Radiographic demonstration of common bile duct varices

Varicose veins may occur along the course of the common bile duct in patients with extrahepatic obstruction of the portal vein. These may cause partial biliary obstruction or excessive bleeding during biliary surgery. The cholangiographic appearance of choledochal varices is described.     

The influence of aspirin on the course of induced midtrimester abortion

Prostaglandins appear to mediate the uterine contractions of abortion and labor, and aspirin has been shown to be an inhibitor of prostaglandin synthesis. In this double-blind, placebo-controlled, prospective, and randomized study, aspirin was administered orally in doses of 600 mg. every 6 hours to patients undergoing induced midtrimester abortions with hyperosmolar urea and oxytocin augmentation. The mean injection-abortion interval was significantly prolonged by aspirin in nulliparous patients (aspirin 32.3 ± 3.3 hr. vs. placebo 21.5 ± 3.5 hr.) and no aspirin-treated nullipara aborted in less than 18 hours. There was no significant difference between treatment groups in the mean injection-abortion interval in the multiparous patients at the dose of aspirin used. The effectiveness of aspirin in the prolongation of the injection-abortion interval has potential therapeutic implications for the treatment of premature labor.     

Quantitative mass spectral evidence for the absence of circulating brain natriuretic peptide (BNP-32) in severe human heart failure

C-terminal brain (B-type) natriuretic peptide (BNP)-32 is a widely used clinical biomarker for the diagnosis, prognosis, and treatment of heart failure (HF). The 32-aa peptide is synthesized primarily in the atrial and ventricular myocardium and constitutes the mature biologically active form of immature BNP (pro-BNP). There has been mounting evidence that suggests BNP circulates in different structural forms that impact HF diagnosis and in vivo activity. Herein, we have developed and used an immunoaffinity purification assay to isolate endogenous BNP-32 from New York Heart Association class IV patient plasma for subsequent analysis by nano-liquid chromatography (LC) electrospray ionization Fourier transform ion cyclotron resonance (FT-ICR) MS. We have introduced stable isotope-labeled BNP-32 to the assayed plasma to enable quantification of endogenous levels of BNP-32. Unlike the chemically nonspecific point-of-care tests (POCTs) and RIAs used worldwide to quantify BNP-32 from plasma, FT-ICR-MS (unprecedented mass measurement accuracy) coupled with LC (retention time) affords extraordinary molecular specificity, and when combined with the use of internal standards is able to confidently identify and quantify BNP-32. The significance of this work is despite exceedingly high circulating levels of BNP-32 in the New York Heart Association class IV patients as determined by POCTs (>290 fmol/ml) nano-LC-electrospray ionization-FT-ICR-MS data did not reveal any endogenous BNP-32. These results provide molecularly specific evidence for the absence of circulating BNP-32 in advanced-stage HF patients and suggest the existence of altered forms of BNP that are contributing to the POCT values.     

Prospective dosing of warfarin based on cytochrome P-450 2C9 genotype

Cytochrome P-450 2C9 (CYP2C9) polymorphisms (CYP2C9*2 and CYP2C9*3) reduce the clearance of warfarin, increase the risk of bleeding, and prolong the time to stable dosing. Whether prospective use of a retrospectively developed algorithm that incorporates CYP2C9 genotype and nongenetic factors can ameliorate the propensity to bleeding and delay in achieving a stable warfarin dose is unknown. We initiated warfarin therapy in 48 orthopedic patients tailored to the following variables: CYP2C9 genotype, age, weight, height, gender, race, and use of simvastatin or amiodarone. By using pharmacogenetics-based dosing, patients with a CYP2C9 variant achieved a stable, therapeutic warfarin dose without excessive delay. However compared to those without a CYP2C9 variant, patients with a variant continued to be at increased risk (hazard ratio 3.6, 95% confidence interval 1.4-9.5, p = 0.01) for an adverse outcome (principally INR > 4), despite pharmacogenetics-based dosing. There was a linear relationship (R(2) = 0.42, p < 0.001) between the pharmacogenetics-predicted warfarin doses and the warfarin maintenance doses, prospectively validating the dosing algorithm. Prospective, perioperative pharmacogenetics-based dosing of warfarin is feasible; however, further evaluation in a randomized, controlled study is recommended.     

