Predictors of early mortality among hospitalized nursing home residents.

BACKGROUND: Emergency admissions from nursing homes (NHs) are associated with high mortality. Understanding the predictors of early mortality in these patients may guide clinicians in choosing appropriate site and level of care. METHODS: We identified all consecutive admissions from NHs (all ages) to an Acute Medical Assessment Unit between January 2005 and December 2007. Analysis was performed at the level of the admission. The predictors of in-patient mortality at 7 days were examined using a generalized estimating equations analysis. RESULTS: A total of 314 patients [32% male, mean age: 84.2 years (SD: 8.3 years)] were admitted during the study period constituting 410 emergency episodes. Twenty-three percent of admissions resulted in hospital mortality with 73% of deaths occurring within 1 week (50% within the first 3 days). For 7-day mortality outcome, patients with a modified early warning score (MEWS) of 4-5 on admission had 12 times the odds of death [95% confidence interval (CI) 1.40-103.56], whereas those with a score of ≥6 had 21 times the odds of death (95% CI 2.71-170.57) compared with those with a score of ≤1. An estimated glomerular filtration rate (eGFR) of 30-60 and <30 ml/min/m(2) was associated with nearly a 3-fold increase in the odds of death at 1 week (95% CI 1.10-7.97) and a 5-fold increase in the odds of death within 1 week (95% CI 1.75-14.96), respectively, compared with eGFR > 60 ml/min/m(2). C-reactive protein (CRP) >100 mg/l on admission was also associated with a 2.5 times higher odds of death (95% CI 1.23-4.95). Taking eight or more different medication items per day was associated with only a third of the odds of death (95% CI 0.09-0.98) compared with patients taking only three or fewer per day. CONCLUSION: In acutely ill NH residents, MEWS is an important predictor of early hospital mortality and can be used in both the community and the hospital settings to identify patients whose death maybe predictable or unavoidable, thus allowing a more holistic approach to management with discussion with patient and relatives for planning of immediate care. In addition, CRP and eGFR levels on admission have also been shown to predict early hospital mortality in these patients and can be used in conjunction with MEWS in the same way to allow decision making on the appropriate level of care at the point of hospital admission.

GSI-I (Z-LLNle-CHO) inhibits γ-secretase and the proteosome to trigger cell death in precursor-B acute lymphoblastic leukemia.

Gamma secretase inhibitors (GSIs) comprise a growing class of compounds that interfere with the membrane-bound Notch signaling protein and its downstream intra-nuclear transcriptional targets. As GSI-I (Z-LLNle-CHO) is also a derivative of a widely used proteosome inhibitor MG-132, we hypothesized that this compound might be active in precursor-B acute lymphoblastic leukemia (ALL) cell lines and patient samples. We found that GSI-I treatment of precursor-B ALL blasts induced apoptotic cell death within 18-24 h. With confirmation using RNA and protein analyses, GSI-I blocked nuclear accumulation of cleaved Notch1 and Notch2, and inhibited Notch targets Hey2 and Myc. Microarray analyses of 207 children with high-risk precursor-B ALL demonstrate that Notch pathway expression is a common feature of these neoplasms. However, microarray studies also implicated additional transcriptional targets in GSI-I-dependent cell death, including genes in the unfolded protein response, nuclear factor-κB and p53 pathways. Z-LLNle-CHO blocks both γ-secretase and proteosome activity, inducing more robust cell death in precursor-B ALL cells than either proteosome-selective or γ-secretase-selective inhibitors alone. Using Z-LLNle-CHO in a nonobese diabetes/severe combined immunodeficiency (NOD/SCID) precursor-B ALL xenograft model, we found that GSI-I alone delayed or prevented engraftment of B-lymphoblasts in 50% of the animals comprising the experimental group, suggesting that this compound is worthy of additional testing.

Advancing the spontaneous hypertensive rat model of attention deficit/hyperactivity disorder.

