Folate-related genes and omphalocele

Women who take folic acid in the periconceptional period greatly reduce their chances of having a child with a neural tube defect (NTD). Using multivitamins may also reduce the risk of having a child with an omphalocele. In this study, we tested single nucleotide polymorphisms in folate-related enzyme genes for association with omphalocele. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase (MTHFD1), the reduced folate carrier (SLC19A1), and transcobalamin II (TCN2) were examined in 25 children with euploid omphalocele and 59 matched controls. Omphalocele cases were significantly more likely to carry the T allele of MTHFR 677C-->T, a known risk factor for NTDs (odds ratio 3.50, 95% confidence interval 1.07-11.47, P=0.035). The MTHFD1 R653Q, SLC19A1 R27H, and TCN2 P259R polymorphisms showed no significant association with omphalocele. In this small study, the thermolabile variant of MTHFR, 677C-->T, was associated with an increased risk for omphalocele. This variant causes reduced enzyme activity, thus suggesting a mechanism by which multivitamins with folic acid might prevent omphalocele. Additional investigation is required.     

Interleukin-12 is produced by macrophages in response to live or killed Bordetella pertussis and enhances the efficacy of an acellular pertussis vaccine by promoting induction of Th1 cells.

Using a murine respiratory infection model, we have demonstrated previously that infection with Bordetella pertussis or immunization with a whole-cell pertussis vaccine induced antigen-specific Th1 cells, which conferred a high level of protection against aerosol challenge. In contrast, immunization with an acellular vaccine, consisting of the B. pertussis components detoxified pertussis toxin, filamentous hemagglutinin, and pertactin adsorbed to alum, generated Th2 cells and was associated with delayed bacterial clearance following challenge. In this study, we demonstrated that addition of interleukin-12 (IL-12) either in vitro or in vivo enhanced type 1 T-cell cytokine responses induced with an acellular vaccine. Furthermore, the rate of bacterial clearance in mice coinjected with IL-12 and the acellular vaccine was similar to that observed following immunization with a potent whole-cell vaccine. Analysis of IL-12 secretion by murine macrophages suggested that this cytokine is produced in vivo following B. pertussis infection or immunization with the whole-cell vaccine. IL-12 was detected in the supernatants of lung, splenic, and peritoneal macrophages infected with live B. pertussis or stimulated with heat-killed whole B. pertussis or B. pertussis lipopolysaccharide. In contrast, IL-12 could not be detected following stimulation of macrophages with the bacterial antigens filamentous hemagglutinin, detoxified pertussis toxin, and pertactin, the components of acellular vaccines. Our findings suggest that induction of endogenous IL-12 may contribute to the high efficacy of pertussis whole-cell vaccines and also demonstrate that it is possible to attain these high levels of protection with a less reactogenic acellular vaccine incorporating IL-12 as an adjuvant.     

Look-alike threats to unit dose safety

Several similar-appearing (look-alike) unit dose products are shown, including ampuls, syringes, and oral drugs. These look-alikes could potentially lead to drug administration errors when one product is mistaken for another. This problem is briefly discussed and some suggestions for helping reduce the likelihood of errors are made. These include calling on manufacturers to use more varied types of packaging and to refrain from producing several different drugs or dosages in similar packaging. The examples shown illustrate the risks of mistaking different look-alike products for one another and the importance of carefully reading package labels.     

Recidivism of the criminally insane in France: a 22-year follow-up

Characteristics of 1096 recidivistic mentally ill criminal offenders admitted to a specialized hospital in France are described. All subjects were mentally ill and had been judged nonresponsible for an act of crime. Crimes against persons (murder or assault) accounted for 42% of the crimes for which these patients were admitted. The remaining causes of admission were crimes against property (theft) and "victimless" crimes. Subject files indicated a wide difference in cause of admission for violent acts among the different diagnostic categories. Although the frequency of readmission and violent acts at readmission did not change for the group as a whole, they did change between admissions for the different diagnostic groups. Results indicate that differences exist between diagnostic categories of mentally ill offenders in terms of not only the type of crime committed but also the likelihood of recidivism.     

