| 1. |
- Ahrenstedt, O, et al.
(författare)
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Enhanced local production of complement components in the small intestines of patients with Crohn's disease.
- 1990
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 322:19, s. 1345-1349
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence that complement components may be formed locally in inflammatory lesions containing monocytes and macrophages. To investigate the role of complement in Crohn's disease we measured jejunal-fluid concentrations of the complement components C4, C3, and factor B by perfusion of a closed segment of the jejunum in 22 patients with Crohn's disease thought to be limited to the terminal ileum. The mean (+/- SEM) jejunal-fluid C4 concentration was 2.0 +/- 0.3 mg per liter, significantly higher than the mean level in 35 healthy controls (0.7 +/- 0.1 mg per liter; P less than 0.001). The mean C3 concentration was 1.0 +/- 0.1 mg per liter in the patients and 0.7 +/- 0.1 mg per liter in the controls (P less than 0.05). The factor B levels were similar in the two groups. Calculated rates of intestinal secretion of these components showed differences of the same magnitude. Leakage of protein from plasma was not increased. The jejunal-fluid:serum ratios of these complement proteins indicated that their appearance in the lumen of the jejunum was due to at least in part to local mucosal synthesis. The increased jejunal secretion of C4, but not C3 or factor B, paralleled the clinical activity of Crohn's disease. Values were normal in first-degree relatives of the patients (n = 13), patients with celiac disease (n = 8), and patients with ulcerative colitis (n = 4). We conclude that increased secretion of complement by clinically unaffected jejunal tissue in patients with Crohn's disease reflects the systemic nature of this disorder and may be due to the stimulated synthesis of complement by activated intestinal monocytes and macrophages.
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| 2. |
- Ahrenstedt, Örjan, et al.
(författare)
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Enhanced local production of the complement components in the small intestine in Crohn's disease
- 1990
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 322, s. 1345-1349
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence that complement components may be formed locally in inflammatory lesions containing monocytes and macrophages. To investigate the role of complement in Crohn's disease we measured jejunal-fluid concentrations of the complement components C4, C3, and factor B by perfusion of a closed segment of the jejunum in 22 patients with Crohn's disease thought to be limited to the terminal ileum.The mean (±SEM) jejunal-fluid C4 concentration was 2.0±0.3 mg per liter, significantly higher than the mean level in 35 healthy controls (0.7±0.1 mg per liter; P<0.001). The mean C3 concentration was 1.0±0.1 mg per liter in the patients and 0.7±0.1 mg per liter in the controls (P<0.05). The factor B levels were similar in the two groups. Calculated rates of intestinal secretion of these components showed differences of the same magnitude. Leakage of protein from plasma was not increased. The jejunal-fluid serum ratios of these complement proteins indicated that their appearance in the lumen of the jejunum was due at least in part to local mucosal synthesis. The increased jejunal secretion of C4, but not C3 or factor B, paralleled the clinical activity of Crohn's disease. Values were normal in first-degree relatives of the patients (n = 13), patients with celiac disease (n = 8), and patients with ulcerative colitis (n = 4).We conclude that increased secretion of complement by clinically unaffected jejunal tissue in patients with Crohn's disease reflects the systemic nature of this disorder and may be due to the stimulated synthesis of complement by activated intestinal monocytes and macrophages.
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| 3. |
- Brittberg, Mats, 1953, et al.
(författare)
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Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.
