A novel,mild, specific and indirect maleimido-based radioiodolabeling method

In an effort to design a mild, non-oxidative and site-specific means of radiolabeling bioactive molecules we have employed maleimido-sulfhydryl chemistry to produce bioactive hormone radioligands. We have prepared two novel radioiodolabeled reagents, 3′-maleimidopropanoyl-3-¹²⁵I-tyramide and its retro analog, N-maleoyl-N′-3-(4-hydroxy-3-¹²⁵I-phenyl)propanoy1 ethylenediamide, by either oxidative radioiodination of the precursors or radiolabeling of the phenolic component prior to its incorporation into the radiolabeling reagents. These reagents were then used to radiolabel analogs of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) in an efficient way, yielding reaction mixtures which were easily purified. The radioligands obtained are stable upon storage and bind in a reversible manner to a single population of binding sites displaying affinity in the low nanomolar range. The potencies of these analogs are comparable to the non-modified PTH and PTHrP analogs. This study demonstrates the utility of the novel maleimido-based indirect radioiodination approach and highlights some of its advantages over either direct oxidative procedures or acylation using the Bolton-Hunter reagent.     

Reproductive Immunology and Microbiology News*

ABSTRACT: Clindamycin is widely used in a variety of obstetric and gynecologic infections. Despite in vitro and clinical evidence of activity against anaerobes, genital organ tissue levels resulting from intravenous administration of the drug have not previously been reported. Following a single intravenous infusion of 600 mg of clindamycin phosphate, tissue levels were determined in operative specimens obtained from ten women. Specimens of cervix, uterus, fallopian tube, and ovary were obtained, and mean Clindamycin levels for each site were: cervix, 2,63 μg/ml; endometrium, 5.58 μg/ml; myometrium, 2.39 μg/ml; fallopian tube, 2.96 μg/ml; and ovary, 3.74 μg/ml. The mean serum level was 6.26 μg/ml at the time of uterine artery interruption. The clindamycin concentrations at all sites exceeded the usual therapeutic minimal inhibitory concentration, substantiating the usefulness of clindamycin in obstetric and gynecologic anaerobic infections.     

A treatment system for combined psychiatric and addictive illness

Patients with combined general psychiatric and addictive disorders are a major public health problem in the US, and are being increasingly recognized as such world-wide. The authors describe a model treatment system for such patients in one municipal hospital in New York. It is composed of three complementary units: a locked ward, a halfway house and a day program. Treatment is based on a peer leadership approach coupled with professional treatment, and provides multiple levels of care to address the needs of respective patients. Of 464 admissions evaluated and treated, most were from disadvantaged minorities, homeless and abusers of cocaine. All were admitted with acute psychiatric or perinatal presentations, and carried Axis I diagnoses in addition to their substance abuse. Clinical experience over 6 years is reviewed, suggesting the feasibility of reorganizing general hospital psychiatric services to address the needs of the dually diagnosed.     

Randomized controlled trial of short-term withdrawal of i.v. immunoglobulin therapy for selected children with human immunodeficiency virus infection

BACKGROUND: The aim of the present paper was to determine whether monthly i.v. immunoglobulin (IVIG) could be safely discontinued in antiretroviral-treated human immunodeficiency virus (HIV)-infected children. METHODS: In a double-blind cross-over trial, children < or =18 years with HIV infection, well controlled on antiretroviral therapy, were randomized to alternating courses of 3 consecutive months of IVIG (400 mg/kg once a month) and 3 consecutive months of placebo for 1 year. The primary outcome was days of fever per month. Secondary outcomes were frequency of serious infections, changes in HIV viral load (VL), CD4+ counts and IgG levels. RESULTS: Fifteen children were enrolled. Using the revised pediatric HIV clinical classification system of the Centers for Disease Control and Prevention, eight were severely symptomatic (C), four were moderately symptomatic (B) and three were mildly symptomatic (A). There were no statistically significant outcome measures. The mean number of days of fever per month with IVIG versus placebo was 0.55 days versus 1.48 days (P = 0.11). The difference was 0.9 days (95% confidence interval: +2.05 to -0.25). There were no serious infections in either period. For the IVIG versus placebo periods, mean CD4 counts were 970 cells/microL versus 906 cells/microL (P = 0.12), VL 2.90 log(10) copies/mL versus 2.82 log(10) copies/mL (P = 0.70) and IgG levels were 17.41 g/L versus 16.6 g/L (P = 0.13). CONCLUSION: In antiretroviral-treated HIV-infected children short-term withdrawal of monthly IVIG was not associated with a significant increase in incidence of infections or a decline in immunologic function (CD4 count, viral load and IgG levels). These results suggest that monthly IVIG can be safely discontinued in HIV-infected children who are clinically stable and receiving combination antiretroviral therapy.     

Patient death and bereavement: what is the dentist's role?

The dentist's role following a patient's death has not been examined to date; neither has the attrition rate of a dental practice because of deaths of patients belonging to that practice. This topic was explored through a survey of 400 Oregon dentists. Seventy-two percent of dentists in active practice who participated in the survey had at least one patient death each year; the mean number of patient deaths per year was five. Following these deaths, most dentists reported providing some type of emotional support to the bereaved survivors. Dentists send sympathy cards 72% of the time and attend funerals 27% of the time; 55% of dentists regard the majority of their patient deaths as unexpected. These deaths are a source of emotional stress for dentists, as are subsequent discussions with survivors. Only 3% of the respondents reported having received formal education in death and bereavement, and 66% of dentists believe that some type of education in dying and bereavement should be included in dental school     

Organizing Quality Assurance in a Maternal-Child Heath Division

The 10-step monitoring and evaluation process is described and applied to a maternal-child health division of a 300-bed tertiary care hospital. Examples of specific important aspects of care and indicators are given. The organized plan developed for this division is examined using the Joint Commission on Accreditation of Healthcare Organization's guidelines.     

The Behavioral Effects of Perinatal Methimazole Administration in Swiss Webster Mice

The Behavioral Effects of Perinatal Methimazole Administrationin Swiss Webster Mice. RICE, S. A., MILLAN, D. P., AND WEST,J. A. (1987). Fundam. Appl. Toxicol. 8, 531–540. Methimazolewas tested for use as a positive control agent in behavioralstudies of mice. Continuous administration of the antithyroidagent via drinking water (0.1 mg/ml) from Day 16 of pregnancythrough Day 10 postpartum produced developmental delays in miceoffspring. Ten methimazole and 12 untreated litters were studied.Developmental milestones were unaltered; i.e., time of pinnadetachment, incisor eruption, eye opening, vaginal patency,and testicular descent were not different between groups. Meanbody weights of methimazole offspring were consistently reduced,but significant differences were isolated to a few days in thepreweaning period and a few weeks during the postweaning period.There was no enduring effect. All preweaning tests showed somesignificant treatment-related changes; methimazole pups weredevelopmentally delayed. Surface righting time was increasedwhile time pivoting and the number of quadrants traveled weredecreased in methimazole pups. Negative geotaxis showed significanttreatment-related increases in the time to orient 180° uphill,the percentage of pups orienting 180° uphill, and the percentageof pups orienting <180°. Ontogeny of swimming abilityalso showed significant delays. The only postweaning test evaluated,time on a rotating rod, showed no treatment-related effects.Brain weights Postnatal Day (PND) 120 were not different betweengroups. In this study, methimazole produced developmental delaysin mice that were detectable by behavioral tests. Thus, methimazolehas potential as a positive control agent for mice, not onlyto validate preweaning test sensitivity, but also to validatea laboratory's ability to perform preweaning behavioral studies.