Assessing the risks of Rn exposure: the influence of cigarette smoking

The principal hazard associated with exposure to Rn progeny is lung cancer. However, most lung cancer is caused by smoking, which raises a dual problem of deriving Rn-progeny cancer risk estimates from miner populations who, in large part, are smokers and applying these estimates to the general population whose lung cancer risk, in large part, is determined by smoking habits. We examine current risk estimates for Rn-progeny-induced lung cancer using a cohort life table methodology. Estimates of lifetime probability of dying of lung cancer, average loss in life expectancy due to premature lung cancer death, and loss in life expectancy per premature lung cancer death are calculated for the general population for 1969 and 1978, nonsmokers, and smokers. These calculations demonstrate that such risk estimates are affected by smoking, and by trends in smoking habits, in several ways. Major smoking-related factors in this interaction are the proportion of smokers in the mining population used to derive lung cancer risk estimates, the proportion of smokers in the "general" population, and the assumed interaction (additive or multiplicative) between lung cancer risk, Rn-progeny exposure, and smoking history. At this time the data are not sufficient to recommend one particular modeling approach. However, our evaluation demonstrates that broad statements about Rn-progeny lung cancer risk such as "x cancers/10(6) person working level month," while informative, are incomplete without further specification. Any risk assessment must clearly state the population assumed to be at risk and the risk model assumed to be operating. Finally, the caveats appropriate to these assumptions should also be enunciated.     

Possible savings with appropriate antibiotic prophylaxis

Antibiotic utilization was studied for one month in 52 patients from two surgical wards and one urology ward in an 835 bed teaching hospital. The use of antibiotics was classified as prophylaxis or treatment and the cost of each regimen was determined. The appropriate antibiotic for prophylaxis was chosen according to the surgical procedure and as a result of a literature review. Using cefazolin as the drug of choice in suitable general surgery cases resulted in a justifiable cost for prophylaxis of $17.64 per patient and a possible saving of up to $67.01 per patient (possible total saving of up to $670.05 for the study population). It was concluded that appropriate antibiotic prophylaxis in surgical patients could lead to significant cost savings. Some techniques for improving antibiotic prescribing are reviewed.     

Early Identification of Patient Satisfaction Two Years After Total Knee Arthroplasty

BackgroundThere are numerous reports of poor satisfaction after total knee arthroplasty (TKA), yet there is little known about when to use evidence-based models of care to improve patient outcomes.ObjectiveThis study aimed to characterize longitudinal changes in patient-reported satisfaction after TKA and to identify factors for early identification of poor satisfaction.MethodsFor a cohort of primary TKA surgeries (n = 86), patient-reported outcomes were captured one week before TKA and 6 weeks, 12 weeks, 6 months, and 1 and 2 years after TKA. “Satisfied” versus “not fully satisfied” patients were defined using a binary response (≥90 vs <90) from a 100-point scale. Wilcoxon signed-rank tests identified changes in satisfaction between follow-up times, and longitudinal analyses examined demographic and questionnaire factors associated with satisfaction.ResultsImprovements in satisfaction occurred within the first 6 months after TKA (P ≤ 0.01). Preoperative patient-reported outcome measures alone were not predictive of satisfaction. Key factors that improved longitudinal satisfaction included higher Oxford Knee Scores (odds ratio (OR) = 2.1, P < .001), general health (EQ-VAS, OR = 1.3, P = .03), and less visual analog scale pain (VAS; OR = 1.7, P < .001). Differences in these factors between satisfied and not fully satisfied patients were identified as early as 6 weeks after surgery.ConclusionVisibly different satisfaction profiles were captured among satisfied and not fully satisfied patient responses, with differences in patient-perceived joint function, general health, and pain severity occurring as early as 6 weeks after surgery. This study provides metrics to support early identification of patients at risk of poor TKA satisfaction, enabling clinicians to apply timely targeted treatment and support interventions, with the aim of improving patient outcomes.     

p63 deficiency activates a program of cellular senescence and leads to accelerated aging

The p53 tumor suppressor plays a key role in organismal aging. A cellular mechanism postulated to drive the aging process is cellular senescence, mediated in part by p53. Although senescent cells accumulate in elderly individuals, most studies have relied on correlating in vitro senescence assays with in vivo phenotypes of aging. Here, using two different mouse models in which the p53-related protein p63 is compromised, we demonstrate that cellular senescence and organismal aging are intimately linked and that these processes are mediated by p63 loss. We found that p63(+/-) mice have a shortened life span and display features of accelerated aging. Both germline and somatically induced p63 deficiency activates widespread cellular senescence with enhanced expression of senescent markers SA-beta-gal, PML, and p16(INK4a). Using an inducible tissue-specific p63 conditional model, we further show that p63 deficiency induces cellular senescence and causes accelerated aging phenotypes in the adult. Our results thus suggest a causative link between cellular senescence and aging in vivo, and demonstrate that p63 deficiency accelerates this process.     

Computer technology of the not-too-distant future

In summary, I think we have all seen great strides made in the practice of laboratory medicine and in the sophistication of laboratory computer systems. Now we find ourselves in an era of increasing regulatory scrutiny and decreasing reimbursement, and face new data and information challenges. But I believe that laboratorians have been and will continue to be pioneers in the incorporation of information systems technology into their profession.