Direct observation and temperature control of the surface Dirac gap in a topological crystalline insulator.

Since the advent of topological insulators hosting Dirac surface states, efforts have been made to gap these states in a controllable way. A new route to accomplish this was opened up by the discovery of topological crystalline insulators where the topological states are protected by crystal symmetries and thus prone to gap formation by structural changes of the lattice. Here we show a temperature-driven gap opening in Dirac surface states within the topological crystalline insulator phase in (Pb,Sn)Se. By using angle-resolved photoelectron spectroscopy, the gap formation and mass acquisition is studied as a function of composition and temperature. The resulting observations lead to the addition of a temperature- and composition-dependent boundary between massless and massive Dirac states in the topological phase diagram for (Pb,Sn)Se (001). Overall, our results experimentally establish the possibility to tune between massless and massive topological states on the surface of a topological system.

CLL family 'Pedigree 14' revisited: 1947-2004.

The notion that inherited predisposition contributes to the development of haematological malignancies is generally thought of as being a relatively new idea. However, Videbaek made a clear enunciation of such a hypothesis in 1947, from a study of tumour incidence in relatives of patients with different leukaemias. To gain further insight into inherited susceptibility to chronic lymphocytic leukaemia (CLL), we followed up the descendants of Videbaek's 'Pedigree 14' series of families. Using the Danish medical and pedigree databases, complete tracing of 222 descendants of the original 57 family members was achieved. To date, 10 family members have been diagnosed with CLL, one with T-cell lymphoma and 17 with nonhaematological cancers, including five with breast cancer. The detailed follow up of this family provides further support for inherited predisposition to CLL and illustrates the value of follow-up studies of previously published family material for genetic analyses.

Pediatric PACS, Astrid Lindgren Children's Hospital at Karolinska Hospital, Stockholm, technical and practical aspects.

We present a filmless pediatric radiology department for the Stockholm area (1.8 million inhabitants) producing 50000 examinations per year. Seventy percent of the examinations are non scheduled, 50% are emergency cases out of office hours. The system is designed for high reliability operating with 99.7% uptime. A large number of daily conferences are held throughout the Children's Hospital at the various specialized departments, distributed through the intranet, with one pediatric radiologist attending. Instant reading is made in the majority of examinations and reports are available with images throughout the hospital including PC's at doctors rooms. The system uses conventional hardware and software with an open systems standard based approach. The system is highly appreciated by clinicians and has improved availability of radiology information.

[Problem-based learning in medical education]. / Problembaseret undervisning på medicinstudiet.

Problem Based Learning (PBL) has not yet been instituted systematically at medical schools in Denmark. We therefore introduced the method in a 10th term course in internal medicine and surgery, eighteen months before graduation, and evaluated the experience after two terms with a total of 93 students and 15 tutors. Compared with traditional education such as bed-side clinics and lectures etc., PBL was the preferred method by 67% of the students, while 28% found the methods equally good and only 2% discredited PBL. The main advantage of PBL was ascribed to motivation and activation, the students finding themselves as being part of the problem-solving situation. The tutors estimated PBL highly when teaching clinical coping strategies, stressing the need for a realistic and appropriate setting. This experience supports the decision to introduce PBL throughout the new medical curriculum in Copenhagen.

[Pseudolymphoma and ventricular maltoma in patients with chronic gastritis, ulcer and Helicobacter pylori infection]. / Pseudolymfom og ventrikelmaltom hos patienter med kronisk gastritis, ulcus og Helicobacter pylori-infektion.

Among 128 patients with malignant B-lymphoproliferative disorders, 19 patients had long lasting dyspepsia and gastroscopy showed chronic active gastritis or gastric ulcer. PCR analysis for TCR and IgH clonality in biopsies showed local involvement of the malignant lymphocyte clone in four patients out of eight indicating presence of these cells in the inflammatory infiltrate. Weak B-cell clonality was found in four patients. A close relationship was seen between lymphocytic clonality and immune response to H. pylori Cag A, and all patients had parietal cell antibodies. Thus, the malignant clone may participate in the local inflammatory reaction, and continued local stimulation by H. pylori as well as parietal cell antigens may lead both to autoimmunity as well as a clonal development of lymphocytes.

"With the rule" astigmatism is not the rule in the elderly. Reykjavik Eye Study: a population based study of refraction and visual acuity in citizens of Reykjavik 50 years and older. Iceland-Japan Co-Working Study Groups.

