Pharmacist-led multi-faceted intervention in an antimicrobial stewardship programme at a dental university hospital in Japan.

BACKGROUND: Antimicrobials are commonly prescribed in dentistry. However, inappropriate antimicrobial prescriptions are common in this field. Optimizing antimicrobial prescriptions in dentistry requires an effective strategy for modifying prescribing behaviour. AIM: To assess the efficacy of pharmacist-led multi-faceted intervention for the proportion of monthly antimicrobial prescriptions in each drug group per 100 oral antimicrobial prescriptions. METHODS: A before-after trial was performed at a university hospital outpatient dental clinic. A pharmacist-led, multi-faceted intervention, including immediate and direct feedback to the prescribers, an explanation of the rules of antimicrobial prescriptions for patients with penicillin allergy, tutorials for dentistry students, and a review of hospital-approved antimicrobials, was implemented from April 2017 to March 2022. Antimicrobials were classified into eight groups, namely, penicillins, first- and second-generation cephalosporins, third-generation cephalosporins, fluoroquinolones, macrolides, clindamycin, carbapenem, and others. FINDINGS: In total, there were 2,643,988 visits to the outpatient dental clinic during the study period. The monthly mean proportion of prescriptions for penicillins increased from 45.6 to 84.1 per 100 oral antimicrobial prescriptions (P<0.001) while that of third-generation cephalosporins decreased from 43.0 to 7.3 (P<0.001) from the pre-intervention to the intervention period. Moreover, the monthly mean proportion of fluoroquinolones, macrolides, and carbapenems decreased from 11.2 to 7.44 (P<0.001). CONCLUSION: The intervention modified dentists' antimicrobial prescribing behaviours, leading to an immediate increase in the number of monthly prescriptions for penicillins and a simultaneous decrease in the number of monthly prescriptions for third-generation cephalosporins and other broad-spectrum, oral antimicrobials.

Appropriateness of surgical antimicrobial prophylaxis in Japanese university hospitals.

BACKGROUND: Surgical antimicrobial prophylaxis (SAP) is one of the major purposes of antimicrobial use. AIM: To determine the adherence to the Japanese SAP guidelines in Japanese university hospitals. METHODS: This was a retrospective cohort study including 15 general hospitals and one dental university hospital. Up to three cases of 18 designated surgeries were evaluated regarding adherence to Japanese SAP guidelines: selection of antibiotics, timing of administration, re-dosing intervals, and duration of SAP. When all items were appropriate, surgery was defined as 'appropriate'. FINDINGS: In total, 688 cases (22-45 cases per surgery) were included. The overall appropriateness was 46.8% (322/688), and the appropriateness of each surgery ranged from 8.0% (2/25, cardiac implantable electronic device implantation) to 92.1% (35/38, distal gastrectomy). The appropriateness of each item was as follows: pre/intraoperative selections, 78.5% (540/688); timing of administrations, 96.0% (630/656); re-dosing intervals, 91.6% (601/656); postoperative selection, 78.9% (543/688); and duration of SAP, 61.4% (423/688). The overall appropriateness of hospitals ranged from 17.6% (9/51) to 73.3% (33/45). The common reasons for inappropriateness were the longer duration (38.5%, 265/688) and choice of antibiotics with a non-optimal antimicrobial spectrum before/during, and after surgery (19.0%, 131/688 and 16.9%, 116/688, respectively), compared to the guideline. CONCLUSIONS: Adherence to the guidelines differed greatly between the surgeries and hospitals. Large-scale multi-centre surveillance of SAP in Japanese hospitals is necessary to identify inappropriate surgeries, factors related to the appropriateness, and incidences of surgical site infections.

Jaw electromyographic activity induced by the application of algesic chemicals to the rat tooth pulp.

The aim of this study was to determine if the application of mustard oil (MO), a small-fiber excitant and inflammatory irritant, or other algesic chemicals (capsaicin, CAP, and bradykinin, BK) to the rat maxillary molar tooth pulp induces electromyographic (EMG) activity of the masseter and digastric muscles, and also to determine if endogenous opioid mechanisms may be involved in any documented EMG changes. Application of MO to the tooth pulp induced a significant increase in EMG activity of the ipsilateral masseter up to 30 min. The application of mineral oil to the pulp or MO application to the pulp-extirpated tooth did not induce any significant EMG increases. The application of CAP or BK to the pulp in contrast had much weaker effects on EMG activity of the jaw muscles. CAP produced a small but prolonged increase in masseter EMG activity, and BK induced a short-lasting increase in digastric EMG activity. The systemic administration of the opiate antagonist naloxone significantly reactivated (i.e. rekindled) the EMG response evoked by MO application to the pulp. Naloxone did not produce any such significant rekindling effect on EMG activity following CAP, BK or mineral oil application to the pulp or following MO application to the pulp-extirpated tooth. The MO, BK and especially CAP groups showed histological evidence of vasodilatation and polymorphonuclear leukocyte infiltration in the pulp tissue and a significant increase in plasma extravasation of Evans Blue dye, whereas mineral oil did not induce these changes. These findings suggest that pulp afferent inputs to the central nervous system evoked by BK. CAP and especially MO may induce enhanced jaw muscle activity. In addition, the naloxone data suggest that an opioid suppresive mechanism may be induced by the pulpal afferent inputs evoked by MO, and may serve to limit the jaw muscle activity elicited by these inputs.

