The origin and development of hyperammonemia following exposure to hydrazine in rabbits

Hydrazine $\rm (N\sb2H\sb4),$ an important liquid propellant and derivative chemical for pharmaceuticals and pesticides, produces coma and convulsions sometimes resulting in death. Hyperammonia was found in rabbits exposed to 18 mg/Kg of hydrazine. Results of Part One of this study of rabbits emphasize the importance of acute ammonia toxicity during the first three hours following exposure to hydrazine. At no time during this post exposure period did a significant reduction of hydrazine to ammonia occur. Therefore, the elevated blood ammonia was apparently secondary to the effects of hydrazine on metabolic pathways. Further, the results support the theory of competitive inhibition of ammonia by hydrazine and emphasize the need to monitor plasma ammonia following toxic exposure to hydrazine.^ In Part Two, urea, ammonia, CO$\sb2,$ pH, glucose, sodium, potassium, chloride and creatinine were measured for up to 4 hours following injection of 18 mg/Kg of hydrazine in each of two groups of five rabbits. One group received normal saline and the other group received 5% dextrose and water/normal saline. Hyperammonemia, minimal metabolic acidosis and hyperglycemia without increased urea were found in the rabbits receiving normal saline intravenous infusion and hydrazine injection. Hence, hypoglycemia does not appear to play a role in the development of hyperammonemia. A significant difference in the elevated ammonia levels between the two groups receiving dextrose and water/normal saline and normal saline at 1 hour occurred. There was no significant difference in the elevated ammonia levels seen between the two groups receiving dextrose and water/normal saline and normal saline at 2.5 and 4 hours. Thus at 1 hour the group receiving dextrose was able to utilize excess glucose to detoxify ammonia, while at 2.5 and 4 hours there was no significant difference in the two groups' ability to detoxify ammonia.^ Findings support the theory that hydrazine inhibits the formation of urea resulting in hyperammonemia. Results suggest that hydrazine at 18 mg/Kg, a known hypoglycemic agent, causes serious hyperammonemia without increasing urea production during hyperglycemia. These experiments support a unified theory for the toxic mechanism of action of hydrazine, i.e., the intermediary metabolic effects of hydrazine are brought about by the formation of hydrazones which encumber ATP synthesis and vitamin B$\sb6$ enzymatic reactions. ^

THE RECOVERY OF ENTEROPATHOGENS FROM CONTAMINATED COOKED FOODS AT HOLDING TEMPERATURES

Hot foods served in foodservice establishments, institutions and homes, have always been regarded as safe, since cooking temperatures are more likely to kill the bacterial agents that may cause foodborne diseases. However, foods that are otherwise served hot have been epidemiologically incriminated for causing foodborne diseases. This situation arises due to the possible post-cooking food contamination. Post-cooking contamination of hot-held food is most threatening for it gives the contaminating agents the possibility of proliferation. On one hand, post-cooking contamination is least understood and on the other, hot-holding of food gives the consumer a false sense of freedom from foodborne diseases. In this study, the dynamics of food contamination before or after cooking and during hot-holding are discussed and a food contamination dynamics model is presented.^ The literature on foodborne cholera, cholera-like diarrhea, shigellosis and E. coli gastroenteritis together with the literature on the occurrence and growth of the causative enteropathogens; 01 V. cholerae, non-01 V. cholerae, S. sonnei, S. flexneri and E. coli were reviewed. The literature on the infective doses of these organisms were also cited.^ In the study, four cooked food types held hot at 40-60(DEGREES)C were deliberately contaminated with 01 V. cholerae, non-01 V. cholerae, S. sonnei, S. flexneri and E. coli, one at a time at each of the hot-holding temperatures. Tested food samples for the recovery of these enteropathogens were withdrawn at various time intervals of hot holding.^ The results showed bacterial recovery to decline with increasing temperature and with increasing hot-holding time within each holding temperature. All the bacterial types except V. cholerae were recovered even after holding the food at 60(DEGREES)C for one hour. V. cholerae was not recovered after hot-holding the food at 50-60(DEGREES)C at certain holding periods. After 48 hrs incubation, V. cholerae was recovered on TCBS agar plates that read negative after the initial 24 hrs of incubation. Effective hot-holding temperatures were determined for each of the food types contaminated by each of the bacterial types.^ Statistical analysis of the collected data showed temperature, bacterial type and their interaction to be significant in enteropathogen recovery. Food type and its interactions with temperature and bacterial type were found not significant. ^

