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Biomedical subjects

P Krause

Publications and source records attributed to P Krause.

At least 19 recordsLinked to original sources

Perioperative factors influencing patient outcome after liver transplantation.

We have previously shown that the development of multiple organ dysfunction syndrome (MODS) after liver transplantation significantly reduced patient survival. Therefore, the question arises of which are the most prominent perioperative donor and recipient factors leading to MODS after transplantation. In total, 634 patients with 700 liver transplants were analyzed. Donor factors included age, increase in transaminases, sex mismatch, requirement for catecholamines, intensive care time, histology, and macroscopic graft appearance. Recipient factors included Child classification, preoperative gastrointestinal (GI) bleeding, mechanical ventilation, hemodialysis, and requirement for catecholamines. MODS was defined by more than two severe organ dysfunctions. The cumulative 2 to 9-year patient survival was 90.9% in patients developing less than 3 severe organ dysfunctions following transplantation. Survival decreased to 60.3% in patients with MODS. Neither any of the donor factors nor the duration of cold ischemia (CIT) was associated with an increase in MODS or decrease in survival. On the other hand, duration of warm ischemia, amount of blood loss, requirement for red packed blood cells, and reoperation had an influence on the development of MODS (40%-56%) and decreased patient survival to 58%-69%. Preoperative therapy with catecholamines, GI bleeding, mechanical ventilation, and hemodialysis were associated with the development of MODS in 54%-88%. Patient survival following MODS decreased to 50%-74%. Initial graft function had a slight influence on the development of MODS, but no influence on the long-term patient survival. In conclusion, patient survival was significantly influenced by the development of postoperative MODS. The most prominent factors in this were recipient and intraoperative ones. No major influence was observed for donor factors, CIT, and initial graft function. Prevention of MODS will further improve the outcome after liver transplantation.

Age Factors↗

Spinal epidural abscess following blunt pelvic trauma.

A 17-year-old patient with pre-existing grade II spondylolisthesis of L5/S1 sustained a partial disruption of the left sacroiliac joint with haematoma of the iliac muscle after a fall. The haematoma probably led to occlusion of the left ureter, resulting in a urinary tract infection. After initial conservative treatment the patient developed fever and radicular pain of the left leg. Magnetic resonance imaging (MRI) revealed a left-sided epidural abscess at L5/S1, which had probably spread from the infected iliac haematoma along the injured sacroiliac joint. Prompt surgical drainage and antibiotic coverage with cefuroxime and flucloxacillin led to rapid clinical improvement. Staphylococcus aureus was identified as the pathogen. At follow-up 6 months postoperatively all symptoms had resolved, while MRI still revealed residual osseous oedema of the sacroiliac joint. The haematoma of the iliac muscle resolved without surgical intervention.

Accidental Falls↗

Hepatocyte-supported serum-free culture of rat liver sinusoidal endothelial cells.

BACKGROUND/AIMS: A major problem in rat liver endothelial cell culture is the rapid loss of cells after 48 h. This study aimed to develop a protocol that allowed easy maintenance and proliferation of sinusoidal endothelial cells in serum-free culture for 5-6 days. METHODS: Cells isolated from adult rat liver by collagenase digestion were purified by centrifugal elutriation and cultured on glutaraldehyde-crosslinked collagen. RESULTS: At high plating densities cells could be maintained serum-free for 6 days in the presence of hydrocortisone and basic fibroblast growth factor; at lower plating densities medium had to be supplemented with additional growth-promoting factors. Conditioned medium of adult rat hepatocytes proved to be the most effective growth stimulus; it increased thymidine incorporation, DNA content and cell number per dish with a half-maximal effect at 20% (v/v). Cell proliferation was also observed with either vascular endothelial growth factor, phorbol ester or conditioned media from FAO or HEPG2 liver cell lines provided the cultures were additionally supplemented with 1% newborn calf serum. Vascular endothelial growth factor was detected in all conditioned media. In the absence of hepatocyte-conditioned medium, 1% serum helped to maintain cultures; it itself exerted a low proliferative effect. Higher serum concentrations (>5%), however, led to cell loss after 48 h. The numerous sieve plates of 6-h-old cells progressively disappeared during culture and were replaced by randomly distributed pores, which later grouped together at cell-cell borders. More than 90% of the cells endocytosed acetylated low-density lipoprotein. CONCLUSIONS: The study shows that cultured hepatocytes secrete growth-promoting substances that stimulate in vitro endothelial cell proliferation in the absence of serum; this effect could be mimicked by the combined addition of vascular endothelial growth factor and 1% serum. The new media formulations should facilitate future research on liver endothelial cells in mono- or coculture.

