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Few studies describe the incidence and nature of psychiatric morbidity in plastic surgery patients. We undertook a review of all referrals from the Plastic Surgery Service to the Psychological Medicine Service over a 1-year period (January-December 2001). Standardised socio-demographic information, nature and cause of injury/defect, surgical intervention, surgical outcome, psychiatric diagnosis and psychiatric follow-up were determined. The majority of patients referred had a significant existing psychiatric illness, had made a suicide/parasuicide attempt, or were burns patients. There was a high rate of referral of plastic surgery inpatients. Liaison with plastic surgery staff to allow rapid identification and early management of psychiatric morbidity is an important role for psychological medicine. We outline a defined categorisation of common contexts in which psychiatric morbidity may present to plastic surgery services.

Interleukin-12 (IL-12) is a key immunoregulatory cytokine which promotes the development of Thl-dependent, cell-mediated immune responses. Acute allograft rejection after organ transplantation and acute graft-versus-host disease (GVHD) after bone-marrow transplantation are generally attributed to cell-mediated immune mechanisms and, therefore, potentially susceptible to immunological intervention at the level of IL-12. Recent data from murine models of transplantation have highlighted the potential of IL-12 as a selective target for immunotherapy. Neutralising endogenous IL-12 for a brief period at the time of transplant promotes long-term deviation from a Th1 to a polarised Th2 alloimmune response. This confers lasting protection from GVHD but is less effective at preventing acute rejection, possibly because Th2-dependent immune responses are also capable of effecting graft rejection.

Background: During allograft rejection, up-regulation of cytokine-inducible nitric oxide synthase (iNOS) leads to the production of large amounts of nitric oxide (NO). The net effect of NO on the alloimmune response is, however, difficult to predict because of its diverse biological effects, which include potentially opposing roles as an effector and immunoregulatory molecule., Methods: In this study, the role of iNOS on the in vitro and in vivo alloimmune response was defined using mutant mice that lack a functional iNOS gene. The ability of spleen cells obtained from iNOS-deficient mutants to proliferate and to produce cytokines in response to irradiated BALB/c stimulator cells was determined, and the rate at which iNOS-deficient mice were able to reject BALB/c skin allografts was observed., Results: Spleen cells from homozygous iNOS-deficient (129xMF1)F1 mice, when compared with cells from heterozygous control mice, showed an increased in vitro proliferative response and produced substantially higher levels of interferon-gamma, and also more interleukin-2 and interleukin-12, in response to allogeneic stimulation. The kinetics of BALB/c skin graft rejection were comparable in heterozygous control animals and iNOS-deficient mice. Moreover, no net effect of iNOS on skin allograft rejection was apparent in mice treated with depleting monoclonal antibodies (mAb) to CD4 or CD8 T cells, either alone or in combination, or in mice treated with both anti-CD8 mAb and a neutralizing anti-tumor necrosis factor mAb., Conclusions: These results show that iNOS has an immunomodulatory effect on the in vitro alloimmune response but lack of iNOS has no net influence on the kinetics of murine skin allograft rejection in either unmodified recipients or recipients in which the early contribution of T-cell subsets and tumor necrosis factor-alpha to graft rejection has been abrogated.

A series of 10 patients with craniofrontonasal dysplasia presenting to the Oxford Craniofacial Unit since 1983 is presented. In addition to the well-described combination of coronal synostosis and frontonasal dysplasia, 9 patients had very characteristic dry, curly or frizzy hair. All the patients were female. Recognition of the syndrome is important for genetic counselling, although the precise mode of genetic transmission is unclear with females predominating and males being less severely affected. Surgical correction was in two stages: early frontal advancement followed by correction of hypertelorism when the child became aware of the deformity. Four patients had their craniosynostosis treated in the Oxford Craniofacial Unit. Three patients had previously had frontal remodelling elsewhere. Nine patients had surgery for hypertelorism. The preferred technique for hypertelorism correction was facial bipartition. Following hypertelorism correction, the excess skin was allowed to redrape and subsequently dealt with by medial canthoplasties, thus avoiding a midline scar. Careful attention to the primary frontal advancement procedure is important to avoid complications following difficult dissection of the frontal bone flap at the time of hypertelorism correction.

The case is described of a 53-year-old man presenting with right-sided low back and thigh pain. Non-urgent investigations showed a metastatic lesion in his right hemipelvis arising from a thyroid primary.

