Voluntary exercise decreases ethanol preference and consumption in C57BL/6 adolescent mice: sex differences and hippocampal BDNF expression.

Adolescence is a period of high vulnerability for alcohol use and abuse. Early alcohol use has been shown to increase the risk for alcohol-related problems later in life; therefore effective preventive treatments targeted toward adolescents would be very valuable. Many epidemiological and longitudinal studies in humans have revealed the beneficial effects of exercise for prevention and treatment of alcohol addiction. Pre-clinical studies have demonstrated that access to a running wheel leads to decreased voluntary alcohol consumption in adult mice, hamsters, and rats. However, age and sex may also influence the effects of exercise on alcohol use. Herein, we studied male and female C57BL/6 adolescent mice using a 24-hour two-bottle choice paradigm to evaluate 21 days of concurrent voluntary exercise on alcohol consumption and preference. Given previously known effects of exercise in increasing the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus and its role in regulating the reward system, BDNF mRNA and protein levels were measured at the end of the behavioral experiment. Our results demonstrate sex differences in the efficacy of voluntary exercise and its effects on decreasing alcohol consumption and preference. We also report increased BDNF expression after 21 days of voluntary exercise in both male and female mice. Interestingly, the distance traveled played an important role in alcohol consumption and preference in female mice but not in male mice. Overall, this study demonstrates sex differences in the effects of voluntary exercise on alcohol consumption in adolescent mice and points out the importance of distance traveled as a limiting factor to the beneficial effects of wheel running in female mice.

Contemporary surgical management of HIV-associated facial lipoatrophy.

OBJECTIVES: The purpose of this study is to describe our experience with facial volume restoration in 39 HIV-associated facial lipoatrophy patients, and formulate a treatment algorithm that can be utilized for these patients based on their disease severity. METHODS: Preoperative and postoperative photographs were evaluated by 2 experienced facial plastic surgeons using grading scales. The reviewers' scores were then compared and the distribution of scores was analyzed. RESULTS: Thirty-nine patients underwent malar silastic implantation. Seven patients required postoperative adjuvant filler injection. Most patients' results were rated good to excellent. There were 4 late complications. CONCLUSION: HIV-associated facial lipoatrophy is a socially disabling condition that causes noticeable disfigurement and stigmatizes the patient. We demonstrate the importance of combining a reliable grading scale with a strategic treatment algorithm that utilizes multiple modalities for volume restoration. EBM RATING: C-4.

Tuberculosis contact investigations in rural Alaska: a unique challenge.

Alaska Natives suffered extraordinary rates of disease and death from tuberculosis (TB) during the first half of the 20th century. Although the epidemic was largely controlled in the 1960s, rates of TB among Alaska Natives remain higher than for other Alaskans, and village outbreaks of TB continue to pose major threats. In 2000, a contact investigation around a case patient with infectious TB involved eight villages in south-western Alaska and found 26 additional persons with TB disease and 48 people with newly positive TB skin tests. Rural Alaska brings unique challenges to TB contact investigations not seen elsewhere in the United States because many villages are accessible only by small aircraft or boat. To conduct an investigation, a public health nurse must fly into the village, bring food and water, and sleep at the village clinic or school. In spite of these obstacles, over the past 4 years contact investigations have been initiated for all TB cases with acid-fast bacilli smear-positive sputum, and the proportion of adequately examined contacts has increased from 51% to 75%. The Alaska TB Program plans to improve contact investigations through ongoing reports to regional public health centers and through a statewide training workshop.

Two-dimensional synthetic aperture imaging in the optical domain.

In scan-mode synthetic aperture imaging radar, spatial resolution in a range is given by a frequency-swept waveform, whereas resolution in the orthogonal direction is derived from the record of phase as the beam footprint executes linear motion over the object. We demonstrate here what is to our knowledge the first two-dimensional imaging that uses exactly this process in the optical domain for a 1 cm x 1 cm object with 90 mumx170 mum resolution.

Myocardial blood flow and myocardial uptake of (201)Tl and (99m)Tc-sestamibi during coronary vasodilation induced by CGS-21680, a selective adenosine A(2A) receptor agonist.

