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CLINICAL REVIEW: Jane C Davies, Eric W F W Alton, and Andrew Bush Cystic fibrosis BMJ 2007; 335: 1255-1259 [Full text]

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a plea for precision in the use of terminology

oscar,m jolobe   (15 December 2007)

Sweat Testing in Cystic Fibrosis : Full or False Proof?

Sanjay H Chotirmall   (16 December 2007)

Cystic Fibrosis Related Vasculitis

Kaushik Guha   (30 December 2007)

Neuropharmacological therapy of cystic fibrosis

Fuad Lechin, Bertha van der Dijs, and Gerardo Hernandez-Adrian   (15 February 2008)

a plea for precision in the use of terminology 15 December 2007
oscar,m jolobe, retired geriatrician manchester medical society, c/o john rylands university library, oxford road, manchester M13 9PP Send response to journal: Re: a plea for precision in the use of terminology	For the sake of those, like myself, who have struggled to understand the molecular basis of genetics, I wish to make a plea for precision in the use of terminology when describing the molecular basis of genetic disorders. Unlike the authors of the clinical review who described the mutation in cystic fibrosis as a "deletion of phenylalanine at codon 508"(1), I would prefer that the mutation should be described as a "deletion of codon CTT in exon 10 (which) results in the loss of phenylalanine at position 508 of the 1480 amino acid protein"(2). The latter description reinforces the concept, which is the correct one, that deletion involves nucleotides(which are contituents of codons), and the concept that codons, in turn, encode amino acids such as phenylalanine. References (1) Davies JC., Alton WFW., Bush A Cystic fibrosis British Medical Journal 2007:335:1255-9 (2)Gelehrter TD., Collins FS., Ginsburg D Principles of Medical Genetics 1998 Chapter 9, page 224 Editors Gelehrter TD., Collins FS., Ginsburg D Lippincott Williams and Wilkins Competing interests: None declared
Sweat Testing in Cystic Fibrosis : Full or False Proof? 16 December 2007
Sanjay H Chotirmall, Doctor Beaumont Hospital, Dublin 9 Send response to journal: Re: Sweat Testing in Cystic Fibrosis : Full or False Proof?	Davies et al(1) write a comprehensive review on a difficult, challenging and emerging area. They outline the gold standard of diagnosis ‘sweat testing’ however there is no mention of the important occurrence of false positive tests. False positive sweat tests occur in the following clinical settings(2) : Adrenal insufficiency, anorexia nervosa, atopic dermatitis, autonomic dysfunction, coeliac disease, ectodermal dysplasia, familial cholestasis (Byler’s disease), fucosidosis, G6PD deficiency, glycogen storage disease type 1, hypogammaglobulinemia, hypoparathyroidism, hypothyroidism, Klinefelter's syndrome, malnutrition, mucopolysaccharidosis type 1, nephrogenic diabetes insipidus, nephrosis, pseudohypoaldosteronism and in some individuals with psychosocial problems. It is important to emphasise that individuals who require ‘sweat testing’ need to be appropriately selected and subsequently the results of such testing interpreted with the knowledge that false positives can occur. References 1. Davies JC, Alton EW, Bush A. Cystic fibrosis. BMJ. 2007 Dec 15;335(7632):1255-9. 2. Rosenstein BJ, Cutting GR. The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J Pediatr. 1998 Apr; 132(4):589-95 Competing interests: None declared
Cystic Fibrosis Related Vasculitis 30 December 2007
Kaushik Guha, SHO in Cardiology Royal Brompton Hospital, Royal Brompton and Harefield NHS Trust, Sydney Street, London, SW3 6NP Send response to journal: Re: Cystic Fibrosis Related Vasculitis	Dear Editor, Davies et al carried out a thorough review of modern day cystic fibrosis medicine. Cystic Fibrosis (CF) is a complex multi-system disorder, which has evolved beyond the original concepts of respiratory and gastro-intestinal disease. One such complication is dermatological involvement. Vasculitis is a significant but under recognised complication of cystic fibrosis. This has been recognised in both paediatric and adult populations. Retrospective analyses have revealed a prevalence of 2-3% in adult populations in both the US and the UK. This compares to an incidence of five- two hundred per million in the general population. The underlying aetiology of the CF related vasculitis is not clear. Many hypotheses currently exist. One theory is that it represents an atypical response to chronic infection and represents a systemic inflammatory response. Another is that it may represent an atypical drug reaction. Immunlogical modulation is well recognised in CF and the development of vasculitis is associated with the development of immuno-complexes. Hypergammaglobulinaemia is also recognised within CF and again is postulated to have a contributory role. CF related vasculitis most frequently presents with myalgia, fever and athralgia. The