normal in post-secretin volume and maximum bicarbonate
`concentration, with a decrease in amylase output. Although
`the biliary juice in post—ce1.'uleir1 fractions did not contain
`G intestinciis, post—secretin pancreatic juice contained lots of
`the protozoa. The patient was treated with 750 mg three
`times daily of metronidazolc for 7 days. The CST after
`treatment was normal and no giardia was found in any
`fraction of duodenal
`juice. Ultrasonography
`showed
`reduction of the cyst size after treatment.
`To our knowledge, there has been no previous report of
`pancreatic infection with giardia, but
`the mechanism of
`diarrhoea and rnalabsorption in giardiasis has been explained
`by decreased pancreatic function,‘ which has been shown to
`be secondary to the inhibitory effect of giardia on trypsin’
`and lipase’ by in-Vitro studies. In our case, diabetes might
`have predisposed to an immunocornprornised state or severe
`diabetic ncuropathy might have affected the tone of 0ddi’s
`sphincter to allow infection with the protozoa.
`
`filtsuro Nakano, Toshihlkn Mlyahara. Tetsuhlde Ito.
`Ycshikatsu Migita, Hajime Nawata
`Third Department of lntcrnal Medicine. Faculty of Medicine. Kyushu university.
`Fukuoka 812. Japan
`
`I Gupta RK, Mehta S. Ginrdiasis in childhood: a study of pancreatic
`t‘1inctions.1m:l‘:‘an}Med Res 1973; 61: 743-48.
`2 Seow F, Kalelaria P. Ngu M. The effect of (Hardin famblia trophozoites
`on lrypsin, chymotrypsin and amylase in mm. Parasitology 1993; 106:
`233-38.
`3 Katelaris I’, Seow F, Ngu M. The cffect of Gicrdfa Iambifa tmphozoites
`on lipolysis in 1-ftro. Parasitology 1991; 103: 35-39.
`
`Response to specific anti-oestrogen
`( Icl182780) in tamoxifen-resistant breast
`cancer
`
`SIl2—Howell and colleagues’ data (Jan 7, p 29) on the novel
`steroidal antimestrogen are encouraging. However, the cited
`response rate of 13/9 (69%), albeit striking, should be
`interpreted with care in relation to other published data.
`First, although there are biological and clinical arguments to
`include patients with 6 months of no change with objective
`responders, this approach is uncommon. Second, the group
`of patients that they selected for treatment would generally
`be regarded as favourable in relation to treatment with a
`second-line agent such as an aromatase inhibitor.
`We have reanalysed the response rate of our two phase L’II
`studies” of two new triazole aromatase inhibitors (vorozole
`and letrozole), which are potent suppressants of plasma
`oestrogen concentrations in postmenopausal patients. In this
`reanalysis we have included only patients who fitted Howell
`and co-workers’ entry criteria. Thus, patients were excluded
`if they had received chemotherapy in addition to tamoxifen,
`failed on adjuvant
`tamoxifen after
`less
`than 2 years
`treatment, or showed intrinsic resistance to tamoxifen in the
`metastatic setting. We have also included patients with no
`change for 6 months in the group of responders.
`6 of 21 and 12 of 24 patients were acceptable for this
`reanalysis
`from the
`lctrozole
`and
`vorozole
`studies,
`respectively. There were 5 and 9 responders, respectively,
`giving a combined response rate of 78% (14118), which is
`clearly not significantly dilferenffrom that with the new anti-
`oestrogen. The response rate cited in each of the original
`papers without
`this selection was 33% (7121 and 8124,
`respectively). Also in accord with Howell and colleagues’
`findings, several of our patients’ responses were of prolonged
`duration [for >2l months in 5‘ of 14).
`The new anti—oestrogen looks likely to be more effective
`than the other mixed agonistfantagonisl
`tnrcmifcnc.
`It
`
`THE LANCET
`
`remains to be seen whether it will be more effective than
`other non-steroidal anti-oestrogens with less agonist activity
`than tamoxifen or toremifene, such as idoxifene.’ Our data
`suggest that it may not be substantially more ellective in
`terms of response rate than aromatase inhibitors, with which
`it
`is conceptually similar in its pure deprivation of the
`ocstrogenic signal.
