Measurement of cardiac output-transtracheal Doppler versus thermodilution

The ABCOM 1 transtracheal Doppler (TTD) has been developed as a non-invasive cardiac output monitor. With this device, cardiac output is continuously calculated from ascending aortic blood flow velocity and aortic diameter obtained via an ultrasound transducer incorporated into the tip of an endotracheal tube. We evaluated the clinical use of the ABCOM 1 monitor and compared cardiac outputs obtained using the TTD system with simultaneous thermodilution (TD) measurements. We found the operation of the ABCOM 1 monitor to be difficult and time-consuming. In our operating rooms, acceptable Doppler signal quality was difficult to obtain. There was no correlation between 36 simultaneously obtained TTD and TD cardiac output measurements. The average difference between measurement techniques and the limits of agreement were unacceptably large (mean difference = 3.04 L.min-1, mean +/- 2 SD = -6.04 to 12.48 L.min-1). Separately analyzing only those measurements during which Doppler signal quality was adequate did not improve agreement between TTD and TD measurements. On the basis of these findings, TTD cannot be recommended as a clinical cardiac output measurement technique.     

Preoperative Evaluation of Pancreatic Masses with Positron Emission Tomography Using 18F-fluorodeoxyglucose: Diagnostic Limitations

Identification of pancreatic cancer in patients presenting with an enlarged pancreatic mass is a major diagnostic problem. Positron emission tomography (PET) using the radiolabeled glucose analogue ¹⁸F-fluorodeoxyglucose (FDG) has been suggested to provide excellent accuracy for noninvasive determination of suspicious pancreatic masses. We conducted a prospective study to verify these results. Forty-two patients admitted for pancreatic surgery underwent PET scanning. Image analysis was based on visual film evaluation and quantification of regional tracer uptake. PET imaging was visually analyzed by three observers blinded for the results of other diagnostic tests; they qualitatively graded the scans using a five-point scale (I = low to V = high) for the presence and intensity of focal FDG uptake. Diagnosis was proven by histology (n= 38) or follow-up (n= 4). Furthermore, the results of PET were compared with helical computed tomography (CT) and conventional ultrasonography (US), done during the routine diagnostic workup before pancreatic cancer surgery. Regarding only the results with scores of IV and V as positive for representing definite malignancy yielded a sensitivity of 71% and a specificity of 64% for film reading. Quantification of regional tracer uptake contributed no significant diagnostic advantage for differentiation between benign and malignant tumors. Helical CT revealed a sensitivity of 74% and a specificity of 45.5% and abdominal US 56% and 50%, respectively. We concluded that PET imaging provides only fair diagnostic accuracy (69%) for characterizing enlarged pancreatic masses. PET does not allow exclusion of malignant tumors. In doubtful cases, the method must be combined with other imaging modalities, such as helical CT. The results indicate that the number of invasive procedures is not significantly reduced by PET imaging.     

Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor.

PURPOSE: To investigate the safety and tolerability and to explore the pharmacokinetic and pharmacodynamic profile of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with solid tumors that express epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: This was a phase I dose-escalation trial of EMD72000 in patients with advanced, EGFR-positive, solid malignancies that were not amenable to any established chemotherapy or radiotherapy treatment. EMD72000 was administered weekly without routine premedication until disease progression or unacceptable toxicity. RESULTS: Twenty-two patients were treated with EMD72000 at five different dose levels (400 to 2,000 mg/wk). National Cancer Institute common toxicity criteria grade 3 headache and fever occurring after the first infusion were dose limiting at 2,000 mg/wk; thus, the maximum-tolerated dose was 1,600 mg/wk. No other severe side effects, especially no allergic reactions or diarrhea, were observed. Acneiform skin reaction was the most common toxicity, but it was mild, with grade 1 in 11 patients (50%) and grade 2 in three patients (14%). Pharmacokinetic analyses demonstrated a predictable pharmacokinetic profile for EMD72000. Pharmacodynamic studies on serial skin biopsies revealed that EMD72000 effectively abrogated EGFR-mediated cell signaling (eg, reduced phosphorylation of EGFR and mitogen-activated protein kinase), with no alteration in total EGFR protein. Objective responses (23%; 95% CI, 8% to 45%) and disease stabilization (27%; 95% CI, 11% to 50%) were achieved at all dose levels, and responding patients received treatment for up to 18 months without cumulative toxicity. CONCLUSION: Treatment with EMD72000 was well tolerated and showed evidence of activity in heavily pretreated patients with EGFR-expressing tumors. EMD72000 at the investigated doses significantly inhibited downstream EGFR-dependent processes.     

Chemical constituents and biological activities of Zanthoxylum usambarense.

Bioassay-guided fractionation of the dichloromethane extracts of the roots and the bark of Zanthoxylum usambarense led to the isolation of two physiologically active compounds, i.e. canthin-6-one 1 (fungicide) and pellitorine 4 (insecticide). Together with oxychelerythrine 2, norchelerythrine 3, (+)-sesamin 5 and (+)-piperitol-3,3-dimethylallyl ether 6, they were isolated for the first time from this plant.     

Spontaneous regression of a breast carcinoma: a case report

Spontaneous regression of malignant tumors is a rare event. It is defined as partial or total disappearance of a proven malignant tumor without adequate medical treatment. The causes of this phenomenon are various. Nevertheless, malignant tumors do regress occasionally for no apparent reason, as evidenced by many clinical observations. We report a case of a 68-year-old woman, who was presented with a several-month history of a painless firm lump, initially of 1 cm in diameter and growing to a large solid regular tumor of 2.5 x 2.5 cm in size, in the upper outer quadrant of her right breast. Preoperative histopathological diagnosis revealed ductal invasive carcinoma. Later on, while awaiting surgical treatment, she suffered an arm injury requiring a 1-month delay of surgery. After recovery, on the date of surgery the tumor disappeared, and, in addition, it was not found in tissue specimens obtained from quadrantectomy. After 78 months of follow-up there was no evidence of relapse. In this report, we discuss clinical and histopathological findings, patient management and possible mechanisms of cancer regression.     

Too old for IVF: are we discriminating against older women?

In vitro fertilization (IVF) in women of advanced age (>42 years) represents only 5%, a comparatively minute part, of the national IVF experience in the United States (US). In view of evolving population dynamics, it, however, also represents proportionally a rather quickly expanding patient need. Because of access restrictions at many IVF programs, this market does not live up to its potential. As best demonstrated by the 2004 US National Summary and Fertility Clinic Report, which for the first time reported pregnancies and births above age 45 year, IVF in women of advanced reproductive age represents a cutting edge area of interest for improving current IVF outcomes. Access to IVF should, therefore, not be withheld based on female age and/or baseline FSH levels. Instead, a definition of acceptable minimal pregnancy and life birth rates could be used to define the limits of offered access to IVF, independent of age and/or baseline FSH levels.