BACKGROUND: We investigated the hemodynamic and coronary vasodilatory effects of CGS-21680, a potent selective adenosine A(2A) agonist, as well as its potential use as a new stress modality in combination with perfusion scintigraphy. METHODS AND RESULTS: A stenosis of the left anterior descending coronary artery (LAD) was produced in dogs to reduce the reactive hyperemic response to <20%. Adenosine and CGS-21680 were then separately infused to maximize left circumflex coronary artery (LCx) flow velocity. (201)Tl (0.5 mCi) and (99m)Tc-sestamibi (5 mCi) were injected at the maximal dose of CGS-21680. Heart rate decreased with adenosine but increased during CGS-21680 infusion (P<0.005). The decrease in systolic blood pressure was more prominent with adenosine than with CGS-21680 (P<0.005). In the control LCx zone, maximal myocardial blood flow (MBF) (measured by radioactive microspheres) increased 3.1-fold during adenosine infusion (P<0.005) and 3.8-fold during CGS-21680 infusion (P<0.005). In the stenotic LAD zone, MBF did not change significantly. During adenosine and CGS-21680 infusion, stenosis/control zone MBF ratios were comparable (0.32+/-0.11 versus 0.27+/-0.10, P=NS), and transmural (201)Tl and (99m)Tc-sestamibi count-activity ratios (0.48+/-0.11 and 0.51+/-0.09, respectively) were also comparable (P=NS). Myocardial scintigraphy uncovered perfusion defects in all dogs. CONCLUSIONS: CGS-21680 elicits coronary vasodilation comparable to that of adenosine and produces profound heterogeneity of MBF and of (201)Tl and (99m)Tc-sestamibi myocardial uptake, rendering it a promising agent for pharmacological myocardial perfusion imaging.

Preparedness for a bioterrorism event in Alaska. Part 1: Detection and identification of a biologic event.

U.S. military and public health experts are increasingly concerned that the general public is at risk for terrorist attacks. Traditional weapons of mass destruction such as explosive and chemical devices remain the most likely forms of terrorism, however the threat of bioterrorism is also present and may be increasing. An intentional biologic event may be covert and if so, will not become apparent for days or even weeks when many ill people present with an unidentified illness. Health care providers will be the first responders during a biologic attack and will be called upon to diagnose diseases such as anthrax, tularemia or even smallpox. In the first of a two-part article, a hypothetical scenario is presented to illustrate how such an attack might first be discovered and the agent identified. As the scenario unfolds, evidence is collected that suggests the outbreak was intentional. Information about epidemiologic clues, disease syndromes and specific high-risk agents are discussed.

Emerging infectious diseases in Alaska and the Arctic: a review and a strategy for the 21st century.

Emergence of new, previously unknown, and drug-resistant infectious diseases pose a major threat to global health. The emergence of infectious diseases in Alaska and the Arctic parallels the resurgence of infectious diseases worldwide. The Centers for Disease Control and Prevention has developed a strategy to revitalize the capacity to protect the public from emerging infectious diseases by improving four major public health activities: surveillance and response, applied research, infrastructure and training, and prevention and control. The plan targets high-priority emerging infectious disease problems and particular groups of people at increased risk. These target areas encompass a number of diseases of special concern in Alaska, such as drug-resistant Streptococcus pneumoniae infections, foodborne botulism, alveolar hydatid disease, viral hepatitis, Helicobacter pylori infections, Haemophilus influenzae type b bacteremia and meningitis, and infections of immunocompromised persons, pregnant women and newborns, and tourists. To address these and other emerging infectious disease issues, including the threat of bioterrorism in Alaska and the Arctic, future issues of Alaska Medicine will include updates on specific emerging infectious diseases for health care providers, clinical laboratory workers, and community public health professionals who form the front lines for recognizing, treating, and preventing emerging infectious diseases.

Myocardial infarction and remodeling in mice: effect of reperfusion.

