Clinical significance of low cobalamin levels in older hospital patients.

BACKGROUND: It is still a commonly held belief that many of the frequently found low cobalamin (Cbl, vitamin B12) levels in older people do not represent deficiency and are therefore without clinical significance and should not be treated. In this study this notion will be challenged. METHODS: In this prospective observational cohort design we studied 28 patients aged 65 years and older with low plasma Cbl (< or =150 pmol/l). A number of haematological (Hb, MCV, five- and six-lobed granulocytes), metabolic (plasma levels of methylmalonic acid and homocysteine), and gastrointestinal (plasma pepsinogen A and C and protein-bound and free Cbl absorption) parameters, and the response to Cbl treatment, were measured. Cbl deficiency was considered to be present when at least one of the following three criteria was fulfilled: (1) haematological or metabolic abnormalities compatible with Cbl deficiency; (2) Cbl malabsorption or atrophic gastritis; (3) a response to Cbl supplementation. RESULTS: Haematological or metabolic abnormalities were identified in 27 patients. Atrophic gastritis and Cbl malabsorption were identified in, respectively, 15 and 23 patients. Each treated patient showed a haematological or metabolic response to Cbl supplementation. All patients were considered Cbl deficient: 18 patients (64%) fulfilled three criteria of Cbl deficiency, eight (29%) fulfilled two criteria and two (7%) fulfilled one criterion. CONCLUSIONS: According to the generally accepted and a wide variety of criteria, we found that older patients with low Cbl levels were cobalamin deficient. Therefore, these patients should receive Cbl supplementation.

Follow-up regimen of differentiated thyroid carcinoma in thyroidectomized patients after thyroid hormone withdrawal.

UNLABELLED: For differentiated, nonmedullary thyroid carcinoma, postsurgical ablation of thyroid remnants and treatment of residual tumor and metastases with 131I is a potentially curative therapy. The aim of this study was to optimize the diagnostic protocol for the follow-up of thyroidectomized patients. METHODS: Two hundred fifty-four patients (187 females, 67 males; mean age, 45 y; range, 8-83 y) were studied retrospectively for a mean follow-up period of 2.7 y (range, 1-12.5 y). An evaluation study consisted of a low-dose 131I diagnostic procedure under hyperthyroid conditions (thyroid-stimulating hormone > 30 MicroU/mL), 201TI scintigraphy, and measurement of thyroglobulin (Tg) under hypothyroid conditions. A total of 254 preablation studies (1 study per patient) and 586 follow-up studies (average number of studies, 2.3 per patient) were evaluated. RESULTS: Before ablation, low-dose 131I screening was useful to estimate the size of the thyroid remnant. Low Tg levels (<10 pmol/L) indicated the absence of metastases. After ablation, undetectable Tg levels indicated the absence of tumor recurrence. When Tg levels were high (>10 pmol/L), local recurrence or metastases were always observed, providing the basis for additional high-dose 131I therapy. In these patients, 201TI imaging did not provide a significant contribution to patient management. In the case of autoantibodies against Tg, both low-dose 131I screening and 201TI scintigraphy may be advocated to allow an aggressive diagnostic work-up. CONCLUSION: Tg plays a key role in follow-up and in making decisions to treat patients with differentiated thyroid carcinoma. The role of 201TI imaging is very limited. In patients with negative low-dose 131I screening, 201TI scintigraphy can be considered when Tg is elevated or cannot be evaluated because of autoantibodies against Tg. Under such circumstances, administration of a therapeutic 131I dose without 201TI imaging can be considered.

Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250.

Clinical tumor targeting studies with chimeric monoclonal antibody G250 (cG250) in renal cell carcinoma (RCC) patients indicated the potential use of this antibody for radioimmunotherapy. Here we report on a phase I activity dose escalation study to determine the safety, the maximum tolerable dose (MTD), and the possible therapeutic potential of 131I-labeled cG250 in patients with progressive metastatic RCC. All patients (n = 12) received a diagnostic i.v. infusion of 5 mg of cG250 labeled with 222 MBq of 131I. If accumulation of the antibody in metastatic lesions was observed, patients were hospitalized and a second, therapeutic, i.v. infusion of 5 mg of cG250 labeled with a high dose of 131I was administered (n = 8). Three patients per dose level were entered, starting at 1665 MBq/m2. If no dose-limiting toxicity occurred, the study continued at the next dose level (555 MBq/m2 increase). Most patients experienced mild nausea without vomiting. No other complaints were reported during hospitalization. In two of two patients who received a dose of 2775 MBq/m2, grade IV hematological toxicity was observed, which was defined as dose limiting. Thus, the MTD was set at 2220 MBq/m2. In one patient (2220 MBq/m2), stable disease (lasting 3-6 months) was achieved, whereas another patient (2220 MBq/m2) showed a partial response that is ongoing (>9 months). The minor responses observed in this phase I trial in patients with an advanced stage of RCC are encouraging and warrant further study in a phase II setting at the MTD to determine the efficacy of radioimmunotherapy for metastatic RCC.

