Effect of intra-arterial papaverine on regional cerebral blood flow in hemodynamically relevant cerebral vasospasm.

BACKGROUND AND PURPOSE: It remains controversial whether the intra-arterial administration of papaverine (IAP) is effective in reversing vasospasm-associated cerebral hypoperfusion after aneurysmal subarachnoid hemorrhage. The aim of the present study was to continuously assess regional cerebral blood flow (rCBF) during and after IAP with the use of quantitative, bedside thermal diffusion flowmetry. METHODS: Eight patients with cerebral vasospasm after subarachnoid hemorrhage (mean flow velocity >120 cm/s; angiographic vessel constriction >33%; hemispheric cerebral blood flow [CBF] <32 mL/100 g per minute) were prospectively entered into the study. Before IAP, thermal diffusion microprobes were implanted into the white matter of each affected vascular territory (n=10) for rCBF monitoring. During and after IAP (300 mg papaverine/50 mL saline over 1 hour), mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, thermal diffusion rCBF (TD-rCBF), and cerebrovascular resistance (CVR) were recorded continuously. RESULTS: IAP significantly increased TD-rCBF from 7.3+/-1.6 to 37.9+/-6.6 mL/100 g per minute (mean+/-SEM), indicating reversal of cerebral hypoperfusion. This TD-rCBF response was dependent on the degree of cerebral vasospasm and reduced perfusion within the vascular territory. Long-term analysis of TD-rCBF, however, demonstrated that this beneficial effect of IAP on cerebral hypoperfusion was only transient: within 3 hours after treatment, TD-rCBF and CVR returned to baseline values. Furthermore, a lack of correlation between transcranial Doppler sonography and thermal diffusion flowmetry suggested that transcranial Doppler sonography is not suited for CBF-based neuromonitoring after IAP. CONCLUSIONS: IAP is not effective in permanently reversing cerebral hypoperfusion in patients with cerebral vasospasm. The need to validate alternative therapeutic strategies that seek to improve cerebral perfusion in vasospasm warrants continued development of CBF-based neuromonitoring strategies.

The organizational environment and evidence-based nursing.

The Province-Wide Nursing Project (PWNP) was designed to remove some of the structural barriers that can impede the ability of nurses in selected health care settings to assess, implement and evaluate best nursing practice. Literature on capacity building and research utilization suggests that the organization is the most important factor in promoting best nursing practice. Therefore, managers and nursing leaders need to encourage the creation of optimum work environments. A survey undertaken by the PWNP Research Centre team assessed the extent to which the 23 agencies in the 4 Participating Complexes provided supportive environments for evidence-based practice. The Characteristics of Agencies in Participating Complexes: Demographics and Resources questionnaire investigated the resources available to help nurses improve their standards of practice in agencies participating in the project. Larger agencies, especially those associated with academic centres, had considerably more resources than agencies in smaller towns. Participation in the Province-Wide Nursing Project enabled agencies to develop strategies to improve the use of evidence in nursing practice.

ICAM-1 affects reperfusion injury and graft function after cardiac transplantation.

