A. Cats

Epidemiology of osteoarthritis: Zoetermeer survey. Comparison of radiological osteoarthritis in a Dutch population with that in 10 other populations.

The prevalence of mild and severe radiological osteoarthritis was investigated in a random sample of 6585 inhabitants of a Dutch village. Radiographs were graded 0-4 according to the criteria described by Kellgren and Lawrence. The prevalence of radiological osteoarthritis increased strongly with age and was highest for cervical spine (peak: men 84.8%, women 84.3%), lumbar spine (peak: 71.9%, women 67.3%), and distal interphalangeal joints of the hands (peak: men 64.4%, women 76%). Prevalence did not exceed 10% in sacroiliac joints, lateral carpometacarpal joints, and tarsometatarsal joints. Severe radiological osteoarthritis (grade 3 or grade 4) was uncommon under age 45; in elderly persons the prevalence of severe radiological osteoarthritis did not exceed 20% except for the cervical and lumbar spine, distal interphalangeal joints of the hands and, in women only, metacarpophalangeal joints, first carpometacarpal joints, first metatarsophalangeal joints, and knees. Overall, differences between men and women were small except for hips and knees; however, severe radiological osteoarthritis was found in a higher proportion in most of the joints in women. Our data were compared with data from similar population surveys. The slope between joint involvement and age was strikingly constant for most of the joints. Differences between populations were mainly differences in level. These differences of prevalence of radiological osteoarthritis may be attributed to interobserver differences--that is, different criteria used to establish radiological osteoarthritis, in addition to genetic or environmental factors, or both.

Clinical significance of rheumatoid factors in early rheumatoid arthritis: results of a follow up study.

Serum rheumatoid factors (RF) were measured yearly in 135 women with rheumatoid arthritis by the Waaler-Rose and latex fixation tests and IgM, IgA, and IgG RF were measured by enzyme linked immunosorbent assays (ELISAs). The patients were followed up from an early phase of the disease for a mean duration of six years. Patients with a persistently positive RF test, irrespective of the type of test used, had more radiological abnormalities, more disease activity, worse functional ability, more extra-articular manifestations, and needed more treatment with second line drugs than patients with persistently negative or variably positive and negative test results during the follow up. Increased RF levels, especially a high level of IgA RF within three years of the onset of symptoms, was prognostic for a more severe disease outcome six years after the onset of symptoms.

Decision analysis in the surgical treatment of colorectal cancer due to a mismatch repair gene defect

Background: In view of the high risk of developing a new primary colorectal carcinoma (CRC), subtotal colectomy rather than segmental resection or hemicolectomy is the preferred treatment in hereditary non-polyposis colorectal cancer (HNPCC) patients. Subtotal colectomy however implies a substantial decrease in quality of life. To date, colonoscopic surveillance has been shown to reduce CRC occurrence. Aims: To compare the potential health effects in terms of life expectancy (LE) for patients undergoing subtotal colectomy or hemicolectomy for CRC. Methods: A decision analysis (Markov) model was created. Information on the 10 year risk of CRC after subtotal colectomy (4%) and hemicolectomy (16%) and stages of CRCs detected within a two year surveillance interval (32% Dukes’ A, 54% Dukes’ B, and 14% Dukes’ C) were derived from two cohort studies. Five year survival rates used for the different Dukes stages (A, B, and C) were 98%, 80%, and 60%, respectively. Remaining LE values were calculated for hypothetical cohorts with an age at CRC diagnosis of 27, 47, and 67 years, respectively. Remaining LE values were also calculated for patients with CRC of Dukes’ stage A. Results: The overall LE gain of subtotal colectomy compared with hemicolectomy at ages 27, 47, and 67 was 2.3, 1, and 0.3 years, respectively. Specifically for Dukes’ stage A, this would be 3.4, 1.5, and 0.4 years. Conclusions: Unless surveillance results improve, subtotal colectomy still seems the preferred treatment for CRC in HNPCC in view of the difference in LE. For older patients, hemicolectomy may be an option as there is no appreciable difference in LE.

