Treatment by limited surgery and specific immunization of guinea pigs with stage II experimental cancer.

The malignant disease produced in guinea pigs by intradermal inoculation of line-10 was allowed to progress to stage II, at which time the dermal tumor and the first draining lymph node were grossly evident. At that stage, the external appearance of the next draining lymph node was normal, but it contained tumor cells. Limited surgery consisting of excision of the dermal tumor and first draining lymph node was not curative; palpable metastases developed in the second and other draining lymph nodes, and at autopsy, some animals were found to have gross, visible lung metastases. Immunization of guinea pigs with a mixture of irradiated syngeneic tumor cells plus mycobacterial cell walls in an oil-in-water emulsion eradicated tumor cells remaining in lymph nodes after limited surgery for stage II experimental cancer and prevented progression of the disease to stage III. Tumor intravenously implanted in the lungs of animals after limited surgery for stage II disease was also eliminated by immunization.

Straight to the point: considering sharp safety in dentistry.

All members of the clinical dental team face a daily risk of a personal sharp injury. A wide range of sharp instruments are used, some of which are specifically designed to easily pierce the skin and mucosa. The instruments are placed, moved, passed between colleagues, used for treatment, replaced and cleaned, all in relatively confined areas. The clinical dental workplace and the decontamination unit are both therefore sharp-risk environments. There is a clear risk of a sharp injury and the potential consequences of occupational exposure to blood-borne pathogens are at least inconvenient and at worst, career and even life threatening. However, good sharp safety is not universally understood and practised throughout the dental profession. This paper considers the risk of sharp injury in dentistry and discusses some of the methods used to improve sharp safety.

Wrong tooth extraction: an examination of 'Never Event' data.

The NHS in England has identified several adverse incidents that involve patients, including operations done at the wrong site, as "never" events. We examined published data from the period April 2012 to October 2015 and found that "wrong tooth/teeth removed" is the most common "wrong site" event, and accounted for between 20% and 25% of wrong site surgery never events, and 6% - 9% of all "never" events. All "wrong tooth/teeth removed" events seem to have been reported only by hospitals or Community Trusts. It is important to find out how these events are recorded and to find ways to prevent them.

Eradication by active specific immunotherapy of established tumor transplants and microscopic lymph node metastases.

Guinea pigs, each with an established syngeneic dermal line 10 tumor and microscopic lymph node metastases, were immunized by injection of a mixture of irradiated line 10 tumor cells and an oil-in-water emulsion containing heat-killed cells of Mycobacterium bovis strain Bacillus Calmette-Guérin. Squalane or squalene-in-water emulsions, prepared by ultrasonication and containing mg doses of mycobacterial cells, were effective adjuvants. Immunization eradicated established dermal tumors (about 10 mm in diameter) and prevented growth of microscopic lymph node metastases. Untreated animals, animals treated by intradermal administration of Bacillus Calmette-Guérin cells attached to oil droplets alone or with irradiated tumor cells alone, all died with progressive tumor growth.

Immunoprophylaxis of transplantable methylcholanthrene-induced murine fibrosarcomas by immunization with embryo cells expressing endogenous murine leukemia virus antigens.

We investigated the nature of a common tumor rejection antigen(s) in chemically induced murine fibrosarcomas. Two methylcholanthrene-induced fibrosarcomas, previously demonstrated to contain a common tumor rejection antigen(s), released infectious ecotropic murine leukemia virus and expressed the murine leukemia virus proteins, a glycoprotein with a molecular weight of 70,000 (gp70) and an envelope protein with a molecular weight of 15,000. To determine whether an antigen(s) specified by a murine leukemia virus might serve as a common tumor rejection antigen(s), primary cultures of syngeneic embryo cells or cultures of an allogeneic embryo cell line were infected with an endogenous ecotropic murine leukemia virus obtained from one of the cross-reacting fibrosarcomas; expression of infectious virus and/or viral proteins by infected and uninfected embryo cells was monitored and correlated with the results of transplantation protection tests. Uninfected allogeneic embryo cells (SC-1) did not release infectious virus or the viral protein gp70; mice immunized with SC-1 cells did not inhibit tumor growth. Uninfected syngeneic embryo cells did not release infectious virus but did release micrograms quantities of gp70 into supernatant fluids; mice immunized with uninfected syngeneic cells inhibited tumor growth in two of seven experiments. Virus-infected syngeneic and allogeneic embryo cells released both infectious ecotropic murine leukemia virus and gp70; mice immunized with virus-infected cells inhibited tumor growth in 11 of 11 experiments. Growth of the two cross-reacting fibrosarcomas was inhibited in mice immunized with virus-infected embryo cells. The results indicate that antigens coded for by endogenous murine leukemia virus may function as common tumor rejection antigen on chemically induced murine fibrosarcomas.

