Association between rs11001553 of DKK1 and non-syndromic tooth agenesis in the Chinese Han population.

Tooth agenesis is one of the most common anomalies of human dentition. Recent genetic studies have provided information regarding a number of genes related to both syndromic and non-syndromic forms of hypodontia. In a previous study, we found that polymorphism in rs11001553 of DKK1 was associated with hypodontia in the Chinese Han population. In this study, we extended this investigation to 89 individuals diagnosed with sporadic non-syndromic oligodontia (40 males and 49 females). These individuals were analyzed with 268 subjects (123 males and 145 females) diagnosed with non-syndromic hypodontia and 190 healthy control subjects (99 males and 91 females). DNA was obtained from whole blood or saliva samples and genotyping was performed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Significant differences were observed in the allele and genotype frequencies of rs11001553 of DKK1. These data demonstrated an association between rs11001553 of DKK1, a tooth development-associated gene, and non-syndromic tooth agenesis in Chinese Han individuals. This information may provide further understanding of the molecular mechanisms of tooth agenesis. Furthermore, DKK1 can be regarded as a marker gene for the risk of tooth agenesis.

Application of multiple correspondence analysis to asses the relation between time after transplantation and sympathetic activity in cardiac transplant recipient.

The aim of the present study was to evidence that the heart reinnervation can occur and it is related with the time after transplantation (evolution with time). Data were evaluated using Multiple Correspondence Analyses (MCA), which is the ideal method to study the relation, probably nonlinear, between the Time After Transplantation (TAT) and the probable restoration of normal heart rate responses of sinus node regulated by the autonomic nervous system. Twenty four nonrejecting transplant recipients (60 +/- 48 months after transplantation) and nine healthy subjects were studied by heart rate variability parameters. Results showed that sympathetic activity is restored some time after transplantation. Until 48 months, the recent HTR are in direct correlation to low values SD and LF and for the oldest transplant recipient, these parameters are similar to that observed in normal subjects.

Design of a methodology for assessing an electrocardiographic telemonitoring system.

Recent studies in Bioengineering show a great interest in telemedicine projects, it is motivated mainly for the fast communication technologies reached during the last decade. Since then many telemedicine projects in different areas have been pursued, among them the electrocardiographic monitoring, as well as methodological reports for the evaluation of these projects. In this work a methodology to evaluate an electrocardiographic telemonitoring system is presented. A procedure to verify the operation of Data Acquisition Module (DAM) of an electrocardiographic telemonitoring system is given, taking as reference defined standards, and procedures for the measurement of the Quality of Service (QoS) parameters required by the system in a Local Area Network (LAN). Finally a graphical model and protocols of evaluation are proposed.

Stress ECG and laboratory database for the assessment of diabetic cardiovascular autonomic neuropathy.

Development of a diabetic patient database in order to study Cardiovascular Autonomic Neuropathy (CAN) using as a primary source, stress ECG is presented. The selected platform (ecgML) allows user-friendly environment to analyze and interpret graphs, signals and data. It also allows the ability to perform annotations and reports done by users from different fields. In order to feed the database, the input data is codify using MatLab. The database is composed by two populations: 1) Type 2 Diabetes mellitus group and 2) a control group with no medical history of cardiovascular disease. At the present, there are 62 records available from these two groups. The database also contains laboratory parameters, concurrent medical diagnoses reports verified by cardiologists and other clinicians, automatic annotations for each beat and trend series from parameters extracted from the ECG signals such as RR intervals and ST segment measurements. All this information will become very useful for CAN investigations.

LF/(LF+HF) index in ventricular repolarization variability correlated and uncorrelated with heart rate variability.

The purpose of this study, was to asses whether LF/(LF+HF) obtained from ventricular repolarization variability (VRV) reflects the state of sympathovagal balance. The VRV time series and heart rate variability (HRV) time series from seventy two electrocardiogram (ECG) records in four different autonomic nervous system (ANS) profiles (athletes, cardiac transplant patient, heart failure patients and normal subjects) were extracted. A dynamic linear parametric model was applied to separate the VRV in two parts, VRV correlated with HRV (VRV(r)) and VRV uncorrelated with HRV (VRV(u)). Spectral indices were obtained from HRV, VRV, VRV(u) and VRV(u) time series. Changes of these indicators from rest to tilt position were analyzed. Results showed that: i) only LF/(LF+HF) from HRV time series increases significantly from rest to tilt in all ANS profiles, this information could not be retrieved in the other three series (VRV, VRV (u) and VRV(u)) ii) LF/(LF+HF) index in HRV series are significantly different between normal subjects and heart failure patients, while cardiac transplant patients show a low coherence between HRV and VRV power spectra and iii) HF rhythm in VRV series seem to be related to the mechanical effect of respiration.