Extraperitoneal laparoscopic lymph node staging: the University of Southern California experience

OBJECTIVES: To describe our experience with extraperitoneal lymph node staging in gynecologic oncology. MATERIALS AND METHODS: The extraperitoneal approach was performed to assess the lymph node histology in patients with gynecologic malignancies. The nodes are approached from a lateral approach after dissecting open the extraperitoneal space bluntly and with insufflation. Bilateral aortic nodes are taken from a left-sided or right-sided approach depending on the patient's characteristics. RESULTS: Forty-six patients underwent this procedure over a 2.5-year period. Thirty-seven patients had cervical cancer. The median BMI was 27.1 (17.7-38.1). The median lymph node yield was 14 (0-60). Two patients had disruption of the peritoneum such that the aortic lymphadenectomy had to be completed transperitoneally. No patients required laparotomy. No patients required transfusion. DISCUSSION: This technique permits histologic evaluation of the retroperitoneal nodes with minimal risk of intraabdominal adhesions. Recovery is rapid and further therapy can be prescribed shortly. The data on the nodes can assist in treatment planning.     

Adjuvant therapy of completely resected dysgerminoma with carboplatin and etoposide: a trial of the Gynecologic Oncology Group

OBJECTIVE: This study was designed to evaluate the effect of adjuvant chemotherapy with carboplatin and etoposide in patients with completely resected stage IB-III dysgerminoma. METHODS: Eligible patients were treated with three courses of carboplatin 400 mg/m(2) on day 1 plus etoposide 120 mg/m(2) on days 1, 2, and 3 every 4 weeks for three courses. RESULTS: Forty-two patients were entered on this trial, of whom 39 were eligible. No patient suffered a recurrence of dysgerminoma, but one patient ultimately died of lung adenocarcinoma. One patient was excluded on pathology review (elements of endodermal sinus tumor were present) developed recurrent tumor and died despite further therapy. As expected, the regimen was well tolerated. Median follow-up of surviving patients is 7.8 years (range: 2.86 months to 10.92 years). CONCLUSION: The regimen used in this study is an alternative to cisplatin, etoposide, and bleomycin (BEP) for selected patients for whom minimizing toxicity (particularly neuropathy) is critical or for whom reduction in the number of treatment days is important.     

Carrier screening for Canavan disease in Australia

This study reports, for the first time, the carrier frequency of Canavan disease in the Ashkenazi Jewish population in Australia, and the identification of a novel mutation in the ASPA gene.     

A pilot study of dendroaspis natriuretic peptide in aneurysmal subarachnoid hemorrhage

OBJECTIVE: Hypovolemia after aneurysmal subarachnoid hemorrhage (SAH) may be mediated by natriuretic peptides and can further impair cerebral perfusion in dysautoregulated and vasospastic arterial territories. Dendroaspis natriuretic peptide (DNP), derived from the venom of Dendroaspis augusticeps, the Green Mamba snake, has recently been discovered in human plasma and atrial myocardium. There is no information regarding the presence or putative role of this peptide in patients with aneurysmal SAH. METHODS: A sensitive and specific DNP radioimmunoassay was performed on venous blood samples obtained on post-SAH Days 1, 3, and 7 from 10 consecutive SAH patients (cases) and randomly from 9 healthy volunteers (controls). Clinical and laboratory data, including daily serum sodium concentration and fluid balance, were collected prospectively up to 7 days after the ictus. RESULTS: Increase in plasma DNP levels occurred in five (63%) of eight patients who had DNP levels measured on Days 1 and 3 (mean increase, 29%). An increase in DNP level was significantly associated with development of a negative fluid balance (P = 0.003) and hyponatremia (P = 0.008). Three (75%) of the four patients who developed cerebral vasospasm during this study experienced an increase in DNP levels from Days 1 to 3. CONCLUSION: The present study is the first to find a significant association between elevated levels of DNP, a new member of the natriuretic peptide family, and the development of diuresis and natriuresis in patients with aneurysmal SAH. Our findings warrant further investigation by means of a large-scale, prospective, case-control study.     

The impact of sildenafil on molecular science and sexual health

OBJECTIVE: Sexual medicine has evolved greatly in the past several years, to a large extent because of the introduction of the phosphodiesterase-5 (PDE5) inhibitor, Viagra (sildenafil citrate), as a highly effective oral therapy for erectile dysfunction. METHODS: Recent literature pertaining to the development and clinical applications of sildenafil citrate was reviewed. RESULTS: The emergence of PDE5 inhibitor therapy for erectile dysfunction represents a major scientific and clinical breakthrough, and it has impacted on the field in such prominent areas as scientific discovery, clinical management, and public health awareness of sexual health disorders. CONCLUSION: The development of sildenafil citrate has had a major role in advancing the field of sexual medicine.