Fracture of the femur in children is a common problem which can be managed in a variety of ways. We treated such fractures in children up to the age of 13 by immobilization in a Thomas splint, after reduction, if necessary, and traction in hospital. After a short period, traction was continued at home using a mobile frame with the Thomas splint. The results of such home traction were assessed in terms of both healing of the fracture and any complications and of the parental attitudes to treatment at home. It was found that traction at home was an acceptable method for the management of such fractures. Results were comparable to other methods of treatment and parental satisfaction was very high, providing there was adequate surveillance by the district nurse and immediate access to advice. The cost-savings of such a treatment are significant.

A total of 91 patients with melanoma of the head and neck treated between 1973 and 1991 were studied prospectively with regard to prognostic features, treatment and outcome. Other than Breslow thickness, the only important prognostic feature was the less aggressive nature of lentigo maligna melanoma. A policy of selective excision margins, 1 cm for impalpable and 2 cm for palpable lesions, was found to be safe, although preliminary biopsy should be used if there is diagnostic uncertainty or where the expected extent of surgery entails a mutilating procedure. Local recurrence rates were not affected by the method of wound closure, which should be determined by the best functional and cosmetic outcome. These results support the trend against prophylactic neck dissection. Such dissection, when indicated for lesions of the face, pinna, anterior scalp and parotid area, should routinely include superficial parotidectomy. Uncontrolled symptomatic loco-regional recurrence is an uncommon complication that may occur despite radical primary surgery. The role of preoperative radiotherapy for high-risk melanoma in this situation warrants investigation.

Conditioned media from 14 short term fibroblast cell lines were mitogenic for human breast cancer cells with different steroid receptor profiles in serum-free culture. Fibroblast-conditioned medium stimulated tritiated thymidine incorporation in short term culture and growth in a longer proliferation study as measured by the MTT colorimetric assay. Conditioned media from benign and malignant epithelial cells were non-stimulatory for breast cancer cells but that derived from endothelial cells showed similar stimulation to fibroblasts. Partial purification of fibroblast-conditioned medium identified a peptide with a molecular weight of approximately 8 kDa that showed no affinity for heparin and was mitogenic for MCF-7 breast cancer cells.

A group of 434 patients treated for primary cutaneous melanoma over an 18-year period by a policy of selective excision margins based on clinical estimation of tumour thickness was studied prospectively. Clinical assessments of tumour as impalpable, palpable but not overtly nodular, and nodular correspond to thicknesses of < or = 0.75, 0.76-1.49 and > or = 1.50 mm respectively. From 1971 to 1987, 330 patients were treated with excision margins of 1, 2 and 3-5 cm based on these respective ranges. During 1988 and 1989, 104 patients were treated after reduction of the maximum width of excision to 2 cm. The overall local recurrence rate was 11 of 434 patients (2.5 per cent), with no recurrence in melanoma < or = 0.75 mm thick and no increase in the local recurrence rate after reduction of the maximum margin from 3 to 2 cm. A policy of 2-cm clearance for palpable and nodular melanoma and 1 cm for impalpable lesions is recommended. Any further reduction must be tested prospectively.

Primary cultures of adult mouse sensory neurons maintained for 8 days in vitro (8 div), in both the presence of non-neuronal cell (NNC) outgrowth and in NNC-reduced cultures, were exposed to doses of ethanol, propanol, acetaldehyde and acrolein. The effects on cell viability were monitored: LD50's of 600 microM acrolein and 100 mM propanol were obtained after 24 h exposures and after 48 h with 1 mM acetaldehyde and 500 mM ethanol. Morphological effects were evident by scanning electron microscopy with sub-acute doses for each agent, using both lower concentrations and shorter exposures. Membrane pitting of the perikaryon and a reduction in the proportion of neurons bearing neurites were common signs of toxic insult. The neurites of treated cells were thicker and more irregular than those of untreated cells; this proved a good indicator of specific neurotoxicity rather than merely a cytotoxic response. Fetal calf serum in the medium lessened the response of neurons to ethanol treatments. Comparison with other in vitro studies suggests these primary cultures are a more sensitive system than established cell lines of neuronal origin for use in neurotoxicity testing.

