Effect of prazosin and beta-blocker monotherapy on serum lipids: a cross-over, placebo-controlled study.

The effects of prazosin and beta-blocker monotherapy on serum concentrations of triglycerides, cholesterol, and lipoprotein cholesterol were evaluated in 16 patients with mild to moderate essential hypertension in a single-blind, cross-over, placebo-controlled study. Initially patients received a bid dose of either prazosin or a beta-blocker sufficient to maintain a sitting diastolic pressure below 95 mm Hg. After a placebo washout, patients were placed on the alternate medication. Fasting serum samples were obtained for lipid analysis during each treatment phase. Beta-blocker therapy was associated with undesirable changes in serum lipids as evidenced by increases in the concentration of total triglyceride (45%, P = .001), total cholesterol (4%, P = .05), LDL cholesterol (6%, P = .05) and VLDL cholesterol (21%, P = .05), and a decrease in the concentration of HDL cholesterol (-9%, P = .05). The ratios of total cholesterol to HDL cholesterol and LDL cholesterol to HDL cholesterol also increased by 15% (P = .005) and 18% (P = .005), respectively. No significant changes in any of the serum lipids were observed during prazosin administration.

Trends in hospital unionization and a predictive model for unionizing success.

Between 1976 and 1980, the average annual increase in hospital expenses was 12.7%. Wages for employees accounted for approximately one-half of this increase. Because employee wages have such a great effect on hospital costs, it is important to study those factors that could curtail management's control over these expenses. One such factor is the establishment of labor unions. This study outlines the structural factors that encourage union activity, as well as the factors that contribute to its success. Variables studied include: the types of employees in the bargaining unit; the total number of employees in the bargaining unit; the number of hospitals in the same city; the control of the hospital and the presence of a profit motive; the number of beds in the hospital; the occupancy level of the hospital; and the region of the country in which the hospital is located.

Radioimmunoassay for normeperidine: studies on the N-dealkylation of meperidine and anileridine.

A sensitive and specific radioimmunoassay for normeperidine has been developed that can detect as little as 100 pg of this metabolite. In competitive binding experiments with [125I]O-tyramyl-normeperidinic acid and an antiserum produced in rabbits immunized with a bovine serum albumin-normeperidinic acid conjugate, meperidine is only 0.01% as effective an inhibitor as normeperidine. Therefore, normeperidine can be determined in physiological fluids and in tissue extracts when relatively large amounts of meperidine or other N-phenylpiperidine esters are present. High pressure liquid chromatography can be used to confirm the results obtained by radioimmunoassay during the in vitro N-dealkylations of meperidine and anileridine to normeperidine. The normeperidine isolated by high pressure liquid chromatography accounts for all of the inhibitory reactivity determined in the enzymatic digests by the radioimmunoassay. Kinetic parameters (Km and Vmax) can be determined for the N-dealkylation of meperidine and anileridine. The formation of normeperidine with time can be followed in rabbits injected with meperidine or anileridine. Plasma levels may also be determined when meperidine is administered as an obsteric analgesic.

Stereochemical analogs of a muscarinic, ganglionic stimulant. 2. Cis and trans olefinic, epoxide, and cyclopropane analogs related to 4-[N-(3-chlorophenyl)carbamoyloxy]-2-butynyltrimethylammonium chloride (McN-A-343).

Preparation of analogs of 4-[N-(3-chlorophenyl) carbamoyloxy]-2-butynyltrimethylammonium chloride [1 (McN-A-343)], cis- and trans-4-[N-(4-chlorophenyl)carbamoyloxy]-2-butenyltrimethylammonium iodides (5 and 6), and the corresponding epoxides and cyclopropanes is reported. Pharmacological testing for ganglion-stimulating activity demonstrated that the trans olefin 6 and trans epoxide 8 have properties similar to 1, while the trans cyclopropane analog 10 was inactive. All cis compounds were inactive. The muscarinic ganglion-stimulating properties of the active compounds are interpreted in terms of similar fit at the receptor level by the alkyltrimethylammonium ion and the ether oxygen 5.7 A distant, as well as an electron-rich center midway between groups in the form of a double bond or unshared electron pairs. Comparison of smooth muscle and ganglion-stimulating properties of the compounds showed that trans epoxide 8 was the most selective for muscarinic ganglionic sites.

Stereochemical analogs of a muscarinic, ganglionic stimulant. 3. 2,3-Substituted bicyclo(2.2.1)hept-5-enes and -heptanes related to 4-(N-(3-chlorophenyl)carbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343).

Preparation of analogs of 4-[N-(3-chlorophenyl)carbamoyloxy]-2-butynyltrimethylammonium chloride (1, McN-A-343), the isomeric 2-trimethylammoniomethyl-3-[N-(4-chlorophenyl)carbamoyloxymethyl]bicyclo [2.2.1]hept-5-ene iodides (10-13), and the corresponding -bicyclo[2.2.1]heptane iodides (14-17) are reported. None of the compounds demonstrated ganglion-stimulating activity similar to 1 or antagonized the effects of 1.

Radioimmunoassay for anileridine, meperidine and other N-substituted phenylpiperidine carboxylic acid esters.

Antibodies that bind an 125I-tyramyl derivative of N-succinylanileridine have been produced in animals immunized with N-succinylanileridine-hemocyanin conjugate. Several congeners and metabolites have been tested as competitors of this antigen-antibody reaction. The concentrations (in picomoles) required for 50% inhibition have been found to be: anileridine (0.2), meperidine (3.5), piminodine (3.8), diphenoxylate (20.5), normeperidine (20.0), meperidine acid (45,000) and anileridine acid (3,400). Although ester hydrolysis results in changes in inhibiting capacities on the order of 10(4), major structural changes in the substituent on the nitrogen of the piperidine ring are not readily recognized by the antibody. This radioimmunoassay can be used to study a variety of N-substituted phenylpiperidine carboxylic acid esters by relating the results to the standard curve obtained for the drug under investigation. For all practical purposes, alphaprodine, morphine and methadone do not interfere with the assay.