302

of actively sensitised

guineapigs to allergen inhalation (Boubekeur K, al, unpublished). Anomalous effects of P-adrenoceptor agonists have become increasingly evident over the past five years, so that to some of us6 the fmdings of Sears et al were predictable. Nonetheless, there is considerable uncertainty as to which properties account for the adverse effects of this drug class in asthmatics and I would recommend that P-adrenoceptor agonists be studied as thoroughly in this context as theophylline has been. Only then will it be possible to make a valid risk/benefit assessment to justify regular use of P-adrenoceptor agonist therapy in asthma. et

Preclinical Research, Sandoz Ltd, CH-4002 Basel, Switzerland

J. MORLEY

C, Morley J, Sanjar S. Viewpoint: untoward effects of beta-adrenoceptor agonists in asthma. Eur Respir J 1990; 3: 228-33. 2. Morley J. Airway hyperreactivity. Lancet 1988, i: 160-61 3. Sanjar S, Kristersson A, Mazzoni L, Morley J, Schaeblin E. Increased airway reactivity in the guinea-pig follows exposure to intravenous isoprenaline. J Physiol 1990; 425: 43-54. 4. Morley J, Chapman ID. The mast cell episode in asthma pharmacology a lesson learned? In: Dune B, ed. Success and creativity in pharmaceutical research and development London: IBC Technical Services (in press). 5. Morley J, Anderson GP, eds New drugs for asthma and allergy. Agents Actions (suppl) (in press) 99: 6. Page C, Sanjar S, Morley J. Pharmacology of ketotifen in asthma. NZ Med J 1986; 1. Newth

125.

Spontaneous abortions after intraperitoneal or

intrauterine insemination

SIR,-Despite encouraging resultsi,2 with direct intraperitoneal insemination (DIPI) few reports have been published about this technique and we know of no accounts of the outcome in such pregnancies, including the spontaneous abortion rate. We have used DIPI alternating with intrauterine insemination (IUI) and have achieved conception rates per couple of 24-5% and 40-0%, respectively, with a mean of 33 inseminations per cycle. The inductions (cervical factor and disordered ovulation, male subfertility, and immunological infertility), the semen indices, and the protocol for ovulation induction, semen preparation, and timing of insemination were similar for the two techniques. However, the spontanous abortion rate was significantly higher after IUI (10/22) than after DIPI (1/11) (p = 0-04, Fisher’s exact test). This suggests that DIPI provides a more physiological gamete interaction than IUI. IUI seems to promote embryonal anomalies severe enough to be recognised by natural selective mechanisms because the high rate of spontaneous abortion was not reflected in congenital malformations. Our results should prompt re-evaluation of the criteria used when choosing IUP and/or DIPI. If a higher conception rate and greater embryo viability after DIPI are confirmed in other series, the preferential or exclusive use of DIPI should be considered. Departments of Medical Genetics, and Hygiene and Epidemiology, Faculty of Medicine, University of Porto, 4200 Porto, Portugal

ALBERTO BARROS

JOAQUINA SILVA JOAQUIM MAIA

1. Forrler A, Dellenbach P, Nisand I, et al Direct intrapentoneal insemination in unexplained and cervical infertility. Lancet 1986, i: 916 2. Forrler A, Badoc E, Moreau L, et al. Direct intraperitoneal insemination: first results confirmed. Lancet 1986; ii: 1468.

Nose-blowing and

CSF rhinorrhoea

SiRj—The spontaneous escape of CSF from the nose, though recognised in otolaryngology.12 Where no underlying cause can be found (primary spontaneous CSF rhinorrhoea), focal bony atrophy from forces imparted by the CSF pressure pulse,3 bone erosion by small encephaloceles,’ or perineural atrophy around olfactory nerve filaments5 are among the more likely explanations. We describe here one of three patients in whom CSF rhinorrhoea occurred after forceful nose-blowing. A computerised tomographic scan revealed bony dehiscences within the anterior cranial fossa. These were found in the cribriform plate and fovea ethmoidalis rare, is

