Eye injuries in patients with major trauma

BACKGROUND: A study was performed to determine the type and frequency of ocular injuries in patients with major trauma. METHODS: All patients with ocular and adnexal injuries (n = 178) among 1,119 patients admitted with major trauma (Injury Severity Score >15) to the Royal Prince Alfred Hospital from July 1990 to December 1997 were analyzed. RESULTS: Sixteen percent of the major trauma cohort had ocular or orbital trauma. Fifty-five percent of patients with injuries involving the face had ocular or orbital injuries. A range of ocular injuries was seen. Analysis of the major trauma cohort showed that motor vehicle drivers, orbital and base of skull fractures, eyelid lacerations, and superficial eye injuries were strongly associated with vision-threatening injury. CONCLUSION: Patients with major trauma and facial injuries have a high risk of vision-threatening injury. Patients with orbital fractures, base of skull fracture, eyelid lacerations, and superficial eye injuries should be assessed by an ophthalmologist as part of the early management of their trauma to determine whether an ocular injury is present.     

Ultrasound Densitometry of the Os Calcis in Patients with Hemiparesis Following a Cerebrovascular Accident

Ultrasound densitometry has been measured in the os calcis of 31 stroke patients (14 women, 17 men), ages 46–87 years, to determine whether bone density is lower than expected for normal subjects at this site, and to investigate whether or not the stroke side has lower values than the nonstroke side. We have also measured a large control group of 268(39 men, 228 women) subjects who showed similar values to other published data. Immobility is a known precursor to bone loss and so we also compared ultrasound Stiffness Index with an index of mobility in 22 of the stroke patients. In healthy subjects, ultrasound densitometry (measured as Stiffness) fell by 25% in females from 48–52 to 68–72 years. Stiffness (expressed as z-score) in patients with stroke was low in females (P < 0.02) but not in males, but both stroke side and nonstroke side were equally low. Stiffness did not decline with time since stroke, but did correlate with mobility after stroke, on the stroke (r = 0.73) and nonstroke (r = 0.62) side. The data suggest that stroke patients, particularly females, have low bone density before the stroke event. The greater ultrasound Stiffness with increasing mobility after stroke may suggest that active rehabilitation after stroke may produce denser bone. Received: 30 July 1997 / Accepted: 10 June 1999     

Expression and immunogenicity of a liver stage malaria epitope presented as a foreign peptide on the surface of RNA-free MS2 bacteriophage capsids.

We have designed a novel vaccine strategy which enables display of short peptides expressed from chimeras of the gene encoding the coat protein of the RNA bacteriophage MS2 and inserted foreign DNA. MS2 coat protein has a beta-hairpin loop at the N-terminus which forms the most radially distinct feature of the mature capsid. The coat protein gene was modified to enable insertion of DNA at the central part of the beta-hairpin loop. Upon expression of the recombinant gene in E. coli, the MS2 coat protein subunits self-assemble into capsids, each comprising 180 copies of the monomer. This system was used to produce chimeras containing a putatively protective epitope, T1, from the immunodominant liver stage antigen-1 (LSA-1) of the malaria parasite Plasmodium falciparum. The immunogenicity of the native MS2 capsid and the recombinant construct was investigated in BALB/c (H-2(d)) mice. The native protein appeared to elicit both humoral and cellular immune responses, observed as a predominance of type 2 cytokines but with a mixed profile of immunoglobulin isotypes. In contrast, the LSA-1 chimera stimulated a type 1-polarised response, with significant upregulation of interferon-gamma, a finding which corroborates naturally acquired resistance to liver stage malaria. These results validate RNA phage capsid display of immunogenic determinants as a basis for the development of novel peptide vaccines and indicate that further evaluation of MS2 coat protein as a vector for malaria epitopes is merited.     

Strategies for biological monitoring of exposure for contemporary-use pesticides

Pesticides are used on a massive scale in the United States. The widespread use of these pesticides has made it virtually impossible for the average person to avoid exposure at some level. Generally, it is believed that low-level exposure to these pesticides does not produce acute toxic effects; however, various cancers and other noncancer health endpoints have been associated with chronic exposure to several groups of pesticides. Therefore, it is imperative that well-designed studies investigate the potential relationship between contemporary pesticide exposure and health effects. For these studies to be accurate, reliable methods for determining individual exposure must be used. Biological monitoring is a useful tool for assessing exposure to some contemporary pesticides. As with any analytical method, biological monitoring entails many difficulties, but, in many instances, they can be overcome by the logical use of available information and information acquired in carefully designed studies. At the Centers for Disease Control and Prevention (CDC), we have acquired extensive experience in the development and application of specific techniques for biological monitoring of a variety of toxicants, including many of the contemporary-use pesticides. We have used these methods to measure the internal dose of pesticides received by people in acute and chronic incidents resulting from both environmental and industrial exposure. Additionally, we have established normative values, or reference ranges, of several pesticides based on measurements of their metabolites in the urine of randomly selected adults in the US population. These data have been successfully used to distinguish overt exposures from 'background' exposure. In this paper, we present several examples of the usefulness of biological monitoring in urine and blood and describe the difficulties involved with developing methods in these matrices. We also present a general strategy, considerations, and recommendations for developing biological monitoring techniques for measuring the internal dose of contemporary-use pesticides.     

