| 1. |
- Bergman, Peter, et al.
(författare)
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Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial
- 2021
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 74
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.
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| 2. |
- Hakansson, HO, et al.
(författare)
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Synthesis and localization of pancreatic secretory proteins in pancreatic acinar-like metaplasia in the distal part of the oesophagus
- 2003
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 38:1, s. 41560-41560
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic acinar-like metaplasia has previously been described in the gastric mucosa and in the distal part of the oesophagus. The resemblance to pancreatic acinar cells prompted us to study the possible occurrence of secretory pancreatic proteins in these cells. Methods: Seven specimens obtained from the distal oesophagus at gastroscopy where routine microscopy showed pancreatic acinar-like metaplasia were selected for this study. Sections were subjected to immunohistochemical detection of trypsinogen, pancreatic elastase, procarboxypeptidase B and pancreatic secretory trypsin inhibitor using specific antisera. An alkaline-phosphatase-conjugated oligodeoxynucleotide probe, complementary to the transcript for trypsinogen 2 (anionic) was used for in situ hybridization. Results: Cells with pancreatic acinar-like metaplasia were immunoreactive to all pancreatic secretory proteins studied. In situ hybridization showed the presence of trypsinogen 2 mRNA in pancreatic acinar-like metaplasia. The pancreatic proteins were not seen in other cells in the distal oesophagus. Conclusion: Pancreatic acinar-like metaplasia is common in the distal oesophagus and pancreatic secretory proteins, including trypsininogen 2, are produced in the oesophageal metaplastic acinar cells. The biological significance of this finding has yet not been thoroughly studied.
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| 3. |
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| 4. |
- Ihse, Ingemar, et al.
(författare)
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Riktlinjer för handläggning av patienter med pankreascancer
- 2002
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Ingår i: Läkartidningen. - 0023-7205. ; 99:15, s. 1676-1683
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of pancreatic cancer has fallen during the last ten years in Sweden. Early signs and symptoms of the disease are still undiscovered and when diagnosis is made the disease is incurable in most patients. Transabdominal ultrasonography is the first-line imaging test followed by spiral computed tomography (CT) and magnetic resonance imaging (MRI) if required for definite diagnosis. Spiral CT is also the imaging test of choice for assessment of resectability of the tumor. Surgical removal of the tumor is the only chance of cure. Markedly improved hospital mortality after pancreaticoduodenectomy is reported and an association between hospital volume and outcome of the operation has been established. Longterm survival after attempted curative resection continues to be dismal, however. Adjuvant treatment should not be given outside clinical studies. Palliative treatment has improved thanks to progress in the field of endoscopy, interventional radiology and in management of pain and nutrition. Palliative chemotherapy should only be given selectively outside clinical studies. Radiotherapy has no proven effects on survival. Special pancreatic cancer treatment teams with catchment areas of 2-4 million inhabitants are recommended by international authorities.
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| 5. |
- Paju, A, et al.
(författare)
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Expression and characterization of trypsinogen produced in the human male genital tract
- 2000
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Ingår i: American Journal of Pathology. - 1525-2191. ; 157:6, s. 2011-2021
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Tidskriftsartikel (refereegranskat)abstract
- Trypsinogen is a serine proteinase produced mainly by the pancreas, but it has recently been found to be expressed also in several cancers such as ovarian and colon cancer and in vascular endothelial cells. In this study, we found that trypsinogen-1 and -2 are present at high concentrations (median levels, 0.4 and 0.5 mg/L, respectively) in human seminal fluid and purified them to homogeneity by immunoaffinity and anion exchange chromatography. Purified trypsinogen isoenzymes displayed a M(r) of 25 to 28 kd in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Most of the trypsinogen-1 purified from seminal fluid was enzymatically active whereas trypsinogen-2 occurred as the proform, which could be activated by enteropeptidase in vitro. Immunohistochemically, trypsinogen protein was detected in the human prostate, urethra, utriculus, ejaculatory duct, seminal vesicles, deferent duct, epididymal glands, and testis. Expression of trypsinogen mRNA in the same organs was demonstrated by in situ hybridization. Trypsinogen mRNA was also detected in the prostate and seminal vesicles by reverse transcriptase-polymerase chain reaction and Northern blotting. Isolated trypsin was shown to activate the proenzyme form of prostate-specific antigen. These results suggest that trypsinogen isoenzymes found in seminal fluid are produced locally in the male genital tract and that they may play a physiological role in the semen.
