The Well-being Model: A New Drug Interaction Model for Positive and Negative Effects

Background: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account.

Methods: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs.

Results: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed.     

Mifepristone in Italy: the case of a drug trapped between ethics and clinical practice

In Italy mifepristone is not yet marketed. Gynaecologists in our hospital asked to use this medication as a less traumatic method for voluntary abortions. We followed the standard procedure defined by the Italian Health Ministry (IMH) for purchasing drugs from abroad but encountered several unexpected barriers. Starting from this case, this paper is aimed at identifying these barriers which we found to be not only professional, but also ethical, religious and moral.     

Peripheral ischemic occlusive arterial disease: comparison of color Doppler sonography and angiography.

We examined 334 legs in 167 consecutive patients with advanced peripheral ischemic disease using color Doppler sonography and angiography. Angiography revealed 714 lesions (369 nonsignificant stenoses, 297 significant stenoses, and 48 occlusions) in the 334 legs examined. Overall, color Doppler sonography revealed diagnostic agreement with angiography in 668 of 714 lesions (93.5%), including 343 of 369 (92.9%) nonsignificant stenoses, 279 of 297 (93.9%) significant stenoses, and 46 of 48 (95.8%) occlusions. Overestimation occurred in 26 of 369 (7%) nonsignificant stenoses and 3 of 297 (1%) significant stenoses. Underestimation was observed in 15 of 297 (5%) significant stenoses and in 2 of 48 (4.2%) occlusions. Peak systolic velocity ratio correlated better (P < 0.01) than peak systolic velocity with diameter reduction percentage as assessed at angiography. Color Doppler sonography is an accurate noninvasive method for evaluating patients with peripheral ischemic disease.     

Nonselective measurement of cyclosporine for therapeutic drug monitoring by fluorescence polarization immunoassay with a rabbit polyclonal antibody: I. Evaluation of the serum methodology and comparison with a sheep polyclonal antibody in an 3H-tracer mediated radioimmunoassay

Among the new techniques available for CyA monitoring, the FPIA offers the advantages of rapidity and simplicity. The present communication assesses the technical performance of this test in comparison with a 3H tracer-based PC-RIA for serum CyA levels using 971 samples obtained during the first 6 posttransplant months from 14 kidney transplant recipients. The FPIA evaluation included verification of CyA concentrations in manufacturer-supplied calibrators and controls by reference methods, determination of intraassay/interassay precision and accuracy, feasibility of specimen dilution and assessed assay sensitivity, and range of linearity. Comparison of FPIA with PC-RIA indicated that trough samples, when assessed by FPIA, averaged 1.3-fold greater than the PC-RIA, whereas non-trough FPIA measurements indicated similarity between the two methods. Although the two assays showed similar trends in most renal transplant recipients, two subjects demonstrated discrepancies, presumably reflecting the differing specificities of the polyclonal antibodies used in each assay. Thus, the FPIA appears to be a useful addition to CyA monitoring technology.     

Dose response and toxicity of doxorubicin microspheres in a rat tumor model.

The therapeutic response and toxic effects of chemotherapy using several doses of doxorubicin in conventional solution form or bound to an ion-exchange resin were compared in a rat tumor model, to assess the relationship of drug dose to therapeutic efficacy and associated toxicity. Single bolus injections of 3.0, 4.5, 6.0, 7.5 and 9.0 mg/kg were administered via the abdominal aorta to rats bearing hindlimb tumors. Tumor size was measured serially and the growth rates of treated groups were compared with a control growth curve. In addition, the effect of empty microspheres on tumor growth rate was assessed. The levels of circulating white blood cells were measured and compared to control levels to provide an indication of the severity of bone marrow toxicity experienced by each form of treatment. Finally, any difference in the distribution of doxorubicin to tumor, hindlimb and cardiac tissue following administration of doxorubicin as free drug or on microspheres was ascertained. Empty ion-exchange resin exerted a small although significant detrimental effect on tumor growth which may be explained by the embolization of microspheres in the precapillary blood vessels of the tumor resulting in a transient delay in tumor growth rate. The lowest dose of doxorubicin produced a significantly better therapeutic response when administered in the free drug form, but higher doses elicited an equivalent delay in tumor growth for both drug microsphere and free drug groups in a dose-dependent manner, with the maximum anti-tumor response occurring at the highest dose. Treatment with free doxorubicin at high doses resulted in significant reductions of circulating white blood cells suggesting the occurrence of bone marrow toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Primary lung cancer in young patients: a study of 82 surgically treated patients.

The aim of this study was to evaluate the prognosis for surgically treated young patients with primary lung cancer, a prognosis generally considered to be very poor. Eighty-two patients less than 40 years of age were operated on at Marie-Lannelongue Hospital between 1982 and 1990. There were 72 male and 10 female patients. Ten patients (12%) had never smoked, whereas 48 patients (59%) had smoked for more than 20 pack-years. The lung cancer was asymptomatic in 27 patients (33%) and symptomatic in the others. Adenocarcinoma was found in 42% of the patients, epidermoid carcinoma in 28%, mixed cell carcinoma in 16%, small cell carcinoma in 8.5%, and undifferentiated large cell carcinoma in 6%. Among the 69 resected tumors, 22 were stage I, ten were stage II, 32 were stage IIIa, and five were stage IIIb. The resection was considered complete and curative in 56 patients (68%) and noncurative in 26 (32%) either because of an incomplete resection (12 in stage IIIa; 1 in stage IIIb) or because of an exploratory thoracotomy only (13). The overall actuarial 5-year survival rate was 41%, and the actuarial 5-year survival for patients who had a complete resection was 56%. The actuarial 5-year survival rates were as follows: patients in stage I, 70%; stage II, 54%; stage IIIa, 28%; stage IIIb, 0%; and patients having exploratory thoracotomy only, 18%. These survival rates are similar to those of patients older than 40 years with similar stages of disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multicolored Asian lady beetle hypersensitivity: a case series and allergist survey.

BACKGROUND: Multicolored Asian lady beetles (Harmonia axyridis) have been used as a biological control agent against crop-destroying aphids in the United States. Outside their natural habitat, H. axyridis seeks refuge in homes during fall and winter, leading to patient complaints and symptoms of rhinitis, wheezing, and urticaria on exposure to the beetles. OBJECTIVE: To gain a better understanding of the character and spectrum of allergic disease provoked by exposure to home-infesting lady beetles. METHODS: Eight patients with allergic symptoms suspected of being caused by H. axyridis and consistent with an IgE-mediated process were identified and interviewed. A whole-body extract from H. axyridis was prepared. Western blots using the patients' serum identified specific IgE antibodies in the extract. Through a novel technique, immunohistochemical analysis using beetle sections overlayed with patient serum was performed. A random survey of allergists from across the United States was also performed to evaluate experience with cases of lady beetle allergy. RESULTS: Western blots revealed IgE binding to 5 proteins with molecular weights of approximately 8.6, 21, 28, 31, and 75 kDa. Specific IgE bound to proteins localized in the beetle's mouth and leg areas. The allergist survey revealed positive responses in North Central, Mid-Atlantic and New England states. CONCLUSION: In 8 patients with allergic symptoms on exposure to high levels of lady beetles, specific IgE bound to proteins from H. axyridis. There was also an increased frequency of suspected cases of lady beetle allergy in endemic areas.