Biomedical subjects
G Holan
Publications and source records attributed to G Holan.
Knowledge of physicians in hospital emergency rooms in Israel on their role in cases of avulsion of permanent incisors.
OBJECTIVE: The purpose of this study was to assess the knowledge of physicians in hospital emergency room care on their possible role in cases of traumatic loss of permanent incisors. METHODS: A questionnaire was sent to directors of emergency room facilities in hospitals in Israel regarding the medical team at the emergency room in the hospital, availability of an in-house dental service and existence of a protocol for management of avulsed teeth. Another questionnaire, completed by physicians in the emergency room, contained demographic questions and questions regarding their knowledge of management of avulsed permanent teeth. RESULTS: The findings of the study showed that only 4% (12 of 335 physicians) would provide an appropriate initial treatment that, if followed by treatment by a dentist as recommended, could save the avulsed tooth. No correlation was found between knowledge of appropriate treatment of avulsed teeth and type of specialty, years of experience, previous exposure to information on trauma to the teeth and gender. The only significant association was found between physicians' knowledge and having a dentist spouse. Most of the physicians had never attended any formal seminar or lecture or received printed instructions on the management of avulsed teeth. CONCLUSIONS: Medical students and physicians in hospitals' emergency rooms should be made aware of their possible role in cases of avulsion of permanent teeth, in order to minimize late complications associated with such injuries. One possible way to achieve this goal is through education during and after training and introduction of a formal protocol for treatment of avulsed permanent teeth and other dental injuries.
Evaluations of unformulated and formulated dendrimer-based microbicide candidates in mouse and guinea pig models of genital herpes.
Prevention of sexually transmitted infections is a priority in developed and developing countries. One approach to prevention is the use of topical microbicides, and one promising approach is the use of dendrimers, highly branched macromolecules synthesized from a polyfunctional core. Three new dendrimer products developed to provide stable and cost-efficient microbicides were initially evaluated in vitro for anti-herpes simplex virus activity and then in vivo by using a mouse model of genital herpes. From these experiments one product, SPL7013, was chosen for further evaluation to define the dose and duration of protection. Unformulated SPL7013 provided significant protection from genital herpes disease and infection at concentrations as low as 1 mg/ml and for at least 1 h following topical (intravaginal) administration of 10 mg/ml. This compound was then formulated into three vehicles and further evaluated in mouse and guinea pig models of genital herpes infection. In the murine evaluations each of the formulations provided significant protection at concentrations of 10 and 50 mg/ml. Formulated compounds provided protection for at least 1 h at a concentration of 10 mg/ml. From these experiments formulation 2V was chosen for dose ranging experiments using the guinea pig model of genital herpes. The guinea pig evaluations suggested that doses of 30 to 50 mg/ml were required for optimal protection. From these studies a lead compound and formulation (2V of SPL7013) was chosen for ongoing evaluations in primate models of simian immunodeficiency virus and Chlamydia trachomatis infection.
[The role of the medical team in emergency units in case of traumatic loss of permanent anterior teeth].
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Potent anti-HIV (type 1 and type 2) activity of polyoxometalates: structure-activity relationship and mechanism of action.
A series of polyoxometalates have been synthesized and evaluated for their inhibitory effects on HIV-1(III(B)) and HIV-1(ROD) replication in MT-4 cells. All compounds showed activity against HIV-1 and HIV-2, but the antiviral potency of the heteropolytungstates varied considerably depending on their chemical structure. The antiviral activity of single, double, and triple Keggin-type of compounds against HIV-1(III(B)) replication was comparable (IC(50): 0.4-0.5 microgram/mL), whereas HIV-2(ROD) appeared to become less sensitive with the increasing number of Keggin structures per compound. The same trend was observed for single and double Dawson structures. Some of these compounds were examined for their inhibitory effect on the replication of HIV-1(RF) and SIV(MAC(251)) in MT-4 cells. Their anti-HIV-1(RF) and anti-SIV(MAC(251)) potencies were comparable to those for the HIV-1(III(B)) or HIV-2(ROD) strain, respectively. The polyoxometalates represent a class of polyanionic compounds, which block the binding of the envelope glycoprotein gp120 of HIV to CD4(+) cells. The compounds interfered with the binding of anti-CD4 mAb to the OKT4A/Leu3a epitope of the CD4 receptor, compound 24 being the most active in this regard, and inhibited the binding of anti-gp120 mAb to infected MT-4 cells. None of the polyoxometalates inhibited the binding of a specific CXCR4 mAb to SUP-T1 cells, suggesting that they do not interact with CXCR4, the main co-receptor for T-tropic HIV strains, and thus act as virus binding, and not as fusion, inhibitors.
