Analysis of quantum coherent semiconductor quantum dot p-i-n junction photovoltaic cells.

A recent hypothesis [M. O. Scully, Phys. Rev. Lett. 104, 207701 (2010).] indicates that the power conversion efficiency of a semiconducting p-i-n junction photovoltaic cell with an intrinsic region consisting of quantum dots can be increased by using quantum coherence to break detailed balance. The limitations of this hypothesis are shown here.

Centrifugation of normal and rheumatoid arthritis blood on Ficoll-Hypaque and Ficoll-Nycodenz solutions.

Attempts to use the rapid single-step Ficoll-Hypaque centrifugation procedure for the purification of mononuclear and polymorphonuclear leucocytes from the blood of normal individuals and rheumatoid arthritis patients have sometimes been unsuccessful, largely because the erythrocytes would not sediment through the centrifugation medium. Re-evaluation of the factors (e.g. Ficoll concentration, temperature, and ratio of the diatrizoate salts) which affect these separations showed that under our conditions it was advantageous to use a medium with a lower viscosity (Ficoll concentration) and/or a higher osmotic strength (increased sodium diatrizoate: meglumine diatrizoate) than had been recommended previously (Ferrante and Thong, 1978; 1980; Ferrante et al., 1982). Higher osmotic strength media must be used for separating the components of blood from rheumatoid arthritis patients than from normal individuals because rheumatoid arthritis erythrocytes have a lower buoyant density than normal erythrocytes.

Endoscopic sphincterotomy for bile duct stones.

This paper reports the results of endoscopic sphincterotomy for bile duct stones in 50 patients. A design for a spincterotomy handle and a suitable stainless steel diathermy wire are described. Sphincterotomy was achieved in 45 patients (90%) and complete stone clearance in 42 (84%); this usually required two endoscopic examinations. Complications occurred in nine patients. Haemorrhage and pancreatitis were the most serious resulting in one laparotomy (haemorrhage) and one death (pancreatitis). Periampullary diverticula in 11 patients (22%) did not influence the success rate or the frequency of complications. A "pre-cut" in 11 patients (22%) permitted a later successful sphincterotomy in eight. Stone size (up to 3.5 cm) did not appear to influence outcome, but complete stone clearance was only achieved in two out of eight with more than ten bile duct calculi. Symptoms have not recurred up to three years after sphincterotomy. The data indicate that endoscopic sphincterotomy is of major value in high-risk patients with bile duct calculi and is also appropriate for most low-risk patients with retained stones after cholecystectomy.

A distinctive pattern of serum bile acid and bilirubin concentrations in benign recurrent intrahepatic cholestasis.

The pattern of serial serum bile acid and bilirubin concentrations in 3 patients with benign recurrent intrahepatic cholestasis (BRIC) was compared with those from patients with other liver diseases. In BRIC the peak bile acid concentration (260- 575 micromol/l was found at the onset of the cholestasis. The bilirubin concentration increased slowly so that maximum values (185-550 micromol/l) were attained between 33 and 51 days after the onset of symptoms. Both the serum bile acid and bilirubin concentrations returned to normal after 79 to 98 days. Percutaneous biliary drainage of extrahepatic biliary obstruction (3) caused a dramatic reduction in the serum bile acid level (mean 89% after 48 hours), but only a slight fall in serum bilirubin (mean 22%). In primary biliary cirrhosis (2) the bile acid and bilirubin concentrations changed in parallel until the onset of liver failure when serum bilirubin, but not bile acids, increased markedly. Serum bile acid and bilirubin concentrations changed in parallel throughout cholestatic viral hepatitis (2), chronic active hepatitis (2) and alcoholic hepatitis (1). The data indicates that a distinctive pattern is found in BRIC and this may be of diagnostic value.

Incidence and significance of juxtapapillary diverticula at endoscopic retrograde cholangiopancreatography.

