Visual mismatch negativity: the detection of stimulus change

Mismatch negativity is an event related potential generated by a mechanism which detects stimulus change. Such a mechanism is important to enable attention to be switched to important changes in the environment. The effect has been extensively studied in the auditory modality. The present investigation was designed to establish whether the enhanced negativity in the visual event related potential evoked by deviant stimuli presented infrequently among a sequence of repeated standard stimuli is really associated with the detection of stimulus change. The experiment set out to distinguish effects associated with stimulus change from those related to the physical attributes of the stimuli or to differences in the refractory state of receptors or neurons. The findings support the hypothesis that deviance-related negativity reflects the operation of a change detection mechanism and not the refractory state of elements of the visual system.     

Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

Background

We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints.

Methods

From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125).

Results

The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9–12.8 months).

Conclusion

The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centres.     

Impalpable testis cancer

OBJECTIVE: To assess the significance of ultrasonographically detected hypoechoic lesions of the testis when the clinical examination is normal, and to highlight the management difficulties thereafter. PATIENTS AND METHODS: Over a 2-year period four patients underwent radical orchidectomy where the sole indication for surgery was a hypoechoic lesion detected on ultrasonography (US). The indications for US were persistent scrotal discomfort in two men, contralateral orchitis, and the follow-up of testicular microlithiasis. The lesions were 4-11 mm in size and one man had several. None of the lesions were palpable; the tumour markers were normal in all patients. RESULTS: Three of the testes contained seminoma; in one there were two foci of seminoma and in all intratubular germ cell neoplasia was also identified. The remaining case was a Leydig-cell tumour. All tumours were staged as pT1 after radical inguinal orchidectomy. CONCLUSION: Impalpable lesions of the testis are likely to be malignant if they are hypoechoic on US and should be considered as seminoma until proved otherwise. The management thereafter is not straightforward, but must ensure an adequate histological diagnosis if the US appearances do not resolve.     

A prospective evaluation of detrusor ultrastructural changes in bladder outlet obstruction

OBJECTIVES: To characterize the ultrastructure of detrusor smooth muscle from the bladders of symptomatic men with bladder outlet obstruction (BOO) caused by benign prostatic enlargement (BPE) and compare this with a matched control group; to determine how detrusor morphology relates to urodynamic findings and to develop a better understanding of the natural development of bladder dysfunction related to BOO. PATIENTS AND METHODS: Twelve men (mean age 66 years, range 52-77) with urodynamically confirmed BOO caused by BPE and 12 age-matched asymptomatic normally voiding controls (mean age 67.8 years, undergoing cystoscopy for other conditions) had detrusor biopsies taken endoscopically. The biopsies were processed for electron microscopy using standard methods. The specimens were randomized and examined at medium power (x 4000) by an examiner unaware of the urodynamic findings. Any ultrastructural patterns identified subjectively were noted. RESULTS: In the BOO group eight of the 12 men had a myohypertrophic pattern, half of which were associated with a degenerative pattern of hypocontractility. Of the remaining four patients, two had the degenerative pattern alone and two were normal. The six men whose biopsies had a degenerative pattern had consistent postvoid residual volumes of > 150 mL; the remainder all had volumes of < 150 mL. There were no ultrastructural abnormalities in the control patients. CONCLUSIONS: There are interesting qualitative ultrastructural changes in the obstructed detrusor, but they are not consistent enough to provide a reliable diagnostic tool. However, there may be an important relationship between the degenerative pattern and postvoid residual volume in BOO.     

