Variation in the prevalence of chronic bronchitis among smokers: a cross-sectional study.

OBJECTIVE: Given the wide variations in prevalence of chronic obstructive pulmonary disease observed between populations with similar levels of exposure to tobacco smoke, we aimed to investigate the possibility of variations in prevalence of chronic bronchitis (CB) between two geographically distinct smoking populations in rural Karnataka, India. DESIGN: The Burden of Obstructive Lung Disease (BOLD) questionnaire was administered to all men aged >30 years in a cross-sectional survey. The χ(2) and Fisher's exact tests were used to compare CB prevalence in the two populations. Logistic regression was used to analyse the impact of multiple variables on the occurrence of CB. RESULTS: Two samples of 2322 and 2182 subjects were included in the study. In non-smokers, CB prevalence did not differ between the populations. However, it was significantly different between smoking populations (44.79% vs. 2.13%, P < 0.0001). Logistic regression indicated that, in addition to smoking, region, age, occupational dust exposure and type of house were associated with higher likelihood of CB. An interaction between smoking and area of residence was found (P < 0.001) and appeared to explain the effect of region (without interaction). CONCLUSION: A significant difference in CB prevalence was observed between male populations from two areas of Karnataka state, including when stratified by smoking status. No significant difference was observed between non-smokers.

Management of Asthma in School age Children On Therapy (MASCOT): a randomised, double-blind, placebo-controlled, parallel study of efficacy and safety.

BACKGROUND: Asthma affects one in eight children in the UK. National management guidelines have been available for many years but, unlike in adults, studies in children have been few, with their methodologies often based on inappropriate adult models. Sound medical evidence in support of the national guidelines for asthma management in children is lacking. The MASCOT study has been developed to address this need. OBJECTIVES: To determine whether adding salmeterol or montelukast to low-dose inhaled corticosteroids (ICSs) can reduce the number of exacerbations requiring treatment with oral corticosteroids in children with uncontrolled asthma. DESIGN: A randomised, double-blind, placebo-controlled trial with a 4-week run-in period on a fluticasone propionate inhaler (100 µg twice daily) with inhaler technique correction. Patients who met the post run-in period eligibility criteria were randomised in the ratio of 1 : 1 : 1 and were followed for 48 weeks. SETTING: Secondary care hospitals based in England and Scotland with recruitment from primary and secondary care. PARTICIPANTS: Children aged 6-14 years with asthma requiring frequent short-acting beta-2 agonist relief, with symptoms of asthma resulting in nocturnal wakening and/or asthma that has interfered with usual activities. INTERVENTIONS: Three groups were compared: (1) inhaled fluticasone propionate 100 µg twice daily plus placebo tablet once daily; (2) inhaled fluticasone propionate 100 µg and salmeterol 50 µg twice daily (combination inhaler) plus placebo tablet once daily; and (3) inhaled fluticasone propionate 100 µg twice daily plus montelukast 5-mg tablet once daily. MAIN OUTCOME MEASURES: The primary outcome was the number of exacerbations requiring treatment with oral corticosteroids over 48 weeks. Secondary outcome measures included quality of life as measured by the Paediatric Asthma Quality of Life Questionnaire with Standardised Activities [PAQLQ(S)] and the Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ); time from randomisation to first exacerbation requiring treatment with a short course of oral corticosteroids; school attendance; hospital admissions; amount of rescue beta-2 agonist therapy prescribed; time from randomisation to treatment withdrawal (because of lack of efficacy or side effects); lung function at 48 weeks (as assessed by spirometry); cost-effectiveness; adverse events. RESULTS: The study was closed prematurely because of poor recruitment and the target sample size of 450 was not achieved. In total, 898 children were screened to enter the trial, 166 were registered for the 4-week run-in period and 63 were randomised (group 1: 19, group 2: 23, group 3: 21), with 38 contributing data for the primary outcome analysis. There were no significant differences between groups for any of the outcomes. Adverse events were similar between the groups except for nervous system disorders, which were more frequently reported on fluticasone plus montelukast. CONCLUSIONS: Based on the results of the MASCOT study it is not possible to conclude whether adding salmeterol or montelukast to ICSs can reduce the number of exacerbations requiring treatment with oral corticosteroids in children with uncontrolled asthma. TRIAL REGISTRATION: Current Controlled Trials ISRCTN03556343. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 4. See the HTA programme website for further project information.

The impact of published recommendations on the management of penetrating abdominal injury.