EFFECTS OF SUPPLEMENTAL DIETARY CALCIUM ON QUANTITATIVE AND QUALITATIVE FECAL FAT EXCRETION IN MAN

Oral calcium supplementation is thought to be a useful interventional agent to decrease colon cancer risk. This is supposedly due, at least in part, to the binding of bile acids and fatty acids by calcium in the colon, thus prohibiting the damaging effects of these substances to the epithelium. To determine the effects of calcium supplementation on fecal fat excretion, 24 subjects kept a fat and calcium constant diet for one week and were supplemented with either 0, 2 or 4 g elemental calcium as calcium carbonate in a double-blind fashion. At the end of the week 72-hour feces was collected, and total fat, neutral fat, fatty acids and the ratio of polyunsaturated and saturated fatty acids (P/S ratio) were measured. Calcium dose-dependently increased the percentual excretion of total fat as related to fat intake: 6.8 +/- 0.9% during 0 g, 7.4 +/- 1.0% during 2 g and 10.2 +/- 1.4% during 4 g, r = 0.44, p = 0.03. This was due to increased fatty acid excretion, excretion of neutral fat was not affected, nor was the P/S ratio. It is concluded that calcium supplementation modestly increases fecal fatty acid excretion. No adverse metabolic effects are to be expected from this in case of long-term calcium supplementation in subjects at increased risk for colon cancer.

Renal findings in rheumatoid arthritis: clinical aspects of 132 necropsies.

Renal abnormalities in 132 necropsied patients with rheumatoid arthritis were studied. Clinical findings before death included extra-articular manifestations of the disease (86% of patients), systemic vasculitis (6%), and uraemia (23%). Necropsy findings included nephrosclerosis (90%), systemic vasculitis (14%) with kidney involvement in 8%, amyloidosis (11%), membranous glomerulopathy (8%), and focal glomerular disease (8%). Association with clinical data suggests that both rheumatoid and non-rheumatoid disease may play a part in the cause of these abnormalities.

Is surveillance of the small bowel indicated for Lynch syndrome families

Background: Small bowel cancer (SBC) is one of the tumours associated with Lynch syndrome (LS). To advise on screening for this tumour it is paramount to be informed about the lifetime risk. The aim of this study was to calculate the lifetime risk of SBC in LS and to identify possible risk factors. Methods: Clinical and pathological data were collected on 1496 proven or putative carriers of a mismatch repair gene mutation from 189 families. Kaplan-Meier survival analysis was used to calculate the lifetime risk and to assess potential risk factors. Results: 28 (1.9%) of the 1496 (putative) mutation carriers were identified with SBC. The median age at diagnosis was 52 years (range 23–69 years). The lifetime risk of developing SBC was 4.2%. There was no difference in risk between males and females (log rank: p = 0.2470), or between MLH1 and MSH2 mutation carriers (log rank: p = 0.2754). SBC was not observed in MSH6 mutation carriers (n = 203). The previous occurrence of colorectal cancer and a family history of SBC did not increase the risk significantly. Conclusions: Approximately, one out of 25 mutation carriers will develop SBC during life. No specific risk factors were identified. The risk appeared to be too low to advise screening by means of an invasive burdensome procedure like double balloon enteroscopy. However, screening by a non-invasive procedure (videocapsule endoscopy) might be considered if future studies will show its cost effectiveness. In patients with unexplained abdominal complaints and/or unexplained iron deficiency anaemia SBC should be considered.

Psoriasis and arthritis.

SummaryIn a population survey of 3659 persons aged 20 years or older, no association was found between psoriasis and rheumatoid arthritis. Inflammatory, degenerative and soft tissue rheumatic diseases occurred in 59% of the psoriatics and 46% of the controls. However, the mean number of rheumatological diagnoses in the psoriatics was 1.1 and in the controls 1.3. Features of psoriasis were found in 41 individuals (1.1%). Features of inflammatory arthritis (RA + past-polyarthritis) were established in 5% and 2.2% of the psoriatics and the controls respectively, but this difference is not significant. Because patients with psoriasis have complaints associated with the locomotor system more frequently than non-psoriatic people, it seems likely that the referral rate of the former to special clinics is higher.

