Variability of exhaled breath condensate leukotriene B4 and 8-isoprostane in COPD patients.

The reproducibility of exhaled breath condensate (EBC) mediators is not well documented in chronic obstructive pulmonary disease (COPD). This study assessed within assay (WA), within (WD) and between day (BD) reproducibility of EBC leukotriene B4 (LTB4) and 8-isoprostane. Three EBC samples were collected from 24 COPD patients separated by 1 h and 1 wk, to assess WD and BD reproducibility. WA reproducibility was assessed by sample analysis by enzyme immunoassay in triplicate. WA coefficient of variation for LTB4 and 8-isoprostane (18.2% and 29.2%, respectively) was lower than corresponding values for WD (47.7% and 65.3%, respectively) and BD (75.7% and 79.1%, respectively). Repeatability coefficient for 8-isoprostane and LTB4 assays were 18.6 pg/ml and 13.2 pg/ml, respectively. Group mean differences for WD and BD were small and statistically nonsignificant. Using the Bland Altman method, there were wide limits of agreement for WD (-51.6 to 47.2 for 8-isoprostane and -31.8 to 31.4 for LTB4) and BD reproducibility (-61.4 to 75.7 for 8-isoprostane and -29.3 to 38.6 for LTB4). This is the first study to fully report the variability of EBC 8-isoprostane and LTB4 in COPD. WA variability and group mean changes were small. However, we observed considerable WD and BD variability for these biomarkers.

Osteoporosis disease management in a rural health care population: hip fracture reduction and reduced costs in postmenopausal women after 5 years.

A 5 year observational study is reported which reviews the implementation of the Geisinger Health System Osteoporosis Disease Management Program. This program includes Osteoporosis Clinical Practice Guidelines, physician and allied health care provider education, community education, and a bone density testing program. All women over the age of 55 years enrolled in the Geisinger Health Plan (GHP) from 1996 to 2000 were included in this analysis. The guidelines led health care providers to increase the evaluation of osteoporosis via bone density measurements and to increase the prescription treatment of osteoporosis. Most importantly, the age-adjusted incidence of hip fractures fell significantly in the entire group as well as in several age strata (65-74, 75-84 and 85+ years). Compared with a predictive model of no intervention, there was an overall reduction in health care costs to GHP estimated to be US$7.8 million over a 5 year period. This report is the first to suggest that an organized Osteoporosis Disease Management Program delivered by a health care system can result in increased evaluation and treatment of osteoporosis with a resultant significant decrease in hip fractures while decreasing the total direct costs of care to a health plan.

Evaluation of preoperative ProstaScint scans in the prediction of nodal disease.

Diagnostic methods are limited for detecting microscopic soft tissue metastases in patients with prostate cancer. Previous studies using (111)Indium Capromab Pendetide (ProstaScint scan) analyzed patients with extensive localized tumor (prostate specific antigen (PSA) >20 ng/ml) not optimal for surgical therapy. We evaluated the role of the ProstaScint trade mark scan in a preoperative population to provide histological documentation and to assess its utility in a surgical population. A total of 22 preoperative patients, underwent a ProstaScint scan. The mean preoperative PSA was 16.0 ng/ml (range 3.9-33 ng/ml). The mean Gleason score at biopsy was 6.9 (range 6-9). Each patient underwent a radical retropubic prostatectomy and bilateral pelvic lymph node dissection, which included resection of both obturator and common iliac lymph nodes. Histologic analysis of the resected lymph nodes provided the standard of comparison with the ProstaScint scan. The results of the scan and pathology for all 22 patients were compared with the bilateral obturator and iliac nodes, creating 88 data points. Nine areas (10%) were positive on the scan. One of these (11%) was a true positive while the other eight (89%) were false positives. Seventy-nine areas (90%) were negative on scan results. Of these, five areas (6%) were false negatives and 74 areas (94%) were true negatives. The scan yielded a sensitivity of 17%, specificity of 90%, negative predictive value (NPV) of 94% and a positive predictive value (PPV) of 11%. The high false positive rate and low PPV of ProstaScint scans overestimates metastatic lymph nodes disease, and is not useful when used preoperatively.

The peripherally inserted central catheter (PICC): a prospective study of its natural history after cubital fossa insertion.