BACKGROUND: In patients with penetrating abdominal injury (PAI), haemodynamic instability and peritonitis are indications for laparotomy, but it remains uncertain whether laparotomy is indicated for evisceration, retained foreign body and pneumoperitoneum. In 1989, a review of 107 patients with PAI revealed a 78.5 per cent laparotomy rate, with 35 per cent considered unnecessary. The aim of this study was to review current practice in the same hospitals. METHODS: A retrospective review included case notes from 224 patients with PAI presenting to three hospitals between 2001 and 2005. RESULTS: Some 206 patients (92.0 per cent) were male and the mean age was 30.5 years. Aetiologies were stabbing (96.4 per cent), impalement (2.7 per cent) and gunshot wound (0.9 per cent). Laparotomy was performed in 48 patients (21.4 per cent), and was positive in 33 and unnecessary or negative in 15. Haemodynamic instability and peritonitis were strong indicators of positive laparotomy; seven of 13 laparotomies for evisceration alone were negative, as were two of four for retained foreign bodies. CONCLUSION: The laparotomy rate fell from 78.5 to 21.4 per cent over 25 years. The rate of unnecessary or negative laparotomy did not change. Isolated evisceration and retained foreign body remain relative indications.

Should pre-operative troponin be a standard requirement in patients undergoing major lower extremity amputation?

OBJECTIVES: The objective of this study was to ascertain the benefit of routine pre-operative cardiac troponin I (cTnI) measurement in patients undergoing major lower extremity amputation for critical limb ischaemia. DESIGN: This was a prospective, blinded observational study. METHODS: All patients scheduled for lower extremity amputation, without evidence of unstable coronary artery disease were recruited prospectively over a period of 1 year. In addition to routine pre-operative evaluation, a blood sample was taken for measurement of serum cTnI. Post-operative screening was conducted for cardiac events with patients followed up to 6 weeks. RESULTS: Ten of the 44 patients included suffered a non-fatal myocardial infarction or died from a cardiac cause post-operatively. A rise in pre-operative cTnI was associated with a very poor outcome (two cardiac deaths and one post-operative myocardial infarction) and was the only significant predictor of post-operative cardiac events. CONCLUSION: Routine pre-operative cTnI measurement may be of use to identify patients at high risk of cardiac complication who would benefit from optimization of cardiac status or in whom surgery could be deferred.

Ten-year experience of carbon dioxide laser ablation as treatment for cutaneous recurrence of malignant melanoma.

BACKGROUND: Cutaneous recurrence of malignant melanoma is distressing for the patient, can be difficult to palliate and is resistant to treatment by conventional methods. Experience with carbon dioxide laser ablation was reviewed to determine the initial efficacy, time to recurrence, number of treatments required and length of palliation achieved. METHODS: Using a departmental database and case notes, a review was carried out of all patients undergoing laser ablation in the authors' unit between September 1992 August 2002. RESULTS: Forty-two patients received 105 (mean 2.5) treatments. The median time to recurrence was 5.2 (range 1.2-72.0) months. Twenty-three patients were still alive, with a median time from first laser ablation of 5.4 (range 0.5-10.0) years. Nineteen patients had died, a median of 0.8 (range 0.1-5.3) years after the first ablation. Ten of the 23 patients were disease-free for more than 1 year. No limbs were amputated because of failure to control disease. CONCLUSION: Laser ablation is a practical and useful method of palliating recurrent cutaneous malignant melanoma.

Revalidation--are we fixing a system that wasn't broken?

In 10 years, the medical profession in the U.K. has moved from a loose system of self regulation, through reluctant and patchy compliance with recorded continuing medical education (CME) to statutory obligations for 5-yearly revalidation which will control the issuing of a licence to practise for all doctors. The profession initially viewed these changes with dismissive cynicism, but the new rules are now being viewed with trepidation and paranoia. Royal Colleges can still play a central role in the development of the Revalidation process and must work together to develop appraisal as a meaningful tool to be used for the benefit of patient and doctor.

Revalidation: the catalyst for change in continuing professional development?

