Desferrithiocin is an effective iron chelator in vivo and in vitro but ferrithiocin is toxic

The efficacy and toxicity of the siderophore desferrithiocin (DFT), which has shown potential application in iron chelation therapy, were assessed in vivo and in vitro. DFT was evaluated in vivo in two ways: firstly, by measuring the effect of a single dose of DFT (10-100 mg/kg) on 59Fe excretion in iron-loaded rats labelled with 59Fe; and secondly, by examining the effect of the daily oral administration for 2 weeks of DFT (10-25 mg/kg/d) on the growing rat. DFT and its ferric complex, ferrithiocin (FT), were assessed in vitro from their effects on transferrin and iron uptake and mobilization from rat hepatocytes in culture using transferrin doubly labelled with 125I and 59Fe. Both oral and subcutaneous DFT were highly effective in promoting iron excretion in vivo, but showed evidence of toxicity after oral administration for 2 weeks at 25 mg/kg/d. In addition, DFT was much more effective than desferrioxamine or pyridoxal isonicotinyl hydrazone in reducing hepatocyte iron in vitro. However, FT was cytotoxic, causing membrane disruption and release of intracellular aspartate aminotransferase. It was concluded that DFT should not be considered for chronic iron chelation therapy without extensive further evaluation.     

Adrenal magnetic resonance imaging in addison’s disease

Magnetic resonance imaging of the adrenal glands was performed in 9 patients with Addison’s disease to evaluate the role of magnetic resonance (MR) in this entity. All patients had bilateral adrenal masses demonstrated by computed tomography (CT); etiologies included adrenal hemorrhage (2 patients), granulomatous disease (1 patient), adrenal lymphoma (3 patients), and adrenal metastases (3 patients). Spin-echo axial images were obtained at repetition times (TR) 0.5, 2.0 s and TE 28, 56 ms, using a Diasonics superconducting magnet operating at 0.35 T. In the patients with lymphoma, metastases, and granulomatous disease, the adrenal masses appeared hypointense or isointense with liver on the T₁-weighted images (TR 0.5 s, TE 28 ms). In cases of adrenal hemorrhage, areas of hyperintensity were seen on TR 0.5, TE 56 ms sequences, due to shortening of T₁ values. In both groups of patients the masses were hyperintense on T₂ weighted sequences. Mean calculated T₁ of the hemorrhagic glands was 449 ms, compared with a mean of 782 ms for mestastases and lymphoma. While MR is not capable of distinguishing between acute inflammatory and metastatic disases of the adrenal glands, it may be equally efficacious as CT in suggesting the diagnosis of adrenal hemorrhage in patients with Addison’s disease.     

Undergraduate and postgraduate dental students''reflection on learning'': a qualitative study

The aim of this study was to explore undergraduate and postgraduate dental students' understanding of a good learning experience by using 'reflection on learning' as described by Schon. Four groups of Year 4 BDS students and one group of postgraduate students in dental public health took part in a series of focus group discussions. The responses were grouped into four broad themes (a) active, practical and positive learning; (b) interactive/together learning; (c) personal learning; (d) theory into practice. Six educational models of good learning proposed by the students are described.     

Tests for presynaptic modulation of corticospinal terminals from peripheral afferents and pyramidal tract in the macaque

The efficacy of sensory input to the spinal cord can be modulated presynaptically during voluntary movement by mechanisms that depolarize afferent terminals and reduce transmitter release. It remains unclear whether similar influences are exerted on the terminals of descending fibres in the corticospinal pathway of Old World primates and man. We investigated two signatures of presynaptic inhibition of the macaque corticospinal pathway following stimulation of the peripheral nerves of the arm (median, radial and ulnar) and the pyramidal tract: (1) increased excitability of corticospinal axon terminals as revealed by changes in antidromically evoked cortical potentials, and (2) changes in the size of the corticospinal monosynaptic field potential in the spinal cord. Conditioning stimulation of the pyramidal tract increased both the terminal excitability and monosynaptic fields with similar time courses. Excitability was maximal between 7.5 and 10 ms following stimulation and returned to baseline within 40 ms. Conditioning stimulation of peripheral nerves produced no statistically significant effect in either measure. We conclude that peripheral afferents do not exert a presynaptic influence on the corticospinal pathway, and that descending volleys may produce autogenic terminal depolarization that is correlated with enhanced transmitter release. Presynaptic inhibition of afferent terminals by descending pathways and the absence of a reciprocal influence of peripheral input on corticospinal efficacy would help to preserve the fidelity of motor commands during centrally initiated movement.     