A prospective cohort study was undertaken to describe the natural history of the cubital fossa peripherally inserted central catheter (PICC), determine which factors influenced the hazard of complication and develop a standard methodology for evaluation of a PICC service. A total of 4349 patient days of PICC observation were analysed using survival analysis techniques. The median time to PICC removal for a complication was 60 days. The most common complications were phlebitis, malposition and tip migration. Complications usually occurred during the first week. There was only one episode of line-related sepsis. Size 3 French gauge catheters had a complication rate of 7.3 per 1,000 line days compared to 14.2 for 4 French catheters (hazard rate 1.26 90% CI 1.02 to 1.55). PICCs requiring two or more attempts at insertion were more likely to develop complications than those inserted at the first attempt: 20 per 1,000 line days vs 10.5 but the confidence intervals were wide (hazard rate 1.91, 90% CI 0.90 to 4.05). Operator (amongst the four experienced operators who inserted all PICCs), arm of placement, or medial or lateral placement in the cubitalfossa did not influence PICC survivaL

Disease management for diabetes mellitus: impact on hemoglobin A1c.

OBJECTIVE: To describe outcomes associated with a health maintenance organization (HMO)-sponsored disease management program for diabetes. STUDY DESIGN: Descriptive study that compared outcomes of patients with diabetes before and after entry into a disease management program. PATIENTS AND METHODS: The study was conducted in a mixed-model HMO with 275,000 members. The disease management program included a Steering Committee, clinical guidelines, primary care site-based diabetes education, coverage of glucose meters and strips, simplified outcomes reporting, and support of clinical leadership. Data were obtained for 5332 continuously enrolled patients who voluntarily entered the disease management program; 3291 patients (61.7%) received 3 months or more of follow-up, and 663 (12.4%) received 1 year or more of follow-up. The primary outcomes were change from baseline of mean hemoglobin A1c (HbA1c) and medication use after 3 months and 1 year of follow-up. RESULTS: The mean baseline HbA1c for all program participants was 8.51% (standard deviation [SD] = 1.86%). At 3 months of follow-up, the mean HbA1c value for 2794 of 3291 participants (84.0%) had decreased to 7.41% (SD = 1.33%; P = .0001). At 1 year of follow-up, the HbA1c value, available for 605 of 663 patients (91.3%), had decreased from a mean baseline value of 8.76% (SD = 1.87%) to 7.41% (SD = 1.24%; P = .0001). Among 663 patients with 1 year of follow-up, insulin use increased from 30.0% to 31.6%, and sulfonylurea use decreased from 40.7% to 33.8%. Troglitazone and metformin use increased from 7.7% and 23.8%, respectively, to 16.4% and 28.8%, respectively. CONCLUSIONS: Our data suggest that a multifaceted disease management program for diabetes can result in significant short-term improvements in glycemic control in the managed care setting. While the improvement in the HbA1c was accompanied by an increase in the use of insulin, troglitazone, and metformin, we suggest the influence of disease management on glycemic control among our participants was significant and should be considered in future studies in this area.

Tuberculin testing: placement and interpretation.

1. The Mantoux skin test is the currently accepted standard for determination of infection with Mycobacterium tuberculosis. It is less than 100% sensitive and specific; however, no better method currently exists. 2. Placement and interpretation of the tuberculin skin test should be provided by health practitioners who are qualified as a result of education and experience. 3. Always produce a "wheal" when administering a tuberculosis (TB) skin test. If a significant amount of the dose leaks from the injection site or the injection is administered subcutaneously, the test should be repeated immediately at another site. 4. Induration, not erythema, should be considered in interpreting the TB skin test. The absence of induration with erythema greater than 10 mm in diameter may indicate the injection was made too deeply and retesting is indicated. 5. A history of BCG vaccination is not a contraindication to PPD skin testing. The larger the reaction to PPD, the greater the probability of TB infection.

Lymphocytosis of large granular lymphocytes in three dogs.

The clinical course and hematologic changes of three dogs with lymphocytosis of cells morphologically resembling large granular lymphocytes are presented. Hemograms from all dogs showed leukocytosis with marked lymphocytosis. Lymphocytes were characterized by abundant basophilic cytoplasm containing distinct granules which varied in size and number. Electron microscopically the granules were membrane-bound with an electron-dense core. Lymphocytes from one dog were positive for alkaline phosphatase activity, and lymphocytes from another dog were positive for alpha naphthyl butyrate esterase activity. Lymphocytes from one dog were positive for surface receptors for the crystalline fraction portion of gamma immunoglobulins.

Characterization of serum growth hormone (GH) and insulin-like growth factor I in active acromegaly with minimal elevation of serum GH.