Remarkably, only five years ago, hospital specialists were under no formal obligation to record participation in Continuing Medical Education (CME). No one seriously doubted that such education took place, but the system had never been challenged. In recent years, and with apparently ever increasing pace, all this is changing. Traditional, didactic, lecture based teaching of undergraduates is slowly vanishing from many undergraduate curricula. Postgraduate hospital training has been brought into line with Europe so that, within 7 years of full registration, it is theoretically possible to become a consultant. The Royal Colleges were charged with developing and monitoring a structured system of CME and chose to use the "points" system of which there was experience elsewhere. Around 70% of surgeons returned their annual CME forms and almost all met the agreed minimum points total. As a meaningful educational exercise which impacted favourably on patient care the points system was impossible to defend vigorously, and was ignored by an important minority. More recently still, our entire profession has been exposed to regular and fundamental criticism. There was a real risk that we would lose the right to self regulation. The GMC has now announced that every doctor will be required to undergo a process of appraisal that will lead to revalidation, allowing the doctor to remain on the national register. A full consultative process is now in place, with the Royal Colleges being required to implement a new system of annual review which will allow profiling of every surgical practice. While it is possible react to these changes with a combination of resentment and paranoia, the profession should grasp this opportunity for change. The sensible introduction of personal portfolios should allow us to maintain and improve standards of care, and allow us to demonstrate these standards to our peers, our employers and our patients. We may yet look back on clinical governance and revalidation as the catalysts which brought about constructive change to a potentially complacent profession.

Intraoperative identification of sentinel lymph node in patients with malignant melanoma.

We report our experience with the technique of lymphatic mapping using patent blue V dye in patients with limb malignant melanoma. The technique is based on the hypothesis that embolic metastases occur along lymphatic channels to a 'sentinel' lymph node: the draining lymph node nearest the site of the primary malignant melanoma. Patent blue V dye (0.5-1.0 ml) is injected intradermally around the site of the melanoma. Immediately the groin or axilla is opened and the blue lymphatic channels followed to the sentinel node. The node is removed and examined by both haematoxylin and eosin (H&E) and immunohistochemical staining. We have carried out this technique in 35 patients, all of whom had 'clinically assessed' stage I disease. In all 35 patients, sentinel nodes were identified, and nine were found to contain unsuspected micrometastases. Our initial evaluation of intraoperative lymphatic mapping is very promising. The technique is practicable and easy to master. If 25% of patients with cutaneous malignant melanoma who are clinically stage I have nodal disease, this has great importance not only for staging and treatment but also for all future therapeutic trials.

A comparison of dosimetric methods in isolated limb perfusion with melphalan for malignant melanoma of the lower extremity.

The three dosimetric schedules currently used in isolated limb perfusion with melphalan for malignant melanoma of the lower limb were compared in a series of 51 patients. The doses prescribed by each of the three methods (based on total body weight (TBW), limb tissue volume (LTV) and total blood volume in the perfusion circuit (TBV)) were calculated for all patients and were then compared using Wilcoxon's signed-rank test. This revealed that the method based on TBV consistently prescribed much lower doses of drug than either of the other two methods. Pharmacokinetic profiles of melphalan obtained by HPLC analysis of blood samples during the procedure also showed that the method did not reliably predict the concentration of melphalan achieved in the perfused limb. The dosimetric schedule based on LTV prescribed slightly higher doses than that based on TBW. However, the technique is more difficult to practise due to the problems of measuring the limb volume by immersion. We conclude that the dosimetric schedule based on TBW is the most appropriate by virtue of its simplicity, the high doses of melphalan which it prescribes, and the well-controlled toxicity which it produces.

A single centre's 10 year experience with isolated limb perfusion in the treatment of recurrent malignant melanoma of the limb.

The aim of this study was to assess whether isolated limb perfusion can be performed safely and whether it offers improved disease-free survival for patients with limb malignant melanoma. Between August 1983 and July 1993, 103 patients (78 female, 25 male) with recurrent limb melanoma were treated by isolated limb perfusion (ILP) in Glasgow, U.K. The mean age of the patients was 62 years; 95 had leg recurrence, 8 had arm recurrence. The mean time from original diagnosis to ILP was 48 months (range 1-290). 102 iliac, 5 femoral, 7 popliteal and 8 axillary perfusions were performed. All patients had stage II (local recurrence within 3 cm of primary site) or stage III (regional metastases; tissues excluding nodes, nodes or combination) disease according to the MD Anderson Cancer Centre Staging System. At a mean follow-up of 30.7 months, 68 patients had died of recurrent disease (mean time to death 22.5 months). The 2 and 5 year survival of the group was 50 and 26%, respectively and disease-free survival was 23 and 12%, respectively. At first perfusion, 76% of patients showed complete response and 23% showed partial response. With repeat perfusion, 47% showed complete response and 53% had partial response. In conclusion, ILP is safe and has an acceptable morbidity. It achieves highly satisfactory local disease control but long-term survival is the exception.