Anatomic and functional changes after either a permanent left anterior descending coronary artery occlusion (PO) or 2 h of occlusion followed by reperfusion (OR) in C57BL/6 mice were examined and compared with those in sham-operated mice. Both interventions generated infarcts comprising 30% of the left ventricle (LV) measured at 24 h and equivalent suppression of LV ejection velocity and filling velocity measured by Doppler ultrasound at 1 wk. Serial follow-up revealed that the ventricular ejection velocity and filling velocity returned to the levels of the sham-operated controls in the OR group at 2 wk and remained there; in contrast, PO animals continued to display suppression of both systolic and diastolic function. In contrast, ejection fractions of PO and OR animals were depressed equivalently (50% from sham-operated controls). Anatomic reconstruction of serial cross sections revealed that the percentage of the LV endocardial area overlying the ventricular scar (expansion ratio) was significantly larger in the PO group vs. the OR group (18 +/- 1.7% vs. 12 +/- 0.9%, P < 0.05). The septum that was never involved in the infarction had a significantly (P < 0.002) increased mass in PO animals (22.5 +/- 1.08 mg) vs. OR (17.8 +/- 1.10 mg) or sham control (14.8 +/- 0.99 mg) animals. Regression analysis demonstrated that the extent of septal hypertrophy correlated with LV expansion ratio. Thus late reperfusion appears to reduce the degree of infarct expansion even under circumstances in which it no longer can alter infarct size. We suggest that reperfusion promoted more effective ventricular repair, less infarct expansion, and significant recovery or preservation of ventricular function.

Primary angioplasty for the treatment of acute myocardial infarction: experience at two community hospitals without cardiac surgery.

OBJECTIVES: We sought to establish the safety and efficacy of primary percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction (AMI) at two community hospitals without on-site cardiac surgery. BACKGROUND: Though randomized studies indicate that primary angioplasty in AMI may result in superior outcomes compared with fibrinolytic therapy, the performance of primary angioplasty at hospitals without cardiac surgery is debated. METHODS: Three experienced operators performed 506 consecutive immediate coronary angiograms with primary angioplasty when appropriate in patients with suspected AMI at two community hospitals without cardiac surgery, following established rigorous program criteria. RESULTS: Clinical high risk predictors (Killip class 3 or 4, age > or = 75 years, anterior AMI, out-of-hospital ventricular fibrillation) and/or angiographic high risk predictors (left main or three-vessel disease or ejection fraction <45%) were present in 69.6%. Angioplasty was performed in 66.2%, with a median time from emergency department presentation to first angiogram of 94 min and a procedural success rate of 94.3%. The in-hospital mortality for the entire study population was 5.3%. Of those without initial cardiogenic shock, the in-hospital mortality was 3.0%. Of 300 patients who were discharged after primary angioplasty, only four died within the first 6 months, with 97.7% follow-up. No patient died or needed emergent aortocoronary bypass surgery because of new myocardial jeopardy caused by a complication of the cardiac catheterization or angioplasty procedure. CONCLUSIONS: Immediate coronary angiography with primary angioplasty when appropriate in patients with AMI can be performed safely and effectively in community hospitals without on-site cardiac surgery when rigorous program criteria are established.

Measles outbreak in Juneau, Alaska, 1996: implications for future outbreak control strategies.

OBJECTIVE: To determine the most effective outbreak control strategy for school-based measles outbreaks as the proportion of children with two doses of measles-containing vaccine (MCV) increases. SETTING: A school-based measles outbreak during 1996 involving 63 cases in Juneau, Alaska (population 29 288), where systematic revaccination with MCV was not implemented. DESIGN: A retrospective evaluation using chain-of-transmission data of three possible outbreak control strategies: no school revaccination, targeted school revaccination (affected schools only), and community-wide school revaccination (all schools). Two-dose MCV coverage among students was estimated from school vaccination records and a survey issued to parents. PRIMARY OUTCOME MEASURES: Potentially preventable cases of measles and doses of MCV administered per case prevented. RESULTS: Two-dose MCV coverage among Juneau students was estimated to be 44% and 53% immediately before and after the outbreak, respectively. Of all the measles cases, an estimated 24 to 28 and 27 to 31 were potentially preventable by the targeted and community-wide school revaccination strategies, respectively. Either strategy might have optimally decreased the outbreak duration by 1 month, sparing one of seven affected schools and 10 of 12 unvaccinated children who had measles. Approximately 133 to 155 and 139 to 160 doses of MCV per case prevented would have been required for targeted and community-wide school revaccination, respectively. CONCLUSIONS: Either targeted or community-wide school revaccination would have been effective control strategies for this outbreak. Targeted school revaccination is probably the intervention of choice for school-based measles outbreaks in larger communities with higher two-dose MCV coverage. As two-dose MCV coverage continues to increase in the United States, public health control measures to respond to outbreaks need to be reevaluated.

Alcohol-related injury death and alcohol availability in remote Alaska.

