School of Oral Health Sciences
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Item Base solubility and marginal sealing in amalgam restored teeth(1991) Grossman, E. S.; Witcomb, M. J.; Matejka, J. M.Item Growth and morphogenetic factors in bone induction: role of osteogenin and related bone morphogenetic proteins in craniofacial and periodontal bone repair.(1992) Ripamonti, Ugo; Reddi, A. H.Bone has considerable potential for repair as illustrated by the phenomenon of fracture healing. Repair and regeneration of bone recapitulate the sequential stages of development. It is well known that demineralized bone matrix has the potential to induce new bone formation locally at a heterotopic site of implantation. The sequential development of bone is reminiscent of endochondral bone differentiation during bone development. The collagenous matrix-induced bone formation is a prototype model for matrix-cell interactions in vivo. The developmental cascade includes migration of progenitor cells by chemotaxis, attachment of cells through fibronectin, proliferation of mesenchymal cells, and differentiation of bone. The bone inductive protein, osteogenin, was isolated by heparin affinity chromatography. Osteogenin initiates new bone formation and is promoted by other growth factors. Recently, the genes for osteogenin and related bone morphogenetic proteins were cloned and expressed. Recombinant osteogenin is osteogenic in vivo. The future prospects for bone induction are bright, and this is an exciting frontier with applications in oral and orthopaedic surgery.Item An ethical dilemma. Availability of antiretroviral therapy after clinical trials with HIV infected patients are ended(1997) Cleaton-Jones, P. E.Guidelines on good clinical practice for drug trials clearly state that ethics committees must ensure that the safety, integrity, and human rights of the subjects participating in a particular trial are protected.1 Fundamental concepts are informed consent and risk or benefit to participants in a trial. For many clinical trials, ethical clearance is straightforward but those involving people infected with HIV generally are not. Here, we are dealing with a condition that is presently incurable with variable progression, drug treatment is expensive, and emotions run high. These matters are common to all countries, but those of us living in Africa have an added burden–Third World conditions and an estimated 13 million people infected with HIV, usually from heterosexual sex.2 In South Africa the most recent published results for the fifth unlinked anonymous national HIV survey show that HIV infection in women attending antenatal clinics has risen from a national average of 1.35% in 1991 to 7.57% in 1994.3 In some parts of the country the rate is as high as 14.35% and is increasing.3 Because of a shortage of resources, antiretroviral drugs for treating HIV are not provided by South African public health services: these are available only in the private sector at great expense. Given this high prevalence of HIV it is understandable that multinational drug companies are attracted to carrying out trials in our country, with its combination of a large infected population and proved medical expertise. Ethics committees are currently receiving trial protocols for combinations of drugs from such companies. All protocols provide for the free supply of trial drugs for a specified period, usually two to three years, for patients satisfying the inclusion criteria. The trials are well designed and comprehensive, but there is no guarantee that the drug treatment will be continued beyond the end of the trial. Therein lies the problem. South African ethics committees use guidelines on ethics for medical research provided by the South African Medical Research Council.4 Comprehensive as these are, they do not solve the following dilemma. What is the responsibility of a trial sponsor to a trial subject who responds to treatment that will not be available after the end of the trial? With most diseases this is not a problem since alternative treatments are available. However, when no other treatment is available to trialists what should be done? If a patient infected with HIV responds to the test drugs, may one ethically withhold the drugs at the end of the trial, thereby depriving the person of benefit? My committee's opinion up to the present has been that it is not ethical to do so and that such trial subjects must continue to receive the antiretroviral treatment after the trial ends until they cease to benefit or are enrolled into another trial. Naturally, most companies have not received this opinion with joy. Their argument is that informed consent, which clearly states the length of a trial, takes care of the problem. In theory this is correct, but South Africa has large numbers of people insufficiently educated to understand the implications of what they are consenting to. In early trials, when monotherapy was the rule, many companies complied with our requirement, but combination therapy has altered company policy. Companies often must purchase another manufacturer's drug to use in conjunction with their own. As a compromise, companies are generally prepared to provide their trial drug until it is no longer under development or is commercially available or they will provide zidovudine alone. Since combination therapy is the current optimal treatment,5 6 can ethics committees allow patients to revert back to a less effective treatment? Furthermore, even if a drug becomes commercially available, is it ethical to halt treatment knowing that neither the health service nor trial subject can afford it? Investigators fall into two clear camps. Some will not undertake trials unless there is an arrangement for their patients to receive drugs long term or to be enrolled in subsequent trials. Others know that their patients would normally receive no treatment at all, so two to three years of treatment is of some benefit at least and may buy time for future breakthroughs. A further complication is the variation in policy of ethics committees. Our committee, established in 1966, is the oldest and most experienced in South Africa and is known to be conservative. Protocols not accepted by us, we know, have been