The effects of congenital brain serotonin deficiency on responses to chronic fluoxetine.

The importance of reversing brain serotonin (5-HT) deficiency and promoting hippocampal neurogenesis in the mechanisms of action for antidepressants remain highly controversial. Here we examined the behavioral, neurochemical and neurogenic effects of chronic fluoxetine (FLX) in a mouse model of congenital 5-HT deficiency, the tryptophan hydroxylase 2 (R439H) knock-in (Tph2KI) mouse. Our results demonstrate that congenital 5-HT deficiency prevents a subset of the signature molecular, cellular and behavioral effects of FLX, despite the fact that FLX restores the 5-HT levels of Tph2KI mice to essentially the levels observed in wild-type mice at baseline. These results suggest that inducing supra-physiological levels of 5-HT, not merely reversing 5-HT deficiency, is required for many of the antidepressant-like effects of FLX. We also demonstrate that co-administration of the 5-HT precursor, 5-hydroxytryptophan (5-HTP), along with FLX rescues the novelty suppressed feeding (NSF) anxiolytic-like effect of FLX in Tph2KI mice, despite still failing to induce neurogenesis. Thus, our results indicate that brain 5-HT deficiency reduces the efficacy of FLX and that supplementation with 5-HTP can restore some antidepressant-like responses in the context of 5-HT deficiency. Our findings also suggest that feeding latency reductions in the NSF induced by chronic 5-HT elevation are not mediated by drug-induced increments in neurogenesis in 5-HT-deficient animals. Overall, these findings shed new light on the impact of 5-HT deficiency on responses to FLX and may have important implications for treatment selection in depression and anxiety disorders.

Shock wave therapy for chronic Achilles tendon pain: a randomized placebo-controlled trial.

UNLABELLED: Shock wave therapy has been used for treatment of several soft tissue disorders that are characterized by chronic pain. We sought to determine if shock wave therapy reduces chronic Achilles tendon pain. Forty-nine patients were enrolled in a double-blind randomized placebo-controlled trial. Each patient was treated once a month for 3 months. The primary outcome measure was a reduction in Achilles tendon pain during walking. At the end of the trial, we found no difference in pain relief between the shock wave therapy group and the control group. There were two patients (62 years and 65 years) with tendon ruptures in the treatment group, suggesting caution when treating older patients. These results provide no support for the use of shock wave therapy for treatment of patients with chronic Achilles tendon pain. However, the confidence intervals include the potential for a clinically relevant treatment effect. LEVEL OF EVIDENCE: Therapeutic study, Level I (systematic review of Level I RCTs-and study results were homogenous). See the Guidelines for Authors for a complete description of levels of evidence.

The Techa River Cohort: study design and follow-up methods.

Residents living on the banks of the Techa River in the Southern Urals region of Russia were exposed to radioactive contamination from the Mayak plutonium production and separation facility that discharged liquid radioactive waste into this river. This paper describes the methods used to establish and follow the Extended Techa River Cohort (ETRC), which includes almost 30,000 people living along the Techa River who were exposed to a complex mixture of radionuclides, largely 90Sr and 137Cs. The system of regular follow-up allows ascertainment of vital status, cause of death and cancer incidence. With over 50 years of follow-up and over 50% deceased, the ETRC now provides a valuable opportunity to study a wide range of health effects, both early and late, associated with protracted internal and external radiation exposures. The wide range of doses allows analysis of the nature of the dose-response relationship based on internal comparisons. Other features of the cohort are the high proportion (40%) exposed under age 20, and the inclusion of both sexes. The limitations of the study include loss to follow-up due to difficulties in tracing some cohort members and migration and incomplete ascertainment of cause of death.

Measurement of analyzing power for proton-carbon elastic scattering in the coulomb-nuclear interference region with a 22-GeV/c polarized proton beam.

The analyzing power for proton-carbon elastic scattering in the Coulomb-nuclear interference region of momentum transfer, 9.0x10(-3)<-t<4.1x10(-2) (GeV/c)(2), was measured with a 21.7 GeV/c polarized proton beam at the Alternating Gradient Synchrotron of Brookhaven National Laboratory. The ratio of hadronic spin-flip to nonflip amplitude, r(5), was obtained from the analyzing power to be Rer(5)=0.088+/-0.058 and Imr(5)=-0.161+/-0.226.

Prescription medication use aboard US submarines during periods underway.