In a retrospective study of 755 atients undergoing endoscopic retrograde cholangiopancreatography from 1973 to 1977 at the Royal Free Hospital, 38 (5%) had a juxtapapillary diverticulum. This resulted in a significantly higher failure rate of cannulation of the ampulla of Vater (40 vs. 20% in the remainder of the group; p less than 0.02). The presence of a juxtapapillary diverticulum was also significantly associated with an increase of cholelithiasis (48 vs. 24%; p less than 0.01), and with jaundice or cholangitis developing after cholecystectomy (27 vs. 8%; p less than 0.001). There was no evidence that the diverticula were the cause of biliary or pancreatic obstruction.

Cervical myelopathy complicating multiple joint replacement in rheumatoid disease.

The incidence of cervical myelopathy and subluxation was investigated in 48 patients with rheumatoid disease who had three or more major lower limb joint replacements. Eight (17%) developed cervical myelopathy requiring cervical fusion. This was the subsequent cause of death in two. Four further patients demonstrated clinical features of myelopathy. Cervical subluxation was present in 29 of 44 (66%) in whom adequate radiographs were available. The development of cervical symptoms and signs could not have been predicted from the sex, age of onset, duration of disease or steroid therapy. Radiographic changes in the cervical spine were independent of major lower limb joint destruction and were often not present when planning a programme of joint replacement. Fifty-one control patients were studied. Cervical myelopathy occurred in 2 (4%) and subluxation in 24 (47%). The development of rheumatoid changes in the cervical spine was unrelated to involvement of the hip or knee joints in the control group. There was a significant (p less than 0.05) increase in the incidence of cervical myelopathy in patients with multiple lower limb joint replacements compared with the control population.

Peptic ulceration in patients with chronic liver disease.

A prospective study was undertaken to determine the frequency of peptic ulceration in different forms of chronic liver disease and the effect of corticosteroid treatment. One hundred sixty-three patients with chronic liver disease underwent upper gastrointestinal endoscopy, 106 for investigation of dyspeptic symptoms and the remaining 57 for assessment of the presence of varices. Twenty-four peptic ulcers were found (14.7%), 12 duodenal, 8 gastric, and 4 prepyloric. Ulcers were found in 5 of 15 patients with hepatitis B surface-antigen-positive chronic active liver disease (33%), 10 of 46 patients with alcoholic liver disease (22%), 5 of 35 with primary biliary cirrhosis (14%), 2 of 19 with miscellaneous chronic liver diseases (10%), and 2 of 25 with cryptogenic cirrhosis (8%). Ulcers were not demonstrated in any of the 23 patients with hepatitis B surface-antigen-negative chronic active hepatitis. Thirty-one patients were receiving prednisolone therapy, 5 had peptic ulcer compared with 19 of the remaining 132 patients. This difference was not significant. Fifty-nine patients presented with gastrointestinal bleeding on 88 separate occasions. Peptic ulcer was the cause in 6% of these. In chronic liver disease peptic ulcers occurred with differing frequencies in different forms of the disease. This was unaffected by corticosteroid therapy. Peptic ulcers were rarely the cause of gastrointestinal bleeding.

Rate and pattern of epithelial cell proliferation in ulcerative colitis.

We investigated the pattern of proliferation of epithelial cells in rectal mucosa taken from normal individuals and patients with ulcerative colitis by incubating mucosa with tritiated thymidine in vitro and processing for autoradiography. We found that patients with ulcerative colitis in remission showed a proliferative pattern similar to that seen in both regenerating and "precancerous' mucosa. Patients with a short history were as likely to show this pattern as those with a long history, and this shows that the abnormal pattern does not signify impending malignant change. We also found that mucosa from patients with ulcerative colitis in remission showed an increased proportion of cells synthesising DNA, a proportion surprisingly close to that seen in an active phase; this suggests that the abnormal pattern seen in remission is the pattern of a regenerating mucosa. We feel that this high rate of mucosal turnover, sustained not just during clinically active disease but throughout remission, leads to the increased incidence of carcinoma and to the development of carcinoma in flat mucosa.

Controlled trial of azathioprine in chronic ulcerative colitis.

