Methotrexate cerebrospinal fluid pharmacokinetics in a patient with lymphoma treated with methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone

The role of "moderate-dose" systemic methotrexate in preventing central nervous system lymphomatous relapse is unknown. Certain patients with diffuse non-Hodgkin's histologic subtypes have an increased risk of relapse in the central nervous system, and it would be helpful to know if intravenous "moderate-dose" methotrexate might treat or possibly protect the meninges from involvement. In part, the rationale behind the recent regimen of methotrexate, bleomycin, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), and dexamethasone (m-BACOD) is to protect the central nervous system, and the empiric proof of this protection awaits the follow-up results of trials currently underway. In the meantime, the systemic and cerebrospinal fluid pharmacokinetics of moderate-dose intravenous methotrexate were studied in one patient whose histologic subtype places him at high risk for central nervous system involvement. Although the central nervous system levels of methotrexate in this patient never reached 1 X 10(-6) M, the levels exceeded 1 X 10(-7) M for at least 24 hours. The implications of peak dose versus sustained exposure to a lower dose of methotrexate are discussed.     

Adrenomedullin, a new peptide, in patients with insulinoma

BACKGROUND: It has been demonstrated that adrenomedullin, a newly discovered peptide, affects the release of insulin from pancreatic islets cells, suggesting a role in the insulin-regulating system. OBJECTIVE: To investigate whether adrenomedullin secretion is modified in patients with insulin-secreting islet cell tumours. DESIGN: The study was performed in nine patients with surgically treated insulinoma. Circulating adrenomedullin was assayed using a specific radioimmunoassay and its localization and distribution in the tumour were determined by means of immunohistochemistry. RESULTS: Adrenomedullin concentrations were significantly greater in patients with insulinoma (6.6 +/- 3.2 fmol/ml) than in controls (2.1 +/- 1.1 fmol/ml). In six patients monitored before and after surgery, plasma adrenomedullin decreased from 6.3 +/- 2.9 fmol/ml to 3.0 +/- 1.6 fmol/ml. Immunoreactive adrenomedullin was localized exclusively in the tumours cells, whereas stroma, surrounding pancreas parenchyma and major ducts were negative for the peptide. CONCLUSIONS: Our findings indicate that circulating adrenomedullin is increased in insulinoma and that this increase is related to the neoplastic phenotype.     

Knowledge, attitudes, and behavior in children with asthma

Psychosocial aspects of asthma were studied by administering questionnaires to 80 children with asthma and their parents. Overall, children demonstrated high levels of knowledge about asthma, an internal health locus of control, and positive self-concepts. Increased knowledge was associated with more internal health locus of control scores, whereas more positive self-concept scores were associated with more adaptive asthma-related behavior. Children who attended a week-long camp did not differ significantly from comparison children on these measures.     

PDGF-A, PDGF-B, TGFbeta, and bFGF mRNA levels in patients with essential thrombocythemia treated with anagrelide

Plasmatic levels of PDGF-AB, TGFbeta1, and bFGF are increased in patients with essential thrombocythemia (ET) while intraplatelet levels are low for PDGF, normal for TGFbeta, and elevated for bFGF. To evaluate the contribution of gene expression to the dysregulated cytokine levels, we studied platelet PDGF-A, PDGF-B, TGFbeta1, and bFGF mRNA in ET patients before and during anagrelide treatment. We found decreased PDGF-A and PDGF-B, increased TGFbeta1, and normal bFGF mRNA levels. During treatment, mRNA levels remained decreased for PDGF-A, were increased for PDGF-B and normal for TGFbeta1. In untreated patients, protein expression of PDGF paralleled its mRNA levels while different patterns of RNA and protein were found for TGFbeta1 and bFGF.     

