Photodynamic laser cyclodestruction with chloroaluminum sulfonated Phthalocyanine (CASPc) or photofrin®(PII) Vs. Nd:YAG laser cyclodestruction in a pigmented rabbit model

Background and Objective: To investigate Photofrin® (PII) and CASPc for photodynamic therapy (PDT) of the ciliary body in rabbits. Study Design/Materials and Methods: PII (10 mg/kg) or CASPc (1 mg/kg) was given by ear vein. Pharmacokinetics were studied in frozen sections by fluorescence microscopy (CCD camera based low light detection system with digital image processing) at 1 and 24 h (8 rabbits;16 eyes). Laser light was delivered (argon pumped dye laser;630 and 675 nm;8 rabbits;16 eyes) by contact fiberoptic. To compensate for iris attenuation, irradiance was 125 mW/cm² (20, 40, 80, or 160 J/cm²). Controls (4 rabbits;8 eyes) received laser light without photochemicals (OD) and for comparison, continuous wave Nd:YAG laser by fiberoptic (0.8–1.2J;OS). Results: Localization studies showed intravascular distribution with some selective ciliary body distribution at 24 h (PII > CASPc). Rabbits treated with PII or CASPc exhibited variable amounts of gross ciliary body edema, infarction, and necrosis by 24–48 h. This response was not seen in PDT control tissues;damage was seen in the iris and ciliary body, with partial vacuolization of the pigment epithelium. Conclusion: PDT may offer a more selective approach to ciliary body destruction. A small but significant thermal effect was seen during PDT from melanin photon uptake with damage to iris and ciliary body. Thermal damage and potential interaction with ocular visual pigments may limit use of these photochemicals and wavelengths for PDT of the ciliary body © 1995 Wiley-Liss, Inc.     

Pulmonary artery dissection in a patient with idiopathic dilatation of the pulmonary artery: a rare cause of sudden cardiac death.

A 31 year old man presented with a left hilar mass. Thoracic tomography showed this mass to be the pulmonary artery, and subsequently idiopathic dilatation of the pulmonary artery was diagnosed. He remained well until 11 years later when he died suddenly. Postmortem examination confirmed idiopathic dilatation of the pulmonary artery with death due to pulmonary artery dissection and cardiac tamponade. It seems likely that idiopathic dilatation of the pulmonary artery predisposed to fatal pulmonary artery dissection.     

Detection of Bacteroides fragilis Enterotoxin Gene by PCR

Bacteroides fragilis constitutes about 1% of the bacterial flora in intestines of normal humans. Enterotoxigenic strains of B. fragilis have been associated with diarrheal diseases in humans and animals. The enterotoxin produced by these isolates induces fluid changes in ligated intestinal loops and an in vitro cytotoxic response in HT-29 cells. We developed a nested PCR to detect the enterotoxin gene of B. fragilis in stool specimens. After DNA extraction, a 367-bp fragment was amplified with two outer primers. The amplicon from this reaction was subjected to a second round of amplification with a set of internal primers. With these inner primers, a 290-bp DNA fragment was obtained which was confirmed as part of the B. fragilis enterotoxin gene by Southern blotting with a nonradioactive internal probe and a chemiluminescence system. By this approach, B. fragilis enterotoxin gene sequences were detected in eight known enterotoxigenic human isolates and nine enterotoxigenic horse isolates. No amplification products were obtained from DNA extracted from 28 nonenterotoxigenic B. fragilis isolates or B. distasonis, B. thetaiotaomicron, B. uniformis, B. ovatus, Escherichia coli, or Clostridium difficile. The sensitivity of this assay allowed us to detect as little as 1 pg of enterotoxin DNA sequences or 100 to 1,000 cells of enterotoxigenic B. fragilis/g of stool. Enterotoxin production of all isolates was confirmed in vitro in HT-29 cells. A 100% correlation was obtained between enterotoxin detection by cytotoxin assay and the nested PCR assay. This rapid and sensitive assay can be used to identify enterotoxigenic B. fragilis and may be used clinically to determine the role of B. fragilis in diarrheal diseases.     

Medicaid expenditures for the disabled under a work incentive program.

