Long-term gastrointestinal complications of Clostridium difficile associated diarrhea (CDAD)

Background. The incidence of Clostridium difficile -associated diarrhea (CDAD) is increasing worldwide likely because of increased use of broad spectrum antibiotics and the introduction of a clonal hyper-virulent strain called the BI strain. Short-term complications of CDAD include recurrent disease, requirement for colectomy, and persistent disease. However, data on the long-term consequences of CDAD are scarce. Among other infectious diseases (Shigella, Salmonella, and Campylobacter), long-term consequences such as irritable bowel syndrome (IBS), chronic dyspepsia/diarrhea, and other GI effects have been noted. Since the mechanism of action of these agents is similar to C.difficile, we hypothesized that patients with CDAD have greater likelihood of developing IBS and other functional gastrointestinal disorders (FGIDs) in the long-term as compared to a general sample of recently hospitalized patients. ^ Objective. To evaluate the long-term gastrointestinal complications of CDAD, (IBS, functional diarrhea, functional abdominal bloating, functional constipation and functional abdominal pain syndrome). ^ Methods. The current study was a secondary analysis of a previously completed observational case-control outcome study. Adult CDAD patients at St. Luke's Episcopal Hospital, Houston (SLEH) were followed up and interviewed by telephone six months after the initial diagnosis thereafter evaluated for the development of IBS and other FGIDs. A total of 46 patients with CDAD infection were recruited at SLEH between May-November 2007. The comparators were patients hospitalized in SLEH within one month before or after the admission of the reference case, hospital length of stay within one week longer or shorter than reference case, and age within 10 years more or less than the reference case. Cases and comparators were compared using Fisher's exact test. A p<0.05 was considered significant. ^ Results. Thirty CDAD patients responded to the questionnaires and were compared to 40 comparators. No comparator developed a FGID, while 3 (10%) CDAD patients developed new onset IBS (p=0.07), 4 (13.3%) developed new onset Functional Diarrhea (p=0.03), and 3 (10%) developed new onset Functional Constipation (p=0.07). No patient developed Functional Abdominal Bloating and Functional Abdominal Pain Syndrome. ^ Conclusion. In this study, new onset functional diarrhea was significantly more common in patients CDAD within six months after initial infection compared to matched controls.^

{\it Hox\/} genes and specification of regional identity in the axial skeleton: Analysis of the individual and combined mutant phenotypes of the paralogous group 4 murine {\it Hox\/} genes; {\it hoxa\/}-4, {\it hoxb\/}-4 and {\it hoxd\/}-4

The Hox gene products are transcription factors involved in specifying regional identity along the anteroposterior body axis. In Drosophila, where these genes are known as HOM-C (Homeotic-complex) genes and where they have been most extensively studied, they are expressed in restricted domains along the anteroposterior axis with different anterior limits. Genetic analysis of a large number of gain- and loss-of-function alleles of these genes has revealed that these genes are important in specifying segmental identity at their anterior limits of expression. Furthermore, there is a functional dominance of posterior genes over anterior genes, such that posterior genes can dominantly specify their developmental programs in spite of the expression of more anterior genes in the same segment. In the mouse, there are four clusters of HOM-C genes, called Hox genes. Thus, there may be up to four genes, called paralogs, that are more highly homologous to each other and to their Drosophila homolog than they are to the other mouse Hox genes. The single mutants for two paralogous genes, hoxa-4 and hoxd-4, presented in this dissertation, are similar to several other mouse Hox mutants in that they show partial, incompletely penetrant homeotic transformations of vertebrae at their anterior limit of expression. These mutants were then bred with hoxb-4 mutants (Ramirez-Solis, et al. 1993) to generate the three possible double mutant combinations as well as the triple mutant. The skeletal phenotypes of these group 4 Hox compound mutants displayed clear alterations in regional identity, such that a nearly complete transformation towards the morphology of the first cervical vertebra occurs. These results suggest a certain degree of functional redundancy among paralogous genes in specifying regional identity. Furthermore, there was a remarkable dose-dependent increase in the number of vertebrae transformed to a first cervical vertebra identity, including the second through the fifth cervical vertebrae in the triple mutant. Thus, these genes are required in a larger anteroposterior domain than is revealed by the single mutant phenotypes alone, such that multiple mutations in these genes result in transformations of vertebrae that are not at their anterior limit of expression. ^