Studies with the mutation,diabetes, in the mouse

Summary The mutation, diabetes (db), that occurred in the C57BL/Ks strain of mice is a unit autosomal recessive gene with full penetrance, and causes metabolic disturbances in homozygous mice resembling diabetes mellitus in man. Abnormal deposition of fat at 3 to 4 weeks of age is followed by hyperglycemia, polyuria and glycosuria. The diabetic condition appears to develop in two stages. In the early stage, there are marked increases in the levels of plasma insulin, the rates of lipogenesis, gluconeogenesis, and glucose oxidation, and there is a reduction of-cell granules in the islet of Langerhans with other changes suggestive of a compensating adaptation to increased insulin demand. On the other hand, the late stage is characterized by a near normal level of circulating insulin, a marked decrease in glucose utilization but with a continued high rate of gluconeogenesis. These findings suggest a defect in the peripheral utilization of insulin rather than in the synthesis and release of the hormone from the pancreas.Supported in part by United States Public Health services grant # AM 06871 from the National Institute of Arthritis and Metabolic Diseases and grant # HD 00468 from the National Institute of Human Development.     

Anabolic treatment with GH,IGF-I,or anabolic steroids in patients with HIV-associated wasting

Wasting, and particularly loss of metabolically active lean tissue, contributes to increased mortality, accelerated disease progression, and impairment of strength and functional status in patients with HIV infection. A variety of protein anabolic agents, including growth hormone, insulin-like growth factor-I, testosterone, nandrolone decanoate, oxandrolone, and oxymetholone, have been studied in patients with HIV-associated wasting. Overall, these studies have demonstrated that treatment with protein anabolic agents can increase lean body mass (LBM) and in some cases provide functional benefits and improvements in quality of life. Further research is needed to determine whether such treatment prolongs survival or reduces the overall health care burden of HIV infection. The advances in identification of successful treatments for HIV-associated wasting can provide a model for using these therapies in other catabolic states, including end-stage renal disease, cancer, chronic obstructive pulmonary disease, and cardiac cachexia.     

Treatment with cimetidine, antacid, or placebo in patients with dyspepsia of unknown origin

Patients with dyspepsia of unknown origin were randomly allocated to a controlled double-blind study to examine the symptomatic effect of cimetidine and antacid especially on the relief of pain, nausea, and bloating. Two hundred and twenty-two patients with no previous history of peptic ulcer disease and no evidence of other organic causes of dyspepsia were treated for 6 weeks with placebo, cimetidine, or antacid. The results showed that cimetidine was superior to both placebo and antacid in relieving pain and nausea but not bloating. Certain background factors, such as epigastric pain and symptoms relieved by solid food, had a significant positive influence on the outcome of treatment. When the impact of background factors was taken into account, cimetidine was found to be more effective than both placebo and antacid also with regard to the number of patients who improved in general well-being.     

Changes in gastrointestinal, pancreatic, biliary, and hepatic function with aging

The understanding of "normal" aging of the gastrointestinal tract, pancreas, and hepatobiliary system is confounded by the difficulty in identifying healthy elderly subjects for study. There appear to be predictable changes in gastric secretion and emptying, intestinal and pancreatic morphology, colorectal motility, and hepatic mass and blood flow with aging. However, the functional significance of these changes is variable. Further investigations will be necessary to resolve currently conflicting data, and validation of animal models of aging will enhance future research into these areas.     

Characteristics Associated with Contact with Rodents In,Around, and Outside Homes in Khon Kaen Province,Thailand

Rodents are an important reservoir for zoonotic diseases. To enhance the evidence on the human-rodent interface, this cross-sectional study was conducted in 2011 to investigate characteristics associated with rodent contact in Khon Kaen Province, Thailand. A standardized, interviewer-administered questionnaire elicited information from 201 adults (101 males and 100 females). Overall, 86.6% of participants reported encountering or seeing evidence of rodents in or near the home, whereas 57.2% encountered rodents while working with crops. Encountering rodents in or near the home was positively associated with the number of agricultural activities, whereas encountering rodents during crop work was positively associated with perceiving that disease can be acquired from rodents, the number of food crops grown, the number of agricultural activities, and living in a house with wooden walls. Surprisingly, neither outcome was associated appreciably with gender, age, or setting (urban, forest, or agricultural). These results provide information on the potential risk of rodent-borne zoonoses; this evidence has implications for risk communication strategies in this province and likely elsewhere.     

