Clinical pharmacology of deoxycoformycin

Deoxycoformycin (DCF) is an inhibitor of adenosine deaminase (ADA). Twenty-one courses of DCF were administered to 13 patients ranging in age from 15 to 78 yr. Eight patients had T-cell disorders, and five patients had non-T-cell malignancies. The i.v. bolus dose was escalated from 5 to 30 mg/sq m/day, and the duration of the courses ranged from 1 to 5 days. The DCF plasma half-life ranged from 4.9 to 6.2 hr and was independent of dose. The dose-limiting toxicities involved the central nervous system (CNS) and the kidneys. Other toxicities included bronchitis, decreases in hematocrit, arthralgias, and myalgias. Mortality was encountered in three patients. These toxic effects may have been secondary to the accumulation of the metabolites adenosine and deoxyadenosine. Deoxyadenosine and adenosine were both detectable in plasma (10(-6) M) and in urine (10(-3) M). Two partial remissions were observed: one in a patient with T-cell ALL and another in a patient with mycosis fungoides. Minimal responses characterized by either declines in peripheral blast counts or partial resolution of adenopathy were observed in five other patients. No responses were observed in six patients. These observations suggest that DCF is effective in the treatment of T-cell lymphoid malignancies.     

Immunohistochemical assay for epidermal growth factor receptor on paraffin-embedded sections: validation against ligand-binding assay and clinical relevance in breast cancer.

Epidermal growth factor receptor (EGFR) has been the subject of much research since it was first described as a prognostic factor in breast cancer. The assay methods used and results obtained vary widely between studies. In this study 88 primary breast cancers were assayed for EGFR using a novel immunohistochemical assay performed on paraffin-embedded sections. The monoclonal antibody used was raised against purified, denatured EGFR, reacts with an epitope on the external domain and does not interfere with ligand binding. Twenty-two per cent of the tumours were EGFR positive using this assay. The results obtained were significantly correlated with those obtained by ligand-binding assay (r = 0.621, P = 0.011). The concordance rate was 82% (P < 0.001). The majority of discordant results could be explained by the presence of benign breast tissue and other non-malignant elements which could be seen to express EGFR on the immunohistochemical assay and were excluded from the score for this, but would be incorporated into ligand-binding assay results. The well-established inverse relationship between EGFR (as measured by this assay) and oestrogen receptor (ER) was seen (chi 2 = 24.9, P < 0.0001). In addition, in this exploratory study on a limited tumour set, EGFR was a significant adverse prognostic factor (on univariate but not multivariate analysis) for both relapse-free survival (P = 0.02) and overall survival (P = 0.03) when measured by this immunohistochemical assay, but was not significant when measured by ligand-binding assay.     

Biliary atresia and noncardiac polysplenic syndrome: US and surgical considerations

Ten percent of children with biliary atresia have an associated complex of anomalies, including polysplenia, azygous continuation of the inferior vena cava, preduodenal portal vein, hepatic arterial anomalies, and bilaterally bilobed lungs. These abnormalities will not be detected if the preoperative workup is limited to hepatobiliary nuclear scanning. Ultrasonography is important in the preoperative evaluation of patients suspected of having biliary atresia. It is important to identify the associated abnormalities preoperatively because they have an impact on the initial portoenterostomy and may preclude subsequent orthotopic liver transplantation.     

Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors.

BACKGROUND: Aromatase inhibitors (AI) are increasingly used in early breast cancer and there is a growing interest in associated long-term side-effects of profound estrogen suppression. Urogenital side-effects due to atrophic vaginitis are often managed with vaginal estrogen preparations. These are generally perceived to result in minimal systemic absorption of estrogen. We followed serum estradiol, follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in seven postmenopausal women using vaginal estrogen preparations whilst on AIs for breast cancer. PATIENTS AND METHODS: Serum was analysed for estradiol, FSH and LH at baseline then 2, 4, 7-10 and 12 weeks since commencement of vaginal estradiol. Estradiol was measured on an assay specifically developed for measuring low levels in postmenopausal women. RESULTS: Serum estradiol levels rose from baseline levels < or = 5 pmol/l consistent with AI therapy to a mean 72 pmol/l at 2 weeks. By 4 weeks this had decreased to < 35 pmol/l in the majority (median 16 pmol/l) although significant further rises were seen in two women. CONCLUSIONS: The vaginal estradiol tablet Vagifem significantly raises systemic estradiol levels, at least in the short term. This reverses the estradiol suppression achieved by aromatase inhibitors in women with breast cancer and is contraindicated.     

Iliocaval arteriovenous fistula presenting with multiple organ failure

Iliac arteriovenous fistulas are an uncommon condition, which may be spontaneous or traumatic in nature. Such fistulas classically present with a triad of high‐output cardiac failure, pulsatile abdominal mass with a bruit and unilateral leg ischaemia or venous congestion. We describe a case of an iliocaval fistula secondary to rupture of a common iliac artery aneurysm, with an unusual presentation of multiple organ failure, masquerading as sepsis. We describe the CT findings of iliocaval fistula, which was the means of diagnosis in this study.