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.     

Role of five platelet membrane glycoprotein polymorphisms in branch retinal vein occlusion.

To determine whether polymorphisms of platelet surface glycoprotein associated with arterial thrombosis are risk factors for branch retinal vein occlusion. A case-control study in which 69 patients with branch retinal vein occlusion and 147 controls who attended the eye clinic for nonvascular complications participated. DNA was extracted from whole blood and analyzed for genotyping of platelet glycoprotein polymorphisms by polymerase chain reactions and specific restricted enzymes. No relationship was found between the four platelet glycoprotein polymorphisms i.e. GPIa C807T, VNTR and Kozak of glycoprotein Ibalpha, the HPA-1 of glycoprotein IIIa and the occurrence of branch retinal vein occlusion. The HPA-2 polymorphism was found in 18 out 60 (30%) patients with branch retinal vein occlusion in comparison with 27 out 142 (19%) of controls, with an estimated odds ratio of 1.8 (95% confidence interval, 0.91-3.65). The four platelet glycoprotein polymorphisms are not risk factors for branch retinal vein occlusion and therefore it seems unnecessary to screen those patients for it. A larger study is required, however, to determine whether HPA-2 is a novel risk factor for branch retinal vein occlusion.     

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.     

Local anesthetics in the aqueous humor in local anesthesia of the eye

Local anesthetics injected retrobulbarly are detectable in the aqueous humor. From 40 patients who received a total dose of 140 mg lidocaine, 15 mg bupivacaine, and 30 mg etidocaine, samples of aqueous humor were taken between 30 and 90 minutes after administration (average 57 minutes). The mean lidocaine concentration was 1.02 micrograms/ml, that of bupivacaine 0.075 micrograms/ml. Etidocaine, used only for facial nerve block in front of the ear, could not be detected in the aqueous humor. All three substances were found in the central venous blood. It therefore appears unlikely that any of them are transported via the blood-aqueous barrier, whether actively or passively. Local anesthetics can inhibit corneal cell proliferation and result in lens opacification when administered into the conjunctival sac. It may be that local anesthetics detected in the aqueous humor have similar effects resulting from contact with the cornea and lens.     

Cystoid macular edema in a pseudophakic patient after switching from latanoprost to BAK-free travoprost.

PURPOSE: The aim of this study was to report a case of cystoid macular edema (CME) in a pseudophakic patient after switching from latanoprost to BAK-free travoprost. METHODS: This study is presented as an interventional case report. RESULTS: Clinical examination showed the development of CME, proven by ocular coherence tomography, after institution of BAK-free travoprost in a patient that was previously treated with Latanoprost. Ocular signs and symptoms responded to stopping travoprost and treatment with topical prednisolone and non-steroidal anti-inflammatory medicines. The intraocular pressure was successfully controlled with brimonidine tartrate 0.15%. CONCLUSIONS: CME is a known adverse effect of all prostaglandin analogs. However, our patient developed this complication after being switched from latanoprost to BAK-free travoprost. This may be due to exacerbation of a previously undiagnosed CME or to the ionic-buffered preservative system (sofZia) alone or in combination with travoprost unique to this product. It is prudent to exercise caution in the use of prostaglandin analogs and prostamides especially in high-risk eyes.     

Bone scintigraphy in tuberculous sacroiliitis

Radionuclide bone imaging is becoming increasingly important in the evaluation of musculoskeletal pain of uncertain cause. A case in which Tc-99m MDP bone imaging was employed to investigate complaints of low back pain is presented. Scan abnormalities directed clinicians towards appropriate further workup and diagnosis of unilateral tuberculous sacroiliitis.     

Percutaneous transluminal coronary angioplasty. A growing surgical problem

The incidence of prior percutaneous transluminal coronary angioplasty in surgical cases is nearly doubling yearly. In 1985, 11.4% of our bypass patients had one or more prior angioplasties. One hundred thirty-five patients with prior angioplasty are compared to 2,205 patients without angioplasty undergoing surgical revascularization. The mortality is 3.2 times higher in the angioplasty patients than in the control patients and the perioperative infarction rate is 2.5 times higher. Forty-four patients were taken directly to the operating room from the catheterization laboratory, 50 were operated on within 10 days, and 41 underwent operation more than 10 days after angioplasty. All of these late failures were of the lesion previously dilated. The infarction rate was less in patients taken immediately to the operating room on an emergency basis than in those whose operation was delayed up to 10 days (30% versus 70%). All patients who died had angioplasty of the anterior descending coronary artery. Angioplasty of this artery increases operative mortality should surgical treatment become necessary acutely. Patients should be informed before angioplasty of the increased surgical risks after a failed angioplasty procedure.