Car seatbelt use during pregnancy in Japan: determinants and policy implications

CONTEXT: Pregnant women are exempted from the current seatbelt legislation in Japan despite the fact that seatbelt use is essential to reduce the risk of fatalities for these women and their fetuses in car crashes. OBJECTIVE: To examine factors that might influence seatbelt use during pregnancy. METHODS: A cross sectional study, with data collected via an anonymous, self administered questionnaire at obstetric clinics in suburban areas of Japan. Altogether 880 pregnant women receiving prenatal care in July 2001 were recruited. The relative effects of factors that might influence seatbelt use during pregnancy were estimated using logistic regression analysis. RESULTS: Almost 70%-80% of pregnant women were consistent seatbelt wearers before pregnancy but seatbelt compliance was reduced by about half at 20 weeks or more gestation. Only 20% had received information on maternal seatbelt use, with one third reporting that seatbelt use is beneficial during pregnancy. Those who perceived that maternal seatbelt use is beneficial tended to maintain use, but daily car users and those who knew that they were exempted from seatbelt legislation were more likely to reduce use. CONCLUSIONS: Knowledge of the legislative exemption for pregnant women, misunderstanding of the benefits, and daily car use contributed to the reduction in seatbelt use after pregnancy.     

Immunomodulation for intestinal transplantation by allograft irradiation, adjunct donor bone marrow infusion, or both

BACKGROUND: The passenger leukocytes in the intestine have a lineage profile that predisposes to graft-versus-host disease (GVHD) in some animal models and have inferior tolerogenic qualities compared with the leukocytes in the liver, other solid organs, and bone marrow. Elimination by ex vivo irradiation of mature lymphoid elements from the bowel allografts is known to eliminate the GVHD risk. We hypothesized that infusion of donor bone marrow cells (BMC) in recipients of irradiated intestine would improve tolerogenesis without increasing the risk of GVHD. METHODS: Orthotopic small intestine transplantation was performed with the GVHD-prone Lewis (LEW)-to-Brown Norway (BN) combination and the reverse GVHD-resistant BN-to-LEW model under a short course of tacrolimus treatment (1 mg/kg/day, days 0-13, 20, 27). Grafts were irradiated ex vivo, using a 137Cs source. In selected experimental groups, donor BMC (2.5 x 10(8)) were infused on the day of small intestine transplantation. RESULTS: The unmodified LEW intestine remained intact, whether transplanted alone or with adjunct donor BMC infusion, but all of the BN recipients died of GVHD after approximately 2 months. Intestinal graft irradiation (10 Gy) effectively prevented the GVHD and prolonged survival to 92.5 days, but all of the BN recipients died with chronic rejection of the LEW grafts, which was prevented by infusion of adjunct donor BMC without causing GVHD. In the GVHD-resistant reverse strain direction (BN-->LEW), all intestinal recipients treated for 27 days with tacrolimus survived > or =150 days without regard for graft irradiation or adjunct BMC, but chronic rejection was severe in the irradiated intestine, moderate in the unaltered graft, and least in the irradiated intestine transplanted with adjunct BMC. Mild arteritis in the 150 day allografts of both strain combinations (i.e., LEW--> BN and BN-->LEW) may have been irradiation associated, but this was prevented when weekly doses of tacrolimus were continued for the duration of the experiment rather than being stopped at 27 days. CONCLUSIONS: Recipients are protected from GVHD by irradiating intestinal allografts, but the resulting leukocyte depletion leads to chronic rejection of the transplanted bowel. The chronic rejection is prevented with adjunct donor BMC without causing GVHD. Although application of the strategy may be limited by the possibility of radiation injury, the results are consistent with the paradigm that we have proposed to explain organ-induced graft acceptance, tolerance, and chronic rejection.     

The effect of neonatal capsaicin on the c-Fos-like immunoreactivity induced in subnucleus oralis neurons by noxious intraoral stimulation

The noxious stimulus-dependent induction of c-Fos-like immunoreactivity (Fos-LI) in neurons in the subnucleus oralis and the medullary dorsal horn (MDH) was significantly suppressed by the selective destruction of unmyelinated primary neurons. The induction of Fos-LI by topical capsaicin application to the lingual mucosal stimulation was almost completely suppressed by neonatal capsaicin treatment. Fos-LI induction by the tooth pulp stimulation and by formalin injection to the lingual mucosa were only partially reduced. These results provide an evidence that the noxious signals from the intraoral structures are transmitted by both unmyelinated and myelinated nociceptors to the subnucleus oralis as well as the MDH.     

