Therapy-related acute myeloid leukemia secondary to inhibitors of topoisomerase II: from the bedside to the target genes.

In the past five years, several groups have reported acute myeloid leukemia (AML) often monoblastic, as a complication of chemotherapy regimens including the epipodophyllotoxins, etoposide and teniposide. This syndrome is distinct clinically, pathologically and cytogenetically from classical therapy-related myelodysplasia and AML. There is also evidence that other topoisomerase II inhibitors, such as the intercalating agents (including doxorubicin, mitoxantrone, and actinomycin D) may be leukemogenic. Furthermore, there may be further interactions from concomitant topoisomerase II inhibitors and alkylating agents. Topoisomerase II inhibitors induce DNA cleavage and other chromosomal aberrations, including sister chromatid exchanges. These clastogenic abnormalities are not fully understood, and may be specific for each cytotoxic agent. Work is in progress to clone breakpoints such as the t(9;11) and t(8;21) and the use of the resultant DNA probes will enhance our understanding of the leukemogenic process. Given the potential diversity in patients with secondary leukemia, cytogenetic studies should be mandatory for both enhancing our knowledge base and guiding treatment in individual patients. Clinicians must also be wary of the leukemogenic potential of 'dose-intense' regimens including agents such as etoposide and doxorubicin.     

Incomplete holism in pre-registration nurse education: the position of the biological sciences

There is an ongoing debate in nurse education concerning the role and delivery of the biological sciences in the nursing curriculum. One of the fundamental questions raised by this debate asks how best can teachers impart biological knowledge in a manner that can be readily applied by students and qualified nurses to inform their clinical practice. This paper will include a discussion of some of the features of pre-registration education that may have influenced the manner in which biological sciences are perceived, taught and used by nurses. It will be argued that nursing may have developed a form of incomplete holism and that this may be in part responsible for the challenges that remain to be met within this area of the nursing curriculum. As a response to incomplete holism an innovative approach within pre-registration education will be introduced. This development involves the use of linked teaching sessions which aim to develop the analytical skills necessary to apply physiological knowledge to nursing practice.     

Rates of Borrelia burgdorferi infection in Ixodes dammini (Acari: Ixodidae) in southwestern Wisconsin.

Ixodes dammini Spielman, Clifford, Piesman & Corwin collected from a study site in southwestern Wisconsin were examined for Borrelia burgdorferi infection. Adult spirochete infection rates varied seasonally (38.1%, spring 1990; 60.3%, fall 1990; 41.2%, spring 1991) and were similar to or higher than rates reported in various studies from the northeastern United States. Statistical comparison of seasonal infection rates indicated a significant difference between the fall 1990 adult population and the subsequent overwintered population of the same cohort (spring 1991). Additionally, a significant decrease in the intensity of spirochete infection was observed in the overwintered adult sample.     

Chronic clonazepam administration decreases gamma-aminobutyric acidA receptor function in cultured cortical neurons

Chronic benzodiazepine administration has been reported to decrease gamma-aminobutyric acidA (GABAA) receptor function in animals and may alter benzodiazepine binding in neuronal cultures. To assess GABAA receptor function in neuronal cultures exposed to chronic clonazepam, we measured muscimol-stimulated chloride uptake in chick cerebral cortical cultures treated acutely and for 2, 4, and 10 days. Acute clonazepam administration (1 microM) led to an increase in GABA-related chloride uptake at lower doses of muscimol. After chronic clonazepam (1 microM), maximal uptake was markedly decreased at day 10, but maximal uptake was unchanged after 2- and 4-day treatments. Benzodiazepine receptor binding was decreased by approximately 60% after 10 days due to a decrease in receptor number. Decreases in chloride uptake were also observed after 10 days of treatment with 0.1 and 10 microM clonazepam. Concomitant treatment with 0.1 microM Ro15-1788 abrogated the effect of 0.1 microM clonazepam on chloride uptake. Chronic clonazepam treatment (1 microM) did not alter total cellular protein, cellular protein synthesis or degradation or percentage of neuronal cells, as determined morphologically and by [3H]ouabain binding.     

