normal in post-secretin volume and maximum bicarbonate
`concentration, with a decrease in amylase output. Although
`the biliary juice in post—cerulein fractions did not contain
`G ltlrestirialis, 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. Ultras-onography
`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 trypsin3
`and lipase’ by in-villa studies. In our case, diabetes might
`have predisposed to an immunocompromised state or severe
`diabctic neuropathy might have affected the tone of Oddi’s
`sphincter to allow infection with the protozoa.
`
`*ltsuro Nakano, Toshihiko Miyahara. Tetsuhide lto,
`Yoshikatsu Mfg.-‘ta. Hajime Nawata
`Third Department of Internal Medicine, Faculty of Medicine. Kyushu University.
`Fukuoka 812. Japan
`
`] Gupta RK, Mehta S. Giardiasis in childhood: a study of pancreatic
`functions. Im'1'.mt_7d/led Res 1973; 61: 743-48.
`2 Seow F, Katelaris P, Ngu M. The effect of Giardia Iamblia trophozoitcs
`on u-ypsin, chymotrypsin and amylase in virro. Parasitology» 1993; 106:
`233-38.
`
`3 Katclaris T’, Scow F, Ngu M. The effect of Giardia lamb-Ea trophozoites
`on lipolysis in oftro. Parasitology 1991; 103: 35499.
`
`Response to specific anti-oestrogen
`(lcl182780) in tamoxifen-resistant breast
`cancer
`
`SIR—l-lowell and colleagues’ data (Jan 7, p 29) on the novel
`steroidal antieoestrogen 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 arornatase inhibitor.
`We have reanalysed the response rate of our two phase UII
`studies‘-9 of two new triazole aromatase inhibitors (vorozolc
`and lctrozole), 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 adiuvant
`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
`letrozolc
`and
`vorozolc
`studies,
`respectively. There were 5 and 9 responders, respectively,
`giving a combined response rate of 78% (14/18), which is
`clearly not significantly different.’ from that with the new anti-
`oesn-ogen. The response rate cited in each of the original
`papers without
`this selection was 33% (7/21 and 8/24,
`rflspcctively). Also in accord with Howell and colleagues’
`findings, several of our patients’ responses were of prolonged
`duration (for >21 months in 5 of 14).
`The new anti—oestrogen looks likely to be more effective
`than the other mixed agonist/antagonist
`toremifene.
`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 effective in
`terms of response rate than aromatase inhibitors, with which
`it
`is conceptually similar in its pure deprivation of the
`oestrogcnic signal.
`
`*M Dowsett, S R DJohnston, T J lveson. I E Smith
`Bteast Unit. Royal Marsden NHS Trust. London SW3 SJJ. UK
`
`1
`
`2
`
`lvcson T], Smim IE, Ahern ], Smithers DA, Trunet P, Dowsett M.
`Phase I study of oral ammatasc inhibitor CGS2026'i' in
`postmenopausal patients with breast cancer. Cancer Res 1993; 53;
`2o6—70.
`Johnston SRD, Smith IE, Doody D, Jacobs 3, Robenshaw H,
`Dowsett M. The clinical and endocrine efibcts of the oral aromatase
`inhibitor vorozole in posttnenopausal patients with advanced breast
`cancer. Cancer Res 1994; 54: 5875-81.
`3 Chander SK, Newton C, Mccague R, Dowsen M, Luqrnani Y,
`Coornbes RC. Pyrrolodine-4~iodotarnoxifen and 4-i()Clt)tatTlOXif¢2l'J., new
`analogues of the antiocstrogen tamoxifen for the treatment of breast
`cancer. Cancer Res 199]; 51: 5851-58.
`
`Budd-Chlatl syndrome and factor V Leiden
`mutation
`
`syndrome is characterised by hepatic
`SIR—Budd—Chiari
`venous outflow obstruction. Although rnyeloproliferative
`diseases
`are usually responsible for
`this obstruction,‘
`deficient or abnormal inhibitors of the haemostatic system,
`antithromhin 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
`thromhophiliai The anticoagulant
`function of APC lies in its capacity to inactivate coagulation
`co—facto1's Va and Vllla. APC resistance is linked to a single
`basepair mutation on the factor V gene,
`resulting in
`Arg‘°“—»Gln substitution in the APC cleavage site and
`characterising factor V Leiden.“
`in
`admitted
`A 2l~year~old
`trisomic woman was
`November, 1994, with fulminant hepatic failure, ascites, and
`peripheral oedema. Aspartate arninoo-ansferase was 8745
`UL, prothrombin time 34 s (normal 12), fibrinc-gen 0-65
`g/L, and D dimers 3-~2 ugfml. (normal EEO-4 pgfmL}. 2 years
`before, she had had an ilio-femoral thrombosis and bilateral
`pulmonary embolism. At that time, protein C, antithroinbin
`1H,
`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
`doppler
`ultrasonography
`showed
`hepatic veins and Budd-Chiari syndrome was histologically
`confirmed. The patient was treated with low-n'1olecular-
`weight heparin (Enoxaparin) and then with vitamin K
`antagonists when prothrombin time reached about l5 s, and
`she was discharged. Coagulation studies would not have
`been informative because of
`the severe hepatoccllular
`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 plasrninogen.
`Resistance
`to AFC,
`assessed by the APC-dependent
`prolongation of the activated partial thromboplastin time,2
`was found in the mother (ratio Zvll, normal 2-48-3-66).
`DNA analysis was done with [Mull digestion of amplified
`factor V DNA fragment.’ Both our patient and her mother
`were heterozygous for the Arg"°“—9Gln mutation.
`The deficiency of free protein S seen previously seems to
`have been acquired, since it was not detected in the family.
`
`Vol 345 ' February 25, 1995
`
`525
`
`Astraleneca Ex. 2038 p. 1
`Mylan Pharms. Inc. V. Astraleneca AB IPR2016-01325