The effect of serotonin(1A) receptor agonism on antipsychotic drug-induced dopamine release in rat striatum and nucleus accumbens

Serotonin (5-HT)(1A) receptor agonism may be of interest in regard to both the antipsychotic action and extrapyramidal symptoms (EPS) of antipsychotic drugs (APD) based, in part, on the effect of 5-HT(1A) receptor stimulation on the release of dopamine (DA) in the nucleus accumbens (NAC) and striatum (STR), respectively. We investigated the effect of R(+)-8-hydroxy-2-(di-n-propylamino)-tetralin (R(+)-8-OH-DPAT) and n-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-n-(2-pyridinyl)cyclohe xanecarboxamide trihydrochloride (WAY100635), a selective 5-HT(1A) receptor agonist and antagonist, respectively, on basal and APD-induced DA release. In both STR and NAC, R(+)-8-OH-DPAT (0.2 mg/kg) decreased basal DA release; R(+)-8-OH-DPAT (0.05 mg/kg) inhibited DA release produced by the 5-HT(2A)/D(2) receptor antagonists clozapine (20 mg/kg), low dose risperidone (0.01 and 0. 03 mg/kg) and amperozide (10 mg/kg), but not that produced by high dose risperidone (0.1 and 1.0 mg/kg) or haloperidol (0.01-1.0 mg/kg), potent D(2) receptor antagonists. This R(+)-8-OH-DPAT-induced inhibition of the effects of clozapine, risperidone and amperozide was antagonized by WAY100635 (0.05 mg/kg). WAY100635 (0.1-0.5 mg/kg) alone increased DA release in the STR but not NAC. The selective 5-HT(2A) receptor antagonist M100907 (1 mg/kg) did not alter the effect of R(+)-8-OH-DPAT or WAY100635 alone on basal DA release in either region. These results suggest that 5-HT(1A) receptor stimulation inhibits basal and some APD-induced DA release in the STR and NAC, and that this effect is unlikely to be mediated by an interaction with 5-HT(2A) receptors. The significance of these results for EPS and antipsychotic action is discussed.     

R(+)-8-OH-DPAT, a selective 5-HT(1A) receptor agonist, attenuated amphetamine-induced dopamine synthesis in rat striatum, but not nucleus accumbens or medial prefrontal cortex

R(+)-8-OH-DPAT (0.05, but not 0.025, 0.1, 1 mg/kg), a 5-HT(1A) receptor agonist, decreased l-3,4-dihydroxyphenylalanine (DOPA) accumulation in rat striatum following NSD-1015, an l-aromatic amino acid decarboxylase inhibitor. Amphetamine (1 mg/kg) increased striatal DOPA accumulation, an effect attenuated by R(+)-8-OH-DPAT (0.05 mg/kg). However, both amphetamine (1 mg/kg) and R(+)-8-OH-DPAT (0.05 mg/kg) decreased cortical DOPA accumulation; there were no additional decreases from their combination. Neither amphetamine (1 mg/kg), R(+)-8-OH-DPAT (0.05 mg/kg), or the combination, significantly affected DOPA accumulation in the nucleus accumbens. The significance of and possible mechanisms for these findings are discussed.     

Quality of life among people living with HIV/AIDS in northern Thailand: MOS-HIV Health Survey

OBJECTIVES: Translation and psychometric evaluation of a Thai version of the Medical Outcomes Study HIV Health Survey (MOS-HIV) in Thailand. METHODS: A cross-sectional survey in Chiang Mai province, northern Thailand, with data collected in face-to-face interviews using a structured questionnaire designed to measure 10 scales of quality of life (QOL). We recruited 200 people with HIV/AIDS attending self-help groups in the municipal area. Standard guidelines were followed for questionnaire translation and psychometric evaluations. RESULTS: Item-level internal consistency and discriminant validity were reasonably established. Success rates were 93.8 and 97.4%, respectively. Scale-level internal consistency reliability of multi-item scales was satisfactory, ranging from 0.74 to 0.88, with all exceeding inter-scale correlations. Principal components analysis of item and scale scores identified two hypothesized dimensions of the MOS-HIV. The mental health component was strongly loaded by health distress, mental health, vitality and cognitive function scales, and physical health by role, physical and social functions, and pain scales. Respondents manifesting symptoms or reporting worsening health status scored significantly lower on all scales. CONCLUSIONS: These preliminary studies have shown the Thai version of the MOS-HIV to have psychometric properties comparable with those reported in previous surveys. Further testing and modification should make it useful as an HIV-specific QOL measure in Thailand.     

