Increasing prevalence of gastroschisis in Utah

Background

Recent studies provide conflicting information about gastroschisis prevalence trends. The authors proposed that prevalence of gastroschisis in live births has increased in Utah and that characteristics of these infants would provide clinically useful information about treatment and outcomes.

Methods

Primary Children's Medical Center (PCMC) is the sole pediatric surgical referral hospital for Utah. The authors used both pediatric surgical and neonatal databases to identify gastroschisis cases at PCMC from 1971 through 2002. Only infants whose mothers had a primary residence in Utah were included. Individual charts were reviewed for infant characteristics for cases from 1998 through 2002. Utah Vital Statistics Reports were used to determine live birth rates and general infant and maternal characteristics.

Results

Gastroschisis prevalence increased from 0.36 to 3.92 cases per 10,000 live births over 31 years (P < .001). Young maternal age, primigravida status, and tobacco use were associated risk factors. Using the time required to achieve full enteric feedings at targeted volume and caloric density as a measurement of outcome, we found no association between delivery mode or surgical closure type (primary or secondary) and time to full feedings. Higher birth weight was associated with decreased time to full feedings (P = .03).

Conclusions

Gastroschisis prevalence has increased 10-fold over the past 3 decades in Utah.     

Multivariate design, synthesis, and biological evaluation of peptide inhibitors of FimC/FimH protein-protein interactions in uropathogenic Escherichia coli

A peptide library targeting protein-protein interactions crucial for pilus assembly in Gram negative bacteria has been designed using statistical molecular design. A nonamer peptide scaffold was used, with seven positions being varied. The selection was performed in the building block space, and previously known structure-activity data were included in the design procedure. This resulted in a heavily reduced library consisting of 32 peptides which was prepared by solid-phase synthesis. The ability of the peptides to inhibit the protein-protein interaction between the periplasmic chaperone FimC and the pilus adhesin FimH was then determined in an ELISA. Novel peptides with the capability to inhibit the FimC/FimH protein-protein interaction to the same extent as the native FimC peptides were discovered. Multivariate QSAR studies of the response in the ELISA gave valuable information on the properties of amino acids which were preferred at the seven positions in the nonamer scaffold. This information can be used in attempts to develop optimized peptides and peptidomimetics that inhibit pilus assembly in pathogenic bacteria.     

Does disease management improve clinical and economic outcomes in patients with chronic diseases? A systematic review

PURPOSE: To assess the clinical and economic effects of disease management in patients with chronic diseases. METHODS: Electronic databases were searched for English-language articles from 1987 to 2001. Articles were included if they used a systematic approach to care and evaluated patients with chronic disease, reported objective measurements of the processes or outcomes of care, and employed acceptable experimental or quasi-experimental study designs as defined by the Cochrane Effective Practice and Organization of Care Group. RESULTS: Two reviewers evaluated 16,917 titles and identified 102 studies that met the inclusion criteria. Identified studies represented 11 chronic conditions: depression, diabetes, rheumatoid arthritis, chronic pain, coronary artery disease, asthma, heart failure, back pain, chronic obstructive pulmonary disease, hypertension, and hyperlipidemia. Disease management programs for patients with depression had the highest percentage of comparisons (48% [41/86]) showing substantial improvements in patient care, whereas programs for patients with chronic obstructive pulmonary disease (9% [2/22]) or chronic pain (8% [1/12]) appeared to be the least effective. Of the outcomes more frequently studied, disease management appeared to improve patient satisfaction (71% [12/17]), patient adherence (47% [17/36]), and disease control (45% [33/74]) most commonly and cost-related outcomes least frequently (11% to 16%). CONCLUSION: Disease management programs were associated with marked improvements in many different processes and outcomes of care. Few studies demonstrated a notable reduction in costs. Further research is needed to understand how disease management can most effectively improve the quality and cost of care for patients with chronic diseases.     

