Emotion regulation: quantitative meta-analysis of functional activation and deactivation.

Emotion regulation is hypothesized to be a multifaceted process by which individuals willfully modulate the intensity and direction of emotional response via prefrontally mediated inhibition of subcortical response-related regions of the brain. Here we employ activation likelihood estimation (ALE) meta-analysis of functional magnetic resonance imaging studies to (1) reveal a consistent network of structures active during emotion regulation, (2) identify the target regions inactivated by the willful regulation process, and (3) investigate the consistency of activated structures associated with downregulation and upregulation. Results reveal signal change in bilateral amygdala/parahippocampal gyrus that decreased in downregulated states and increased in upregulated states, while cortical regions including superior frontal gyrus, cingulate, and premotor areas exhibited enhanced activity across all regulation conditions. These results provide consistent evidence for the role of amygdala activity in experienced emotional intensity, where intentional dampening and exaggeration are clearly expressed. However, the execution of emotional upregulation and downregulation may involve distinct subsets of frontocortical structures.

The accuracy of "one-stop" diagnosis for 1,110 patients presenting to a symptomatic breast clinic.

UNLABELLED: To minimise delay in diagnosis and reduce patient anxiety, triple assessment with immediate reporting has been used in our symptomatic breast clinic since 1991. This article examines the accuracy of the diagnostic modalities used and the efficacy of the "one-stop" diagnostic policy. The data on 1,110 new patients presenting to the symptomatic breast clinic between January and July 1993, were analysed and subsequent three year follow-up and outcome established. Fine needle aspiration cytology (FNAC) gave the highest predictive value (97.3%) with a sensitivity of 93.5% and a specificity of 98.1%. Ultrasonography provided a 97.0% prediction with a sensitivity of 88.9% and a specificity of 97.4%, whereas mammography had a prediction of 96.4% with sensitivity of 93.2% and a specificity of 96.7%. When the mammogram or ultrasound scan were reported as unequivocally benign (M1), there were no missed cancers. The false positive and false negative rates for FNAC were 0% and 1.4%, respectively. Following assessment, a diagnosis was made in 96% of patients. Sixty-two percent of the patients were discharged at the first clinic visit. Four breast malignancies were subsequently diagnosed in the discharged group; two with new microcalcifications due to ductal carcinoma in situ, one with invasive disease in a different quadrant of the breast from that originally investigated, and in one patient the cancer was missed. CONCLUSION: A "one-stop" symptomatic breast clinic provides an accurate and effective means of establishing a correct diagnosis.

Pyoderma faciale in a patient with Crohn's disease.

We wish to report the progress of a patient with pyoderma faciale and Crohn's disease. The patient is interesting in that on two occasions the relapse in her skin condition coincided with the introduction of non-steroidal anti-inflammatory drugs. Therapy with isotretinoin was effective and well tolerated.

Skin lesion removal: practice by general practitioners in Grampian Region before and after April 1990.

The introduction of new GP contracts in April 1990 incorporated a financial incentive to undertake minor surgical procedures. Previous reports have noted large increases in the number of GP-derived skin specimens after April 1990. Our present study intended to address whether similar changes have occurred in Grampian Region as well as, more specifically, noting whether there have been changes in the quality of practice following the 1st April 1990. A retrospective study of skin biopsies removed by general practitioners in Grampian Region was undertaken. Cases were selected from four periods of six months (1st April to end of September) in 1987, 1988, 1989 and 1990. All skin specimens sent by general practitioners to the Department of Pathology, Aberdeen Royal Infirmary, were included. Following April 1990 there was a two-fold increase in skin specimen numbers--an increase significantly greater than increases observed over previous years (p < 0.01). Of particular note was the contribution made to this increase by Aberdeen City GPs whose contribution rose five-fold (p < 0.0001). Non-benign lesions (ie malignant plus carcinoma-in-situ-) represented 6% of lesions excised. A non-benign clinical diagnosis or an indication of suspicion was written on only one third of request forms for histopathologically diagnosed non-benign lesions. The proportion of histologically incompletely excised lesions rose over the four years (p < 0.01); moreover the increase in total numbers of lesions resulted in a striking increase in the actual numbers of incompletely excised lesions after April 1990.

Imaging of neonatal pulmonary sequestration including Doppler ultrasound.

Seven cases of neonatal pulmonary sequestration are reviewed which illustrate the varied clinical presentations and radiological findings. In four patients, real time ultrasound scanning was used to image the chest and the features are described. In three cases, the systemic supplying artery was demonstrated by duplex Doppler scanning and further invasive investigations were avoided; after a chest radiograph, this should be the examination of choice in the investigation of a neonate with a possible pulmonary sequestration.

