Leukemoid reaction: a diagnostic clue in metastatic carcinoma mimicking classic Hodgkin lymphoma

We report on 2 patients who were initially suspected to have classic Hodgkin lymphoma because of lymphadenopathy and the presence of Reed-Sternberg-like cells. Both patients had an associated leukemoid reaction (using a threshold leukocyte count of 50 000/microL) and were eventually diagnosed with metastatic carcinoma. Disseminated carcinoma can mimic Hodgkin lymphoma clinically, radiologically, and histologically. Reed-Sternberg-like cells may be found in carcinomas, and they represent a particularly challenging diagnostic pitfall for the unwary. When these cells lead to a suspicion of Hodgkin lymphoma, the presence of a leukemoid reaction should prompt the pathologist to question the diagnosis. Misdiagnosis can be avoided by the use of cytokeratin whenever a leukemoid reaction is present in a suspected case of Hodgkin lymphoma.     

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre– or post–liver transplant

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre– or post–liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6–29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre–LT and 26 post–LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre–LT and three post–LT. Overall, transplant free survival was 42.8% at 4 years and post–LT survival was 87.9% at 5 years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post–LT, with post–LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.     

Histomorphological Patterns of Endometrium in Infertility

Background

Endometrium is the most sensitive indicator of ovarian function and endometrial biopsy is one of the most important investigations in infertility. The current study was carried out to investigate the histomorphological patterns of endometrium in infertile women and to compare the results with other similar studies.

Materials and Methods

A cross-sectional study on 2,080 infertile women was carried out to find the incidence of various histomorphological patterns in hematoxylin-eosin stained sections of endometrium and compare them with other Indian studies.

Results

In the current study majority of cases (88.50 %) were of primary infertility; the highest number of cases was in the age group of 21–30 years and the oldest patient was of 50 years age. The various abnormalities observed were anovulatory endometrium (15.75 %), inadequate proliferative (1.90 %), inadequate secretory (9.52 %), glandulo-stromal disparity (GSD) (4.21 %), hyperplasia (1.10 %), and endometritis (1.63 %). In 3.0 % cases menstrual cycle history was not available and curettage was done at inappropriate period of the cycle in 11.63 %. Comparison with other studies revealed the results matching with some and differing with others.

Conclusion

In the current study, anovulatory endometrium and luteal phase defect are the major causes of infertility, and tuberculous endometritis, non-specific endometritis and GSD are minor contributing factors. These are treatable causes. Premenstrual endometrial biopsy, if accompanied by information of menstrual cycle and date of biopsy, can be a very reliable diagnostic tool for hormonal dysfunction and intrinsic endometrial factors in infertility.     

A nonlinear quasi-static model of intracranial aneurysms

Abstract

Biomathematical modelsof intracranial aneurysms can provide qualitative and quantitative information on stagesof aneurysm development through elucidationof biophysical interactions and phenomena. However, most current aneurysm models, based on Laplace’s law, are renditionsof static, linearly elastic spheres. The primary goalof this study is to:1. develop a nonlinear constitutive quasi-static model and 2. derive an expression for the critical size/pressureof an aneurysm, with subsequent applications to clinical data. A constitutive modelof an aneurysm, based on experimental dataof tissue specimens available in the literature, was incorporated into a time-dependent setof equations describing the dynamic behaviorof a saccular aneurysm in response to pulsatile blood flow. The setof differential equations was solved numerically, yielding mathematical expressions for aneurysm radius and pressure. This model was applied to clinical data obtained from24 patients presenting with ruptured aneurysms. Aneurysm development and eventu.al rupture exhibited an inverse relationship between aneurysm size and blood pressure. In general, the model revealed that rupture becomes highly probable for an aneurysm diameter greater than 2.0mm and a systemic blood pressure greater than125 mmHg. However, an interesting observation was that the critical pressure demonstrated a minimal sensitivity to the critical radius, substantiating similar clinical and experimental observations that blood pressure was not correlated, to any degree, with aneurysm rupture. Undulations in the aneurysm wall, presented by irregularmultilobulated morphologies, could play an important role in aneurysm rupture. However, dueto the large variation in results, more extensive studies will be necessary for further evaluation and validationof this model.[Neural Res 1997; 19: 489-496]     

Value of Posterior and Right Ventricular Leads in Comparison to the Standard 12-Lead Electrocardiogram in Evaluation of ST-Segment Elevation in Suspected Acute Myocardial Infarction

In this multicenter prospective trial, we studied posterior (V₇ to V₉) and right ventricular (V₄R to V₆R) leads to assess their accuracy compared with standard 12-lead electrocardiograms (ECGs) for the diagnosis of acute myocardial infarction (AMI). Patients aged >34 years with suspected AMI received posterior and right ventricular leads immediately after the initial 12-lead ECG. ST elevation of 0.1 mV in 2 leads was blindly determined and inter-rater reliability estimated. AMI was diagnosed by World Health Organization criteria. The diagnostic value of nonstandard leads was determined when 12-lead ST elevation was absent and present and multivariate stepwise regression analysis was also performed. Of 533 study patients, 64.7% (345 of 533) had AMI and 24.8% received thrombolytic therapy. Posterior and right ventricular leads increased sensitivity for AMI by 8.4% (

