Effect of obstructive sleep apnoea on retinal microvascular function: a randomised controlled trial.

PURPOSE: Retinal microvascular endothelial dysfunction is thought to be of importance in the development of ocular vascular diseases. Obstructive sleep apnoea (OSA) causes macrovascular endothelial dysfunction, but the effect of OSA on retinal microvascular endothelial function is not known. We aimed to determine the effect of OSA on retinal microvascular function. METHODS: We conducted a multi-centre, double-blind, randomised, parallel, controlled trial in patients with known moderate-to-severe OSA, established on continuous positive airway pressure (CPAP). Participants were randomised to 14 nights of either continued CPAP or sham CPAP to generate a return of OSA. Retinal vascular responses to flickering light were measured using dynamic vessel analysis both at baseline and after 14 nights of intervention. The primary outcome was the change from baseline to follow-up in the area under the curve of the arteriolar response to flickering light, sham CPAP versus continued CPAP. RESULTS: Nineteen patients were randomised to sham CPAP, and 18 patients were randomised to continued CPAP. There was no significant effect of CPAP withdrawal and return of OSA on retinal responses, with a change in the area under the curve of the arteriole response to flickering light of + 3.8 arbitrary units (95% CI - 10.6 to + 18.2, p = 0.59), sham CPAP versus continued CPAP. CONCLUSIONS: CPAP withdrawal and a return of OSA had no significant effect on retinal microvascular responses. This contrasts with the effect of CPAP withdrawal on macrovascular endothelial function and suggests that OSA has different effects on macrovascular and microvascular endothelial function. ISRCTN 78082983, 23/10/2014, Prospectively registered.

Bacteriophages: an overview of the control strategies against multiple bacterial infections in different fields.

Bacteriophages (phages/viruses) need host bacteria to replicate and propagate. Primarily, a bacteriophage contains a head/capsid to encapsidate the genetic material. Some phages contain tails. Phages encode endolysins to hydrolyze bacterial cell wall. The two main classes of phages are lytic or virulent and lysogenic or temperate. In comparison with antibiotics, to deal with bacterial infections, phage therapy is thought to be more effective. In 1921, the use of phages against bacterial infections was first demonstrated. Later on, in humans, phage therapy was used to treat skin infections caused by Pseudomonas species. Furthermore, phages were successfully employed against infections in animals - calves, lambs, and pigs infected with Escherichia coli. In agriculture, for instance, phages have successfully been used e.g., Apple blossom infection, caused by Erwinia amylovora, was effectively catered with the use of bacteriophages. Bacteriophages were also used to control E. coli, Salmonella, Listeria, and Campylobacter contamination in food. Comparatively, phage display is a recently discovered technology, whereby, bacteriophages play a significant role. This review is an effort to collect almost recent and relevant information regarding applications and complications associated with the use of bacteriophages.

Impact of Concomitant Mitral Valve Surgery With LVAD Placement: Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to evaluate the outcomes of concomitant mitral valve surgery for significant preexisting mitral regurgitation (MR) in patients undergoing continuous-flow left ventricular assist device (CF-LVAD) implantation. Electronic search was performed to identify all studies in the English literature examining concurrent mitral valve surgery in patients with CF-LVAD implantation. Identified articles were systematically assessed for inclusion and exclusion criteria. Of 2319 studies identified, 8 studies were included. Among 445 patients with moderate to severe or severe MR, 113 (25.4%) patients received concurrent mitral valvular intervention during CF-LVAD implantation. There were no significant differences in cardiopulmonary bypass time (MR Surgery 154 min vs. no MR Surgery 119 min, P = 0.64) or hospital length of stay (MR Surgery 21 days vs. no MR Surgery 18 days, P = 0.93). On follow-up, there were no significant differences in freedom from greater than moderate MR (MR Surgery 100% vs. no MR Surgery 74%, P = 0.12) or left ventricular end-diastolic diameter (MR Surgery: 60 mm vs. no MR Surgery 65 mm, P = 0.51). Survival was comparable at 6-months (MR Surgery 77% vs. no MR Surgery 81%, P = 0.75), 1-year (MR Surgery 72% vs. no MR Surgery 80%, P = 0.36), and 2-years of follow-up (MR Surgery 65% vs. no MR Surgery 70%, P = 0.56). The results of our systematic review and meta-analysis of 8 studies consisting of 445 patients demonstrates that the addition of mitral valve intervention to CF-LVAD implantation appears to be safe with comparable survival to those undergoing CF-LVAD implantation alone. Large prospective randomized clinical trials are needed to elucidate whether concomitant mitral valve intervention during CF-LVAD implantation in patients with severe MR is necessary.