Acute leukemia occurring 19 years after treatment of acute lymphoblastic leukemia

A 22-year-old woman presented with acute lymphoblastic leukemia (ALL) during pregnancy. She had been successfully treated for ALL at the age of 3 years and had received maintenance treatment for 11 years. Complete remission of 3 years or more is an important factor for long-term survival and potential cure. Relapses may occur in the first 5 years after maintenance is discontinued. Later relapses are distinctly unusual. We have found six more cases of ALL occurring long after the initial remission in the English literature. It is unclear whether late relapse represents true relapse or a second leukemia. Life-long follow-up of children with ALL may be necessary.     

A comparison of glycine, sarcosine, N,N-dimethylglycine, glycinebetaine and N-modified betaines as liposome cryoprotectants.

Glycinebetaine has previously been shown to be effective at reducing leakage from liposomes which are frozen then thawed. This study involved the preparation of a series of N-modified betaines and the comparison of their cryoprotective activities with those of glycine, sarcosine, N,N-dimethylglycine and glycinebetaine. All the compounds investigated, with the exception of (dimethyloctylammonio)acetate, reduced the degree of leakage, after freezing and thawing, with additive concentrations up to 0.6 M. Reducing the degree of N-terminal methylation of glycinebetaine appeared to increase the leakage from liposomes at additive concentrations between 0.2 and 0.6 M. (Dimethylethylammonio)acetate, (dimethylisopropylammonio)acetate and (N,N,N',N'-tetramethylethylenediammonio)-N,N'-diacetate appeared to be no more effective than glycinebetaine, whereas improved protection was afforded by (triethylammonio)acetate and (diethylmethylammonio)acetate at most concentrations. This study demonstrates that the cryoprotective activity of glycinebetaine may be improved with modifications to the N-terminal.     

Second births among teenage mothers: program results and statistical methods

This paper uses survival analysis to examine three large-scale, multi-site, randomized, controlled programs that attempted to prevent or delay second births to teenagers. Statistically significant differences in the hypothesized direction were found between the intervention and the control groups in the Elmira and Memphis Home Visitation sites. No statistically significant differences in the hypothesized direction were found in the Teen Parent Welfare Demonstration overall or in any of its three sites or in all New Chance sites combined. Delaying second pregnancies among teenagers requires intensive efforts. Survival analysis is a more accurate and useful way of presenting program results than simple analysis of the proportion of women with a second birth.     

Meningococcal disease in the United States--1986. Meningococcal Disease Study Group

Active surveillance for invasive meningococcal disease was conducted during 1986 and 1987 in six areas of the United States with a total population of approximately 34 million persons. The incidence of meningococcal disease was 1.3:10(5). The highest incidence of disease among the surveillance areas was in Los Angeles County (1.65:10(5). Neisseria meningitidis serogroups B and C caused about equal amounts of disease, which reflects a recent increase in the incidence of group C disease. Group C caused more than half of the cases of meningococcal disease in Los Angeles and Tennessee but less than one-third of the cases in Missouri and Oklahoma. Multilocus enzyme electrophoresis demonstrated that a group of closely related isolates of N. meningitidis was prevalent in Los Angeles during the surveillance period and was associated with an increased incidence of meningococcal disease there.     

Development of a Novel Scale to Assess Life Fulfilment as Part of the Further Refinement of a Quality-of-Life Model for Epilepsy

Summary: We have been involved in developing a health-related quality-of-life model for use as an outcome measure in epilepsy. As part of the further development of this model, we have developed a measure of life fulfilment. This scale is based on methods previously described by Krupinski in 1980. The value of Krupinski's approach is the opportunity for patients to weight the numerous aspects of their quality of life and assess the discrepancy between their actual and desired circumstances. The life fulfilment scale has been shown to be reliable (α= 0.7) and valid. The scale is currently being applied to several clinical studies in epilepsy. We believe that the scale provides a valuable contribution to our health-related quality-of-life model.