A double-blind controlled trial of azathioprine in a dose of 2-2.5 mg/kg body weight over six months was conducted among 44 patients with active chronic ulcerative colitis. Three patients treated with placebo did not complete the trial because their disease became so severe that colectomy was performed. Among patients who completed the trial the mean dose of prednisolone necessary to control the disease decreased in those treated with azathioprine and those treated with placebo; the reduction was greater among those who took azathioprine (p less than 0.001). Activity of the disease apparently improved in both treatment groups but a significant (p less than 0.001) trend was observed only in those patients treated with azathioprine. No serious side effects from azathioprine occurred during the trial but seven of 24 patients had to stop the drug because of nausea. Azathioprine may have a role in the treatment of a few patients wih troublesome chronic colitis for whom conventional drug treatment is ineffectual, or for whom continuous systemic corticosteroid treatment is needed to control symptoms, and for whom surgical treatment is inappropriate.

An epidemic of type B viral hepatitis: its course and outcome.

Between June and August, 1977 there was a small epidemic of type B viral hepatitis in a market town in South-East England during which 4 people developed acute hepatitis. Their close friends and contacts were all negative for hepatitis B surface antigen (HBsAg) at this time. One year later, in July 1978, 3 of the original 4 patients were available for follow-up. All were HBsAg negative but hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc) positive. Two had disturbed liver function tests and chronic persistent hepatitis on liver biopsy. Also at this time 2 of the original contacts were found to show evidence, from the serum markers, of previous infection by the type B virus. Both had abnormal liver function tests and showed chronic persistent or chronic active hepatitis on liver biopsy. A further subject was identified who had had an overt hepatitis 1 year previously and who also showed evidence of continuing liver disease. The origin of the epidemic and its spread through the group were identified. The varying modes of transmission, and the variation in clinical picture and sequelae are discussed. The importance of anti-HBc as a marker of hepatitis B virus infection is emphasised.

Late results of the Royal Free Hospital prospective controlled trial of prednisolone therapy in hepatitis B surface antigen negative chronic active hepatitis.

A long-term follow-up of at least 10 years or until death of 44 patients taking part in a controlled prospective trial of prednisolone therapy in hepatitis B antigen negative chronic active hepatitis (lupoid hepatitis) has been performed at the Royal Free Hospital, London. Patients presenting between 1963 and 1967 were randomly allocated into control and treatment groups. Ten year life table survival curves showed a significantly improved survival in the treatment group where 63% of patients were alive at 10 years compared with only 27% in the control group (log rank test, P = 0.03). The median survival in the treatment group was 12.2 years compared with 3.3 years in the control group. The mean duration of treatment was 4.5 years. Age, presence of antinuclear factor, cirrhosis, or level of serum transaminases at presentation did not appear to affect survival. Male patients if untreated had a poorer prognosis than females (P = 0.02). The natural history of chronic active hepatitis appeared from clinical, biochemical, and histological findings to be from an active hepatitis or cirrhosis to inactive macronodular cirrhosis. Prednisolone therapy significantly improved survival by reducing mortality in the early active phase of the disease.

Enhanced chemotaxis of monocytes in rheumatoid arthritis.

The migration responsiveness to zymosan-activated serum of monocytes isolated from the blood of 19 rheumatoid arthritis (RA) patients and 19 healthy subjects was measured. The chemotaxis of RA monocytes, but not their random migration or chemokinesis, was significantly greater than that of monocytes from normal healthy subjects. To investigate whether this effect were due to soluble factors present in RA blood, the migration of monocytes from healthy subjects was assessed in the presence of sera from 28 RA patients and 21 healthy subjects. The inability of RA sera to modify the migration of normal monocytes implies that the enhanced chemotaxis of RA monocytes is attributable to the inherent property of these cells and not due to the activity of serum modifying factors.

Scanning electron microscopy of rheumatoid arthritis peripheral blood polymorphonuclear leucocytes.

