Phase II evaluation of dibromodulcitol and actinomycin D,hydroxyurea, and cyclophosphamide in previously untreated patients with malignant melanoma

In this Eastern Cooperative Oncology Group (ECOG) phase II study, dibromodulcitol (DBD) and a combination of actinomycin D, hydroxyurea, and cyclophosphamide (AHC) were compared with methyl-CCNU, the current ECOG standard, in patients who had received no prior chemotherapy for disseminated malignant melanoma. The response rates were 6% (3/50) for AHC, 9% (3/34) for DBD, and 14% (7/49) for methyl-CCNU. Median survival times were 4, 5, and 6 months, respectively. Neither regimen appears to offer any advantage over methyl-CCNU as front-line therapy for patients with disseminated melanoma.     

PCR with arbitrary primers: approach with care

New techniques have recently been described that employ the polymerase chain reaction (PCR) to amplify arbitrary regions of a genome using a single primer. The techniques reveal polymorphisms in insect taxa that lack allozyme variation and, for the first time, permit genetic polymorphisms to be rapidly analysed in small arthropods (e.g. mites, endoparasitic wasps). The methods have been used in identification of sub-species and cryptic species, and have applications in population genetics and genetic fingerprinting. They are fairly inexpensive, do not require the use of radioactivity, are relatively simple to learn and can easily be adapted to most laboratories. However, their application is not without technical problems and practical limitations. The purpose of this note is to indicate the critical factors to consider before launching into their use. We chiefly emphasize that most polymorphisms revealed by these methods segregate as dominant markers. Furthermore, application of these techniques requires extensive standardization and may not prove to be reproducible among various laboratories especially those employing different types of thermal cyclers. There are some unique features of these polymorphisms to consider when using them in genetic fingerprinting. In addition, because the techniques amplify arbitrary regions of genomes, similarly sized fragments amplified between two species may not be homologous. This argument and empirical observations suggest that PCR with arbitrary primers will have limited application in molecular systematics above the intraspecific level.     

Distribution of lung disease

Radiologists rely on imaging patterns to arrive at a diagnosis. The different morphological patterns in the lungs are well known, but less emphasis has traditionally been placed on the pattern of distribution. This important feature greatly assists in the differential diagnosis regarding many pulmonary diseases and is the focus of this article. Chest radiographs often result in a narrow differential if one understands the regional differences and microenvironments within the lung and takes into consideration the ancillary imaging findings. High-resolution computed tomography offers additional information at the level of the secondary pulmonary lobule to fine-tune the distribution pattern and, consequently, the differential diagnosis. Disease distribution is often as important as the morphologic appearance of the disorder. This article will approach pulmonary diseases from the perspective of distribution patterns, highlighting the more common patterns. The goal of this review article is to give radiologists a conceptual framework that may be applied in their daily work environment.     

Pulmonary effects of inhaled diesel exhaust in aged mice

Pulmonary morbidity and mortality resulting from exposure to fine particulate matter (PM) increases with age. The present studies analyzed potential mechanisms underlying increased susceptibility of the elderly to PM using diesel exhaust (DE) as a model. Mice (2 m and 18 m) were exposed to DE (0, 300, and 1000 μg/m³) for 3 h once (single) or 3 h/day for 3 days (repeated). Bronchoalveolar lavage fluid (BAL), serum and lung tissue were collected 0 and 24 h later. Exposure to DE resulted in structural alterations in the lungs of older but not younger mice, including patchy thickening of the alveolar septa and inflammatory cell localization in alveolar spaces. These effects were most pronounced 24 h after a single exposure to the higher dose of DE. Significant increases in BAL nitrogen oxides were also noted in older mice, as well as expression of lipocalin 24p3, an oxidative stress marker in the lung with no effects in younger mice. Following DE inhalation, expression of Tumor Necrosis Factor alpha (TNFα) was upregulated in lungs of both younger and older mice; however, this was attenuated in older animals. Whereas exposure to DE resulted in increases in lung Interleukin-6 (IL-6) expression in both older and younger mice, IL-8 increased only in older animals. In younger mice, constitutive expression of manganese superoxide dismutase (MnSOD) decreased after DE exposure, while in older mice, constitutive MnSOD was not detectable and DE had no effect on expression of this antioxidant. Taken together, these results suggest that altered generation of inflammatory mediators and MnSOD may contribute to increased susceptibility of older mice to inhaled DE.     

Discrepancy between training,competition and laboratory measures of maximum heart rate in NCAA division 2 distance runners

A percentage of either measured or predicted maximum heart rate is commonly used to prescribe and measure exercise intensity. However, maximum heart rate in athletes may be greater during competition or training than during laboratory exercise testing. Thus, the aim of the present investigation was to determine if endurance-trained runners train and compete at or above laboratory measures of ''maximum'' heart rate. Maximum heart rates were measured utilising a treadmill graded exercise test (GXT) in a laboratory setting using 10 female and 10 male National Collegiate Athletic Association (NCAA) division 2 cross-country and distance event track athletes. Maximum training and competition heart rates were measured during a high-intensity interval training day (TR HR) and during competition (COMP HR) at an NCAA meet. TR HR (207 ± 5.0 b·min^-1; means ± SEM) and COMP HR (206 ± 4 b·min^-1) were significantly (p < 0.05) higher than maximum heart rates obtained during the GXT (194 ± 2 b·min^-1). The heart rate at the ventilatory threshold measured in the laboratory occurred at 83.3 ± 2.5% of the heart rate at VO₂ max with no differences between the men and women. However, the heart rate at the ventilatory threshold measured in the laboratory was only 77% of the maximal COMP HR or TR HR. In order to optimize training-induced adaptation, training intensity for NCAA division 2 distance event runners should not be based on laboratory assessment of maximum heart rate, but instead on maximum heart rate obtained either during training or during competition.

Key points

• A percentage of maximum heart rate is commonly used to prescribe and measure exercise intensity. However, maximum heart rate may be greater during competition or training than during laboratory exercise testing.
• Heart rates during training and competition were significantly higher than maximum heart rates obtained during laboratory exercise testing.
• To optimize training-induced adaptation, training intensity for NCAA division 2 distance event runners should not be based on laboratory assessment of maximum heart rate, but instead on maximum heart rate measure obtained either during training or during competition.

Key words: Competition, heart rate, laboratory, performance, running, training