Isothermal and kinetic screening of methyl red and methyl orange dyes adsorption from water by Delonix regia biochar-sulfur oxide (DRB-SO).

In this study, Delonix regia seed pods (DRSPs) as a locally available material were refluxed in 90% H2SO4 to yield a novel D. regia seed pods biochar-sulfur oxide (DRB-SO). FTIR, BET, BJH, SEM, EDX, XRD, DSC and TGA were applied to investigate the characterizations of the prepared DRB-SO. Various adsorption parameters like pH effect, dye concentration effect, adsorbent dose, reaction time isotherm and kinetic study were carried out to explain the process of adsorption of methyl orange (MO) and methyl red (MR) onto DRB-SO. Langmuir's adsorption model perfectly explained the adsorption process onto the surface of DRB-SO as a monolayer. The maximum adsorption efficiency of DRB-SO was (98%) and (99.6%) for MO and MR respectively which attained after 150 min with an adsorbent dose of 0.75 g/L. The pseudo-second-order kinetic model best explained the process of adsorption of MO and MR dyes by DRB-SO. The highest observed adsorption amount was as high as 144.9 mg/g for MO dye and 285.7 mg/g for MR dye, comparable with other reported materials based on activated carbon materials. All of the outcomes signposted a prodigious perspective of the fabricated biochar composite material in wastewater treatment. Using the regenerating DRB-SO through an acid-base regeneration process, six cycles of adsorption/desorption were examined. Over the course of the cycles, there was a minor decrease in the adsorption and desorption processes. Also, it was revealed what the most plausible mechanism was for DRB-SO to absorb the ions of the MO and MR dyes.

Impact of lung cancer screening on surgical stage distribution and surgical practice: a regional analysis of patients operated in and out of a screening program.

OBJECTIVES: The aim of this study was to assess variations in surgical stage distribution in 2 centres within the same UK region. One centre was covered by an active screening program started in November 2018 and the other was not covered by screening. METHODS: Retrospective analysis of 1895 patients undergoing lung resections (2018-2022) in 2 centres. Temporal distribution was tested using Chi-squared for trends. A lowess curve was used to plot the proportion of stage 1A patients amongst those operated over the years. RESULTS: The surgical populations in the 2 centres were similar. In the screening unit (SU), we observed a 18% increase in the proportion of patients with clinical stage IA in the recent phase compared to the early phase (59% vs 50%, P = 0.004), whilst this increase was not seen in the unit without screening. This difference was attributable to an increase of cT1aN0 patients in the SU (16% vs 11%, P = 0.035) which was not observed in the other unit (10% vs 8.2%, P = 0.41). In the SU, there was also a three-fold increase in the proportion of sublobar resections performed in the recent phase compared to the early one (35% vs 12%, P < 0.001). This finding was not evident in the unit without screening. CONCLUSIONS: Lung cancer screening is associated with a higher proportion of lung cancers being detected at an earlier stage with a consequent increased practice of sublobar resections.

Predictive network analysis identifies JMJD6 and other potential key drivers in Alzheimer's disease.

