Postoperative Cognitive Dysfunction in Middle-aged Patients

Background: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent.

Methods: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living.

Results: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months.     

Health-related quality of life and pressure ulceration assessment in patients treated in the community

Little is known of the impact of pressure ulceration on adult patients' health-related quality of life. The purpose of this study was to determine the impact pressure ulceration has on pressure ulcer patients cared for in the community. A case control study design was used by drawing a random sample from patients receiving community nursing care, stratified by the presence of pressure ulceration. In all, 75 patients with pressure ulcers were compared with 100 controls without ulcers using the four-point ulcer grading scale described by United Kingdom consensus guidelines. Patients were interviewed using the Short Form-36 (SF-36) questionnaire and activities of daily living assessed using the modified Barthel scale. Patients with pressure ulcers had significantly poorer physical function (mean difference (d) = 37.6, 95% CI 28.6-46.6, p < 0.001) and social functioning (d = 33.9, 95 % CI 24.0-43.9, p < 0.001) than published age- and sex-matched normative data from the United Kingdom. The difference between cases and controls was much smaller in these domains, with neither approaching statistical significance. After adjustment for age and gender, scores for bodily pain were poorer in patients with no ulceration (d = -10.5, 95% CI - 20.6 to - 0.4, p = 0.042) indicating greater pain in these patients compared with the cases with ulceration. Activities of daily living determined by the modified Barthel scale showed reduced self-care (d = -7.6, 95% CI -12.5 to - 2.7, p = 0.010) and mobility (d = -9.2, 95% CI -14.6 to - 3.8, p = 0.001) in patients with pressure ulceration. The overall ability to perform these activities was also significantly poorer in this group (d = -16.3, 95% CI -27.3 to -5.3, p = 0.004). While patients with pressure ulceration experience some deficits in their health-related quality of life compared with a normal population, these differences are similar to those experienced by other patients receiving community nursing care.     

Modic changes following lumbar disc herniation

Only a small proportion (20%) of patients with LBP can be diagnosed based on a patho-anatomical entity. Therefore, the identification of relevant subgroups, preferably on a patoanatomical basis, is strongly needed. Modic changes have been described by several authors as being closely linked with LBP. The aims of this study were to describe the prevalence of Modic changes, their development as well as their association to LBP, previous disc contour, and surgery in patients with previous severe sciatica. This is a longitudinal cohort study where the patients were recruited from an RCT comparing two active conservative treatments, the 181 patients, who at baseline had radicular pain in or below the knee; all underwent a physical examination and MRI. MRI’s, pain history and physical examination of 166 patients were obtained at follow-up 14 months later. The prevalence of Modic changes type 1 increased from 9% at baseline to 29% at follow-up. At that time, a strong association between Modic changes and non-specific LBP was noted. Apparently, Modic changes type 1 was more strongly associated with non-specific lumbar pain than Modic changes type 2. The development of new Modic changes was closely related to the level of a previous disc herniation. A lumbar disc herniation is a strong risk factor for developing Modic changes (especially type 1) during the following year. Furthermore, Modic changes are strongly associated with LBP.     

Combined Administration of Meningococcal Serogroup B Outer Membrane Vesicle Vaccine and Conjugated Serogroup C Vaccine Indicated for Prevention of Meningococcal Disease Is Safe and Immunogenic