Catalysis of protein folding by chaperones in pathogenic bacteria

Molecular chaperones are thought to inhibit off-pathway interactions such as aggregation from occurring without influencing the on-pathway formation of native structure. Here, we present a mechanism whereby the family of PapD-like chaperones, which are involved in the formation of adhesive pili in pathogenic bacteria, function by suppressing aggregation while simultaneously catalyzing the folding of subunits that make up the pilus. We also show that the Arg-8 residue, invariant in the cleft of all known PapD-like chaperones, makes up part of the active site of the chaperone. The data argue for a temporal mechanism of catalyzed folding. The terminal carboxylate group of a pilus subunit anchors to the active site of the chaperone by hydrogen bonding. This bonding spatially fixes the COOH terminus of the subunit in the correct context for beta-sheet formation, using the edge of the NH(2)-terminal domain of the chaperone as a nucleation site.     

Symposium report on urothelial dysfunction: pathophysiology and novel therapies

PURPOSE: The basic premise of this symposium (Workshop 7) at the 2004 International Continence Society meeting in Paris was to elucidate different mechanisms of urothelial cell pathology, explore their impact on bladder function and discuss novel therapeutic interventions. RESULTS: The topics included 1) urothelial structure and function, 2) the role of adenosine triphosphate in urothelial signaling and cystitis, 3) lamina propria myofibroblasts and purinergic receptors, 4) antiproliferative factor involvement in interstitial cystitis, 5) the urothelium as a reservoir for bacterial infections, 6) radiation cystitis, nitric oxide and gene therapy, and 7) intravesical treatments. DISCUSSION: It was agreed that the urothelium can no longer be regarded merely as a passive barrier separating urine from the underlying tissues. The epithelial cells of the urothelium form part of an integrated network that also includes afferent and possibly efferent nerves, and suburothelial myofibroblasts. It has a central role in several functions, including bladder wall sensation, local blood flow modulation, pathogen removal and active barrier provision. These functions are achieved through several autocrine and paracrine pathways that involve transmitter release from the urothelium and its ability to integrate incoming signals through its battery of membrane receptors. Several pathological processes were discussed using this knowledge, including the role of small glycoproteins released during interstitial cystitis, the molecular basis of radiation induced urothelial damage, the origin of recurrent urinary tract infections and the mode of action of potential intravesical treatments for overactive bladder. CONCLUSIONS: Overall it was concluded that the urothelium has a key role in regulating lower urinary tract physiology and pathology.     

Aneurysms of the coronary arteries in the adult. Clincial and angiographic features.

One thousand coronary arteriograms were reviewed to determine the incidence, clinical presentation and angiographic features of aneurysms of the coronary artery (ACA) in adults with angina. Criteria for the angiographic diagnosis are described and the angiographic aspects are emphasized. The incidence of ACA was 1.1%. Saccular and fusiform aneurysms were seen. Single aneurysms were present in 7 patients. One patient had an abdominal aneurysm. Five patients underwent surgery; two had postoperative selective coronary angiography one year later and all five underwent follow-up left ventricular angiography. The most likely etiology of the aneurysms in this series is atherosclerosis.     

High altitude pulmonary edema. Epidemiologic observations in Peru

The incidence of high altitude pulmonary edema was examined by a survey (via questionnaire) of residents living at 3,750 meters (12,303 feet) in the mining community of La Oroya, Peru. Ninety-seven subjects made a total of 1,157 ascents to high altitude after a stay at sea level of longer than 14 days. Sixty-four subjects experienced at least one episode of high-altitude pulmonary edema. The incidence was higher in subjects aged 13 to 20 years, where 17 percent (15) of 90 ascents resulted in episodes of high-altitude pulmonary edema, than in subjects 21 years or older (3 percent; 18/686 ascents). Young subjects (2 to 12 years old) had more severe episodes of high-altitude pulmonary edema (81 percent; 30/37 episodes) than adults (22 percent; 4/18 episodes). No episodes were observed in children under two years old. Five subjects under 21 years of age experienced recurrent episodes. Our estimated incidence of severe episodes of high altitude pulmonary edema per ascent in adults (0.6 percent; 4/686) is similar to that reported by other workers (incidence of 0.15 to 0.57 percent) in various parts of the world.