To advance the spontaneous hypertensive rat (SHR) model of attention deficit/hyperactivity disorder (ADHD), experiments examined the SHR in tasks recognized to assess functioning of the prefrontal cortex or dorsal striatal. Tasks included odor-delayed win-shift (nonspatial working and reference memory), win-stay (habit learning), and attentional set-shifting (attention and behavioral flexibility). In Experiment 1, the SHR strain was compared with Wistar-Kyoto (WKY) and Wistar-Kyoto Hypertensive (WKHT) strains on the first 2 tasks. In Experiment 2, oral methylphenidate (1.5 mg/kg) and vehicle (water) were evaluated on all 3 tasks in SHR and WKY strains. Results demonstrated that the SHR made significantly more errors in the odor-delayed win-shift, win-stay, and attentional set-shifting tasks compared with the WKY. Similar performances in the WKY and WKHT indicated that deficits observed in the SHR were not related solely to hypertension. Treating the SHR with methylphenidate eliminated strain differences in all 3 tasks. These findings provide evidence that the SHR is a valid model for studying ADHD-associated neurocognitive deficits. Moreover, the current behavioral approach is appropriate to assess novel medications developed to target ADHD-associated neurocognitive deficits.

Transcription-mediated amplification and hybridisation protection assay to determine BCR-ABL transcript levels in patients with chronic myeloid leukaemia.

Detection of BCR-ABL transcripts in chronic myeloid leukaemia (CML) is used to confirm the diagnosis and to monitor residual disease. Quantitative techniques are required to predict response to therapy or early relapse. We have evaluated an assay in which transcription-mediated amplification (TMA) of BCR-ABL and ABL transcripts is achieved using reverse transcriptase and RNA polymerase. The products are quantified in the hybridisation protection assay (HPA) using acridinium ester-labelled DNA probes and chemiluminescence. The method is a single tube procedure which uses small amounts of RNA (<500 ng/triplicate analysis), is technically simple (requiring just two waterbaths and a luminometer), rapid (total assay time <4 h) and sensitive (capable of detecting one BCR-ABL-positive K562 cell in the presence of 10(4)-10(5) BCR-ABL-negative cells). BCR-ABL signals from patient RNA samples were quantified relative to known amounts of K562 RNA and normalised to levels of ABL. BCR-ABL/ABL ratios ranged from 0.15 to 1.59 (median 0.65) in RNA from diagnostic blood or bone marrow of 18 CML patients and were < or =0.0001 in 20 normal controls. Sequential samples analysed from six CML patients post-allogeneic bone marrow transplantation who relapsed and received donor lymphocyte infusions showed BCR-ABL/ABL ratios which reflected patient status or treatment. A BCR-ABL/ABL ratio of 0.01 served as a useful arbitrary indicator value, with results above and below this value generally correlating with relapse or remission, respectively.

Cardiopulmonary effects of sevoflurane in Garnett's greater bush baby (Otolemur garnettii).

PURPOSE: A study was conducted to assess the cardiopulmonary and anesthetic effects of sevoflurane anesthesia on Garnett's Greater Bush Baby (Otolemur garnettii). METHODS: Anesthesia was induced in ten animals with 8% sevoflurane and was maintained by use of 2.5% sevoflurane for 30 minutes. Induction and recovery times were recorded. Heart and respiratory rates (RR), end-tidal carbon dioxide concentration (ET CO2), arterial blood pressures, relative arterial blood oxygen saturation (SpO2), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and pH were monitored. Pre- and poststudy CBC and serum biochemical values were compared. RESULTS: Anesthesia induction was rapid (75+/-8.7 seconds [mean +/- SEM]) and smooth. Heart rate significantly increased initially, then decreased significantly over the remaining 30 minutes. There were no significant changes in RR, SpO2, ETCO2, or arterial blood pressure. The PaO2 values significantly increased in the 10- to 30-minute samples. The PaCO2 values remained steady in the 10- to 30-minute samples. A significant decrease was seen in white blood count, calcium, and total protein (TP) values, compared with values in pre-anesthesia samples. Recovery from anesthesia was smooth and rapid, with extubation at 24+/-5.8 seconds. CONCLUSIONS: At the concentrations used in this study, sevoflurane appears to be a safe and effective agent for induction and maintenance of anesthesia in O. garnettii.

Cardiopulmonary and anesthetic effects of medetomidine-ketamine-butorphanol and antagonism with atipamezole in servals (Felis serval).