In most patients with acromegaly basal serum GH concentrations are elevated and remain above 5 micrograms/L after oral glucose administration. In some patients, however, serum insulin-like growth factor I (IGF-I) concentrations are elevated with only minimal elevations of serum GH. We studied the serum GH and IGF-I of two such patients to determine whether these peptide hormones are normal in this clinical situation. The serum GH of these patients was found to bind normally to receptors of the IM-9 lymphocyte. The elution pattern of IGF-I extracted from the patients' serum was similar to that of (Thr59) human IGF-I after passage through a Bio-Rad P-60 column in 0.5 M acetic acid. The IGF-I was further characterized by isoelectric focusing and C18 reverse phase high pressure liquid chromatography (HPLC). The isoelectric points of the IGF-I components were similar to those of IGF-I in normal serum. The IGF-I in one patient had two components by HPLC, while that of the other patient had only one major component. The IGF-I components isolated by HPLC were normally active in stimulating [3H] alpha-aminoisobutyric acid uptake by normal human fibroblasts. The elevated serum IGF-I concentrations of these two patients were GH dependent. Transsphenoidal adenomectomy in one patient resulted in a decline in serum IGF-I to a high normal concentration. Lowering the serum GH to subnormal concentrations by the administration of the somatostatin analog SMS 201-995 (Sandoz) restored normal IGF-I concentrations in the second patient. We conclude that the GH and IGF-I of these two patients cannot account for their apparent enhanced GH responsiveness.

Thyroid abnormalities in patients previously treated with irradiation for acne vulgaris.

Of 1,203 patients who received radiation treatment for acne vulgaris between 1940 and 1968, 302 patients were recalled and examined, 121 at Geisinger Medical Center and the remainder by their local physicians. Radiation records were reviewed on all patients. Lead-rubber and cones had been used as shielding. Mean age at the time of exposure was 21 years and mean total exposure was 692 R. Palpable nodular thyroid disease was found in eight patients (2.6%). Of these, thyroid carcinoma was detected in two patients (0.66%). Although the number of patients examined was small, the incidence of carcinomas was unexpectedly high. We conclude that follow-up examination is worthwhile for patients previously treated by irradiation for acne vulgaris.

Epidermal growth factor: identification of a new hormone in human urine.

Epidermal growth factor is a polypeptide hormone that was previously identified only in mice. It causes proliferation and keratinization of epidermal tissues. An immune affinity column extraction technique was used to purify partially a substance from human urine which was similar to the mouse hormone in both its biological activity and immunoreactivity.

Dissimilation of Methionine by Achromobacter starkeyi.

Methionine was decomposed by some bacteria which were isolated from soil. The sulfur of the methionine was liberated as methanethiol, and part of this became oxidized to dimethyl disulfide. Detailed studies with one of these cultures, Achromobacter starkeyi, indicated that the first step in methionine decomposition was its oxidadative deamination to alpha-keto-gamma-methyl mercaptobutyrate by a constitutive amino acid oxidase. The following steps were carried out by inducible enzymes, the synthesis of which was inhibited by chloramphenicol. alpha-Keto-gamma-methyl mercaptobutyrate was split producing methanethiol and alpha-keto butyrate which was oxidized to propionate. The metabolism of propionate was similar to that described for animal tissues; the propionate was carboxylated to succinate via methyl malonyl coenzyme A, and the succinate was metabolized through the Krebs cycle.

Dissimilation of methionine by a demethiolase of Aspergillus species.

Enzyme preparations obtained from the mycelium of Aspergillus species broke down methionine by co-dissimilation. The deaminase and demethiolase activities of crude extracts were increased 100-fold by precipitation with (NH(4))(2)SO(4) and column chromatography on diethylaminoethyl cellulose. The enzyme acted on d-methionine but not on l-methionine. The enzyme was labile: it was inactivated by oxygen and ascorbic acid but ethylenediaminetetraacetic acid and mercaptoethanol preserved its activity. Enzyme activity decreased even at 4 and -30 C and was lost rapidly above 45 C. It was most rapid at 35 C and at pH 8.0 to 9.0. For the following reasons, it was concluded that deamination and demethiolation of methionine were effected by the same enzyme: both activities increased equally at each stage of purification; ammonia, methanethiol, and alpha-keto butyric acid were formed in amounts equivalent to the amount of methionine dissimilated; the K(m) and optimal pH for formation of both keto acid and methanethiol were the same; both activities remained in the same fractions that were separated by electrophoresis and the activities were equivalent. The purified enzyme demethiolated alpha-keto methionine and alpha-hydroxy methionine and split the sulfur linkage of ethionine but did not cleave cystathionine. Few amino acids were deaminated. The enzyme was sensitive to some carbonyl and sulfhydryl reagents and was relatively insensitive to heavy metals other than Hg(++). The K(m) was 1.3 x 10(-3) to 1.5 x 10(-3)m at pH 7.0. No requirement for cofactors was noted, and attempts to dissociate the enzyme, including dialysis with hydroxylamine, were unsuccessful.