Nephrotoxicity of ibandronate and zoledronate in Wistar rats with normal renal function and after unilateral nephrectomy.

A previous animal study compared the nephrotoxic effect of ibandronate (IBN) and zoledronate (ZOL), but interpretation of these study results was limited because of the model of minimal nephrotoxic dosage with a dosage ratio of 1:3. The present study investigated the nephrotoxicity of ibandronate and zoledronate in a 1.5:1 dose ratio, as used in clinical practice and compared the nephrotoxicity in rats with normal and with mildly to moderately impaired renal function. We compared rats with normal renal function (SHAM) and with impaired renal function after unilateral nephrectomy (UNX), treated either with ibandronate 1.5mg/kg, zoledronate 1mg/kg or placebo once (1×) or nine (9×) times. Renal function and markers of tubular toxicity were measured over a 27 week period. After last bisphosphonate treatment the rats were sacrificed and kidneys examined histologically. All bisphosphonate treated animals showed a significant tubular toxicity, which was temporary except in the ZOL-UNX-9×-group. Also the renal function was only transiently reduced except in the ZOL-UNX-9×-group. Histologically, bisphosphonate treatment led to cortical tubuloepithelial degeneration/necrosis and medullary tubuloepithelial swelling which were slightly more pronounced in ibandronate treated animals, when compared to zoledronate treated animals, especially with impaired renal function. In contrast to the previous study we found a similar nephrotoxicity of ibandronate and zoledronate in rats with normal renal function. In rats with impaired renal function the peak of toxicity had not even been fully reached until end of experiment in the zoledronate treated animals. The peak of toxicity seems to be more severe and delayed in rats with impaired renal function compared with rats with normal renal function.

Determination of renal tissue ibandronate levels in rats with normal and mildly impaired renal function.

BACKGROUND: After entering the blood, bisphosphonates are immediately bound to bone or excreted unchanged by the kidney. During renal excretion about 0.5% of administrated dosage remains in kidney tissue. The renal tissue level of bisphosphonates (RTL) decreases over time and remains at about 0.15% after 3weeks, but the influence of renal insufficiency (RI) is unclear. METHOD: We investigated the influence of mild to moderate RI on RTL of ibandronate (IBD). First a method for determination of RTL was implemented and validated. We measured RTL in rats with normal renal function (SHAM) and after unilateral nephrectomy (UNX). In each case one SHAM and one UNX groups received one or alternatively 9 times every 3weeks a dosage of 1.5mg/kg IBD. After the last dosage the rats were sacrificed and RTL of IBD were determined. RESULTS: In SHAM-rats IBD concentrations increased from 272.7ng/g kidney after one injection to 428.9ng/g kidney after nine injections (p<0.0001). RTL in UNX rats likewise increased significantly (p<0.0001) from 289.9ng/g kidney to 520.2ng/g kidney. CONCLUSION: Our study found a 1.6 fold increase of RTL in SHAM rats and a 1.8 fold increase of RTL in UNX rats after nine versus one injection. As steady state is generally reached after five half-lives we anticipate no further accumulation on continued treatment.

Inhibition of human angiogenesis with heparin and hydrocortisone.

Angiogenesis is a critical determinant of tumor growth and the development of metastases. Heparin, steroids, and heparin/steroid combinations have been used in a variety of in vitro models and in vivo in animal models as effective inhibitors of angiogenesis. We tested heparin, steroid and heparin/steroid combinations at a variety of concentrations to determine their effect on the human 'angiogenic switch' from a resting to a proliferative endothelium in vessels from three placentas (initiation), and the effect of these compounds on the subsequent growth of a human angiogenic response (promotion). Using full-thickness human placental vein discs cultured in three-dimensional fibrin-thrombin clots, we demonstrated that heparin (300, 3000 micrograms/ml), steroid (350, 3500 micrograms/ml), and combinations of heparin/steroid at these doses effectively blocked both initiation and promotion of a human angiogenic response in a dose-dependent fashion. We also demonstrated that high-dose steroid or heparin/steroid treatment for 15 days resulted in disruption of vessel integrity, while treatment with heparin alone produced a suppressed growth rate but had intact vessel architecture. High-dose heparin/steroid treatment could also disrupt a developed angiogenic response and retard further development of an angiogenic response following the cessation of treatment.

Penetrating neck injuries.

Penetrating neck trauma may be managed operatively or nonoperatively, depending on precise anatomic location. Conservative management of zone II injuries is currently an issue under debate. We present a brief case report followed by a description of the current strategies for operative exploration and diagnostic maneuvers in penetrating neck injuries. Support for both expectant and operative management of zone II injuries is given. We conclude that for zone II injuries, mandatory exploration by an experienced surgeon is a safe approach and that conservative management must be undertaken with extreme caution.

Infections within the peritoneal cavity: a historical perspective.