Effect of dietary restriction upon the age-associated decline of lymphocyte DNA repair activity in mice

Effects of dietary restriction (DR) on DNA repair capacity of mouse splenocytes after ultraviolet (UV)-induced damage were assessed. Two mouse cohorts received restricted amounts of purified hypocaloric diets; one was minimally restricted (∼75% of the caloric intake of mice fed a commercial diet ad libitum), the other was severely restricted (∼50% caloric restriction). An inverse correlation between age and DNA repair was present in the two cohorts; however, the regression lines of the two cohorts showed different slopes. DR appears to decelerate the age-associated decline of DNA repair capacity, and this delay might account in part for the improved immune function shown by old mice on DR.     

Assessment of cardiovascular autonomic function.

Autonomic assessment has played an important role in elucidating the role of the autonomic nervous system in diverse clinical and research settings. The techniques most widely used in the clinical setting entail the measurement of an end-organ response to a physiological provocation. The non-invasive measures of cardiovascular parasympathetic function involve the analysis of heart rate variability while the measures of cardiovascular sympathetic function assess the blood pressure response to physiological stimuli. Prolonged tilt-table testing, with or without pharmacological provocation, has become an important tool in the investigation of a predisposition to neurally mediated (vasovagal) syncope. Frequency domain analyses of heart rate and blood pressure variability, microneurography, occlusion plethysmography, laser Doppler imaging and flowmetry, and cardiac sympathetic imaging are currently research tools but may find a place in the clinical assessment of autonomic function in the future.     

Monocular contribution to the peak time of the binocular pattern visual evoked potential

The contribution of each monocular pathway to the timing of the binocular pattern visual evoked potential was assessed in situations where a significant interocular timing discrepancy was observed. Monocular and binocular pattern visual evoked potentials to 0.5° checks were recorded from normal subjects, normal subjects in whom one eye was blurred, patients with monocular amblyopia, and patients with resolved unilateral optic neuritis. Normal subjects showed facilitation, while suppression was evidenced in subjects with monocular blurring. In patients with amblyopia, the affected pathway had no effect on binocular pattern visual evoked potential latency, suggesting that the amblyopic eye was suppressed. In contrast, all patients with optic neuritis showed binocular averaging. Our results show that different forms of binocular interaction are evidenced in normal subjects, in amblyopia and in optic neuritis, and suggest that a comparative analysis of monocular and binocular pattern visual evoked potential peak times brings valuable information to the clinical evaluation that could be used to distinguish disease processes further.Abbreviation BPVEP binocular pattern visual evoked potential     

Force, pressure, and motion measurements in the foot: current concepts

Modern foot-pressure measurement studies have successfully debunked the tripod theory; on the contrary, the highest peak loads under the forefoot occur as often as not under the third metatarsal head and not the first and fifth. This does not necessarily mean that the first metatarsophalangeal joint does not sustain the highest pressures; calculations based on the measured pressures under the metatarsals and digits show that it does. One must bear in mind that the hallux consistently bears significantly more pressure than any of the other toes. It is likely that the pressure borne by the first metatarsal head and hallux combined consistently exceed that for the other four metatarsal heads and their respective digits. In other words, the first ray probably has the consistently highest load in normal feet, even when the second or third metatarsal head achieves a greater peak pressure than the first metatarsal head. Three lines of evidence suggest the role that pressure plays in forefoot pathology. First, metatarsalgia is commonly associated with hallux valgus. It often arises following or is exacerbated by hallux valgus surgery (especially arthroplastic procedures). Patients with hallux valgus demonstrate increased peak pressure under the lateral metatarsal heads that actually increases following the Keller procedure. Second, the peak pressure under callosities are, on the average, higher than normal. Third, diabetic plantar ulcers occur at sites of high pressure. The correlations between peak loads on the lateral column and both age and weight merit some attention, since it is common experience that the prevalence of symptomatic foot lesions is higher in older populations. The correlation with body weight may be unexpected. One would expect that, on the average, body weight would correlate with the weight-bearing surface area of the foot and, therefore, the pressure would be relatively constant. The increased pressure under the medial column suggests a relative instability of the medial column with advancing age and weight. Pressure should not be construed as the only factor. The large overlap in peak pressures found under diabetic ulcers and intact skin in both normal and diabetic feet makes this apparent. However, while peak pressures have been extensively studied, there has been no attempt to measure the duration or frequency of loading on a day-to-day basis. According to Brand, it is not the absolute loads applied to a part but repetitive pressure that is responsible for tissue breakdown, especially when such repetitive loads are applied without any interim period for the tissues to recover.(ABSTRACT TRUNCATED AT 400 WORDS)