In vitro caries inhibition effects by conventional and resin-modified glass-ionomer restorations.

The ability of a material to inhibit recurrent caries formation is an important clinical therapeutic property. The objectives of this study were to develop an initial anticariogenicity profile (from fluoride release, to fluoride uptake, to resistance to an artificial caries challenge), testing the ability of conventional versus resin-modified glass-ionomer restorations to resist decay, and to study the effect of using intermediary dentin bonding agent components on the development of surface and wall carious lesions adjacent to a resin-modified glass-ionomer restoration. Cumulative fluoride release was measured from the immersion of disk-shaped specimens into deionized distilled water for 24 hours, 1, 2, 4, and 10 weeks. For the fluoride uptake and artificial caries test, standardized restorations were placed along the cementoenamel junction of extracted human molars. Secondary ion mass spectroscopy was used to determine the depth of fluoride uptake into the adjacent axial dentin from the restoration after 1 and 10 weeks. For the artificial caries test, the teeth were immersed into an acidified gelatin gel, pH 4.0, for 10 weeks. The development of recurrent decay was assessed using polarizing light microscopy. Statistical analyses were conducted using ANOVA and Fishers' LSD test (P < or = 0.05). There was generally greater fluoride release and uptake from the conventional glass ionomers, equivalent or less from the resin-modified glass ionomers, and none from the resin composite restorations. The use of an acid conditioner and primer from a dentin bonding system significantly increased the depth of fluoride uptake at 1 week. The additional use of an intermediary adhesive resin layer, however, significantly decreased the depth of fluoride uptake. The maximum depth of fluoride uptake into dentin was 300 microns at 10 weeks. Both conventional and resin-modified glass-ionomer restorations imparted resistance to dentin against the development of recurrent wall carious lesions in vitro. This was attributed to material fluoride release and uptake.

Clinical trial of fusidic acid for lepromatous leprosy.

Fusidic acid was assessed for antileprosy activity in nine lepromatous leprosy patients. Patients received fusidic acid at either 500 mg/day for 12 weeks or 750 mg/day for 4 weeks followed by 500 mg/day for 8 weeks. All patients showed time-dependent clinical improvement and decreases in bacillary morphological index, radiorespirometric activity and PCR signal, and in serum phenolic glycolipid I. Fusidic acid appears to be a weakly bactericidal antileprosy agent which may have a role in the multidrug treatment of leprosy pending an evaluation of lepra-reaction-suppressive activity.

Clinical trial of clarithromycin for lepromatous leprosy.

Clarithromycin was administered to nine previously untreated lepromatous leprosy patients. Patients received two 1,500-mg doses on the first day, followed by 7 days of no treatment, in order to evaluate the potential efficacy of intermittent therapy. Patients then received 1,000 mg daily for 2 weeks followed by 500 mg daily for 9 weeks. The efficacy of therapy was monitored clinically, by changes in morphological index, mouse footpad infectivity, and radiorespirometric activity of Mycobacterium leprae obtained from serial biopsies and by serum levels of phenolic glycolipid I. Clarithromycin was well tolerated, with only minor side effects noted in two patients. Most patients showed reductions in morphological index and radiorespirometry 1 week after the first two doses. Within 3 weeks of starting treatment (total of 17 g of clarithromycin), biopsy-derived M. leprae specimens from all patients had a morphological index of zero, were noninfectious for mice, and had less than 1% of the radiorespirometric activity of pretreatment specimens. Reductions in serum phenolic glycolipid I levels were observed for most patients at 3 weeks. Significant clinical improvement was evident after 4 weeks of treatment. All analyses indicate that clarithromycin is rapidly bactericidal for M. leprae in humans.

Clinical trial of sparfloxacin for lepromatous leprosy.

Nine previously untreated patients with lepromatous leprosy were treated with 200 mg of sparfloxacin daily for 12 weeks to determine whether this drug is bactericidal for Mycobacterium leprae in humans. The efficacy of therapy was monitored both clinically and by measuring changes in morphological index, mouse footpad infectivity, and the radiorespirometric activity of M. leprae organisms obtained from serial biopsy specimens and also by determining titers of phenolic glycolipid-I in serum. Most patients showed clinical improvement within 2 weeks of treatment; this was accompanied by significant reductions in the morphological index, mouse footpad infectivity, and bacillary radiorespirometric activity. After 4 weeks of treatment, all patients had a morphological index of zero and specimens from most patients were noninfectious for mice, while the median decrease in radiorespirometric activity was > 99%. Overall results by the rapid radiorespirometric assay paralleled those of the mouse footpad and morphological index assays. Sparfloxacin given at 200 mg once daily appears to be rapidly bactericidal in humans, with activity similar to that observed in a previous clinical trial with 400 mg of ofloxacin.

