Subgingival microflora and treatment in prepubertal periodontitis associated with chronic idiopathic neutropenia

Prepubertal periodontitis affects both primary and permanent dentition. The purpose of this study was to examine the composition of subgingival microflora of the permanent dentition in an 11-year-old Caucasian female, who had premature exfoliation of her deciduous teeth on her 5th year of age, and the response of this condition to the antibiotic therapy and supportive periodontal care. Gingival tissues were highly inflamed and alveolar bone loss was detected radiographically. The girl had experienced frequent upper respiratory tract infections, tonsilitis and recurrent otitis media. Her mother had history of early onset periodontitis associated with chronic idiopathic neutropenia. Blood chemistry tests and immunological examinations were also performed. Subgingival plaque samples were collected from the proximal sites of permanent molars, incisors, canines and maxillary premolars. 27 different microbial species were isolated from the subgingival microflora. Among the predominant species were Porphyromonas gingivalis (17.6%-7.3%), Prevotella intermedia (12.4%-4.7%), Capnocytophaga sputigena (14.4%-10.4%), Capnocytophaga ochracea (13.2%-6.9%) and Actinobacillus actinomycetemcomitans (9.3%-5.5%). Periodontal treatment consisted of scaling, root planing in conjunction with antibiotic administration of Augmentin 312.5 mg and Flagyl 200 mg, each t.i.d. for 10 days. 3 weeks after the antibiotic therapy, bacterial samples were collected from the same sites. All the periodontal pathogens were recovered in lower levels and A.actinomycetemcomitans was almost eliminated in the 3-week period. The evaluation of clinical indices at 3, 6 and 12 months showed that periodontal treatment in conjunction with antibiotics was effective and rapidly followed by marked clinical improvement. The microbiological monitoring at 3, 6 and 12 months after antibiotic treatment and each time prior to supportive periodontal care, revealed that the periodontal pathogens fluctuated in low levels even 12 months after treatment and could be maintained at low level by supportive periodontal care at 3-month intervals.     

Subgingival microbiota in adult Chinese: prevalence and relation to periodontal disease progression

The "checkerboard" Dna-Dna hybridization technology was used to study the epidemiology of 18 microbial species associated with various states of periodontal health and disease, in a sample of 148 Chinese subjects never exposed to systematic dental therapeutic intervention, aged 30 to 39 and 50 to 59 years. Our aims were to: 1) describe the prevalence of these microorganisms; 2) correlate the microbiological and clinical profiles of the subjects; and 3) examine the association between the microbiological variables and the longitudinal changes of periodontal status that occurred over a preceding 10-year period. A maximum of 14 subgingival samples were obtained from each subject-1,864 in all. The frequency of occurrence of the 18 species examined was high in this Chinese population, on both the subject and the tooth site level. However, all species were not found equally capable of reaching high numbers in the subgingival samples and, as a rule, colonized heavily only limited proportions of tooth sites within each mouth. There was a profound increase of certain species such as Porphyromonas gingivalis, Treponema denticola, and Bacteroides forsythus in deep pockets or progressing sites. Multivariate techniques using the subgingival profile could effectively discriminate between deep/shallow pockets and progressing/ stable tooth sites. The microbiological variables showed an enhanced discriminating potential when classifications were performed on the individual subject level. Colonization by P. gingivalis, B. forsythus, Campylobacter rectus, and T. denticola at levels exceeding certain thresholds entailed a significantly increased probability (odds ratios > 4) for an individual subject to harbor deep pockets or progressing tooth sites.     

