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.     

McArdle's disease with myoadenylate deaminase deficiency: observations in a combined enzyme deficiency

Exercise and work potential of a patient with coexistent myophosphorylase and myoadenylate deaminase (AMPDA) deficiency was compared with that of three patients with myophosphorylase deficiency alone. The patient with the combined defect failed to produce an abnormal rise in serum ammonia or hypoxanthine as seen in the other patients after forearm exercise. Maximum oxygen consumption and work rates during cycle ergometer testing were similar in all patients, but well below controls. The occurrence of two defects involving short-term energy metabolism in muscle presents an opportunity to define further the metabolic role of AMPDA.     

Diagnostic value of load tests in the evaluation of nonspecific changes in the electrocardiogram

The paper describes the examinations of 353 patients with various cardiovascular pathologies and changes in the end-portion of the ECG ventricular complex. For that purpose potassium chloride, obsidan, orthostatic and hyperventilation tests were used. The examinations demonstrated that the ECG changes were of functional nature in 178 patients, of organic nature in 155 patients and of mixed nature in 20 patients which was important for reliable diagnostic and expertise conclusions.     

The surgical management of resistant club foot by rotation skin flap and extensive soft tissue release

Summary Resistant club foot remains an unsolved problem because of the complex aetiological and pathological factors, and is still seen quite frequently, especially in developing countries. The posteromedial skin contracture is a potent deforming force which is responsible for many failures or relapses. I report the results of an operation in which a rotation skin flap was combined with an extensive soft-tissue release. The age of the children was from 9 months to 10 years. The follow-up period was from one to 9 years with an average of 43 months, and in 50 cases for more than 5 years. I consider that the outcome has been excellent or good in 94 out of 100 feet.

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Résumé Le pied bot invétéré demeure un problème mal résolu en raison de la complexité des facteurs étiologiques et anatomiques et il est encore bien souvent rencontré, notamment dans les pays en voie de développement. La rétraction cutanée postéro-interne représente un puissant élément de la déformation, qui est responsable de bon nombre d'échecs ou de récidives. Nous rapportons les résultats d'une opération qui associe un lambeau cutané de rotation à la libération des parties molles. L'âge des enfants était compris entre neuf mois et dix ans. Le recul est de un à neuf ans, avec une moyenne de 43 mois. Cinquante enfants ont été suivis plus de cinq ans. Les résultats sont excellents ou bons dans 94% des cas.

     

A correctable complication of advanced congestive heart failure

Hyponatremia is a common complication of chronic advanced CHF unresponsive to the usual therapeutic measures. Thus low levels of serum sodium are a significant marker for severe CHF refractory to the more conventional measures. The combined use of ACE inhibitors and diuretics is generally very effective in correcting the hyponatremic state and often helpful in reversing CHF.     

Acquired renal cystic disease: two cases of associated adenocarcinoma and a renal ultrasound survey of a peritoneal dialysis population

Long-term dialysis patients frequently develop acquired renal cystic disease (ARCD). The discovery of ARCD and renal cell carcinoma in one of our hemodialysis patients led us to review the literature. ARCD has been described mainly in the maintenance hemodialysis (MH) population. Therefore, we investigated 20 peritoneal dialysis (PD) patients for ARCD using ultrasonography. Seven patients (35%) had detectable cysts and two patients (10%) had multiple bilateral cysts. One patient had a large asymptomatic complex cyst that proved to be an adenocarcinoma. Our study suggests that ARCD is relatively common in the PD population, and we speculate that it may be related more to length of time in end-stage renal disease (ESRD) than to the mode of dialysis. The potential for malignant change appears to justify a routine screening examination with ultrasonography and/or computerized tomography (CT) to detect this recently described and probably underrecognized entity.     

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.     

Stereotaxic biopsy and positron emission tomography correlation of cerebral gliomas

Computer-directed stereotaxis was used to obtain tissue diagnosis in two cases of cerebral glioma, one low grade, and the other high grade. Both lesions had a similar computed tomographic appearance. Positron emission tomography was performed in each case using [18F]fluorodeoxyglucose. A correlation was made in each case between the metabolic activity of the tumor as measured by positron emission tomography, the radiographic appearance, and the tumor histology.