Microemulsion formulation increases cyclosporin bioavailability in cystic fibrosis

ACE inhibitors and diabetics with albuminuria SiR-In their review of diabetic

nephropathy, Mogensen and colleagues (Oct 21, p 1080) recommend angiotensin I converting enzyme (ACE) inhibitors as first-line treatment for all diabetics with microalbuminuria, once glycaemic control is adequate. It is risky to favour one treatment strategy from data obtained on a surrogate endpoint, while a clinical benefit remains to be demonstrated. For instance, successful reduction of ventricular arrhythmias with class I antiarrhythmic drugs has led to increased frequency of sudden death after myocardial infarction.’ Microalbuminuria is a marker for continuing renal failure in insulin-dependent diabetic subjects, and for cardiovascular events in non-insulin-dependent diabetics. Early treatment with ACE inhibitors seems clinically useful 1

reduce the chance of renal failure in normotensive insulindependent and non-insulin-dependent diabetics with microalbuminuria: glomerular filtration rate degradation can be prevented by this strategy in these patients." However, data are not available to support claims that ACE inhibitors

to

peculiar protection to non-insulin-dependent against cardiovascular events. Pathophysiological arguments that blocking the reninangiotensin system may reduce classic cardiovascular and renal risks for non-insulin-dependent diabetics with microalbuminuria, are not convincing. We have started the non DIABHYCAR (diabete insulino-dependant, hypertension, micro ou macroalbuminurie, evenements cardiovasculaires et ramipril) study: a 3-year double-blind, placebo-controlled, multicentre trial comparing ramipril 1-25 mg per day with placebo for these patients with

provide

diabetics

microalbuminuria or macroalbuminuria. The incidence of cardiovascular events and renal failure is used as primary outcome. Until this and other controlled trials indicate whether ACE inhibition gives a clinical benefit for this group of patients with microalbuminuria, we believe it is necessary to refrain from overprescribing ACE inhibitors for these diabetics.5

tDIABHYCAR Study Group: A Girault-Louvel, M Marre (Angers); J P Boissel, M Lievre (Lyon); F Alhenc-Gelas, F Cambien, G Chatellier, P Gueret, J Menard, Ph Passa, P F Plouin, D Vasmant, Cl Weisselberg (Paris), France *M Marre, M Lievre, G Chatellier, P F Plouin, for the DIABHYCAR Study Group† Service de Médecine B, Centre France

such an outcome is to be achieved, it is important that such schemata are properly followed. Many diabetic patients are seen regularly in hospital-based clinics, which should provide an ideal setting for efficient screening. Yet, in many such clinics, a substantial proportion of patients are screened by junior doctors who are inexperienced in the management of diabetes. We conducted a telephone survey of 50 junior hospital doctors who participate regularly in adult diabetic clinics at 48 centres around the UK. We asked the same questions of each doctor and the survey yielded the following notable results. Only 44% were aware that all adult insulin-dependent diabetic patients more than 5 years from diagnosis should be screened for microalbuminuria. Only 34% were aware that all non insulin-dependent diabetic patients should be screened for this abnormality. When we asked what tests should be used to diagnose microalbuminuria, 18% identified an earlymorning specimen as being useful, and 34% suggested a timed collection to make the diagnosis. When asked what should be taken when a diagnosis of measures microalbuminuria is confirmed, the following answers were given: 38% said they would monitor for and treat hypertension; 38% would aim to improve glycaemic control; 12% would screen for other complications; 54% would consider the use of an ACE inhibitor. 42 participants wished to state what level of blood pressure would require active management in a patient with insulin-dependent diabetes, or non-insulin-dependent diabetes with complications. Of those, only 11 considered a systolic pressure of 140 mm Hg worthy of treatment, but 34 would treat a diastolic pressure of 90 mm Hg. Only 32% of participants had ever heard of the St Vincent Declaration.2°3 Only seven clinics (14%) of those contacted had written guidelines for the management of microalbuminuria and hypertension. Effective screening of people with diabetes is vital. The junior doctors who participated in our survey do not have sufficient experience to know when to screen for microalbuminuria, or how to manage such patients. We suggest that straightforward schemata for the screening of diabetic patients, such as those produced by Mogensen and co-workers for microalbuminuria, should be available for reference in diabetic clinics and that measures should be taken locally to ensure that they are put into practice. *Catherine J Wills, Sarah Keir Department of Medicine, Bristol Royal Infirmary, Bristol BS2 8HW, UK