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| 6. |
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| 7. |
- Lindkvist, Björn, et al.
(författare)
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Long-term nicotine exposure causes increased concentrations of trypsinogens and amylase in pancreatic extracts in the rat.
- 2008
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Ingår i: Pancreas. - 0885-3177. ; 37:3, s. 288-294
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Tidskriftsartikel (refereegranskat)abstract
- To develop radioimmunoassays (RIAs) for rat trypsinogens 1 and 2 and to investigate the effect of nicotine exposure on concentration and production of pancreatic zymogens in the rat. METHODS: Male Sprague-Dawley rats were supplied with either normal or nicotine-containing (0.77 mM) water for 28 days and were then killed. Rabbit antibodies for the activation peptides of trypsinogens 1 and 2 were obtained for use in the RIAs. Concentrations of the both trypsinogens in pancreatic extracts were measured by the RIAs after activation by enterokinase. DNA and amylase were measured using commercial kits. mRNA for trypsinogens 1 and 2, procolipase, and cholecystokinin receptor was measured by in situ hybridization. RESULTS: The specificity of the RIA for the trypsinogen 1 activation peptide was satisfactory. The RIA for the trypsinogen 2 activation peptide showed a limited cross-reaction toward the synthetic trypsinogen 1 activation peptide, but the importance of this cross-reaction was moderate when investigated in samples of activated trypsinogens. Weight gain was reduced in nicotine-treated animals. Concentrations of amylase, trypsinogen 1, trypsinogen 2, and the ratio of trypsinogen 2 to 1 were all increased in pancreatic extracts of nicotine-fed animals. Total DNA and mRNA for the trypsinogens, procolipase, and cholecystokinin receptor were not affected by nicotine exposure. CONCLUSIONS: The combination of increased proenzyme concentrations and unaffected mRNA levels suggests that nicotine impairs secretion rather than production of pancreatic zymogens.
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| 8. |
- Borgström, Emilie W., et al.
(författare)
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Three Adult Cases of STAT1 Gain-of-Function with Chronic Mucocutaneous Candidiasis Treated with JAK Inhibitors
- 2023
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Ingår i: Journal of Clinical Immunology. - : Springer. - 0271-9142 .- 1573-2592. ; 43, s. 136-150
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Tidskriftsartikel (refereegranskat)abstract
- Purpose; The aim of this study was to characterize clinical effects and biomarkers in three patients with chronic mucocutaneous candidiasis (CMC) caused by gain-of-function (GOF) mutations in the STAT1 gene during treatment with Janus kinase (JAK) inhibitors.Methods: Mass cytometry (CyTOF) was used to characterize mononuclear leukocyte populations and Olink assay to quantify 265 plasma proteins. Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) was used to quantify the reactivity against Candida albicans.Results: Overall, JAK inhibitors improved clinical symptoms of CMC, but caused side effects in two patients. Absolute numbers of neutrophils, T cells, B cells, and NK cells were sustained during baricitinib treatment. Detailed analysis of cellular subsets, using CyTOF, revealed increased expression of CD45, CD52, and CD99 in NK cells, reflecting a more functional phenotype. Conversely, monocytes and eosinophils downregulated CD16, consistent with reduced inflammation. Moreover, T and B cells showed increased expression of activation markers during treatment. In one patient with a remarkable clinical effect of baricitinib treatment, the immune response to C. albicans increased after 7 weeks of treatment. Alterations in plasma biomarkers involved downregulation of cellular markers CXCL10, annexin A1, granzyme B, granzyme H, and oncostatin M, whereas FGF21 was the only upregulated marker after 7 weeks. After 3 months, IFN-gamma and CXCL10 were downregulated.Conclusions: The clinical effect of JAK inhibitor treatment of CMC is promising. Several biological variables were altered during baricitinib treatment demonstrating that lymphocytes, NK cells, monocytes, and eosinophils were affected. In parallel, cellular reactivity against C. albicans was enhanced.
