Influence of estrogen levels on anticholinergic activity of tricyclic antidepressives

Anticholinergic activity of a number of tricyclic antidepressives and nomifensine was demonstrated and their order of affinity for the cholinergic receptors of rat jejunum was determined. The influence of ethinyl estradiol and a conjugated estrogen product, Premarin on the binding of several tricyclic antidepressives to the hepatic mixed function oxidase system was investigated. The influence of these steroids on the metabolism of the antidepressives was evaluated and ethinyl estradiol was shown to have a marked influence on the metabolism of the antidepressives studied, while conjugated estrogens were shown to have little effect.     

Northern Ireland: Political violence and self- reported physical symptoms in a community sample

In order to investigate the possible relationship between physical health and political violence in Northern Ireland a random sample of residents of four electoral areas (two with relatively high violence and two with relatively low violence) was interviewed at home. Each person was asked to rate their health in terms of common physical symptoms, to indicate their use of family doctor and hospital services, and to rate the level of political violence in their neighbourhood. Analysis of covariance (with a measure of psychological well-being, a measure of trait neuroticism plus age and socioeconomic status as covariates) revealed that women reported more physical symptoms than did men, people in the ‘high’ violence areas reported more symptoms than did those in the ‘low’ violence areas, while those who rated their own neighbourhood most highly in terms of perceived violence also reported the greatest number of physical symptoms. However, a series of χ² tests revealed no association between political violence or perceived political violence and uptake of services.     

Single-antibiotic use for penetrating abdominal trauma

A prospective randomized study compared the use of moxalactam disodium vs clindamycin phosphate and tobramycin sulfate for treatment of 190 patients with penetrating abdominal trauma. Twenty-seven patients were disqualified because of early death or failure to follow the protocol. The patients in each group were comparable regarding the cause and severity of injury. No significant difference was seen in the incidence of intra-abdominal infection between the moxalactam-treated group (13%) and the clindamycin- and tobramycin-treated group (9%). The intra-abdominal infection rate in patients with colon injuries (21%) was significantly increased when compared with the patients without colon injuries (6%), but the antibiotic regimen did not significantly change the infection rate. No evidence of bleeding problems from moxalactam were noted. Changes in prothrombin and partial thromboplastin times appeared to be related to shock rather than the use of moxalactam. The most severe coagulopathies occurred prior to moxalactam therapy and were seen only in those patients who had shock requiring 10 or more units of blood. Moxalactam is as effective as combination (clindamycin and tobramycin) antimicrobial therapy in patients with penetrating abdominal trauma.     

Calcium paradox in an in vivo model of multidose cardioplegia and moderate hypothermia. Prevention with diltiazem or trace calcium levels

The production and prevention of calcium paradox injury in myocardium was studied in a canine model of cardiopulmonary bypass with multidose, moderately hypothermic, crystalloid cardioplegic solution. During 4 1/2 hours of global ischemia, three groups of six dogs each received one of three histidine-buffered cardioplegic solutions (500 ml initially and 250 ml every 30 minutes) at 27 degrees C. Group 1 cardioplegic solution was calcium free, group 2 solution contained a trace amount of calcium chloride (70 mumols /L), and group 3 cardioplegic solution was calcium free but contained diltiazem (150 micrograms/kg body weight). Left ventricular function measured as percent control of developed pressure revealed significantly greater (p less than 0.05) recovery in groups 2 and 3. Triphenyltetrazolium chloride staining showed 35% +/- 9% (mean +/- standard error) of heart mass necrosis in group 1 versus 0% and 0.5% +/- 0.4% in groups 2 and 3, respectively (p less than 0.001). Electron microscopy revealed ultrastructural changes characteristic of calcium paradox injury in group 1 myocardium. Calcium paradox injury was produced in an in vivo model of global myocardial ischemia and multidose cardioplegia despite moderate hypothermia and non-coronary collateral flow. The addition of either trace levels of calcium or diltiazem to the cardioplegic solution was effective in preventing this injury.     

Management of the injured colon: evolving practice at an urban trauma center

The records of 239 patients surviving more than 24 hours with full-thickness intraperitoneal colonic injuries over a 7-year period were reviewed. During the first 3 years, 29% (31/106) of the patients were managed by primary repair without colostomy. In the next 4 years, almost twice as many patients, 56% (75/133), with similar colonic trauma were treated without fecal diversion (p less than 0.05). Although there was no difference in the mean Trauma Score in the patients with primary repair in the two time periods, the Injury Severity Score (mean +/- sd) in the patients without colostomy in the later periods was significantly higher (17.8 +/- 2.1 vs. 20.2 +/- 5.1) (p less than 0.001). No patient suffered because of the increased incidence of primary repairs. These patients had five abdominal abscesses and only one leak, whereas the patients with colostomy had 15 intraperitoneal abscesses. Because of the safety when primary repair is performed, more liberal use of primary colonic repair following penetrating trauma is warranted.     

DNA-directed alkylating agents. 3. Structure-activity relationships for acridine-linked aniline mustards: consequences of varying the length of the linker chain

Four series of acridine-linked aniline mustards have been prepared and evaluated for in vitro cytotoxicity, in vivo antitumor activity, and DNA cross-linking ability. The anilines were attached to the DNA-intercalating acridine chromophores by link groups (-O-, -CH2-, -S-, and -SO2-) of widely varying electronic properties, providing four series of widely differing mustard reactivity where the alkyl chain linking the acridine and mustard moieties was varied from two to five carbons. Relationships were sought between chain length and biological properties. Within each series, increasing the chain length did not alter the reactivity of the alkylating moiety but did appear to position it differently on the DNA, since cross-linking ability (measured by agarose gel assay) altered with chain length, being maximal with the C4 analogue. The in vivo antitumor activities of the compounds depended to some extent on the reactivity of the mustard, with the least reactive SO2 compounds being inactive. However, DNA-targeting did appear to allow the use of less reactive mustards, since the S-linked acridine mustards showed significant activity whereas the parent S-mustard did not. Within each active series, the most active compound was the C4 homologue, suggesting some relationship between activity and extent of DNA alkylation.     

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 2: Ring-Substituted Derivatives

A range of 18 derivatives of flavone-8-acetic acid (FAA) with substituents on the 2-phenyl group have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. There was no clear-cut relationship between in vitro and in vivo activity but the activity in each situation was found to be very sensitive to the precise substitution pattern with closely related isomers giving widely different activities. Some of the compounds, notably 10b,cj , and r , were active in vivo and these require further studies in order to evaluate their potential for development.