[Objective evaluation procedures in cases of possible diagnostic error].
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Biomedical subjects
Publications and source records attributed to A Knol.
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Cisplatin (CDDP) is an extremely active drug in the treatment of germ-cell tumours. Earlier, we found an unexpected inverse correlation between the total amount of sulfhydryl groups and CDDP sensitivity in a panel of 3 human germ-cell-tumour and 3 colon-carcinoma cell lines. Major components of the sulfhydryl groups are glutathione and metallothionein (MT). We further investigated a possible role of MT in the CDDP sensitivity of germ-cell tumours. MT levels and functionality of the germ-cell-tumour and colon-carcinoma cell lines were found to be inversely correlated with CDDP sensitivity. No difference in sub-cellular localization of MT could be observed among the types of cell lines. In agreement with the in vitro data, immunohistochemical detection of MT was high in 11/14 primary human germ-cell tumours and low in 7/7 human colon carcinomas. MT-protein expression in primary germ-cell tumours did not discriminate between responding and non-responding patients. As compared with the primary tumours, MT-protein expression decreased in 5/7 post-chemotherapy residual vital tumours or remained undetectable (2/7). MT-protein expression in the germ-cell tumours was not related to total p53-protein expression. In summary, over-expression of MT was found in germ-cell tumours, both in cell lines and in human tumours. Although MT-protein over-expression seems to be associated with the CDDP sensitivity of germ-cell tumours, MT-protein expression in primary germ-cell tumours did not differ between responding and non-responding patients and therefore cannot be used to predict response to chemotherapy.
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AIMS: To determine whether there is an association between use of fluoroquinolones and tendinitis in a large population under everyday circumstances. METHODS: A retrospective cohort study was carried out in a dynamic population. Data came from the IPCI-database which consists of all data on consultations, morbidity, prescriptions and other interventions, as registered by GPs in a source population of approximately 250 000 persons. For this study data were collected from 41 general practices in the period from January 1st, 1995 through December 31st, 1996. All persons treated with either fluoroquinolones, amoxicillin, trimethoprim, cotrimoxazole or nitrofurantoin were followed from the first day of treatment until the outcome of interest, death, transfer to another practice, or end of the study period, whichever came first. The risk window was defined as the legend duration +1 month. Potential cases were defined as a registration of a tendinitis or tendon rupture. Patients with a history of tendinitis or tendon rupture, preceding trauma or inadequate diagnoses were excluded on the basis of a review of the patient profiles and additional clinical data, blinded as to the exposure status. Results were adjusted for age, gender, concurrent corticosteroid exposure and number of GP visits. RESULTS: There were 1841 users of fluoroquinolones and 9406 users of the other antibacterial drugs with an average duration of 9 and 7 days, respectively. Tendinitis or tendon rupture was registered in 97 profiles, but after review only 22 complied with the case definition. The adjusted relative risk of tendinitis to fluoroquinolones was 3. 7 (95%CI: 0.9-15.1) for Achilles tendinitis and 1.3 (95%CI: 0.4-4.7) for other types of tendinitis. Achilles tendinitis to ofloxacin had a relative risk of 10.1 (95%CI: 2.2-46.0) and an excess risk of 15 cases per 100 000 exposure days. CONCLUSIONS: Although the numbers in our study are small, our results suggest that some fluoroquinolones may increase the risk of Achilles tendinitis, and that this risk increase is highest for ofloxacin.
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Patients with hypertension can be treated by inhibition of angiotensin-converting enzyme (ACE). A major side-effect of the use of ACE-inhibitors is the development of a life threatening dyspneu by angioedema of oropharyngeal and laryngeal tissue. This severe complication is caused by interaction of ACE-inhibitors with prostaglandin and bradykinin metabolisms. Minor manifestations of angioedema can be followed by severe reactions. It is wise to stop ACE-inhibitors immediately.
Four cases were reported to the Netherlands Pharmacovigilance Foundation LAREB of Achilles tendinitis, as a suspected adverse reaction to pefloxacin; the patients were two men of 64 years old, one of 33 and one of 76 years old. More than twenty cases of tendinitis have previously been described in the literature in association with pefloxacin and various other fluoroquinolone derivatives; tendon rupture was a frequent complication. In the data base of the WHO Collaborating Centre for International Drug Monitoring tendon disorders are a very rare reaction, with the exception of fluoroquinolone derivatives. More information is needed with regard to the frequency of tendinopathy during the use of pefloxacin and the other drugs in this group. Achilles tendon rupture is an serious condition, often requiring surgical treatment. Patients using a fluoroquinolone derivative should be informed of the risk of developing tendinitis and tendon rupture.
We compared a newly available nonabsorbable monofilament ophthalmic suture, 9/0 Novafil (Davis & Geck), with 10/0 nylon (Alcon), currently the most popular suture for closure of corneoscleral sections. Surgery was performed on nine rats and ten rabbits. In each case a 120 degrees corneoscleral section was made in each eye and closed with interrupted sutures of 9/0 Novafil in one eye and 10/0 nylon in the other. We compared their handling qualities during surgery, as well as their effect on postoperative wound inflammation. In addition we examined the suture material from each eye of the rats by scanning electron microscopy (SEM) after 3 months, and we compared the surgically induced astigmatism in the rabbits in the two suture groups. Both suture materials were easy to handle and well tolerated. Nylon sutures from six of the eight rat eyes studied showed SEM evidence of surface disintegration after 3 months, whereas all the Novafil sutures remained intact.