Altered prepulse inhibition in rats treated prenatally with the antimitotic Ara-C: an animal model for sensorimotor gating deficits in schizophrenia

Rationale Sensorimotor gating disruption is one of many neurocognitive deficits seen in schizophrenia. Disorganized thought is one of the cardinal symptoms associated with sensorimotor gating. In an attempt to model sensorimotor gating deficits in rats relevant to the neurodevelopmental hypothesis for schizophrenia, we have used prenatal injections of the antimitotic drug, cytosine arabinoside (Ara-C) to subtly perturb the development of the rat CNS and disrupt sensorimotor gating.Objective To produce rats with either basal sensorimotor gating deficits or increased vulnerability to the disruption of sensorimotor function by apomorphine or phencyclidine (PCP). Prepulse inhibition (PPI) of the acoustic startle response was used to assess sensorimotor gating.Methods Three different cohorts of pregnant Sprague Dawley female rats were injected with Ara-C (30 mg/kg in saline) or saline at embryonic days 19.5 and 20.5. The Ara-C and control rats were tested for acoustic startle response and PPI at preadolescent and post-adolescent ages; postnatal day (Pnd) 35 and 56, respectively. Apomorphine (2.0 mg/kg) or phencyclidine (3.0 mg/kg), was given prior to PPI sessions in order to disrupt PPI.Results At Pnd 35, Ara-C treatment did not significantly affect acoustic startle amplitudes or PPI. However, at PND 56, Ara-C treated rats had significantly lower acoustic startle amplitudes and significantly diminished sensorimotor gating. Pharmacological challenge with the dopamine agonist apomorphine and the glutamate antagonist PCP significantly disrupted sensorimotor gating in the control subjects. Apomorphine did not further disrupt the existing deficit in the Ara-C treated rats. Ara-C treatment did not cause gross loss of neuronal tissue, although there was a subtle and variable disorganization of the pyramidal cell layer in the hippocampal CA_2/3 region.Conclusion The results provide evidence to suggest that late embryonic exposure to Ara-C disrupts the circuitry involved in mediating PPI. While the dopamine agonist apomorphine caused a significant disruption in the control rats it did not further disrupt the existing deficit in the Ara-C treated rats. These data provide evidence to support the contention that modest neurodevelopmental insults can significantly affect sensorimotor gating processes in an adult onset dependent manner.     

Posttraumatic stress disorder and treatment seeking in a national screening sample

The behavioral model of service use was employed to identify predictors of mental health treatment seeking and treatment readiness among individual with PTSD (N = 2,713) in data from the 1996 National Anxiety Disorders Screening Day (NADSD). This model examines the contribution of predisposing (age, sex, marital status, race/ethnicity, education), enabling (employment, geographic location), perceived need (interference of symptoms with daily life), and evaluated need (other diagnoses) factors to treatment seeking and treatment readiness for individuals with PTSD. Results indicate that although need factors (interference by anxiety symptoms with daily life, diagnosis of panic disorder) are related to both receiving and readiness for treatment, predisposing (age, marital status, minority race) factors influence which individuals receive treatment for PTSD.     

Drug interaction potential of soy extract and Panax ginseng

To determine if soy extract or Panax ginseng increases the urinary excretion of the 6-beta-hydroxycortisol/cortisol ratio as a marker of cytochrome P450 (CYP) 3A enzyme induction, subjects received a soy extract containing 50 mg isoflavones twice daily (n = 20) or Panax ginseng 100 mg standardized to 4% ginsenosides twice daily (n = 20) for 14 days. Neither Panax ginseng nor soy extract significantly altered the urinary 6-beta-OH-cortisol/cortisol ratio, suggesting that unlike St. John's wort, they are not CYP3A inducers. Studies in vitro using human liver microsomes were performed to determine the effect of soy extract on probe substrates of CYP and UDP glucuronosyltransferase (UGT). Unhydrolyzed soy extract produced very little inhibition of CYP1A2, CYP2A6, and CYP2D6 and a trend of activation of CYP3A4. Hydrolyzed soy extract showed inhibition of all of the CYPs tested, particularly CYP2C9 and CYP3A4. UGT2B15 was the only UGT significantly inhibited. Even though both soy extract and ginseng have been shown to activate CYP3A4 in vitro, there is a lack of an in vitro correlation with the in vivo effects.     

Patient-Physician Relationship and Service Utilization: Preliminary Findings

BACKGROUND: Difficult physician-patient encounters pose a challenge in all aspects of health care. Characteristics of both physicians and patients affect the office encounter and utilization of services. The objectives of this study were to explore the impact of patients' characteristics and the patient-physician relationship on service utilization. METHOD: A sample of 22 family practice patients and their physicians completed questionnaires prior to and/or after an office visit. Chart review yielded demographic information and history. The number of office visits and phone calls were obtained from billing records. RESULTS: The number of patient-reported physical problems was correlated with negative affect (r = 0.63, p <.002), the number of phone calls to the office (r = 0.52, p <.02), and the difficulty of the encounter as perceived by the physician (r = 0.58, p <.005). The number of phone calls also correlated with the number of life events (r = 0.43, p <.05) and the patient's perception of the physician's warmth (r = 0.48, p <.03) and understanding (r = 0.44, p <.04). CONCLUSION: Life stress, negative affect, physical complaints, and the patients' perception of their physician impact utilization. Armed with information about patient characteristics prior to the office visit, the physician can increase efficiency and facilitate a more productive encounter.     