readily approved in the private sector or at other institutions. To be fair to all concerned we have sought personal opinions from research coordinators in HIV trial groups in Canada and Australia. In Canada continuation of drug treatment beyond the trial is expected, but this is simpler because a drug company can continue to supply its own drug to be added to the antiretroviral treatment available from the public health services. In Australia it is accepted that drug companies are unlikely to provide long term treatment, and colleagues there believe that monotherapy, with at least a double nucleoside, after completion of a trial is acceptable when no other treatment is available. Realistically, the level of illness required for inclusion into trials is such that many subjects may not survive past the trial period. Surely, agreement can be made on a response to the trial drugs so that only those responding may continue treatment; those not responding may be taken out of the trial to free resources for the responders beyond the trial. This has been debated at length in our committee with investigators, trial sponsors, and potential subjects. The most strident voices of all are those of patients infected with HIV, who feel that the decision to participate in a trial is theirs alone, not that of an ethics committee acting in a paternalistic manner. But ethics committees have to ensure that patients are not exploited and that benefit outweighs risk.Item Effect of amalgam type on artificial caries(1994) Grossman, E. S.; Matejka, J. M.Item Advances in osteogenin and related bone morphogenetic proteins in bone induction and repair(1992) Luyten, F. P.; Cunningham, N. S.; Vukicevic, S.; et alBone matrix is a repository of growth and differentiation factors as demonstrated by the induction of local cartilage and bone formation in rats. The bone inductive activity, termed osteogenin, can be dissociatively extracted, and it was isolated by heparin affinity, hydroxyapatite and molecular sieve chromatography. Osteogenin has been purified to homogeneity from bovine bone matrix and the sequences of several tryptic peptides have been determined. The sequences were similar to portions of the amino acid sequence deduced from the cDNA clone of bone morphogenetic protein-3 (BMP-3). The carboxyl-terminal quarter of osteogenin has sequence identity to the corresponding regions of two related proteins BMP-2A and BMP-2B. The bone inductive proteins are members of the TGF-beta superfamily, by virtue of the location of the highly conserved cysteines in their carboxyl-terminal region. Osteogenin and related BMPs initiate cartilage and bone formation in vivo. The study of the mechanism of action of these proteins will add considerable new information on the molecular signals controlling endochondral bone formation. In vitro data indicate that osteogenin stimulates the expression of the osteogenic and chondrogenic phenotypes. Our results demonstrate their profound influence on proteoglycan synthesis and degradation in bovine cartilage explant cultures. High affinity specific binding sites have been identified in both MC3T3 cells and articular chondrocytes. In vivo experiments demonstrate the efficacy of primate osteogenin in restoring large calvarial defects in adult baboons, establishing a primary role for osteogenin in therapeutic initiation and promotion of osteogenesis.Item Social class, parents' education and dental caries in 3- to 5-year-old children(1990) Chosack, A.; Cleaton-Jones, P.; Matejka, J.; et alThe caries prevalence of 1273-, 4- and 5-y-old white children was determined with mirror and probe under natural light at mother and child clinics. The social class of the family, the educational level of the mother and that of the father were determined from a questionnaire filled in by the accompanying adult at the time of examination. Both social class and parent's education had a statistically significant influence on the caries prevalence: those in the lower social classes and with parents without tertiary education had a much higher prevalence of cariesItem Desegregating health statistics and health research in South Africa(1997) Walker, A. R. P.; Sitas, F.; Cleaton-Jones, P. E.; et alItem Epidemiological profile of graduates of the Wits Dental Faculty 1927 - 1995(1996) Cleaton-Jones, P.; Volchansky, A.; Copland, L.The Wits dental school was first proposed in 1921 but had no premises until a private dental clinic was taken over in 1924 by the University, the same year that the Bachelor of Dental Surgery regulations were agreed to. In 1925 the first dental students registered and a year later, in 1926, the first seven lecturers in dental surgery were appointed. Since the first two graduates in 1927, 1916 dentists have graduated from the school as have 63 oral hygienists. Of the dentists 116 are female and 127 are black, Chinese, coloured or Indian. Regarding postgraduate qualifications, 346 have been awarded by the University on behalf of the dental school. This paper describes patterns in numbers of graduates, proportions registered in South Africa and contrasts registered South African dental school graduates with registered graduates from outside the country. It is clear that the Wits dental school has made a major contribution to South African society.Item Transcutaneous electrical nerve stimulation in the treatment of myofascial pain dysfunction(1998) Kruger, L. R.; van der Linden, W. J.; Cleaton-Jones, P. E.The effect of transcutaneous electrical nerve stimulation (TENS) plus conservative therapy (ibuprofen, bite plate, self-physiotherapy) on myofascial pain dysfunction (MPD) was determined. A single-blind trial as done in 10 patients with MPD with subthreshold TENS (frequency 35 Hz, pulse width 100 milliseconds, modulation 50%) compared with sham TENS at 8 visits over 14 weeks. Pain was assessed on a visual analogue scale before and after TENS at each visit and the data were analysed with the analysis of variance (ANOVA) for repeated measures. A highly significant effect was seen for time (F = 4.80, P = 0.0003) but not for TENS. Subthreshold TENS did not increase the symptom relief produced by conservative treatment with the protocol used.Item Paediatric maxillofacial trauma(1996) Bamjee, Y.