MenBvac and Menjugate are safe and efficacious vaccines. The purpose of this study was to evaluate safety and immunogenicity of the combination (MenB/C) of the lyophilized active components of the conjugated group C vaccine Menjugate when reconstituted with the full liquid group B outer membrane vesicle vaccine MenBvac compared to MenBvac and Menjugate given separately. At 6-week intervals, healthy adults were given one dose of MenB/C followed by two doses of MenBvac (MenB/C group), three doses of MenBvac (MenB group), or one dose of Menjugate and two doses of placebo (MenC group). Injection site reactions were frequent in all groups. However, most reactions were short lasting and mild or moderate in intensity, and the vaccines were found to be well tolerated, with no vaccine-related serious adverse events. MenB/C was immunogenic with regard to both serogroup B and C meningococci. Both the serum bactericidal assay and the enzyme-linked immunosorbent assay analyses showed that the immune responses of the combination vaccine were similar to the immune responses of its separate components MenBvac and Menjugate for both serogroup B and C. In conclusion, the combined MenB/C vaccine is safe and immunogenic. The two vaccines do not interact negatively with each other and can easily be administered in the same syringe. The induced immune responses suggest that the combined vaccine is likely to confer protection against systemic group B disease caused by the vaccine strain as well as against group C meningococcal disease.     

Lipopolysaccharide contamination of beta-lactoglobulin affects the immune response against intraperitoneally and orally administered antigen

BACKGROUND: Microbial components in the environment are potent activators of the immune system with capacity to shift the active immune response towards priming of Th1 and/or Th2 cells. Lipopolysaccharide (LPS), a cell-wall component of Gram-negative bacteria, is extensively present in food products like cow's milk. It is not well established, however, how this presence of LPS affects oral tolerance induction. METHODS: We studied the effect of LPS contamination in a commercial preparation of the cow milk protein beta-lactoglobulin (beta-LG) on antigen-specific immune responses. IgG1/IgG2a production upon intraperitoneal immunization without adjuvant was measured, and oral tolerance induction against beta-LG after administration of either an aqueous solution or water-in-oil (w/o) emulsion of beta-LG was evaluated. RESULTS: LPS contamination of beta-LG provoked a beta-LG-specific IgG2a response, as well as an enhanced beta-LG-specific IgG1 response upon intraperitoneal immunization. Oral tolerance induction to beta-LG was induced by aqueous solutions of beta-LG with and without LPS administration. Conversely, oral administration of w/o-emulsified beta-LG prevented oral tolerance to beta-LG only when the beta-LG was contaminated with LPS. CONCLUSIONS: LPS contamination of an aqueous protein solution does not affect oral tolerance induction, whereas LPS present in emulsion prevents oral tolerance induction towards the food protein.     

Trends in HIV prevalence among public sexually transmitted disease clinic attendees in the Western region of the United States (1989-1999)

OBJECTIVES: Using data from anonymous unlinked testing of routinely collected sera, trends in HIV are compared among sexually transmitted disease patients in 4 Western urban centers. METHODS: Between 1989 and 1999, remnant sera obtained for routine syphilis testing from 256,819 patient visits to Denver, Los Angeles, San Francisco, and Seattle clinics were tested for HIV antibodies in an unlinked survey. HIV antibody test results were linked to anonymous demographic and risk information abstracted from the medical record. RESULTS: Overall cumulative HIV seroprevalences among women and among men who had sex exclusively with women were < or = 2%, declined over time, and did not exceed 8% among those who injected drugs. In contrast, cumulative HIV seroprevalences among men who have sex with men ranged from 13% in Seattle to 30% in San Francisco and declined a mean of 2.1% (95% CI, 1.6, 2.6) to 2.8% (CI 2.6, 3.1) per year, after adjustment. CONCLUSIONS: HIV infection declined over time across counties. Relative levels of HIV differed little by demographic and behavioral risk group despite differences in the severity of each county's epidemic. Because of the unique contribution of unlinked serosurveillance studies in monitoring these trends, their reinstitution in high-risk settings should be considered.     

