`
`THE LANCET
`
`normal in p-ost-secretin volume and maximum bicarbonate
`concentration, with a decrease in amylase output. Although
`the biliary juice in post—cemlein fractions did not contain
`G imaginable, 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
`treaunent 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 trypsin3
`and lipase3 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.
`
`*Itsuro Nakano, Toshihi‘ko Miyahara. Tetsuhide lto,
`Yoshlkatsu Migita, Hajime Nawata
`Third Department of Internal Medicine. Faculty of Medicine. Kyushu University.
`Fukuoka 812. Japan
`
`1 Gupta BK, Mehta S. Giardiasis in childhood: 3 study of pancreatic
`functions. Indiaaned Res 1973: 61: 743—48.
`2 Seow F, Katelaris P, Ngu M. The effect of Giardia Iambt’iu trophozoites
`on trypsin, chimiotrypsin and amylase in vi'tm. Parasitologv 1993; 106:
`233—38.
`3 Katelaris P, Seow F, Ngu M. The effect of Gi'ardz‘u lamblia trophozoites
`on lipolysis in vitro. Parasitologr [991; 103: 35839.
`
`
`
`Response to specific anti-oestrogen
`(ICI182780) in tamoxifen-resistant breast
`cancer
`
`SIR—vHowell 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
`secondsline agent such as an aromatase inhibitor.
`We have reanalysed the response rate of our two phase UH
`studies“2 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
`letrozole
`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~
`oestrogen. The response rate cited in each of the original
`papers without
`this selection was 33% (7/21 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 he more effective
`than the other mixed agonistfantagonist
`torernifenc.
`It
`
`V01345 - February 25, 1995
`
`remains to be seen whether it will be more effective than
`
`other non-steroidal anti-oesu-ogens with less agonist activity
`than tamoxifen or toremifene, such as idoxifenc.’ 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. l E Smith
`Breast Unit. Royal Marsden NHS Trust. London SW3 SJJ. UK
`
`1
`
`2
`
`Iveson T], Smith IE, Ahern J, Smithers DA, Trunet P, Dowsctt M.
`Phase I study of oral aromatase inhibitor (36320267 in
`postmenopausal patients with breast cancer. Cancer Res 1993; 53:
`ace—70.
`Johnston 8RD, Smith IE, Doody 1), Jacobs 3, Robenshaw H,
`Dowsett M. The clinical and endocrine effects of the oral aromatase
`inhibitor vorozole in postmenopausal patients with advanced breast
`cancer. Caviar Re: 1994; 54: 5875—81.
`3 Chander SK, Newton C, McCague R, Dowsett M, Luqmani Y,
`Coombes RC. Pyrrolodine-rl—iodotamoxifen and 4—iodotamoxifen, new
`analogues of the antioestrogen tamoxifen for the treatment of breast
`cancer. Cancer Res 1991; 51: SSH—‘38.
`
`Budd-Chlarl syndrome and factor 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 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 coaguladon
`(re-factors Va and Villa. APC resistance is linked to a single
`basepair mutation on the factor V gene,
`resulting in
`ArgmaGln substitution in the APC cleavage site and
`characterising factor V Leiden."4
`in
`admitted
`A 21-year—old
`trisomic woman was
`November, 1994, with fialminant hepatic failure, aseites, and
`peripheral oedema. Aspartate aminotransfcrase was 8745
`UIL, prothrombin time 34 5 (normal 12), fibrinogen 0‘65
`311., and D dimers 3-2 ug/mL (normal Ell-4 pg/n'tL). 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
`continued. 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
`insufiiciency. We therefore examined the family although
`there was no familial history of thrombosis. The father,
`mother, and two brothers did not have deficiency in
`antithrornhin HI, proteins C or S, or plasminogen.
`Resistance
`to APC,
`assessed by the AFC-dependent
`prolongation of the activated partial thromboplastin time,2
`was found in the mother (ratio 211, normal 2-48—3’66).
`DNA analysis was done with Mitt] digestion of amplified
`factor V DNA fragment.’ Both our patient and her mother
`were heterozygous for the ArgiM—sGln 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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