Psoriasis and arthritis: I. A population study

In a population survey of 3659 persons aged 20 years or older, no association was found between psoriasis and rheumatoid arthritis. Inflammatory, degenerative and soft tissue rheumatic diseases occurred in 59% of the psoriatics and 46% of the controls. However, the mean number of rheumatological diagnoses in the psoriatics was 1.1 and in the controls 1.3. Features of psoriasis were found in 41 individuals (1.1%). Features of inflammatory arthritis (RA + past-polyarthritis) were established in 5% and 2.2% of the psoriatics and the controls respectively, but this difference is not significant. Because patients with psoriasis have complaints associated with the locomotor system more frequently than non-psoriatic people, it seems likely that the referral rate of the former to special clinics is higher.

PHASE-II AND PHARMACOKINETIC STUDY OF LOBAPLATIN IN PATIENTS WITH RELAPSED OVARIAN-CANCER

In phase I studies, lobaplatin showed activity in ovarian cancer patients pretreated with platinum. A phase II trial with lobaplatin was performed in patients with refractory or relapsed ovarian cancer to define activity and pharmacokinetics. Twenty-two patients were treated with lobaplatin administered as an intravenous bolus every 4 weeks. Dependent on creatinine clearance (CRCL) patients received 30 or 50 mg m-2 lobaplatin as the starting dose. Twenty-two patients received 78 courses (median 3, range 1-6). In eight patients total platinum (TPt) in plasma and urine, free platinum (FPt) in plasma ultrafiltrate (both measured by atomic absorption spectrometry) and lobaplatin in plasma ultrafiltrate measured (by high-performance liquid chromatography) were measured. Toxicity was confined to mild nausea and vomiting, mild leucocytopenia (WHO grade 3 in 18% of the courses), and renal function-related thrombocytopenia (WHO grade 3/4 in 53% of the courses). A correlation was found between CRCL and reduction in platelet count (r = -0.77; P < 0.01). No renal toxicity was encountered. Five of 21 evaluable patients (24%) achieved a response (four complete remissions and one partial remission). Remissions occurred mainly in patients who relapsed more than 6 months after primary treatment. The median survival from start of lobaplatin treatment was 8 months. The mean areas under the curve (AUCs) were 4.2 +/- 0.5, 3.0 +/- 0.6, and 3.2 +/- 1.1 h mgl-1 for TPt, FPt and lobaplatin respectively. The free platinum fraction (FPt/TPt) was initially very high, indicating low protein binding. FPt was essentially present as intact lobaplatin. Four hours after infusion 54 +/- 5% and 24 h after infusion 74 +/- 3% of the lobaplatin dose was excreted in the urine. In conclusion, lobaplatin is a platinum compound with anti-tumour activity in patients with relapsed ovarian cancer, especially in those who have platinum-sensitive tumours. The main toxicity of lobaplatin is thrombocytopenia and its dose should be corrected according to renal function.

Rheumatoid factors in rheumatoid arthritis and vasculitis

SummaryTo study the occurrence of rheumatoid factors (RF) in relation to the activity of rheumatoid arthritis and the occurrence of vasculitis, RF of IgM, IgA, and IgG classes were measured in sera from 35 patients with definite or classic rheumatoid arthritis (RA) using ELISA. For 26 patients, the RF levels were studied longitudinally and compared with changes in the articular index. Although IgM RF was occasionally found in patients without RA, IgA and/or IgG RF were almost exclusively associated with RA. The titers of IgM, IgA, and IgG RF were significantly higher in sera from patients with clinically diagnosed rheumatoid vasculitis than in sera from patients without vasculitis. No significant correlation between changes in the articular index and changes in titer of any class-specific RF could be found for the group of RA patients as a whole. However, in individual patients, increases or decreases in IgM and IgG RF titer were significantly correlated with an increase or decrease in the articular index.