Maternal or fetal origin of rhesus monkey (Macaca mulatta) amniotic fluid leukocytes can be identified by polymerase chain reaction using the zinc finger Y gene.

Leukocytes can be found in substantial numbers within the intrauterine tissues and amniotic fluid of women, and play a central role in the pathophysiology of infection-related preterm labor by their production of proinflammatory mediators. It remains unclear whether these leukocytes represent a fetal immune response, a maternal response, or a combination of the two. The objective of this study was to develop a test in the rhesus monkey (Macaca mulatta) suitable for determining the percentage of male fetal cells present in a population of leukocytes recovered from blood or amniotic fluid. We found inadequate specificity for rhesus monkey cells using commercial human Y-chromosome paint kits (fluorescence in situ hybridization (FISH)). Human-specific primers for the repetitive Y chromosome DYZ-1 locus employed in the polymerase chain reaction (PCR) produced an unacceptable percentage of false positives. However, we successfully developed a PCR-based test using rhesus-specific primers for the zinc finger Y (ZFY) locus. Densitometry of PCR products from known ratios of male and female adult peripheral leukocytes generated a linear standard curve which provided quantitative results and required only 400 cells per sample. The rhesus beta globin (RBG) gene served as an internal control. The PCR test correctly discriminated the sex of peripheral leukocytes in 20 adult males, 20 adult females, two male fetuses, and one female fetus. Serial samples of amniotic fluid from four chronically catheterized rhesus monkeys bearing male fetuses were used to confirm the utility of this assay for quantifying fetal cells in amniotic fluid. In conclusion, we have developed a PCR test which is suitable for distinguishing male from female cells in adult and fetal blood and in amniotic fluid, which lends itself to a variety of diagnostic and biologic applications in the rhesus monkey and potentially in other nonhuman primates.

Absence of gender differences in clinical outcomes in patients with cardiogenic shock complicating acute myocardial infarction. A report from the SHOCK Trial Registry.

OBJECTIVES: The aim of this study was to assess the impact of gender on clinical course and in-hospital mortality in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). BACKGROUND: Previous studies have demonstrated higher mortality for women compared with men with ST elevation myocardial infarctions and higher rates of CS after AMI. The influence of gender and its interaction with various treatment strategies on clinical outcomes once CS develops is unclear. METHODS: Using the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK? (SHOCK) Registry database of 1,190 patients with suspected CS in the setting of AMI, we examined shock etiologies by gender. Among the 884 patients with predominant left ventricular (LV) failure, we compared the patient demographics, angiographic and hemodynamic findings, treatment approaches as well as the clinical outcomes of women versus men. This study had a 97% power to detect a 10% absolute difference in mortality by gender. RESULTS: Left ventricular failure was the most frequent cause of CS for both gender groups. Women in the SHOCK Registry had a significantly higher incidence of mechanical complications including ventricular septal rupture and acute severe mitral regurgitation. Among patients with predominant LV failure, women were, on average, 4.6 years older, had a higher incidence of hypertension, diabetes and a lower cardiac index. The overall mortality rate for the entire cohort was high (61%). After adjustment for differences in patient demographics and treatment approaches, there was no significant difference in in-hospital mortality between the two gender groups (odds ratio = 1.03, 95% confidence interval of 0.73 to 1.43, p = 0.88). Mortality was also similar for women and men who were selected for revascularization (44% vs. 38%, p = 0.244). CONCLUSIONS: Women with CS complicating AMI had more frequent adverse clinical characteristics and mechanical complications. Women derived the same benefit as men from revascularization, and gender was not independently associated with in-hospital mortality in the SHOCK Registry.

Redox signal transduction by the ArcB sensor kinase of Haemophilus influenzae lacking the PAS domain.