Efficacy of desloratadine, 5 mg, compared with fexofenadine, 180 mg, in patients with symptomatic seasonal allergic rhinitis.

This is the first U.S.-based study to compare efficacy and safety of desloratadine with fexofenadine in subjects with symptomatic seasonal allergic rhinitis (SAR). In this double-blind study, subjects were randomized to desloratadine, 5 mg (n = 290),fexofenadine, 180 mg (n = 288), or placebo (n = 144) once daily for 15 days. Primary end point was mean change from baseline to study end in morning instantaneous total symptom score (AM NOW TSS) excluding congestion. Secondary measures included change from baseline in the morning/evening reflective TSS (AM/PM PRIOR TSS) excluding congestion, AM NOW individual symptom score (AM NOW ISS) including congestion, and the AM/PM PRIOR ISS including congestion. Subjects self-evaluated their symptoms on a five-point scale. Mean AM NOW TSSs were significantly reduced from baseline at day 15 with desloratadine (p = 0.006) and fexofenadine (p = 0.024) versus placebo. Desloratadine and fexofenadine were not statistically different (p = 0.491); the upper limit of the 95% CI for desloratadine to fexofenadine (0.259) was within the prespecified noninferiority margin of 0.7 U. Decrease in mean AM/PM PRIOR TSS excluding congestion was comparable between desloratadine and fexofenadine (p = 0.405; CI = 0.221) but was significantly greater with both active treatments versus placebo (desloratadine, p < 0.001;fexofenadine, p = 0.003). Desloratadine and fexofenadine provided greater reduction in the AM NOW ISS and AM/PM PRIOR ISS (both including congestion) versus placebo; reductions were comparable between active treatments. All treatments were well tolerated. Desloratadine, 5 mg, and fexofenadine, 180 mg, provide comparable efficacy and tolerability in the treatment of SAR. Both treatments are significantly more effective than placebo.     

Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma

Approximately 60% of patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) are curable with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemoimmunotherapy. Epratuzumab (E) is an unlabeled anti-CD22 monoclonal antibody with efficacy in relapsed DLBCL. This phase 2 trial tested the safety and efficacy of combining E with R-CHOP (ER-CHOP) in untreated DLBCL. A secondary aim was to assess the efficacy of interim positron emission tomography (PET) to predict outcome in DLBCL. Standard R-CHOP with the addition of E 360 mg/m(2) intravenously was administered for 6 cycles. A total of 107 patients were enrolled in the study. Toxicity was similar to standard R-CHOP. Overall response rate in the 81 eligible patients was 96% (74% CR/CRu) by computed tomography scan and 88% by PET. By intention to treat analysis, at a median follow-up of 43 months, the event-free survival (EFS) and overall survival (OS) at 3 years in all 107 patients were 70% and 80%, respectively. Interim PET was not associated with EFS or OS. Comparison with a cohort of 215 patients who were treated with R-CHOP showed an improved EFS in the ER-CHOP patients. ER-CHOP is well tolerated and results appear promising as a combination therapy. This study was registered at www.clinicaltrials.gov as #NCT00301821.     

Laboratory findings in patients with psoriasis, with special reference to immunological parameters, associations with arthropathy and sacro-iliitis

Twenty-five male and 25 female consecutive patients hospitalized because of psoriasis were examined. The clinical and radiographical findings are presented in detail elsewhere. Increased serum IgA, C3, C4, and C3PA concentrations were found in patients both with and without arthropathy and/or sacro-iliitis. Increased IgG concentrations were found in patients without arthropathy, and of C1 inhibitor concentrations in patients with arthropathy and/or sacro-iliitis. IgG and IgA concentrations were lower in patients with arthropathy than in those without, the difference being most significant in patients with arthropathy of large joints. An association was found between increased C4 concentration and sacro-iliitis, increased CRP concentration and sacro-iliitis and increased C3 concentration and phalangeal joint arthropathy. C4 and CRP concentrations were not associated. A close association between CRP and SAA was observed. Our results indicate that psoriatic arthropathy is not a single uniform joint disease, but represents different forms of arthropathy.