Conducting qualitative research in the health sector: researcher issues and dilemmas.

This article contributes to bridging the gap between research activity and the practical implementation of management decision making in the health sector by reflecting upon some of the issues and dilemmas for researchers, whether academics or managers, in conducting qualitative research in this sector. The article presents the methodological issues addressed by a team of researchers engaged on a project about manager learning and development in an NHS Trust, and highlights concerns about ethical issues that emerged from the research process. The study had involved a series of interviews with senior managers and clinical staff, doctors, nurses and therapists, and it addressed issues surrounding change within the organization, the impact on individuals' jobs, and the resultant learning and development required and undertaken. The article emphasizes that engaging in reflection on the research process is valuable and suggests that it should become a mainstream part of such research. It concludes that there is an important role of qualitative management research in the health sector and that for it to be acceptable and valued, it must be operationally sensitive, ethically robust and methodologically rigorous.     

Selective NMDA NR2B antagonists induce antinociception without motor dysfunction: correlation with restricted localisation of NR2B subunit in dorsal horn.

The present study investigated the regional distribution of the N-methyl-D-aspartate (NMDA) receptor containing the NR2B subunit protein in rat lumbar spinal cord and examined whether selective NR2B antagonists would exhibit antinociception with reduced side-effect liability than subtype non-selective NMDA antagonists and anticonvulsants. Immunocytochemical studies showed the NR2B subunit had a restricted distribution, with moderate labelling of fibres in laminas I and II of the dorsal horn suggesting a presynaptic location on primary afferent fibers and possible involvement in pain transmission. In the in vivo studies, the NMDA/glycine antagonists (MK-801, 0.02-1 mg/kg i.p., L-687,414 10-300 mg/kg i.p., and L-701,324 1-10 mg/kg i.p.) and the anticonvulsant, gabapentin (10-500 mg/kg p.o.), induced rotarod deficits at antinociceptive doses. In contrast, the selective NR2B antagonists, (+/-)-CP-101,606 (1-100 mg/kg p.o.) and (+/-)-Ro 25-6981 (3-100 mg/kg i.p.) showed a significant dose window. (+/-)-CP-101,606 caused no motor impairment or stimulation in rats at doses up to 100 mg/kg p.o., which is far in excess of those inhibiting allodynia in neuropathic rats (ID50 4.1 mg/kg, p.o.). (+/-)-Ro 25-6981 also showed a significant separation (ID50 allodynia 3.8 mg/kg, i.p.), however, some disruption of rotarod performance was observed at 100 mg/kg. The anticonvulsant lamotrigine (3-500 mg/kg p.o.) also showed a good dose window. These findings demonstrate that NR2B antagonists may have clinical utility for the treatment of neuropathic and other pain conditions in man with a reduced side-effect profile than existing NMDA antagonists.     

Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein

Abnormal processing of amyloid precursor protein (APP), in particular the generation of beta-amyloid (Abeta) peptides, has been implicated in the pathogenesis of Alzheimer's disease. This study examined the consequences of deleting the APP gene on hippocampal synaptic plasticity, and upon the biophysical properties of morphologically identified neurones in APP-null mice. The hippocampus of APP-null mice had a characteristic increase in gliosis throughout the CA1 region and a disruption of staining for the dendritic marker MAP2 and the presynaptic marker synaptophysin. The disruption of MAP2 staining was associated with a significant reduction in overall dendritic length and projection depth of biocytin labeled CA1 neurones. In two groups of APP-null mice that were examined at 8-12 months, and 20-24 months of age, there was an impairment in the formation of long-term potentiation (LTP) in the CA1 region compared to isogenic age matched controls. This LTP deficit was not associated with an alteration in the amplitude of EPSPs at low stimulus frequencies (0.033 Hz) or facilitation during a 100 Hz stimulus train, but was associated with a reduction in post-tetanic potentiation. Paired-pulse depression of GABA-mediated inhibitory post-synaptic currents was also attenuated in APP-null mice. These data demonstrate that the impaired synaptic plasticity in APP deficient mice is associated with abnormal neuronal morphology and synaptic function within the hippocampus.     

Propofol hydroxylation by dog liver microsomes: assay development and dog breed differences.

