Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.      

Selection of strains for quality assessment of the disk induction method for detection of inducible clindamycin resistance in Staphylococci: a CLSI collaborative study

A nine-laboratory collaborative study was conducted to select positive and negative quality assessment control strains for the detection of inducible clindamycin resistance in staphylococci. Four strains of Staphylococcus aureus were tested as unknowns on 10 different days in each laboratory using the recently recommended CLSI (formerly NCCLS) disk diffusion method and the inoculum purity control method. Strains contained either macrolide-lincosamide-streptogramin B (MLSB) resistance genes encoded by erm(A) or erm(C) or a macrolide resistance efflux pump encoded by msr(A). Based upon the results of this study, strain UT 32 (now designated ATCC strain BAA-977) containing erm(A) is recommended as the positive control organism for inducible clindamycin resistance. Strain UT 25 (now designated ATCC BAA-976), which harbors the efflux pump encoded by msr(A), is recommended as the negative control organism.     

Application of Scanning Acoustic Microscopy for Assessing Stress Distribution in Atherosclerotic Plaque

Scanning acoustic microscopy (SAM) was equipped to assess the acoustic properties of normal and atherosclerotic coronary arteries. The SAM image in the atherosclerotic lesion clearly demonstrated that the sound speed was higher than that in the normal intima, and that the variation of elasticity was found within the fibrous cap of the plaque. Young's elastic modulus of each region was calculated and the finite element analysis was applied to derive the stress distribution in these arterial walls. In a case of normal coronary artery, the stress was dominant in the intima and the distribution was rather homogeneous and in a case of atherosclerosis, high stress was concentrated to the relatively soft lesion in the fibrous cap overlying lipid pool. SAM provides information on the physical properties, which cannot be obtained by the optical microscope. The results would help in understanding the pathological features of atherosclerosis. © 2001 Biomedical Engineering Society. PAC01: 8764-t, 8763Df, 8719Xx, 8719Rr     

Comparison of inoculation methods for testing enterococci by using vancomycin screening agar.

One hundred four recent clinical isolates of Enterococcus species were screened for vancomycin resistance by using inocula of 10(5) or 10(6) CFU dispensed by pipet and by use of a cotton swab dipped in a 0.5 McFarland standard organism suspension applied to the surface of brain heart infusion agar containing 6 micrograms of vancomycin per ml. The three inoculation methods were equivalent in the detection of nonsusceptible isolates. The use of swab inoculation was convenient and less costly than the use of micropipets.     

Sociotropic cognition moderates stress-induced cardiovascular responsiveness in women through effects on total peripheral resistance, but not cardiac output.

Although cardiovascular disease (CVD) remains the leading cause of mortality in women, few studies have examined the role of psychosocial factors in its development. This study examined the moderating effects of sociotropic cognition (SC), a need for social acceptance and approval, on psychosocial stress-induced cardiovascular responsiveness (CVR) and affect reactivity in women. Sixty-eight normotensive, college-aged females were randomly assigned to a low or high social threat condition. Measures of systolic, diastolic and mean arterial blood pressures (SBP, DBP and MAP, respectively), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR) and negative affect were collected during rest, and under conditions of high vs. low interpersonal threat. A two-step hierarchical regression analysis was performed to predict all response variables (BPs, HR, CO, TPR and affect). Increases in SBP, DBP, MAP, TPR and negative affect were greater in the high threat than low threat condition. Changes in SBP, MAP and TPR positively covaried with SC under conditions of high interpersonal threat, but showed no significant covariation in the low threat condition. The data suggest that an excessive need for social acceptance may contribute to rises in BP through an increase in TPR, but not CO under conditions of high social threat.     

The health care supervisor and the early communication patterns of new employees: the uncertainty of assimilation

Without a doubt, a supervisor's most valuable resources are the employees placed in trust with that supervisor. It is the challenge of every supervisor to focus the vast energies of this resource on accomplishing the mission of the organization. Within the context of new employees, what happens during those first days of employment may determine how well they will contribute, if at all, to accomplishing this organizational mission. While new employee assimilation has many factors that affect its success or failure, the nature of communication that occurs with the supervisor is critical. As was shown in this study, new employees do, in fact, have a specific set of communication needs of which the supervisor should be cognizant.     

