446
`
`and hypoechogenic pancreas. Endoscopy revealed superficial
`gastric and duodenal erosions.
`Drug-induced pancreatitis was suspected and mesalazine was
`stopped and parenteral nutrition started. The abdominal pain
`disappeared and amylase activity fell to normal. 48 h later, with the
`patient’s consent, the drug was reintroduced, and within 12 h the
`pain recurred and amylase activity rose. The drug was stopped and
`after a few days of parenteral nutrition the patient was discharged
`free of symptoms.
`The positive rechallenge confirms our suspicion of 5-ASA
`pancreatic toxicity. The mechanism is unknown. Pancreatitis
`should be suspected if a patient with Crohn’s disease presents with
`new abdominal complaints while on treatment not only with
`azathioprine, corticosteroids, or sulphasalazine but also with
`5-ASA.
`
`trial" of naloxone is required, it is our experience that for adults a
`smaller initial dose (0-4-0-8 mg; 5-10 µg/kg) will usually result in
`the desired clinical effect with minimum signs of withdrawal. Only a
`few narcotic overdoses or types of opioids require larger initial doses
`of naloxone to reverse the effects and in these cases it can be given
`in incremental amounts. In cases where the confirmation of narcotic
`use is not urgent-ie, the patient is haemodynamically stable
`without respiratory depression-we suggest that the use of
`naloxone be deferred until more important diagnostic procedures
`have been done.
`
`Department of Laboratory Medicine,
`Johns Hopkins Hospital,
`Baltimore, MD 21205, USA, and
`Division of Emergency Medicine,
`Johns Hopkins University School of Medicine
`
`CAROLINE POPPER
`GABOR D. KELEN
`GAIL CUNNINGHAM
`
`Department of Medicine,
`Division of Gastroenterology,
`Cllniques Universitaires Saint-Luc,
`Catholic University of Louvain,
`B1200 Brussels, Belgium
`
`P. DEPREZ
`CH. DESCAMPS
`R. FIASSE
`
`1. Goldfrank LR, ed. Toxicologic emergencies: a comprehensive handbook in problem
`solving. New York- Appleton-Century-Crofts, 1982: 3-18: 126-27.
`2. Rumack BH, ed. The treatment of poisoning: a systemic approach. Denver: Rocky
`Mountain Poison Center, 1978: 326-58.
`
`1. Altman HS, Phillips G, Bank S, Klotz H. Pancreatitis associated with duodenal
`Crohn’s disease. Am J Gastroenterol 1983; 78: 174-77.
`2. Mallory A, Kem F. Drug-induced pancreatitis: a critical review. Gastroenterology
`1980; 78: 813-20.
`3. Block MB, Genant HK, Kirsner JB. Pancreatitis as an adverse reaction to
`salicylazosulfapyridine. N Engl J Med 1970; 282: 380-82.
`4. Faintuch J, Mott CB, Machado MC. Pancreatitis and pancreatic necrosis during
`sulfasalazine therapy. Int Surg 1988; 70: 271-72.
`5. Suryapranata H, De Vries H. Pancreatitis associated with sulphasalazine. Br Med J
`1986; 292: 732.
`6. Poldermans D, van Blankenstein M. Pancreatitis induced by disodium azodisalicylate.
`Am J Gastroenterol 1988; 83: 578-80.
`7. Grimaud JC, Maillot A, Bremondy A, Thervet L, Salducci J. Faut-il toujours accuser
`la sulfapyridine? A propos d’un cas de pancréatite aigue induite par la mésalazine.
`Gastroenterol Clin Bwl 1989; 13: 432.
`8- Sachedina B, Saibil F, Cohen LB, Whittey J. Acute pancreatitis due to 5-
`ammosalicylate. Ann Intern Med 1989; 110: 490-92.
`
`NALOXONE HAZARD IN DRUG ABUSER
`
`SIR,-Naloxone is widely believed to be innocuous. We disagree
`with this view and share Dr Gibbs and colleagues’ (July 15, p 159)
`opinion, that "naloxone should be used cautiously in opioid-
`dependent patients". We report a case of extreme agitation
`following the administration of naloxone to an adult opiate abuser
`who was a victim of a motor vehicle accident.
`A 35-year-old woman was the belted driver in a head-on collision
`(35-40 mph). She was immobilised on a back-board in the
`ambulance and was in a somewhat confused lethargic state on
`arrival at hospital. She had a forehead laceration, but it was unclear
`whether she had transiently lost consciousness. Blood pressure was
`150/80 mm Hg, pulse 110/min, and respiratory rate 12/min. She
`was uncooperative. Needle track marks were noted in both
`antecubital fossae, and 2 mg naloxone was given intravenously.