Physicians in antiquity dreaded abdominal infections. Despite the fact that peritonitis was extremely common, reports of successful surgical interventions were only anecdotal before the past century. Medicine's comprehension of the pathophysiology of the peritoneal cavity is still evolving. The history of our understanding of the process could be considered to be as recent as the current literature. Despite this, the mortality rates for patients with secondary peritonitis have fallen in the last century from almost 100 per cent to less than 10 per cent.

Laparoscopic fundoplication in children with previous abdominal surgery.

BACKGROUND/PURPOSE: In our institution, many children requiring antireflux surgery for gastroesophageal reflux have had previous abdominal surgery, usually gastrostomy tube or ventriculoperitoneal (VP) shunt placement. The authors review their laparoscopic Nissen fundoplication (LNF) experience in children with previous abdominal surgery assessing surgical outcome. METHODS: A total of 82 consecutive LNFs performed at our institution between January 1996 and September 1998 were reviewed. Follow-up ranged from 1 month to 32 months (average, 8.9 months). LNF was performed without dividing short gastric vessels (Rosetti modification) through a standard 5-port technique. RESULTS: A total of 26 of 82 patients (31.7%) had previous abdominal surgery and were divided into 2 groups: gastrostomy (n = 17) and VP shunt (n = 11) with 2 crossovers. A total of 14 of 17 (82.3%) in the gastrostomy group had percutaneous endoscopic gastrostomy (PEG) placement versus 3 of 17 (17.6%) by open technique (open). Four patients in the VP group had multiple surgeries (range, 1 to 10, average, 2.3). LNF was completed in 25 of 26 (96.2%). One operation was converted to an open procedure because of severe adhesions. In 13 of 17 (76.5%) the previous gastrostomy was not taken down. In 4 of 17 (23.5%), the gastrostomy was taken down to complete the procedure: 2 of 3 (66.7%) of the open group versus 2 of 14 (14.3%) of the PEG group. All 11 (100%) of the VP group had successful LNF. Two of 11 (18.2%) had shunt dysfunction at 2 months (shunt infection) and 4 months (clogged distal shunt), respectively. There have been no cases of recurrent reflux, and all gastrostomies and VP shunts were functional at the time of this report. CONCLUSIONS: Previous abdominal surgery is common in children with gastroesophageal reflux disease requiring an antireflux procedure. The authors conclude from these preliminary results that laparoscopic Nissen fundoplication can be performed safely with minimal morbidity and excellent functional results in children with gastrostomies or ventriculoperitoneal shunts.

Periodontal conditions in Swiss Army recruits.

The purpose of the present study was to assess the oral hygiene and periodontal conditions of a young male population representative for Switzerland. 757 Swiss Army recruits were examined for their oral health status including the assessment of Plaque Index (PlI), Retention Index (RI) and Sulcus Bleeding Index (SBI) as well as Probing Depth (PD) and Loss of Probing Attachment (LA). All the teeth of the right maxillary and mandibular dental arch were evaluated on four aspects. One recruit yielded a status of juvenile periodontitis and was excluded from further analysis. 2.3% of the teeth had been lost, mainly as a result of orthodontic therapy. Mean PlI and SBI for all 756 recruits approximated 0.6, while the mean RI was around 0.1. The mean PD was 2.3 mm, and the mean LA of 0.9 mm was measured. PD and LA were slightly higher on proximal than on buccal or oral aspects. Site specific analysis for all parameters are presented. Since only 0.4% of the recruits showed probing depths of greater than or equal to 5 mm and only 1% of the subjects showed LA greater than or equal to 4 mm on any surfaces it may be concluded that severe signs of chronic adult periodontitis are absent in 99% of young male Swiss citizens.

In vivo early human dental plaque formation on different supporting substances. A scanning electron microscopic and bacteriological study.

Different studies have shown that various substances may have an influence on early human dental plaque formation. The purpose of the present study was to compare on tooth substances and supporting prosthetic materials the amount of plaque deposition by SEM and the quantity of selected bacteria using anaerobic culturing techniques. 5 bridges, replacing a missing molar or premolar, were incorporated in 3 patients. In the midbuccal area of each pontic, a semi-precision attachment was placed allowing the insertion of the following test facings: enamel, dentine, non gamma 2-amalgam, alloys of 85% and 55% gold, silver-palladium, chrome-cobalt, chrome-cobalt-titanium, and ceramic. For each material, 2 facings were fabricated. After 4 and 24 hours in situ, bacteriological samples were taken and processed for further identification. After a 2nd period of 4 and 24 hours in situ, the same facings were carefully removed and prepared for SEM-examination. All 4-hour specimens exhibited various areas covered by plaque, the amount of which varied with the different supporting substances. The very smooth surfaces (e.g., gold) harbored sparse deposits, while the rougher (e.g., amalgam) were covered by more plaque. After 24 hours of plaque development, an increase in the number of micro-organisms was noted for all the specimens. After 4 and 24 hours of plaque accumulation, no specific trends suggesting a preferential colonization on the different substances were observed. This study has shown that the amount of early deposits on different substances seems to be related to the degree of their surface roughness, while plaque formation was qualitatively similar.