Hospitalier Universitaire, 49033 ANGERS Cedex 01, 1

1

2

3

4

5

The Cardic Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med 1992; 327: 227-33. Fabbri P, Bouhanick B, Freneau E, et al. Comparison of two treatment strategies with Angiotensin I Converting Enzyme Inhibitors in normotensive IDDM patients with microalbuminuria. Diabetes 1995; 44 (suppl 1): 24A (abstract 84). Mathiesen ER, Hommel E, Smith U, Parving HH. Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria: 8 years follow-up. Diabetologia 1995; 38: 1746 (Abstract 176). Ravid M, Savin H, Jutrin I, Bental T, Katz B, Lishner M. Long-term stabilizing effect of angiotensin converting enzyme inhibition on plasma creatinine and proteinuria in normotensive type II diabetic patients. Ann Intern Med 1993; 118: 577-81. Herings RM, De Boer A, Stricker BHCh, Leufkens HGM, Porsius A. Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme. Lancet 1995; 345: 1195-98.

SiR-Mogensen and colleagues propose a straightforward scheme for screening and managing diabetic patients with microalbuminuria. This is a welcome guide which, if implemented widely, should help to reduce the number of patients who develop end-stage renal failure. However, if 1638

2

WHO and IDF. Diabetes care and research in Europe: the St Vincent Declaration. Diabetic Medicine 1990; 7: 360. Krans HMJ, Porta M, Keen H. Diabetes care and research in Europe: the St Vincent Declaration Action Programme. World Health Organization, Copenhagen, 1992: 29-32.

Microemulsion formulation increases cyclosporin bioavailability in cystic fibrosis SiR-Patients undergoing lung transplantation for cystic fibrosis have poor absorption of cyclosporin.’ A microemulsion formulation of cyclosporin (Neoral) has been shown to have improved and more consistent absorption in cardiac transplant recipients.2 We have investigated the bioavailability of Neoral in 10 patients (7 males) with a mean age of 28-3 (SD 1-8) who have received lung transplants for cystic fibrosis. Mean time since was 67-5 12-h weeks. (23-3) transplantation pharmacokinetic profile was obtained on Sandimmun and the day after patients took Neoral. Patients were allowed to reach steady-state trough levels, at which time a further 12-h pharmacokinetic profile was obtained. The mean area under

Since Jan, 1995, we have identified 175 new patients with MRSA (both hospital and community cases; mostly MRSA16 strains). All were isolated, even though about half were simply colonised, often only in the nose. If simple rules for high-quality infection control are followed, it will not matter if there is a transiently colonised member of staff or a chronically colonised patient: spread should not occur. Furthermore, MRSA will not be the only organism to be kept in check. *E Louise

Teare, A J Peacock

Chelmsford Public Health

Figure: Pharmacokinetic profile a

or

Sandimmun and of Neoral in

representative patient

the curve (AUC) on Sandimmun was 3909 (705) ng/h/mL and the mean AUC for Neoral corrected for dose was 8920 (2214) ng/h/mL (p<0-05) (figure). Mean CmaX obtained with Sandimmun was 576 (96) ng/mL and with Neoral was 1575 (336) ng/mL (p<0-05). There was no significant difference between Cmm of Sandimmun (228 [63] ng/mL) and Neoral (328 [76] ng/mL). Despite larger AUC and Cm on Neoral there was no deterioration in renal function. Respiratory function tests also remained stable. *Ghada W Mikhail, Nicholas R Banner,

Hilary Eadon, Paula Rogers, Neil Leaver, Asghar Khaghani, Magdi H Yacoub

Department of Cardiothoracic Transplantation, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK

1 Tsang VT, Johnston A, Heritier F, Yacoub MH. Cyclosponn pharmacokinetics in heart-lung transplant recipients with cystic fibrosis. Effects of pancreatic enzymes and ranititidine. Eur J Clin Pharmacol 1994; 46 (3): 261-65. 2 Mikhail G, Eadon H, Leaver N, Yacoub MH. Use of Neoral in heart transplant recipients. Transplant Proc 1994; 26: 2985-87.

