A survey of medical image registration on graphics hardware.

The rapidly increasing performance of graphics processors, improving programming support and excellent performance-price ratio make graphics processing units (GPUs) a good option for a variety of computationally intensive tasks. Within this survey, we give an overview of GPU accelerated image registration. We address both, GPU experienced readers with an interest in accelerated image registration, as well as registration experts who are interested in using GPUs. We survey programming models and interfaces and analyze different approaches to programming on the GPU. We furthermore discuss the inherent advantages and challenges of current hardware architectures, which leads to a description of the details of the important building blocks for successful implementations.

Preprandial vs. postprandial insulin lispro-a comparative crossover trial in patients with Type 1 diabetes.

AIMS: Administration of bolus insulin after eating may be a useful therapeutic option for some patients. This 6-month, crossover study compared metabolic effects of routine use of preprandial vs. postprandial injection of bolus insulin lispro. METHODS: Thirty-one patients with Type 1 diabetes injected insulin lispro either preprandially or postprandially for a 3-month period followed by the alternate regimen for a further 3 months. HbA1c, fructosamine and eight-point self-determined blood glucose profiles were measured and analysed using an anova model appropriate for a crossover design. RESULTS: Mean HbA1c decreased slightly from baseline with preprandial (-0.15 +/- 0.41%) and increased slightly with postprandial (0.11 +/- 0.48%) insulin lispro so that there was a significant (P = 0.008) difference between treatments in final HbA1c level. Mean fructosamine also decreased slightly with preprandial (-15 +/- 31 micro mol/l) but was almost unchanged (1 +/- 39 micro mol/l) with postprandial insulin lispro. Overall daily blood glucose was not different (P = 0.312) for preprandial compared with postprandial administration. However, mean preprandial glucose was lower (7.5 +/- 2.01 vs. 6.6 +/- 1.22 mmol/l; P = 0.026), whereas mean postprandial glucose was higher (7.7 +/- 1.8 vs. 8.7 +/- 2.1 mmol/l; P = 0.031) with postprandial insulin lispro administration. Mean blood glucose excursions were higher with postprandial compared with preprandial insulin lispro, indicating greater daily fluctuations. No difference in incidence of hypoglycaemia was observed with the two treatment regimens. CONCLUSIONS: Postprandial insulin lispro administration appeared to be an acceptable treatment regimen and may be of benefit in certain situations. However, the benefits of postprandial administration may have to be balanced against poorer glycaemic control with continuous long-term use.

Gemcitabine and vincristine: an effective outpatient regimen with low myelotoxicity for stage IV non-small cell lung cancer.

The activity and tolerability of gemcitabine and the non-overlapping toxicity of gemcitabine plus vincristine were the basis for testing this regimen patients with non-small cell lung cancer (NSCLC). Forty patients (25 male/15 female, median age 52 years) with stage IV NSCLC and a Karnofsky Performance Status score > or = 60 entered the trial. Patients received gemcitabine 1000 mg/m2 on days 1, 8 and 15 and vincristine 1.4 mg/m2 on days 1 and 15, every 4 weeks. The overall response rate was 16/40 (40%) (N = 40); with 2 complete and 14 partial responses; additional 14 patients had minor responses or stable disease. Median duration of remission was 4.5 months, and the median survival was 9 months. In two patients with grade 2 generalized vesicular rash and severe malaise, respectively, treatment-related toxicity led to early termination of treatment. Among patients treated for more than two months, vincristine doses were reduced/omitted for 55% of cycles because of grade 1-2 peripheral neuropathy. Myelotoxicity was frequent but rarely clinically significant. Mean platelet counts on day 1 of cycles 2,3 and 4 were significantly higher than the pre-treatment or post-treatment values. We conclude that vincristine plus gemcitabine is an an active and well tolerated regimen. Its interesting "platelet-saving" effect deserves further investigation.

Vinorelbine-gemcitabine in advanced non-small-cell lung cancer (NSCLC): an AASLC phase II trial. Austrian Association for the Study of Lung Cancer.

