The influence of vitamin C on systemic markers of endothelial and inflammatory cell activation in smokers and non-smokers.

OBJECTIVE AND DESIGN: To determine the influence of vitamin C supplementation (500 mg, bd, 14 days) on the circulating concentrations of soluble ICAM-1 (a marker of endothelial activation), neopterin (a marker of monocyte activation), and neutrophil elastase (a marker of neutrophil activation) in smokers and non-smokers in a randomised, double-blind, placebo-controlled trial in a hospital setting. SUBJECTS: Twenty smokers (serum cotinine > or = 20 ng ml(-1)) and 20 age- and gender-matched non-smokers (serum cotinine < or = 13.7 ng ml(-1)). RESULTS: At baseline, there was a significant elevation in the concentration of sICAM-1 in smokers (median 247, IQR 199 to 357 ng ml(-1)) compared to non-smokers (median 207, IQR 189 to 227 ng ml(-1); p = 0.014). Vitamin C supplementation did not influence the circulating concentrations of ICAM-1 or neopterin, or leukocyte elastase activity, in smokers, non-smokers, or in the total population. CONCLUSIONS: Markers of monocyte and neutrophil activation were not influenced by smoking status in this study population. However, sICAM-1 concentrations were significantly elevated in tobacco smokers, reflecting tobacco-induced vascular activation that is unaffected by Vitamin C supplementation.

A trial of ciprofloxacin and metronidazole vs gentamicin and metronidazole for penetrating abdominal trauma.

OBJECTIVES: To determine whether a combination of ciprofloxacin hydrochloride and metronidazole hydrochloride would be as effective or more effective than a combination of gentamicin sulfate and metronidazole hydrochloride for preventing infection in patients with penetrating abdominal trauma, to evaluate the factors associated with increased risk of infection, and to determine the serum peak and trough levels of gentamicin with the dosage regimen of 2.5 mg/kg every 12 hours. DESIGN: Randomized double-blind study. SETTING: Level I trauma center. PATIENTS: Eighty-four patients with penetrating intra-abdominal injuries (gunshot wound, 69; stab wound, 15) thought to require laparotomy. INTERVENTIONS: The patients were randomized during treatment in the emergency department to be given a combination of ciprofloxacin hydrochloride, 400 mg every 12 hours, and metronidazole hydrochloride, 500 mg every 6 hours, or a combination of gentamicin sulfate, 2.5 mg/kg every 12 hours, and metronidazole hydrochloride, 500 mg every 6 hours. RESULTS: Of 68 patients with intra-abdominal injuries who could be observed for at least 48 hours after laparotomy, posttraumatic infections developed in 12 (18%), and nosocomial infections developed in 6 (9%). The incidence of posttraumatic infections in patients who were given gentamicin and metronidazole (5/33 [15%]) was not significantly lower than the incidence in patients who were given ciprofloxacin and metronidazole (7 of 35 [20%]; P=.75). The presence of any infection increased the mean+/-SD length of hospital stay from 8.7+/-3.5 days to 23.3+/-10.9 days and increased the mean+/-SD hospital charges from $24 507+/-$9860 to $104920+/-$49083 (P<.001). Univariate analysis showed the factors most significantly associated with infection were as follows: (1) the use of blood transfusions (P<.001), (2) the penetrating abdominal trauma index of 35 or more (P<.002), (3) injury to the colon requiring a colostomy (P=.004), and (4) a trauma score of less than 12 (P<.02). Multivariate analysis showed the only significant factor was the receipt of blood transfusions (F=10.165; P<.005). CONCLUSIONS: Ciprofloxacin and gentamicin, each in combination with metronidazole, were equivalent in their ability to prevent infections after penetrating abdominal trauma; other factors, especially the receipt of blood transfusions, had much more effect on the incidence of infection. Infection greatly increases the length of hospital stay and hospital charges. The use of an increased dosing regimen of 2.5 mg/kg every 12 hours of gentamicin sulfate was effective at obtaining a therapeutic peak serum concentration.

Contribution of individual drugs to gingival overgrowth in adult and juvenile renal transplant patients treated with multiple therapy.