Clinical evaluation of leukocyte-depleted blood cardioplegia for pediatric open heart operation

Background. Blood cardioplegia (BCP) is widely used for myocardial protection during open heart operation. However, BCP may have a chance to induce neutrophil-mediated myocardial injury during aortic cross-clamping. We clinically evaluated the myocardial protective effect of leukocyte-depleted blood cardioplegia (LDBCP) for initial and intermittent BCP administration in pediatric patients.

Methods. Fifty patients undergoing open heart operation for congenital heart disease between January 1997 and March 1999 were reviewed. Twenty-five were administered LDBCP for myocardial protection during ischemic periods (LDBCP group), and the remaining 25 were given BCP without leukocyte depletion (BCP group).

Results. The difference in plasma concentrations of malondialdehyde between coronary sinus effluent blood and arterial blood just after reperfusion in the LDBCP group (1.68 ± 0.56 μmol/L) was significantly lower than that in the BCP group (2.35 ± 0.62 μmol/L; p < 0.01). The LDBCP group showed significantly lower plasma concentrations of human heart fatty acid-binding protein at 50 minutes after reperfusion (LDBCP group, 103.5 ± 38.7 IU/L; BCP group, 144.8 ± 48.8 IU/L; p < 0.01) and the peak value of creatine kinase-MB during the first 24 postoperative hours (LDBCP group, 17.0 ± 8.5 IU/L; BCP group, 26.0 ± 11.6 IU/L; p < 0.01) than did the BCP group. The maximum dose of catecholamine was significantly smaller in the LDBCP group (LDBCP group, 3.20 ± 2.18 μg · kg⁻¹ · min⁻¹; BCP group, 5.60 ± 2.83 μg · kg⁻¹· min⁻¹; p < 0.01).

Conclusions. These results suggest the usefulness of LDBCP for protection from the myocardial injury that can be induced by BCP administration during aortic cross-clamping.     

N-desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of M1 muscarinic receptors.

The active moiety of clozapine, the prototypical antipsychotic drug, consists of clozapine and its major metabolite, N-desmethylclozapine (NDMC). Previous studies have suggested that NDMC may be more important than the patent compound itself for the improvement in cognition in patients with schizophrenia treated with clozapine. While the pharmacology of clozapine and NDMC are similar in most respects, NDMC has been shown to be an M1 muscarinic receptor partial agonist whereas clozapine is an M1 antagonist in vitro and in vivo. We hypothesized that NDMC may improve cognition by increasing dopamine (DA) and acetylcholine (ACh) release in medial prefrontal cortex (mPFC) via direct stimulation of M1 receptors, whereas both NDMC and clozapine itself would do so by other mechanisms as well, and that clozapine would inhibit the M1 agonist effect of NDMC. In the present study, using microdialysis in awake, freely moving rats, we found that NDMC at doses of 10 and 20, but not 5 mg/kg, significantly increased DA and ACh release in the mPFC and HIP, but not in the nucleus accumbens (NAC). The M1-preferring antagonist, telenzepine (3 mg/kg), completely blocked NDMC (10 mg/kg)-induced increases in cortical DA and ACh release. Clozapine (1.25 mg/kg), which by itself had no effect on DA or ACh release in the cortex, blocked NDMC (10 mg/kg)-induced ACh, but not DA, release in the mPFC. The 5-HT1A receptor antagonist, WAY100635 (0.2 mg/kg) blocked NDMC (20 mg/kg)-induced cortical DA but not ACh release. These findings suggest that: (1) NDMC is an M1 agonist while clozapine is an M1 antagonist in vivo; (2) M1 agonism of NDMC can contribute to the release of cortical ACh and DA release; (3) NDMC, because of its M1 agonism, may more effectively treat the cognitive impairments observed in schizophrenia than clozapine itself; and (4) M1 receptor agonism may be a valuable target for the development of drugs that can improve cognitive deficit in schizophrenia, and perhaps other neuropsychiatric disorders as well.