BACKGROUND: The effects of increased expression of intercellular adhesion molecule (ICAM-1), an important mediator of neutrophil-mediated reperfusion injury (RI), were assessed in donor cardiac allografts in a heterotopic rat transplantation model. METHODS: At -24 h, PVG donors were untreated (n = 35) or treated (n = 37) with lipopolysaccharide (LPS, 5 mg/kg ip). Hearts were procured at 0 h, stored at 4 degrees C for 45 min, and grafted heterotopically into ACI recipients pretreated with vehicle or anti-ICAM-1 (1A29) mAb. Intracardiac balloons (n = 8 per group) were used to measure allograft left ventricular function (dP/dt) prior to harvest and following reperfusion. RI was assessed at 6, 12, and 24 h by myeloperoxidase (MPO) levels, percentage wet weight (%w/w), and percentage contraction band necrosis (%CBN). RESULTS: At 12 h, LPS-pretreated grafts showed increased ICAM-1 expression by Northern blot (n = 3) and immunohistochemistry (n = 3) and significantly increased MPO (0.33 +/- 0.2 U/mg vs 0.05 +/- 0.04 U/mg at 12 h), %w/w (81.7 +/- 1.8% vs 79.2 +/- 0.7% at 12 h), and %CBN (15.2 +/- 1. 9% vs 11.4 +/- 2.0% at 24 h). LPS pretreatment had no effect on graft function at early time points (baseline to 2 h) but led to depressed dP/dt at later time points with trends toward significance at 12 h (2101 +/- 1653 mmHg/s vs 173 +/- 201 mmHg/s, P = 0.06, ANOVA). Recipient 1A29 treatment (n = 6 per group) reversed the effects of LPS pretreatment in all three RI parameters and significantly improved functional recovery. CONCLUSIONS: Alteration of cardiac graft phenotype to that likely seen in clinical organ donors leads to increased delayed-onset myocardial RI following transplantation in this model. The blockade of this increased RI following 1A29 mAb treatment supports a central role for ICAM-1 in this process.

Modulation of cytokine-induced cardiac myocyte apoptosis by nitric oxide, Bak, and Bcl-x.

-Cytokine-induced NO production depresses myocardial contractility and has been shown to be cytotoxic to cardiac myocytes. However, the mechanisms of cytokine-induced cardiac myocyte cell death are unclear. To analyze these mechanisms in detail, we treated neonatal cardiac myocytes in serum-free culture with a combination of the macrophage-derived cytokines interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma. These cytokines caused a time-dependent induction of cardiac myocyte apoptosis, but not necrosis, beginning 72 hours after treatment, as determined by nuclear morphology, DNA internucleosomal cleavage, and cleavage of poly(ADP-ribose) polymerase, reflecting caspase activation. Apoptosis was preceded by a >50-fold induction of inducible NO synthase mRNA and the release of large amounts (5 to 8 nmol/ microgram protein) of NO metabolites (NOx) into the medium. Cell death was completely blocked by an NO synthase inhibitor and attenuated by antioxidants (N-acetylcysteine and DTT) and the caspase inhibitor ZVAD-fmk. Cytokines also mediated an NO-dependent, sustained increase in myocyte expression of the Bcl-2 homologs Bak and Bcl-x(L). The NO donor S-nitrosoglutathione also induced apoptosis and cell levels of Bak, but not of Bcl-x(L). All effects of cytokines, including poly(ADP-ribose) polymerase cleavage, could be attributed to interleukin-1beta; interferon-gamma and tumor necrosis factor-alpha had no independent effects on apoptosis or on NOx production. We conclude that cytokine toxicity to neonatal cardiac myocytes results from the induction of NO and subsequent activation of apoptosis, at least in part through the generation of oxygen free radicals. The rate and extent of this apoptosis is modulated by alterations in the cellular balance of Bak and Bcl-x(L), which respond differentially to cytokine-induced and exogenous NO and by the availability of oxidant species.

Horizontal canal benign paroxysmal positioning vertigo (h-BPPV): transition of canalolithiasis to cupulolithiasis.

We report on 2 patients with typical features of horizontal canal benign paroxysmal positioning vertigo (h-BPPV). A vigorous head positioning in these patients from supine to a bending-over, head-on-the-knees position reversed the direction of nystagmus from geotropic initially to ageotropic when rolling the head from side to side while supine. We explain this by a conversion of canalolithiasis into cupulolithiasis and conclude that (1) canalolithiasis and cupulolithiasis may sequentially occur in the same semicircular canal with subsequent positioning maneuvers and (2) positional nystagmus beating toward the uppermost ear is not a pathognomonic sign of central vestibular disturbance but can indicate occasional cupulolithiasis.

Diarrheal deaths in children living in New Mexico: toward a strategy of preventive interventions.