Animals↗

Reintroduction of influenza A to a nursing building.

We report an outbreak of influenza A from a four-building veterans' facility in King, Wisconsin. Influenza was isolated in 154 of 721 residents over a 121-day period. Building A had 2 cases, no isolates for 40 days, followed by 27 cases. Building B had 25 cases, no isolates for 75 days, followed by 4 cases. Building C had 23 cases, no isolates for 14 days, followed by 17 cases. Influenza A may be reintroduced to a nursing building. Surveillance with contingency plans for restarting of prophylaxis must continue for the duration of influenza in the community.

Aged↗

Elevated expression of hormone-regulated rat hepatocyte functions in a new serum-free hepatocyte-stromal cell coculture model.

The specific performance of the adult hepatic parenchymal cell is maintained and controlled by factors deriving from the stromal bed; the chemical nature of these factors is unknown. This study aimed to develop a serum-free hierarchical hepatocyte-nonparenchymal (stromal) cell coculture system. Hepatic stromal cells proliferated on crosslinked collagen in serum-free medium with epidermal growth factor, basic fibroblast growth factor, and hepatocyte-conditioned medium; cell type composition changed during the 2-wk culture period. During the first wk, the culture consisted of proliferating sinusoidal endothelial cells with well-preserved sieve plates, proliferating hepatic stellate cells, and partially activated Kupffer cells. The number of endothelial cells declined thereafter; stellate cells and Kupffer cells became the prominent cell types after 8 d. Hepatocytes were seeded onto stromal cells precultured for 4-14 d; they adhered to stellate and Kupffer cells, but spared the islands of endothelial cells. Stellate cells spread out on top of the hepatocytes; Kupffer cell extensions established multiple contacts to hepatocytes and stellate cells. Hepatocyte viability was maintained by coculture; the positive influence of stromal cell signals on hepatocyte differentiation became evident after 48 h; a strong improvement of cell responsiveness toward hormones could be observed in cocultured hepatocytes. Hierarchial hepatocyte coculture enhanced the glucagon-dependent increases in phosphoenolpyruvate carboxykinase activity and messenger ribonucleic acid (mRNA) content three- and twofold, respectively; glucagon-activated urea production was elevated twofold. Coculturing also stimulated glycogen deposition; basal synthesis was increased by 30% and the responsiveness toward insulin and glucose was elevated by 100 and 55%, respectively. The insulin-dependent rise in the glucokinase mRNA content was increased twofold in cocultured hepatocytes. It can be concluded that long-term signals from stromal cells maintain hepatocyte differentiation. This coculture model should, therefore, provide the technical basis for the investigation of stroma-derived differentiation factors.

Animals↗

Mushroom body ablation impairs short-term memory and long-term memory of courtship conditioning in Drosophila melanogaster.

We have evaluated the role of the Drosophila mushroom bodies (MBs) in courtship conditioning, in which experience with mated females causes males to reduce their courtship toward virgins (Siegel and Hall, 1979). Whereas previous studies indicated that MB ablation abolished learning in an olfactory conditioning paradigm (deBelle and Heisenberg, 1994), MB-ablated males were able to learn in the courtship paradigm. They resumed courting at naive levels within 30 min after training, however, while the courtship of control males remained depressed 1 hr after training. We also describe a novel courtship conditioning paradigm that established long-term memory, lasting 9 days. In MB-ablated males, memory dissipated completely within 1 day. Our results indicate that the MBs are not required for learning and immediate recall of courtship conditioning but are required for consolidation of short-term and long-term associative memories.

Animals↗

Mortality following isolation of various respiratory viruses in nursing home residents.

OBJECTIVE: To compare mortality following isolation of influenza A to mortality following isolation of other respiratory viruses in a nursing home. SETTING: The Wisconsin Veterans Home, a 688-bed skilled nursing facility for veterans and their spouses. PARTICIPANTS: All residents with respiratory viral isolates obtained between 1988 and 1999. DESIGN: Thirty-day mortality was determined following each culture-proven illness. RESULTS: Thirty-day mortality following isolation of viral respiratory pathogens was 4.7% (15/322) for influenza A; 5.4% (7/129) for influenza B; 6.1% (3/49) for parainfluenza type 1; 0% (0/26) for parainfluenza types 2, 3, and 4; 0% (0/26) for respiratory syncytial virus (RSV); and 1.6% (1/61) for rhinovirus. CONCLUSIONS: Mortality following isolation of certain other respiratory viruses may be comparable to that following influenza A (although influenza A mortality might be higher without vaccination and antiviral agents). The use of uniform secretion precautions for all viral respiratory illness deserves consideration in nursing homes.