PURPOSE: To study refractive state and visual acuity in citizens of Reykjavik 50 years and older. METHODS: 1700 persons were randomly selected from the national population census. 1379 could be located and qualified whereof 1045 participated. Evaluation of refraction was performed using Nidek ARK 900 autorefracto-keratometer. Visual acuity was tested on a Snellen chart. RESULTS: The prevalence of hypermetropia increases with age by 0.3 D in five years. The prevalence of "against the rule" astigmatism increased on average 5.3% and oblique 3.9% in five years. Analysis of corneal astigmatism measured by keratometer shows an "against the rule" change with age. CONCLUSIONS: Hypermetropia increases by age. The prevalence of astigmatism increases and the axis turns to "against the rule". The changes in total astigmatism and corneal astigmatism is almost parallel which might indicate that the "against the rule" change is related to changes in the cornea.

Emerging concepts in the management of the malignant haematological disorders.

A comprehensive review of novel cytoreductive agents is presented. Such novel agents may be found among chemical compounds directed against specific molecular targets (cytostatics) or within the biological substances selectively aimed at the malignant clone (immunotherapy). It is stated that the purposes of immunotherapy in general are to generate a T-lymphocytic response against the tumour cells, e.g., graft versus leukaemia (GvL) effect, natural killer T-cell cytolysis, antibody-dependent cytolysis etc.; or to reprogramme the immune system of the tumour-bearing host by DNA and/or RNA manipulation with subsequent interference with the signalling pathway in the tumour cells. Some immunotherapeutic modalities are shortly described: donor T-lymphocyte infusion and GvL effect, polyclonal antibodies, monoclonal antibodies, vaccines, gene replacement therapy, suicide gene therapy, antisense oligonucleotides, alterations of DNA-RNA transcript factors and malignant antigenic drive etc. Most likely, a sequence of different treatment modalities will be used in the future comprising an initial debulking by means of standard chemotherapy and/or irradiation followed by target unspecific immunotherapy (polyclonal immunoglobulins, GvL effect etc.) and finally target specific elimination of residual tumour, probably with repeated use of the minimum effective pharmacologic dose (MEPD) of the agents used. In contrast, the current use of high-dose myeloablative chemotherapy with the use of maximum tolerable dose (MTD) and associated severe organ toxicity, and high rates of secondary malignancies will probably be substituted in the future. An effective supportive treatment will be highly necessary, especially related to prevention and treatment of infections.

Autoimmunity in Waldenström's macroglobulinaemia.

Fifty-seven consecutive patients with Waldenström's Macroglobuliemia were studied retrospectively for autoimmune manifestations. 28 patients or 51% (16 women and 13 men) had clinical and/or serological autoimmune manifestations, two or more of these being concomitant in 20 (12 women and 8 men). The predominant findings were Coombs' positive autoimmune hemolytic anemia (16%), seropositive rheumatoid arthritis (16%), inflammatory gastric ulcer with parietal cell autoantibodies (12%), and IgM-cardiolipin syndrome (11%). 40% of the autoimmune manifestations were present at the time of diagnosis of the Waldenström's Macroglobulinaemia and 60% were observed over a mean period of 4.7 years. All patients had an IgM M-component. There was no correlation between autoimmunity and the size of the M-component or the degree of hypo-IgG and hypo-IgA gammaglobulinemia. The only correlation between autoimmunity and infection was found in patients with gastric ulcer and parietal cell autoantibodies, in whom the infection was caused by Helicobacter pylori.

Pharmacoeconomic considerations in treating patients with acute leukaemia.

Whereas individual cost-effectiveness analyses of new agents for acute leukaemia should be performed in target populations, any meaningful pharmacoeconomic evaluation of treatment options for this condition should include the many types of costs and outcomes in unselected, representative groups of patients. Both direct costs (e.g. costs for medication and hospitalisation) and indirect costs (e.g. lost productivity costs and reduced quality of life) are important parameters to assess, as are the costs of chronic adverse effects, research and development costs for new agents, and costs of procedure-related deaths. Complete remission, cure and survival are the 'success' response criteria for acute leukaemia treatments, in addition to prolonged life with acceptable quality of life for patients with incurable acute leukaemia. Death is 'failure', caused either by resistant disease (relapse and progressive disease) inspite of optimal chemotherapy or, sometimes, by insufficient treatment. All of these parameters should be taken into account when a pharmacoeconomic evaluation is performed (either for administrative or scientific purposes) in order to ensure a comprehensive and reliable background for the evaluation in question. Treatment of acute leukaemia is expensive with a total cost of about $US3000 per patient per day during the induction. Although 80% of children with acute leukaemia are cured, only less than 50% of adults are cured. Thus, a great cost is associated with death during treatment and only optimal medical treatment with full-scale combination chemotherapy and full supportive treatment can keep the number of deaths to a minimum.