Identical effects of indomethacin on renal function in healthy uninephrectomized subjects and in healthy control subjects

1. Animal studies have shown that prostaglandins are important for renal function after unilateral nephrectomy. In order to investigate the importance of prostaglandins for renal function in the fully adapted remnant kidney in healthy uninephrectomized subjects, the acute effects of indomethacin on renal haemodynamics, lithium clearance, urinary excretion rates of prostaglandin E2, sodium and water, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and arginine vasopressin were measured in 14 healthy uninephrectomized subjects (median time after nephrectomy 1.7 years) and in 14 matched healthy control subjects. In addition, nine healthy control subjects were studied without indomethacin and served as a time-control group. 2. Before indomethacin ingestion there was a significantly higher single-kidney urinary excretion rate of prostaglandin E2 in the uninephrectomized group (uninephrectomized group, 349.2 fmol/min; control group, 76.6 fmol/min; time-control group, 96.3 fmol/min). 3. Indomethacin ingestion resulted in equal changes in all parameters in both groups. These were significant decreases in glomerular filtration rate (-11.3% versus -14.6%), renal plasma flow (-6.5% versus -13.0%), urinary flow rate (-49.8% versus -49.4%), fractional sodium excretion (-44.5% versus -47.4%), lithium clearance (33.2% versus -23.8%) and urinary excretion rate of prostaglandin E2 (-93.8% versus -86.7%) (uninephrectomized versus control subjects, values are medians). In the time-control group no changes were observed in these parameters. 4. It is concluded that healthy uninephrectomized subjects with a fully adapted remnant kidney have a normal renal response to acute indomethacin-induced inhibition of prostaglandin synthesis.     

Eosinophils in peripheral blood and nasal mucus, in asthmatic and healthy subjects

This article examines common suppositions about the reasons for female predominance (gender discrepancy, sexual dimorphism) in the autoimmune rheumatic diseases. It suggests that estrogenic hormones are an insufficient explanation. Many illnesses similar to rheumatic diseases are not characterized by sexual dimorphism, nor by evident autoimmunity, yet the populations affected have the same hormonal background. In most other illnesses that are sexually dimorphic, an environmental, behavioral, or genetic reason is present. It is likely that rheumatic illnesses will have similar explanations. For the autoimmune rheumatic diseases, further work in the fields of environmental, genetic, chromosomal, and in utero sex differentiation is indicated.     

Serum antibodies reacting with subgingival species in refractory periodontitis subjects

The purpose of this investigation was to compare the levels of serum IgG antibody to 85 subgingival species in 32 refractory periodontitis, 56 successfully treated, and 33 periodontally healthy subjects. Refractory subjects showed mean full mouth attachment loss and/or >3 sites showing attachment loss >2.5 mm within 1 year after 2 treatment modalities, scaling and root planing and surgery plus systemically administered tetracycline. Successfully-treated subjects showed mean attachment level gain and no sites with attachment loss >2.5 mm, 1 year post-therapy. Periodontally healthy subjects exhibited no pocket or attachment level >3 mm, and no evidence of progressing attachment loss during 1 year of monitoring. Baseline serum was obtained from each subject and tested against 85 subgingival species, including reference strains and strains isolated from refractory subjects, using checkerboard immunoblotting. Significance of differences in levels of serum antibody among groups were sought using the Kruskal-Wallis test. Refractory subjects constituted a heterogeneous group based on their serum antibody response to subgingival species. Some individuals had antibody reactions to many subgingival species, while other subjects showed fewer or low numbers of responses. On average, refractory subjects exhibited higher numbers and levels of serum antibody reactions to a wide range of subgingival species than successfully treated or periodontally healthy subjects. Differences in serum antibody among clinical groups were more striking at higher threshold levels of antibody (>50 microg/ml and > 100 microg/ml). The data showed that a subject was 10.1 x more likely to be refractory if the subject exhibited antibody reactions with >9 subgingival species at >50 microg/ml (p<0.001, after adjusting for multiple comparisons). Serum antibody to a subset of the test species differed among the clinical groups. Porphyromonas gingivalis, Bacteroidesforsythus, and some strains isolated from refractory subjects (a novel Neisseria sp., Enterococcus faecalis, Prevotella loescheii and Prevotella oulora) elicited high serum antibody in the successfully treated and refractory subjects. High levels of serum antibody to a Microbacterium lacticum-like organism, Streptococcus oralis, Streptococcus constellatus, Actinobacillus actinonmycetemcomitans serotype c and Haemophilus aphrophilus significantly increased the likelihood of a subject being refractory to conventional periodontal therapy.     