Despite decades of genetic studies on late-onset Alzheimer's disease, the underlying molecular mechanisms remain unclear. To better comprehend its complex etiology, we use an integrative approach to build robust predictive (causal) network models using two large human multi-omics datasets. We delineate bulk-tissue gene expression into single cell-type gene expression and integrate clinical and pathologic traits, single nucleotide variation, and deconvoluted gene expression for the construction of cell type-specific predictive network models. Here, we focus on neuron-specific network models and prioritize 19 predicted key drivers modulating Alzheimer's pathology, which we then validate by knockdown in human induced pluripotent stem cell-derived neurons. We find that neuronal knockdown of 10 of the 19 targets significantly modulates levels of amyloid-beta and/or phosphorylated tau peptides, most notably JMJD6. We also confirm our network structure by RNA sequencing in the neurons following knockdown of each of the 10 targets, which additionally predicts that they are upstream regulators of REST and VGF. Our work thus identifies robust neuronal key drivers of the Alzheimer's-associated network state which may represent therapeutic targets with relevance to both amyloid and tau pathology in Alzheimer's disease.

Oxidative stress and redox signaling in CRPC progression: therapeutic potential of clinically-tested Nrf2-activators.

Androgen deprivation therapy (ADT) is the mainstay regimen in patients with androgen-dependent prostate cancer (PCa). However, the selection of androgen-independent cancer cells leads to castrate resistant prostate cancer (CRPC). The aggressive phenotype of CRPC cells underscores the need to elucidate mechanisms and therapeutic strategies to suppress CRPC outgrowth. Despite ADT, the activation of androgen receptor (AR) transcription factor continues via crosstalk with parallel signaling pathways. Understanding of how these signaling cascades are initiated and amplified post-ADT is lacking. Hormone deprivation can increase oxidative stress and the resultant reactive oxygen species (ROS) may activate both AR and non-AR signaling. Moreover, ROS-induced inflammatory cytokines may further amplify these redox signaling pathways to augment AR function. However, clinical trials using ROS quenching small molecule antioxidants have not suppressed CRPC progression, suggesting that more potent and persistent suppression of redox signaling in CRPC cells will be needed. The transcription factor Nrf2 increases the expression of numerous antioxidant enzymes and downregulates the function of inflammatory transcription factors, e.g., nuclear factor kappa B. We documented that Nrf2 overexpression can suppress AR-mediated transcription in CRPC cell lines. Furthermore, two Nrf2 activating agents, sulforaphane (a phytochemical) and bardoxolone-methyl (a drug in clinical trial) suppress AR levels and sensitize CRPC cells to anti-androgens. These observations implicate the benefits of potent Nrf2-activators to suppress the lethal signaling cascades that lead to CRPC outgrowth. This review article will address the redox signaling networks that augment AR signaling during PCa progression to CRPC, and the possible utility of Nrf2-activating agents as an adjunct to ADT.

Predictors of depressive symptoms post-acute coronary syndrome.

