new bone densitometer--the Lunar EXPERT

Dual energy X-ray absorptiometry (DXA) is one of the most widely used techniques in the management of osteoporosis and other skeletal diseases. Although patient doses from DXA are generally low, it is still necessary to measure them to assess the risk of radiation injury. We report on a study to estimate the effective dose (ED) to patients and staff from a new DXA scanner--the Lunar EXPERT, and make a comparison with a similar study carried out on a Lunar DPX-L. The entrance surface doses were measured to be 895 microGy and 10.25 microGy for the EXPERT and DPX-L, respectively. The EXPERT maximum EDs were calculated to be 74.7 microSv and 44.9 microSv for the anteroposterior (AP) lumbar spine and the proximal femur, respectively. More than 50% reduction in ED could be achieved by using a smaller scanning width. The maximum EDs for the DPX-L were calculated to be 0.21 microSv and 0.15 microSv for the AP lumbar spine and the proximal femur, respectively. The scattered dose rates (ambient dose equivalent) were measured to be less than 2 and less than 1 microSv h-1 at 50 cm and 100 cm, respectively, for the DPX-L, and the equivalent values for the EXPERT were 240 and 64 microSv h-1. Although both the patient dose and scattered dose rates are quite low relative to other radiological examinations, good practice aimed at dose reduction should still be implemented. Whilst protection for the operator is not needed for the DPX-L system, it may be (depending on the size of the room) for the EXPERT system.     

The pharmacokinetics of acetyl starch as a plasma volume expander in patients undergoing elective surgery

Acetyl starch (ACS) is a new synthetic colloid solution for plasma volume expansion and is now undergoing phase 2 clinical trials. We compared the pharmacokinetics of ACS with those of hydroxyethyl starch (HES) in 32 patients (ASA physical status I and II) undergoing elective surgery. In this randomized, double-blind trial, patients received either 15 mL/kg ACS 6% (average molecular weight [Mw] 200,000/molar substitution [MS] 0.5) or HES 6% (Mw 200,000/MS 0.5) i.v. up to a maximal dose of 1000 mL. Plasma colloid concentrations were measured by repetitive arterial blood sampling over 24.5 h. Plasma colloid concentrations were detected using a high-pressure liquid chromatography controlled enzymatic test. Standard pharmacokinetics were calculated, including initial half-life (t(1/2init)), i.e., the time required for a 50% decline of the maximal plasma colloid concentration at the end of drug infusion. Whereas HES was eliminated by second-order kinetics, ACS followed first-order characteristics. In the first hours after i.v. administration, t(1/2init) and clearances were similar in both groups. However, the terminal half-life of HES was significantly longer than that of ACS (9.29 +/- 1.43 h vs 4.37 +/- 1.06 h). After 16.5 and 24.5 h, ACS showed significantly lower plasma concentrations than HES, which indicates that the final degradation of ACS by esterases and amylase was significantly more rapid. ACS might be an alternative plasma volume expander, which avoids the accumulation of persisting macromolecules. Implications: We studied the pharmacokinetics of acetyl starch, a newly developed colloid solution for plasma volume substitution, compared with hydroxyethyl starch in 32 surgical patients undergoing elective major general surgical procedures. In contrast to hydroxyethyl starch, this new agent undergoes rapid and nearly complete enzymatic degradation.     

Antitumor activity of tricyclic pyrone analogs, a new synthetic class of microtubule de-stabilizing agents, in the murine EMT-6 mammary tumor cell line in vitro

Methods of both linkage analysis and association analysis may be model-based or model-free. The former are useful for initial exploratory analysis, the latter for more detailed multivariate genometric analysis. Linkage leads to an association, but that association may be solely intrafamilial. Allelic association may be due to pleiotropy, linkage disequilibrium, meiotic drive, selection, or population stratification. Using non-transmitted parental alleles as controls for alleles transmitted to cases, in conjunction with a McNemar-type test, does not detect association in the absence of linkage. Model-based analyses should use models that approximate the complexity of the disease being studied in order to be both robust and powerful.     

Mutations in the carboxyl terminus of the agouti protein decrease agouti inhibition of ligand binding to the melanocortin receptors

Several mutations that cause ectopic expression of the agouti gene result in obesity, hyperinsulinemia, and yellow coat color. A candidate pathway for agouti induced obesity and hyperinsulinemia is through altered signaling by melanocortin receptors, as agouti normally regulates coat coloration through antagonism of melanocortin receptor 1. Furthermore, melanocortin peptides mediate functions including steroidogenesis, lipolysis, and thermoregulation. We report apparent inhibition dissociation constants for mouse and human agouti protein inhibition of ligand binding to the melanocortin receptors, to determine which of these receptors might be involved in agouti induced diabetes. The similarity in the apparent K(I) values for agouti inhibition of ligand binding to the brain melanocortin receptors 3 and 4 (mouse: K(I) app = 190 +/- 74 and 54 +/- 18 nM; human: K(I) app = 140 +/- 56 and 70 +/- 18 nM, respectively) suggests that the MC3-R is a potential candidate for a receptor mediating the effects of agouti protein overexpression. Agouti residues important for melanocortin receptor inhibition were identified through the analysis of deletion constructs and site-specific variants. Val83 is important for inhibition of binding to MC1-R (K(I) app for Val83Ala agouti increased 13-fold relative to wild-type protein). Arg85, Pro86, and Pro89 are important for selective inhibition of binding between MC1-R and MC3-R and MC4-R as their apparent K(I) values are essentially unchanged at MC1-R, while they have increased 6-10-fold relative to wild-type protein at MC3-R and MC4-R.