Three groups of afferent pulpal feline nerve fibres show different electrophysiological response properties.

Responses were recorded, after the application of four types of stimuli (slow or rapid elevation of temperature, hydrostatic negative pressure through thin dentine, and bradykinin directly applied to exposed pulp), from functional single fibres innervating the cat lower canine tooth pulp, dissected from the inferior alveolar nerve. A total of 278 single pulpal fibres were isolated. A fibres (n = 220) were divided into two groups: one (FA; fast A fibre, n = 160) consisting of those whose conduction velocities (CVs) were more than 2 m/s both inside and outside the tooth pulp, and the other (SA delta; slow A delta fibre, n = 60) consisting of those whose intrapulpal CVs were less than 2 m/s and extrapulpal CVs greater than 2 m/s. Fifty eight C fibres (C) were also found. None of FA, 40% of SA delta and 52% of C responded to continuous heat. None of C, 47% of FA and 45% of SA delta responded to rapid elevation of temperature. None of C, 20% of FA and 20% of SA delta responded to hydrostatic pressure. None of FA, 83% of SA delta and all of C responded to bradykinin. It was found that 21 of 60 SA delta responded to both types of stimuli that reportedly activate only A (rapid heat and hydrostatic negative pressure) or C (continuous slow heat and bradykinin) nerve fibres and that 29 SA delta responded to slow heating and/or bradykinin, similar to C fibres.

Increased blood flow and nerve firing in the cat canine tooth in response to stimulation of the second premolar pulp.

Mustard oil or mechanical stimulation was applied to maxillary second premolar tooth pulps and pulpal blood flow and or intradental nerve activity in the ipsilateral canine tooth were recorded in the cat. Mustard oil application to the second premolar pulp significantly increased blood flow in the canine tooth pulp to 162.0+/-65.8% (n = 16) of the prestimulation flow compared to control data obtained with application of mineral oil (107.0+/-5.1%, n = 6) (Mann-Whitney U-test, p = 0.0009). Sectioning of the infraorbital nerve and its branches on the experimental side (n = 4) did not affect this increase in pulpal blood flow. The paraperiosteal injection of 2% lidocaine (1.0 ml) without vasoconstrictor significantly inhibited the increase in canine pulpal blood flow induced by mustard oil application to the second premolar pulp (109.8+/-6.8% of the prestimulation level, n = 7) (Mann-Whitney U-test, p = 0.0013). Sporadic firing or sometimes bursts of action potentials in the canine pulp nerves were recorded during and/or after the mustard oil application to the second premolar pulp in three of 16 cases. Four single pulp nerve units firing in synchrony with the mechanical stimulation of the second premolar pulp were recorded in two of eight canines, which substantiated the existence of branched afferents innervating both teeth. These findings suggest that stimulation of the second premolar pulp may induce axon reflex-related vasodilation and intradental nerve firing in the canine pulp via branched afferent fibres innervating both the second premolar and canine teeth.

Elevation of tissue PO2 with improvement of tissue perfusion by topically applied CO2.

Local absorption of CO2 was examined, by tissue gas analysis with medical mass spectrometry, in rabbits placed in a bath. The results obtained clearly showed that (1) Elevation of subcutaneous tissue PO2 was followed by elevation of PCO2 in the subcutaneous tissue. (2) Local absorption of CO2 through skin was confirmed by elevation of the levels of subcutaneous PO2 and PCO2 at the site exposed to CO2. (3) Tissue perfusion during the CO2 bath was moderately higher than that observed with tap water bathing. The mechanism of oxygen release into the tissue by CO2 bathing is thought to involve increased [H+] and PCO2 in the red blood cells, which shifts the hemoglobin dissociation curve to the right, thus facilitating oxygen release at the tissue level. There is, therefore a good possibility, that the improved tissue perfusion together with the increased oxygen in the tissue will favourably affect wound healing and chronic degenerative disorders, thus facilitating rehabilitation.

