Summer in the country: changes in medical students' perceptions following an innovative rural community experience.

PURPOSE: The University of Missouri School of Medicine developed the Summer Community Program through which rising second-year medical students work alongside rural, community-based physician preceptors. This program is part of a comprehensive, longitudinal pipeline designed to increase student interest in rural practice. The authors describe the Summer Community Program, explain changes in students' perceptions of rural practice and rural lifestyle post program, and report participants' specialty choices and first practice locations. METHOD: The authors analyzed 229 participant responses (1996-2010) to pre- and postexperience questionnaires focused on perceptions of rural practice and lifestyle. The authors calculated the likelihood of participants matching into primary care compared with nonparticipants and analyzed participants' first practice locations. RESULTS: After the experience, participants' perceptions toward rural practice and lifestyle changed favorably, and 72% (n=208) reported more interest in rural practice. Compared with nonparticipants, summer participants were more likely to enter a primary care residency (relative risk [RR]=1.31; 95% confidence interval [CI]: 1.12-1.50) and twice as likely to choose specifically family medicine (RR=2.21; 95% CI: 1.68-2.88). Forty-six percent (n=78) of participants chose rural locations for their first practices. CONCLUSIONS: This program has positively influenced students' perceptions of rural practice and lifestyle and increased their interest in rural practice. Participants entered primary care and family medicine residencies at higher rates than nonparticipants, and nearly half started their medical practices in rural locations. Replicating this program may increase interest in rural medicine and address rural physician workforce needs.

Influencing residency choice and practice location through a longitudinal rural pipeline program.

PURPOSE: The University of Missouri School of Medicine developed the Rural Track Pipeline Program (MU-RTPP) to increase the supply and retention of rural physicians statewide. The MU-RTPP features a preadmissions program for rural students (Rural Scholars), a Summer Community Program for rising second-year students, a six-month Rural Track Clerkship (RTC) Program for third-year students, and a Rural Track Elective Program for fourth-year students. The purpose of this study is to report the specialty choices and first practice locations of Rural Scholars, RTC-only participants, and Rural Track Clerkship Plus (RTC+) participants (students who participated in the RTC Program plus an additional MU-RTPP component). METHOD: The authors compared the residency specialty choices of 48 Rural Scholars (tracked since 2002) with those of 506 nonparticipants and the residency specialty choices of 83 RTC participants and 75 RTC+ participants (tracked since 1997) with those of 840 nonparticipants. The authors calculated the relative risk (RR) for the likelihood of participants matching into primary care compared with nonparticipants and analyzed first practice location. RESULTS: Rural Scholars were more than twice as likely to match into family medicine (RR=2.6; 95% confidence interval 1.5-4.4). RTC and RTC+ participants entered primary care, especially family medicine, at rates significantly higher than nonparticipants. Over 57% of students who participated in the RTC program (and potentially other MU-RTPP offerings) chose a rural location for their first practice. CONCLUSIONS: The longitudinal MU-RTPP successfully recruits students for rural and primary care practice to address the health care needs of Missouri.

Prospective audit of emergency department transit times associated with entonox analgesia for reduction of the acute, traumatic dislocated shoulder.

AIM: To establish current UK practice for the management of the acute traumatic shoulder dislocation with respect to analgesia and reduction manoeuvres. To compare the transit times of patients through an emergency department (ED) after the use of intravenous analgesia and/ or sedation compared to entonox +/- simple oral analgesia. METHODS: A postal questionnaire was sent to 100 UK ED consultants to establish current practice. The treating clinicians were allowed to choose the method of analgesia provided to reduce the patient's dislocated shoulder, provided the patient was happy with it. They administered either (1) traditional intravenous morphine and/or midazolam or (2) entonox +/- simple oral analgesia to facilitate reduction. A prospective audit was conducted to compare the transit times of the two groups of patients. RESULTS: The postal questionnaire revealed that intravenous morphine and midazolam are widely used during reduction of the acute shoulder dislocation in the UK. The audit showed that this was associated with a significantly prolonged transit time through the ED, compared to entonox alone, (mean 77 min versus 177 min, respectively, p<0.001) without compromise in reduction success. CONCLUSION: Entonox +/- simple oral analgesia significantly decreases ED transit times as compared to IV morphine and/or midazolam for the reduction of the acute traumatic dislocated shoulder. Further studies should be done into patient pain scores and into the best combination of oral analgesia and entonox.