BENZENE MYELOCLASTOGENICITY AND METABOLISM IN CD-1 MICE: A CORRELATION

Benzene was studied in its target organ of effect, the bone marrow, with the micronucleus test and metaphase chromosomal analysis. Groups of 5 or 10, male and female CD-1 mice were treated with one or two p.o. or i.p. doses of benzene (440 mg/kg) or toluene (430, 860 or 1720 mg/kg) or both, and sacrificed 30 or 54h after the first dose. Benzene-treated animals were pretreated with phenobarbital (PB), 3-methylcholanthrene (3MC), (beta)-naphthoflavone ((beta)NF), SKF-525A, or Aroclor 1254. Toluene showed no clastogenic activity and reduced the clastogenic effect of co-administered benzene. None of the pretreatments protected against benzene clastogenicity. 3MC and (beta)NF greatly promoted benzene myeloclastogenicity. Dose response curves for benzene myeloclastogenicity were much steeper with 3MC induction than without. Micronuclei (MN) were 4-6 times higher by p.o. than i.p. benzene administration. This was not due to bacterial flora since no difference was found between germ-free and conventional males gavaged with benzene. A sensitive high-pressure liquid chromatographic method was developed and used to explore the relation between metabolic profiles of benzene in urine and MN after various pretreatments. Phenol (PH), trans-trans-muconic acid (MA) and hydroquinone (HQ) in the 48h male mouse urine accounted, respectively, for 12.8-22.8, 1.8-4.7 and 1.5-3.7% of the single oral dose of benzene (880, 440 and 220 mg/kg). Catechol (CT) was seen in trace amounts. MA was identified by ultraviolet and infrared spectroscopy and elemental analysis. Urinary metabolites--especially MA, HQ, and phenol glucuronide--correlated well with MN and were dependent on both the dose and the metabolism of benzene. Benzene metabolism was most inducible by cytochrome P-448 enzyme inducers, by p.o. > i.p., in males > females, and inhibited by toluene. Ph, CT or HQ administered p.o., 250, 150 and 250 mg/kg, respectively, or at 150 mg/kg x 2 after 3MC pretreatment, failed to reproduce the potent myeloclastogenicity of benzene. In fact, only HQ was mildly clastogenic. ^

THE APPLICATION OF PATH ANALYSIS TO ASSESSMENT OF IRON NUTRITIONAL STATUS IN MAN

Path analysis has been applied to components of the iron metabolic system with the intent of suggesting an integrated procedure for better evaluating iron nutritional status at the community level. The primary variables of interest in this study were (1) iron stores, (2) total iron-binding capacity, (3) serum ferritin, (4) serum iron, (5) transferrin saturation, and (6) hemoglobin concentration. Correlation coefficients for relationships among these variables were obtained from published literature and postulated in a series of models using measures of those variables that are feasible to include in a community nutritional survey. Models were built upon known information about the metabolism of iron and were limited by what had been reported in the literature in terms of correlation coefficients or quantitative relationships. Data were pooled from various studies and correlations of the same bivariate relationships were averaged after z- transformations. Correlation matrices were then constructed by transforming the average values back into correlation coefficients. The results of path analysis in this study indicate that hemoglobin is not a good indicator of early iron deficiency. It does not account for variance in iron stores. On the other hand, 91% of the variance in iron stores is explained by serum ferritin and total iron-binding capacity. In addition, the magnitude of the path coefficient (.78) of the serum ferritin-iron stores relationship signifies that serum ferritin is the most important predictor of iron stores in the proposed model. Finally, drawing upon known relations among variables and the amount of variance explained in path models, it is suggested that the following blood measures should be made in assessing community iron deficiency: (1) serum ferritin, (2) total iron-binding capacity, (3) serum iron, (4) transferrin saturation, and (5) hemoglobin concentration. These measures (with acceptable ranges and cut-off points) could make possible the complete evaluation of all three stages of iron deficiency in those persons surveyed at the community level. ^

HEAD OF HOUSEHOLD STRUCTURE: ITS INFLUENCE ON THE DIETARY QUALITY OF U.S. HOUSEHOLDS, 1977-78 (UNITED STATES, NATIONWIDE FOOD CONSUMPTION SURVEY)

Using analysis of variance, household data collected in the Spring portion of the 1977-78 Nationwide Food Consumption Survey conducted by the United States Department of Agriculture were analyzed to examine the relationship between household characteristics and dietary quality of the household food supply. Results indicated that head of household structure was a statistically significant variable, with female headed households having higher dietary quality.^ Further analysis indicated that neither race, degree of urbanization, regional location, the education level of the female head, nor her employment status were significant variables in influencing dietary quality. The influence of head of household structure remained significant when these variables were controlled. However, income, household size, and family life cycle stage had statistically significant effects on dietary quality, and when individually controlled, the influence of head of household structure disappeared. ^