PURPOSE: The purpose of the present phase 11 trial was to determine the efficacy and toxicity of vinorelbine-gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: From December 1997 to February 1999, 78 chemotherapy-naive patients (median age 60 years, Karnofsky performance status of 100, 90, 80 and 70 present in 5%, 41%, 36% and 18% of the patients, respectively) with stage IIIB (17%) or IV (83%) NSCLC (65% adenocarcinomas, 22% squamous-cell carcinomas, 10% large-cell carcinomas, 3% mixed-cell carcinomas) received 25 mg/m2 vinorelbine and 1200 mg/m2 gemcitabine on days 1, 8 and 15 of a four-week cycle. RESULTS: In an intent-to-treat analysis, partial responses were seen in 19% of the patients. The median duration of response was 4.4 months. The median survival time was seven months and the one-year survival rate was 32%. Myelosuppression was the main side effect with WHO grade 3/4 neutropenia and thrombocytopenia in 35% and 11% of the patients, respectively. Other side effects were usually mild to moderate. CONCLUSIONS: Vinorelbine-gemcitabine is active, well tolerated and easy to administer on an outpatient basis in advanced NSCLC. Thus a randomized comparison of this combination with platinum-based protocols is warranted in patients with advanced NSCLC.

In vitro release of vancomycin and tobramycin from impregnated human and bovine bone grafts.

In order to combine the effects of bone repair and eradication of infection, with both Gram-positive and Gram-negative pathogens, the behaviour of a compound of bone graft and antibiotics was investigated. Samples of human and bovine bone, cancellous and cortical, were processed and incubated with vancomycin and tobramycin, respectively. The compound was placed in 5% human albumin and the surrounding liquid was exchanged completely every 24 h. Concentrations of antibiotics in the fluid were measured over < or = 28 days using high pressure liquid chromatography and a bioassay. All tested combinations eluted mainly in the initial phase with a logarithmic decrease over the testing period. The concentration of antibiotics in the albumin was well above the MIC for common pathogens throughout the investigation in all tested specimens. The highest initial concentrations were measured in the compound of bovine bone together with vancomycin (24395.8 +/- 1138.9 mg/L), decreasing to 9.02 +/- 1.3 mg/L after 11 exchanges. Human and bovine bone did not have significantly different properties. The storage capability of cortical bone was generally lower than that of cancellous bone. Tobramycin concentrations were significantly lower in the initial phase; however, it eluted more steadily and over a longer period, so that from day 6 onwards, its concentration was greater than that of vancomycin. After 28 days, the tobramycin concentration was 18.09 +/- 2.46 mg/L (bovine cancellous bone). In conclusion, bone, if processed adequately, is an excellent carrier for vancomycin and tobramycin. Cortical bone is as suitable as cancellous bone. The pharmacokinetics of human and bovine bone are comparable. Using an antibiotic-graft compound, eradication of pathogens and grafting of bony defects may be accomplished in a one-stage procedure.

Single-agent gemcitabine as second- and third-line treatment in metastatic breast cancer.

In the present study, 25 patients with breast cancer pretreated with one or two anthracycline-based regimens for visceral metastases were enrolled. Patients were treated with gemcitabine 1250 mg/m2 on days 1, 8 and 15, q28d. Nine patients received gemcitabine as second-line treatment, whereas 16 patients received gemcitabine as third-line cytotoxic treatment, respectively. In the second-line setting, two (22%) patients gained PR (RR 22%) and four (44%) patients experienced SD (P=0.2), respectively. In the third-line-setting, one (6%) patient gained CR, one patient PR (6%) and four patients (25%) SD, respectively, resulting in a response rate (RR) of 12%. In the second-line-setting, median time to progression was 5.1 +/- 4.0 months (range: 1.6-13.9) versus 3.5-2.5 months (range: 1.3-10.4) in the third-line-setting. Median overall survival was 12.6 +/- 9.1 months (range: 3.9-30.8) versus 7.5 +/- 6.7 months (range: 2.0-26.0), respectively. Overall, no patient experienced treatment limiting toxicities. We conclude from the present study that gemcitabine induced an overall RR of 16% following prior treatment with anthracyclines. However, median time to progression and median overall survival were limited. In the search for efficacious treatment of patients with metastatic breast cancer, gemcitabine constitutes a valid tool in anthracycline-resistant disease and thus might represent a valuable option for combination chemotherapy in controlled trials in this condition.

