An assessment of the effects of exposure to vibration, smoking, alcohol and diabetes on the prevalence of Dupuytren's disease in 97,537 miners.

A consecutive sample of 97,537 miners seeking compensation for Hand-Arm Vibration Syndrome were examined in a medical assessment process which included documentation of age, hand dominance, Dupuytren's disease, years of vibration exposure, history of diabetes, smoking habits and units of alcohol consumption per week. The prime determinant of prevalence of Dupuytren's disease was age, and all other factors investigated were corrected for age. There was no statistically significant correlation between years of exposure to vibration and the prevalence of Dupuytren's disease. There was a statistically significant association with smoking, alcohol consumption and diabetes mellitus, with the heaviest smokers having an odds ratio (OR) of 1.31 (95% CI, 1.17, 1.47), the heaviest drinkers (in excess of 22 units a week) having an OR of 1.59 (95% CI, 1.47, 1.72) and diabetes mellitus patients having an increase in the odds of having Dupuytren's disease of 1.52 (95% CI 1.30, 1.77).

Carpal tunnel syndrome in association with hand-arm vibration syndrome: a review of claimants seeking compensation in the Mining Industry.

Twenty six thousand eight hundred and forty-two miners seeking compensation were clinically assessed for vascular and neurosensory impairment arising from exposure to occupational hand-arm vibration (Hand-Arm Vibration Syndrome). They were also assessed clinically for Carpal Tunnel Syndrome which, if present, would result in additional compensation. Fifteen per cent were assessed as having both HAVS and CTS. Thirty-eight per cent of claimants had nocturnal wakening, 1.3% wasting of abductor pollicis brevis, 15% had a positive Tinel's test and 20% had a positive Phalen's test. The 15% prevalence reported is lower than the rates cited previously in several small population studies of workers exposed to vibration. This paper reports the results of the assessment process and discusses the difficulty of discriminating Carpal Tunnel Syndrome from diffuse neurosensory impairment arising from HAVS.

Use of sensorineural tests in a large volume of medico-legal compensation claims for HAVS.

BACKGROUND: The Department of Trade and Industry set up a contract to examine miners and ex-miners claiming compensation for hand-arm vibration syndrome (HAVS). They had been exposed to hand-transmitted vibration. Over 100,000 have now been examined using sensorineural tests as part of that process. AIMS: The purpose of this paper was to examine the internal consistency of the vibrotactile threshold test (VTT) and the thermal aesthesiometry test (TA). METHODS: In 18 centres across the UK, nurses were trained to perform the measurement of VTT and TA in a controlled standardized manner. These tests were to aid the staging of the neurological component of the Stockholm Workshop Scales. The staging of this component was modified by dividing stage 2SN into 2SN (early) and 2SN (late). The test results and an automatic neurological staging were presented to the examining doctor following the clinical examination. The results of these sensorineural tests were held on a central database. The results and analysis of the first 57,000 tests are reported. RESULTS: The correlations within the VTT and TA scores were consistent with reliable measures. However, these correlations were not of such strength as to allow reliance on the results of a single test when making an assessment of the severity of neurological damage. CONCLUSIONS: Different end organs and nerve fibres should be tested when making an assessment of damage in the sensorineural component of HAVS. The correlations demonstrated for the VTT and TA suggest that they are of value in assessing these claimants and would be for other vibration exposed workers.

Cold provocation testing and hand-arm vibration syndrome--an audit of the results of the Department of Trade and Industry scheme for the evaluation of miners.

BACKGROUND: Hand-arm vibration syndrome (HAVS) is a major industrial disease that causes considerable morbidity among workers exposed to vibration. Compensation is paid to those affected in civil claims against employers and (in the UK) in claims made under Social Security legislation rules for Prescribed Disease A11. Diagnostic tests have been proposed but most are not objective. The cold provocation test (CPT), which is objective, is often included in the evaluation of HAVS. METHODS: A continuous audit was made of the findings recorded at the 18 HAVS test centres in the UK established to evaluate miners. The audit, and its outcome, were monitored by the Medical Reference Panel who advise the Department of Trade and Industry. This audit report constitutes the second analysis of the findings relating to the CPT. RESULTS: The CPT, with measurement of digital rewarming times, is of no value in assessing vibration-induced damage to the hands. CONCLUSION: In its present format, the CPT should not be used for evaluating the vascular component of HAVS.

Thyroid aspiration cytology in Newcastle: a six year cytology/histology correlation study.

