Photolytic degradation of benorylate: effects of the photoproducts on cultured hepatocytes

The photodegradation of benorylate [4'-(acetamido)phenyl-2-acetoxybenzoate], a drug frequently used in rheumatoid arthritis therapy, has been examined under different sets of experimental conditions. Several photoproducts have been isolated and identified on the basis of their IR, NMR, and MS spectra. The most significant photochemical process is the photo-Fries rearrangement of benorylate, leading to 5-acetamido-2'-acetoxy-2-hydroxybenzophenone (1). This compound undergoes a rapid transacylation to the isomeric 5'-acetamido-2'-acetoxy-2-hydroxybenzophenone (2). A primary culture of rat hepatocytes has been used to evaluate the possible toxicity of these two benzophenones, keeping in mind the following criteria: leakage of cytosolic enzymes, attachment index to culture plates, gluconeogenesis from lactate and fructose, glycogen balance, and albumin synthesis. At the concentrations assayed, neither of the two major photoproducts of benorylate (benzophenones 1 and 2) had significant toxic effects on liver cells in culture.     

Influence of water conductivity on the efficiency and the reproducibility of electrohydraulic shock wave generation.

In an electrohydraulic generator, two underwater metal electrodes are connected with a capacitor charged to a high voltage. When the circuit is switched on, a plasma is generated reaching temperatures of thousands of K, resulting in a compressive pressure pulse. The formation of the plasma is a nonreproducible phenomenon inducing great variations of the pressure pulse. When the electrodes are immersed in an electrolyte instead of degassed water, the conditions of electrical discharge are dramatically modified. The latency time and the amplitude of the oscillations of the discharge current decrease as the conductivity of the electrolyte increases. For a conductivity of 7 omega.cm, there is no latency, and the critically damped discharge is achieved. The expanding pressure wave is increased by 10%, and the mean peak pressure value over 120 shocks at the second focus after focalization is increased by 50%. The relative standard deviation of the pressure value at the second focus is only 5%, while it is about 30% in ordinary water. The fragmentation efficiency is considerably increased because total fragmentation is obtained in 220 shocks instead of 450 shocks in ordinary water when standard stones are used, and in 131 shocks instead of 304 shocks when gallstones are used. Last, we show that the wear of the electrodes is reduced by a factor 8 when electrolyte is used. The improvement is supposed to have two causes: First, the energy is delivered into the medium in a shorter time, and, second, the center of the shock wave is always located at the same place. The decreased wear should make it possible to treat a much greater number of patients without changing electrodes, and the enhancement of the pressure should increase the efficiency of the fragmentation of the gallstones without aggravating the patient's pain.     

Functional consequences of focal photocoagulation in diabetic macular edema

We studied the iatrogenic effect of focal photocoagulation in the treatment of diabetic macular edema in 74 eyes followed from 1 to 6 months. We measured visual acuity, Amsler test and static perimetry, before and after photocoagulation. In the same periods we obtained retinographies. One month after photocoagulation visual acuity was the same or better in 97.2% of the patients followed and after six months in 95.5%. Hard exudates diminished or disappeared in 48.5% of the patients in the first month, in 77.2% in the third month and in 82.4% of the patients followed during six months. In the analysis of static perimetry we found that 33% of the patients showed absolute scotomas, 40% of the patients showed relative scotomas related to photocoagulation areas. The exploration with Amsler test showed that 9% of the patients had absolute scotomas and 41% relative scotomas.     

Beta-2-microglobulin as the main component of primary amyloidosis located in the larynx

A case of primary amyloidosis located in the larynx in which Beta-2-microglobulin (β2m) was the main component of the tissue is presented. Indirect immunofluorescence performed with monoclonal anti-human β2m antibody (BBM1) showed a positive reaction, as did Congo red stain, and both patterns were similar. A significant increase in serum β2m was observed; however, the clinical condition associated with this elevation remains unclear. We suggest that β2m is not only the main component of secondary amyloidosis in terminal nephropathy patients undergoing hemodialysis for prolonged periods, but that it could be part of the structure of other types of amyloid—either primary or secondary.     

Characteristic distribution of HTLV type I and HTLV type II carriers among native ethnic groups in South America.

