Effect of radiotherapy and chemotherapy on pulmonary function after treatment for breast cancer and lymphoma: A follow-up study.

PURPOSE: To determine the changes in pulmonary function tests (PFTs) 0 to 48 months after treatment for breast cancer and lymphoma. PATIENTS AND METHODS: The alveolar volume (V(A)), vital capacity, forced expiratory volume in 1 second, and corrected transfer factor of carbon monoxide (T(L,COc)) were measured in 69 breast cancer and 41 lymphoma patients before treatment and 3, 18, and 48 months after treatment with radiotherapy alone or radiotherapy in combination with chemotherapy (mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine; cyclophosphamide, epidoxorubicin, fluorouracil; cyclophosphamide, thiotepa, carboplatin; cyclophosphamide, methotrexate, fluorouracil). The three-dimensional dose distribution in the lung of each patient was converted to the mean lung dose. Statistical analysis was used to evaluate the changes in PFT values over time in relation to age, sex, smoking, chemotherapy, and the mean lung dose. RESULTS: After an initial reduction in PFT values at 3 months, significant recovery was seen at 18 months for all patients. Thereafter, no further improvement could be demonstrated. Reductions in spirometry values and V(A) were related to the mean lung dose only (0.9% per Gy at 3 months and 0.4% per Gy mean dose at 18 months). T(L,COc) decreased 1. 1% per Gy mean dose and additionally decreased 6% when chemotherapy was given after radiotherapy. Chemotherapy administered before radiotherapy reduced baseline T(L,COc) values by 8% to 21%. All patients showed an improvement of 5% at 18 months. CONCLUSION: On the basis of the mean lung dose and the chemotherapy regimen, the changes in PFT values can be estimated before treatment within 10% of the values actually observed in 72% to 85% of our patients with healthy lungs.     

Quantitative assessment of Langerhans' cells in human cervical intraepithelial neoplasia and wart virus infection

Langerhans' cell density was assessed quantitatively in cervical wart virus infection (cervical condyloma), cervical intraepithelial neoplasia, and koilocytic dysplasia with use of an antibody to S100 protein and an indirect immunoperoxidase technique. When compared with normal ectocervix, Langerhans' cell density was significantly decreased in cervical wart virus infection and significantly increased in cervical intraepithelial neoplasia. In koilocytic dysplasia, intermediate Langerhans' cell densities were obtained. In addition to being increased within the lesions of cervical intraepithelial neoplasia, Langerhans' cell density was increased in the adjacent normal ectocervix. Human papillomavirus, by reducing intraepithelial Langerhans' cell density, may decrease local immune surveillance and thus have a promoter effect in the development of cervical cancer. Following the development of cervical intraepithelial neoplasia the increase in intraepithelial Langerhans' cell density suggests a specific immune response directed against neoantigens associated with malignant transformation. If a permissive wart virus infection persists after transformation to cervical intraepithelial neoplasia (koilocytic dysplasia), continued depletion of Langerhans' cells results in intermediate densities.     

Retinal perfusion response to a slow multifocal M-sequence flicker stimulation

PURPOSE: To assess, if a slow multifocal stimulus (mfS) can provoke a perfusion response that can be measured with the Retinal Vessel Analyzer (RVA). METHODS: Seventeen eyes were examined. Pupils were dilated. A 120-second baseline recording was obtained with the RVA. The subject then turned to view an mfS for 56 s. The mfS consisted of 103 hexagons flickering according to an m-sequence with a stimulus base interval of 53.3 ms (L(max) = 100 cd/m(2), L(min) < 1 cd/m(2)). Immediately thereafter, the subject turned to the RVA, where measurements were resumed as soon as the same retinal vessel was targeted and continued for 104 s. Stimulation and recording was repeated twice. The diameter of a retinal vein and artery was measured for a length of at least 1 mm. The maximum vessel response was obtained by linear interpolation of the measured response within the 20 s following mfS. RESULTS: On average, veins dilated by 6.8% and arteries by 7% following mfS (p > 0.005). Such a dilatation could be observed in 9 veins and 7 arteries. Three venous and 2 arterial measurements did not show a dilatation following mfS. However, 13 of 34 measurements could not be analyzed due to signal problems or because the time from the end of mfS and the uptake of measurement exceeded 20 s. CONCLUSION: This slow multifocal ERG stimulus results in a dilatation of arteries and veins that can be measured with the RVA. Coupling an mfS to the RVA has the potential to topographically map changes in retinal perfusion in relation to the respective retinal area stimulated. When implementing the mfS into the RVA setup in order not to lose time due to the refixation in the RVA following mfS, one is required to take the transient nature of this perfusion change into consideration.     

Indoleamine 2,3-dioxygenase in immune suppression and cancer

The extrahepatic enzyme indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan degradation in the first and rate-limiting step towards biosynthesis of the central metabolic co-factor nicotinamide adenine dinucleotide (NAD). While this pathway has been known for decades, the actual physiological role for IDO in mammals remained obscure, because (i.) most cell types do not express the downstream enzymes in the NAD biosynthesis pathway and (ii.) mammals salvage rather than synthesize NAD to meet their metabolic needs. An immunological role for IDO was hinted at with the observation that IDO expression is stimulated by interferon-gamma and subsequently confirmed by the discovery of its physiological importance in protecting the fetus from maternal immunity. Similarly, elevations in tryptophan catabolism in cancer patients were known since the 1950s, but the basis and meaning of this phenomenon were uncertain until it was shown that IDO, which is commonly elevated in tumors and draining lymph nodes, suppresses T cell immunity in the tumor microenvironment. Indeed, by creating peripheral tolerance to tumor antigens, IDO can undermine immune responses that thwart tumor cell survival in the context of an underlying inflammatory environment that facilitates tumor outgrowth. In preclinical studies, small molecule inhibitors of IDO compromise this mechanism of immunosuppression and strongly leverage the efficacy of a variety of classical chemotherapeutic agents, supporting the clinical development of IDO inhibitors as a therapeutic goal. This essay summarizes key findings that implicate IDO as an important mediator of peripheral tolerance and discusses the development of anti-cancer modalities that incorporate the use of IDO inhibitors.     

Ultrasound of the paediatric urogenital tract

Pathology in the urinary tract is one of the most frequent queries when children are referred for an ultrasound examination. Comprehensive ultrasound examinations can answer most clinical questions of the urogenital tract with minimal patient preparation and without the use of ionising radiation. Therefore, optimised imaging protocols should be available in all radiology departments where children are examined. This review suggests a preferred imaging protocol for urogenital imaging in children and gives an overview of the different structures of the urogenital tract, the normal age-related sonographic anatomy, and gives examples of the most commonly encountered diseases of the urogenital system in children.