Pharmacokinetic and safety evaluations of ketoprofen gels in subjects with adult periodontitis

This clinical trial used a randomized, partially double-blind, controlled parallel design to evaluate the pharmacokinetics and safety of the NSAID, ketoprofen (KTP), in gel formulations. Forty-two subjects, ages 35 to 57 years, with generalized, moderate to advanced adult periodontitis were recruited and randomized to one of 5 treatments over a 14 1/2-day treatment period: (1) 0.5% KTP gel; (2) 1.0% KTP gel; (3) 1.0% KTP alternate gel; (4) 2.0% KTP gel; and (5) 25 mg KTP capsule (positive control). Plasma samples were obtained on days 1 (pre-dosing, 0.5, 1, 2, 3, 6 hr), 8 (pre-dosing, 2 hr), 15 (pre-dosing, 2 hr), and 22 (7 days post-treatment). Plasma KTP concentrations were determined by means of high-performance liquid chromatography. Significant differences in mean area under the plasma concentration vs. time curve (AUC(0-infinity)) among the groups were detected (p < 0.001), with the 25 mg p.o. capsule exhibiting the largest value (5054 ng-hr/mL), the 2.0% gel exhibiting an intermediate value (2244 ng-hr/mL), the 1.0% gels exhibiting lower but comparable values (1516 for the alternate formulation vs. 1461 ng-hr/mL), and the 0.5% gel showing the lowest value (736 ng-hr/mL). Significant differences in dose- and weight-adjusted maximum plasma concentration (Cmax/dose/kg) were detected overall such that the 25 mg p.o. capsule demonstrated higher values as compared with the 4 gel formulations (p = 0.001). The 5 treatments exhibited similar mean times of maximum plasma concentration (tmax) values ranging from 0.6 to 1 hr. Systemic exposures relative to dose and body weight were lower for the gel formulations than for the capsule. The relative systemic bioavailability of the gels compared with peroral administration ranged from 54% to 69%.     

Different sensitivity to sodium valproate in healthy, non-tumoral and tumoral hyperprolactinemic subjects

GABAergic drugs affect PRL secretion in both rat and man. Sodium valproate (SV) inhibits GABA transaminase so increasing the endogenous GABAergic tone. The aim of this study was to evaluate the effects of SV at low and high doses on PRL release in healthy subjects and hyperprolactinemic patients. Fifteen patients with prolactinomas, 8 patients with non-tumoral hyperprolactinemia and 10 healthy subjects were studied: in non consecutive days, all subjects received placebo and SV at the dose of 400 and 800 mg po. Serum PRL levels were assessed 30, 15 and 5 min before and every 30 min for 4 hours after administration. SV at the dose of 400 mg induced a significant decrease of serum PRL in healthy subjects (p < 0.05), whereas no effect was noted in both tumoral and non-tumoral hyperprolactinemia. The administration of 800 mg SV induced a significant decrease of PRL levels in healthy subjects and in patients with non-tumoral hyperprolactinemia (p < 0.05). Conversely, in prolactinomas a paradoxical increase of serum PRL concentration (p < 0.05) was observed 120 min after the administration of the drug. These data confirm the inhibitory activity of SV on PRL release in healthy subjects, and suggest the existence of a partial resistance to GABA in non-tumoral hyperprolactinemia. In prolactinomas, the paradoxical PRL increase after high dose of SV suggests the existence of a complete pituitary resistance to GABA. This finding might be explained by the appearance of the stimulatory effect of GABA at hypothalamic level that could have been unmasked by the lack of pituitary GABA effects on adenomatous lactotrophs.     