Drug regimens for transplantation often consist of multiple therapeutic agents and may result in drug-induced gingival overgrowth (DIGO). The aim of this study was to investigate the contribution of individual drugs in renal transplant patients. 147 adults (19-84 years) and 60 juveniles (3-18 years) were scored for DIGO and other clinical variables. Duration of treatment, dosage of drugs per kg body weight and serum cyclosporin levels were recorded. 44% of adults and 27% of children had DIGO. All patients were receiving prednisolone. More adults than children were administered cyclosporin, the reverse was true of azathioprine (p<0.01). Explanatory models were evaluated by stepwise ordinal polynomial logistic regression. Statistically significant explanation (p<0.05) of DIGO was afforded by prednisolone, nifedipine and azathioprine concentrations in adults and by cyclosporin, nifedipine and azathioprine concentrations in juveniles. Prednisolone and azathioprine were inversely related to the degree of DIGO. Plaque and irregularity scores, lip coverage and mouthbreathing status showed significant additional explanation in adults, replacing nifedipine and azathioprine in the final model. Irregularity was additionally explanatory in children, but no other clinical variables. A larger proportion of the variance of DIGO was explained by the available variables in children than in adults (pseudo r2=0.50 versus 0.25). The degree of DIGO in renal transplant patients is influenced by the dosage of a number of individual components of multiple drug therapy independently of the presence of local clinical factors.

Adjunctive systemic and locally delivered metronidazole in the treatment of periodontitis: a controlled clinical study.

OBJECTIVE: To compare clinical and microbiological responses following non-surgical treatment of moderate to advanced adult periodontitis using subgingival scaling with and without adjunctive topical or systemic metronidazole. DESIGN: A single blind randomised clinical trial of 90 subjects, stratified for periodontitis disease severity and smoking status, divided into three treatment groups: 1. Subgingival scaling using ultrasonic scalers and local anaesthesia; 2. Subgingival scaling using ultrasonic scalers and local anaesthesia plus seven days of systemic metronidazole (200 mg tds); 3. Subgingival scaling using ultrasonic scalers and local anaesthesia plus two applications of 25% metronidazole gel one week apart in all sites with probing depths more than 4 mm. Evaluations were made before treatment, and 8 weeks and 24 weeks post treatment. MAIN OUTCOME MEASURES: Probing depths, probing attachment levels and bleeding on probing were measured using a Florida probe. Bacterial morphotypes were evaluated with darkfield microscopy. Results were analysed for all sites with baseline probing depths equal to or greater than Florida probe recordings of 4.6 mm using analysis of variance. RESULTS: 84 subjects completed the trial and the three treatment groups did not differ at baseline for any clinical parameter. Mean probing depths were reduced following treatment by greater than 1.6 mm (Group 1 = 1.68 mm, Group 2 = 1.62 mm, Group 3 = 1.74 mm at six months post treatment) but no significant differences were detected between treatment groups at any time point. Similarly, no significant differences were detectable between treatments for changes in mean probing attachment levels, bleeding on probing, plaque scores or proportions of bacterial morphotypes. CONCLUSIONS: This study does not support the routine use of adjunctive metronidazole in the non-surgical treatment of periodontitis.

Metabolic responses and nutritional therapy in patients with severe head injuries.

The severe hypermetabolism and hypercatabolism seen in patients with severe head injuries results in malnutrition that occurs very rapidly and can cause impaired healing and an increased tendency to infection and multiple organ failure. Thus, early adequate nutritional support plays a role in functional outcome. Total enteral nutrition (TEN) is preferred over total parenteral nutrition (TPN), but TPN should be supplied promptly while increasing TEN to a goal of at least 25 to 35 nonprotein kcal/kg/d and 2.0 to 2.5 g protein/kg/d. Nutritional formulas high in branched chain amino acids, glutamine, arginine, vitamins E and C, and zinc may also have some advantages. Growth hormone may improve anabolism. Hyperglycemia, especially glucose levels exceeding 200 mg/dL, must be prevented and/or treated promptly with insulin or decreased glucose intake. Careful monitoring with indirect calorimetry and nitrogen balance studies should help prevent inadequate protein or excessive carbohydrate intake.

The AAPT1 gene of soybean complements a cholinephosphotransferase-deficient mutant of yeast.