Effect of mandibular titanium reconstructive plates on radiation dose

BACKGROUND: The effects of the mandibular titanium alloy plates on the radiation-tissue interactions are not clearly defined. Photon beam radiation may be modified after striking a metal plate used to reconstruct the mandible after oncologic surgery. The purpose of this study was to determine, in a human mandible model, the effects of a titanium alloy plate on the radiation dose received at the bone/titanium (plate and screws) interface and bone/soft tissue interface. METHODS: We used an adult male human head and neck ex vivo model. A medical grade titanium alloy 6-hole plate, 2.4 mm, was fixed in the midline of the mandible. The mandible was then irradiated using 6 MV photon beams. Thermoluminescent dosimeters were used to measure the radiation doses anterior and posterior to the mandible. The experiment was then repeated without the plate and screws. RESULTS: The difference between the average doses received by the mandible reconstructed with plate/screws and a mandible without plate/screws was +2.1% at the buccal aspect of the mandible and +3.0% at the lingual aspect; respective P values were.741 and .323. Thus, these differences were not statistically significant. CONCLUSION: In this study, we did not observe any significant influence of titanium alloy plate/screws on the radiation doses received by tissues anterior or posterior to the mandible.     

The voltage-dependent sodium channel in mammalian CNS and PNS: antibody characterization and immunocytochemical localization

Monoclonal and polyclonal antibodies were generated against the voltage-dependent sodium channel purified from rat brain, and were used to characterize and localize sodium channels within mammalian central nervous system (CNS) and peripheral nervous system (PNS). These antibodies immunoblot and immunoprecipitate from labeled membrane proteins a 260-kDa polypeptide, as well as immunoprecipitate sodium channels saturated with [3H]saxitoxin. These monoclonal and polyclonal antibodies do not, however, recognize sodium channels in cardiac or skeletal muscle. Immunocytochemical analyses of cultured CNS and PNS neurons and immuno-ultrastructural localization of sodium channel reactivity within CNS tissue in situ indicate that these probes provide a unique tool for studying the level of expression, organization and turnover of sodium channels within the CNS and PNS.     

Childhood antecedents of homelessness in psychiatric patients

OBJECTIVE: This study examined the relationship between childhood experience and homelessness in psychiatric patients. METHOD: Three large and diverse samples of homeless patients (N = 512) were compared with a sample of patients who had never been homeless (N = 271), with respect to childhood experience of foster care, group home placement, and running away. One of the homeless samples and the never homeless sample were drawn from patients admitted to a state mental hospital. In this state hospital population, risk ratios for lifetime prevalence of homelessness could be derived. RESULTS: In the three homeless samples, over 15% had a history of foster care, over 10% had a history of group home placement, and over 20% had a history of running away. These figures compared with 2%, 1%, and 5%, respectively, in the never homeless sample. In the state hospital, the lifetime prevalence of homelessness in patients with any one of these childhood experiences was about threefold that of other patients. A history of homelessness was reported by the great majority of state hospital patients who had had one of these childhood experiences. CONCLUSIONS: These childhood experiences were strongly associated with adult homelessness in these psychiatric patients. It might be possible to prevent homelessness in some cases by interventions aimed at patients with such childhood histories.     

The Cancer and Diet Intervention Project: a community-based intervention to reduce nutrition-related risk of cancer

This paper describes a community-based intervention programdesigned to lower diet-related risk of cancer. The program isone of the first to attempt to make operational cancer-relateddietary guidelines. It was designed as a feasibility study fora possible larger-scale multi-community study. The interventionwas structured in three parts: mass media, grocery store environmentmodification including point-of-purchase labelling and a home-basededucation course, and was undertaken in one rural midwest communitywith a similar community as a comparison. Formative evaluationwas undertaken to define and tune intervention strategies. Communityleaders were involved in the intervention from its inception.The initial intense program ran for 3 months with a maintenanceperiod of 12 months. The dietary intervention was focused onan eating pattern message (designed to reduce fat consumptionand increase fiber intake) for which criteria for specific foodswere developed. Outcome variables included knowledge, attitudesand practices related to diet and cancer. These were measuredin a series of cross-sectional samples in each community. Thestudy design allowed estimation of dose-response effects withinthe intervention community. Novel aspects of the evaluationdesign included a specific attempt to measure the effect ofself-selection into an intense information-giving interventioncomponent and two new ways of measuring community dietary change.Cost-effectiveness evaluation was included.