1410

reports,3-6 however, including some suggesting increased fertilisation rates4,5 though cleavage and implantation were impaired;’ miscarriage rates were also increased, and eventual birth rates reduced 5,6 though generally lower than ours. We defined fertilisation in terms of cleaving embryos, which may explain some discrepancy between reports of fertilisation and cleavage rates. Our findings strongly emphasise the need to advise infertile couples to stop smoking, especially if they are having complex treatment such as IVF. How quickly the benefit of stopping may be gained has yet to be investigated. D. J. ROWLANDS A. MCDERMOTT M. G. R. HULL

University of Bristol IVF Unit, St Michael’s Hospital, Bristol BS2 8EG, UK

MGR, Eddowes HA, Fahy U, et al. Expectations of assisted conception for infertility. BMJ 1992; 304: 1465. 2. Elenenbogen A, Lipitz S, Mashiach S, Dor J, Levran D, Ben-Rafael Z. The effect of smoking on the outcome of in-vitro fertilisation-embryo transfer. Hum Reprod 1991; 3: 242. 3. Trapp M, Kemeter P, Feichtinger W. Smoking and in-vitro fertilisation. Hum Reprod 1986; 1: 357. 4. Hughes EG, YoungLai EV, Ward SM. Cigarette smoking and outcomes of in-vitro fertilization and embryo transfer: a prospective cohort study. Hum Reprod 1992; 7: 1. Hull

may also contribute to the pathogenesis of this abnormal healing process. SP antagonists may have a role in the treatment of

hypertrophic scars. RAFT Department of Research in Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex, UK

Department of Anatomy and Developmental Biology, University College, London WC1

Ondansetron and chest

KL, Bree TM, Hennessey JF. The effect of patient smoking habit on the outcome of IVF and GIFT treatment. Aust NZ J Obstet Gynaecol 1990; 30: 340. 6. Pattinson HA, Taylor PJ, Pattinson MH. The effect of cigarette smoking on ovarian function and early pregnancy outcome of in vitro fertilisation. Fertil Steril 1991; 55: 780.

Painful hypertrophic

scarring and neuropeptides

scar

hypertrophy

often

complicates injury

or

surgery to the skin. The lumpy, erythematous scar is confined to the area of injury, unlike true keloid scar which extends beyond the original wound. In practice, this distinction is often blurred and the aetiology is not known in either case.’ Painful itching commonly accompanies hypertrophic scar and is frequently the predominant clinical complaint, contrasting with the insensitivity of mature non-hypertrophic scars. However, the neurological aspects of hypertrophic scar tissue have received little attention, although the scar tissue may hamper regenerating nerves.2 Specimens of painful hypertrophic scar (n = 9), insensitive non-hypertrophic flat scar (5), and control scar (3) were obtained from eight women (aged 23-56) and three men (23-59). The specimens were studied histologically and immunohistochemically for vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), met-enkephalin, leu-enkephalin, and dopamine P-hydroxylase (DBH). Normal skin contained all the neuropeptides except for SOM and DBH immunoreactive nerves. In patients with flat nonhypertrophic scar, neuropeptides and DBH-containing nerves were absent. In patients with hypertrophic scars, neuropeptide and DBH-containing nerves were seen at a higher density than in controls. Only immunoreactive nerves penetrated the densely packed collagen matrix, oriented in the direction of fibroblasts. SP and CGRP were found at the base of the epidermis in the hypertrophic scar but not in the non-hypertrophic scar or the

control skin. SP and CGRP

RAHIMA CROWE D. ANGUS MCGROUTHER GEOFFREY BURNSTOCK

1. Rockwell WB, Cohen IK, Erlich HP. Keloids and hypertrophic scars: a comprehensive review. Plast Reconstr Surg 1989; 84: 827-37. 2. Waris T. Reinnervation of free skin autografts m the rat. Scund J Plast Reconstr Surg 1978; 12: 85-93 3. Foreman JC, Jordan CC, Dehme P, Renner H. Structure-activity relanonships for substance P-related peptides that cause wheal and flare reactions in human skin. J Physiol 1983; 335: 449-65. 4. Nilsson J, von Euler AM, Dalsgaard C-J. Stimulation of connective tissue cell growth by substance P and substance K. Nature 1985; 315: 61-63. 5. Linares HA. Proteoglycan-lymphocyte association in the development of hypertrophic scars. Burns 1990; 16: 21-24.

358. 5. Harrison

SIR,--Cutaneous

NICHOLAS PARKHOUSE

are released by nociceptive sensory nerves and mediate neurogenic inflammation.3 The increased density of these neuropeptides in the hypertrophic tissue suggests penetration of the scar by regenerating nociceptive nerves. Prolonged low threshold activity in these nerves may result in hyperaesthesia, spontaneous painful itching, erythema, and other features of inflammation, including perivascular lymphocytic infiltration.4 Furthermore, SP stimulates the proliferation of human skin fibroblasts in vitro and is inhibited by the specific SP agonist, spantide.5 Our results indicate that hypertrophic scars differ from nonhypertrophic scars in the degree to which they are penetrated by nerve fibres, especially nociceptive nerves. Low threshold activity of these nerves may not only be responsible for painful itching but

pain

SIR,-Dr Ballard and colleagues (Oct 31, p 1107) report the development of chest pain in five elderly patients (four of whom had an established history of ischaemic heart disease) receiving ondansetron and chemotherapy for the treatment of advanced cancer. Included in this report are two further patients who experienced other cardiac events. After reviewing these cases we believe that the cases offer no proof that ondansetron is causally related to the events described. A thorough review of Glaxo’s experience with ondansetron in over 14 000 patients in clinical trials and the spontaneously reported adverse events from over 4 million patient-treatments worldwide show no evidence of a causal relation between ondansetron and episodes of chest pain and cardiac abnormalities. Thus these events almost certainly result from the effects of the patient’s cancer, the effects of chemotherapy, or underlying cardiac disease. Ballard and colleagues note that angina is mentioned in the product information for ondansetron in the USA but not in the UK. It is not unusual for the content of the product information to vary from country to country depending on regulatory practice. In this case, in view of there being rare reports of angina, the US Food and Drug Administration, while recognising that there is no evidence of a cause-effect relation, requested that reference to angina be made in the US product information. Because there is no evidence of a causal relation between ondansetron and angina it has not been included in the product information for most other countries, including the UK. Glaxo Research Institute, Research Triangle Park, North Carolina, USA

JAMES B. D. PALMER

International Medical Affairs, Glaxo Group Research, Stockley Park West,

Uxbridge UB11 1BT, UK

YVONNE L. GREENSTREET

Visual loss associated with

bromocriptine

SIR,-We have observed transient visual loss in a patient treated bromocriptine. This otherwise healthy 73-year-old woman

with

presented with a 4 year history of progressive visual loss, which had been diagnosed as glaucoma. Visual field examination revealed a temporal field defect in the right eye and a three quadrant loss in the left, with sparing of the inferior nasal field. Magnetic resonance imaging revealed a large pituitary tumour with suprasellar extension and compression of the optic chiasm. In the face of progressive visual loss, the patient was started on bromocriptine while awaiting results of a complete endocrinological evaluation. Within 2 h after the initial dose of 2-5 mg, the patient noted light-headedness and dizziness, which prompted her to sit. Within minutes, while fully awake and conversant, she had rapid onset of

Ondansetron and chest pain.

1410 reports,3-6 however, including some suggesting increased fertilisation rates4,5 though cleavage and implantation were impaired;’ miscarriage rat...
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