To confirm the geographic and ethnic segregation of HTLV-I and HTLV-II carriers in native populations in South America, we have conducted a seroepidemiological study of native populations in South America, including HTLV-I carriers distributed among seven ethnic groups in the Andes highlands of Colombia, Peru, Bolivia, Argentina, and Chile, and two ethnic groups on Chiloe Island and Easter Island; and HTLV-II carriers distributed among seven ethnic groups of the lowlands along the Atlantic coast of Colombia, Orinoco, Amazon, and Patagonia, and one ethnic group on Chiloe Island. The incidence rate of HTLV-I and HTLV-II carriers varied among the ethnic groups, ranging from 0.8 to 6.8% for HTLV-I seropositivity and from 1.4 to 57.9% for HTLV-II seropositivity. A new HTLV-I focus was found among the Peruvian Aymara (1.6%), the Bolivian Aymara (5.3%) and Quechua (4.5%), the Argentine Puna (2.3%), and the Chilean Atacama (4.1%), while on HTLV-II focus was found among the Brazilian Kayapo (57.9%), the Paraguayan Chaco (16.4%), and the Chilean Alacalf (34.8%) and Yahgan (9.1%). The distribution of HTLV-I/II foci showed a geographic clustering of HTLV-I foci in the Andes highlands and of HTLV-II foci in the lowlands of South America. It was thus suggested that South American natives might be divided into two major ethnic groups by HTLV-I and HTLV-II carrier state.     

Breast Specimen Orientation

Lumpectomy specimens are commonly divided into six sides: superficial, deep, superior, inferior, medial, and lateral. Orienting stitches are placed on the specimen during surgery to allow reorientation by pathology. Despite those efforts, specimen disorientation may occur. The aim of this study was to assess the correlation in orientation between surgeons and pathologists. Lumpectomy specimens were routinely oriented. An additional Prolene suture was randomly placed by the surgeon on one side to be localized by pathology. The results were recorded and the disorientation rate calculated. Specimen size and presence of skin and/or muscle were also recorded. There were 122 lumpectomy specimens prospectively entered. Average specimen volume was 95.5 cm³. Twenty-four specimens had segments of skin or muscle. The additional sutures were evenly divided between the six sides. The overall disorientation rate was 31.1% (95% confidence interval, 23.1–40.2).The side-specific disorientation rates were 43%, 40%, 35%, 29%, 28%, and 14% for the deep, superficial, lateral, medial, superior, and inferior surfaces, respectively (no statistical difference). Presence of skin or muscle on the specimen did not contribute to better orientation. Specimen volumes, however, were highly associated with orientation. Specimens of <20 cm³ had a disorientation rate of 78%, while larger specimen had a disorientation rate of 20% (p < .001). Specimen orientation with stitches placed on two surfaces is associated with a high disorientation rate. Better orientation techniques are necessary to minimize the specimen disorientation.     

Willingness to pay for a reduction in mortality risk after a myocardial infarction: an application of the contingent valuation method to the case of eplerenone

In order to allocate health care resources more efficiently, it is necessary to relate health improvements provided by new medicines to their cost. It is necessary to ascertain when the additional cost of introducing a new health technology is justified by the additional health gain produced. Eplerenone is a new medicine that reduces the risk of death after myocardial infarction (MI) but produces additional cost to the health system. The contingent valuation approach can be used to measure the monetary value of this risk reduction and to estimate society’s willingness to pay (WTP) for a new medicine that reduces the risk of death after MI by 2% points. We used a contingent valuation approach to evaluate WTP amongst members of the general population. We used the ex-ante and the ex-post approach. In the ex-ante approach, subjects are asked if they would accept an increase in their taxes in order to have access to eplerenone should they need it in the future. In the ex-post approach, subjects are asked if they would pay a certain amount of money as co-payment per month during 5 years if they suffered an MI. We used the dichotomous choice method, using five bids in each approach. The WTP was estimated using both single-bound and double-bound dichotomous choice (SBDC, DBDC). Extensive piloting (n = 187) preceded the final survey (n = 350). The WTP in the ex-ante case was €58 per year under both SBDC and DBDC. In the ex-post case, monthly WTP was €141 for the SBDC and €85 for the DBDC. Subjects with higher income and subjects with a higher perception of risk showed a higher WTP (P < 0.05). Society is willing to pay an additional amount of money in order to give eplerenone to present and future patients. We estimate that €85 per month is a conservative estimate of the monetary value of a 2% risk reduction in mortality after MI and to spend this additional amount of money in Eplerenone can be considered an efficient policy.