Bronchoscopy-associated Mycobacterium xenopi pseudoinfections

Mycobacterium xenopi typically accounts for less than 0.3% of all clinical mycobacterial isolates. Over a 37-mo period, 21 (35%) of 60 mycobacterial isolates from a Michigan hospital were identified as M. xenopi. Hospital, laboratory, and bronchoscopy records were reviewed to determine case characteristics, develop a case series, and calculate procedure-specific M. xenopi isolation rates. A case-control study was conducted to elucidate aspects of the bronchoscopy procedure associated with M. xenopi isolation. Bronchoscope cleaning procedures were reviewed, and hospital water systems were cultured. Four isolates were from three patients with disease attributable to M. xenopi. Of the other isolates, specimens obtained by bronchoscopy were more likely to yield M. xenopi than were specimens obtained by other routes (relative risk, 9.7; 95% confidence intervals, 3.2, 29.6). Bronchoscopes were disinfected in a 0.13% glutaraldehyde-phenate and tap-water bath and then were rinsed in tap water. Water from the hot water tank supplying this area yielded M. xenopi. Mycobacteria were cultured from bronchoscopes after disinfection. M. xenopi in the tap water appears to have contaminated the bronchoscopes during cleaning. Adequate disinfection of contaminated bronchoscopes and careful collection of specimens to avoid contamination with contaminated water are essential, both for limiting diagnostic confusion caused by mycobacterial pseudoinfections and for reducing risks of disease transmission.     

Personal social networks and HIV status among women on methadone

This objective of this study was to examine the association between a women's HIV status and specific (IDUs) characteristics of her social networks with respect to (1) number of injection drug users (2) number of drug partners and (3) number of HIV-positive contacts in her personal networks, after controlling for the respondent's demographic characteristics and drug use. Participants were recruited through posted announcements in three methadone clinics in Harlem, New York City. Individuals were considered eligible if they were enrolled as patients in one of the clinics for at least three months. A social network questionnaire modeled after the General Social Survey network section was developed by the investigators. Face-to-face interviews were conducted by trained interviewers and included demographics, drug use, self-reported HIV status of the woman and her network members, and the social network structures. Univariate analyses found that HIV-positive and HIV-negative women had different network profiles. HIV-positive women were more likely to associate with a higher number of current drug users, injection drug users, injection drug users who were HIV-positive, drug partners, drug partners who used injection drugs, and drug partners who were HIV-positive. Multivariate analyses indicated that HIV-positive respondents were more likely to associate with HIV-positive network members than their HIV-negative counterparts. The findings suggest that to better understand the spread of HIV among female drug users and to design more effective HIV/AIDS prevention programmes, efforts should move beyond focusing on individual attributes to address the contextual dynamics of social networks.     

Pigs fed cholesterol neonatally have increased cerebrum cholesterol as young adults

Sixty-eight female neonatal pigs selected for seven (Experiment 1) or eight (Experiment 2) generations for high (HG) or low (LG) plasma cholesterol were used to test the hypothesis that neonatal dietary cholesterol fed during the first 4 or 8 wk of postnatal life increases the cholesterol content of the cerebrum in young adulthood following free access to a high-fat (15%), high-cholesterol (0.5%) diet from 8 to 20 or 24 wk of age. Pigs were removed from their dams at 1 d of age and given free access to a sow-milk replacer diet containing 9.5% coconut fat and 0 or 0.5 % cholesterol. All pigs (except four HG and four LG pigs in Experiment 2, which were deprived of cholesterol throughout the study) were fed the high-fat, high-cholesterol diet from 8 wk to termination at 20 or 24 wk of age. Cerebrum weight and cholesterol concentration were higher in pigs fed cholesterol neonatally than in those deprived of cholesterol neonatally in both experiments, but weight and cholesterol concentration were unaffected by genetic line. Cholesterol concentrations in longissimus and semitendinosus muscles and in subcutaneous fat were unaffected by diet or genetic line. We conclude that dietary cholesterol deprivation during the first 4 to 8 wk of life in piglets is associated with lower cholesterol concentration and total content in the young adult cerebrum than in pigs supplemented with cholesterol in early life. These data support previous observations and suggest the possibility of a metabolic need for neonatal dietary cholesterol in normal brain development.     