Aspiration of an avulsed primary incisor. A case report.
A 7-year-old girl had injured her maxillary primary incisors in a playground. One of the already-mobile incisors had been avulsed. The child who had a cough and breathing difficulties during sleep was diagnosed as suffering from upper respiratory infection and was treated with antibiotics. A few days later because her body temperature was elevated a chest radiograph was taken. The radiograph revealed an aspirated tooth in her right bronchus with atelectasis of the lower lobe. The tooth was removed by bronchoscopy. Dentists should suspect any tooth that has been avulsed and not found as possibly aspirated.
Dendrimers, a new class of candidate topical microbicides with activity against herpes simplex virus infection.
Dendrimers are large highly branched macromolecules synthesized from a polyfunctional core. They have shown a variety of biological properties, including, in some instances, antiviral activity. In this study, five dendrimers were evaluated for in vitro activity against herpes simplex virus (HSV) types 1 and 2 by cytopathic effect (CPE) inhibition and plaque reduction (PR) assay in human foreskin fibroblast cells. All of the compounds were active against both virus types in the CPE inhibition assay, in which drug was added to the cells prior to the addition of virus. Antiviral activity was reduced or lost in the PR assays, in which the cells were incubated with the virus before the drug was added. The prophylactic efficacy suggested that the dendrimers might have potential as topical microbicides, products intended to be applied to the vaginal or rectal mucosa to protect against sexually transmitted infections. Three dendrimers were evaluated for this application against genital HSV infection in mice. Two of the compounds, BRI-2999 and BRI-6741, significantly reduced infection rates when 15 microl of a 100-mg/ml solution was administered immediately prior to intravaginal challenge, and the most effective compound, BRI-2999, provided significant protection even when applied 30 min before challenge. This is the first report of microbicidal activity by dendrimers in vivo.
Polyanionic (i.e., polysulfonate) dendrimers can inhibit the replication of human immunodeficiency virus by interfering with both virus adsorption and later steps (reverse transcriptase/integrase) in the virus replicative cycle.
Polyanionic dendrimers were synthesized and evaluated for their antiviral effects. Phenyldicarboxylic acid (BRI6195) and naphthyldisulfonic acid (BRI2923) dendrimers were found to inhibit the replication of human immunodeficiency virus type 1 (HIV-1; strain III(B)) in MT-4 cells at a EC(50) of 0.1 and 0.3 microg/ml, respectively. The dendrimers were not toxic to MT-4 cells up to the highest concentrations tested (250 microg/ml). These compounds were also effective against various other HIV-1 strains, including clinical isolates, HIV-2 strains, simian immunodeficiency virus (SIV, strain MAC(251)), and HIV-1 strains that were resistant to reverse transcriptase inhibitors. HIV strains containing mutations in the envelope glycoprotein gp120 (engendering resistance to known adsorption inhibitors) displayed reduced sensitivity to the dendrimers. The compounds inhibited the binding of wild-type virus and recombinant virus (containing wild-type gp120) to MT-4 cells at concentrations comparable to those that inhibited the replication of HIV-1(III(B)) in these cells. Cellular uptake studies indicated that BRI2923, but not BRI6195, permeates into MT-4 and CEM cells. Accordingly, the naphtyldisulfonic acid dendrimer (BRI2923) proved able to inhibit later steps of the replication cycle of HIV, i.e., reverse transcriptase and integrase. NL4.3 strains resistant to BRI2923 were selected after passage of the virus in the presence of increasing concentrations of BRI2923. The virus mutants showed 15-fold reduced sensitivity to BRI2923 and cross-resistance to known adsorption inhibitors. However, these virus mutants were not cross-resistant to reverse transcriptase inhibitors or protease inhibitors. We identified several mutations in the envelope glycoprotein gp120 gene (i.e., V2, V3, and C3, V4, and C4 regions) of the BRI2923-resistant NL4.3 strains that were not present in the wild-type NL4.3 strain, whereas no mutations were found in the reverse transcriptase or integrase genes.