CONTEXT: Injury is a major public health problem in Alaska, and alcohol consumption and injury death are associated. OBJECTIVE: To determine the association between injury death, particularly alcohol-related injury death, and alcohol availability in remote Alaska. DESIGN, SETTING, AND PARTICIPANTS: Survey using death certificate data and medical examiner records to compare mortality rates for total injury and alcohol-related injury during 1990 through 1993 among Alaskans aged 15 years and older who had resided in remote villages of fewer than 1000 persons. MAIN OUTCOME MEASURES: Rate ratios of injury death among residents of wet villages (ie, those without a restrictive alcohol law) as compared with injury death among residents of dry villages (ie, those with laws that prohibited the sale and importation of alcohol). RESULTS: Of 302 injury deaths, blood alcohol concentrations (BACs) were available for 200 deaths (66.2%). Of these, 130 (65.0%) had a BAC greater than or equal to 17 mmol/L (> or =80 mg/dL) and were, therefore, classified as alcohol related. The total injury mortality rate was greater among Alaska Natives from wet villages (rate ratio [RR],1.6; 95% confidence interval [CI], 1.3-2.1), whereas this difference was not present for nonnatives (RR, 1.1; 95% CI, 0.3-3.8). For Alaska Natives, the alcohol-related injury mortality rate was greater among residents of wet villages (RR, 2.7; 95% CI, 1.9-3.8) than among residents of dry villages. The strength of this association was greatest for deaths due to motor vehicle injury, homicide, and hypothermia. CONCLUSIONS: Although insufficient data existed to adjust for the effects of all potential confounders, residence in a wet village was associated with alcohol-related injury death among Alaska Native residents of remote Alaska villages. These findings indicate that measures limiting access to alcoholic beverages in this region may decrease alcohol-related injury deaths.

Outbreak of viral gastroenteritis due to a contaminated well. International consequences.

CONTEXT: Small round-structured viruses (SRSVs) are known to cause viral gastroenteritis, but until now have not been confirmed in the implicated vehicle in outbreaks. OBJECTIVE: Investigation of a gastroenteritis outbreak. DESIGN: After applying epidemiologic methods to locate the outbreak source, we conducted environmental and laboratory investigations to elucidate the cause. SETTING: Tourists traveling by bus through Alaska and the Yukon Territory of Canada. PARTICIPANTS: Staff of a restaurant at a business complex implicated as the outbreak source, convenience sample of persons on buses that had stopped there, and bus employees. MAIN OUTCOME MEASURES: Odds ratios (ORs) for illness associated with exposures. Water samples from the restaurant and stool specimens from tourists and restaurant staff were examined by nucleic acid amplification using reverse transcription polymerase chain reaction and sequencing of viral amplification products. RESULTS: The itineraries of groups of tourists manifesting vomiting or diarrhea were traced back to a restaurant where buses had stopped 33 to 36 hours previously. Water consumption was associated with illness (OR, 5.3; 95% confidence interval [CI], 2.3-12.6). Eighteen of 26 employees of the business complex were ill; although not the index case, an employee ill shortly before the outbreak lived in a building connected to a septic pit, which was found to contaminate the well supplying the restaurant's water. Genotype 2/P2B SRSV was identified in stool specimens of 2 tourists and 1 restaurant employee. Stools and water samples yielded identical amplification product sequences. CONCLUSIONS: The investigation documented SRSVs in a vehicle epidemiologically linked to a gastroenteritis outbreak. The findings demonstrate the power of molecular detection and identification and underscore the importance of fundamental public health practices such as restaurant inspection, assurance of a safe water supply, and disease surveillance.

[The current status of vaccination and antibiotic prophylaxis in splenectomy. I: Adults]. / Standortbestimmung der Impf- und Antibioticaprophylaxe bei Splenektomie. Teil I: Erwachsene.

The prevention of severe late postsplenectomy infection by vaccination and antibiotic prophylaxis is controversial. This paper reviews the literature and presents a protocol for postsplenectomy adults. Prophylaxis should be adapted to the underlying disease. Every patient has to be informed about the consequences of splenectomy. Depending on the underlying disease, vaccination is recommended against pneumococci, Hemophilus influenzae and Neisseria meningitidis. Long-term antibiotic prophylaxis is not advised in adults.

[Current status of vaccination and antibiotic prophylaxis in splenectomy. II: Children]. / Standortbestimmung der Impf- und Antibioticaprophylaxe bei Splenektomie. Teil II: Kinder.