Evaluation of tissue perfusion in ischemic legs of dogs by CO2 clearance rate.

Improvement in tissue perfusion following surgically induced ischemia in limbs of dogs was experimentally evaluated to clarify the improvement of hemodynamics following walking exercise in chronic, peripheral arterial occlusive diseases. With the use of a computer system in conjunction with medical mass spectrometry, the local tissue perfusion rate was calculated on the basis of the clearance curve of tissue partial pressure of CO2 following electrical stimulation of the ischemic leg to simulate exercise. Ischemia was created in the leg by ligation of the proximal and peripheral arteries. In one month, intermittent claudication improved in accordance with improvement in muscle tissue perfusion. Angiographic evidence of distal runoff became visible six months after surgery, indicating that tissue perfusion played an important role in peripheral hemodynamics. The local tissue perfusion rate improved from 9.51 +/- 2.62 ml/100 g/min to 12.41 +/- 2.42 in one month, to 14.59 +/- 3.19 in three months, to 15.11 +/- 3.24 in six months and to 17.19 +/- 2.63 in twelve months. The improvement of ischemic symptoms following long-term exercise is attributed to improvements in tissue perfusion or collateral circulation.

Epstein-Barr virus-related antibody pattern in uveitis.

Epstein-Barr virus-related antibody titers were determined in 30 patients with anterior uveitis, 45 with pan-uveitis, including 19 with Behçet's disease, 11 with Vogt-Koyanagi-Harada's disease and 15 with unclassified pan-uveitis, and 144 age-matched healthy controls. The frequencies of anti-VCA (viro-capsid antigen) and anti-EA (early antigen) in uveitis patients and in controls were similar, but the frequency of sera with elevated titers (greater than or equal to 1:160) and the geometric mean titer of anti-VCA in the patients with anterior uveitis was significantly higher than in the controls (P less than 0.025, P less than 0.01) and in the patients with pan-uveitis (P less than 0.001). The frequency of sera with elevated titers of anti-EBNA (Epstein-Barr virus associated nuclear antigen) (greater than or equal to 1:160) in the patients with pan-uveitis was significantly lower than in the controls (P less than 0.02) and in the patients with anterior uveitis (P less than 0.01). Among the patients with pan-uveitis, there was no significant difference in the pattern of antibodies. These data are compatible with the interpretation that there may be both anatomical and immunological differences between anterior and pan-uveitis.

[Anti-lipopolysaccharide antibody and lens--immunohistological study].

The relationship between lipopolysaccharide and lens protein was studied using the indirect immunofluorescence test. The anti-lens protein serum and anti-lipopolysaccharide serum reacted strongly with sections of rabbit lens, although normal rabbit serum did not react.

[Plasma fibrinopeptide A, fibrinopeptide B beta 15-42 and 4 other coagulation factors levels in patients with diabetic retinopathy].

Fibrinopeptide A (FPA), fibrinopeptide B beta 15-42 (FPB beta 15-42) and other coagulation factors (anti-thrombin III, thrombin-antithrombin complex, alpha 2-macroglobulin, plasmin inhibitor complex) were measured in the plasma of 101 patients with diabetes mellitus (DM). The levels in 80 healthy adults were also measured for comparative purposes. The mean levels of FPA, FPB beta 15-42 and the other 4 coagulation factors in the DM patients were significantly higher than in the controls (p < 0.05). The mean levels of FPA and FPB beta 15-42 in patients with diabetic retinopathy (DR) were higher than in those without DR, that is in those with proliferative diabetic retinopathy (PDR) higher than in those with simple diabetic retinopathy (SDR). In patients after panretinal photocoagulation (PRP), the mean level of FPA was higher and that of FPB beta 15-42 was lower than in patients before PRP. In the SDR group, the level of FPB beta 15-42 was significantly correlated with the progression of diabetic retinopathy. We suggest that there was a close correlation between plasma FPA and FPB beta 15-42 levels and activity or progression of disease, and that the investigation of these levels may be useful for the judging of prognosis or effect of therapies of diabetic retinopathy.

[A case of Churg-Strauss syndrome presented as right thalamic hemorrhage].

Intracerebral hemorrhage is an uncommon sequel of Churg-Strauss syndrome (CSS). We report the first case of CSS accompanied by right thalamic hemorrhage. The patient was 59-year-old male who experienced a sudden onset of left hemiplegia. Magnetic resonance imaging of the brain revealed right thalamic hemorrhage. Although several reports had pointed out a close relationship between hypertension and cerebral hemorrhage in patients with CSS, this patient had no apparent prior history of hypertension. The cause of thalamic hemorrhage in this patient might be probably due to cerebral vasculitis and an effect of abnormal coagulation and fibrinolytic agents.

