Comparison of fiberendoscopy and Watson capsule for small intestinal biopsy in infants and children

We analyzed the results of 607 small bowel biopsies performed over a seven-year period: 284 biopsies were obtained using a fiberendoscope and 323 biopsies using a Watson capsule. Three to six specimens were removed during endoscopy. The biopsy fragments obtained with the fiberendoscope were deeper than those obtained with the Watson capsule (p less than 0.0001) and were more often located in the duodenum (p less than 0.0001). The failure rate of the fiberendoscope biopsies (1%) was lower than for the Watson capsule biopsies (9%) (p less than 0.0001). Multiple biopsies increased the diagnostic value of fiberendoscopy which was 95% versus 85% for Watson capsule. The mean duration of the endoscopic procedure recorded in 30 children was 6.5 min for four to six samples, i.e. 1.5 min per biopsy specimen. Fiberendoscopy appears to be an efficient and safe method for performing small bowel biopsies in infants and children.     

Gene therapy for pancreatic cancer--current and prospective strategies

Pancreatic ductal adenocarcinoma is one of the most common causes of cancer death in the developed world. Long-term survival is currently only achieved through surgical resection. Most patients have locally advanced or metastatic disease at the time of diagnosis and are therefore not amenable to resection, whilst chemotherapy and radiotherapy are by and large ineffective. Gene therapy offers an alternative to current adjuvant strategies. With approximately two-thirds of all gene therapy trials worldwide directed at cancer, the gene therapy approaches that are currently being explored for pancreatic cancer are specifically examined. Gene delivery systems, genetic targets, and combined gene delivery with chemotherapy are discussed in the context of pancreatic cancer treatment.     

Heat shock protein expression independently predicts clinical outcome in prostate cancer

Heat shock proteins (hsps) occupy a central role in the regulation of intracellular homeostasis, and differential expression of individual hsps occurs in a broad range of neoplastic processes. This study was performed to test the hypothesis that the particular patterns by which individual hsps become specifically modulated in human prostate cancers are correlated with behavioral phenotype and hence may be of value in determining the most appropriate clinical management of individual patients. Monoclonal antibodies specific for each hsp protein were used to assess expression of hsp27, hsp60, and hsp70 in formalin-fixed, paraffin wax-embedded, archival tissue specimens of early prostatic adenocarcinomas (pT1-2N0M0) removed at radical prostatectomy (n = 25) and in advanced cancers (n = 95) identified at transurethral resection of prostate (TURP). These findings were compared with similar data from control prostates (n = 10) removed at primary cystectomy for urinary bladder neoplasia not involving the prostate and also at TURP for benign prostatic hyperplasia (n = 50). Western blotting of whole cell lysates derived from established human prostatic epithelial cell lines PNT2, LNCaP, DU145, and PC3 was compared with expression of hsps by the primary human tissues. This study found that early in situ neoplastic transformation of normal prostatic epithelium was consistently associated with loss of hsp27 expression and that the level of hsp27 expression by individual prostate cancers was correlated with their Gleason grade. In advanced cancers, hsp27 expression was invariably associated with poor clinical outcome (P = 0.0001). Data from cell lines supported the primary tissue findings, with elevated hsp27 expression only in aggressive malignant cell lines and androgen-insensitive cell lines. Expression of hsp60 was significantly increased in both early and advanced prostate cancer when compared with nonneoplastic prostatic epithelium (P < 0.0001), as well as in malignant prostate cancer cell lines. Expression of hsp70 was unaltered in early prostate cancers when compared with nonneoplastic prostatic epithelium but showed a diminished expression in morphologically advanced cancers (P = 0.0029). No consistent correlation was found between levels of hsp60 or hsp70 expression and phenotypic behavior of individual primary prostatic cancers. Thus, patterns of hsp expression have been confirmed to be specifically and consistently modulated in both early and advanced human prostate cancers. Whereas absence of hsp27 is a reliable objective marker of early prostatic neoplasia, reexpression of this protein by an individual invasive prostatic carcinoma invariably heralds poor clinical prognosis. Because this protein has been shown to alter the balance between proliferation and apoptosis, understanding the mechanism(s) by which individual hsps regulate intracellular homeostasis may assist in explaining some key processes that occur during evolution of human prostate cancers. We suggest that hsp27 expression provides novel diagnostic and prognostic information on individual patient survival which, if obtained at the time of primary diagnosis, would assist in determining tumor-specific management strategies. Development of techniques to therapeutically modulate hsp27 expression raises the possibility of novel targeted approaches to regulate this homeostatic mechanism, thus allowing better control over tumor cell proliferation and hence patient survival.     