Aminoalcoholphosphotransferases (AAPTases) utilize diacylglycerols and cytidine diphosphate (CDP)-aminoalcohols as substrates in the synthesis of the abundant membrane lipids phosphatidylcholine and phosphatidylethanolamine. A soybean cDNA encoding an AAPTase that demonstrates high levels of CDP-choline:sn-1,2-diacylglycerol cholinephosphotransferase activity was isolated by complementation of a yeast strain deficient in this function and was designated AAPT1. The deduced amino acid sequence of the soybean cDNA showed nearly equal similarity to each of the two characterized AAPTase sequences from yeast, cholinephosphotransferase and ethanolaminephosphotransferase (CDP-ethanolamine:sn-1,2-diacylglycerol ethanolaminephosphotransferase). Moreover, assays of soybean AAPT1-encoded enzyme activity in yeast microsomal membranes revealed that the addition of CDP-ethanolamine to the reaction inhibited incorporation of 14C-CDP-choline into phosphatidylcholine in a manner very similar to that observed using unlabeled CDP-choline. Although DNA gel blot analysis suggested that AAPT1-like sequences are represented in soybean as a small multigene family, the same AAPT1 isoform isolated from a young leaf cDNA library was also recovered from a developing seed cDNA library. Expression assays in yeast using soybean AAPT1 cDNAs that differed only in length suggested that sequences in the 5'leader of the transcript were responsible for the negative regulation of gene activity in this heterologous system. The inhibition of translation mediated by a short open reading frame located 124 bp upstream of the AAPT1 reading frame is one model proposed for the observed down-regulation of gene activity.

The effect of restorative materials on the wear of human enamel.

The wear of human dental enamel against amalgam, Concise composite, SR-Isosit Inlay/Onlay composite, Vitadur-N glazed porcelain, unglazed IPS Empress ceramic, and enamel (control) was investigated by use of a modified stress cycling machine. Testing was carried out in water and in citric acid (pH 4) and the enamel-material couples were subjected to 25,000 cycles of wear with a maximum load of 40 N. Tooth profile reduction was measured at baseline and at 5000 cyclic intervals with a computer image analysis program. The depth of the wear scars on material specimens was analyzed with a profilometer. All materials produced increased enamel wear in acid. Vitadur-N glazed porcelain was found to be the most destructive to human dental enamel, and this was closely followed by Empress and enamel.

Cytotoxicity of potential retrograde root-filling materials.

The cytotoxicity of potential retrograde root-filling materials was assessed using the Millipore filter method. A light-cured glass ionomer cement, Vitrebond (VB), and three reinforced zinc oxide-eugenol cements, Kalzinol, IRM and ethoxybenzoic acid (EBA) cement, were compared with amalgam. Twenty standardized pellets of each material, 10 fresh and 10 aged by storage in sterile distilled water for 72 h were produced. Ten filters were included as controls: five filters with a cell monolayer, but without test specimens, and another five without cells but with test specimens. Fresh IRM exhibited the most pronounced cytotoxic effect and the difference was statistically significant compared with all the other materials. There was no statistically significant difference between fresh VB, Kalzinol, EBA cement and amalgam. When aged, Kalzinol was the most cytotoxic and the difference was statistically significant compared with the other materials. Aged IRM was the second most cytotoxic material and this too was statistically different. The cytotoxicity of VB, EBA, and amalgam did not differ significantly from one another.

Fluoride, calcium and inorganic phosphorus concentrations in approximal plaque collected from young adults 1 and 24 h after toothbrushing with fluoride toothpastes.

A within-subject double-blind cross-over study was carried out to examine whether the chemical composition of approximal plaque was altered 1 and 24 h after brushing with fluoride toothpaste. Three fluoride toothpastes were tested, containing either sodium monofluorophosphate with calcium glycerophosphate supplement and calcium carbonate abrasive, a combination of sodium monofluorophosphate and sodium fluoride with the same supplement and abrasive or sodium fluoride with a silica abrasive. A fluoride-free toothpaste with a silica abrasive acted as the control. 19 subjects used the toothpastes separately in randomised order for 1 week each prior to collection of plaque. Contralateral half-mouth approximal plaque samples were collected 1 and 24 h after the last use of each toothpaste. Fluoride, calcium and inorganic phosphorus concentrations of plaque were estimated. The results indicated that brushing with toothpastes containing fluoride and/or calcium supplements resulted in increased concentrations of these constituents in approximal plaque 1 h after brushing. These elevated levels of inorganic ions were not observed in the samples collected 24 h after brushing. It was concluded that the potentially beneficial effect of a raised concentration of fluoride and calcium in approximal plaque observed soon after brushing is lost during the following 24 h.

