Subclinical hypocalcemia, plasma biochemical parameters, lipid metabolism, postpartum disease, and fertility in postparturient dairy cows.

A study was conducted to evaluate the potential association between Ca status at calving and postpartum energy balance, liver lipid infiltration, disease occurrence, milk yield and quality parameters, and fertility in Holstein cows. One hundred cows were assigned to 1 of 2 groups based on whole-blood ionized Ca concentration ([iCa]) on the day of calving [d 0; hypocalcemic [iCa] <1.0 mmol/L (n=51); normocalcemic [iCa] ≥ 1.0 mmol/L (n=49)]. Cows were blocked based on calving date and parity. Blood samples were collected approximately 14 d from expected calving date (d -14), the day of calving (d 0), and on d 3, 7, 14, 21, and 35 postpartum for measurement of plasma nonesterified fatty acid, iCa, total Ca, glucose, and total and direct bilirubin concentrations, and plasma aspartate aminotransferase and gamma glutamyl transferase activities. Liver biopsies were obtained from a subset of cows on d 0, 7, and 35 for quantification of lipid content. Milk samples were collected on d 3, 7, 14, 21, and 35 postpartum for measurement of somatic cell count and percentages of protein, fat, and solids-not-fat. Data for peak test-day milk yield, services per conception, and days open were obtained from Dairy Herd Improvement Association herd records. Disease occurrence was determined based on herd treatment records. Hypocalcemic cows had significantly higher nonesterified fatty acids on d 0. Hypocalcemic cows also had significantly more lipid in hepatocytes on d 7 and 35 postpartum. However, no statistically significant differences were observed between groups for plasma aspartate aminotransferase and gamma glutamyl transferase activities or total and direct bilirubin concentrations. Milk protein percentage was lower in hypocalcemic cows on d 21 and 35. However other milk quality variables (somatic cell count, milk fat percentage, and solids-not-fat) and milk yield variables (peak test-day milk yield and 305-d mature-equivalent 4% fat-corrected milk yield) did not differ between groups. No differences were observed between groups in the occurrence of clinical mastitis, ketosis, displaced abomasum, dystocia, retained placenta, metritis, or fertility measures (percentage cycling at 50-60 d postpartum, services per conception, or days open). These data suggest that early lactation fatty acid metabolism differs between cows with subclinical hypocalcemia and their normocalcemic counterparts.

Responding to patient safety incidents: the "seven pillars".

BACKGROUND: Although acknowledged to be an ethical imperative for providers, disclosure following patient safety incidents remains the exception. The appropriate response to a patient safety incident and the disclosure of medical errors are neither easy nor obvious. An inadequate response to patient harm or an inappropriate disclosure may frustrate practitioners, dent their professional reputation, and alienate patients. METHODS: The authors have presented a descriptive study on the comprehensive process for responding to patient safety incidents, including the disclosure of medical errors adopted at a large, urban tertiary care centre in the United States. RESULTS: In the first two years post-implementation, the "seven pillars" process has led to more than 2,000 incident reports annually, prompted more than 100 investigations with root cause analysis, translated into close to 200 system improvements and served as the foundation of almost 106 disclosure conversations and 20 full disclosures of inappropriate or unreasonable care causing harm to patients. CONCLUSIONS: Adopting a policy of transparency represents a major shift in organisational focus and may take several years to implement. In our experience, the ability to rapidly learn from, respond to, and modify practices based on investigation to improve the safety and quality of patient care is grounded in transparency.

Attention-deficit hyperactivity disorder and fluctuating asymmetry in another college sample.

Attention deficit/hyperactivity disorder (AD/HD) represents a developmental lag that may be reflected in fluctuating asymmetry (FA), i.e., differences from perfect symmetry in traits that display bilateral symmetry. Burton et al. (2003 Am. J. Hum. Biol. 15:601-619) found a statistical trend for FA to increase (as dermatoglyphic index or as total index) as the behavioral measure for AD/HDness (Rasch logit values derived from the Wender Utah Rating Scale, or WURS) increased in males but not in females. The objective here was to do a similar study in an independently collected sample of college students (n = 222; 61 male, 161 female) not selected for AD/HD, looking at FA vs. symptoms for AD/HD based on Rasch versions of responses to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) (Barkley and Murphy 1998 Attention-Deficit Hyperactivity Disorder, New York: Guilford Press, p. 95-96) and the more comparable shortened WURS. FAs were lowest for body and ear height, and highest for eye width and nose width, and ranged from 0.01 +/- 0.001 (mean +/- SE) for foot and ankle widths to 0.13 +/- 0.01 in eye and nose widths for both sexes; the sexes did not differ significantly. Males displayed higher AD/HD symptom rates overall. There was a significant correlation between body FA and the WURS measure in females after Bonferroni correction (P = 0.002, r(2) = 0.058). Thus, AD/HD symptoms levels increased with an increase in body FA in female college students not selected for AD/HD.

Review article: Mycobacterium avium subsp. paratuberculosis as one cause of Crohn's disease.