Children are exposed to a greater risk than adults for severe late postsplenectomy infection. Therefore, prophylaxis against bacterial infections need to be more extensive. This paper presents a protocol for preventive measures in children. Repeated education of the patient and his/her parents about the consequences of splenic loss is mandatory. Vaccinations against Streptococcus pneumoniae and Hemophilus influenzae are highly recommended and also against Neisseria meningitidis in certain situations. The importance of long-term antibiotic prophylaxis in children is emphasized. Recent advances in vaccine development and the increasing problems with antibiotic resistance are discussed.

[Use of Ga-67 SPECT in patients with malignant lymphoma after primary chemotherapy for further treatment planning: comparison with spiral CT]. / Einsatz der Ga-67-SPECT bei Patienten mit malignen Lymphomen nach primärer Chemotherapie für die weitere Therapieplanung: Vergleich mit einem Spiral-CT.

PURPOSE: To compare the diagnostic value of gallium scintigraphy using a SPECT technique with spiral CT for evaluating activity following chemotherapy in patients with malignant lymphoma and to determine treatment options. MATERIAL AND METHOD: The results of gallium scintigraphy in 28 patients with malignant lymphoma (19 Hodgkin's disease, 9 high grade non-Hodgkin's lymphoma) following curative treatment were compared with the CT morphology in relation to inactive regions and residual masses. RESULTS: Ga-67-SPECT proved superior to CT for evaluating the activity in 85 initially involved nodes (sensitivity 94.4% against 83.3%; specificity 100% against 92.5%). It was, however, inferior for demonstrating organ involvement in 28 instances. In seven patients with residual masses, Ga-67-SPECT directly affected staging and further therapy. CONCLUSION: The increasing use of secondary treatment schemes for curative purposes makes Ga-67-SPECT a suitable method for the early recognition of residual activity in Hodgkin's disease and high grade non-Hodgkin's lymphoma.

Calcaneal fractures: operative versus nonoperative treatment.

BACKGROUND: The purpose of this report is to compare the late results after operative and nonoperative treatment of intra-articular calcaneal fractures. METHODS: From 1982 to 1992 we treated 250 calcaneal fractures of which 193 were intra-articular. Because of a change in operative indication, most fractures were treated nonoperatively before 1989 and operatively thereafter. Follow-up was possible at an average of 5.1 years for 124 intra-articular calcaneal fractures. Out of these, two groups of 33 nonoperatively and 30 operatively treated cases were formed matching each other with regard to prognostic parameters. Results were assessed by a clinical score considering pain, gait, footwear, and return to work. Pre- and postoperative tuber joint angle measurements were evaluated for their prognostic significance. RESULTS: In this series of patients, the only statistically significant advantage of operative therapy was concerning return to work. There was no correlation between tuber joint angle and end results. Only when the extremes of the spectrum (nonoperative and operative cases with tuber joint angle < 0 degrees vs. > 25 degrees) were tested against each other was a significant advantage in the group with near normal joint angles found. Thus, open reduction and internal fixation of intra-articular calcaneal fractures can only be expected to benefit those patients with near anatomic reconstruction.

[Dislocated intra-articular calcaneus fractures. Long-term follow-up after open reposition and osteosynthesis]. / Dislozierte intraartikuläre Kalkaneusfrakturen. Langzeitnachuntersuchung nach offener Reposition und Osteosynthese.

A series of 98 patients with a total of 105 intra-articular fractures of the os calcis were operated on during a 10-year period between 1983 and 1992. We were able to follow up 60 patients with 64 fractures an average of 44 months (range, 18-105 months) postoperatively. At the time of follow up, 83.9% of patients had been back to work, 78.6% with the same employer as before. Five of the patients followed up had had to retire from work; each of these had one or more severe coexisting injuries. A compromising nerve injury occurred postoperatively in 3 out of 58 patients with closed fractures, in all cases following surgery with a medial or bilateral approach. In only 1 of the 58 patients followed up after closed fractures did a deep infection requiring arthrodesis occur. One patient had sympathetic reflex dystrophy (Sudeck). A good functional result in the lower ankle joint correlated with a good outcome. In contrast, postoperative improvement of the tuber angle and the degree of arthrosis seen radiographically did not. We conclude that operative repair of intraarticular calcaneal fractures is a procedure that can safely be procedure used to restore the ability to work in the majority of patients. The medial approach should preferably not be used, nor should the metal be extracted from the medial approach if this can be avoided.