THE EFFECT OF CAFFEINE CONSUMPTION ON MORTALITY IN HYPERTENSIVE INDIVIDUALS

The effect of caffeine consumption on mortality was evaluated in a historical cohort study of 10064 hypertensive individuals participating in the Hypertension Detection and Follow-Up Program (HDFP) from 1973 to 1979. The study cohort was stratified into caffeine consumption groups (none, low, medium and high) based on their total level of caffeine intake from beverages (coffee and tea) and certain medications at the One-year follow-up home visit. Stratification was also made by sex, race, type of care and age. The total relative risks (RRs) when computed across strata for each caffeine consumer group (low, medium and high) were not significantly different when compared to the noncaffeine consumer group for all-cause or cause-specific mortality rates. The point estimates and 95 per cent confidence intervals for relative risks of all-cause mortality when compared to nonconsumers were as follows: Low = 0.82 (0.65-1.03), Medium: = 0.82 (0.62-1.82) and High = 0.90 (0.63-1.28). For all sex, race combinations there was an increase in the per cent of current smokers within each caffeine consumer group as the level of caffeine consumption increased. Cigarette smoking was an important confounder correlated with caffeine consumption and associated with mortality in this cohort. When confounding by cigarette smoking was adjusted for in the analysis, no association was found between the level of caffeine consumption and all-cause or cause-specific mortality. ^

THE EFFECT OF IRON SUPPLEMENT ON THE GROWTH OF RURAL INDONESIAN SCHOOL CHILDREN

The effect of oral iron supplementation on blood iron levels and physical growth in 119 Indonesian rural school children was assessed in the double-blind study. The children were classified into anemic and normal groups according to their initial hemoglobin and transferrin saturation levels and were randomly assigned to either iron or placebo treatment for twelve weeks. Biochemical, anthropometric and morbidity data were collected prior to and after the treatment period. Before treatment, anemic subjects were smaller and had higher morbidity than normal subjects. Treatment with 10 mg ferrous sulfate/kg/day for twelve weeks resulted in a significant improvement in blood iron biochemical status of the anemic subjects and in their growth velocity and morbidity. ^

Mexico: A new heavy weight in a global world

In the last three decades, obesity has been gaining recognition as a serious public health problem in Mexico. This epidemic developed insidiously in a country that was still focused on chronic under-nutrition in the population. During that same period, macro-economic reforms projected Mexico into the global economic arena. Foreign investments, trade in goods and services, and technological transfers were promoted through participation in numerous trade agreements between Mexico and other countries. The North American Trade Agreement (NAFTA), signed in 1994, promised an integrated market between the three North American countries: Canada, the United States, and Mexico. Although these trade policies were likely to have effects on the available food supply in Mexico, this association has not been elucidated. In this case study, we examine how these trade liberalization policies may have influenced the food supply in Mexico.^ Information on the trade of food commodities between the United States and Mexico and the nature of foreign investment in Mexico was compiled using public data available through American, Mexican, and other international published reports for 1986 through 2011. After the implementation of NAFTA, an increase in trade and investments was observed between Mexico and its two North American partners, but most of the trade increase occurred between the US and Mexico. Since the liberalization of trade policies between these counties, exports of fruit and vegetables into the U.S. from Mexico have increased, while exports of cereals, fats, vegetable oils, meat, dairy products and processed foods from the U.S. into Mexico have increased. During this same time period, there has been an increase in the foreign direct investment in the food industry in Mexico, as well as changes in the types and amounts of dietary energy available on a population level. Specifically, between 1990 to 2006, the dietary energy supply per person has increased 6.1% available animal protein has increased 35.8%, and available fat has increased 18.9%.^ Thus, this case study suggests that the recent changes in food-related industries through foreign direct investment and market liberalization may be likely contributors to the obesogenic food environment in Mexico. Although this initial case study provides interesting data, whether trade liberalization policies should be considered hazardous for health as a distal determinant of the obesity epidemic needs to be further examined using a more stringent study design or further follow up of the US Mexico trade data.^

Anesthetic choices and breast cancer recurrence: A retrospective cohort study of risk factors