The Arc (anoxic redox control) two-component signal transduction system of Escherichia coli, which comprises the tripartite ArcB sensor kinase and the ArcA response regulator, modulates the expression of numerous operons in response to redox conditions of growth. We demonstrate that the arcA and arcB genes of Haemophilus influenzae specify a two-component system. The Arc proteins of the two bacterial species sufficiently resemble each other that they can participate in heterologous transphosphorylation in vitro. Moreover, the Arc system of H. influenzae mediates transcriptional control according to the redox condition of growth both autologously in its own host and homologously in E. coli, indicating a high degree of functional conservation of the signal transduction system. The H. influenzae ArcB, however, lacks the PAS domain present in the region of E. coli ArcB linking the transmembrane to the cytosolic catalytic domains. Because the PAS domain participates in signal reception in a variety of sensory proteins, including sensors of molecular oxygen and redox state, a similar role was previously ascribed to it in ArcB. Our results demonstrate that the ArcB protein of H. influenzae mediates signal transduction in response to redox conditions of growth despite the absence of the PAS domain.

Cutaneous leishmaniasis: a report of two cases seen at a tertiary dermatological centre in Singapore.

Cutaneous leishmaniasis (CL) is not common in South-East Asia and often presents as a granulomatous plaque on the exposed areas, with a high index of suspicion required for diagnosis. Two such cases were seen at the National Skin Centre recently, and both were Gurkha men with a history of travel to Belize. They were treated with intravenous sodium stibogluconate with success. A discussion on CL and its management follows.

Prognostic significance of cerebrospinal fluid cyclic adenosine monophosphate in neonatal asphyxia.

OBJECTIVE: In piglets prolonged asphyxia resulted in decreased cerebrospinal fluid (CSF) 3;,5;-cyclic adenosine monophosphate (cAMP) during recovery; this was associated with reduced pial arteriolar responses to stimuli that use cAMP as a second messenger. We hypothesized that asphyxia in human neonates results in decreased CSF cAMP and that low CSF cAMP is associated with abnormal outcome. DESIGN: We studied 27 infants with evidence of hypoxic-ischemic insult; 19 were term (group 1) and 8 were preterm (group 2). The normal values of CSF cAMP were determined from 75 infants with no asphyxia; 44 were term (group 3) and 31 were preterm (group 4). CSF cAMP was measured by using radioimmunoassay procedures. RESULTS: CSF cAMP levels in infants with asphyxia (groups 1 and 2) were 12 +/- 9. 5 and 7.9 +/- 7.1 pmol/mL, respectively, significantly lower than those of groups 3 and 4 (control infants), that is, 21.1 +/- 8.7 and 27.1 +/- 9.2 pmol/mL, respectively (P <.0001). Among infants with asphyxia, 3 died and 10 had abnormal neurologic outcome. Univariate analysis showed that abnormal outcomes were significantly related to CSF cAMP levels, phenobarbital use, and multi-organ failure. However, only CSF cAMP was retained in the model by stepwise logistic regression. CSF cAMP of 10.0 pmol/mL discriminated between those with normal and those with abnormal neurologic outcome. Low CSF cAMP concentration was associated with abnormal long-term outcome, estimated odds ratio of 12.4 (95% CI, 2.1-109.3; P <.006), and sensitivity, specificity, and positive and negative predictive values of 85%, 69%, 73%, and 80%, respectively. CONCLUSION: CSF cAMP concentrations were decreased in infants with asphyxia. Low CSF cAMP levels were associated with poor neurologic outcome.

[No difference in frequency of family practitioner consultation by Turkish, Surinam and Moroccan 0-14-year-old children from Dutch children, but difference in reason for contact]. / Geen verschil in frequentie van huisartsbezoek door Turkse, Surinaamse en Marokkaanse kinderen van 0-14 jaar en door Nederlandse, maar wel in contactredenen.

OBJECTIVE: To determine whether consultation behaviour of Turkish, Surinam and Moroccan children (0-14 years old) with a GP differs from that of a comparable group of Dutch children. DESIGN: Cohort study with comparison of matched groups. SETTING: 103 general practices in the Netherlands. METHODS: Data on 63.753 children collected in the Dutch National Survey were used. 161 GPs registered all contacts between patient and practice during 1 year (in 4 parts of each 3 months). Sociodemographic characteristics of all 103 practice populations were gathered. For each Turkish, Surinam and Moroccan child a Dutch child was selected with similar age, gender, socio-economic status, degree of urbanisation, season of registration and sickness insurance coverage. Consult frequency, number of encounters per episode of care, morbidity presented, duration of encounter and percentages of encounters during evening, night and weekend were registered. RESULTS: There were no significant differences in consult frequency between the three ethnic groups and their Dutch reference group, nor were there any differences in number of encounters during an episode of care. The morbidity presented did vary compared with Dutch children. Turkish children consulted the GP more often for gastrointestinal problems (relative risk (RR): 1,81) and respiratory problems (RR: 1,27), but less often for ear problems (RR: 0,54). Surinam children consulted the GP less often for musculoskeletal problems (RR: 0,65), but more often for respiratory problems (RR: 1,20). Moroccan children consulted the GP less often for ear problems (RR: 0,51). For a larger percentage of ethnic children the duration of encounter was less than ten minutes. CONCLUSION: Turkish, Surinam and Moroccan children do not consult a GP more often than a comparable group of Dutch children. The morbidity presented differed.