OBJECTIVE: We examined the influence of gender on the prevalence of acute coronary syndrome (ACS) and the severity of depressive symptoms post-ACS. METHODS: Patients received a Zung self-assessment questionnaire at hospital discharge for unstable angina (UA) or acute myocardial infarction (AMI) and returned it by mail. Major depressive symptoms were diagnosed based on a summed depressive symptoms (SDS) score of >50. Depressive symptomatology was modeled by stepwise multivariable logistic regression with the following predictors: gender, age, hypertension, diabetes mellitus, history of smoking, hypercholesterolemia, peripheral vascular disease, prior stroke, prior myocardial infarction (MI), and prior percutaneous coronary intervention or coronary artery bypass graft surgery. We also modeled severity of depressive symptoms via stepwise multiple linear regression with the same predictor variables. RESULTS: A total of 944 patients were surveyed: 716 men and 228 women, mean (SD) age, 67 (13) years and 71 (12) years, respectively. Of these patients, 250 (35%) men and 103 (45%) women had depressive symptoms (P = 0.005). No significant difference was observed between men and women in rates of cardiac catheterization; severity of coronary artery disease; treatment with antiplatelet agents, beta-blockers, angiotensin-converting enzyme inhibitors, or statins; or percutaneous or surgical revascularization rates during or post-ACS. Significant predictors of the presence of depressive symptoms were female gender (odds ratio [OR] = 1.64; 95% CI, 1.19-1.28), diabetes mellitus (OR = 1.42; 95% CI, 1.03-1.97), prior MI (OR = 1.56; 95% CI, 1.15-2.20), and smoking (OR = 1.41; 95% CI, 1.01-1.97). Variables significantly associated with a higher severity of depressive symptoms were female gender, prior MI, smoking, and stroke. Men with prior MI had significantly higher mean (SD) SDS scores than did men without prior MI in all age groups (48.4 [11] vs 44.6 [11], respectively; P < 0.001). In addition, significantly more men with prior MI had depressive symptoms compared with those without prior MI (45% vs 32%; P = 0.001). However, prior MI did not appear to affect SDS scores in women (49.1 [12] for prior MI vs 48.5 [12] for no prior MI; P = NS), and there was no significant difference in the percentage of women who had depressive symptoms with or without a history of prior MI. Depressive symptoms were much more severe in women with UA (SDS = 49.0 [12]) compared with women with AMI (SDS = 45.0 [12]; P = NS), or men with AMI (45.0 [12]; P = 0.004) or UA (46.0 [11]; P = 0.007) (analysis of variance, P = 0.003). CONCLUSIONS: Female gender is a significant independent predictor of depressive symptoms and their severity post-UA and post-AMI. History of prior MI is associated with a higher frequency and severity of depressive symptoms in men. These findings call for routine screening for depressive symptoms in men with prior MI and in women who present with ACS.

Short- and long-term outcomes of pneumonectomy in a tertiary center.

BACKGROUND: Surgery is the most important therapeutic modality for lung cancer. Surgical outcomes are normally reported as 30-day or 90-day mortality or 5-year survival; 10-year survival is rarely mentioned in national data or international studies. METHODS: Three hundred and six patients (79% male) underwent pneumonectomy, mainly for lung cancer, from January 1998 to February 2013. Their short- and long-term outcomes up to September 2014 were analyzed retrospectively. The mean age was 64 years (range 22-82 years) and 24% were aged ≥70 years. Thoracoscore was used to calculate the risk of hospital mortality. RESULTS: Operative mortality was 4.5% whereas predicted mortality was 8%. The operative mortality for cancer patients was 3.3%; the national mortality for lung cancer is 6.5%. Only 2 patients died in hospital after a pneumonectomy in the last 5 years. Half of the patients who died in hospital were ≥70 years old; 29% (4 patients) died after urgent operations for nonmalignant disease. Overall 5- and 10-year survival was 32% and 20%. Median and mean survival was 26 and 57 months, respectively. Long-term survival was better in females aged <70 years, in left pneumonectomy patients, and in those with squamous cell lung cancer. CONCLUSION: Our mortality for pneumonectomy was 50% less than the national mortality rate and significantly lower than that predicted by the Thoracoscore for lung cancer. This confirms that pneumonectomy is still an effective modality for the treatment of lung cancer, with low operative mortality and good long-term survival, especially in younger patients.

Gender differences in the link between depression and cardiovascular disease.

OBJECTIVES: Cardiovascular disease is the leading cause of mortality in women costing more than 500,000 lives each year in the United States alone. Major depression in healthy subjects increases cardiovascular mortality in both men and women. The presence of major depression in patients with recent acute myocardial infarction (AMI) or unstable angina more than doubles the risk of cardiac death in both men and women. In the presence of depression, lack of social integration has an additive effect on cardiac events. Depression is more prevalent in women with coronary heart disease (CHD) than in men. Psychologic counseling as well as cognitive behavioral treatment in women post-AMI seems to adversely affect prognosis, whereas it has neutral effects in men. Pharmacologic treatment of depression with serotonin reuptake inhibitors is safe in men and women post-AMI and is particularly effective in patients with recurrent depression. Whether effective treatment of depression lowers cardiac mortality remains to be proven.