regions. This supports the theory that congenital bony dehiscences and meningocele formation are likely predisposing factors for this condition. The features of these three cases are similar, so only one is reported here. A 42-year-old woman (the others were women, aged 46 and 43) presented with an 18-month history of intermittent but copious left-sided clear rhinorrhoea. This symptom had developed after an episode of forceful nose-blowing, which she did regularly in the morning. There were no other symptoms. The fluid proved to be CSF, so a contrast computed tomography (CT) scan was done. This revealed bony dehiscence and leakage of contrast within the region of the cribriform plate. These findings were confirmed at operation and the defect was closed with a fascia lata graft and

nasoseptal flap. Skull base dehiscences are quite commonIt is eaay to understand how the Valsalva-like action of nose blowing, by increasing intracranial pressure, could lead to dural rupture at such sites. In regions of dehiscence, forces imparted by the CSF will not be counteracted by an equal and opposite force from the skull base, making rupture likely at sites of dehiscence. In western culture nose-blowing is an acceptable practice. Elsewhere it is socially abhorrent-for example, the Chinese regard the act of blowing your nose and then placing the used handkerchief in a pocket as disgusting, a view which is not at all unreasonable. Spontaneous CSF rhinorrhoea seems to be more common in middle age and in women. Could it be that women prefer to blow their noses, while men and children sniff instead? Department of Surgery and Library, Royal National Throat, Nose and Ear Hospital, London WC1X8DA, UK

N. S. TOLLEY P. SCHWARTZ

surgical treatment of spontaneous cerebrospinal rhinorrhea. Arch Otolaryngol 1960; 72: 254-55. 2. McCoy G. Cerebrospinal rhinorrhea: a comprehensive review and a definition of the responsibility of the rhinologist in diagnosis and treatment. Laryngoscope 1963, 73: 1 Troland CE The

1125-57. 3 Ommaya AK Spinal fluid fistulae Clin Neurosurg 1976; 23: 363-92 4. Anderson WM, Schwartz GA, Gammon GD Chronic spontaneous

cerebrospinal

fluid rhinorrhea Arch Intern Med 1961, 107: 723-31. 5. St Clair Thomson. The cerebrospinal fluid its spontaneous escape from the nose with observations of its composition and function in human subjects. London Cassell, 1899: 10. 6. Ohnishi T. Bony defects and dehiscences of the roof of ethmoid cells Rhinology 1981, 19: 195-202.

Role of TNF in cerebral malaria SIR,-Dr Phillips and Dr Solomon (Dec 1, p 1355) presenta stimulating overview of the approaches to the understanding of the pathophysiology of cerebral malaria, but we believe their description of the possible role of tumour necrosis factor (TNF) deserves

comment.

Most importantly, to describe the TNF doses that can provoke focal neurological deficits and other changes reminiscent of mild malaria in tumour patients as "large" may have misled readers into assuming that such doses result in high serum concentrations of TNF, of the order of those associated with severe complicated malaria (700-800 pg/ml, ’Medgenix IRMA’),u These experimental doses are typically too small to induce even a transient detectable rise (greater than 20 pg/ml) in serum TNF.3 It is therefore not surprising that patients with severe malaria, in whom quantities of TNF much greater than those given experimentally are being generated, had correspondingly more extreme symptoms,

including neurological changes. Phillips and Solomon seek explanations for occasional discrepancies between serum TNF levels and malarial illness. Experimentally, TNF clears from plasma quickly, but its toxic effects are much slower to dissipate,4 so one should expect some sick individuals to have low serum TNF. Thus, in a synchronous infection we should expect serum TNF to correlate more closely with time since schizogony than with the illness of the patient. Kwiatkowski and colleaguesresults in vitro are consistent with this proposal. We agree with Phillips and Solomon that single measurements of circulating TNF are unlikely to reflect the true pathophysiological processes operating locally in cerebral malaria.

Nose-blowing and CSF rhinorrhoea.

302 of actively sensitised guineapigs to allergen inhalation (Boubekeur K, al, unpublished). Anomalous effects of P-adrenoceptor agonists have becom...
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