Synthesis and antimicrobial studies of hydrazone derivatives of 4-[3-(2,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid and 4-[3-(3,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid.

Microbial resistance to antibiotics is an unresolved global concern, which needs urgent and coordinated action. One of the guidelines of the Centers for Disease Control and Preventions (CDC) to combat antibiotic resistance is the development of new antibiotics to treat drug-resistant bacteria. In our effort to find new antibiotics, we report the synthesis and antimicrobial studies of 30 new pyrazole derivatives. These novel molecules have been synthesized by using readily available starting materials and benign reaction conditions. Some of these molecules have shown activity with MIC values as low as 0.78 µg/mL against four bacterial strains; Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Acinetobacter baumannii. Furthermore, active molecules are non-toxic to mammalian cell line.

Brain morphometry, T2-weighted hyperintensities, and IQ in children with neurofibromatosis type 1.

BACKGROUND: Larger gray matter (GM) volume in healthy children is correlated with higher IQ. Children with neurofibromatosis type 1 (NF1) have larger brains, their magnetic resonance images frequently show T2-weighted hyperintensities, and their IQs are lower. OBJECTIVES: To confirm the hypotheses that (1) children with NF1 have larger GM and white matter volumes, (2) the greatest volume differences are in the frontal and parietal regions and in children with NF1 with hyperintensities, and (3) GM volume is inversely related to IQ in children with NF1. DESIGN: Wechsler Intelligence Scale for Children-Third Edition IQ testing and measurement of cerebral volumes and hyperintensities in brain magnetic resonance images were performed on 36 children with NF1 and on 36 matched relatives who served as control subjects. RESULTS: Gray matter and white matter volumes were significantly larger in children with NF1. The greatest difference was observed in cerebral white matter volume, predominantly in the frontal lobes, whereas the greatest difference in GM volume was in the temporal, parietal, and occipital regions. In controls, IQ was significantly related to GM volume, but in children with NF1, IQ was not inversely associated with GM volume, although IQs of children with NF1 were significantly lower. CONCLUSIONS: Children with NF1 do not have the normal relationship between GM volume and IQ. Larger GM volume in the posterior brain regions and larger white matter volumes in the frontal brain regions contribute to the larger brain volume in children with NF1.

Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213.

The objective of this study was to identify biologic parameters that were associated with either exceptionally good or poor outcome in childhood acute myeloid leukemia (AML). Among the children with AML who entered Children's Cancer Group trial 213, 498 patients without Down syndrome or acute promyelocytic leukemia (APL) comprise the basis for this report. Univariate comparisons of the proportion of patients attaining complete remission after induction (CR) indicate that, at diagnosis, male gender, low platelet count (< or =20 000/microl), hepatomegaly, myelodysplastic syndrome (MDS), French-American- British (FAB) category M5, high (>15%) bone marrow (BM) blasts on day 14 of the first course of induction, and +8 are associated with lower CR rates, while abnormal 16 is associated with a higher CR rate. Multivariate analysis suggests high platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 are independent prognostic factors associated with better CR. Univariate analysis demonstrated a significant favorable relationship between platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, low percentage of BM blasts (< or =15%), and abnormal 16 with overall survival. Absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 were determined to be independent prognostic factors associated with better survival.

Examining the association between parenting stress and the development of early childhood caries.

OBJECTIVES: Numerous studies have explored the effects of pediatric health on parenting stress, but very little work has been carried out to explore the opposite and equally as compelling relationship of how parenting stress might affect child health, especially as it relates to oral health. This study examined the association between parenting stress and early childhood caries (ECC) in 97, 4- to 5-year-old Australian children attending preschools in the North Brisbane Health Region, Australia. METHODS: Using a cross-sectional study design, clinical examinations were conducted to evaluate the caries status of each child. Two caregiver questionnaires were completed -- one soliciting demographic and oral health behavior information, and the other, information on parenting stress. RESULTS: This study demonstrated a significant bivariate association between parenting stress and ECC experience as measured by dmft; however, the association did not persist in the two-part forward-selection logistic and linear regression models. A negative association between social desirability (defensive responding) and extent of caries was also determined. CONCLUSIONS: Our findings suggest the need to conduct longitudinal studies to give proper consideration to the temporal aspect of caries development and clarify the results obtained by on the relationship between parenting stress and oral health. Further study is also warranted to more clearly elucidate the association between social desirability (defensive responding) in parents and their children's ECC experience.

