Linking dose delivery accuracy and planning target margin in radiosurgery based on dose-volume histograms derived from measurement-guided dose reconstruction.

In radiosurgery (SRS), the geometric uncertainties of machine-related delivery including image-guidance and hence the planning target volume (PTV) are often evaluated by the end-to-end gamma (γ) comparison that carries no information about the clinical relevance of deviations of individual SRS plans during delivery quality assurance (DQA). A proof-of-concept method was proposed to derive the PTV against both the plan- and the machine-specific delivery errors directly from the clinically relevant dose-volume histograms (DVHs) using measured-guided dose reconstruction (MGDR) during DQA. A liquid-filled detector array and a rotating phantom were used to measure sixteen arc-based radiosurgery treatments with 1 and 2 mm gross tumor volume (GTV)-to-PTV margins, producing MGDR-3D dose distribution on both the phantom and the patient CT for γ index and clinical DVH evaluations, respectively. The PTV was considered optimal when the MGDR showed the desired prescription dose coverage (V pres ) of the GTV (100% in this study). Associations of the binary V pres outcomes (

Dosimetric evaluation of four-dimensional dose distributions of CyberKnife and volumetric-modulated arc radiotherapy in stereotactic body lung radiotherapy.

Advanced image-guided stereotatic body lung radiotherapy techniques using volumetric-modulated arc radiotherapy (VMAT) with four-dimensional cone-beam computed tomography (4D CBCT) and CyberKnife with real-time target tracking have been clinically implemented by different authors. However, dosimetric comparisons between these techniques are lacking. In this study, 4D CT scans of 14 patients were used to create VMAT and CyberKnife treatment plans using 4D dose calculations. The GTV and the organs at risk (OARs) were defined on the end-exhale images for CyberKnife planning and were then deformed to the midventilation images (MidV) for VMAT optimization. Direct 4D Monte Carlo dose optimizations were performed for CyberKnife (4D(CK)). Four-dimensional dose calculations were also applied to VMAT plans to generate the 4D dose distributions (4D(VMAT)) on the exhale images for direct comparisons with the 4D(CK) plans. 4D(CK) and 4D(VMAT) showed comparable target conformity (1.31 ± 0.13 vs. 1.39 ± 0.24, p = 0.05). GTV mean doses were significantly higher with 4D(CK). Statistical differences of dose volume metrics were not observed in the majority of OARs studied, except for esophagus, with 4D(VMAT) yielding marginally higher D1% than 4D(CK). The normal tissue volumes receiving 80%, 50%, and 30% of the prescription dose (V80%, V50%, and V30%) were higher with 4D(VMAT), whereas 4D(CK) yielded slightly higher V10% in posterior lesions than 4D(VMAT). VMAT resulted in much less monitor units and therefore greater delivery efficiency than CyberKnife. In general, it was possible to produce dosimetrically acceptable plans with both techniques. The selection of treatment modality should consider the dosimetric results as well as the patient's tolerance of the treatment process specific to the SBRT technique.

[Continuous spinal anesthesia for femoral fracture in two patients with severe aortic stenosis]. / Rachianesthésie continue pour fracture du col fémoral chez deux patients présentant un rétrécissement aortique serré.

Neuraxial blockade is usually not recommended in patients with aortic stenosis. However, neuroaxial blockade techniques such as continuous spinal or epidural anaesthesia can be tailored to minimize potentially dramatic consequences of decrease in systemic vascular resistance, often encountered after standard single shot spinal anaesthesia. We report the cases of two severe aortic stenosis patients (aortic valve area<0.5 cm2) that underwent hip surgery under continuous spinal anaesthesia. Small doses of isobaric 0.25% bupivacaine titrated to limit total dose below 5 mg, injected through the intrathecal catheter allowed the control of haemodynamic parameters. No clinical complication occurred in these two patients.

Unmet need for recommended preventive health services among clients of California syringe exchange programs: implications for quality improvement.