- 1994
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Ingår i: The New England journal of medicine. - 0028-4793. ; 331:14, s. 889-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Full-thickness defects of articular cartilage in the knee have a poor capacity for repair. They may progress to osteoarthritis and require total knee replacement. We performed autologous chondrocyte transplantation in 23 people with deep cartilage defects in the knee. METHODS. The patients ranged in age from 14 to 48 years and had full-thickness cartilage defects that ranged in size from 1.6 to 6.5 cm2. Healthy chondrocytes obtained from an uninvolved area of the injured knee during arthroscopy were isolated and cultured in the laboratory for 14 to 21 days. The cultured chondrocytes were then injected into the area of the defect. The defect was covered with a sutured periosteal flap taken from the proximal medial tibia. Evaluation included clinical examination according to explicit criteria and arthroscopic examination with a biopsy of the transplantation site. RESULTS. Patients were followed for 16 to 66 months (mean, 39). Initially, the transplants eliminated knee locking and reduced pain and swelling in all patients. After three months, arthroscopy showed that the transplants were level with the surrounding tissue and spongy when probed, with visible borders. A second arthroscopic examination showed that in many instances the transplants had the same macroscopic appearance as they had earlier but were firmer when probed and similar in appearance to the surrounding cartilage. Two years after transplantation, 14 of the 16 patients with femoral condylar transplants had good-to-excellent results. Two patients required a second operation because of severe central wear in the transplants, with locking and pain. A mean of 36 months after transplantation, the results were excellent or good in two of the seven patients with patellar transplants, fair in three, and poor in two; two patients required a second operation because of severe chondromalacia. Biopsies showed that 11 of the 15 femoral transplants and 1 of the 7 patellar transplants had the appearance of hyaline cartilage. CONCLUSION. Cultured autologous chondrocytes can be used to repair deep cartilage defects in the femorotibial articular surface of the knee joint.
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| 4. |
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| 5. |
- Kremer, B, et al.
(författare)
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A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats.
- 1994
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 330:20, s. 1401-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Huntington's disease is associated with an expanded sequence of CAG repeats in a gene on chromosome 4p16.3. However, neither the sensitivity of expanded CAG repeats in affected persons of different ethnic origins nor the specificity of such repeats for Huntington's disease as compared with other neuropsychiatric disorders has been determined.METHODS: We studied 1007 patients with diagnosed Huntington's disease from 565 families and 43 national and ethnic groups. In addition, the length of the CAG repeat was determined in 113 control subjects with a family history of Alzheimer's disease (44 patients), schizophrenia (39), major depression (16), senile chorea (5), benign hereditary chorea (5), neuroacanthocytosis (2), and dentatorubropallidoluysian atrophy (2). The number of CAG repeats was also assessed in 1595 control chromosomes, with the size of adjacent polymorphic CCG trinucleotide repeats taken into account.RESULTS: Of 1007 patients with signs and symptoms compatible with a diagnosis of Huntington's disease, 995 had an expanded CAG repeat that included from 36 to 121 repeats (median, 44) (sensitivity, 98.8 percent; 95 percent confidence interval, 97.7 to 99.4 percent). There were no significant differences among national and ethnic groups in the number of repeats. No CAG expansion was found in the 110 control subjects with other neuropsychiatric disorders (specificity, 100 percent; 95 percent confidence interval, 95.2 to 100 percent). In 1581 of the 1595 control chromosomes (99.1 percent), the number of CAG repeats ranged from 10 to 29 (median, 18). In 12 control chromosomes (0.75 percent), intermediate-sized CAG sequences with 30 to 35 repeats were found, and 2 normal chromosomes unexpectedly had expanded CAG sequences, of 39 and 37 repeats.CONCLUSIONS: CAG trinucleotide expansion is the molecular basis of Huntington's disease worldwide and is a highly sensitive and specific marker for inheritance of the disease mutation.
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| 6. |
- Sigurdsson, H, et al.
(författare)
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Indicators of prognosis in node-negative breast cancer
- 1990
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 322:15, s. 1045-1053
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Tidskriftsartikel (refereegranskat)abstract
- Measures of the proliferative activity of tumor cells have prognostic value in patients with node-negative breast cancer. We studied 367 women in southern Sweden who had undergone surgical resection for such cancer. Tumor specimens were analyzed with DNA flow cytometry in order to estimate both the DNA content (ploidy) and the fraction of cells in the synthetic phase of the cell cycle (S phase). The median duration of follow-up was four years; 28 percent of the patients received adjuvant therapy, usually with tamoxifen (n = 83). A multivariate analysis based on complete data on 250 patients included the following covariates: age (greater than or equal to 75, 50 to 74, and less than or equal to 49 years), tumor size (less than or equal to 20 vs. greater than 20 mm), concentration of estrogen and progesterone receptors (less than 10 vs. greater than or equal to 10 fmol per milligram of protein), ploidy (diploid vs. nondiploid), and S-phase category (fraction of cells in S phase: less than 7.0 percent, 7.0 to 11.9 percent, and greater than or equal to 12 percent). The S-phase fraction yielded the most prognostic information, followed by progesterone-receptor status and tumor size. A prognostic model based on these three variables identified 37 percent of the patients as constituting a high-risk group with a fourfold increased risk of distant recurrence. In the remaining 63 percent of the patients, the five-year overall survival rate (92 +/- 4 [+/- SE] percent) did not differ from the expected age-adjusted rate for Swedish women. We conclude that a prognostic index that includes indicators of the proliferative activity of tumor cells may be able to identify women with node-negative breast cancer in whom the risk of recurrence is sufficiently low that adjuvant chemotherapy can be avoided.