Autoimmunity and extranodal lymphocytic infiltrates in lymphoproliferative disorders.

OBJECTIVE: To examine the relationship between autoimmunity and extranodal lymphocytic infiltrates in different lymphoproliferative disorders with immunoglobulin alterations. SUBJECTS AND DESIGN: A clinical review combined with a retrospective cohort study of 380 patients, 28 with monoclonal gammopathy of undetermined significance, three with common variable immunodeficiency, 147 with chronic lymphocytic leukaemia, 57 with Waldenström's macroglobulinaemia and 145 with non-Hodgkin's malignant lymphoma. SETTING: A university hospital and The State Serum Institute in Copenhagen. INTERVENTION: Clinical examination of each patient with special attention to chronic inflammatory and autoimmune manifestations. Biopsies were taken from non-infectious infiltrates, some of which were additionally tested with PCR analysis for gene rearrangements. Serological screening with a test battery for various autoantibodies was used in combination with techniques for the detection of M-components and monoclonal B-cell proliferation. MAIN OUTCOME MEASURES: Clinical and/or serological autoimmune manifestations, M-component and other immunoglobulin alterations, and inflammatory tissue changes were studied in patients with chronic inflammatory, polyclonal or oligoclonal pseudolymphomas and in monoclonal, malignant extranodal lymphomas. RESULTS: In 380 consecutive patients, 49 (12.9%) had extranodal manifestations, of whom 47 also had autoimmune manifestations. Nearly half of the 47 patients had more than one autoimmune manifestation. There was a strong correlation between clinical signs and corresponding autoantibodies such as anti-SSA and -SSB antibodies in Sjögren's syndrome (10 cases), antithyroid peroxidase antibodies in thyroiditis and Graves' disease (10 cases), and parietal cell antibodies in gastric ulcers with maltoma (12 cases). Clinical and serological signs of autoimmunity correlated strongly with female sex (34, 72% women; and 13, 28% men) and with immunoglobulin alterations. CONCLUSIONS: To our knowledge this is the first systematic review of B-lymphoproliferative and autoimmune disorders indicating that pseudolymphoma and malignant lymphomas, including maltomas, may develop in the context of a permanent autoantigenic drive.

[Age and sex specific prevalence of lens opacifications in Iceland.].

OBJECTIVES: Cataract is one of the most common causes for blindness in the world, though not in Iceland due to availability of cataract surgery. The aim of this study was to establish the age and sex specific prevalence of lens opacification and its severity in Iceland. MATERIAL AND METHODS: One thousand seven hundred citizens of Reykjavik 50 years and older were randomly selected from the national population census and offered to participate in an extensive eye study. The lenses were examined on the slitlamp microscope by two experienced ophthalmologists. Three types of lens opacification were considered separately namely cortical, nuclear and posterior subcapsular and graded according to severity using the World Health Organisation protocol. Of those randomized 68.2% of persons aged 50-79 attended and 35.8% of those 80 years and older. A total of 1045 persons; 461 males and 584 females, were examined. RESULTS: The percentage of persons with clear lenses decreased rapidly with increasing age. Of subjects age 50-59 years 45% had clear lenses, 24% of those 60-69 years and 6% of persons 70-79 year old. No subject 80 years or older was found to have a clear lens. Concurrent with this increase in the prevalence, there was an increase in severity of lens opacification. Opacification of the cortex was most common or 67%. There was a strong correlation between opacification in one eye and opacification in the contralateral eye or 84%. Conciusions: Lens opacification is an age-related phenomenon. Early cortical opacification is common after the age of 50 years and vision-disturbing cataract is common in persons older than 70 years. In coming years considerable increase in cataract surgery may be expected because of increase in the population 70 years and older.

Helicoidal peripapillary chorioretinal degeneration: electrophysiology and psychophysics in 17 patients.