Since January 1997, automated medical records from U.S. submarines have been stored in a centralized database as part of a descriptive epidemiology study. 200 medical encounter notes were randomly selected from 1,017 initial health visits during submarine underway periods between April 1996 and January 1998. Medication prescription appropriateness was assessed using a modified Medication Appropriateness Index (MAI) described in the literature. Seven diagnostic categories accounted for 51.4% of all diagnoses: acute upper respiratory infections (17.6%), superficial wounds (9.7%), elevated blood pressure without the diagnosis of hypertension (7.9%), sprain/strains (4.7%), skin infections (4.3%), eye disorders (3.6%), and ear disorders (3.6%). Prescribed medications were consistent with the care of minor health problems. Mean number of medications prescribed per encounter was 1.4 +/- 1.1 (S.D.). 84% of prescribed medications were assigned a modified MAI summary score of 0, indicating the prescription was appropriate in all aspects. However, anti-infective medication prescriptions demonstrated a significant proportion of non-zero summary scores suggesting some room for improvement in the prescribing practices for this specific medication category.

Helicobacter pylori infection in rural China: exposure to domestic animals during childhood and adulthood.

Little is known about the mode of transmission of Helicobacter pylori, one of the most common human bacterial infections. Some domestic animals, including the cat, have been suggested as a reservoir of H. pylori disease, but the data have been inconsistent. This paper evaluates the role of exposure to pets and other domestic animals in the etiology of H. pylori in a rural area of China with a high prevalence of H. pylori infection. In this double-blind, population-based, cross-sectional investigation, interviews were completed with 3,288 (1994 seropositive, 1,019 seronegative, 275 indeterminate) H. pylori-infected adults enrolled in a randomized intervention trial in Linqu County, Shandong Province, China. We found no evidence to suggest that exposure to pets or other domestic animals during either childhood or adulthood was related to the prevalence of H. pylori infection. In fact, odds ratios (ORs) were reduced for subjects who had kept a cat (OR = 0.7, 95% CI = 0.4-1.0) or any animal (OR = 0.5, 95% CI = 0.3-0.9) in the house as an adult, or a cat as a child (OR = 0.7, 95% CI =0.5-1.0). ORs were also reduced for all 11 types of animal studied that subjects had kept in their courtyard as an adult. These findings suggest that zoonotic transmission, including that from domestic cats, is an unlikely route of H. pylori infection in this rural Chinese population.

Accidents and injuries among U.S. Navy crewmembers during extended submarine patrols, 1997 to 1999.

Accidents and injuries, the most common cause of morbidity in military populations, result in a significant number of work days lost each year and account for 75% of all active duty deaths. Rates of accidents and injuries during U.S. Navy submarine deployments have not been evaluated previously. A database designed to monitor the health of submarine crew-members was used to examine the rates and causes of accidents among deployed crewmembers aboard 196 submarine patrols between 1997 and mid 1999. The most common category of injuries was open wounds, followed by sprains and strains, contusions, superficial injuries, burns, and others. Rates of accidents and injuries decreased with increasing age and duration of military service. Among submariners working in supply departments, the rates were more than two times those of crewmembers working in other departments. Based on these data, among a submarine crew of 100 men at sea for 100 days, approximately four to five accidents or injuries might be expected and would result in an average of about 2 days of light or no duty per injury. Rates of accidents and injuries were very low; however, focused safety training could reduce rates among younger and less experienced crewmembers as well as among those working in particular areas of the submarine.

Gene expression in the developing mouse retina by EST sequencing and microarray analysis.

Retinal development occurs in mice between embryonic day E11.5 and post-natal day P8 as uncommitted neuroblasts assume retinal cell fates. The genetic pathways regulating retinal development are being identified but little is understood about the global networks that link these pathways together or the complexity of the expressed gene set required to form the retina. At E14.5, the retina contains mostly uncommitted neuroblasts and newly differentiated neurons. Here we report a sequence analysis of an E14.5 retinal cDNA library. To date, we have archived 15 268 ESTs and have annotated 9035, which represent 5288 genes. The fraction of singly occurring ESTs as a function of total EST accrual suggests that the total number of expressed genes in the library could approach 27 000. The 9035 ESTs were categorized by their known or putative functions. Representation of the genes involved in eye development was significantly higher in the retinal clone set compared with the NIA mouse 15K cDNA clone set. Screening with a microarray containing 864 cDNA clones using wild-type and brn-3b (-/-) retinal cDNA probes revealed a potential regulatory linkage between the transcription factor Brn-3b and expression of GAP-43, a protein associated with axon growth. The retinal EST database will be a valuable platform for gene expression profiling and a new source for gene discovery.

Mortality among workers exposed to cutting oil mist: update of previous reports.

