Weight loss in patients with hematological neoplasias is associated with immune system stimulation

Summary Weight loss is the main symptom of so-called tumor cachexia. The pathogenetic mechanisms underlying cachexia are poorly understood; however, it appears that enhanced formation of cytokines such as interferon- and tumor necrosis factor- are involved. In 94 patients suffering from hematological neoplasias we compared body weight changes with serum neopterin, tryptophan, and kynurenine. Biochemical changes, the formation of neopterin, the degradation of tryptophan are closely related to interferon- activity. The majority of our patients had increased neopterin and decreased tryptophan concentrations. Weight loss was seen particularly in patients with higher neopterin and lower tryptophan values. An association between higher neopterin levels and greater weight loss was apparent at study entry and during the follow-up of patients. Our data support the concept that weight loss is closely linked to endogenous interferon- activity.Abbreviations NHL non-Hodgkin's lymphoma - HD Hodgkin's disease - MM multiple myeloma - MGUS monoclonal gammopathy of unknown significance - IFN- interferon- - TNF- tumor necrosis factor-     

Neopterin as a new biochemical marker in the clinical assessment of ulcerative colitis

In previous publications we showed that neopterin, a pyrazino-pyrimidin compound, represents a biochemical marker for the assessment of cellular immune responses. We thought that the evaluation of this marker molecule might enable insight into the activity of cellular immune responses underlying ulcerative colitis (UC). Evaluation of urinary neopterin excretion in 25 consecutive untreated UC patients revealed striking correlations between neopterin levels and the severity of disease: elevated levels were observed in 9 out of 9 patients with moderately severe to severe, in 3 of 4 with mild and in none of 12 patients with quiescent disease. Further evidence for a correlation between disease activity and neopterin excretion was obtained on the basis of long-term follow-up studies performed in 4 cases. These studies indicated normalization of neopterin levels when clinical remission was achieved. Thereafter, the relative significance of neopterin excretion for determination of clinical stage was assessed by linear correlation analyses and was compared with conventional clinical parameters such as anemia, number of motions per day, raised temperature, ESR and extent of bowel involvement. The logarithm of neopterin excretion and the extent of bowel involvement were the two single parameters most closely related to the clinical stage of ulcerative colitis. We, therefore, conclude that evaluation of neopterin excretion in ulcerative colitis patients represents a new and useful tool for the clinical monitoring of disease activity.     

Direct interaction of the Fanconi anaemia protein FANCG with BRCA2/FANCD1

Fanconi anaemia (FA) is an autosomal recessive genetic disorder characterized by progressive bone marrow failure, multiple congenital abnormalities, and an increased risk of cancer. FA cells are characterized by chromosomal instability and hypersensitivity to DNA interstrand crosslinking agents. At least eight complementation groups exist (FA-A to G), and the genes for all of these except FA-B have been cloned. Functional linkage between the FA pathway and genes involved in susceptibility to breast cancer has been demonstrated by the interaction of the FANCA and FANCD2 proteins with BRCA1, and the discovery that the FANCD1 gene is identical to BRCA2. Here we have used the yeast two-hybrid system to test for direct interaction between BRCA2 or its effector RAD51 and the FANCA, FANCC and FANCG proteins. We found that FANCG was capable of binding to two separate sites in the BRCA2 protein, located either side of the BRC repeats. Furthermore, FANCG could be co-immunoprecipitated with BRCA2 from human cells, and FANCG co-localized in nuclear foci with both BRCA2 and RAD51 following DNA damage with mitomycin C. These results demonstrate that BRCA2 is directly connected to a pathway that is deficient in interstrand crosslink repair, and that at least one other FA protein is closely associated with the homologous recombination DNA repair machinery.     

Functional properties of crossed spinocerebellar tract neurones with cell bodies in the S1 segment.

Functional properties of a crossed spinocerebellar tract with cell bodies located in laminae VII and IX of the S1 segment were investigated using intracellular recording. The neurones were found to be excited by group I and II muscle afferents and afferents of skin, joint and interosseus nerves. Volleys from group II muscle afferents and cutaneous afferents evoked inhibition in these cells. It is concluded that S1 spinocerebellar neurones convey a similar type of information to that of dorsal spinocerebellar tract and ventral spinocerebellar tract neurones but integrate it in a different way.     

Drug usage guidelines, Part 2: Analysis of program outcome

The effect of integrating a Drug Usage Guidelines (DUG) program with a hospital formulary system was analyzed. Significant changes were observed in both the number of requests submitted to the P & T Committee and the number of drugs added to the formulary after implementation of the DUG program. Failure to follow the DUG submission protocol, particularly with respect to the requirement for supportive clinical data from the primary literature, led to delayed consideration and eventual withdrawal of several highly promoted drug products. The initial involvement of physicians in the planning and implementation of the DUG program has been an important factor in the continued success of the program.     

Memory impairment associated with progression of Huntington's disease

Huntington's Disease (HD) has been described as one example of a "subcortical" dementia, characterized by slowed cognitive processing and impairment of memory. We examined the relationship between slowed cognitive processing and memory impairment as a function of disease progression in patients with HD. Results from three experiments suggest that in the early stages of HD there is slowed cognition with intact memory acquisition and retrieval processes. In later stages, cognition is further slowed and specific impairments of memory become evident. Thus, memory impairment in HD would appear to change qualitatively with progression of the disease.     

Soft tissue pseudotumor following intramuscular injection of “DPT”: a pitfall in magnetic resonance imaging

We report the time-dependent magnetic resonance imaging (MRI) changes that resulted from an intramuscular injection of a commonly-used pediatric sedation regimen (DPT). These changes at the site of injection consist of a focal abnormality characterized by a slight increase in signal intensity on T1 weighted images and markedly increased signal intensity on T2 weighted images. Alterations in signal are detectable almost immediately after the injection and progress over the first 31 hours. This abnormality, which could be mistaken for real disease, persists up to 36 days following injection.     

Strengthening the formulary system by implementing a drug usage guidelines program

The development and implementation of a Drug Usage Guidelines (DUG) program in a 1,200-bed, federal teaching hospital are described. The program was designed to promote effective formulary control through established procedures for the review and evaluation of drugs submitted to the Pharmacy and Therapeutics (P & T) Committee for addition to the formulary. The procedures required the submission of the DUG and an oral presentation to the Committee prior to any final vote on the request. Anticipated potential benefits of the DUG program are to: (1) stimulate rational drug therapy, (2) provide reliable drug information to the professional staff in a usable format, (3) promote a thorough evaluation of therapeutic agents before approving for formulary inclusion, and (4) provide physician-generated guidelines for use as criteria in drug utilization review audits.