Granzyme M has a critical role in providing innate immune protection in ulcerative colitis.

Inflammatory bowel disease (IBD) is an immunoregulatory disorder, associated with a chronic and inappropriate mucosal immune response to commensal bacteria, underlying disease states such as ulcerative colitis (UC) and Crohn's disease (CD) in humans. Granzyme M (GrzM) is a serine protease expressed by cytotoxic lymphocytes, in particular natural killer (NK) cells. Granzymes are thought to be involved in triggering cell death in eukaryotic target cells; however, some evidence supports their role in inflammation. The role of GrzM in the innate immune response to mucosal inflammation has never been examined. Here, we discover that patients with UC, unlike patients with CD, display high levels of GrzM mRNA expression in the inflamed colon. By taking advantage of well-established models of experimental UC, we revealed that GrzM-deficient mice have greater levels of inflammatory indicators during dextran sulfate sodium (DSS)-induced IBD, including increased weight loss, greater colon length reduction and more severe intestinal histopathology. The absence of GrzM expression also had effects on gut permeability, tissue cytokine/chemokine dynamics, and neutrophil infiltration during disease. These findings demonstrate, for the first time, that GrzM has a critical role during early stages of inflammation in UC, and that in its absence colonic inflammation is enhanced.

PU.1 cooperates with IRF4 and IRF8 to suppress pre-B-cell leukemia.

The Ets family transcription factor PU.1 and the interferon regulatory factor (IRF)4 and IRF8 regulate gene expression by binding to composite DNA sequences known as Ets/interferon consensus elements. Although all three factors are expressed from the onset of B-cell development, single deficiency of these factors in B-cell progenitors only mildly impacts on bone marrow B lymphopoiesis. Here we tested whether PU.1 cooperates with IRF factors in regulating early B-cell development. Lack of PU.1 and IRF4 resulted in a partial block in development the pre-B-cell stage. The combined deletion of PU.1 and IRF8 reduced recirculating B-cell numbers. Strikingly, all PU.1/IRF4 and ~50% of PU.1/IRF8 double deficient mice developed pre-B-cell acute lymphoblastic leukemia (B-ALL) associated with reduced expression of the established B-lineage tumor suppressor genes, Ikaros and Spi-B. These genes are directly regulated by PU.1/IRF4/IRF8, and restoration of Ikaros or Spi-B expression inhibited leukemic cell growth. In summary, we demonstrate that PU.1, IRF4 and IRF8 cooperate to regulate early B-cell development and to prevent pre-B-ALL formation.

The Enigma of Rapid Repeat Pregnancy: A Qualitative Study of Teen Mothers.

STUDY OBJECTIVE: Rapid repeat pregnancy accounts for 18% of teen pregnancies and leads to adverse health, economic, and developmental outcomes for teen mothers and their children. Few interventions have been successful in reducing rapid repeat pregnancy. In this qualitative study we examined adolescent mothers' perceptions of their decision-making and behaviors that helped prevent or promote a rapid repeat pregnancy. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Semistructured interviews were conducted with 31 adolescent mothers, aged 16-21 years; 15 of these subjects experienced a repeat pregnancy within a year of their first child's birth and 16 had not. Two researchers used a grounded, inductive technique to identify emergent themes; interviews were subsequently coded accordingly. Counts were tabulated of the number of times themes were endorsed among those with or without a repeat pregnancy. RESULTS: Four overarching themes emerged from the interviews: intentionality regarding pregnancy planning, patients' degree of independence in making contraceptive choices, sense of control over life experience, and barriers to follow-through on contraceptive planning. Teens who had not experienced a rapid repeat pregnancy more often endorsed themes of intentionality in preventing or promoting a pregnancy, independence in decision-making, and feelings of control over their experience. Ambivalence and lack of decision-making about seeking another pregnancy were frequently endorsed by mothers who had experienced a second pregnancy. CONCLUSION: Decision-making regarding seeking or preventing a rapid repeat pregnancy is complex for teen mothers; techniques to help support decision-making or to delay pregnancy until decision-repeat making is complete might be important in reducing rapid pregnancy.

