IMMUNOHISTOLOGICAL AND ELUTION STUDIES OF THE HUMAN PLACENTA

An immunohistological survey of 28 full-term human placentas has demonstrated deposits of IgG, β1C, β1E, and fibrinogen/fibrin in areas of fibrinoid necrosis and on the trophoblast basement membrane in approximately 35% of placental villi. Traces of IgM were detected at similar sites in 18 of 28 full-term placentas. In 11 specimens of immature placentas (10–18 wk gestation) traces of IgG and β1C and deposits of fibrinogen/fibrin were also present, but IgM was not detected in this material. IgG was recovered in acidic eluates from an homogenized placenta which behaved as an antibody reactive with unidentified material present in fibrinoid deposits and on the thickened trophoblast basement membrane of some villi. It could not be determined whether this IgG was derived from the maternal or fetal circulation.     

Capacity of deoxycytidine to selectively antagonize cytotoxicity of 5-halogenated analogs of deoxycytidine without loss of antiherpetic activity.

Enzyme kinetic studies from this laboratory (M. Dobersen and S. Greer, Biochemistry 17:920-928, 1978) suggested that deoxycytidine could antagonize the toxicity of 5-halogenated analogs of deoxycytidine without interfering with their antiviral activity. Antagonism by deoxycytidine of the toxicity of 5-chlorodeoxycytidine without impairing its anti-herpes simplex virus type 2 activity is demonstrated in the present studies. Tetrahydrouridine, an inhibitor of cytidine deaminase, was utilized. The high Km for deoxycytidine (0.6 mM) with respect to the herpes pyrimidine nucleoside kinase as compared with the low Km for 5-chlorodeoxycytidine (1.1 microM) accounts for the absence of antagonism of the antiviral activity. The high Km for 5-chlorodeoxycytidine (56 microM) as compared with the low Km of deoxycytidine (2 microM) with respect to mammalian deoxycytidine kinase accounts, in great part, for the antagonism of toxicity. In addition, antagonism of toxicity by deoxycytidine is the result of factors other than the kinetic parameters of nucleoside kinases, as indicated by its antagonism of the cytotoxicity of 5-chlorodeoxyuridine. This may be attributed to replenishment of low dCTP pools, diminished because of effector inhibition of ribonucleoside diphosphate reductase by Cl-dUTP. Resistance of the herpes-encoded enzymes to effector control may also play a role in the selective antagonism. Cell culture studies with high concentrations of tetrahydrouridine and 2'-deoxytetrahydrouridine suggest that competition by deoxycytidine for deaminases may not play a major role. The fact that deoxycytidine antagonizes the toxicity of chlorodeoxyuridine also argues against competition for the deaminases as a major reason for its effect. Limited studies with a topical herpes simplex virus type 2 infection system indicate heightened efficacy of 5-chlorodeoxycytidine (and tetrahydrouridine) when deoxycytidine is coadministered. The concepts of selective antagonism of a chemotherapeutic agent derived from these studies may be applied to other approaches that extent beyond viral chemotherapy.     

The VR1 antagonist capsazepine reverses mechanical hyperalgesia in models of inflammatory and neuropathic pain

Vanilloid receptor type 1 (VR1) (TRPV1) is a ligand-gated ion channel expressed on sensory nerves that responds to noxious heat, protons, and chemical stimuli such as capsaicin. Herein, we have examined the activity of the VR1 antagonist capsazepine in models of inflammatory and neuropathic pain in the rat, mouse, and guinea pig. In na?ve animals, subcutaneous administration of capsazepine (10-100 mg/kg s.c.) did not affect withdrawal thresholds to noxious thermal or mechanical stimuli. However, pretreatment with capsazepine prevented the development of mechanical hyperalgesia induced by intraplantar injection of capsaicin, with a similar potency in all three species. Capsazepine (up to 100 mg/kg s.c.) did not affect mechanical hyperalgesia in the Freund's complete adjuvant (FCA)-inflamed hind paw of the rat or mouse. Strikingly, capsazepine (3-30 mg/kg s.c.) produced up to 44% reversal of FCA-induced mechanical hyperalgesia in the guinea pig. Capsazepine also produced significant reversal of carageenan-induced thermal hyperalgesia in the guinea pig at 30 mg/kg s.c., but was ineffective in the rat. Similarly, in the partial sciatic nerve ligation model of neuropathic pain, capsazepine was surprisingly effective in the guinea pig, producing up to 80% reversal of mechanical hyperalgesia (1-30 mg/kg s.c.) but had no effect in the rat or mouse. These data show that VR1 antagonists have antihyperalgesic activity in animal models of chronic inflammatory and neuropathic pain, and illustrate species differences in the in vivo pharmacology of VR1 that correlate with differences in pharmacology previously seen in vitro.     

RN to BSN education: what do RNs think?