Genetic linkage between erm(B) and vanA in Enterococcus hirae of poultry origin

Vancomycin-resistant enterococci (VRE) have frequently been isolated from Norwegian poultry production following the prohibition of the glycopeptide growth promoter avoparcin since 1995. In the present study, a close genetic linkage between the vanA and erm(B) determinants in an Enterococcus hirae isolate of poultry origin is demonstrated, a result that indicates a mechanism for co-selection and maintenance of vancomycin resistance in absence of selective pressure from avoparcin. A total of 36 vanA-positive enterococci of poultry origin, also phenotypically resistant to erythromycin and/or tetracycline, were analyzed by PCR for identification of erm and tet resistance determinants. An E. hirae isolate harbored erm(B) and tet(K), and in this isolate vanA and erm(B) were located on a BamHI fragment of an approximately 50-kb plasmid. Approximately 3 kb of this fragment was amplified by PCR with vanA and erm(B) primers. Sequence analysis of the region between erm(B) and vanZ of Tn1546 showed a truncated IS1216V inserted downstream of the erm(B) stop codon, aligned with a conserved copy of the 3'-inverted terminal repeat of Tn1546. Mating experiments with the E. hirae isolate as donor and E. faecalis JH2-2 as recipient did not result in any transconjugants, indicating that the vanA/erm(B)-carrying plasmid was nonconjugative under the given experimental conditions.     

Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion

Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injuries in order to restore the lost liver mass and ensure maintenance of the multiple liver functions. Major players in the regeneration process are mature residual cells, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired by liver-damaging agents, hepatic progenitor cells are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells may generate new hepatocytes and biliary cells to restore liver homeostasis. In recent years, hepatic progenitor cells have been the subject of increasing interest due to their therapeutic potential in numerous liver diseases as alternative or supportive/complementary tools to liver transplantation. While the first investigations on hepatic progenitor cells have focused on their origin and phenotypic characterization, recent attention has focused on the influence of the hepatic microenvironment on their activation and proliferation. This microenvironment comprises the extracellular matrix, epithelial and non-epithelial resident liver cells, and recruited inflammatory cells as well as the variety of growth-modulating molecules produced and/or harboured by these elements. The cellular and molecular responses to different regenerative stimuli seem to depend on the injury inflicted and consequently on the molecular microenvironment created in the liver by a certain insult. This review will focus on molecular responses controlling activation and expansion of the hepatic progenitor cell niche, emphasizing similarities and differences in the microenvironments orchestrating regeneration by recruitment of progenitor cell populations or by replication of mature cells.     

Assessment of HER‐2/neu overexpression and/or gene amplification in breast carcinomas: should in situ hybridization be the method of choice?

AIMS: Since the release of Herceptin, pathology laboratories have been requested to test breast carcinomas for HER-2/neu overexpression and/or gene amplification. Standardized IHC and FISH are mandatory in order to get reliable results, but there are problems even with standardized procedures. We decided to evaluate the two methods to determine which, or possibly if both, should be the primary investigation method(s). METHODS AND RESULTS: The material consisted of 215 primary invasive breast carcinomas with complete clinical follow-up of 15 years. HER-2/neu protein expression was determined for all specimens, whereas FISH for assessing HER-2/neu gene signal number was done in 165 cases. IHC was double-checked with two or three different antibodies in 35 tumours, including all cases with discrepancies between IHC and FISH. Among these, there were discrepancies in a third. IHC overexpression of HER-2/neu was found in 13% and gene amplification in 18%. Discordance between IHC and FISH was found in 11 cases (8%). Five tumours were IHC+/FISH- and six were IHC-/FISH+. IHC and FISH positive cases as well as FISH only positive tumours had the same prognosis respecting survival. Tumours with >2 but 4 gene signals per nucleus. In contrast, cases with IHC overexpression without gene amplification had a prognosis similar to that of IHC-/FISH- tumours. CONCLUSIONS: From our data, it seems to be more important to assess HER-2/neu gene amplification than IHC overexpression. Failure to detect FISH-amplified (IHC-negative) cases would have an adverse effect on the survival of these patients. On the other hand, IHC overexpression tumours without gene amplification appear to belong to a better prognostic group, and failure to detect them would probably not have a negative effect on the survival of these women. Even though FISH is a more complex and expensive procedure, it should be considered the method of choice for primary assessment of HER-2/neu status in breast cancer patients.