Pharmacokinetic studies indicate that clearance of propofol, an anesthetic agent, is slower in greyhounds compared with other dog breeds. Biotransformation of propofol to 2,6-diisopropyl-1,4-quinol (4-hydroxypropofol) by cytochrome P-450 in the liver is proposed as a critical initial step in the elimination of this drug in dogs. Breed differences in the activity of this enzyme could therefore explain pharmacokinetic differences. An in vitro propofol hydroxylase assay was developed and then used to compare enzyme activities in liver microsomes from male greyhound, beagle, and mixed-breed dogs (five each). HPLC of incubate identified only one NADPH-dependent metabolite, which had a chromatographic retention time and UV absorbance, fluorescence, and mass spectra that were identical with authentic 4-hydroxypropofol standard. HPLC with fluorescence detection provided a highly sensitive quantitation method for 4-hydroxypropofol with a quantitation limit of 8 ng/ml using optimized excitation/emission wavelengths (288 nm/330 nm, respectively). Estimates of apparent K(m) and V(max) for propofol hydroxylation by microsomes from a male beagle dog were 7.3 microM and 3.8 nmol/mg/min, respectively. At a substrate concentration of 20 microM, propofol hydroxylase activity was significantly lower (p =.032) in greyhound microsomes (1.7 +/- 0.4 nmol/mg/min) compared with beagle microsomes (5.1 +/- 1.3 nmol/mg/min) but was not statistically different (p =.42) compared with mixed-breed microsomes (3.1 +/- 1.2 nmol/mg/min). These results indicate that there are breed differences in propofol hydroxylase activity and that deficient hydroxylation of propofol by one or more hepatic cytochrome P-450 isoforms may contribute to slow pharmacokinetic clearance of propofol by greyhounds.     

Vinflunine (20′,20′-difluoro- 3′,4′-dihydrovinorelbine), a novel Vinca alkaloid, which participates in P-glycoprotein (Pgp)-mediated multidrug resistance in vivo and in vitro

Vinflunine (VFL) is a novel derivative of vinorelbine (NVB, Navelbine®), which has shown markedly superior antitumor activity to NVB, in various experimental animal models. To establish whether this new Vinca alkaloid participates in P-glycoprotein (Pgp)-mediated multidrug resistance (MDR), VFL-resistant murine P388 cells (P388/VFL) were established in vivo and used in conjunction with the well established MDR P388/ADR subline, to define the in vivo resistance profile for VFL. P388/VFL cells proved cross-resistant to drugs implicated in MDR (other Vinca alkaloids, doxorubicin, etoposide), but not to campothecin or cisplatin and showed an increased expression of Pgp, without any detectable alterations in topoisomerase II or in glutathione metabolism. The P388/ADR cells proved cross-resistant to VFL both in vivo and in vitro, and this VFL resistance was efficiently modulated by verapamil in vitro. Cellular transport experiments with tritiated-VFL revealed differential uptake by P388 sensitive and P388/ADR resistant cells, comparable with data obtained using tritiated-NVB. In various in vitro models of human MDR tumor cells, whilst full sensitivity was retained in cells expressing alternative non-Pgp-mediated MDR mechanisms, cross resistance was identified in Pgp-overexpressing cells. Differences were, however, noted in terms of the drug resistance profiles relative to the other Vincas, with tumor cell lines proving generally least cross-resistant to VFL. Overall, these results suggest that VFL, like other Vinca alkaloids, participates in Pgp-mediated MDR, with tumor cells selected for resistance to VFL overexpressing Pgp, yet MDR tumor cell lines proved generally less cross resistant to VFL relative to the other Vinca alkaloids.     

Intraoperative laparoscopic complications

PURPOSE: The aim of this study was to assess various intraoperative and postoperative complications associated with laparoscopic colorectal surgery. Specifically, the impact of surgical experience and procedure type on complications was analyzed. METHODS: All patients who underwent laparoscopic surgery were analyzed by age, sex, surgical indications, procedure performed, procedure length, intraoperative and postoperative complications, incidence and causes for conversion, duration of postoperative ileus, and length of hospital stay. Patients were classified for type of procedure and chronologically into four consecutive groups. Procedures were also categorized into four different groups: GI, total abdominal colectomies; GII, segmental resections; GIII, diverting procedures; GIV, others (abdominoperineal resection, Hartmann's creation or closure, anterior resection, and rectopexy). RESULTS: Between August 1991 and October 1995, 167 patients of a mean age of 49.6 (15–88) years underwent laparoscopic colorectal procedures. All procedures were electively performed. Common indications for surgery included inflammatory disease in 70 (42 percent), neoplasia in 56 (33 percent), functional bowel disorders in 30 (18 percent), and other forms of colorectal disorders in 11 (7 percent) patients. The most significant variable affecting intraoperative laparoscopic complication rate was surgical experience measured as the time interval during which surgery was performed (P=0.02). Total complication rate decreased from 29 percent during the first period to 11 percent by the second period (P<0.04) and 7 percent during the third period (P<0.005). Thus, the learning curve appeared to have required more than 50 cases to achieve. Moreover, even after performance of 94 (1991–1993) procedures in GI and GIV, these procedures were associated with higher complication rates than were those procedures in GII and GIII (P=0.04). CONCLUSION: Surgical experience and case selection are the most critical variables by which the surgeon can decrease the intraoperative laparoscopic complication rate.