Evaluation of Mycobacterium avium complex lung disease in women

Mycobacterium avium complex (MAC) is a ubiquitous organism responsible for most pulmonary and disseminated disease caused by non-tuberculosis (NTM) mycobacteria. Though MAC lung disease without predisposing factors is uncommon, in recent years it has been increasingly described in middle-aged and elderly women. Recognition and correct diagnosis, is often delayed due to the indolent nature of the disease. It is unclear if these women have significant clinical disease as or if their airways are simply colonized by the bacterium. This study describes the clinical presentation, identifies risk factors, and describes the clinical significance of MAC lung disease in HIV-negative women aged 50 or greater. ^ A hybrid study design utilizing both cross-sectional and case-control methodologies was used. A comparison population was selected from previously identified tuberculosis suspects found throughout Harris County. The study population had at least one acid fast bacillus pulmonary culture performed between 1/1/1998 and 12/31/2000 from a pulmonary source. Clinical presentation and symptoms were analyzed using a cross-sectional design. Past medical history and other risk factors were evaluated using a traditional case-control study design. Differences in categorical variables were estimated with the Chi Square or Fisher's Exact test as appropriate. Odds ratios and 95% confidence intervals were utilized to evaluate associations. Multivariate logistic regression was used to identify predictive factors for MAC. All statistical tests were two-sided and P-values <0.05 were considered statistically significant. ^ Culture confirmed MAC pulmonary cases were more likely to be white, have bronchiectasis, scoliosis, evidence of cavitation and pleural changes on chest radiography and granulomas on histopathologic examination than women whose pulmonary cultures were AFB negative. After controlling for selected risk factors, white race continued to be significantly associated with MAC lung disease (OR = 4.6, 95% CI = 2.3, 9.2). In addition, asthma history, smoking history and alcohol use were less likely to be evident among MAC cases in a multivariate analysis. Right upper and right middle lobe disease was further noted among clinically significant cases. Based on population data, MAC lung disease appears to represent a significant clinical syndrome in HIV-negative women thus supporting the theory of the Lady Windermere Syndrome. ^

Symposium for dental treatment of medically complex children: Practice based culminating experience a continuing education course

The purpose of this Continuing Education Course is to provide oral health professionals with information to address the unique dental needs of medically complex children. The objective is to train dentists to treat special needs patients so these children have more access to oral healthcare. ^ Under the auspice of Dell Children Hospital of Austin, Lisa Jacob DDS MS is administering this Continuing Education Course for dentists and dental staff from the 46 counties of central Texas served by the hospital.^ Needs assessment was determined through a survey questionnaire to collect data about the number of special needs patients seen by general dentists in Central Texas.^ In recent years, an increasing number of continuing education courses have been developed to help dentists learn techniques for providing dentistry in more understanding ways to patients with special needs. Dentists and dental staff are trained to provide care specifically in dentistry, regardless of who the patient is. This means dentists can perform a clinical examination, carry out procedures to diagnose and treat oral diseases, and provide restorations such as fillings and crowns. ^ Four prominent speakers will provide an instructional tool to address the need for dentists to increase their competence and comfort level in caring for individuals with developmental disabilities. Each speaker will address one of the most frequently encountered cases of medically complex children. The four topics selected by Dr. Lisa Jacob are Cancer, Mental Disability, Downs Syndrome, and Craniofacial Syndromes.^ The public health implications of this continuing education course are presented in providing dental service to this underserved population. When general dentist turn away patients with special needs because of lack of knowledge to treat them, these patients will, more than likely, postpone or abandon needed dental visits because of difficulties reaching pediatric dentists who may not be available in certain areas.^

Assessing the Environmental Protection Agency's guidelines for cumulative risk assessment: Are they suitable for state agencies and EPA regional offices?

In the field of health risk analysis, cumulative risk assessment (CRA) is a necessary, although undeniably more complex approach to understanding the mixture of stressors, whether chemical or psychosocial, that exist in our environment, in all the pathways through which the chemicals may evolve—air, soil, or water, as well as the accumulation of these exposures over time. Related, or attached to the developing awareness of scientists understanding this mix of combined health effects is the burgeoning of the environmental justice movement, in which educated community advocates and even affected community members have called attention to evidence of a higher pollution burden in minority and/or lower SES communities. The intention of this paper is to 1) examine the development and understanding of CRA, primarily by the U.S. Environmental Protection Agency; 2) to assess several states agencies and some EPA regional offices' interpretation of CRA, again based primarily on EPA guidance, and 3) to analyze how CRA might be refined in its implementation—giving some cues as to how the EPA may more effectively interact with communities interested in CRA.^