We reviewed 26 childhood diarrheal deaths examined by the New Mexico Office of the Medical Investigator, from 1980 through 1989, to identify circumstances surrounding the illness that might lead to strategies for prevention. Children who died were younger than 9 months of age (88%) and were from minority groups (American Indian 54%, Hispanic 23%); 12 (46%) had seen a physician within 3 days of death. Interventions to avert these deaths include educating parents to seek earlier treatment and health care providers to recognize that acutely dehydrating diarrhea can be fatal.

Laboratory-based surveillance for rotavirus United States, January 1989-May 1991.

Geographic and temporal trends of rotavirus detections in the United States for the period January 1989-May 1991 were determined by analyzing data reported monthly by 47 virology laboratories participating in the North American Rotavirus Surveillance System. Reports included complete information on the number of specimens tested, the number of test results positive for rotavirus, and the method used to detect rotavirus. Consistent trends in regional and geographic area were identified, with distinctly different peaks of rotavirus activity in the western and eastern states. Each year in the western states, rotavirus activity began in November and peaked in December-January, whereas in the eastern states activity began in January and peaked in February-March. These differences do not correlate with obvious trends in strain variation of rotavirus and remain unexplained. Unexpected reporting of summer rotavirus activity by some laboratories in 1989 was traced to the use of a single diagnostic kit and to two questionable laboratory practices: having more than six medical technologists perform the test and failure to use controls with the test. Laboratory-based surveillance of rotavirus activity has proven to be useful in identifying and correcting problems in laboratory methods for detecting rotavirus and will be a sensitive means for monitoring coverage of the rotavirus vaccine now being developed.

Immunogenicity of tetravalent rhesus rotavirus vaccine administered with buffer and oral polio vaccine.

Between January and November 1989, we studied 174 infants aged 6 to 16 weeks in a randomized clinical trial to (1) determine the immunogenicity of a single dose of tetravalent rhesus rotavirus vaccine (RRV-TV) when administered with three different buffer regimens: no antacid buffer and small-volume (2.5-mL) and large-volume (30-mL) antacid buffer; and (2) examine the potential interference of RRV-TV on the immune response to oral polio vaccine. Immunogenicity of RRV-TV, measured as a fourfold rise in antibody titers to rotavirus, was similar in the groups receiving small- and large-dose buffer (45% and 49%, respectively) and significantly less in the group that received RRV-TV alone (23%). Administration of RRV-TV with oral polio vaccine did not significantly interfere with the neutralization response of oral polio vaccine poliovirus serotypes 1, 2, or 3, and overall, 29%, 87%, and 24% of the infants had a fourfold rise in titer to each serotype, respectively.

Characterization of human cardiac myosin heavy chain genes.

We have isolated and analyzed the structure of the genes coding for the alpha and beta forms of the human cardiac myosin heavy chain (MYHC). Detailed analysis of four overlapping MYHC genomic clones shows that the alpha-MYHC and beta-MYHC genes constitute a total length of 51 kilobases and are tandemly linked. The beta-MYHC-encoding gene, predominantly expressed in the normal human ventricle and also in slow-twitch skeletal muscle, is located 4.5 kilobases upstream of the alpha-MYHC-encoding gene, which is predominantly expressed in normal human atrium. We have determined the nucleotide sequences of the beta form of the MYHC gene, which is 100% homologous to the cardiac MYHC cDNA clone (pHMC3). It is unlikely that the divergence of a few nucleotide sequences from the cardiac beta-MYHC cDNA clone (pHMC3) reported in a MYHC cDNA clone (pSMHCZ) from skeletal muscle is due to a splicing mechanism. This finding suggests that the same beta form of the cardiac MYHC gene is expressed in both ventricular and slow-twitch skeletal muscle. The promoter regions of both alpha- and beta-MYHC genes, as well as the first four coding regions in the respective genes, have also been sequenced. The sequences in the 5'-flanking region of the alpha- and beta-MYHC-encoding genes diverge extensively from one another, suggesting that expression of the alpha- and beta-MYHC genes is independently regulated.