Aged↗

Non-influenza respiratory viruses may overlap and obscure influenza activity.

OBJECTIVE: To report the number and timing of influenza A isolates, as well as overlapping respiratory viruses. Co-circulating respiratory viruses may obscure the determination of influenza activity. DESIGN: Prospective clinical surveillance for the new onset of respiratory illness followed by viral cultures during seven separate influenza seasons. SETTING: The Wisconsin Veterans Home, a skilled nursing facility for veterans and their spouses. RESULTS: Influenza A isolates were encountered in greater numbers than non-influenza A isolates during three seasons. Seasonal variability is striking. In December 1992, we identified a large outbreak of respiratory illness. Influenza type B was cultured from 102 residents. In December 1995, influenza A was cultured from 285 people in Wisconsin. At that time, we identified outbreaks of respiratory illness in two of our four buildings. Based on statewide data, we suspected an influenza outbreak; however, 26 isolates of parainfluenza virus type 1 were cultured with no influenza. The potential importance of culturing at the end of the season was demonstrated in 1991-1992 when an outbreak of respiratory syncytial virus (RSV) overlapped and extended beyond influenza A activity. CONCLUSIONS: When interpreting new clinical respiratory illnesses as a basis for declaring an outbreak of influenza A, clinicians should realize that co-circulating respiratory viruses can account for clinical illnesses. Clinicians might utilize healthcare dollars efficiently by performing cultures to focus the timing of influenza A chemoprophylaxis. Cultures could be performed when clinical outbreak criteria are approached to confirm an outbreak. Culturing of new respiratory illness could begin again before the anticipated discontinuation of prophylaxis (approximately 2 weeks).

Aged↗

Duration of antiviral prophylaxis during nursing home outbreaks of influenza A: a comparison of 2 protocols.

BACKGROUND: We performed a randomized trial of 2 protocols guiding the duration of antiviral chemoprophylaxis during outbreaks of influenza A in a rural, 700-bed nursing home for veterans and their spouses with 14 nursing units in 4 buildings. METHODS: Half of all residents volunteered to participate. Nursing units were randomized, and the effectiveness of short-term (minimum, 14 days and 7 days without the onset of a case in the building) vs long-term (minimum, 21 days and 7 days without the onset of a case in the 4-building facility) prophylaxis was compared using amantadine hydrochloride in the influenza seasons of 1991-1992 and 1993-1994 and rimantadine hydrochloride in the influenza season of 1994-1995. A "case" is defined as an incident of a respiratory tract illness and the isolation of an influenza virus organism. We compared the number of cases after the discontinuation of short- vs long-term chemoprophylaxis. Prospective surveillance identified residents with new respiratory tract symptoms, and specimens for viral cultures were obtained even in the absence of temperature elevation. RESULTS: We documented influenza A virus activity during 3 seasons (32, 68, and 12 patients, respectively). During the 1991-1992, 1993-1994, and 1994-1995 influenza seasons, the patients on 11 floors were assigned to receive short-term chemoprophylaxis and those on 10 floors were assigned to long-term chemoprophylaxis. Only in 1993-1994 did chemoprophylaxis extend beyond 14 or 21 days when new cases continued beyond 14 days. Amantadine-resistant strains were circulating at that time. None of the participants in the prospective, controlled study had influenza develop after the termination of short- or long-term chemoprophylaxis. CONCLUSION: Antiviral chemoprophylaxis can be administered for the longer duration of 14 days or, in the absence of new culture-confirmed illness in the nursing building, for 7 days.

Aged↗

The distribution of lead within ancient and modern human teeth: implications for long-term and historical exposure monitoring.

The preservation of lead within human tissue makes it possible to monitor long-term exposure to the element and to model changing sources of lead pollution throughout the lifetime of an individual. Dental tissues have recently been shown to be particularly useful for this purpose. Enamel, for instance, forms at known stages of life and is chemically stable in vivo whereas dentine is remodelled in a predictable fashion. The relative stability of enamel is reflected in its excellent post-mortem preservation. This raises the possibility of using historical or archaeological material to reconstruct long-term trends and establish baseline data relating to exposure among pre-industrial or even prehistoric populations. The use of archaeological material is currently problematic, however, because of the site-specific nature of diagenesis and incomplete understanding of its chemistry, particularly in respect of lead uptake into dental tissue from the burial environment. A detailed study of lead distribution within both ancient and modern human teeth is presented. Conclusions are drawn on the pattern of lead distribution resulting from tissue formation and the manner of its alteration in the burial environment. In particular, attention is drawn to a consistent enrichment of lead within the outer 30 microns of the enamel of both ancient and modern teeth which appears to be unrelated to diagenesis. The implications for current approaches to long-term monitoring and for the reconstruction of historical and archaeological exposure patterns are discussed.