Inactivation of Cryptosporidium parvum oocysts using medium- and low-pressure ultraviolet radiation.

The effect of ultraviolet radiation from low- and medium-pressure mercury arc lamps on Cryptosporidium parvum oocysts was studied using a collimated beam apparatus. Experiments were conducted using parasites suspended in both filtered surface water and phosphate buffered laboratory water. Inactivation of oocysts was measured as reduction in infectivity using a CD-1 neonatal mouse model and was found to be a non-linear function of UV dose over the range of germicidal doses tested (0.8-119 mJ/cm2). Oocyst inactivation increased rapidly with UV dose at doses less than 25 mJ/cm2 with two and three log-units inactivation at approximately 10 and 25 mJ/cm2, respectively. The cause of significant leveling-off and tailing in the UV inactivation curve at higher doses was not determined. Maximum measured oocyst inactivation ranged from 3.4 to greater than 4.9 log-units and was dependent on different batches of parasites. Water type and temperature, the concentration of oocysts in the suspension, and the UV irradiance did not have significant impacts on oocyst inactivation. When compared on the basis of germicidal UV dose, the oocysts were equally sensitive to low- and medium-pressure UV radiation. With respect to Cryptosporidium, both low- and medium-pressure ultraviolet radiation are attractive alternatives to conventional chemical disinfection methods in drinking water treatment.

Studies directed toward the total synthesis of azaspiracid: stereoselective construction of C(1)-C(12), C(13)-C(19), and C(21)-C(25) fragments.

[reaction: see text] The efficient entry to the C(1)-C(12), C(13)-C(19), and C(21)-C(25) fragments of azaspiracid is outlined. The C(1)-C(12) portion is constructed using a key asymmetric allenyl borane addition to the corresponding alpha,beta-unsaturated aldehyde. The synthesis of the C(13)-C(19) portion utilizes an Evans asymmetric alkylation followed by Sharpless asymmetric dihydroxylation. In addition, a novel solution to the mismatched effects of a neighboring chiral oxazolidinone during a Sharpless dihydroxylation is detailed.

Delayed behavioral effects following intrahippocampal injection of aggregated A beta (1-42).

Beta amyloid protein (A beta) is the major extracellular component of Alzheimer's disease (AD) plaques. In the current study, A beta (1-42) was aggregated in vitro using a method which produces A beta aggregates similar to those found in the AD brain. Twelve male Sprague-Dawley rats were trained in two-lever operant chambers under an alternating lever cyclic-ratio (ALCR) schedule. When performance was stable on the ALCR schedule, six subjects were injected (bilaterally into the CA3 area of the dorsal hippocampus) with 5.0 microliters aggregated A beta in suspension, and the remaining six subjects were injected with 5.0 microliters sterile water. Behavioral testing resumed 5 days after surgery and continued for 90 days post-injection. Aggregated A beta injection did not affect the number of lever switching errors made in a daily session but did affect the number of incorrect lever response perseverations. After approximately 30 days post-injection, aggregated A beta injection detrimentally affected ability to track the changing parameters of the schedule, and decreased the efficiency by which subjects obtained reinforcers. From approximately day 50 post-injection onward, A beta-injected subjects demonstrated significantly higher numbers of incorrect lever response perseverations than did sterile water-injected subjects. These effects appeared to be central rather than peripheral, as A beta injection did not decrease running response rates under the ALCR schedule. The delayed onset of behavioral effects seen in this and other behavioral studies may be a result of a cascade of potentially harmful responses induced through glial activation following aggregated A beta injection.

Measuring delirium severity in older general hospital inpatients without dementia. The Delirium Severity Scale.

The authors evaluated the validity, reliability, and sensitivity to change of the Delirium Severity Scale (DSS), a 10-minute assessment consisting of Forward Digit Span and Similarities. Twenty-two older inpatients with delirium but not dementia and 15 control patients were administered the DSS during hospitalization. Scores were significantly inversely correlated with experts' quantitative ratings of severity at all three time-points examined. The DSS showed significant improvement over time (P < 0.001) and significant correlation with improvement in expert ratings (P = 0.026). The DSS shows promise as a valid and reliable measure sensitive to changing symptom severity.