Randomized double-blind placebo-controlled multicenter evaluation of efficacy and dose finding of midodrine hydrochloride in women with mild to moderate stress urinary incontinence: a phase II study.

Midodrine is a potent and selective alpha1-receptor agonist and its potential to increase urethral closure pressure could be useful in the treatment of female stress incontinence. The aim of this randomized double-blind placebo-controlled multicenter study was to evaluate the efficacy and safety of midodrine for the treatment of stress urinary incontinence. The primary criterion of efficacy was the maximum urethral closure pressure at rest. Voiding diaries, symptom and incontinence questionnaires and patient/investigator global assessment were also used to evaluate its efficacy. After 4 weeks of treatment no significant changes in MUCP were found. The global assessment by the patient and investigator did indicate that patients on active treatment had a more positive assessment than the placebo group. In conclusion, midodrine did not cause significant improvements in urodynamic parameters, but there were subjective improvements in some of the patients in the treated groups. Furthermore midodrine was well tolerated.

Postprandial insulin lispro. A new therapeutic option for type 1 diabetic patients.

OBJECTIVE: For intensified insulin therapy of type 1 diabetes, bolus injection of regular human insulin 30-15 min before a meal is currently recommended. This randomized study is aimed to determine whether insulin lispro (LIS), a new insulin analog with a rapid onset of action, can provide comparable blood glucose (BG) control by injection after the meal. RESEARCH DESIGN AND METHODS: Eighteen type 1 diabetic subjects injected regular insulin (REG) at 40, 20, or 0 min before or LIS at 20 or 0 min before or 15 min after the start of a standardized test meal. BG excursions and area under the curve of BG excursions (AUC) at the six visits were compared by analysis of variance. Hypoglycemic events (BG < or = 2.78 mmol/l) were evaluated in relation to the achieved postprandial BG control. RESULTS: Mean AUC values were 2.00, 2.55, and 3.33 mmol.h.l-1 for REG given 40, 20, and 0 min before the test meal, respectively, and -2.19, -2.15, and 1.98 mmol.h.l-1 for LIS given 20 and 0 min before and 15 min after the start of the test meal, respectively. LIS injected 20 min (-20) or immediately (0) before the meal was significantly more effective in controlling postprandial BG excursion (P < 0.001) than any REG treatment. Postprandial injection of LIS (15) did not compromise postprandial BG control and resulted in less hypoglycemia. REG -40 and LIS -20 were associated with early hypoglycemia, but other hypoglycemic events were equally distributed among groups. CONCLUSIONS: The optimal time for bolus insulin injection was 20 min before the meal for REG and immediately before the meal for LIS. LIS injected immediately after a standard meal provided postprandial BG control at least as good as REG injected from 40 to 0 min before the meal. Postprandial injection of LIS is an attractive new therapeutic option.

Vinorelbine/gemcitabine in advanced non-small cell lung cancer (NSCLC): a phase I trial.