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| 9. |
- Johansen, Dorthe, et al.
(författare)
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Different Markers of Alcohol Consumption, Smoking and Body Mass Index in Relation to Risk of Pancreatic Cancer. A Prospective Cohort Study within the Malmö Preventive Project.
- 2009
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 9:5, s. 677-686
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: The association between alcohol consumption and pancreatic cancer is not clear. This study investigates different prediagnostic measurements of alcohol consumption, a laboratory marker (gamma-glutamyltransferase; gamma-GT), and a score measuring alcohol addiction (Mm-MAST), in relation to the risk of pancreatic cancer. Furthermore, the study investigated whether smoking and alcohol consumption interact with each other, or if the risk of pancreatic cancer associated with these factors is modified by obesity or weight gain. Methods: A cohort of 33,346 subjects provided prediagnostic information on the above factors. During a mean follow-up of 22.1 years, 183 cases of pancreatic cancer occurred. Cox's analysis yielded relative risks (RR) with 95% confidence intervals (CI). Results: The highest gamma-GT quartile was associated with a high risk of pancreatic cancer (RR = 2.15, 95% CI = 1.34-3.44), and this association was even stronger in subjects that reported a previous weight gain (RR = 3.61, 95% CI = 1.29-10.09). A high Mm-MAST score was also associated with pancreatic cancer (p = 0.02). Current smoking was associated with pancreatic cancer (RR = 2.34, 95% CI = 1.60-3.43), and obese smokers had an even higher risk (RR = 7.45, 95% CI = 1.65-33.64). Conclusion: High alcohol intake is associated with subsequent risk of pancreatic cancer and this risk may be higher following weight gain. The risk associated with smoking may be even higher in obese subjects. and IAP.
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| 10. |
- Lindkvist, Björn, et al.
(författare)
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A Prospective Cohort Study of Smoking in Acute Pancreatitis.
- 2008
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Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 8:1, s. 63-70
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Little is known about risk factors for acute pancreatitis other than gallstones and alcohol consumption. The aim of this study was to investigate if smoking or body mass index (BMI) are associated with acute pancreatitis and to determine relative risks (RR) for acute pancreatitis related to smoking, BMI, and alcohol consumption. Methods: From 1974 to 1992, selected birth-year cohorts of residents in Malmo, Sweden (born 1921-1949) were invited to a health-screening investigation including physical examination, blood sampling and a questionnaire. In total, 33,346 individuals participated. Cases of acute pancreatitis were identified from diagnosis registries (n = 179). Incidence rates were calculated in different risk factor categories. A Cox's analysis revealed RR. Results: Current versus never smoking at baseline was associated with acute pancreatitis (RR 2.14, 95% confidence interval (CI) 1.48-3.09) after adjustment for age, sex, BMI and alcohol consumption. This association was stronger in heavy smokers (20-30 cigarettes/day) (RR 3.19, 95% CI 2.03-5.00). Smoking was associated with a RR of 3.57 (95% CI 0.98-13.0) for acute pancreatitis in subjects who reported no alcohol consumption. An increased risk for acute pancreatitis was also found for high versus low risk, self-reported alcohol consumption (RR 2.55, 95% CI 1.59-4.08) and for gamma-GT levels in the highest versus the lowest quartile (RR 2.14, 95% CI 1.32-3.49). There was also a weak correlation between BMI and acute pancreatitis. Conclusions: Smoking is associated with the incidence of acute pancreatitis in a dose-response manner. Copyright (c) 2008 S. Karger AG, Basel and IAP.
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