A growing pool of recent research points to the importance of ethnicity in psychopharmacologic management of depression and anxiety disorders, with sometimes profound implications for efficacy and safety. Such research has provided provocative findings that illustrate important interethnic pharmacogenetic, pharmacokinetic, and pharmacodynamic differences, especially for African Americans. We did a systematic literature review of psychopharmacologic treatment considerations among African Americans with anxiety and mood disturbance seen by primary care physicians, who provide most psychopharmacologic treatment. The findings commonly point to a greater percentage of "poor metabolizers" among African Americans compared with Euro-Americans. General treatment considerations include greater attention to adverse effects and better clinical response and poorer compliance for a given dose, potential need for lower starting doses and slower increases, use of plasma drug levels if available, determination of past responses to a similar drug, and integration of pharmacogenetic information into an overall socioculturally and ethnically sensitive approach to assessment and treatment.

Antidepressive Agents↗

PubMedDate not supplied

Sources of error with use of Goldmann-type tonometers.

There are many sources of error in the use of Goldmann-type applanation tonometers. In clinically normal corneas hypofluorescence of the precorneal tear film, accommodation, the Valsalva maneuver and vertical gaze are preventable causes of large tonometric errors. Repeated tonometry may induce a decline in the intraocular pressure (IOP). Variations in the corneal resistance to indentation between eyes cause significant errors. The most significant cause of error in clinically abnormal eyes is corneal epithelial edema, which causes a marked underestimation of IOP. Measurements obtained with Goldmann-type tonometers can be used with confidence to monitor changes in the IOP of an individual, but should not be relied on to determine the absolute manometric pressure within an eye or to compare the IOPs in eyes of different individuals.

Contact Lenses↗

PubMedDate not supplied

Congenital aneurysm of the left coronary sinus and left main coronary artery with fistulous communication to the right atrium in pregnancy.

We describe a unique case of a left coronary arteriovenous fistula arising from a left sinus of Valsalva aneurysm in a pregnant woman. The relevant diagnostic contributions of two-dimensional echocardiography, color flow Doppler, magnetic resonance imaging, and angiography are discussed. The hemodynamic manifestations of this anomaly in pregnancy and the eventual surgical correction are reviewed.

Adult↗

PubMedDate not supplied

Successful therapy of a human lung cancer xenograft using MAb RS7 labeled with residualizing radioiodine.

We have recently reported that a radioiodinated, DTPA-appended peptide, designated IMP-R1, is a residualizing iodine label that overcomes many of the limitations that have impeded the development of residualizing iodine for clinical use. In this study the potential of 131I-IMP-R1-RS7, an internalizing anti-EGP-1 monoclonal antibody, was evaluated by performing preclinical therapy studies in nude mice bearing Calu-3 human non-small cell carcinoma of the lung xenografis. Elimination of 6 of 9 established tumors (mean tumor volume=0.3 cm(3)) was observed using a single dose of 350 microCi/mouse of 131I-IMP-R1-RS7, with all animals tolerating the dose. At the same dose and specific activity of 131I-RS7, labeled using the conventional chloramine-T method, there were four deaths, and one complete remission in nine treated mice. At the maximum tolerated dose of conventionally 131I-labeled RS7, 275 microCi, mean stable disease for approximately 5 weeks was observed, with no complete responses. Specificity of the therapeutic effect was shown in an isotype-matched control experiment, where 131I-IMP-R1-RS7 was markedly more effective than the (131)I-IMP-R1-labeled control antibody. These studies demonstrate that (131)I-IMP-R1-RS7 provides a therapeutic advantage in comparison to conventional 131I-labeled RS7, as predicted by the increased tumor accretion observed previously in targeting studies. A direct comparison of the maximum tolerated doses of (131)I-IMP-R1-RS7 (350 microCi) and 90Y-DOTA-RS7 (105 microCi) was performed in this tumor model using large established tumors (mean tumor volume=0.85 cm(3)). Anti-tumor efficacy and toxicity of the two treatments were comparable.