Adult polycystic kidney disease and lattice corneal dystrophy: occurrence in a single family.

Most ophthalmologic disorders reported with renal cystic disease have been associated with either medullary cystic disease or juvenile nephrophthisis. A family we investigated demonstrated two previously unreported autosomal dominant disorders: adult polycystic kidney disease and lattice corneal dystrophy.

Neuropsychological effects of cranial irradiation in young children with acute lymphoblastic leukemia 9 months after diagnosis. The Children's Cancer Group.

STUDY OBJECTIVE: To determine the effects of cranial irradiation on neuropsychological test performance evident 9 months after diagnosis. DESIGN: A companion study to a randomized clinical trial (CCG-105). SETTING: Institutions participating in Childrens Cancer Group cooperative treatment trials. PATIENTS: Seventy-four children aged 3.0 to 6.5 years with average-risk acute lymphoblastic leukemia. Children with central nervous system leukemia at the time of diagnosis, preexisting mental retardation, or Down's syndrome or for whom English was not the primary language were not eligible for study. INTERVENTIONS: Children were randomized to receive treatment with one of four systemic chemotherapy regimens and either intrathecal methotrexate sodium during induction and consolidation plus 18 Gy of cranial irradiation or intrathecal methotrexate during induction, consolidation, and maintenance as central nervous system prophylaxis. MEASUREMENT AND RESULTS: The groups were comparable with regard to chronologic age, sex, and family socioeconomic status. Children who received cranial irradiation plus intrathecal methotrexate scored significantly lower on the McCarthy Motor Scale (P < .05) and the Token Test (P < .05) than children who received intrathecal methotrexate alone. The groups did not differ significantly on the McCarthy General Cognitive Index, Developmental Test of Visual Motor Integration, or Peabody Picture Vocabulary Test-Revised. CONCLUSIONS: Findings suggest that the combined effects of cranial irradiation and intrathecal methotrexate therapy on neuropsychological performance may be evident in young children as early as 9 months after diagnosis. Follow-up assessment of these children will reveal whether these effects remain constant, intensify, or resolve.

Effect of the pediatrician on the mother-infant relationship.

Child development literature suggests a relationship between mother-child interaction and enhanced infant development. We conducted a randomized clinical trial to determine if a pediatrician's guidance improves the mother-infant relationship and the infant's development. Thirty-two normal mothers and their healthy first-born infants were followed by one pediatrician at 2, 4, 8, 15, and 21 weeks of age. These dyads were randomly assigned to a control group, who received customary care, or to an intervention group, who also received guidance based on the infant's developmental status at each age. Just prior to a 27-week visit, the mother-infant relationship was assessed by a person blind to group assignment. Infant development was assessed with the Bayley Mental Scales of Infant Development and two of the Uzguris-Hunt Ordinal Scales. Intervention group mothers were rated significantly higher on sensitivity, cooperation, appropriateness of interaction, and appropriateness of play (P less than .05). Experimental infants were advanced on the Vocal Imitation ordinal scale. This study shows the effectiveness of this intervention on both the mother-infant relationship and infant development and supports pediatric involvement in this biosocial approach to well child care.

Outcome in children with fetal mild ventriculomegaly: a case series.

