Book Reviews Editor

INLANDER, CHARLES B., LEVIN, LOWELL B., AND WEINER, E.D. Medicine on Trial: The Appalling Story of Medical Ineptitude and the Arrogance that Overlooks It.     

Continuous venous infusion of doxorubicin in advanced sarcomas

Seventeen patients with advanced sarcoma were treated with continuous venous infusion of doxorubicin for a mean of 118 days, achieving total doses up to 1097 mg/m2. Three partial responses and one minor response were obtained. Major toxic effects were stomatitis and hand-foot syndrome. There was a low incidence of leukopenia (18%) and clinical cardiotoxicity (11%). Continuous venous infusion is a safe means of administering doxorubicin, with a response rate similar to that observed with bolus doxorubicin in metastatic sarcoma.     

The relationship between personality and DSM-III axis I disorders in the population: results from an epidemiological survey.

OBJECTIVE: The aim of this study was to assess the relationships between specific personality disorders and DSM-III axis I conditions in a community sample. METHOD: A total of 810 subjects were examined by psychiatrists in the second stage of the Eastern Baltimore Mental Health Survey, part of the Epidemiological Catchment Area Program of the National Institute of Mental Health. A semistructured examination, the Standardized Psychiatric Examination, was employed to assess axis I and axis II conditions. Scales for compulsive and antisocial personality disorders were derived from DSM-III criteria. The relationships between scores on these personality disorder scales and the presence of generalized anxiety disorder, alcohol use disorders (alcohol abuse and alcohol dependence), and simple phobia were evaluated by using logistic regression. RESULTS: Higher compulsive personality scores were associated with a greater odds of generalized anxiety disorder and simple phobia but a smaller odds of alcohol use disorders. In contrast, higher antisocial personality scores were associated with a greater odds of alcohol use disorders but a smaller odds of generalized anxiety disorder. There was no relationship between antisocial personality scores and simple phobia. CONCLUSIONS: Personality disorders have specific relationships to axis I conditions, which suggests different vulnerabilities but also different protective influences.     

Cardiac Surgery in Nonagenarians

A bstract Objectives and Background : The purpose of this study was to document our initial experience with patients 90 years of age and older and to determine whether cardiac surgery is justified in this age group. Cardiac surgery in octogenarians has proven to be a successful and worthwhile procedure. A small group of nonagenarians with severe coronary artery disease (CAD) and aortic valve disease refractory to medical therapy have been considered for surgery. Methods : Fourteen patients aged 90 or more underwent cardiac surgery for symptomatic CAD or aortic valvular disease refractory to medical therapy. Eight patients underwent isolated coronary artery bypass grafting (CABG) and six patients underwent aortic valve replacement (AVR). All patients were in NYHA Class IV preoperatively. Results : Hospital mortality occurred in one patient (7%). Hospital morbidity occurred in 10 patients (71%) and included 7 cardiac, 5 neurological, 1 gastrointestinal, 1 infectious, and 1 pulmonary event. All survivors left the hospital symptomatically improved. The mean length of stay was 26 days. Four CABG patients went on to die at a mean of 2 years and 2 months, and 3 remain alive at a mean of 2 years and 4 months. Three AVR patients expired at a mean of 3 years and 4 months, and 3 remain alive at 4 years and 1 month. Conclusions : Cardiac surgery in carefully selected nonagenarians is justified and can be performed with acceptable results.     

The pharmacokinetics of 125I-atrial natriuretic factor in anaesthetized rats. Effects of neutral endopeptidase inhibition with candoxatrilat and of ANF-C receptor blockade.

The effects of candoxatrilat (cis-4-([2-carboxy-3-(2-methoxyethoxy)propyl]-1-cyclopentanecarbonyla mino)- 1-cyclohexane carboxylic acid) and the ring-deleted atrial natriuretic factor (ANF) analogue C-ANF4-23 (des[Gln18, Ser19, Gly20, Leu21, Gly22]ANF4-23-NH2) on the clearance of (3-[125I]iodotyrosyl28)ANF (125I-ANF) were studied in both intact and nephrectomized anaesthetized rats. HPLC analysis was used to verify that the 125I-labelled material isolated by solid phase extraction of rat plasma was intact ANF. In intact animals, clearance of 125I-ANF was biphasic with a T1/2 alpha of 17 sec and T1/2 beta of 95 sec. Volume of distribution (Vd) was 564 mL/kg and plasma clearance (Clp) 248 mL/min/kg. Candoxatrilat, over the dose range 0.01-10 mg/kg i.v., increased T1/2 beta (by a maximum of 56%) and decreased Clp (by up to 52%) with no effect on T1/2 alpha or Vd. C-ANF4-23 (10 micrograms/kg+1 microgram/kg/min i.v.) reduced Vd (by 57%) and Clp (by 54%) with no effect on T1/2 beta, whilst abolishing the T1/2 alpha phase in over 50% of animals. Increasing the dose of C-ANF4-23 did not increase the effect on any of these parameters, apart from a small increase in T1/2 beta. Combining the two agents resulted in a substantial decrease in Clp (76%) whilst the reduction in Vd and increase in T1/2 beta were comparable to those seen with C-ANF4-23 and candoxatrilat alone, respectively. In nephrectomized rats, the pharmacokinetics of 125I-ANF and the changes induced by candoxatrilat were similar to those observed in intact animals, whilst the effects of C-ANF4-23 alone were greater than in intact animals. The combination of C-ANF4-23 and candoxatrilat again produced a substantial increase in T1/2 beta (153%) and decreases in Vd (55%) and Clp (78%) in nephrectomized animals, although these changes could not be distinguished from those seen in intact animals treated with the same combination. Our studies indicate that neutral endopeptidase and ANF-C receptors are both major, and approximately equal, clearance mechanisms for 125I-ANF, together accounting for at least 75% of the total clearance of this peptide in the rat.     

Ethical and metaethical criteria for an emerging technology: risk assessment

This paper examines ethical criteria for the shaping of an emergingtechnology applied internationally in environmental regulation:quantitative risk assessment-risk management. The role of thephysician in its application, especially in the genetic testingthat will be employed, underlines the importance of understandingthe nature and prospects for reshaping of this technology toenable ethical practice. The Cartesian or mechanistic model(which currently dominates the technology) excludes factorsof emotion, making the connection between assessment and managementunfruitful functionally and ethically, and makes the model unresponsiveto human needs. The emotional factors, nested and mediated inthe organic hierarchy of the ecologically-defined community,constitute key psychological, social, cultural and politicalelements of the total burden of risk. Ethical criteria consistentwith an open society are suggested for reshaping the model toenable effective management.