Time perception in organically healthy and brain damaged subjects

The aims of this study were to investigate whether brain lesions are associated with an impairment of time judgement and whether there is any relationship between alterations of time experience and the side and localization of brain lesions. References were made to the literature dealing with different definitions of the concept of time and the notions derived from time as a categorial entity, such as time experience, time perception and time awareness. To begin with, the philosophical and psychological approach was considered. There upon definitions as given by the natural sciences, conceptual classifications, phenomenological investigations as well as psychopathological considerations were analysed. Furthermore, the literature on disorders of time judgement was reviewed against the background of alterations of time experience in patients with brain lesions. In the present study patients with definite single brain lesions were examined and compared with a group of normal subjects. Three methods for testing time judgement (method of production, method of reproduction and time estimation) were applied to each subject. The results showed that in a substantial proportion of brain-damaged patients a subjective impression of changes in the rate at which time passed was reported, mostly in form of an apparent slowing down. No difference could be demonstrated between left or right cerebral lesions or between different localizations within one hemisphere. On the testing for objective time judgement the brain-damaged patients showed a tendency to under-or overestimation of time intervals, often exceeding the pre-established normal boundaries by far. We observed a certain "vulnerability" of the right hemisphere on the tasks for time judgement, especially in the case of right-sided parieto-occipital lesions.     

Effect of triclosan on the subgingival microbiota of periodontitis-susceptible subjects

The present study evaluated the long-term effect of (i) meticulous self-performed, supragingival plaque control and (ii) the use of a triclosan/copolymer containing dentifrice in adult subjects susceptible to destructive periodontitis. 40 individuals were recruited into the trial. 3-5 years prior to the baseline examination, they had all been treated by nonsurgical means- for advanced periodontal disease. During the subsequent maintenance phase, all subjects had at different time intervals exhibited sites with recurrent periodontitis. At a baseline examination, 6 surfaces per tooth were examined regarding bleeding on probing, probing pocket depth, and probing attachment level. The deepest pocket site in each quadrant (i.e. 4 sites per subject) was selected and samples of the subgingival bacteria were taken. At baseline, all volunteers received detailed information on proper oral hygiene techniques. This information was repeated on an individual need basis during the course of the subsequent 36-months. No professional subgingival therapy was delivered between the baseline and the 36-month examinations. The subjects were randomly distributed into 2 equal groups of 20 individuals each, 1 test and 1 control group. The members of the test group were supplied with a fluoridated dentifrice containing triclosan/copolymer (Total, Colgate), while the controls received a corresponding dentifrice but without triclosan/copolymer. The findings demonstrated that in subjects with advanced and recurrent periodontitis, carefully practiced supragingival plaque control had some effects on the subgingival microbiota, but also that this was insufficient to prevent disease progression. In a corresponding group of subjects, however, who used a triclosan/copolymer dentifrice, the subgingival microbiota was reduced in both quantitative and qualitative terms and recurrent periodontitis was almost entirely prevented.     

The rate of periodontal attachment loss in subjects with established periodontitis

A stepwise approach to determine attachment level changes was utilized to assess the nature of progression of periodontal disease. Following initial screening, 51 subjects with established periodontitis were monitored quarterly for 9 more months. Probing depth (PD) and relative attachment level (RAL) were recorded using an automated, pressure sensitive probe system. To establish intra-examiner error, repeated measurements were performed for all sites at the final visit. An overall standard deviation (SD) for RAL repeated measurements was initially calculated (0.76 mm) using all 6,935 double measurements. Sites were sorted by factors which contribute to the error of attachment level measurements; i.e., pocket depth (shallow, moderate, deep), tooth type (molar, non-molar) and location (buccal, lingual). Data were sorted by the above 12 groups, and SD for repeated measurements was calculated separately for them. The ratio between these SD and the overall SD served as the corrective factor. Each patient's initial threshold (2 SD) was multiplied by these corrective factors thus resulting in 12 thresholds for each subject. Next, linear, exponential and logarithmic regression models were tested for each site, and the regression model showing the highest R value was chosen for that site. AL changes were tested against the patient's threshold for that site. Sites with attachment loss exceeding the threshold were deemed active. Five hundred eighty-one sites (8.3%) exhibited attachment loss exceeding the various thresholds. Of these, linear progression occurred in 195, logarithmic in 224, and exponential in 162 sites. Individual patient's attachment loss ranged from 0.6 to 19.4% of all sites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Apolipoprotein E and its alleles in healthy subjects and in atherosclerosis