Peripheral blood polymorphonuclear leucocytes (PMNs) were isolated from six normal individuals and from 27 patients with rheumatoid arthritis (RA) by the Ficoll-Hypaque rapid single step centrifugation technique, fixed in suspension, and examined by scanning electron microscopy (SEM). In addition, four of the preparations from normal individuals and eight from patients with RA were examined by transmission electron microscopy (TEM). Most PMNs in preparations from normal subjects were spherical, unpolarised, and had their surface membrane elaborated into irregular ridges and small ruffles; they contained few phagocytic vacuoles and large numbers of electron dense primary and secondary granules. A minority of the cells were non-spherical, polarised, and had portions of their surface membrane elaborated into ruffled pseudopodia. In contrast, preparations of RA PMNs frequently contained fewer unpolarised PMNs and a higher number of polarised PMNs than did preparations of normal PMNs. Some preparations of RA PMNs also contained substantial numbers of spherical cells whose surface was covered mainly by bulges and blebs. Concurrent examination by TEM showed that RA PMNs frequently contained more phagocytic vacuoles and fewer electron dense primary and secondary granules than normal PMNs. The morphological and ultrastructural changes seen in RA PMNs resembled those which normal PMNs are known to undergo on exposure to C5a in vitro, during adherence to endothelial cells in vivo, or during phagocytosis in vivo or in vitro. Our observations, therefore, provide a useful morphological correlation to those in vitro studies in which differences in the functional activity of RA and normal PMNs have been shown. The possibility that the difference seen between RA and normal PMNs is artefactual and does not represent the genuine in vivo states of these cells is discussed.

Changes in normal polymorphonuclear leucocyte motility after ingestion of IgG aggregates.

Changes in normal polymorphonuclear leucocyte (PMN) motility after membrane-binding and internalisation of IgG aggregates (a model of soluble immune complexes) have been studied by the micropore filter assay. The results have confirmed that IgG aggregates stimulate as well as inhibit PMN chemotaxis. These effects are dependent on the size and concentration of the IgG aggregates in solution as well as the length of time of incubation. Stimulated chemotaxis was observed in a small subset of the whole PMN population which was apparent only when cell distribution through the filters was analysed. These results indicate the need for caution when drawing conclusions about PMN function from results obtained by these assay techniques.

Impaired polymorphonuclear leucocyte chemotaxis in rheumatoid arthritis.

This study has investigated the chemotactic activity of polymorphonuclear cells (PMNs) isolated from the blood of patients with either articular rheumatoid arthritis (RA) or RA with extra-articular manifestations. A double fluorochrome immunofluorescent staining test has been employed to identify cell-associated immunoglobulins, probably immune complexes. The results suggest an inverse relationship between PMN chemotaxis and staining for cell-associated immunoglobulins, either surface bound or internalised. PMNs from RA patients showed reduced chemotaxis, and this was further reduced when RA PMNs were incubated for 30 minutes in autologous serum. A similar reduction in chemotaxis of normal PMNs occurred after incubation in RA sera. Preincubation of both RA and normal PMNs in RA serum (but not normal serum) resulted in an increase in the number of cells in which cell-associated immunoglobulins were demonstrable. This further reduction in RA PMN chemotaxis after exposure to autologous serum, together with an increase in immunoglobulin staining, may indicate selection of certain PMNs at the time of venepuncture due to cell margination. Such a selection process would call for a re-evaluation of previous studies of RA PMN function in relation to the disease process.

Immunoglobulin inclusions in rheumatoid arthritis polymorphonuclear cells: lack of correlation with circulating immune complexes.