`
`*M Dowsett, S R D Johnston, T J fveson. I E Smith
`Breast Unit. Royal Marsden l'dHSTrus1. London SW3 6JJ. UK
`
`1
`
`2
`
`lveson T], Smith IE, Ahem J, Srnithcrs DA, Trunet P, Dowsett M.
`Phase I study of oral aromatase inhibitor CZGS2026'l in
`postmenopausal patients with breast cancer. Cancer Res I993; 53:
`2663.70.
`Johnston SRD, Smith H3, Doody D, iacobs S, Robertshaw H,
`Dowsett M. The clinical and endocrine cfiects of the oral aromatase
`inhibitor vorozole in postmenopausal patients with advanced breast
`cancer. Cancer Res 1994', 54: 5875-51.
`3 Chander SK. Newton C, McCague R, Dowsctt M, Luqmani Y.
`Coon-lbes RC. Pynolodine-4~iodotarnoxifen and 4rioclotatn-oxifen, new
`analogues of the anrioestrogcn tamoxifen for the treatment ofbreast
`cancer. Cancer Res 199]; 51: 5851-58.
`
`Budd-Chlarl syndrome and factor V Leiden
`mutation
`
`Sm—Budd—Chiari syndrome is characterised by hepatic
`venous outflow obsu-ucnon. Although rnyeioproliferative
`diseases
`are usually responsible for
`this obstruction,‘
`deficient or abnormal inhibitors of the haemostatic system,
`antithrombin III, protein C, and protein S, and anti+
`phospholipid antibodies can be involved. A defect
`in
`anticoagulant response to activated protein C [APC) is a
`new mechanism for
`thrombophiliaf The anticoagulant
`function of APC lies in its capacity to inactivate coagulation
`co-Factors Va and V'IIIa. APC resistance is linked to a single
`basepair mutation on the factor V gene,
`resulting in
`Arg”""wG1n substitution in the APC cleavage site and
`characterising factor V Leiden.’-‘
`in
`admitted
`A 21-yearaold
`trisomic woman was
`November, 1994, with fulminant hepatic failure, ascites, and
`peripheral oedema. Aspartate arninon-ansfcrase was 8745
`U/L. prothrombin time 34 5 (normal 12.}, tibrioogen 0-65
`g/L, and D dimers 3-2 ug/ml. (normal £0-4 pg/mL). 2 years
`before, she had had an ilio-femoral thrombosis and bilateral
`pulmonary embolism. At that time, protein C, antithrombin
`III,
`and antiphospholipid antibodies were normal or
`negative, but
`free protein S was
`low at 46% (normal
`65-120). She had been treated with unfractionated heparin,
`followed by vitamin K antagonists for 6 months.
`occluded
`Hepatic
`dopplcr
`ultrasonography
`showed
`hepatic veins and Budd-Chiari syndrome was histologically
`confirmed. The patient was treated with low-rnolecuian
`weight heparin (Enoxapario) and then with vitamin K
`antagonists when prothrombin time reached about :5 s, and
`she was discharged. Coagulation studies would not have
`been informative because of
`the severe hepatocellular
`insufficiency. We therefore examined the family although
`there was no familial history of thrombosis. The father,
`mother, and two brothers did not have deficiency in
`antithrombin III, proteins C or S, or plasrninogeri.
`Resistance
`to AFC,
`assessed by the APC-dependent
`prolongation of the activated partial thromboplastin timef
`was found in the mother (ratio 211, normal 2-43—3‘66).
`DNA analysis was done with A1221] digestion of amplified
`factor V DNA fragment.-‘ Both our patient and her mother
`were heterozygous for the Arg’°“——>Gln mutation.
`The deficiency of free protein S seen previously seems to
`have been acquired, since it was not detected in the family.
`
`Vol 345 - Fcbruaty 25, 1995
`
`525
`
`Astrazeneca Ex. 2038 p. 1
`Mylan Pharms. Inc. V. Astrazeneca AB IPR20 16-0 13 16