Acid phosphatase activity in mononuclear phagocytes and the U937 cell line: monocyte-derived macrophages express tartrate-resistant acid phosphatase

Tartrate-resistant acid phosphatase (TRAcP) is used as a marker for osteoclasts, which are believed to be derived from phagocytic cells or phagocyte stem cell precursors. To further investigate the relationship between monocytic phagocytes and osteoclasts, acid phosphatase (AcP) activity was measured by three different techniques in human peripheral blood monocytes, monocyte-derived macrophages, and the U937 cell line. We found that cytochemistry and gel electrophoresis led to similar results, but that the colorimetric assay was inconsistent. Normal human peripheral monocytes expressed both tartrate-sensitive and -resistant AcP. In culture these cells formed polykaryons and expressed TRAcP activity that was further identified as an isoenzyme associated with bone tissue. In contrast, the U937 cells did not express TRAcP activity as measured by gel electrophoresis. Both U937 cells and monocytes possess material that interferes with interpretation of the colorimetric assay of AcP. The presence of TRAcP in monocyte-derived macrophages further supports the relationship between phagocytic cells and bone osteoclasts.     

Congenital abnormalities of the aortic arch: MR imaging

Thirty-four patients, 1 month to 63 years old, with known or suspected congenital abnormalities of the aortic arch underwent magnetic resonance (MR) imaging. Sixteen patients were studied retrospectively, 18 prospectively. In all retrospective studies, the aortic arch abnormality was seen with MR imaging. In the prospective studies, MR imaging enabled diagnosis in 15 of 18 (83%) patients. Twenty-nine of 34 patients underwent two-dimensional echocardiography; nine were studied retrospectively, 20 prospectively. In the prospective studies, echocardiography enabled diagnosis in 13 of 20 (65%) patients. Although two-dimensional echocardiography has a high sensitivity in the detection of aortic arch abnormalities in the neonate, arch abnormalities in the neonate, its sensitivity is lower in older children, adults, and postoperative patients. The authors' experience shows that MR imaging is an important, noninvasive modality in the evaluation of older children, adults, and postoperative patients with congenital aortic arch abnormalities.     

Digital imaging of the chest

During the past several years, image acquisition in nuclear medicine, computed tomography, ultrasonography, subtraction angiography, and magnetic resonance has been by digitization. Despite these advances, research in the development of digital imaging in conventional radiography has lagged behind. Although studies with a variety of digital techniques have been carried out on several fronts, we still do not possess a method that has captured the imagination of the majority of radiologists and other physicians to a point where it could replace conventional screen-film imaging. This article reviews the current status and general principles of the technology, focusing on the four digital radiographic techniques that have shown the greatest promise - film digitization, an image intensifier - based system, photostimulable phosphor plates, and a scanned projection system. The physical aspects of each of the four systems and the clinical results that have been reported to date, as well as the advantages and disadvantages of each system, are presented.     

The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy

BACKGROUND: The administration of blood components from donors who subsequently develop Creutzfeldt-Jakob disease has raised the issue of blood as a possible vehicle for iatrogenic disease. STUDY DESIGN AND METHODS: We examined infectivity in blood components and Cohn plasma fractions in normal human blood that had been "spiked" with trypsinized cells from a scrapie-infected hamster brain, and in blood of clinically ill mice that had been inoculated with a mouse-adapted strain of human transmissible spongiform encephalopathy. Infectivity was assayed by intracerebral inoculation of the blood specimens into healthy animals. RESULTS: Most of the infectivity in spiked human blood was associated with cellular blood components; the smaller amount present in plasma, when fractionated, was found mainly in cryoprecipitate (the source of factor VIII) and fraction I+II+III (the source of fibrinogen and immunoglobulin); almost none was recovered in fraction IV (the source of vitamin-K-dependent proteins) and fraction V (the source of albumin). Mice infected with the human strain of spongiform encephalopathy had very low levels of endogenous infectivity in buffy coat, plasma, cryoprecipitate, and fraction I+II+III, and no detectable infectivity in fractions IV or V. CONCLUSION: Convergent results from exogenous spiking and endogenous infectivity experiments, in which decreasing levels of infectivity occurred in cellular blood components, plasma, and plasma fractions, suggest a potential but minimal risk of acquiring Creutzfeldt-Jakob disease from the administration of human plasma protein concentrates.