To examine responses of natural killer cell activity (NKCA) to interleukin-1 beta (IL-1 beta) during pregnancy, we determined splenic NKCA as well as blood and brain indicators in virgin and pregnant rats (14 or 21 days gestation) with intracerebroventricular (i.c.v.) administration of IL-1 beta. NKCA was reduced and blood beta-endorphin (beta EP) was increased with the progress of pregnancy. I.c.v. administration of IL-1 beta reduced NKCA and corticotropin-releasing hormone (CRH) in the median eminence (ME), and increased beta EP in virgin rats, but did not change any parameters in pregnant rats with 21 days gestation. These data suggest that the immunosuppressive effect of central administration of IL-1 beta is blocked by pregnancy. CRH in the ME and opioid system seem to be involved in the inhibitory effect of pregnancy on IL-1 beta-induced immunosuppression.     

Pupillographic assessment of sleepiness in sleep-deprived healthy subjects

Medical research frequently involves the statistical comparison of >2 groups, often using data obtained through the application of complex experimental designs. Fortunately, inferential statistical methodologies exist to address these situations. Analysis of variance (ANOVA) in its many forms is used to simultaneously test the equality of all groups in a study. One-way (with 1 independent variable), 2-way (with 2 independent variables), and repeated-measures (patients serve as their own controls) ANOVAs are forms of this technique. Each form has been developed to analyze data from a specific experimental design. Analysis of covariance (ANCOVA) allows the researcher to control for confounding variables that may influence the response of the dependent variable. Finally, multivariate analysis of variance (MANOVA) evaluates the simultaneous responses of multiple dependent variables to > or = 1 independent variable. Whereas ANOVA is the correct alternative to statistically inappropriate multiple t-tests, MANOVA is the correct alternative to statistically inappropriate multiple univariate ANOVA calculations. Use of each of these statistical methods requires an appropriate experimental design and data meeting a number of assumptions. When used properly, each of these methods provides a powerful statistical analysis technique.     

Comparative pharmacokinetics of cefamandole, cephapirin, and cephalothin in healthy subjects and effect of repeated dosing

Studies on cyclic activity of the thyroid and seasonal variations in oxygen consumption (VO2) under experimental conditions in which surfacing was either allowed or prevented were made in H. fossilis to try to establish a relationship between these measures and to ascertain the possible role of the thyroid in the regulation of metabolic rate. A good correlation was found between the activity of the thyroid and VO2 in this species. This finding was further confirmed by the administration of L-thyroxine or thiouracil to this fish. The thyroxine-and thiouracil-treated animals showed significantly higher (P less than 0-05) and lower (P less than 0-01) rates of VO2 respectively, thus indicating the probable role of the thyroid in the regulation of metabolic rate.     

Reliability of cephalic thermal thresholds in healthy subjects

Reproducibility and normal variation of cephalic warm and cold detection thresholds were investigated in three healthy subject groups. The face, the mastoid process, and the hands were studied. No significant intra-observer test-retest difference (n = 20) was found. Good reliability (intra-class correlation coefficient [ICC] > 0.4) was found for 13 of 14 measurements. A small significant inter-observer difference (n = 20) was found for cold thresholds. Good reliability (ICC > 0.4) was observed for both cold and warm thresholds in most of the test locations (6 of 8). In general, the largest variability was found in the mastoid and frontal lateral regions. Thermal thresholds varied with investigation site in 56 controls (ANOVA, p < 0.0005). No significant gender differences were found for cephalic warm and cold thresholds. Most cold thresholds (4 of 5) but also some warm thresholds (2 of 5) increased with age at the cephalic sites. Our results reveal the frontal medial, the maxillar medial, and lateral regions as the most reliable cephalic test locations. The mastoid region may also be useful for investigating the upper cervical small-fiber function.     