Mild enlargement of the lateral ventricles is associated with schizophrenia and other neurodevelopmental disorders. While it has been hypothesized that ventricle abnormalities associated with neurodevelopmental disorders arise during fetal brain development, there is little direct evidence to support this hypothesis. Using ultrasound, it is possible to image the fetal ventricles in utero. Fetal mild ventriculomegaly (MVM) has been associated with developmental delays in early childhood, though longer-term neurodevelopmental outcome has not been studied. Follow-up of five children (aged 4--9 years) with mild enlargement of the lateral ventricles on prenatal ultrasound and two unaffected co-twins is reported: one child had attention deficit hyperactivity disorder (ADHD), one had autism, and two had evidence of learning disorders. These cases suggest that the mild enlargement of the lateral ventricles associated with these neurodevelopmental disorders arises during fetal brain development and can be detected with prenatal ultrasound. In addition, the presence of mildly enlarged, asymmetric ventricles in two children on prenatal ultrasound and on follow-up MRI at age 6 years indicates that ventricle structure present in utero can persist well into childhood brain development. The study of fetal ventricle development with ultrasound may provide important insights into neurodevelopmental disorders and allow the identification of children at high risk.

MRI morphometric analysis and neuropsychological function in patients with neurofibromatosis.

Volumes of cerebral gray and white matter were measured in 22 children with neurofibromatosis type 1 (NF1) and in 20 controls. Judgment of Line Orientation (JLO) and the Developmental Test of Visual-Motor Integration (DTVMI) were administered to 16 of the NF1 patients. General linear models analysis of covariance revealed significantly larger brain volumes in NF1 children than in controls, particularly in white matter, and particularly in girls. JLO and DTVMI performance were positively related to right-hemisphere gray-matter volume. The results implicate a failure of growth control in NF1, leading to aberrant neurodevelopment. Our findings also suggest a basis for refined understanding of learning disabilities, which are a prominent feature of NF1.

Satieties and cross-satieties for three diets in the rat.

In food-deprived rats, intake of a 2 M glucose solution is independent of deprivation level. However, subsequent intake of laboratory chow does vary with deprivation, though the immediately-preceding glucose meal did not. If deprivation is severe, the rat may eat as much chow as if the prior glucose meal had not occurred. In the converse case, a preload of chow has no suppressant effect whatever on intake of glucose, at any deprivation level. As with chow, intake of milk after a glucose load varies with food deprivation, even though the preceding intake of glucose did not. In contrast to the chow case, however, there is cross-satiety between milk and glucose in both directions; a meal of either one suppresses subsequent intake of the other. We conclude: (1) Intake of different diets is limited (satiated) by different postingestive mechanisms with different functional properties; some are sensitive to deprivation, others not. (2) Offering a new diet can change the properties of satiety, as if it recruited a new satiety mechanism and disengaged the old one. (3) The interactions among different satiety mechanisms are complex and non-reciprocal. Glucose and milk both contribute to a satiety mechanism that limits intake of both. A glucose preload can augment or accelerate satiety for chow, and thus reduce chow meal size; but the converse is not true. A single state or variable, "satiety" in the abstract, probably does not exist.

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and polymerase chain reaction for differentiation of Prevotella intermedia and Prevotella nigrescens.

Isolates previously thought to be Prevotella intermedia have been shown to be a closely related species now known as Prevotella nigrescens. The purpose of this study was to determine the efficacy of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and polymerase chain reaction (PCR) to differentiate endodontic isolates of P. nigrescens from P. intermedia. Fifty-six strains of black-pigmented bacteria isolated from endodontic infections and conventionally identified as P. intermedia were used in this study. Using SDS-PAGE, novel polypeptide bands were used to differentiate P. nigrescens from P. intermedia. PCR was accomplished with specific primers for the 16S ribosomal RNA gene of both strains. Of 56 endodontic isolates, 41 (73%) strains were identified by SDS-PAGE as P. nigrescens and 15 (27%) strains as P. intermedia. Of the 41 strains of P. nigrescens identified by SDS-PAGE, PCR identified 37 strains as P. nigrescens. Restriction endonuclease digestion of amplified 16S ribosomal RNA genes indicated that the remaining four strains originally identified by SDS-PAGE as P. nigrescens were actually strains of Prevotella distinct from P. nigrescens and P. intermedia. Of 15 strains of P. intermedia identified by SDS-PAGE, PCR identified 14 strains as P. intermedia; but, one strain was identified as P. nigrescens. The results indicated that PCR was a more precise method than SDS-PAGE to differentiate P. intermedia from P. nigrescens. This study confirms that P. nigrescens is more commonly isolated in pure culture from endodontic infections than P. intermedia.