Parents' preferences for return of results in pediatric genomic research.

BACKGROUND: The aim of this study was to ascertain parental preferences for the return of genetic research results on themselves and their children and their choices for genetic research results to receive. METHODS: A mail survey was sent to 6,874 families seen at Boston Children's Hospital. The survey included questions assessing the respondents' preferences regarding the types of result they wanted to receive on themselves and their children. RESULTS: Most of the 1,060 respondents 'probably' or 'definitely' wanted to receive genetic research results about themselves (84.6%) and their children (88.0%). Among those who wanted to receive results, 83.4% wanted to receive all research results for themselves and 87.8% for their children. When questions about specific types of research results were combined into a composite measure, fewer respondents chose to receive all results for themselves (53.5%) and for their children (56.9%). CONCLUSION: Although most parents report a desire to receive all research results on a general question, almost half chose to receive only a subset of research results when presented with specific types of research results. Our findings suggest that participants might not understand the implications of their choice of individual research results to receive unless faced with specific types of results.

Humanized immune system (HIS) mice as a tool to study human NK cell development.

The study of human hematopoiesis is conditioned by access to nondiseased human tissue samples that harbor the cellular substrates for this developmental process. Technical and ethical concerns limit the availability to tissues derived from the fetal and newborn periods, while adult samples are generally restricted to peripheral blood. Access to a small animal model that faithfully recapitulates the process of human hematopoiesis would provide an important tool. Natural killer (NK) cells comprise between 10% and 15% of human peripheral blood lymphocytes and appear conserved in several species. NK cells are implicated in the recognition of pathogen-infected cells and in the clearance of certain tumor cells. In this chapter, we discuss NK cell developmental pathways and the use of humanized murine models for the study of human hematopoiesis and, in particular, human NK cell development.

Structure and irregularity in the spontaneous behavior of young infants.

Persistent, irregular fluctuations in spontaneous motor activity are common in the young of many vertebrate species, but whether the irregularity is intrinsic to the dynamics of motor activation or the result of random perturbations is not known. Analysis of the second-by-second variation in the general body movement of awake human infants 1 and 3 months after birth revealed low dimensional structure in the characteristically irregular motor activity and exponential rates of divergence of initially similar states of motor activation. Results support the conclusion that irregularity is an intrinsic property of the dynamics of motor activation involving relatively few effective degrees of freedom and raise questions about the advantages or disadvantages of irregularity built into early behavioral organization.

Comparison of three nonradiographic methods of mixed dentition analysis in cleft lip and palate patients.

PURPOSE: The purpose of this study was to investigate whether the application of mixed dentition analyses in cleft lip and palate patients differed from noncleft patients and to investigate which method provided the most accurate prediction in cleft lip and palate patients. METHODS: Study casts of 30 cleft lip and palate patients and 30 noncleft patients were used in this study. Each patient had dental casts at two stages of dental development. The methods compared included the Moyers, the Tanaka & Johnston (T/J) and the Boston University (BU) prediction methods. RESULTS: Analyses for both groups indicated that the predicted values yielded by each method were significantly different from one another but were all significantly correlated with actual tooth size. Moyers 50% and BU had the smallest mean difference values and no significant difference between the predicted and actual values for both cleft and noncleft control groups. CONCLUSIONS: Types of cleft had no effect on the size of the mandibular permanent canines and premolars. The application of mixed dentition analyses in cleft lip and palate patients does not differ from noncleft patients. Both Moyers 50% and the BU method have high accuracy and correlation in prediction of unerupted teeth in both groups.

The integration of body movement and attention in young infants.

The normal development of adaptive behavior in humans depends on the integration of visual attention and body movement, yet little is known about the initial state of movement-attention coupling at the beginning of postnatal life. We studied 1- and 3-month-old infants during extended periods of visual exploration and found that spontaneous shifts of gaze are preceded by rapid changes in general body movement. The results reveal a tight link between motor activation and overt attention on a time scale of seconds or less. This link undergoes substantial developmental change in the first few weeks after birth. During that time, phasic motor activation may play a key role in visual exploration by helping to unlock gaze when the environment is unchanging.