Thirty-six human monoclonal immunoglobulins with antibody activity against cytoskeleton proteins, thyroglobulin, and native DNA: immunologic studies and clinical correlations

Six hundred and twelve monoclonal Ig (MIg) were studied for their antibody activity against the following autoantigens: actin, tubulin, thyroglobulin, myosin, myoglobin, fetuin, albumin, transferrin, and double-stranded DNA (dsDNA). Of these 612 MIg, 36 (i.e., 5.75%) were shown to possess antibody activity. Thirty-two of these 36 (5.22% of the total) were mainly directed against actin. The four others were directed, respectively, against tubulin, myosin, thyroglobulin, and dsDNA. The interaction of the MIg with the respective antigen was demonstrated by immunoenzymatic methods with monospecific antisera and by blotting experiments. Furthermore, this interaction in the 12 cases studied was mediated by the dimeric fragment F(ab')2 of the MIg. The MIg with antitubulin, antithyroglobulin, and anti-dsDNA activities were exclusively inhibited by their homologous antigens. Those with antiactin activity were predominantly inhibited by actin and also by tubulin and thyroglobulin. The one binding to myosin was, for the most part, inhibited by myosin and also significantly by actin and tubulin. Retrospective clinical analysis was possible for 31/36 patients. Twenty- six of 31 had malignant lymphoplasmocytic disorders. The five others were followed for miscellaneous disorders without overt signs of multiple myeloma (MM) or Waldenstrom's macroglobulinemia (WM). The correlation between the antibody activity of the MIg and the clinical features is discussed. These results indicate that a high proportion of MIg possess antibody activity against actin (5.22%). This incidence contrasts sharply with the positive reactions found toward all the other antigens tested: only one each for dsDNA, tubulin, thyroglobulin, and myosin, and none against myoglobin, fetuin, albumin, and transferrin. The significance of these results and the relationship between MIg and natural antibodies are discussed.     

Detection of hepatic metastases by proton spectroscopic imaging. Work in progress

Fourteen patients with hepatic metastases underwent magnetic resonance (MR) imaging using both the conventional spin-echo (SE) technique and the opposed phase of the proton spectroscopic imaging method. The opposed image showed more lesions than the conventional SE image in five patients and provided better contrast between the liver parenchyma and metastases in two patients. Four of these seven patients had associated fatty infiltration of the liver. When compared with the computed tomography (CT) scan, the opposed image either showed more lesions or provided better contrast in six patients, four of whom had fatty infiltration. More significantly, the MR image showed several 1-cm lesions not shown by the CT scan in one patient. Our study discloses the possible explanations for the increased sensitivity of the opposed image in detecting hepatic metastases.     

Hydrostatic versus increased permeability pulmonary edema: diagnosis based on radiographic criteria in critically ill patients

To evaluate radiographic criteria recently proposed for determining causes of pulmonary edema, the authors studied 45 patients with severe pulmonary edema. Hydrostatic and increased permeability edemas were distinguished by means of the ratio of pulmonary edema fluid protein to plasma protein concentration and clinical and hemodynamic data. Chest radiographs were classified as showing hydrostatic, increased permeability, or mixed edema by three independent readers without knowledge of the clinical diagnosis. Overall, 87% of patients with hydrostatic edema but only 60% of patients with increased permeability edema were correctly identified. A patchy, peripheral distribution of edema was the single most discriminating criterion and was relatively specific for increased permeability edema, occurring in 13% of patients with hydrostatic and 50% with increased permeability edema (P less than .05). Some features considered more typical of hydrostatic edema were commonly found in patients with increased permeability, including a widened vascular pedicle (56%), pleural effusions (36%), peribronchial cuffs (72%), and septal lines (40%). The authors conclude that chest radiography is limited in the differentiation of type of pulmonary edema in severe cases.     

Variable magnetic resonance imaging parameters: effect on detection and characterization of lesions

With change in the imaging technique and magnetic field strength used in magnetic resonance imaging, wide variations in the delineation of pathologic features occur. Using imaging data from patients with known pathologic conditions, we evaluated the intensity images in spin-echo and inversion-recovery imaging at varying repetition times, echo times, and inversion times over broad ranges and changing magnetic field strengths. Differences in conspicuity and the apparent size of the lesions are important to consider in diagnosing and evaluating pathologic conditions, especially when different imagers and techniques are employed.     

Technetium labelled red blood cell scintigraphy in the diagnosis of intestinal haemorrhage.

99m-Technetium labelled red blood cell scintigraphy was used in the investigation of 15 adult patients with suspected small or large bowel bleeding requiring at least five units of blood (mean 14.3 units) and one neonate with rectal bleeding. Scintigraphy was found to be an accurate method of detecting the site of haemorrhage and was superior to angiography. This technique may be of particular value in patients with profuse colonic haemorrhage when the view at colonoscopy is poor.