Subclinical renal dysfunction in rheumatoid arthritis

We studied renal function in 35 patients with chronic, seropositive rheumatoid arthritis (RA), of whom 7 had vasculitis, 10 had hypergammaglobulinemia, and 18 had neither of these 2 conditions. Findings included a decreased glomerular filtration rate in 8 patients, (micro)proteinuria in 11, a defective urine concentration in 10, and increased urinary tubular enzyme levels in 15. These results indicate that subclinical renal dysfunction is common in patients with chronic, seropositive RA. In addition, vasculitis and hypergammaglobulinemia were not identified as risk factors for renal dysfunction in the RA patients studied.     

Cyclosporin treatment for rheumatoid arthritis: a placebo controlled, double blind, multicentre study.

The efficacy and safety of cyclosporin for patients with rheumatoid arthritis (RA) were assessed in a six month double blind, placebo controlled, multicentre study. The initial dosage of the drug was 10 mg/kg daily for two months. There were many discontinuations in both the cyclosporin group (eight out of 17) and the placebo group (six out of 19). Of the patients who completed the six months of therapy, those who had received cyclosporin showed a significant improvement in the number of swollen joints, the Ritchie articular index, and pain at active movement and at rest, compared not only with their condition at the start of the study, but also with the end results of the placebo group. Major adverse reactions to the drug were gastrointestinal disturbances and nephrotoxicity, which were probably due to the relatively high dosages of cyclosporin given in combination with non-steroidal anti-inflammatory drugs.     

Diminished clearance of soluble aggregates of human immunoglobulin G in patients with rheumatoid arthritis

Investigation of the capacity of the mononuclear phagocyte system to remove immune complexes from the circulation was performed by the administration of 125I-labelled aggregates of human immunoglobulin G (AIgG) to patients with seropositive rheumatoid arthritis and healthy volunteers. It was found that the rate at which AIgG disappeared from the circulation was significantly prolonged in patients with RA, t1/2 61 +/- 49 min, versus 26 +/- 8 min in healthy volunteers (p less than 0.01). We were not able to establish a correlation between the t1/2 of AIgG and immune complex levels in the circulation, or between t1/2 and articular disease activity (Ritchie index). The sites of removal of AIgG from the circulation were analysed by determining radioactivity levels detectable over liver, spleen and heart. No correlation was found between t1/2 and liver/spleen uptake ratios. We have demonstrated that the removal of AIgG from the circulation of patients with RA is abnormal, though the biological significance of this finding remains to be determined.     

Lifestyle and the risk of rheumatoid arthritis: cigarette smoking and alcohol consumption.

In a search for aspects of behaviour related to oral contraceptive use which might explain the favourable effect of oral contraception on the onset of rheumatoid arthritis (RA), cigarette smoking and alcohol consumption were studied as possible risk factors. Information on cigarette smoking and alcohol consumption was obtained by interview at the first visit to the outpatient clinic of 135 young women with confirmed definite or classical RA of recent onset and 378 control patients with soft tissue rheumatism or osteoarthritis. The diagnosis in all patients was confirmed by at least two years of follow up. Of the patients with RA, 44/135 (33%) were current cigarette smokers compared with 181/378 (48%) of the controls. The percentage of smokers among the controls was similar to that of women smokers in the general population. The adjusted risk of RA in women who smoked at least one cigarette a day was 0.61 (95% confidence interval (CI) 0.42 to 0.89). Thirty one (23%) patients with RA and 137 (36%) controls were alcohol drinkers. The risk of RA in women who consumed alcohol at least once a day was 0.52 (95% CI 0.33 to 0.84). The low relative risk estimates for cigarette smoking and alcohol consumption were mutually independent and also independent of oral contraceptive use, the presence of the HLA-DR4 antigen, or a positive family history of RA. The low incidence of alcohol consumption in the patients with RA might be due to the discontinuation of alcohol consumption after disease onset. The low incidence of cigarette smoking in the patients might reflect a protective effect of cigarette smoking on RA onset, possibly induced by changes in the immune system.     

Clinical heterogeneity of familial colorectal cancer and its influence on screening protocols.

The age at onset of non-polyposis colorectal cancer (CRC) was investigated in 49 families with at least three relatives affected in two successive generations. Forty one of these families satisfy the accepted minimum criteria for hereditary non-polyposis CRC. The remaining eight families were distinguished by a late age of disease onset and, hence, could not be included in the group. The condition in these latter families has been designated provisionally, as late onset familial CRC. The hereditary non-polyposis CRC families include 194 patients, 110 men and 84 women (mean age at diagnosis: 44 years; range: 16-74 years). Ninety two per cent of the patients were diagnosed by age 60. Colorectal cancer was diagnosed at progressively earlier ages in successive generations (p < 0.0005). The late onset CRC families comprised 30 patients, 20 men and 10 women (mean age at diagnosis: 62 years; range: 51-77 years). Fifty eight per cent of the CRCs in the patients belonging to the hereditary non-polyposis CRC families were located in the right colon compared with 13% in the late onset familial CRC group (p < 0.001). Multiple CRCs were found in 23% of the cases in the former but in only 3% in the latter families (p < 0.05). Adenomas associated with CRC were reported in 14.5% of the cases in the hereditary non-polyposis CRC families and in 30% of the cases in the late onset familial CRC group (p = NS). Extracolonic cancers, frequently encountered in hereditary non-polyposis CRC, were not found in the late onset CRC families. These findings indicate that there is a distinct clinical entity of non-polyposis CRC in which colorectal cancer develops at a more advanced age than in hereditary non-polyposis CRC. Future molecular genetic studies should confirm this hypothesis. In the meantime, recognition of these late onset familial CRC families, which will rest on clinical observations, is important because of the implications for the screening protocol.     