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| 7. |
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| 8. |
- Svensson, Bengt-Göran, et al.
(författare)
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Exposure to dioxins and dibenzofurans through the consumption of fish
- 1991
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 324, s. 8-12
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Tidskriftsartikel (refereegranskat)abstract
- Background.In some regions, including the Baltic Sea, fatty fish such as salmon and herring contain high levels of polychlorinated dibenzodioxins and dibenzofurans. We investigated human exposure to these potentially toxic substances in relation to the consumption of fish from the Baltic Sea.Methods.Plasma levels of 10 different dibenzofurans and 7 dioxins were analyzed in three groups of Swedish men: one group with a high intake of fish (fish eaten almost daily; n = 11), one with a moderate intake of fish (about once per week; n = 9), and one with no consumption of fish (usually because of allergy; n = 9).Results.Plasma levels of several of the compounds we measured were higher in the men with a high intake of fish than in those who consumed moderate amounts, and the levels were higher in those who ate moderate amounts of fish than in those who ate none. The median amounts of the most toxic dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) were 8.0 pg per gram of plasma lipid (range, 2.0 to 13) in the high-intake group, 2.6 pg per gram (range, 1.2 to 4.2) in the moderate-intake group, and 1.8 pg per gram (range, 1.0 to 2.5) in the nonconsumers (P = 0.001 and 0.02, respectively). There were consistent and statistically significant associations between the reported amount of fish eaten and the plasma levels of several of the dibenzofurans and dioxins.Conclusions.Contaminated fish such as those from the Baltic Sea are an important source of exposure to polychlorinated dibenzofurans and dibenzodioxins in persons who eat fish regularly. However, the clinical consequences of such exposure remain uncertain.
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| 9. |
- Widner, H, et al.
(författare)
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Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
- 1992
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 327:22, s. 63-1556
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intracerebral transplantation of fetal dopaminergic neurons is a promising new approach for the treatment of Parkinson's disease. Patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have a relatively stable lesion limited to the nigrostriatal system, rendering them ideal candidates for transplantation. Improvement of motor function after neural grafting has previously been observed in nonhuman primates with MPTP-induced parkinsonism.METHODS: We grafted human fetal tissue from the ventral mesencephalon (obtained six to eight weeks after conception) bilaterally to the caudate and putamen in two immunosuppressed patients with severe MPTP-induced parkinsonism, using a stereotaxic technique. The patients were assessed regularly with clinical rating scales, timed tests of motor performance, and [18F]fluorodopa positron-emission tomography during the 18 months before the operation and the 22 to 24 months after the operation.RESULTS: Both patients had substantial, sustained improvement in motor function and became much more independent. Postoperatively, the second patient's maintenance dose of levodopa was decreased to 150 mg daily, which was 30 percent of the original dose. Striatal uptake of fluorodopa was unchanged 5 to 6 months postoperatively but was markedly and bilaterally increased at 12 to 13 and 22 to 24 months in both patients, closely paralleling the patients' clinical improvement. There were no serious complications.CONCLUSIONS: Bilateral implantation of fetal mesencephalic tissue can induce substantial long-term functional improvement in patients with parkinsonism and severe dopamine depletion and is accompanied by increased uptake of fluorodopa by the striatum. The results in these patients resemble those obtained in MPTP-treated primates and suggest that this will be a useful model for the assessment of transplantation therapies in Parkinson's disease.
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