First-trimester hyperglycosylated human chorionic gonadotropin and development of hypertension.

OBJECTIVE: This study aimed to determine whether urine levels of hyperglycosylated human chorionic gonadotropin (HhCG) in the first trimester are predictive of subsequent development of hypertension during pregnancy METHOD: This prospective cohort study consisted of women seeking care before 12 weeks gestation. A clean catch urine was obtained at the first prenatal visit and tested for HhCG and creatinine levels. The median HhCG levels and multiples of the median (MoM) by gestational age were compared between the groups that either developed hypertension or did not. RESULTS: Urine HhCG were determined for 204 women between 4 weeks 4 days to 11 weeks 6 days. The median HhCG of those who developed gestational hypertension (n = 7) or preeclampsia (n = 15) did not differ from the group that did not (median: 284 ng/mg creatinine vs 365 ng/mg; p = 0.55). If the MoM of HhCG for the no hypertension group was 1.00, the MoM of HhCG for the hypertension group was 0.93 (p = 0.93). A possible association was observed after 10 weeks between low HhCG levels and the development of late-onset hypertension (≥34 weeks). CONCLUSIONS: Prenatal screening for subsequent hypertension is unreliable with a single measurement of maternal urine HhCG at 10 weeks or less.

Phagocytic clearance of electric field induced 'apoptosis-mimetic' cells.

Cells undergoing apoptosis lose lipid asymmetry that is often manifested by the exposure of phosphatidylserine (PS) to the outer surface of the cell membrane. Macrophages and other cell types recognize externalized PS to signal phagocytosis, thereby eliciting a non-inflammatory response. PS exposure is obligatory in the recognition and clearance of apoptotic cells. Here, we find that externally applied moderate electric field induces PS externalization in a mouse B-cell (FOX-NY) membrane without procaspase-3 activation, a major characteristic of apoptotic cells. The field-induced PS inversion is caused as a result of electroporation and/or a process involving membrane reorganizations and recovery that ensues following field exposure. Using a mouse macrophage cell line (J7444A.1) from the same strain, we show phagocytic clearance of PS expressing B-cells and demonstrate that this is in part due to the apoptosis mimicry of the field exposed cells.

Single turnover chemistry and regulation of O2 activation by the oxygenase component of naphthalene 1,2-dioxygenase.

Naphthalene 1,2-dioxygenase (NDOS) is a three-component enzyme that catalyzes cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene formation from naphthalene, O2, and NADH. We have determined the conditions for a single turnover of NDOS for the first time and studied the regulation of catalysis. As isolated, the alpha3beta3 oxygenase component (NDO) has up to three catalytic pairs of metal centers (one mononuclear Fe2+ and one diferric Rieske iron-sulfur cluster). This form of NDO is unreactive with O2. However, upon reduction of the Rieske cluster and exposure to naphthalene and O2, approximately 0.85 cis-diol product per occupied mononuclear iron site rapidly forms. Substrate binding is required for oxygen reactivity. Stopped-flow and chemical quench analyses indicate that the rate constant of the single turnover product-forming reaction significantly exceeds the NDOS turnover number. UV-visible and electron paramagnetic resonance spectroscopies show that during catalysis, one mononuclear iron and one Rieske cluster are oxidized per product formed, satisfying the two-electron reaction stoichiometry. The addition of oxidized or reduced NDOS ferredoxin component (NDF) increases both the product yield and rate of oxidation of formerly unreactive Rieske clusters. The results show that NDO alone catalyzes dioxygenase chemistry, whereas NDF appears to serve only an electron transport role, in this case redistributing electrons to competent active sites.

Modified lactone/carboxylate salt equilibria in vivo by liposomal delivery of 9-nitro-camptothecin.