AIMS: To characterise retinal function using electrophysiological and psychophysical tests in 17 patients with helicoidal peripapillary chorioretinal degeneration. METHODS: The electroretinogram (ERG) was recorded using gold foil corneal electrodes. The electro-oculogram (EOG) was recorded using a standard protocol. Dark adaptometry was recorded with an SST-1 dark adaptometer and colour vision assessed with Ishihara plates and Farnsworth D-15. RESULTS: All subjects had a recordable ERG. The amplitudes and implicit times of the a- and b-waves were within normal limits at all luminances in five subjects (age 21-70 years, mean 40 years). The ERG of six (age 26-55 years, mean 40.7 years) had subnormal amplitudes at all luminances, but normal implicit times, and six (age 38-81 years, mean 60.7 years) had abnormal ERGs with marked reduction of a- and b-waves, and delayed implicit times of the b-wave. The implicit times of the a-wave were normal in all subjects. A reduction in the b/a wave ratios was not found, nor was there selective loss of scotopic, mixed rod/cone, or cone responses. The light/dark ratio of the EOG was subnormal (150-185%) or abnormal (below 150%) in all but three subjects. Two patients with normal EOG showed normal ERGs in both eyes, but one had subnormal ERGs in both eyes. The scotopic sensitivity was normal in all subjects and dark adaptation showed a normal time course. Colour vision was normal in all patients. CONCLUSION: The results suggest that in most cases the function of the retinal pigment epithelium is affected by this disease before any changes in the function of the sensory retina are detectable by our methods, and that retinal dysfunction is focal rather than diffuse.

Combined bilateral submandibular and sublingual swelling, macroglossus, and carpal tunnel syndrome caused by light chain amyloidosis.

Three cases of light chain kappa amyloidosis in multiple myeloma patients are described with remarkable involvement of the tongue and swelling of the sublingual and submandibular regions, and without signs of nephropathy despite Bence Jones kappa proteinuria. All three patients had carpal tunnel syndrome at the beginning of their disease course and only moderate gastrointestinal involvement. Primarily for prognostic reasons, amyloidosis should be suspected in such cases, even in the presence of these highly unusual manifestations, and the diagnosis should be confirmed by unambigously-positive biopsies.

Subcutaneous lesions and bacteraemia due to Stenotrophomonas maltophilia in three leukaemic patients with neutropenia.

Subcutaneous lesions were seen in three of 13 neutropenia patients who had Stenotrophomonas (Xanthomonas) maltophilia bacteraemia. The characteristic clinical presentation resembled leukaemic infiltrates, and were different from deep ulcers or subcutaneous nodules caused by Pseudomonas aeruginosa. The three patients had acute leukaemia and were treated with intensive combination chemotherapy. All had previously been treated with broad-spectrum antibiotics, and each patient recovered after proper combination antibiotic treatment given according to sensitivity testing.

Multiple autoimmune manifestations in monoclonal gammopathy of undetermined significance and chronic lymphocytic leukemia.

In 18 cases of monoclonal gammopathy of undetermined significance, MGUS (monoclonal gammopathy of undetermined significance), admitted for diagnosed or suspected peripheral neuropathy, 11 patients showed other co-existing autoimmune manifestations. Two had POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-component, and skin symptoms), the others mainly endocrinopathy and polyclonal pseudolymphoma. There were 13 cases of sensorimotor neuropathy, two cases of neuritis, while neuropathy could not be confirmed in three cases. Compared with a retrospective review of autoimmunity in a randomly selected CLL (chronic lymphocytic leukemia) cohort of 115 patients, 13 out of 42 patients with clinical and/or laboratory features of autoimmunity showed co-expression of autoimmune signs, the dominating traits being Coombs positive AIHA (auto-immune hemolytic anemia), platelet autoantibodies, endocrinopathy mainly associated with the thyroid gland, serological and/or rheumatological symptoms, but only one case of sensorimotor neuropathy. Viewed from a current model of acquired autoimmunity it is perhaps not surprising that such autoimmunity is seen predominantly in patients with monoclonal gammopathy. Thus, a high concentration of cross-reacting polyreactive autoantibodies related to the M-component might be present in these patients. Furthermore, quantitative defects of the immunoglobulins including the hypogammaglobulinemia associated with M-components can presumably give rise to a defect of the anti-idiotypic network's regulation of natural autoantibodies and autoimmune manifestations in vivo. Such autoimmune manifestations, which are easily overlooked in CLL may call for additional treatment with immunosuppression and/or intravenous, polyclonal IgG.