`Within 3 min the patient became very agitated and combative,
`requiring physical restraint. It was difficult to maintain venous
`access and radiography was impossible. A total of 4 mg morphine
`sulphate and 25 mg droperidol was given intravenously without
`subsequent change in her agitation. A further 5 mg of droperidol
`also failed to have an effect. After 47 min the patient’s state
`continued to hinder diagnostic evaluation and it was felt that her
`agitation could aggravate injuries she may have sustained. She was
`therefore intubated and ventilated following the administration of
`pancuronium (20 mg) We could then examine the head, cervical
`spine, and abdomen by computed tomography (CT). CT scans,
`radiographs, arterial blood gases, haematocrit, serum electrolytes,
`and urinalysis were normal. Toxicological analysis revealed the
`presence of large quantities of opiates and cocaine. Her family later
`confirmed that she had used large amounts of heroin shortly before
`the accident. It is likely that the administration of naloxone either
`precipitated acute opiate withdrawal or allowed the effects of
`another drug to predominate.
`This case illustrates the management dilemma and the possible
`iatrogenic complications that can arise following the routine
`administration of opiate antagonists in this setting. If a "diagnostic
`
`SEX RATIO OF INFANTS FOLLOWING ASSISTED
`REPRODUCTION
`
`SIR,-Dr Thatcher and colleagues (May 6, p 1025) reported a
`significantly high sex ratio in favour of male infants following
`in-vitro fertilisation, and Mr Al-Shawaf and Professor Craft (July 1,
`p 53) reported that 13 babies born after gamete intrafallopian
`transfer (GIFT) were boys.
`I have found much evidence that the sex of human zygotes is
`affected by parental hormones-high levels of oestrogen favouring
`male infants.1,2 Thatcher et al say their regimen may result in high
`oestradiol levels. To control ovarian stimulation, Al-Shawaf and
`Craft used goserelin acetate, a gonadotropin releasing hormone
`(GnRH) analogue: and 209 women treated with another GnRH
`analogue, leuprolide acetate (also for the control of ovarian
`stimulation) were reported to have higher peripheral serum
`osetradiol2 levels than did 202 controls.3 Many data from other IVF
`centres suggest that in general IVF births show no disturbance of
`the sex ratio. I suggest that the high male sex ratios in the two
`examples cited above result from the high maternal oestrogen levels
`induced in these fertility centres rather than from the use of either
`technique.
`
`MRC Mammalian Development Unit,
`University College London,
`London NW1 2HE
`
`WILLIAM H. JAMES
`
`1. James WH. The human sex ratio, part 1: a review of the literature. Hum Biol 1987; 59:
`721-52.
`2. James WH. The human sex ratio, part 2: a hypothesis and a program of research. Hum
`Bwl 1987; 59: 873-900.
`3. Stone BA, Serafini PC, Quinn K, Quinn P, Kerin JF, Marrs RP. Gonadotropin and
`estradiol levels during ovarian stimulation in women treated with leuprolide
`acetate. Obstet Gynecol 1989; 73: 990.
`
`BRAIN DAMAGE BY NEONATAL HYPOGLYCAEMIA
`
`SIR,-Your April 22 editorial draws attention to two 1988
`papers1,2 and suggests that plasma glucose levels below 2-6 mmoljl
`in the neonatal period may be dangerous, even in symptom-free
`babies. If this is so there are important implications for clinical
`practice.
`Koh et all examined evoked potentials in 17 children and
`recorded changes at different levels of blood glucose. Only 5
`patients were newborn. Weights and gestations are not given. All
`had brainstem auditory responses (ABR) measured. Normal
`patterns were seen at blood glucose levels between 19 and 4.2
`mmol/1. Blood glucose values before the first abnormal finding were
`0-7,1 -4,1 -4,1 ’9, and 2-5 mmol/l-ie, below 2 mmol/1 in four babies.
`The baby with an abnormal ABR at 25 mmol/1 was being fasted
`and was described as drowsy. This baby was 1 of 2 in whom the
`ABR remained abnormal despite raising the blood glucose: the
`
`Adapt & Opiant Exhibit 2019
`Nalox-1 Pharmaceuticals, LLC v. Adapt Pharma Limited et al.
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