Proteolytic and oxidoreductase activity of Treponema denticola ATCC 35405 grown in an aerobic and anaerobic gaseous environment.

The cells of a human oral spirochete, Treponema denticola ATCC 35405, and of seven clinical isolates of this organism obtained from the subgingival dental plaque of periodontitis patients were studied for their ability to grow in an aerobic and an anaerobic environment, and for their profile of peptidohydrolase and oxidoreductase enzymes. The growth yield of aerobically grown cultures was either comparable to or higher than that of anaerobically grown ones regardless of whether prereduced broth, freshly prepared broth or oxidized broth was used. However, elimination of certain supplements from the growth media resulted in poor growth regardless of the nature of the gaseous environment. The microscopic morphology and motility of the cells were not affected by differences in the gaseous atmosphere. Quantitative studies on several peptidohydrolase activities suggest that anaerobically grown cells displayed higher specific activity especially toward N alpha-L-prolyl-2-naphthylamine, indicating that increased synthesis of proline iminopeptidase enzymes (or enzyme) of the cells was associated with anaerobic growth conditions. The formation of enzymes hydrolysing N alpha-benzoyl-DL-arginyl-2-naphthylamine (and the corresponding p-nitroaniline) was not affected to the same extent. Growth experiments suggest that T. denticola ATCC 35405 is a facultatively anaerobic spirochete instead of an obligate anaerobe as reported in previous literature. The quantitative enzyme studies suggest that the gaseous growth atmosphere of the cells can exert a selective effect on the activity levels of certain peptidolytic enzymes of this organism. Such effects were not observed when the whole cells were studied by means of qualitative or semi-quantitative enzyme tests. The activities of catalase, peroxidase and superoxide dismutase of the cells were low and variable. Because of this, it was not possible to relate these oxidoreductase activities to the composition of the gaseous atmosphere.

Unilateral VATER association.

We describe a case of unilateral "VATER association." In addition to the VATER manifestations, the patient had hemihypoplasia, unilateral congenital paralysis of a leg, and delayed ossification of the femoral head and carpal bones. All of the manifestations involved the left side of the body. The only drug exposure identified was a Chinese herbal medicine taken by the mother during early pregnancy.

Plasmid content of some oral microorganisms isolated from subgingival plaque.

Eighty-five strains of bacterial species selected from the predominant cultivable dental plaque flora of patients with different periodontal pathologies were examined for their plasmid content. Microorganisms studied included: Actinomyces viscosus, A. odontolyticus, Bacteroides asaccharolyticus (B. gingivalis), B. melaninogenicus subspecies intermedius, and subspecies melaninogenicus, Capnocytophaga ochracea (B. ochraceus), and Fusobacterium nucleatum. Three B. melaninogenicus isolates showed plasmids of approximately 2.7-2.9 Mdalton (mega-dalton) molecular size. Restriction enzyme digests of the plasmids demonstrated dissimilar patterns when electrophoresed on agarose gels. In other microorganisms, including the Actinomyces species, plasmids were not observed.

Trypsin-like activity in subgingival plaque. A diagnostic marker for spirochetes and periodontal disease?