BACKGROUND: Comprehensive preventive services are recommended for injection drug users (IDU), including screening tests, vaccinations, risk reduction counseling, and sterile syringes. Syringe exchange programs (SEP) may facilitate receipt of preventive services by IDUs, but whether SEP clients receive recommended preventive care is not known. We examined use of recommended preventive services by clients of 23 SEPs throughout California. METHODS: Five hundred and sixty SEP clients were recruited from 23 SEPs throughout California between March and September 2003. Receipt of 10 recommended preventive services and source of care (SEP versus non-SEP providers) was ascertained from client interviews. RESULTS: On average, SEP clients received only 13% of recommended preventive services and 49% of clients received none of the recommended services. Of services that were received, 76% were received from SEPs. In multivariate analysis, use of drug treatment and more frequent SEP visits were associated with receipt of recommended preventive services by clients. CONCLUSIONS: SEPs are often the only source of preventive care for their IDU clients. Still, SEP clients fail to receive most recommended preventive services. Interventions to increase use of preventive services and improve the quality of preventive care received by IDUs, such as increased access to drug treatment and SEPs, are needed.

Genetic diversity among elite Sorghum lines revealed by restriction fragment length polymorphisms and random amplified polymorphic DNAs.

The genetic diversity of sorghum, as compared to corn, is less well characterized at the genetic and molecular levels despite its worldwide economic importance. The objectives of this study were to: (1) investigate genetic diversity for restriction fragment length polymorphism (RFLPs) and random amplified polymorphic DNAs (RAPDs) in elite sorghum lines, (2) compare similarities based on molecular markers with pedigree relationships, and (3) examine the potential of RFLPs and RAPDs for assigning sorghum lines to the A/B (sterile) and R (restorer) groups. Using four restriction enzymes, polymorphism was detected with 61% of the RFLP probes used, compared to 77% of the random primers. One hundred and sixteen (64%) probe-enzyme combinations yielded multiple-band profiles compared to 98% of the random primers. RFLP profiles generated 290 polymorphic bands compared to 177 polymorphic RAPDs. Pair-wise comparisons of polymorphic RFLPs and RAPDs were used to calculate Nei and Jaccard coefficients. These were employed to generate phenograms using UPGMA and neighborjoining clustering methods. Analysis of RFLP data with Jaccard's coefficient and neighbor-joining clustering produced the phenogram with the closest topology to the known pedigree.

Excimer laser ablative treatment of microbial keratitis.

The 193-nm excimer laser was used to ablate experimental septate fungal (Fusarium) and an atypical mycobacterial (Mycobacterium fortuitum) keratitis in an animal model. The infections were allowed to proceed for 24 and 72 hours. After incubation, ablation with a 193-nm excimer laser with 5.0-mm treatment zones was performed until all suppurative areas were treated. The corneas were excised, halved, homogenized, and plated. All cultures were negative in the 24-hour group. However, in those corneas in which the infections were allowed to proceed to 72 hours, post-treatment cultures were positive for both organisms. Histopathologic examination confirmed that 24-hour infections had been eradicated and that 72-hour infections had organisms present. Three of the eight eyes in the M. fortuitum group perforated during treatment, even though the treatment depth by computer preselection was only 150 microns. Excimer laser photoablation may be a useful technique to eradicate early, localized microbial infections. However, it is apparent that advanced infections with deep stromal involvement and suppuration cannot be eradicated using this technique. Because corneas may be perforated inadvertently during treatment, excimer laser treatment of infectious keratitis should be approached with caution and used for superficial and well circumscribed lesions.

Corneal flattening by shallow circular trephination in human eye bank eyes.

Recent reports documenting central keratometric changes after removal of failed epikeratoplasty lenticules, compared to preoperative keratometry measurements, suggest that the annular corneal wound alters corneal curvature. Central corneal steepening has also been reported following circular and hexagonal keratotomy. We performed standard epikeratoplasty trephination with a Hessburg-Barron suction trephine followed by a peripheral lamellar spreading keratotomy on seven human eye bank eyes to determine the effect of these incisions on corneal topography. In seven human eye bank eyes, the mean acute central keratometric flattening from the shallow trephine incision was 2.81 D (SD 2.28, P = .017), with no significant change in keratometry due to peripheral lamellar spreading (P = .916). Computerized numeric and three-dimensional graphic analysis of the keratographs demonstrated this central topographic flattening. Further studies are needed to investigate the reversibility of host corneal changes induced by epikeratoplasty procedures.

Corneal steepening in human eye bank eyes by combined hexagonal and transverse keratotomy.

An interrupted 5 mm diameter hexagonal keratotomy was modified to include six paracentral transverse incisions to augment the central corneal steepening. This combined modified-hexagonal and transverse (or hexagonal-transverse) keratotomy was performed on human eye bank eyes to an estimated 85% corneal depth yielding a mean of 7.50 +/- 1.69 diopter increase in central keratometric power (P less than .001); this finding was confirmed by keratography. These results encourage further studies of this procedure and its potential to surgically correct mild amounts of hyperopia.