Diagnosis and management of rhinitis.

This article reviews the differential diagnoses for rhinitis, medications available for the treatment of rhinitis, and special circumstances (such as pregnancy or medication side-effects) that may influence a clinician's decision. Considering the economic impact of rhinitis, the cost of prescription medications, and quality-of-life issues that are affected by rhinitis, physicians dealing with managed care organizations should make their diagnosis and treatment decisions carefully.

Fibrillar beta-amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivo.

To determine the stability of beta-amyloid peptide (Abeta) and the glial and neuronal changes induced by Abeta in the CNS in vivo, we made single injections of fibrillar Abeta (fAbeta), soluble Abeta (sAbeta), or vehicle into the rat striatum. Injected fAbeta is stable in vivo for at least 30 d after injection, whereas sAbeta is primarily cleared within 1 d. After injection of fAbeta, microglia phagocytize fAbeta aggregates, whereas nearby astrocytes form a virtual wall between fAbeta-containing microglia and the surrounding neuropil. Similar glial changes are not observed after sAbeta injection. Microglia and astrocytes near the injected fAbeta show a significant increase in inducible nitric oxide synthase (iNOS) expression compared with that seen with sAbeta or vehicle injection. Injection of fAbeta but not sAbeta or vehicle induces a significant loss of parvalbumin- and neuronal nitric oxide synthase-immunoreactive neurons, whereas the number of calbindin-immunoreactive neurons remains unchanged. These data demonstrate that fAbeta is remarkably stable in the CNS in vivo and suggest that fAbeta neurotoxicity is mediated in large part by factors released from activated microglia and astrocytes, as opposed to direct interaction between Abeta fibrils and neurons.

Intrahypothalamic discriminative stimulus effects of neuropeptide Y.

Neuropeptide Y (NPY) is one of the most ubiquitous neurotransmitters in the CNS and has been implicated in a variety of psychological and physiological functions. The current study investigated whether intrahypothalamic (I.H.) administrations of NPY were behaviorally discriminable from saline injections. Rats were trained to differentially respond based on whether they received I.H. injections of NPY (0.5 microg/0.5 microl) or saline (0.5 microl 0.9% NaCl). Subjects demonstrated discriminative control (85% correct in 8 out of 10 consecutive sessions) after a mean of 32 sessions. The ability of subjects to discriminate I.H. NPY from saline was dose dependent, with the lowest NPY dose tested (0.03 microg/0.5 microl) generalizing to saline. The opioid antagonist naloxone blocked the discrimination of NPY when administered I.P. (3.0 mg/kg) or I.H. (50 microg/0.5 microl).

New insights into the neuropathology and cell biology of Alzheimer's disease.

Several lines of evidence, including newly discovered genetic mutations, suggest that beta-amyloid (A beta) is directly involved in the neuropathology observed in familial and sporadic forms of Alzheimer's disease (AD). Rather than exerting its neurotoxicity directly, results from our laboratory suggest that fibrillar A beta (fA beta) activates microglia and astrocytes upon injection into the rat brain. The microglia and astrocytes, in turn, form a functional barrier between A beta and surrounding neurons. An increase in inducible nitric oxide synthase (iNOS) immunoreactivity is observed in activated microglia and astrocytes, and specific subpopulations of neurons are lost in fA beta injection areas versus controls. These data, coupled with recent discoveries of the A beta association with the receptor for advanced glycation end products (RAGE) and the class A scavenger receptors (SR), support the hypothesized role of inflammatory mechanisms in AD neurotoxicity.

Naloxone administration following operant training of sucrose/water discrimination in the rat.

The suppression of food intake observed following naloxone administration has often been ascribed to palatability or taste. Unfortunately, many confounds become apparent when attempts are made to isolate such factors in the investigation of ingestive behaviors. In the present study, rats (two groups) were trained to discriminate either a 10% or 5% sucrose solution from water (0.1 ml). These mildly food deprived subjects (95% of free-feeding weight) were trained to press the appropriate lever in a two-lever operant chamber following sampling of sucrose or water; successful responding was reinforced by delivery of a 45 mg grain food pellet. Following random exposure to reduced sucrose concentrations tested under extinction, a sucrose concentration gradient (1.0, 0.5, 0.1, 0.05, 0.01 and 0.005% sucrose solution) was established for both training groups under i.p. saline administration. Data collected under i.p. saline were then compared to those collected following random i.pf1p4loxone administration (3.0, 1.0, 0.3 and 0.1 mg/kg). No significant differences were observed between the sucrose concentration gradients obtained under saline and those obtained under naloxone, suggesting that the anorectic effect of naloxone is not primarily determined by discrimination of sweet taste.