Immunogenetic heterogeneity of rheumatoid arthritis.

Association of HLA-DR4/Dw4 with rheumatoid arthritis (RA) is well established, but conflicting data exist on a possible association with the severity of the disease, including its extra-articular manifestations. In order to investigate whether a subgroup of RA is preferentially associated with DR4, HLA typing was performed in two groups of patients with severe extra-articular manifestations (Felty's syndrome and histologically proved leucocytoclastic vasculitis), patients with severe joint destruction (seropositive and seronegative), a group with only mild joint destruction, and in healthy controls. The frequency of HLA-DR4 was significantly raised in all patient groups compared with that in healthy controls. The two groups with severe extra-articular manifestations, however, both had a DR4 frequency of 92%, which was significantly (p = 0.002) higher than the 62.7% found in the remaining patients. No significant differences were observed between severe or mild joint destruction and seropositivity or seronegativity in the groups without the above-mentioned extra-articular manifestations. From these data we concluded that DR4 is preferentially associated with severe extra-articular disease manifestations of RA. This observation provides an immunogenetic basis for the disease heterogeneity and for the immunological analogy between RA and leprosy.     

The Prognostic Significance of an R1 Resection in Gastric Cancer Patients Treated with Adjuvant Chemoradiotherapy

Background

A microscopically irradical (R1) resection is a well-known adverse prognostic factor after gastric cancer surgery. However, the prognostic significance of an R1 resection in gastric cancer patients who are treated with chemoradiotherapy (CRT) after the operation has been poorly studied. Therefore, the aim of this study was to evaluate the effect of an R1 resection on (recurrence-free) survival in gastric cancer patients who were treated with CRT after surgery.

Methods

Gastric cancer patients who had undergone a resection with curative intent followed by adjuvant CRT at our institute between 2001 and 2011 were included. CRT consisted of radiotherapy (45 Gy/25 fractions) combined with concurrent capecitabine (with or without cisplatin) or 5-fluorouracil/leucovorin.

Results

A consecutive series of 110 patients was studied, including 80 (73 %) patients who had undergone an R0 resection and 30 (27 %) patients with an R1 resection. Pathologic T-classification (p = 0.26), N-classification (p = 0.77), and histologic subtype according to Laurén (p = 0.071) were not significantly different between these groups. Three-year recurrence-free survival (45 vs. 35 %, p = 0.34) and overall survival (47 vs. 48 %, p = 0.58) did not significantly differ between patients who had undergone an R0 or R1 resection. In a multivariate analysis, pathologic T-classification and N-classification were independent prognostic factors for survival.

Conclusions

A R1 resection was not an adverse prognostic factor in gastric cancer patients who had undergone CRT after the operation.     

Are enzymatic tests good indicators of coronary reperfusion?

OBJECTIVE--To assess the accuracy of four enzymatic tests, including early release rates of creatine kinase and alpha-hydroxybutyrate dehydrogenase, in assessing coronary reperfusion after thrombolytic therapy. DESIGN--A prospective clinical trial identifying patients with a successful thrombolytic treatment. PATIENTS--Eighty nine patients with acute myocardial infarction were studied. Arteriography showed a closed infarct related artery in all of them. Reperfusion due to thrombolysis occurred in 74 patients and there was no reperfusion in 15 patients. RESULTS--The 74 patients showing coronary reperfusion had a significantly shorter time to peak creatine kinase activity, higher early release rates for creatine kinase and alpha-hydroxybutyrate dehydrogenase, and a more rapid release of alpha-hydroxybutyrate dehydrogenase (ratio of cumulative release of alpha-hydroxybutyrate dehydrogenase during the first 24 hours to that 72 hours after infarction). All these differences were statistically significant (p less than 0.001). Optimum cut off levels were determined with decision level plots and the accuracy of the four enzymatic tests was calculated. Accuracy was low for all four tests (73%, 70%, 70%, and 82%). CONCLUSION--None of the four enzymatic tests accurately predicted the perfusion state of the infarct related coronary artery after thrombolysis. These tests cannot be used reliably in routine clinical practice as non-angiographic markers of coronary reperfusion.     

Pulp revascularization for immature replanted teeth: a case report

Immature avulsed teeth are not usually treated with pulp revascularization because of the possibility of complications. However, this therapy has shown success in the treatment of immature teeth with periapical lesions. This report describes the case of an immature replanted tooth that was successfully treated by pulp revascularization. An 8‐year‐old boy suffered avulsion on his maxillary left lateral incisor. The tooth showed incomplete root development and was replanted after 30 minutes. After diagnosis, revascularization therapy was performed by irrigating the root canal and applying a calcium hydroxide paste and 2% chlorhexidine gel for 21 days. In the second session, the intracanal dressing was removed and a blood clot was stimulated up to the cervical third of the root canal. Mineral trioxide aggregate was placed as a cervical barrier at the entrance of the root canal and the crown was restored. During the follow‐up period, periapical repair, apical closure and calcification in the apical 4 mm of the root canal was observed. An avulsed immature tooth replanted after a brief extra‐alveolar period and maintained in a viable storage medium may be treated with revascularization.