Adjuvant-antigen requirements for active specific immunotherapy of microscopic metastases remaining after surgery.

We studied the conditions required for eradication by immunization of occult lymph node metastases which remained after surgical removal of an intradermally transplanted cavian hepatoma. Guinea pigs that received no postsurgical treatment all died with progressively growing lymph node metastases. The growth of these metastases could be prevented in a significant proportion of the animals by postsurgical treatment with vaccines containing oil-in-water emulsions of Mycobacterium bovis strain Bacillus Calmette-Guérin (BCG) cell walls admixed with live or irradiated tumor cells. Vaccines containing living tumor cells cured most of the guinea pigs but produced tumors at the vaccine sites in a few animals. Irradiated tumor cell vaccines were not tumorigenic but required more tumor cells for successful therapy. Therapy was dependent both on the dose of tumor cells and on that of BCG cell walls. Microgram doses of BCG cell walls were required for a therapeutic effect; milligram doses of BCG cell walls inhibited the therapeutic response. Animals rendered tumor free by postsurgical vaccine therapy rejected an intradermal challenge with living tumor cells.

Root perforations: aetiology, management strategies and outcomes. The hole truth.

The purpose of this clinical article is to emphasise that root perforations can occur both during and after endodontic treatment. These reduce the chance of a successful treatment outcome and can jeopardise the survival of the tooth. The aetiology and diagnosis of root perforations are described. The article also focusses on the non-surgical and surgical management of root perforations and describes how selection of the appropriate treatment depends on an accurate diagnosis.

It's only teething...a report of the myths and modern approaches to teething.

Paediatric dentistry is not my usual field of work. I am now based almost entirely in restorative dentistry and it is five years since I worked in the dental department of a children's hospital. An essay on teething would appear to be an unusual choice of topic. With the current professional climate of 'general professional education' and 'lifelong learning' I can easily justify my time and effort studying a subject somewhat removed from my regular work. However, to be completely honest, I have reached that age when many of my friends, relatives and colleagues are enjoying the sleepless nights that accompany expanding families. Add to this the fact that I have recently married into a family of midwives, health visitors, nurses and new mothers. I was not sure that I was giving the best, most up to date advice when asked about teething. So some reading around was required. If only it were that simple. I now feel equipped to give a little more help than simply saying, "It's only teething..."

A survey of referrals to a restorative dentistry department in a district general hospital.

This study reports on referrals to a specialist Restorative Dentistry service based in a district general hospital in the United Kingdom. The service encompasses the subspecialties of Endodontics, Periodontics and fixed/removable Prosthodontics and is part of the National Health Service. A prospective, cross-sectional, observational study of consecutive referrals to new patient clinics of a full-time consultant in Restorative Dentistry over a three-month period was undertaken. 277 patients were examined of which 63% were female. 86% of referrals were from general dental practitioners and 79% of patients were from Leicestershire. 44% of referrals were for treatment within the department and 57% were discharged to the practitioners with a treatment plan. The results illustrate the utilisation of a specialist service and show that requests for Endodontic and Periodontal treatment occur most frequently.

Preventing wrong tooth extraction: experience in development and implementation of an outpatient safety checklist.

Extraction of the wrong tooth or teeth is a serious and avoidable clinical error causing harm to the patient. All NHS Trusts in England are required to use a surgical safety checklist in operating theatres to prevent incorrect site surgery and ensure safe management of patients. However, the majority of patients have dental extractions and other oral surgical procedures undertaken on an outpatient basis and these patients are also at risk of having an incorrect site surgical procedure such as a wrong tooth extraction. We describe our experience in developing, introducing and refining a surgical safety checklist for outpatient oral surgery along with the key strategic actions needed to ensure effective cultural change and optimum patient safety in the outpatient setting.