Seven (three male and four female) 4-7-yr old captive servals (Felis serval) weighing 13.7 +/- 2.3 kg were used to evaluate the cardiopulmonary and anesthetic effects of combined intramuscular injections of medetomidine (47.4 +/- 10.3 microg/kg), ketamine (1.0 +/- 0.2 mg/kg), and butorphanol (0.2 +/- 0.03 mg/kg). Inductions were smooth and rapid (11.7 +/- 4.3 min) and resulted in good muscle relaxation. Significant decreases in heart rate (85 +/- 12 beats/min) at 10 min after injection and respiratory rate (27 +/- 10 breaths/min) at 5 min after injection continued throughout the immobilization period. Rectal temperature and arterial blood pressure did not change significantly. The PaO2 decreased significantly, and PaCO2 increased significantly during immobilization but remained within clinically acceptable limits. Hypoxemia (PaO2 < 60 mm Hg) was not noted, and arterial blood oxygen saturation (SaO2) was greater than 90% at all times. Relative arterial oxygen saturation (SpO2) values, indicated by pulse oximetry, were lower than SaO2 values. All animals could be safely handled while sedated. Administration of atipamezole (236.8 +/- 51.2 microg/kg half i.v. and half s.c.), an alpha2 antagonist, resulted in rapid (4.1 +/- 3 min to standing) and smooth recoveries.

Management of geriatric patients. A common occurrence.

The anesthetic and perioperative care of geriatric animals requires increased vigilance and support. The margin of acceptable physiological variation is probably more narrow than in younger patients. Underlying disease, which is often subclinical, influences metabolism and recovery from anesthetics and also predisposes the patients to adverse outcome. Limited respiratory and cardiovascular reserve diminishes the ability of many older patients to meet the challenges of anesthesia and surgery or other stressful medical procedures. The psychological, as well as physiological, stress of hospitalization is increased in many geriatric patients.

Alpha 2 agonists and antagonists.

The alpha 2 agonists can produce reliable dose-dependent sedation and analgesia in most species. Nevertheless, they can also produce significant physiological adverse side effects depending on dose, rate, route of administration, and the concurrent use of other CNS depressants. For this reason, it may be best to use a low dose of an alpha 2 agonist as a preanesthetic agent. The alpha 2 agonists are best suited for young, healthy, exercise-tolerant patients. The combining of low doses of alpha 2, opioid, and benzodiazepine agonists results in a synergistic CNS depressant response while minimizing the undesirable side effects of these three classes of drugs. Each group of drugs has specific antagonists available for their reversal, thus allowing veterinarians to reverse one or more of the agonists depending on the desired response. This may represent a significant advantage to the use of low-dose alpha 2 agonists in combination with opioids and benzodiazepines.

Cardiovascular effects of the alpha2-adrenergic receptor agonist medetomidine in clinically normal cats anesthetized with isoflurane.

OBJECTIVE: To assess the cardiovascular effects of the alpha2-adrenergic receptor agonist medetomidine in healthy cats anesthetized with 2% isoflurane. ANIMALS: 11 clinically normal cats. PROCEDURE: Cats were anesthetized with isoflurane, and catheters were inserted for measurement of aortic, left ventricular, and right atrial pressures. For data collection, end-tidal isoflurane concentration was reduced to 2%, and end-tidal CO2 was maintained at 35 to 40 mm of Hg by use of positive-pressure ventilation. After measurement of baseline data, medetomidine (0.01 mg/kg of body weight, i.m.) was administered and data were collected continuously for 75 minutes. At the end of data collection, incisions were closed and cats were allowed to recover from anesthesia. RESULTS: Medetomidine significantly increased mean arterial pressure and systemic vascular resistance. The increase in mean arterial pressure was maximal at 17.8 +/- 7 minutes after medetomidine administration. Medetomidine also increased left ventricular peak systolic pressure, left ventricular end diastolic pressure, and right atrial pressure. Medetomidine significantly decreased heart rate and mean aortic flow. CONCLUSIONS: The low dosage of medetomidine (0.01 mg/kg, i.m.) promoted severe vasoconstriction in isoflurane-anesthetized cats, and resulted in sustained increases in left ventricular preload and afterload.

Sporadic meningococcal disease in adults: results of a 5-year population-based study.