The lactone stability of camptothecins is critical for their anticancer activity. A stable liposomal 9-nitro-camptothecin formulation was developed to circumvent the drawbacks of low aqueous solubility and lactone instability and to provide sustained release of the agent in blood circulation. The potential merits of the formulation were demonstrated by its profoundly improved lactone stability in vivo, favorable pharmacokinetic and biodistribution characteristics in rats, and enhanced preclinical efficacy in tumor-bearing athymic mice.

Hereditary hemochromatosis.

Genetic (hereditary) hemochromatosis is probably the most common autosomal recessive disorder found in white Americans, of whom about 5/1,000 (0.5 percent) are homozygous for the associated gene. The hemochromatosis gene is probably located close to the HLA-A locus on the short arm of chromosome 6. Homozygous individuals may develop severe and potentially lethal hemochromatosis, especially after age 39. Hereditary hemochromatosis involves an increased rate of iron absorption from the gut with subsequent progressive storage of iron in soft organs of the body. Excess iron storage eventually produces pituitary, pancreatic, cardiac, and liver dysfunction and death may result from cardiac arrhythmias, congestive heart failure, and/or hepatic failure or cancer. Early diagnosis can prevent these excess iron-induced problems. Iron overload owing to HLA-linked hereditary hemochromatosis can be distinguished from other causes of hemochromatosis by liver biopsies and interpretations. Patients at risk for genetic hemochromatosis should be screened, identified, and treated as early as age 20 to prevent or minimize the deadly complications of hemochromatosis. Population screening should include measurements of serum iron concentration, total iron binding capacity (TIBC), percent saturation of transferrin, and serum ferritin concentrations. Family members of hereditary hemochromatosis patients are at increased risk and should be tested. Screening, identification and early treatment (phlebotomies, sometimes in combination with the use of Desferal or other iron-chelating agents) may help prevent or reduce iron-related organ damage and premature deaths. Early diagnosis and treatment will reduce the population of aging individuals with severe, complicated hemochromatosis and dramatically reduce medical costs (billions of U.S. dollars per annum) associated with the management of this disease.

Methodological and nutritional issues in assessing the oral health of aged subjects.

Despite several serious methodological difficulties in epidemiological research on the oral health of elderly subjects, sufficient data are available to conclude that the prevalence of dental diseases is high in persons aged greater than 65 y in the US. An estimated 41% are completely edentulous, and dental caries, including root-surface caries, and destructive periodontal disease are widespread. Whether nutrition is related to the oral health problems of older persons is unclear: this question has received little research attention, and the results have generally been equivocal. There is some evidence that loss of teeth may be associated with suboptimal intake of nutrients and with changes in food preference.

Periodontal disease in adolescents: some clinical and microbiologic correlates of attachment loss.

The influence of several clinical and microbiological variables on the site-specific risk of attachment loss was studied in Navajo Indian adolescents aged 14-19. Diagnoses were made at mesio-buccal sites of the four first permanent molars. Case-control analytical methods were used, with A. actinomycetemcomitans, B. gingivalis, and B. intermedius considered the "risk" variables, and with calculus, gingival bleeding, age, and gender treated as possible confounders. The presence of B. intermedius significantly increased the likelihood that attachment loss would be diagnosed at a site (odds ratio = 2.86). However, this association was confounded by calculus and gingival bleeding; when either or both were present, the effect of B. intermedius was markedly weaker. Step-wise multiple logistic regression analyses showed that, of the variables considered, the combination of calculus, gingival bleeding, and B. intermedius gave the most parsimonious explanation of the presence of attachment loss. The chance that attachment loss would be diagnosed was increased five times when calculus was present, 16.5 times in the presence of both calculus and gingival bleeding, and 37 times when these variables plus B. intermedius were observed at a particular site.

Oral health effects of smokeless tobacco use in Navajo Indian adolescents.