Metastatic follicular carcinoma of the thyroid: reappearance of radioiodine uptake.

Dedifferentiation of well-differentiated thyroid carcinoma is a well-known phenomenon that may lead to the disappearance of radioiodine uptake in tumors and the inability to treat patients with radioiodine. We report a patient in whom the 131I uptake progressively diminished to such low levels after a cumulative dose of 31.5 GBq that further 131I administration was considered nonbeneficial. Thereafter, metastases in the lungs and skeleton progressed. Because of the absence of any other therapeutic options, nearly 2 yr later we decided to reperform 131I measurements and scanning under hypothyroid conditions. All known metastatic lesions this time showed intense 131I uptake, more than 10-fold the previously measured values. High-dose 131I treatment was restarted.

99mTc-pertechnetate uptake measurement in the rabbit knee-joint. II. Kinetics of 99mTcO-4 in normal and arthritic rabbit knee-joints.

The kinetics of 99mTechnetium pertechnetate (99mTcO-4) in the rabbit knee-joint were studied by external counting of the radio-isotope after intravenous injection. We studied joints with antigen-induced arthritis in the acute and chronic phase of joint inflammation as well as non-inflamed joints. In both inflamed and non-inflamed joints, a rapid increase in radioactivity was followed by a plateau lasting for at least one hour. The time needed to reach 95% of the plateau count rate (tp) was significantly increased in inflamed as compared with non-inflamed knee-joints. Moreover, tp values were significantly higher in acutely than in chronically inflamed joints. No correlation was found between 99mTcO1 uptake and tp values. The study of kinetics of 99mTcO-4 in the rabbit knee-joint provides information additional to quantitation of inflammation by 99mTcO-1 uptake measurements, since kinetic data characterize the type of joint inflammation.

Detection and quantification of experimental joint inflammation in mice by measurement of 99mTc-pertechnetate uptake.

We adapted the method of 99mTc-pertechnetate (99mTc) uptake measurements to the mouse knee for detection and quantification of arthritis because clinical assessment of mouse knee-joint arthritis is not reliable. The main points to ensure reproducibility of measurements were proper fixation and positioning of the knee and careful shielding of the rest of the body from the gamma-radiation detector. 99mTc uptake was calculated as the mean of three countings. The variation coefficient of these countings ranged from 0.007 to 0.082 in non-arthritic joints and from 0.025 to 0.081 in arthritic joints. Arthritis was scored as the ratio of the 99mTc uptake in the right knee versus that in the left knee. This ratio averaged 1.06 (S.D. 0.05) in non-arthritic mice 20 minutes after 99mTc administration i.p. On the second day after induction of arthritis in the right knee, this ratio ranged from 1.44 to 1.96; this was significantly higher (P less than 0.005) than in non-arthritic mice, and the increase remained significant during at least 20 days. 99mTc uptake measurements seem to be a useful method to detect and quantify arthritis of the knee joint in mice.

Antigen handling in antigen-induced joint inflammation: kinetics of a second intra-articularly injected dose of antigen in an already established antigen-induced joint inflammation.

The fate of a second intra-articularly (i.a.) injected dose of bovine serum albumin (BSA) in an already established BSA-induced knee-joint inflammation was compared with that of a paired first arthritis-inducing injection of the same dose of BSA into the contralateral knee of immunized rabbits. External counting of i.a. radiolabelled BSA indicated more rapid initial elimination but approximately two-fold increase in long-term retention of BSA after a second i.a. injection as compared with a first one. Direct counting of dissected joint structures confirmed these data and localized the retained BSA predominantly in hyaline articular cartilage, menisci and ligaments, both after a first and after a second injection. Since the protocol used in these studies per se excluded systemic factors as possible determinants of the difference in antigen retention observed, local alterations in the already inflamed joint caused this difference. Control studies indicated that both humoral immune factors and non-specific inflammatory changes within the chronically inflamed joint determine the phenomenon. Local alterations in an immune-induced chronically-inflamed joint increase its antigen-binding capacity, a mechanism of possible relevance to the chronic course and the occurrence of exacerbations characteristic of some forms of human arthritis.

Antigen-induced arthritis: inflammation and antigen handling.

Data are summarized indicating that the degree and duration of antigen induced arthritis (AIA) influences handling of intra-articular (i.a.) antigen. Long term antigen retention was less in chronic as compared with transient joint inflammation, whereas i.a. antigen was cleared more rapidly from the joint in severe than in moderate AIA. In addition, the presence of ungoing AIA enhances initial elimination of i.a. injected antigen from the joint.