The Scottish Royal Colleges: a prospective survey of continuing medical education undertaken by their examiners.

OBJECTIVE: To measure the amount and nature of Continuing Medical Education (CME) activity undertaken by the examiners of the three Scottish Royal Colleges. The data obtained to be compared with recommendations for formal CME participation published by the medical Royal Colleges and Faculties. DESIGN: All examiners in active clinical practice prospectively surveyed over a 12 month period by completing a monthly return from a specially designed loose-leaf diary. RESULTS: 75% of the examiners who submitted all 12 monthly diary pages completed at least 100 hours CME during the year while 95% achieved 50 hours or more. This time was distributed approximately equally between hospital-based activities and activities for which study leave might have been taken. Although the mean total number of hours of CME undertaken by consultants based in district general hospitals was also over 100 hours in the year, this was significantly lower than the figure for teaching hospital consultants. The type of CME activity was described as general (16%), specialty (49%) and subspecialty (35%). The examiners surveyed found that specialist society and international specialist meetings were perceived to be the most valuable of those attended. CONCLUSIONS: The current recommendations for implementing formal CME systems for consultants are in line with the current activity levels of this group and should safeguard existing educational activity rather than impose new standards. This study suggests that the profession should not be unduly anxious about the introduction of a structured CME system although it is likely that some form of obligatory scheme will be required to achieve a more uniform response.

Single-centre prospective study of isolated limb perfusion with melphalan in the treatment of subungual malignant melanoma.

Subungual melanoma is rare and experience in treating this condition with isolated limb perfusion is limited. Between 1985 and 1990, 24 patients were treated by digital amputation and isolated limb perfusion with melphalan and mild hyperthermia. The disease was staged according to the M.D. Anderson classification: stage I (17 patients), stage IIIA (one), stage IIIB (two) and stage IIIAB (four). Thirteen lesions were on the foot and 11 on the hand. Seven patients have developed locoregional recurrence. The estimated overall 2- and 5-year probabilities of survival were 77 and 46 per cent respectively, while for disease-free survival the rates were 58 and 51 per cent. When these results were compared retrospectively with those in 111 patients treated by amputation alone, no significant difference in survival was demonstrated. This experience suggests that isolated limb perfusion with melphalan and mild hyperthermia confers no additional survival benefit over appropriate surgery.

Carbon dioxide laser ablation as an alternative treatment for cutaneous metastases from malignant melanoma.

Surgical excision of cutaneous malignant melanoma metastases is practical only when the number of lesions is small. In some patients isolated limb perfusion is not possible or fails to achieve control, and carbon dioxide laser ablation is then an alternative treatment. Between September 1992 and September 1994, 19 patients aged 45-94 years were treated with carbon dioxide laser. Two patients had received no previous limb perfusion, while the remaining 17 had up to three previous perfusions. The number of lesions per patient ranged from three to 40 nodules. A Sharplan 1030 portable carbon dioxide laser was used, which generates a beam wavelength of 10.6 microns and has a maximum power output of 80 W. All procedures were carried out under general anaesthesia. Each lesion was destroyed with a focused laser beam of 10-20 W with a spot size of 0.5-1.0 mm. At a mean follow-up of 15 months, five patients have died from the disease. Among the 14 survivors, eight have had no limb recurrence of the disease, three have had one further treatment and three a further two treatments to control cutaneous metastases at new sites. Early experience suggests that carbon dioxide laser ablation of cutaneous metastases is an effective palliative treatment after failed isolated limb perfusion, and there may be a group of patients in whom laser ablation should be the initial treatment of choice.

Endogenous prostaglandin E2 mediates inhibition of rat thick ascending limb Cl reabsorption in chronic hypercalcemia.