A discriminating direct immunofluorescent test has been used to identify immunoglobulin inclusions in polymorphonuclear leucocytes (PMNs) isolated from the blood of patients with rheumatoid arthritis. These inclusions are thought to represent phagocytosed immune complexes, since normal PMNs incubated in RA sera known to contain raised levels of immune complexes developed similar immunoglobulin inclusions. Inclusions did not develop in normal PMNs incubated in normal serum. No correlation was found between the percentage of either RA blood PMNs with immunoglobulin inclusions or normal PMNs developing inclusions after incubation in RA sera, and levels of immune complexes in the corresponding sera. Using heat-aggregated IgG as a laboratory model of immune complexes, a simple relationship has been demonstrated between the uptake of IgG aggregates by normal PMNs and the concentrations of IgG aggregates in the test solutions over a concentration range of 12.5-200 micrograms . ml-1. These results indicate that the C1q- PEG test gives no measure of the actual amounts of immune complexes available in serum for phagocytosis.

Rheumatoid blood decreases the adherence of polymorphonuclear cells (PMNs) to cultured endothelium.

Rheumatoid sera and plasma inhibited the adherence of normal blood polymorphonuclear cells (PMNs) to cultured porcine endothelium. This inhibition of adhesion was not seen when PMNs were treated with the plasma or serum from normal subjects or patients with other inflammatory arthropathies. The abrogation of PMN adherence was directly related to the levels of circulating immune complexes and was not dependent upon the type of anti-inflammatory therapy that the patients were receiving nor on any of the recorded clinical parameters. A similar inhibition of adhesion was seen with heat induced aggregated human IgG (HAGG) provided that serum was present in the culture medium. In view of these results we propose that circulating immune complexes in RA may have a significant role in controlling the interaction of PMNs with vascular endothelium and in perpetuating the entry of these cells into the synovial fluid of the inflamed joints.

A tannic acid based preparation procedure which enables leucocytes to be examined subsequently by either SEM or TEM.

A modification of the glutaraldehyde-osmium tetroxide-tannic acid-uranyl acetate (GOTU) fixation procedure is described which allows human leucocytes to be examined subsequently by either transmission electron microscopy (TEM) or scanning electron microscopy (SEM).

Pepsinogen--an immunoglobulin binding artefact in 'collagen' preparations.

It has previously been shown that extracts of human articular cartilage, many many of which contain type II collagen, react with heat-aggregated immunoglobulin and artificially prepared immune complexes. Sera from patients with rheumatoid arthritis and psoriatic arthritis, but not from patients with inflammatory bowel disease, react with these extracts. There are two distinct patterns of binding, either as low molecular weight immune complexes or as free antibody directed against collagen. Aggregate-binding activity identified in extracts of human articular cartilage following pepsin digestion was found to be distinct from collagen in its salt solubility. Further purification of this aggregate-binding factor by SDS gel electrophoresis has shown it to be an artefact resulting from the binding of small immune complexes to pepsinogen present in the pepsin preparation used to digest the cartilage.

Polymorphonuclear leukocyte function in ulcerative colitis and Crohn's disease.

The aim of this study was to determine whether polymorphonuclear leukocyte chemotaxis, adhesion, and electrophoretic mobility were altered in inflammatory bowel disease and whether such alterations could be related to prior ingestion of immune complexes. Polymorphonuclear leukocytes from patients with ulcerative colitis and Crohn's disease showed significantly impaired stimulated migration (P less than 0.05), increased adhesiveness (P less than 0.01 in ulcerative colitis, P less than 0.001 in Crohn's disease), and reduced electrophoretic mobility (P less than 0.02 in ulcerative colitis, P less than 0.001 in Crohn's disease) compared with healthy controls. The disease control of patients with rheumatoid arthritis demonstrated reduced stimulated migration (P less than 0.025) but normal adhesion. Preincubating normal cells in inflammatory bowel disease sera suggested that the altered migration and adhesion were due to circulating serum factors. Circulating immune complexes, detected by the C1q PEG binding assay, were present in 12.5% of patients with ulcerative colitis and 30% with Crohn's disease. Direct immunofluorescence of polymorphonuclear leukocytes suggested binding and/or ingestion of complexes in 57% of patients with ulcerative colitis, and 67% with Crohn's disease. There was a direct correlation between positive immunofluorescence and impaired cell migration in ulcerative colitis (P less than 0.05), but no such relationship was found in the other parameters of polymorph function.