Alleviation of experimental cyclosporin A toxicity by substitution of fish muscle oil as drug vehicle.

The toxicity of cyclosporin A (CsA) formulated in either olive oil (OO) or fish muscle oil (FO) was investigated in groups of normal Sprague-Dawley rats or in animals which had undergone laparotomy or unilateral nephrectomy. CsA (25 mg/kg/day for 14 days) was administered by gavage from the time of operation, and indices of renal and hepatic function were determined at regular intervals. Urinary thromboxane B2 (TxB2) excretion and whole blood CsA concentrations were determined on day 14, when renal histology was also examined. Compared to CsA/OO treatment, and observed only in normal animals, body weight was significantly increased following administration of CsA/FO, to values similar to those observed following treatment with FO alone. Although there was evidence of renal dysfunction in all CsA-treated animals, irrespective of drug vehicle, elevations in plasma urea and urinary N-acetyl-beta-D-glucosaminidase activity were significantly more pronounced in rats given CsA/OO compared with CsA/FO. Indeed, compared with pretreatment values, no significant changes in these parameters were observed in CsA/FO-treated nephrectomized animals. Whilst there were no great differences in plasma creatinine or creatinine clearance rates between CsA/OO- and CsA/FO-treated groups, animals given CsA/FO showed less evidence of renal structural change as assessed by proximal tubular cell vacuolation, basophilia and microcalcification. The extent of hepatic impairment was also significantly less pronounced when FO was used as drug vehicle. Groups of CsA/FO-treated animals also demonstrated significantly lower whole blood CsA levels compared with CsA/OO groups; moreover, TxB2 excretion was significantly lower in the former group.(ABSTRACT TRUNCATED AT 250 WORDS)

The potential of cyclosporin A as an anti-tumour agent.

Cyclosporin A (CsA) has become established as the agent of choice for the prevention of organ allograft rejection and has shown considerable promise in the clinical management of certain autoimmune disorders. The impact of CsA as an immunotherapeutic agent of major importance is attributable to its powerful, selective inhibitory action on T-lymphocyte activation and proliferation. Moreover, CsA lacks the myelotoxic and other major side effects associated with cytotoxic immunosuppressive agents, such as cyclophosphamide or azathioprine. It is now clear that CsA has a potential therapeutic role in the treatment of malignancies, especially T-cell cancers. Recent studies suggest that there may be several areas of application for CsA, either as a direct antiproliferative agent or in combination with other drugs, including inhibitors of polyamine biosynthesis or cytotoxic anti-tumour agents, including vincristine and adriamycin. In addition, CsA and non-immunosuppressive analogues have been shown to restore multi-drug sensitivity in cancer cells with acquired drug resistance. A further application of CsA may be to prevent the induction of human immune responses to therapeutic mouse monoclonal antibodies directed against tumour antigens, thereby enhancing the efficiency and safety of this form of cancer immunotherapy. Due to our incomplete understanding of the antiproliferative properties of CsA, further exploration of its potential as an anti-tumour agent must be accompanied by detailed studies aimed at elucidating its action on subcellular molecular events in both normal and malignant cells.

Influence of cyclosporin A and alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, on two rodent T-cell cancers in vivo.

We have examined the influence of cyclosporin A (CsA), administered together with the polyamine antimetabolite, alpha-difluoromethylornithine (DFMO), on growth of the Roser acute T-cell leukaemia in PVG rats and on growth of the EL4 lymphoma in C57BL/6 mice. CsA or DFMO alone, administered from the time of tumour injection, markedly reduced numbers of circulating lymphoblasts in leukaemic rats, although survival was prolonged only in those animals given DFMO. Drug combination further reduced blood-borne tumour cells, but had no additional effects on tumour growth within organs or on host survival, compared to that achieved with DFMO treatment alone. Neither CsA nor DFMO, administered from the time of tumour-cell injection, nor both drugs in combination, affected peritoneal growth of the EL4 lymphoma or organ infiltration. Host survival was prolonged by DFMO. As anticipated, DFMO inhibited polyamine synthesis in vivo, but the observed anti-tumour effect of CsA was not accompanied by an alteration in polyamine biosynthesis. By reducing polyamine synthesis, however, DFMO may enhance the vulnerability of those malignant T cells which are susceptible to the as yet unexplained selective inhibitory action of CsA in vivo.

Influence of cyclosporin A on growth of an acute T-cell leukaemia in PVG rats.