BACKGROUND: Earlier reports of the mortality experience of this cohort of automotive workers followed from 1938 to 1967 who were exposed to cutting oil mist noted an excess of gastrointestinal cancer. The present report describes the mortality experience of these workers followed for mortality through 1980. METHODS: Cause-specific standardized mortality ratios were calculated by comparing the observed number of deaths to the expected numbers based on rates for the U.S. male population. RESULTS: The SMRs for liver and biliary tract, and testicular cancers were significantly elevated. Among the subset of workers with heavy oil mist exposure, SMRs were significantly elevated for cancers of the lung and testis, and for Hodgkin's disease. The risk of death due to lung cancer was greatest among workers with heavy exposure to oil mist employed for 15 or more years. Mortality due to stomach cancer was in excess among workers with heavy exposure to oil mist who were employed for 5 or more years. There were significant excesses of deaths due to asthma and emphysema. CONCLUSIONS: Further studies with information on the presence of contaminants and additives in oil mists will help elucidate the relationship between oil mist exposure and cancer.

Planning recommendations for international emergency medicine and out-of-hospital care system development.

OBJECTIVES: To present suggestions on planning for development of emergency medicine (EM) and out-of-hospital care in countries that are in an early phase of this process, and to provide basic background information for planners not already familiar with EM. METHODS: The techniques and programs used by the authors and others in assisting in EM development in other countries to date are described. CONCLUSIONS: Some aspects of EM system development have applicability to most countries, but other aspects must be decided by planners based on country-specific factors. Because of the very recent initiation of many EM system development efforts in other countries, to the authors' knowledge there have not yet been extensive evaluative reports of the efficacy of these efforts. Further studies are needed on the relative effectiveness and cost-benefit of different EM development efforts.

A method for monitoring the health of US Navy submarine crewmembers during periods of isolation.

BACKGROUND: With the expansion of the manned space program, an essential consideration in planning is the medical support necessary for long-term missions. Information on analogous populations serving in isolated and/or contained environments may be useful in predicting health risks for astronauts. METHODS: The present study evaluates rates of health events that occur in a highly screened, healthy military population during periods of isolation. A centralized database was designed to collect medical encounter data from U.S. Navy submarines and contains demographic information, crew rosters for each patrol, medical encounter notes, accident reports, medical evacuation reports, vital signs and laboratory data. The population included in the present analysis is composed of crewmembers aboard 136 submarine patrols between January 1, 1997 and December 31, 1998. RESULTS: A total of 2,044 initial visits to medical staff and 973 re-visits for the same condition were recorded during these patrols. Potentially mission-impacting medical events reported among crewmembers were rare (i.e., among a crew of 10 individuals, only 1-2 medical events would be expected to occur during a 100 d-mission). The most common category of medical events was injury, followed by respiratory illnesses (URIs), skin problems (minor infections, ingrown toenail), symptoms and ill-defined conditions, digestive disorders, infectious conditions, sensory organ problems (ear and eye), and musculoskeletal conditions.

Blunted stress cortisol response in abstinent alcoholic and polysubstance-abusing men.

BACKGROUND: This study tested cortisol responses to a psychological stressor in controls (CT) versus patients who were diagnosed as alcohol dependent (AD) or alcohol and stimulant dependent (ADSD) by DSM-IV criteria and who were abstinent for 3 to 4 weeks from alcohol and illicit drugs. Alcohol increases cortisol secretion acutely and during withdrawal. However, there is little information about abnormalities of hypothalamic-pituitary-adrenocortical (HPA) reactivity in recovering alcoholics. METHODS: Accordingly, we tested HPA function in the laboratory between 7:00 and 9:30 AM on control versus stress days. Stress consisted of a 20-min public speaking challenge with preparation and delivery of two short speeches, ostensibly evaluated for quality of delivery, whereas control involved relaxing for the same period. Cortisol was measured in saliva collected at baseline, stress or control, and recovery period, and also at home at 9:00 PM on one of the two days. RESULTS: The three groups did not differ in diurnal patterns of cortisol secretion on the rest day and 9:00 PM sample, which indicated that AD and ADSD patients had intact diurnal HPA regulation at rest. During speech stress, the CT subjects showed the expected cortisol increase (p < 0.0001), whereas neither AD nor ADSD patients responded significantly. Cortisol values were not accounted for by covariates such as depression, posttraumatic stress disorder, glucose metabolism, or anthropometric or demographic characteristics. CONCLUSIONS: The apparent stress hyporesponsiveness of the AD and ADSD patients suggests a persistent disruption of HPA function, perhaps due to incomplete recovery from prior abuse, or to a preexisting alteration in neural systems that regulate HPA responses to stress.

The genes ABI1 and ABI2 are involved in abscisic acid- and drought-inducible expression of the Daucus carota L. Dc3 promoter in guard cells of transgenic Arabidopsis thaliana (L.) Heynh.