Morphologic changes of K-Sol preserved human corneas.

Supplementation of tissue culture medium with chondroitin sulfate has been shown to enhance donor corneal preservation. We assessed the efficacy of one of these chondroitin-supplemented media (K-Sol) in comparison with McCarey-Kaufman (MK) medium in maintaining corneal cellular morphology. Thirty-six human corneas, obtained within 8.6 h after death, were placed into K-Sol medium for up to 20 days preservation, and five paired control corneas were placed into MK medium for up to 6 days preservation. Specular photomicrographs were obtained every second to third day for a predetermined storage interval, then studied morphologically in a masked protocol by light microscopy, transmission electron microscopy, and scanning electron microscopy. Endothelial cell loss by specular microscopy averaged 5.8% after 1 week (6 to 8 days) and 7.4% after 13 days in K-Sol medium. Epithelial changes were erratic throughout the 20 day K-Sol preservation period. However, substantial keratocyte changes occurred after 10 days, and endothelial morphology uniformly deteriorated after 17 days. The morphologic data suggest that human corneas may be able to be preserved in K-Sol medium at 4 degrees C for up to 10 days but should be cautiously used thereafter.

Tobramycin in ophthalmology.

Selman Waksman's laboratory at Rutgers University discovered the first aminoglycoside antibiotic, streptomycin, in 1943. Other aminoglycoside antibiotics, such as gentamicin and tobramycin, soon followed. Tobramycin is compatible with most intravenous fluids and tear substitutes, but it is incompatible with heparin and some beta-lactam antibiotics such as penicillin and cephalosporins. Due to tobramycin's broad spectrum of activity, it has proven useful in controlling both superficial and deep infections of the eye and ocular adnexa (i.e., blepharitis, conjunctivitis, keratitis, and endophthalmitis). However, since tobramycin has been associated with neuromuscular blockade, as well as possessing ototoxic and nephrotoxic effects, care must be taken to minimize toxicity by monitoring patients undergoing systemic tobramycin therapy.

Comparative bioavailability and efficacy of fortified topical tobramycin.

Topical treatment of severe ocular infections may require the use of antibiotics fortified in concentration beyond commercially available preparations. The authors studied tear pharmacokinetics, tissue bioavailability, epithelial toxicity, and comparative antibacterial efficacy of topical tobramycin concentrations ranging from 0.3-5.0%. Tear pharmacodynamics demonstrate bioassay-measurable levels with each preparation up to 6 hr after a single 50-microliter drop challenge. Comparing various fortified concentration levels yields progressive parallel-biphasic decay curves in antibiotic tear-film concentrations. Both tear and corneal data demonstrate increases in measured antibiotic levels largely proportional to the increases in drug concentration instilled. Tobramycin was undetectable in corneas treated with 0.3% tobramycin, yet measurable with higher drug levels. A rabbit epithelial wound-healing model demonstrated progressive toxicity ranging from no effect of 0.3% tobramycin on healing rates compared with paired controls, to a significant decrease in re-epithelialization rates with 1.1% (P = 0.03) and 4.0% (P = 0.02) tobramycin. Finally, a Pseudomonas aeruginosa keratitis model in the rat demonstrates the antibiotic efficacy of topical tobramycin treatment over untreated controls (P less than 0.00001), and a progressively enhanced efficacy with increasing tobramycin concentrations is suggested. Concentration enhancement of topical ocular medication is useful in the treatment of severe ocular infection.

A metabolic comparison of cysteine and methionine supplements in the diet of a rat.

Adult male Long-Evans rats (250-300 g) were fed diets containing 15% of casein not supplemented with amino acids, supplemented with 0.505% cysteine or supplemented with 0.620% methionine for a period of 17 days. Rats fed the diets supplemented with cysteine had an increased incorporation of the 14C-radioactivity from [U-14C]alanine into liver glycogen and a decreased incorporation from [U-14C]acetate into fatty acids. Pyruvate carboxylase activity was slightly increased and citrate cleavage enzyme activity decreased in the livers of those rats fed the diets supplemented with cysteine. Rats fed diets supplemented with methionine had a decreased liver phosphoenolpyruvate carboxykinase activity. Based on these data it appears that rats fed diets supplemented with cysteine adapt metabolically to store energy as glycogen, while those fed diets supplemented with methionine tend to store energy as lipid.