Improving patient safety in a UK dental hospital: long-term use of clinical audit.

The improvement of patient safety has been a long-term aim of healthcare organisations and following recent negative events within the UK, the focus on safety has rightly increased. For over twenty years, clinical audit has been the tool most frequently used to measure safety-related aspects of healthcare and when done so correctly, can lead to sustained improvements. This paper explains how clinical audit is used as a safety improvement tool in an English dental hospital and gives several examples of projects that have resulted in long-term improvements in secondary dental care.

Measuring patient safety in a UK dental hospital: development of a dental clinical effectiveness dashboard.

Patient safety is an important marker of quality for any healthcare organisation. In 2008, the British Government white paper entitled High quality care for all, resulting from a review led by Lord Darzi, identified patient safety as a key component of quality and discussed how it might be measured, analysed and acted upon. National and local clinically curated metrics were suggested, which could be displayed via a 'clinical dashboard'. This paper explains the development of a clinical effectiveness dashboard focused on patient safety in an English dental hospital and how it has helped us identify relevant patient safety issues in secondary dental care.

The aetiology and management of labial and vertical migration of maxillary incisors: 'do you catch my drift?'.

Labial and vertical migration of maxillary incisors is a common complaint seen in general and specialist practices alike. Tooth movement in the aesthetic zone may cause significant concern to the patient, and a challenging management case for the dental team. This paper describes the aetiology, stabilisation and management of such cases.

In vitro and in vivo cytotoxicity induced by an attenuated Salmonella: relation to bacterial carrier state and resistance to tumour growth.

In vivo and in vitro parameters of tumour resistance were examined after immunization of mice with the attenuated 11RX strain of S. enteritidis. During the bacterial carrier state produced by intraperitoneal (i.p.) or intravenous (i.v.) injection of 11RX the mice were resistant to i.p. tumour growth, could destroy i.p. injected 125I- or 131I-labelled tumour cells in vivo and had non-specifically cytotoxic peritoneal cells (PC) which could lyse 51Cr-labelled tumour cells in vitro. Most of the in vivo and in vitro cytotoxic activity could be attributed to activated macrophages (La Posta et al., 1982). The predominantly local nature of 11RX-induced anti-tumour activity was indicated by the superiority of the i.p. route of infection for induction of tumour resistance and in vivo and in vitro cytotoxicity. After i.v. injection of 11RX, none of the anti-tumour effects outlasted the bacterial carrier state. However, after i.p. infection, a dichotomy was observed between in vitro and in vivo anti-tumour effects. In vitro PC cytotoxicity lasted only for the length of the 11RX carrier state (approximately 30 days), whereas resistance to i.p. tumour growth lasted for 60 to 100 day s and was correlated closely with cytotoxic activity measured in vivo. Possible reasons for this dichotomy are discussed.

Relationship between tumour resistance and the in vitro and in vivo cytotoxicity elicited by Salmonella antigens in immunized mice.

Immunization of mice with the attenuated 11RX strain of Salmonella enteritidis (11RX) induces resistance to intraperitoneal (i.p.) tumour growth. Tumour resistance is much greater and lasts for a longer time following i.p. immunization than following intravenous (i.v.) immunization. This paper extends our previous observations that, after this resistance is lost, it can be recalled by a T cell-mediated reaction to an antigenic extract of the bacteria (11RX antigen) which is not protective in unimmunized mice. The duration of this sensitization to 11RX antigen was determined in mice immunized i.p. or i.v. with live 11RX by challenging them at various times after immunization with 131I (or 125I)-labelled Ehrlich ascites tumour (EAT) cells alone or mixed with 11RX antigen. In vivo killing of EAT cells was assayed by monitoring whole-body retention of radioactivity and this was correlated in the same mice with suppression of tumour growth and survival of the mice. The resistance recalled by 11RX antigen was short-lived and in vivo cytotoxic activity had subsided by 6 days after antigen injection. 11RX antigen also recalled the ability of the peritoneal cells to lyse 51Cr-labelled EAT cells in vitro and a close correlation was found between this activity and the cytotoxicity measured in vivo. The adherence properties of the cytotoxic cells and their inhibition by trypan blue indicated that they were macrophages.