Background: The impact of anesthetic techniques for breast cancer surgery traditionally has been centered on the incidence of acute pain syndromes and complications immediately after surgery. Evaluating anesthesia management beyond short-term effects is an emerging science. Several animal studies have concluded that regional anesthesia independently reduces cancer recurrence and metastasis. A small number of retrospective clinical studies indicate that reductions in cancer recurrence are attributable to anesthesia technique; however, individual risk factors need to be taken into consideration. ^ Purpose: The aims were to: 1) investigate differences in patient, disease and treatment factors between women who received surgical treatment for breast cancer with paravertebral regional and general anesthesia compared to women who received general anesthesia alone; 2) explore patient, disease and treatment factors associated with recurrence of breast cancer; and 3) test the association between type of anesthesia and breast cancer recurrence and survival over 22–46 months following surgery. ^ Methods: This retrospective cohort study included 358 patients with stage 0-III disease who received a partial or total mastectomy without axillary node dissection between October 2006 and October 2008 at a large academic cancer center. Follow-up ended in August 2010 with a median follow-up time of 28.8 months. ^ Results: The patient demographics were equally represented across anesthesia groups. Mean BMI (kg/m2) was greater for the patients who received general anesthesia (GA) alone (29±6.8) compared to those that received paravertebral regional block (PVB) with GA (28±5.1), p=0.001. The PVB with GA group had more advanced stages of disease (p=0.01) and longer surgeries (p=0.01) than the GA only group. Breast cancer recurrence was detected in only 1.7% of the study population. The mean age was 51±18 in those who had a recurrence compared to 58±11 in the non-recurrent group (p=0.06). Overall, no association between anesthesia type and recurrence was found (p=0.53), with an unadjusted estimated hazard ratio of 1.84 (95% CI 0.34–10.08). ^ Conclusions: In contrast to previous retrospective studies in cancer patients receiving surgical and anesthesia treatment, this study was unable to detect a difference in relating type of anesthesia with decreased breast cancer recurrence. Nonetheless, a significant association between BMI and type of anesthesia was observed and should be taken into account in future studies. Because the overall rate of recurrence was very small in this population, a larger study would be needed to detect any differences in rates of recurrence attributable to type of anesthesia. ^

"Gangsterism," HIV, and "tik:" An exploration of Cape Town youth

Since early 2000, the Western Cape of South Africa has been documented as an area for monitoring the spread of HIV. The majority of HIV cases occur within individuals between the ages of 15-49 years, and the epidemic is believed to be complicated by the increased use of crystal methamphetamine (CM), or “tik.” Eighty percent of current CM users in Cape Town are under the age of 21 years, and almost 18% of current HIV cases are in individuals under the age of 24 years. Gang membership in youth may also be complicating the HIV problem as gangs feed the social acceptability of “tik” and encourage sexual violence. With almost half the population of Cape Town in their mid-twenties, the threat of a new HIV epidemic complicated by CM use has become a concern in the young adults of the city. Research into the relationships between gang membership and drugs/violence has been extensively studied in the Cape Flats. Yet, few have examined the role of gangs in the perpetuation of HIV. Therefore, the purpose of this investigation was exploratory in nature. Key informant interviews from Cape Town youth were used as case illustrations to generate potential hypotheses on the interrelationships between “gangsterism,” “tik” use, and HIV. Such awareness is important if effective efforts to reduce HIV incidence in Cape Town (and Sub-Saharan Africa) are to transpire. If the problem of CM is not addressed quickly, the Cape Flats may find itself with a higher rate of an already uncontrollable HIV epidemic. ^

Using intervention mapping to develop a community garden program at the women's home

This culminating experience was a practice based intervention conducted by an organization, utilizing an intervention mapping approach for the program planning. It took place summer 2010 through spring 2011 and included incorporating a community garden into the Gusto wellness program at The Women's Home. This organization offers long-term residential care, and therapeutic services. Literature relating to community gardens and nutrition behavior change was reviewed. Short-term objectives included: 1) Conducting a needs assessment using focus groups, 2) Designing gardening program components based on intervention mapping guidelines, 3) Constructing a garden bed at Midtown Community Garden for use of The Women's Home, 4) Planning and implementing gardening education, and 5) Assessing feasibility of the garden program. The target population included 24 residents living at the residential dormitory of The Women's Home at the time of this project. The major variables are intervention mapping constructs including: 1) Needs assessment, 2) Preparing matrices of change objectives, 3) Selecting theory-informed intervention methods and practical strategies, 4) Producing program components and materials, 5) Planning program adoption, implementation, and sustainability, and 6) Planning for evaluation. The specific focus was lack of access to fresh fruits and vegetables (FV) for this population. Focus group responses revealed interest in community garden participation. Matrices of change were developed for lack of FV access based on performance objectives for behavioral and environmental factors and related determinants and theory. Methods and strategies were developed to implement a community garden and encourage participation. Program components included initiating a garden club, networking activities, creating gardening curriculum, and participating at Midtown Community Garden. Adoption and implementation performance objectives were outlined, and many were carried out. Evaluation questions were designed and outcomes of the garden project were discussed. ^ Outcomes of the project included exposure of garden topics and activities for The Women's Home residents, focus group responses revealing an interest in gardening among this population, gardening program components designed based on intervention mapping steps, and a constructed garden bed that was used for planting vegetables and flowers through fall 2010. Limited resources and budget along with a lack of a residential coordinator at The Women's Home were the main limiting factors for this project. Future garden projects can be developed using the intervention mapping process.^