Sparfloxacin is more bactericidal than ofloxacin against Mycobacterium leprae in mice.

The comparative bactericidal activities of sparfloxacin and ofloxacin against Mycobacterium leprae in mice were determined using the proportional bactericidal test at doses of 12.5 mg/kg-100 mg/kg. Significant bactericidal activity was found at 12.5 mg/kg sparfloxacin and 25 mg/kg ofloxacin. Sparfloxacin was significantly more bactericidal than ofloxacin at all doses, and the results with 25 mg/kg sparfloxacin were nearly identical to those obtained with 100 mg/kg ofloxacin. These results, together with pharmacokinetic and toxicological data in mice and man, suggest that sparfloxacin may have a higher therapeutic index than ofloxacin in leprosy, and that the tentative standard dosage of 200 mg sparfloxacin daily should be appropriate for a clinical trial.

Effects of fixation on polymerase chain reaction detection of Mycobacterium leprae.

The effects of standard fixatives (10% neutral buffered formalin, ethanol and mercury based) on the detection of Mycobacterium leprae DNA by the polymerase chain reaction (PCR) were studied. Mercury-based fixatives (Zenker's and Carnoy-Lebrun's fluids) strongly inhibited PCR amplification of M. leprae DNA. Ten percent neutral buffered formalin was inhibitory, but significant inhibition was observed only when fixation times exceeded 24 h. Ethanol-based fixatives provided the best medium for holding specimens for subsequent PCR with both free bacilli and skin biopsy specimens containing M. leprae. The M. leprae-specific, 360-bp region of the 18-kDa protein gene could be amplified from paraffin-embedded sections of formalin-fixed skin biopsy specimens from patients with either multibacillary or paucibacillary infections when proper fixation conditions were used. Results of the study demonstrate that tissues properly fixed with two standard fixatives (10% neutral buffered formalin and 50 or 70% ethanol) can be analyzed by PCR for the presence of M. leprae with no loss in specificity and only minimal diminution in sensitivity compared with the specificities and sensitivities obtained by use of freshly prepared, unfixed specimens.

Prevalence of IgM antibodies to phenolic glycolipid I among household contacts and controls in Korea and the Philippines.

Phenolic glycolipid I (PGL-I) is a Mycobacterium leprae-specific antigen and the antibodies to the antigen may suggest an M. leprae infection. To compare the M. leprae transmission among the populations, we compared the prevalence of anti-PGL-I IgM antibodies among household contacts and controls between Korea and the Philippines. In Korea (prevalence of leprosy--0.04: 1000), the prevalence of anti-PGL-I antibodies were 4.8% among controls and 8.0% among contacts, respectively. On the other hand, the seroprevalence rate was 10.8% among controls and 13.4% among contacts in the Philippines (prevalence of leprosy--0.70: 1000). Interestingly, a marked difference was noted in the prevalance of anti-PGL-I antibodies among children between the countries; 10-14% among children under 10 years old and 15-18% among those aged between 10 and 19 in the Philippines compared to 0% and 2.9-6.4% in Korea, respectively. This study, therefore suggests that a high prevalance of anti-PGL-I IgM antibodies among children may indicate an active transmission of M. leprae, resulting in a higher incidence of leprosy in the population.

Ligamentotaxis and bone grafting for comminuted fractures of the distal radius.

The conventional treatment of comminuted fractures in the distal radius has been unsatisfactory. We therefore made a prospective study using the principle of ligamentotoxis and primary cancellous bone grafting as the uniform method of treatment. Ligamentotaxis was maintained by using an external fixator for three weeks only, after which a carefully monitored programme of rehabilitation was given. We have reviewed 72 consecutive distal radial fractures after a follow-up of 7 to 40 months (average 11 months). Reduction had been maintained during healing and over 80% of patients regained full range of movement in hands, wrists and forearms with strong and pain-free wrist function. Complications were infrequent and gave no real problems. We conclude that distraction, external fixation and bone grafting appears to be an excellent method of treating comminuted fractures of the distal radius.