Dens invaginatus in a primary canine: a case report.
This article describes an unusual case of dens invaginatus in a primary canine. A 5-year-old boy presented with an infected mandibular primary canine. A periapical radiograph showed a developmental disturbance in the crown diagnosed as dens invaginatus. A necrotic pulp has been removed from the tooth and the root canal obturated with a resorbable paste. Six weeks later the tooth was found to be asymptomatic. A composite restoration replaced the temporary filling material. Dens invaginatus may appear in the primary dentition, and early diagnosis is important for preventative treatment.
Traumatic injuries to the chin: a survey in a paediatric dental practice.
OBJECTIVE: The aim of the study was to provide data on the prevalence of clinical signs of traumatic injuries to the chin and of parental report of such injuries in a group of children visiting a private paediatric dental practice. SAMPLE AND METHODS: The study group comprised 303 children (151 boys and 152 girls) whose dental age was within the limits in which all primary molars are present. The children visited the author's private practice for purposes other than chin injury and its dental implications. Data collected included age, gender, presence and location of fractures in primary molars, presence of a scar on the child's chin, and parental report of previous chin injuries. RESULTS: Fractured primary molars were detected in 96 (31.7%) children. 79 (26%) children had a scar on the chin and previous chin injuries were reported for 110 (36.3%) children. Boys presented a higher prevalence of evidence of chin injuries than girls. The male/female ratios for fractured molars, scar on the chin and previous trauma were 1.5:1, 1.8:1 and 1.5:1 respectively. These differences were statistically significant (chi 2, P = 0.012, P = 0.002 and P = 0.008 respectively). CONCLUSIONS: It is concluded from this survey that traumatic injuries to the chin are not infrequent and the incidence of injuries to the chin is higher in boys than in girls.
Tube-like mineralization in the dental pulp of traumatized primary incisors.
Mineralization in the pulp is a common finding in permanent as well as primary teeth and is associated with caries, aging, traumatic injuries and systemic conditions. This article describes an unusual pattern of pulpal calcification. A tube-like calcified structure formed in the dental pulp of primary incisors following mild traumatic injuries. It was studied by clinical, radiographic and histologic evaluation and by scanning electron microscopy. The tube-like structure was found to extend along the entire length of the pulp canal. Generally it was separated from the root dentin by normal pulp tissue, but was connected to the dentin in some sites. It had the histologic appearance of osteodentin with cell inclusions in a ring-like formation that was incomplete in places. The scanning electron microscope study showed rough inner and outer surfaces of a tube-like structure with openings that seemed to be dentinal tubules.
Immediate esthetic treatment of an avulsed/replanted permanent incisor with extensive root resorption: a case report.
This article describes the treatment of a 10 year-old patient with complete root resorption of the maxillary permanent incisor following avulsion and replantation 4 years earlier. The remaining natural crown was used to immediately solve the esthetic problem created by its extraction. The crown was attached with an orthodontic wire and composite resin to adjacent teeth. This temporary treatment does not elicit any damage to adjacent teeth, and can be easily removed. Therefore, it does not affect any plans that might be considered in the future as the permanent treatment.
Investigation of the uptake of drugs by individual cells using a scanning proton microprobe (SPM).
In this paper we demonstrate the use of micro-PIXE (proton induced X-ray emission) for measuring the quantitative uptake of anti-AIDS drugs, containing metal atoms, by individual Vero cells (African green monkey kidney cell line). Hetero-polytungstates, which are assessed to present an activity against the HIV virus, were studied using Vero cells. It was found that unlike other techniques, SPM offers both the sensitivity and the spatial resolution to carry out these programs of investigations. The use of elemental analysis in single cells of cultured cell lines has shown to have distinct advantages over peripheral blood lymphocytes.
The use of a scanning proton microprobe to observe anti-HIV drugs within cells.
A series of inorganic polyanions (viz. heteropolytungstates) has been shown to have antiviral activity but there was no evidence to indicate that the drugs reached their site of antiviral (HIV) activity intact. We have shown that with a scanning proton microprobe it is possible to analyse the metal content of individual cells (PBLs) treated with such a polyoxometalate drug and to determine the atomic ratio of the metals within the cell. This was found to be near that in the drug. The distribution of the metals (tungsten and cobalt) within the cell was measured and it was shown that both metals were located in the same region within the cell. These findings would suggest that the drug had entered the cells intact.