Antiarthritic profile of BF-389--a novel anti-inflammatory agent with low ulcerogenic liability.

BF-389, dihydro-4-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-methyl-2H-1,2- oxazin-3(4H)-one, is a potent, orally active, antiarthritic and analgesic agent with low ulcerogenic potential. A comparison of the activity profiles of BF-389 and naproxen showed similarities in: (1) suppression of developing and chronic adjuvant arthritis (AA); (2) maximal inhibitory response, as shown by the E(max) values in the developing and established AA models; (3) inhibition of bone degenerative changes associated with chronic adjuvant arthritis; and (4) analgesic activity in the acetic acid and phenylquinone writhing assays. Though BF-389 has been shown to be a potent inhibitor of cyclooxygenase, IC50 = 0.84 +/- 0.25 microM against the production of PGE2 in vitro, there is a great difference from most cyclooxygenase inhibitors; it also inhibits the 5-lipoxygenase enzyme. For BF-389, the IC50 for in vitro LTB4 formation was found to be 3.65 +/- 1.19 microM. The ulcerogenic potential of BF-389 was compared to that of naproxen using a five-day in vivo ulcerogenic rat assay. The UD50 for naproxen was found to be approximately 30 mg/kg/day, p.o. Based upon efficacy in the DEV AA and EST AA models, UD50/ED50 values for naproxen were estimated to be 0.7 and 1.9, respectively. For BF-389 the UD50 was shown to be 520 (389-695) mg/kg/day, p.o., and the corresponding UD50/ED50 values were calculated to be 84 and 28, respectively, thus demonstrating the wide margin of safety between efficacy and ulcerogenicity in rats.

Asymptomatic syndrome of polycythemic hyperviscosity: effect of partial plasma exchange transfusion.

We determined the cerebral hemodynamic changes in infants with asymptomatic polycythemic hyperviscosity syndrome and whether treatment with partial plasma exchange transfusion (PPET) would affect hemodynamics as well as outcome. From a routine cord blood hematocrit screening, 71 babies were identified as needing to be tested for polycythemic hyperviscosity. In addition to clinical evaluation, each infant had radial artery hematocrit and viscosity determinations, blood gas determinations, cerebral blood flow velocity studies, cranial ultrasonography, and noninvasive intracranial pressure determination. Babies with symptomatic hyperviscosity (n = 17) were treated by PPET, whereas those with asymptomatic hyperviscosity (n = 28) were randomly selected to have PPET (n = 14) or to be observed (n = 14). The remaining babies (n = 26) with normal viscosity served as control subjects. Both hematocrit and viscosity decreased after PPET but remained unchanged in babies with hyperviscosity who were merely observed. Reversal of cerebral blood flow velocity abnormalities was observed after PPET in the infants with symptomatic hyperviscosity, whereas those who had no symptoms had normal results on Doppler studies at the outset, and no significant changes occurred with either PPET or observation. There were two deaths in the group with symptoms. A total of 46 babies returned for follow-up evaluation at a mean age of 30 +/- 7.7 months. Outcome of the control group was no better than that of those who had hyperviscosity, and outcomes did not differ between the babies with symptomatic and those with asymptomatic hyperviscosity, nor between those treated with PPET and those who were only observed. Multivariate analysis revealed that other perinatal risk factors and race rather than polycythemia or PPET, significantly influenced long-term outcome.

Hb Chad or alpha 223(B4)Glu----Lys beta 2 observed in members of a Surinam family in association with alpha-thalassemia-2 and with Hb S.