Benchmarking in health-system pharmacy: experience at Glens Falls Hospital.

The experience of Glens Falls Hospital (GFH) with the Benchmarking Program coordinated by The Clinical Pharmacokinetics Laboratory at Millard Fillmore Hospital is described. GFH, a community hospital in upstate New York with 442 licensed beds, serves a patient population drawn from a five-county area. In 1998, GFH developed a multidisciplinary pharmacy task force charged with generating strategic initiatives for curtailing drug costs. Proposals for various programs, including specific goals, were developed with the aid of trends reported in the individual hospital reports provided by the Benchmarking Program. The data obtained through these reports helped GFH's pharmacy staff establish goals for the appropriate use of many agents, including vancomycin, and allowed GFH to assess the impact of its initiatives through comparisons with similar hospitals across the United States. In 1995, vancomycin expenditures at GFH substantially exceeded those for benchmark hospitals of similar types, but, with the implementation of new vancomycin guidelines aimed at reducing inappropriate use in 1996, the difference was eliminated. The individual hospital reports generated by the Benchmarking Program provide valuable data that can be used to assess pharmacy performance, set drug expenditure goals, and design programs to reduce antimicrobial resistance.

Future caries susceptibility in children with early childhood caries following treatment under general anesthesia.

PURPOSE: The purpose of this study was to assess the susceptibility of children to the future development of caries following comprehensive treatment for early childhood caries (ECC) under general anesthesia. METHODS: The patients selected for this retrospective study were identified by analyzing dental records of children receiving treatment at the Franciscan Children's Hospital & Rehabilitation Center, Boston, MA (FCH & RC). In total, 4,143 records were reviewed. Of these, ECC was diagnosed in 42 patients before their admission to the operating room. Thirty-one control children were selected randomly from the dental records reviewed at FCH & RC. The control group was initially caries-free. The caries status of the children diagnosed with ECC was evaluated and compared with the control group. Children in both groups were seen for recall at intervals of six to nine months over a two-year period. The carious lesions were recorded in two categories; new smooth surface caries (NSSC) and new pit and fissure caries (NPFC). RESULTS: Thirty-three of 42 (79%) ECC children compared to nine of 31 (29%) control children had detectable carious lesions at subsequent recall visits. Children with ECC demonstrated a mean number of 3.2 +/- 3.3 new carious lesions compared to a mean of only 0.8 +/- 1.6 carious lesions in the control group. These differences were statistically significant (t71 = 3.8; P < 0.001). In addition, of the 42 patients treated for ECC under general anesthesia, seven (17%) required retreatment under general anesthesia within two years following their initial full-mouth rehabilitation. The prevalence of NSSC in the ECC group was significantly higher than the control group (t71 = 3.5; P < 0.001). CONCLUSIONS: Despite increased preventive measures implemented for children who experienced ECC, this study concluded that this group of children is still highly predisposed to greater caries incidence in later years. These findings strongly suggest that more aggressive preventive therapies may be required to prevent the future development of carious lesions in children who experienced ECC.

The nurse's role in delivery of radioisotope for ictal SPECT scan.

The Medical College of Georgia Hospital and Clinics (MCG) was one of the first centers in the United States (US) to institute a video electroencephalography (EEG) epilepsy monitoring unit and epilepsy surgery program. In order to surgically remove the area in the brain giving rise to seizures, the epileptogenic zone must be identified and localized. One of the newer methods used to identify the epileptogenic seizure focus is the ictal Single Photon Emission Computed Tomography (SPECT) scan, which MCG began performing in 1993. The nurses staffing the six bed Epilepsy Monitoring Unit (EMU) are trained by the Nuclear Radiology Department and Radiation Safety Officer to bandle the radioisotope during mixing, calibration and injection. The bedside nursing protocol developed assures patient and staff radiation safety and efficacious injection. Over 300 patients have been injected by nurses with a high degree of safety to patients and staff. This has resulted in positive scans that aid diagnosis. The success of the ictal SPECT protocol can be attributed to the active collaboration of our multidisciplinary team.