OBJECTIVE: To define the incidence, demographics, clinical features, and risk factors for sporadic meningococcal disease in adults (> or = 18 years) residing in metropolitan Atlanta. DESIGN: Prospective, population-based surveillance, with retrospective review of clinical and laboratory records. SETTING: Eight-county metropolitan Atlanta area. PATIENTS: All adult patients in whom Neisseria meningitidis was isolated from normally sterile sites (blood, cerebrospinal fluid) during the period 1 December 1988 to 30 November 1993. MEASUREMENTS: Incidence, relative risk, clinical and laboratory parameters, and serogroup of meningococcal isolates. RESULTS: For the 5-year period, 44 (33%) of 132 cases of meningococcal disease in Atlanta occurred in adults (annual incidence, 0.50/100,000 adults per year). Twenty-three (52%) of the 44 adults presented without rash or meningitis, the two most obvious signs of meningococcal disease. Pneumonia, sinusitis, or purulent tracheobronchitis, but without rash, were the likely sources of meningococcal bacteremia in 15 (34%) of the 44 adults. Twelve of the 15 patients with meningococcal respiratory infection were older than 50 years of age or were immunocompromised (or both), and three fourths of the 15 patients had disease caused by serogroups B, Y, and W-135. Overall, two thirds of adults older than 24 years of age with meningococcal disease had one or more immunocompromising conditions (for example, low complement 50 level [CH50], corticosteroid use, congestive heart failure, multiple myeloma, human immunodeficiency virus infection). Meningococcemia or meningococcal meningitis, often caused by serogroup C, were the presentations in 14 of 15 adults 18 to 24 years old; only 2 had an identified underlying condition. CONCLUSIONS: In this 5-year population-based study, one third of all cases of sporadic meningococcal disease occurred in adults. Over half of the adults presented without rash or meningitis. Pneumonia, sinusitis, and tracheobronchitis are important sources of bacteremic meningococcal disease, especially in immunocompromised patients and elderly persons.

Communicating hydrocephalus in dogs with congenital ciliary dysfunction.

Magnetic resonance imaging (MRI) and radionuclide ventriculography were performed in 5 dogs with congenital ciliary dysfunction (CDD) and 3 normal dogs. Ventricular and brain dimensions and volumes, and CSF flow rates were measured or calculated from the MR images and radionuclide clearance. All CCD dogs had hydrocephalus based on previously published criteria of a percent vertical brain dimension (PVBD) greater than 14%. The PVBD was significantly larger (p = 0.001) in the dogs with CCD (mean +/- SD) 33.00 +/- 5.42% than in normal dogs (11.07 +/- 0.61%. The ventricular volume was significantly larger (p = 0.021) in CCD dogs 10,841 +/- 4,127 mm3 compared to the volume measured in normal dogs 3,069 +/- 1,167 mm3. The CSF flow rate was not significantly different p = 0.876) between CCD dogs (253.00 +/- 147.25 mm3/h) and normal dogs (267.667 +/- 47.61 mm3/h). This suggests that the ventricular dilation in CCD dogs is not due to impedance of CSF flow from the ventricular system by dysfunctional ependymal cilia.

Butorphanol tartrate for partial reversal of oxymorphone-induced postoperative respiratory depression in the dog.

A randomized, blinded, crossover study was designed to evaluate the respiratory, cardiovascular, and behavioral effects of butorphanol given postoperatively to oxymorphone-premedicated and surgically stimulated dogs. Nine healthy adult dogs were premedicated intramuscularly with atropine (0.04 mg/kg), acepromazine (0.10 mg/kg), and oxymorphone (0.2 mg/kg). Anesthesia was induced with thiamylal (12 mg/kg) and maintained with halothane in oxygen. According to the protocol of a concurrent study, all dogs had percutaneous endoscopic gastrostomy (PEG) feeding tubes placed during the first anesthetic episode and removed during the second anesthetic episode. All dogs received postoperatively either butorphanol tartrate (0.2 mg/kg) or an isovolumetric dose of saline placebo, both given intravenously. Respiratory rate (RR), tidal volume (TV), minute ventilation (MV), end-tidal CO2 concentration (ETCO2), heart rate (HR), and indirect diastolic (DP), systolic (SP) and mean arterial (MAP) blood pressures were measured at times 0, 2, 5, 10, 20, 40, 80, and 120 minutes after injection. The time from injection of the test drug until extubation was recorded. RR, MV, HR, and DP were significantly (P < .05) increased, while ETCO2 was significantly decreased, for a minimum of 30 minutes in butorphanol-treated dogs compared with saline controls. TV, SP, and MAP were transiently (< or = 15 minutes) increased in butorphanol-treated dogs compared with saline controls. There was no significant difference between the times to extubation in the butorphanol-treated dogs versus the saline control dogs.