Changes in hemostasis after laparoscopic cholecystectomy

Background: The aim of this work was to study hemostasis in laparoscopic cholecystectomy in order to determine if there are any changes that indicate a greater risk of thrombosis. Methods: The study was carried out in 20 patients who underwent laparoscopic surgery for noncomplicated cholelithiasis. The average age was 59.4 years (range, 34–77). A total of 75% were female. Mean operation time was 70 min (ranges 35–120). Pneumoperitoneum at 14 mmHg was performed on all patients, who were positioned in the 30° reverse Trendelenburg position. Postoperative mobilization was acheived in 24 hs and patients were discharged 48 hs after the operation. The control group was composed of 12 patients, who were evenly distributed by age, sex, and length of surgery. These patients underwent Bassini herniorraphy for inguinal hernia without any complications or relapse. The following hemostatic parameters were studied: prothrombin activity (PA), activated partial thromboplastin time (APTT), fibinogen (Fg), anti-thrombin III (ATIII), plasma fibrinolytic activity (PFA), euglobulin fibrinolytic activity (EFA), and D-dimer (D-D). Samples were obtained at the following times: (a) under basal conditions the day before surgery, (b) preoperatively, (c) at the end of the operation, (d) 24 hs after the operation, and (e) On the 7th day following the operation. Results: No patient showed any clinical manifestations of thromboembolic disease immediately after surgery or during a medium follow-up period of 16 months (range, 15–18 months). All hemostatic parameters values were within normal range in the basal samples of both groups. In both groups, the mean value of PA showed a significant decrease (p < 0.05) in the second, third, and fourth basal samples, returning to normal levels by the fifth determination. The mean value of fibrinogen decreased slightly in the second and third samples, increasing significantly with respect to the fourth and fifth determinations in both groups (p < 0.05). The mean value of APTT in both groups was slightly enhanced in the second and third determinations in relation to the first and fifth. The global activity of fibrinolysis (PFA and EFA) increased significantly in the third sample with respect to the other determinations in the group who had laparoscopic surgery (p < 0.005). Only EFA increased in the control group (p < 0.05). D-D decreased in the preoperative second determination followed by a significant enhancement immediate postoperatively (third), and 24 hs (fourth) (p < 0.05); it returned to normal basal values on the seventh day. No significant differences were found between the two groups. Conclusions: These results indicate that laparoscopic cholecystectomy leads to no greater activation of plasma coagulation than low-risk surgery. On the contrary, the increase of fibrinolytic activity in plasma would extend a certain degree of hypocoagulability during surgery, maintaining it for 24 hs and thus possibly reducing thromboembolic risk in patients undergoing this type of surgery. Received: 25 February 1998/Accepted: 18 August 1998     

The influence of smoking on vitamin D status and calcium metabolism

OBJECTIVE: To assess the influence of smoking on serum parathyroid hormone (PTH), serum vitamin D metabolites, serum ionized calcium, serum phosphate, and biochemical markers of bone turnover in a cohort of 510 healthy Danish perimenopausal women. DESIGN: A cross-sectional study. SETTING: Copenhagen, Denmark. SUBJECTS: Five-hundred-and-ten healthy women aged 45-58 y, included 3-24 months after last menstrual bleeding. None were using hormone replacement therapy. METHODS: The women were grouped according to their current smoking status. The two groups were compared with regard to serum levels of 25-hydroxyvitamin D (25OHD) and 1, 25-dihydroxyvitamin D (1,25-(OH)2D), intact PTH, ionized calcium and phosphate, osteocalcin, as well as urine pyridinolines. Bone mineral density (BMD) was measured with DEXA-scans. Multiple regression analyses were performed to detect the effect of potentially confounding lifestyle factors, such as calcium and vitamin D intakes, alcohol and coffee consumption, sunbathing, and physical exercise. RESULTS: Fifty percent were current smokers. Smokers had significantly reduced levels of serum 25OHD (P=0.02), 1,25(OH)2D (P=0.001), and PTH (P<0.001). There was no difference in serum ionized calcium between smokers and non-smokers. We found a negative effect of smoking on serum osteocalcin (P=0.01), while urinary pyridinolines were similar in the two groups. The small differences in lifestyle between the two groups could not explain these findings. Smokers had small but significant reductions in bone mineral density. CONCLUSIONS: Smoking has a significant effect on calcium and vitamin D metabolism, which is not likely to be explained by other confounding lifestyle factors. The depression of the vitamin D-PTH system seen among smokers may represent another potential mechanism for the deleterious effects of smoking on the skeleton, and may contribute to the reported risk of osteoporosis among smokers. Sponsorship: Grants from the Karen Elise Jensens Foundation.     

The health effects of worksite HIV/AIDS interventions: a review of the research literature

PURPOSE: To examine the individual and organizational health effects of HIV/AIDS interventions conducted at the worksite. SEARCH METHODS: This review is part of a series of reviews that used search methods described in an introductory article. To supplement these methods, HIV/AIDS-specific periodicals were searched to include journals that might not be incorporated in the computerized databases. Twelve of the 20 articles identified through the Centers for Disease Control and Prevention and our own subsequent searches met the criteria and were included in this review. FINDINGS: Ten of the 12 studies reviewed reported positive effects of employee education programs on knowledge or attitudes. Nine of the studies involved health care workers or employees with potential occupational exposure to HIV, and nine lacked a comparison or control group. None of the studies however, examined the effects of policies, manager training, or family education on the organization or person. CONCLUSIONS: Methodologic weaknesses in many of the studies reviewed, coupled with the small number of studies, led us to conclude that the research literature on worksite HIV/AIDS interventions is weak. Impact is, however, plausible. Future research should be directed toward developing valid measures of key variables, controlling for confounding factors, and ultimately examining the impact of organizational factors.