Taxonomic screening of subgingival plaque organisms with various enzyme assays have shown that Treponema denticola, Bacteroides gingivalis and an unspeciated Capnocytophaga species possess a trypsin-like enzyme (TLE) that can be detected by the hydrolysis of N-benzoyl-DL-arginine-2-naphthylamide (BANA). As these organisms can be considered to be periodontopathic, it was of interest to determine whether this BANA hydrolyzing enzyme could be detected directly in subgingival plaque samples. Subgingival plaque samples were collected from single sites of known pocket depth, and after dispersal by vortexing, aliquots were incubated overnight with BANA and were counted microscopically. The color reactions were developed with fast garnet, read by the eye and classified as positive (red to red-orange), negative (yellow) and questionable. In the BANA-positive plaques, the spirochetes averaged 43% of the microscopic count, whereas in the BANA negative plaques the spirochetes averaged 8% of the microscopic count. The average pocket depth of BANA-positive plaques was 6.7 mm, whereas the average pocket depth of BANA-negative plaques was 4.5 mm. When both of these parameters were combined, the presence of a positive BANA reaction was usually indicative of subgingival plaques containing greater than 34% spirochetes removed from sites that had probing depths of 7 mm or more. Seventy-one per cent of the plaques removed from untreated periodontal patients were BANA-positive, while only 8% of the plaques removed from successfully treated patients seen at maintenance recall visits were BANA-positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial profiles of subgingival plaques in periodontitis.

In this report over 400 subgingival plaque samples taken from over 110 patients were examined microscopically and culturally for 30 bacterial parameters. The patients could be placed into six disease categories based upon clinical criteria. The bacterial profile of each clinical category was generally distinctive of that category. Periodontal patients who had been successfully treated and maintained had plaques that were populated by significantly higher proportions of Streptococcus sanguis, Actinomyces viscosus, A. odontolyticus and S. mutans and significantly lower proportions of B. gingivalis and spirochetes compared to the five untreated disease categories. The spirochetes were the overwhelming microbial type in the plaques of adult periodontitis (AP) patients, averaging about 45% of the microscopic count. The bacteriological results could not distinguish between ADA Type III and IV periodontitis, suggesting that the same type of infection was occurring in an active site in any AP patient. The patients designated as early onset periodontitis (EOP) differed from the other patients by their relative youth and by their significantly higher proportions of Bacteroides gingivalis and/or B. intermedius. Two types of EOP were recognized in which the most diseased variant was characterized by having an average of 49% spirochetes in the plaque. Four localized juvenile periodontitis (LJP) patients were notable in not having detectable A. actinomycetemcomitans. The data indicate that the various types of periodontitis, with the possible exception of LJP are specific anaerobic infections involving spirochetes and to a lesser extent B. gingivalis and B. intermedius.

The bacteriology of acute necrotizing ulcerative gingivitis.

Plaque samples from 22 ulcerated sites in eight patients with ANUG were cultured using quantitative anaerobic procedures and were examined microscopically. The partial characterization of the predominant cultivable flora revealed a constant flora comprised of a limited number of bacterial types and a variable flora composed of a heterogeneous array of bacterial types. This constant flora would appear to be pathognomonic of acute necrotizing ulcerative gingivitis (ANUG) and included the various Treponema and Selenomonas sp., which comprised about 32 and 6%, respectively, of the microscopic count; B. melaninogenicus ssp. intermedius and Fusobacterium sp., which averaged 24 and 3%, respectively, of the viable count. One week of metronidazole treatment caused a prompt resolution of clinical symptoms, which coincided with a significant reduction in the plaque proportions of the Treponema sp., B. melaninogenicus ssp., intermedius and Fusobacterium sp. for at least 2 to 3 months following treatment. Thus, the same anaerobic species which were numerically associated with the ANUG lesion were also selectively reduced in the plaque flora following resolution of the infection. This supports a role for the above species in the ulcerative stage of the lesion but does not demonstrate that these specific anaerobes initiated the infection. although not confirmed by the data, it was proposed that these particular anaerobic species gained ascendency in the plaque as a result of being selected through the availability of host-derived nutrients in individuals who had undergone certain physiological and psychological stresses.

Humoral immune response to selected subgingival plaque microorganisms in insulin-dependent diabetic children.

