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Objective: To provide clinical support that conversion from captopril to lisinopril at a daily oral dosage ratio of 5:1 maintains comparable therapeutic efficacy, and to estimate retrospectively cost savings because of conversion from captopril to lisinopril therapy at the study site and with the associated overall drug conversion program instituted by Kaiser Permanente., Design: An open-label, randomized, prospective, parallel study was performed in 56 patients with mild-to-moderate hypertension. In a 4-week preroandomization period, oral maintenance dosages of captopril were established. Patients then were randomly assigned either to continue taking captopril or to change to lisinopril at an initial conversion ratio of captopril 5 mg to lisinopril 1 mg. Blood pressures were evaluated 2, 4, 8, and 12 weeks postrandomization. If necessary, dosages were adjusted to maintain adequate efficacy (i.e., systolic pressure < 160 mm Hg and diastolic pressure < 90 mm Hg in the prerandomization period; diastolic pressure < 90 mm Hg postrandomization). Cost savings for the study site and to the overall program with respect to conversion from captopril were defined as the difference between the estimated drug costs and the drug costs projected if the conversion had not been made., Setting: Woodland Hills Medical Center of the Southern California Region of Kaiser Permanente Medical Care Program., Main Outcome Measures: The main outcome measures were systolic and diastolic blood pressure. The measure for the retrospective cost savings analysis was estimated cost savings based on the number of prescriptions written for captopril and lisinopril from December 1988 through December 1993, and the average wholesale price., Participants: Members of the Kaiser Permanente Medical Care Program who were diagnosed with mild-to-moderate hypertension and whose hypertension was controlled by captopril alone. Retrospectively, mild-to-moderate hypertension would have been classified as stages 1-3, based on the current guidelines of the Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure., Results: The blood pressures of patients in whom captopril therapy was switched to lisinopril therapy were maintained throughout the entire study within the defined acceptable limits of control when the conversion was initiated at a daily oral dosage ratio of 5:1. The final dosage conversion ratio was not significantly different statistically from the theoretical dosage conversion ratio of 5:1., Conclusions: The conversion from captopril (in equally divided daily doses) to lisinopril (once daily) at a dosage ratio of 5:1 maintained comparable control of mild-to-moderate hypertension with no increase in adverse effects. In addition, the cost savings associated with an overall drug conversion program were substantial, and the conversion provided a preferred once-daily dosing regimen.

Ventilatory failure occurred in a patient suffering from proximal neurogenic muscular atrophy resembling the adult form of Kugelberg-Welander syndrome. Diaphragmatic paralysis was diagnosed when patient was found to be unable to generate a transdiaphragmatic pressure difference on deep inspiration. Post-mortem examination revealed nearly complete replacement of the diaphragm by fat and fibrous tissue. Although uncommonly reported in the medical literature, ventilatory failure secondary to diaphragm dysfunction should be added to the list of complications encountered in the clinical setting of chronic proximal spinal muscular atrophy.

The antibody response of genetically inbred rats to poly(Glu52Lys33Tyr15) is controlled by a complex polygenic system which includes at least two autosomal genes and a sex influence, which may also be genetically determined. The genetic control of the quantity, binding constants, and specificity of the antibody formed linked to the major histocompatibility locus. Factors other than the major genetic ones and the sex influence also affect the quantity of antibody formed, since animals of the same genotype can make significantly different amounts of antibody, depending upon the crosses by which they acquire the major histocompatibility alleles. After immunization with poly(Glu52Lys33Tyr15) the low responders make fewer antibody-producing cells, are not capable of mounting a delayed hypersensitivity reaction to the polypeptide and appear to be deficient in their ability to produce the specific IgM antibody. Immunization of the low responders with antigen aggregated with methylated bovine serum albumin enhances the quantity of antibody formed, increases the binding constants and crossreactivity of the antibody and enhances the delayed hypersensitivity response. In contrast to the findings with the L-amino acid polypeptide, there does not appear to be any genetic control over the antibody response to the D-amino acid enantiomorph poly(DGlu52DLys33DTyr15), which is minimal in all strains.