Neuropsychologic and academic functioning of children with sickle cell anemia.

This study compared neuropsychologic test results and academic functioning among 28 school-age children with sickle cell anemia (SCA), and 28 healthy, age-, sex-, and socioeconomically matched black peers followed at a tertiary care center. Children with SCA scored significantly lower on reading and spelling achievement scores than healthy matched peers. Also, older children with SCA performed significantly less well on tests of visual-motor and attention skills than younger children with SCA. These results were unrelated to most measures of physical illness severity. The data suggest that sickle cell anemia may be associated with subtle neuropsychological and learning deficits that can contribute to decreased school performance.

Portal blood flow in beef steers: comparison of techniques and relation to hepatic blood flow, cardiac output and oxygen uptake.

We compared two techniques for measuring blood flow through portal-drained viscera (PDV) of beef steers and measured portions of cardiac output and total oxygen uptake attributable to PDV and hepatic tissues. Four steers (198 +/- 2 kg), equipped with chronic catheters in appropriate vessels, a transit-time ultrasound probe around the hepatic portal vein and a temporary cardiac output thermodilution catheter, were fed a 60:40 hay: concentrate diet. Treatments, designed to alter blood flow, were: 12 equal meals every 2 h (CNTL); CNTL plus 2 mg clenbuterol in one meal (CLEN); and a 65-h fast (FAST). Blood flow through PDV was measured by dilution of p-aminohippurate (PAH) and transit-time ultrasound. Hepatic blood flow was measured by PAH dilution and cardiac output was measured by thermodilution. Blood flow measured by transit-time ultrasound was consistently slower (45%, P less than .01) than blood flow measured by PAH dilution. Necropsy revealed anatomical constraints that precluded proper placement and function of the flow probes. Cardiac output (liters/h) was greater (P less than .05) for CLEN (3,082) than for CNTL (1,655) or FAST (1,047). Percentage of cardiac output flowing through PDV and hepatic tissues was less (P less than .05) for CLEN (23 and 24%) than for CNTL (31 and 38%) or FAST (32 and 38%). Whole body oxygen uptake (mmol/h) was greatest (P less than .05) for CLEN (4,220), intermediate for CNTL (2,999) and least for FAST (1,965). Percentage of oxygen uptake attributable to hepatic tissues was greater (P less than .05) for FAST (31%) than for CLEN (18%), with CNTL intermediate (24%). Percentage of oxygen uptake attributable to PDV (22%) was not affected (P greater than .05) by treatments.

Effects of dietary concentrate level on nutrient absorption, liver metabolism, and urea kinetics of beef steers fed isonitrogenous and isoenergetic diets.

Six multicatheterized beef steers (421 +/- 21 kg BW) were used to predict the effect of dietary concentrate level on blood flow and net flux of urea and other metabolites across splanchnic tissues. Diets ranged from 0% (switchgrass hay) to 90% concentrate (10% switchgrass hay, 89% cracked corn, 1% urea). Daily DMI varied from 8.01 to 5.34 kg/d. Nitrogen intake (99 g/d) and calculated ME intake (16.8 Mcal/d) were equal among diets. As dietary concentrate increased from 0 to 90%, liver blood flow decreased from 850 to 795 L/h, portal-drained visceral (PDV) blood flow decreased from 750 to 620 L/h, and mesenteric-drained visceral (MDV) blood flow decreased from 270 to 250 L/h. Liver release of urea N was 94 mmol/h when dietary concentrate was less than 20%, then increased to 146 mmol/h at 55% concentrate. Urinary excretion of urea N was 13 mmol/h or less when dietary concentrate was 20% or less, increased to 53 mmol/h at 55% concentrate, then continued to increase to 76 mmol/h at 90% concentrate. Transfer of urea N to PDV ranged from 71 to 91 mmol/h and transfer to MDV ranged from 0 to 10 mmol/h among diets. As dietary concentrate increased from 27 to 63%, VFA release by PDV decreased, net MDV and splanchnic release of glucose increased, and splanchnic tissues switched from net uptake to net release of L-lactate. Net PDV release or liver removal of ammonia or alpha-amino N and net liver release of glucose were not affected. We conclude that the liver responded to changes in the percentage of dietary concentrate by altering urea production and by altering the role of lactate in intermediary metabolism.