Microbiological and clinical effects of chlorhexidine digluconate and hydrogen peroxide mouthrinses on developing plaque and gingivitis.

While the ability of chlorhexidine (CHX) to prevent plaque formation and inhibit the development of gingivitis has been well documented in the literature, the therapeutic value of hydrogen peroxide (H2O2) in preventing gingivitis is in dispute. The purpose of this study was to compare the clinical and microbiological effects of an established therapeutic agent, such as chlorhexidine with that of H2O2 in the experimental gingivitis model. Following a period of stringent oral hygiene, 32 subjects were allocated to 1 of 3 treatment groups which were balanced on the basis of their pre-experimental gingivitis scores. The subjects then refrained from any oral hygiene for 21 days. During this period, they rinsed twice a day with either a placebo, 0.12% CHX, or a 1% H2O2 mouthrinse. After 21 days, supragingival and marginal plaque was collected from each subject and assayed for total cultivable microbiota, total facultative anaerobes, facultative Streptococci, Actinomyces, Fusobacterium, Veillonella and Capnocytophaga. At the end of the experimental period, the group rinsing with 0.12% CHX showed 95% reduction in gingivitis incidence, 100% reduction in bleeding sites, and 80% reduction in plaque scores compared to the group rinsing with placebo. Conversely, the group using 1% H2O2 showed a marginal reduction in gingivitis incidence of 15% and a 28% reduction in bleeding sites compared to the placebo group, but no significant reduction in plaque scores. The microbiological results showed that 0.12% CHX was an excellent broad-spectrum antimicrobial agent which significantly reduced the number of both facultative and obligate anaerobes in plaque.(ABSTRACT TRUNCATED AT 250 WORDS)

Bleeding on probing. A predictor for the progression of periodontal disease?

Bleeding on probing (BOP) is a widely used criterion to diagnose gingival inflammation. The purpose of the present retrospective study was to evaluate its prognostic value in identifying sites at risk for periodontal breakdown during the maintenance phase of periodontal therapy. 55 patients who had been treated for advanced periodontitis participated in a recall system for at least 4 years, at regular intervals of 3-5 months. At the start of every appointment, BOP to the bottom of the pocket was registered at 4 sites of every tooth. A random selection of 1054 pockets was made and subdivided into 5 categories according to the incidence of BOP during the last 4 recall appointments. All pockets with a BOP incidence of 4/4 and 3/4 were selected, while only interproximal sites with a BOP incidence of 2/4, 1/4 and 0/4 were chosen. Subsequently, these categories were grouped according to whether or not the attachment level had been maintained from the time prior to the last 4 recall visits. Greater than or equal to 2 mm was defined as loss of clinical attachment. The results indicated that pockets with a probing depth of greater than or equal to 5 mm had a significantly higher incidence of BOP. Patients with 16% or more BOP sites had a higher chance of loosing attachment. Pockets with an incidence of BOP of 4/4 had a 30% chance of loosing attachment. This chance decreased to 14% with BOP of 3/4, 6% with BOP of 2/4, 3% with BOP of 1/4 and 1.5% with BOP of 0/4.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and antibacterial properties of controlled release SnF2.

Two clinical studies were performed to evaluate the safety and efficacy of an intracoronal device for the controlled release of SnF2. SnF2-polycarboxylate cement, containing approximately 72 mg F-, was placed in subjects' molars requiring two-surface restorations. In the trial for safety, eight subjects had the restoration in place for 34 days. The salivary fluoride levels were elevated to a mean of 0.3/10(6) over the experimental period. Urinary fluoride levels were only above baseline levels during the first few days. The restoration's physical properties were adequate; however, subjects experienced gingival irritation in areas where the restoration was contacted with gingiva. In the trial for efficacy, fourteen subjects had either a SnF2-polycarboxylate or a placebo restoration placed in a molar tooth during a 2 week period of no oral hygiene. During the experimental period, the control subjects had higher levels of salivary total CFU, Streptococcus sanguis and Streptococcus mutans: while the subjects with the SnF2 restoration had increased S. sanguis and decreased S. mutans levels. No differences in G.I. or PL 1 scores were noted between groups. Further development of this controlled release system should include using the SnF2-polycarboxylate restoration in more than one tooth per subject to increase the fluoride reservoir, and not allowing the restoration to contact gingival tissues.

The effect of supragingival plaque control on the composition of the subgingival microbial flora in ligature-induced periodontitis in the monkey.

The influence of supragingival plaque control on the subgingival microflora and clinical parameters of ligature-induced periodontitis in the Cynomolgus monkey was investigated. No clinical changes were observed during the six-week experimental period. The total cultivable flora and the proportions of total black-pigmented Bacteroides (BPB) and asaccharolytic black-pigmented Bacteroides decreased significantly in the cleaned test sites as compared to those in the non-cleaned controls. The study suggests that six wk of supragingival plaque control in the presence of periodontal disease may alter the periodontitis-associated microflora in the monkey, but not sufficiently to alter clinical signs of disease in this time period.