Primary cultures derived from adult mouse dorsal root ganglia have been maintained in the presence or absence of 5 X 10(-6)M cytosine arabinoside for periods of up to 4 weeks. In cultures in which cytosine arabinoside is present, the non-neuronal cell population is effectively reduced. When uncoated plastic substrata are used there is also a concurrent decrease in the number of neurons if the medium is supplemented with cytosine arabinoside. The effects on neuron survival of substrata coated with fibronectin, polyornithine, polylysine, and exudates prepared from mouse liver cells were studied. It was shown that neuronal densities similar to those with uninhibited media may be retained in the presence of cytosine arabinoside if fibronectin-coated substrata are prepared. With the other coating agents neuronal survival was also enhanced but to a lesser extent. The study offers a means therefore of producing purer cultures of dorsal root ganglia neurons than has previously been possible from adult mammalian sources.

Ethylation and isopropylation of guanine in alkaline solution, or of adenine in formic acid, by alkyl methanesulphonates gave the following products: 1-, N2-, 3-, O6-, 7- and 9-alkylguanines; 1-, 3-, 7- and 9-alkyladenines. The products were identified from their characteristic u.v-absorption spectra, by comparison with either known ethyladenines or with the corresponding known methyladenines, and were also characterized by mass spectrometry. Their chromatographic properties on paper, t.l.c. and various columns were determined. DNA was alkylated in neutral solution with 14C-labelled alkyl methanesulphonates and the ratios of the alkylpurines formed were obtained, and compared for alkylation by methyl, ethyl and isopropyl methanesulphonates and by N-methyl-N-nitrosourea. The extents of alkylation at O-6 of guanine relative to those at N-7 of guanine varied with the reactivity of the methylating agents according to the predictions of Swain & Scott (1953) relating nucleophilicity of the groups alkylated with the substrate constants of the alkylating agents. The relative extents of alkylation at N-3 of adenine did not follow this correlation.

Adult mouse DRG neurones have been maintained for 14 days in cultures where non-neuronal cell proliferation was inhibited by the inclusion of 5 x 10(-6) microM-cytosine arabinoside (AraC) in the medium from the onset of culture. On uncoated plastic neurone numbers significantly declined in the absence of non-neuronal cell outgrowth compared with uninhibited co-cultures. However, when neurones were maintained in the presence of AraC on certain coated surfaces this decrease in neurone numbers was not observed. Combinations of fibronectin (FN) and laminin (LAM) proved most effective for 7 and 14 days in vitro, although either was beneficial if used separately. Microexudates produced by the fibroblast line, 3T6, also significantly improved neuronal counts for 14 days in vitro. However, a microexudate derived from primary cultures of mouse hepatocytes, although advantageous for 7 days in vitro, was not effective in maintaining neurones over the 14-day culture period, reminiscent of previous observations when synthetic cationic agents were used. Electrophoretic analysis of the fibroblast exudate indicated that fibronectin was present in the substrate-attached material generated by this cell line. The reduction in non-neuronal cell growth facilitated the monitoring of neuronal structural detail by scanning electron microscopy. Examination of neurite extension, indicative of neurone differentiation, was particularly improved. FN/LAM and the fibroblast-derived exudate increased nerve fibre growth, whilst the hepatocyte exudate had little effect on neurite regeneration, and polylysine had a detrimental effect. The data demonstrate that substrata can have a significant effect on maintenance and differentiation of adult neurones in primary culture.(ABSTRACT TRUNCATED AT 250 WORDS)

1. DNA was treated with N-methyl-N-nitrosourea at pH7-8, 37 degrees C, degraded to yield 3- and 7-methylpurines and deoxyribonucleosides and the reaction products were separated by chromatography on ion-exchange resins. The following methods for identification and determination of products were used: with unlabelled N-methyl-N-nitrosourea, u.v. absorption; use of methyl-(14)C-labelled N-methyl-N-nitrosourea and use of [(14)C]thymine-labelled DNA. 2. The synthesis of O(4)-methylthymidine and its identification by u.v. and mass spectroscopy are reported. 3. 3-Methylthymidine and O(4)-methylthymidine were found as methylation products from N-methyl-N-nitrosourea with thymidine and with DNA, in relatively small yields. Unidentified products containing thymine were found in enzymic digests of N-methyl-N-nitrosourea-treated DNA, which may be phosphotriesters. 4. The possible role of formation of methylthymines in mutagenesis by N-methyl-N-nitrosourea is discussed.