Vinorelbine and gemcitabine are both active as single agents in advanced non-small cell lung cancer (NSCLC). Because of their different mechanisms of action, good tolerability and possible administration on an out-patient basis, vinorelbine/gemcitabine should be an interesting combination for palliative chemotherapy. Thus, we initiated a phase I dose-escalation trial in order to determine the maximum tolerated doses of vinorelbine/gemcitabine that can be administered without haematopoietic growth factors, the dose-limiting toxicities and the most frequent side-effects of this novel combination. 40 chemotherapy-naïve patients with advanced NSCLC were treated with different doses of vinorelbine/gemcitabine on days 1, 8 and 15, and this treatment cycle was repeated on day 29. Vinorelbine and gemcitabine were escalated from 10 to 30 mg/m2 and 600 to 1200 mg/m2, respectively. A total of 63 treatment cycles were administered and 27 patients received at least two treatment cycles. Dose-limiting toxicities were leucopenia plus thrombocytopenia (2 patients) and mucositis (1 patient). The maximum tolerated dose was established at 25 mg/m2 vinorelbine combined with 1200 mg/m2 gemcitabine. Frequent side-effects were leucopenia, anaemia, nausea/vomiting, flu-like symptoms, skin rashes and elevation of liver enzymes. The recommended phase II doses are 20-25 mg/m2 vinorelbine combined with 1000-1200 mg/m2 gemcitabine on days 1, 8 and 15, but myelosuppression will have to be carefully monitored.

[Maintenance therapy with 20 mg fluoxetine. Results of an administration study of 1,737 depressed patients]. / Erhaltungstherapie mit 20 mg Fluoxetin. Ergebnis einer Anwendungsbeobachtung an 1737 depressiven Patienten/innen.

An application study was carried out in 1993/94 on the use of fluoxetine for the continuation therapy of depression. 1737 patients received fluoxetine at a dosage of 20 mg per day over a period of 6 months. Diagnosis was made by clinical evaluation of phenomenology and ICD-10 classification. Over the observation period physicians rated the course of illness according to severity of the depression, somatic complaints and therapeutic efficacy on a scale graded 1-4. Side effects and concomitant medication were also noted. Coincidentally, patients recorded subjective satisfaction with therapy, as well as side effects. In a subsample of 423 patients the physicians additionally used a modified version of the Hamilton Depression Rating Scale (HRDS) for behavioural ratings. Standard assessment was performed after the 2nd and 6th weeks of treatment and again after the 3rd and 6th months. The rating scale showed a decrease in depressive symptomatology and somatic complaints at the end of treatment in 53% and 44% of patients, respectively. Treatment efficacy was rated as excellent in 82% of cases, as evaluated by the physicians; patients were satisfied in 89% of cases. These results are strengthened by the reduction from 22.4 +/- 7.0 to 9.2 +/- 6.4 in the subsample of 423 patients according to the HRDS, equivalent to a decrease in depression symptomatology of 59%. This study is the first open phase IV trial in Austria investigating continuation therapy with 20 mg fluoxetine per day and confirms results obtained in international multicentre placebo-controlled studies involving considerably smaller numbers of patients.

[Antihypertensive therapy and coronary heart disease: significance of the effect of concomitant cardiovascular risk factors]. / Antihypertensive Therapie und koronare Herzkrankheit: die Bedeutung der Beeinflussung begleitender kardiovaskulärer Risikofaktoren.

Antihypertensive therapy as it was performed in the past has not provided the degree of protection against coronary heart disease as was originally predicted by epidemiologic evidence. An improvement of outcome of antihypertensive therapy can only be achieved if coronary risk is maximally reduced. Therefore, in treating hypertensive patients, one has to take care of a diligent search for the presence of other coexisting coronary risk factors, of a vigorous use of life-style modifications (nondrug therapy), and of a greater individual selectivity of antihypertensive agents for initial and chronic use, preferring those that may provide additional benefits for other coexisting coronary risks.

[Helicobacter pylori: clinical pictures of an infectious disease with pathogen persistence]. / Helicobacter pylori: Krankheitsbilder einer Infektionskrankheit mit Erregerpersistenz.

It is the aim of this paper to provide survey of the very fast developing field of medical research on Helicobacter pylori which includes as different branches as gastroenterology, pharmacology or microbiology. After examination of the several diseases, pathological mechanisms, the diagnostical techniques and the therapeutical regimens, the authors of this study favorize an early indication for eradication of helicobater pylori. Since research on Helicobacter pylori is divided into many fields, there is the attempt to come to a clear and more rational point of view concerning therapeutical strategies and management of the infection. It is another focal point to emphasize the important role that chronical gastritis induced by Helicobacter pylori plays as an important risk factor for gastric carcinoma.