Plasma flow and net nutrient flux across gut and liver of cattle fed twice daily.

The objectives of this study were 1) to quantify daily patterns of plasma flow and metabolite flux through portal-drained viscera (PDV) and liver in cattle fed twice daily and 2) to identify an interval for blood sampling that would approximate the average daily plasma flow and nutrient flux values. Data are from three experiments in which multicatheterized cattle were fed at or near ad libitum intake twice daily. Five lactating primiparous Holstein cows (506 kg, fed at 0730 and 1930) ate 17.3 kg DM/d as chopped alfalfa hay:corn grain plus supplement (urea and minerals) 50:50 (Exp 1). Five beef steers (474 kg, fed at 0900 and 2100) ate 8.3 kg DM/d as chopped switchgrass hay:corn grain plus supplement 37:63 (Exp 2). Six beef steers (306 kg fed at 0900 and 2100) ate 6.9 kg DM/d as chopped alfalfa hay (Exp 3). Plasma flow (by dilution of para-aminohippurate) was measured hourly for 24 h. Plasma flows (mean +/- SE) through PDV were 1,264 +/- 147, 538 +/- 56, and 499 +/- 26 L/h for Exp. 1, 2, and 3, respectively. Corresponding liver flows were 1,662 +/- 216, 642 +/- 41, and 591 +/- 30 L/h. The within-animal differences from their respective daily means were estimated as a function of time of day using nonparametric smoothing. Across experiments, PDV and liver flows were above the daily mean from 1200 to 1400, were not different from the daily mean from 1600 to 1700, and were below the daily mean from 1930 to 2130. Metabolites measured were ammonia, urea, alpha-amino N, and glucose. In general, metabolite flux was not different from the average daily mean values between 1200 and 1600. Blood sampling over 12 h or one 12-h feeding cycle is sufficient for daily plasma flow and metabolite flux estimation in cattle fed twice daily.

Multiple radiopaque masses in the jaws.

In this report, the less common oral findings occurring in Gardner's syndrome are described, which occurred concurrently with colorectal polyposis. In addition, what clinically appeared as small intestinal polyps, microscopically represented nodular lymphoid hyperplasia, as reported in the literature. Review of the literature showed the oral findings reported here are not common and that enzyme assays can help detect polyps at an early stage of this complex syndrome.

Exophytic mass of the floor of the mouth.

A tissue mass in the floor of the mouth was found to be an unusual, exophytic squamous cell carcinoma. The patient also had synchronous hepatic metastasis from an occult primary adenocarcinoma. The case is discussed from the standpoint of the differential diagnosis of lesions that may appear as masses of the floor of the mouth. Individuals with one primary cancer are at increased risk for developing second malignancies which may be in either the same anatomic area or in other organ systems. This case report emphasizes the need for the clinician to periodically follow-up any patient with a history of malignancy.

Rapidly expanding pigmented lesion of the buccal mucosa.

A case of oral melanoacanthoma was presented. The differential diagnosis of pigmented lesions of the oral mucous membrane includes a wide variety of categories of disease including local and systemic manifestations of hereditary and developmental conditions, reactive and inflammatory lesions, neoplasms, and metabolic diseases. For some of these lesions the histopathological pattern is diagnostic; for others, the tissue structure and organization are nonspecific and intelligent evaluation requires clinicopathological correlation. This discussion of oral mucosal pigmented lesions emphasizes the importance of the clinical parameters in the differential diagnosis of this group of lesions.

Mixed density lesion of the anterior maxilla.

A case of COC which developed as a mixed lucent-opaque lesion in the anterior maxilla of a young person is discussed from the standpoint of clinical and radiographic differential diagnosis. Current concepts of the pathology of the COC and EOGCT are discussed.