Phase I trial of doxorubicin-containing low temperature sensitive liposomes in spontaneous canine tumors.

PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. EXPERIMENTAL DESIGN: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. RESULTS: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the dose-limiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received > or = 2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 +/- 6.17 ng/mg tissue. CONCLUSION: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted.     

Schwangerschaft bei rheumatoider Arthritis oder Spondyloarthritiden

The activity of a rheumatic disease can be influenced by pregnancy and puerperium. Prospective studies have shown an improvement in joint involvement in rheumatoid arthritis in two thirds to three quarters of pregnancies. After birth, an exacerbation is common. In spondylarthropathies there is no relevant change in disease activity. The fetal outcome is not impaired in patients with rheumatoid arthritis and inflammatory spondylarthropathies. Every pregnancy in women with a rheumatic disease should be considered as high-risk, and such pregnancies require close collaboration between rheumatologists and obstetricians.     

Ekkrines Porokarzinom neben multiplen anderen epithelialen Hauttumoren

Ohne Zusammenfassung     

High-resolution optical coherence tomography as a non-destructive monitoring tool for the engineering of skin equivalents

BACKGROUND: Three dimensional skin equivalents are widely used in dermatopharmacological and toxicological studies and as autologous transplants in wound healing. In pharmacology, there is tremendous need for monitoring the response of engineered skin equivalents to external treatment. Transplantation of skin equivalents for wound healing requires careful verification of their quality prior to transplantation. Optical coherence tomography (OCT) is a non-contact, non-destructive imaging technique for living tissues offering the potential to fulfill these needs. This work presents an analysis of OCT for high-resolution monitoring of skin equivalents at different stages during the culture process. METHODS: We developed a high-resolution OCT imaging setup based on a commercially available OCT system. A broadband femtosecond laser light source replaces the original superluminescence diode. Tomograms of living skin equivalents were recorded with an axial resolution of 3 mum and correlated with histology and immunofluorescence images. Comparison with standard low-resolution OCT is presented to emphasize the advantages of high-resolution OCT for this application. RESULTS: OCT is particularly able to distinguish between different layers of skin equivalents including stratum corneum, epidermal and dermal layer as well as the basement membrane zone. The high-resolution OCT scans correlate closely with two key benchmarks, histology and immunofluorescence imaging. CONCLUSIONS: This study clearly demonstrates the benefits of high-resolution OCT for identifying living tissue structure and morphology. Compared with the current gold standard histology, OCT offers non-destructive tissue imaging, enabling high-resolution evaluation of living tissue morphology and structure as it evolves.     

Extreme Photosensitivität seit der Kindheit

Ohne Zusammenfassung     

A case of Darier''s disease successfully treated with topical tacrolimus

Tacrolimus is a macrolide that inhibits T-cell activation. The most extensive experience with topical tacrolimus has been in treating atopic dermatitis but it has been used in various skin diseases, including Hailey-Hailey disease, with encouraging results. We report a case of extensive Darier's disease successfully treated with topical tacrolimus, after suspension of oral isotretrinoin due to major depression.     

Diagnostic difficulties of pelvic splenosis: case report.

We report the case of a 38-year-old woman who presented with chronic lower abdominal pain. Her past medical history included a splenectomy due to abdominal trauma. Ultrasound examination revealed four pelvic tumors which, upon laparotomy, were found to be the result of splenosis. Approximately 100 cases of splenosis have been reported but only a minority of them have been published in the gynecological literature. Our case indicates that those involved in pelvic scanning (even of asymptomatic women) and/or treating those complaining of lower abdominal pain or presenting with pelvic tumors should be aware of splenosis as a possible diagnosis.     

The impact of two-dimensional versus three-dimensional ultrasound exposure on maternal-fetal attachment and maternal health behavior in pregnancy.

OBJECTIVE: To explore the impact of timing and type of ultrasound, particularly three-dimensional (3D), exposure on maternal-fetal attachment and maternal health behavior during pregnancy. METHODS: Subjects were 68 women aged 18 years or older expecting their first child who presented for a routine ultrasound scan at around either 12 or 18 weeks' gestation in Nepean Hospital, Western Sydney. Women completed questionnaires assessing maternal-fetal attachment and health behavior, and were then allocated arbitrarily to either two-dimensional (2D) or 3D ultrasound examination. Repeat questionnaires were completed 1 week later. RESULTS: Maternal-fetal attachment increased after both 2D and 3D ultrasound exposure, and the effect was moderated by the timing of exposure, with women receiving their first ultrasound examination at around 12 weeks showing the greatest change. Alcohol consumption was the only behavior to show significant change following ultrasound exposure, with a reduction in the reported average number of drinks per week. There was no significant difference in the pattern of change for 2D compared with 3D ultrasound exposure, and no effect of ultrasound exposure on maternal perception of the fetus. CONCLUSIONS: Ultrasound has a positive impact on maternal-fetal attachment, particularly in the first trimester. 3D ultrasound did not offer enhanced benefits. Associations between ultrasound exposure and alcohol consumption warrant further investigation. Larger samples are needed to clarify the moderating effects of gestational age and type of ultrasound exposure.