Positive end-expiratory pressure and the damaged right ventricle. An experimental open versus closed chest study

Hemodynamic changes after isolated impairment of right ventricular function (produced by increasing afterload by temporary banding of the pulmonary artery) were studied in 22 ventilated pigs during increased levels of positive end-expiratory pressure (4, 8, 12, and 16 cm H2O). In the open chest group, application of positive end-expiratory pressure produced only a slight decrease of cardiac index. After right ventricular damage a decrease of cardiac index of more than 25% occurred only when higher levels of positive end-expiratory pressure were applied. In contrast to the open chest group, the closed chest group showed more distinct cardiovascular responses after positive end-expiratory pressure. In the damaged right ventricle with a positive end-expiratory pressure of 16 cm H2O, right ventricular end-diastolic pressure increased more than 100%. With positive end-expiratory pressure, cardiac index decreased 34% before and 47% after right ventricular damage. We conclude that positive end-expiratory pressure induces a more pronounced decrease in cardiac index if right ventricular function is impaired. During open chest conditions with lower levels of positive end-expiratory pressure, these changes are only small, however, and probably irrelevant. During closed chest conditions, the hemodynamic changes are much more pronounced. High right ventricular end-diastolic pressures resulting from impaired right ventricular contractility as well as from high levels of positive end-expiratory pressure may have an impact on biventricular function and right ventricular coronary driving pressure.     

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.     

Monocrotaline-induced cardiopulmonary injury in rats. Modification by the neutrophil elastase inhibitor SC39026

Rats were killed after 6 weeks of continuous ingestion of the pneumotoxic alkaloid monocrotaline (2.2 mg/kg/day), the neutrophil elastase inhibitor SC39026 (60 mg/kg/day), or both. Pulmonary reactions were evaluated by light and electron microscopy. Lung endothelial function was monitored by angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Lung hydroxyproline content was measured as an index of interstitial fibrosis. Cardiac right ventricular hypertrophy was determined by the right ventricle to the left ventricle plus septum weight ratio (RV/LV + S). Rats receiving SC39026 alone did not differ significantly from untreated control animals with respect to any of the quantitative endpoints, although rarefaction of Type I pneumocytes was observed in the electron micrographs of these animals. Monocrotaline-treated rats, in contrast, developed a significant increase in RV/LV + S, and exhibited pulmonary edema, inflammation, fibrosis, and muscularization and occlusive mural thickening of the pulmonary small arteries and arterioles. These monocrotaline-induced structural changes were accompanied by decreased lung ACE and PLA activities, and increased PGI2 and TXA2 production, and by an increase in lung hydroxyproline content. Cotreatment with SC39026 ameliorated the monocrotaline-induced pulmonary vascular wall thickening and the cardiac right ventricular hypertrophy. These data suggest that inappropriate neutrophil elastase activity contributes to monocrotaline pulmonary vasculopathy and hypertension. On the other hand, cotreatment with SC39026 had no significant effect on the severity of the monocrotaline-induced lung inflammatory reaction, the pulmonary endothelial dysfunction, or the increase in lung hydroxyproline content.     

Spontaneous fractures of the lesser metatarsals secondary to an amputated hallux and peripheral neuropathy

A general overview of the literature concerning the development of diabetic neuropathic arthropathy is discussed. A case report is presented dealing with spontaneous fractures of the lesser metatarsal in a patient with an amputated hallux and peripheral neuropathy secondary to diabetes mellitus.