Congress enacted Section 1619 of the Social Security Act to enable the disabled receiving Supplemental Security Income (SSI) to obtain jobs and still retain Medicaid health benefits. Congress intended this work incentive to remove the fear of the severely disabled that by obtaining employment they would lose Medicaid benefits. Based on data from 11 States, our analysis found that Medicaid expenditures for Section 1619 enrollees were relatively small and only one-half the average Medicaid expenditure for the disabled. Retaining Medicaid appears to provide a significant work incentive because Medicaid expenditures represent 13 percent of Section 1619 enrollees' earnings.     

Zinc, copper, manganese, and iron balance of parenterally fed very low birth weight preterm infants receiving a trace element supplement

To evaluate a pediatric trace element supplement (Ped-El, Pharmacia) 18 metabolic balance studies were completed in 13 infants (mean birth weight 909 +/- 67 g, x +/- SEM; mean gestational age 27.2 +/- 1 weeks) who received total parenteral nutrition. The supplement supplied 40 micrograms/kg/day of zinc resulting in negative retention of 226 micrograms/kg/day. Copper infused at 20 micrograms/kg/day led to a positive retention of 8 micrograms/kg/day and an increase in serum Cu (p less than 0.05) not related to Cu intakes. Manganese infused at 40 micrograms/kg/day was nearly all retained (88 +/- 16% retention). Iron infused at 120 micrograms/kg/day led to a positive retention of 93 micrograms/kg/day. Although plasma ferritin and percent transferrin saturation were elevated, only plasma Fe values were correlated with Fe intake. This trace element supplement does not appear suitable for very low birth weight preterm infants.     

Alcoholic-like drinking in simian social groups

We have developed two protocols for inducing sustained, high-dose, alcohol-reinforced, oral alcohol drinking among some members of Macaca nemestrina social groups. Both protocols initially co-present alcohol and the entire daily food supply in a 2-h daily drinking session, with a later return to continuous availability of food. One protocol presents unflavored aqueous alcohol to partially food-deprived subjects; the other compares the drinking of flavored alcohol solutions with the drinking of equally palatable isocaloric non-alcohol solutions when monkeys are not deprived of food. Daily high-dose drinking developed in both protocols, with biomedical changes similar to those of early human alcoholism. Daily drinking to blood alcohol concentrations above 100 mg/dl was sustained in some animals after return to baseline food conditions, and this may have been related to social rank within the groups. Alcohol reinforced drinking of the flavored solutions. Although food deprivation initially produced heavier drinking, drinking with the two protocols was equivalent after return to baseline feeding conditions. These procedures open new opportunities for examining combined social and genetic influences on alcoholic-like drinking.     

Classic Benzodiazepines Modulate the Open-Close Equilibrium in α1β2γ2L γ-Aminobutyric Acid Type A Receptors

Background: Classic benzodiazepine agonists induce their clinical effects by binding to a site on [gamma]-aminobutyric acid type A (GABAA) receptors and enhancing receptor activity. There are conflicting data regarding whether the benzodiazepine site is allosterically coupled to [gamma]-aminobutyric acid binding versus the channel open-close (gating) equilibrium. The authors tested the hypothesis that benzodiazepine site ligands modulate [alpha]1[beta]2[gamma]2L GABAA receptor gating both in the absence of orthosteric agonists and when the orthosteric sites are occupied.

Methods: GABAA receptors were recombinantly expressed in Xenopus oocytes and studied using two-microelectrode voltage clamp electrophysiology. To test gating effects in the absence of orthosteric agonist, the authors used spontaneously active GABAA receptors containing a leucine-to-threonine mutation at residue 264 on the [alpha]1 subunit. To examine effects on gating when orthosteric sites were fully occupied, they activated wild-type receptors with high concentrations of a partial agonist, piperidine-4-sulfonic acid.

Results: In the absence of orthosteric agonists, the channel activity of [alpha]1L264T[beta]2[gamma]2L receptors was increased by diazepam and midazolam and reduced by the inverse benzodiazepine agonist FG7142. Flumazenil displayed very weak agonism and blocked midazolam from further activating mutant channels. In wild-type receptors activated with saturating concentrations of piperidine-4-sulfonic acid, midazolam increased maximal efficacy.