DNA content and mucosal dysplasia in ulcerative colitis

In an unselected population of 108 patients with ulcerative colitis in an ongoing endoscopic cancer surveillance program, high-grade dysplasia was diagnosed in 3, low-grade dysplasia in 11, and mucosal changes indefinite for dysplasia in 11 patients. The abnormal biopsy specimens from these 25 patients and samples from other parts of the large bowel obtained at the same examination were investigated by flow cytometric DNA analysis. One hundred thirty-six of 160 samples (85 percent) gave evaluable DNA histograms and, accordingly, 23 patients were retrospectively investigated. Six patients (26 percent) showed aneuploidy (abnormal DNA stemlines) and 1 had possible aneuploidy. All 3 patients with high-grade dysplasia showed aneuploidy (or possible aneuploidy) preceding or coexisting with the severe dysplastic changes. In 1 of these patients, the presence of aneuploidy preceded two diploid carcinomas. One patient was found to have had aneuploidy for seven years without evident malignant transformation. Further prospective studies are necessary to determine the value of DNA analysis in relation to morphologic examination in surveillance of patients with ulcerative colitis.     

Visualising skin perfusion in isolated human abdominal skin flaps using dynamic infrared thermography and indocyanine green fluorescence video angiography

This experimental study compared the direct technique indocyanine green fluorescence angiography (ICG-FA) and the indirect technique dynamic infrared thermography (DIRT) for visualising skin perfusion. Eight isolated human transverse abdominal skin flaps, obtained from female patients undergoing abdominoplasty, were used. A total of 19 selected vessels were individually perfused. Warm and cold perfusate was used for visualising skin perfusion with DIRT. Both techniques were tested for repeatability, making up a total of 34 perfusions. Qualitative analysis of the rate and pattern of perfusion visualised by both techniques was carried out. The extent of the perfused area indicated by the indirect DIRT technique corresponded well with the perfused area indicated by the direct ICG-FA technique. The appearance of distinct hot spots in the IR images provided additional information on the distribution of perforating vessels. It is concluded that in experimental situations the non-invasive DIRT technique is a good alternative to the invasive ICG-FA technique for visualising skin perfusion.     

Automated interpretation of ventilation-perfusion lung scintigrams for the diagnosis of pulmonary embolism using artificial neural networks

The purpose of this study was to develop a completely automated method for the interpretation of ventilation-perfusion (V-P) lung scintigrams used in the diagnosis of pulmonary embolism. An artificial neural network was trained for the diagnosis of pulmonary embolism using 18 automatically obtained features from each set of V-P scintigrams. The techniques used to process the images included their alignment to templates, the construction of quotient images based on the ventilation and perfusion images, and the calculation of measures describing V-P mismatches in the quotient images. The templates represented lungs of normal size and shape without any pathological changes. Images that could not be properly aligned to the templates were detected and excluded automatically. After exclusion of those V-P scintigrams not properly aligned to the templates, 478 V-P scintigrams remained in a training group of consecutive patients with suspected pulmonary embolism, and a further 87 V-P scintigrams formed a separate test group comprising patients who had undergone pulmonary angiography. The performance of the neural network, measured as the area under the receiver operating characteristic curve, was 0.87 (95% confidence limits 0.82–0.92) in the training group and 0.79 (0.69–0.88) in the test group. It is concluded that a completely automated method can be used for the interpretation of V-P scintigrams. The performance of this method is similar to others previously presented, whereby features were extracted manually. Received 30 September and in revised form 14 December 1999     

Vitamin D Receptor Gene Polymorphism and Parathyroid Calcium Sensor Protein (CAS/gp330) Expression in Primary Hyperparathyroidism

b , a , and T , comprise a novel risk factor for postmenopausal primary hyperparathyroidism (pHPT) by their presumed coupling to reduced VDR expression. This study examines VDR gene polymorphisms, parathyroid calcium-regulated cytoplasmic calcium concentrations ([Ca ²⁺ ] _i ) and parathyroid expression of a calcium sensor protein (CAS/gp330). Genomic DNA was obtained from 66 postmenopausal women with pHPT and 66 age-matched female controls. Polymorphic VDR alleles were detected after polymerase chain reaction (PCR) and restriction digestion. Cryosections of pathologic parathyroid glands from 41 of the patients were immunostained with a monoclonal anti-CAS/gp330 antibody. Homozygosity for the VDR alleles b , a , and T was overrepresented in pHPT ( p < 0.01–0.05) but did not couple to ED ₅₀ for calcium-regulated [Ca ²⁺ ] _i . The enlarged parathyroid glands possessed heterogeneous down-regulation of CAS/gp330. This down-regulation was the least conspicuous in the BB genotype, and these few patients generally had larger parathyroid lesions ( p < 0.05). The VDR haplotype baT is a risk factor for pHPT possibly by hampering the regulatory actions of calcitriol. In contrast the BAt haplotype seems to be underrepresented in pHPT and to couple to larger parathyroid lesions as well as less deranged CAS/gp330 expression and parathyroid cell function. HPT in these individuals may relate to genetic events principally altering the regulation of cell proliferation, rather than calcium sensing of the parathyroid cells.     