Relationship between calcium and inorganic phosphorus concentrations of both resting and stimulated saliva and dental plaque in children and young adults.

Calcium and inorganic phosphorus concentrations of both resting and paraffin-wax stimulated whole saliva and dental plaque were estimated in 39 young adults and 98 children aged 12-14 yr. Plaque was collected from the adults after 48 h without tooth-brushing and consumption of a standardized diet. Plaque was collected from the children without any dietary or oral hygiene restrictions. The results from the study with children provided consistent evidence for a statistically significant relationship between salivary and plaque concentrations of both calcium and inorganic phosphorus. However, multiple regression indicated that only the concentrations in the stimulated secretion were directly associated with concentrations in plaque. The apparent relationship between concentrations in resting saliva and plaque was due to correlation between resting and stimulated saliva. These relationships were less apparent in the young adults, in whom the controlled conditions resulted in a narrower range of mineral concentrations in dental plaque.

Relationships between the biochemical composition of both free smooth surface and approximal plaque and salivary composition and a 24-hour retrospective dietary history of sugar intake in adolescents.

The relationships between the composition of both free smooth surface and approximal plaque and salivary composition and sugar intake assessed from a retrospective 24-hour dietary history were investigated. The inorganic phosphorus concentrations of both types of plaque collected from the permanent dentition were directly related to concentrations in stimulated whole saliva of 45 males aged 12-13 years. The calcium, inorganic phosphorus, water-soluble carbohydrate and protein concentrations of free smooth surface plaque were related to both the time since the last reported sugar intake and the amount of sugar and number of sugar intakes consumed in the previous 24 h as assessed from the retrospective diet histories of 75 females aged 14-15 years. A similar relationship with the reported time since sugar was observed for the calcium and carbohydrate concentrations in approximal plaque, but an association with the reported 24-hour sugar intake was not observed. Fewer statistically significant correlation coefficients were observed between the composition of both types of plaque and the reported sugar intake in the male subjects. The results indicate that the composition of both types of plaque are related to the composition of saliva and the time elapsed since the last sugar intake, but the relationship between the composition of plaque and sugar intake may differ between free smooth surface and approximal plaque.

The relationship between the biochemical composition of dental plaque from both approximal and free smooth surfaces of teeth and subsequent 3-year caries increment in adolescents.

The biochemical composition of both types of plaque and the subsequent caries increment were investigated in 39 males aged 11-12 years at the time of plaque collection. The calcium concentration of free smooth-surface plaque was inversely related to both total and approximal 3-year DFS increment (p less than 0.01). A relationship between calcium concentrations in approximal plaque and subsequent caries was restricted to the 3-year increment on approximal surfaces (p less than 0.05). There was evidence for a direct relationship between caries increment and both magnesium and organic phosphorus concentrations in plaque on the free smooth surfaces only (p less than 0.05). In contrast, a direct relationship between total caries increment and both total and intracellular carbohydrate concentrations reached statistical significance for approximal plaque only (p less than 0.05). Regression analysis indicated that the combination of the calcium and inorganic phosphorus concentrations of free smooth-surface plaque and the intracellular carbohydrate concentrations of approximal plaque explained 40% of the variation in subsequent caries increment.

Collection and biochemical analysis of human dental plaque from the approximal tooth surfaces and comparison with plaque from free smooth surfaces.

The composition of approximal plaque was compared with that normally collected from the free smooth surfaces in investigation of 45 males aged 11-14 years and 75 females aged 13 years. Statistically significant differences in calcium, inorganic and organic phosphorus, magnesium, fluoride and carbohydrate were observed between free smooth-surface and approximal plaque. The concentrations were always lower in the approximal sample, ranging from 55 to 70 per cent of those in free smooth-surface plaque. A subsequent comparison in 12 students indicated that the concentration of total lipids in approximal plaque was about twice that of free smooth-surface plaque, a difference which could explain the quantitative disparity in total composition between the two types of plaque in the studies with children. The differences are consistent with approximal plaque having reduced access to a range of environmental factors due to diffusion limitation in its deeper layers.