In vivo cytotoxic responses induced by allogeneic normal and neoplastic cells in mice: relative lack of immunogenicity of B16 melanoma cells.

It has been previously reported from this laboratory that the C57BL/6 melanoma B16 will grow in allogeneic mice provided that donor-derived passenger leukocytes are first removed by in vitro passage of the tumor cells. In this paper we report that allogeneic and syngeneic mice support similar survival of [125I]iododeoxyuridine-labeled B16 cells (125I-B16 cells) as indicated by whole-body retention of 125I. B16 failed to induce the early cytotoxic response which was induced by semiallogeneic peritoneal cells (PC) and by two other allogeneic tumors (EL4 lymphoma and MC-2 sarcoma). They were nevertheless rapidly destroyed by the response induced by PC or EL4. B16 did show some immunogenicity as indicated by regression of some primary B16 tumors (45% ip and the majority of footpad tumors) and by the slow cytotoxic response to secondary 125I-B16 challenge following preimmunization with live or irradiated B16 cells. An equivalent response was induced by preimmunization with a 100-fold lower dose of PC. These findings are discussed in relation to the requirement for inductive stimuli, in addition to antigen, for the stimulation of in vivo cytotoxic responses.

In vivo H-2K and H-2D antigen expression in two allogeneic mouse tumours of low immunogenicity.

The B16 melanoma of C57BL/6 mice immunizes very poorly, even against its own major histocompatibility complex (MHC) antigens. B16 cells expressed both H-2K and H-2D antigens in vitro as judged by binding of monoclonal antibodies to these antigens in indirect immunofluorescence staining. The in vivo MHC antigen expression of B16 was examined and compared with that of a second C57BL/6 tumour, the Lewis lung carcinoma (3LL), whose defective immunogenicity has been attributed to a selective deficiency in H-2K antigen expression. We found that 125I-labelled cells of both tumours expressed sufficient allo-antigen in vivo to be lysed in BALB/c mice which had been pre-immunized with C57BL/6 lymphoid cells. 125I-B16 cells were also lysed in MHC-recombinant mice which had been immunized against either H-2Kb or H-2Db, indicating that B16 cells express both of these MHC antigens in vivo. This contrasted with our findings with 125I-3LL cells which were destroyed in mice immunized against H-2Db but not in those immunized against H-2Kb. Thus, B16 illustrates a different deficiency in tumour cell immunogenicity which appears not to be attributable to an absence of either of the class I MHC antigens.

Defects in tumor cell immunogenicity: lymphokine signals in in vitro cytolytic responses to tumor alloantigens.

The B16 melanoma of C57BL/6 mice illustrates a deficiency in immunostimulation which may be important in some host-tumor relationships. B16 immunizes very poorly, even against its own major histocompatibility complex (MHC) antigens. We have compared the anti-MHC cytolytic response induced in vitro by B16 and by other tumors of both lymphoid and nonlymphoid origin. We have also studied the role of indomethacin and exogenous lymphokines in facilitating these responses and examined the relationship of specific and nonspecific effector cells induced. In contrast to normal lymphoid cells and two lymphoid tumor cells (EL4 and WEHI-265), the three nonlymphoid tumors, B16, Lewis lung tumor (3LL), and MC-2 fibrosarcoma, failed to induce primary cytolytic responses by themselves. MC-2 and B16 represented two different defects in immunogenicity. MC-2, which we have shown previously to induce an in vivo cytolytic response, could also immunize in vitro provided that prostaglandin production was blocked with indomethacin. In contrast B16, which is poorly immunogenic in vivo, immunized in vitro only if a concanavalin A-induced lymphokine supernatant (CS) was added as an exogenous source of "signal 2." High concentrations of the interleukin 2-containing Con A-induced spleen cell culture supernatant-induced non-H-2b-specific lymphokine-activated killer (LAK) cells in the absence of B16 stimulator cells. However, lymphokine concentrations too low to induce LAK cells enabled the otherwise nonimmunogenic B16 cells to induce specific cytolytic activity.