Archaeology↗

Position-related changes in voiding dynamics in men.

OBJECTIVES: To investigate by urodynamic study position-related changes in uroflowmetry and postvoid residual urine volume (PVR) in men because altered bladder function in the supine position may be a predisposing factor for urinary tract infections in the institutionalized elderly. METHODS: Two healthy men, 34 and 59 years of age and living at home, and 53 nursing home residents (mean age 71.8 years, range 46 to 92) were evaluated with uroflowmetry in the standing and recumbent positions (lying on the left or right side); corresponding PVRs were measured by transabdominal ultrasonic bladder scanning. The two healthy men were monitored longitudinally with multiple recordings in both voiding positions, and the nursing home residents were subjected to two observations: one measurement of the variable parameters in either position. Differences were considered to be significant at P < 0.05. RESULTS: The 34-year-old man performed 51 3 flows (368 standing and 145 recumbent). The mean of all the peak flow rates in the upright (28.2 +/- 4.2 mL/s) versus the recumbent (16.8 +/- 4.1 mL/s) position revealed a highly significant difference (P = 0.0001). Sixteen urinary flows and corresponding PVRs were completed by this subject in either voiding position. The difference between PVRs in the standing (13.1 +/- 14.7 mL) versus recumbent (15.3 +/- 17.5 mL) position was not statistically significant. The 59-year-old man completed 156 flows (128 standing and 28 recumbent). A highly significant difference was noted between the mean of all peak flows in the upright (18.9 +/- 4.1 mL/s) versus recumbent (12.6 +/- 2.0 mL/s) position (P = 0.0001). Thirty-seven urinary flows and corresponding PVRs were completed by this individual (10 PVRs were determined after voiding in the standing and 27 after voiding in the recumbent position). No significant difference was noted between PVRs in the standing (24.6 +/- 34.4 mL) versus recumbent (16.5 +/- 60.0 mL) position. In the nursing home residents, the difference between the mean peak flow rates in the standing (14.5 +/- 8.6 mL/s) versus recumbent (12.4 +/- 6.7 mL/s) position also reached statistical significance (P = 0.0084). The difference between PVRs in the standing (60.5 +/- 125.6 mL) versus recumbent (84.8 +/- 186.2 mL) position barely reached statistical significance (P = 0.0497). CONCLUSIONS: The urinary flow rate decreases in the recumbent position. Bedridden residents may be predisposed to urinary tract infections because of alterations in voiding dynamics in the supine position. This area needs further study.

Adult↗

Immune response to influenza vaccination in institutionalized elderly: effect on different T-cell subsets.

Humoral and cellular immunological responses to influenza vaccination were measured in volunteers in a long-term care facility. All participants were vaccinated with the commercially available 1994-95 trivalent influenza vaccine and blood samples were collected before and 6 and 12 weeks after vaccination. Cytokine and granzyme B in peripheral blood mononuclear cell (PBMC) cultures after virus stimulation, and serum antibody titres were measured for each of these time points. In general, the measures of the immunological response to vaccination were low and variably significant. The major finding was the difference with respect to post-vaccination measures for the two strains of influenza A contained in the vaccine. Geometric mean antibody titres were significantly higher for A/Texas/36/91 at all time points in the study when compared to A/Shangdong/09/93. There was a corresponding rise for interleukin-10 (IL-10) to the A/Texas/36/91 strain while no increase in IL-10 was observed in A/Shangdong/09/93-stimulated cultures after vaccination. In contrast, granzyme B rose after vaccination only in cultures stimulated with A/Shangdong/09/93. Interferon-gamma levels were also significantly higher in these PBMC cultures. There was a poor interleukin-2 (IL-2) response to both strains of influenza A. These data suggest that different strains or subtypes of influenza A may preferentially enhance T-helper type 1 versus type 2 responses through vaccination in institutionalized seniors.

Adult↗

Efficacy of zanamivir for chemoprophylaxis of nursing home influenza outbreaks.