Electrocardiographic changes during insulin-induced hypoglycemia in healthy subjects

Hypoglycemia is associated with alterations of the ECG, a phenomenon which might be used for the development of a hypoglycemia detection device. We investigated the reproducibility and magnitude of ECG alterations during insulin-induced hypoglycemia in nine healthy volunteers. The subjects were studied twice with an identical study protocol on two different study days. During hypoglycemia frequent ECG recordings were done with a conventional 12 lead ECG. S.c. injection of 0.15 U/kg of regular insulin induced a fourfold increase in insulinemia on both study days as well as a mean decline in blood glucose by 1.6 mmol/l to a minimum of 2.8 mmol/l within 60 min after injection. Blood potassium levels declined by a mean of 0.25 mmol/l to minimal values of 3.69 mmol/l. On both study days, a progressive flattening of the T-waves was observed during the experiments. R-waves remained constant leading to an increase in RT ratios by at least 50% in comparison to baseline values. These changes were most pronounced in leads I, V3, V5 and V6. The magnitude and reproducibility of the observed ECG changes during hypoglycemia may allow the development of a hypoglycemia detection device.     

Tolerance and pharmacokinetics of single-dose atorvastatin, a potent inhibitor of HMG-CoA reductase, in healthy subjects

Tolerance and pharmacokinetics after single-dose administration of atorvastatin, an investigational inhibitor of HMG-CoA reductase, were examined in 22 healthy volunteers in a three-period, partially-blinded study. Participants received capsule and solution doses of atorvastatin (0.5 to 120 mg) and placebo at weekly intervals. Atorvastatin was well tolerated at doses as high as 80 mg. The adverse event profile was similar after administration of atorvastatin capsules and placebo. Atorvastatin solution was slightly less well tolerated. The most common side effect after administration of capsules and solution was headache, followed by sporadic reports of diarrhea, flatulence, and nausea. At the 120-mg solution dose, one participant experienced mild, transient restlessness, euphoria, and mental confusion that were considered to be dose-limiting side effects. Mean concentrations of atorvastatin, maximum concentration (Cmax), and area under the concentration-time curve from time 0 to the time of the last detectable concentration (AUCo-tldc) increased with increasing dose. Plasma elimination half-life (t1/2) ranged from 14.7 to 57.6 hours. The bioavailability of atorvastatin capsules was similar to that of solution. These results suggest that atorvastatin is well tolerated after single doses as high as 80 mg, and may require administration only once daily.     

N-acetyl-beta-glucosaminidase, beta-glucuronidase and beta-galactosidase in the leukocytes, serum and urine of healthy subjects and patients with immunocytoma

The activity of GlcNAc-ase, GlcUA-ase and Gal-ase was determined in the leukocytes serum and urine of 23 patients with M. M., 11 patients with other neoplasms including 9 with lymphoreticular proliferative processes without associated monoclonal gammapathy. The range of normal enzyme activity was established in the investigations carried out in 45 health subjects. In the group of patients with M. M. without complications. normal activity of GlcNAc-ase, GlcUA-ase and Gal-ase was found in the leukocytes. In the group of patients with white blood cell count below 2.5 g/l and in cases after long-term treatment with Alkeran the activity of GlcNAc-ase and GlcUA-ase in the leukocytes was reduced. In the patients with M. M. the activity of GlcNAc-ase was raised in the serum and urine, and this activity was higher in cases with longer duration of the disease and more advanced pathological process. The patients with M-IgG protein showed a higher GlcNAc-ase activity in the serum and urine than those with protein M-IgA. A higher activity of GlcNAc-ase in the serum and urine than those with protein M-IgGK than in those with M-IgG gamma. In patients with M. M with renal complications the urinary activity of GlcNAc-ase was higher than in patients with M. M. without renal complications. In CLL the activity of GlcNAc-ase was found to be decreased in the leukocytes and raised in the urine. In patients with Hodgkin's disease the activity of the studied enzymes was raised in leukocytes while the results of their determinations in serum and urine were equivocal.