Three different hemoglobinopathies, i.e. Hb S, Hb Chad [alpha 23 (B4)Glu----Lys], and alpha-thalassemia-2 (-3.7) have been observed in eight members of a family from Surinam. The proposita had all three abnormalities, while her mother and four of her half-brothers had Hb Chad together with an alpha-thalassemia-2 heterozygosity or homozygosity. Gene mapping and dot-blot analysis of amplified DNA identified a G----A mutation in codon 23 of the alpha 2 alpha 1 hybrid gene resulting in the Glu----Lys substitution. The quantity of the alpha-Chad chain averaged 31.5% in its carriers with an additional alpha-thalassemia-2 heterozygosity [-alpha Chad(-3.7 kb)/alpha alpha], and 43% in the two carriers with an additional alpha-thalassemia-2 homozygosity [-alpha Chad (-3.7 kb)/-alpha (3.7 kb)]. These quantities are considerably higher than those reported for families from Chad, China, and Japan; the low levels of 14.5-24% Hb Chad in members of previously reported cases suggest a mutation on a chromosome with two alpha-globin genes [alpha alpha Chad/alpha alpha or alpha Chad alpha/alpha alpha].

Studies on zoapatle, II. Leucanthanolide, a novel sesquiterpene lactone from Montanoa leucantha ssp. leucantha.

PIP: A sesquiterpene lactone given the trivial name leucanthanolide, from the Mexican zoapatle plant (Montanoa leucantha), long used as an herbal remedy, was isolated and was found to have cytotoxicity but no uterine activity. The compound was isolated from the fraction containing zoapatanol, a substance being investigated for its ability to induce menses, abortion and labor. The compound has a molecular formula of C19H2606, a 5-membered lactone ring, an ester group, and a germacradienolide skeleton. It was evaluated for abortifacient activity in pregnant guinea pigs by intraperitoneal injection on day 22 of gestation. 3 of 5 animals had abnormal fetuses, but there was no evidence of early uterine activity. Cytotoxic testing in vitro was done on KB and P-388 test systems in cell culture. The ED50 of leucanthanolide was 0.57 mcg/ml (KB) and 0.93 (P-388). In comparison, the ethyl acetate fraction had an ED50 of 1.35 mcg/ml and 5.2 mcg/ml respectively.^ieng

Growth retardation and renal osteodystrophy in children with chronic renal failure.

Height, expressed as standard deviation scores for chronological age and for bone age, was studied in relation to glomerular filtration rate, bone age delay, and bone histology in 47 children with chronic renal disease and GFR less than 80 ml/min/1.73 m2. In multiple regression in all 47 patients, only GFR and bone age delay significantly affected height; 40% of children were short (height standard deviation score less than -2) for chronological age, and 9% were short for bone age. Renal osteodystrophy, which only occurred at GFR less than 30 ml/min/1.73 m2, significantly affected height only in children with congenital renal disease and GFR less than 20 ml/min/1.73 m2. Although radiological and biochemical changes of renal osteodystrophy were seen more often in short children, histological bone disease occurred just as frequently in tall children as in short children. Thus much of the observed height retardation in chronic renal failure is associated with delayed skeletal maturation. In addition, although severe renal osteodystrophy may contribute to growth retardation in advanced renal failure, our data suggest that milder degrees of bone disease evident only on histological study cannot be implicated in the etiology of growth failure in chronic renal impairment.

Hematologic and selenium status of low-birth-weight infants fed formulas with and without iron.

Preterm infants with birth weights between 1,001 and 1,600 gm were randomly assigned at one week of age to three groups and fed a standard milk-based formula, the same formula with iron, or a soy-based formula with iron. Hematologic values and selenium status were then studied prospectively for five weeks. Rates of decline in hematocrit and hemoglobin did not differ significantly among the three groups and did not correlate with red cell selenium values or glutathione peroxidase activity. Attainment of vitamin E sufficiency was variable among the infants, with no significant intergroup differences. Plasma selenium concentrations did not change significantly, but plasma glutathione peroxidase activity declined consistently in all three groups. Under the conditions of this study, iron at a concentration of 12 mg/L of infant formula did not accelerate hemolysis; nor was there evidence of a direct association between selenium values and early anemia of prematurity.

[Intestinal pneumatosis. Analysis of 30 cured cases]. / Neumatósis intestinal: Análisis de 30 casos que curaron.

The study included 30 patients with gastroenteritis and pneumatosis intestinalis, seen at the pediatric hospital of the IMSS, who followed a satisfactory course. Complications and associated diseases were found in these patients to be less severe than in other patients who died. Lethality in this type of patients (33%) is analyzed together with the clinical records in 33 cases of death from gastroenteritis and pneumatosis intestinalis during the period from January 1974 to April 1975. It was found that the period of hospital stay was shorter than in the group that recovered; that complications leading to death were severe and of acute evolution among which, bronchopneumonia, septic shock, intestinal infarct and others, predominated. Decrease in lethality may be considered to lie in an earlier diagnosis together with prevention and treatment of pneumatosis intestinalis and its complications.