Our objective was to examine the effect of cyclosporin A (CsA; 25 or 12.5 mg/kg) on growth of an acute (Roser) T-cell leukaemia in male PVG rats. The leukaemic blasts were shown (by immunocytochemical analysis) to have a mature, T-helper-cell phenotype, i.e., OX-19 (CD5) +/- , W3/25 (CD4)+, OX44+, MHC-class I+, OX-26+, corresponding to a population comprising 5% of normal rat medullary thymocytes. Animals received 20 X 10(3) viable tumour cells intramuscularly (day 0) and were given either CsA (25 or 12.5 mg/kg) or drug vehicle by gavage from day 0 or day 14, by which latter time leukaemic blasts normally appeared in the circulation. Administration of the higher dose of CsA from day 0 or day 14 significantly delayed the appearance of leukaemic cells in the peripheral circulation, whereas treatment with 12.5 mg/kg was without significant effect. CsA whole blood levels on day 17 were twice as high in leukaemic rats as in normal controls. Leukaemic infiltration of the spleen and the liver was reduced on day 17 after 25 mg/kg CsA, but no such effect was observed in lymph nodes or kidneys. A heterogeneous, host "reactive" cell population, which developed in response to the leukaemia, was inhibited by CsA, indicating that the effect of the drug was probably not mediated by host defence mechanisms. In CsA-treated leukaemic animals, there was biochemical evidence of synergistic impairment of glomerular and tubular function.

Comparison of fructosamine with glycosylated hemoglobin and plasma proteins as measures of glycemic control.

The relative value of fructosamine as an alternative to glycosylated hemoglobin (HbA1) and other measures of glycemic control was assessed in 100 insulin-dependent (IDDM) and 104 non-insulin-dependent (NIDDM) diabetic patients. We measured HbA1 (by electrophoretic and affinity methods), plasma glucose, glycosylated plasma proteins, and fructosamine in blood taken at a single clinic visit. The values were compared both by correlation analysis and by considering whether the various indices of glycemic control placed the patients in the same clinical decision categories as they were in by the HbA1 (affinity) result. Fructosamine correlated moderately well with HbA1 (affinity; r = .8) and placed 71% of IDDM and 72% of NIDDM patients in the same clinical category of good, moderate, or poor control. Differences can probably be partly attributed to the different periods over which HbA1 and fructosamine reflect average glycemia and partly to imprecision.

Antibody coating and quantitative cultures of bacteria in sputum and bronchial brush specimens from patients with stable chronic bronchitis.

Antibody coating of bacterial isolates has been proposed as a method of identifying bacteria responsible for chronic lower respiratory infections. This study was designed to determine the specificity of antibody coating by examining bronchial secretions obtained from a group of patients with chronic bronchitis who had no clinical evidence of acute infection. Routine and quantitative bacterial cultures were performed at the same time. The bronchial brush specimens contained potentially pathogenic bacteria in all 18 patients examined, and 17 of these 18 specimens had antibody coating of bacteria. Quantitative cultures yielded greater than 10(4) colony forming units in only one patient and he subsequently developed a lower respiratory tract infection. We conclude that in patients with chronic bronchitis, the determination of antibody coating of bacterial isolates does not significantly increase the specificity of routine culture. Quantitative cultures of specimens obtained via the protected brush catheter are useful in identifying potential pathogens.

Diagnosis and prognosis of right ventricular infarction.

The values of several non-invasive methods for the diagnosis of right ventricular necrosis in inferior myocardial infarction were compared in 51 consecutive patients who underwent serial radionuclide ventriculography, pyrophosphate scintigraphy, and cross sectional echocardiography. In addition a unipolar electrocardiographic lead V4R was recorded on admission, daily, and during episodes of further pain. Profound right ventricular dysfunction was evident in 50% of patients studied by radionuclide methods after inferior myocardial infarction but recognition on clinical groups alone was poor. Functionally important right ventricular infarction was best detected and followed serially by radionuclide ventriculography. Echocardiographic methods for evaluating right ventricular ejection fraction correlated poorly with radionuclide methods. Increased uptake of radioactivity by the right ventricle on pyrophosphate scintigraphy usually indicated poor right ventricular function, but a scan that was negative in the right ventricular territory did not exclude dysfunction. ST segment elevation in V4R was not specific for right ventricular infarction and its routine use may lead to overdiagnosis of this condition. Serial measurements suggest that profound right ventricular dysfunction persists after acute inferior infarction and is associated with considerable morbidity and mortality. Of 25 patients with severe right ventricular dysfunction, six died in the late hospital period. In the remaining 19 patients mean right ventricular ejection fraction over a two month period did not improve; six patients had persistent right ventricular dyskinesia and features of chronic right ventricular failure developed in three survivors.