Animals↗

PubMedDate not supplied

Labeling of monoclonal antibodies with diethylenetriaminepentaacetic acid-appended radioiodinated peptides containing D-amino acids.

The optimal use of radioiodinated internalizing monoclonal antibodies (mAbs) for radioimmunotherapy necessitates the development of practical methods for increasing the level of retention of 131I in the tumor. Lysosomally trapped ("residualizing") iodine radiolabels that have been previously designed are based mostly on carbohydrate-tyramine adducts, but these methods have drawbacks of low overall yields and/or high levels of mAb aggregation. We have developed a method using thiol-reactive diethylenetriaminepentaacetic acid (DTPA)-peptide adducts wherein the peptides are assembled with one or more D-amino acids, including D-tyrosine. Two such substrates, R-Gly-D-Tyr-D-Lys[1-(p-thiocarbonylaminobenzyl)DTPA], referred to as IMP-R1, and [R-D-Ala-D-Tyr-D-Tyr-D-Lys]2(CA-DTPA), referred to as IMP-R2, wherein R is 4-(N-maleimidomethyl)cyclohexane-1-carbonyl, were synthesized by preparing functional group-protected peptides on a solid phase, selectively derivatizing the lysine side chain with 1-(p-isothiocyanatobenzyl)DTPA or DTPA dianhydride (CA-DTPA), deprotecting other functional groups, and finally derivatizing the peptide's N-terminus so it contained a maleimide group. Radioiodinations of the peptides followed by conjugations to disulfide-reduced mAbs, carried out as a one-vial procedure, resulted in 32-89% overall yields, at specific activities of 1.8-11. 1 mCi/mg, with less than 2% aggregation. Two internalizing mAbs, LL2 (anti-CD 22 B-cell lymphoma mAb) and RS7 (an anti-adenocarcinoma mAb which targets EGP-1 antigen), labeled with this procedure exhibited a 2-3-fold better cellular retention in Ramos and Calu-3 tumor cell lines, in vitro, respectively, compared to the same mAbs radioiodinated with the chloramine-T method. The rationale for the new approach, syntheses, radiochemistry and in vitro data are presented.

Amino Acid Sequence↗

PubMedDate not supplied

[Age-dependency of isotope drainage in diuretic renograms].

OBJECTIVE: The aim of the study was to establish normal values of the isotope drainage in diuretic scintigrams for children of different age-groups. Isotope drainage was determined 30 minutes after the application of technetium- (99m)MAG 3 as well as 15 minutes after the following application of furosemide. METHODS: We analysed the data from 274 investigations in sonographically normal renal units (RU) contralateral to kidneys with ureteropelvic junction obstruction or non-refluxing primary megaureters. RESULTS: There was a significant age-dependency of isotope drainage during the first weeks of life. In 79 RU the results of the first diuretic renogramm were compared with the follow-up examinations. The reliability of the measurements was lowest in children initially investigated during the first six weeks of life. If both the investigations were performed thereafter, no significant difference was found between the results. CONCLUSIONS: The isotope drainage of the sonographically normal contralateral RU seems to be a sufficient marker for the meaningfulness of the diuretic renogram. In urinary tract dilatation, mistakes regarding the interpretation of isotope drainage may be minimized by taking the measurements in the normal contralateral RU in account and by comparing them with age-referred normal values.

Child↗

PubMedDate not supplied

Home care of the pediatric patient with a tracheotomy.

Forty-seven infants and children with tracheotomies were cared for at home for a follow-up period of 1,581 months. There were two relevant fatalities which gave a death rate of 0.13 deaths per 100 months. The average age at the time of tracheotomy was 13 months and the tracheotomy was in place for an average of 33 months per patient. The ability to care for these children was provided through coordinated, intensive training and a home-care program in which the inpatient nurse, nurse practitioner, social worker, pediatrician, and otorhinolaryngologist worked as a team.

Child↗