Recent reports have suggested that the use of smokeless tobacco is increasing in adolescents, and is particularly high in Native Americans, causing concern about possible effects on oral health. In this study, 226 Navajo Indians, aged 14-19, were interviewed regarding their use of smokeless tobacco (ST), cigarettes, and alcohol. Midbuccal and mesiobuccal sites on all fully erupted permanent teeth (excluding third molars) were examined for the presence of gingival bleeding, gingival recession, calculus, and loss of periodontal attachment. The oral mucosa was examined for evidence of leukoplakia. 64.2% (145) of the subjects (75.4% of the boys and 49.0% of the girls) were users of ST. Of these, over 95% used snuff alone or in combination with chewing tobacco. 55.9% used ST one or more days per week. 52.2% consumed alcohol, usually beer or wine, and 54.0% smoked cigarettes. 25.5% (37) of the users and 3.7% (3) of the non-users had leukoplakia. The duration (in years) and frequency of ST use (days per week) were highly significant risk factors associated with leukoplakia. However, the concomitant use of alcohol or cigarettes did not appear to increase the prevalence of these lesions. No consistent relationship was observed between the use of ST and gingival bleeding, calculus, gingival recession, or attachment loss, either when comparing users to non-users or when comparing the segment where the tobacco quid was habitually placed to a within-subject control segment. In view of these results, there is little doubt that smokeless tobacco is significantly related to the etiology of leukoplakia. As some evidence exists that smokeless tobacco use is a significant risk factor associated with oral carcinoma, intervention programs to discourage the use of smokeless tobacco by adolescents should be a public health priority.

Periodontal disease in adolescents: epidemiologic findings in Navajo Indians.

A cross-sectional epidemiologic survey was conducted of 618 Navajo Indians, aged 14-19, resident in a boarding school in New Mexico. Periodontal status was assessed by clinical measurements of attachment level and gingival bleeding, and evidence of alveolar bone loss from standardized bitewing radiographs. Attachment level and gingival bleeding were measured at 24 posterior interproximal sites (six sites in each quadrant): the mesio-buccal aspect of the second molar; the disto-buccal and mesio-buccal aspects of the first molar and second premolar; and the disto-buccal aspect of the first premolar. Alveolar bone level was measured from radiographs at the corresponding approximal surfaces of the same teeth. Attachment loss was considered present when the distance from the CEJ to the base of the pocket was greater than 1 mm; bone loss was considered present when the radiographic distance from the CEJ to the alveolar crest was greater than 2 mm, and gingival bleeding was considered present if bleeding occurred immediately after gentle probing. Attachment loss was evident at one or more sites in 88.7% of the population, 45.9% of the subjects had attachment loss at eight or more sites, and 101 subjects (16.3%) had one or more sites with at least 4.0 mm of attachment loss. Bone loss was present at one or more sites in 89.2% of the population, 28.6% had eight or more affected sites, and 4.7% (29 subjects) had one or more sites with at least 2.0 mm of bone loss. Gingival bleeding was evident at one or more sites in 70.6% of the population, and 19.7% had eight or more affected sites.(ABSTRACT TRUNCATED AT 250 WORDS)

The extent and severity index: a simple method for use in epidemiologic studies of periodontal disease.

Periodontal indices such as the PI, PDI and CPITN ignore a substantial amount of the information ordinarily available in epidemiologic studies of periodontal disease. The extent and severity index (ESI) is an attempt to preserve the maximum amount of information from a clinical examination consistent with the need to achieve a reasonable degree of data reduction. The ESI uses estimates of attachment level from probing measurements of 14 sites in one maxillary quadrant and 14 in the contralateral mandibular quadrant. The index is calculated to summarize jointly the extent and the average severity of disease within the group being studied. Application of this bi-variate statistic to a set of epidemiologic data was carried out to illustrate its use. This analysis suggested that disease extent and disease severity are not highly redundant measures and thus provide independently meaningful information. The ESI is a simple, reproducible method which appears to yield an informative description of the periodontal disease status of a population. Use of the index requires only minimal training of examiners. The index is intended to permit direct comparisons among epidemiologic studies of different populations and by different investigators.