While most employers want more baccalaureate prepared registered nurses (RNs) in their staffing mix, returning to school is not easy for the RN. This qualitative program evaluation study explores the perceptions of 6 RNs who completed an on-campus, part-time baccalaureate program. Findings reveal that while these RNs originally questioned the value of further education, degree completion had a positive impact on their personal and professional lives. Implications for RN to BSN program design and recruitment into formal education programs are presented.     

Influence of race,insurance status,and geographic access to plastic surgeons on immediate breast reconstruction rates

Background

This study evaluates the rates of immediate breast reconstruction (IBR) among racial and insurance status subgroups, in the setting of a changing plastic surgeon workforce.

A nurse-led, unit-based program to reduce restraint use in acute care

Although the effectiveness of restraints is not proven, the dangers of restraints are clear. Many advocate for the reduction of restraint use in tertiary care settings. The Joint Commission on the Accreditation of Healthcare Organizations is setting the standard by insisting that hospital administrations create a culture that emphasizes restraint reduction. Despite the importance of this task, very little is available in the literature to direct or guide this effort. The purpose of this article is to describe a unit-based Restraint Reduction Program that was successful on a neurology/neurosurgery unit.     

Utilization of oral hypoglycemic agents in a drug-insured U.S. population

OBJECTIVE: Clinical trials provide information regarding the safety and efficacy of medications used to manage type 2 diabetes but do not elucidate drug effectiveness in a typical managed care environment. The aim of this study was to characterize "real-world" drug utilization patterns from both a prescriber and a patient perspective. RESEARCH DESIGN AND METHODS: We conducted a retrospective analysis of a large administrative pharmacy claims database, using data on continuously pharmacy benefit-eligible members prescribed oral hypoglycemic agents (OHAs). RESULTS: The 12-month persistence rate for the OHA cohort was low, ranging from 31% for alpha-glucosidase inhibitors to 60% for metformin; compliance rates varied between 70 and 80%. During the first 12 months of therapy, 36% of the patients remaining on therapy at 12 months had one or more therapy modifications. The mean number of therapy changes increased with the length of patient follow-up, with more than half of all patients experiencing at least one therapy change over the duration of follow-up. CONCLUSIONS: These findings document the wide variation in utilization patterns associated with pharmacological management of type 2 diabetes, suggesting that opportunity exists to optimize its pharmacological management.     

The effects of GABA(B) agonists and gabapentin on mechanical hyperalgesia in models of neuropathic and inflammatory pain in the rat

We have examined the effects of a novel GABA(B) agonist, CGP35024, in models of chronic neuropathic (partial sciatic ligation) and inflammatory (Freund's complete adjuvant) pain in the rat, and its inhibitory action on spinal transmission in vitro. The effects of CGP35024 were compared with L-baclofen and gabapentin. CGP35024 and L-baclofen reversed neuropathic mechanical hyperalgesia following single subcutaneous or intrathecal administration, but did not affect inflammatory mechanical hyperalgesia. Gabapentin only moderately affected neuropathic hyperalgesia following a single administration by either route, but produced significant reversal following daily administration for 5 days. It was only weakly active against inflammatory hyperalgesia following single or repeated administration. The antihyperalgesic effects of L-baclofen and CGP35024, but not gabapentin, were blocked by the selective GABA(B) receptor antagonist CGP56433A. CGP35024 was seven times more potent against neuropathic hyperalgesia than in the rotarod test for motor co-ordination, whilst L-baclofen was approximately equipotent in the two tests. In the isolated hemisected spinal cord from the rat, CGP35024, L-baclofen and gabapentin all inhibited capsaicin-evoked ventral root potentials (VRPs). CGP35024 and L-baclofen, but not gabapentin, also inhibited the polysynaptic and monosynaptic phases of electrically-evoked VRPs, as well as the 'wind-up' response to repetitive stimulation. These data indicate that CGP35024 and L-baclofen modulate nociceptive transmission in the spinal cord to inhibit neuropathic hyperalgesia, and that CGP35024 has a therapeutic window for antihyperalgesia over spasmolysis.     

Depression among immigrant Mexican women and Southeast Asian refugee women in the U. S

Although immigrants and refugees share the experience of adapting to a new country, life experiences and circumstances surrounding leaving their homelands are vastly different. The most salient difference is their motivation for leaving. Immigrants typically leave their homeland to seek improved economic opportunities and/or to join other family members. Refugees leave their homeland under the threat of injury or loss of life due to political or religious persecution and severe deprivation of basic life necessities. Since the decision to migrate is often viewed as a positive change for immigrant women in comparison to refugee women, mental health problems may be under -detected. The researchers will describe the prevalence of depression in two of the largest groups of migrant women in the U.S., immigrant Mexican women (N=220) and refugee Southeast Asian women (N=163). The purpose of this paper is to compare and contrast life circumstances that may impact on the prevalence of depression in both groups of women. The issues presented are important for nurses internationally who assess and design interventions for immigrant and refugee populations of women.