The hypothesis that endogenous PGE2 mediates defective thick ascending limb (TAL) Cl reabsorption (percent delivered load: FRCl%) in rats with vitamin D-induced chronic hypercalcemia (HC) was tested by measuring FRCl% in loop segments microperfused in vivo in HC and control rats treated acutely with indomethacin (Indo) or its vehicle, and obtaining the corresponding outer medullary [PGE2]. Microperfusion conditions were developed in which FRCl% was exclusively furosemide sensitive. To determine the cellular mechanism, tubules were perfused acutely with forskolin (FSK), cAMP, or the protein kinase C inhibitor staurosporine (SSP). Outer medullary [PGE2] in HC rats was 9 to 10 times greater than control and could be normalized by Indo. FRCl% was 20% lower in HC rats infused with vehicle, and Indo, FSK, and cAMP returned FRCl% to normal despite sustained HC. Indo or FSK had no effect on FRCl% in control rats and Indo did not prevent inhibition of FRCl% by luminal PGE2 (1 microM). Luminal SSP (10(-7), 10(-8) M) in HC did not return FRCl% to control values. We conclude that impaired TAL FRCl% in HC occurs at a pre-cAMP site and is due to endogenous PGE2 and not to HC.

K infusion corrects thick ascending limb Cl reabsorption in K-depleted rats by an aldosterone-independent mechanism.

Others have provided evidence that thick ascending limb (TAL) NaCl reabsorption is aldosterone dependent in adrenalectomized animals. In rats fed a K-free diet, plasma K concentration ([K]) is reduced and plasma aldosterone concentration [Aldo] is decreased. Because aldosterone release is regulated by extracellular fluid (ECF) [K], the purpose of the present study was to determine whether aldosterone deficiency mediates inhibition of TAL NaCl transport in K-depleted rats (K-Dep). Cl reabsorption was measured in functionally isolated loop segments microperfused in vivo (22 nl/min) using a modified perfusate that minimizes proximal nephron reabsorption. The results of our studies show that the defect in TAL Cl reabsorption in K-Dep rats is quantitatively significant and can be rapidly reversed by the acute systemic infusion of K. However, acute administration of aldosterone, in the presence of sustained K-Dep, failed to reverse the impairment in TAL Cl reabsorption in K-Dep rats. Furthermore, acute infusion of K, in the presence of an aldosterone antagonist, in K-Dep rats rapidly corrected the defect in TAL Cl reabsorption. Additional studies showed that despite normalization of ECF [K] by acute K infusion in K-Dep rats, plasma [Aldo] failed to increase. In contrast, acute infusion of KCl in control rats increased plasma [Aldo] by 46%, but Cl reabsorption was unchanged. In summary, these results provide conclusive evidence that the correction of defective TAL Cl reabsorption in response to the acute administration of K in K-Dep rats occurs via an aldosterone-independent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Elective lymph node dissection in the management of malignant melanoma.

The surgical management of regional nodes in patients with cancer has been controversial for many years. This paper reviews the role of elective lymph node dissection in the management of malignant melanoma. The evidence for and against elective lymphadenectomy is discussed and a policy of therapeutic, rather than elective, lymph node excision recommended.

The pharmacokinetic advantages of isolated limb perfusion with melphalan for malignant melanoma.

We describe melphalan pharmacokinetics in 26 patients treated by isolated limb perfusion (ILP). Group A (n = 11) were treated with a bolus of melphalan (1.5 mg kg-1), and in a phase I study the dose was increased to 1.75 mg kg-1. The higher dose was given as a bolus to Group B (n = 9), and by divided dose to Group C (n = 6). Using high performance liquid chromatography (HPLC) the concentrations of melphalan in the arterial and venous perfusate (during ILP) and in the systemic circulation (during and after ILP) were measured. Areas under the concentration time curves for perfusate (AUCa, AUCv) and systemic (AUCs) data were calculated. In all three groups the peak concentrations of melphalan were much higher in the perfusate than in the systemic circulation. The pharmacokinetic advantages of ILP can be quantified by the ratio of AUCa/AUCs, median value 37.8 (2.1-131). AUCa and AUCv were both significantly greater in Group B than in Group A (P values less than 0.01, Mann-Whitney). In Groups B and C acceptable 'toxic' reactions occurred but were not simply related to melphalan levels. Our phase I study has allowed us to increase the dose of melphalan to 1.75 mg kg-1, but we found no pharmacokinetic advantage from divided dose administration.

Peripheral arterial thrombosis related to commercial airline flights: another manifestation of the economy class syndrome.

Venous thromboembolism is a well recognised complication of air travel, particularly on long haul flights. This has been attributed to relative immobility in cramped surroundings and to dehydration secondary to alcohol consumption and low cabin humidity. Under these conditions thrombosis at other sites would be expected, and indeed myocardial ischaemia is the commonest emergency in commercial flights. Peripheral arterial thrombosis, however, is not reported, even in comprehensive reviews of flying related medical emergencies. We report on three patients who developed acute lower limb ischaemia following long haul air flights.