`
`THE LANCET
`
`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 intestinalis, post-secretin pancreatic juice contained lots of
`the protozoa. The patient was treated with 750 mg three
`times daily of metronidazole 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 malabsorption 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 immunocompromised state or severe
`diabetic neuropathy might have affected the tone of Oddi’s
`sphincter to allow infection with the protozoa.
`
`*/tsuro Nakano, Toshihiko Miyahara, Tetsuhide Ito,
`Yoshikatsu Migita, Hajime Nawata
`Third Department of Internal Medicine, Faculty of Medicine, Kyushu University,
`Fukuoka 812, Japan
`
`1 Gupta RK, Mehta S. Giardiasis in childhood: a study of pancreatic
`functions. Indian 7 Med Res 1973; 61: 743-48.
`2 Seow F, Katelaris P, Ngu M. Theeffect of Giardia lamblia trophozoites
`on trypsin, chymotrypsin and amylase in vitro. Parasitology 1993; 106:
`233-38.
`3. Katelaris P, Seow F, Ngu M. Theeffect of Giardia lamblia trophozoites
`on lipolysis in vitro. Parasitology 1991; 103: 35-39.
`
`
`
`Responseto specific anti-oestrogen
`(1Cl1482780) in tamoxifen-resistant breast
`cancer
`
`Sir—Howell and colleagues’ data (Jan 7, p 29) on the novel
`steroidal anti-oestrogen 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 [/IT
`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 whofitted Howell
`and co-workers’ entry criteria. Thus, patients were excluded
`if they had received chemotherapyin 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
`letrozole
`and
`vorozole
`studies,
`respectively. There were 5 and 9 responders, respectively,
`giving a combined response rate of 78% (14/18), which is
`clearly not significantly differenrfrom that with the new anti-
`oestrogen. The response rate cited in each of the original
`papers without
`this selection was 33% (7/21 and 8/24,
`respectively). 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
`
`Vol 345 * February 25, 1995
`
`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
`oestrogenic signal.
`
`*M Dowsett, S R D Johnston, T J lveson, | E Smith
`Breast Unit, Royal Marsden NHS Trust, London SW3 6JJ, UK
`
`1
`
`2
`
`Iveson TJ, Smith IE, Ahern J, Smithers DA, Trunet P, Dowsett M.
`Phase I study of oral aromatase inhibitor CGS20267 in
`postmenopausal patients with breast cancer. Cancer Res 1993; 53:
`266-70.
`Johnston SRD, Smith IE, Doody D, Jacobs S, Robertshaw H,
`Dowsett M. Theclinical and endocrine effects of the oral aromatase
`inhibitor vorozole in postmenopausal patients with advanced breast
`cancer. Cancer Res 1994; 54; 5875-81.
`3 Chander SK, Newton C, McCague R, Dowsett M, Luqmani Y,
`Coombes RC. Pyrrolodine-4-jodotamoxifen and 4-iodotamoxifen, new
`analogues of the antioestrogen tamoxifen for the treatment of breast
`eancer. Cancer Res 1991; 51: 5851-58.
`
`Budd-Chiari syndrome andfactor V Leiden
`mutation
`
`syndrome is characterised by hepatic
`Sir—Budd-Chiari
`venous outflow obstruction, Although myeloproliferative
`diseases
`are usually responsible for
`this obstruction,'
`deficient or abnormal inhibitors of the haemostatic system,
`antithrombin II, 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
`thrombophilia. The anticoagulant
`function of APC lies in its capacity to inactivate coagulation
`co-factors Va and VIIa. APC resistance is linked to a single
`basepair mutation on the factor V gene,
`resulting in
`Arg**»GlIn substitution in the APC cleavage site and
`characterising factor V Leiden.**
`in
`admitted
`A 2\-year-old
`trisomic woman was
`November, 1994, with fulminant hepatic failure, ascites, and
`peripheral oedema, Aspartate aminotransferase was 8745
`U/L, prothrombin time 34 s (normal 12), fibrinogen 0-65
`g/L, and D dimers 3-2 g/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
`Il,
`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-molecular-
`weight heparin (Enoxaparin) and then with vitamin K
`antagonists when prothrombin time reached about 15 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 IJ, proteins C or S, or plasminogen.
`Resistance
`to APC,
`assessed by the APC-dependent
`prolongation of the activated partial thromboplastin time,’
`was found in the mother (ratio 2:11, normal 2:48—3-66).
`DNAanalysis was done with Mn/l 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.
`
`525
`
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