A prospective study of calciotropic hormones in pregnancy and post partum: reciprocal changes in serum intact parathyroid hormone and 1,25-dihydroxyvitamin D.

OBJECTIVE: The purpose of this study was to examine the hormones regulating calcium homeostasis longitudinally in pregnancy and post partum. STUDY DESIGN: Twenty-three women with normal pregnancies were studied in the second and third trimesters and post partum. At each time blood was analyzed for ionized calcium, vitamin D metabolites, and intact parathyroid hormone, and a 24-hour urine specimen was analyzed for creatinine, calcium, and sodium. RESULTS: Urinary calcium excretion was 250% to 300% higher during pregnancy than post partum (p < 0.00001). 1,25-Dihydroxyvitamin D levels were equivalent in the second and third trimesters but were twofold higher than postpartum values (p < 0.01). Ionized calcium was similar at all time points. Intact parathyroid hormone in the second and third trimesters was 50% of postpartum levels (p < 0.001). CONCLUSION: Pregnancy is associated with an increase in the levels of 1,25-dihydroxyvitamin D and a concomitant reciprocal fall in intact parathyroid hormone levels. The increase in serum 1,25-dihydroxyvitamin D values appears to be a key factor in providing for the increase in maternal calcium requirements during pregnancy.

Olfactory conditioning impairment following posttraining NMDA receptor blockade in neonatal rats.

Six-day-old Sprague-Dawley rat pups were exposed to peppermint odor paired with tactile stimulation (stroking the skin with a paint brush) for twenty 10-s conditioning trials, and their olfactory preference was tested the next day. In Experiment 1, pups that had received an injection of the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 (0.1 mg/kg, i.p.) either 30 min before or immediately after conditioning spent less time over the conditioned odor than saline-treated controls. In Experiment 2, pups received an injection of either MK-801 or saline 0, 30, or 60 min after the training period. There was a reduction in the preference for the conditioned odor in the animals receiving MK-801 immediately following training, but treatment with the drug at the other intervals did not produce a performance impairment. The impairment following immediate posttraining injection occurred with either 0.05 or 0.1, but not with 0.01 mg/kg of MK-801 (Experiment 3). Experiment 4 provided control data to confirm that pups that had experienced the procedures used in Experiments 1-3 showed greater preference for the conditioned odor than did naive pups or those receiving exposure to the odor without stroking. The data indicate that immediate posttraining activation of N-methyl-D-aspartate receptors is required for normal olfactory learning in neonatal rats.

Serum anticholinergic activity and behavior following atropine sulfate administration in the rat.

Anticholinergic agents such as atropine and scopolamine have long been suggested to produce delirium-like states in humans and experimental animals. Evidence for an anticholinergic mechanism in the pathogenesis of human delirium has accumulated, leading to studies of the behavioral effects of the anticholinergic drug atropine in animals. The current study addresses the adequacy of animal models of delirium in terms of sensitivity, specificity and pharmacological relevance. A multiple fixed-ratio fixed-interval reinforcement schedule was used to test the effects of relatively low doses of atropine on behavior in rats. Additionally, total serum anticholinergic activity (SAA) was measured under dose and time course conditions identical to those used in the behavioral study. Atropine reduced high and low rates of responding in a dose-dependent manner, and SAA increased in a dose dependent manner. SAA at atropine doses of 0.1 mg/kg to 1.0 mg/kg was similar to that found in delirious humans. These behavioral and serum level data suggest that relatively low doses of atropine, substantially below those used in previous attempts to model delirium using rats, may be more pharmacologically relevant to delirium and may minimize non-specific peripheral effects of this drug.

Beta 2-agonist metered dose inhaler overuse: psychological and demographic profiles.