Juvenile diabetics have been shown to have an increased susceptibility to gingivitis and periodontitis following puberty. However, little data are available on changes in the microbial flora that occur at the onset of puberty. This study was performed to determine if antibacterial antibody titers to selected periodontal disease-associated microorganisms might be helpful in revealing changes in plaque flora at the onset and conclusion of puberty. Sera was obtained from 35 subjects (ages 7 to 18 years) selected from a population of insulin-dependent diabetics. The subjects were given a thorough medical examination which included an assessment of sexual maturation and a dental examination which included the recording of onset and magnitude of bleeding according to the papillary bleeding score. Antibody titers to A. naeslundii (AN), B. intermedius (BI), B. gingivalis (BG), F. nucleatum (FN), A. actinomycetemcomitans (AA), C. ochracea (CO) and T. denticola (TD) were determined using the microELISA. Stratification of antibody titers by age groups (less than or equal to 12 years, 12 to 15 years, greater than 15 years) revealed that titers to AN increased significantly (P less than 0.025, ANOVA) and progressively (P less than 0.05, regression analysis) with increasing age. In contrast, the titers to FN were maximal in the under 12 year group and decreased with age (ANOVA, P less than 0.05; regression analysis, P less than 0.05). There were no significant variations in titers observed for the other microorganisms. Stratification by sexual maturity revealed a similar progressive decrease of the titer to FN (ANOVA, P less than 0.05; regression analysis, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Metronidazole in periodontitis. I. Clinical and bacteriological results after 15 to 30 weeks.

The statistical association of certain anaerobic organisms such as black pigmented bacteroides (BPB) species and spirochetes with clinical signs of active periodontitis, i.e. bleeding upon probing and bone loss, suggests that the lesions may actually reflect a "specific infection" involving these or unidentified species. All the known oral species of BPB and spirochetes are anaerobes which suggests that antimicrobial treatment directed specifically against anaerobes might be effective in periodontal therapy. In this report, the short-term results of metronidazole treatment plus mechanical debridement in patients with extensive periodontal disease and of a double-blind clinical study in which metronidazole plus mechanical debridement is compared to placebo plus mechanical debridement are described. The findings indicate that 1 week of systemic metronidazole can optimize the clinical reduction of pockets and increase the apparent attachment in periodontitis patients who receive concurrent mechanical debridement of their root surfaces. In patients with extensive clinical involvement, metronidazole resulted in a significant reduction in the number of sites exhibiting pocket depths and attachment loss greater than or equal to 7 mm. When metronidazole plus mechanical debridement was compared with placebo plus mechanical debridement in a double-blind study, the metronidazole patients exhibited a significant improvement in those sites initially greater than or equal to 7 mm. The beneficial effect of the metronidazole was associated with a significant and sustained reduction of certain anaerobic organisms such as Bacteroides gingivalis and the large spirochetes. These data indicate that treatment aimed specifically toward the anaerobic component of the plaque flora can be associated with impressive clinical improvements 15 to 30 weeks after the initiation of treatment.

Puberty gingivitis in insulin-dependent diabetic children. I. Cross-sectional observations.

This cross-sectional study examined the gingivitis occurring at puberty in a population of insulin-dependent juvenile diabetics. Seventy-seven children between the ages of 6 and 15 years were examined for gingivitis levels, stages of pubertal maturation and blood levels of glucose and glycosylated hemoglobin. Bacterial plaque was sampled from one or more approximal tooth surfaces of every subject and cultured under anaerobic and aerobic conditions on nonselective and selective media. The total cultivable flora and percentage of certain presumptive periodontopathic bacteria were determined. Before puberty, children with "high" levels of glycosylated hemoglobin also had higher gingivitis levels than children with "normal" metabolic control of diabetes. During puberty, the level of gingivitis increased independently from both fasting blood glucose levels and per cent glycosylated hemoglobin. The microbiota of marginal plaque was predominantly composed of facultatively anaerobic bacteria. The percentages of Capnocytophaga sp and Actinomyces naeslundii were statistically higher at the onset of puberty, suggesting that a specific bacterial shift in the microbial composition of marginal plaque occurs in response to host changes in juvenile diabetic children at this age period.