Detection of postoperative pseudoaneurysms following abdominal aortic aneurysm repair in Behçet's disease by MRA

We report the development of two anastomotic pseudoaneurysms in a patient with Beh?et's disease eighteen months after abdominal aortic aneurysm repair. Major asymptomatic vascular complications should be suspected in patients with Beh?et's disease with a history of vascular surgery and treated expediently due to the risk of rupture. Magnetic resonance angiography, contrast-enhanced computed tomography or ultrasound scanning should be performed at least every 6 months after vascular surgery.     

Antitumor polycyclic acridines. Part 12. Physical and biological properties of 8,13-diethyl-6-methylquino[4,3,2-kl]acridinium iodide: a lead compound in anticancer drug design

The biophysical and biological characterization of 8,13-diethyl-6-methylquino[4,3,2-k]lacridinium iodide (6) is reported. The compound binds to DNA, as measured by UV, fluorescence, and circular dichroism studies, and stabilizes the double helix and higher order DNA structures (DNA triplexes and quadruplexes) against thermal denaturation. Unlike many DNA ligands, (6) shows no specificity for binding to specific base pair combinations and does not inhibit topoisomerase I (topo I) or topo II activity. Furthermore, the biological fingerprint elicited by (6) in in vitro evaluations does not compare with clinical agents of the topo II inhibition class. The compound provokes cell cycle arrest in response to DNA damage and the biological sequelae are dependent on the p53 status of the cell line. DNA damage by (6) upregulates p53 and p21(CIP/WAF1) proteins. The unusual structure of (6) and its ease of synthesis in a "one-pot" reaction are features that are being exploited in the design and development of a new series of G-quadruplex stabilizing telomerase inhibitors. However, although the second-generation compounds that resulted from (6) present strong telomerase inhibition, (6) in itself presents yet a different mode of action, with a strong preference for triplex DNA, sequences often found in a number of genes.     

An update on epidermal growth factor receptor inhibitors

The epidermal growth factor receptor (EGFR) is part of a family of plasma membrane receptor tyrosine kinases that control many important cellular functions, from cell growth and proliferation to cell death. Dysregulation of the EGFR signal transduction pathway has been implicated in tumorigenesis and cancer progression, making it a clinically relevant target for novel anticancer treatments. This paper reviews recent progress in the development of cancer therapies that are directed toward particular aspects of the extracellular and intracellular domains of EGFR. Promising new compounds in the advanced stages of clinical testing are emphasized.     

Case reports: postpartum cerebral angiopathy in a patient with chronic migraine with aura

A 25-year-old woman with a history of chronic severe migraine with aura presented in an apoplectic state 1 week after the delivery of her third child. She developed a severe headache and within hours lapsed into a coma. A CT scan of the brain showed cerebral edema and an occipital hemorrhage. A four-vessel angiogram showed diffuse arterial narrowing of all the intracranial vessels with segmental narrowing of the suprasellar portion of the internal carotid arteries bilaterally. She had no risk factors for stroke or vasculitis. Her pregnancy and delivery were uneventful with no preeclampsia or eclampsia. Apart from ergometrine at the time of the delivery, no vasoconstrictor drugs were used. She recovered spontaneously. Serial CT scans of the brain demonstrated resolution of the edema and hemorrhage with the development of cortical and watershed infarcts. A repeat cerebral angiogram was normal. She was, therefore, diagnosed as having suffered from postpartum cerebral angiopathy, a form of reversible cerebral vasoconstriction, called the Call or Call-Fleming syndrome. The relationship between migraine and postpartum angiopathy in the development of reversible cerebral vasoconstriction is discussed.     

Review of current treatment practices for carcinoma of the head and neck

The past two decades have witnessed a paradigm shift in the treatment of squamous cell carcinoma of the head and neck. Innovation in chemotherapy, radiotherapy and surgery has led to the assimilation of these modalities into our treatment algorithms. This modern multipart treatment plan has led to improved survival; however, this has come at the cost of increased toxicity. New and future therapies will be more tumour specific and, ideally, less toxic. Current research centres on these tumour-specific therapies with the anticipation of improved survival with decreased toxicity. This article will review the standard of care, recent advances and unfulfilled needs in the treatment of squamous cell carcinoma of the head and neck.     

Incidence of chemotherapy-induced, long-term amenorrhea in patients with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane

BACKGROUND: Twenty-five percent of all women with breast carcinoma are premenopausal and are at risk for chemotherapy-induced menopause with long-term side effects. Although there is considerable documentation of the rates of chemotherapy-induced amenorrhea with classic adjuvant regimens, there are inadequate data that address the impact of taxanes on menstrual function in this setting. The objective of this analysis was to determine the incidence of long-term amenorrhea (> or = 12 mos) in women with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane-based chemotherapy, with or without subsequent tamoxifen. METHODS: The authors identified 235 premenopausal women with breast carcinoma age 40 years or younger who were treated with adjuvant anthracycline and taxane-based chemotherapy at Memorial Sloan-Kettering Cancer Center from January 1997 to June 2003. RESULTS: One hundred sixty-six patients met all eligibility criteria and had sufficient follow-up for evaluation. The median age of patients at diagnosis was 36 years (range, 27-40 yrs). All patients had regular pretreatment menses, 25 patients (15%) developed long-term amenorrhea, and 141 patients (85%) resumed menstruation. Eighty-two patients (49%) also received tamoxifen: The incidence of amenorrhea among them was 17%. There was a statistically significant association between age and the development of amenorrhea, with older women at higher risk (P < 0.01). CONCLUSIONS: The sequential addition of a taxane to standard adjuvant anthracycline-based chemotherapy did not appear to produce a high rate of chemotherapy-related amenorrhea compared with historic controls. To increase the information available to assist young patients who are considering adjuvant therapy, prospective studies should incorporate menstrual function ascertainment by patient-reported history and assays of ovarian function.     