BACKGROUND: Fine needle aspiration cytology (FNAC) is a well-established technique for pre-operative investigation of thyroid nodule(s). Thyroid FNAC was introduced in the teaching hospitals of Newcastle upon Tyne in 1981, initially with a small group of clinicians as aspirators. Audit results for 1981-1986 inclusive showed an unsatisfactory rate of 25.3% and prediction of malignancy with a sensitivity of 93.5%. FNAC has become more popular locally for the investigation of thyroid disease and the number of clinicians performing aspirates has increased. The results for recent years have, therefore, been audited. METHODS: Medical records were reviewed for 239 patients with a dominant thyroid nodule who had FNAC carried out in the 6 year period 1990-1995 and subsequent partial or complete thyroidectomy. RESULTS: Histology of thyroid specimens showed 60 follicular adenomas and 34 malignant lesions (including 19 papillary, 10 follicular and 3 medullary carcinomas, one lymphoma and one follicular neoplasm with indeterminate malignant potential). A total of 302 FNAC had been carried out on these 239 patients. On cytological grounds the unsatisfactory sample (AC0 and AC1) rate was 43.1% on initial aspiration which was reduced to 32.2% on repeated aspiration. FNAC predicted neoplasia (AC3, AC4 and AC5) with a sensitivity of 86.8%, a specificity of 67.0%, a negative predictive value of 87.5% and a positive predictive value of 65.5%. Malignancy was predicted by FNAC (AC3, AC4 and AC5) with a sensitivity of 88.9%. A FNAC report of AC5 had a positive predictive value for malignancy of 100%. CONCLUSIONS: FNAC is an invaluable and minimally invasive procedure for the pre-operative assessment of patients with a dominant thyroid nodule. It is, however, important that the number of aspirators and cytopathologists be kept small to maintain expertise and also that the results of FNAC be subjected to ongoing audit.

Drains for thyroidectomy/parathyroidectomy: fact or fiction?

BACKGROUND: Many authorities advocate draining the neck routinely after thyroid and parathyroid surgery with no scientific evidence to support this practice. We aimed to establish if the routine use of drains following thyroid/parathyroid surgery is of any value. METHOD: Medical records of patients who underwent thyroidectomy or parathyroidectomy under the care of a single endocrine surgeon (GP) over a 14-year period were reviewed. For the first 6 years, the neck was routinely drained (drain group) and for the subsequent 8 years the neck was only drained if the surgeon felt it necessary according to the operative situation (selective group). RESULTS: A total of 606 procedures (425 thyroidectomy and 181 parathyroidectomy) were performed on 582 patients. Drains were routinely used in 134 (22%) procedures (drain group) and were selectively used in 472 (78%) (selective group) of which 191 (40%) were drained. In all patients, there was a significant increase in the rate of postoperative bleeding/haematoma in patients with a drain (8/314 versus 1/282, Fisher's exact, P < 0.05). Wound infection occurred only in the patients with a drain. There was no difference in the incidence of postoperative bleeding and airways obstruction between the drain and selective groups. CONCLUSION: We conclude that the routine use of neck drains is unnecessary and may indeed be harmful, drain insertion being associated with an increased incidence of wound infection. Drains should, therefore, be used selectively after thyroidectomy and parathyroidectomy.

Insulin-stimulated phosphorylation of initiation factor 4E is mediated by the MAP kinase pathway.

The cap-binding initiation factor 4E (eIF4E) is regulated by phosphorylation and by the inhibitory binding protein 4E-BP1. Here we show that insulin-induced phosphorylation of eIF4E is not significantly affected by rapamycin, but is sensitive to wortmannin, which inhibits phosphatidylinositol 3'-kinase and blocks the activation of MAP kinase. Since PD098059, an inhibitor of MAP kinase activation, also blocks insulin-induced phosphorylation of eIF4E, the MAP kinase pathway seems to mediate this effect. Phosphorylated eIF4E can still bind to 4E-BP1. These data illustrate that (i) distinct signalling pathways mediate the phosphorylation of eIF4E and 4E-BP1 and (ii) phosphorylation of eIF4E, unlike that of 4E-BP1, does not lead directly to the release of 4E-BP1.

Flow cytometric crossmatching in renal transplantation--outcome after five years.

The association of a positive flow cytometric crossmatch between recipient IgG directed against donor T lymphocytes and poor outcome is well described in renal transplantation. Until now, no long-term follow-up on such patients has been available. A total of 117 renal transplant patients were followed up for a period of 5 years. Of these, 21 were known to have donor T cell-directed IgG and 5 had B lymphocyte-directed IgG. Both groups of patients with these antibodies had a significantly poorer outcome at 5 years than did the group of patients without IgG (P < 0.0001 Handel Maenzel test). Patients with antibody detected preoperatively were tested again, either at the time of graft failure or at 5 years posttransplantation. The sera were tested against stored donor cells and the intensity of surface IgG compared with the preoperative levels. In those recipients who lost their grafts, the levels increased in 60% of cases but those that retained their grafts also had an increase in levels of donor-directed antibody in 50% of cases. The changing levels of antibody therefore appeared to have little relevance to outcome. However, when IgG isotypes were considered, for those who experienced graft failure and also had a gamma 3 isotype, a rise in IgG was demonstrated in all cases. Conversely, successful grafts with gamma 3 had a decline in levels between preoperative and 5-year samples in three of the four cases (p not significant).