A number of theories regarding the aetiology of Crohn's disease have been proposed. Diet, infections, other unidentified environmental factors and immune disregulation, all working under the influence of a genetic predisposition, have been viewed with suspicion. Many now believe that Crohn's disease is a syndrome caused by several aetiologies. The two leading theories are the infectious and autoimmune theories. The leading infectious candidate is Mycobacterium avium subspecies paratuberculosis (Mycobacterium paratuberculosis), the causative agent of Johne's disease, an inflammatory bowel disease in a variety of mammals including cattle, sheep, deer, bison, monkeys and chimpanzees. The evidence to support M. paratuberculosis infection as a cause of Crohn's disease is mounting rapidly. Technical advances have allowed the identification and/or isolation of M. paratuberculosis from a significantly higher proportion of Crohn's disease tissues than from controls. These methodologies include: (i) improved culture techniques; (ii) development of M. paratuberculosis-specific polymerase chain reaction assays; (iii) development of a novel in situ hybridization method; (iv) efficacy of macrolide and anti-mycobacterial drug therapies; and (v) discovery of Crohn's disease-specific seroreactivity against two specific M. paratuberculosis recombinant antigens. The causal role for M. paratuberculosis in Crohn's disease and correlation of infection with specific stratification(s) of the disorder need to be investigated. The data implicating Crohn's as an autoimmune disorder may be viewed in a manner that supports the mycobacterial theory. The mycobacterial theory and the autoimmune theory are complementary; the first deals with the aetiology of the disorder, the second deals with its pathogenesis. Combined therapies directed against a mycobacterial aetiology and inflammation may be the optimal treatment of the disease.

Use of short-term culture for identification of Mycobacterium avium subsp. paratuberculosis in tissue from Crohn's disease patients.

OBJECTIVE: To investigate the role of Mycobacterium avium subsp. paratuberculosis (MAP) in Crohn's disease (CD), using short-term mycobacterial culture media. METHODS: Sixty-three tissue specimens from 27 CD patients and 36 controls were processed and inoculated into a modified 7H9 broth base medium and incubated at 37 degrees C and 5% CO2 for up to 1 year. Acid-fast staining, determination of mycobactin dependency, PCR analysis using two IS900-derived oligonucleotides and hybridization with an internal probe were performed. RESULTS: MAP was present in six of seven (86%) surgically resected tissue samples and in four of 20 (20%) biopsies, with an overall 37% from CD patients, as compared to two of 36 (5.6%) of control specimens. The presence of MAP in Mycobacterial Growth Indicator Tube (MGIT) cultures was detected within 10-12 weeks for surgically resected tissue and after 40 weeks for biopsy specimens, with no MAP growth detected in 12B* Bactec cultures. CONCLUSIONS: Because MAP was present in 86% of resected tissue compared to 20% of biopsy specimens from CD patients, we speculate that MAP resides in the submucosal layer closer to the active part of the ulcer rather than on the surface of the mucosal cells. Thus, surgically resected tissue cultured in MGIT medium is a favorable protocol for rapid cultivation of MAP and for investigating its role in CD pathogenesis. The data support the mycobacterial role in CD pathogenesis.

Antibiotics as primary therapy for Crohn's disease.

Crohn's disease, an inflammatory bowel disease of unknown cause, was initially considered to have an infectious etiology. As the infectious agent could not be identified, it was grouped among the immune disorders. As a result, research and clinical trials were directed towards the autoimmune theory and patients were treated with steroids, immunomodulators, aminosalicylates and, most recently, anti-tumor necrosis factor-alpha. Because of the inconsistency of treatment success and the failure to cure Crohn's disease, many physicians turned to antibiotics in search for alternative solutions, especially when other regimens failed. Attention has recently been directed toward possible infectious causes of Crohn's disease. Although it is still unknown whether microbial agents are etiologically involved in the pathogenesis of Crohn's disease, there has been a growing interest in trying antibiotics in the management of Crohn's disease. This review summarizes the data available regarding antibiotic treatment of Crohn's disease in relation to a possible mycobacterial etiology. Multidrug therapies are in clinical trials and the results of these randomized, controlled, double-blind studies are needed before guidelines about whether to include antibiotics as part of the treatment of Crohn's disease management can be made.

Monitoring intensive care unit performance using statistical quality control charts.

This paper discusses results of a study in which mortality rates and APACHE II severity of illness scores of Intensive Care Unit (ICU) patients were monitored for a five-year period (1986-1990) using statistical quality control charts. The purpose of the study was to determine whether severity of illness of patients and mortality rates had changed significantly over this time horizon. The results show that the Intensive Care Unit process is stable and in statistical control. There is no apparent trend in the severity of illness scores nor mortality rates measured both at ten days and six months from the last ICU admission. Quality control charts, which have been used extensively to detect changes in industrial processes on a short term basis, provide a simple method of monitoring the ICU process over an extended time horizon.

Differential activation of mixed venous and arterial neutrophils in patients with sepsis syndrome and acute lung injury.

