Pharmacological properties of fluphenazine-mustard, an irreversible calmodulin antagonist

We describe an improved synthesis and properties of fluphenazine-mustard, a potent phenothiazine having an alkylating chlorethylamine chain in its structure. The drug possesses anticalmodulin activity equivalent to the parent compound, but unlike fluphenazine dihydrochloride, the mustard derivative irreversibly antagonizes the ability of calmodulin to activate cyclic nucleotide phosphodiesterase. This property is partially calcium-dependent and can be overcome by coincubation with excess fluphenazine dihydrochloride. The compound irreversibly inactivated calmodulin when incubated with intact cells and caused single-stranded breakage of DNA. Fluphenazine-mustard possesses potent antiproliferative and cytotoxic properties against malignant cell lines that are likely to be mediated through both of these actions.     

Renal magnesium wasting in two families with autosomal dominant inheritance

Hypomagnesemia due to isolated renal magnesium loss was demonstrated in two unrelated families with autosomal dominant mode of inheritance. Magnesium infusions performed in two patients showed not only a reduced renal magnesium threshold but also a lowered renal tubular maximum for magnesium. All members of both families who presented with hypomagnesemia had also a lowered excretion of calcium in the urine, presumably as a consequence of increased reabsorption in Henle's loop.     

A comparison of the effects of climbing fiber deafferentation in adult and weanling rats

The climbing fiber input to the cerebellar cortex was destroyed using both electrolytic and chemical (3-acetylpyridine) lesions. The long-term effects of climbing fiber deafferentation on the ansiform lobule of weanling and adult rats were examined at both the light and electron microscopic levels. Image analysis of Golgi-impregnated Purkinje cells indicated a significantly lower number of smooth branches and spiny branchlets following climbing fiber deafferentation of both adult and weanling rats. The results suggest that the lower number of smooth branches and spiny branchlets following climbing fiber deafferentation of the weanling rat is the result of a loss of postnatal growth rather than transneuronal degeneration. Ultrastructural evidence is provided in confirmation of these quantitative findings. Formation of ectopic dendritic spines was found following climbing fiber deafferentation of the weanling rat, but not the adult. It is shown that ectopic spines and the denervated dendritic thorns of these animals were synaptically innervated by the parallel fiber system and basket axons. The formation of ectopic spines on climbing fiber deafferentated Purkinje cells may represent a form of dendritic plasticity. Ultrastructurally, the dendritic arborizations of weanling deafferentated Purkinje cells showed no signs of transneuronal degeneration. However, the primary response to climbing fiber deafferentation in the adult rat was marked transneuronal degeneration of the Purkinje cell dendrites. It is suggested that the inability of the adult Purkinje cell to form ectopic spines and to replace the excitatory postsynaptic potential of the climbing fiber varicosity is directly related to the Purkinje cell's subsequent transneuronal degeneration.     

'Reprofessionalization' or 'occupational imperialism'?: some reflections on pharmacy in Britain

Drawing upon preliminary research findings, this paper considers whether pharmacists in Britain face a crisis in their occupational status and identity as a result of changes in their work and market situations. It further examines some of the ways in which they are responding to the challenges and opportunities presented. The paper also comments on the utility of the concepts of 'reprofessionalization' and 'occupational imperialism' in the study of British pharmacy.     

The effectiveness of intrauterine transfusions

The results of treatment with intrauterine transfusion are presented. The analysis comprised 48 successful transfusions into 29 foetuses. The reference group consisted of 11 transfusions which proved nonfeasible or ineffective and 54 untreated cases. Following blood treatment, the newborn mortality rate dropped more than threefold. Long-term follow-up of 21 children generally showed their good physical and mental development. We also present 4 cases of supsequent pregnancies after intrauterine blood treatment in a preceding pregnancy, showing that it is possible to save the next baby of the same mother.     

Left ventricular volume, mass, and function following surgical correction of chronic aortic regurgitation

Following surgical correction of chronic aortic regurgitation, left ventricular (LV) volume falls to normal or near normal in most patients; this change generally occurs within the first week after surgery. During the ensuing six months, a significant regression of LV hypertrophy occurs, but most patients do not achieve a normal LV mass. The systolic ejection fraction may increase while the LV end-diastolic pressure almost uniformly falls to normal. Postoperative studies of LV volume mass and function should be aimed at identifying those patients which do not undergo these favorable changes so that medical therapy can be directed at this high risk group.