Use of a flavivirus RNA-dependent RNA polymerase assay to investigate the antiviral activity of selected compounds.
We have developed an assay using flavivirus RNA-dependent RNA polymerase to test the inhibitory activity of potential antiviral agents. The effects of antiviral agents on RNA synthesis were examined in this assay using extracts of Vero cells infected with dengue virus type 2 or Kunjin virus. Several different classes of known polymerase inhibitors were tested. The synthesis of double-stranded replicative form RNA was inhibited in a dose-dependent fashion in the presence of the polyoxometalate HPA-23 [(NH4)18(NaW21Sb9O86)17].14 H2O and several structurally related compounds.
Extraction of primary canine tooth buds: prevalence and associated dental abnormalities in a group of Ethiopian Jewish children.
Recent publications have described a common belief, held in rural areas in Africa, that unerupted primary canines cause diarrhoea, vomiting and fever in infants. To relieve these symptoms a traditional native healer extracts these tooth buds. The emigration of Ethiopian Jews to Israel in 1991 allowed an investigation of this practice among this community. A group of 59 children (27 boys and 32 girls) aged 3-12 years were examined clinically and radiographically. Evidence was found of extraction of 63 primary canine buds in 35 (59%) of the children. Extraction of one canine was found in 16 children, two in 13 children and three in three children, and three children had all four canines extracted. Forty-six (74%) mandibular compared to only 16 (26%) maxillary canines had been extracted; the extractions were equally divided between both sides of the jaws. Another 19 primary canines had hypoplastic defects, probably the result of unsuccessful extractions. Associated dental abnormalities included hypoplasia of the permanent successors and adjacent primary and permanent teeth, displacement of permanent teeth, midline shift to the extraction side, missing primary lateral incisors (probably accidentally extracted) and distal eruption of permanent lateral incisors, leaving their primary predecessors retained. Parental enquiry revealed that the practice is more common in rural rather than urban areas and still exists in the Ethiopian community in Israel. The findings of this survey should urge the authorities to take steps to stop this practice.
Structure of a dideoxynucleoside active against the HIV (AIDS) virus.
N4-Benzoyl-2',3'-dideoxycytidine, C16H17-N3O4.2H2O, M(r) = 351.4, monoclinic, P2(1), a = 4.691 (1), b = 14.448 (2), c = 12.924 (3) A, beta = 97.63 (1) degree, V = 868.2 (1) A3, Dm(flotation) = 1.34 (1), Dx = 1.344 Mg m-3, Z = 2, F(000) = 372, lambda = 1.5418 A, mu(Cu K alpha) = 0.65 mm-1, T = 292 (1) K, final R = 0.038 for 1437 observed data. The glycosidic torsion angle C(6)--N(1)--C(1')--O(4') is 20.6 (5) degrees and the pucker of the furanose ring is C(3') endo. Free rotation about the exocyclic C(4')--C(5') bond allows the hydroxymethyl substituent to adopt two orientations, trans and gauche, the latter resulting in a short contact, H(6)...O(5") of 2.21 (4) A, indicative of a relatively strong C--H...O intramolecular hydrogen-bonding interaction.
Influence of wearing latex gloves on electric pulp tester readings in children.
Electric pulp testers operated by completing an electric circuit. Latex examination gloves have been claimed to interrupt this circuit and lead to false-negative results. This study was conducted to evaluate the influence of wearing latex gloves on electric pulp tester (EPT) readings. The pulps of 80 maxillary permanent incisors of 22 children 10-13 1/2 years old were tested using the Pelton & Crane 'Vitapulp' instrument. Each tooth was tested twice: with gloves and with bare hands. Teeth failing to respond to the EPT without gloves were excluded from the study. All EPT readings ranged between 1 and 9.5. Five teeth gave the same responses with gloved and ungloved hands. Only five teeth did not respond when gloves were worn, and all of these gave readings near the top of the EPT scale when tested without gloves. The other 70 teeth presented significantly higher readings with gloves than without gloves. It is concluded that removal of examination gloves during the operation of the EPT is necessary only if no response is obtained.