commonest sign is that of cutaneous vasculitis. This is described as a palpable purpuric rash within the literature..5 CF related vasculitis can lead to neural, gastrointestinal and renal involvement.3 The histology found on renal biopsy is that of Henoch-Schlonein Purpura, but these are performed infrequently, hence the degree of renal involvement is of some conjecture.3 Histological examination of the cutaneous vasculitis reveals a leukocytoclastic vasculitis.3 Markers of immune activation may be raised, normal or decreased, this includes complement along with other conventional markers of vasculitides. Vasculitis has been managed with a variety of agents including corticosteroids, immunosuppressive therapy and cytotoxic therapy. Corticosteroids have been deemed mandatory in the treatment of extra- cutaneous vasculitis. Other therapies utilised include azathioprine, and methotrexate.3,7 Though CF related vasculitis is a relatively infrequently occurring complication, it is under reported and recognised. It may represent part of the inflammatory response spectrum and should be sought for and monitored and treated accordingly. 1. Davies JC, Alton EF & Bush A. Clinical Review: Cystic Fibrosis. BMJ; 335; 1255-1259. 2. Schidlow DV, Panitch HB, Zaeri N et al. Purpuric rashes in cystic fibrosis. Am J Dis Child 1989;143:1030-1032. 3. Finnegan MJ, Hinchcliffe J, Russell-Jones D, et al. Vasculitis complicating cystic fibrosis. Q J M 1989;72:609-621. 4. Jack A. Kastelik, Siobhan A Mulrennan and Alyn H. Morice.May, 2002. Vasculitis in cystic fibrosis [online].www.cysticfibrosismedicine 5. Hodson ME. Vasculitis and arthropathy in cystic fibrosis. J R Soc Med 1992; 85:38-40. 6. Matthews WJJ, Williams M, Oliphint B, Geha R, Colten HR. Hypogammaglobulinemia in patients with cystic fibrosis. N Engl J Med 1980; 302:245-249. 7. Jennette JC, Falk RJ. Small-vessel vasculitis. N Engl J Med 1997;337 :1512 -1523. 8. Elborn JS. How can we prevent multisystem complications of cystic fibrosis? Semin Respir Crit Care Med. 2007 Jun;28(3):303-11. Competing interests: None declared
Neuropharmacological therapy of cystic fibrosis 15 February 2008
Fuad Lechin, Chief of Dep. of Neuroimmunopharmacology, Faculty of Medicine, Universidad Central de Venezuela Apartado 80.983, Caracas 1080-A, Venezuela, Bertha van der Dijs, and Gerardo Hernandez-Adrian Send response to journal: Re: Neuropharmacological therapy of cystic fibrosis	In their review on cystic fibrosis (CF), Davies et al. (1) do not mention our successful therapeutical results obtained throughout the neuropharmacological strategy addressed to revert the central nervous system (CNS) plus the autonomic nervous system (ANS) unbalance which underlies this disease. We have treated 6 CF patients with small doses of noradrenaline (NA) + serotonin (5HT) upptake-inhibitor (doxepin) because those patients showed adrenal sympathetic hyperactivity which alternated with parasympathetic rebounds (2). The former depends on the adrenaline Cl(Ad) medullary nuclei whereas the latter depends on the parasympathetic cholinergic (ACh) medullary vagal complex (3). Predominance of the latter is responsible for the overexcitation of the intestinal enterochromaffin cells, which release 5-HT during postprandial and sleep periods (4). Conversely, hyperactivity of the Cl(Ad) nuclei which are directly responsible for the exocrine secretion of the pancreas (5, 6). Normalization of circulating neurotransmitters: noradrenaline, adrenaline dopamine, platelet serotonin, and plasma serotonin, was obtained in all cases. Disappearance of the pancreatic cysts was registered in the two patients presented this abnormality (2). Fuad Lechin, MD, PhD; Bertha van der Dijs, MD; Gerardo Hernández- Adrián, MD Universidad Central de Venezuela flechin@telcel.net.ve References. 1. Davies JC, Alton EW , Bush A. Cystic fibrosis. Review. BMJ 2008; 335:1255-9. 2. Lechin F, van der Dijs B, Orozco B, Hernandez-Adrian G. Rodriguez S, Baez S. Similar autonomic nervous system disorders underlting cystic fibrosis and pancreatic cysts allowed common neuropharmacological therapy: Report of four cases. J Applied Res 2005;5:299-304. 3. Lechin F, van der Dijs B. Central nervous system (CNS) circuitry involved in the hyperinsulinism syndrome. Neuroendocrinology 2006; 84:222- 34. 4. Lechin F, van der Dijs B, Lechin ME. Neurocircuitry and Neuroautonomic Disorders: Reviews and Therapeutic Strategies. Chapter 9. Basel: Karger, 2002, pp. 57-59. 5. Barlow TE, Greenwell JR, Harper AA, Scratcherd T. The effect of adrenaline and noradrenaline on the blood flow, electrical conductance and external secretion of the pancreas. J Physiol 1971;217:665-78 6. Tobe T, Izumikawa F, Sano M, Tanaka C. Release mechanisms of 5-HT in mammalian gastrointestinal tract—especially vagal release of 5-HT. In: Endocrine Gut-Pancreas, edited by Fujita T. Amsterdam: Elsevier, 1976. Competing interests: None declared