Allogeneic hematopoietic stem-cell transplantation, mixed chimerism, and tolerance in living related donor renal allograft recipients

OBJECTIVE: We designed a prospective, randomized, and controlled clinical trial to evaluate the efficacy and safety of achieving a mixed chimerism-associated tolerance protocol for recipients of living related donor (LRD) renal allografts. PATIENTS AND METHODS: Sixty-six consecutive patients were divided into two equal groups of 33 patients with end-stage renal disease. They were enrolled for transplantation after negative lymphocytotoxicity cross-matching (LCM). Both groups (treated [Tn] and control [Cn]) showed similar clinical and laboratory parameters and donor HLA match profiles. The Tn group underwent thymic transplantation of donor renal tissue, two donor-specific transfusions, low-intensity conditioning, and high-dose hematopoietic stem-cell transplantation (HSCT) before renal transplantation. The conditioning regimen included low-dose, target-specific irradiation (to abdominal and inguinal lymph nodes, bone marrow [BM] from thoracolumbar vertebrae and part of the pelvis on alternate days, 100 rad x 4), anti-T-cell antibodies (1.5 mg/kg body weight [BW]), cyclophosphamide (10 mg/kg BW x 2 consecutive days), and cyclosporine (CyA; >3 mg/kg BW/d). Unfractionated HSCT procured from the donor marrow was administered into the BM, portal and peripheral circulations, within 24 hours of achieving CD 4+/CD 8+ T-cell count less than 10% of normal. This infusion was supplemented with a dose of peripherally mobilized stem cells (mean total dose of 20 x 10(8) cells/kg recipient BW) administered peripherally. Renal transplantation was performed after negative LCM. Donor-specific cytotoxic antibodies were eliminated with intravenous immunoglobulins and plasmapheresis before renal transplantation. Mixed chimerism was evaluated before and after transplantation at monthly intervals in patients with donors of opposite gender by the FISH technique. Both groups received CyA and prednisolone for immunosuppression; Cn subjects also received mycophenolate mofetil/azathioprine. Rejection was treated with standard treatment. Immunosuppression was withdrawn 6 months after renal transplantation for patients with consistently positive chimerism. Clinical tolerance was defined as stable allograft function for more than 100 days without immunosuppression and confirmed by allograft biopsy. RESULTS: Over a mean follow-up of 210 days, all Tn patients showed stable allograft function with mean serum creatinines (SCr) of 1.20 mg/dL, no rejection/CMV infections/graft or patient loss. A low-level donor-specific cytotoxic antibody was observed in all Tn patients. The CyA toxicity was noted in 10 (30.3%) patients. Persistent mixed hematopoietic chimerism was seen in all 21 patients irrespective of donor-recipient HLA matching (mean 0.5% before and 1 +/- 0.3% after transplantation). All four patients on drug withdrawal have shown donor-specific tolerance at a mean follow-up of 129.8 days. Other Tn patients are in the process of being weaned off immunosuppression. Mean SCr of controls was 1.45 mg/dL over a mean follow-up of 216 days. Acute rejection was observed in 17 (51.5%) patients; no CMV infection/patient loss was noted and one (3.03%) graft was lost in controls. No patient was lost in controls. No graft-versus-host disease was observed in Tn patients. CONCLUSION: We have achieved mixed hematopoietic chimerism-associated tolerance with high-dose HSCT, intrathymic donor renal tissue transplantation, and minimal conditioning without any adverse effects.     

Thiazolidinediones in type 2 diabetes--have they lived up to expectations?

The thiazolidinediones have been in clinical use for the management of type 2 diabetes for the past five years. These agents reduce insulin resistance by acting as ligands that regulate gene expression related to the proliferation and differentiation of adipose tissue. Overall, data from several clinical studies suggest that their hypoglycaemic efficacy is slightly less than sulphonylureas and metformin but greater than acarbose and the glinides. In the short term, treatment with thiazolidinediones is associated with weight gain, expansion of plasma volume, fluid retention, peripheral oedema, an increased risk of congestive heart failure when combined with insulin, and an idiosyncratic hepatotoxic reaction to troglitazone. The long term consequences of these effects are not known. Contrary to expectations, despite being insulin sensitisers these agents do not favourably influence the other components of the metabolic syndrome that are believed to be aggravated by insulin resistance. Dyslipidaemia and elevated blood pressure, which are major risk factors of cardiovascular disease in type 2 diabetes, are not favourably improved with thiazolidinedione treatment. Unlike the sulphonylureas and metformin, which have been shown in recent long term randomised studies to reduce cardiovascular risk substantially, there is no data on the long term cardiovascular safety of the thiazolidinediones. At present, in the absence of long term data, the thiazolidinediones in clinical use are moderately effective hypoglycaemic drugs with no particular advantage over existing treatments in type 2 diabetes.