Increased risk of meningitis and bacteremia due to Listeria monocytogenes in patients with human immunodeficiency virus infection.

The incidence, demographics, and clinical outcome of infections due to Listeria monocytogenes in individuals infected with the human immunodeficiency virus (HIV) were evaluated by prospective population-based surveillance. During a 2-year study period, 37 cases of invasive listeriosis occurred in metropolitan Atlanta (annual incidence, 0.8 case per 100,000 population). Seven of these cases occurred in known HIV-infected individuals (19% of all cases); five had an AIDS-defining illness, and the other two had CD4 lymphocyte cell counts of < 200/microL. The estimated incidence of listeriosis among HIV-infected patients in metropolitan Atlanta was 52 cases per 100,000 patients per year, and among patients with AIDS it was 115 cases per 100,000 patients per year, rates 65-145 times higher than those among the general population. HIV-associated cases occurred in adults who were 29-62 years of age and in postnatal infants who were 2 and 6 months of age. Mortality among the HIV-infected group was 29%. L. monocytogenes serotypes 1/2a, 1/2b, and 4b were isolated from the HIV-infected patients. L. monocytogenes is an important opportunistic pathogen in HIV-infected patients.

A population-based assessment of invasive disease due to group B Streptococcus in nonpregnant adults.

BACKGROUND: Group B streptococci (Streptococcus agalactiae) are a major cause of meningitis and septicemia in neonates and pregnant women, but the importance of group B streptococcal disease in nonpregnant adults has not been clearly defined. METHODS: We conducted a prospective surveillance of the pathogens responsible for meningitis for a period of 24 months in 35 hospitals and a referral laboratory in metropolitan Atlanta. We reviewed the clinical and laboratory records of all the nonpregnant adults identified as having invasive group B streptococcal disease during this period. RESULTS: During 1989 and 1990 there were 424 patients with invasive group B streptococcal disease (annual incidence, 9.2 cases per 100,000 population). Of these patients, 46 percent were 1 month of age or younger, 6 percent were older than 1 month but younger than 18 years of age, and 48 percent were 18 or older. Men and nonpregnant women accounted for 68 percent (n = 140) of all cases among adults (annual incidence, 4.4 per 100,000). Clinical and laboratory records were available for 137. In the nonpregnant adult patients (age, 18 to 99 years), the most common clinical diagnoses were skin, soft-tissue, or bone infection (in 36 percent); bacteremia with no identified source (30 percent); urosepsis (14 percent); pneumonia (9 percent); and peritonitis (7 percent). Risk factors included older age (> or = 60 years), the presence of diabetes mellitus, the presence of malignant neoplasms, and infection with the human immunodeficiency virus. The mortality rate in nonpregnant adults was 21 percent, accounting for 67 percent of all deaths related to group B streptococcal infection during the surveillance period. CONCLUSIONS: Invasive group B streptococcal infection is a major problem not only in pregnant women and neonates but also in nonpregnant adults, especially those who are elderly and those who have chronic diseases.

Localization of 14 functional J regions in the human T-cell receptor alpha-chain locus.

Nearly 60 unique J alpha regions have been identified in human T-cell receptor (TCR) alpha chains to date, yet fewer than one-third of these have been localized within the alpha-chain locus. We report a rapid method for the mapping of productively rearranged J alpha regions using oligonucleotide probes and overlapping phage clones spanning 80 kb of the TCR-alpha locus. Fourteen J alpha regions were mapped using this technique; the positions of five of these have been verified by genomic cloning.

An attempt to eradicate Herpesvirus simiae from a rhesus monkey breeding colony.

In the fall of 1987 an attempt to establish a Herpesvirus simiae (B-virus)-negative rhesus monkey (Macaca mulatta) breeding colony was initiated at the Armstrong Laboratory. A serologic testing program was used to identify all monkeys into groups that were either positive or negative to B-virus based on serologic tests. Segregation of the groups allowed the creation of breeding harems that were exclusively seropositive or -negative to B-virus. Animals that were serologically positive were kept in breeding to maintain infant production levels not unlike those previous to segregation. Decreasing numbers of animals converted to a positive status during the first three serum tests for B-virus in the program. During 1990, an increase in the number of monkeys converting to positive status and the discovery of an indeterminate status demonstrated that latency of B-virus in the rhesus may have the potential to defeat an eradication attempt not conscientiously pursued.