Aiman Zaher

Plasma expansion by polyethylene-glycol-modified albumin

Systemic inflammatory response conditions are associated with capillary leak and haemodynamic compromise. Fluid resuscitation to reverse the ensuing hypovolaemia is, however, complicated by the decreased endothelium reflection coefficient to albumin and other colloids. We developed PEG-Alb (albumin covalently linked to polyethylene glycol) as a potential resuscitative agent. PEG was covalently linked to human albumin at multiple sites on the protein. The modified protein was heterogeneous when examined by SDS/PAGE, size-exclusion chromatography and SELDI-TOF MS (surface-enhanced laser-desorption ionization-time of flight MS). Based on size-exclusion chromatography and osmotic pressure data, the effective volume of PEG-Alb is increased 13- to 16-fold compared with unmodified albumin. In an LPS (lipopolysaccharide) model of shock, rats treated with PEG-Alb showed better blood pressure, lower Hct (haematocrit) consistent with haemodilution and less lung injury than rats treated with unmodified albumin or saline. In a CLP (caecal ligation and puncture) model of sepsis, PEG-Alb was more effective than albumin or saline in maintaining blood pressure and in decreasing Hct. When fluorescein-labelled PEG-Alb and Texas Red-labelled albumin were administered to rats with LPS- or CLP-induced shock, PEG-Alb was retained within blood vessels, whereas albumin extravasates into the interstitial space. Based on these data, PEG-Alb appears to be retained within blood vessels in models of capillary leak. PEG-Alb may ultimately be effective in the clinical treatment of shock associated with capillary leak.

The c-myc x E2F-1/p21 interactive gene expression index augments cytomorphologic diagnosis of lung cancer in fine-needle aspirate specimens

Morphological analysis of cytologic samples obtained by fine-needle aspirate (FNA) or bronchoscopy is an important method for diagnosing bronchogenic carcinoma. However, this approach has only about 65 to 80% diagnostic sensitivity. Based on previous studies, the c-myc x E2F-1/p21WAF1/CIP1 (p21 hereafter) gene expression index is highly sensitive and specific for distinguishing normal from malignant bronchial epithelial tissues. In an effort to improve sensitivity of diagnosing lung cancer in cytologic specimens, we used Standardized Reverse Transcriptase Polymerase Chain Reaction (StaRT-PCR) to measure the c-myc x E2F-1/p21 index in cDNA samples from 14 normal lung samples (6 normal lung parenchyma and 8 normal bronchial epithelial cell [NBEC] biopsies), and 16 FNA biopsies from 14 suspected tumors. Based on cytomorphologic criteria, 11 of the 14 suspected tumors were diagnosed as bronchogenic carcinoma and three specimens were non-diagnostic. Subsequent biopsy samples confirmed that the three non-diagnostic samples were derived from lung carcinomas. The index value for each bronchogenic carcinoma was above a cut-off value of 7000 and the index value of all but one normal sample was below 7000. Thus the c-myc x E2F-1/p21 index may augment cytomorphologic diagnosis of bronchogenic carcinoma biopsy samples, particularly those considered non-diagnostic by cytomorphologic criteria.

Tumor markers in the detection of recurrent transitional cell carcinoma of the bladder: a brief review.

OBJECTIVE To determine the status of the most promising tumor markers of bladder cancer, including comparison with cytology, technical complexity and utility in patient management. STUDY DESIGN An extensive literature search was performed, and multiple markers were evaluated. The markers with the greatest potential for use as an adjunct to cytology were reviewed to determine the value of clinical implementation. Markers with a paucity of clinical research and poor results in clinical trials were omitted from review, as were genetic and cytologic prognostic determinants. RESULTS NMP22, bladder tumor antigen, fibrin/fibrinogen degradation products, telomerase and QUANTICYT image analysis cytometry produced the most favorable and reproducible results. Each test obtained favorable sensitivities in comparison with cytology, especially in the detection of low grade lesions. Many also retrospectively placed patients in high- and low-risk groups based on the test results, allowing increased follow-up time between cystoscopies. However, inability to detect some high grade lesions reduces their utility. CONCLUSION Continued clinical trials using these and other predictors of bladder cancer will eventually find a test that is suitable, in sensitivity and specificity, for use in urology clinics. Until that time, these tests may be useful in conjunction with cytology to prolong the interval between cystoscopies.

Pathologic quiz case: a 30-year-old man with recurrent pneumonia. Intralobar bronchopulmonary sequestration.

30-year-old African American man presented to the hospital with a 2-week history of a productive cough, shortness of breath, chills, hemoptysis, and pleuritic chest pain in the left posterior chest. His past medical history was significant for moderate alcohol consumption, recurrent pneumonias, smoking one-half pack of cigarettes per day for 15 years, and Mycobacterium tuberculosis exposure with positive purified protein derivative. Physical examination revealed an area of dullness to percussion in the left lower lung field with diminished breath sounds. No wheezes, rales, or rhonchi were noted. Laboratory workup, including complete blood count and electrolyte levels, was within normal limits. Pulmonary function testing showed severe restriction of forced and slow vital capacities with superimposed airflow obstruction. Chest radiographs were obtained that revealed near complete whiteout of the left lower lung field. Contrast-enhanced computed tomographic scan of the chest revealed an enhancing, inhomogeneous lesion, 7.5 3 6 cm in size, in the left lower lobe (Figure 1, white arrow) with what appeared to be a branch of the aorta penetrating the mass (Figure 1,

Pathologic quiz case. A 49-year-old white man with a nodular mass in the liver.

A white man presented with a complaint of increased shortness of breath, which was progressive over 2 weeks. He also said he had a history of night sweats and chills, but no significant weight loss. His past medical history was significant for smoking 1 pack per day for 25 years and 30 years of occupational exposure to toxins, including asphalt and polyvinyl chloride. Abdominal computed tomography showed a single low-density lesion, measuring 4 3 3 cm, in the right lower part of the liver (Figure 1 [view is looking toward the head, from below, taken at the level of the fourth lumbar