The ABA INSENSITIVE1 (ABI1) and ABI2 genes encode homologous type-2C protein phosphatases with redundant yet distinct functions in abscisic acid (ABA) responses. Results from Northern blot analysis showed that ABA- and mannitol-inducible expression of the COR47 and COR78/LTI78/RD29A (COR78) genes was more impaired in the abi2 mutant of Arabidopsis thaliana (L.) Heynh than in the abi1 mutant. Furthermore, ABA-plus-mannitol treatments were additive towards COR47 gene expression; however, the ABA-deficient aba1 mutant showed reduced COR expression relative to the wild type in response to mannitol and ABA-plus-mannitol treatments. These results support the notion that drought- and ABA-signalling pathways are separate yet overlapping. To facilitate quantitative analysis of the genetic control of tissue-specific ABA- and desiccation-response pathways, we analyzed ABA- and mannitol-inducible expression of a carrot (Daucus carota L.) Dc3 promoter:uidA (beta-glucuronidase; GUS) chimaeric reporter (Dc3-GUS) in transgenic wild-type, ABA-deficient aba1, and ABA-insensitive abi1 and abi2 mutants. The Dc3 promoter directed ABA- and mannitol-inducible GUS expression in Arabidopsis guard cells and the two treatments were additive. The aba1, abi1, and abi2 mutant genotypes had reduced GUS expression in guard cells of cotyledons in response to mannitol, whereas abi1 and abi2 mutants were reduced in ABA-inducible GUS expression, consistent with overlapping ABA- and drought-response pathways. Quantitative fluorometric GUS assays of leaf extracts showed that abi2 mutants responded less to exogenous ABA than did abi1 mutants, and abi2 mutants responded more to mannitol than did abi1 mutants. We conclude that Dc3-GUS Arabidopsis is a tractable system in which to study tissue-specific ABA and drought signalling and suggest that ABI2 functions predominantly over ABI1 in COR78 and COR47 gene expression and guard-cell Dc3-GUS expression.

Stochastic effects of environmental radiation exposure in populations living near the Mayak Industrial Association: preliminary report on study of cancer morbidity.

The Mayak Industrial Association, located in the South Ural Mountains, began operation in 1948 and was the first Russian site for the production and separation of plutonium. During the early days of operation, technological failures resulted in the release of large amounts of radioactive waste into the Techa River. Residents who lived in villages on the banks of the Techa and Iset Rivers were exposed to varying levels of radioactivity. The objective of this study is to assess stochastic (carcinogenic) effects in populations exposed to offsite releases of radioactive materials from the Mayak nuclear facility in Russia. Subjects of the present study are those individuals who lived during the period January 1950 through December 1960 in any of the exposed villages along the Techa River in Chelyabinsk Oblast. Death certificates and cancer incidence data have been routinely collected in the past from a five-rayon catchment area of Chelyabinsk Oblast. The registry of exposed residents along the Techa River assembled and maintained by the Urals Research Center for Radiation Medicine for the past 40 y is the basis for identifying study subjects for this project. Specific study objectives are to evaluate the incidence of cancer among current and former residents of Chelyabinsk Oblast who are in the exposed Techa River cohort; integrate results from the dose-reconstruction study to estimate doses for risk assessment; and develop a structure for maintaining continued follow-up of the cohort for cancer incidence. In the earlier part of our collaborative effort, the focus has been to enhance the cancer morbidity registry by updating it with cancer cases diagnosed through 1997, to conduct a series of validation procedures to ensure completeness and accuracy of the registry, and to reduce the numbers of subjects lost to follow-up. A feasibility study to determine cancer morbidity in migrants from the catchment area has been proposed. Our preliminary analyses of cancer morbidity underscore the importance of examining both cancer mortality and cancer morbidity in conducting a comprehensive analysis of the occurrence of cancer in this important cohort.

International emergency medical services: assessment of developing prehospital systems abroad.

Many developing countries are experiencing a greater need for prehospital systems because of urbanization and changing population demographics, leading to greater death rates from trauma and cardiac illnesses. While emergency medical services (EMS) systems may take a variety of forms, they usually contain some system components similar to those found in the United States. In evaluating EMS abroad, it may be useful to compare the developing system type to one of five models of EMS delivery: hospital-based, municipal, private, volunteer, and complex. Using community-based services and available health providers can enable a developing system to function within a primary health network without overtaxing scarce resources. Developing such an approach can lead to creative and effective solutions for prehospital care in developing countries.

ATS1 and ATS3: two novel embryo-specific genes in Arabidopsis thaliana.