Flow cytometric crossmatching in renal transplantation--the long-term outcome.

The association of a positive flow cytometric crossmatch between recipient IgG directed against donor T lymphocytes and poor outcome is well described in renal transplantation. Until now no long-term follow-up on such patients has been available. In this study, 117 renal transplant patients were followed up for a period of 5 years. Of these 21 were known to have donor T cell directed IgG and five had B lymphocyte directed IgG. Both groups of patients with these antibodies had a significantly poorer outcome at 5 years than did the group of patients without IgG (p < 0.0001, Handel Maenzel test). Patients with antibody detected preoperatively were tested again either at the time of graft failure or at 5 years post-transplantation. The sera were tested against stored donor cells and the intensity of surface IgG compared with the preoperative levels. In those recipients who lost their grafts the levels increased in 60% of cases, but those who retained their grafts also had an increase in levels of donor directed antibody in 50% of cases. The changing levels of antibody therefore appeared to have little relevance to outcome. However when IgG isotypes were considered, in those who experienced graft failure and also had a gamma 3 isotype, a rise in IgG was demonstrated in all cases. Conversely, successful grafts with gamma 3 had a decline in levels between preoperative and 5-year samples in three of the four cases (not significant).

The value of posttransplant monitoring of interleukin (IL)-2, IL-3, IL-4, IL-6, IL-8, and soluble CD23 in the plasma of renal allograft recipients.

Over the past few years, the central role of cytokines in the amplification of the immune response has been reported and several studies have examined the relationship between the plasma level of individual lymphokines during renal allograft rejection. The aim of the present investigation was to study simultaneously IL-2, IL-3, IL-4, IL-6, IL-8, and soluble CD23. Analysis of results has allowed both the prognostic value and any possible interrelationships between the measured cytokines to be determined. We studied 16 renal transplant recipients for the first 14 days after transplantation. Seven patients showed clinical evidence of acute allograft rejection and 5 showed excellent stable graft function with no signs of rejection. Primary nonfunction was seen in 4 patients. The plasma levels of each cytokine were measured by commercially available ELISA and immunoradiometric assay kits. As reported in previous studies, plasma IL-2 levels, whenever found at detectable levels, were predictive of impending graft rejection. Serial monitoring of IL-4 and IL-6 was more reliable for the differential diagnosis of rejection, particularly toward the end of the first week after transplantation. IL-3, IL-8, and soluble CD23 were not diagnostic or predictive of rejection, due to the occurrence of significantly high levels in transplant patients who showed no evidence of clinical rejection. While the value of cytokine monitoring has been shown in this study, it should be remembered that infection, although not seen in these studies, may have a profound affect on the results obtained.

Renal allograft rejection. Tubular epithelial cells present alloantigen in the presence of costimulatory CD28 antibody.

Renal tubular epithelial cells can be induced to express potentially immunogenic levels of class II MHC antigens but fail to stimulate the activation of allospecific T lymphocytes. The current series of experiments was performed to determine whether the failure of lymphocyte activation in this system is caused by defective T cell costimulation. It was found that cultured renal epithelial cells expressed class II MHC antigens and the immunoregulatory adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and lymphocyte function-associated antigen-3 after stimulation with IFN-gamma, but that the B7 ligand for CD28 was not expressed. Mixed cell culture experiments were set up in which lymphocytes were mixed with IFN-gamma-treated allogeneic renal cells. Lymphoproliferation and IL-2 production were only observed if bivalent anti-CD28 antibodies were titrated into these cultures. The requirement for antigen stimulation was retained by these lymphocytes, as no proliferation was observed after stimulation by class II MHC antigen nonexpressing, resting renal cells. Further experiments demonstrated that the effectiveness of the anti-CD28 antibody-mediated signal was enhanced by cross-linking with a secondary anti-kappa-chain antibody. These data are consistent with the concept that a costimulatory signal generated by ligation of CD28 is of central importance to the development of an immune response to alloantigen. Furthermore, these results indicate that tubular epithelial cells within a rejecting renal allograft are unlikely to initiate direct activation of infiltrating allospecific lymphocytes.