[The effect of hyperbaric oxygenation on nitrite and nitrate production in rats treated with endotoxin].

The effect of hyperbaric oxygenation (HBO; 3 ATA, 90 min) on production of stable endproducts of nitric oxide (NO); nitrite (NO2-) and nitrate (NO3-), in plasma was studied in anesthetized rats treated with lipopolysaccharide (LPS). Intravenous injection of LPS (1 mg.kg-1) increased NO2-/NO3- production in plasma significantly 5-6 hrs after treatment, compared with non-treated rats. Production of NO2-/NO3- was not influenced by HBO performed 3 hrs after LPS injection. HBO performed 1 hr after LPS treatment, however, depressed NO2-/NO3- production significantly, compared with HBO performed 3 hrs after LPS, although NO2- production remained increased. These data suggest that HBO may influence the NO2-/NO3- production in NO producing processes in rats treated with LPS.

[Response properties of pulpal nerve fibers with different conduction velocities].

Tapering and branching of the nerve fibers cause the conduction velocity (CV) along the axon to be unequal. The purpose of this study was to investigate the response properties of the myelinated and unmyelinated nerve fibers in the cat tooth pulp. Electrophysiological recordings were made from the functional single fibers innervating the lower canine tooth pulp in 25 adult cats anesthetized with pentobarbital sodium after the application of four types of stimuli to the canine tooth. A total of 272 single pulpal nerve fibers was identified. A-fibers (n = 215) were divided into two groups: One (Ac, n = 55) consisting of the fibers whose intrapulpal CVs were less than 2 m/s and the extra-pulpal CVs of more than 2 m/s, and the other (At, n = 160) consisting of the fibers whose CVs were more than 2m/s both inside and outside the tooth pulp. Fifty-seven C-fibers (C) were also found. None of C, 47% of At and 46% of Ac responded to the rapid elevation of the temperature. None of At, 38% of Ac and 53% of C responded to the continuous heat. None of C, 20% of At and 20% of Ac responded to the hydrostatic pressure. None of At, 86% of Ac and all of C responded to bradykinin. These results suggest that the functional difference between the pulpal A-and C-fibers is not clear and that the Ac-fibers may complicate the dental and pulpal pain.

[Response properties of the neurons in the cervical cord to stimulation of the inferior alveolar nerve in the cat].

The purpose of this study was to investigate the neuronal mechanisms of the clinical symptoms of unusual muscle stiffness and/or pain in the neck and shoulder sometimes observed in patients suffering from chronic pulpal or periodontal diseases. Physiological properties of the neurons responding to the inferior alveolar nerve stimulation (inferior alveolar nerve driven-neurons: IANDNs) were studied by recording single unit activities in the upper cervical cord in cats anesthetized with alpha-chloralose. The results were as follows: (1) IANDNs were widely distributed from the dorsal horn to the ventral horn in the gray matter of the cervical cord (C2 and C3). (2) IANDNs were subdivided into two types of neurons based on the latencies of the spike responses: fast-type (F-type) (n = 60) and slow-type (S-type) (n = 101). (3) Two possible pathways from the inferior alveolar nerve to the cervical spinal cord participating in these spike responses were assumed: one was through the trigeminal spinal nucleus and the other through Probst's tract by way of the trigeminal mesencephalic nucleus. These results suggest that the impulses originating from dental inflammatory loci might drive IANDNs in C2 or C3 and that their activities may evoke contraction of the neck muscles, resulting in their stiffness and cervical back pain.

Neuron-immune interactions in the sensitized thalamus induced by mustard oil application to rat molar pulp.

We have reported that mustard oil application to the rat dental pulp induces neuronal activation in the thalamus. To address the mechanisms involved in the thalamic changes, we performed neuronal responsiveness recording, immunohistochemistry, and molecular biological analysis. After mustard oil application, neuronal responsiveness was increased in the mediodorsal nucleus. When MK801 (an N-methyl-D-aspartate receptor antagonist) was applied to the mediodorsal nucleus, the enhanced responsiveness was decreased. N-methyl-D-aspartate receptor 2D, glial fibrillary acidic protein, and antigen-presenting cell-related gene mRNAs in the contralateral thalamus were up-regulated at 10 minutes after mustard oil application, but were down-regulated within 10 minutes after the antagonist application. OX6-expressing microglia and glial fibrillary acidic protein-expressing astrocytes did not increase until 60 minutes after mustard oil application. These results suggested that the thalamic neurons play some roles in regulating the glial cell activation in the mediodorsal nucleus via N-methyl-D-aspartate receptor 2D during pulp inflammation-induced central sensitization.