Phylogenetic analysis of the Bunocotylinae dollfus, 1950 (Digenea: Hemiuridae)

We investigated the functional determinants of the cutaneous expression of elements of the hypothalamic-pituitary-adrenal axis. In the present work, the presence of adrenocorticotropin (ACTH) peptide in skin of C57/BL6 mouse was demonstrated by reversed-phase HPLC analysis combined with specific radioimmunoassay. ACTH concentration that was low in telogen, increased during anagen in two steps: a rapid phase in anagen I, and a slower rise that reached its peak in anagen VI. Immunofluorescence localized the ACTH antigen to the basal layer of epidermis, outer root sheath of hair follicle and subcutaneous muscle of anagen VI skin. At physiological plasma concentration (10-9 M), ACTH selectively stimulated DNA synthesis in dermis, while pharmacological doses (10-7-10-6 M) inhibited DNA synthesis in both dermis and epidermis. In conclusion, we suggest that local production of ACTH may represent a regulatory element in the control of skin functions including hair growth.     

Ligaments and articular contact guide passive knee flexion

The aim of this study was to test the hypothesis that the coupled features of passive knee flexion are guided by articular contact and by the isometric fascicles of the ACL, PCL and MCL. A three-dimensional mathematical model of the knee was developed, in which the articular surfaces in the lateral and medial compartments and the isometric fascicles in the ACL, PCL and MCL were represented as five constraints in a one degree-of-freedom parallel spatial mechanism. Mechanism analysis techniques were used to predict the path of motion of the tibia relative to the femur. Using a set of anatomical parameters obtained from a cadaver specimen, the model predicts coupled internal rotation and ab/adduction with flexion. These predictions correspond well to measurements of the cadaver specimen's motion. The model also predicts posterior translation of contact on the tibia with flexion. Although this is a well-known feature of passive knee flexion, the model predicts more translation than has been reported from experiments in the literature. Modelling of uncertainty in the anatomical parameters demonstrated that the discrepancy between theoretical predictions and experimental measurement can be attributed to parameter sensitivity of the model. This study shows that the ligaments and articular surfaces work together to guide passive knee motion. A principal implication of the work is that both articular surface geometry and ligament geometry must be preserved or replicated by surgical reconstruction and replacement procedures to ensure normal knee kinematics and by extension, mechanics.     

Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B

BACKGROUND: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer. METHODS: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5-fluorouracil on day 1 of each chemotherapy cycle, with 5-fluorouracil administration repeated on day 8. The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study. RESULTS: At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P<.0001 and two-sided P = .004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average +/- standard error) is 79% +/- 2% for patients on the high-dose arm, 77% +/- 2% for the patients on the moderate-dose arm, and 72% +/- 2% for patients on the low-dose arm; disease-free survival is 66% +/- 2%, 61% +/- 2%, and 56% +/- 2%, respectively. CONCLUSION: Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival.     

Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease

Previously we have formulated transmission models of untreated tuberculosis epidemics (Blower et al., Nature, Medicine 1 (1995), 815-821); in this paper, we present time-dependent uncertainty and sensitivity analyses in order to quantitatively understand the transmission dynamics of tuberculosis epidemics in the absence of treatment. The time-dependent uncertainty analysis enabled us to evaluate the variability in the epidemiological outcome variables of the model during the progression of a tuberculosis epidemic. Calculated values (from the uncertainty analysis) for the disease incidence, disease prevalence, and mortality rates were approximately consistent with historical data. The time-dependent sensitivity analysis revealed that only a few of the model's input parameters significantly affected the severity of a tuberculosis epidemic; these parameters were the disease reactivation rate, the fraction of infected individuals who develop tuberculosis soon after infection, the number of individuals that an infectious individual infects per year, the disease death rate, and the population recruitment rate. Our analysis demonstrates that it is possible to improve our understanding of the behavior of tuberculosis epidemics by applying time-dependent uncertainty and sensitivity analysis to a transmission model.