Polymerase chain reaction for detection ofBorrelia burgdorferi DNA in skin lesions of early and late Lyme borreliosis

The aim of this study was to evaluate the polymerase chain reaction (PCR) as a diagnostic tool for Lyme borreliosis on large numbers of samples from clinically well-defined cases of early and late cutaneous borreliosis. Skin biopsy specimens from patients with erythema migrans and acrodermatitis chronica atrophicans were analysed blindly together with an equal number of control biopsies. Using two different dilutions of each DNA specimen increased the number of total positives detected. All of the 76 control biopsies were PCR negative. Biopsy specimens from 18 of 26 (69 %) erythema migrans lesions and from 22 of 36 (61 %) acrodermatitis chronica atrophicans lesions were PCR positive. Fourteen post-therapy biopsies from patients with acrodermatitis chronica atrophicans were all negative, supporting the opinion that antibiotic therapy is successful in this chronic manifestation of Lyme borreliosis.     

Serum amyloid P component scintigraphy in familial amyloid polyneuropathy: regression of visceral amyloid following liver transplantation

Familial amyloid polyneuropathy (FAP) associated with transthyretin (TTR) mutations is the commonest type of hereditary amyloidosis. Plasma TTR is produced almost exclusively in the liver and orthotopic liver transplantation is the only available treatment, although the clinical outcome varies. Serum amyloid P component (SAP) scintigraphy is a method for identifying and quantitatively monitoring amyloid deposits in vivo, but it has not previously been used to study the outcome of visceral amyloid deposits in FAP following liver transplantation. Whole body scintigraphy following injection of iodine-123 labelled SAP was performed in 17 patients with FAP associated with TTR Met30 and in five asymptomatic gene carriers. Follow-up studies were performed in ten patients, eight of whom had undergone orthotopic liver transplantation 1–5 years beforehand. There was abnormal uptake of ¹²³I-SAP in all FAP patients, including the kidneys in each case, the spleen in five cases and the adrenal glands in three cases. Renal amyloid deposits were also present in three of the asymptomatic carriers. Follow-up studies 1–5 years after liver transplantation showed that there had been substantial regression of the visceral amyloid deposits in two patients and modest improvement in three cases. The amyloid deposits were unchanged in two patients. In conclusion, ¹²³I-SAP scintigraphy identified unsuspected visceral amyloid in each patient with FAP due to TTR Met30. The universal presence of renal amyloid probably underlies the high frequency of renal failure that occurs in FAP following liver transplantation. The variable capacity of patients to mobilise amyloid deposits following liver transplantation may contribute to their long-term clinical outcome. Received 12 February and in revised form 16 April 1998     

Serum osteocalcin and fracture susceptibility in elderly women

Summary The purpose of this investigation was to evaluate the bone turnover by using bone metabolic markers in relation to previous fracture history and independent of bone mass. Patients and controls were recruited from a population-based study of 193 women, all living in the same city and aged 60, 70, and 80 years. The bone mineral content (BMC) was measured bilaterally in the distal forearm by single-photon absorptiometry (SPA). At the same time, serum samples were obtained for biochemical analysis. Of the 193 women, we identified 26 with at least one major fracture during the past few years. Each of these 26 women with a certified recent previous fracture was individually matched with a woman from the same study group of equal BMC and age but without a fracture history. In the two groups, the serum samples were analyzed for osteocalcin, C-terminal procollagen peptide (PICP), alkaline phosphatase, bone-specific alkaline phosphatase, calcium, phosphate, and albumin. The serum concentration of osteocalcin was 20% lower in the women with a previous fracture than in the controls (P = 0.03). The other markers of bone formation gave similar values in the two groups. There was a significant correlation between the osteocalcin and PICP concentrations (P = 0.001). Our findings indicate that the susceptibility to fractures independent of factors such as age and BMC may be related to a decreased bone turnover.     

Epidemiological explanation of an outbreak of gastro-enteritis in Sweden in the absence of detailed microbiological information

Waterborne gastroenteritis outbreaks have often gone undetected or been incompletely defined in terms of source and extent. Methods which allow detection or clarification of such events are therefore useful. We describe the methods used to detect and investigate such an outbreak. In autumn 1996 high school absence rates and the rate of parents absent from work to care for sick children suggested a health problem in a Swedish town which had a history of unexplained outbreaks of gastrointestinal disease. A systematic sample of 300 households was surveyed by post. Respondents represented 10% of the total population of the town. Questions concerning symptoms and exposures were included. The same questionnaire was used in a nearby town as a control. Sixty four percent of respondents reported an acute gastrointestinal illness during a two month period. Diarrhoea (90%) and abdominal pain (88%) were the most frequent symptoms among the sick. Two percent of those sick sought medical care. Exposures associated with disease were being a member of a large household, young age, and consumption of water from the community water supply. Attack rate showed a dose response relationship with increasing frequency of water consumption. The peak incidence of gastrointestinal illness occurred shortly after raw water quality control data had shown a rise in indicator bacteria. Further analysis, dividing those infected into groups according to when they became ill and whether they were the first member of their household to fall ill, supported the hypothesis of primary cases being infected from the water supply with some secondary person to person spread.     

Discordance between malignant hyperthermia susceptibility and RYR1 mutation C1840T in two Scandinavian MH families exhibiting this mutation

The ryanodine receptor 1 (RYR1) mutation C1840T has been reported to segregate with malignant hyperthermia (MH) susceptibility in several families. We have investigated several Scandinavian MH families with respect to five different RYR1 mutations reported to cause predisposition to MH, and we here report on two of the families in which the C1840T mutation was detected. In these two families there was recombination between MH susceptibility and this mutation in one and three individuals, respectively. These findings may suggest that it is necessary to reconsider the specificity of the IVCT and the role of C1840T as a cause of MH susceptibility in some families exhibiting this mutation.