Laboratory, Chelmsford CM2 OYX. UK

SiR-Woodrow and colleagues show some welcome sense. We have often observed how the phobic isolation of patients with commensal methicillin-resistant MRSA has acted as a barrier not only to proper nursing care and the rehabilitation necessary to enable discharge, but also to the basic human necessity of human contact. Patients may feel dirty, or that they are themselves to blame, and relatives may feel discouraged from visiting. In short, the fear of the organism does more harm than the organism itself. The patient described by Woodrow and colleagues also illustrates the unwisdom of attempting antimicrobial treatment when the organisms almost certainly doing no harm, and is in a site (such as a chronic leg ulcer) from which eradication is anyway unlikely. The consequent selection of an even more multiply resistant strain must in the long run be even more of a threat to other patients than the presence of the original strain, and one might question the ethics of exposing a patient to multiple courses of antibacterials as an infection-control measure. The problem of MRSA has been created by excessive antibiotic use: in the absence of invasive disease, further antibiotics are likely only to make the situation worse. *E J Dunstan, A N H Main, J Rowe Department

In hot

of

Elderly Care Medicine, Selly Oak Hospital, Birmingham B29 6JD,

UK

pursuit of MRSA

SiR-We found the letter from Woodrow and colleagues (Nov 4, p 1225) refreshing. Like them, we believe that the approach to methicillin-resistant Staphylococcus aureus (MRSA) needs rethinking. We have cultured MRSA from beds, dust on the floor, fans and other repositories, and this is living proof that control of MRSA is a vital clinical issuethere is no point in high-tech medicine if the patient dies of a hospital-acquired infection. The two-way passage of MRSA between the community and the hospital means that MRSA is endemic. Thus, it is impossible to know at any one time, which patient and/or staff member is colonised (sometimes transiently). The emphasis needs to be placed on a high standard of infection control at all times, including rigorous attention to environmental cleaning by well-trained domestic staff. We have set up a link-nurse system whereby one nurse, and a deputy on each ward and hospital department assumes responsibility (with the ward sister) for ensuring that high infection-control standards are maintained. The link-nurse system provides the infection control team with constant surveillance of any hospital-acquired infection. We have widely distributed posters emphasising that "hands must be washed before and after every significant patient contact". MRSA patients may require isolation. We try to keep our orthopaedic and ophthalmology wards clear of MRSA by insistence on pre-entry screening (for patients not admitted from home). If clinical circumstances dictate that a patient must be admitted to one of these wards before screening results being available, then the patient is isolated in a side room.

HIV in the over-50s in south London SiR-Little is known about the prevalence of HIV-1 infection in people over 50 years old. ’,2 Such people are sexually active and so at risk, and there is likely to be an increasing case-load amongst senior citizens3-in the USA 10% of AIDS cases are aged 50 years or more. In an analysis of sera sent specifically for HIV-1 testing to our laboratory 1985-94, an HIV-1 seroprevalence of 4-9% (56/1142) was found in men and 1-2% (5/411) in women. Seropositivity fluctuated annually from 2-2% to 10-5% in men and 0% to 9-7% in women although no increasing trend was noted. To provide an indication of HIV-1 seroprevalence, all sera sent from patients aged 50 and over for non-HIV-1-related investigations at a south London laboratory, over 18 months (July 1, 1993 to Dec 31, 1994) were retrospectively analysed. Patients submitting sera for voluntary named HIV-1 testing, from known HIV-1-positive patients and duplicate sera were excluded. Samples were anonymised and stratified by gender and age into 3 age bands and stored at -20°C. Of 1872 specimens, 75-2% (739/983) of male and 64-6% (574/889) of female specimens had sufficient sera for analysis by all three test systems: HIV-1 and HIV-2 by Diagnostic Pasteur Sanofi Access System (Diagnostic Pasteur Sanofi, France); positive samples confirmed by ELISA (BioElisa, HIV-1+HIV-2, Spain) and by immunoblotting for HIV-1 and HIV-2 (InnoLia HIV1/HIV2, Innogenetics Inc, Belgium) (table). High HIV-1 seropositivity was found in males (10/739 or 1-4%) with numbers declining with increasing age from 1639