Neutrophil (PMN) functions, such as production of toxic oxygen (O2) metabolites, adherence, and chemotactic properties, are modified during local tissue inflammation and sepsis. We hypothesized that PMN would be primed during their transit through injured tissue beds, which in turn can lead to modulation or retention of the primed PMN by downstream tissues like the lungs. We tested this hypothesis by measuring the transpulmonary gradient of hydrogen peroxide (H2O2) production by zymosan-activated PMN. We examined the mixed venous to arterial difference in H2O2(delta H2O2) produced by zymosan-activated PMN in septic patients without lung infiltrates, patients with lung injury, and a control group of patients undergoing elective surgery or coronary catheterization. Septic patients had higher mixed venous H2O2/10(6) PMN, whereas lung injury patients had higher arterial H2O2/10(6) PMN. The control group had the same H2O2/10(6) PMN in mixed venous and arterial blood. The delta H2O2 in septic, lung injury, and control groups were 0.35 +/- 0.22, -0.31 +/- 0.48, and -0.01 +/- 0.04 nmol H2O2/10(6) PMN, respectively. The mixed venous to arterial H2O2 gradient distinguished septic patients from the control and lung injury patients (p less than 0.05). Our results are consistent with the hypothesis that in septic patients PMN are primed in the periphery and downregulated or sequestered in the lung, and in lung injury patients PMN are primed in the lung and sequestered in the periphery. Alternatively, neutrophil-endothelial interactions may downregulate toxic O2 metabolite production by PMN during their transit through microvascular beds.

Effect of sodium azide on hydrogen peroxide production by zymosan-activated human neutrophils.

Stimulated neutrophils (PMNs) produce large quantities of superoxide anion, which is the precursor for hydrogen peroxide (H2O2). We developed a new fluorimetric assay to measure the H2O2 released by zymosan A-activated PMNs utilizing the oxidation of p-hydroxyphenylacetic acid by H2O2 to its fluorescent dimer in the presence of horseradish peroxidase. Zymosan-activated PMNs isolated from nine healthy volunteers and 20 patients with acute hypoxemic respiratory failure (AHRF) released after 90 min 2.3 +/- 0.3 and 2.4 +/- 1.3 nmol H2O2/10(6) PMNs, respectively. Inhibition of the heme enzymes by 1.0 mM sodium azide (NaN3) increased the H2O2 production to 21.6 +/- 4.4 nmol H2O2/10(6) PMNs in the control group (P less than 0.001), and to 22.5 +/- 14.7 nmol H2O2/10(6) PMNs in patients with AHRF (P less than 0.001). Incubation temperature, room temperature or 37 degrees C, did not change the total amount of H2O2 produced after 90 min by zymosan-activated PMN. Addition of NaN3 improved both the sensitivity and reproducibility of the measurement of H2O2 and allowed detection of H2O2 released by PMNs with coefficients of variation of less than 5% at PMN concentrations as low as 0.1 x 10(6) cells/ml. The amount of H2O2 released by activated PMNs did not distinguish healthy controls from patients with AHRF.

The epidemiology of Pseudomonas aeruginosa in oncology patients in a general hospital.

Pseudomonas aeruginosa colonization and infection was studied over a 6-mo period in a 36-bed mixed general medical-oncology unit. We used selective media for serial surveillance cultures on 283 patients, the environment, and personnel. Twelve percent of patients were colonized on admission and 10% acquired P. aeruginosa. Using serotyping and multilocus enzyme electrophoresis, we identified 63 genetically distinctive strains; four prevalent strains accounted for 21% of isolates. Only 5 of 33 nosocomial acquisitions were due to horizontal transmission. Nine acquisitions were linked to environmental sources (e.g., sink surfaces), which often harbored antibiotic-resistant strains but posed a risk only to oncology patients. Although significant Pseudomonas infections occurred in only 11% of colonized patients, 63% of colonized severely neutropenic patients--predominantly those who had acquired the prevalent, often environmentally linked strains--developed infections. Thus, P. aeruginosa was a significant pathogen in oncology patients; typing by multilocus enzyme electrophoresis allowed the detection of important environmental sources.

Diagnostic peritoneal lavage in intra-abdominal sepsis.

Despite the advent of sophisticated diagnostic technology the diagnosis of the surgical abdomen in the Intensive Care Unit continues to pose a problem for the surgeon. A retrospective analysis was carried out to evaluate the utility of diagnostic peritoneal lavage to diagnose intra-abdominal surgical disease. Diagnostic peritoneal lavage was carried out in patients in whom the physical exam was deemed unreliable, such as in patients with cardiopulmonary instability or mental obtundation. Patients were included in the study if autopsy or laparotomy confirmation of the lavage data was available. Forty four patients met the inclusion criteria and formed the basis of this study. Of the twenty three patients with a positive lavage, three false-positive diagnostic peritoneal lavages were discovered, either at laparotomy or postmortem exam. Of the twenty one patients where diagnostic peritoneal lavage was negative, no false-negatives were discovered at autopsy or laparatomy. Therefore, this test is 100 per cent sensitive and 88 per cent specific. It is concluded that a negative diagnostic peritoneal lavage makes intra-abdominal surgical disease highly unlikely. However, a positive lavage may require further diagnostic work-up.