The role and impact of transitional care utilization in colorectal cancer

BACKGROUND Although one out of every five gastrointestinal cancer patients needs transitional care (home-based skilled care or placement in skilled nursing or rehabilitation facilities) following treatment, few studies have examined outcomes in this population compared to patients who return home without assistance. This study has two primary goals: 1. To evaluate long-term cancer-specific outcomes in colorectal cancer patients utilizing transitional care compared to those that return home without assistance following therapy 2. To compare results using standard regression techniques and propensity scores. ^ METHODS Patients undergoing curative surgery for colorectal adenocarcinoma will be identified using data from a tertiary care Veterans Administration hospital. Survival and recurrence will then be determined from VA records and the Social Security Death Index. ^ The association between transitional care utilization and overall and disease-free survival will be evaluated using Cox proportional hazards regression to adjust for confounding factors. Predictors of transitional care utilization will be assessed using multiple logistic regression to generate a propensity score which will also be used to assess differences in survival based on transitional care use. ^ POTENTIAL SIGNIFICANCE If transitional care utilization is associated with worse survival and recurrence following therapy then it will be important to subsequently assess the mechanism in order to target interventions to improve outcomes. If there is no difference in cancer-specific outcomes, then this project can potentially highlight benefits of supportive therapy following colorectal cancer resection.^

Anal warts and their predictors among HIV-infected women

Human papillomavirus (HPV) is a necessary cause of cervical cancer and is also strongly associated with anal cancer. While different factors such as CD4+ cell count, HIV RNA viral load, smoking status, and cytological screening results have been identified as risk factors for the infection of HPV high-risk types and associated cancers, much less is known about the association between those risk factors and the infection of HPV low-risk types and anogential warts. In this dissertation, a public dataset (release P09) obtained from the Women's Interagency HIV Study (WIHS) was used to examine the effects of those risk factors on the size of the largest anal warts in HIV-infected women in the United States. Linear mixed modeling was used to address this research question. ^ The prevalence of anal warts at baseline for WIHS participants was higher than other populations. Incidence of anal warts in HIV-infected women was significantly higher than that of HIV-uninfected women [4.15 cases per 100 person-years (95% CI: 3.83–4.77) vs. 1.30 cases per 100 person-years (95% CI: 1.00–1.58), respectively]. There appeared to be an inverse association between the size of the largest anal wart and CD4+ cell count at baseline visit, however it was not statistically significant. There was no association between size of the largest anal wart and CD4+ cell count or HIV RNA viral load over time among HIV-infected women. There was also no association between the size of the largest anal wart and current smoking over time in HIV-infected women, even though smokers had larger warts at baseline than non-smokers. Finally, even though a woman with Pap smear results of ASCUS/LGSIL was found to have an anal wart larger than a woman with normal cervical Pap smear results the relationship between the size of the largest anal wart with cervical Pap smear results over time remains unclear. ^ Although the associations between these risk factors and the size of the largest anal wart over time in HIV-infected women could not be firmly established, this dissertation poses several questions concerning anal wart development for further exploration: (1) the role of immune function (i.e., CD4+ cell count), (2) the role of smoking status and the interaction between smoking status with other risk factors (e.g., CD4+ cell count or HIV RNA viral load), (3) the molecular mechanism of smoking on anal warts over time, (4) the potential for development of a screening program using anal Pap smear in HIV-infected women, and (5) how cost-effective and efficacious would an anal Pap smear screening program be in this high-risk population. ^

Data Management Policies and Issues with Life Science Data

Data management and sharing are relatively new concepts in the health and life sciences fields. This presentation will cover some basic policies as well as the impediments to data sharing unique to health and life sciences data.