A modified protocol for differential display of mRNA was used to identify and clone genes expressed in developing Arabidopsis thaliana seeds. Two novel embryo-specific genes designated ATS1 and ATS3 (Arabidopsis thaliana seed gene) were identified. In situ hybridization showed that, spatially, ATS1 is expressed in a pattern similar to the Arabidopsis GEA1 gene and that ATS3 is expressed in a pattern similar to the Arabidopsis seed storage protein genes. Southern analysis of Arabidopsis genomic DNA indicated that ATS1 is a member of a small gene family and that ATS3 is present as a single copy in the diploid genome. Sequence analysis of both genes showed that ATS1 is similar to the rice EFA27 gene and that ATS3 is unique. Western analysis and light level immunocytochemistry using antisera raised against the putative ATS1 and ATS3 translation products verified that ATS1 and ATS3 proteins are seed-specific and accumulate in a spatial pattern similar to their respective transcripts. Taken together, these data show that ATS1 and ATS3 are novel embryo-specific genes in Arabidopsis.

Emergency medical services in China.

The objective of this article is to identify and describe Chinese emergency medical services (EMS) components. Chinese EMS system development began in the 1980s with "importing" of EMS principles from other systems. China is now attempting to unify these principles. Chinese EMS systems are absent in most rural areas. Urban ambulance dispatch or "rescue" centers provide both transport and inpatient care. Ambulances are staffed with either a physician or a driver. There is not extensive overlap between hospital emergency physicians and ambulance physicians and no out-of-hospital providers at the paramedic or emergency medical technician level exist. Access to EMS is accomplished by dialing 1-2-0. Emergency calls go directly to the rescue center and a physician is dispatched. No on-line radio communication between hospitals and ambulances typically takes place. China has assimilated both traditional and unique EMS components and is undergoing development. It remains unclear whether a systematized EMS structure will emerge.

Solid-phase extraction cleanup and liquid chromatography with ultraviolet detection of ephedrine alkaloids in herbal products.

A solid-phase extraction (SPE) cleanup and a liquid chromatographic (LC) method with UV detection is presented for analysis of up to 7 ephedrine alkaloids in herbal products. Alkaloids from herbal products are extracted with acidified buffer, isolated on a propylsulfonic acid SPE column, eluted with a high-ionic-strength buffer, and separated by LC with detection at 255 nm. LC separation is performed by isocratic elution on a YMC phenyl column with 0.1 M sodium acetate-acetic acid (pH = 4.8) containing triethyl-amine and 2% acetonitrile. Ephedrine alkaloids are completely separated in 15 min. Average recovery of 5 common alkaloids from 3 spiked matrixes is 90%, with an average relative standard deviation (RSD) of 4.4% for alkaloid spikes between 0.5 and 16 mg/g. Average quantitation of ephedrine and pseudoephedrine from 6 herbal products is 97% of declared label claims, and average quantitation of synephrine from an herbal dietary product is 85% of label claim (RSD, 3.2%). Recoveries of synephrine, norephedrine, ephedrine, pseudoephedrine, N-methylephedrine, and N-methylpseudoephedrine spiked in 4 herbal products averaged 95%. Results of ruggedness testing and of a second laboratory validation of the procedure are also presented.

Exposure of prehospital care providers to violence.

OBJECTIVE: To evaluate the experience of prehospital care providers with violence. METHODS: A survey addressing experiences with prehospital violence was administered to a convenience sample of emergency medical services (EMS) providers in a southern California metropolitan area. Descriptive statistics are reported. RESULTS: Of 774 EMS providers surveyed, 522 (67%) returned the questionnaire. Members of law enforcement were excluded because their experience with violence, weapons, and tactics is not typical of most paramedics. This left a sample of 490 for further analysis. These prehospital care providers had a median of ten years' experience on the job. They tended to be male (93%) and white (80%). All together, 61% recounted assault on the job, with 25% reporting injury from the assault. Respondents reported a median of three episodes, and the number of assaults for each individual was unrelated to the number of years of experience on the job (r = 0.068). Of those injured, 37% required medical attention. On the other hand, 35% reported that their company had a specific protocol for managing violent situations and 28% stated ever having received formal training in the management of violent encounters. This limited training notwithstanding, nearly all (95%) providers described restraining patients. Use of protective gear was reported (73%), and some (19%) admitted to ever carrying a weapon on the job. CONCLUSIONS: By their own report, EMS providers encounter a substantial amount of violence and injury due to assault on the job. Formal training and protocols to provide a standardized safe approach for such encounters are lacking. Although the limitations of survey data are recognized, further research characterizing the level of violence and potential interventions seems warranted.