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) but decreased specificity by 7.0% (

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). The likelihood ratios of a positive test for 12, 12 + posterior, and 12 + right ventricular ECGs were 6.4, 5.6, and 4.5, respectively. Increased AMI rates (positive predictive values) were found when ST elevation was present on 6 nonstandard leads (69.1%), on 12 leads only (88.4%), and on both 6 and 12 leads (96.8%; p <0.001). Treatment rates with thrombolytic therapy increased in parallel with this electrocardiographic gradient. Logistic regression analysis showed that 4 leads were independently predictive of AMI (p <0.001): leads I, II, V₃, V₅R; V₉ approached statistical significance (

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). The standard ECG is not optimal for detecting ST-segment elevation in AMI, but its accuracy is only modestly improved by the addition of posterior and right ventricular leads.In this multicenter prospective trial, 0.1 mV of ST-segment elevation in posterior (V₇ to V₉) and right ventricular (V₄R to V₆R) leads was found to increase the sensitivity of the electrocardiogram for acute myocardial infarction by 8.4% (

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), but decrease specificity by 7.0% (

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); logistic regression analysis showed that 4 leads were predictive of AMI at p <0.001: I, II, V₃, V₅; V₉ approached statistical significance (

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). The standard electrocardiogram is not optimal for detecting ST elevation in acute myocardial infarction, but its accuracy is only modestly improved by the addition of posterior and right ventricular leads.     

Analysis and reproducibility of 3'-Deoxy-3'-[18F]fluorothymidine positron emission tomography imaging in patients with non-small cell lung cancer

PURPOSE: Imaging tumor proliferation with 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) and positron emission tomography is being developed with the goal of monitoring antineoplastic therapy. This study assessed the methods to measure FLT retention in patients with non-small cell lung cancer (NSCLC) to measure the reproducibility of this approach. EXPERIMENTAL DESIGN: Nine patients with NSCLC who were untreated or had progressed after previous therapy were imaged twice using FLT and positron emission tomography within 2 to 7 days. Reproducibility (that is, error) was measured as the percent difference between the two patient scans. Dynamic imaging was obtained during the first 60 min after injection. Activity in the blood was assessed from aortic images and the fraction of unmetabolized FLT was measured. Regions of interest were drawn on the plane with the highest activity and the adjacent planes to measure standardized uptake value (SUV(mean)) and kinetic variables of FLT flux. RESULTS: We found that the SUV(mean) obtained from 30 to 60 min had a mean error of 3.6% (range, 0.6-6.9%; SD, 2.3%) and the first and second scans were highly correlated (r(2) = 0.99; P < 0.0001). Using shorter imaging times from 25 to 30 min or from 55 to 60 min postinjection also resulted in small error rates; SUV(mean) mean errors were 8.4% and 5.7%, respectively. Compartmental and graphical kinetic analyses were also fairly reproducible (r(2) = 0.59; P = 0.0152 and r(2) = 0.58; P = 0.0175 respectively). CONCLUSION: FLT imaging of patients with NSCLC was quite reproducible with a worst case SUV(mean) error of 21% when using a short imaging time.     

Transdermal lontophoretic delivery of colchicine encapsulated in liposomes

Iontophoresis is useful for the transdermal delivery of charged drugs. However, nonionized drugs either have a low flux (due to electro-osmosis) or cannot be delivered using this technique. Because ionized or nonionized drugs can be encapsulated in charged liposomes, it was hypothesized that charged liposomes can deliver neutral or nonionized drug efficiently by iontophoresis. Colchicine, a neutral drug, was encapsulated in large unilamellar vesicles (LUVs), prepared with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) along with cholesterol (1:0.5 mole ratio). Multilamellar vesicles (MLVs) were prepared by the thin-film hydration method and LUVs were obtained by extruding MLVs through polycarbonate filters of 200 nm pore size. Positive charge was induced in the liposomes by adding stearylamine and negative charge by adding dicetyl phosphate. Nonencapsulated drug was separated from LUVs by the Ficoll density gradient method. Positively charged LUVs were delivered under the anode, negatively charged LUVs under the cathode, and neutral LUVs without current using Franz cells and human cadaver skin. Plain colchicine as well as colchicine encapsulated in positively charged LUVs was delivered better under the anode compared with the cathode and passive conditions. Delivery of colchicine encapsulated in positively charged DSPC liposomes was four to five times greater than that of plain colchicine and two to three times greater than that of colchicine encapsulated in DMPC or DPPC liposomes. Because LUVs prepared with DMPC and DPPC were fluid at 37°C, the encapsulated drug leaked during iontophoresis and therefore the delivery was less. Delivery of colchicine was lower under the cathode due to the change in pH during iontophoresis, which, as observed in high-performance liquid chromatographic analysis, caused degradation of the drug. Thus, it can be concluded that iontophoresis of colchicine encapsulated in positively charged DSPC liposomes can improve its delivery across human cadaver skin