OBJECTIVE: To identify psychological and demographic correlates of children and adolescents known to overuse beta 2-agonist metered dose inhalers (beta-MDIs). DESIGN: During residential care for severe asthma, demographic and psychological characteristics of 17 children and adolescents known to be beta-MDI overusers were compared with 38 asthmatic subjects of similar age without such history. RESULTS: beta-MDI overuse occurred among all groups; however, males, minorities, and those from lower socioeconomic groups were overrepresented. Overusers scored significantly lower on standardized IQ tests. Subtests of arithmetic for numeric reasoning, comprehension for understanding of social values, and picture completion for visual attention to detail were also significantly lower in beta-MDI overusers, as were reading achievement tests. Testing also revealed tendencies toward dominant, shrewd, and undisciplined personality traits in the overusers. CONCLUSION: Recognition of these characteristics of children prone to beta-MDI overuse will raise the clinician's awareness of this potential. Greater efforts and alternative approaches toward education and treatment of the at-risk patient and family are indicated.

Alternating lever cyclic-ratio schedule analysis of the effects of atropine sulfate.

Cholinergic dysfunction has been implicated in the behavioral and memory impairment that is the hallmark of conditions such as delirium and Alzheimer's Disease. Anticholinergic drugs have been widely used in procedures designed to mimic aspects of the pathology of these conditions in rats. Procedures in use vary widely in sensitivity and behavioral specificity and may be confounded by administration of high drug doses that may not be physiologically relevant. The current study proposes the use of rats responding on an alternating lever cyclic-ratio schedule to study the effects of the anticholinergic compound atropine sulfate. This procedure enables simultaneous measurement of anticipatory ratio tracking (postreinforcement pause durations), perseverations (lever switching errors), and nonspecific peripheral drug effects (running response rates). Results of this study suggest that the schedule is sensitive to low drug doses (0.1-1.0 mg/kg atropine), measures the ability to track changing ratio conditions and to execute lever alternation, and allows for monitoring of peripheral drug effects during behavioral testing. The procedure's sensitivity and low effective dose range may make it useful in the study of behaviors related to anticholinergic effects.

Naloxone effects on sucrose-motivated behavior.

The opioid system plays an important role in feeding. In general, opioid agonists typically increase feeding and opioid antagonists decrease feeding in non-food restricted animals. In food restricted animals the effects of these drugs are substantially reduced. Opioid antagonists have shown a marked effectiveness at reducing consumption of sweet foods. Explanations for this robust effect have typically focused on drug induced changes in taste, taste perception, or palatability. The current study relates the effects of the opioid antagonist naloxone on motivation to obtain different sucrose concentrations to the drug's effects on unrestricted sucrose solution consumption. Changes in motivation to respond were assessed under a progressive ratio reinforcement schedule (PR) which required increased response cost for each successive unit of sucrose solution. Motivation, as measured by the PR, increased as sucrose concentration increased and naloxone produced a dose-dependent decrease in motivation to respond for a given sucrose concentration. Thus, the effectiveness of naloxone was indirectly related to strength of the sucrose concentration. Under unrestricted access to sucrose solutions, naloxone reduced consumption greatest under the higher concentrations. The data suggest at least part of naloxone's effects on sweet tasting food may be mediated through endogenous opioid reward systems that are reflected in measures of motivation.

Effect of naloxone on intake of cornstarch, sucrose, and polycose diets in restricted and nonrestricted rats.

We studied the effect of the opioid receptor antagonist naloxone on intake of three isocaloric diets containing cornstarch, sucrose, or Polycose as the predominant carbohydrate in ad libitum-fed and food-restricted rats. A large body of evidence suggests that opioids affect palatability (reward)-rater than hunger (energy deficit)-driven food intake. We expected food intake to be driven by both energy needs and palatability in ad libitum-fed rats, whereas in food-restricted rats we expected intake to be driven by energy needs with a relatively small palatability component in the preferred sucrose and Polycose diet groups. In the ad libitum-fed rats, naloxone significantly reduced nocturnal intake of all three diets at doses of 0.3, 1.0, and 3.0 mg/kg. In contrast, naloxone failed to alter intake of the cornstarch diet in chronically food-restricted rats. However, naloxone decreased intake of the sucrose diet in food-restricted rats at doses of 0.3, 1.0, and 3.0 mg/kg and decreased intake of the Polycose diet at the 3 mg/kg dose. These data lend further support to the notion that opioids are involved in some other component of feeding than that induced by energy needs.