Despite vaccination, influenza remains a common of morbidity in nursing homes. Chemoprophylaxis of residents with currently available antivirals is not always effective and new agents effective against both influenza A and B are needed. In a randomized, unblinded pilot study, we compared 14 day chemoprophylaxis with zanamivir, an antiviral which inhibits influenza neuraminidase, to standard of care during sequential influenza A and influenza B outbreaks in a 735 bed nursing home. Influenza A outbreaks were declared on 6/14 epidemic units. Sixty-five volunteers on four epidemic units were randomized to zanamivir and on two epidemic units, 23 volunteers were randomized to rimantadine. During the 14 days of prophylaxis, only four new febrile respiratory illnesses were detected. One volunteer receiving rimantadine prophylaxis developed laboratory-confirmed influenza. Influenza B outbreaks were declared on 3/14 epidemic units. Thirty-five volunteers on two epidemic units were randomized to zanamivir and 18 volunteers on one epidemic unit were randomized to no drug. During the 14 days of prophylaxis, only one new febrile respiratory illness was detected. One volunteer randomized to receive no drug developed laboratory-confirmed influenza. Zanamivir appears comparably effective to standard of care in preventing influenza-like illness and laboratory-confirmed influenza in nursing homes, but requires further testing.

Aged↗

Assessment of markers of the cell-mediated immune response after influenza virus infection in frail older adults.

The purpose of this study was to determine whether measures of the cell-mediated immune response to influenza virus could be used as markers of influenza virus infection. We studied 23 subjects who developed upper respiratory, lower respiratory, or systemic symptoms during a small outbreak of influenza in a nursing home population. Influenza virus culture from nasopharyngeal swabs yielded influenza virus isolates from 7 of the 23 subjects. Only three of the subjects had a fourfold rise in antibody titer to the influenza virus antigen positivity after the infection. Granzyme B and cytokine levels were measured in peripheral blood mononuclear cells (PBMC) obtained from all subjects and stimulated with live influenza virus. Elevated granzyme B levels in virus-stimulated PBMC in combination with lower respiratory tract or systemic symptoms in study subjects was a significant predictor of culture-confirmed influenza virus infection compared to those from whom influenza virus could not be identified. Cytokine levels did not distinguish between the two groups in a similar type of analysis. Granzyme B in combination with the clinical profile of symptoms may be a useful retrospective marker for influenza virus infection.

Aged↗

Outbreaks of influenza A and B in a highly immunized nursing home population.

BACKGROUND: Large outbreaks of influenza A and B may occur in nursing homes despite high resident vaccination rates, even when the vaccine strain is matched to the circulating strain. This study reports the occurrence of separate influenza A and B outbreaks in a nursing home where more than 85% of residents were vaccinated. METHODS: Prospective surveillance was used to identify symptomatic residents in a rural Wisconsin nursing home with 680 residents. Viral cultures were obtained from all consenting residents identified with new respiratory symptoms even in the absence of temperature elevation. A "case" refers to a resident with a respiratory illness and an influenza isolate. RESULTS: During the 1992-93 season, 86% of 670 total residents were vaccinated, 104 (15.5%) were cases with influenza B. During the 1993-94 season, 89% of 690 total residents were vaccinated, 68 (9.8%) were cases with influenza A. The antigenic matches between vaccine and epidemic strains were characterized as "identical or minimal difference" by the Centers for Disease Control and Prevention. CONCLUSIONS: There is still a need to protect residents from infectious secretions and for contingency plans to permit the rapid use of antiviral agents. Future efforts are needed to develop vaccines that provide greater protection and to improve staff vaccination rates.

Aged↗

Report of an outbreak: nursing home architecture and influenza-A attack rates.

OBJECTIVE: To determine factors that might account for a significantly lower attack rate in a newly constructed nursing building during an epidemic of type A influenza. SETTING: A four-building, long-term care facility for veterans and their spouses, with an average daily census of 690. DESIGN: Prospective surveillance with retrospective analysis. PARTICIPANTS: Symptomatic residents submitting to viral culture. MEASUREMENTS: Number of respiratory illnesses and influenza cultures in consenting symptomatic residents. Building characteristics. RESULTS: An influenza A (H3N2) outbreak was culture-confirmed in 68 nursing home residents. Influenza A was isolated in 3/184 (2%) residents in Building A, 31/196 (16%) in Building B, 18/194 (9%) in Building C, and 16/116 (14%) in Building D. Denominators are average daily census during the outbreak. Building A had significantly fewer culture-confirmed cases than the other buildings (P < .001). Fewer residents in Building A, 47% compared with 61% in Buildings B, C, and D, were participants in a formal study of influenza. Eight of 15 respiratory illnesses identified during the outbreak that were not cultured occurred in Building A. These factors could not account for the difference in attack rates. Building A has a unique ventilation system, more square feet of public space per resident, and does not contain office space that serves the entire four-building facility. CONCLUSION: Our retrospective observation suggests that architectural design may influence the attack rate of influenza A in nursing homes.

Disease Outbreaks↗